bulletin - unitbv

ISSN 2065-2216

TRANSILVANIA UNIVERSITY OF BRAŞOV

BULLETIN

OF THE

TRANSILVANIA UNIVERSITY

OF

BRAŞOV

VOL. 1 (50) – 2008

SERIES VI MEDICAL SCIENCES

Published by

Transilvania University Press

Braşov, Romania

2008

EDITORIAL BOARD

Editor in Chief

Prof. dr. eng. Ion VIŞA

Co-editors

Prof. dr. eng. Elena Helerea

Prof. dr. eng. Anca Duţă

Prof. dr. med Liliana Rogozea

Coordinating Editor series VI

Prof.dr. chem. Gheorghe COMAN

Final Technical Supervision

Mat. Gabriela MAILAT

Roxana CIOBANU

English Language Supervision

Lect. drd. Lucian RADU

Web-site: http://but.unitbv.ro/BU2008/

Adresa: B-dul Eroilor nr. 29, CP 500036, Braşov, România

Telefon: 0268/413000

E-mail: [email protected]

© All rights reserved

SCIENTIFIC COMMITTEE

Assoc. Prof. chem. Mihaela BADEA, Ph.D., Transilvania University of Brasov, Romania

Prof. Salem ABDEL-BADEEH, Ph.D., Ain Shams University, Cairo, Egypt

Prof. Cristina BORZAN, M.D., Ph.D., UMF Iuliu Haţieganu, Cluj-Napoca, Romania

Prof. Sorin BUZINSCHI, M.D., Ph.D., Transilvania University of Brasov, Romania

Dr. Daniel CATALAN, European Center for Disease Prevention and Control

Prof. chem. Gheorghe COMAN, Ph.D., Transilvania University of Brasov, Romania

Prof. Nina CADIZ, Ph.D., University of the Philippines Los Banos

Assoc. Prof. Carmen DOMNARIU, M.D., Ph.D., University Lucian Blaga, Sibiu, Romania

Prof. Alin CUCU, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Dan DUMITRASCU, M.D., Ph.D., UMF Iuliu Hatieganu, Cluj-Napoca, Romania

Prof. Leonida GHERASIM, M.D., Ph.D, UMF Carol Davila, Bucharest, Member of

Romanian Academy, Romania

Prof. Ove HELLZEN, Ph.D., Faculty of Health Sciences, Norway

Prof. Kornelia HELEMBAI, Ph.D., University of Szeged, Hungary

Prof. Teodor LEASU, M.D., Ph.D., Transilvania University of Brasov, Member of the

World Academy of Medicine, Romania

Prof. Jean-Louis MARTY, Ph.D., Universite Perpignan, France

Prof. Dan MINEA, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Aurel MIRONESCU, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Nicolae MIU, M.D., Ph.D., UMF Iuliu Hatieganu, Cluj-Napoca, Romania

Assoc. Prof. Marius MOGA, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Ioana MOISIL, Ph.D., University Lucian Blaga, Sibiu, Romania

Prof. Dimitrie NANU, M.D., Ph.D., UMF Carol Davila, Bucharest, Romania

Assoc. Prof. Laurenţiu NEDELCU, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Codruta NEMET, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Gilvanda NUNEZ, Ph.D., Federal University of Maranhao, Potugalia

Prof. Lazar ONISÂI, M.D., Ph.D., Transilvania University of Brasov, Romania

Assoc. Prof. Candan OZTURK, Ph.D., Dokuz Eylul University, Turkey

Prof. farm. Honorius POPESCU, Ph.D., UMF Iuliu Haţieganu, Cluj-Napoca, Member of

the “Academie Internationale d’Histoire de la Pharmacie”, Romania

Assoc. Prof. Mariusz PUSZCZEWICZ, M.D., Ph.D., Poznan University of Medical

Science, Poland

Prof. Mariana RADOI., M.D., Ph.D., Transilvania University of Brasov, Romania

Assoc. Prof. Patrizia RESTANI, M.D., Ph.D., State University of Milan, Italy

Prof. Ilia REUBEN, M.D., Ph.D., Ben Gurion University of the Negev, Israel

Prof. Liliana ROGOZEA, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Iosif SAMOTA, M.D., Ph.D., Transilvania University of Brasov, Romania

Prof. Erich SORATIN, M.D., Ph.D., Medical University Graz, Austria

CONTENT

Fleancu, A., Sechel, G, Onisâi, L.L.,

Bold, C.L., Fleancu, C., Banuta, I.A.

Grecu, A. : Imagistic Study upon Urinary Malformative Pathology ....................... 1

Sechel, G., Fleancu, A., Ţurcanu, M., Diaconu, S.: Anatomic and Imagistic

Correlations In Bronchial Tree Segmentation ......................................................... 9

Onisâi, L.L., Scârneciu, I., Greavu, M., Peri, G.: The Anterolateral Abdominal

Wall - Vascularisation Development during Morphogenesis ................................ 17

Badea, M., Munteanu, M., Lazoriec, L., Coman, G., Restani, P.: Competitive

Elisa for Aflatoxins and Ochratoxins Detection ..................................................... 21

Nunes, G.S., Badea, M., Medel, M.-L., Noguer, T., Marty, J.-L.: Ultrasensitive

Biosensors for the Detection of Insecticide Residues in Fruit Juices ..................... 29

Restani, P., Caruso, D., Giavarini, F., Moro, E., Persico, A., Uberti, F.,

Ballabio, C., Colombo, M. L., Badea, M.: Analytical Monitoring as a Tool to

Detect Illegal Substances in Foods and Food Supplements .................................. 37

Idomir, M., Nemet, C., Pascu, A., Moleavin, I.: Imipenem Resistance among

Gram Negative Bacilli ............................................................................................ 43

Neculoiu, D., Moleavin, I., Anghel, M., Cristea, A.: Non-Organ Specific

Autoantibodies and the Response to the Therapy in Chronic Hepatitis C............. 47

Agache, I.: Acquired Angioedema in Systemic Lupus Erythematosus ............................ 55 Ifteni, G., Rus, H., Rădoi, M., Pamfil, G.: The Relationship between the Risk

Profile of Arterial Hypertension and the Features of Metabolic

Syndrome-Study on 129 Patients ........................................................................... 61

Scârneciu, C., Nedelcu, I., Scârneciu, I., Scârneciu, V.: Hyperthyroidism at

debut and the left ventricle mass ............................................................................ 67

Rus, H., Rădoi, M., Ciurea, C., Nan, M., Suta, C., Boda, D.: Effect of

Treatement with Omega-3 Fattyacids and Atorvastatin in Patients with

Combined Dyslipidemia.......................................................................................... 75

Bobescu, E., Rădoi, M., Galajda, Z., Datcu, G.: In Patients with Non-St Acute

Coronary Syndrome Diabetes Mellitus and Metabolic Syndrome have an

Important Impact on Prognosis, Left Ventricular Systolic Function,

Inflammatory Syndrome and Oxidative stress ....................................................... 81

Hussain, S., Afzal, N., Kohen, I., Manu, P. : C Reactive Protein and Clozapine-

Induced Fever ........................................................................................................ 89

Man, M. A., Alexandrescu, D., Pop, M., Râjnoveanu, R., Goron, M., Arghir, O.:

Smoking-Risk Factor for Metastasis in Breast Cancer........................................... 93

Falup-Pecurariu, O., Răşină, A., Falup-Pecurariu, C.: Antibiotic Susceptibility

Changes of Staphylococcus Aureus a Retrospective Study ....................................... 99

Burtea, V., Moşoiu, C.: Stigmatization of People with Schizophrenia in Clinical

Settings.................................................................................................................. 107

Ifteni, P., Burtea, V.: The Major Depressive Disorder with Mtabolic Syndrome -

Study on 90 Patients ........................................................................................... 111

Moşoiu, C., Burtea, V.: Positive and Negative Syndrome Scale Clustering of

Schizophrenia ....................................................................................................... 115

II Bulletin of the Transilvania University of Braşov � Vol. 1 (50)� Series VI

Falup-Pecurariu, C., Postelnicu, A., Pamfil, G., Monescu, V.,

Falup-Pecurariu, O., Alexandru, R.: Hemodynamics of the Posterior Cerebral

Artery .................................................................................................................. 119

Buzescu, M.: Comparative Study on the Efficacy of Different Protection

Methods In Chronic Acoustic Trauma .................................................................. 127

Mişarcă, C., Cucu, A., Durach, L.: Enteral Nutrition in the Treatment of Severe

Acute Pancreatitis ................................................................................................ 133

Scârneciu, I., Lupu, S., Onisâi, L.L., Scârneciu, C., Lupu, A.M., Scârneciu, V. D.:

Extracorporeal Shockwave Lithotripsy (ESWL) as a Mean of Treatment

in Urinary Lithiasis.............................................................................................. 139

Fanea, R., Voroneanu, M., Oros, C.: The Patient- Risk Marker for

Medical Emergencies in the Dental and Oral Surgery Office ............................. 145

Comşa, F.: Ultrastructural Changes in a Case of Recurrence after Varicose

Veins Surgery ....................................................................................................... 151

Alexandrescu, D.: Integrated Positron-Emission Tomography and the Staging

of Nodular Non-Small-Cell Lung Cancer ........................................................... 157

Baum, E.: Significance of Embryonic Stem Cells in Regenerative Medicine ................ 163

Bălescu, A., Leaşu, F., Rogozea, L., Chefneux, E.:

Health Promotion and

Elaboration of a Preventive Strategy for Brasov County .................................... 169

Cersosimo, G.: Drugs and Medicine in Youth Culture .................................................. 175

Rogozea, L., Bălescu, A., Domaradzki, J., Wierzejska, E., Baritz, M., Cristea, L.:

Dilemmas and Factors Involved in Promoting Men’s Health in Brasov

County .................................................................................................................. 195

Fătu-Tutoveanu, A.: A Decadent Age - 1900. Freud and Cocaine................................. 203

Authors Index.................................................................................................................. 211

IMAGISTIC STUDY UPON URINARY

MALFORMATIVE PATHOLOGY

A. FLEANCU

1 G. SECHEL

1 L.L. ONISÂI

1

C.L. BOLD1 C. FLEANCU

1 I.A. BANUTA

1

A. GRECU1

Abstract: The present paper has the purpose of realizing an incidence

study of reno-ureteral malformations. It is based on imagistic data obtained

from patients who want in cause services for any type of pathology.

Therefore, a bond with afferent simptomathology was made. It has come to

the conclusion that the majority of urinary malformations are mute form

clinical point of view and only a small percentage of these generate hydro-

nephrosis, urinal infections or a modification of biological parameters

Key words: renal malformation, urography, ecography, computer-

tomography

1 Transilvania University of Brasov, Faculty of Medicine

1. Aim of the Study

The paper aims at analysing the

frequency of reno-ureteral malformations

and of their different types, by correlating

data obtained through dissection and

imagistic methods. The study tries to

research the connections with possible

associated pathologies. [4]

2. Method and Material

Using cases from „Rapid Diagnostic

Polyclinic - Medis” from Brasov (patients

that had abdominal examination in the

period January 2007- December 2007),

144 cases of reno-ureteral malformations

were analysed using: ecography,

urography and computer-tomography. The

study was completed by dissecting 36 adult

bodies belonging to the laboratories of the

Medicine Faculty of Brasov.

3. Results

1. The total number of imagistic

investigated cases was 7200.

2. 4 of 36 cases examined by dissection

were found with renal malformations:

horseshoe kidney, ectopic kidney (2

cases) and big renal pelvis.

3. The presence of reno-ureteral malfor-

mations is very small. (See graphic 1)

Graphic 1. The frequency of reno-

ureteral malformations among general

population

Bulletin of the Transilvania University of Braşov • Vol. 1(50) – 2008 � Series VI

2

4. Polycystic kidney is the most frequent

between all reno-ureteral malfor-

mations. It is followed by pielo-caliceal

duplication and renal ectopy. Very rare

are the unique congenital kidney, the

horseshoe kidney, the sigmoid kidney

and also abnormal forms of the bladder.

(See graphic 2)

Graphic 2. The frequency of reno-

ureteral malformation types in comparison

with all types of malformations

5. Widely used, malformations are

discovered through echography (ECO)

– non-invasive method with advantages

such as low cost and easy access to the

in need technology. Computed-

tomography (CT) is used to diagnose or

discover the malformation of another

organ. For symptomathologic cases the

chosen selection imagistic method is

intra-venous urography (IVU). (See

graphic 3)

Dead-

Bodies

IVU

CT

ECO

7%

27%

5%

61%

Graphic 3. Investigation methods used to

stand out urinary system anomalies

6. The percentage of reno-ureteral

malformations associated with other

types of malformations is 3.4% as seen

in Graphic 4.

The associated malformations are:

- Left agenesis, double right kidney

- Association with double inferior cava

vein

- Left agenesis, right sigmoid kidney

- Left agenesis, ectopic right kidney

presenting big calices, megabazinet

and megaureter

- Right agenesis + double uterus [2]

All cases of renal malformations had

different origin and distribution for the

renal veins and arteries and also for the

ones for the gonads

Graphic 4

Imagistic Study upon Urinary Malformative Pathology 3

4. Cases

I. Renal malformations of form

A. Polycystic Kidney

Fig.1. Multiple cystic injuries on the

right kidney - echographic section

B. Parapielic Cysts

Fig. 2. Parapielic cysts on left kidney –

echographic section

C. Horseshoe Kidney

Fig.3. Horseshoe kidney –

Echographic aspect

Fig. 4. Horseshoe kidney - CT aspect:

urographic reconstruction; axial section;

VRT reconstruction

D. Sigmoid Kidney

Fig. 5. Sigmoid kidney situated under the

bifurcation level of the aorta, each with its

bifidus ureter and its anterior malrotation

of the hilar region, the arterial

vascularisation has the provenience from

the common iliac arteries.

- Coronary CT sections injected with

contrast substances


4

Fig. 6. Anterior malrotation and bifidus

ureter on both kidneys.

Two ureters on both kidneys – One

leaves the superior pole and the other from

the hilar region - CT aspect - Axial section;

Sagital section

Fig. 7. Axial section – ecographic aspect

VRT (CT) Reconstruction

E. Hypoplasic Kidney

Fig. 8. Left hypoplasic kidney – VRT

(CT) reconstruction

II. Renal Malformations of Number

A. Unilateral renal agenesis

Fig. 9. Left unique congenital kidney

associated with double uterus; 17 weeks

pregnancy – echographic sections


Fig. 10. Characteristics of the right

kidney: unique, congenital, ectopic-pelvic;

big calices, big renal pelvis, big right

ureter urographic footage

B. Multiple kidney

Fig. 11. Left sided double kidney (2

conglomerate kidney); unique right kidney

– echographic sections

III. Renal Malformations Of Position

– Ectopic Kidney

Fig. 12. Pelvic right kidney with ureter and

vascular pedicule both short – Dissection

material

Fig. 13. Ectopic pelvic right kidney situated

under the bifurcation level of the aorta;

anterior malrotation of the hilar region;

ureter and vascular pedicule both short –

Dissection material

Fig. 14. Ectopic pelvic right kidney with two

arterial sources – a polar artery which came

from the aorta and a renal artery which came

from the bifurcation of the aorta and goes

into the hilar region – VRT (CT)

reconstruction


6

Fig. 15. Same case as Fig 14 - Renal

vein goes to common left iliac vein which

presents a descending sinuous route –

coronary CT reconstruction

IV. Malformations of Form Regarding

Excretory Ways

A. Congenital megaureter

Fig. 16. Big renal pelvis – Dissection

material

Fig. 17. Left megaureter

– urographic footage

B. Ureterocel

Fig. 18. Right ureterocel – urographic

footage

V. Malformations of Number Regarding

Excretory Ways

A. Pielo-caliceal duplication

Fig. 19. Double pielon, simetrical left

kidney – echographic sections

Fig. 20. Left sided double ureter –

urographic footage


VI. Malformations of Position Regarding

Excretory Ways

– Vesical Diverticulitis

Fig. 21. Large bladder diverticuli that

are not evacuated during micturition; thick

vesical mucous membrane

Fig. 22. Right posterior-lateral big

diverticuli; Left posterior-lateral small

diverticuli – pelvic CT axial section

5. Conclusions

1. Reno-ureteral malformations have a

2% presence among general population

and a 6% presence among all malfo–

rmations.

2. Polycystic kidney is the most frequent

between all reno-ureteral malforma–

tions. It is followed by pielo-caliceal

duplication and renal ectopy. Very rare

are the unique congenital kidney, the

horseshoe kidney, the sigmoid kidney

and also abnormal forms of the. [1]

3. The most popular imagistic method is

echography because it is very

accessible and non-invasive but it

brings poor information about the

relationships, the vascularization and

specially keeping the functionality of

the malformed segment.

4. Urography is very specific in finding

malformative cases due to its

simptomathology. It gives informations

about functions but not about

relationships and vascularization.

5. Complete morphological and function–

nal data are given by Computed

Tomography 2D and 3D

reconstructions by meanings like

injecting contrast substances. [3]

6. Most of the malformations are disco-

vered at a late stage and by chance, as

they are well tolerated (pielo-caliceal

duplication, the horseshoe kidney or

the unique congenital kidney); the

malformations discovered at an earlier

stage are those that generate hydro-

nefrosis (the syndrome of pielo-

ureteral junction), urinal infections or

modification of biological parameters

(the polycystic kidney).

Sometimes, the malformation is discovered

by investigating a suspicion of an

abdominal-pelvine tumour (the horseshoe

kidney or the ectopic kidney)

References

1. Belsare, S.M., Chimmalgi, M., Vidya

S.A. & Sant S.M.: Ectopic kidney and

associated anomalies: A Case Report

2. Fernandez Rodriguez, A., Arrabal

Martin, M., Mijan Ortiz, J.L., Palao

Yago, F., Zuliaga Gomez, A.:

Renoureteral malformation and

lithiasis


8

3. Lee, J.K.T., Sagel, S.S., Stanley, Jay,

R.J., Heiken, P.: Computed Body

Tomography with MRI correlation,

Vol. 2. 2006.

4. Tidy, C.: Congenital Urogenital

Malformation

5. Torra, R.: Polycystic Kidney Disease

ANATOMIC AND IMAGISTIC

CORRELATIONS IN BRONCHIAL

TREE SEGMENTATION

G. SECHEL

1 A. FLEANCU

1

M. ŢURCANU1 S. DIACONU

1

Abstract: The present paper aims at studying the distribution of the

intrapulmonary bronchial tree and at underlining the possible anatomic

variants with a certain importance for the surgical treatment at this level.

This study comprises an analysis of 55 cases, for the period 2003-2008, using

dissection, CT exam and resin injected models (experimental). As a

conclusion, the experimentally obtained model using the corrosion technique

allowed the study of the bronchial divisions at a segmental and sub-

segmental level, having some disadvantages at a bronchiolar level. The CT

exam in lung windows permitted the study of the bronchus’ trajectory, section

by section, showing its reconstruction and relations with the other

anatomical elements using modern detailed imagistic techniques

Key words: bronchial tree, resin injected models, computer tomography

1 Transilvania University of Brasov, Faculty of Medicine

Introduction

The bronchial tree consists of 2 main

bronchi, left and right plus a tracheal

bronchus that detaches from the trachea’s

right side. After entering the lung, the main

bronchi divide into lobar bronchi, for the

pulmonary lobe, then into segmental ones,

into bronchioles and finally into lobular

bronchioles - for the lung’s lobule. Lobular

bronchioles divide into terminal bron-

chioles and then into respiratory ones

ending in the alveoli. [8]

Fig. 1. The segments of the bronchial tree.


10

Bronchial nomenclature Table 1

A comprehensive bronchial nomen-

clature is given in Figure 1 and Table 1. [6] The right main bronchus (BPD) is divided

itself into right superior lobar bronchus (BLSD) and intermediary trunk (IT). BLSD has a horizontal trajectory (1-2 cm) then divides into 3 segmental branches: B1, B2, B3. The intermediary trunk has a vertical trajectory about 3cm, from BLSD’s origin to intermediary lobar bronchus’ origin (BLM). On the posterior and internal side of the hilum, the pulmonary parenchyma frames the inter-azygo-esophageal recess, delimitated on the interior by the azygos vein and the esophagus. The intermediary lobar bronchus (BLM) detaches from the anterior lateral side of IT, and it is separated at the origin from the inferior lobar bronchus by a small triangular tissue. After 1-2 cm, it is divided into segmental bronchi, B4 (external) and B5

(internal). Nelson’s bronchus (B6) is generally located superior to BLM. [7]

For the left lung, the segmental bronchi B1 and B3 can be seen like 2 round hypo-densities or like a common trunk (B1+3). They are separated from the left main bronchus (BPS) by the left pulmonary artery. [4]

BLSS is situated lower than BLSD; it detaches from the exterior and anterior side of the main left bronchus and its origin corresponds to the middle part of the IT from the right hilum. BLSS is also divided into B1+3. B2 has a horizontal trajectory and it is located to the anterior. The lingular bronchus (B4+5) appears on the distal side of the superior lobar bronchus and has an oblique trajectory, almost parallel to B2. BLIS is generally divided into 2 trunks: B7+8 and B9+10. [3, 5]

Table 2

The normal findings and the most common bronchial variants in the studied patients

Anatomic and Imagistic Correlations in Bronchial Tree Segmentation 11

Material and Method

For this study there were analyzed 55

cases and 5 animals during 5 years using

these 3 methods within the framework of

the Quick Diagnosis Clinic and the

anatomy laboratories (fig. 2,3):

1. The dissection method on 8%

formolised human bodies;

2. The corrosion technique

For the experimental part of this

study, there have been used the

bronchial trees taken over from 5

pigs and 1 cow. The method

consists of the injection with

pigmented resin (treated with other

substances in order to modify the

fluidity and the viscosity) as well

as in the corrosion with caustic

soda. The modifications of the

fluidity or the main material’s

compounds (even changing the

pigment) implied the extension of

the experiments, from 1 lot to 3,

better results being noticed.

3. Computer tomography thoracal

exam on 35 cases, in order to

investigate various diseases.

Were used:

• CT thoracic exam, spiral acquisi–

tion on a CT Somatom Emotion 6

device. Technique: KV: 130;

Effective mAs: 70; Slice

collimation: 2.0 mm; Increment:

2.5 mm; Kernel B41s (B70s –

parenchyma window)

• MPR in various plans and other

special reconstructions emphasize

the ramifications of the broncho-

pulmonary tree

• also MINIP and VRT recon–

structions.

Fig. 2. The aspect of the bronchial tree;

the dissection method

Fig. 3. Transversal section at the level of the

bifurcation of the trachea, emphasizing the

main bronchus and the lobar. The results of

the corrosion technique can be classified into

3 categories depending on the 3 lots under

study and on the technique in use, the focus

being laid upon the main material, fluidity,

viscosity, pigment, accelerator, stabilizer,

restoration time, corrosion time.


12

Concerning the first lot, the organs were

taken over from a pig and were treated

with high fluidity resin; a yellow pigment

was used; the quantity of stabilizer was too

small for the main material so the

restoration time was longer – 12-15

minutes for the areas with more than 6mm

in diameter; 3-24 hours for thin areas; the

final process lasting up to 6 weeks (fig. 4).

Fig. 4. Bronchial tree obtained by

corrosion method, first lot.

Results

The technique used for the second and

the third lot is almost the same, excepting

some modifications of the main material

and of the stabilizer. The organs of the

second lot were taken from a pig and a

cow and for the last lot, just from a pig.

The resin was treated with blue pigment

for the second lot and red pigment for the

3rd

one; also, the quantities used were

smaller.

Concerning the connection between the

results and the technique, in the second lot,

the time of stabilization decreased (8

minutes for areas with more than 6mm in

diameter, 25-30 minutes for thinner areas;

the stabilization lasted 30 hours) because

of the bigger quantity of stabilizer. Thus,

the lobar, segmental and sub-segmental

ramifications could be seen (figure 5).


corrosion method, second lot

Dealing with the third lot, the quantity of

stabilizer was smaller and the fluidity was

increased; the time of stabilization was

shorter with 1-2 minutes, but the main

disadvantage of the method is the

modification of the bronchial branches

(figure 6). The final stabilization for both

methods takes 6 days.


corrosion method, third lot.

Nine axial CT levels were used for this

study:

1. Thoracic Inlet and Sternoclavicular

Junction.

These CT planes run charac–

teristically parallel to the clavicles

and at a lower level – the first rib.

The trachea can be seen midline and

it is surrounded by the 2 lobes of the

thyroid gland. Another mediastinal

organ, the oesophagus, is located


posterior to the trachea, slightly on

the left of the midline. Anterior and

lateral to the trachea, the mediastinal

vessels can be noticed: the three major

branches of the aortic arch (the

brachiocephalic, left common carotid,

left subclavian arteries) and the two

brachioceplaic veins, located posterior

to the clavicular heads. [2]

2. Crossing Left Brachiocephalic Vein

At this level, the junction between

the manubrium and body of the

sternum can be seen. The two

brachiocephalic veins are situated

anterior to the trachea. The left

brachiocephalic vein is longer and

joins the superior vein cava.

3. Aortic Arch

The anterior portion of the arch is

situated anterior to the trachea and

comes into medial contact with the

superior vena cava. The middle part

of the arch is located on the left side

of the trachea and the posterior

portion – at the junction of the aortic

arch and the descending aorta is

lateral to the oesophagus.

4. Aortopulmonary Window

This region contains the distal

trachea, mediastinal fat (beneath the

arch medial to the descending aorta

and above the left pulmonary artery)

and some lymph nodes.

5. Left Pulmonary Artery

The left pulmonary artery (which is

the division of the main pulmonary

artery) lies to the left and lateral to

the carina as it crosses over the main

stem bronchus.

6. Main and Right Pulmonary Artery

The right pulmonary artery extends

posterior and to the right from the

main pulmonary artery, coursing

posterior to the superior vena cava and

anterior to the intermediary bronchus.

7. Left Atrium

The left atrium is delimitated by the

aortic root and right atrium to the

anterior and by the azygos vein, the

oesophagus and the descending

aorta to the posterior.

8. Cardiac Ventricles

The right ventricle is situated

anterior to and to the right of the left

ventricle. The two ventricles are

separated by an oblique

interventricular septum.

9. Retrocrural Space

The retrocrural space, at the level of the

aponeurotic hiatus in the diaphragm,

contains the esophagus, the descending

aorta, the azygos and hemiazygos

veins, the thoracic duct and the

associated lymphatic nodes. [9]

Fig. 7. Transversal section at T5 level, corresponding to the axial CT section at the level

of the left pulmonary artery. The right upper lobar bronchus, as well as the RMB, the left

pulmonary artery and the LMB can be noticed.


14

Fig. 8.Coronary CT section, parenchyma window, emphasizing the apical segment of the

RSLB

Fig. 9. LSLB, CT reconstruction showing the lingular segment


Fig. 10a Fig. 10b

Fig. 10. CT exam, coronary section, MINIP reconstructions, emphasizing the bronchial

tree: a: LSLB; the common trunk B1+B2; RMLB; B4+B5; LSLB; B1+B2+B3; small

aberrant bronchus from B1 (B*1); common trunk B4+B5+LILB. From TI, cranial to the

emergence of RMLB can be noticed B6. b: Aberrant bronchus from IT with a posterior

direction (B*2).

Fig. 11a Fig. 11b Fig. 11c

Fig. 11.: a: from RILB: common trunk: B8+B9 with B10; separately, B7 and from LILB:

points out B9 and the common trunk B7+B8 with B10; b: B9 appears between the

lingular segments and the other base segments of the LILB; c: the separate origin of B3

from RSLB.

Conclusions

1. Using the dissection method we

could see the classical variants

concerning the main bronchus’

position at the level of the

pulmonary hilum.

2. The visualization of the segmental

and sub-segmental bronchi could

be emphasized by using the

corrosion technique in the 3rd

case. In the experimental studied

cases, the presence of an aberrant

right superior bronchus could be

noticed.

3. Bronchial anatomy is adequately

demonstrated with the appropriate

spiral computed tomographic tech-

nique on cross-sectional images,

multiplanar reconstruction images,

and three-dimensional reconstruc-

tion images. Contrary to the nume-

rous variations of lobar or segmen-

tal bronchial subdivisions, abnor-

mal bronchi originating from the

trachea or main bronchi are rare.


16

4. The most common variants are:

- for BLSD: bifurcation B1+B2, B3,

followed by the trifurcation B1, B2,

B3

- for BLSS: in all the cases –

bifurcation in B4+B5 and

separately, B1, B2, B3

- for BLID: separately B6, B7;

bifurcation B8+B9, B10 and also

the variant: B9+B10, B8

- for BLIS: separately B6;

trifurcation B7+B8, B9, B10

References

1. Berrocal, T., Madrid, C., Novo, S.,

Gutierrez, J., Arjonilla, A. and

Gomez-Leon, N.: Congenital

Anomalies of the Tracheobronchial

Tree, Lung, and Mediastinum:

Embryology, Radiology, and

Pathology. In: RadioGraphics, January

1, 2004; 24(1): e17.

2. Gamsu, G.: Computed tomography of

the body. In: Moss A.A., Gamsu G.,

Genant H.K., Saunders Edit, 1983;

271 – 320.

3. Ghaye, B., Szapiro, D., Fanchamps,

J.-M., Dondelinger, R.F.: Congenital

Bronchial Abnormalities Revisited. In:

RG, Vol 21, Nr 1; Jan-Feb 2001;

105 – 118.

4. Jardin, M., Remy, J.: Segmental

bronchovascular anatomy of the lower

lobes: CT analysis. In: A.J.R., 1986;

147, 457 – 468.

5. Mastora, I., Ioan-Mihalcea, A.,

Lupescu, L., Georgescu, S.A.:

Anatomia tomodensitometrica a

hilurilor pulmonare; Imagistica

medicală, vol 2; 1998; 40 – 46.

6. Osborne, D., Vock, P., Godwin, D.J.

et al.: CT identification of pulmonary

segments: 50 normal subjects. In:

A.J.R., 1984; 142, 47 – 52.

7. Read, R., St. Cyr, J., Marek, J.,

Whitman, G., Hopeman, A.: Bronchial

anomaly of the right upper lobe. In:

Ann Thorac Surg 1990; 50:980–981.

8. Remy, J., Remy-Jardin, M., Artaud,

D., Fribourg, M.: Multiplanar and

three-dimensional reconstruction

techniques in CT: impact on chest

diseases. In: Eur Radiol 1998;

8:335–351.

9. Sagel, S.S.: Computed Body Tomo–

graphy with MRI Correlation, vol I.,

cap. Lung. 2006; 421 – 555.

THE ANTEROLATERAL ABDOMINAL

WALL - VASCULARISATION

DEVELOPMENT DURING

MORPHOGENESIS

L.L. ONISÂI

1 I. SCARNECIU

2

M. GREAVU3 G. PERI

4

Abstract: The present paper aims to do an objective research over the

ontogenesis process of the vascularisation of the antero-lateral abdominal wall

and, using the results obtained, to verify the validity of the theories formulated

until now; it also aims to elaborate a theory regarding the process, if the analyzed

elements allow it. To fulfil the objectives of this study, we have used dissections,

video images through transillumination, photographic pictures and histological

studies. We have carried out a microscopic study that aims to minutely observe the

processes that happen in dynamic time from early ages on. We have also run a

macroscopic study through the inspection of the vessels at the level of the antero-

lateral abdominal wall.

Key words: somatic, transilumination, plasmodiums.

1 Transilvania University of Brasov, Department of Anatomy, Faculty of Medicine Brasov 2Transilvania University of Brasov, Faculty of Medicine Brasov, Urology Clinic, Clinic Emergency County

Hospital Brasov, 3 Transilvania University of Brasov 4 Department of Anatomy, Faculty of Medicine Palermo

1. Materials and Method

This study was carried out on a number

of 15 subjects: 9 adult embryos and foetus

and 6 human adult corpses. The

macroscopic study involved the inspection

of the antero-lateral abdominal wall,

supplemented by the dissection, the

parietal and umbilical morphometry and

the study by transillumination. The

microscopic study consisted in the

prelevation of parts of the embryos, foetus

and adults studied macroscopically. The

research team carried out Hemalum Eosin

Sofran colouring, the Van Gusson method

and silver impregnation. We also used the

method using the lemon juice and gold

chloride according to Roschin. Moreover,

for the observation of the vessels of the

right abdominal muscle, we used for the

compounds, the method of China ink

injection, clarification, followed by

transillumination and photography.

2. Results

At the same time with the swing of the

cephalic and caudal folds, followed by the

closure of the embryonic body, the parietal

vascular and nervous elements in the

ventral wall are differentiated. They are

well individualized starting with the

seventh week, so that by the occurrence of

the fascicular structures of the right

Bulletin of the Transilvania University of Braşov • Vol. 15(50) - 2008 � Series VI

18

abdominal muscle, the vessels and the

nerves appear in the conjunctive

intrafascicular tissue.

Fig. 1. Blood vessels in formation 18 mm

embryo (week 7), case 11, objective 40x, VG

colouring; in parasagital superumbilical

section. We can see the subcutaneous zone of

the anterolateral abdominal wall where, in

parallel with muscular differentiation, in a

major area as compared to the fascie

exoabdominale, blood vessels appear, the

lumen of which contains red blood corpuscles.

The differentiation of the vessels of the

right abdominal muscle is done in parallel

with the transformation of the myoblasts

into plasmodiums in the weeks 8-14. By

the dissection of the thoracic-abdominal

wall at the foetus of 30-34 weeks, the

presence of the intern thoracic arteries is

highlighted; these arteries are trifurcated at

the end, each one in a medial branch, a

median branch and a lateral one.

Fig. 2. 87 mm foetus (week 12), case 38, in

sagital superumbilical section (all along the

muscle), HE colouring, objective 10x. There

are vessels and nerves which belong to the

muscle, in conjunctive tissue between the

fascicles of the right abdominal muscle.

The first two final branches of the intern

thoracic artery take part to the

vascularization of the right abdominal

muscle. The higher epigastric artery

engages between the right abdominal

muscle, located at the anterior side, and the

posterior strip of its sheath located at the

posterior side, having a path nearly

identical to that of the preperitoneal

arteries located between the peritoneum

and the posterior face of the sheath of the

right abdominal muscle.

Fig. 3. 87 mm foetus (week 12), case 38,

in sagital section in the superumbilical

portion, HE colouring, objective 20x. In

the mesenchyme found between the

muscular fascicles we can see: a ramified

vessel flanked by three nervous threads.

They belong to the conjunctive interstice of

the right abdominal muscle.

Between the two arteries there are

anastomosis which segmentally pass by the

posterior strip of the sheath of the right

abdominal muscle and in this manner the

two arteries (the higher epigastric artery

and the preperitoneal one) irrigate the right

abdominal muscle too. Crossing the

distance from the xiphoid process to the

umbilical point, the two arteries finish in

the arterial periumbilical anastomotic

network. In the three zones of the right

abdominal muscle, the arterial device has

large polygonal holes formed of the fine

vessels of capillary diameter. Each

muscular fascicle is surrounded by 8-10

capillary vessels of continuous type. While

The Anterolateral Abdominal Wall - Vascularisation Development during Morphogenesis 19

aging, the vascular holes which are formed

between muscle fibers rarefy.

Fig. 4. 115 mm foetus (week 14), case 40,

in cross section in the superumbilical

portion, HE colouring, objective 20x.

Between the muscular fascicles there is a

vessel of large gauge; there are also

parietal vessels which are transversely

divided and take part in the


muscle.

Their diameter increases gradually. The

system of the intern thoracic arteries and

the lower epigastric arteries represent the

main sources which ensure the


muscle. The superumbilical portion of the

right abdominal muscle is more

vascularized than the underumbilical

portion; this is an area containing a parallel

distribution between muscle fibers and the

small arteries at the level of this muscle.

3. Conclusions and Discussions

The anterolateral abdominal wall

contains elements coming from the

primary mesenchyme, secondary

mesenchyme, endoderm, ectoderm. The

vessels and the nerves appear the first on

this level. The vascularization of the right

abdominal muscle is mainly assured by

muscular branches of the lower epigastric

artery and by branches of the internal

thoracic artery. The anatomical structures

of innervation and vascularization of the

anterolateral wall develop successively.

They appear in the interstice between the

former and posterior muscular plans

corresponding to the development of the

former abdominal muscles. In the case of a

much reduced number of subjects (2 adult

foetus and 2 subjects) we found a variable

number of openings in the posterior strip

of the sheath of the muscle abdominal right

determined by the branches anastomotic

between the higher epigastric artery and

the preperitoneal arteries. At an obese

adult subject, preperitoneal grease

penetrates and widens these openings,

acting in such a manner that they become

real; the grease gets to the space delimited

by the posterior strip of the sheath of the

right abdominal muscle and the muscular

mass on which it creates compression. In

the adults preperitoneal grease can transmit

prolongations in the sheath of the right

abdominal muscle and towards the thorax.

As of the period of foetus, the intern

thoracic artery is trifurcated constantly in a

medial branch (the preperitoneal artery), a

middle branch (the higher epigastric

artery) and a lateral branch (the musculo-

phrenic artery). The first two branches take

part in the vascularization of the

superumbilical portion of the right

abdominal muscle. The preperitoneal

arteries, not mentioned in the literature of

specialty, are branches of the intern

thoracic artery around which preperitoneal

grease accumulates. The arteries which

ensure the vascularization of the

anterolateral abdominal wall ramify richly

between the fascicles of the right

abdominal muscle. Interfascicular

anastomosis form intermittent arcades.

References

1. Albu, I., Georgia, R.: Anatomie

Topografică. Cluj Napoca. Ed. ALL

1999, pp. 204-238.

2. Benson, H.J., Gunstream, S.E., Talaro,

A., Talaro, K.P.: Anathomy and

physiology. WCB Publ., 1992.


20

3. Chiriac, M., Zamfir, M., Antohe, D.:

Anatomia trunchiului, Vol. 1. Iaşi. Ed.

Universitară Iasi, 1999, pp. 334-346.

4. Dietrich, K., Felberbaum, R.: Der

Gynäkologe; Die europäische

Gesellschaft für humane Repro-

duktionsmedizin und Embryologie

(ESHRE); Springer Berlin /

Heidelberg; 2002, pp. 444-446.

5. Garcia-Martinez, V., Schoenwolf,

G.C.: Positional Control of Mesoderm

Movement and Fate during Avian

Gastrulation and Neurulation. In:

Acta.Anat., 1992, pp. 249-256.

6. Oligny, L.L.: Pediatric and

Developmental Pathology; Human

Molecular Embryogenesis: An

Overview. Springer New York; 2001,

pp. 324-343.

7. Onisai, L.L.: Anatomia peretilor

trunchiului. Braşov. Ed. Univ.

Transilvania, Brasov, 1997, pp. 104-

116, 142-158, 170-172.

8. Onisai, L.L.: The development of

rectus abdominis muscles. In:

Romanian J. of Anat., vol 1; nr. 2-3,

1999, pp. 67-70.

9. Ordahl, C.P.: Myogenic Lineages

within the developing somite. In:

Development, 1993, pp. 341-353.

10. Williams, P.L.: Gray’s Anatomy, 38 th

New York. Ed. Churchill Livingstone,

1995.

1Transilvania University of Brasov, Faculty of Medicine, Romania

2University of Milan, Dept. of Pharmacological Sciences, Italy

COMPETITIVE ELISA FOR AFLATOXINS

AND OCHRATOXINS DETECTION

M. BADEA1 M. MUNTEANU

1 L. LAZORIEC

1

G. COMAN1 P. RESTANI

2

Abstract. Mycotoxins have attracted worldwide attention because of their

impact on humans and animals health.

The most frequent toxigenic fungi in Europe are Aspergillus, Penicillium and

Fusarium species. They produce aflatoxin B1 transformed into aflatoxin M1

found in the milk, as well as Ochratoxins and Zearalenone. These mycotoxins

are under continuous survey in Europe, but the regulatory aspects still need

to be set up and/or harmonised at European level.

Direct competitive ELISA was used for aflatoxin M1 and ochratoxin A

detection from reference and real samples (milk, coffee). Calibration curves

were plotted and limits of quantification were calculated. A recovery degree

of 98.66% was obtained for spiked sample (coffee).

Key words: aflatoxins, ochratoxins, ELISA, milk, coffee

1. Introduction

Humans and animals are continuously

exposed to different amounts of

exogenously chemicals that have been

shown to have carcinogenic or mutagenic

properties in experimental systems (cells

models, lab animal studies). Exposure can

occur when these agents are present in

different media (food, air or water), and

also endogenously when they are products

of metabolism or pathophysiologic states

such as inflammation [3, 20].

Aflatoxins belong to a large group of

mycotoxins, toxic metabolites that

contaminate food and feed commodities

during growth of certain spoilage molds. In

addition to causing acute toxicity,

aflatoxins are also liver carcinogens in

experimental animals and extensive quality

control measures are necessary to

minimize levels in human foods.

Aflatoxin-contaminated feed was

discovered to be a liver carcinogen in rats

even before the active agent was isolated

and characterized.

Bioassays in various species fish [5],

birds [19], rodents [13] and sub-human

primates eventually revealed that AFB1 is

a liver carcinogen in all animals tested.

Aflatoxin M1 is produced as a metabolite

of aflatoxin B1. It is secreted with the milk

after the feeding of aflatoxin B1 content

feedstuffs to lactating cows. As aflatoxin

M1 is relatively stable towards the

pasteurizing process, not only a

comprehensive routine check of the raw

materials to be processed is required, but

also of the final products.

Ochratoxigenic fungi are natural

contaminants of cereal and the produced

toxins are harmful to humans and animals.

Ochratoxin A (OTA) is among the most

important mycotoxins, and the

Bulletin of the Transilvania University of Braşov ▪ Vol. 1 (50) - 2008 � Series VI

22

International Agency for Research on

Cancer (IARC) classifies it as possibly

carcinogenic to humans (group 2B) [12].

Ochratoxins induce a caspase-

dependent mitochondrial apoptotic

pathway. The mitochondrial alterations

include: loss of the mitochondrial

transmembrane potential, PTPC opening,

and cytochrome c (but not AIF) release.

OTA is a potent nephrotoxin and renal

carcinogen. However, the pathological

lesions observed in kidneys of rats treated

with OTA appear be rather different from

the clinical and pathological characteristics

of endemic nephropathy. Moreover, in-

creasing evidence suggests that OTA does

not bind to DNA but induces tumors by an

epigenetic, threshold mechanism [11].

The common mycotoxin ochratoxin-A

(OTA) accumulates in brain, causes

oxidative stress, and elicits a DNA repair

response that varies across brain regions

and neuronal populations [17].

2. Analytical Procedures for Mycotoxins

Detection

The fact that mycotoxins are usually

present in agricultural commodities and

products as minor constituents in

concentrations ranging from (sub) µg—

mg/kg, means that the possibilities to

determine mycotoxins are limited to

certain trace analytical methods.

Food processes (sorting, trimming,

cleaning, milling, brewing, cooking,

baking, frying, roasting, canning, flaking,

alkaline cooking, and extrusion) have

variable effects on mycotoxins, with those

that utilize the highest temperatures having

greatest effects. In general the processes

reduce mycotoxin concentrations

significantly, but do not eliminate them

completely [4].

Therefore, the development of methods

for toxic contaminants analysis has been

constantly in demand. In the last ten years,

among the techniques applied in the

detection, analysis and characterization of

mycotoxins, chromatography has so far

been widely accepted because there always

seems to be a need to separate some

primary and secondary fungal metabolites.

Information on the techniques and

methodologies and techniques are

presented in specialty literature [1, 2, 10].

HPLC replace in many laboratories TLC

techniques because of their ability to

analyze a wide variety of compounds,

including compounds that are easily

degraded by heat, light or air, the ease of

adaptation to confirmatory procedures, the

automation, The recent improvement in

instrumentation, including the develop-

ment of increasingly sensitive fluorescence

and electrochemical detectors and short,

high-resolution, reversed-phase columns

[7, 16].

Both normal and reverse-phases HPLC

using fluorescence detection have been

already become the most accepted methods

for the determination of aflatoxins and

ochratoxins due to its several advantages

over other analytical methods [8, 9].

Pieto Simon and colab. investigated two

indirect competitive enzyme-linked immu-

nosorbent assay (ELISA) strategies for the

development of OTA electrochemical

immunosensors based on different OTA

immobilisation procedures [14].

Immunosensors based on avidin/biotin-

OTA showed enhanced performance

characteristics compared to those based on

the adsorption of bovine serum albumin

(BSA)-OTA conjugate. Performance of

polyclonal and monoclonal antibodies

against OTA was compared, showing at

least one-order of magnitude lower IC(50)

values when working with MAb. Alkaline

phosphatase and horseradish peroxidase

were used as labels for secondary

antibodies. The methods were evaluated

and optimized as useful screening tools to

assess OTA levels in wine.

Membrane-based immunoassay has been

developed by Saha and colab. [15] for

simultaneous estimation of aflatoxin B1

(AFB1) and ochratoxin A (OTA) in chili

Competitive Elisa for Aflatoxins and Ochratoxins Detection 23

samples. The method uses a low cost test

device consisting of a membrane with

immobilized anti-AFB1 and anti-OTA

antibodies and a filter paper attached to a

polyethylene card below the membrane.

The AFB1 and OTA values obtained for

spiked and naturally contaminated chili

samples by the simultaneous method were

in good correlation with those measured by

individual ELISA. The combined estima-

tion of both the mycotoxins is more

economical in respect of time, work and

materials than two separate assays.

3. Materials and Methods

Competitive enzyme immunoassay

RIDASCREEN® FAST Ochratoxin A (R-

Biopharm AG, Darmstadt, Germany) was

used for the quantitative analysis of

ochratoxin A in standard and real samples

(coffee kept on humidified medium). For

real sample was used 5 g ground coffee

into a suitable container and was added

12,5mL boiled water. The sample had been

shaking vigorously for three minutes, then

was filtered through Whatman paper. It

was diluted 1 mL filtrate with 1mL

distilled water, and from this mixture, was

used 50 µL per well in the test. Because it

was estimated a lower level of ochratoxin

A in coffee samples, there were prepared

also spiking samples: it was added 5 µL

solution standard 4 (20 ppb OTA) to coffee

sample and after were made the extraction

in boiled water and similar steps indicated

by kit.

The amount of aflatoxin M1 in reference

and real (cow milk) samples was

determined by ELISA test using

Ridascreen Aflatoxin M1 kit (R-Biopharm

AG, Darmstadt, Germany). For real

samples, cow milk was centrifugated for

degreasing: 10 min (10oC). After centri-

fugation, there was removed upper cream

layer completely by aspirating through a

Pasteur pipette. Use the defatted super-

natant directly in the test for aflatoxin M1

detection (50 µL per well). The same

procedure was used also for spiked milk

sample with known concentration of

aflatoxin M1 (8 µL solution standard 5).

4. Results and Discussions

Antibodies are coated on to the wells of

the ELISA plate (Fig.1.). The test sample

(standards and real samples) and enzyme-

labelled mycotoxins (aflatoxin M1 or

ochratoxin A) are added to the wells. If no

toxin is present in the sample, the enzyme

labelled toxin will bind to the capture

antibody coated to the wells. If mycotoxin

is present in the sample, it will compete

with the labelled toxin for binding to the

antibody. During washing procedures any

unbound labelled enzyme will be washed

away.

The intensity of obtained product of the

enzymatic reaction (after substrate was

added) is proportional to the amount of

mycotoxin-enzyme bound to the well; i.e.,

the colour intensity decreases with increa-

sing concentrations of the mycotoxin in the

sample (Fig.2.).

Calibration curves were plotted using the

standards from kit for both methods (Fig.3,

Fig.4.). Linearizations were made for mean

of the obtained values. Data were plotted

using standard deviation correction. Each

StDev values were lower than 8% for all

detections.


24

E E E EE

S - substrate S - substrate

E

E E E E E

E E E E

S P S P P P PS S S

High mycotoxin level in sample No mycotoxin in sample

capture

antibody

mycotoxin

in sample

enzyme labelled

mycotoxin

Fig.1. Direct competitive ELISA procedure for mycotoxins

(aflatoxin M1 and ochratoxin A) detection

Fig. 2. Colored plated as result of direct competitive ELISA for mycotoxin detection of

aflatoxin M1


y = -0,0182x + 71,549

R2 = 0,8865

0

20

40

60

80

100

0 500 1000 1500 2000 2500

Aflatoxin M1 (ppt)

% m

axim

um

ab

sorb

ance

Fig.3. Calibration curve for aflatoxin M1 using RIDASCREEN kit

y = -1,2268x + 79,853

R2 = 0,9752

0

20

40

60

80

100

0 10 20 30 40 50

OTA (ppb)

% m

axim

um

ab

sorb

ance

Fig.4. Calibration curve for ochratoxin A (OTA) using RIDASCREEN kit

Detection limit for OTA depends on the sample (dilution factor of the sample

preparation), and was obtained from 0.5 to 5 ppb.

Limit of quantification (LOQ) was investigated by repeated spiking experiments at the

lowere end of the standard curve. It was obtained LOQ at 500ng/L (ppt).

Calibration curves were used for interpolation for real samples. For coffee samples

tested the experimental data shown a very good recovery degree 98.66% (Table 1).


26

Table 1

Spiked and unspiked coffee samples characterization using calibration curve for OTA

OTA concentration (ppb)

Solvent Extraction

with boiled

water

Extraction from

spiked sample with

8 µL standard 4

Water with 8 µL

standard 4

Recovery

degree (%)

Boiled

water 46.04 58.71 13.47 98.66

A Supplement for green coffee, wine and

dried fruits in combination with the

RIDA® Ochratoxin A Immunaffinity

columns is available on request at R-

Biopharm and provide more accurate

values for tested samples [18].

It is known that aflatoxin M1 (AFM1) in

milk is not affected during the process of

cheese production, and the level of AFM1 in

cheese remains same as in the milk. Each

country include specific regulations for

maximum admitted limit of AFM1 in milk,

milk products and cheese (Table 2.) [6.].

Maximum admitted limit of AFM1 in milk, milk products and cheese Table 2

Maximum admitted limit of AFM1 (µg/kg or µg/L) Country

Milk and products Cheese

Germany 0.05

Netherlands 0.200

Switzerland 0.05 0.250

USA 0.5

Turkey 0.05 0.250

Romania 0.05

Tested milk samples do not present

higher level of mycotoxins than the

maximum admitted limit for AFM1, so the

milk samples may be used by children and

adults without risk.

5. Conclusions

Animal feed, food samples need to be

checked with regularity for aflatoxins and

ochratoxins levels and storage conditions

of samples need to be strictly controlled

(humidity, temperature). Because of

important toxicological effects of

aflatoxins and ohratoxins on infants,

children and humans, the samples will be

controlled using very fast, accurate and

specific analytical methods. Competitive

ELISA is one of the most important

techniques that may be used and

implemented on all laboratories for food

control and food safety.

Acknowledgments

The research studies were made in the

frame of Excellence Research Project for

Young Researchers cod 163, no.

5898/2006: Detection of some toxic

compounds from water, food and

biological samples using enzymatic,

chromatographic and spectral methods

(coordinator Transilvania University of

Brasov, Romania).


References

1. Betina, V.: Thin-layer chromatogra–

phy of mycotoxins. Chromatogr.,

334(3) (1985) 211-276.

2. Betina, V.: Chromatographic methods

as tools in the field of mycotoxins. In:

J Chromatogr. 477(2) (1989) 187-233.

3. Boermans, H.J., Leung, M.C.:

Mycotoxins and the pet food industry:

toxicological evidence and risk

assessment. In: Int J Food Microbiol.

20;119(1-2) (2007) 95-102.

4. Bullerman, L.B., Bianchini, A.:

Stability of mycotoxins during food

processing. In: Int J Food Microbiol.,

119(1-2) (2007) 140-146.

5. Carlson, D.B., Williams, D.E.,

Spitsbergen, J.M., Ross, P.F., Bacon,

C.W., Meredith, F.I., Riley, R.T.:

Fumonisin B1 promotes aflatoxin B1

and N-methyl-N'-nitro-nitrosogua–

nidine-initiated liver tumors in

rainbow trout. In: Toxicol Appl

Pharmacol., 172(1) (2001)

29-36.

6. Creppy, E. E.: Update of survey,

regulation and toxic effects of

mycotoxins in Europe. In: Toxicol.

Letters 127 (2002) 19-28.

7. Holcomb, M., Wilson, D.M.,

Trucksess, M.W., Thompson Jr., H.C.:

Determination of aflatoxins in food

products by chromatography. In: J.

Chromatogr. 624 (1992) 341.

8. Howell, M.V., Taylor, P.W.: Deter–

mination of aflatoxins, ochratoxin a,

and zearalenone in mixed feeds, with

detection by thin layer chromatography

or high performance liquid

chromatography. In: J Assoc Off

Anal Chem., 64(6): (1981) 1356-1363.

9. Jaimez, J., Fente, C.A., Vazquez, B.I.,

Franco, C.M., Cepeda, A., Mahuzier,

G., Prognon, P.: Application of the

assay of aflatoxins by liquid

chromatography with fluorescence

detection in food analysis. In: J

Chromatogr A., 882(1-2) (2000) 1-10.

10. Lin, L., Zhang, J., Wang, P., Wang,

Y., Chen, J.: Thin-layer chroma–

tography of mycotoxins and comparison

with other chromatographic methods.

In: Journal of Chromatography A, 815

(1998): 3–20.

11. Mally, A, Hard, G.C., Dekant, W.:

Ochratoxin A as a potential etiologic

factor in endemic nephropathy:

lessons from toxicity studies in rats.

In: Food Chem Toxicol. 45(11) (2007)

2254-2260.

12. Marin-Kuan, M, Cavin, C., Delatour,

T., Schilter, B.: Ochratoxin A

carcinogenicity involves a complex

network of epigenetic mechanisms. In:

Toxicon., 1;52(2) (2008) 195-202

13. Miranda, D.D., Arçari, D.P., Ladeira,

M.S., Calori-Domingues, M.A.,

Romero, A.C., Salvadori, D.M., Gloria,

E.M., Pedrazzoli, J. Jr, Ribeiro, M.L.:

Analysis of DNA damage induced by

aflatoxin B1 in Dunkin-Hartley guinea

pigs. In: Mycopathologia.163(5),

(2007), 275-80.

14. Prieto-Simón, B., Campàs, M., Marty,

J.L., Noguer, T.: Novel highly-

performing immunosensor-based

strategy for ochratoxin A detection in

wine samples, Biosens Bioelectron.

23(7) (2008) 995-1002.

15. Saha, D., Acharya, D., Roy, D.,

Shrestha, D., Dhar, T.K.:

Simultaneous enzyme immunoassay

for the screening of aflatoxin B1 and

ochratoxin A in chili samples. In: Anal

Chim Acta. 584(2): (2007) 343-349.

16. Santos, E.A., Vargas, E.A.: Immuno–

affinity column clean-up and thin

layer chromatography for

determination of ochratoxin A in

green coffee. In: Food Addit Contam.

19(5) (2002) 447-458.

17. Sava, V., Velasquez, A., Song, S.,

Sanchez-Ramos, J.: Adult hippocam–

pal neural stem/progenitor cells in

vitro are vulnerable to the mycotoxin

ochratoxin-A. Toxicol Sci. 98(1)

(2007) 187-197.


28

18. Sibanda, L., De Saeger, S., Van

Peteghem, C.: Development of a

portable field immunoassay for the

detection of aflatoxin M1 in milk. In:

Int J Food Microbiol., 48(3) (1999)

203-209.

19. Tessari, E.N., Oliveira, C.A., Cardoso,

A.L., Ledoux, D.R., Rottinghaus,

G.E.: Effects of aflatoxin B1 and

fumonisin B1 on body weight,

antibody titres and histology of broiler

chicks. In: Br Poult Sci. 47(3) (2006)

357-64.

20. Wogan, G. N., Hecht, S. S., Felton, J.

S., Conney, A. H., Loeb, L. A.:

Environmental and chemical

carcinogenesis. Seminars in Cancer

Biology 14 (2004) 473–486.

1 Universidade Federal do Maranhão, Brazil 2

Transilvania University of Brasov, Romania. 3 Unversité de Perpignan via Domitia, France

ULTRASENSITIVE BIOSENSORS FOR THE

DETECTION OF INSECTICIDE RESIDUES

IN FRUIT JUICES

G. S. NUNES

1 M. BADEA

2 M.-L. MEDEL

3

T. NOGUER3 J.-L. MARTY

3

Abstract: A highly sensitive and rapid fruit juice-screening test based on

disposable screen-printed TCNQ-modified biosensor was developed, which is

suitable for monitoring anticholinesterase pesticides. The biosensor analysis

was based on direct measurement of enzyme inhibition in pH-adjusted

samples. It could detect levels of carbofuran, carbaryl and chlorpyrifos oxon

of 0.2, 0.9 and 1.1 µg.L-1, respectively, and thus clearly fulfills the demands

of both Brazilian and EU regulation.

To evaluate the biosensor efficiency, recovery rates were determined and

were on average 93.9% (RSD from 5.9 to 18.5%) in untreated fruit juices.

The proposed AChE-biosensor has shown enough sensitivity and

reproducibility to be used as a complementary technique to the

chromatographic ones in food pesticide monitoring.

Key words: TCNQ-modified biosensor; AChE-inhibitor pesticides; fruit

juices

1. Introduction

According to the necessity of

substituting the standard methods

utilized in quantitative and qualitative

analysis, large studies were required in

recent years, in order to develop faster,

easier, and less expensive techniques,

with similar or lower detection limits.

Traditional methods for carbamate deter-

mination in foods are based on gas chro-

matography (GC) or high-performance li-

quid chromatography (HPLC); this last

analytical technique normally employing the

highly sensitive fluorescence detection [7,

12]. Organophosphates are normally

analyzed by gas chromatography with a

nitrogen-phosphorous selective detector [17].

Hyphenated chromatographic methods,

such as GC and/or HPLC combined with

mass spectrometry (MS) have been also

used to detect and to confirm residues of

carbamate and organophosphorate insecti–

cides in food samples [3, 5, 9].


30

Because of the numerous problems

involved with traditional analytical

methods, such as the large time involved in

classical sample preparation, it is necessary

to develop fastest, easier, more sensitive,

cost-effective and environmentally cleaner

analytical techniques.

Analysis using the biosensor technology

is part of a research area that offers the

advantages of miniaturization, easy sample

manipulation, and the possibility of in-situ

determination which further diminishes the

errors resulted from sample processing

operations, with simple and low-cost

instrumentation, fast response times,

minimum sample pretreatment, and high

sample throughput. Biosensors are devices

consisting of biological active protein

species immobilized on the surface of

physical transducers [15].

Despite all advantages of biosensors, only

a few works employing this analytical tool

for the anticholinesterase pesticides in food

samples have been reported [1, 8, 10, 14].

This work employs an amperometric

biosensor for the detection of AChE

inhibitors in commercial fruit juices by

exploiting their capacity to inhibit AChE

enzymes. Different inhibition assays

utilizing natural fruit juices for performing

the electrochemical measurement with

buffered or solvent-extracted samples were

tested. To evaluate assays efficiencies,

fruit juices samples were spiked with some

AChE inhibitors and the matrix effects

were also evaluated.


2.1. Reagents, samples and other materials

The inhibitor standards [N-methyl–

carbamates (NMCs): carbofuran and

carbaryl; organophosphates (OPs):

chlorpyrifos and chlorpyrifos-oxon] used

in this work varied in purity from 96 to

99.9%. Carbofuran and carbaryl were

provided by Sigma-Aldrich (Seelze,

Germany). Chlorpyrifos and chlorpyrifos

oxon were supplied by Chem Service

(West Chester, PA). Stock solutions were

prepared by dissolution of the active

principles with a sufficient volume of

grade HPLC-methanol (Merck, Augsburg,

Germany), followed by dilution with

distilled water to 10-2

mol.L-1

con-

centration. Working solutions were kept at

4oC for a maximum of one week. Table 1

presents some general chemical and

toxicological information on these

compounds.

Acetylcholinesterase enzyme from

electric eel (ee), specific activity of 8000

AU.mg-1

, acetylthiocholine chloride

(ATChCl) substrate, 5,5’dithio (2-nitro–

benzoic acid) (DTNB) and polyethylene

glycol 600 (PEG) were purchased from

Sigma Chemicals Co (St Louis, MO).

AChE stock and working solutions were

prepared by dissolution of the enzyme in

NaCl 0.9 % (w/v) solution and storing in a

freezer for a maximum of two months.

Substrate solutions were prepared by

dilution with phosphate buffer solution

containing 0.1 mol.L-1

KCl (PBS), pH 7.5.

PBST solutions were prepared by dilution

of Tween 20 (Aldrich Chem. Co,

Steinheim, Germany) in already prepared

PBS up to 1.0% (v/v) final content.

Hydroxyethyl-cellulose (HEC) and

pyridine-2-aldoxime methochloride (2-

PAM) were obtained from Sigma-Aldrich

Co (Steinheim, Germany). Photocrosslin-

kable poly(vinyl alcohol) bearing styryl-

pyridinium groups (SPP-S-13-bio-PVA-

SbQ of betaine form and polymerization

degree of 1700) was obtained from Toyo

Gosei Co (Chiba, Japan). All other

reagents were analytical grade.

Printing pastes (Electrodag PF-410,

423SS, 6037SS) were purchased from

Acheson (Plymouth, UK) and the mediator

TCNQ from Aldrich Co (Steinheim,

Germany). Graphite T15 was supplied by

Lonza A. G. (Basel, Switzerland). The

surface area of both reference and working

electrode was 0.17 cm2. The screen-printed

electrodes containing TCNQ as mediator

Ultrasensitive Biosensors for the Detection of Insecticide Residues in Fruit Juices 31

used in this study were prepared according

to procedures previously described [2, 9].

2.2. Electrochemicals measurements

The screen-printed electrode was

immersed in a beaker containing 5 mL of

PBS pH 7.5 under constant magnetic

stirring. The pesticide determination was

carried out in a three-step procedure. The

electrode response was first measured in

PBS, and then ATChCl was added,

corresponding to the current before the

inhibition, I0. The electrode was carefully

washed with PBS, and then incubated for

10 min with pesticide solutions at known

concentrations or with spiked fruit juice

untreated/treated samples. After incu-

bation, the cleaning procedure started by

washing the biosensor with 5 mL PBS

containing 1% Tween 20 (PBST) by

continuous agitation during 10 min

followed by washing with PBS. The

second value, corresponding to I, was

reported as the current intensity after

inhibition. Inhibition results were

determined using the following formula:

I(%) = (1 – Io/I) 100 and then related to the

inhibitor concentration present in the

pesticide solutions or spiked juice samples

[11]. Fig. 1 details the sample treatment

and inhibition procedure. Reactivation of

inhibited AChE was performed with

pyridine 2-aldoxime methiodime (2-PAM,

Aldrich Chem. Co, Steinheim, Germany),

according to previously described

procedures [4, 11].

2.3. Reproducibility studies

To establish the reproducibility of the

biosensors, 20 different electrodes

belonging to the same set and fabricated in

the same day were tested by performing

the enzymatic reaction with ATCh

substrate and then recording the current

value, in nA. To evaluate the operational

stability of each electrode, the response of

the biosensor was measured five times by

injecting the same amount of substrate,

resulting in a total of 100 electrochemical

measurements. The response for each

biosensor, represented by the average

current (n = 5) was recorded in a quality

control chart.

2.4. Samples treatments and recovery studies

In order to verify the efficiency of the

inhibition assays in fruit juices, some

samples were spiked with different levels

of AChE inhibitors, depending on the

enzyme sensitivity. The biosensors were

then incubated for 10 min with the samples

under constant stirring. After each

incubation step the biosensor was carefully

washed by immersing it in PBST during 10

min under stirring and then washed well

with PBS. The recoveries were calculated

by comparison between the inhibitions

obtained in the spiked with those of the

solution containing identical pesticide

concentration. Several samples were

analyzed directly with the biosensor

without previous sample treatments; only a

simple adjustment of the pH to ~ 7.5 was

performed. Some samples were treated by

PBS- and organic solvent extraction in

order to decrease the matrix effect. During

solvent extraction, one off-line solid-phase

extraction (SPE) step was needed. For this

purpose, 3 mL Bakerbond SPETM

columns (J. T. Baker, Deventer, Holland)

packed with 500 mg plus polar octadecyl

silica (C18) were used. SPE cartridges

were preconditioned with 10 mL methanol

and after the sample elution; the final

residue was recovered with 500 µL

methanol before dilution with 5 mL PBS.

For the reproducibility study, a control

chart was constructed with the 20

measurements. A conventional statistical

program was used to compare the recovery

averages at 95% significance level

according to the Student’s t test [6].

Limits of detection were calculated with

basis of 10 % enzyme inhibition caused by

pesticide solutions [9].


32

Limits of quantification (LOQ) were

determined through inhibition assays

performed with spiked untreated and

treated samples (n = 3). For each tested

method, two blanks were carried out.


3.1. Biosensor response and stability

The AChE-biosensor was based on the

enzymatic inhibition by carbamates and

organophosphates pesticides and it has

been previously optimized in order to

achieve the highest sensitivity and the

shortest analysis time. When AChE is

immobilized on the working electrode

surface, its interaction with the substrate

produces an electroactive specie. In this

strategy, acetylthiocholine (ATCh) can

substitute the original substrate of AChE

[2]. Thus, ATCh is hydrolyzed in the same

manner as the original substrate, producing

thiocoline and the corresponding

carboxylic acid (acetic acid, in this case).

The electrons generated during this

electrochemical reaction are collected and

the final current is a quantitative measure

of the enzyme activity.

According to Fig. 2, it can be seen that

current intensities obtained during reaction

between enzyme and substrate have not

exceeded the (upper and lower) warning

and action lines established according to a

statistical method described by Vandeginst

and Quadt [16]. The relative standard

deviation was 5.5 %.

3.2. Biosensor sensitivity for the selected

insecticides

The biosensor sensitivity could be

evaluated by performing the enzyme

inhibition with different pesticide

concentrations. In this work, each

experimental point was the average of five

measurements. The inhibition assays

showed a high level of intra-laboratory

reproducibility with an average relative

standard deviation of 8.6 %.

From the complexity of the mechanisms

and kinetics of AChE inhibition the

calibration curves (inhibitor concentration

versus relative inhibition) will not have a

linear correlation for some pesticides,

mainly the carbamates that usually

promote a reversible inhibition (Table 2).

Acceptable linear correlations were

obtained for the pesticides: carbofuran,

chlorpyrifos and chlorpyrifos oxon,

whereas that carbaryl gave a nonlinear

polynomial regression. In some cases,

nonlinear regression models are preferable

in order to improve the relative inhibition

versus concentration correlation and at the

same time to increase the concentration

working range of the calibration diagrams.

Chemical and toxicological information of the selected inhibitors Table 1

Usual Name Water

solubility

(mg.L-1

) a

LD50

(in rats)

(mg.Kg-1

) a

Inhibition constant (Ki) related to

AChE (ee)

(M-1

.min-1

) b

Carbaryl 40 400 - 650 5.5x104

Carbofuran 320 5 - 13 2.5x106

Chlorpyrifos 2 135 - 163 4.5x104

Chlorpyrifos oxon 3 45-60 1.6x105

a Sources: US National Library of Medicine [13];

b Ki values for carbaryl and carbofuran were previously determined; for chlorpyrifos and chlorpyrifos

oxon compounds, Ki values were spectrophotometrically determined in this work.

AChE (ee): commercial acetylcholinesterase extracted from electric eel.


Fig.1. Scheme for the incubation of the biosensor with fruit juice samples. Operational

conditions: 10 min of biosensor incubation in the pesticide solution; washing of biosensor

with PBS between electrochemical measurements; [substrate]= 1x10-3

M; current

measuring during enzymatic reaction before (Io) and after (I) inhibition.

Fig.2. Control chart for the reproducibility study of the electrochemical measurements.

Repeatability of 20 measurements performed with different electrodes whose enzymatic

immobilization was carried out according to the experimental part

Biosensor sensitivity and working ranges for the selected pesticides Table 2

Pesticide Working range

(µµµµg.L-1

)

LOD

(µµµµg.L-1

)

Type of

calibration curve

R2

Carbaryl 1.5 - 1050 0.9

Polynomial 0.987

Carbofuran 0.2 – 2.3 0.2 Linear 0.978

Chlorpyrifos 7.0 - 90

4.5 Linear 0.986

Chlorpyrifos oxon 1.5 – 150 1.1 Linear 0.990


34

The sensitivities for the selected

pesticides proved to be adequate with

statistically different (p < 0.05) limits of

detection (LOD) values. More suitable

LODs were determined for three

pesticides: carbofuran, carbaryl and

chlorpyrifos oxon, 0.2, 0.9 and 1.1 µg.L-1

,

respectively. Among the studied pesticides

carbofuran is the strongest inhibitor for the

AChE (from electric eel) enzyme as is

confirmed by the higher inhibition

constant, Ki (Table 1). For chlorpyrifos a

higher LOD value (4.5µg.L-1

) was

obtained; it has presented the weaker

inhibition capacity. The concentration

values of working ranges, which are in the

range between 0.2 and 1,050 µg.L-1

depending on the insecticide, are thus

sufficient for the control of maximum

allowed residues in food, according to the

Brazilian and EU regulations [18, 19].

In this work, carbofuran has shown to be

a great AChE inhibitor when the biosensor

contained an enzymatic charge equivalent

to a relative activity of 1 AU/electrode.

Recoveries for the selected pesticides

using the optimized AChE-biosensor are

calculated. For most cases, the higher

pesticide concentration zones give better

accuracy (higher recoveries) and good

reproducibility (lower RDS %). Relative

standard deviations (RSD) varied from 5.9

to 18.5 % (from 5.9 to 14.8 %, from 6.5 to

12.6 %, from 7.4 to 18.4 %, and from 7.6

to 14.3 %, respectively, for orange, apple,

grape and pineapple juices). It is

convenient to mention that lower

reproducibility was also observed for

higher pesticide concentrations during

calibration curve construction.

In this work, a value lower than 10 %

inhibition was considered as the limit of

statistically confidence level for the LOD

calculation (Table 2) because inhibitions

found in lower concentrations lead to

higher errors in the current intensity

recorder, in some cases coinciding with the

apparatus noise depending on the

potentiostat sensitivity.

5. Conclusions

In this study, the use of cholinesterase-

based biosensors for the detection of some

carbamate and organophosphorus

pesticides was evaluated. The previously

developed ChE-biosensor based on a

screen printed electrochemical system was

chosen as biosensor. As a biorecognition

element, AChE from electric eel was used.

This enzyme was more sensitive to the

carbofuran pesticide, followed by

chlorpyrifos oxon (a metabolite product of

chlorpyrifos). Good inhibition results were

also obtained with carbaryl and the

detection of these pesticides can be

achieved in fruit samples without any

complicated pretreatment.

The use of amperometric biosensors to

detect and quantify carbamate and

organophosphorus pesticides is still novel

because it still requires several approaches

in order to improve the selectivity and to

reduce or eliminate numerous problems

before the biosensor can be applied for

routine analysis. These problems include

the skills required for the biosensor

construction, limited dynamic ranges in

some cases in trace levels, and the need for

frequent calibration. In order to apply the

AChE-biosensor in screening works and to

use it as a complementary analytical tool,

the necessity to construct portable devices

is evident.

Acknowledgments

Gilvanda S. Nunes would like to thank

CNPq (Conselho Nacional de

Desenvolvimento Científico-Tecnológico,

Brazil) and CAPES (Coordenação de

Aperfeiçoamento de Pessoal de Nível

Superior, Brazil) for the fellowship and

financial support, respectively. Mihaela

Badea would like to thank UEFISCSU for

the support with 5898/2006 and 1469/2006

CEEX research grants.


References

1. Albareda-Sirvent, M., Merkoçi, A.,

Alegret, S.: Pesticida determination in

tap water and juice simples using

disposable amperometric biosensors

made using thick-film technology. In:

Anal. Chim. Acta, 2001, 442, 35-44.

2. Andreescu, S., Noguer, T., Magearu,

V., Marty, J.-L.: Screen-printed

electrode based on AChE for the

detection of pesticides in presence of

organic solvents. In: Talanta, 2002,

57, 169-176.

3. Caballo-López, A., Luque de Castro,

M. D.: Continuous ultrasound-assisted

extraction coupled to on line

filtration-solid-phase extraction-

column liquid chromatography-

postcolumn derivatisation –

fluorescence detection for the

determination of N-methylcarbamates

in soil and food. In: J. Chromatogr. A

2003, 998, 51-59.

4. Gulla, K. C., Gouda, M. D., Thakur,

M. S., Karanth, N. G.: Reactivation of

immobilized acetylcholinesterase in an

amperometric biosensor for

organophosphorus pesticide. In:

Biochim. Biophys. Acta 2002, 1597,

133-139.

5. Jansson, C., Pihlström, T., Österdahl,

B.-G., Markides, K. E.: A new multi-

residue method for analysis of pesti–

cide residues in fruit and vegetables

using liquid chromatography with

tandem mass spectrometric detection.

In: J. Chromatogr. A 2004, 1023, 93-

104.

6. Newilly, M.: Précision des dosages de

traces: répétabilité et limite de

detéction. Paris. Lavoisier Tec Doc,

FR, 1996, 459 p.

7. Nunes, G. S., Barcelo, D.: Analysis of

carbamate insecticides in foodstuffs

using chromatography and

immunoassay techniques. In: Trends

Anal. Chem. 1999, 18, 99-107.

8. Nunes, G. S., Barcelo, D., Grabaric, B.

S., Diaz-Cruz, J. M., Ribeiro, M. L.:

Evaluation of a highly sensitive

amperometric biosensor with low

cholinesterase charge immobilized on

a chemically modified carbon paste

electrode for trace determination of

carbamates in fruit, vegetable and

water samples. In: Anal. Chim. Acta

1999, 399, 37-49.

9. Nunes, G. S., Montesinos, T.,

Marques, P.B.O., Fournier, D., Marty,

J.-L.: Acetylcholine enzyme sensor for

determining methamidophos insecti–

cide. Evaluation of some genetically

modified acetylcholinesterases from

“Drosophila melanogaster”. In: Anal.

Chim.Acta 2001, 434, 1-8.

10. Nunes, G.S., Skladal, P., Yamanaka,

H., Barcelo. D.: Determination of

carbamate residues in crop samples

by cholinesterase-based biosensors

and chromatographic techniques. In:

Anal. Chim. Acta 1998, 362, 59-68.

11. Okazaki, S., Nakagawa, H., Fukuda,

K., Askura, S., Kiuchi, H., Shigemori,

T., Takshi, S.: Reactivation of an

amperometric organophosphate

pesticide biosensor by 2-

pyridinealdoxime methochloride. In:

Sens. Actuators B 2000, 66, 131-134.

12. Pacioni, N. L., Veglia, A. V.:

Determination of carbaryl and

carbofuran in fruits and tap water by

β-cyclodextrin enhanced fluorimetric

method. In: Anal. Chim. Acta 2003,

488, 193-202.

13. Parker, G. A.: Validation of methods

used in the Florida Department of

Agriculture and Consumer Services

Chemical Residue Laboratory. In: J.

Assoc. Off. Anal. Chem. 1991, 74,

868-871.

14. Schulze, H., Scherbaum, E.,

Anastassiades, M., Vorlova, S.,

Schmid, R.D., Bachmann, T.T.:

Development, validation, and

application of an acetylcholinesterase-

biosensor test for the direct detection


36

of insecticide residues in infant food.

In: Biosens. Bioelectron. 2002, 17,

1095-1105. 15. Turner, A.P.F., Karube, I., Wilson,

G.S.: Biosensors: fundamentals and

applications. Oxford. Oxford

University Press, 1987, 770 p.

16. Vandeginst, B.G.M., Quadt, J.F.A.:

Statistical quality control. In: Analusis

1994, 22, M 30-34.

17. AOAC. Association Official

Analytical Chemistry. Methods 970.52

and 968.24. In: Helrich, K. Ed.

Official Methods of Analysis of

AOAC. 15th Ed. Arlington, VA, 1990

18. Brasil. International Life Sciences

Institute of Brazil - ILSE, Relação de

substâncias para uso fitossanitário e

domissanitário:Portarias doMinistério

da Agricultura, São Paulo, SP, 1995.

19. EC, European Communities. Council

Directives 76/895/EEC, 86/362/EEC,

86/363/EEC and 90/642/EEC.

Maximum levels for pesticide residues

in and on cereals, foodstuffs of animal

origin and certain products of plant

origin, including fruits and vegetables.

Commission Directive 2000/24/EC,

April, 28, 2000.

ANALYTICAL MONITORING AS A TOOL

TO DETECT ILLEGAL SUBSTANCES IN

FOODS AND FOOD SUPPLEMENTS

P. RESTANI

1 D. CARUSO1 F. GIAVARINI

1

E. MORO1 A. PERSICO

1 F. UBERTI

1

C. BALLABIO1 M. L. COLOMBO

2 M. BADEA

3

Abstract: From time immemorial, foods have been used to provide an

unsuspected vehicle of poisons. More recently, new criminal approaches use

foods and food supplements which contain illicit substances having

pharmacological effects, facilitating the international transport of drugs,

drug-pushing and the consumption of banned ingredients. Specially targeted

is the world of sport, where athletes often believe they cannot succeed

without taking performance-enhancing drugs. The misuse of substances

having pharmacological activity has become so widespread in sport that the

health of many athletes is compromised. This paper illustrates the use of

analysis of sports supplements as part of a broad system of monitoring the

availability of banned products. Specifically, the illegal inclusion of

ephedrine in a food supplement consisting largely of herbal ingredients has

been demonstrated using HPLC separation followed by mass spectrometry

Key words: food supplements, criminal activity, poisoning, food

contamination, herbal supplements, doping.

1 Dept. of Pharmacological Sciences, University of Milan, Italy. 2 Dept. of Drug Science and Technology, University of Turin, Italy. 3 3Dept. of Fundamental and Prophylactic Disciplines, Transilvania University of Brasov, Romania.

1. Introduction

Foods play a critical role in the health of

human beings and are often an important

part of social, religious and cultural

activity. Several expressions illustrate the

importance of foods in daily life, the most

famous being “We are what we eat”. Most

traditions have a particular, easily recog-

nizable cuisine, which is sometimes the

focus of epidemiological studies (Medit-

erranean diet, vegetarian diet, etc.).

More recently, foods have been

identified as a means of decreasing crime

and violence, since healthy food can

reduce aggressive behaviour. “We are what

we eat” has become “we do what we eat”.

Thus, subjects on a vegetarian diet are

often considered less aggressive than

omnivorous ones. On the other hand, foods

can pose a risk to human health if they

contain unusual or unsuspected ingre-

dients. Numerous cases of accidental food

poisoning have been described in the

scientific and popular literature, in

particular the ingestion of poisonous

mushrooms or plants harvested by inexpert

collectors [2, 3, 6].

Since ancient times, food and water have

been used as tools for homicide, both


38

because victims usually have confidence in

their meals and because detecting the fatal

agent can be difficult. Traditional poisons

such as salts of arsenic have often been

used in murder [4], but more recent

investigations have hypothesized poiso-

nous plants as the causative agent or

identified them analytically [8].

The most recent criminal approach

involving foods is to use them to mask

illicit substances, facilitating their transport

across borders and wide distribution. Food

supplements play an important role here, in

particular those containing herbal ingre-

dients. The use of food supplements has

increased enormously in recent years since

consumers believe that natural products are

good or right for the body, whereas some-

thing of synthetic or industrial origin is bad

or wrong. The use of food supplements

containing herbal ingredients has become

common among athletes even when the

scientific rationale is non-existent.

The uncontrolled use of food supple-

ments can represent a health risk,

particularly when the herbal ingredients

have known pharmacological properties.

Herbal ingredients are often undetectable

by the usual anti-doping tests [1], which

make those with stimulant properties

particularly attractive to those seeking

performance enhancement without penalty.

The main hazards in the use of herbal

supplements include: effects due to the

specific pharmacological properties (agita-

tion, insomnia, tachycardia); the risk of

exceeding the appropriate dose to obtain a

pronounced enhancing effect; the risk of

allergy and intolerances – several products

specifically developed for sport activities

actually contain proteins from animal and

vegetable sources that are listed as major

allergens; and finally, the possible pre-

sence of banned ingredients (hormones,

etc) that have been added to enhance the

desired effects [1].

Food supplements containing plants with

known stimulant substances must be

regarded as potential health hazards. The

best-known case is that regarding dietary

supplements containing Ephedra deriva-

tives. Substantial evidence of harm emer-

ged in 2003, when a major study reported

more than 16,000 adverse events asso-

ciated with the use of ephedra-containing

dietary supplements, including heart

palpitations, tremors and insomnia. The

study also found little evidence of the

claimed efficacy of Ephedra in boosting

physical activities and weight loss. In 2004

the FDA banned sales of dietary supple-

ments containing ephedrine alkaloids

(Ephedra species) [11] because such

supplements presented an unreasonable

risk of illness or injury for the consumers

[5], and in the USA the sale of products

containing Ephedra alkaloids is now

considered criminal unless they have been

medically prescribed [10]. Ephedrine is

banned as an ingredient of food or food

supplement in the European Union; in Italy

ephedra alkaloids are banned by the anti-

doping national legislation [9].

This international ban, based as it is on

data illustrating adverse effects of Ephedra

alkaloids, stimulated a series of activities

to monitor food supplements present on the

market and developed for sport. There are

thousands of products on the market

containing herbal ingredients. The quality

control of these products is often

unsatisfactory and their market is wide and

complex, with modern ways of distribution

including athletes’ training centers and

direct delivery from purchase on the

Internet.

As part of the monitoring activity in

Italy, we have received several different

food supplements obtained in “alternative”

markets (away from the usual commercial

outlets) to be analyzed, with the aim of

detecting ingredients included in the list of

doping substances. Amongst the products

received, we describe a food supplement

containing herbal ingredients amongst

which the presence of ephedrine was

suspected and then demonstrated.

Dilemmas and Factors Involved in Health Promotion for Men’s in Brasov County 39

2. Material and Methods

2.1. Ephedrine

Standard ephedrine was purchased from

Sigma Aldrich Chemie GMBH (Germany)

(CAS n. 299-42-3) at the highest available

purification level (98%).

2.2. Food supplement

The product examined was a mixture of

ingredients, prepared in capsules,

described as a formula maximizing high

performance energy levels.

2.3. Sample preparation

Ephedrine was extracted from the food

supplement according to the method

described by Roman [7]. Briefly, a

weighed amount (1 g) of powder obtained

from 10 capsules randomly selected was

extracted with methanol–50 mM aqueous

potassium phosphate monobasic (3:97,

v/v). The extract was treated by solid-

phase extraction (SPE) on a strong cation-

exchange column. Ephedrine was eluted

from the column with methanol–ammo-

nium hydroxide (95:5, v/v). The eluate was

diluted with phosphoric acid and the

solution was injected into a HPLC system.

2.4. HPLC

An 880-PU Liquid Chromatographic

Pump (Jasco Corporation, Tokyo, Japan)

connected to a 975 UV detector (Jasco,

Tokyo, Japan) was used for the analyses.

UV detection was set at 210 nm. The

analytical column was an Inertsil ODS-2

RP-C18 column (5µm, 150x4.6 mm i.d.;

GL Sciences Inc., Japan) maintained at

40°C and protected by an RP18 guard

column (Merck). The LC mobile phases

were: A H2O + 0.025% trifluoroacetic acid

(TFA) and B acetonitrile (ACN) + 0.025%

TFA. The gradient (flow rate 0.6 mL/min)

was as follows: T0 90%A, T20min 10%A.

The injection volume was 25 µL and the

injector needle was washed with ACN–

water 1:1 (v/v). On-line data acquisition

and calculations were done by a Data Jet

Integrator (Thermo Separation Products,

Riviera Beach, FL, USA) and Winner 386

Autolab software (Thermo Separation

Products).

2.5. Mass spectrometry

Positive electrospray ionization (ESI+)

used a mass spectrometer with linear ion

trap (LTQ, ThermoElectron Co, San Jose,

CA, USA) equipped with a Surveyor liquid

chromatography (LC) Pump Plus and a

Surveyor Autosampler Plus (Thermo-

Electron Co, San Jose, CA, USA).

Peaks of the LC-MS/MS analysis were

measured using a Dell workstation by

means of the software Excalibur® release

2.0 SR2 (ThermoElectron Co, San Jose,

CA, USA).

The mass spectrometer was operated in

positive-ion mode with the ESI source

using nitrogen as sheath, auxiliary and

sweep gas at flow rates of 23, 8 and 2

(arbitrary units) respectively. Other ion-

source parameters: vaporizer temperature

450°C, ion-source collision energy 20V,

capillary temperature 275°C. The mass

spectrometer was operated in MS/MS

mode with helium as collision gas.

Samples were analyzed employing the

transitions 166 �148 .

3. Results

Analysis of the food supplement began

with the HPLC separation to determine

whether there was a peak having the same

retention time as ephedrine. Fig. 1 shows

the chromatogram of the purified

ephedrine and Fig. 2 that of the food

supplement extract. Even though the latter

chromatogram is complex, a peak having

the same retention time of ephedrine (9.5-

9.8 minutes) was clearly identifiable. The

presence of ephedrine was not indicated in

the label. To confirm the identity of

analyze, we performed further analyses by

mass spectrometry.


40

Fig.1. HPLC chromatogram of purified ephedrine

Fig. 2. HPLC chromatogram of food supplement extract

The chromatogram of the standard

ephedrine shows a single major peak, and

the mass spectrum yielded a signal at m/z

166 (the pseudomolecular ion of

ephedrine) and another at m/z 148,

corresponding to the [M-18]+ ion (Fig. 3).


Fig. 3. Total ion current (upper panel) and corresponding mass spectrum (lower panel) of

the ephedrine standard recorded by LTQ Ion-Trap mass spectrometers

To improve the specificity of the

identification, we applied ESI-ion trap

multistage tandem mass spectrometry

(ESI-IT-MSn) (Figure 4) and used multiple

reaction monitoring (MRM) of the MS3

148 to identify ephedrine in the sample

(Fig. 5).

A

B

Fig. 4. Multistage tandem spectra (ESI-IT-MS1) of ephedrine recorded by LTQ Ion-Trap

mass spectrometers. Upper panel: Ephedrine MS2 (transition m/z 166�148) Lower panel:

ephedrine MS3 (transition m/z 148�133, 117).


42

Fig.5. SIM (Single Ion Monitoring, Panel A) and MRM (Panel B) chromatograms of the

food supplement. The arrow indicates peaks corresponding to the ephedrine.

4. Discussion

Analyses of food supplements for

athletes in recent years in Italy have shown

that in several cases illicit substances had

been included in the formulae. Molecules

whose effects could be dangerous for

athletes were identified, including

evodiamine, vinpocetine and yohimbine.

Athletes use ergogenic products to face

physical and emotional stress in a sport

competition, but products need to be

conscientiously evaluated in terms of the

risk/benefit ratio. All athletes, whether

beginners or professionals, must fully

understand that the intake of some

substances can have severe adverse effects,

particularly products obtained in

“alternative” markets that are only

interested in profit. Continuous monitoring

of the products present in these markets is

the only effective tool to prevent the

distribution of food supplements

containing banned ingredients, and the

availability of suitable analytical methods

is critical if this goal is to be attained.

References

1. Caprino, L., Braganò, M.C., Botrè, F.:

Herbal supplements in sports: use and

abuse (italian). In: Ann Ist Super

Sanità (2005) 41: 35-38.

2. Chodorowski, Z., Waldman, W., Sein,

Anand, J.: Acute poisoning with

Tricholoma equestre. In: Przegl Lek

(2002) 5: 386-7.

3. Feinfeld, D.A., Mofenson, H.C.,

Caraccio, T., Kee, M.: Poisoning by

amatoxin-containing mushrooms in

suburban New York--report of four

cases. In: Clin Toxicol 1994, 32(6):

715-21.

4. Fernando, P.R.: Atempted homicide

with arsenic. In: Clin Toxicol., (1979)

14: 575-577.

5. Mandavilli, A.: Natural-born killers.

In: Nature Medicine (2003) 9:

634-635.

6. Manriquez, O., Veras, J., Rios J.C.,

Concha, F., Paris E.: Analysis of 156

cases of plant intoxication received in

the Toxicologic Information Center at

Catholic University of Chile. In: Vet

Hum Toxicol (2002) 44: 31-32.

7. Roman, M.C.: Determination of

ephedrine alkaloids in botanicals and

dietary supplements by HPLC-UV:

collaborative study. In: Journal AOAC

International (2004) 87:1-14.

8. Weakley-Jones, B., Gerber, J.E.,

Biggs, G.: Colchicine poisoning: case

report of two homicides. In: Am J

Forensic Medicine and Pathology

(2001) 22: 203-206.

9. *** Ministry of Health (2008) Italian

decree dated 4 April 2008

10. http://www.amin-

law.com/cpanel/preview.asp?ID=38

11. http://www.cfsan.fda.gov/~dms/ds-

ephed.html

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Time (min)

0 50

100

0 50

100

9.50

9.51

IMIPENEM RESISTANCE AMONG GRAM

NEGATIVE BACILLI

M. IDOMIR

1 C. NEMET

1

A. PASCU1 I. MOLEAVIN

1

Abstract: Gram negative bacilli are bacteria frequently implicated in human

pathology. The aim of our study has consisted in the detection of Gram negative

strains resistant to imipenem. The obtained frequency of resistant strains was

0.2% for Escherichia coli, 1.4% for Proteus spp., 3.9% for Enterobacter spp. and

22.5% for Pseudomonas aeruginosa. The obtained results have demonstrated

that imipenem remains an important solution for the therapy of infections

produced by multidrug resistant Gram negative bacilli but the selection of

resistant strains represents a threat that needs to be in the attention of the

practitioners.

Key words: imipenem, carbapenems, Gram negative bacilli.

1 Transilvania University of Braşov, Faculty of Medicine.

1. Introduction

Gram negative bacilli are bacteria that are

frequently implicated in human pathology,

in nosocomial and communitary infections.

In present, these pathogenic microorganisms

represent a significant cause of morbidity and

mortality. [1]

The hospital environment favorises the

selection of some multidrug resistant strains

due to the exposure to a wide range of anti-

microbial agents.

Different mechanisms are implicated in the

installation of the resistance to antimicrobial

substances among Gram negative bacilli like

enzyme production (cephalosporinases and

β - lactamases), variability of the antibiotic

target and modification of outer membrane

permeability. [1,7]

Many β - lactams are strong β - lactamases

inducers and they are also rapidly inactivated

by these enzymes. [7]

Carbapenems and β - lactam β - lactamase

inhibitor combinations are often used in the

therapy of the infections produced by Gram

negative bacilii. These antibiotics are strong

β-lactamases inducers too, but have a more

stable β-lactam ring that resists usually to

the action of these enzymes. [7]

The resistance to carbapenems of the germs

belonging to the Enterobacteriaceae family

is rare but is considered to be an emerging

clinical threat. This aspect has been observed

especially at Enterobacter spp. and Serratia

spp. but also at Proteus spp., Salmonella

enterica, Klebsiella pneumoniae, Citrobacter

freundii. [1,2] In the case of Escherichia coli

spp., the resistance to carbapenems, especially

to imipenem, is very rare. [4,5]

Recent studies have ilustrated that the main

mechanisms of resistance to imipenem for

E. coli are the hiperproduction of AmpC

β - lactamases and the loss of porins and for

Enterobacter, the production of chromosomal

cephalosporinases and the decrease of porin

synthesis in outer membrane.[1,5]

Metallo β-lactamases are very important

too. In the last decade, they were detected

Bulletin of the Transilvania University of Braşov • Vol. 1 (50) - 2008 � Series VI

44

in nosocomial P. aeruginosa strains. More

recently, it was observed that these enzymes

can be also produced by other Gram negative

bacilli. Carbapenems, mainly imipenem and

meropenem, are very useful for the therapy

of infections produced by multidrug resistant

Pseudomonas spp. but their use can lead to the

selection of resistant subpopulations. [6,7]

The main mechanisms implicated in the

resistance to imipenem to the P. aeruginosa

strains are the production of MBLs (Metallo

β-lactamases) and deficiency of the outer

membrane porins. [3,6]

2. Material and Method

The retrospective study has included Gram

negative bacilli isolated from the patients

hospitalized in 2007 in the Clinical County

Emergency Hospital of Braşov.

The aim of our study has consisted in the

detection of Gram negative strains, resistant

to imipenem.

The analysis of the sensibility to imipenem

for the isolated strains was performed using

the difusimetric Kirby-Bauer method.

The interpretation of the antibiogram results

were based on the CLSI (Clinical Laboratory

Standard Institute) reccomandation.

3. Results

During the retrospective study there have

been tested to imipenem the bacterian strains

belonging to different genre of Gram negative

bacilli: 450 strains of Escherichia coli, 282

strains of Enterobacter species, 73 strains of

Proteus spp. and 102 strains of Pseudomonas

aeruginosa.

Table 1

Germs S IS R

E. coli 449 - 1

Enterobacter spp. 268 3 11

Proteus sp. 172 - 3

P. aeruginosa 75 4 23

Table 1 ilustrates the number of sensitive

(S) strains, intermediate sensitive (IS) strains

and resistant (R) strains to imipenem.

As shown in figure 1, only 0.2% of E. coli

strains were resistant to imipenem.

Sensitive

99,8%

Resistant

0,2%

Sensitive Intermediate sensitive Resistant

Fig 1. The susceptibility to imipenem of E. coli

Imipenem Resistance among Gram Negative Bacilli

45

It was also determinated the resistance to

imipenem of Enterobacter spp. isolated from

the patients. Althaugh the Enterobacter spp.

strains were multiresistant, the percentage of

resistant pathogenic strains to this antibiotic

was of only 3.9%, in the conditions of our

study.

95,0%

1,1% 3,9%


Fig 2. The susceptibility to imipenem

of Enterobacter spp.

For the Proteus species that were isolated

from different prelevates during our study

it was also obtained a very low percentage

of resistant strains.

Resistant

1,7%

Sensitive

98,3%


Fig. 3. The susceptibility to imipenem

of Proteus spp.

We have also analyzed the percentage of

Pseudomonas aeruginosa strains that were

resistant to the tested antibiotic.

The obtained results show that the level

of resistance to imipenem for P. aeruginosa

was 22.5% so much higher than for the other

species analyzed during the study.

73,5%

3,9%

22,5%


Fig. 4. The susceptibility to imipenem

of Pseudomonas aeruginosa

4. Conclusions

1. According to the data from other studies

and in the conditions of the current study,

the E. coli strains resistent to imipenem

were very rare.

2. The percentage of resistant Proteus spp.

strains (1.4%) was very low.

3. Althaugh the Enterobacter spp. strains

were often multiresistent, the percentage

of resistant strains to imipenem was of

only 3.9% in the conditions of our study.

4. The level of resistance to imipenem of

Pseudomonas aeruginosa was 22.5%, so

much higher than for the other species.

5. The obtained results have demonstrated

that imipenem remains a solution for the

therapy of infections produced by multi-

drug resistant Gram negative bacilli but

the selection of resistant strains represents

a threat and needs to be in the attention

of the practitioners.

Bulletin of the Transilvania University of Braşov • Vol. 1 (50) - 2008 � Series VI

46

References

1. Bornet, C., Davin-Regli, A., Bosi, C.,

Pages, J-M., et al: Imipenem resistance

of Enterobacter aerogenes mediated by

outer membrane permeability. In: Journal

of Clinical Microbiology, vol. 38, no.

3, 2000, p. 1048-1052.

2. Hae Kyung, L., Park, Y.-J., Kim, J.-Y.,

Chang, E. et al: Prevalence of decreased

susceptibility to carbapenems among

Serratia marcescens, Enterobacter cloacae,

and Citrobacter freundii and investigation

of carbapenemases. In: Diagnostic Micro-

biology and Infectious Disease, vol. 52,

no. 4, 2005, p. 331-336.

3. Mendiratta, D., Vijayshri, D., Narang,

P.: Metallo-[beta]-lactamase producing

Pseudomonas aeruginosa in a hospital

from a rural area. In: Indian Journal of

Medical Research, vol. 121, 2005,

p. 701 -703.

4. Oteo, J., Delgado-Iribarren, A., Vega,

D., Bautista, V., et al: Emergence of

imipenem resistance in clinical E. coli

during therapy. In: International Journal

of Antimicrobial Agents, volume 32, issue

6, p. 534-537.

5. Pavez, M., Neves, P., Dropa, M., Matte,

M.-H., et al: Emergence of carbapenem-

resistant Escherichia coli producing CMY

-2-type AmpC beta-lactamase in Brazil,

In: Journal of Medical Microbiology,

57 (12), 2008, p. 1590-1592.

6. Pournaras, S., Ikonomidis, A., Marko-

giannakis, A., et al: Characterization

of clinical isolates of Pseudomonas

aeruginosa heterogeneously resistant to

carbapenems. In: Journal of Medical

Microbiology, vol. 56, 2007, p. 66-70.

7. Zhanel, G.G., Wiebe, R., Dilay, L., et al:

Comparative review of the carbapenems,

In: Drugs, 67(7), 2007, p. 1027-1052.

NON-ORGAN SPECIFIC

AUTOANTIBODIES AND

THE RESPONSE TO THE THERAPY

IN CHRONIC HEPATITIS C

D. NECULOIU

1 I. MOLEAVIN

2 M. ANGHEL

1

M. NECULOIU3 A. CRISTEA

4

Abstract: There is little data on clinical relevance of non-organ-specific

auto-antibodies (NOSA) in the standard antiviral therapy with interferon-

alpha (IFN-α) and ribavirina. ANA, ASMA, AMA, ANCA, LKM1 were

determined on 36 patients with chronic hepatitis C. The presence of these

auto antibodies was analyzed in the antiviral therapy with IFN-α pegilat and

ribavirin, according to the demographic, biochemical, histological and

virologic parameters. NOSA prevalence was 61%, 22 patients of 36 had at

least one autoantibody at the start and during antiviral therapy. NOSA has

been associated with increased levels of HCV RNA (ribonucleic acid-

hepatitis C) at the beginning of treatment (p<0.05). NOSA absence was

associated with a favourable response to treatment, namely with early

virologic response (p<0.05) and virologic response at the end of treatment

(p<0.05). Therefore, despite a good response to treatment, adding ribavirin

to the treatment with IFN-α could increase immunological differences that

may affect treatment results.

Key words: non-organ specific autoantibodies, C hepatitis, early virologic

response, ribavirin, interferon-alpha

1 Clinical Emergency County Hospital Brasov. 2 Dept. of Public Health and Medical Management, Transilvania University Brasov. 3 Dept. of Urology, Faculty of medicine, Transilvania University Brasov. 4 Clinical Emergency County Hospital Cluj-Napoca,

1. Introduction

The immunological extrahepatic mani-

festations in chronic hepatitis C (CHC) and

B are very different [11]. The presence of

specific and non specific organ auto-

antibodies (NOSA) occurs to a great

number of patients with chronic viral

hepatitis [13]. The high prevalence of

NOSA in chronic infection with hepatitis

viruses, has led to the investigation of their

clinical relevance. In some studies the

prevalence NOSA, including antinuclear

antibodies (ANA), anti-smooth muscle

antibodies (ASMA), antimitocondrial anti-

bodies (AMA), anticitoplasma neutrophilic

antibodies (ANCA), antimicrozomal

hepatic-renal antibodies (LKM1), antimi-

crozomal liver antibodies (LM), has been

investigated before, during and after the

therapy with IFN alpha [14]. However

there is little information regarding the

NOSA prevalence in standard therapy with

IFN alpha and ribavirin in CHC. NOSA


48

prevalence should also be investigated in

standard therapy, being known the immu-

no-modulatory function of ribavirin [9].

In recent years the combination between

RBV and IFN-alpha has increased to 40%,

the rate of biochemical and virologic res-

ponse of the patients with chronic viral

hepatitis C [17]. The effective treatment with

ribavirin in CHC appears to be correlated

with both its immunomodulatory and anti-

inflammatory effects [2]. In particular it

seems that RBV modulates the balance

between subsets of Th1 and Th2

lymphocytes in specific immune response by

activating the type 1 cytokine [19]. However,

RBV may increase the non-viral immune

response and can trigger autoimmune

phenomena to the predisposed patients. [4].

Previous analyses on the influence of

NOSA on hepatitis C virus clearance

during the IFN-alpha monotherapy are

contradictory; some studies have shown a

decreased response to the treatment for the

NOSA positive patients, other analyses

could not demonstrate any influence on

therapy [18].

In contrast there are few studies that

have investigated NOSA relevance and

biochemical and virological response of

the patients treated with IFN-alpha pegilat

and RBV [21]. This combination repre-

sents the standard therapy in the treatment

of CHC, and has proven to be superior to

the interferon monotherapy [15].

In this study we have determined the

NOSA prevalence in patients with chronic

viral hepatitis C and analyzed the

relationship between the NOSA presence

and biochemical and histological activity of

liver, and the impact of these auto antibodies

efficiency on the antiviral therapy which

combines IFN-alpha with RBV.

2. Material and Method

Patients. The patients were tested

retrospectively, 36 patients with CHC. The

demographic and clinic parameter are

show in Tabel 1. In this study, all patients

were treated during a period of 12 months

with standard doses of Pegasis

(180µg/week) and RBV in variable doses

1000-1200mg/day, depending on body

weight.

All patients were positive for anti-VHC

and ARN HVC and were diagnosed with

CHC. The laboratory parameters included

parameters of haematology, coagulation,

biochemistry. Average daily consumption

of alcohol was less than 40 grams. HBs

and HIV tests were negative.

All patients were tested according to the

score system for autoimmune hepatitis

diagnosis. Using this algorithm, none of

the investigated patients obtained more

than 10 points, excluding any association

of an autoimmune hepatitis [1].

Clinical data of the patients Table 1

Age, years 46,22±7,6

Sex (Male/Female) 20/16

Naive/Retreated 20/16

HCV RNA level

(<800.000/>800.000UI/ml)

18/18

NOSA (+/-) 22/14

Hisological activity index 7,69±1,39

Virological response at the end of

the treatment (+/-)

18/18

Auto-antibodies testing. ANA, SMA,

AMA, LKM1, LM were determined by

indirect imunofluorescence on the sections

of liver to cryostat, kidneys and stomachs

of rat: initial serum dilution was 1:80 for

ANA 1: 40 for the other auto antibodies.

ANCA were tested by indirect imuno-

fluorescence on human polymorpho-

nuclears. Standard protocols for testing

were used for the tested antibodies [20].

For each patient NOSA was determined

before the start of the antiviral treatment,

and two serum samples were collected: one

after three months from the beginning of

the treatment and another at the end of it.

Virus testing.Virological tests to detect

anti-HCV antibodies were realized with

ELISA kits of third generation (HCV AB

ETI-K, Sorin Biomedica), and the viral

Non-Organ Specific Autoantibodies and the Response to the Therapy in Chronic Hepatitis C 49

load was done by the RT-PCR method,

quantitative method with HCV Monitor kits

version 2.0, the Cobas Amplicor (Roche)

analyzer. HCV RNA level was tested at the

beginning of treatment (HCV RNA start),

then after 3 months from the beginning of

treatment (HCV RNA 3 months) for

determining early virologic response (EVR)

and at the end of the treatment (VR-end).

Hepatic Histology. All patients were

subjected to liver biopsy and histological

parameters were classified according to the

Knodell score, actualized version proposed

by Ishak and collaborators [12].

Hepatic fibrosis was appreciated by the old

Knodell system: 0 absence of fibrosis, 1 portal

fibrosis; 3 fibrosis in bridges; 4 cirrhosis.

Statistical analysis. In the case of

qualitative variables the Fisher test was

used, and in the case of correlation studies

between a qualitative variable and a

quantitative one the Student test was used,

and the threshold for statistical

significance was set to 0.05.

3. Results

The prevalence of auto antibodies in this

study was the following: 22 patients of 36

had at least one autoantibody (ANA, SMA,

LKM, ANCA) at the start of the treatment

and during it at a titter greater than 1:80 for

ANA, and 1:40 for other auto antibodies

(Table 2). ANA was the most common

auto antibody (38.8%) followed by the

SMA (22.8%). AMA has not been

detected, and ANCA, LM and LKM were

found in a smaller number of cases.

Table 2

The prevalence of NOSA at the patients

with chronic hepatitis C.

n (%)

ANA 14 (38.8)

AMA 0

LKM 4 (11.1)

LM 1 (2.7)

SMA 8 (22.2)

ANCA 2 (5.5)

NOSA 22 (61.1)

Subsequently the patients were divided

into two groups: one group consists of

patients with NOSA negative and the second

group with NOSA positive (Table 3).

Table 3

The comparison of demographic, biochemical, histological and virological parameters

at NOSA positive and NOSA negative patients.

NOSA-Negativ p-value NOSA-

Pozitive

Sex(Male/Female) 6/8 0.221 14/8

Age, years 44.85±6.06 0.205 48.72±10.09

Naiv/retreted 10/4 0.126 10/12

ASAT 0 75.5729.7 0.737 72.09±30.34

ALAT 0 46,56±17,23 0.221 86.09±20.37

ASAT 3 43±20,28 0.482 49.09±27.62

ALAT 3 54.42±36,07 0.425 46.54±22.73

HCV-RNA viremia level (high/low) 10/4 0.004 5/17

EVR(+/-) 7/7 0.05 18/4

VR-end(+/-) 6/8 0.021 18/4

Hisological activity index 8±1.56 0.406 7.63±1.32

Knodel IV(1/3) 4/10 0.311 10/12


50

Between the two groups there were no

differences according to the sex, age,

histological activity index, and Knodell

appreciation score of fibrosis, ASAT and

ALAT levels, at the beginning and after 3

months. In the case of viral load at the

beginning of treatment, represented by the

level of HCV RNA, a high viral load, more

than 800,000 IU / ml is positively

correlated to the presence of NOSA. 21

patients had at the beginning a high viral

load of which 17 patients were NOSA

positive at the beginning or during the

treatment (Figure 1).

Fig. 1. Viral load and the

presence/absence of NOSA

In terms of response to the interferon

therapy, 22 patients received an early

virological response, of which 10 (45%)

patients had NOSA, and 12 (55%) patients

had no NOSA. Instead of the 14 patients

without early virological response, 12

(85.71%) patients had NOSA and 2

(14.28%) patients were NOSA negative

(Figure 2). So the presence of NOSA has

been statistically associated in unvaried

analysis, with a lower RPV (p=0,003).

Fig. 2. EVR and the presence/absence of

NOSA

HCV RNA level was detected at the end

of treatment, for the establishment of

virologic response It was found that 18

patients had detectable levels of HCV

RNA, and the other 18 patients responded

to treatment with undetectable levels of the

viral RNA. Among patients without

therapeutic response at the end of

treatment, 14 (77.7%) had auto antibodies

at the beginning or during treatment, and 4

(22.2%) were NOSA negative (Figure 3).

So the NOSA presence has been associated

statistically in Fisher test, with a weaker

virological response at the end of treatment

(p=0.02)

Fig. 3. VR-end and the presence/absence of

NOSA


We examined the prevalence, and the

aspect of imunofluorescence titer ANA,

SMA, LKM, at patients with or without

response to antiviral therapy (Table 4).

ANA had the highest prevalence being

present at 14 patients (38.8%), with a

higher frequency at patients who didn’t

obtain a virological response at the end of

treatment (p=0.03). The NOSA titers

didn’t differ between the two groups. ANA

had in all cases speckled pattern, it was

homogenous only in one case, SMA had

aspect of SMA-V in all cases, and ANCA

had an atypical aspect: p ANCA.

ANA, SMA, ANCA: prevalence, pattern and titer Table 4

4.Discussions

RBV is an analogue of nucleotides,

which increases the efficiency of antiviral

treatment in chronic viral hepatitis C, when

it is administered in combination with IFN-

alpha pegilat. Balance of cytokines

associated with Th1 and Th2 has a

primordial importance in antiviral therapy

[16], and superiority of standard treatment

can be attributed to the immunomodulatory

properties of RBV [8].

In this study 22 patients had at least

one detected autoantibody. ANA and

SMA had the highest prevalence; it is

comparable with previous studies that

have shown similar frequencies of these

auto antibodies [3].

Most ANA had a speckled pattern and

SMA aspect of SMA-V. The appearance of

the ANA imunofluorescence has no

clinically significance taking into account

that the target antigen for ANA is variable

in chronic liver diseases. One patient has a

homogeneous appearance, which would

suggest a target antigen at the level of

nuclear lamina.

In some studies positive nonspecific

organ auto antibodies have been associated

with clinical and laboratory distinct cha-

racteristics. Casani and collaborators [7]

have found an association between NOSA

and gender (female type), and ALT, AST

values, and the score of necro-inflamatory

activity in the liver biopsy. Any

association between the incidences of

NOSA, sex, transaminase level and necro-

inflamatory activity hasn’t been found in

this study. These differences may be due to

small lot of patients taken in the study,

similar to other studies, which could not

confirm these associations [5].

Clinically, it is pointed out the difference

between effective therapy for patients with

and without NOSA. NOSA absence before

and during therapy was associated with a

favourable response to treatment. The

study is conducted on the immunological

parameters of a small series of patients,

and the positive response to treatment is

defined as virology response at the end of

treatment.

This study differs from other studies that,

no association between the presence or

VR-end + VR-end - p-value

ANA [n(%)] 4 (28,5) 10 (71,42) 0,03

ANA titer 1:80 (1:80 - 1:160) 1:80 (1:80 – 1:160)

Speckled ANApattern 3 (75%) 10 (100%) 0,46

SMA [n(%)] 5 (62,5) 3 (37.5)

SMA titer 1:40 (1:40-1:80) 1:40 (1:40-1:80)

SMA-V pattern 5 (100%) 3 (100%)

ANCA [n(%)] 1 1 0.63

ANCA titer 1:40 1:40

Atipycal p-ANCA 1 (100%) 1 (100%)


52

absence of NOSA and effective antiviral

therapy have found. [10] However,

previous studies assumed interferon

monotherapy, and in two other studies,

which include a larger number of patients,

a weaker response to treatment in the case

of auto antibodies presence was

demonstrated [6].

Regarding the results published so far,

these auto antibodies can be interpreted as

markers for activation of nonspecific

lymphocytes in their response to the

infection with hepatitis C virus. This could

be associated with a decreasing of the

specific immune response and a failure in

eliminating the virus and its persistence in

the body.

This assumption could be supported by

the fact that patients with NOSA have a

higher viral load compared with patients

without auto antibodies. RBV has

immunomodulatory distinct properties, and

can modulate the immune response

balance and the specific and non specific

antiviral response of individual patients.

Therefore, despite a general benefit of

ribavirin, association of this immuno-

modulator to the therapy with interferon

could reveal individual differences of the

immune balance, Th1 versus Th2, which

were not evident in studies that have

investigated only interferon monotherapy.

A recent study has shown that adding

ribavirin to interferon therapy, does not

alter the aspect of thyroid auto antibodies,

but grows the risk of hypothyroidism [6].

It is stressed that the safety and efficacy

of therapy, is missing to patients with

hepatitis C and autoimmune abnormalities.

Thus it is compulsory to take into account

the negative potential of the autoimmune

reaction at patients with CHC and NOSA

positive during the therapy with interferon.

To confirm these suppositions studies are

necessary to be done on a larger number of

patients.

These observations are related to the

immunopathologic discrimination between

CHC, autoimmune hepatitis and auto-

immune syndrome overlap-hepatitis C

[18]. In this study we have involved the

revised score system for the diagnosis of

autoimmune hepatitis to exclude a hepatic

autoimmune predominant disease. More-

over, only one patient had low SMA titter

without any SMA-V aspect, one patient

had homogenous ANA and no patient had

LKM 1 antibody, which are usually

associated with autoimmune hepatitis.

5. Conclusions

We have proved the negative

relationship between the effectiveness of

antiviral combined therapy with interferon-

alpha and ribavirin for chronic viral

hepatitis C and the presence of nonspecific

organ antibodies. However studies on a

larger number of patients are necessary

before making decisions regarding

treatment. Future studies should include

the measurement of other immune

parameters: markers of activation of

lymphocytes and cytokines, and genetic

studies to elucidate physiopathological

associations between the presence of auto

antibodies and the reducing of the

effectiveness of treatment with antiviral

interferon-alpha and ribavirin.

References

1. Alvarez, F., Berg, P.A., Bianchi, F.B.,

Bianchi, L., Burroughs, A.K. et al.:

International Autoimmune Hepatitis

Group Report: review of criteria for

diagnosis of autoimmune hepatitis. In:

J Hepatol 1999, 31:929-938.

2. Beragamini, A., Bolacchi, F.,

Cepparulo, M., Demin, F., Uccella, I.,

Bongiovanni, B. et al.: Treatment with

ribavirin and interferon-a reduces

interferon-g expression in patients

with chronic hepatitis C. In: Clinical

Experimental Immunology 2001,

123:459–464.


3. Bianchi, F. B., Muratori, P., Granito,

A., Pappas, G., Ferri, S., Muratori, L.:

Hepatitis C and autoreactivity. In: Dig

Liv Dis. 2007; 39 (1) :22-24.

4. Bogdanos, D.P., Mieli-Vergani, G.,

Vergani, D.: Non-organspecific

autoantibodies in hepatitis C virus

infection: do they matter? In: Clin

Infect Dis 2005; 40: 508-510.

5. Bogdanos, D.P., Invernizzi, P.,

Mackay, I.R., Vergani, D.:

Autoimmune liver serology: Current

diagnostic and clinical challenges. In:

World J Gastroenterol 2008; 14(21):

3374-3387.

6. Carella, C., Mazziotti, G., Morisco, F.,

Rotondi, M., Carella, C., Mazziotti,

G., Morisco, F., Rotondi, M., Cioffi,

M., Tuccillo, C., Sorvillo, F.,

Caporaso, N., Amato G.: The addition

of ribavirin to interferon-alpha

therapy in patients with hepatitis C

virus related chronic hepatitis does

not modify the thyroid autoantibody

pattern but increases the risk of

developing hypothyroidism. In: Eur J

Endocrinol 2002, 146:743-749.

7. Cassani, F., Cataleta, M., Valentini,

P., Muratori, P., Giostra, F.,

Francesconi, R., Muratori, L., Lenzi,

M., Bianchi, G., Zauli, D., Bianchi,

F.B.: Serum autoantibodies in chronic

hepatitis C: comparison with

autoimmune hepatitis and impact on

the disease profile. Cassani F.,

Cataleta M., Valentini P., Muratori P.,

Giostra F., Francesconi. In:

Hepatology 1997, 26:561-566.

8. Fang, S.H., Lai, M.Y., Hwang, L.H.,

Yang, P.M., Chen, P.J., Chiang, B.L.,

Chen, D.S.: Ribavirin enhances

interferon-gamma levels in patients

with chronic hepatitis C treated with

interferon-alpha. In: J Biomed Sci

2001, 8: 484-491.

9. Fang, S.H., Hwang, L.H., Chen, D.S.,

Chiang, B.L.: Ribavirin enhancement

of hepatitis C virus core antigen-

specific type 1 T helper cell response

correlates with the increased IL-12

level. In: J Hepatol 2000, 33:791-798.

10. Gregorio, G.V., McFarlane, B.,

Bracken, P., Vergani, D., Mieli-

Vergani, G.: Organ and non-organ

specific autoantibody titres and IgG

levels as markers of disease activity: a

longitudinal study in childhood

autoimmune liver disease. In:

Autoimmunity 2002; 35: 515-519

11. Han, S.H. Extrahepatic manifestations

of chronic hepatitis. B.Clin Liver Dis.

2004, 8 (2):403-18.

12. Ishak, K., Baptista, A., Bianchi L.,

Callea F., De Groote J., Gudat F., Denk

H., Desmet V., Korb G., MacSween

R.N., et al.: Histological grading and

staging of chronic hepatitis. J Hepatol.

1995, 22(6):696-699.

13. Muratori, P., Muratori, L., Sroffolini,

T., Pappas, G., et al.: Prevalence of

non-organ specific autoantibodies in

HCV-infected subjects in the general

population. In: Clin Exp Immunol.

2003; 131: 118–121

14. Muratori P., Muratori L., Verucchi G.,

Attard L., Bianchi F. B., Lenzi M.

Non–Organ-Specific Autoantibodies

in Children with Chronic Hepatitis C:

Clinical Significance and Impact on

Interferon Treatment. In: Clin Inf Dis.

2003; 37:1320–6.

15. National Institutes of Health Consensus

Development Conference Statement:

Management of Hepatitis C 2002 (June

10-12, 2002). In: Gastroenterology

2002, 123:2082-2099.

16. Piazzolla, G., Tortorella C., Fiore G.,

Fanelli M., Pisconti A., Antonaci S.:

Interleukin-12 p40/p70 ratio and in vivo

responsiveness to IFN-alpha treatment

in chronic hepatitis C. In: J Interferon

Cytokine Res 2001, 21:453-461.

17. Poynard, T., Marcellin, P., Lee, S.,

Niederau, C., Minuk, G.S., Ideo, G. et

al.: Randomised trial of interferon a2b

plus ribavirin for 48 weeks or for 24


54

weeks versus interferon a2b plus

placebo for 48 weeks for treatment of

chronic infection with hepatitis C virus.

In: Lancet 1998, 352:1426–1432.

18. Selmi, C., Mackay, I.R., Gershwin,

M.E.: The immunological milieu of the

liver. In: Semin Liver Dis 2007; 27:

129-139.

19. Tam, R.C., Pai, B., Bard, J., Lim, C.,

Averett, D.R., Phan, U.T. et al.:

Ribavirin polarizes human T cell

responses toward a type 1 cytokine

profile. In: Journal of Hepatology

1999, 30: 376–382.

20. Vergani, D., Alvarez, F., Bianchi,

F.B., Cancado, E.L., Mackay, I.R.,

Manns, M.P., Nishioka, M., Penner, E.

Liver autoimmune serology: a

consensus statement from the

committee for autoimmune serology of

the International Autoimmune

Hepatitis Group. In: J Hepatol 2004;

41: 677-6.

21. Wasmuth, H.E., Stolte, C., Geier, A.,

Dietrich, C.G., Gartung, C., Lorenze,

J., Matern, S., Lammert, F.: The

presence of non-organ-specific auto-

antibodies is associated with a

negative response to combination

therapy with interferon and ribavirin

for chronic hepatitis C. In: BMC

Infect Dis. 2004, 13:41-42.

ACQUIRED ANGIOEDEMA IN SYSTEMIC

LUPUS ERYTHEMATOSUS

Ioana AGACHE

1

Abstract: Angioedema due to acquired C1-inhibitor (C1-INH) deficiency

(also referred to as acquired angioedema) is a rare, life-threatening disease

with poorly defined aetiology, therapy, and prognosis. The article reports on

acquired angioedema in 8 patients with systemic lupus erythematosus (SLE)

representing 16.66% of the total 48 SLE monitored in our clinic. Sex ratio

was 1/7, medium age 45.5±12.61 years. In 7 cases angioedema preceded the

diagnosis of SLE with 13.28 ±7.8 months, one case developed angioedema 15

years after SLE diagnosis. At the time of acquired angioedema diagnosis the

medium C1-INH concentrations were 0.094±0.039 g/L and C4 was

decreased in all cases, medium values 14.42± 4.83 mg/dl. Angioedema

localization was at face/eyelids in 5(62.5%) cases, larynx in 3(37.5%) cases

and 2(25%) cases had severe abdominal pain. 3(37.5%) patients also

associated pruritic erythematous rash. Compared with the SLE patients not

having angioedema, in the acquired angioedema group there was increased

incidence of systemic symptoms, immune cytopenias, kidney involvement,

antiRo and anti Sm antibodies. Patients evolved with a medium of

angioedema attacks of 6.87/year until SLE was diagnosed; after treatment

for SLE was started the frequency decreased to 2.28 attacks/year and entered

into angioedema complete remission after 11.5 months. C1-INH concentra-

tion reached normal values after 12± 2.16 months in all 7 cases where

angioedema preceded SLE diagnosis and remained low in the SLE patient

developing angioedema after SLE was diagnosed. Acquired angioedema

responded best to SLE treatment with hydroxyclorochine or

immunosuppressant

Key words: angioedema, systemic lupus erythematosus

1 Dept. of Immunology-Allergology, Faculty of Medicine, Transylvania University Brasov

1. Background

Angioedema due to an acquired

deficiency in the inhibitor of the first

component of human complement (CI-

INH) is a rare syndrome that is usually

identified as acquired angioedema (AAE).

Compared to hereditary angioedema

(HAE), angioedema due to acquired C1-

inhibitor deficiency is very rare and less is

known in terms of aetiology, evolution and

treatment. Like HAE it can be a life-

threatening disease.

Acquired angioedema is frequently

associated with lymphoproliferative disea-

ses ranging from monoclonal gammo-

pathies of uncertain significance (MGUS)

to non-Hodgkin's lymphoma (NHL) and/or

anti-C1-INH inactivating autoantibodies in

patients with autoimmune disease or

neoplasm [5, 6, 10]. The coexistence of

true B cell malignancy, non-malignant B

cell proliferation and pathogenic auto-


56

immune responses suggests that AAE

patients are all affected by altered B cell

proliferation control although their clinical

evolution may vary.

The main pathogenetic mechanisms of

acquired angioedema are represented by

the excessive production of autoantibodies

anti C1INH and/or increased complement

activation with increased consumption of

C1INH [3, 4, 6]. The reduction in C1-INH

leads to activation of the classical comple-

ment pathway and complement consum-

ption, as well as activation of the contact

system leading to the generation of the

vasoactive peptide bradykinin, increased

vascular permeability, and angioedema.

Clinical manifestations in angioedema

due to acquired C1-INH deficiency are

similar to HAE (subcutaneous, non-pruritic

swelling, involvement of the upper

respiratory tract, and abdominal pain due

to partial obstruction of the gastrointestinal

tract), except that laryngeal attacks are

more frequent, thus increasing the potential

life-threatening character of the disease

[12]. Unlike those with HAE, AAE

patients have no family history of

angioedema and are characterised by the

late onset of symptoms and various

responses to treatment due to the

hypercatabolism of C1-INH. Adults or

elderly patients are most commonly

affected [4, 6].

Diagnostic hallmarks for acquired angio-

edema are low plasma C1INH, low C4,

low C1q and normal C3. Low plasma C1q

is the most important feature of acquired

angioedema [13]. Type I AAE is charac-

terised by accelerated catabolism of C1-

INH and type II AAE characterised by the

presence of autoantibodies to C1-INH.

Less is known on the long-term treat-

ment of AAE compared to HAE. The key

to successful management of AAE is the

control of underlying disease. Recent data

showed that AAE in Sjogren syndrome

responds to rituximab [12].

Aim of the study: Incidence and

prognosis of acquired angioedema in patients

with systemic lupus erythematosus (SLE).

Study design: Study group included 48

SLE patients monitored in the Clinical

Immunology Department of Brasov

County Hospital between 2003 and 2007,

mean age 46.10± 14.30 years, 91.67%

females, and mean SLE duration 6.99±5.41

years.

SLE patients were retrospectively

evaluated for:

• incidence of acquired angioedema

• temporal relation between AAE and

SLE diagnosis

• clinical manifestations of acquired

angioedema

• demographic, clinical and immu-

nologic features of SLE in patients

with acquired angioedema compared

to SLE patients with no angioedema

• evolution of AAE under SLE treat-

ment: number of attacks, C1INH

plasma concentration after 1 year of

SLE treatment and C4 plasma concen-

tration after 6 months of SLE

treatment

• evolution of SLE in patients

associating acquired angioedema

Diagnosis of acquired angioedema was

made combining clinical manifestations with

the presence of low plasma C1INH, low

plasma C4 and normal plasma C3 and by

exclusion of monoclonal gammopathies or B

cell lymphoproliferative diseases and of

other known triggers of angioedema (ACE

inhibitors, analgesics and non steroidal anti-

inflammatory drugs). None of the patients

had a family history of angioedema.

SLE was diagnosed according to ARA

criteria and SLE remission according to

ACR criteria.

Plasma C1INH was determined in

collaboration with Pasteur Institute using a

third generation ELISA method (normal

values 0.15-0.35 g/L), C3 and C4

concentrations were determined using an

Acquired Angioedema in Systemic Lupus Erythematosus 57

immune turbidimetric method (normal C 4

values 20-40 mg/dl, normal C3 values 90-

120 mg/dl).

Data were analysed using Chi test

(Statistica 7). Data are presented as median

(range) values unless otherwise stated.

2. Results

8 (16.66%) SLE patients had recurrent

angioedema with no obvious triggers, sex

ratio 1/7 and medium age 45.5±12.61 years

(minimum 24, maximum 65 years). Mean

plasma C1INH concentration at the

diagnosis of acquired angioedema was

0.094±0.039 g/L (normal values 0.15-0.35

g/L) and mean plasma C4 concentration

was 14.42± 4.83 mg/dl (normal values 20-

40 mg/dl).

AAE preceded the diagnosis of SLE in 7

cases with 13.28 ±7.8 months (minimum 6,

maximum 24 months) and 1 case develop-

ped angioedema 15 years after SLE

diagnosis.

Angioedema was localized at face/

eyelids in 5 (62.5%) cases, 3 (37.5%) cases

had laryngeal oedema and 2(25%) cases

had severe abdominal pain. 3 (37.5%)

cases also associated erythematous rash.

The criteria used to diagnose SLE in the

above described patients with acquired

angioedema are presented in table 1.

Table 1: SLE diagnosis in patients with acquired angioedema

Case 1 Butterfly rash, photosensitivity, oral mucosa erosions, non-erosive arthritis,

pericarditis, proteinuria, autoimmune haemolytic anaemia, ANA and anti Sm

antibodies

Case 2 Butterfly rash, photosensitivity, pleurisy, autoimmune thrombocytopenia, ANA and

anti Ro antibodies

Case 3 Butterfly rash, photosensitivity, oral mucosa erosions, non-erosive arthritis, pleurisy,

proteinuria, autoimmune haemolytic anaemia, ANA and anti double stranded DNA

antibodies

Case 4 Photosensitivity, oral mucosa erosions, autoimmune thrombocytopenia, ANA and anti

Sm antibodies

Case 5 Photosensitivity, non-erosive arthritis, proteinuria, ANA and anti Sm antibodies

Case 6 Butterfly rash, photosensitivity, oral mucosa erosions, ANA and anti double stranded

DNA antibodies

Case 7 Photosensitivity, oral mucosa erosions, pleuro-pericarditis, ANA and anti Sm

antibodies

Case 8 Butterfly rash, discoid rash, photosensitivity, oral mucosa erosions, non-erosive

arthritis, pericarditis, proteinuria, autoimmune haemolytic anaemia, ANA and anti Sm

antibodies

Abbreviations: ANA = antinuclear antibodies

There were no significant differences for

age, mean disease duration or sex ratio

between SLE patients with or without

acquired angioedema (table 2).

Immune cytopenias, kidney involvement

and systemic symptoms were more

frequently encountered in SLE patients

with AAE compared to SLE patients with

no angioedema: 6(75%) vs. 13(32.5%)

(p<0.05) for systemic symptoms; 6(75%)

vs. 14(35%) (p<0.05) for immune

cytopenias; 6(75%) vs. 11(27.5%)

(p<0.05) for kidney involvement (table 2).


58

When comparing SLE immunologic

features of SLE patients with or without

acquired angioedema a significant

increased incidence of anti Sm antibodies

and of anti Ro antibodies was observed in

association with AAE: 5(62.5%) vs.

9(22.5%) (p<0.05) for anti Sm antibodies

and 8(100%) vs. 19(47.5%) (p<0.05) for

anti Ro antibodies (table 2).

Table 2: Comparison between SLE patients with or without acquired angioedema

Group A: 8 SLE

patients with

acquired angioedema

Group A: 40 SLE

patients without

angioedema

Chi test

sex ratio

1/7 3/37 NS

mean age (years) 45.5±12.61 46.7±15.99 NS

Demographic

features of SLE

patients

mean disease duration

(years)

5.46±3.785 8.53±7.04 NS

systemic symptoms 6(75%) 13(32.5%) p<0.05

serositis 5(62.5%) 16(40%) NS

arthritis 6(75%) 25(62.5%) NS

heart involvement 3(37.5%) 11(27.5%) NS

kidney involvement 6(75%) 11(27.5%) p<0.05

pulmonary

hypertension

4(50%) 13(32.5%) NS

CNS involvement 0 5(12.5%) NS

Clinical features

of SLE patients

immune cytopenias 6(75%) 14(35%) p<0.05

Double strain anti

DNA antibodies

1(12.5%) 17(42.5%) NS

anti Sm antibodies 5(62.5%) 9(22.5%) p<0.05

anti Ro antibodies 8(100%) 19(47.5%) p<0.05

Immunologic

features of SLE

patients

antiphospholipid

antibodies

2(25%) 14(35%) NS

All attacks of AAE were treated with

intramuscular epinephrine and high-dose

oral or iv systemic steroids. None of the

attacks necessitated fresh plasma for C1-

INH replacement or intubations for the

laryngeal oedema.

After SLE was diagnosed treatment was

started with hydroxyclorochine in 5

patients and with cyclophosphamide in 2

patients. The patient with acquired

angioedema starting after SLE was

diagnosed oral steroid in medium doses

was continued.

Patients with acquired angioedema were

followed for a mean period of 47.5 ±10.08

months (minimum 36 months, maximum

64 months) for SLE evolution and for

evolution of angioedema: number of

attacks, C1INH plasma concentration after

1 year of SLE treatment and C4 plasma

concentration after 6 months of SLE

treatment.

SLE patients with associated AAE

preceding the diagnosis of SLE entered

into complete SLE remission in 4 cases

and into partial SLE remission in 3 cases.

The patient with acquired angioedema

after SLE diagnosis and treated only with

oral steroids died 2 years after AAE was

diagnosed due to an abdominal attack of

angioedema with surgical intervention.

Acquired Angioedema in Systemic Lupus Erythematosus 59

Patients evolved with a medium of

angioedema attacks of 6.87/year until SLE

was diagnosed. After treatment for SLE

was started the frequency decreased to

2.28 attacks/year and angioedema entered

into complete remission after 11.5 months

in all the 7 cases were angioedema pre-

ceded SLE diagnosis. The patient with

acquired angioedema starting after SLE

was diagnosed continued to experience

frequent and severe angioedema attacks.

C1-INH concentration reached normal

values (mean values 0.24±0.05 g/L,

minimum 0.19 g/L, maximum 0.34 g/L)

after 12± 2.16 months in all the 7 cases

with acquired angioedema preceding SLE

and remained low in the SLE patient

developing AAE after SLE diagnosis,

despite steroids used to treat SLE. C4

increased after SLE treatment was started

from 14.42 ± 4.83 mg/dL to 25.24 ± 8.6

mg/dL (normal C4 values 20-40 mg.dL)

after 7.28± 2.92 months in all 7 cases were

angioedema preceded SLE diagnosis. The

patient with AAE starting after SLE was

diagnosed and treated only with medium

doses oral steroids continued to have low

C4 concentrations.

3. Discussion

The incidence of AAE in SLE patients in

this study (16.66%) is higher compared to

other reports from literature (4%) [7]. This

may be due to the fact that 7 patients out of

8 were first diagnosed with AAE and

afterwards observed for SLE development.

Other studies included patients with

already diagnosed SLE and observed the

incidence of AAE during SLE evolution.

Due to the fact that antibodies against

C1-INH were not measured the differential

diagnosis between type I AAE character-

rised by accelerated catabolism of C1-INH

and type II AAE characterised by the

presence of autoantibodies to C1-INH

could not be done. However, from the

clinical standpoint this distinction is not

always useful and the incidence of

autoantibodies to C1-INH in SLE seems

very low, compared to the functional

deficit of C1-INH which seems to be the

main mechanism of angioedema in SLE [1,

7, 9]. A study of eight SLE patients with

persistently low levels of C4 antigen

showed a normal level of C1-INH antigen

but an abnormal profile of C1-INH

function in seven including dysfunctional

inhibition of C1r and/or C1s and increased

functional levels against C1s [8].

This article reports on 8 patients with

SLE and acquired angioedema and

pinpoints the evolution of acquired

angioedema preceding SLE full

development with several years,

concordant with other case reports in

literature [11]. Thus, all patients with this

rare condition and no obvious cause (B cell

lymphoma or monoclonal gammopathy)

should be followed for SLE development.

SLE patients associating acquired angio-

edema have a peculiar profile with increased

incidence of immune cytopenias, kidney

involvement and systemic symptoms,

normal C3 concentration and anti Ro and

anti Sm antibodies. In these SLE patients

development of antibodies anti C1INH

should be actively seek and treatment with

drugs with potential induction of angioedema

(ACE inhibitors, analgesics, NSAIDS) at

least cautioned.

In the present study there were no life-

threatening events due to angioedema,

except the death due the abdominal attack

of angioedema with surgical intervention.

This is in contrast with other reports

highlighting the severity of AAE in SLE

patients [9, 11]. There were no obvious

triggers of AAE attacks in contrast with

other reports showing infections as main

triggers [11]. As in other observations the

frequency of the attacks was closely

correlated with SLE activity.

In a previous report high dose steroids in

conjunction with immunosupressants were

needed to control AAE in an SLE patient

[11]. In our study acquired angioedema

responded best to SLE treatment with


60

hydroxyclorochine or immunosuppressant

and did not respond to respond to medium

doses oral steroids.

References

1. Cicardi, M, Bisiani, G, Cugno, M,

Spath, P, Agostini, A.: Autoimmune C1

inhibitor deficiency: report of eight

patients. In: Am J Med 1993; 95:

169-175.

2. Cicardi, M, Zingale, L.C., Pappalardo,

E., Folcione, A., Agostoni, A.:

Autoantibodies and lympho-

proliferative diseases in acquired C1-

inhibitor deficiencies. In: Medicine

(Baltimore) 2003; 82:274-81.

3. Cheng, W.Y., Smith, W.B., Russell,

W.J.: Acute upper airway obstruction

from acquired angioedema. In: Emerg

Med Australas. 2007; 19 :65-7.

4. Cugno, M., Castelli, R., Cicardi, M.:

Angioedema due to acquired C1-

inhibitor deficiency: A bridging condi-

tion between autoimmunity and lym-

phoproliferation. In: Autoimmun Rev.

2008; 8:156-9.

5. Greaves, M., Lawlor, F.: Angioedema:

manifestations and management. In: J

Am Acad Dermatol 1991; 25:155-61.

6. Jazwinska, E.C., Gatenby, P.A.,

Dunckley, H., Serjeantson, S.W.: C1

inhibitor functional deficiency in

systemic lupus erythematosus (SLE). In:

Clin Exp Immunol 1993; 93: 968 – 973.

7. Lahiri, M., Lim, A.Y.: Angioedema

and systemic lupus erythematosus--a

complementary association? In: Ann

Acad Med Singapore. 2007;36:142-5.

8. Malbran, A, Hammer, C.H., Frank,

M.M., Fries, L.F.: Acquired

angioedema: observations on the

mechanism of action of autoantibodies

directed against C1 esterase inhibitor.

In: J Allergy Clin Immunol 1988; 81:

1199-204.

9. Markovic, S.N., Inwards, D.J., Frigas,

E.A., Phyliky, R.P.: Acquired C1

esterase inhibitor deficiency. In: Ann

Intern Med 2000;132:144-50.

10. Nzeako, U.C., Frigas, E., Tremaine,

W.J.: Hereditary angioedema: a

broad review for clinicians. In: Arch

Intern Med 2001;161:2417-29.

11. Odi-Ros, J., Paredes, J., Detarsio, G.,

Vilardell, M.: Autoantibodies to C1

inhibitor in patients with lupus

disease. In: J Rheumatol 1997; 24:

1856 ± 1858.

12. Sánchez-Cano, D., Callejas-Rubio,

J.L., Lara-Jiménez, M.A., López-

Trascasa, M., Circadi, M., Ortego-

Centeno, N.: Successful use of

rituximab in acquired C1 inhibitor

deficiency secondary to Sjogren's

syndrome. In: Lupus. 2008; 17: 228-9.

13. Thong, B.Y.H., Thumboo, J., Howe,

H.S., Feng, P.H.: Life-threatening

angioedema in systemic lupus

erythematosus. In: Lupus 2001; 10;

304-308.

THE RELATIONSHIP BETWEEN THE RISK

PROFILE OF ARTERIAL HYPERTENSION

AND THE FEATURES OF METABOLIC

SYNDROME-STUDY ON 129 PATIENTS

G. IFTENI

1 H. RUS

1

M. RADOI1 G. PAMFIL

2

Abstract: The objective of study was to assess the severe evolution of

arterial hypertension evaluated by ambulatory blood pressure monitoring in

middle aged hypertensive patients with metabolic syndrome and its

relationship with anthropometric and biochemical parameters and with the

presence of type 2 diabetes mellitus.

Methods: 129 hypertensive patients diagnosed with metabolic syndrome (MetS)

according to the Adult Treatment Panel (ATP) III criteria were evaluated by

ambulatory blood pressure monitoring (ABPM) parameters: 24-hour variability

(diurnal index), heart rate, pulse pressure; anthropometric parameters: body

mass index, waist circumference and laboratory data: serum levels of

triglycerides, cholesterol, LDL-cholesterol, HDL-cholesterol, uric acid. Statistical

analysis including two-taliled Student test-t for comparison of means between two

groups and multivariate logistic regression analysis was performed to identify

independent predictors for the evolution with diurnal index lower than 10% (non-

dipper status).

Results: the non-dipper status was present in 76% of the hypertensive patients

with MetS, significantly frequent in patients with type 2 diabetes mellitus

(p=0.0033). The „non-dipper” status was associated with increased mean values

of waist circumference (121.17 cm versus 115.29 cm, p=0.0245), body mass index

(32.19 kg/m² versus 28.65 kg/m², p=0.0003), duration of diabetes mellitus (2.89

years versus 1.45 years, p=0.0338), heart rate (75.86 beats/min versus 71.13

beats/min, p=0.0467) and triglycerides (266.11mg/dL versus 220.87 mg/dL, p=

0.0078). Independent risk predictors for nondipping status were body mass index

and triglyceride levels (p<0.0001).

Conclusion: In hypertensive patients with MetS the risc for „non-dipper” status is

in relation with increasing of waist circumference, body mass index, heart rate,

triglycerides and with the presence and duration of type 2 diabetes mellitus.

Key words: arterial hypertension, metabolic syndrom.

1 Transilvania University of Brasov, Dep of Internal Medicina. 2 Medical College, Brasov.

1. Background

The National Cholesterol Education

Program (NCEP)-Adult Treatment Panel

(ATP) III [16] considered obesity as

epidemic and the association with

cardiovascular risk as the characteristic of

the metabolic syndrome. The ATP III

criteria for the diagnosis of metabolic

syndrome are based on the categorial


62

presence of at least 3 of the following 5

criteria: abdominal obesity (waist

circumference >102 cm in men, and >88 in

women), arterial hypertension (history of

hypertension, systolic blood pressure ≥130

mmHg, and diastolic blood pressure ≥85

mmHg), impaired fasting glucose (fasting

blood glucose level >110 mg/dL), impared

glucose tolerance or type 2diabetes mellitus,

hypertriglyceridemia (>150 mg/dL), low

high-density lioprotein-cholesterol (HDL-C).

Large scales of clinical trials reveald that

hypertension is a classical risk factor for

cardiovascular diseases. The close

relationship of hypertension with glucose

intolerance and diabets melitus type 2 was

observed in epidemiological trials. Further

more, the sub-group of hypertensive subjects

with the lack of nocturnal decline in blood

pressure was reffered as ”non-dipping

pattern” and has been associated with a

greater extent of target organ damages [1,2].

Despite the high frecquency of the „non-

dipping” pattern in diabetes mellitus [12]

and its close relationship with insuline

resistance [4], the association of „non-

dipping” pattern with metabolic syndrome

failed to be proven by some authors [3].

2. Objectives

The present study aimed to examine the

relationship between the risk profile of

arterial hypertension assesed by ambulatory

blood pressure monitoring and the defining

features of metabolic syndrome using the

ATP III criteria for diagnosis.

3. Methods

The study population included 129

patients diagnosed with arterial

hypertension and metabolic syndrome.

Metabolic syndrome was evaluated

according to NCEP-ATP III criteria.

Patients agreed to participate to the study

procedures. Patients with one of the

following conditions such as secondary

hypertension, congestive heart failure,

previous myocardial infarction, cardiac

valve disease, chronic renal failure and any

condition preventing technically adequate

ABPM (atrial fibrillation, other arrhythmias)

were excluded from the study. The patients

were evaluated by detailed questionnaire and

physical examination. The questionnaire

provided information about cardiovascular

risk factors such as smoking and diabetes

mellitus and about past medical history

regarding hypertension duration and its

medical treatment. ABPM was carried out on

the non dominant arm using Schiller BR-102

plus device after validation of its readings.

Recordings were analyzed to obtain 24 hour

daytime and nighttime averages of systolic

blood pressure (SBP), diastolic blood

pressure (DBP), mean arterial blood pressure

(MABP), the degree of day-night decrease in

SBP and DBP, pulse pressure (PP), mean

heart rate (HR). Nocturnal “non-dipping”

refers to a 10% or lesser magnitude reduction

(diurnal index) in average SBP and/or DBP

during the night compared with daytime SBP

average values. Statistical analysis was

carried out using Statistical 6 programs.

Comparison of parametric values between

two groups was performed by means of two-

tailed Student`S t-test. Multivariate logistic

regression analysis was used to identify

independent predictors for the development

of “non-dipping” status. A value of p<0.05

was considered statistically significant.

4. Results

The study population consists of 66 women

(51.2%) with mean age of 55.4 years, and

63 men (48.8%) with mean age of 50.6 years.

Diabetes mellitus was diagnosed in

65 patients (50.4). The study population was

divided in two groups according to the values

of diurnal index (DI). Group 1 included

98 patients (76%) with „non-dipper” status

(DI ≤10%) and group 2, 31 patients (24%)

with „dipper” status (DI >10%).

The Relationship between the Risk Profile of Arterial Hypertension and the Features …. 63

The patients form group 1 had statistical

significant high mean values of the following

parameters: waist circumferences [121.17

cm vs 115.29 cm, p=0.0245], hip

circumferences [115.45 cm vs110.42 cm,

p = 0.0501], body mass index [32.19 kg/m2

vs 28.65 kg/m2, p=0.0003], duration of type

2 diabetes mellitus [2.89 years vs 1.45 years,

p=0.0338], glicozilated hemoglobin [6.44 %

vs 5.32%, p=0.0247], triglycerides levels

[266.11 mg/dL vs 220.87 mg/dL, p=0.0078]

and mean heart rate [75.86 beats/min vs

71.13 beats/min, p=0.0467] (Table 1).

Table 1

Nondipper status and the mean values of anthropometric parameters and metabolic

anomalies in adult hypertensive patients with metabolic syndrome

Group 1

DI ≤ 10%

Group 2

DI > 10% P value

mean SD mean SD

Age (years) 53.12 11.08 53.16 9.67 0.9861

Weight (kg) 84.84 15.58 90.16 16.72 0.1057

Body mass index (kg/m2) 32.19 5.06 28.65 3.06 0.0003

Waist/ Hip ratio 1.06 0.11 1.05 0.15 0.8628

Waist circumference (cm) 121.17 12.31 115.29 13.27 0.0245

Hip circumference (cm) 115.45 12.79 110.42 10.93 0.0501

Duration of diabetes mellitus (years) 2.89 3.34 1.45 2.92 0.0338

Duration of hypertension (years) 7.04 5.03 6.58 5.13 0.6597

Glycemia (mg/dL) 131.91 44.30 118.42 47.80 0.1496

Glycemia at 2 hours post OGTT (mg/dL) 215.26 72.91 192.84 77.99 0.1448

HbA1C (%) 6.44 2.40 5.32 2.33 0.0247

Cholesterol total (mg/dL) 235.41 46.73 234.84 51.11 0.9540

HDL-cholesterol (mg/dL) 43.32 10.56 45.19 11.79 0.40338

LDL-cholesterol (mg/dL) 171.64 46.65 164.52 43.64 0.4531

Triglyceride (mg/dL) 266.11 82.24 220.87 77.50 0.0078

Acid uric (g/L) 7.38 2.02 7.07 2.12 0.4763

Microalbuminuria (mcg/min) 233.49 180.40 186.58 183.41 0.2111

TAST (mmHg) 132.94 12.79 130.90 11.40 0.4298

TADT (mmHg) 85.80 9.49 82.87 8.39 0.1272

PP (mmHg) 47.63 10.34 46.87 11.72 0.7298


64

Group 1

DI ≤ 10%

Group 2

DI > 10% P value

mean SD mean SD

MAPT (mmHg) 102.12 10.56 98.77 7.90 0.1089

CHT (mmHg) 103.76 19.94 99.55 20.39 0.3105

TASD (mmHg) 138.59 31.41 133.87 11.53 0.4150

TADD (mmHg) 88.10 10.09 85.45 8.65 0.1904

MAPD (mmHg) 103.89 10.62 101.61 8.20 0.2764

CHD (mmHg) 108.24 21.86 104.45 21.28 0.3984

TASN (mmHg) 124.80 14.42 120.55 14.22 0.1538

TADN (mmHg) 77.62 9.44 73.84 11.39 0.0676

MAPN (mmHg) 92.95 10.46 89.45 10.77 0.1102

CHN (mmHg) 86.92 17.37 83.74 18.67 0.3851

Heart rate (beats/min) 75.86 11.69 71.13 10.50 0.0467

OGTT =oral glucose tolerance test, TAST= 24 hour systolic arterial pressure, TADT= 24 hour

diastolic arterial pressure, PP= pulse pressure, MAPT= 24 hour mean arterial pressure, CHT= 24

hour hypertensive charge index, TASD= daytime systolic arterial pressure, TADD= daytime

diastolic arterial pressure, MAPD= daytime mean arterial pressure, CHD= daytime hypertensive

charge index, TASN= nighttime systolic arterial pressure, TADN= nighttime diastolic arterial

pressure, CHN= nighttime hypertensive charge index.

In order to identify independent risk

predictors for the evolution with “non-

dipping” profile we used multiple logistic

regressions, and the results showed body

mass index and triglycerides as risk

predictors for “non-dipping” status.

5. Discussion

Our data presenting 76% of „nondipper”

status in patients with metabolic syndrome

with the recent data revieled that in

patients with MS the nighttimes systolic

blood pressure is a frequent phenomemon

and that the nighttimes systolic blood

pressure is higher in patients with high

MS-Score than in those with low MS-

Score [15].

Various other studies investigating the

effects of „dipping” and „non-dipping”

patterns demonstrated that „non-dipping”

patterns have been associated with an

increased risk of end-organ damage [2],

such as cerebro-vascular and cardio-

vascular events. [7, 10, 14]. A diminished

nocturnal decline in blood pressure has

also been reported as a risk factor for

cardiovascular mortality, independent of

the overall blood pressure load during a

24-h period, in the general population. [10].

Nighttimes blood pressure appears to convey

additional risk information about CHF

beyond office-measured blood pressure and

other established risk factors for CHF [9].

Although, underlying mechanism are stil

unknown, sympatenic overall activity,

functional and structural vascular alterations,

early autonomic neuropathy have been seen

in patients with „non-dipping” blood

pressure profile. [8, 13]

Our study is a cross sectional prospective

study that asses the relations between the

anthropometric and biochemical

parameters of the metabolic syndrome and

the severity of the clinical profile of

arterial hypertension. We observed

significant corelations between low diurnal

index and anthropometric parameters:

waist circumference and body mass index.

Among the biochemical parameters, the

high mean leves of triglycerides were in

statistical significant correlation with the

evolution of „non-dipper” status.

Epidemiological studies showed that in

obese patients, hypertension is correlated

The Relationship between the Risk Profile of Arterial Hypertension and the Features …. 65

with high body mass index. In the

Framingham study, 70% of the new cases

of hypertension were related to the excess

of adipose tissue [6] and 78% of cases of

hypertension in men and 65% in women

were attributed to obesity. Other popula-

tional studies showed that arterial pressure

measured at office is closely related with

body mass index and waist/hip ratio [5].

Kotsis et al observed that 55% of patients

with normal weight had „dipper” profile in

contrast to 35% of the obese patients. In

the group of patients with normal blood

pressure after blood pressure measuring at

the office or using ABPM, the „dipper”

status was found in 60% of the

underweight patients, 58.6% of normal

weight subjects, 30.6% of overweight and

28% of the obese patients. In the

hypertensive group the „dipper” status was

found in 50.8% of the underweight

patients, 38.5% of normal weight, 30.5%

of overweight and 27.3% of the obese

patients [11].

Conclusions

In hypertensive patients with metabolic

syndrome the risk of „nondipper” status is

in relationship with increased waist

circumference, body mass index, heart

rate, triglycerides and with the presence

and duration of type 2 diabetes mellitus.

References

1. Bianchi, S., Bigazzi, R., Baldari, G.,

Sgherri, G., Campese, V.M.: Diurnal

variation of blood pressure and

microalbuminuria in essential

hypertension. In: Am J Hypertens

1994; 7: 23-29.

2. Cuspidi, C., Meani, S., Fussi, V.,

Severgnini, B., Valerio, C., Catini, E.,

Leonetti, G., Magrini, F., Zanchetti,

A.: Metabolic synddrome and target

organ damage in untreated essentila

hypertensives. In: J Hypertens

2004a;22:1991-1998.

3. Cuspidi, C., Meani, S., Fussi, V.,

Severgnini, B., Valerio, C., Catini, E.,

Sala, C., Magnaghi, F., Zanchetti, A.:

Is the nocturnal fall in blood pressure

reduced in essential hypertensive

patients with metabolic syndrome? In:

Blood Press. 2004c; 13: 230-235.

4. Della Mea, P., Luia, M., Bandolin, V.,

Guzzon, S., Sonino, N., Vettor, R.,

Fallo, F.: Adiponectin, insulin

resistance and left ventricular

structure in dipper and nondipper

essential hypertensives patients. In:

Am J Hypertens 2005; 18: 30-35.

5. Doll, S., Paccaud, F., Bovet, P.,

Burnier, M., Wietlisbach, V. Body

mass index, abdominal adiposity and

blood pressure: consistency of their

association across developing and

developed countries. In: Int J Obes

Relat Metab Disord. 2002; 26: 48-57.

6. Garrison, R.J., Kannel, W.B., Stokes,

J., Castelli, W.P.: Incidence and

precursors of hypertension in young

adults: the Framingham Offspring

Study. In: Prev Med 1978; 16: 235-

251.

7. Higashi, Y., Nakagawa, K., Kimura,

M., Noma, K., Hara, K., Sasaki, S.,

Goto, C., Oshima, T., Chayama, K.,

Yoshizumi, M.: Circadian variation of

blood pressure and endotelial function

in patients with essential hypertension

a comparison of dippers and non-

dippers. In: J Am. Coll. Cardiol. 2002;

40: 2039-2043.

8. Hommel, E., Mathiesen, E.R., Giese,

J., Niesen, M.D., Schutten, H.,

Parving, H.H.: On the pathogenesis of

arterial blood pressure elevation early

in the course of diabetic nephropathy.


66

In: Scand J Clin Lab Invest 1989; 49:

537-544.

9. Ingelsson, E., Björklund-Bodegård,

K., Lind, L., Ärnlöv, J., Sundström, J.:

Diurnal Blood Pressure Pattern and

Risk of Congestive Heart Failure. In:

JAMA. 2006; 295: 2859-2866.

10. Kario, K., Pickering T.G., Matsuo T.,

Hoshide S., Schwartz J.E., Shimada K.

Stroke prognosis and abnormal

nocturnal blood pressure falls in older

hypertensives. Hypertension 2001; 38:

852-857.

11. Kotsis, V., Stabouli, S., Bouldin, M.,

Low, A., Toumanidis, S., Zakopoulos,

N.: Impact of obesity on 24-Hour

Ambulatory Blood Pressure and

Hypertension. In: Hypertension 2005;

45: 602-607.

12. Perk, G., Meckler, J., Ben Ishay, D.,

Bursztyn, M.: Non dipping in diabetic

patients: insights from the siesta. In: J

Hum Hypertens 2002; 16: 435-438.

13. Sherwood, A., Steffen, P.R.,

Blumenthal, J.A., Kuhn, C.,

Hinderliter, A.L.: Night time blood

pressure dipping the role of the

sympatetic nervous sistem. In: Am J

Hypertens 2002; 15 :111-118.

14. Staessen, J.A., Thijs, L., Fagard, R.,

O’Brian, E.T., Clement, D., de Leeuw,

P.W., Mancia, G., Nachev, G.,

Palatini, P., Tuomilehto J., Webster,

J.: Predicting cardiovascular risk

using conventional vs ambulatory

blood pressure in older patients with

systolic hypertension. In: JAMA 1999;

282: 539-546.

15. Tartan, Z., Uyarel, H., Kasikcioglu,

H., Alper, A.T., Ozay, B., Bilsel, T.,

Gul, M., Recep, Ozturk, R., Cam, N.:

Metabolic Syndrome as a Predictor of

Non-Dipping Hypertension. In: The

Tohoku Journal of Experimental

Medicine 2006; 210 (1):57-66.

16. *** NCEP. Expert panel on detection,

evaluation and treatment of high

blood pressure in adults. Executive

summary of the third report of the

National Cholesterol Education

Program (NCEP) expert panel on

detection and evaluation and

treatment of high blood cholesterol in

adults (Adult Treatment Panel III). In:

JAMA 2001;285:2486-2497.

HYPERTHYROIDISM AT DEBUT AND

THE LEFT VENTRICLE MASS

C. SCARNECIU

1 L. NEDELCU

1

I. SCARNECIU2 V. SCARNECIU

3

Abstract: It’s a well known fact that thyroidian hormones stimulate by

direct nuclear action the production of proteins in general, which can lead to

cardiac hypertrophy. We have performed a prospective study on 72

hyperthyroidian patients with ages between 18 and 49 years, newly

diagnosed, without cardiovascular problems of other nature. These patients

were ecocardigraphicaly evaluated at admission and after receiving the

euthyroidism results, these were compared to a control lot formed out of 25

persons. Through 2D ecography a dimension increase in the left ventricle

was observed in all hyperthyroidian patients, on 66% reaching sizes that

define hypertrophy. The increasing of the left ventricle was symmetric,

affecting the septum as well as the ventricular walls. The increasing

procentage was about 25% on average being correlated with the level of

thyroidian hormones and not the disease duration or the type of affliction.

The left ventricular mass grows early in thyreotoxicosis, proportional with

the level of thyroidian hormones and not the type of disease, this being at

least partially reversible when reaching euthyroidism

Key words: thyreotoxicosis, hypertrophy, reversible, left ventricle.

1 Transilvania University of Brasov, Faculty of Medicine, Dep of Internal Medicine. 2 Transilvania University of Brasov, Faculty of Medicine, Dep of Urology. 3 Transilvania University of Brasov, Faculty of Medicine.

Introduction

It’s a well known fact that thyrodidian

hormones through direct nuclear action

stimulate the production of proteins in

general, leading to cardiac hypertrophy.

Through ecographic study we wanted to

highlight if the effect appears early and

what its scale is. Also we wanted to verify

if the effect is reversible when reaching

euthyroidism.

Material and Method

We have performed a study on newly

diagnosed patients with clinical manifested

hyperthyroidism, admitted throughout a

period of 3.5 years at the Endocrinology

Clinic, part of the Emergency County

Hospital Brasov which were selected in

order that they would not present any

cardiovascular affliction of any other

origin or hypekinethical syndrome, with

ages between 18 and 49 (36.7 years

average) and with a 3.39 month period

until the diagnostic was presented and a

free fraction average value of the

thyritoxin(FT4) of 58,76pmol/l.

The 72 hyperthyroidian patients newly

diagnosed have formed the H lot which

was biochemical and ecographical

evaluated at admission and after a period


68

of 8-12 weeks, after obtaining

euthyroidism, under the name of

euthyroidian (E) lot, made of only 37

subjects from the initial enrolment.

The results obtained have been reported

to a control lot formed out of 25 healthy

subjects with a comparable percentage of

age and sex.

For a reliable comparative a 4th lot was

used, actually being a sub lot of H lot,

formed out of 37 hyperthyroidian patients

which were re-evaluated in the

euthyroidism stage, named lot HR

(reevaluated hyperthyroidians).

Through 2D echocardiography the left

ventricular mass (MVS) was determined

using the forward formula:

( ) ( )[ ] 6.1304.133

−−++= DtdPPSIVDtdxMVS

(Penn) (1)

where:

- Dtd: left ventricle telediastolic

diameter

- SIV:intraventricular septum thickness

- PP: thickness of the posterior left

ventricle wall

Table 1

Nominal and pathological values for the left ventricle mass (Devereux)

Normal values Hypertrophy

Men Women Men Women

MVS

g45176 ± g40121± 2/134 mg>

2/110 mg>

Results

Using the formula (1) the left ventricle mass

was calculated in the H lot (toxic)

comparative with the E lot and the control lot.

Taking into consideration the 3 variables

in the Penn formula and illustrated in the

lower table (table 1) proves the fact that in

H lot a growth in thickness of the septum

and in particular the ventricle wall (which

remains large especially for the

euthyroidians comparative to the control

lot) is produced. The average telediastolic

diameter of the left ventricle remains also

the same at comparable values with the

other two lots. Because between the

cardiac frequency and the telediastolic

volume exists an backward correlation,

finding equal telediastolic volumes for the

hyperthyroidian patients actually means a

heightened precharge which is being

correlated with a high cardiac flow.

Table 2

Medium values if the telediastolic diameter of the left ventricle, average thickness of the

interventricular septum and the posterior left ventricle wall

Lots DTD

[ ml ]

SIV

[ mm ]

PP

[ mm ]

H 44,15 ± 5,35 10,44 ± 1,41 11,23 ± 1,29

HR 45,08 ± 6,41 10,89 ± 1,32 10,24 ± 1,41

E 42,22 ± 3,94 10,84 ± 0,96 9,78 ± 1,51

M 43,68 ± 3,15 9,76 ± 1,16 8,90 ± 1,02

Hyperthyroidism at Debut and the Left Ventricle Mass 69

Table 3

Table containing the levels of results through comparison of average DTD,

SIV and PP between lots.

Lots DTD

p

SIV

p

PP

p

H vs M- p= 0.35 p<0,0001comp p<0,0001

HR vs E p= 0.03 p= 0,39 p= 0.11

E vs M p= 0.11 p= 0.0003 p= 0.01

From Table 3 the results are the

following: there aren’t any significant

statistic differences between the

teledistolic diameter in the H lot in

comparison with the control lot and also

the E lot in comparison with the control

lot. Although if we compare the same

patients in the hyperthyroidism stage with

patients in the euthyroidism stage, the

difference between the left ventricle

telediastolic diameter will be statistically

significant, probably being the expression

of a heightened precharge in hyper–

thyroidism. Comparing the size difference

of the intraventricular septum and the

posterior ventricular wall, the conclusion is

that in hyperthyroidism the hypertrophy is

not completely reversible when

contracting euthyroidism. After using the

Devereauz formula to calculate the

ventricular mass we found that 66.66% of

the H lot and 59.46& from the HR lot have

left ventricle hypertrophy in comparison

with 11% out of the E lot and 0% from the

control lot.

Table 4

Table containing the average values +/- standard error, minimal and maximal values

of ventricular mass and % of patients with left ventricular hypertrophy in the 4 lots

Lot MVS average

+/- ES [g/m2]

MVS

minimum

[g/m2]

MVS

maximum

[g/m2]

% HVS

H ( n= 72 ) 115 ± 2,82 71,68 175,72 66,66

HR ( n = 37 ) 122,16 ± 4,23 83,86 175,72 59,46

E ( n = 37 ) 97,65 ± 3,62 65 152,91 11,11

M (n = 25 ) 86,71 ± 2,80 54,89 108,69 0

.

As seen in table 4 the percentage of

patients with left ventricle hypertrophy is

comparable between the E lot and the HR

lot.


70

The difference between (in percentage)

patients with left ventricle hypertrophy in

the E lot in comparison with the control lot

is according to the left ventricle mass

difference, which suggests the fact that in

hyperthyroidism, hypertrophy is only

partially reversible. In order to clear out

this aspect a supervision over a log period

of time of the E lot is necessary.

Comparing the left ventricle mass values

in the HR lot with the E lot a decrease in

heart weight with an average percentage of

26.67%+/- 18.84% is observed. The

decrease in heart weight takes place

regardless of the initial value, but not

always reaching values that define

ventricular hypertrophy.

Fig 1. The variation of the left ventricle mass drop before and after treatment in the HR

lot compared to the E lot.

After calculating the average left ventricle mass in the 3 lots results as shown in the

next table have been found:


Table 6

left ventricle mass +/- standard error in the 4 lots and the

percentual difference between the 4 o them

Lots MVS medie

[g/m2]

H versus

M %

HRversus

E %

HR versus

M %

E versus

M %

H 115,36

± 18,84 HR 122,17

± 25,76

E 97,65

± 22,03

M 86,71

± 14

24,84

25,11

29,03

11,2

From the analysis of the results (table 6)

the following have resulted: a 24.84%

average increase in left ventricle mass for

the H lot. But comparing to the HR and the

control lot the average percentage

difference (left ventricle mass) if of

29.03%, the regression percentage of left

ventricle mass for the HR lot in

comparison with the E lot is also around

25%, therefore comparable with the

differential percentage between the H and

control lots. There is a difference between

the E lot and the control lot regarding the

left ventricle mass of about 11.2% which

has a statistic importance and could mean

3 different things:

1. the rise of the left ventricle mass for

the H lot is not completely reversible

2. the HR lot and E lot are little

comparable with the H lot, and the

mass increase is completely

reversible

3. evaluation of the E lot has been

made to fast and disease regression

has not been produced, therefore the

hypertrophy is completely reversible

A long term investigation of the E lot is

necessary until reaching the moment when

the rise in TSH is produced at comparable

values with the control lot in order to

validate the results.


72

Table 7

Table that contains left ventricle mass values for the H lot considering age, sex

affliction and disease evolution time and the FT4 level

Criterion MVS [g/m2]

H

MVS [g/m2]

HR

Male 140,69 140,18 Sex

Female 112,20 117,97

under 20 years 92,15 92,15

[20 – 29 ] years 114,43 117,47

[30 – 39] years 105,33 120,06

Age Group

[40 – 49] years 122,84 129,57

Graves’ Disease 112,51 124,32

GPN 120,27 119,59

Adenoma 112,39 92,15

Iodine 124,46 -

Disease

Hyperthyroidsm 112,76 -

under 1 month 138,98 -

[1 – 3) months 110,76 116,15

[3 – 6) months 107,55 126,5

Duration of

Disease Evolution

Over and equal

with 6 months

128,28 138,84

under 40 pmol/l 100,4 114,63

[40 – 57) pmol/l 112,62 122,33

[57 – 76) pmol/l 117,41 92,15

[76 – 95) pmol 132,74 142,81

Concentration

FT4

Over and equal

with 95 pmol/l

131,93 131,93

As seen in table 7 the left ventricle mass

in the H lot is larger for male patients and

increases with age. Also it gets larger with

the FT4 growth until the saturation value

[76-95]pmol/l. The left ventricle mass

increases since the beginning if the disease

correlates with hormone levels than

evolution stage of the disease. There aren’t

any significant differences regardless of

the disease type. The left ventricular mass

growth is better correlated with thyroidian

hormone levels/ The left ventricle mass

growth suddenly rises to a maximum value

of 76pmol/l, after which the rising is far

slower.


Table 8

Table that contains left ventricular mass decrease in the H lot judging by sex, age,

affliction, disease evolution, and FT4 levels.

Criterion %MVS [g/m2]

HR

Male 24,97 Sex

Female 27,07

under 20 years 41,70

[20 – 29 ] years 19,46

[30 – 39] years 29,86

Age Group

[40 – 49] years 25,55

Graves’ Disease 28,98

GPN 19,17

Disease

Adenoma 41,70

[1 – 3) months 30,54

[3 – 6) months 15,80

Duration of

Disease Evolution

Over and equal 6 months 20,02

under 40 pmol/l 11,48

[40 – 57) pmol/l 14,70

[57 – 76) pmol/l 40,70

[76 – 95) pmol 40,37

Concentration FT4

Over and equal with 95 pmol/l 41,68

The left ventricle mass percentage is

equivalent for patients of different sex,

larger for young patients, in dissonance with

the absolute value of the left ventricular

mass, which is larger for older patients.

The left ventricular mass growth

percentage has a small value even from the

beginning of the disease and is better

correlated with the initial thyroidian

hormone levels than with the time of

evolution of the disease.

There aren’t any substantial differences

regardless of the disease type.

The left ventricle mass decrease

correlates best with the initial thyroidian

hormone levels. This suddenly grows to a

maximum value of 76pmol/l after this the

growth is very much slower.


74

The left ventricle mass growth in the H

lot is positively correlated with the FT4

levels (r=0.74), with the heart frequency at

the moment of examination (r = 0.49) and

negative, although the correlation is weak

(r=0.29) with TSH levels.

Conclusions

In conclusion the left ventricular mass in

the H lot grows early, regardless of the

initial heart weight. 66% of all tyrotoxic

patients reach values that define

hypertrophy.

Growth was symmetrical, afflicting the

septum as well as the ventricular walls.

Growth percentage was an average of 25%

correlating with thyroidian hormone levels

(r=0.74) therefore correlating with

tyreotoxicosis also and not with the disease

type.

The effect is reversible, at least partially

when contracting euthyroidism.

References

1. Biondi, B., Palmieri, E. A., Gaetano,

L., Deradino Fazio: Effects of

Thyroid Hormone on Cardiac

Function: The Relative Importance

of Heart Rate, Loading Conditions,

and Myocardial Contractility in the

Regulation of Cardiac Performance

in Human Hyperthyroidism, 2002,

In: The Journal of Clinical

Endocrinology & Metabolism 87(3):

968-974.

2. Braunwald – Heard disease – A Text

Book of cardiovascular medicine –

VI –Edition WB Saunders Comp.,

2005.

3. Gherasim, L. şi colaboratorii:

Medicina Internă. Bolile

cardiovasculare şi metabolice. Vol

I+II, Ed. Medicală, 2004.

4. Kahaly G.: The Thyroid and the

Heart. Thyroid International 4,

1998:2-21.

5. Klein, I., Levery, G.S.: The

cardiovascular system in

thyrotoxicosis. In: Braverman LE,

Utinger RD, eds. The thyroid, 8th

ed.

Philadelphia. Lippincott-Raven,

2001.

6. Scarneciu, C. C.: Afectarea cardio–

vasculara in tirotoxicoz. Ed.

Universitatii Transilvania, Brasov,

2007.

7. Scarneciu, C. C., Scarneciu, I., Rus,

H.: Evaluarea ecocardiografica a

functiei diastolice a ventriculului

stang in hipertiroidism la debut. In:

Medicina interna, Vol. V, nr.6, 2007.

8. Scarneciu, C. C., Scarneciu, I.,

Nedelcu, L., Rus, H.: Tireotoxicoza

la debut şsi funcţia sistolică a

ventriculului stâng. Medicina

interna, Vol. V, nr. 4, 2008.

9. Toft, A.D., Boon, N.A.: Thyroid

disease and the heart. In: Heart

2000, 84: 445-460.

EFFECT OF TREATEMENT WITH

OMEGA-3 FATTYACIDS AND

ATORVASTATIN IN PATIENTS WITH

COMBINED DYSLIPIDEMIA

H. RUS

1 M. RĂDOI

1 C. CIUREA

1

M. NAN1 C. SUTA

2 D. BODA

3

Abstract:

Objective: Treatment with omega-3 free fatty acids determine a significant

reduction of the serum level of tryglicerides, reduce the risk of coronary

artery disease-related death, nonfatal cardiac events, and suppress the

cardiac arrhythmias. We evaluate the effectiveness of omega-3 free fatty

acids added to atorvastatin in patients with combined dyslipidemia.

Material and method: We evaluate 40 patients, 20 males (50%), age between

35 and 55 years old, nonsmokers, nonhypertensive, and with no diagnosed

coronary artery disease, randomized in Group A (20p.) treated 8 weeks with

atorvastatin 20mg/day and Group B (20p.) Treated free fatty acids 3Gr/day

last 4 weeks added to atorvastatin 20mg/day 8 weeks.

Statistical analysis pair t-Student test.

Results: Adding omega-3 fatty acids 3gr/day to the treatment with

atorvastatin significantly reduce the plasmatic level of total cholesterol(

280mg/dl vs 256mg/dl, p < 0,003), tryglicerides (180 vs 170 mg/dl, p <0,01),

and nonHDL Cholesterol (-4% Vs 1,5%, P <0,004).

Conclusions: combining the atorvastatin treatment with omega-3 free fatty

acids in patients with combined dyslipidemia, causes an important decrease

of plasma tryglicerides, and in a lesser degree LDL and total cholesterol.

Key words: omega-3 fattyacids, atorvastatin, dyslipidemia.

1 Transilvania University of Brasov, Internal Medicine Dept., Faculty of Medicine. 2 Research Assistant, Heart Institute “N. Stancioiu” , Cluj-Napoca. 3 Research Assistant, University “Carol Davilla”, Bucharest.

Due to the growing incidence of

cardiovascular pathology the decrease of

the lipids serum level represents a main

element in the strategy of decrease of

cardiovascular risk In this frame the LDL

cholesterol is the main therapeutic target of

the European Guides of modern treatment

in dyslipidemias. Decreasing the level of

LDL associates an decreased risk of

cardiovascular morbimortalitaty.

In the case combined dyslipidemias the

problem is more complex by reason of

having new targets: decrease of the

plasmatic level of tryglicerides (TG), and

growth of HDL cholesterol [1].

Atorvastatin, as a member of statin class,

represents at this moment a basic element

of the therapeutic arsenal used to the

reduce LDL cholesterol.

Bulletin of the Transilvania University of Braşov • Vol. 1(50) – 2008 ▪ Series VI

76

The other classes of drugs besides

statines, are being used generally added to

a statin in the sight of improving the lipidic

parameters [3].

Therapeutic target for LDL of 100 mg/dl

to the patients with high risks, respectively

70 mg/dl to ones with very high risk is

hard to touch, as showed Neptune clinical

trial, realized with one drug just for 27%

from patients. The therapeutic current

arsenal associates to statines drugs

different classes.

Fibrates reduces TG up to 50%, and raise

HDL with as far as 15%, but with the

exception of fenofibrate brought high risk

of myopathia and rabdomyolisis.

Niacine reduces LDL Col (10-20%),

raise HDL (up to 40%), and diminishes TG

(30%), but is hard to tolerated due to the

adverse reactions binded of the

disengagement from prostaglandine: flush,

diarrhea, hypotension.

Cholelstiramina and her modern

derivates, reduce LDL cholesterol with 10-

25%, but frequently associates distur-

bances of intestinal transits.

The acids omega 3, biochemical basic

component of the fishy oil, reduces

significantly the plasmatic level of TG,

effect depending on dose, reduces the

cardiovascular deadly risk post myocardial

infarct, reduce the risk of nonfatal cardiac

events, and reduce the degree of malignity

of cardiac arrhythmias. Just in utilization

as the alimentary supplements, signi-

ficantly reduce the level TG and LDL Col

and raise HDL cholesterol.

They do not increase glicemia, and are

not associated with rabdomyolisis or the

hepatic affectation [4].

The partnership of acids omega 3 with

statines was evaluated also in another trial.

Thus the association of pravastatin 40mg

day with fish oil 6gr day for 12 weeks

produce reduce of VLDL and IDL with as

far as 35%.

As far as we know there was no trial that

evaluates the effects on lipid profile of

combining atorvastatine with omega-3 free

fatty acids [6].

Objective

Impact of the treatment with acids

omega-3 fatty acids added atorvastatine,

versus atorvastatine alone, from the view

of improvement the lipidic profile, in

patients with combined dyslipidemia.

Materials and Method

We evaluate 40 patients, 20 men (50%),

age contained between 35 and 55 years,

non-smokers, with no history of

hypertension, valvular disease or coronary

artery disease.

The patients were randomized on 2 arms:

group A and B which contained each 20

patients. The 2 groups of patients are

homogeneous to evaluated criteria: age, sex:

glycaemia, plasmatic levels of lipids, index

of corporal mass (IMC), arterial blood

pressure as systolic (TAS), respectively

diastolic (TAD) blood pressure.

General characteristic of the two groups of patients Table 1

Parameter Group A Group B

Age 35-45 38-48, p<0,5

Glycaemia a jeune mg/dl 98 101, p<0,3

Total cholesterol mg/dl 245 250,p<0,25

HDL Col mg/dl 44 46,p<0,3

TG mg/dl 288 266,p<0,26

TAS mm Hg 128 118,p<0,22

TAD mm Hg 76 80,p<0,08

BMI 27,5 27, p<0,04

Effect of Treatment with Omega-3 Fattyacids and Atorvastatin … 77

Patients from both lots received the

treatments with atorvastatin 20 mg/day for

4 weeks thereto treated differently.

Group A- continued the treatment with

atorvastatin 20mg day but associate acids

omega3 in dose of 3 gr/day (3x1 dragee-

Omacor, in order to assured a standard of

purity.

The group B was treated on whole period

of pursuits, 2 month, with atorvastatin

20mg day.

The evaluation of the patients is realized

to enlistment and to ultimate 2 months.

Analyze statistics: Analyzes between the

two groups through T-Student.

Results.

The treatment with atorvastatin 20 mg

day for 4 weeks to the patients with mixt

dyslipidemia causes a significant decrease

of the plasmatic level of cholesterol the

total (280 vs 256mg/dl, p < 0,003).

Combining the treatment with omega-3

fatty acids with atorvastatin increase the

variation of the cholesterol plasmatic level

(-9.1 Vs 6.65%, P <0,04).

The level of LDL cholesterol is reduced

statistically significant in both groups. At

the end of the study there was no

statistically significant difference between

the two groups. (-2.7 vs 2.6%, p<0,2). In

relation with LDL level adding omega-3

fatty acids to atorvastatin does not have an

additional effect.

Treatment with atorvastatin significantly

reduces triglycerides plasmatic level (180

vs 170 mg/dl, p<0.01). At the group of

patients treated with omega-3 that decrease

it is more important than in the group

treated only with atorvastatin (-4.7vs 1.6%,

p<0,002).

HDL cholesterol plasmatic level,

following the 2 month of treatment with

atorvastatin, is increased. That increment is

more important in the group of patients

treated with omega 3 free fatty acids (3.6

vs 1.5%, p<0,012).

If we consider non HDL cholesterol as a

marker of therapeutic efficiency, treatment

with omega-3 free fatty acids added to

atorvastatin produce an increase of

statines’s plasmatic level in comparison

with the treatment with atorvastatin (3.5 vs

1.6, p<0,004).

Reduction of the plasmatic level of non

HDL cholesterol is more important in the

group treated with omega-3 fatty acids (-4

vs 1.5%, p<0,004).

The fraction total cholesterol /HDL is

more reduced, at the end of the study in

patients with combined treatment (-1.3 vs

0,9,p<0,01).

Conclusions:

Combining the atorvastatin treatment

with omega-3 free fatty acids in patients

with combined dyslipidemia, causes an

important decrease of plasma triglycerides,

and in a lesser degree LDL and total

cholesterol.


78

Table 2

The dynamics of lipid plasmatic level in patients from Group A

Parameter

Enrolment

media±

standard

deviation

Median at

enrolment

After 8 weeks

media±

standard

deviation

Median at

the end of

study

Percentage of

changing

Col total 266±70 266 200±76 200 -9.1, p<0,005

LDL Col 98±18 98 90±11 86 -2.7, p<0,045

HDL Col 46±15 46 49±12 50 3.5, p<0,004

TG 180±26 180 176±24 170 -4.7, p<0,0042

Non HDL

Col 137±24 137 124±35 122 -4, p<0,008

Col

total/HDL 5±0.8 5.6 3.9±0.9 3.9 -1.7, p<0,04

Table 3

The dynamics of lipid plasmatic level in patients from Group B

Parameter

Enrolment

media±

standard

deviation

Median at

enrolment

After 8 weeks

media±

standard

deviation

Median at

the end of

study

Percentage of

changing

Col total 280±70 280 260±70 256 -6.65, p<0.0045

LDL Col 105±8 105 88±22 83 -2.6, p<0.035

HDL Col 44±9.2 44 42±8,8 46 1.6, p<0.004

TG 186±26 186 180±35 176 -1.6, p<0.040

Non HDL Col 146±26 146 136±28 132 -2.3, p<0,007

Col total/HDL 6,3±0.8 6.3 5.4±0.7 5.4 -0.9, p<0038

Effect of Treatment with Omega-3 Fattyacids and Atorvastatin … 79

Conclusions

Association of omega3 free fatty acids to

atorvastatin, in patients with combined

dyslidemia, produce an important

favorable change in the lipid plasmatic

level. The main change is important

reducing of triglycerides in patients treated

with the combined treatment. That aspect

of variation in relation with the combined

treatment show a lesser dynamics for LDL

and total cholesterol

Discussions

Reduction of the cardiovascular risk

represents a main issue when we judge the

medical treatment in patients with

dyslipidemias. Association of multiple

drugs in order to change lipid levels,

according to the recent guidelines,

represent a therapeutic target [3].

If as for now the target lipid plasmatic

levels refer mostly on LDL, in patients

with hypertrigliceridemia reducing non

HDL cholesterol is an indication.

In that context adding omega-3 free fatty

acids in high dose (3gr) induce an

important change of lipid profile with TG

and non HDL reduction, and increase of

HDL.

The dosage of atorvastatin used was in

relation with some other trials.

References

1. Ballantyne, C.M., Bertolami, M.,

Hernandez Garcia, H.R., Nul, D.,

Stein, E.A., Theroux, P., Weiss, R.,

Cain, V.A. and Raichlen, J.S.:

Achieving LDL cholesterol, non-HDL

cholesterol, and apolipoprotein B

target levels in high-risk patients:

Measuring Effective Reductions in

Cholesterol Using Rosuvastatin

Therapy (MERCURY) II, In: Am

Heart J 151 (2006), pp. 975–979.

2. Expert Panel on Detection Evaluation

and Treatment of High Blood

Cholesterol in Adults, Third report of

the National Cholesterol Education

Program (NCEP) Expert Panel on

Detection, Evaluation, and Treatment

of High Blood Cholesterol in Adults

(Adult Treatment Panel III) final

report, Circulation 106 (2002), pp.

3143–3421.

3. Grundy, S.M., Cleeman, J.I., Merz

C.N., Brewer Jr., H.B., Clark, L.T.,

Hunninghake, D.B., Pasternak, R.C.,

Smith Jr., S.C. and Stone, N.J.:

Implications of recent clinical trials

for the National Cholesterol

Education Program Adult Treatment

Panel III guidelines. In: Circulation

110 (2004), pp. 227–239.

4. Jacobson, T.A.: The safety of

aggressive statin therapy: how much

can low-density lipoprotein

cholesterol be lowered? In: Mayo

Clin Proc 81 (2006), pp. 1225–1231.

5. McKenney, J.M., Jones, P.H.,

Adamczyk, M.A., Cain, V.A.,

Bryzinski, B.S. and Blasetto, J.W.:

Comparison of the efficacy of

rosuvastatin versus atorvastatin,

simvastatin, and pravastatin in

achieving lipid goals: results from the

STELLAR trial. In: Curr Med Res

Opin 19 (2003), pp. 689–698.

6. Pearson, T.A., Laurora, I., Chu, H. and

Kafonek, S.: The Lipid Treatment

Assessment Project (L-TAP): a

multicenter survey to evaluate the

percentages of dyslipidemic patients

receiving lipid-lowering therapy and

achieving low-density lipoprotein


80

cholesterol goals. In: Arch Intern Med

160 (2000), pp. 459–467.

7. Wiviott, S.D., Cannon, C.P., Morrow,

D.A., Ray, K.K., Pfeffer, M.A. and

Braunwald, E.: Can low-density

lipoprotein be too low? The safety and

efficacy of achieving very low low-

density lipoprotein with intensive

statin therapy: a PROVE IT-TIMI 22

substudy. In: J Am Coll Cardiol 46

(2005), pp. 1411–1416.

IN PATIENTS WITH NON-ST ACUTE

CORONARY SYNDROME DIABETES

MELLITUS AND METABOLIC SYNDROME

HAVE AN IMPORTANT IMPACT ON

PROGNOSIS, LEFT VENTRICULAR

SYSTOLIC FUNCTION, INFLAMMATORY

SYNDROME AND OXIDATIVE STRESS

E. BOBESCU

1,2 M. RĂDOI

1,2 Z. GALAJDA

3 G. DATCU

4

Abstract: Aims: To evaluate oxidative stress, inflammatory syndrome, left

ventricular systolic function and prognosis in patients with non ST acute

coronary syndrome and metabolic syndrome or diabetes mellitus. Methods:

172 patients (pts) with non ST acute coronary syndrome (ACS) were included

in a prospective study for a period of 3 years and were divided in three

groups in relation with association of metabolic syndrome (MS) or diabetes

mellitus (DM). Results: In non ST ACS patients, presence of metabolic

syndrome or diabetes mellitus were associated with significant higher

incidence of inflammatory syndrome (p< 0.05) and oxidative stress (p< 0.05)

at 1 and 6 months and with a significant increased incidence of left ventricle

systolic dysfunction (p< 0.05) at 1,2 and 3 years. Incidence of cardiovascular

death, acute myocardial infarction and unstable angina with readmission, at

1.2 and 3 years were significantly higher (p< 0.05) in comparison with ACS

nonMS nonDM group. It was no significant differences between non ST

acute coronary syndrome with metabolic syndrome and with diabetes

mellitus groups at 1.2 and 3 years of follow up. Conclusions: In non ST acute

coronary syndrome patients, presence of metabolic syndrome or diabetes

mellitus were associated with a significant higher incidence of inflammatory

syndrome, oxidative stress at 1 and 6 months and a significant higher

incidence of low ejection fraction, unstable angina with readmission, acute

myocardial infarction and cardiovascular death at 1.2 and 3 years of follow

up.

Key words: acute coronary syndrome, metabolic syndrome, diabetes

mellitus, inflammatory syndrome, oxidative stress, prognosis.

1 Transilvania” University - Faculty of Medicine. 2 Clinic County Emergency Hospital- Clinic of Cardiology, Brasov, Romania. 3 Institute of Cardiology, Cardiac Surgery Center, Medical and Health Science Center, University of

Debrecen, Hungary. 4 University of Medicine and Pharmacy ”Gr.T.Popa Iasi, Romania.

Bulletin of the Transilvania University of Braşov ▪ Vol. 1 (50) – 2008 ▪ Series VI 82

Background In patients with diabetes mellitus, 75%

of deaths are represented by cardiovascular deaths. Cardiovascular risk is 3-5 folds higher in diabetic’s patients and 3 folds higher in metabolic syndrome. Incidence of metabolic syndrome in patients with acute coronary syndrome is 29-46%, with increased incidence of heart failure, and worse long-term mortality compared to those without metabolic syndrome. The main causes of this burden of disease in diabetes mellitus and metabolic syndrome are high LDL cholesterol, low HDL cholesterol serum values, prothrombotic status - high plasminogen activator inhibitor-1 (PAI-1) and fibrinogen, endothelial dysfunction, high leucocytes adhesively to endothelium and mycroalbu-minuria [1, 2, 4, 5, 12, 19, 21, 24, 25].

Methods

172 patients (pts) with non ST ACS were included in a prospective study for a period of 3 years and were divided in three groups in relation with association of MS or DM.

Clinic evaluation, electrocardiography and echocardiography were performed initial and at 1, 6 months, 1, 2 and 3 years. Biologic markers were determinate initial, at 1 and 6 months. C-reactive protein serum level (Immune-turbidimetry method) and fibrinogen plasma level (Turbidimetry method) were determinate as markers of inflammatory syndrome. Anti ox-LDL antibody titers (ELISA technique INOVA kit manufacturer) and total antioxidant status (TAS) serum level (ABTS

® Method-

RANDOX kits) were measured for oxidative stress evaluation. Left ventricular ejection fraction was measured by 2-D Echocardiography, volume/ dimension Simpson’s method [5-9, 11, 14, 16, 31].

Groups of study

ACS non SM non DM - 37 patients with acute non ST coronary syndrome without metabolic syndrome and diabetes mellitus; ACS MS - 79 patients with acute non ST coronary syndrome and metabolic syndrome and diabetes mellitus; ACS DM – 59 patients with acute non ST coronary syndrome and diabetes mellitus (Figure 1).

A C S

MS

7 6 p

(4 4 .2 % )

A C S n o n S M

n o n D M

3 7 p

(2 1 .5 % )

A C S

D M

5 9 p

(3 4 .3 % )

Fig. 1. Groups of study

Statistical Analysis

Comparison between groups was

performed using Chi-squared test and multiple regression analysis. A value of p < 0.05 was considered statistically significant.

Results and discussions

Baseline characteristics of patients were

represented by additional markers, old and new factors with role in cardiovascular risk evaluation and optimal standard medical

therapy in accordance with ESC and ACC/AHA guideline update for the management of patients’ non ST-segment elevation acute coronary syndrome

[3, 5-7,

10]. It was no significant differences in baseline characteristics between study groups.

Inflammatory syndrome

The incidence of high serum level C-

reactive protein (CRP>5 mg/l) was significantly higher at 1 month in ACS MS

In Patients with Non-St Acute Coronary Syndrome Diabetes Mellitus and Metabolic … 83

group 68.4% and ACS DM group 69.8% (p<0.05) and at 6 months in ACS MS group 35.5% and ACS DM group 42.4%

(p<0.01) in comparison with ACS nonMS non DM group 32.4% at 1 month and 16.2% at 6 months of follow up (Table 1).

C reactive protein > 0.5 mg/dl Table 1

initial p 1 month p 6 months p

ACS 22(67.6%) 12(32.4%) 6(16.2%)

ACS MS 57(75%) ns 52(68.4%) < 0.05 27(35.5%) < 0.01

ACS DM 46(77.9%) ns 41(69.8%) < 0.05 25(42.4%) < 0.01

ACS - non ST acute coronary syndrome, MS – metabolic syndrome; DM- diabetes mellitus

These results are in concordance with already published data about C reactive protein, an important inflammatory marker with high predictive value in subgroups of patients with non ST acute coronary syndrome patients: women, older, smokers, diabetics, patients with metabolic syndrome. Presence of high serum values of C reactive protein is associated with 3-4 fold higher incidences of cardiovascular events [1, 3, 5, 13, 15, 21, 23, 26, 28, 29].

High plasma values of fibrinogen has a significant increased incidence at 1 month in ACS MS group 64.4% and ACS DM group 64.4% (p<0.05) and at 6 months in ACS MS group 32.9% and ACS DM group 39% (p<0.01) in comparison with ACS nonMS nonDM group 32.4% at 1 month and 13.5% at 6 months of follow up. (Table 2).

Fibrinogen > 400 mg/dl Table 2


ACS 21(66.2%) 12(32.4%) 5(13.5%)

ACS MS 55(72.3%) ns 49(64.4%) < 0.05 25(32.9%) < 0.05 ACS DM 43(72.9%) ns 38(64.4%) < 0.05 23(39%) < 0.05


Already published data demonstrated that

hyperfibrinogenemia may be consi-

dered a component of the metabolic

syndrome. In multivariate analyses, both plasma insulin and the

metabolic syndrome

were significantly and independently asso-ciated with

plasma fibrinogen. This finding

may also explain the increased cardio-vascular risk

associated with hyperinsuli-

nemia/ insulin resistance. An association between initial hyperfibrinogenaemia and the subsequent occurrence of macroangio-pathy, as well as the evidence that a high fibrinogen concentration enhances the risk of cardiovascular disease in diabetic patients, has been reported. Fibrinogen was the first new risk factor evaluated in athe-

rosclerosis and results of epidemiological studies demonstrated a 1.8 fold higher incidence of acute cardiovascular events in patients with high fibrinogen plasma level [1, 3, 5, 10, 13, 15, 23, 26, 28, 29].

Oxidative Stress

The incidence of low total antioxidant status serum level was significantly increased at 1 month in ACS MS group 52.6% and ACS DM group 55.9% (p<0.05) and at 6 months in ACS MS group 27.6% and ACS DM group 32.2% (p<0.05) in comparison with ACS nonMS non DM group 27% at 1 month and 8.1% at 6 months (Table 3).


Total antioxidant status < 1,3 mmol/dl Table 3


ACS nonSM nonDM 27(73%) 8(27%) 4(10.8%)

ACS MS 62(81.6%) ns 40(52.6%) < 0.05 21(27.6%) < 0.05

ACS DM 51(86.4%) ns 33(55.9%) < 0.05 19(32.2%) < 0.05


High anti ox-LDL antibody serum titers has a significant increased incidence only at 6 months in ACS MS group 35.5% (p<0.01) and ACS DM group 42.4%

(p<0.01) in comparison with ACS nonMS non DM group - 16.2% at 6 months of follow up (Table 4).

Anti ox-LDL antibody >150 mU/ml Table 4


ACS

nonSM nonDM 29 (78.4%) 18 (48.6%) 6 (16.2%)

ACS MS 63 (82.9%) ns 44 (57.9%) ns 28 (36.8%) < 0.05

ACS DM 53 (89.8%) ns 35 (59.3%) ns 25 (42.4%) < 0.05


Antioxidant defence has many compo-

nents and deficiency of any of these com-

ponents produces the reduction of total

antioxidant status. Methods of total anti-

oxidant capacity evaluation are useful in

myocardial ischemia when a depletion of

total antioxidant status is produced. This

depletion is higher in smokers, patients

with diabetes, metabolic syndrome, hyper-

tension and heart failure when oxidative

stress is increased. The mediators produced

in response to major cardiovascular risk

factors including advances glycates end-

products (AGEs), LDL and ox-LDL,

angiotensin II and cytokines stimulate

generation of reactive oxygen species

(ROS) at endothelial level by a variety of

enzymatic and non-enzymatic sources:

ciclo-oxygenase, lipo-oxygenaze, Cyt

P450, NAD(P)H oxidase, xantin-oxidase,

mitochondrial respiration, uncoupled NO-

sintetase and decreased endogenous anti-

oxidant defense superoxid dismutase, cata-

lase, glutation-peroxidase and non-enzy-

matic - glutathione, α tocopherol, ascorbat.

ROS became the second messenger that

transmits the signals which modulated

gene expression in cardiovascular disease

such as adhesion molecules, proliferate

genes, cytokines, metalloproteinase. Anti

ox- LDL antibodies has been determinate

in acute coronary syndrome patients and a

positive correlation between plasma titre of

anti ox- LDL antibodies and athero-

sclerosis progression has been demon-

strated [16-18, 20, 22, 27].

Echocardiography

The incidence of a low left ventricular

ejection fraction (<40%) as a measure of

left ventricle systolic dysfunction was

significantly increased at 1 year in ACS

MS group 28.9% and ACS DM group

33.9% (p<0.05), at 2 years in ACS MS

group 28.9% and ACS DM group 35.6%

(p<0.05) and at 3 years in ACS MS group

30.2% and ACS DM group 35.6%

(p<0.05) in comparison with ACS nonMS

non DM group: 16.2% at 1 year, 16.2% at

2 years and 13.5 % at 3 years. (Table 5)


Left ventricular ejection fraction < 40%: Table 5

1 month 6 months 1 year 2 years 3 years

ACS nonSM, nonDM

9(24.3%) 7(18.9%) 6(16.2%) 6(16.2%) 5(13.5%)

ACS MS 17(22.3%) 19(25%) 22(28.9%) p<0.05

22(28.9%) p<0.05

23(30.2%) p<0.05

ACS DM 14(23.7%) 17(28.8%) 20(33.9%) p<0.05

21(35.6%) p<0.05

22(37.3%) p<0.05


Already published data demonstrated that

evaluation of ejection fraction with bidi-mensional echocardiography is correlated with angiographic determination of left ventricle function and a low ejection fraction is associated with increased incidence of cardiovascular death. [18, 20, 24, 25]

Major acute Cardiovascular Events

(MACE)

The incidence of MACE was significantly higher in patients with non ST

acute coronary syndrome patients and metabolic syndrome or diabetes mellitus.

Cardiovascular mortality was significantly increased at 1 year in ACS MS group 13.2% and ACS DM group 18.6% (p<0.05), at 2 years in ACS MS group 17.1% and ACS DM group 23.7% (p<0.05) and at 3 years in ACS MS group 18.4% and ACS DM group 23.7% (p<0.05) in comparison with ACS nonMS non DM group: 5.4% at 1 year, 5.4% at 2 years and 5.4 % at 3 years of follow up. (Table 6)

Cardiovascular death Table 6


A significant increased incidence of

acute myocardial infarction was observed at 1 year in ACS MS group 15.8% and ACS DM group 18.6% (p<0.05), at 2 years in ACS MS group 19.7% and ACS DM group 25.4% (p<0.05) and at 3 years in

ACS MS group 23.7% and ACS DM group 28.8% (p<0.05) in comparison with ACS nonMS non DM group: 2.7% at 1 year, 5.4% at 2 years and 5.4 % at 3 years of follow up. (Table 7)

Acute myocardial infarction Table 7



ACS

nonSM nonDM 0 1(2.7%) 2(5.4%) 2(5.4%) 2(5.4%)

ACS MS 4(5.3%) 8(10.5%) 10(13.2%)

p<0.05

13(17.1%)

p<0.05

14(18.4%)

p<0.05

ACS DM 4(6.8%) 7(11.8%) 11(18.6%)

p<0.05

14(23.7%)

p<0.05

14(23.7%)

p<0.05


ACS nonSM nonDM

1(2.7%) 1(2.7%) 1(2.7%) 2(5.4%) 2(5.4%)

ACS MS 5(6.6%) 9(11.8%) 12(15.8% p<0.05

15(19.7%) p<0.05

18(23.7%) p<0.025

ACS DM 5(8.5%) 8(13.5%) 11(18.6%) p<0.05

15(25.4%) p<0.05

17(28.8%) p<0.025


The incidence of readmission for unstable angina was significantly higher at 1 year in ACS MS group 32.9% and ACS DM group 35.6% (p<0.05), at 2 years in ACS MS group 42.2% and ACS DM group 47.5% (p<0.05) and at 3 years in ACS MS

group 51.3% and ACS DM group 55.9% (p<0.05) in comparison with ACS nonMS non DM group: 13.5% at 1 year, 18.9% at 2 years and 24.3 % at 3 years of follow up. (Table 8)

Unstable angina with readmission: Table 8


ACS nonSM nonDM

1(2.7%) 2(5.4%) 5(13.5%) 7(18.9%) 9(24.3%)

ACS MS 7(9.2%) 11(13.2%) 25(32.9%) p<0.05

32(42.1%) p<0.05

39(51.3%) p<0.025

ACS DM 6(10.2%) 8(13.5%) 21(35.6%) p<0.05

28(47.5%) p<0.05

33(55.9%) p<0.025


It was no significant differences between

non ST acute coronary syndrome with metabolic syndrome and with diabetes mellitus groups at 1, 6 months, 1, 2 and 3 years of follow up.

All this clinic results are in concordance with already published data: in patients with diabetes mellitus 75% of deaths are represented by cardiovascular deaths and cardiovascular risk is 3-5 folds higher in diabetic’s patients and 3 folds higher in metabolic syndrome. Incidence of meta-bolic syndrome in patients with acute coro-nary syndrome is 29-46%, with an increa-sed incidence of heart failure, and long-term mortality compared to those without metabolic syndrome [4, 5, 12, 17, 25, 28, 30, 31]

Conclusions In non ST acute coronary syndrome

patients, presence of metabolic syndrome or diabetes mellitus was associated with significant higher incidence of inflamma-tory syndrome and oxidative stress at 1 and 6 months of follow up.

The incidence of low left ventricular ejection fraction, cardiovascular death, acute myocardial infarction, unstable angi-na with readmission at 1,2 and 3 years of follow up was significantly increased in

patients with acute non ST coronary syndrome associated with metabolic syn-drome or diabetes mellitus.

It was no significant differences between non ST acute coronary syndrome with metabolic syndrome and with diabetes mellitus groups, both cardiovascular risk factors seems to have a similar impact on short and long term prognosis.

References

1. Alberts, B.: Molecular Biology of the

Cell, 3rd

edn. New York. Garland Publishing, 1996.

2. Anderson, H.V., Cannon, C.P.: Stone PH, et al: One-year results of the

Thrombolysis In Myocardial Infarction

(TIMI) IIIB clinical trial: A rando-

mized comparison of tissue-type plas-

minogen activator versus placebo and

early invasive versus early conser-

vative strategies in unstable angina

and non-Q-wave myocardial

infarction. In: J Am Coll Cardiol 26: 1643-1650, 1995.

3. Antman, E.M., Cohen, M., Bernink, P.J.L.M. et al.: The TIMI risk score for

unstable angina/non-ST elevation MI:

A method for prognostication and

therapeutic decision making. In: JAMA 284:835-842, 2000.


4. Assman, G., Schulte, H., von Eckardstein, A. et al.: High-density

lipoprotein cholesterol as a predictor

of coronary heart disease risk. The

PROCAM experience and pathophy-

siological implications for reverse

cholesterol transport. In: Atherosclerosis 124: S11-S20. 1996.

5. Braunwald, E., Antman, E.M., Califf, R.M. et al.: ACC AHA guideline update for the management of patients

with unstable angina and non-ST-

segment elevation, myocardial

infarction - 2002: summary article: a report of the American College of Cardiology, American Heart Asso-ciation, Task Force on Practice Guide-lines (Committee on the Management of Patients with Unstable Angina). Circulation 2002; 106: 1893-1900.

6. Braunwald, E., Antman, E.M., Beasley, J.W. et al.: ACC/ AHA

guidelines for the management of

patients with unstable angina/non-ST

segment elevation myocardial

infarction: A report of the American

College of Car- diology/American

Heart Association Task Force on

Practice Guidelines (Committee on the Management of Unstable Angina and Non-ST Segment Elevation Myocardial Infarction). In: J Am CoIl Cardiol 36:970-1062, 2000.

7. Braunwald, E.: Application of current

guidelines to the management of unsta-

ble angina and non-ST-elevation myo-

cardial infarction. In: Circulation 2003; 108: 28111-28137.

8. Buja, L.M., Willerson, J.T.: Role of

inflammation in coronary plaque

disruption. In: Circulation. 1994; 89: 503-505.

9. Cheitlin, M.D., Alpert, J.S., Amstrong, W.F., et al.: ACC/AHA guidelines for

the clinical application of Echocardio-

graphy: Executive summary. A report

of the American College of Cardio-

logy/ American Heart Association

Task Force on practice guidelines

(Committee on Clinical Application of

Echocardiography); Developed in

collaboration with the American

Society of Echocardiography. In: J Am CoIl Cardiol 29:862-879, 1997.

10. Ernst, E., Resch, K.L.: Fibrinogen as a

cardiovascular risk factor: A meta-

nalysis and review of the literature. In: Ann Intern Med 118:956-963, 1993.

11. Fisman, E.Z., Tenenbaum, A.: Cardio-

vascular Diabetology: Clinical, Meta-

bolic and Inflammatory Facets. In: Adv Cardiol. Basel, Karger, 2008, vol 45, pp. 114-126.

12. Fuster, V., Badimon, L., Badimon, J.J. et al.: The pathogenesis of coronary

artery disease and the acute coronary

syndromes. In: N EngI J Med. 1992; 326: 242-250,310-318.

13. Fuster, V., Lewis, A.: Mechanisms

leading to myocardial infarction:

insights from studies of vascular

biology. In: Circulation. 1994; 90: 2126-2146. Conner Memorial Lecture.

14. Goldberg, R.J., Currie, K., White, K. et al.: Six-month outcomes in a

multinational registry of patients

hospitalized with an acute coronary

syndrome (The Global Registry of Acute Coronary Events [GRACE]). In: Am J Cardiol 2004; 93: 288-293.

15. Granger, C.B., Goldberg, R.J., Dabbous, O. et al.: The Global

Registry of Acute Registry of Acute

Coronary Events Investigators.

Predictors of hospital mortality in the

global registry of acute coronary

events. In: Arch Intern Med 2003; 163:2345-2353.

16. Halliwell, B.: Antioxidant character-

rization. Methodology and mechanism. In: Biochem. Pharmacol, (2005) 49, 1341.

17. Hasdai, D., Behar, S., Wallentin, L. et al.: A prospective survey of the

characterristics, treatments and

outcomes of patients with acute

coronary syndromes in Europe and the

Mediterranean basin. The Euro Heart

Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). In: Eur Heart J2002; 23: 1190-1201.

18. Hochman, J.S., Tamis, J.E., Thompson, T.D. et al.: Sex, clinical

presentation. and outcome in patients


with acute coronary syndromes.

Global Use of Strategies to Open

Occluded Coronary Arteries in Acute

Coronary Syndromes IIb Investigators. In: N Engl J Med 341:226-232, 1999.

19. Hyde, T.A., French, J.K., Wong, C.K. et al.: Four-year survival of patients

with acute coronary syndromes without ST-segment elevation and

prognostic significance of 0.5-mm ST-

segment depression. In: Am J Cardiol 1999; 84: 379-85.

20. Iayes, R.L.I., Beshansky, J.R., D' Agostino, R.B. et al.: Do patients

coronary risk factor reports predict

acute cardiac ischemia in the

emergency department? A multicenter

study. In: J Clin Epidemiol 1992; 45:621-6.

21. International Task Force for Preven-tion of Coronary Heart Disease. Su-mmary of the Expert Panel Meeting: Cholesterol- lowering with statins- are they all the same? New Orleans March 7 2004

22. Jaber, W.A., Prior, D.L., Marso, S.P. et al.: CHF on presentation is associated

with markedly worse outcomes among

patients with acute coronary syndro-

mes: PURSUIT trial findings (abstract). In: Circulation 100 (Suppl. I): I-433, 1999.

23. Koenig, W., Sund, M., Froelich, M. et al.: C-reactive protein, a sensitive

marker of inflammation, predicts

future risk of coronary heart disease in

initially healthy middle-aged men:

Results from the MONICA (Monitoring

Trends and Determinants in Cardio-

vascular Disease) Augsberg Cohort Study, 1984 to 1992. In: Circulation 99:237-242, 1999.

24. Lakka, H.M., Laaksonen, D.E., Timo, A. et al: The Metabolic Syndrome and

Total and Cardiovascular Disease

Mortality in Middle-aged Men. In: JAMA. 2002; 288: 2709-2716.

25. Manson, I.E., Coldjtz, G.A., Stampfer M.I., et al.: A prospective study of

obesity and risk of coronary heart

disease in women. In: N Engl J Med 322: 882-889, 1990.

26. Morrow, D.A., Rifai, N., Antman, E.M., et al.: C-reactive protein is a

potent predictor of mortality

independently of and in combination

with troponin T in acute coronary

syndromes: a TIMI II A substudy.

Thrombolysis in Myocardial

Infarction. In: J Am CoIl Cardiol 1998; 31: 1460-5.

27. Ridker, P.M., Buring I.E., Shih, I. et al: Prospective study of C-reactive

protein and the risk of future

cardiovascular events among

apparently healthy women. In: Circulation 98: 731-733, 1998.

28. Ridker, P.M., Hennekens, C.H., Buring, I.E. et al.: C-reactive protein

and other markers of inflammation in

the prediction of cardiovascular

disease in women. In: N Engl I Med 342:836-843, 2000.

29. Ridker, P.M., Rifai, N., Clearfield, M. et al.: The Air Force/Texas Coronary

Atherosclerosis Prevention Study

Investigators. Measurement of C-

reactive protein for the targeting of

statin therapy in the primary preven-

tion of acute coronary events. In: N Engl J Med. 2001; 344: 1959-1965.

30. Roivairien, M., Viik-Kajander, M., Palosuo, T. et al: Infections,

inflammation, and the risk of

coronary heart disease. In: Circulation 101:252-257, 2000.

31. Rosengren, A., Wedel, H., Wilhelmsen, L.: Body weight and

weight gain during adult life in men

in relation to coronary heart disease

and mortality. A prospective

population study. In: Eur Heart J 20:269-271 1999.

C REACTIVE PROTEIN AND CLOZAPINE-

INDUCED FEVER

S. HUSSAIN

1 N. AFZAL

1

I. KOHEN1 P.MANU

Abstract: We report a case of recurrent clozapine-induced fever which was

associated with a rise in C reactive protein (CRP). The patient was a 73-

year-old man with Lewy Body dementia who was admitted for psychosis. He

was treated with clozapine and developed a benign fever that was associated

with a rise in CRP. The CRP initially normalized off clozapine. However,

after the patient was rechallenged with clozapine, the CRP became elevated

with a subsequent recurrence of fever. We postulate that the elevation in CRP

and the subsequent fever was caused by the effects of clozapine on the

cytokine system via interleukin- 6 and tumour necrosis factor-alpha resulting

in an inflammatory response with an acute phase reaction.

Key words: clozapine, immunomodulatory, C reactive.

1 The Zucker Hillside Hospital, Glen Oaks and Albert Einstein College of Medicine, Bronx, New York.

1. Introduction

Clozapine-related fever is a common

adverse reaction that is usually benign but

can be challenging to assess and diagnose.

[16] The differential diagnosis must

include other dangerous conditions inclu-

ding agranulocytosis and neuroleptic

malignant syndrome (NMS). [9]

We describe a case of an elderly patient

who developed clozapine fever two weeks

after beginning treatment with clozapine.

We will discuss the relationship between

clozapine fever and C reactive protein

(CRP). We propose that an increase in

CRP in the absence of evidence for

infectious or inflammatory causes may be

used to predict recurrence of clozapine

fever and be a useful tool in its

management.

2. Case Report

Mr. H is a 73 year old male with a

diagnosis of Lewy Body dementia (LBD)

who was admitted to a geriatric inpatient

psychiatric unit after presenting with

depressive symptoms with suicidal idea-

tion and a plan to kill himself. He also had

worsening psychotic symptoms in the form

of command auditory hallucinations telling

him to kill himself. His medications at

home included quetiapine 100 mg at

bedtime and donepezil 10 mg daily. On

admission, the patient was afebrile with a

normal complete blood count (CBC) and

no findings of infection on a urinalysis or a

chest x-ray.

In the psychiatric hospital, quetiapine

was titrated up to 300 mg at bedtime over

two weeks for persistent psychotic

symptoms. However, the patient did not

improve and continued to report

derogatory voices telling him to hurt self.


90

As such, clozapine was started at a 12.5

mg dose at bedtime while the quetiapine

was tapered off. The clozapine dose was

titrated up to 75mg at bedtime over the

next 15 days, while the quetiapine dose

was reduced to 50 mg at bedtime. On the

15th day on clozapine, the patient deve-

loped a fever with a maximum temperature

(Tmax) of 101.1 F. All other vital signs

were stable. He appeared lethargic and

complained of abdominal pain and

tenderness. The patient did not have

rigidity on exam. He was transferred to a

medical hospital and had an extensive

workup for the fever including a chest x-

ray, urinalysis, abdominal x-ray, compu-

terized tomography scan (CT scan) of his

brain and abdomen and pelvis, and blood

work including complete metabolic panel

(CMP) and CBC. The only abnormal

finding was an elevated white blood count

at 12.3 x 10 3 /uL with an absolute

neutrophil count (ANC) of 8.8. His

creatinine phosphokinase (CPK) was

normal at 74. His electrocardiogram and

cardiac enzymes were normal as well. The

quetiapine and clozapine were discon-

tinued and the fever resolved in two days.

The patient was readmitted to the

psychiatric hospital. He was afebrile with a

WBC of 12.6 x 10 3 /uL and an ANC of

8.9. His CRP was slightly elevated at 3.96

mg/dL (normal range of 0-0.49 mg/dL) on

readmission to the psychiatric unit (2 days

off clozapine). The CRP was rechecked

again a week later (off clozapine) and was

trending down at 0.60 mg/dL with a

normal WBC of 9.16 x 10 3 /uL. Two days

later, a repeat CRP was within normal

limits at 0.30 mg/dL. The patient continued

to be afebrile.

The patient remained psychotic with

command auditory hallucinations to kill

himself. Ten days after being transferred

back to the psychiatric hospital, he was

restarted on clozapine 12.5 mg at bedtime.

After three days, the clozapine dose was

raised to 25 mg at bedtime. His CRP after

three days at this dose was elevated at 4.36

mg/dL with a WBC of 12.8 x 10 3 /uL.

The patient was afebrile and asympto-

matic. However, two days later, the patient

again became febrile with a Tmax of

101.7F and was transferred to the medical

hospital. Again, the patient did not have

rigidity on exam. At that time, he had a

medical workup with a CT head, chest x-

ray, urinalysis and blood work which did

not reveal any abnormalities except for an

elevated WBC. The clozapine was stopped

and his fever resolved within two days

without any other interventions. No repeat

CRP was done. The patient was started on

lorazepam 0.5 mg twice a day and was

discharged to a skilled nursing facility

from the medical hospital.

3. Discussion

Clozapine became available in 1990 as

an atypical antipsychotic medication with a

low risk of extrapyramidal symptoms.

Common side effects include weight gain,

hyperglycemia, hyperlipidemia, hyper-

triglyceridemia, tachycardia, sedation,

hypersalivation, hypotension, and

constipation. Rare complications include

agranulocytosis (absolute neutrophil count

<0.5 x 10 3 /uL), cardiovascular or

respiratory arrest, myocarditis, and

seizures. [9]

A common adverse effect of clozapine is

a mild to high-grade fever that is usually

benign. The reported rate of clozapine

fever in the literature varies from 0.5-55%.

[16] The fever lasts 2.5 days on average

and generally resolves between days 8 and

16 of treatment even if clozapine is

continued. The fever typically occurs

within the first month of therapy.

Typically, clozapine fever is not correlated

with clozapine dose. [6, 11, 15] At one

year follow-up, clozapine-induced fever

has not been linked to neutropenia or

agranulocytosis. [15] Some case reports

have shown that patients with clozapine

fever may have mild leukocytosis, but

C Reactive Protein and Clozapine-Induced Fever 91

rarely manifest other physical signs

indicating an infection. [16]

The differential diagnosis of clozapine

fever must include more serious and

potentially fatal conditions including

neuroleptic malignant syndrome (NMS)

and agranulocytosis. [11] The prevalence

of agranulocytosis in patients on clozapine

is 0.38-1.3%. [16] Agranulocytosis may

predispose patients to neutropenic sepsis

which has a mortality rate of 3-4%. [4]

NMS is typically diagnosed based on

clinical signs including severe muscular

rigidity (classic “lead pipe” rigidity),

hyperthermia (temp >38 degrees Celsius),

autonomic instability and changes in

consciousness. [1] Onset varies from 1 day

to 30 days from starting an antipsychotic.

Most cases occur within the first week. [2]

NMS has a mortality rate of up to 10% if

not diagnosed and treated promptly. [14]

There are also reports of an “atypical”

presentation of NMS that may be caused

by clozapine and other atypical antipsy-

chotics (such as aripiprazole and or

olanzapine). This form of NMS commonly

presents with tachycardia, mental status

changes, and diaphoresis. It is less likely to

be associated with extrapyramidal

symptoms or a rapid rise in CPK. [7]

The mechanism of clozapine fever is still

not clearly understood. One theory

involves the immunomodulating effects of

clozapine. [6, 10] Interleukin- 6 (IL-6) and

tumor necrosis factor alpha (TNF-alpha)

are cytokines released by monocytes and

tissue macrophages that mediate the

primary host response during infla-

mmation, infection, and fever. [8] They are

not detectable in healthy humans. [5]

These cytokines stimulate the acute phase

reaction and lead to a systemic reaction

including fever, elevated erythrocyte sedi-

mentation rate (ESR), increased secretion

of glucocorticoids, and activation of

complement and clotting cascades. They

also increase production of CRP. Several

studies have reported that patients with

schizophrenia have increased activation of

monocytes and T cells as well as baseline

increases in serum IL-6 levels. [3, 13]

One in vivo study evaluated the effects

of clozapine on rectal temperatures, blood

cell counts, and cytokine and soluble

cytokine receptor plasma levels during six

weeks of clozapine treatment in 27 patients

with schizophrenia. The study revealed

significant increases in TNF-alpha and

soluble interleukin-2 receptor (sIL-2R)

after six weeks of treatment. IL-6 and

leukocyte counts only transiently increased

at week two but did not differ from

baseline after six weeks. [9] The twelve

patients who developed fever had

pronounced increases in TNF-alpha and

sIL-2R at week two. They also showed an

increase in plasma IL-6 levels and

granulocyte counts at two weeks. In

addition, the patients’ fevers subsided

without any interventions even when

clozapine was continued. [12

4. Conclusion

Clozapine fever is generally benign but

can be difficult to assess and manage. This

case report may provide a tool for

monitoring and possibly predicting

clozapine fever. Further research is needed

to evaluate whether the data can be

generalized to patients with schizophrenia

and other psychotic disorders. In addition,

future studies are needed to determine

whether an increase in CRP may predict

the emergence or recurrence of clozapine

fever.

References

1. American Psychiatric Association:

Diagnostic and Statistical Manual of

Mental Disorders, 4th ed. Washington,

DC, American Psychiatric Association,

1994.

2. Caroff, S.N., Mann, S.C.: Neuroleptic

malignant syndrome. In : Psycho-

pharmacol Bull 1998; 24: 25-9.


92

3. Ganguli, R., Yang, Z., Shurin, G.:

Serum interleukin-6 concentration in

schizophrenia: elevation associated

with duration of illness. In: Psychiatry

Res 1994; 51: 1-10.

4. Gerson, S.L.: G-CSF and the mana-

gement of clozapine induced agra-

nulocytosis. In: J Clin Psychiatry 1994;

55: 139-42.

5. Gudewill, S., Pollmacher, T., Vedder,

H.: Nocturnal plasma levels of cyto-

kines in healthy men. In: Eur Arch

Psychiatry Clin Neurosci 1992; 242:

53-6.

6. Jeong, S.H., Ahn, Y.M., Koo, Y.J.:

The characteristics of clozapine-

induced fever. In: Schizophr Res 2002;

56: 191-3.

7. Karagianis, J.I., Phillips, L.S., Hogan,

K.P., et al.: Clozapine-associated

neuroleptic malignant syndrome: Two

new cases and a review of the

literature. In: Ann Pharmacother 1999;

33: 623-30. DOI 10.1345/aph.1K141.

8. Kluger, M.J.: Fever: role of pyogens

and cryogens. In: Physiol Rev 1991;

71: 93-117.

9. Lowe, C.M., Grube, R.R., Scated,

A.C.: Characterization and clinical

management of clozapine-induced

fever. In: Ann Pharmacother 2007; 41:

1700-4. DOI 10.1345/aph.1K126

10. Maes, M., Bosmans E., Kenis G., et

al.: In vivo immunomodulatory effects

of clozapine in schizophrenia. In:

Schizophr Res 1997; 26: 221-5.

11. Nittenson, N.C., Kando, J.C.,

Frakenburg, F.R., et al.: Fever

associated with clozapine admi-

nistration. In: Am J Psychiatry 1195;

152: 1102.

12. Pollmacher, T., Hinze-Selch, D.,

Mullington, J.: Effects of clozapine on

plasma cytokines and soluble cytokine

receptor levels. In: J Clin Psycho-

pharmacol 1996; 16: 403-9.

13. Smith, R.S.: A comprehensive macro-

phage-T-lymphocyte theory of

schizophrenia. In: Med Hypotheses

1992; 39: 248-57.

14. Strawn, J.R., Keck, P.E., Caroff, S.N.:

Neuroleptic Malignant Syndrome. In:

Am J Psychiatry 2007; 164: 870-6.

15. Tham, J.C., Dickson, R.A.: Clozapine-

induced fevers and 1-year disconti-

nuation rate. In: J Clin Psychiatry

2002; 63: 880-4.

16. Young, C.R., Bowers, M.B., Mazure,

C.M.: Management of the adverse

effects of clozapine. In: Schizophr Bull

1998; 24; 381-90.

1 UMF Iuliu Hatieganu Cluj Napoca. 2 „Transylvania” University Brasov. 3 Pneumology Hospital Baia Mare. 4 Ovidius University Constanţa.

SMOKING-RISK FACTOR FOR

METASTASIS IN BREAST CANCER

M. A. MAN

1 D. ALEXANDRESCU

2

M. POP1 R. RÂJNOVEANU

1

M. GORON3 O. ARGHIR

4

Abstract: Breast cancer is one of the most frequent neoplasia in women.

The discovery of metastasis risk factors can influence the evolution of the

disease. Environmental factors, especially smoking, play a very important

role in the evolution of many neoplasms. We evaluated the status of smokers

of patients with metastases against the witness batch, patients with breast

cancer without metastases. We compared the age arithmetical mean of

patients who smoked to that of patients who did not smoke (p = 0, 00029) and

we observed there is a significant difference between the age means of

smokers and that of non smokers. Our study results suggest that smoking,

represented a risk factor, significantly influences the apparition of metastases

(p = 0, 001044). Systemic effects of smoking may play a role in influencing

the course of breast cancer and other cancers

Keyword: metastasis, smoking, breast cancer

1. Introduction

Breast cancer is one of the most frequent

neoplasia in women (27% of the total types

of breast cancer). It represents the second

cause of death in the USA after pulmonary

cancer [2, 4]. Of the total patients suffering

from breast cancer, 10% already have

metastases and 50% will develop

metastases in time. Approximately 60% to

70% of the women who die of breast

cancer present pulmonary determination

upon autopsy. In 21% of cases the lung is

the sole metastases focus [7]. Patients with

metastases are not curable by conventional

therapy. Despite the inability to treat

recurrence and metastasized cancer, the

early discovery of metastases and

application of a palliative treatment

improves the quality of life and increases

the survival rate. The discovery of

metastasis risk factors can influence the

evolution of the disease.

The purpose of the study is that of

discovering metastasizing environment

related risk factors, mostly smoking.


We conducted a survey during January

2000 and December 2005 on 120 patients

admitted with the Cluj-Napoca Oncology

Institute, “Leon Daniello” Pneumology

Clinical Hospital, the Department of

Oncology and Radiotherapy of the Cluj County Hospital.

Bulletin of the Transilvania University of Braşov • Vol. 1(50) - 2008 ▪ Series VI

94

We introduced in the study patients

diagnosed with breast carcinoma and

pulmonary metastases. Seventeen of our

patients with pulmonary metastases

completed a questionnaire referring to the

statute of smoker (smoker, non smoker,

former smoker, passive smoker). The

questionnnaires were compiled according

to standards and helped evaluate the level

of education and knowledge of the patients

in regard to the harmfulness of smoking

and its influence on primary diseases. The

results were than compared with the results

of a witness batch of 25 patients with

breast cancer who did not present

pulmonary metastases.

Inclusion criteria:

- Patients with a confirmed mammary

tumour (confirmed by histopathology

of cytology) who on onset or during

their evolution presented pulmonary or

pleural metastases (confirmed or not

from a histology point of view).

Exclusion criteria:

- Patients with a unique lesion who

weren’t confirmed by histology reports

were excluded due to the difficulty in

differentiating a metastatic lesion from

a primitive pulmonary carcinoma.

3. Results

Environmental factors, especially

smoking, play a very important role in the

evolution of many neoplasms. We

evaluated the status of smokers of patients

with metastases against the witness batch,

patients with breast cancer without metas-

tases (Fig. 1) and frequency of pulmonary

metastatic involvement (Table 1).

Smoking history

With metastasis

Without metastasis

Total

nonsmoker 5 20 25

smoker 4 2 6

Former smoker 7 2 9

Passive smoker 1 1 2

Total 17 25 42

Fig. 1. Smoking history at patients with and without metastasis

Smoking – Risk Factor for Metastasis in Breast Cancer

95

Frequency of Pulmonary Metastatic Involvement Table 1

Type of Invol-

vement

Parenchymal

nodules

Pleural effusion Lymphangitic

carcinomatosis

No patients (17) 10 8 2

The average onset age was 22, 42857

years and the average yearly number of

cigarette packets was 67, 08333. Smoking

significantly influences the apparition of

metastases (p = 0,001044).

We compared the age arithmetical mean

of patients with metastases to that of

patients without metastases and we

obtained p = 0,3 so we concluded there is

no significant difference between the age

mean of patients with metastases and that

of patients without metastases (Table 2).

Mean age of patients with and without metastasis Table 2

No

patients

Mean age

Standard

Deviation

P

with

metastastasis 17 50,29 7,86 Age

without

metastasis 25 53,32 10,01

0,30

We also compared the age arithmetical

mean of patients who smoked to that of

patients who did not smoke (p = 0, 00029)

and we observed there is a significant

difference between the age means of

smokers and that of non smokers (Table 3).

Breast cancer and its complications are

more easily triggered for smokers than for

non smokers.

Mean age of patients smokers/nonsmokers Table 3

No.patients

Mean age

Standard

Deviation

P

Nonsmokers 27 55,70 8,71 Age

smokers 15 45,60 6,16 0,00029

For persons who had breast cancer but

no metastases we compared the age

arithmetical mean of smokers and non

smokers (p = 0,015) and we noticed a

significant difference between the age

mean of smoking patients and non


96

smoking patients among those without

metastases. Cancer is more rapidly

triggered among smokers than among non

smokers.

For patients who have metastases we

compared the age arithmetic mean of

smoking persons who smoke and persons

who do not smoke (p = 0,0064) and we

concluded that there is an important

difference between the age means of

persons who smoke and those who do not

smoke among those who have metastases.

Metastases of breast cancer appear faster

among smokers than among non smokers.

The results of the statistical analysis

emphasized that smoking is a risk factor

for the apparition of pulmonary metastases.

Smoking is considered the most

important negative prognosis factor of all

other environmental factors [8]. Our

comparative survey indicates that smoking

represents a risk factors for metastasizing

as it significantly influences the apparition

of metastases (p = 0,001044).

Recent studies reported that smoking

increases the risk of breast carcinoma only

if smoking begun at an early age or before

the first pregnancy when the epithelial

tissue is more susceptible to the aggression

of the environment. Other studies report

smoking as a risk factor for breast

carcinoma only in the case of very young

women or women with a family history of

breast carcinoma [3].

Several epidemiology surveys have

indicated that smoking increases the death

rate of breast carcinoma patients compared

with non smokers suffering from the same

affection in conditions where smoking is

not associated with the increase of breast

cancer incidence. This suggests that

smoking can influence in an unfavourable

manner the biology and natural history of

breast cancer. Many clinical studies have

associated smoking with an increase of

metastases in lung, breast and bladder

neoplasia [9].

Smoking produces numerous effects at a

pulmonary and systemic level, effects that

might contribute in the increase of

attraction towards metastasizing of the

breast carcinoma and other types of cancer.

Two epidemiology surveys have

demonstrated the association between

smoking and pulmonary metastases among

women with breast carcinoma. Smoking

was associated with the unfavourable

evolution of other tumours, which suggests

the possibility of side effects of smoking

on the biology of cancer.

The specific mechanism that uses smoke

exposure as a way to produce pulmonary

metastases is not completely known.

Smoking can produce systemic effects that

include the increase of vascular and

epithelial permeability, changes at the level

of local immunity, modifications of anti

tumour defence system, status of

coagulation, platelets’ stickiness, and

increase in the adhesion of molecules. In

addition, exposure to smoking affects the

metastatic potential of tumour cells by

influencing the effects of the signal’s

transduction. In his study, Murin has not

found any differentiation between the

statute of active smoker, passive smoker or

former smoker [6].

Nistrosamine 4 (Methyl nidrosamino) - 1

- (3 - piridy) – 1 – butanane (NNH) was

identified as the most potent carcinogen

from the cigarette smoke. It mimics the

increase factors that stimulate

phosphorilate and µ and n – calpain

activation (family of protease cysteins

implicated in proteolysis which next to

metallo-proteins dissolves the basal

membrane of blood vessels favouring

invasion, increases access to blood of

lymph vessels for dissemination [10].

Nicotine also induces c-SRC activation

also known as Ci protein kinase (which

induces µ and n-calpains phosphorilate)

[10].

The role of smoking was emphasized on

the increase adherence of tumor

proliferation and extravasations. Subse-

quent, smoking no longer affects the rate

Smoking – Risk Factor for Metastasis in Breast Cancer

97

of increase of metastases after these have

already developed [6].

The results of the study revealed that

38% of the patients who smoked had

pulmonary metastases compared to 29% of

patients who never smoked. Of the patients

who smoked accidentally at the moment of

diagnosis of breast carcinoma, 24, 1% of

them developed pulmonary metastases

compared to 15, 3% of those who never

smoked (p = 0,06) [5].

Harry and collaborators report the

existence of metastasized axillaries gan-

glions more frequent with smokers than

with non smoker. He claims the presence

of larger metastases and records the asso-

ciation smoking – unfavourable prognosis

factors in other neoplasia (myeloid

leukemia, prostate carcinoma, melanoma,

and also the endometriosis of the uterine

cervix, bladder, and colon) either by

stimulation of malignant cells or by the

inhibition of the host’s defence system [1].

Conclusion

1. A number of clinical and pathologic

factors, such as tumour size, nodal

involvement, and degree of tumour

differentiation,

are predictors of

disease course.

2. Much of the apparent heterogeneity

in the risk of disease progression,

and in the

sites of disease

progression, remains unexplained.

3. An effect of smoking on the

development of

metastasis disease

from breast cancer provides an

intriguing and biologically plausible

explanation for the higher rate of

fatal breast cancer among smokers.

4. Systemic effects of smoking may

play a role in adversely influencing

the course of other cancers. 5. The effect of

smoking on the natural

history of breast cancer and other

non-pulmonary malignancies

warrants further investigation.

References

1. Daniell, H. W.: Breast Cancer in

Smokers. In: Chest; 2003; 123:1771-

1772.

2. De Vito, V.: Principles of Molecular

Cell Biology of Cancer. In: Cancer

Metastasis 1998, Lippincott,

Philadelphia, p.134-148.

3. Hanajina, N, Hirose, K., Tajina, K.,

Rohan, T., Kalle, E.: Alchool, Tabacco

and Brest Cancer Colaborative

reanalysis of Individual Data From 53

Epidemiological Studies Including

58.515 Women With Brest Cancer and

95.067 Women without the disease.

In: British Journal of Cancer; 2002;

1.234-1.245.

4. Moosa, A. R., Stephen, C., Schimpff,

M., Robson, M.C.: Comprehensive

Textbook of Oncology. Baltimore,

Maryland USA. Williams & Wilkins,

1986, 855-863.

5. Murin, S., Inciardi, J.: Cigarette

Smoking And The Risk Of Pulmonary

metastasis from Breast Cancer. In:

Chest 2001, 119, 1.635-1.640.

6. Murin, S., Pinkerton, K.E., Hubbardi,

N., Erickson, K.: The effect of Cigarette

Smoke Exposure on Pulmonary

Metastatic Disease in a Murine model

of metastatic breast Cancer. In: Chest;

125; 2004; 1467-1471.

7. Naunov, G. N, Mac Donald, I.C,

Weinneiste, N., Kerkvliet Nadkarni,

K.V., Wison, S.M, Maris, V.L.,

Groam, A.C, Chambers, A.F.:

Persistence of solitary mamary

carcinom cells in a secondary site: a

posible contribution to dormancy. In:

Cancer Research 62, 2002, 2162-2168.

8. Reynolds, P., Hurleg, S., Goldberg,

D., Andan-Cutrer, H., Bernstein, H.,

Deaper, D.: Active Smoking, House

Hold Passive Smoking and Breast

Cancer: Evidence From The

California Teachers Study, Journal of

The National Cancer Institute 96,

2004.


98

9. Xu, L., Deng, X. M.: Tobaco –

specific Nitrosamine 4 –

(Methylnitrasamino)-1-(3-pyrydil)-1-

butanane induces Phosphorylation of

micro- and n-Calpain in Association

with increased Secretion, Cell

Migration and Invasion, Journal

Biology chemically; vol279; 51; dec

2004, 53683-53690.

10. Xu, L., Ming Deng, X.: Protein

Kinase Ci promotes Nicotine-Induced

Migration and Invasion of Cancer

Cells via Phosphorylation of micro-

and n- Calpains. In: Journal Biology

Chemicaly; vol.281; 7; Feb. 2006;

4457-4466.

ANTIBIOTIC SUSCEPTIBILITY

CHANGES OF

STAPHYLOCOCCUS AUREUS

A RETROSPECTIVE STUDY

O. FALUP-PECURARIU

1 A. RĂŞINĂ2

C. FALUP-PECURARIU3

Abstract: Antibiotherapy resistance is an emerging health care issue due to

the extended usage of antibiotics.

The aim of the study was to determine the changes in antibiotherapy

resistance of Staphylococcus aureus over a 5 years period between 2003 to

2007. Patients and method: retrospective study over a 5 years period that

analyzed the resistance trends of Staphylococcus aureus in the cultures of

newborns, that were taken at the Newborn Department of the Children’

Hospital of the Transilvania University. Results: 116 strains were studied,

strains from skin lesions, umbilical secretion, blood culture, eye secretion,

nasal and pharyngeal swab. From these 94 were resistant to penicillin,

74.1% sensible to meticillin, 9.48% resistant to gentamicin, 72% sensible to

ciprofloxacin and 72% sensible to clindamicin. Conclusions: there was in

our study a slight predominance of boys. We observe a constant trend

towards metcillin resistance. Most of the meticillin resistant strains were

isolated from skin lesions. Still active antibiotics are clindamicin, gentamicin

and rifampicin

Key words: Staphylococcus aureurs, newborn, antibiotic resistance

1 Transilvania University of Brasov, Dept. of Pediatrics 2 Children’s Hospital Braşov 3 Transilvania University of Brasov, Dept. of Neurology, Transilvania University of Braşov

Introduction

Staphylococcus aureus causes 96000

diseases each year causing around 16000

deaths per year. It is still one of the major

pathogen determining sepsis, endocarditis,

arthritis, osteomielitis and soft tissues

infections. It is one of the most aggressive

nosocomial agents [2]. It comprises about

27 different species of Staphylococcus,

which are divided due to their ability to

secrete an enzyme called coagulase: in

coagulase negative and positive staphy-

lococcus. A complex of factors and

interactions between the host, the

environment and the bug itself determines

the transmission of the pathogen.

Throughout the world, there are over 2

billion healthy carriers and 53 million

carriers of MRSA [12]. Shortly after

penicillin became available Staphy-

lococcus developed strains resistant to beta

lactamase [13]. During the years 1999-

2002 in Europe 53264 strains of

Staphylococcus, where cultured from

which 5-20% was MRSA. Romania had 83


100

strains in 2005, the MRSA being 61% in

2005 compared to 31% in 2002.

The aim of the study was to establish

the antibiotic sensibility of the strains,

evaluation of the MRSA strains over a five

years period and to establish which the still

active ones are.

Patients and methods: retrospective

study over a 5 years period at patients

admitted at the Newborn Department of

the Childrens’ Hospital Brasov Romania

between 01.01.2003-01.07.2007 in order to

establish the antibiotic susceptibility of

Staphylococcus strains and its variation

trends in time.

Results

We have studied 116 patients at which

we identified infections with S. aureus and

we included both hospital acquired and

community acquired Staphylococcus.

Sex distribution in the study group Table 1

Sex Total

Male Female

Percentage 100% 56,89% 43,11%

Subjects 116 66 50

75,86%

92,24%

8,62%

0,00%

15,51%

7,75%

over 2500

under 1500

1500 -2500g

Birth weight Actual weight

Fig.1. Weight repartition.


umbilical

secretion;

23,27%

nasal swab;

10,34%

Hemoculture;

10,34%

eye secretion;

8,62%

pharyngeal

swab; 5,17%

Skin; 32,75%

Fig. 2. Main isolation areas in the study group

Penicillin susceptibility of Staphylococcus aureus Table 2

Penicillin resistence

Total

No Yes

Strains 116 22 94

Percent 100% 19% 81%

Answer changes to penicillin from 2003 to 2007 Table 3

Year Strains sensitive to

penicillin Percent

Resistant strains at

penicillin Percent

2003 6 33% 12 67%

2004 5 25% 15 75%

2005 3 15% 17 85%

2006 4 10% 26 90%

2007 4 11% 24 89%

Total 22 - 94 -


102

Table 4

Percentage distribution of penicillin

resistance due to the analyzed culture

place

Total

Hemo-

culture Pus

Carri

age

Strains

94 9 64 18

Percen-

tage

100% 10% 70% 20%

Table 5

Meticillin susceptibility

MSSA MRSA MISA

Strains 86 25 5

Percentage 74,1% 21,5 % 4,%

Table 6

MRSA distribution on pathological

products

Total

Hemo-

culture Pus

Carri

age

Strains 25 1 20 4

Percent

age

100

% 4% 80% 16%

Table 7

Meticillin evolution between 2003 and

2007

Year

Oxacillin

resistant strains Percent

2003 1 6%

2004 2 10%

2005 9 45%

2006 3 10%

2007 10 36%

0

5

10

15

20

25

30

35

2007 2006 2005 2004 2003

MRSA cases MSSA cases

Fig. 3. Meticillin resistance evolution between 2003 and 2007.


Staphylococcus resistance at gentamicin Table 8

Resistance at gentamicin

Total

Yes No

Strains 116 11 105

Percentage 100% 9,48% 90,52%

Aminoglicoside resistance at isolation place Table 9

Place Percent Patients

Skin lesions 72% 8

Eye secretion 9% 1

Hemoculture 18% 2

Total 100% 11

Fluorchinolone resistance of Staphylococcus Tabel 10

Strains

Total

Sensible Intermediate

resistant Resistant

Strains 116 102 3 11

Percent 100% 91% 3% 9%

MRSA susceptibility to gentamicin and ciprofloxacin Table 11

MRSA Strains Percent

MRSA-gentamicinoresistent 9 11%

MRSA sensible to ciprofloxacin 18 72%

MRSA gentamicino-resistent ciprofloxacino-sensible 4 3%


104

Susceptibility MRSA strains at macrolides Table 12

MRSA Staphylococcus Strains Percent

MRSA 25 100%

MRSA sensitive to eritromicin and

clindamicin 3 12%

MRSA sensitive to clindamicin 7 28%

MRSA sensitive to erythromycin 17 68%

MRSA resistant at clindamicin and

erythromycin 2 8%

Antibiotic resistance for Staphylococcus aureus between 2003- 2007 Table 13

Resistance to antibiotic% / year

Antibiotic

2003 2004 2005 2006 2007

Penicillin 66% 75% 85% 86% 86%

Oxacillin 5% 10% 45% 10% 35%

Gentamicin 5,5% 10% 10% 6,6% 13,2%

Erythromycin 33% 25% 10% 43% 43%

Ciprofloxacin 0% 10% 6% 10% 13%

Cotrimoxazol 22% 40% 15% 14% 46%

Discussions

Antibiotic resistance is the consequence

of their extensive usage. We face o high

level of antibiotic resistance, at a

diminishing rate of new antibiotic

introduction.

Staphylococcus aureus is producing

toxins that affect the morphology and

function of the host cell. It has five

cytolitic toxins that are capable to induce

lesions of the cell membrane and thus to

destroy the cell, these are the alpha, beta,

gamma toxins and leucocidin [1].


Among the studied strains 94 were

penicillin resistant representing 81% a rate

which is comparable with other countries

Sweden 86%, France 87% [14]. The

majority of MRSA were from skin lesions

[4]. Our strains were sensitive to

clindamicin and erythromycin.

Other authors reported the MRSA

Staphylococcus would be resistant also to

clindamicin and eitromicin [6].

Our data are still comparable with the

data coming from a study from Bogota

were the MRSA was 26% from which

3.2% being multiresistant [3]. From the

studied strains, three strains were resistant

to vancomicin. Recently similar strains

were reported in different countries, among

which, cited are the U.S.A, France, Spain,

Italy, Germany [8, 9, 11]. These strains are

named VISA with intermediate resistance

to vancomicin or GISA with intermediate

resistance to glicopeptides. All the VISA

described strains were MRSA.

Also from the studied strains, 11 were

resistant to gentamicin and 11 to

ciprofloxacin [5].

The resistance to gentamicin is mediated

through inactivating enzymes aminozid

acetiltransferase that causes resistance to

all aminoglicosides’, aminozid nucleotidil

transferase that causes resistance at

amikacin and tobramicin among other

antibiotics, aminozid phopfotransferase

that causes resistance also at amikacin and

isepamicin.

The action mechanism is modifying the

action target, ribosomal 50S encoded by

the ermA genes but also by the ermB ermC

and there are two described mechanisms

for these: constitutive and inducible one.

The resistance mechanisms towards

fluoroquinolones is modification of AND

girase and topoisomerase IV due to

mutation at gene gyrA and parC, efflux

pumps, diminished penetration of bacterial

wall [10]. In addition, there are described

inactivating enzymes and active efflux.

Antibiotic resistance is the consequence

of their extensive usage. Among the

studied strains 94 were penicillin resistant

representing 81% a rate which is

comparable with other countries Sweden

86%, France 87% (14). The majority of

MRSA were from skin lesions [7].

The limits of our study were a short

period of time only 5 years, relative small

number of strains 116, including criteria

were quiet strict only strains from the

newborn department and culture

Staphylococcus positive.

Conclusions

1. In the study group there was a slight

predominance of male.

2. We are facing a slight but constant

increase of meticcilllin resistance.

3. Most of the isolated MRSA are from

skin lesions.

4. Three of the studied strains have an

intermediate resistance at

vancomicin.

5. Still active antibiotics are

aminoglicoside, clindamicin and

rifampicin.

References

1. Ayliffe, G.: The progressive

intercontinental spread of methicillin-

resistant Staphylococcus aureus. In:

Clinical Infectious Diseases 1997; 24

Suppl 1: S74-9.

2. Celebi, S., Hacimustafaoglu, M.,

Ozdemir, O., Ozakin, C.: Mosocomial

Gram-positive bacterial infections in

children: results of a 7 year study. In:

Pediatr Int 2007, 49(6): 875-882.

3. Cortes, J.A., Andrés Gómez, C.,

Cuervo, S.I., Leal, A.L.: Community-

acquired methicillin-resistant Sta–

phylococcus aureus in Bogotá,

Colombia. In: Rev. Salud pública, 9, 3

Bogotá jul./sep. 2007.

4. Frank, A.L., Marcinak, J.F., Mangat,

P.D., Schreckenberger, P.C.: Comm-

unity- acquired and clindamycin-

susceptible methicillin-resistant Sta-


106

phylococcus aureus in children. In: Pe-

diatric Infect Dis J. 1999; 18: 993-

1000.

5. Gregory, J., Moran, M. D.,

Kirshnadasan. A.: MRSA infections

among patients in the emergency

departament. In: New Engl J Med

2006; 355:666-74.

6. Hand, W.L., King-Thompson, N.L.,

Steinberg, T.H.: Interactions of anti-

biotic and phagocytes. In: J

Antimicrob Chemother. 1983; 12

(suppl C):1-11.

7. Herold, B.C., Immergluck, L.C.,

Maranan, M.C. et al.: Community

acquiered meticillin resistant

Staphylococcus aureus in children

with no predisposing factor. In:

JAMA.1998; 279: 593-598. 8. Howden, B.P., Ward, P.B., Charles,

P.G., Korman, T.K., Fuller, A., du

Cros, P., Grbasch, E.A., Roberts, S.A.,

Robson, J., Read K., Bak, N., Hurley,

J., Johnson, P.D., Morris, A.J., Mayall,

B.C., Grayson, M.L.: Treatment

outcomes of serious infections caused

by methicillin-resistant Staphylococcus

aureus with reduced vancomycin

susceptibility. In: Clin Infect Dis 2004;

38:521-528.

9. Kantzanou, M., Tassios, P.T., Tseleni-

Kotsovili, A., Legakis, N.J., Vatopoulos,

A.C.: Reduced susceptibility to

vancomycin of nosocomial isolates of

methicillin-resistant Staphylococcus

aureus. In: J Antimicrob Chemother

1999; 43:729-31.

10. Lowy, F.D.: Staphylococcus aureus

infections. In: New Engl J Med. 1998;

339: 520-32.

11. Marchese, A., Balistreri, G., Tonoli,

E., Debbia, E.A., Schito, G.C.: Hetero-

geneous vancomycin resistance in

methicillin-resistant Staphylococcus

aureus strains isolated in a large

Italian hospital. In: J. Microbiol 2000;

38:866-869.

12. NNIS System - National Nosocomial

Infections Surveillance (NNIS) System

Report, data summary from January

1992 through June 2003, issued

August 2003. In: Am J Infect Control,

2003, 31: 481-498.

13. Santos, F., Mankarious, L.A., Eavey,

R.D.: Methicillin-resistant Staphylo-

coccus aureus: pediatric otitis. In:

Arch Otolaryngol Head Neck Surg.

2000; 126:1383-1385.

14. Van der Mee-Marquet, Epinette, C.,

Loyau, J. et al. : S.: aureus strains

isolated from bloodstream infections

changed significantly in 2006. In: J

Clin Microb, 2007; 851-857.

STIGMATIZATION OF PEOPLE WITH

SCHIZOPHRENIA IN CLINICAL

SETTINGS

V. BURTEA

1 C. MOŞOIU

1

Abstract: The stigmatizing of, and discrimination against, people with

mental disorders is as old as humanity. It is also known that stigma and

discrimination negatively affect the treatment and recovery of people with

mental illness. The main target of the study is to begin to collect robust data

about stigma in schizophrenia in order to make possible to carry out specific

programmes against it. Our study intended to measure the stigma of people

with schizophrenia using the Stigma Experiences Scale -Consumer Version,

hospitalized in Psychiatric and Neurologic Hospital Brasov between 1 iulie

2007-1 July 2008, in order to see how this problem is managed in clinical

settings. Conclusions of the study reflected the opinion of the respondents:

they think that they were been harassed because of mental illness, they

considered that they rights were been denied and that stigma affected

negatively their quality of life

Key words: Stigmatization, patients with schizophrenia.

1 Transilvania University of Brasov, Dep of Psychiatry.

Introduction

Stigma is not a static concept, but a

social construction that is linked to values

placed on social identities, a process

consisting of two fundamental compo-

nents: the recognition of the differentiating

“mama” and the subsequent devaluation of

the bearer [1]. Thus, stigma could be

conceived of as a relational construct that

is based on attributes, which may change

with time and from one culture to another.

Stigma develops within a social matrix of

relationships and interactions so that new

conditions could become stigmatizing and

conditions that may be stigmatizing at one

time or within a given culture could come

to be accepted later so that their bearers

stop being stigmatized. Furthermore,

stigma can be understood within a three-

dimensional axis involving perspective,

identity and reactions. Stigma is different,

whether it be perceived by the person who

does the stigmatizing (perceiver) or by the

person who is being stigmatized

(target).cultural perceptions of mental

illness consider it as posing a tangible

threat to the health of society because it

engenders two kinds of fear: the fear of

potential immediate physical threat of

attack and fear that we may all share in

losing our own sanity [3].


108

Methods

We assess the stigmatization of people

with schizophrenia the Stigma Experiences

Scale-Consumer Version with 10 items: as

in table A.

The Stigma Experiences Scale-

Consumer Version

Scale item:

1. Do you think that people think less

of you if they know you have a

mental illness?

2. Do you think that the average

person is afraid of someone with a

serious mental illness?

3. Have you ever been teased, bullied

or harassed because you have a

mental illness?

4. Have you felt that you have been

treated unfairly or that your rights

have been denied because you have

a mental illness?

5. Have your experiences with stigma

affected your recovery?


caused you to think less about

yourself or your abilities?


affected your ability to make or

keep friends?


affected your ability to interact with

your family?


affected your satisfaction or quality

of life?

10. Do you avoid situations that may be

stigmatizing to you?

The first two items refer to expectation

of stigma and are scored on a 5-point

Likert-type scale using the response

categories of never, rarely, some times,

often and always. These responses were

recoded into a binary variable, with 1

reflecting a high expectation of stigma

(often and always), and zero reflecting no

or low expectation (never, rarely, and

sometimes).

The remaining eight items used three

response categories: no, unsure and yes.

These were also recoded into binary

categories reflecting the presence (yes) or

absence (no and unsure) of each

experience.

We assess 32 patients with schizophrenia

according with DSM-IV criteria

hospitalized in. the period 1 July 2007-1

July 2008 in the Psychiatric and

Neurological Hospital Brasov. Region of

residence, age, gender, were recorded. All

the respondents were in pension. More

detailed information on the development

and testing of this scale is published by

Stuart, Milov and Koller [4].

Statistical Methods

The responses recorded on the 5 point

scales were converted into scores as

follows: scores 1 and 2 were coded as

negative, scores 4 and 5 were coded as

positive, and those who were unsure or

could not answer the question were

assigned to the central code 3. An overall

opinion score was obtained by summing

the scores of all items. The resulting score

varies from 10-34

Stigmatization of People with Schizophrenia in Clinical Settings 109

Table 1

Item never rarely sometimes often always

1 0 0 7 20 5

2 0 10 10 7 5

no unsure yes

3 1 9 22

4 0 7 25

5 3 26 3

6 10 12 10

7 1 3 28

8 15 7 10

9 3 6 23

10 3 2 27

Conclusions

1. The greatest part of responders

(25 from 32) considered that

people think less about them and

sometimes they are afraid of them.

2. A great part of responders (22 of

32) admit that they were been

harassed because of mental illness

and also they considered that their

rights were been denied because

the mental illness.

3. The patients with schizophrenia

investigated did not consider that

stigma affected their recovery,

their abilities or capacity to make

friends, but appreciate very

affected they family life.

4. The greatest part of patients

considered that stigma affected

negatively their quality of life and

they avoid situations that may be

stigmatizing to them.

Discussions

As Link and Phelan point out, stigma is a

social cause of disease which compromises

a person's ability to cape with mental

illness and produces stress. The

disadvantages with regard to power,

prestige and social connections translate

into the possibility that individuals with

mental illness will have restricted life

styles and life chances, including but not

limited to social relationships, community

living options, and citizenship right [2].On

the other hand there are clear and

significant seltings differences, and the

small sample investigated make from these

results only a first step for understanding

the real dimensions of stigma about

schizophrenia in Romania. But even these

first analyses suggest that stigma is the

"most formidable" obstacle to future

progress in the arena of mental illness and

health [5].


110

References

1. Davidio, J.F., Major, B and Crocker,

J.: Stigma: Introduction and

overview. In T.F. Heatherton, R.E.

Kleck, MR. Hebl and J.G Hull. The

social Psychology of Stigma. New

York: Guilford Press, 2000.

2. Failer, J.L.: Who Qualifies for Rights

Homelessness, Mental Illness, and

Civil Commitment. Ithaca, NY:

Cornell University Press, 2002.

3. Link, B.G., Phelan, J.C.:

Conceptualizing stigma. In: Annual

Review of Sociology 27, (2001)

363-385.

4. Stuart, H, Milev, R., and Koller, M.:

The inventory of stigmatizing

experiences: its development and

reliability. In: Word Psychiatry 4 S1,

(2005) : 35-39.

5. US Department of Health and Human

Services (1999) Mental Health: A

Report of the Surgeon General.

Rockville, MD: US. Department of

Health and Human Servicies,

Substance Abuse and Mental Services

Administration, Center for Mental

Health, National Institute of Mental

Health.

THE MAJOR DEPRESSIVE DISORDER

WITH METABOLIC SYNDROME - STUDY

ON 90 PATIENTS

P. IFTENI

1 V. BURTEA

1

Abstract: Patients with severe depression have elevated rates of

cardiovascular disease (CVD) and diabetes compared with the general

population, but little is known about the prevalence of the metabolic

syndrome that predisposes patients with depression to metabolic syndrome.

Key words: depressive disorder, metabolic syndrome.

1 Transilvania University of Brasov, Faculty of Medicine.

1. Background

Major depressive disorder is the most

prevalent psychiatric illness in the United

States, affecting more than 12% of men and

more than 21% of women in their lifetime

[3]. Previous studies indicate that prevalence

of major depression has increased during the

past century, although these trends may, in

part, be explained by methodological

problems [6]. Depression has been

associated with a variety of diseases;

specifically it has been implicated in the

development of cardiovascular disease

(CVD) and all-cause mortality [2, 5].

However, little is understood about

mechanisms that may account for poor

health outcomes associated with depression.

Previous reports have speculated that

depression may be linked to adverse health

outcomes through an association with the

metabolic syndrome [1, 2, 4].

2. Objectives

Previous reports have suggested that

depression may lead to the development of

cardiovascular disease through its

association with the metabolic syndrome;

however, little is known about the

relationship between depression and the

metabolic syndrome. The aim of this study

was to establish an association between

depression and the development of

metabolic syndrome.

3. Methods

Our study included 90 participants, aged

18 to 65 years, hospitalized in Psychiatry

and Neurology Hospital Brasov. The

interview on the lifetime prevalence of a

major depressive episode (MDE) was

based on criteria specified in the

Diagnostic and Statistical Manual of

Mental Disorders, Forth Edition, Revised

(DSM-IV-TR) [9]. The Diagnostic

Interview Schedule also yielded

information about number of episodes, age

of first episode, and the presence of a

current episode. The severity of depression

was evaluated using HAM-21 (Hamilton

Depression Scale), GAF (Global

Assessment of Functioning), CGI (Clinical

Global Impression), number of episodes

and the time between episodes.


112

Consistent with the operational

definition, the metabolic syndrome was

defined as having 3 or more of the

following: [3] High blood pressure:

_130/85 mm Hg or antihypertensive

medication use; [6] High triglycerides:

_150 mg/dL; [5] Low HDL cholesterol:

_40 mg/dL in men or _50 mg/dL in

women; [7] High fasting glucose: _110

mg/dL or antidiabetic medication use; or

[1] Abdominal obesity: waist circumfe-

rence _102 cm in men or _88 cm in

women [8].

4. Results

Subjects with metabolic syndrome were

older (p<0.001), had largest waist

circumferences (p<0.03) and BMIs

(p<0.001). The overall prevalence of the

metabolic syndrome in patients with

depression was 34.44% (N=31), with

36,54% (N=19) women and 31,57%

(N=12) men. Table 1 displays the analysis

of sociodemographic characteristics of the

study sample.

Anthropometric Characteristics of the Study Sample Table 1

MDD

Variable Mean (SD) MS absent MS present p

Age, years 40.5 44.4 36.5 <0.001

Height, meters 1.68 1.67 1.69 0.90

Weight, kilograms 86.1 97.4 74.6 <0.001

BMI 30.1 34.5 28.3 <0.001

Waist 104.9 113.3 97.6 <0.001

Compared with those having normal

waist circumference and normal blood

pressure, subjects with larger waist and

high blood pressure had higher rate of

metabolic syndrome.

As anticipated, age is a major factor in

development of metabolic syndrome

(figure 1). In patients with major

depressive disorder, the onset of metabolic

syndrome is earlier than general

population.

We observed a trend toward increased

rates of low HDL and large waist

circumferences.

In fact, we observed a graded

relationship between severity of depression

and number of metabolic syndrome

components present (figure 2).

The Major Depressive Disorder with Metabolic Syndrome - Study on 90 Patients 113

0

10

20

30

40

50

60

70

18-29 30-39 40-49 50-59

age

Fig. 1. Relation between Age and Prevalence of Metabolic Syndrome

0

10

20

30

40

50

60

1 2 3 4 5

Number of Metabolic Syndrome Components

women men

Fig. 2. Relation between HAM-21

Score and the Number of Metabolic Syndrome Elements

0

10

20

30

40

50

60

normal weight over weight obese

Fig.3. Relation between BMI and prevalence of Metabolic Syndrome


114

Conclusions

This is the first study in Romania who

tried to examine the relationship between

depression and the metabolic syndrome, as

defined by the ATP III guidelines, in a

representative sample of patients, during a

period of four years. The results presented

here demonstrate that patients with major

depressive disorder were more than twice

as likely to have the metabolic syndrome

compared with those with no history of

depression.

Specifically, depression appeared to be

most closely associated with high blood

pressure and large waist circumferences.

The co-morbidity of depression and the

metabolic syndrome, in terms of severity

of depression, demonstrate that the

elements of metabolic syndrome aggravate

depression through increased CGI score

and decreased GAF score. The relapses

were more frequently in patients with

depression and metabolic syndrome and

the periods between episodes were

significantly shorter.

References

1. Bjorntorp, P.: Stress and

cardiovascular disease. In: Acta

Physiol Scand Suppl 1997; 640: 144-8.

2. Chrousos, G.P.: The role of stress and

the hypothalamic-pituitary-adrenal

axis in the pathogenesis of the meta-

bolic syndrome: neuro-endocrine and

target tissue-related causes. In: Int J

Obes 2000; 24: S50–5.

3. Kessler, R.C., McGonagle, K.A.,

Zhao, S., Nelson, C.B., Hughes, M.,

Eshleman, S., Wittchen, H., Kendler,

K.S.: Lifetime and 12-month

prevalence of DSMIII–R psychiatric

disorders in the United States: results

from the National Comorbidity Study.

In: Arch Gen Psychiatry 1994; 51:

8–19.

4. Kinder, L.S., Kamarck, T.W., Baum,

A., Orchard, T.J.: Depressive

symptomatology and coronary heart

disease in Type I diabetes mellitus: a

study of possible mechanisms. In:

Health Psychol 2002; 21: 542–52.

5. Musselman, D.L., Evans, D.L.,

Nemeroff, C.B.: The relationship of

depression to cardiovascular disease.

In: Arch Gen Psychiatry 1998; 55:

580–92.

6. Simon, G.E., VonKorff, M.:

Reevaluation of secular trends in

depression rates. In: Am J Epidemiol

1992; 135: 1411–22.

7. Wulsin, L.R., Vaillant, G.E., Wells,

V.E.: A systematic review of the

mortality of depression. In: Psychosom

Med 1999; 61: 6–17.

8. *** Centers for Disease Control and

Prevention. The Third National Health

and Nutrition Examination Survey

(NHANES III 1988–94) Reference

Manuals and Reports. Bethesda, MD:

National Center for Health Statistics,

1996.

9. *** Diagnostic and statistical manual of

mental disorders, 3rd ed. revised.

Washington, DC: American

Psychiatric Association, 1987.

POSITIVE AND NEGATIVE SYNDROME

SCALE CLUSTERING OF

SCHIZOPHRENIA

C. MOŞOIU

1 V. BURTEA

1

Abstract: Clustering deals with finding a structure in a collection of unlabeled

data with the aid of unsupervised learning. The aim of the study was to investigate

evidence of a more complex structure of schizophrenia. Analysis with hierarchical

clustering was applied to a sample of schizophrenic patients who had been scored

on the Positive and Negative Syndrome Scale.

Key words: schizophrenia, clustering, evaluation scale.

1 Transilvania University of Brasov, Dep Fundam. and Prophylactic Disciplines.

1. Introduction

The aim of this article is to investigate

the subtypes of schizophrenia with the aid

of a method of cluster analysis that was

applied to the Positive and Negative

Syndrome Scale (PANSS).

Clustering can be considered the most

important unsupervised learning method and

it deals with finding a structure in a

collection of unlabeled data. Loose definition

of clustering is the process of organizing

objects into groups whose members are

similar. A cluster is a collection of objects

which are “similar” between them and are

“dissimilar” to the objects belonging to other

clusters. The similarity criterion is distance:

two or more objects belong to the same

cluster if they are “close” according to a

given distance (e.g.geometrical distance) in

distance-based clustering.

Another kind of clustering is conceptual

clustering which means that objects belong

to the same cluster if this one defines a

concept common to all objects. In other

words, objects are grouped according to

their fit to descriptive concepts, not

according to simple similarity measures.


The aim of the study was to investigate

evidence of a more complex structure of

schizophrenia than the relatively simple

negative-positive symptoms concept [2, 3, 5,

6]. For this purpose, hierarchical duster

analysis was applied to a sample of patients

who had been scored on the Positive and

Negative Syndrome Scale (PANSS) [4]. This

particular instrument was chosen because of

its known validity and its widespread use and

because it includes negative, positive, and

general psychopathology items (such as

depression and anxiety).

A total of 38 patients were included.

(mean age = 38.7 years, mean duration

of illness = 12,8 years, 43% males). The

patients used in this investigation

belonged to a cohort of schizophrenia

patients at the Braşov psychiatric unit.

The patients were rated as having

schizophrenia according to diagnostic

criteria defined by DSM IV- TR [1].


116

We used a clustering approach based on

hierarchical method. Method produces a

series of solutions, beginning with one in

which each individual is regarded as a

single member in cluster to the final

solution in which all individuals are

contained in a single cluster. The series of

solutions can be represented as a sequence

of partitions such that its root is a cluster

covering all the points and the leaves are

clusters containing only one point. In the

middle, child clusters partition the points

assigned to their common parent according

to a dissimilarity level. The tree resulting

from the application of clustering method

was suggestive for four distinct clusters in

the data (see Table 1).

Table 1

Mean scores of positive, negative, and general psychopathological items in the PANSS

Symptomatology Cluster 1

(Mean)

Cluster 2

(Mean)

Cluster 3

(Mean)

Cluster 4

(Mean)

POSITIVE SYMPTOMS

Delusions 1,15 2,07 2,98 3,65

Conceptual

Disorganization

1,18 1,13 1,88 2,30

Hallucinatory Behavior 1,09 1,33 3,23 5,06

Excitement 1,12 1,67 2,54 1,79

Grandiosity 1,20 1,54 1,63 2,11

Suspiciousness

/Persecution

1,45 1,98 2,78 2,96

Hostility 1,32 1,55 3,25 1,24

NEGATIVE SYMPTOMS

Blunted Affect 1,30 4,23 4,22 1,23

Emotional Withdrawal 1,15 3,86 3,89 2,06

Poor Rapport 1,90 5,22 3,04 1,55

Passive/apathetic social

withdrawal

2,30 3,65 2,99 1,89

Difficulty in abstract

thinking

1,75 5,69 3,34 3,15

Lack of spontaneity and

flow of conversation

1,05 4,02 2,90 1,75

Stereotyped thinking 1,86 4,53 4,11 1,45

Positive and Negative Syndrome Scale Clustering of Schizophrenia 117

GENERAL PSYCHOPATHOLOGY SCALE

Somatic concern 2.14 1,09 2,66 3,02

Anxiety 1,95 1,68 3,08 2,15

Guilt feelings 1,34 1,45 3,56 2,09

Tension 1,04 1,83 2,23 1,89

Mannerisms and posturing 1,74 2,34 2,10 1,15

Depression 2,13 1,79 1,98 1,65

Motor retardation 1,87 1,44 2,78 2,01

Uncooperativeness 2,12 1,89 1,65 1,85

Unusual thought content 1,23 1,56 2,77 2,86

Disorientation 1,06 1,38 1,45 1,05

Poor attention 1,88 2,15 3,12 2,98

Lack of judgment and

insight

2,35 1,37 2,66 3,25

Disturbance of volition 1,90 1,48 1,87 1,02

Poor impulse control 1,27 1,85 4,36 1,39

Preoccupation 1,33 1,67 3,78 1,43

Active social avoidance 1,65 1,91 2,07 1,91

As a disorganized cluster did not appear

in this four-cluster solution, the five-duster

solution was also examined. This consisted

in a disorganized one (n = 11) and a non-

disorganized one (n = 5) obtained by

subdividing the positive duster found at the

four-group level (see Table 2).

Mean scores for disorganized cluster Table 2

Item Disorganized Non-disorganized

Delusions 3,81 3,24

Conceptual disorganization 3,25 1,95

Hallucinatory behavior 3,98 4,96

Excitement 1,89 2,75

Grandiosity 2,34 2,50

Suspiciousness/persecution 2,88 3,80

Poor attention 3,25 2,14

Lack of judgment and insight 3,54 4,88


118

3. Conclusions

The first cluster (n = 5) had low scores

on all the negative, positive, and general

psychopathological items of the PANSS

and contains patients characterized by a

mild symptomatology.

The second cluster (n = 7) contains

patients having high scores on negative

items and on some general items

(mannerisms and posturing, depression,

motor retardation, poor attention, lack of

judgment and insight) and low scores on

positive.

The third duster (n = 11) is a mixed one

because of high scores on the positive,

negative, and general psychopathological

items.

The fourth duster (n = 15) contains

patients that were higher on positive items

and some general psychopathological

items (somatic concerns, anxiety, tension,

unusual thought content, poor attention).

Conceptual disorganization, excitement,

grandiosity, and poor attention were

significantly more severe in the

disorganized than in the non-disorganized

cluster. Also delusions, hallucinatory

behaviour, suspiciousness/ persecution,

and lack of judgment and insight were

more severe in the non-disorganized

cluster.

4. Discussion

Data gathered from this small sample of

schizophrenic patients identify four or five

clusters of symptoms instead of

positive/negative concepts. Further studies

based on larger samples need to be

performed in order to improve validity

and reliability of clustering method and

maybe to discover latent variables on the

sample.

References

1. American Psychiatric Association.

DSM-IV-TR: Diagnostic and

Statistical Manual of Mental

Disorders. 4th ed., revised.

Washington, DC: The Association,

2002.

2. Blanchard, J.J., Horan, W.P., Collins

L.M.: Examining the latent structure

of negative symptoms: is there a

distinct subtype of negative symptom

schizophrenia? In: Schizophr Res.

2005; 77: 151–165.

3. Gottesman, I.I., Gould, T.D.: The

endophenotype concept in psychiatry:

etymology and strategic intentions. In:

Am J Psychiatry. 2003; 160: 636–645.

4. Kay, S.R., Fiszbein, A., Opler, L.A.:

The Positive and Negative Syndrome

Scale (PANSS) for schizophrenia. In:

Schizophrenia Bulletin, 13(2): 261-

276, 1987.

5. Kendell, R., Jablensky, A.:

Distinguishing between the validity

and the utility of psychiatric

diagnoses. In: Am J Psychiatry.

2003;160:4–12

6. Lindenmayer, J.P., Brown, E., Baker,

R.W., et al.: An excitement subscale of

the positive and negative syndrome

scale. In: Schizophr Res. 2004; 68:

331–337.

HEMODYNAMICS OF THE POSTERIOR

CEREBRAL ARTERY

C. FALUP-PECURARIU

1 A. POSTELNICU

2

G. PAMFIL3 V. MONESCU

4

O. FALUP-PECURARIU5 R. ALEXANDRU

6

Abstract: Willis Circle is a key element during cerebral autoregulation.

There are mathematical models which evaluate its global hemodynamics or

part of them. The aim of this study is to evaluate flow rates and pressures of

the posterior cerebral artery in 1D Willis Circle model with variables

geometries. Based on 1D model we varied lengths and diameters of each

component artery and developed 3D models. We used lengths and diameters

and by using Statistic 7 software, we developed colour-coded graphs. We

obtained colour spectrums together with legends. We elaborated flow rates

based on lengths and diameters for each component artery of Willis Circle.

Variation trend of flow rates for segment P1 of PCA obtained by spine

method demonstrated that biggest flow rates were obtained for minimal

lengths and maximal diameters. The smallest flow rates were obtained for

smallest diameters independent by length.

Key words: Willis Circle, posterior cerebral artery, hemodynamics,

mathematical model.

1 Dept. of Neurology, Transilvania University of Braşov 2 Dept. of Thermotechnics and Fluid Mechanics, Transilvania University of Braşov 3 Dept. of Automathics, Transilvania University of Braşov 4 Dept. of Mathematics, Transilvania University of Braşov 5 Dept. of Pediatrics, Transilvania University of Braşov 6 Student, Faculty of Medicine, Transilvania University of Braşov

1. Introduction

Willis Circle was described for the first

time by Johann Wepfer (1620-1695).

Thomas Willis (1621-1675) described this

completely, so this circle takes his names.

Afterwards many authors have studied its

morphology and its variants: Vicq D’Azir,

Duret, de Vriese, Alpers (cit. by Alpers

and Berry (1963) [3], Lazorthes and

Goauze (1968) [9], Lazorthes et al. (1976)

[10], Lazorthes et al. (1979) [11],

Lazorthes et al. [12], Batujeff 1889, Mori

1893, Cavatorti 1908, Busse 1921,

Mitterwalkner 1955, Decker and Hipp

1958, Servida and Mortillaro 1963,

Cavallotti 1980 (cit. by Padget (1948)

[14]).

2. Anatomy

Posterior cerebral artery (PCA) born

from bifurcation of basilar artery at ponto-

mesencephalic sulk (Bracard et al. [6],

Arseni and Popoviciu [4]). Branches with

cortical destination are born constantly at

P1 and P2 segments.


120

Banias-Palaghiţă (1999) [5] published

mean lengths of 6.46 mm for posterior

cerebral artery. Branches P1 of PCA have

greater values in the right. At women the

mean length was 6.8 mm and for men 6.5

mm. Posterior cerebral artery had mean

value of 11.6 mm with a mean value of

12.1 mm in the right and 11,83 mm in the

left. At women mean value was 11.92 mm

and at men 11.34 mm [5].

The aim of this study is to evaluate flow

rates and pressures at posterior cerebral

artery in 1D Willis Circle model with

variables geometries.

Material and Method

Based on 1D model we developed 3D

models. We used lengths and diameters

and by using Statistic 7 software we

developed colour coded graphs. We

obtained colour spectrums together with

legends. We elaborated flow rates based on

lengths and diameters for each component

artery of Willis Circle. In the followings

we will present data regarding posterior

cerebral artery (PCA).

Graphic 1. Distribution of variations of lengths, diameters

and flow rates at right PCA segment P1

In this case the most of the points were at

diameter of 3 mm and respectively 3.5

mm. For lengths most of the points were at

15, 20 and 25 mm.

Most of combinations of points were at

minimal lengths (15 mm) and maximal

diameter (3 and 3,5 mm), followed by

diameters of 20 and 3 mm, respectively 20

and 3.5 mm, 25 and 3 mm, respectively 20

and 35 mm, 25 and 3 mm, 25 and 3,5 mm.

Hemodynamics of the Posterior Cerebral Artery 121

350

300 250 200

150 100

50 0

Graphic 2. Distribution of lengths, diameters and flow rates at right posterior cerebral

artery level, segment P1

The biggest flow rates (350 cm3/s) were

obtained for lengths from 14 to 20 mm and

for diameters from 2 to 3 mm. The

smallest flow rates were obtained for

lengths bigger than 16 mm and diameters

below 2 mm. For lengths bigger than 16

mm and diameters smaller than 1 mm we

obtained negative flow rates.

900 750 600

450 300

150 0

Graphic 3. Distribution of length, diameter and flow rates variations at right posterior

cerebral artery level segment P1 by spline method


122

By using spline method we obtained the

same trend at flow rates. The most

important flow rates were at diameters

between 3 and 3.5 mm.



In this case the most of the points were at

diameter level of 8 and respectively 3 mm.

For lengths these points were for value of

20, 70 and 80 mm.

The most of the points for combination

were for minimal lengths (20 mm) and

maximal diameters (8.5 mm), followed by

combination of lengths and diameters of 70

and 8.5 mm, respectively of 80 and 8.5

mm.


600 500 400

300 200

100 0


cerebral artery level segment P2

The biggest flow rates were obtained for

smallest lengths (bellow 50 mm) and

diameters between 7 and 9 mm. For

lengths higher than 50 mm and diameters

below 2 mm we obtained negative flow

rates. The smallest flow rates were

obtained for lengths higher than 50 mm

and diameters below 3 mm.


124

900 750 600

450 300

150 0



This method shows values of flow rates

below 150 cm3/s for lengths between 10

and 90 mm and diameters of 3 mm. The

biggest flow rates were obtained for

lengths of 10-50 mm and diameters of 4-8

mm. The graph 6 shows eliptic trends for

biggest flow rates.

Discussions

The role of posterior cerebral artery-

posterior communicating artery is double:

anastomotic between carotid artery and

posterior communicating artery and

precommunicant segment of PCA and

nutritive for cerebral territory in function

(Bracard et al. (1984) [6], Arseni and

Popoviciu (1984) [4]).

PCA was born at posterior part of

internal carotid artery in supracavernous

part (C1-C2), with lenght of 15 mm (7-25

mm) [9, 10]. Cortical and central branches

are alimented by basilar artery. From

morphologic point of view, it is described

posterior cerebral artery which is born

from basilar artery and is anasmomosed

with posterior communicating artery born

from internal carotid artery. Secondarly, it

gives a branch which anastomosis with

basilar artery [9, 10].

There are few data regarding

hemodynamics of PCA. Usually this is

studied through a global model of Willis

Circle. Alastruaey et al.[2] used a 1D

model for blood flow in Willis Circle.

They involved cardiac cycle in the system.

The main conclusion is that Willis Cirlce is

enough in order to compensate hemo-

dynamics in normal subjects. The commu-

nicating arteries are important when an

afferent artery is occluded, anterior part

being more important than posterior. Willis

Circle has a key role in cerebral

autoregulation [1, 7, 8, 13, 15, 18, 19, 20,

21]. There are global models for its

hemodynamics [16, 17] and during focal

cerebral attacks [17]


Conclusions

1. Variation trend of flow rates for

segment P1 of PCA obtained by spine

method demonstrated that biggest

flow rates (bigger than 600 cm3/s)

were obtained for minimal lenghts

and maximal diameters.

2. The smallest flow rates were obtained

for smallest diameters (below 3 mm)

independent by lenght.

References

1. Aaslid, R., Newell D.W., Stooss R.,

Sorteberg, W., Lindegaard, K.F.:

Assessment of cerebral autoregulation

dynamics from simultaneous arterial

and venous transcranial Doppler

recordings in humans. In: Stroke.

1991; 22: 1148-1154.

2. Alastruey, J., Parker, K.H., Peiró, J.,

Byrd, S.M., Sherwin, S.J.: Modelling

the circle of Willis to assess the effects

of anatomical variations and

occlusions on cerebral flows. In: J

Biomech. 2007; 40(8): 1794-805.

3. Alpers, B.J., Berry, R.G.: Circle of

Willis in cerebral vascular disorders.

In: Arch Neurol. 1963; 8: 398-402.

4. Arseni, C., Popoviciu, L.: Bolile

vasculare ale creierului şi măduvei

spinării, partea I-a. Ed. Academiei

RSR, 1984.

5. Banias-Palaghita, L.: Morfologia

normală şi aspecte particulare ale

Poligonului Willis la om. Târgu-

Mureş. 1999. Teză de doctorat.

Conducător ştiinţific Prof. Dr. Ion

Pascu.

6. Bracard, S., Roland, J., Picard, L.:

Variations des arteres de l’encephal,

Livre 1, Tome 2. Paris. Ed.Masson,

Paris 1984.

7. Giulioni, M., Ursino, M.: Impact of

cerebral perfusion pressure and

autoregulation on intracranial

dynamics: a modeling study. In:

Neurosurgery. 1996; 39: 1005-14.

8. Irikura, K., Morii, S., Miyasaka, Y.,

Yamada, M., Tokiwa, K., Yada, K.:

Impaired autoregulation in an

experimental model of chronic

cerebral hypoperfusion in rats. In:

Stroke. 1996; 27: 1399-404.

9. Lazorthes, G., Gouaze A.: Les voies

anastomotiques de supleance de la

vascularization arterielle de l’axe

cerebro-medullaire. In : C.R. Ass.

Anat. 1968; 139:103-222.

10. Lazorthes, G., Gouaze, A., Salamon,

G.: Vascularisation et circulation de

l’encephale. Tome premier. Anatomie

descriptive et fonctionelle. Paris.

Masson Ed., 1976.

11. Lazorthes, G., Gouaze, A., Santini,

J.J., Salamon, G.: Le cercle arteriel de

cerveau. In : Anatomia Clinica. 1979;

1:241-258.

12. Lazorthes, G., Gouaze, A., Santini,

J.J., Salamon, G.: The arterial circle

of the brain (circulus arteriosus

cerebri). In: Anatomia Clinica 1.

1979; 241-257.

13. Newell D.W., Aaslid R., Lam A.,

Mayberg T.S., Winn H.R.:

Comparison of flow and velocity

during dynamic autoregulation testing

in humans, Stroke. 1994; 25:793-7.

14. Padget, D.H.: The development of

cranial arteries in human body. In:

Cont Embryol Carneg Instit. 1948;

32:105-261.

15. Paulson, O.B., Olesen, J., Christensen,

M.S.: Restoration of autoregulation of

cerebral blood flow by hypocapnia.

In: Neurology, 1972; 22:286-93.

16. Pascu, I.: A computerized model of the

Circle of Willis. Note I: simulation of

the autoregulation of cerebral blood

flow. In: Revista Medicala 1989; 5-8.

17. Skinhoj, E., Hoedt-Rasmussen, K.,

Paulson, O.B., Lassen, N.A.: Regional

cerebral blood flow and its

autoregulation in patients with

transient focal cerebral ischemic

attacks. In: Neurology. 1970; 20:

485-93.


126

18. Strandgaard, S.: Autoregulation of

cerebral blood flow in hypertensive

patients. The modifying influence of

prolonged antihypertensive treatment

on the tolerance to acute, drug-

induced hypotension. In: Circulation.

1976; 53:720-727.

19. Strandgaard, S., Olesen, J., Skinhoj,

Lassen, N.A.: Autoregulation of brain

circulation in severe hypertension. In:

Br Med J. 1973; 1:507-510.

20. Vavilala, M.S., Lee, L.A., Lee M.,

Graham, A., Visco, E., Lam, A.M.:

Cerebral autoregulation in children

during sevoflurane anaesthesia. In:

Br J Anaesth. 2003; 90:636-41.

21. White, R.P., Markus, H.S.: Impaired

dynamic cerebral autoregulation in

carotid artery stenosis. Stroke. 1997;

28:1340-4.

COMPARATIVE STUDY ON THE

EFFICACY OF DIFFERENT PROTECTION

METHODS IN CHRONIC ACOUSTIC

TRAUMA

Mădălina BUZESCU

1

Abstract: This study aims at evaluating the medical and economic efficacy

of the main known protective methods in order to prevent hearing loss due to

chronic acoustic trauma. The study subjects work in various noisy

environments and have different professions, requiring various education

levels and hearing capabilities. These conditions lead to various possibilities

and acceptability for the hearing protection. The study subjects’ hearing

levels were evaluated by pure tone audiometry, after testing the noise levels

with the help of a sonodosimeter. The protection methods used and analyzed

were mechanic protection devices and two kinds of antioxidant therapy – a

combination of vitamins A, C and E with Selenium and alpha-lipoic acid, in a

6 month therapy. The data were computed using a suitable statistic software.

The results showed a reduced acceptability for the mechanical protection

devices in the industrial environment, a very high efficiency of the

antioxidant therapy with alpha-lipoic acid and a lower level of protection

with vitamins and Selenium. The conclusions of the study underline the

importance of implementing educational programs in order to provide a

more extended use of the protection devices in the industrial noisy

environments and the efficacy of the antioxidant preventive therapy for the

professionals whose hearing is essential in order to accomplish their work

Key words: acoustic trauma, antioxidant, alpha-lipoic acid.


1. Introduction

Acoustic trauma is defined as an

alteration of the hearing caused by

exposure of the cochlea to excessive

acoustic pressure.

Noise is an acoustic perception of

various type and intensity, having an

unpleasant character, capable to lead to

reactions or changes of the organism and

especially of the hearing.

The measuring unit used for the sound

intensity is the decibel (dB). The decibel

scale is a logarithmic scale where 0 dB

approximates the hearing level at medium

frequencies in young adults with

discomfort level at 85-95 dB and pain level

between 120 and 140 dB.

The harmful level is the sound level that,

reached or surpassed, requires the use of a

method to prevent the risk of hearing loss by

acoustic trauma. The usual criteria establish

an average of 8 hours daily in an average

noise of 85 dB, value from which there is

required the implementation of an acoustic

prevention program [2].


128

The sound level determination is made

with the help of a sonodosimeter,

instrument that measures the noise level on

a specified interval, which deposits the

measured values and computes the sound

as a relation between the noise level and

duration, describing the results as dose,

temporal average and other parameters

such as maximal level or sound level

exposure.

The impact of noise on the cochlea

depends, besides intensity, on other sound

characters, especially its variability.

The effects of noise on human organism

are primarily auditory, leading to cellular

alterations in the cochlea. Recent

researches claims that, the molecular

support of deafness through acoustic

trauma is the elevation of the level of

reactive oxygen species with important

role in the death of cochlear hair cells, by

necrosis as well as by apoptosis. These

new discoveries are the basis for new

protection strategies with antioxidant drugs

[7].

Besides the effects on hearing, noise

exposure also leads to sleep, cardio-

vascular, respiratory, metabolic, beha-

vioural and hormonal disorders. These

effects lead us to consider noise as a stress

factor.

The most simple and widely known

protection, the insulating devices, suitable

especially in industrial environments, do

not meet as much success as they should,

due to various reasons. Other, more recent,

protection methods, use internal use of

antioxidants, to avoid extensive destruction

of cochlear hearing cells by high pressure

noise levels.

Cochlear noise aggression reduction can

also be reached by limitation of workers’

exposure to noise, changing of their

program and location and projects for

technical improvement leading to a more

silent function of the equipments [6].


The study represents a clinical, statistic,

prospective, longitudinal research, exten-

ded on a 5-year period of time, from

October 1999 to October 2004.

4225 subjects working in potentially

noisy environments were routinely tested

with a screening audiometer by pure tone

audiometry, resulting 730 subjects with

hearing loss of over 20 dB at least one ear.

Of these 730 patients, after a diagnostic,

standard hearing evaluation with a clinic

audiometer, in a silent testing room, 512

patients were diagnosed with hearing

losses of various degrees. These were

included in the study after verifying their

professional noise exposure with the help

of a sonodosimeter Norsonic NOR 116.

In the industrial environment, where the

use of insulating hearing protection devices

is suitable, the effective use of these devices

was researched, as well as their efficacy in

the prevention of acoustic trauma. Other

directions of research in these subjects were

the motivations of refusal of these devices.

There were also gathered three groups of

subjects for the study of antioxidant therapy

(group A, treated with alpha-lipoic acid,

group B, treated with vitamins A, C, E and

Selenium and group C, control, with

placebo).

Another study group was formed by

musicians working in symphonic or

modern musical environments, as well as

by people exposed to leisure acoustic

trauma. These subjects can not benefit

from hearing insulating devices, so only

the efficacy of antioxidant therapy was

searched among them, by completing the

three groups of study (A, B and C)

previously described for the workers.

The hearing tests were made at more

than 24 hours after noise exposure, at the

beginning of the therapy, as well as at its

finish, the main parameter used in the

statistical analysis being the hearing

threshold at 4000 Hz, where the typical

“V” for acoustic trauma appears.

Comparative Study on the Efficacy of Different Protection Methods in Chronic Acoustic Trauma 129

From the 730 subjects diagnosed with

hearing loss by the screening hearing test,

512 were diagnosed with sensorineural

hearing loss in standard, silent, clinic

conditions, 432 fulfilled the inclusion and

exclusion criteria and 24 were excluded

after measuring the noise level at the

working locations (levels under 85 dB).

From the 418 subjects included in the

study, 179 either abandoned the study by

not showing up at re-evaluations, or

changed their working places to less noisy

environments (57% of the subjects

finalized the study).

Inclusion criteria:

- “V”-shaped hearing loss around 4000

Hz over 20 dB in at least one ear

- Age 18 – 55 years

- Daily exposure (5 days/week) to noise

over 85 dB for at least 6 hours

Exclusion criteria:

- anaemia, diabetes mellitus

- chronic hepatic disorders

- known hypersensitivity to alpha-

lipoic acid, vitamins A, C, E,

Selenium, starch

- associated transmission hearing loss

- history of malignant tumours

- family history of sensorineural

hearing losses

There were randomly selected three

groups: two study groups (A, B) and a

control group (C).

- Group A (83 subjects, average age

39.5 years) – received 600 mg

alpha-lipoic acid /day for 6 months;

- Group B (95 subjects, average age

39,1 years) – received an antioxidant

complex composed of vitamin A

5000 I.U, vitamin C 100mg, vitamin

E 50 I.U., Selenium 50µg /day for 6

months;

- Group C (61 subjects, average age

38,9 years) – received placebo -

starch for 6 months;

- The hearing test was repeated in all

subjects of the three groups after 6

months (+/- 7 days).

3. Results

In the group of industrial workers, 4%

were exposed to 75-85, while 96% were

exposed to over 85 dB noise levels. From

the workers exposed to industrial noise less

than 85 dB, 88% (21 subjects) are aware of

the risk of irreversible hearing loss by

acoustic trauma and 69% (17 workers)

consider their work dangerous and harmful

from this point of view.

Among de workers exposed to over 85

dB noise levels, only 39% (273 subjects)

are aware of the risk they are exposed to.

These workers declared that noise is

affecting mostly their hearing (77%) and

the nervous system (61%). They admit

having received information on the risk of

professional acoustic trauma from their

direct chiefs (44%), people in charge with

professional health (44%) or enterprise

doctors (12%).

Besides the effects on hearing, noise also

caused neurosis (diagnosed by history

taking, in presence of asthenia and

insomnia) – 23% of patients with hearing

loss (168 subjects), and sleeping disorders

(38% of subjects with hearing loss) in this

study.

An interesting correlation was

established between chronic, professional

acoustic trauma and high blood pressure.

Table 1

Statistic results on correlation of acoustic

trauma to high blood pressure levels.

n 4225

Acoustic trauma

HBP with without Total

with 174 1052 1226

(148,6) (1077,4)

with 338 2661 2999

(363,4) (2635,6)

Total 512 3713 4225

Pearson X2 6,98

DF 1

p 0,0083


130

The Pearson’s statistic test shows a

statistically significant correlation between

acoustic trauma and high blood pressure.

Wearing hearing protection devices is

admitted only by 21% (861) of the

subjects. Those who do not use these

devices motivate that the employers did

not offer them this devices (55% - 2255

subjects), that these devices affect the

communication with their colleagues (14%

- 574 subjects), ear discomfort or pain (6%

- 246 subjects) or other reasons (5%).

The average hearing threshold at 4 kHz

among the workers who systematically

used hearing protection devices was 18,2

dB, compared to the 24,3 dB average

hearing threshold of those who never do

that. This comparison was made between

selected groups of the two categories, in

order to have comparable average ages (31

years). The statistic significant difference

of 6,1 dB (p<0,01) proves the very high

efficacy of hearing insulating protective

devices in noisy industrial environment.

However, these devices, with their actual

use, seem to have a slight impact on the

workers’ hearing conservation.

The voluntary, leisure exposure to

phonic pollution was explored in subjects

without professional noise exposure.

From the 108 subjects who admitted to

attend at least twice a week discotheques

or listen at least 2 hours a day loud music

in headphones, 11 subjects (10%) showed

hearing losses of at least 20 dB in at least

one ear at 4 kHz (average hearing loss –

24,5 dB). The average age of this group

was 23.7 years and 80% of the, (86

subjects) never thought of the risk of

hearing loss. From the 11 subjects with

hearing loss at 4 kHz, only 2 people (18%)

had noticed having a hearing problem.

These subjects also had among the highest

hearing losses in the group (30 respectively

40 dB at 4 kHz).

Before applying the statistical t-test

(Student) to establish the significance of

the outcomes, the normality of the

distribution of the collected data was

statistically evaluated (Shapiro-Wilk test),

to assure the results’ reliability.

A synthesis of statistical outcomes in the

study on antioxidant therapy for prevention

of chronic acoustic trauma is presented in

the table below:

Table 2

Synthesis of statistical results on

antioxidant therapy in chronic acoustic

trauma

Gr. A

(n=83)

Gr. B

(n=95)

Gr. C

(n=61)

Average age 39,5 39,1 38,9

Average initial

hearing

threshold (dB)

22,5 17,9 18,4

Average final

hearing

threshold (dB)

20 16,8 19,1

Difference (dB) 2,5 0,4 - 0,7

p < 0,01 0,0110 0,0031

4. Discussions

A major factor influencing the efficacy

of acoustic trauma preventive methods is

the awareness of the subjects exposed to

noise regarding this risk [3]. The outcomes

of this study show a strange distribution of

awareness on this risk, workers in louder

working places being less informed and

caring for their hearing than those working

in less noise. An explanation for this would

be that very noisy industrial environments

(especially in heavy industry) are usually

populated with less educated and qualified

workers. Usually, people study hard to

accomplish as high educational levels as

possible, in order to avoid such stressing,

noisy working places.

The major stress caused by high noise

levels also explains the statistically

significant correlation between acoustic

trauma and high blood pressure levels.

In spite of their good protecting

properties, the insulating hearing

protection devices do not seem to offer the

Comparative Study on the Efficacy of Different Protection Methods in Chronic Acoustic Trauma 131

ideal solution in the industrial field,

because of their insufficient use by

workers.

A recent study of the University in Sao

Paolo, Brazil, systematically analyzed the

programs that promote the use of hearing

protection devices, considering that

hearing loss due to acoustic trauma can

only be prevented by reducing exposure to

noise. The conclusion of this evaluation is

that firmer educational interventions are

necessary to increase the frequency of

using hearing protection devices among

workers exposed to loud noise [4].

Similar to the present study, another

research, carried out in Australia, indicated

a reduced awareness on the risk of acoustic

trauma and, by consequence, a minimal

self-protective behaviour [5].

The key factors that hinder the progress

in promoting hearing loss prevention

methods arise from the numerous variables

implied. These variables are even harder to

control because they include behavioural

factors such as the attitude regarding noise

and if noise is a secondary consequence or

a product of the professional activity.

Acoustic trauma caused by leisure noise,

especially music, is only responsible for

0.2% of hearing losses, but this percent

drastically increases if we consider only

the age group 18 to 25 (53%), showing that

leisure musical acoustic trauma is

increasing, especially by listening music in

headphones and discotheques, situations

where the noise level often surpasses 100

dB. As painful noise level is around 120-

140 dB, the harmful level of 90 dB is often

surpassed and the harmful effects of noise,

underestimated.

The results of the study on antioxidant

therapy efficacy in protection against

acoustic trauma showed a statistical

significant hearing improvement in 6

months by therapy with alpha-lipoic acid, a

stationary evolution of hearing in people

exposed to noise treated with the ACESe

complex and a statistically significant

hearing loss in the control group of

subjects exposed to loud noise and

receiving placebo for 6 months.

The use of mechanic insulating hearing

protection devices is the safest, for long

periods of time tested method to prevent

acoustic trauma, so intensive promotion

programs to spread their use should be a

priority for all noisy industrial fields’

employers.

Comparing the three methods described

above (mechanic hearing protection

devices, alpha-lipoic acid therapy and

vitamins ACE + Selenium therapy) only

regarding the hearing level outcomes

would recommend alpha-lipoic acid as the

best method for protection. However,

economic reasons would surely limit its

wide use among all those who work in

noisy environments. Moreover, the limited

awareness on acoustic trauma of industrial

workers makes it hard to expect that these

would be more compliant to swallowing

daily a tablet of alpha-lipoic acid.

Outcomes of the vitamins ACE and

Selenium therapy study are similar to the

protection offered by daily, systematically

use of hearing protective devices. The cost

of this therapy being about four times

lower than the one with alpha-lipoic acid,

these results suggest that it is a good

protective alternative for workers who are

aware of the acoustic trauma risk but do

not accept mechanic protection devices for

different reasons.

Hearing protection methods in musical

professions usually exclude the use of

insulating protection devices, antioxidant

therapy showing here its most important

benefits [1]. The choice of antioxidant

therapy in this professional group should

consider, besides individual hyper-

sensitivities to any of the components, the

individual susceptibility to hearing loss or

other possible systemic benefits of the

antioxidant therapies.


132

5. Conclusions

Acoustic trauma in noisy industrial

environments should be reduced by

implementing intensive educational

programs to increase awareness of hearing

loss risk and systematically use of efficient

hearing protection devices. Employers

should also be convinced to provide

efficient and comfortable hearing

protection devices.

For professionals who can not use such

devices, the use of acoustic trauma

preventive antioxidant therapy might be a

good alternative that should be evaluated

in other wider, double-blind controlled

studies.

References

1. Buzescu, M.: Actual aspects in the

non-prosthetic therapy of

sensorineural hearing loss. In:

Revista Română de ORL 2007; 29(2):

pp. 122-7.

2. Calogero, B., Giannini, P., Marciano,

E.: Recent advances in hearing

screening. In: Adv Otorhinolaryngol

1987; 37: pp.60-78.

3. Crandell, C., Mills, T.L., Gauthier, R.:

Knowledge, behaviours, and attitudes

about hearing loss and hearing

protection among racial/ethnically

diverse young adults. In: J Natl Med

Assoc. 2004 Feb; 96(2): pp. 176-86.

4. Daniel, E.: Noise and Hearing Loss: a

review. In: J Sch Health. 2007; 77(5):

pp. 225-31.

5. Dineen, R., Reid, J., Livy, P.: Knock

out noise injury. Noise Effects. 7th In:

International Congress on Noise as a

Public Health Problem. Sydney,

Australia: pp. 135-138, 1998.

6. El Dib, R.P., Atallah, A.N., Andriolo,

R.B., Soares, B.G., Verbeek, J.: A

systematic review of the interventions

to promote the wearing of hearing

protection. In: Sao Paulo Med J. 2007

Nov 1; 125(6): pp. 362-9.

7. Fetoni, A.R., Ferraresi, A., Greca, C.,

Rizzo, D., Sergi, B., Tringali, G.,

Piacentin, R., Troiani, D.: Antioxidant

protection against acoustic trauma by

co-administration of idebenone and

vitamin E. In: Neuroreport. 2008,

19(3): pp. 277-81.

ENTERAL NUTRITION IN THE

TREATMENT OF SEVERE ACUTE

PANCREATITIS

C. MIŞARCĂ1

A. CUCU1 L. DURACH

1

Abstract: Development, septic complication, and accentuated catabolism

in patients with AP were the reasons that motivated our study.

Material and method: We study prospectively and retrospectively 186 cases

of severe AP in patients operated between 1998 and 2005 in Surgery Clinic

(I-III) of Brasov County Hospital.

Results: Within the group of 186 patients in 72 the treatment of choice was

laparostomy in association to antibiotics and in 54 cases enteral nutrition

through jejunostomy was added. The cases taken into study were divided in

two groups - group A: 32 patients with enteral feeding by jejunostomy and

group B: 18 patients without enteral feeding. The evaluation was performed

by clinical and paraclinical methods. On feeding jejunostomy (Witzel type)

was first administrated normal saline solution (20ml/h) and then Survimed

after minimum 24 h, starting with 20-25ml/h reaching 100ml/h. Antibiotic

therapy - imipenem or quinolone were used. Conclusions: enteral nutrition

ensure rehabilitation of intestinal physiology, prevents bacterial

translocation, it is cost effective and improves life quality.

Key words: acute pancreatitis, enteral feeding, feeding jejunostomy

1 Transilvania University of Brasov, Chirurgical Dep, Faculty of Medicine, Brasov County Clinical

Emergency Hospital

1. Introduction

Acute Pancreatitis represents the

anatomo-clinical expression of the acute

pancreatic and peripancreatic auto

digestion [1]. The main features of Acute

Pancreatitis are: severe ness, asynchronism

in evolution and outset of complication and

hyper catabolism (inflammatory stress,

edema, sepsis).

The clinical classification of Acute

Pancreatitis (Atlanta 1992) consists of two

aspects:

• Mild – minimal organ and system

dysfunction, completely reversible

• Severe – systemic complications, pan-

creatic and peripancreatic collections

For a long time, oral feeding was seen as

harmful in Acute Pancreatitis, by the fact it

would stimulate the exocrine secretion of

the pancreas and thus its autodigestion. On

the other hand, in patients with protracted

evolutions and complications of necrotic

Acute Pancreatitis, nutritional deficits

occur.

Approximately 80% of patients with

Acute Pancreatitis have mild-to-moderate

forms of the disease, with mortality rate of

1%. Such patients require only the usual

treatment, without special nutritional

support and return to normal diet by day 3

-7 [6] (table 1).


134

Treatment in acute pancreatitis Table 1

1. Day 2 - 5 No oral intake

Analgesics

Blood volume and electrolyte compensation

2.Day 3–7 (no pain) Oral intake

Diet - high carbohydrates

- moderate proteins

- no lipids

3. Beyond day 7 Normal diet, no entra lipids

In the context of inflammatory stress and

acute pain, basal metabolism increases and

should sepsis occur, about 80% of patients

become hypermetabolic. In these patients

nitrogen balance is negative (over 40g.

/day), with protein catabolism and

subsequent malnutrition.

In severe Acute Pancreatitis, several

questions need to be answered: is nutrition

necessary and possible? What kind of

nutrition: parenteral or enteral? Give what,

how and in what amount?

Parenteral nutrition can be held

responsible for [6]:

• Hepatobiliary complications:

o Fatty liver (after two weeks – 80%);

o Intrahepatic cholestasis (after 20

days – 50%);

o Biliary sludge (after 4 – 6 weeks – 50%)

o Periportal cholangitis, biliary

fibrosis and cirrhosis.

• Enhancement of the intestinal flora and

bacterial translocation;

• Pulmonary hypertension and decrease

in gas exchange due to arachidonic

acid (long chain lipids);

• Increase in oxygen consumption

(medium chain lipids);

• Hyperglycemia by inhibition of insulin

secretion (glucose i.v.).


A retrospective and prospective study

was carried out in the Surgical Clinics I

and III of the Brasov County Clinical

Emergency Hospital on 186 cases of

severe Acute Pancreatitis that underwent

surgery, from 1998 to 2005 (Fig. 2).

Sex ratio:

38%

62%

Men Women

Fig. 2. Sex ratio

Ages ranged 20 – 70 years, mainly 20

– 50 years.

Etiology was (Fig. 3):

Enteral Nutrition in the Treatment of Severe Acute Pancreatitis 135

42

15

96

0

5

10

15

20

25

30

35

40

45

Alcohol Biliary Dislipidemia Uncertain

Aetiology in acute pancreatitis

Fig. 3. Aetiology in acute pancreatitis

Of the 186 cases treated surgically, in 72

patients a laparostomy was performed in

association with enteral feeding by

jejunostomy (54 cases) and antibiotics (all

72 patients).

The cases taken into study were divided

in two groups:

• Group A – 32 patients with enteral

feeding by jejunostomy;

• Group B – 18 patients without enteral

feeding.

The evaluation was performed by

clinical and paraclinical methods:

I. Clinical Methods

1. Nutritional history: anamnesis

(preoperatively) – changing in diet,

oral feeding ability, gastrointestinal

symptoms, functional capacity and

status of the gastrointestinal tract [2].

2. Physical data – anthropometrical

marks:

A) Actual body weight (kg) over height

(m) is the usual parameter in

monitoring nutrition.

B) Ideal body weight (IW) as

recommended according to sex, age

and height. The easiest formula is

Broca’s index (BI):

B.I. = height (cm) – 100

I.W. (men) = B.I. – (B.I.- 52) * 0,2

I.W. (women) = B.I. – (B.I. - 52) * 0.4

C) Body mass index (BMI) – BMI is

weight (kg) / height2 (m2), normal

values are: 20-25 in men, 19-24 in

women, with a lower limit of

18,5kg/m2.

D) Mid upper arm circumference

(MUAC)

E) Weight loss – per cent of weight loss

= [(regular weight – actual

weight)/(regular weight )] * 100

F) Skin fold – easy to measure, a good

indicator of the nutrition status [7].

A large study performed in Great Britain

on 1561 cases detected malnutrition in

18,3%. [3]. Those patients had:

- BMI < 20 kg/m2;

- MUAC < 25 cm;

- Weight loss > 10%.

A correlation between BMI and MUAC

was noted:

- BMI = 1,06 MUAC – 5,8 (overall);

- BMI = 1,01 MUAC – 4,7 (men);

- BMI = 1,10 MUAC – 6,7 (women).

The study showed that: if BMI =

20kg/m2, then MUAC is 24,8cm in men

and 24,6cm in women of 55 years of age.

If BMI = 18,5kg/m2, then MUAC is

23,2cm in men and 23cm in women.


136

In many cases, due to the condition of

the patients, BMI is not available (patients

cannot be moved for weighing and

measuring). Since MUAC can be easily

measured, a good approximation would be

- BMI = MUAC – 5 (4).

As a general view:

- normal weight : BMI ≥ 20 kg/m2

and MUAC ≥ 25cm;

- low weight: 20 > BMI ≥ 18,5

kg/m2 and 25 > MUAC ≥ 23,5cm;

- very low weight: BMI < 18,5kg/m2

and MUAC < 23,5cm.

An increase in mortality rate was noted if

weight loss exceeds 10% or MUAC drops

significantly. No correlation increase

mortality – BMI drops was found [7].

II. Biological Markers:

a. Serum proteins;

b. WBC count (also a marker for

sepsis);

c. Lymphocyte count;

d. BUN and nitrogen balance;

e. Serum creatinin;

f. Procalcitonin (marker for sepsis);

g. Glycemia;

h. Natrium and potassium.

III. Energy and Fluid Necessities in

Severe Acute Pancreatitis: Energy necessities:

• Normocaloric regimen – 30 kcal./kg

body mass;

• Hypercaloric regimen – 40-50 kcal./kg

body mass (in Acute Pancreatitis);

Fluid necessities:

• 40 ml./kg body mass

• Altered by:

o Fever – increase of 12,5% / degree

Celsius above normal;

o Perspiration – increase of 10 – 25%;

o Hyperventilation – increase of

10 – 60%;

o Major gastric and/or renal losses.

Fluids needed for repletion:

Na normal

Na de normal - Na actual*

+

++

x

weight(kg) x 0,6

Nutrient necessities:

- Proteins necessities

o 15 – 20 % of the energy intake;,

o 1.2 – 1.5 g/kg body mass daily for

BUN < 100 mg/dl.

- Carbohydrates necessities

o 30 – 70 % of the energy intake;

o 2 – 5 g/kg body mass daily, for

glycaemia < 150 mg/dl.

- Lipids necessities

o 15 – 30 % of the energy intake;

o 0.5 – 1 g/kg body mass daily, for

triglycerides < 300 mg/dl.

In our study the initial weight of patients

was distributed as follows (Fig. 4.):

Fig. 4. Initial weight of patients

The 32 patients in group A received

enteral nutrition by jejunostomy, whereas

those in group B (18 patients) did not.

16%

20%64%

Over weightNormal weightUnder weight

Enteral Nutrition in the Treatment of Severe Acute Pancreatitis 137

Fig.5. Feeding jejunostomy

The regimen for enteral nutrition

consisted of:

• Normal saline : 20ml./h starting 12

– 24 h postoperativelySurvimed 20

– 25ml./h, progressively increasing

to 100ml./h (according to digestive

tolerance)

• Methilene blue to certify the

resumption of intestinal absorption

Pay repeated measurement, we noted that

body weight loss in patients with severe

Acute Pancreatitis was significantly lower

in group A (enteral nutrition) in

comparison to group B (no enteral

nutrition), as shown in the chart. (Fig. 6)

MUAC was also measured, showing a

significantly lower decrease in group A.

(Fig. 7.)

1st week 2nd week 3rd week one

month

Group A Group B

Fig. 6 Fig. 7

The same, the values of the biological parameters returned to normal more quickly in

group A. (table 8).

1 st week 2nd week 3rd week one month

Group A Group B


138

Biological parameters Table 9

PPrreeooppeerraattiivveellyy 11 wweeeekk 11 mmoonntthh

SSeerruumm aallbbuummiinn

((mmgg//ddll))

2277--2288 2288--2299 2266 2255..55 3344 3311

WWBBCC ccoouunntt

((110033//mmmm

33))

1100--2299 1100--2299 88--1100 88--1144 66--88 66--88

BBUUNN ((mmgg//ddll)) 00..55--00..77 00..55--00..77 00..44--00..66 00..66--00..88 00..22--00..66 00..22--00..66

CCrreeaattiinniinn

((mmgg//ddll))

00..66--11..66 00..66--11..66 00..66--11..44 00..88--11..66 00..66--11..22 00..66--11..33

GGllyycceemmiiaa

((mmgg//ddll))

110000--335500 110000--335500 8800--220000 9900--332200 8800--113300 8800--113300

The feeding jejunostomy catheter was

kept functional for 4 – 15 days, until 50%

of the energy necessities could be given by

mouth. In 3 patients, the jejunostomy had

to be reactivated.

This study allows us to draw a few

conclusions on enteral nutrition in severe

Acute Pancreatitis:

• Ensures the return to intestinal

physiological state;

• Preempts bacterial translocation

by maintaining intestinal

peristalsis;

• Avoids malnutrition;

• Gives good digestive tolerance;

• Betters the quality of life;

• Requires lower costs in

comparison to parenteral

nutrition.

References

1. Beger, H. G.: Surgery in acute

pancreatitis. In: Hepato-

Gastroenterol., 1991, 38 : 92-96.

2. Beuran, M., Grigorescu, M., Pascu,

O.: Actualităţi în patologia

pancreatică. Cluj-Napoca. Ed.

Medicală „Iuliu Haţieganu” 2005, pp.

61-133.

3. Gepts, W., Le Compte, Ph.: The

pancreatic isles in diabetes, in

Diabetes mellitus. In: Skyler I.,

Cathill G. (sub red.), New York

Medical Books, 1981.

4. Gerzof, S. G., Banks, P. A., Robbins

A. H. et al.: Early diagnosis of

pancreatic infection by computed

tomography-guided aspiration. In:

Gastroenterology, 1987, 93 : 131-20.

5. Gianotti, L., Braga, M., Alexander,

J.W.: L’intestino: organo cardine

nella patogenesi delle complicanze

settiche in corso di pancreatite acuta.

Chir-Ital., 1995, 47(2) : 14-24.

6. Meier, R., Sobotka, L.: Suportul

nutriţional în pancreatita acută şi

cronică. In: Rev. Rom. Anest. Terap.

Int., 2001, vol. 9, 1 : 21-24.

7. Powell-Tuck, J., Hennessy, E. M.: A

comparison of mid upper arm

circumference, body mass index and

weight loss as indices of

undernutrition in acutely hospitalized

patients. In: Clinical Nutrition, 2003,

vol.22, 3 : 307-312.

EXTRACORPOREAL SHOCKWAVE

LITHOTRIPSY (ESWL) AS A MEAN OF

TREATMENT IN URINARY LITHIASIS

I. SCÂRNECIU

1 S. LUPU

2 L. L. ONISÂI

3

C. C. SCÂRNECIU4 A. M. LUPU

5

V. D. SCÂRNECIU6

Abstract: In the present, Extracorporeal Shockwave Lithotripsy (ESWL)

represent the mean modality to treat urinary lithiasis, covering 80-90% from

treatment indications. Lithotripsy machines become more performant and

benefit of two methods to localize stones: ultrasonographic and fluoroscopic.

There are still more controversies about the results of using different types of

machines

Key words: renal lithiasis, ESW

1 Transilvania University of Brasov, Faculty of Medicine Brasov, Urology Clinic, Clinic Emergency County

Hospital Brasov. 2 Urology Clinic, Clinic Emergency County Hospital Brasov. 3 Transilvania University of Brasov, Department of Anatomy, Faculty of Medicine Brasov. 4 Transilvania University of Brasov, Department of Internal Medicine. 5 Radiology and Medical Imagistics Department, Clinic Emergency County Hospital Brasov. 6 Transilvania University of Brasov, Faculty of Medicine Brasov.

1. Introduction

Extracorporeal Shockwave Lithotripsy

(or ESWL) was described and used for the

first time in 1980, as research result made

by a German company specialized in the

manufacture of supersonic planes. Under

the effect of the shockwave generated

outside the organism, urinary stones are

disintegrated in small fragments which can

subsequently be eliminated naturally.


Devices can generate shockwave using

electrohydraulic, piezoelectric or

electromagnetic systems, and the stone

locating is made through echographic or

radiographic guiding. The two imagistic

guiding systems have both advantages and

disadvantages: echographic guiding system

is non-radiating and can be used in

locating and visualization of radio-opaque

stones or radio-transparent renal stones;

radiographic guiding system (florroscopic)

is radiating and can be used in locating and

visualization of radio-opaque stones both

renal and uretheral. State of the art,


Devices is equipped with dual-localization

systems, this way, covering a large palette

of imagistic guiding possibilities. [1, 2, 3]

From the moment they are emitted,

shockwaves spread through tissues with a

inessential energy dispersal, even though at

the urinary stone level cavitations (by the

cavitations „bubbles”) and erosion

phenomenon occur or force elements

directly performed by the shockwave.

These phenomenon lead to the calculus


140

disintegration and are formed at a solid-

liquid level (large density difference).

Phenomenon exercised by the cavitations

„bubbles” produced at the solid-liquid

level represent the most important aspect

in all researches made in order to increase


Device efficiency. [1, 2, 3, 4, 5]

ESWL represents a modern approach to

non-invasiv treatment of stones under 12-

20 mm, which covers about 90% of

treatment reference for urinary lithiasis

disease. [1, 2, 3, 7, 8]

The purpose of the study is to evaluate

the efficiency of ESWL in the treatment of

renal stones, but also complications that

may occur and most important the

restrictions of this modern treatment

method, as seen from the experience of the

Urology Clinic, Brasov.

Materials and Method

During the period May 2005 –

November 2008, 412 patients have been

treated by using ESWL at the Urology

Clinic, part of the Emergency County

Hospital in Brasov.

The investigation protocol was standard,

recommended by both The European and

the Romanian Association of Urology, and

it has contained the clinical examination,

usual laboratory investigation (including

urine exam and uroculture), abdominal

echography, reno-vesical radiography,

intravenous urography and in selected

cases retrograde pyelography.

The number of male patients treated with

ESWL was of 195 patients, and the female

patients count was 217. Renal stones were

bilateral in 32 cases, 183 patients in the

right kidney and 197 patients in the left

kidney.

Basinet stones were most frequently

encountered (119 cases), those located in

the middle caliceal group being present in

97 cases, a number of 73 cases calculus

were encountered in the upper caliceal

group and the lower caliceal group had an

incidence of 82 cases. Multiple lythiasis

was encountered in 47 cases.

Imagisticaly speaking, radio-opaque

stones were present in 261 cases and radio-

transparent stones in 151 cases.

The calculus scale treated with ESWL

ranged between 7 and 24 mm (193 cases

under 10 mm, 211 between 10 and 20 mm

and 8 cases above 20 mm).

All procedures were made by using a

Piezolith 2003 (Richard Wolf)


Device with echographic guiding.


sessions required analgesic treatment for

241 patients (58.5% of all cases),

consisting of injectable administration

before the session of Algocalmin, Piafen or

Fortral, combined or not with a systemic

anti-inflamator.

After the Extracorporeal Shockwave

Lithotripsy, all patients have received

antibiotic, analgesic, antispastic and anti-

inflammatory treatment.

Patients were observed for a period of 3

months, being re-evaluated by echography

or reno-vesical radiography and in some

cases by i.v. urography or chemical

analysis of eliminated calculus.

2. Results

Each session of Extracorporeal

Shockwave Lithotripsy usually lasts

between 30 and 50 (including the time

necessary for positioning the patient on the


table). A longer period was needed for

non-cooperant patients, with very thin

patients (positioning them on the table is

more difficult), patients with severe

alteration to their spinal cord (congenital or

degenerative) or patients with a low

threshold of sensibility. Then number of

administrated to each patient was between

1000 and 3000 at frequencies between 60

and 120 per minute (2500 impulses each

session).

Extracorporeal Shockwave Lithotripsy (ESWL) as a Mean of Treatment in Urinary Lithiasis 141

Total disintegration and elimination of

renal stones has been achieved in 93% of

the cases (384 patients). Between 1 and 9

sessions were needed to totally fragment

the calculus. In the great majority of

situations (334 patients) 1 or 2 sessions

have assured the „stone-free” status. 298

patients (72.3%) have eliminated

fragments in the first 24 hours since the

session.

For 24 of all patients assembling of an

ureteral stent was needed, after the renal

push-back of some lobar ureteral calculus

(16 patients), even in case of higher

dimension calculi (aprox. 20mm) when the

use of ESWL could cause the popup of

some high dimension fragments which

uretheral passage would be difficult if not

impossible (8 patients).

Also, Extracorporeal Shockwave

Lithotripsy has been timed in some cases

or urinary infection or cases that presented

us this febrile episode during the

internment (13 patients). In these cases

patients received antibiotherapy and have

been re-evaluated by 2 criteria:

aproximatively 3 weeks of afebrile

condition and sterile urine culture.

Not more than 2 sessions of ESWL were

made in one internment (1 day break). In

all situations patients were re-evaluated at

30 days after ESWL.

The chemical composition of the renal

calculi has an exquisite influence on the

rate of success when using ESWL.

Extracorporeal Shockwave Lithotripsy of

stones made of uric acid were

accompanied by a 30 day rate of success of

95%, and in case of calcium oxalate calculi

the rate of success was of 82% for

dehydrate, also 31% for monohydrate

calculi.

The number of cases that required more

than 2 sessions was 78, especially when

dealing with monohydrate calcium oxalate

with a scale pf over 15 mm.

Uric acid calculi and dehydrate oxalate

have disintegrated into small fragments

with a more easy elimination.

During the procedure 25 patients have

presented with vomiting sensation (anti-

emetic treatment has been administrated),

in 7 cases session halt was necessary

because of patients experiencing vomiting.

Minimal tegumentary lesions were

highlighted in 71 of all cases at the spot of

shockwave penetration, which

spontaneously disappeared in a maximum

period of 24 hours after the procedure.

Haematuria was minimal after each

procedure (considered normal) and has not

caused therapeutically problems, being

present for more than 24 hours.

In 31 patients the evolution has been

complicated by some of the fragments

hitting different segments of the urether

(steinstrasse), 21 of these complications

evolved favourably, with spontaneous

elimination of fragments within a period of

3 days (helped by diuretics, antispastic

medication, antiinflamatory and in some

cases alfa-blockers). 10 of the patients

required uretheroscopy with ballistic

intracorporeal lithotripsy and/or fragment

extraction.

Fig. 1. Renovesical radiography: radio-

opaque image in right renal area (stone)


142

Fig. 2. Intravenous urography at the

same patient

Fig. 3. Renovesical radiography:

residual radio-opaque image in right renal

area after the first ESWL session

Fig. 4. Renovesical radiography: small

residual fragment in the right renal area

and multiple radio-opaque images in the

hypothetic right uretheral tract (steintrasse

after the second ESWL session)

Fig. 5. Renovesical radiography: „stone-

free”status

Extracorporeal Shockwave Lithotripsy (ESWL) as a Mean of Treatment in Urinary Lithiasis 143

3. Discussions

Renal lithiasis treatment before the

discovery of Extracorporeal Shockwave

Lithotripsy was and unique one: surgical

procedure. The discovery of ESWL

represented a true revolution in

therapeutically guidance of this pathology,


being a less invasive method (but not

without complications) used for the

treatment of 80-90% of all renal lithiasis

cases. The European Association of

Urology recommends active treatment with

ESWL in all cases of renal stones over 6-7

mm in diameter.[1,2,3,4,7]

Since the discovery of the first


Device, these have been miniaturised; have

become cheaper and more adaptable. With

all this, even the older (like the one used in

our clinic) have proved to be very efficient,

even if a better collaboration with the

patient is necessary (a more difficult

position on the table, less comfortable for

the patient). In this context, there was

many articles who said that the newest


Devices have won in comfort but lost in

efficiency and reliability. [1,7]

Throughout the studied group no major

complications has been encountered, even

if there are theoretically possible (renal

haematoma and urosepsis are redoubtable

and life threatening).

There are a few factors influencing the

success of Extracorporeal Shockwave

Lithotripsy: calculus scale, the chemical

composition of the calculus, the multitude

of calculi, their localization in different

segments of renal sections (lower success

rate in case of localization in the lower

caliceal group), anathomic particularities

of the degree of renal functionability. High

dimension stones or tougher stones

(monohydrate calcium oxalate) necessitate

many sessions. [1, 3, 5, 7, 8]

4. Conclusions


(ESWL) represents for the moment the

first intent treatment for the most of the

patients with renal and uretheral stones,

being associated with a lower rate of

complication.

Percutaneous nephrolitotomy (NLP)

stands as the gold-standard in case of

stones with dimensions over 20 mm, even

if the procedure is more invasive and

accompanied by a higher rate of morbidity,

not at all negligible.

Monohydrate calcium oxalate stones

usually calls for repeated sessions of

Extracorporeal Shockwave Lithotripsy for

a complete fragmentation. In contrast,

dehydrate oxalate calculi and especially

the uric acid is much easier to approach by

ESWL.

Even if less comfortable for the patient,


Devices of the first generations have a

remarkable success and an excellent

reliability.

References

1. Athanasios, N., Argyropoulus, D.,

Tolley, A.: Optimizing Shock Wave

Lithotripsy in the 21st Century. In:

European Urology, vol. 52, Issue 2,

August 2007, p. 344-350.

2. Grasso, M., Hsu, J., Spaliviero, M.:

Extracorporeal Shockwave Litho-

tripsy, emedicine by WebMD, 2008.

3. Lingeman, J.E., Lifshitz, D.A., Evan,

A.P.: Surgical management of urinary

lithiasis. In: Walsh P, Retik A,

Vaughan D, Wein A, Campbell’s

Urology, 8th edition, Elsevier Science

(USA), 2003, CD-rom edition.

4. Manu, R.: Litotripsia extracorporeală

cu unde de şoc (ESWL). In Urologie

Clinică. Bucureşti. Ed. Medicală

Amaltea, 1998, pag. 162-164.

5. Putman, S.S., Hamilton, B.D.,

Johnson, D.B.: The use of shock wave


144

lithotripsy for renal calculi. Curr Opin

Urol. Mar 2004; 14(2): 117-21.

[Medline].

6. Rassweiller, J.J., Renner, C., Chaussy,

C., Thuroff, S.: Treatment of renal

stones by extracorporeal shockwave

lithotripsy: an update. In: Eur Urol

2001; 39: 187-99.

7. Tiselius, H.G., Ackermann, D., Alken,

P., Buck, C., Conort, P., Galluci, M.:

Working Party on Lithiasis. European

Association of Urology. Guidelines on

urolithiasis. In: Eur Urol 2001,

40:362-71.

8. Yang, H.S., Park, K.S., Min, B.K.:

Extracorporeal shock wave lithotripsy

experience with wolf piezolith 2300

device in 500 patients with upper

urinary tract calculi. In: Korean J

Urol. 1993 Feb; 34(1):109-115.

1Apollonia Dental Medicine Faculty , Petre Andrei University Iaşi

2Dental Medicine Faculty , U.M.F. „Gr. T. Popa” Iaşi

THE PATIENT- RISK MARKER FOR

MEDICAL EMERGENCIES IN THE

DENTAL AND ORAL SURGERY OFFICE

R. FANEA

1 M. VORONEANU

2 C. OROS

2

Abstract: Systemic vision on the case is clinically essential to

understanding the particulars involved in the patient, allowing the detection

of potential factors which could cause emergency dental office.

Therapeutic attitude must be individualized for each case, linking data

obtained through the clinical case history and paraclinical exams, in order to

obtain favorable results. Interdisciplinary approach allows the patient's

knowledge of systemic pathology associated with the medication followed

and particularities that dental treatment involved. Main sources in medical

emergencies in dental office are lacunars evaluations of the patients

constants, spontaneously neuro - psychical reactions or a lack of special

training of the medical staff. Our study was performed on 1680 patients. The

level of installed medical emergencies was 3, 85% distributed as come : 38%

vaso-vagal sincopa ,35% cardio-vascular emergencies, 11% alergic

emergencies, 9% neurologic emergencies,7% other emergencies .

Key words: medical emergencies in dental office, patient systemic risk,

dental fear

1. Introduction

Health care in dentistry and surgery

dentoalveolar, involving two apparently

different aspects: a technically well-

defined, the strict specialist and one less

area that includes the virtually all the

particulars that the patient is presented to

the dental office [7]. Whatever the precise

technique would be dental and physician's

skill if not taken into account the specific

conditions of each patient, medical service

may not be up to a higher level, the final

outcome may be compromised by the

appearance of complications with high

medical risk. Preoperatory stage is

absolutely necessary to know the patient,

anesthetic risk assessment [1]. Many

doctors are concerned about the idea of not

losing too much time in discussion with

patients and to move as quickly as the

dental care itself.

Many accidents that occur in dental

offices are attributable to just a superficial

examination incomplete, messy. Patient

exam limited to oral cavity is totally

inadequate, causing the wrong conclusions,

often generating accidents and serious

complications [2, 3]. Patients to be

subjected to an oral surgical intervention

have more or less a combination of general

potential problems, known or unknown.

Bulletin of the Transilvania University of Braşov � Vol. 1 (50) – 2008 � Series VI 146

Unfortunately, the investigation into

dental patient usually stops more on the

history of the pathological condition

brought on the ill treatment and

counseling. From the viewpoint of an

organic exam, typically the only practical

measure values and Heart Rate of arterial

pressure. [4,8]


The aim of our study was to evaluate

clinically, statistically - incidentally the

role of risk factors assign patient that can

lead to a medical emergency. Our study

has compressed a lot human composed of

1680 patients randomly selected to the

addressability their problems oral surgery

solve oral and maxillo-facial surgery clinic

(ambulatory), in University Clinic of

Faculty of Dental Medicine of Iasi, in

1.03.2006-1.05.2008.

Directions of research have sought to

identify risk factors related to specific

patient -age, gender, general illness,

anxiety level involved in spontaneous

medical emergencies that can take place in

dental office.

In the batch of 1680 patients as a first

stage of the study seemed interesting to us

to get distribution on variable patient with

land under specific conditions versus

patient apparently healthy. Statistics

deduction have led us to the following

percentage results:

• to 38.57% interpretation of the case

history of medical-surgical led us to

identify a particular field;

• to 61.43% of the case history we

could not detected information

regarding the presence of serious

systemic diseases, with immediate

impact on therapeutic plan (Graph 1).

Graph. 1

In the batch of 1680 patients we practiced

dental surgery maneuvers. Labor operation

that was in first place in the top of

interventions were: (Graph 2)

• Tooth extraction………………8.14%

• incision, drainage and evacuation

of perimaxilary abscess………22.93%

• APIC resection ………………15.32%

• endodontic drainage ………...10.76%

• face wound suture ……….9.00%

• gingivectomia…………… 3.85%

The Patient – Risk Marker for Medical Emergencies in the Dental and Oral Surgery… 147

Graph 2

Statistics deduction have led us to the

following percentage results: (Graph 3)

• 93.43 % have not triggered an

medical emergency during oral surgery;

• 6.57 % triggered medical

emergencies during oral surgery.

Graph 3


For general assessment status, we

designed a questionnaire identifying their

own risk assessment and emergency care:

Analysis of data obtained with the help

of medical questionnaire from the lot of

patients who triggered an emergency

medical treatment performed during the

ambulatory surgical dentoalveolar he

revealed the following distribution:

1. Gender index (Graph 4)

- women ................................... 41.8%

- men ..................................... .58.2%


Graph 4

2. Age index (Graph 5)

-age group 14-21 years ……………10%

- age group 21 - 30 years …………..22%

- age group 31-40 years ……………..48%

-age group 41-60 years ……………..11%

-age group 61-70 years ………………9%

Graph 5

3. Systemic illness index (Graph 6)

- cardiovascular diseases .............. 31.4.7%

-metabolic disease ...........................18.8%

-neurological disease ……………… 3.8%

- patients "apparently" healthy .........46.0%

The Patient – Risk Marker for Medical Emergencies in the Dental and Oral Surgery… 149

Graph 6

4. DAS index (Dental anxiety score):

(Graph 7)

- DAS-C 1 (patient calm) .................17.6%

- DAS-C 2 (restless patient ) ........... 19.3%

- DAS-C 3 (moderate patient anxious)

.........................................................25.00%

- DAS C-4 (strong patient anxious) ............

…………………………………….38.04%

Graph 7

Simple deduction statistical data explored

us out - based on the percentages obtained

majority on each index studied, an issue

crucial to the practice of dental surgery level

of dental anxiety and the status of the

patient's general benchmarks that are

requires the greatest attention from the

physician in order to prevent medical

emergencies. Transposition in terms of the

results of medical tests specific data we have

helped in developing our research results:

• Women (with a statistical average

of 48.3%) and men (with a statistical

average of 51.6%) have the potential


trigger an emergency medical men are

more often involved in triggering an

unforeseen medical event during dental or

dentoalveolar surgery.

• During dental or surgical

maneuvers, installing a medical emergency

is influenced by patient age, patients younger

21 - 30 years (with an average percentage of

22%), 31-40 years (with an average of 47

percentage 5%) were more likely to launch

an unforeseen medical event.

• During dental or dentoalveolar

surgery installing an emergency medical

field is influenced by the patient. Although

the largest is owned by patients "apparently

healthy" (with a statistical average of 51%)

patients had pre-existing general showed a

certain tendency to launch an unforeseen

medical event: cardiovascular diseases (with

a statistical average of 23. 35%), metabolic

diseases (with a statistical average of 17. 9%),

pulmonary disease (with a statistical average

of 11.7%) and neurological disorders (with a

statistical average of 3. 8%).

• During dental or dentoalveolar

surgery, installing a medical emergency is

strongly influenced by the level of anxiety

of the patient. Thus our research showed

that 38% of patients, who have triggered

medical emergencies, are part of the

category of patients with strong anxiety,

responsive (DAS C-4). Is closely patients

and moderate anxious DAS C-3 (with a

statistical average of 32.1%), followed by

patients slightly uneasy DAS C-2 (with a

statistical average of 25%) and finally

patients calm DAS-C 1 (with a statistical

average of 23.26%).

Conclusions

During dental treatment to patients with

general illness and patient apparently

healthy- fear, pain triggers compensatory

vegetative and humoral mechanisms,

leading to the amendment primarily to

cardio-vascular parameters. Medical

emergencies although not a right and a

notable frequency in the practice of

dentistry, they are not exceptions,

therefore, identify risk factors puzzle in

which the patient is the central piece, is the

first essential step.

References

1. Academy Report: Periodontal

management of patients with

cardiovascular diseases. In: J.

Periodont., 73: 954-968, 2002.

2. ACC/ AHA: Guideline update for the

management of patients with unstable

angina and non-ST-segment elevation

myocardial infarction. Summary

article: a report of the American

College of Cardiology American

Heart Association task force on

practice guidelines (Committee on the

Management of Patients With

Unstable Angina). In: J. Amer. Coll.

Cardiolog. 40: 1366-1374, 2002.

3. AHA Guideline: Evidence Based

Guidelines for Cardiovascular

Disease Prevention in women. In: J.

Circulation, 109: 672-693, 2004.

4. American Dental Association:

Council on Community Health,

Hospital Institution and Medical

Affairs. Patients with cardiovascular

disease. In: Oral Health Care

Guidelines,1-13, 1990.

5. American Heart Association: Heart

Disease and Stroke Statistics. Update,

Dallas, 2004.

6. Balan, H., Iordache, N.: Urgenţe

medico-chirurgicale. (curs pentru

stud. an V, Facultatea de Medicină

Dentară, U.M.F. “Carol Davila”).

Bucureşti. Ed. Medicală, 2005.

7. Jowett, N.I., Cabot, L.B.: Patients

with cardiac disease: considerations

for the dental practitioner. In: Brit.

Dent. J. , 189: 297-302, 2002.

8. Voroneanu, M., Bucur, A, Vicol, C.,

Dinescu, N.N.: Actualităţi privind riscul

urgenţelor medicale în cabinetul de

medicină dentară. Iaşi. Ed. PIM, 2007.

ULTRASTRUCTURAL CHANGES IN A

CASE OF RECURRENCE AFTER

VARICOSE VEINS SURGERY

Florin COMŞA

1

Abstract: Heredity plays an important role in varicose veins disease. The

weak wall theory with secondary valvulare incompetence has been proposed

as the most likely cause for primary varicose vein disease. Ultrastructural

wall changes in varicose veins have been deeply studied. We present a case

of varicose vein recurrence in which we have been searching for histological

changes using light and electron microscopy in comparison with those found

in primary varicose vein disease

Key words: Varicose veins recurrence, smooth muscle cells, electron

microscope

1 Diagnostic and Treatment Center „Dr. Victor Babeş”, Bucharest.

1. Introduction

In the varicose veins disease, the

heredity is an important key element [3, 6,

7]. More than a half of the affected persons

have positive family records for the

varicose veins disease, which suggests a

genetically inherited bad quality of the

veins wall. The parietal theory with

secondary valvulare insufficiency has been

referred to as the most likely cause of

primary varicose veins disease, offering an

explanation why the varicose veins

dilatations are often located under a

competent valve [2].

In the last decade, the clinical and

experimental studies revealed a deficiency

of the vein wall as a cause of varicose

veins disease. Varicose veins dilatation at

the level of the inferior lower limbs can

occur even in the absence of valvulare

incompetence. Moreover, when a vein is

subject to high pressures (which is for

example the case in the insufficiency of a

perforating vein or when the vein is used

as a graft in an arterial by-pass) the wall

hypertrophies itself in a first stage and

afterwards distends uniformly or non-

uniformly. The alternation of the

apparently normal segments with those

much dilated ones noticed at the level of

varicose veins has nothing to do with the

disposing of the valve or its functionality,

most of the dilated varicose veins segments

being located immediately under the

valves which appear competent on Doppler

examination.

2. Case Report

We present the case of Ms. EL, a 36

years old patient, which was hospitalized

at „Dr. Victor Babeş” Diagnosis and

Treatment Center on the date of November

5th, 2007. The reason for hospitalization

was the recurrence and development of

dilatation of the superficial venous net-

work at the level of the right pelvic limb.


152

The disease developed insidiously over

15 years prior to the dilatations of the

superficial veins network for which the

patient underwent surgery – stripping of

the internal long saphenous vein in 1998

under general endotracheal anaesthesia.

The family history indicates the mother

having suffered of varicose veins disease.

The clinical examination finds dilatations

of the superficial venous network at the

level of the right inferior lower limb.

Pulmonary radiography Chest X-Ray

showed no pleura-pulmonary lesions with

active – in progress character. The

laboratory tests were normal, except for

some high values for eosinophils 4.19 %

(VN 0-4%) and for monocits 10.2% (VN

2-8%). Normal EKG.

The venous ultrasound exam showed many

dilated perforating veins which were marked

prior to surgical procedure. (Fig. 1).

Fig. 1. Dilatated perforating vein

The diagnosis was: relapsed varicose

veins on the right pelvic limb and a surgery

was done under tronculare and loco-regional

anaesthesia with lidocain 1%, and consisted

of a segmentary phlebectomy with ligature

of the perforating veins.

Post-surgery outcome was favorable the

patient being discharged in the same day (50

minutes after surgery). At the subsequent

check-ups, 1 month and 6 months after

surgery, the patient did not present any

symptoms and the surgical wounds were

normally cured with thin scars.

3. Discussion

In the case we studied light microscopy

which shows the following changes:

segmental thickness of the endothelial

layer, thickness of media, activated

endothelial cells with clear vacuoles, lipid

droplets within the media and increased

quantities of extra cellular matrix in

endothelial and media layer (Fig. 2).

Fig. 2. In thickened area of endothelial

layer (L) one can see smooth muscle cells

(SMCs) smaller than in media (M) in an

abundant extra cellular matrix (*). Extra

cellular matrix (*) can also be seen in

media (M). Some endothelial cells (→) fell

into the venous lumen (L). Light micro-

scopy (LM), toluidine blue stain (20x).

Ultrastructural Changes in a Case of Recurrence After Varicose Veins Surger 153

Electron microscopy showed endothelial

lesions (activated endothelial cells with

clear vacuoles in cytoplasm (Fig. 3),

elongated cells starting to desquamate into

the lumen (Fig.4), basal lamina thickened

and discreetly lamellate, collagen fibbers

in the sub-endothelial layer and disor-

ganization of internal elastic lamina), SMC

lesions (SMCs activated with large

perinuclear rough endoplasmic reticulum

and polyribosome (Fig. 5), SMCs lamina

basal thickened), migration of SMCs from

media to intimae layer, disorganization of

internal elastic lamina, lot of fibrilar

collagen (type I or III), fibroblasts in media

(Fig. 6).

Fig. 3. Endothelial cell (End) with

plasmalema (mb) discreetly lamellated.

Internal elastic lamina (el) is discontinuous

and some SMCs (CMN) surrounded by

collagen fibers (col) seem to migrate beneath

endothelial layer (→). L – vascular lumen.

Electron microscopy (EM). 15.000x.

Fig.4. Detail from Fig. 2. Elongated

endothelial cells (End) as well as some

SMCs (CMN) have lipid droplets (*).

SMCs (CMN*) with large perinuclear

rough endoplasmic reticulum. Col –

collagen fibers, el-lamina elastica, L-

vascular lumen. EM. 9.100x.

Fig. 5. SMC (CMN) with large rough

endoplasmic reticulum. Col –collagen

fibers, N – nuclei. EM. 11.000x.


154

Fig.6. Fibroblasts (Fb) from media

surrounded by collagen fibers (col) which

seem to phagocyte lipid droplets (#).

EM. 9.100x.

The results of our study confirm the

results from other studies (from primary

varicose vein disease).

The diameter of vessel depends not only

on the transmural pressure and tension

generated in the vessel wall, but also on

any increase in the wall area due to

hyperplasia and/or hypertrophy of the

different wall elements such as SMCs.

This hyperplasia and/or hypertrophy

appear in order to counteract the distending

force; this equilibrium has been disrupted

in varicose vein [1, 3]. The relaxation of

muscle cells associated with their

gradually increasing decay, as well as the

decreased tensile strength and elasticity of

the connective tissue fibbers are direct

reasons for the elongation and lateral

blowouts of the veins. The exact

mechanism of intimae thickening in

varicose veins is a matter of controversy

and various explanations have been put

forward by different investigators [1, 2, 3,

4, 5, 6, 7, 9, 11].

Light microscopy examination (Fig. 2)

showed lumen diameter increased

generalized thickness of the wall and

hypertrophy of the sub-endothelial tissues,

which made the venous wall to protrude

into lumen [6]. It was highlighted

elongation of the intimae, which was

disposed in many folds and invaginations,

alternating with zones of descuamation and

discontinuity of endothelial layer. Electron

microscopy showed in normal veins intact

endothelium layer, with endothelial cells

even disposed on the sub-endothelial layer

[6, 7]. In varicose veins section, the

endothelial layer was disposed with folds

and invaginations, endothelial cells

become crowded, hypertrophied and

vertically elongated containing micro-

filaments in the cytoplasm mainly related

to their supposed contractility.

Underneath these cells were seen clear

vacuoles (Fig. 7), lipid droplets and ghost

bodies [7]. Within the folds the endothelial

cells became more compressed, more

elongated, some of them even lost into the

lumen (Fig. 2). Some of these

invaginations close completely, forming

veritable traps for blood elements like

erythrocytes [7]. Along the invaginations,

the elongated endothelial cells start to

accumulate lipid droplets and start to peel

of the intimae, until they fell into the

lumen leaving behind bear intimae [6].

Fig.7. In media of the vein focal

distribution of the lipid droplets (v) located

between the normal SMCs can be seen.

LM, toluidine blue stains (10x).

Ultrastructural Changes in a Case of Recurrence After Varicose Veins Surger 155

In sections of the distal calf varicosities,

break down of the intimal surface and loss

of the endothelial cells exposed the basal

lamina and the subintimal tissues to the

lumen (Fig. 5). This let blood components,

like platelets, erythrocytes and lipid

droplets, to stick to the bare intimae and

migrate through the wall and lay within the

wall [6, 7]. When SMCs come into close

contact with monocytes, their capacity for

collagen phagocytosis, decomposition and

disintegration is increased. This might

explain the process of clinical superficial

thrombophlebitis, which sometimes

complicates cases of varicose veins. The

rational surgical approach would therefore

be, as proposed by Venturi et al. [1], to

remove the whole long saphenous vein,

rather than removing only the varices.

Electron microscopy examination of

varicose vein sections showed in tunica

intimae and media wide separation of the

SMCs by an increased amount of extra-

cellular matrix and variable bands of

collagen fibbers. These changes were

present in both the medial and intimal

SMCs. SMCs were abnormal in shape and

lost their regular fusiform appearance, with

extension of plasmalemal projections,

some of which separated completely from

the cell surface [6, 7] forming ghost

bodies. With the loss of their cellular

integrity, some SMCs split into fiber-like

material, possibly collagen fibers, small

fragments that are widely scattered in the

extracellular space. Another ability of

SMCs is to phagocytose not only collagen

and elastic fibers (Fig. 7), but also other

damaged SMCs [6].

The only logic treatment is the surgical

one consisting of segmentary phlebectomy

with ligature of the incompetent

perforating veins.

The recurrence of varicose vein can lead

to skin alterations, superficial thrombo-

phlebitis and venous ulcer. Natural evo-

lution of this disease is severe and inva-

lidating in case it is untreated or treated

conventional. Ligature of the incompetent

perforating veins and segmentary phleb-

ectomy is therefore the elective treatment.

Each treatment must be personalized

accordingly to the disease stage.

The peculiarity of this case is the period

from initial surgical procedure and

recurrence of varicose vein.

Conclusion

Among paraclinical examinations, the

venous ultrasound exam has a great value,

allowing an accurate assessment of the

condition of the superficial and deep

venous system and of the perforating veins

as well as of the anatomic situation of

every specific case.

The surgical procedure must follow to

the ligature of the incompetent perforating

veins as much as possible and remove the

varicose veins packs in order to suppress

the deep venous reflux because of the risk

of local complications, among which

venous ulcer is the most dreadful.

Regular clinical exams during the whole

lifetime of the patients suffering from

varicose veins are totally justified as

proven by the 9 years recurrence in the

above presented case.

Electronic microscopy indicates the same

type of changes in varicose veins disease

and in its recurrence.

References

1. Amould, T., Michiels, C., Janssens, D.,

Berma, N. and Remacle, J.: Effect of

Ginkor Fort on Hypoxia-induced

neutrophils adherence to human

saphenous vein endothelium. In: J.

Cardiovasc. Pharmacol. 1998, 31:

456–463.

2. Coleridge-Smith, P.D.: The micro-

circulation in venous hypertension. In:

Vasc. Med. 1997, 2: 203–213.

3. Janssens, D., Michiels, C., Guillaume,

G., Cuisinier, B., Lonagie, Y. and

Remacle, J.: Increase in circulating

endothelial cells in patients with


156

primary chronic venous insufficiency:

protective effect of Ginkor Forte in a

randomized double-blind, placebo-

controlled trial. In: J. Cardiovasc.

Pharmacol. 1999, 33: 7–11.

4. Khan, A.A., Eid, R.A. and Hamdi, A.:

Structural changes in the tunica intima

of varicose veins: A histopathological

and ultrastructural study. In: Pathol.

2000, 32: 253–257.

5. Lengyel, L. and Acsady, G.Y.:

Histomorphological and patho–

biochemical changes of varicose veins:

a possible explanation of the

development of varicosis. In: Acta

Morphol. Hungar. 1990, 38: 259– 267.

6. Mahmoud, A.W. and Refaat, A.E.

Smooth Muscle Changes in Varicose

Veins: An Ultrastructural Study. In: J.

Smooth Muscle Res. 2001, 37 (5, 6):

123–135.

7. Mahmoud, A.W. and Refaat, A.E.

Intimal Changes in Varicose Veins: an

Ultrastructural Study. In: J. Smooth

Muscle Res. 2002, 38 (3): 63–74.

8. Obitsu, T.: Histopathological studies

of the valves of varicose veins. In:

Phlebol. 1990, 5: 245–254.

9. Psaila, J.V. and Melhuish, J.: Visco–

elastic properties and collagen content

of the long saphenous vein in normal

and varicose veins. Br. J. Surg. 1989,

76: 37–40.

10. Travers, J.P., Brookes, C.E., Evans, J.,

Baker, D.M., Kent, C., Makin, G.S.

and Mayhew, T.M.: Assessment of

wall structure and composition of

varicose veins with reference to

collagen, elastin and smooth muscle

content. In: Eur. J. Vasc. Endovasc.

Surg. 1996, 11: 230–237.

11. Venturi, M., Bonavina, L., Annoni, F.,

Colombo, L., Butera, C., Peracchia, A.

and Mussini, E.: Biochemical assay of

coragen and elastin in the normal and

varicose vein wan. In: J. Surg. Res.

1996, 60: 245–248.

INTEGRATED POSITRON-EMISSION

TOMOGRAPHY AND THE STAGING OF

NODULAR NON-SMALL-CELL LUNG

CANCER

Dana ALEXANDRESCU

1

Abstract: We compared the diagnostic accuracy of integrated positron-

emission tomography and computed tomography (PET-CT) with that of CT

alone, that of PET alone and that of conventional visual correlation of PET

and CT in determining the stage of disease in non-small-cell lung cancer,

less than 3 cm

Key words: Integrated positron-emission tomography, stadialisation of

disease in non-small-cell lung cancer.


1. Introduction

Computed tomography (CT) has an

important role in the initial determination

of the stage of disease in lung cancer. CT

provides excellent morphologic infor-

mation on the extent of disease but has

limited ability to differentiate between

benign and malignant lesions in an organ

or in lymph nodes. Whole-body positron-

emission tomography (PET) with

fludeoxyglucose F18 ([18 F]fluoro-2-

deoxy-D-glucose) has a higher rate of

detection of mediastinal lymph-node

metastases as well as of extrathoracic

metastases [4, 6, 8, 10, 12, 14]. It has also

proved effective in the management of

non-small-cell lung cancer [4, 6, 11, 13].

Since commercial PET scanners provide

nominal spatial resolution of 4.5 to 6 mm

in the center of the axial field of view,

even lesions that are less than 1 cm in

diameter can be detected on the basis of an

increased uptake of fludeoxyglucose F 18.

However, fludeoxyglucose F 18 is also

taken up by muscles and inflammatory

processes. Furthermore, PET provides

imprecise information on the exact

location of focal abnormalities. Thus, even

if the results of PET and CT are visually

correlated, the precise location of lesions is

sometimes difficult to determine. Recently,

integrated PET-CT scanners have been

introduced [1]. Initial results in oncology

have been encouraging. Therefore, we

prospectively compared the accuracy of

integrated PET-CT with that of other

imaging methods in staging nodular non-

small-cell lung cancer.

Materials and Methods

46 patients with proven or suspected

non-small-cell lung cancer were enrolled

in the study at the Universitary Hospital

Luzern. All performed PET-CT scan at the

University Hospital of Zürich, Switzerland,

a teaching and tertiary care hospital and a

major referral site for patients with cancer.


158

Thoracic surgeons from Cantonal

Hospital Luzern at the facility have been

using PET routinely preoperative

assessment of disease stage since 1996. All

patients underwent conventional staging

based on a review of the medical history,

physical findings and results of blood tests,

bronchoscopy and contrast-enhanced CT

of the chest and upper abdomen and all

also underwent integrated whole-body

PET-CT.

All patients were referred for surgery

between July 2002 - December 2005 in

Thoracic Surgical Department of the

Universitary Hospital Luzern and were

included in the study after giving written

informed consent in accordance with the

regulations of the institutional review

board. Seven patients were excluded from

further study because histologic analysis

revealed in 3 cases benign tumors and in 4

cases metastases of oral cavity and

pharynx carcinoma, large intestine carci-

noma, breast carcinoma and melanoma.

Thus, 39 patients (28 men and 11 women)

with a mean age of 61.59 (range, 38 and

78) remained in the study. Histologic

analysis revealed adenocarcinoma in 5

patients, squamous-cell carcinoma in 9

patients, large-cell carcinoma in one case

and tipic carcinoma in one patient.

Patients received an intravenous

injection of 350 to 400 MBq of fludeo-

xyglucose F 18 and then rested for appro-

ximately 50 minutes before undergoing

imaging. Image acquisition was performed

with use of an integrated PET-CT device

(Discovery LS, GE Medical Systems)

consisting of an Advance NXi PET

scanner and a four-slice Light Speed Plus

CT scanner. The axes of both systems were

mechanically aligned so that shifting the

examination table by 60 cm moved the

patient from the CT into the PET gantry.

The resulting PET and CT images were

coregistered on hardware.

An unenhanced CT image was obtained

from the patient’s head to the pelvic floor

with use of a standardized protocol

involving 140kV, 80 mA, a tube-rotation

time of 0.5 second per rotation, a pich of 6,

and a section thickness of 5 mm, which

was matched to the section thickness of the

PET images. Immediately after CT, PET

was performed that covered the identical

axial field of view. The acquisition time

for PET was 4 minutes per table position

and 24 minutes in all. Patients were

instructed to hold their breath in normal

expiration for 22 seconds during the

acquisition of the CT images and to

breathe shallowly during the acquisition of

the PET images. PET-image data sets were

reconstructed iteratively with segmented

correction for attenuation with use of the

CT data. Corregistered images were

displayed by means of eNTEGRA

software (GE Medical Systems) [2, 7, 9].

Lung resections were performed with

mediastinal lymph-node dissection, which

consisted of dissection of all nodes at

stations 2 through 4 and 7 through 9 on the

right side and of stations 4 through 9 on

the left side, according to the mapping

system of the American Thoracic Society.

The images were prospectively analyzed

by a nuclear-radiology physician and a

thoracic surgeon (both with more than 10

years of medical experience) and assigned

a TNM stage. After reviewing the CT

images for each patient, the reviewers

assessed attenuation-corrected PET

images. Thus, the reviewers interpreted the

PET images with the knowledge of the CT

findings and visually correlated the PET

and CT images. This approach was chosen

because it represents the standard practice

of combined reading of PET and CT

images. On the basis of their visual

correlation, the reviewers again assigned a

TNM stage. When a clear differentiation

between different tumor stages was not

possible, both stages were noted and the

findings were deemed equivocal. They

analyzed also the attenuation-corrected

PET images, co-rregistered PET-CT

images and assigned a TNM stage. Finally,

TNM stages based on the various imaging

Integrated Positron-Emission Tomography and the Staging of Nodular Non-Small-Cell Lung Cancer 159

procedures were correlated with patho-

logical stages. Statistical analysis was

carried out with SPSS software. To

identify any improvements in the accuracy

of staging associated with the use of co-

registered PET-CT, the tumor and node

stage of each imaging method was

assessed by means of a score ranging from

0 to 2, in which a score of 0 indicated

incorrect findings, a score of 1 correct but

equivocal findings and a score of 2 correct

findings. If the stage was correctly

determined (that is, it matched the stage

determined by conventional means), but

owing to equivocal findings, more than

one stage was noted by review board, the

result was classified as correct but

equivocal. A paired sign test and Wilcoxon

test were used to compare co-rregistered

PET-CT with the other imaging methods.

Results

As compared with visual correlation,

integrated PET-CT provided additional

information consisted of the exact location

of lymph nodes, precise evaluation of

chest-wall infiltration and of mediastinal

invasion, correct differentiation between

tumour and peritumoural inflammation or

atelectasis and elimination of distant

metastases.

Over-all, integrated PET-CT provided

more accurate information on the stage of

disease than did the other two imaging

methods, including visual correlation of

PET and CT. Statistically significant

improvements were found particularly in

terms of the tumour stage (Table 1).

Table 1

Comparison of the Diagnostic Accuracy of Integrated PET-CT with CT Alone, PET

Alone and Visual Correlation of PET and CT images

Variable P Value

Wilcoxon Test Paired sign Test

Tumour stage (n=39)

PET-CT vs. CT alone 0.001 0.002

PET-CT vs. PET alone <0.001 < 0.001

PET-CT vs. visual correlation of PET and CT 0.017 0.021

Node stage (n=39)

PET-CT vs. CT alone 0.003 0.007

PET-CT vs. PET alone 0.019 0.039

PET-CT vs. visual correlation of PET and CT 0.011 0.021

In 39 patients the tumour stage was

confirmed histologically. Table 2 shows

the diagnostic accuracy of the various

imaging methods:


160

Table 2

Diagnostic Accuracy of the Imaging Methods

with Respect to Tumor Stage in 39 patients

Imaging Method Classification

Correct

Classification

Correct but

Equivocal

Classification

Incorrect

Imaging Method (Score of 2) (Score of 1) (Score of 0)

No.of.patients (%)

CT alone 20 (51.28) 9 (23.07) 10 (25.64)

PET alone 15 (38.46) 15 (38.46) 9 (23.07)

Visual correlation

of PET and CT 25 (64.10) 5 (12.82) 9 (23.07)

Integrated PET-CT 33 (84.61) 4 (10.25) 2 (5.12)

In all 39 patients, the node stage was

confirmed histologically.

Table 3 shows the diagnostic accuracy of

the various imaging methods:

Table 3

Diagnostic Accuracy of the Imaging Methods

with Respect to Node Stage in 39 patients

Imaging Method Classification

Correct

Classification

Correct but

Equivocal

Classification

Incorrect

Imaging Method (Score of 2) (Score of 1) (Score of 0)

No.of.patients (%)

CT alone 21 (53.84) 4 (10.25) 14 (35.89)

PET alone 23 (58.97) 11 (28.20) 5 (12.82)

Visual correlation

of PET and CT 25 (64.10) 1 (2.56) 13 (33.33)

Integrated PET-CT 33 (84.61) 1 (2.56) 5 (12.82)

Integrated Positron-Emission Tomography and the Staging of Nodular Non-Small-Cell Lung Cancer 161

Conclusion

1. The results suggest that integrated

PET-CT is superior to PET alone, CT

alone, or visual correlation of PET

with CT in determining the stage of

disease in non-small-cell lung cancer.

2. The anatomical correlation of the

radionuclide uptake made possible a

more precise delineation of the

location of the primary tumour.

3. With integrated PET-CT were found

significant improvements in tumour

staging, improved the diagnosis of

chest-wall infiltration and mediastinal

invasion by the tumour.

References

1. Beyer, T., Townsend, D.W., Brun, T,

et al.: A combined PET/CT scanner for

clinical oncology. In: J Nucl Med

2000; 41: 1369-79.

2. Camara, O., Colliot, O., Delso, G.,

Bloch, I.: Apport de contraintes

anatomique au recalage non lineaire

d’image TDM et TEP dans les regions

thoracique et abdominales, n

Reconnaissance des Formes et

Intelligence Artificielle RFIA 2004.

Toulouse. France, 2004; 97-806 .

3. Dietlein, M., Weber, K., Gandjour, A.,

et al.: Cost-effectiveness of FDG-PET

for the management of potentially

operable non-s mall cell lung cancer:

priority for a PET-based strategy after

nodal-negative CT results. In: Eur J

Nucl Med 2000; 27: 1598-609.

4. Dwamena, B.A., Sonnad S.S.,

Angobaldo J.O., Wahl R.L..

Metastases from non-small cell lung

cancer: mediastinal staging in the

1990s-meta-analytic comparison of

PET and CT. Radiology 1999; 213:

530-6.

5. Gupta, N.C., Graeber, G.M., Rogers,

J.S. II, Bishop, H.A.: Comparative

efficacy of positron emission

tomography with FDG computed

tomographic scanning in preoperative

staging of non-small cell lung cancer.

In: Ann Surg 1999; 229: 286-91.

6. Kalff, V., Hicks, R.J., MacManus

M.P., et al.: Clinical impact of (18)F

fluorodeoxyglucose positron emission

tomography in patients with non-

small-cell lung cancer: a prospective

study. In: J Clin Oncol 2001; 19:.111-8

7. Lardinois, D., Werder W., Hany T. F.,

Kamel E.M., Korom, S., Seifert, B.,

Schulthess G. K. von, Steinert, H. C.:

Staging of non-small-cell lung cancer

with integrated positron-emission

tomography and computed

tomography. In : N. Engl J Med 2003,

348: 2500-7.

8. Marom, E.M., McAdams, H.P.,

Erasmus, J.J., et al.: Staging non-small

cell lung cancer with whole-body PET.

In: Radiology 1999; 212: 803-9.

9. Nagel, C.C.A., Bosmans, G., Dekker,

A.L.A.J., Öllers, M.C., De Ruysscher,

D.K.M., Lambin, P., Minken, A.W.H.,

Lang, N., Schäfers, K.P.: Phased

attenuation correction in respiration

correlated CT/PET. In: Med Phys

2006, 33: 1840-1847.

10. Pieterman, R.M., van Putten, J.W.G.,

Meuzelaar, J.J., et al.: Preoperative

staging of non-small-cell lung cancer

with positron-emission tomography.

In: N Engl J Med 2000; 343: 254-61.

11. Seltzer, M.A., Yap, C.S., Silverman,

D.H., et al.: The impact of PET on the

management of lung cancer: the

referring physician’s perspective. In: J

Nucl Med 2002; 43: 752-6.


162

12. Steinert, H.C., Hauser M., Allemann

F., et al.: Non-small cell lung cancer:

nodal staging with FDG PET versus

CT with correlative lymph node

mapping and sampling. In: Radiology

1997, 202: 441-6.

13. van Tinteren, H., Hoekstra, O.S., Smit,

E.F., et al.: Effectiveness of positron

emission tomography in the

preoperative assessment of patients

with suspected non-small-cell lung

cancer_the PLUS multicenter

randomised trial. In: Lancet 2002,

359: 1388-93.

14. Weder, W., Schmid, R.A., Bruchhas,

H., Hillinger, S., von Schulthess, G.K.,

Steinert, H.C.: Detection of extra-

thoracic metastases by positron

emission tomography in lung cancer.

In: Ann Thorac Surg 1998; 66: 886-92.

1Poznan University of Medical Sciences

SIGNIFICANCE OF EMBRYONIC STEM

CELLS IN REGENERATIVE

MEDICINE

Ewa BAUM

1

Abstract: The turn of 21

st century is a period of rapid progress in the field

of biological sciences. Scientific discoveries constitute the foundation for the

development of new medical technologies that are used in the treatment of

various conditions. An example of this is the use of stem cells in organ

transplantation. Stem cells, which are present not only in the bodies of

foetuses, but also in adult people, are used for repairing damaged tissue and

organs. The development of techniques for isolating, breeding and

reimplanting stem cells makes it possible to use them for these purposes.

However, using stem cells in organ transplants, especially embryonic stem

cells, is also the source of ethical dilemmas that result from the fact that

biological material is transferred from a donor to a recipient. Experts believe

that the future of stem cells in organ transplantation depends not only on the

advancement of biology, but also, to an equal extent, on the solving of the

ethical considerations associated with this type of therapy. Finally questions

of both essential and ethical significance of the embryonic stem cells in

regenerative medicine are also the result of progress in medical sciences.

Keyword: Ethics, embryonic steam, transplant

The term regenerative medicine

encompasses a field of medicine aiming at

the recreation of damaged human cells and

organs. One of the pioneers in this field,

Professor Ioannis V. Yannas, claims that if

any part of a human body is damaged, the

whole effort of the organism is targeted at

the healing process and at limiting the

systemic reactions at the expense of the

damaged organ which atrophies [25]. Such

a reaction is determined by the human

body’s restricted capacity to regenerate.

Hence, for many years, scientists looked

for ways to overcome this weakness and

this was one of the reasons for the

development of transplantation science, i.e.

the science of organ grafting. Progress in

this field depended not only on the

surgeons’ efficiency of surgeons, but also

on the knowledge of immunology which

was necessary to stop the rejection of

grafted organs. The first transplantation

attempt was a kidney transplant on a pair

of twins in 1954, followed by

transplantations of the liver (1963), the

pancreas (1966) and the heart (1967) [8].

The ensuing transplantation, performed in

1968, was that of bone marrow and the

significance of this procedure proved

extremely important. Contrary to the

previous transplantations which included

mature, fully morphologically and

functionally developed organs, the

transplantation of bone marrow introduced

into the host organism undifferentiated

elementary marrow cells which are then

transformed, in the host organism, into

differentiated blood cells [8].


164

We can accept that the bone marrow

transplantation was a pioneering albeit

unconscious example of using stems cells

in medicine.

Concurrently to the development of

transplantation science, significant

progress was made in in vitro cell growth

techniques. This launched a new field of

regenerative medicine referred to as tissue

engineering, a term introduced by

Professor Yuan-Cheng B. Fung of the

University of California, San Diego, USA

[8]. Attempts were made to concurrently

and jointly grow, in in vitro conditions,

living tissue which could be transplanted

into living organisms. This was how the

so-called ‘artificial biological skin’

developed. It was approved for clinical

practice in the USA in 1988. Different

variations of this product appeared in the

following years. An alternative approach

included the creation of substrates that

consisted of biologic connective tissue

components, e.g. glycosaminoglycans and

collagen, which, after being implanted in

an organism, became a base for the growth

of autologous cells from the host’s skin.

This was introduced to clinical practice in

2002 under the name Integra®. The initial

success in the field of tissue engineering

gave an impulse for further research

concerning other tissue and organs. One of

the most spectacular projects, due to the

expectations of millions of diabetic

patients, was the research (launched in the

1970’s) on the growing of pancreas cells

that could be implanted to provide a source

of insulin for the host organism [2]. The

turn of the millennium was a time of great

optimism about the possibility of growing

new organs in vitro. In the year 2000, the

Time magazine pronounced tissue

engineering the most attractive field of

science that, in the subsequent years, was

to provide innovative solutions in the

treatment of numerous diseases. Such

hopes were very high and many people

optimistically assumed that, in the near

future, it would be possible to grow organs

in vitro and to implant them in human

bodies to replace damaged tissue or organs

[10]. However, contrary to these

expectations and despite the funding

involved in the experimental and clinical

studies, the remote therapeutic effects were

not satisfying. Some of the skin

preparations were degraded in the

recipients’ bodies initiating the process of

connective tissue hyperplasia and

cicatrisation, whilst the attempts of

growing pancreas cells that were meant to

be a source of insulin in living organisms

came to nothing [12]. Consequently,

discouraged by the lack of anticipated

clinical effects, the private investors who

had provided 90 percent of the funding for

research on tissue engineering withdrew

from these operations. The lack of funding

stopped further studies whilst scientist

came to understand that it was not possible

to fully imitate the conditions that occurred

in a living organism (with multiple mutual

effects of various cell types) in the

relatively simple in vitro system.

As the hopes related to tissue

engineering declined some new biological

discoveries were made that directly or

indirectly provided new potential for the

advancement of regenerative medicine. In

1996, the sheep Dolly was cloned in

Scotland [22] and this was followed by the

first new reports about the isolation of

human embryonic stem cells [20, 17]. At

the start of the 21st century, stem cells

became the new hope of regenerative

medicine.

Stem Cells, Definitions

During the development of a human

organism, initiated with the formation of

the zygote as a result of the fertilisation of

an ovum with a sperm, a rapid growth of

the number of cells occurs accompanied by

their differentiation towards tissue or

organs. In the early stages of development

cells are featured by the capacity to

differentiate towards any type of tissue,

Significance of Embryonic Stem Cells in Regenerative Medicine

165

however, as the cells begin to specialise

this capacity is gradually lost. These cells

are called stem cells and their basic

characteristics include:

� An unlimited cell division capacity

� The ability to differentiate into other

specialised cells

Stem cells are divided into the following

types, according to the source which they

originate from:

A. Embryonic stem cells which occur

during embryogenesis displaying the

features of totipotent and pluripotent

cells,

B. Foetal stem cells obtained from

foetal tissue and blood displaying

the features of multipotent stem

cells,

C. Umbilical cord blood stem cells

displaying the features of

multipotent stem cells,

D. Adult stem cells displaying the

features of multipotent and

unipotent stem cells.

Embryonic Stem Cells

Embryonic stem cells are relatively easy

to multiply in vitro, whilst the high activity

of the telomerase enzyme stops them from

ageing, making them similar to neoplastic

cells [13]. They can differentiate into all

types of somatic cells. This feature makes

them suitable for the recreation of all types

of tissue, but also leads to potential threats:

embryonic stem cells may differentiate in

the body in the desired direction, e.g.

transform into liver cells, whilst also being

capable of transforming into intermixed

cells of various tissues causing organ

function disorders. The implantation of

embryonic stem cells in mice may lead to

the formation of teratoma, a tumour

containing various types of cells and tissue

deprived of their proper structure and

function [16]. Another potential threat is

the formation of neoplastic cell lines from

stem cells, which becomes a potential

hazard to the recipient’s health and life.

The presence of stem cells that initiate the

formation of neoplastic tissue has been

described in relation to tumours occurring

in the haematopoietic system [3], the

central nervous system [18] and the

mammary gland [11]. The lack of

neoplastic stem cell elimination during

cancer therapy can be one of the causes of

tumour recurrence [6].

Many discoveries which brought closer

the possibility of using embryonic stem

cells in therapy were made at the end of

the 20th century. Embryonic stem cells

were isolated firstly from mice [14] and

then from humans [20], to enable the

development of in vitro growth methods. It

is now possible to provide growth

conditions that initiate the differentiation

of human stem cells towards more

specialised cells [20]. A haploid ovum has

even been grown from stem cells

originating from mice [4].

However, creating a method of isolating,

growing and differentiating stem cells in

vitro is only the first step confirming their

usefulness in regenerative medicine. An

important factor which requires further

assessment is their survival and

functioning within the host. Methods of

differentiating human embryonic stem

cells towards specialised cells are already

available [1], but the potential to test their

properties after reimplantation in a living

human organism is limited due to ethical

concerns. A viable option is to observe

experiments with animals and cautiously

apply the results of these to the conditions

of a human organism. It seems that the

initial results of experimental stem cell

research with animals are promising. A

brief description of selected results is given

below:

• The implantation of cardiomyocytes

from differentiated stem cells to

dystrophic mice results in the

integration of these cells in the

animals’ cardiac muscle and the taking

up of the contractile function. The

presence of these functionally efficient


166

cells in the cardiac muscle was

confirmed throughout the whole

observation period, i.e. seven weeks,

and no neoplastic transformation

features were recorded. According to

the authors, it is possible to preserve

the contractile capacity of cardio-

myocytes in in vitro cultures for at

least eleven months [9].

• Min et al. proved on an experimental

model of cardionecrosis in a rat that

the implantation of embryonic stem

cells to the damaged myocardium led

to an improvement in its contractile

properties [15].

• Embryonic stem cells of monkeys

which were differentiated in an in vitro

culture into endothelium cells and

implanted under the animals’ skin

initiated the formation of new blood

vessels and stimulated the growth of

the remaining endothelial cells [7].

• Embryonic stem cells of mice which

were differentiated in an in vitro

culture became capable of producing

insulin. The implantation of these cells

in mice with experimentally triggered

diabetes led to the normalisation of

glucose levels and body weight [19].

• Embryonic stem cells of mice which

were differentiated in an in vitro

culture into hepatocytes were

implemented in mice with acute

hepatic damage following poisoning

with carbon tetrachloride. The cells

were integrated into the structure of

the hepatic parenchyma and undertook

the metabolic functions that are typical

for this organ [24].

The current advancement of modern

biology techniques enables the therapeutic

cloning of embryonic stem cells containing

genetic material from the donor. Despite

the fact that this still carries a biological

risk and, what is more, is associated with

ethical concerns, the results of these

research projects may be used in less

controversial circumstances in the future.

The procedure involves the implanting of a

nucleus from an adult patient’s cell into an

enucleated ovum followed by

embryogenesis stimulation. A thus created

embryo has stem cells that are

immunologically and genetically identical

to the adult donor. Such embryos can be

used to repair damaged tissue or organs in

the donor [23]. The study results which are

currently available confirm the effecti-

veness of this method in relation to human

cells whose genetic material was used to

grow pluripotent cells divided in in vitro

cultures (over 70 passages). These did not

exhibit changes in the karyotype and

displayed the capacity to differentiate

towards specialised cells [5]. The

advantage of this technique is the possi-

bility of growing autologous pluripotent

stem cells whilst reducing the risk of the

donor’s immunologic reaction to the graft.

The recent progress of research on stem

cells and their application in regenerative

medicine raises great hopes. It is,

nevertheless, necessary to remember the

expectations and disappointments related

to regenerative medicine so far [8, 10]. The

usage of stem cells in this field of medicine

has its ethical concerns [21] in addition to

important biological limitations. The

quantity of biological issues related to

using stem cells in medicine is tantamount

to the extent of hope generated by the

advancement of biological sciences.

However, the final and indisputable factor

that verifies the potential of using new

therapeutic methods in medicine is their

compliance with the generally accepted

ethical principles.

References

1. Amit, M., Carpenter, M.K., Inokuma,

M.S. i wsp.: Clonally derived human

embryonic stem cell lines maintain

pluripotency and prolferative potential

for prolonged periods of culture. In:

Dev. Biol. 2000: 227: 271-278.

Significance of Embryonic Stem Cells in Regenerative Medicine

167

2. Chick, W.L., Like, A.A., Lauris, V. i

wsp.: A hybrid artificial pancreas. In:

Trans. Am. Soc. Artif. Organs 1975:

21: 8-15.

3. Dick, J.E.: Acute myeloid leukemia

stem cells. In: Ann N Y Acad. Sci.

2005: 1044: 1-5.

4. Hubner, K., Fuhrmann, G.,

Christenson, L.K. i wsp. Derivation of

oocytes from mouse embryonic stem

cells. In: Science 2003: 300: 1251-

1256.

5. Hwang, W.S., Ryu, Y.J., Park, J.H., i

wsp.: Evidence of a pluripotent human

embryonic stem cell line derived from

a cloned blastocyst. In: Science 2004:

303: 1669-1674.

6. Jordan, C.T., Guzman, M.L., Noble,

M.: Cancer Stem Cells. In: N. Engl. J.

Med. 2006: 355: 1253-1261.

7. Kaufman, D.S., Lewis, R.L., Hanson,

E.T. i wsp. Functional endothelial

cells derived from rhesus monkey

embryonic stem cells. In: Blood 2003:

103: 1325-1332.

8. Kemp, P.: History of regenerative

medicine: looking backwards to move

forwards. In: Regenerative Medicine

2006: 1: 653-669

9. Klug, M.G., Soonpaa, M.H., Koh,

G.Y. i wsp. Genetically selected

cardiomyocytes from differentiating

embryonic stem cells for stable

intracardiac grafts. In: J. Clin. Invest.

1996: 98: 216-224.

10. Kratz, G., Huss, F.: Tissue engineering

– body parts from the Petri dish.

Scand. In: J. Surg. 2003: 92: 241-247.

11. Li, Y., Rosen, J.M.: Stem/progenitor

cells in mouse mammary gland

development and breast cancer. In: J.

Mammary Gland. Biol. Neoplasia

2005: 10: 17-24.

12. Lysaght, M.J., Hazlehurst, A.L.: Tissue

engineering: the end of the beginning.

In: Tissue Eng. 2004: 10: 309-320.

13. Mantell, L.L., Greider, C.W.:

Telomerase activity in germline and

embryonic cells of Xenopus. In:

EMBO J. 1994: 13: 3211-3217

14. Martin, G.R.: Isolation of a pluripotent

cell line from early mouse embryos

cultured in medium conditioned by

teratocarcinoma stem cells. In: Proc.

Natl Acad. Sci USA 1981: 78: 7634-

7638.

15. Min, J.Y., Yang, Y., Converso, K.L. i

wsp. Transplantation of embryonic

stem cells improves cardiac function in

postinfarcted rats. J. Appl. Physiol.

2002: 92: 288 – 296.

16. Morange, M.: What history tells us VII.

Twenty-five years ago: the production

of mouse embryonic stem cells. In: J.

Biosci. 2006: 31: 537-541.

17. Shamblott, M.J., Axelman, J., Wang,

S. i wsp.: Derivation of pluripotent

stem cells from cultured human

primordial stem cells. In:

Proc. Natl. Acad. Sc i. USA 1998:

95: 13726-13731.

18. Singh, S.K., Clarke, I.D., Terasaki, M.

i wsp.: Identification of a cancer stem

cell in human brain tumors. In: Cancer

Res. 2003: 63: 5821-5828.

19. Soria, B., Roche, E., Berna, G., i wsp.:

Insulin- secreting cells derived from

embryonic stem cells normalize

glycemia in streptozocin-induced

diabetic mice. In: Diabetes 2000:

49: 157-162.

20. Thomson, J.A., Itskovitz-Eldor, J.:

Embryonic stem cell lines derived from

human blastocytes. In: Science 1998:

282: 1145-1147.

21. Weissman, I.L.: Stem cells- scientific,

medical and political issues. In: N.

Engl. J. Med. 2002: 346: 1576-1579.

22. Wilmut, I, Schnieke, A.E., McWhir, J.,

i wsp.: Viable offspring derived from

fetal and adult mammalian cells. In:

Nature 1997: 385: 810-813.


168

23. Wobus, A.M., Boheler, K.R.:

Embryonic stem cells: prospects for

developmental biology and cell

therapy. In: Physiol. Rev. 2005: 85:

635-678.

24. Yamamaoto, H., Quinn, G, Asari, A., i

wsp.: Differentiation of embryonic

stem cells into hepatocytes: biological

functions and therapeutic application.

In: Hepatology 2003: 37: 983-993.

25. Yannas, I.V.: Regenerative Medicine.

Springer NY, USA, 2005.

1 „Transilvania” University of Brasov. 2 The Public Health Authority Brasov.

HEALTH PROMOTION AND

ELABORATION OF A

PREVENTIVE STRATEGY FOR

BRASOV COUNTY

A. BĂLESCU

1 F. LEAŞU

1

L. ROGOZEA1 E. CHEFNEUX

2

Abstract: The Romanian population is characterized both by a pronounce

ageing and the existence of risk factors which make the population growth to

be negative. It also has been found that not only social and economic factors

can have an influence on health in childhood, but also education can be very

effective for affecting mother’s and child’s health.

Key word: Infant mortality, health promotion, strategy.

1. European Context

Many European governments consider

health promotion an efficient method to

reduce health care costs. The role and the

importance of promoting health are well

known from Avicenna who said that:

“Medicine is the art of preserving health

and likely to cure the disease”. In our days,

organizing health systems is mostly a

matter of financing and than a matter of

preventing health.

In the last years there was a concern of

the decision factors regarding the increase

of health care costs. As a result, they start

to evaluate the health system and to create

new professionals trained to evaluate this

system.

The worldwide infant mortality rate is

68‰ in 2007, according to UNICEF. [8].

But UNICEF noted in a press release that

the improvements have been felt

worldwide. In industrialized countries,

there is now an average of just six deaths

for every 1,000 births. In Africa, the

continent with the worst rates, Eritrea,

Ethiopia, Malawi, Mozambique and Niger

have slashed their death rates.

In 2006 the infant mortality was for the

first time fewer than 10 millions death,

compared to almost 13 millions in 1990.

[8]

On the entire planet, the infant mortality

is reduced with 27% between 1990 (93

death at 1.000 children which were born

alive) and 2007 (68 for 1000). This

decrease is not an enough to reach the

standards required by the Organization of

United Nations, a 67% decrease of infant

mortality until 2015.

The international conference from Alma

Ata, in 12th September 1978, emphasized

the need of an urgent action, in order to

protect and promote health in every state

of the world. After 30 years, the numbers

of infant mortality are still showing a

serious contrast between poor and rich

countries. [6]


170

Because in western and central Africa

are 168 deaths for 1.000 births, this part of

the continent has the biggest problems in

the entire health system, while in the

industrialized countries are 6 deaths for

1.000 birth.

The mother’s and the baby’s health

represents, in this context, one of the major

problems in most of the countries, and also

an essential element in the primary

assistance of health situation. [10, 11]

In the circumstances of the death

increase, in the first year of life, or in the

next four years, the life expectancy at

birth, in the previous mentioned period, is

small. First of all infant mortality is the

primary factor that influence the value of

this synthetic indicator of measure, for

the infant mortality phenomenon in

special, but also for the health situation

in general. Infant mortality is considered

to be a demographical phenomenon in

the socio economical changes of one

population. [9, 12]

The same belief is authentic also for the

youthful and motherly. At the same time

the measure of all this components of

general mortality, offer an evaluation for

the medical assistant motherly-infantile

activity. [1, 3, 4]

16

4

7

413

12

6

3

43

4 4 4

6

2

4 4 45

4

3

64

14

16

11

7

34

3

413

5

0

2

4

6

8

10

12

14

16

Alb

an

ia

Au

str

ia

Bela

rus

Belg

ia

Bo

sn

ia-H

erc

eg

Bu

lgaria

Cro

ati

a

Rep

ub

lica

Dan

em

arca

Fin

lan

da

Fran

taG

erm

an

ia

Gre

cia

Un

garia

Isla

nd

a

Irla

nd

a

Italia

Lu

xem

bu

rg

Malt

a

Ola

nd

a

No

rveg

ia

Po

lon

ia

Po

rtu

galia

Mo

ldo

va

Ro

man

ia

Ru

sia

Slo

vacia

Slo

ven

ia

Sp

an

iaS

ued

ia

Elv

eti

a

Ucra

ina

An

glia

Fig. 1. Infant mortality in Europe

2. National Context

Furthermore, for Romania the study of

the mortality phenomenon at this

population groups, represents a special

interest because of the high level that it

has, comparing to the others European

countries, as it is shown in the previous

graphic, which presents in analogy the

situation in 2005.

The present health situation in Romania

is the result of its evolution in the last 50

years. After 1955 there was a serious

improvement in the health system that last

until early 70’s, when the primal factors of

evaluation the health situation ware getting

worse.

The health response at the socio-

economical condition represents a long

term effect of complex interaction of

proximal and distal determinations. On the

changes of transitions that ware included

recently, the difficulty that concern

material and social achievement that is

generated by the changes of the system.

Health Promotion and Elaboration of a Preventive Strategy for Brasov County

171

Between European countries, Romania

still faces the mortality issue having a high

rate of infant mortality, in 2006-

13,9%from new born children, decreasing

since 1997 (22%).

The numbers in 2006 was give by the

Health Ministry, and its shows that median

deaths of the new born come to 13,91from

1.000. According to UE in 2007 in

Romania ware 12 from 1.000 also in

decrease.

Even so, Romania remains on the first

place in Europe at the infant mortality

chapter. In Island for instance, the ratio is 2

from 1000 and in Finland is 3.

The studies of the decrease rate of infant

mortality regarding the national product

for each person and with the outlay share

for health taken from national gross

product, shows that Romania has an

unfavourable situation comparing to the

other countries that have almost the same

level. [13, 15, 16]

Over 60% from the total of deaths

happen form the first month to the 11 one.

The mortality ratio from this period in

rural environment is over 1.5 bigger than

in town.

The infant mortality decreased quickly

after the Second War until 1965 when the

reducing action almost stopped. In 1990the

number of infant mortality ratio was 26.9%

on the entire country, having oscillations

between 15.9% - 46.5% in districts, and in

1992 the rate decrease at 23.4%.

[2, 5, 7, 14]

The infant mortality continued to

diminish so that, in 2002 was 18.6 deaths

from 1000 of new born. Comparing with the

previous year there was a notable decrease at

the children under 1 month from 9.2% to

8.4%, and also for those that are in post-

neonatal period, from 9.2% to 8.9%. It is

very important to mention that infant

mortality had a downward line that rise from

5.8% in 2001 at 6.2% in 2002. [15]

6,2

3,8

3,6

5,5

7,2

74

,6

11

,4

8,4

7,5

6,4

4,5

11

,4

2,6

6,3

4,8

6,4

7,6

7,5

7,5

7,5

66,4

6,4

9,5

5,4

5

7,6

5,5

7,4

9,7

4,2

6,2

5,4

5,3

7

6,2

3,8

4,9

8,5

3,8

5,4

3,2

0

2

4

6

8

10

12

Ta

ra

Alb

a

Ara

d

Arg

es

Bac

au

Bih

or

Bis

trit

a-N

Bo

tos

an

i

Bras

ov

Bra

ila

Bu

za

u

Ca

ras

-Se

v

Ca

lara

si

Clu

j

Co

ns

tan

ta

Co

vas

na

Da

mb

ov

ita

Do

lj

Ga

lati

Giu

rg

iu

Go

rj

Ha

rgh

ita

Hu

ned

oa

ra

Ialo

mit

a

Ias

i

Ilfo

v

Mara

mu

res

Me

he

din

ti

Mu

re

s

Ne

am

t

Olt

Pra

ho

va

Sa

tu-M

are

Sa

laj

Sib

iu

Su

ce

av

a

Te

leo

rm

an

Tim

is

Tu

lce

a

Vas

lui

Valc

ea

Vra

nc

ea

M.B

ucu

res

ti

Fig. 2. Infant mortality in Romania

Bulletin of the Transilvania University of Braşov � Vol. 1 (50) - 2008 � Series VI

172

3. Regional Context

The studies in the Brasov district were

made on the descriptive epidemiological

methods basis, looking at documents

decease, under one year, from 1996 to

2006.

Various sources of information:

• Current demographical statistic date,

given by The Estimate Centre, Statistic

Orderly and by the Medical

documentation of the Ministry of

Health and Family

• Current demographical statistic date at

the level from the Analyze Laboratory

and from the Situation Evaluation of

Public Health Authority from this

district.

The results could be obtained with the

help of the Microsoft Office Pack. What is

more, all the graphics were realised with

the same program.

Based on this facts, there could be

determinate the indicator of frequency and

the indicator of structure.

Fig. 3. Infant mortality in Brasov

4. Methods and Preventive Strategies

The methods and preventive strategies

are based on:

1. The application of methodology, and

the norms respect, recommended by

The Ministry of Health and Family,

regarding children’s supervision in the

first year of life, by the family doctors.

2. The realisation of some inspections by

the doctors, who are also inspectors,

from the ASP district and by the

District House of Health Assurance.

3. The identification of the new born that

presents a risk factor, which require a

different supervision and ask for the

identification of the groups (pregnant

woman, new born children)exposed to

a high risk of ill and even death.

Health Promotion and Elaboration of a Preventive Strategy for Brasov County

173

4. The available resource assignment

based on the general thesis: “to assure

for everybody the best services, but to

offer a special treatment for those who

really need it.”

In the health domain motherly-infant, the

general objectives of the strategy are:

1. The transaction of a practical method

of evaluation for the risks on which

the persons (mother and children) are

liable at.

2. The launching of some local strategy

of intervention, taking in consideration

the risks and the existent resources.

3. The examination of the efficiency of

those strategies.

The organization of some lectures about

taking care of the pregnancy and of the

baby between 0-1 year, for the family

doctors, with the help of District Medical

College, and with the support Public

Health Direction, and also some lectures

for those that have a smaller level of

education.

In this context is imposed

• The development of the neonatology

services in every hospital from the

district.

• The insurance with at least a member

in every local area.

• The elaboration and the

implementation of the education

programs for health addressed to

women between 15 and 35 years.

Conclusions

• The infant mortality in Romania holds

itself at a high level comparing to the

European countries, with U.E. and

even with the previous socialist

countries: Romania is on the last level

along Ukraine, Bulgaria, Moldova and

Russian Federation.

• Looking back at the results of the

studies, in Brasov the infant mortality

rate kept itself under national

standards, until 2006 when this level

was crossed.

• The post-neonatal mortality (28 days at

least) in Brasov (8.4/1000) cross in

2006 the national level and also the

level of some other district such as

Cluj (2.3/1000) and of some towns that

are localized in the same geographical

area: Sibiu (5.3/1000) and Covasna

(4.8/1000).

• For the number of the new born deaths

is to blame prenatal causes and of

course congenital malformations, the

evolution bend after death month looks

as a “J” and not as an “U”, as it should.

• The program development in order to

promote health is a necessity, that should

be well organised in order to benefit by

the entire infrastructure of ASP.

• It is obvious that today, because of the

improper undernormed, the health

system is obligated to manage by their

self so that they found a solution based

on voluntaries. Moreover is found to

be important a discipline such as

Health Promoting and The Primal

Assistance of Health Scale that should

involve future practitioner in health at

the primal preventive objective.

• The same that is in the OMS

documents:” Promoting reproducing

health and maternal one”- The United

National Elements for the population

that struggled for the implement of this

program of planning volunteers. As a

result the woman that live in a country

which is in course of development

have at less than three children

comparing to six in the 60’ period

creating a delay on the rise population

in entire globe. In 1969 just 20% from

the couples ware practising familial

planning, but now this is made by 61%

from couples. In this context is

required that maternal health

promotion to incline more and more

for the development of life conditions

of mothers and of the new birth

children, in order to improve programs

of reducing the motherly-infant

mortality.


174

References

1. Beaglehole, R., Bonita, R., Kjellström,

T.: Bazele Epidemiologie. Bucureşti.

Ed. “ALL Educational”, 1997.

2. Bocşan, I.S. sub. red. : Asistenţa primară

a stării de sănătate: aplicaţii în

epidemiologie şi statistică. Ed. Presa

Universitară Clujeană, 1996.

3. Dabis, F., Drucker J. : Epidemiologie

d’Intervention. Paris. Arnette, 1992.

4. Dever, A.: Epidemiology in health

services management. ASPEN

publication, 1984.

5. Enăchescu, D., Marcu, M. Gr.:

Sănătate Publică şi Management

Sanitar. Ed. ALL, Bucureşti, 1995.

6. Forster, D.R., Jozan, P.: Health in

Eastern Europe. The Lancet, feb. 24,

1990.

7. Geormăneanu, M., Muntean, I.:

Pediatria, vol. I şi II. Bucureşti. Ed.

Medicală, 1995.

8. Global child mortality rates continue

to drop, UNICEF reports

9. Kontula, O.: Reproductive health

behaviour of young Europeans. Vol.2:

The role of education and information,

in Population Studies No. 45. Council

of Europe Publishing. Council of

Europe. Strasbourg 2004. in press

10. Kontula, O.: Trends in Teenage Sexual

Behaviour, Pregnancies, Sexually

Transmitted Infections and HIV

infections in Europe. In ‘Reproductive

health behaviour of young Europeans.’

Vol.1. Population Studies No. 42.

Council of Europe Publishing. Council

of Europe. Strasbourg 2003. pp. 77-

137.

11. Last, M.J.: A Dictionary of Epidemiology.

Oxford University Press, 1993.

12. Lavoie, A. : Les Problèmes de Sante

Prioritaires – une perspective

epidemiologique. Ottawa. Agence

D’Arc Inc., 1987.

13. Marcu, A.: Epidemiologia utilizată în

studiul mortalităţii infantile. Bucureşti,

1992.

14. Marcu, A. (coord.) : Metode utilizate în

monitorizarea stării de sănătate.

Bucureşti. Ed. Institutului de Sănătate

Publică, 2002.

15. Marcu, M. Gr., Mincă, D. G.: Sănătate

Publică şi Management Sanitar.

Bucureşti. Ed. Universitară “Carol

Davila”, 2003.

16. Zarcovici, G., Enăchescu, D.:

Probleme privind politicile de sănătate

în ţările Europei Centrale şi de

Răsărit. Bucureşti. Ed. InfoMedica,

1989.

1 University of Salerno, Italy.

DRUGS AND MEDICINE IN THE CONTEXT

OF YOUTH CULTURE

Giuseppina CERSOSIMO

1

Abstract: The study is interested in a specific social category (youth) in

relation to an important factor influencing health and well being

(medicine/drugs). As the dimension of health is a key element in the analysis

of individual life courses, this research is carried out of two considerations

(the health dimension/the importance of the body to young people and the

factors that contribute to the medicalization of young people’s lives (such as

prescription drugs). Field research (such as the one carried on in the

University of Salerno and presented in the present study) reveals that, as

shown by the reality under examination, there is a desire to resolve internal

problems typical of the younger generation through the application of

externally introduced elements (pharmaceutical products). The conclusions

of the field research regard the fact that for young people drugs are a means

of maintaining constant the rhythms and activities relative to and in parallel

with existential frequencies and patterns. Another conclusion is that it is

possible to understand how the perception of young people on both health

and illness is dependent upon a series of social configurations in which they

are involved and which contribute to forming the identity structure of

individual young people.

Keywords: youth, drug, medicine, field research, pharmaceutics

1. Reasons for the Research

In the generational continuum the term

“young” has acquired numerous socio-

historical connotations but it has almost

always been viewed by society in general

as a synonym of differentiation and/or

contestation, establishing a “condition”

and a privileged image of change. A

specific focus on the young people of

southern Italy has occasionally been

undertaken, but only in part, and without

sufficient care to the differences present in

this part of the country and to the

heterogeneities that have been, and

continue to be, an essential part of its

modernisation. The processes by which

youth identities are built up are often

founded on and, at the same time,

determine a central role for young people

as consumers and yet a minor role as they

are effectively relegated to the margins of

society.

The causes of this confinement process

can be sought by investigating the ways in

which the social, political and cultural

establishment builds up young people in

the contemporary context as necessary and

integrated social subjects, on the one hand,

and yet places them in a marginal,

generalised and undifferentiated condition

on the other.

Bulletin of the Transilvania University of Braşov ▪ Vol. 1 (50) - 2008 ▪ Series VI

176

This type of circumstances gives rise to a

non-predetermined process of entry,

presence, exit and absence from social

roles that has clearly contradictory effects

on the personality and that, obviously,

makes the subjects’ extrinsication

objectively precarious, partial and often

temporary. In terms of existential

condition, in Italy and, more specifically,

in Southern Italy, this accentuates

situations of anxiety, tensions, a painfully

long wait for employment and, at the same

time, it exalts collective dimensions, the

need for self-representation of the

individual and symbolic manifestations. It

must also be remembered that, in a society

of symbols, health also becomes a

consumer product, a symbol of potential

and social status and, hence, a projection

of the idea of health as social prestige

(transferred first and foremost into the

representation of the body). This prestige

is achieved through the sometimes

relentless pursuit of what is considered

individual wellbeing, with the result that it

may give rise to stress and malaise.

The number of people enrolled at gyms

for physical fitness does not only indicate

awareness in the achievement of

wellbeing: control over one’s own body is

not merely a personal factor, it must be

flaunted and this ostentation encapsulates

the contradictions of the modern

conception of the body, its use and its

language (Rella, 2000; Sassatelli, 2000).

With regard to these premises, in the

research sphere there emerges the issue of

conducting a series of investigations in

southern Italy that can truly capture the

structural processes present in this part of

the country as well as the effects of

territorial dimensions on single individuals

at the intersection of urban and community

realities, in the perspective of establishing

a relationship with the dynamics of

everyday life and with the processes and

problems of individual (and collective) life

courses, within the historical context of the

relationship between the establishment and

young people.

The numerous research studies carried

out in Italy on the youth issue have

investigated different areas of the

problematic dimension of young people,

from unemployment and the various

processes of education, both in and out of

school, to forms of refusal (or self-

segregation) of communication,

dimensions of aggregation and the

resulting dynamics that give rise to life

processes, forms of solitude that end up in

mental illness and, finally, to the failure of

any attempt of interaction, which

culminates in suicide (1). However, the

research carried out on the condition of

young people seems to have left several

central (and extensive) existential areas

unexplored, for instance concerning problem

issues such as maternity, love, running away

from home, unexpected events, sudden life

changes, health, the urban condition and so

on. There thus emerges a clear contradiction

between the considerable research that has

addressed the “youth condition” over the

years and the number of issues that have been

neglected, not to mention the specific areas of

southern Italy which, in the majority of cases

are not even taken into consideration (2).

These premises may therefore contribute

to clarifying the reasons why, in agreement

with the observations now being made

along the lines of existing research, this

investigation needs to be carried out on

young people, prescription drugs, health

and medicine. This research is carried out

with two considerations in mind: on the

one hand, the health dimension and the

importance of the body to young people;

and, on the other, the factors that

contribute (prescription drugs) to the

medicalization of young people’s lives.

Drugs and Medicine in the Context of Youth Culture

177

The dimension of health is a key element

in the analysis of individual life courses, of

well-being and malaise, of citizenship

rights, and of the system of social, gender

and generational inequalities.

The race to improve performance

sometimes turns well-being and malaise

into the two sides of the same coin, first in

a diachronic and then in a synchronic

perspective. Our research is intended to

pinpoint, by means of a quantitative and

qualitative methodology, when, where and

why young people request both medical

and pharmacological help in order to

improve their relationships. This

perception stems from a structured and

consolidated awareness of a me/self, that is

to say of how a person feels they are

perceived by “significant” others [29].

The body contributes to the emergence

of these dynamics. We may then assert that

one of the motivations pushing young

people to take excessive care of their own

body is that a body language shared [by the

other] legitimates the role of one’s own

look to the point of considering it as the

matrix of a “status or non status” of health

that has been called the “body idiom”, a

conventional reasoning that plays a symbolic

and normative role [40]. The body idiom, a

performer without a voice, conveys a non-

verbal communication that allows spectators

to capture an important image of the

individual’s outer balance, through his

capacity to send images while concealing

any state of anxiety, depression or other.

Medicalization of the everyday life of the

young people involves a process by which

nonmedical problems become defined and

treated as medical problems, usually in

terms of illness and disorders [13]. In other

words, medicalization can be described as

the extension of medical categories in

everyday life.

Recently, The Lancet (369/2007) has

dedicated ample space to the issue of

medicalization. Here, McLellan states the

question clearly: “Once upon a time,

plenty of children were unruly, some

adults were shy, and bald men wore hats.

Now all of these descriptions might be

attributed to diseases - entities with names,

diagnostic criteria, and an increasing array

of therapeutic options” (2007: 627).

Therefore the Lancet raised this issue by

publishing a number of papers that tried to

shed a new light on some crucial aspects of

the medicalization process by looking at it

from a new perspective. While in the past,

according to the early definition given by

[21] the term medicalization meant a

process promoted mainly by the doctor,

today many promoting agents have come

to the fore. Jonathan Metzl and Rebecca

Herzig (2007) identify some of them, such

as the patients and the practice of “direct-

to-consumer advertising”, and the

pharmaceutical companies with their

economic policies.

Other authors think that while “young

people, who were once considered as the

passive victims of medicalization, now play

an active role, especially in the decision-

making process. The key factor seems to be

the influence of medicine upon the ethical

attitude of young individuals, the

relationship with ourselves, our judgment

about the kind of person we wish to

become and the kind of life we wish to

lead” [34].

In the U.S., for instance, with the

liberalisation of Direct-To-Consumer

(DTC) advertising, the physician-patient

relationship has undergone significant

changes. Hollon (2005) states that patient

requests for prescription drugs consistently

affect the prescription attitudes of

physicians. About 40% of appointments in

which the discussion involves DTC

advertised drugs end up with that drug

being prescribed. Then, through a

metanalysis of a great deal of research,


178

Hollon demonstrates that almost 80% of

physicians are convinced that DTC ads

encourage people to look for treatments

they do not really need (2005: 2031).

All this can be attributed to the fact that

nowadays young people are increasingly

"demanding", nor can we deny that there is

a different health culture today. Health is

not only “lack of pathology”, but also

“enhancement”; furthermore, an enlarged

“health literacy” [23] pushes the patients to

become consumers who look after their

wellbeing (Ingrosso 2007).

In this context, it would be worthwhile to

focus on the Drugs National Agency’s

report of a steady growth in prescriptions

of anxiolytic and antidepressive drugs in

Italy over the last few years. Most of these

treatments are prescribed by general

practitioners, who have to face a huge

demand for medicalization from younger

people as a result of difficulties in the

socio-relational sphere. A set of symptoms

is increasingly becoming a “disorder” and

in today’s society we are witnessing a

growing medicalization, not only of what

is pathological, but also of what can be

“improved” (the cases of Viagra and

cosmetic surgery are emblematic).

In mass media communication health

turns into a fashion, a consumer product, a

look. There is an increase in fitness

practices that promote a “well-shaped”

body and mind able to yield a high

performance level that is fit for the society

of the perfectible and which therefore

requires flexible procedures at work and in

present-day social life. The consumption of

new substances, with a greater or lesser

doping effect is increasing to meet the

demands for efficiency, visibility or

compensation for fears of inadequacy and

isolation [8]. Because of the mocking

paradox of mass society, in which the

relational dimension of “being there”

rather than “being” haunts the present time

of everybody and the process of “staying

with” seems more important than

“staying”, solitude, exorcised in a thousand

ways, materializes again as a companion

escorting individuals, above all younger

people, on their social pathway [9].

Thus normality, in contemporary society,

seems to take a violent and de-structuring

semantic twist: from an expression aimed

at recognizing a status of “good health”, of

“being like” to a concept of hedonistic

perfectibility and implementation.

This article, based on research conducted

amongst young people living in the

southern regions of Italy, discusses the

largely under-researched theme of the

association between pharmaceutical use,

health and young people.

Field research reveals that, as shown by

the reality under examination, there is a

desire to resolve internal problems typical

of the younger generation through the

application of externally introduced

elements (pharmaceutical products).

In adolescence, assumption of

pharmaceuticals is seen as an answer to

problems of insecurity or, in some cases,

identity. Drugs are also seen as a means of

resolving difficulties relative to the process

of transition, to contradictions and to

situations typical of the younger generation

such as anxiety problems, mortality, future

prospects and to the inevitable upheavals

arising from a confusion of subjectivity.

For young people, prescription drugs seem

to represent what Valéry says art

represented for the author. He identified

the original motivation for artistic creation

in that aesthetic need that belongs solely to

the “author”, who initially displays

indifference towards a possible

“audience”. At first there is the anxiety

(spleen) of a man who feels horror for the

void – in our case, the time and space of

uncertainty experienced by the youth

population – which is both a void of space


179

and time. The restlessness characterising

sensibility can indeed be related to the

sense of “instability” that the subject

experiences when faced by empty space

and waiting. In short, the need to fill up an

empty gap in time or to fill an empty space

is a natural need because it is innate to man

(Valéry, 1935). Zygmunt Bauman recalls

the complex mechanisms underlying the

construction of uncertainty and insecurity:

if our society tends to reassure the public

dimension of subjects but attacks them in

their every private niche, what is

manifested in terms of the subject’s

potential crisis, i.e. the erosion of

confidence in his/her body and lifestyle

certainly assumes a “striking” nature for

the individual, especially if it is a young

person (Bauman, 2000).

Therefore, in young people, there is an

increasing need to distance themselves

from times and spaces that can suspend (or

suggest that they are unable to follow and

control) the frenetic rhythms of everyday

life. The anxiety of contemporary reality,

the uncertainties of the existential process,

the question marks looming over one’s

own future (not actually expressed but

present on the individual level, often

unsaid but not necessarily unlived or

unperceived), the crises within one’s

symbolic universes [2], the discontinuities

in relational processes, the crisis of an

increasingly rarefied and unsatisfactory

relationship with the historic reference

institutions of socialisation are all elements

that exert a dynamic effect also in the

creation and maintenance of the ability to

control one’s own body, subjectivity,

individuality and inherent differences. The

latter become guaranteed by prescription

drugs, the means by which the individual

may not be obliged to interrupt the dynamics

of their own existential frequency but remain

able to keep up with it.

For young people, drugs are a means of

maintaining constant the rhythms and

activities relative to and in parallel with

existential frequencies and patterns.

Young people seem to have accepted the

idea that, in a physical and cultural

colonisation process, the pharmacological

world is invading all walks of life. The

self-proclaimed objective is to help

individuals to constantly improve their

daily abilities by reducing difficulties,

ensuring certitude and the capacity to

exteriorise.

The research also demonstrates that

some habits of youth regarding the use of

pharmaceutical products (drugs) are the

products of a social construction

originating in the primary social group -

the family - which then become

fashionable within peer group structures.

2. Premiss and Methodology

Judging from this research, in a process

of physical and cultural colonisation,

pharmacology is invading every aspect of

the life (and body). The self-proclaimed

objective is to help individuals (at both a

physical and psychological level) to

constantly improve their capacity in the

course of daily life by reducing difficulties,

ensuring certitude and facilitating a greater

degree of exteriority.

These considerations have led to the

decision to investigate what may be, or

could be, the reaction of young people and

the generation preceding towards the

assumption of pharmaceuticals.

Moreover, when a subject abandons,

delegates and places trust in

pharmacological and medicinal treatment,

health protection becomes an act of faith,

independent of the effect which the

pharmacy has upon the organism.

It is therefore important to understand

the trust, or lack of it, towards individual


180

organisms and also the kind of relationship

which exists between the assumption of

pharmaceuticals and the various levels of

information and disinformation. Starting

from this hypothesis, field research was

carried on a sample base of 550 students

from the University of Salerno. In order to

obtain a balanced cross-section, the

samples were taken from faculties and

degree courses in Mathematics, Pharmacy,

Engineering, Economics, Law, Sociology

and the Communication Sciences. Only

511 young people answered the

questionnaire: 49% male, 51% female, one

third attending science faculties, and two

thirds attending humanistic ones. The

sampling procedure employed the two-

phase cluster technique. The first phase

sampled the Faculties present at the

University of Salerno, while the second

phase selected the lessons timetabled for

the period of the investigation (according

to the degree courses, the sample included

all the courses from the first to the final

year so that its composition was

representative of the university student

population in terms of age and course

attended).

The origin of the sample is

heterogeneous: 56% come from Campania

while the remaining 44% are from other

Italian regions (Basilicata (21%), Puglia

(10%) and Calabria (13%).

Principally, research was aimed at the

relationship which students have with the

use or abuse of pharmaceuticals and the

relative degree of information or

disinformation regarding their use. In

particular, the investigation was geared

towards analysing and understanding: a)

how the daily discomforts encountered by

young people are faced and overcome - or

kept in check - by the use of

pharmacological substances; b) the social

importance which drugs assume in the

various existential life-patterns of young

people; c) to evaluate the varying extent to

which factors relating to social context and

cultural roots have an influence – and to

what measure - on behaviour patterns.

3. Drug Indoctrination

Young people appear to want to resolve

internal problems and conditions typical of

youth by resorting to external remedies to

their problems and to their condition:

pharmaceuticals. Indeed, the majority of

the sample admitted to the occasional use

of pharmaceuticals (40.3%); 32.1% stated

that recourse was “hardly ever”, whereas

4.3% maintained “never”. 16% of the

sample accounted for “fairly regular use”

and 7% classed themselves as “frequent

users”. However reassuring on the surface,

these statistics do not conform to answers

posed by a check question to which only

3.1% failed to reply and 0.4% attested that

they never used pharmaceuticals at all. The

vast majority of the remainder of the

sample is distributed amongst a percentage

of assumption of various pharmacological

compounds whenever symptoms –

however minor or trivial – present

themselves.

Drugs are legitimised by a reassuring

importance which is both expressed and

perceived: “drugs have an essential role;

above all, they validate the ability to

intervene on the part of a doctor – ‘I am

prescribing this, therefore I know what you

have’ would appear to be the comment of the

doctor making out a prescription and

avoiding further examination or referring the

patient to a specialist or hospital - an

alternative which could be interpreted as a

sign of incompetence” (Dupuy/Karsenty

1974).

Beginning with this encouraging

legitimisation, drugs become the mediator

between the potential subjects who

consume them or are likely to (at this


181

stage, it is no longer important whether

they are prescribed by a doctor or on the

suggestion of a chemist or family and

friends) and the progressive scientific

society.

From this research it is also possible to

evaluate the real success of

pharmaceuticals.

The investigation illustrates how drugs

are perceived by young people and how

that perception contributes towards a

guarantee of the success of officially

recognised medicines and, alternatively,

how they can enrich and improve the

quality of life.

One of the first results of the sample is

the almost unanimous recognition of the

role which drugs have acquired in

guaranteeing the state of health of the

individual, data which evidences the

widely held conviction, amongst the

young, of the scientific foundations on

which social progress is based.

Moreover, such data becomes even more

convincing when confronted with figures

of 19.7% and 26.4% of the university

student sample, all of whom maintain that

drugs are not yet fully capable of

guaranteeing an improved state of health.

This poll result underlines the desire and

trust that young people place in future

advances in the field of scientific and

pharmacological research which are geared

towards the improvement of the actual

governance of well-being. The

expectations, therefore, given to the role of

pharmacy are clear: to guarantee continuity

to the existential life pattern of the

individual. In particular when one

considers that only 6% of the sample do

not trust drugs or are simply incapable of

assuming a personal position over the

question.

A perspective which seems to remain

unchanged even when young people are

asked in which alternative they place most

faith: in official medicine, in homeopathy

(3) or otherwise. Here again, with the

impossibility of alternative medicine

asserting itself to the same degree, the

sample places unequivocal trust in official

medicine.

When the influence of socio-

demographic variables are considered in

relation to the subject gender, it becomes

evident that belief in pharmacological

discovery is analogous for both males and

females. However, when the relative

erudition of the parents is taken into

consideration, different data is forthcoming

– indeed, in parallel with the elevation of

family scholarship, there is a

corresponding increase of trust in official

medicine and pharmaceutical remedies.

The argument discussed so far is

confirmed by the section of the

questionnaire devoted to the level of

compliance (assumption of

pharmaceuticals and degree of therapeutic

efficacy) and also illustrates to what extent

individual subjects are prepared to delegate

or abandon themselves to pharmaceuticals

- or to place their unreserved trust in them

- in order to improve their psycho-physical

potential. This was so much so that when a

sample was taken from senior secondary

school students, 80.8% echoed agreement

with 79.9% of the university student

sample affirming that the effect which

pharmaceuticals had upon the organism

was “fairly good”.

Furthermore, when the 13.6% of the first

sample and the 15.7% of the control

sample are taken into consideration and

which state that the physical effects of

pharmaceuticals are “sufficient”, it can be

added that 95% of the sample base of

young people examined demonstrate that

pharmaceuticals have an increasing

tendency to co-exist in the existential

pattern of the subject. Moreover, drugs are

assuming an increasingly reassuring


182

characteristic within the individual lives of

young people.

It is then, perhaps, no accident that in

another section of the questionnaire 97%

of the sample – 9.7 students out of 10 –

state that they have taken and are taking

pharmacological substances.

This same percentage is also confirmed

by the answers to a control question which

underlines how drugs – from anti-anxiety

to anti-inflammatory – are assumed

conscientiously and appropriately for

several symptoms. Young people, when

affected by certain maladies, are no longer

prepared to wait for a natural

counterbalancing reaction from the body

itself but prefer to accelerate the process

with chemical products.

In an attempt to explain the relationship

between the trust invested in drugs and the

effect that any pharmaceutical product may

have on the organism, the following

question was posed: “Before taking any

kind of drug, do you read the

accompanying instructions?” (while

conscious that, despite the advice given in

the legal decree no. 44 - 18.02.97, such

instructions are still a long way short of

offering clear warnings and explanations

over an arc of three hundred and sixty

degrees).

70.6% of the sample read the

accompanying instructions, 10.4% do not

bother, whereas 18.6% were inconstant. As

regards the majority (70%) the comment

made was: young people who read the

accompanying instructions (nick-named

“little liar”) already have good reason to

be wary of the side-effects which even the

most mundane substances can provoke.

However, this would appear to be short-

sighted, it is impossible to guarantee that

all the possible undesirable side-effects, as

documented in the “instructions for use”,

have been previously identified and

confronted (4). This is a possible answer as

to why drugs are increasingly successful

between and with young people:

paradoxically, it is as though a vague

understanding of the nature of a drug is

also its certificate of guarantee for use.

Besides which, at this point we are

facing that which Luhmann defined as the

negative aspects and/or the “malfunction”

of modernity. In other words, society finds

itself having to confront consequences

determined through its own structural

selection, such as ecological problems in

the modern world and increasing tension

fuelled by the attempts to maintain the

actual level of social well-being.

It is, then, precisely this tension created

through the maintenance of well-being

which could provide an answer, in

Luhmannian terms, to the taking of

pharmaceuticals on the part of young

people at risk. The risk that a young person

makes in taking pharmacy without first

referring to the “instructions for use” or,

alternatively, when conscious of the likely

side-effects, is determined by an appraisal

of the potential damage which, in itself,

derives from a decision taken by the self-

same person (Luhmann, 1993).

The motivations referring to those of

sample quote who declare to not reading

the accompanying instructions (56.9%) are

particularly interesting: those who do not

read the instructions say it is because they

have prior knowledge, whereas the residual

37.2% argue that the instructions are

difficult to understand and that it is better

not to bother (always remembering that the

subjects are at a university level, which

provokes reflection upon the greater part of

the population who, under completely

different circumstances, must be unable to

read or understand the indications

anyway).

In this instance, we are confronted by the

category at dangerous discussed by

Luhmann, in other words, the potential


183

damage to which the individual is

unaware, inasmuch that the obscure

terminology adopted to describe the

pharmacy does not permit the person who

is about to take the medicine to understand

the implications of doing so.

Moreover, the last consideration with

reference to the sample raises a bi-lateral

observation: a) could this contribute to

successful economic returns for

pharmacological multi-nationals?; b) could

the success of pharmaceuticals amongst

young people be part of a generalised and

voluntary disinformation strategy

concerning potential pharmacy users?

This type of behaviour could indeed be

common to other processes in which young

individuals decide to assume certain

substances: they are aware that

assimilation will, in any case, modify the

condition of their body. Nevertheless, the

knowledge of the final result of the

process, however approximate, is

sufficiently satisfying to annul any

information regarding the internal bodily

process leading to the final result. Thus, it

is the end result which is decisive;

regardless of any harmful side-effects, the

determining factor is the modification.

4. Pharmaceuticals in General and

Alternative Therapy

Interesting research data comes out of

21% of the sample who have prior

knowledge of pharmaceuticals in general,

data which is subsequently confirmed by a

later question to which 22% of the sample

attribute therapeutic properties and effects

to commercial medicines already marketed

by well-known pharmaceutical companies.

The data relative to the information

which young people have of

pharmaceuticals in general underlines

concepts and signals which public opinion

has been indicating for some time. Signals

systemised in the understanding and belief

of the individual - not at an “emotive” but

rather at a “rational” and “conceptual”

level – in certain therapeutic schemes

which are no longer simply tied to well-

known pharmaceuticals (and which have

become part of a way of life) but to

pharmaceuticals in general (5) as is also

the case with therapeutic treatments related

to alternative medicine.

Trusting in this form of therapy is

dependant upon whatever kind of

familiarity and information the young

person may possess – together with the

existing relationships, discussed

previously, such as doctor/patient or with

other important socialising elements. This

would explain why 17.4% of the sample

believe in unofficial forms of medicine and

why, out of this 17.4%, 14.1% claim to

have greater faith in homeopathic

medicine. Indeed, the function of

homeopathic medicine would seem to

vindicate that therapeutic mandate which,

in the words of Thomas Sandoz is “a

profane rite of exorcism”. To follow, to

recognise and to trust in this practice has

the effect of rationalising some of the

procedures of improvement, both of the

cure and of the therapy of the actual state

of well-being or indisposition. This could

occur through a decomposition of the

function of the vindication of homeopathy

in “four projects” (Sandoz, 2001).

In the first place, homeopathy introduces

the possibility of contrasting medical

impotence by seeking auxiliary solutions

outside of the parameters of the biomedical

verdict (or medical practitioner), thereby

overcoming the innate passivity of the

subject towards illness.

Secondly, homeopathy encourages the

fight against the mounting uncertainty

which afflicts people suffering from illness

(regarding the origins, the prognosis, etc.)


184

by directly including and involving them in

a cultured dialogue of explanation.

Furthermore, homeopathy overcomes

that silence which can often follow the

pronouncements of experts, maintaining

intact latent resources in the subject which

official medicine has a tendency to nullify.

Finally – the fourth and last project –

homeopathy endorses opposition to the

modern movement towards the

medicalization of society and opposes

scientific reasoning and materialism which

is perceived as “the power of dominating

forces” (Sandoz, cit.)

Thus, whilst not “justifying

assimilation” of homeopathic therapy over

that of official medicine, the myth of the

therapeutic potential of homeopathy may

be attributable to the power of its

credibility, a factor which exercised a

distinct fascination over part of the

research sample. Young people exorcise

uncertainty – to which, in terms of health

care rights, official medicine is still

incapable of responding – by resorting to

alternative medicines and medicaments

which facilitate (or are said to facilitate)

aggregation in the dramatically decisive

moments of their existence.

5. From the Recognition of Professional

Status to the Recognition of Social

Status

In order to isolate and verify some of the

answers previously given by the sample, in

the fifth section individuals were asked to

indicate in which subject – family doctor,

specialist, chemist, friends/family – they

invested most trust when looking for

advice or a pharmacological prescription.

Replies indicate that, of the four subjects,

in terms of trust, social and professional

recognition and the expedience of

prescriptions, specialists were adjudicated

most competent (49.7%). This figure was

followed by general practitioners

(37.2%), friends/family (5.7%) and,

lastly, chemists (3,7%).

Turning to various exponents of the

structural-functionalist school, such as

Talcott Parsons or William Goode, it could

be said that such a high level of

recognition of the professional status of

medical practitioners - greater even than

that given to specialists - has taken shape

in the wake of the organisational reform of

labour within industrial and urban society

(1968; 1969). A development which has

privileged the division of functions and

tasks and produced a consequent demand

for qualified or specialised services outside

of the family environment.

All of which, however, has led to an

ulterior consequence: the ever-increasing

fragmentation of medical knowledge, a

phenomenon which has had an inevitable

effect upon the ability to prescribe any

required pharmacy. Moreover, in the midst

of this fragmentation process, although a

deeper bodily understanding has evolved,

it is often difficult to grasp that what is

being lost is the link between states of

illness not attributable to a specific part of

the body but rather to the body in its

entirety. Thus, the importance given to

medicine and pharmacy is a consequence

of the values attached to health, life and

death. According to these authors the

progress of knowledge and preparation has

induced a need: recourse to medicine in

order to legitimise professional status.

However, the symbolic

commutationalists and theoreticians of the

Chicago school – in particular, E. Freidson

(1970) – refute both concepts: inasmuch

that the rise in status of the medical

profession automatically depends on the

new division of labour and, that it stems,

fundamentally, from the progression of

knowledge.


185

The medical profession, in this respect,

gains professional status through those

who, averaging out a multiplicity of

considerations, manage to persuade

themselves of the unsubstitutional nature –

in terms of character and service - of their

competence and their ability. (in other

words, a professionality which, rather than

being achieved, is recognised by others).

Knowledge certainly contributes to the

definition of professionalism but it is not

easy to establish that precise moment in

which such recognition legitimises and

confirms the privileges of professional

status (Parsons, 1968).

Moreover, this research verifies that

young people’s trust is placed – as they

themselves confirm in one of the replies to

the questionnaire – in those representatives

of official health care with whom they deal

directly in daily life. Trust in medicines

prescribed by specialist practitioners,

greater than that invested in the

representatives previously mentioned,

would not appear to be different as regards

the type, whereas the level of trust given to

such professional figures increases in

correspondence to the educational quotient

of the family and, in consequence to

parental professionalism and the nature of

their work.

The research also opens the possibility of

analysing the way in which a prescription -

or the recommendation by a specialist of a

particular medicine and its subsequent

acquisition - results in a dual-recognition:

on one side, that of professional status and,

on the other, that of social status within the

family.

6. The Perception of Young People

towards Change

What also becomes evident from the

questionnaire is the perception among

young people that medicines have changed

in substance and role. It is in the

transformation of the role (and objectives)

of medicines that the “personal data bank”

of any subject “needing” medicine is being

modified and filters back, through the

various generations, to young people and

children.

Today, medicines are no longer merely

therapeutic, no longer is there recourse to

pills when a state of illness is diagnosed

(indeed, not long ago, pharmacy was only

resorted to after immunity mechanisms

were found to be insufficient) but rather,

for many, medicine has become a means of

prevention, both in short and long-term

circumstances.

The sample would appear to be

conscious of this process which has seen

conceptions of pharmaceutical use move

from care, treatment and cure of illness

through to a preventative means of

forestalling it. As regards this data, it

perhaps worth reflecting that many young

people, approximately 66% of the sample,

turn to pharmacy at the first sign of a

possible attack of influenza or similar

discomfort.

This fact must also lead us to reflect on

how these continually ambivalent young

people are at the same time subjects of

transformation and objects of

subordination with respect to consumer

processes: it contributes to temporarily

assigning them with citizenship and to

structuring their identity, and as such it

must be recognised, albeit tacitly. The

ironic paradox is that, in this case, unlike

in clothing fashion, tastes in music or any

other area of commercialised leisure time,

this is a consumption that acts directly on

them personally, on their body and on their

identity. Therefore, prescription drugs have

today become a consumer product for

young people, through which to assert,

construct and project an individual and a

collective identity – on this issue,


186

advertising never presents us examples of

isolated subjects coming into contact with

a substance, but we are always shown this

practice being manifested within a group

of people bound together by friendship,

affection, etc.. In many cases among

campus students, therefore, prescription

drugs assume the role of a “fashion” with

the characteristics described by Simmel:

«fashion is imitation of a given model and

thus satisfies the need for a social

approach, it leads the individual along the

road everyone follows, from a universal

model which reduces the behaviour of the

individual to a mere example. But

nevertheless, fashion satisfies a need for

difference, the tendency towards

differentiation, variation and

distinguishing oneself from the others»

(Simmel, 1905, pp. 30-1). It must not be

forgotten that the prescription drug at the

centre of attention (like all the others) will

have different effects on the individual

bodies and on the individual identities

(and, in spite of everything, this is the very

expectation of the individuals): hence,

analogous performance for different and

differentiated results. A consideration

which has repercussions in a subsequent

observation which reveals how the sample

cross-section under examination are

influenced and socialised towards

pharmacy.

Evidently, pharmaceutical use plays a

constituent role in the existential life

pattern of any individual. From the outset,

there is a consecration of the positive

nature of pharmacy which, subsequently,

has inevitable repercussions on initial

impressions: the first use of pharmacy is

that administered by parents to their

children. Clearly, this introduces an

element which both anticipates and

reinforces, beyond all other reasoning, the

socialisation of the substance: how could

our parents have possibly given us harmful

substances? And, given that for every child

parents “know all”, children assume that

they must be far better informed about

such substances than they could ever be.

It is, therefore, during the process of

cognitive and cultural differentiation

between child and parent that individuals

begin to acquire an awareness and,

contemporarily, ask questions about

pharmacy.

It would appear that the greater part of

the sample under examination have grown

up with the idea (probably due to the

argument previously outlined) that

medicine is good for them. Only a minor

number of the young people interviewed

introduced a different evaluation, arguing

that, in the meantime on their part, they

had converted to alternative therapy in the

conviction that such cures are not harmful.

Despite differences of faculty or degree

course, the sample group, with absolutely

no variation, continue to grow up under the

belief that for whatever anxiety, ache or

indisposition it can be easily overcome

with the aid of medicine: “for every health

problem or illness there is a suitable

pharmaceutical remedy”. An awareness

which, as testified by the sample, derives

from the principal agents of socialisation.

Fragmentary information such as that

relative to the theme health/illness (the

index of individual and social patterns

followed by young people) should perhaps

also be introduced; such information

derives in 40.1% of cases from television

and, in 20.4%, from parents.

Besides the mass-communication

influence of television on young people

regarding information relative to health

and illness, 4.3% of the sample also

nominates the radio and 11% specialised

publications. As regards this last assertion,

it would seem likely that the word

“specialised” covers an ample range: that

is to say, not merely those specialised


187

journals and periodicals which have

proliferated over the last ten years or so

and which specifically deal with health and

illness, but rather the inserts, notebooks or

weekly supplements which have become

standard to every daily newspaper and the

weekly and fortnightly publications which

come out at both a national and local level.

Despite the well-known fact that Italians

read little (particularly daily newspapers),

it is also true that in the case of health (and

pharmacy), a veritable communication

network exists from which, it would

appear, it has become extremely difficult

to escape. In consequence, for certain

themes - such as those relative to the

physical aspect - they become, in a real

sense, communal mass movements;

whereas, for many other medical

questions, particularly those of an

“intimate” nature, reflections either do not

exist or, alternatively, fail to become

interlocutory - an observation which is

particularly apposite when such questions

are directed at precisely those subjects who

have – and ought to assume - the

responsibility of replying.

Moreover, considering the statistics of

those who advise young people when not

visiting a medical practitioner (and who,

notwithstanding, take medicine for

physical or psycho-physical disturbance),

57.3% are parents, 5.9% are family

members, 4.1% are relatives, 4.9% are

friends and 17.8% take advice from a

chemist. Only 2.4% state that they do not

assume medicines unless it is on the advice

of a doctor. To this data other sources of

information can also be taken into account,

all of which, nevertheless, are constituent

elements in a pattern of socialisation.

Above all, an attempt was made to

corroborate the role and the effects of the

information or disinformation supplied to

young people by secondary agents of

socialisation.

At the end of 1999, the specialised

journal “Sanità. Il Sole 24 Ore” published

an article saying: “The fight for

promotional exposure together with

research into synergic relations with

sales personnel has resulted in a series of

heterogeneous initiatives. Some of them a

little embarrassing. A promotional

campaign, launched in 1998 by a

multinational operating in the

pharmaceutical sector, created a

promotional tie-up between one of the best

known headache pills and a compact disc

of relaxing melodies. Chemists were

expected to pull out the promo from under

the counter each time they sold a packet of

the pills.”

This advertising spot was transmitted

many times a day on both radio and

television, despite the fact that WHO

(World Health Organisation - the

international health agency of ONU)

recommends that the role of the mass-

communications media, due to its

enormous influence upon public opinion

and perception, should be: “…to control

the authenticity and importance of every

fact relating to pharmaceutical products…

avoid becoming the spokesmen for

promotional campaigns in favour of the

pharmaceutical industry…” (WHO, 1983).

Information broadcast by the mass media

– television, radio, newspapers, magazines

and specialist journals – is disciplined

under the legislative decree n. 541, 30

December 1992. This decree prohibits the

media from transmitting messages

contrived to persuade their audience to buy

products which proclaim to be uniquely

capable of improving a state of health or,

indeed, to allude that failure to assume

such products could lead to deterioration.

The decree also prohibits the marketing of

medicinal products which encourage the

belief that the guarantee of relief and

fitness is determined by natural products.


188

26.1% of the sample admitted to taking

pharmaceutical products without a medical

prescription. The principal agents of

socialisation influencing the choice of

pharmacy to be taken – as underlined by

WHO – were, in order of importance,

television, radio, specialised journals and

internet. For young people, then, such

mediums are suggestive and seductive.

Statistics which take on far greater

validity when confronted with the 30.3%

of the sample who admit to receiving

information relative to health and illness

through the communication channels listed

previously, either to avoid choosing

medicines autonomously or having to visit

a doctor for minor aliments.

Seductive propaganda has the effect of

inducing individuals to associate a series of

natural properties - in other words, rendering

them harmless – to certain products.

The success of pharmacology, of official

medicine and even that of alternative

medicine, is largely determined by the

influence of the mass media. The

underlying message communicated is that

of a fascinating ideal designed to overcome

any form of subjective analysis - as for

example when facing a statement of

propaganda such as: “better a tried and

tested traditional remedy which has no

harmful side-effects on the body”. A

slogan which is then linked to the image of

a slim and beautiful woman visually

eulogising the product at hand.

In other words, audio-visual

communication designed to neutralise

rational responses towards the assumption

of a therapeutically orientated product.

How many of the young people

interviewed are conscious of the

“provenance” of products within the field

of alternative medicine? How many of

them are aware that bio-therapy/herbalist

and homeopathic remedies are, in any case,

laboratory derivatives? Are they equally

alive to the idea that the herbal extractions

from which such palliatives are “made”

are cultivated and chemically treated:

manure, fertilizers, insecticides – chemical

additives essential for the optimisation of

the process of cultivation and industrial

production of “medicinal” herbs?

The effects, the therapeutic properties of

herbs – which, once upon a time, grew

spontaneously and naturally – are today

largely the end-products of chemical or

bio-chemical cultivation; whatever

substances administered, herbal-based cure

is the most traditional form of pharmacy

associated to official medicine. In modern

society, these so-called biological-

derivatives – widely considered to be both

therapeutic and non-toxic – are also the

end-products of a laboratory-produced

chemical process (6).

Clearly, commercial media is primarily

interested in constructing messages which

emphasise the beneficial effects of

pharmaceutical products and conceal any

undesirable side effects; whilst, at the same

time, ignoring an equally interesting and

opportune occasion to inform individuals

of the correct usage and circumstances

under which the product is consumed.

Apart from the media, the other principal

socialising agent which has an influence

over the use of medicines and medical

information, is the family. Much research

demonstrates that, as regards the

assumption of pharmacy, the level of

education and relative medical knowledge

of the mother determines differential

behaviour on the part of the children.

In the book “To grow up well and better:

one reply to the most frequent questions of

mothers” (AA.VV., 2000) it is made

evident how much this relationship is

dependant upon a continual flow of

information regarding those medicines

utilised for curing their own children, from

aspirins to anti-histamines.


189

In the opinion of the authors, the most

interesting aspect of the research is to have

been able to evince that, in terms of the

information and health education

requirements of Italian mothers, no

differences are imposed by geographical

and cultural variables (always

remembering that the survey deals with an

indeterminate sample covering mothers

residing in totally opposed cultural and

geographical realities such as Milan and

Matera). The research clarifies why the

socio-demographic variables taken into

consideration during the predisposition of

the questionnaire – such as educational

qualifications and place of birth – do not

influence the way in which young people

are informed about, or socialised towards,

the use of pharmacy as a means of

regularising their state of health.

At this point, it becomes clear (given that

57.3% of the sample state that

pharmaceuticals are taken on the advice of

the parent and, in particular, the mother)

that, in the case of medicines, the principal

factor of influence over young people is

also the most powerful agent of primary

socialisation. This data, relative to the

influence emanating from the previously

defined primary socialisation agent, is

confirmed by 5.9% who state that

pharmacy is taken on family advice; by

4.1% who receive advice from relatives

and a further 4.9% who follow the

indications of friends.

Moreover, in this investigative section of

the questionnaire we can observe that not

only do the young people in our sample

advise their friends on the drugs to take, on

the basis of their previous experience, but,

at the same time, they themselves receive

advice from parents, neighbours, family

members or friends when they do not turn

to their doctor, while only 2.3% claim not

to take drugs unless prescribed or

recommended by their doctor. There seems

to emerge another consideration of that

fashion that «gives the individual the

certainty that he is not alone in this action

and proceeds on the basis of previous

experience as if on a solid platform that

alleviates the activity of the moment from

the difficulty of sustaining oneself»

(Simmel, cit., p. 30).

Socialisation of drugs, which for young

people is the product of peer group

influence, explains the widespread social

recognition which is attributed to one

medicine rather than another. For example,

it could be supposed that the limited

success of generic medicines amongst the

sample group, as previously stated, is

probably due to their fledgeling

appearance on the generic pharmaceutical

(7) market and a limited notoriety within

family peer group structures. Moreover, in

the absence of customary recognition and

use of the product, young people ignore it

(at least, for the moment).

However, as time passes and new

pharmaceutical products claim more

attention and greater acceptance amongst

the primary socialisation agents, the same

process of the usage of generics (which at

present can be seen to operate with well-

known multinational pharmaceutical

products) will also become the rule.

Indeed, it is hardly casual that young

people refuse to assume “new” drugs – in

the face of advice from doctors, nurses,

medical orderlies and/or a chemists – even

when the motive for their use (and the

substitution of well-known alternatives) is

justified by a potentially superior

therapeutic effect coupled with minor

collateral consequences (8).

Pharmaceuticals have been invested,

through advertising and peer-group habits,

with a whole range of precise

connotations. Above all, on the part of

consumers, they have become consumer

products; chemical composition,


190

therapeutic efficacy and undesirable side-

effects have become secondary

considerations: “Any pharmaceutical

carries more importance as a label than as

a medicine” (Bert, 1977).

7. Interim Conclusions for the Base of

Further Research

An extension of this research would

entail taking into consideration a

constructivist approach which consented –

as regards youth health themes,

environment and the inherent self-

awareness of the subjects themselves – to

understand how perception towards certain

interrogatives (such as conceptions of

illness and well-being from both a personal

and general perspective) are individually

constructed in parallel with the assembly

of information and experience.

Regarding any consideration of the

possible understanding that young Salerno

students may have towards the subject of

health naturally depends upon the

importance that each individual attributes

to the argument - not forgetting those

factors which can influence the

construction (or non-construction) of that

importance (social-demographic variables:

age; sex; the provenance of both student

and family; schooling, etc.) – in other

words, precisely that importance motivated

both from within the subject and from

individual external experience (Luhmann,

1971). Nevertheless, it can be safely

assumed that any young person will have

acquired a rudimental understanding of

pharmaceuticals, not only as regards their

potential efficacy relative to health and

illness but also in terms of subjective

analysis and active response to such

themes.

And, whereas the field of medicine often

encounters transitory difficulties

determined by the massive growth in

technological and pharmacological

innovation, it is also true that, despite

everything, medicine as a discipline enjoys

notable recognition on the part of young

people. This is confirmed, for example, by

those young people who, often

ingenuously, undergo cures, therapy and

even cosmetic surgery in order to resolve

inter-personal and existential relationships.

Young people now seem to be aware of

these dynamics and have established a

fatalistic attitude of yielding,

relinquishment, refuge and delegation to

discovery and scientific research and to

those who hold this knowledge and

represent for them one of the few

certainties for the improvement of their

future. Baudrillard certainly springs to

mind in this connection: «it is with

generalised individual somatisation, with

the body becoming an object of prestige

and salvation (…) that the medical class

establishes itself in the position of social

super-privilege it currently occupies »

(Baudrillard, 1976, p. 199).

In order to interpret the new ways of

appealing to young people - through the

schematics of perception, understanding

and information of health within an

individual context and of those instruments

and techniques which govern or re-educate

these aspects - the starting point is

undoubtedly the theory of Norbert Elias.

Moreover, it is only by following a

progressive approach over an extended

period that transformation can be

satisfactorily identified. Indeed, to

successfully reveal the mutation of interest

of young people in matters of health - from

initial curiosity through to conversion -

matched with gradual improvements in

well-being, the minimum research period

required would be twenty years. Long-term

analysis of this nature could identify the

various phases and figures of influence

through, for example, an analysis of the


191

internal mechanics of groups of teachers,

of parents and of those institutions

principally concerned with the health and

welfare of young people.

Through the employment of a process of

semantic destructuralisation, what also

needs to be considered is that, in an

attempt to come to grips with the crisis

within modern medicine, analysis would

appear to be orientated towards

understanding in terms of “Canons and

Procedures” (“Rules and Regulations”) -

Cavicchi, 2000 - rather than attempting to

reduce the crisis to a single scientific

paradigm.

Khun himself asserted that scientific

change was a product of rupture and

conflict, inasmuch that the employment of

canons and procedures as a solution to

crisis clearly indicates how some difficult

moments can be overcome through

different interpretations and theories.

At which point new semantic categories

– set up to overcome the impasse in which

the medical-scientific community finds

itself languishing – step into play.

Interpreting the crisis from the

etymological point of view of choice,

shows how (through changes in the criteria

used by the social-medical-health

community for communicating matters of

health, diagnosis and the construction of a

supportive reference base for operative

medical opinion) the institutions charged

with the promotion and distribution - in

terms of prevention and information - of

“public health” amongst young people can

be influenced into varying their

procedures.

It is not, however, simply a question of

isolating the interdependent factors and the

interaction between those subjects who

modify the existing situation in order to

create a new one, but rather the whole

range of factors – reinforced through

reciprocal inter-reaction – which ensure

the modification and restructuring of this

cognitive process relative to the theme of

health. As a result, it is possible to

understand how the perception that young

people have of both health and illness is

dependent upon a series of social

configurations in which they are involved

and which contribute to forming the

identity structure of individual young

people. On the basis of this premise, albeit

brief, any network of collaboration

installed between institutions, public or

private, whose objective is that of creating

a policy aimed at the younger generation

and geared towards the promotion of

culture, the environment, the safeguard of

rights, working conditions, self-realisation

and the pursuit of personal interests, needs

to give priority to both the theme of youth

and health and the consequences and

effects upon the individual, upon

individual identities and the inter-personal

relationships established with and within

society.

Notes

(1) The problem of suicide, which is

obviously related to the strength of the

social bond, is rooted in the history of

society and, at the same time, of the

sociological tradition, albeit in the

awareness of the different dynamics

attributed throughout the ages to the

choice to end one’s own existence. From

Durkheim’s work on the relationship

between the differing degree of social

interaction and suicide « A society is

highly integrated when its individuals are

kept dependent on it » (Durkheim, 1897).

(2) Think of the utterly insignificant number

on the youth issue in southern Italy

conducted by Cavalli (1990), Leccardi

(1994), Trigilia (1995), Giannotti (1996),

Merico and Rauty (1999), Rauty (1999)

and Siebert (1999).


192

(3) Homeopathic medicine falls into the

category of alternative medicine.

Originating in the late XVIII Century,

this therapeutic approach was first given

credibility through the work of doctor

Samuel Christian Hahnermann. The most

sensational discovery was that the effect

of therapy was inversely proportional to

its quantity. For the homeopath, as

opposed to orthodox colleagues,

diagnosis and therapy concerns the entire

body, referred to as the “unitary

organism”. In the majority of cases,

medications and other elements used in

homeopathic medicine are individually

prepared using biological raw materials

of natural vegetable or animal origin. The

homeopathic term for these medications

is “tintura madre” (“mother tincture”).

(4) When references are made to values not

taken into consideration within the

territory, this is principally an allusion to

the historical importance of popular

medicine in Southern Italy and of its

particular role relative to the poorest and

least literate of the social community

(though not exclusively so) and, in

particular, to those lacking the necessary

resources to undergo or resort to

traditional methods of treatment. This has

given rise to a practical relationship

between traditional pharmaceuticals

incorporating natural products (above all,

herbs) linked to those organisational

structures and individuals invested with

the specific task of propagating its

validity and function: the process of

modernisation, which would appear to be

in a permanent state of evolution, has

given itself the task of accelerating this

process towards the eventual “triumph”

of official medicine (in all of its aspects).

In reference to popular medicine, see,

amongst others: Marino, 1991; and,

Seppilli, 1989.

(5) “Quite good” is not a possible reply to

the questionnaire itself but rather a

convenient expression adopted by the

author to indicate the approximate

percentage of replies ranging from

“discreet” to “very high”.

(6) By definition, alternative medicine

expresses an optional – or, indeed, in

opposition – to official medicine: Its

success is rooted in the inability of

scientific medicine – evidence-based

medicine – to adequately respond to

matters of health as well as the diagnosis

of illness. For debate, see Cavicchi

(2000)

(7) The term generic pharmaceuticals

(medicines?) describes those medicines

which have the same active principles

and chemical composition as well-known

brand names (following years of

successful marketing on the part of the

pharmaceutical companies). A typical

example might be: Aulin = well-known

pharmaceutical; Nimesulide = generic

pharmaceutical.

(8) In the documentation of all

pharmacological research, it is stated that

collateral effects are those resulting from

research upon human organisms; to

which end, a sample group of patients

volunteers to assume, experiment, test

and reveal any positive or negative side-

effects of the medicine.

(9) In Europe, such remedies are associated

to the culture of pre-industrial society

and, as opposed to knowledge of

primitive cultures, are “a product of the

re-elaboration of popular and past

traditions on the part of the general

populace” (Velimirovic, 1982). In

consequence, two distinct and opposed

definitions of medicine or traditional

remedies emerge: on the one hand, an

almost parallel confluence between

traditional and alternative medicine and,

on the other, the romantic idea of a

popular medicine with its own origins but

with no foundations and quite separate

from evidence-based medicine.


193

References

1. Bauman, Z.: In Search of Politics.

Milano. Feltrinelli, 2000.

2. Berger, P. e Luckmann, P.: The social

construction of reality : a treatise in

the sociology of knowledge, NY,

Garden City, 1967 [tr.it., La realtà

come costruzione sociale, Il Mulino,

Bologna, 1969].

3. Berlinguer, G.: Medicina e politica.

Bari. De Donato, 1973.

4. Berlinguer, G.: Il corpo come merce e

come valore. In Rodotà S., “Questioni

di bioetica”, Roma-Bari.Laterza, 1997.

5. Bert, G.: Il farmaco come segno e

come mediazione. Milano. Feltrinelli,

1977.

6. Cavalli, A. (a cura di): I giovani del

mezzogiorno. Bologna. il Mulino,

1990.

7. Cavicchi, I.: La medicina della scelta.

Torino. Bollati Boringhieri, 2000.

8. Cersosimo, G.: La coesistenza di

benessere e malessere. In: L’odore

della Bellezza. Wellness e Fitness (a

cura di) D. Scafoglio. Salerno. Marlin

Editore, 2007.

9. Cersosimo, G., Rauty, R.: Riflessioni

sul controllo sociale: dalla normalità

della devianza alla normalità della

malattia. Keiron , n. 5, 2001, pp. 128-

139.

10. Ciacci, M., Gualandi, V. (a cura di):

La costruzione sociale della devianza.

Bologna. Il Mulino, 1977.

11. Clarke, A. E., Mamo, L., Shim, J. K.,

Fishman, J.R., Fosket, J. R.:

Technoscience and the New

Biomedicalization: Western Roots,

Global Rhizomes. In: Sciences

sociales et santé 18, 2000, 2, 11–42.

12. Conrad, P.: Medicalization, Etiology

and Hyperactivity: A Reply to Whalen

and Henker. In: Social Problems 1977,

24:596-98.

13. Conrad, P.: The medicalization of

Society: On the Transformation of

Human Conditions into Treatable

Disorders. Baltimore. Jhons Hopkins

University Press, 2007.

14. Conrad, P., Schneider, J. V.: Deviance

and Medicalization: From Badness to

Sickness. St. Louis: Mosby, 1980.

15. Dupuy, J.P., Karsenty, S. : L’invasion

pharmaceutique, Paris. Seuil, 1974.

16. Duster, T.: Medicalisation of race.

Lancet, 2007, 369:702-04

17. Giannotti, G. et al.: Anziani e giovani

nel Salento. Un contributo per le

politiche e le attività sociali educative

del territorio, Lecce.Piero Manni,

1996.

18. Goffman, E.: Asylums: Essays on the

Social Situation of Mental Patients

and Other Inmates. Torino. Einaudi,

1968.

19. Goffman, E.: Stigma. Bari. Laterza,

1970.

20. Goode, W.J.: The teorical limits of

professionalization, In: A. Etzioni (a

cura di), The Semi-Professions and

Their Organization: Teachers, Nurses,

Social Workers. New York. The Fre

Press, 1969.

21. Illich, I.: Limits to Medicine. Medical

Nemesis: The expropriation of Health.

London. Calder & Boyars, 1975.

22. Jennings, D.: The Confusion between

Disease and Illness in Clinical

Medicine. In: Can. Med. Ass. J., 1986,

135, 865-870.

23. Kickbush, I, Maag, D.: Lo sviluppo

della Health Literacy nelle moderne

società della salute, in Ingrosso M. (a

cura di) (2007), op.cit.

24. Leccardi, C.: Crescere nel

Mezzogiorno. Giovani e adulti in una

comunità calabrese degli anni

novanta. Rubbettino, Soveria

Mannelli, 1994.


194

25. Luhmann, N.: Sozale Systeme:

Grundrisz einer allgemeinen Theorie.

Frankfurt am Main. Suhrkamp, 1988

[tr. it., Sistemi sociali. Fondamenti di

una teoria generale, il Mulino,

Bologna, 1990].

26. Luhmann, N. : Soziologie des Risikos.

Berlin-New-York, 1993 [tr. it.,

Sociologia del Rischio, Mondadori,

Milano, 1996].

27. Luhmann N., «Tautology and Paradox

in the Self- Descripition of Modern

Society», Sociological Theory, 6,

1988, p. 36.

28. MCLellan, F.: Medicalisation: a

medical nemesis. Lancet , 2007,

369:627-8.

29. Mead, G.H.: Mind, Self and Society.

The University Chicago Press, 1932.

30. Merico, M., Rauty, R.: Giovani a

Montoro Inferiore tra modernità e

tradizione. Forino. Phorograf, 1999.

31. Metzl, J.M., Herzig, R.M.:

Medicalisation in the 21st century:

introduction. Lancet, 2007, 369:697-8.

32. Parsons, T.: Profession. In:

International Encyclopedia of the

Social Sciences, 1968, p. 536.

33. Rauty R. (a cura di), 1999, Una

tranquilla estraneità. Caratteri della

condizione giovanile ad Avellino,

Tipografia Grappone, Mercogliano.

34. Rose, N.: Beyond medicalisation.

Lancet, 2007, 369:700-702.

35. Sandoz T. (2001), «L’homéopathie

comme rituel de conjuration»,

Medicina e Storia. Rivista di Medicina

e Storia della Sanità, 1, pp. 73-98.

36. Seppilli, T.: Medicine e magie.

Milano. Electa, 1989.

37. Siebert, R.: Cenerentola non abita più

qui. Uno sguardo di donna sulla

realtà meridionale. Torino.

Rosemberg & Sellier, 1999.

38. Trigilia C. (a cura. di), 1995, Cultura e

sviluppo. L’associazionismo nel

Mezzogiorno, Meridiana Libri, Roma.

39. Velimirovic, B., Velimirovic, H.:

Therapeutischer Pluralismus?. In:

Curare, vol. 5, 1, 1982.

40. Williams, S. J., Bendelow, G.: The

Lived Body. Sociological Themes,

Embodied Issues. London & New

York. Routledge, 1998.

41. World Health Organization: Self-help

and Health in Europe. Ginevra. Who-

Oms, 1983.

1 University of Salerno, Italy.

DRUGS AND MEDICINE IN THE CONTEXT

OF YOUTH CULTURE

Giuseppina CERSOSIMO

1

Abstract: The study is interested in a specific social category (youth) in

relation to an important factor influencing health and well being

(medicine/drugs). As the dimension of health is a key element in the analysis

of individual life courses, this research is carried out of two considerations

(the health dimension/the importance of the body to young people and the

factors that contribute to the medicalization of young people’s lives (such as

prescription drugs). Field research (such as the one carried on in the

University of Salerno and presented in the present study) reveals that, as

shown by the reality under examination, there is a desire to resolve internal

problems typical of the younger generation through the application of

externally introduced elements (pharmaceutical products). The conclusions

of the field research regard the fact that for young people drugs are a means

of maintaining constant the rhythms and activities relative to and in parallel

with existential frequencies and patterns. Another conclusion is that it is

possible to understand how the perception of young people on both health

and illness is dependent upon a series of social configurations in which they

are involved and which contribute to forming the identity structure of

individual young people.

Keywords: youth, drug, medicine, field research, pharmaceutics

1. Reasons for the Research

In the generational continuum the term

“young” has acquired numerous socio-

historical connotations but it has almost

always been viewed by society in general

as a synonym of differentiation and/or

contestation, establishing a “condition”

and a privileged image of change. A

specific focus on the young people of

southern Italy has occasionally been

undertaken, but only in part, and without

sufficient care to the differences present in

this part of the country and to the

heterogeneities that have been, and

continue to be, an essential part of its

modernisation. The processes by which

youth identities are built up are often

founded on and, at the same time,

determine a central role for young people

as consumers and yet a minor role as they

are effectively relegated to the margins of

society.

The causes of this confinement process

can be sought by investigating the ways in

which the social, political and cultural

establishment builds up young people in

the contemporary context as necessary and

integrated social subjects, on the one hand,

and yet places them in a marginal,

generalised and undifferentiated condition

on the other.


176

This type of circumstances gives rise to a

non-predetermined process of entry,

presence, exit and absence from social

roles that has clearly contradictory effects

on the personality and that, obviously,

makes the subjects’ extrinsication

objectively precarious, partial and often

temporary. In terms of existential

condition, in Italy and, more specifically,

in Southern Italy, this accentuates

situations of anxiety, tensions, a painfully

long wait for employment and, at the same

time, it exalts collective dimensions, the

need for self-representation of the

individual and symbolic manifestations. It

must also be remembered that, in a society

of symbols, health also becomes a

consumer product, a symbol of potential

and social status and, hence, a projection

of the idea of health as social prestige

(transferred first and foremost into the

representation of the body). This prestige

is achieved through the sometimes

relentless pursuit of what is considered

individual wellbeing, with the result that it

may give rise to stress and malaise.

The number of people enrolled at gyms

for physical fitness does not only indicate

awareness in the achievement of

wellbeing: control over one’s own body is

not merely a personal factor, it must be

flaunted and this ostentation encapsulates

the contradictions of the modern

conception of the body, its use and its

language (Rella, 2000; Sassatelli, 2000).

With regard to these premises, in the

research sphere there emerges the issue of

conducting a series of investigations in

southern Italy that can truly capture the

structural processes present in this part of

the country as well as the effects of

territorial dimensions on single individuals

at the intersection of urban and community

realities, in the perspective of establishing

a relationship with the dynamics of

everyday life and with the processes and

problems of individual (and collective) life

courses, within the historical context of the

relationship between the establishment and

young people.

The numerous research studies carried

out in Italy on the youth issue have

investigated different areas of the

problematic dimension of young people,

from unemployment and the various

processes of education, both in and out of

school, to forms of refusal (or self-

segregation) of communication,

dimensions of aggregation and the

resulting dynamics that give rise to life

processes, forms of solitude that end up in

mental illness and, finally, to the failure of

any attempt of interaction, which

culminates in suicide (1). However, the

research carried out on the condition of

young people seems to have left several

central (and extensive) existential areas

unexplored, for instance concerning problem

issues such as maternity, love, running away

from home, unexpected events, sudden life

changes, health, the urban condition and so

on. There thus emerges a clear contradiction

between the considerable research that has

addressed the “youth condition” over the

years and the number of issues that have been

neglected, not to mention the specific areas of

southern Italy which, in the majority of cases

are not even taken into consideration (2).

These premises may therefore contribute

to clarifying the reasons why, in agreement

with the observations now being made

along the lines of existing research, this

investigation needs to be carried out on

young people, prescription drugs, health

and medicine. This research is carried out

with two considerations in mind: on the

one hand, the health dimension and the

importance of the body to young people;

and, on the other, the factors that

contribute (prescription drugs) to the

medicalization of young people’s lives.


177

The dimension of health is a key element

in the analysis of individual life courses, of

well-being and malaise, of citizenship

rights, and of the system of social, gender

and generational inequalities.

The race to improve performance

sometimes turns well-being and malaise

into the two sides of the same coin, first in

a diachronic and then in a synchronic

perspective. Our research is intended to

pinpoint, by means of a quantitative and

qualitative methodology, when, where and

why young people request both medical

and pharmacological help in order to

improve their relationships. This

perception stems from a structured and

consolidated awareness of a me/self, that is

to say of how a person feels they are

perceived by “significant” others [29].

The body contributes to the emergence

of these dynamics. We may then assert that

one of the motivations pushing young

people to take excessive care of their own

body is that a body language shared [by the

other] legitimates the role of one’s own

look to the point of considering it as the

matrix of a “status or non status” of health

that has been called the “body idiom”, a

conventional reasoning that plays a symbolic

and normative role [40]. The body idiom, a

performer without a voice, conveys a non-

verbal communication that allows spectators

to capture an important image of the

individual’s outer balance, through his

capacity to send images while concealing

any state of anxiety, depression or other.

Medicalization of the everyday life of the

young people involves a process by which

nonmedical problems become defined and

treated as medical problems, usually in

terms of illness and disorders [13]. In other

words, medicalization can be described as

the extension of medical categories in

everyday life.

Recently, The Lancet (369/2007) has

dedicated ample space to the issue of

medicalization. Here, McLellan states the

question clearly: “Once upon a time,

plenty of children were unruly, some

adults were shy, and bald men wore hats.

Now all of these descriptions might be

attributed to diseases - entities with names,

diagnostic criteria, and an increasing array

of therapeutic options” [28: 627].

Therefore the Lancet raised this issue by

publishing a number of papers that tried to

shed a new light on some crucial aspects of

the medicalization process by looking at it

from a new perspective. While in the past,

according to the early definition given by

[21] the term medicalization meant a

process promoted mainly by the doctor,

today many promoting agents have come

to the fore. Jonathan Metzl and Rebecca

Herzig [31] identify some of them, such as

the patients and the practice of “direct-to-

consumer advertising”, and the

pharmaceutical companies with their

economic policies.

Other authors think that while “young

people, who were once considered as the

passive victims of medicalization, now play

an active role, especially in the decision-

making process. The key factor seems to be

the influence of medicine upon the ethical

attitude of young individuals, the

relationship with ourselves, our judgment

about the kind of person we wish to

become and the kind of life we wish to

lead” [34].

In the U.S., for instance, with the

liberalisation of Direct-To-Consumer

(DTC) advertising, the physician-patient

relationship has undergone significant

changes. Hollon (2005) states that patient

requests for prescription drugs consistently

affect the prescription attitudes of

physicians. About 40% of appointments in

which the discussion involves DTC

advertised drugs end up with that drug

being prescribed. Then, through a

metanalysis of a great deal of research,


178

Hollon demonstrates that almost 80% of

physicians are convinced that DTC ads

encourage people to look for treatments

they do not really need (2005: 2031).

All this can be attributed to the fact that

nowadays young people are increasingly

"demanding", nor can we deny that there is

a different health culture today. Health is

not only “lack of pathology”, but also

“enhancement”; furthermore, an enlarged

“health literacy” [23] pushes the patients to

become consumers who look after their

wellbeing (Ingrosso 2007).

In this context, it would be worthwhile to

focus on the Drugs National Agency’s

report of a steady growth in prescriptions

of anxiolytic and antidepressive drugs in

Italy over the last few years. Most of these

treatments are prescribed by general

practitioners, who have to face a huge

demand for medicalization from younger

people as a result of difficulties in the

socio-relational sphere. A set of symptoms

is increasingly becoming a “disorder” and

in today’s society we are witnessing a

growing medicalization, not only of what

is pathological, but also of what can be

“improved” (the cases of Viagra and

cosmetic surgery are emblematic).

In mass media communication health

turns into a fashion, a consumer product, a

look. There is an increase in fitness

practices that promote a “well-shaped”

body and mind able to yield a high

performance level that is fit for the society

of the perfectible and which therefore

requires flexible procedures at work and in

present-day social life. The consumption of

new substances, with a greater or lesser

doping effect is increasing to meet the

demands for efficiency, visibility or

compensation for fears of inadequacy and

isolation [8]. Because of the mocking

paradox of mass society, in which the

relational dimension of “being there”

rather than “being” haunts the present time

of everybody and the process of “staying

with” seems more important than

“staying”, solitude, exorcised in a thousand

ways, materializes again as a companion

escorting individuals, above all younger

people, on their social pathway [9].

Thus normality, in contemporary society,

seems to take a violent and de-structuring

semantic twist: from an expression aimed

at recognizing a status of “good health”, of

“being like” to a concept of hedonistic

perfectibility and implementation.

This article, based on research conducted

amongst young people living in the

southern regions of Italy, discusses the

largely under-researched theme of the

association between pharmaceutical use,

health and young people.

Field research reveals that, as shown by

the reality under examination, there is a

desire to resolve internal problems typical

of the younger generation through the

application of externally introduced

elements (pharmaceutical products).

In adolescence, assumption of

pharmaceuticals is seen as an answer to

problems of insecurity or, in some cases,

identity. Drugs are also seen as a means of

resolving difficulties relative to the process

of transition, to contradictions and to

situations typical of the younger generation

such as anxiety problems, mortality, future

prospects and to the inevitable upheavals

arising from a confusion of subjectivity.

For young people, prescription drugs seem

to represent what Valéry says art

represented for the author. He identified

the original motivation for artistic creation

in that aesthetic need that belongs solely to

the “author”, who initially displays

indifference towards a possible

“audience”. At first there is the anxiety

(spleen) of a man who feels horror for the

void – in our case, the time and space of

uncertainty experienced by the youth

population – which is both a void of space


179

and time. The restlessness characterising

sensibility can indeed be related to the

sense of “instability” that the subject

experiences when faced by empty space

and waiting. In short, the need to fill up an

empty gap in time or to fill an empty space

is a natural need because it is innate to man

(Valéry, 1935). Zygmunt Bauman recalls

the complex mechanisms underlying the

construction of uncertainty and insecurity:

if our society tends to reassure the public

dimension of subjects but attacks them in

their every private niche, what is

manifested in terms of the subject’s

potential crisis, i.e. the erosion of

confidence in his/her body and lifestyle

certainly assumes a “striking” nature for

the individual, especially if it is a young

person [1].

Therefore, in young people, there is an

increasing need to distance themselves

from times and spaces that can suspend (or

suggest that they are unable to follow and

control) the frenetic rhythms of everyday

life. The anxiety of contemporary reality,

the uncertainties of the existential process,

the question marks looming over one’s

own future (not actually expressed but

present on the individual level, often

unsaid but not necessarily unlived or

unperceived), the crises within one’s

symbolic universes [2], the discontinuities

in relational processes, the crisis of an

increasingly rarefied and unsatisfactory

relationship with the historic reference

institutions of socialisation are all elements

that exert a dynamic effect also in the

creation and maintenance of the ability to

control one’s own body, subjectivity,

individuality and inherent differences. The

latter become guaranteed by prescription

drugs, the means by which the individual

may not be obliged to interrupt the dynamics

of their own existential frequency but remain

able to keep up with it.

For young people, drugs are a means of

maintaining constant the rhythms and

activities relative to and in parallel with

existential frequencies and patterns.

Young people seem to have accepted the

idea that, in a physical and cultural

colonisation process, the pharmacological

world is invading all walks of life. The

self-proclaimed objective is to help

individuals to constantly improve their

daily abilities by reducing difficulties,

ensuring certitude and the capacity to

exteriorise.

The research also demonstrates that

some habits of youth regarding the use of

pharmaceutical products (drugs) are the

products of a social construction

originating in the primary social group -

the family - which then become

fashionable within peer group structures.

2. Premiss and Methodology

Judging from this research, in a process

of physical and cultural colonisation,

pharmacology is invading every aspect of

the life (and body). The self-proclaimed

objective is to help individuals (at both a

physical and psychological level) to

constantly improve their capacity in the

course of daily life by reducing difficulties,

ensuring certitude and facilitating a greater

degree of exteriority.

These considerations have led to the

decision to investigate what may be, or

could be, the reaction of young people and

the generation preceding towards the

assumption of pharmaceuticals.

Moreover, when a subject abandons,

delegates and places trust in

pharmacological and medicinal treatment,

health protection becomes an act of faith,

independent of the effect which the

pharmacy has upon the organism.

It is therefore important to understand

the trust, or lack of it, towards individual


180

organisms and also the kind of relationship

which exists between the assumption of

pharmaceuticals and the various levels of

information and disinformation. Starting

from this hypothesis, field research was

carried on a sample base of 550 students

from the University of Salerno. In order to

obtain a balanced cross-section, the

samples were taken from faculties and

degree courses in Mathematics, Pharmacy,

Engineering, Economics, Law, Sociology

and the Communication Sciences. Only 511

young people answered the questionnaire:

49% male, 51% female, one third attending

science faculties, and two thirds attending

humanistic ones. The sampling procedure

employed the two-phase cluster technique.

The first phase sampled the Faculties present

at the University of Salerno, while the

second phase selected the lessons timetabled

for the period of the investigation (according

to the degree courses, the sample included all

the courses from the first to the final year so

that its composition was representative of the

university student population in terms of age

and course attended).

The origin of the sample is

heterogeneous: 56% come from Campania

while the remaining 44% are from other

Italian regions (Basilicata (21%), Puglia

(10%) and Calabria (13%).

Principally, research was aimed at the

relationship which students have with the

use or abuse of pharmaceuticals and the

relative degree of information or

disinformation regarding their use. In

particular, the investigation was geared

towards analysing and understanding: a)

how the daily discomforts encountered by

young people are faced and overcome - or

kept in check - by the use of

pharmacological substances; b) the social

importance which drugs assume in the

various existential life-patterns of young

people; c) to evaluate the varying extent to

which factors relating to social context and

cultural roots have an influence – and to

what measure - on behaviour patterns.

3. Drug Indoctrination

Young people appear to want to resolve

internal problems and conditions typical of

youth by resorting to external remedies to

their problems and to their condition:

pharmaceuticals. Indeed, the majority of

the sample admitted to the occasional use

of pharmaceuticals (40.3%); 32.1% stated

that recourse was “hardly ever”, whereas

4.3% maintained “never”. 16% of the

sample accounted for “fairly regular use”

and 7% classed themselves as “frequent

users”. However reassuring on the surface,

these statistics do not conform to answers

posed by a check question to which only

3.1% failed to reply and 0.4% attested that

they never used pharmaceuticals at all. The

vast majority of the remainder of the

sample is distributed amongst a percentage

of assumption of various pharmacological

compounds whenever symptoms –

however minor or trivial – present

themselves.

Drugs are legitimised by a reassuring

importance which is both expressed and

perceived: “drugs have an essential role;

above all, they validate the ability to

intervene on the part of a doctor – ‘I am

prescribing this, therefore I know what you

have’ would appear to be the comment of the

doctor making out a prescription and

avoiding further examination or referring the

patient to a specialist or hospital - an

alternative which could be interpreted as a

sign of incompetence” [15].

Beginning with this encouraging

legitimisation, drugs become the mediator

between the potential subjects who

consume them or are likely to (at this

stage, it is no longer important whether

they are prescribed by a doctor or on the

suggestion of a chemist or family and


181

friends) and the progressive scientific

society.

From this research it is also possible to

evaluate the real success of

pharmaceuticals.

The investigation illustrates how drugs

are perceived by young people and how

that perception contributes towards a

guarantee of the success of officially

recognised medicines and, alternatively,

how they can enrich and improve the

quality of life.

One of the first results of the sample is

the almost unanimous recognition of the

role which drugs have acquired in

guaranteeing the state of health of the

individual, data which evidences the

widely held conviction, amongst the

young, of the scientific foundations on

which social progress is based.

Moreover, such data becomes even more

convincing when confronted with figures

of 19.7% and 26.4% of the university

student sample, all of whom maintain that

drugs are not yet fully capable of

guaranteeing an improved state of health.

This poll result underlines the desire and

trust that young people place in future

advances in the field of scientific and

pharmacological research which are geared

towards the improvement of the actual

governance of well-being. The

expectations, therefore, given to the role of

pharmacy are clear: to guarantee continuity

to the existential life pattern of the

individual. In particular when one

considers that only 6% of the sample do

not trust drugs or are simply incapable of

assuming a personal position over the

question.

A perspective which seems to remain

unchanged even when young people are

asked in which alternative they place most

faith: in official medicine, in homeopathy

(3) or otherwise. Here again, with the

impossibility of alternative medicine

asserting itself to the same degree, the

sample places unequivocal trust in official

medicine.

When the influence of socio-

demographic variables are considered in

relation to the subject gender, it becomes

evident that belief in pharmacological

discovery is analogous for both males and

females. However, when the relative

erudition of the parents is taken into

consideration, different data is forthcoming

– indeed, in parallel with the elevation of

family scholarship, there is a

corresponding increase of trust in official

medicine and pharmaceutical remedies.

The argument discussed so far is

confirmed by the section of the

questionnaire devoted to the level of

compliance (assumption of

pharmaceuticals and degree of therapeutic

efficacy) and also illustrates to what extent

individual subjects are prepared to delegate

or abandon themselves to pharmaceuticals

- or to place their unreserved trust in them

- in order to improve their psycho-physical

potential. This was so much so that when a

sample was taken from senior secondary

school students, 80.8% echoed agreement

with 79.9% of the university student

sample affirming that the effect which

pharmaceuticals had upon the organism

was “fairly good”.

Furthermore, when the 13.6% of the first

sample and the 15.7% of the control

sample are taken into consideration and

which state that the physical effects of

pharmaceuticals are “sufficient”, it can be

added that 95% of the sample base of

young people examined demonstrate that

pharmaceuticals have an increasing

tendency to co-exist in the existential

pattern of the subject. Moreover, drugs are

assuming an increasingly reassuring

characteristic within the individual lives of

young people.


182

It is then, perhaps, no accident that in

another section of the questionnaire 97%

of the sample – 9.7 students out of 10 –

state that they have taken and are taking

pharmacological substances.

This same percentage is also confirmed

by the answers to a control question which

underlines how drugs – from anti-anxiety

to anti-inflammatory – are assumed

conscientiously and appropriately for

several symptoms. Young people, when

affected by certain maladies, are no longer

prepared to wait for a natural

counterbalancing reaction from the body

itself but prefer to accelerate the process

with chemical products.

In an attempt to explain the relationship

between the trust invested in drugs and the

effect that any pharmaceutical product may

have on the organism, the following

question was posed: “Before taking any

kind of drug, do you read the

accompanying instructions?” (while

conscious that, despite the advice given in

the legal decree no. 44 - 18.02.97, such

instructions are still a long way short of

offering clear warnings and explanations

over an arc of three hundred and sixty

degrees).

70.6% of the sample read the

accompanying instructions, 10.4% do not

bother, whereas 18.6% were inconstant. As

regards the majority (70%) the comment

made was: young people who read the

accompanying instructions (nick-named

“little liar”) already have good reason to

be wary of the side-effects which even the

most mundane substances can provoke.

However, this would appear to be short-

sighted, it is impossible to guarantee that

all the possible undesirable side-effects, as

documented in the “instructions for use”,

have been previously identified and

confronted (4). This is a possible answer as

to why drugs are increasingly successful

between and with young people:

paradoxically, it is as though a vague

understanding of the nature of a drug is

also its certificate of guarantee for use.

Besides which, at this point we are

facing that which Luhmann defined as the

negative aspects and/or the “malfunction”

of modernity. In other words, society finds

itself having to confront consequences

determined through its own structural

selection, such as ecological problems in

the modern world and increasing tension

fuelled by the attempts to maintain the

actual level of social well-being.

It is, then, precisely this tension created

through the maintenance of well-being

which could provide an answer, in

Luhmannian terms, to the taking of

pharmaceuticals on the part of young

people at risk. The risk that a young person

makes in taking pharmacy without first

referring to the “instructions for use” or,

alternatively, when conscious of the likely

side-effects, is determined by an appraisal

of the potential damage which, in itself,

derives from a decision taken by the self-

same person [26].

The motivations referring to those of

sample quote who declare to not reading

the accompanying instructions (56.9%) are

particularly interesting: those who do not

read the instructions say it is because they

have prior knowledge, whereas the residual

37.2% argue that the instructions are

difficult to understand and that it is better

not to bother (always remembering that the

subjects are at a university level, which

provokes reflection upon the greater part of

the population who, under completely

different circumstances, must be unable to

read or understand the indications

anyway).

In this instance, we are confronted by the

category at dangerous discussed by

Luhmann, in other words, the potential

damage to which the individual is

unaware, inasmuch that the obscure


183

terminology adopted to describe the

pharmacy does not permit the person who

is about to take the medicine to understand

the implications of doing so.

Moreover, the last consideration with

reference to the sample raises a bi-lateral

observation: a) could this contribute to

successful economic returns for

pharmacological multi-nationals?; b) could

the success of pharmaceuticals amongst

young people be part of a generalised and

voluntary disinformation strategy

concerning potential pharmacy users?

This type of behaviour could indeed be

common to other processes in which young

individuals decide to assume certain

substances: they are aware that

assimilation will, in any case, modify the

condition of their body. Nevertheless, the

knowledge of the final result of the

process, however approximate, is

sufficiently satisfying to annul any

information regarding the internal bodily

process leading to the final result. Thus, it

is the end result which is decisive;

regardless of any harmful side-effects, the

determining factor is the modification.

4. Pharmaceuticals in General and

Alternative Therapy

Interesting research data comes out of

21% of the sample who have prior

knowledge of pharmaceuticals in general,

data which is subsequently confirmed by a

later question to which 22% of the sample

attribute therapeutic properties and effects

to commercial medicines already marketed

by well-known pharmaceutical companies.

The data relative to the information

which young people have of

pharmaceuticals in general underlines

concepts and signals which public opinion

has been indicating for some time. Signals

systemised in the understanding and belief

of the individual - not at an “emotive” but

rather at a “rational” and “conceptual”

level – in certain therapeutic schemes

which are no longer simply tied to well-

known pharmaceuticals (and which have

become part of a way of life) but to

pharmaceuticals in general (5) as is also

the case with therapeutic treatments related

to alternative medicine.

Trusting in this form of therapy is

dependant upon whatever kind of

familiarity and information the young

person may possess – together with the

existing relationships, discussed

previously, such as doctor/patient or with

other important socialising elements. This

would explain why 17.4% of the sample

believe in unofficial forms of medicine and

why, out of this 17.4%, 14.1% claim to

have greater faith in homeopathic

medicine. Indeed, the function of

homeopathic medicine would seem to

vindicate that therapeutic mandate which,

in the words of Thomas Sandoz is “a

profane rite of exorcism”. To follow, to

recognise and to trust in this practice has

the effect of rationalising some of the

procedures of improvement, both of the

cure and of the therapy of the actual state

of well-being or indisposition. This could

occur through a decomposition of the

function of the vindication of homeopathy

in “four projects” [35].

In the first place, homeopathy introduces

the possibility of contrasting medical

impotence by seeking auxiliary solutions

outside of the parameters of the biomedical

verdict (or medical practitioner), thereby

overcoming the innate passivity of the

subject towards illness.

Secondly, homeopathy encourages the

fight against the mounting uncertainty

which afflicts people suffering from illness

(regarding the origins, the prognosis, etc.)

by directly including and involving them in

a cultured dialogue of explanation.


184

Furthermore, homeopathy overcomes

that silence which can often follow the

pronouncements of experts, maintaining

intact latent resources in the subject which

official medicine has a tendency to nullify.

Finally – the fourth and last project –

homeopathy endorses opposition to the

modern movement towards the

medicalization of society and opposes

scientific reasoning and materialism which

is perceived as “the power of dominating

forces” [35].

Thus, whilst not “justifying

assimilation” of homeopathic therapy over

that of official medicine, the myth of the

therapeutic potential of homeopathy may

be attributable to the power of its

credibility, a factor which exercised a

distinct fascination over part of the

research sample. Young people exorcise

uncertainty – to which, in terms of health

care rights, official medicine is still

incapable of responding – by resorting to

alternative medicines and medicaments

which facilitate (or are said to facilitate)

aggregation in the dramatically decisive

moments of their existence.

5. From the Recognition of Professional

Status to the Recognition of Social

Status

In order to isolate and verify some of the

answers previously given by the sample, in

the fifth section individuals were asked to

indicate in which subject – family doctor,

specialist, chemist, friends/family – they

invested most trust when looking for

advice or a pharmacological prescription.

Replies indicate that, of the four subjects,

in terms of trust, social and professional

recognition and the expedience of

prescriptions, specialists were adjudicated

most competent (49.7%). This figure was

followed by general practitioners

(37.2%), friends/family (5.7%) and,

lastly, chemists (3,7%).

Turning to various exponents of the

structural-functionalist school, such as

Talcott Parsons [32] or William Goode

[20], it could be said that such a high level

of recognition of the professional status of

medical practitioners - greater even than

that given to specialists - has taken shape

in the wake of the organisational reform of

labour within industrial and urban society.

A development which has privileged the

division of functions and tasks and

produced a consequent demand for

qualified or specialised services outside of

the family environment.

All of which, however, has led to an

ulterior consequence: the ever-increasing

fragmentation of medical knowledge, a

phenomenon which has had an inevitable

effect upon the ability to prescribe any

required pharmacy. Moreover, in the midst

of this fragmentation process, although a

deeper bodily understanding has evolved,

it is often difficult to grasp that what is

being lost is the link between states of

illness not attributable to a specific part of

the body but rather to the body in its

entirety. Thus, the importance given to

medicine and pharmacy is a consequence

of the values attached to health, life and

death. According to these authors the

progress of knowledge and preparation has

induced a need: recourse to medicine in

order to legitimise professional status.

However, the symbolic commutational–

ists and theoreticians of the Chicago school

– in particular, E. Freidson (1970) – refute

both concepts: inasmuch that the rise in

status of the medical profession

automatically depends on the new division

of labour and, that it stems, fundamentally,

from the progression of knowledge.

The medical profession, in this respect,

gains professional status through those

who, averaging out a multiplicity of


185

considerations, manage to persuade

themselves of the unsubstitutional nature –

in terms of character and service - of their

competence and their ability. (in other

words, a professionality which, rather than

being achieved, is recognised by others).

Knowledge certainly contributes to the

definition of professionalism but it is not

easy to establish that precise moment in

which such recognition legitimises and

confirms the privileges of professional

status [32].

Moreover, this research verifies that

young people’s trust is placed – as they

themselves confirm in one of the replies to

the questionnaire – in those representatives

of official health care with whom they deal

directly in daily life. Trust in medicines

prescribed by specialist practitioners,

greater than that invested in the

representatives previously mentioned,

would not appear to be different as regards

the type, whereas the level of trust given to

such professional figures increases in

correspondence to the educational quotient

of the family and, in consequence to

parental professionalism and the nature of

their work.

The research also opens the possibility of

analysing the way in which a prescription -

or the recommendation by a specialist of a

particular medicine and its subsequent

acquisition - results in a dual-recognition:

on one side, that of professional status and,

on the other, that of social status within the

family.

6. The Perception of Young People

towards Change

What also becomes evident from the

questionnaire is the perception among

young people that medicines have changed

in substance and role. It is in the

transformation of the role (and objectives)

of medicines that the “personal data bank”

of any subject “needing” medicine is being

modified and filters back, through the

various generations, to young people and

children.

Today, medicines are no longer merely

therapeutic, no longer is there recourse to

pills when a state of illness is diagnosed

(indeed, not long ago, pharmacy was only

resorted to after immunity mechanisms

were found to be insufficient) but rather,

for many, medicine has become a means of

prevention, both in short and long-term

circumstances.

The sample would appear to be

conscious of this process which has seen

conceptions of pharmaceutical use move

from care, treatment and cure of illness

through to a preventative means of

forestalling it. As regards this data, it

perhaps worth reflecting that many young

people, approximately 66% of the sample,

turn to pharmacy at the first sign of a

possible attack of influenza or similar

discomfort.

This fact must also lead us to reflect on

how these continually ambivalent young

people are at the same time subjects of

transformation and objects of

subordination with respect to consumer

processes: it contributes to temporarily

assigning them with citizenship and to

structuring their identity, and as such it

must be recognised, albeit tacitly. The

ironic paradox is that, in this case, unlike

in clothing fashion, tastes in music or any

other area of commercialised leisure time,

this is a consumption that acts directly on

them personally, on their body and on their

identity. Therefore, prescription drugs have

today become a consumer product for

young people, through which to assert,

construct and project an individual and a

collective identity – on this issue,

advertising never presents us examples of

isolated subjects coming into contact with

a substance, but we are always shown this


186

practice being manifested within a group

of people bound together by friendship,

affection, etc.. In many cases among

campus students, therefore, prescription

drugs assume the role of a “fashion” with

the characteristics described by Simmel:

«fashion is imitation of a given model and

thus satisfies the need for a social

approach, it leads the individual along the

road everyone follows, from a universal

model which reduces the behaviour of the

individual to a mere example. But

nevertheless, fashion satisfies a need for

difference, the tendency towards

differentiation, variation and distinguish–

ing oneself from the others» (Simmel, 1905,

pp. 30-1). It must not be forgotten that the

prescription drug at the centre of attention

(like all the others) will have different

effects on the individual bodies and on the

individual identities (and, in spite of

everything, this is the very expectation of

the individuals): hence, analogous

performance for different and differentiated

results. A consideration which has

repercussions in a subsequent observation

which reveals how the sample cross-section

under examination are influenced and

socialised towards pharmacy.

Evidently, pharmaceutical use plays a

constituent role in the existential life

pattern of any individual. From the outset,

there is a consecration of the positive

nature of pharmacy which, subsequently,

has inevitable repercussions on initial

impressions: the first use of pharmacy is

that administered by parents to their

children. Clearly, this introduces an

element which both anticipates and

reinforces, beyond all other reasoning, the

socialisation of the substance: how could

our parents have possibly given us harmful

substances? And, given that for every child

parents “know all”, children assume that

they must be far better informed about

such substances than they could ever be.

It is, therefore, during the process of

cognitive and cultural differentiation

between child and parent that individuals

begin to acquire an awareness and,

contemporarily, ask questions about

pharmacy.

It would appear that the greater part of

the sample under examination have grown

up with the idea (probably due to the

argument previously outlined) that

medicine is good for them. Only a minor

number of the young people interviewed

introduced a different evaluation, arguing

that, in the meantime on their part, they

had converted to alternative therapy in the

conviction that such cures are not harmful.

Despite differences of faculty or degree

course, the sample group, with absolutely

no variation, continue to grow up under the

belief that for whatever anxiety, ache or

indisposition it can be easily overcome

with the aid of medicine: “for every health

problem or illness there is a suitable

pharmaceutical remedy”. An awareness

which, as testified by the sample, derives

from the principal agents of socialisation.

Fragmentary information such as that

relative to the theme health/illness (the

index of individual and social patterns

followed by young people) should perhaps

also be introduced; such information

derives in 40.1% of cases from television

and, in 20.4%, from parents.

Besides the mass-communication

influence of television on young people

regarding information relative to health

and illness, 4.3% of the sample also

nominates the radio and 11% specialised

publications. As regards this last assertion,

it would seem likely that the word

“specialised” covers an ample range: that

is to say, not merely those specialised

journals and periodicals which have

proliferated over the last ten years or so

and which specifically deal with health and

illness, but rather the inserts, notebooks or


187

weekly supplements which have become

standard to every daily newspaper and the

weekly and fortnightly publications which

come out at both a national and local level.

Despite the well-known fact that Italians

read little (particularly daily newspapers),

it is also true that in the case of health (and

pharmacy), a veritable communication

network exists from which, it would

appear, it has become extremely difficult

to escape. In consequence, for certain

themes - such as those relative to the

physical aspect - they become, in a real

sense, communal mass movements;

whereas, for many other medical

questions, particularly those of an

“intimate” nature, reflections either do not

exist or, alternatively, fail to become

interlocutory - an observation which is

particularly apposite when such questions

are directed at precisely those subjects who

have – and ought to assume - the

responsibility of replying.

Moreover, considering the statistics of

those who advise young people when not

visiting a medical practitioner (and who,

notwithstanding, take medicine for

physical or psycho-physical disturbance),

57.3% are parents, 5.9% are family

members, 4.1% are relatives, 4.9% are

friends and 17.8% take advice from a

chemist. Only 2.4% state that they do not

assume medicines unless it is on the advice

of a doctor. To this data other sources of

information can also be taken into account,

all of which, nevertheless, are constituent

elements in a pattern of socialisation.

Above all, an attempt was made to

corroborate the role and the effects of the

information or disinformation supplied to

young people by secondary agents of

socialisation.

At the end of 1999, the specialised

journal “Sanità. Il Sole 24 Ore” published

an article saying: “The fight for

promotional exposure together with

research into synergic relations with

sales personnel has resulted in a series of

heterogeneous initiatives. Some of them a

little embarrassing. A promotional

campaign, launched in 1998 by a

multinational operating in the

pharmaceutical sector, created a

promotional tie-up between one of the best

known headache pills and a compact disc

of relaxing melodies. Chemists were

expected to pull out the promo from under

the counter each time they sold a packet of

the pills.”

This advertising spot was transmitted

many times a day on both radio and

television, despite the fact that WHO

(World Health Organisation - the

international health agency of ONU)

recommends that the role of the mass-

communications media, due to its

enormous influence upon public opinion

and perception, should be: “…to control

the authenticity and importance of every

fact relating to pharmaceutical products…

avoid becoming the spokesmen for

promotional campaigns in favour of the

pharmaceutical industry…” [41].

Information broadcast by the mass media

– television, radio, newspapers, magazines

and specialist journals – is disciplined

under the legislative decree n. 541, 30

December 1992. This decree prohibits the

media from transmitting messages

contrived to persuade their audience to buy

products which proclaim to be uniquely

capable of improving a state of health or,

indeed, to allude that failure to assume

such products could lead to deterioration.

The decree also prohibits the marketing of

medicinal products which encourage the

belief that the guarantee of relief and

fitness is determined by natural products.

26.1% of the sample admitted to taking

pharmaceutical products without a medical

prescription. The principal agents of

socialisation influencing the choice of


188

pharmacy to be taken – as underlined by

WHO – were, in order of importance,

television, radio, specialised journals and

internet. For young people, then, such

mediums are suggestive and seductive.

Statistics which take on far greater

validity when confronted with the 30.3%

of the sample who admit to receiving

information relative to health and illness

through the communication channels listed

previously, either to avoid choosing

medicines autonomously or having to visit

a doctor for minor aliments.

Seductive propaganda has the effect of

inducing individuals to associate a series of

natural properties - in other words, rendering

them harmless – to certain products.

The success of pharmacology, of official

medicine and even that of alternative

medicine, is largely determined by the

influence of the mass media. The

underlying message communicated is that

of a fascinating ideal designed to overcome

any form of subjective analysis - as for

example when facing a statement of

propaganda such as: “better a tried and

tested traditional remedy which has no

harmful side-effects on the body”. A

slogan which is then linked to the image of

a slim and beautiful woman visually

eulogising the product at hand.

In other words, audio-visual

communication designed to neutralise

rational responses towards the assumption

of a therapeutically orientated product.

How many of the young people

interviewed are conscious of the

“provenance” of products within the field

of alternative medicine? How many of

them are aware that bio-therapy/herbalist

and homeopathic remedies are, in any case,

laboratory derivatives? Are they equally

alive to the idea that the herbal extractions

from which such palliatives are “made”

are cultivated and chemically treated:

manure, fertilizers, insecticides – chemical

additives essential for the optimisation of

the process of cultivation and industrial

production of “medicinal” herbs?

The effects, the therapeutic properties of

herbs – which, once upon a time, grew

spontaneously and naturally – are today

largely the end-products of chemical or

bio-chemical cultivation; whatever

substances administered, herbal-based cure

is the most traditional form of pharmacy

associated to official medicine. In modern

society, these so-called biological-

derivatives – widely considered to be both

therapeutic and non-toxic – are also the

end-products of a laboratory-produced

chemical process (6).

Clearly, commercial media is primarily

interested in constructing messages which

emphasise the beneficial effects of

pharmaceutical products and conceal any

undesirable side effects; whilst, at the same

time, ignoring an equally interesting and

opportune occasion to inform individuals

of the correct usage and circumstances

under which the product is consumed.

Apart from the media, the other principal

socialising agent which has an influence

over the use of medicines and medical

information, is the family. Much research

demonstrates that, as regards the

assumption of pharmacy, the level of

education and relative medical knowledge

of the mother determines differential

behaviour on the part of the children.

In the book “To grow up well and better:

one reply to the most frequent questions of

mothers” (AA.VV., 2000) it is made

evident how much this relationship is

dependant upon a continual flow of

information regarding those medicines

utilised for curing their own children, from

aspirins to anti-histamines.

In the opinion of the authors, the most

interesting aspect of the research is to have

been able to evince that, in terms of the

information and health education


189

requirements of Italian mothers, no

differences are imposed by geographical

and cultural variables (always remember–

ing that the survey deals with an

indeterminate sample covering mothers

residing in totally opposed cultural and

geographical realities such as Milan and

Matera). The research clarifies why the

socio-demographic variables taken into

consideration during the predisposition of

the questionnaire – such as educational

qualifications and place of birth – do not

influence the way in which young people

are informed about, or socialised towards,

the use of pharmacy as a means of

regularising their state of health.

At this point, it becomes clear (given that

57.3% of the sample state that

pharmaceuticals are taken on the advice of

the parent and, in particular, the mother)

that, in the case of medicines, the principal

factor of influence over young people is

also the most powerful agent of primary

socialisation. This data, relative to the

influence emanating from the previously

defined primary socialisation agent, is

confirmed by 5.9% who state that

pharmacy is taken on family advice; by

4.1% who receive advice from relatives

and a further 4.9% who follow the

indications of friends.

Moreover, in this investigative section of

the questionnaire we can observe that not

only do the young people in our sample

advise their friends on the drugs to take, on

the basis of their previous experience, but,

at the same time, they themselves receive

advice from parents, neighbours, family

members or friends when they do not turn

to their doctor, while only 2.3% claim not

to take drugs unless prescribed or

recommended by their doctor. There seems

to emerge another consideration of that

fashion that «gives the individual the

certainty that he is not alone in this action

and proceeds on the basis of previous

experience as if on a solid platform that

alleviates the activity of the moment from

the difficulty of sustaining oneself»

(Simmel, cit., p. 30).

Socialisation of drugs, which for young

people is the product of peer group

influence, explains the widespread social

recognition which is attributed to one

medicine rather than another. For example,

it could be supposed that the limited

success of generic medicines amongst the

sample group, as previously stated, is

probably due to their fledgeling

appearance on the generic pharmaceutical

(7) market and a limited notoriety within

family peer group structures. Moreover, in

the absence of customary recognition and

use of the product, young people ignore it

(at least, for the moment).

However, as time passes and new

pharmaceutical products claim more

attention and greater acceptance amongst

the primary socialisation agents, the same

process of the usage of generics (which at

present can be seen to operate with well-

known multinational pharmaceutical

products) will also become the rule.

Indeed, it is hardly casual that young

people refuse to assume “new” drugs – in

the face of advice from doctors, nurses,

medical orderlies and/or a chemists – even

when the motive for their use (and the

substitution of well-known alternatives) is

justified by a potentially superior

therapeutic effect coupled with minor

collateral consequences (8).

Pharmaceuticals have been invested,

through advertising and peer-group habits,

with a whole range of precise

connotations. Above all, on the part of

consumers, they have become consumer

products; chemical composition,

therapeutic efficacy and undesirable side-

effects have become secondary

considerations: “Any pharmaceutical

carries more importance as a label than as

a medicine” [5].


190

7. Interim Conclusions for the Base of

Further Research

An extension of this research would

entail taking into consideration a

constructivist approach which consented –

as regards youth health themes,

environment and the inherent self-

awareness of the subjects themselves – to

understand how perception towards certain

interrogatives (such as conceptions of

illness and well-being from both a personal

and general perspective) are individually

constructed in parallel with the assembly

of information and experience.

Regarding any consideration of the

possible understanding that young Salerno

students may have towards the subject of

health naturally depends upon the

importance that each individual attributes

to the argument - not forgetting those

factors which can influence the

construction (or non-construction) of that

importance (social-demographic variables:

age; sex; the provenance of both student

and family; schooling, etc.) – in other

words, precisely that importance motivated

both from within the subject and from

individual external experience (Luhmann,

1971). Nevertheless, it can be safely

assumed that any young person will have

acquired a rudimental understanding of

pharmaceuticals, not only as regards their

potential efficacy relative to health and

illness but also in terms of subjective

analysis and active response to such

themes.

And, whereas the field of medicine often

encounters transitory difficulties

determined by the massive growth in

technological and pharmacological

innovation, it is also true that, despite

everything, medicine as a discipline enjoys

notable recognition on the part of young

people. This is confirmed, for example, by

those young people who, often

ingenuously, undergo cures, therapy and

even cosmetic surgery in order to resolve

inter-personal and existential relationships.

Young people now seem to be aware of

these dynamics and have established a

fatalistic attitude of yielding,

relinquishment, refuge and delegation to

discovery and scientific research and to

those who hold this knowledge and

represent for them one of the few

certainties for the improvement of their

future. Baudrillard (1976) certainly springs

to mind in this connection: «it is with

generalised individual somatisation, with

the body becoming an object of prestige

and salvation (…) that the medical class

establishes itself in the position of social

super-privilege it currently occupies »

In order to interpret the new ways of

appealing to young people - through the

schematics of perception, understanding

and information of health within an

individual context and of those instruments

and techniques which govern or re-educate

these aspects - the starting point is

undoubtedly the theory of Norbert Elias.

Moreover, it is only by following a

progressive approach over an extended

period that transformation can be

satisfactorily identified. Indeed, to

successfully reveal the mutation of interest

of young people in matters of health - from

initial curiosity through to conversion -

matched with gradual improvements in

well-being, the minimum research period

required would be twenty years. Long-term

analysis of this nature could identify the

various phases and figures of influence

through, for example, an analysis of the

internal mechanics of groups of teachers,

of parents and of those institutions

principally concerned with the health and

welfare of young people.

Through the employment of a process of

semantic destructuralisation, what also

needs to be considered is that, in an


191

attempt to come to grips with the crisis

within modern medicine, analysis would

appear to be orientated towards

understanding in terms of “Canons and

Procedures” (“Rules and Regulations”) –

[7] - rather than attempting to reduce the

crisis to a single scientific paradigm.

Khun himself asserted that scientific

change was a product of rupture and

conflict, inasmuch that the employment of

canons and procedures as a solution to

crisis clearly indicates how some difficult

moments can be overcome through

different interpretations and theories.

At which point new semantic categories

– set up to overcome the impasse in which

the medical-scientific community finds

itself languishing – step into play.

Interpreting the crisis from the

etymological point of view of choice,

shows how (through changes in the criteria

used by the social-medical-health

community for communicating matters of

health, diagnosis and the construction of a

supportive reference base for operative

medical opinion) the institutions charged

with the promotion and distribution - in

terms of prevention and information - of

“public health” amongst young people can

be influenced into varying their

procedures.

It is not, however, simply a question of

isolating the interdependent factors and the

interaction between those subjects who

modify the existing situation in order to

create a new one, but rather the whole

range of factors – reinforced through

reciprocal inter-reaction – which ensure

the modification and restructuring of this

cognitive process relative to the theme of

health. As a result, it is possible to

understand how the perception that young

people have of both health and illness is

dependent upon a series of social

configurations in which they are involved

and which contribute to forming the

identity structure of individual young

people. On the basis of this premise, albeit

brief, any network of collaboration

installed between institutions, public or

private, whose objective is that of creating

a policy aimed at the younger generation

and geared towards the promotion of

culture, the environment, the safeguard of

rights, working conditions, self-realisation

and the pursuit of personal interests, needs

to give priority to both the theme of youth

and health and the consequences and

effects upon the individual, upon

individual identities and the inter-personal

relationships established with and within

society.

Notes

(1) The problem of suicide, which is

obviously related to the strength of the

social bond, is rooted in the history of

society and, at the same time, of the

sociological tradition, albeit in the

awareness of the different dynamics

attributed throughout the ages to the

choice to end one’s own existence. From

Durkheim’s work on the relationship

between the differing degree of social

interaction and suicide « A society is

highly integrated when its individuals are

kept dependent on it » (Durkheim, 1897).

(2) Think of the utterly insignificant number

on the youth issue in southern Italy

conducted by [6], [24], [38], [17], [30]

[33] and [37].

(3) Homeopathic medicine falls into the

category of alternative medicine.

Originating in the late XVIII Century,

this therapeutic approach was first given

credibility through the work of doctor

Samuel Christian Hahnermann. The most

sensational discovery was that the effect

of therapy was inversely proportional to

its quantity. For the homeopath, as

opposed to orthodox colleagues,

diagnosis and therapy concerns the entire


192

body, referred to as the “unitary

organism”. In the majority of cases,

medications and other elements used in

homeopathic medicine are individually

prepared using biological raw materials

of natural vegetable or animal origin. The

homeopathic term for these medications

is “tintura madre” (“mother tincture”).

(4) When references are made to values not

taken into consideration within the

territory, this is principally an allusion to

the historical importance of popular

medicine in Southern Italy and of its

particular role relative to the poorest and

least literate of the social community

(though not exclusively so) and, in

particular, to those lacking the necessary

resources to undergo or resort to

traditional methods of treatment. This has

given rise to a practical relationship

between traditional pharmaceuticals

incorporating natural products (above all,

herbs) linked to those organisational

structures and individuals invested with

the specific task of propagating its

validity and function: the process of

modernisation, which would appear to be

in a permanent state of evolution, has

given itself the task of accelerating this

process towards the eventual “triumph”

of official medicine (in all of its aspects).

In reference to popular medicine, see,

amongst others [36].

(5) “Quite good” is not a possible reply to

the questionnaire itself but rather a

convenient expression adopted by the

author to indicate the approximate

percentage of replies ranging from

“discreet” to “very high”.

(6) By definition, alternative medicine

expresses an optional – or, indeed, in

opposition – to official medicine: Its

success is rooted in the inability of

scientific medicine – evidence-based

medicine – to adequately respond to

matters of health as well as the diagnosis

of illness. For debate, see [7].

(7) The term generic pharmaceuticals

(medicines?) describes those medicines

which have the same active principles

and chemical composition as well-known

brand names (following years of

successful marketing on the part of the

pharmaceutical companies). A typical

example might be: Aulin = well-known

pharmaceutical; Nimesulide = generic

pharmaceutical.

(8) In the documentation of all

pharmacological research, it is stated that

collateral effects are those resulting from

research upon human organisms; to

which end, a sample group of patients

volunteers to assume, experiment, test

and reveal any positive or negative side-

effects of the medicine.

(9) In Europe, such remedies are associated

to the culture of pre-industrial society

and, as opposed to knowledge of

primitive cultures, are “a product of the

re-elaboration of popular and past

traditions on the part of the general

populace” [39]. In consequence, two

distinct and opposed definitions of

medicine or traditional remedies emerge:

on the one hand, an almost parallel

confluence between traditional and

alternative medicine and, on the other, the

romantic idea of a popular medicine with

its own origins but with no foundations

and quite separate from evidence-based

medicine.

References

1. Bauman, Z.: In Search of Politics.

Milano. Feltrinelli, 2000.

2. Berger, P. e Luckmann, P.: The social

construction of reality : a treatise in

the sociology of knowledge, NY,

Garden City, 1967 [tr.it., La realtà

come costruzione sociale, Il Mulino,

Bologna, 1969].

3. Berlinguer, G.: Medicina e politica.

Bari. De Donato, 1973.


193

4. Berlinguer, G.: Il corpo come merce e

come valore. In Rodotà S., “Questioni

di bioetica”, Roma-Bari.Laterza, 1997.

5. Bert, G.: Il farmaco come segno e

come mediazione. Milano. Feltrinelli,

1977.

6. Cavalli, A. (a cura di): I giovani del

mezzogiorno. Bologna. Il Mulino,

1990.

7. Cavicchi, I.: La medicina della scelta.

Torino. Bollati Boringhieri, 2000.

8. Cersosimo, G.: La coesistenza di

benessere e malessere. In: L’odore

della Bellezza. Wellness e Fitness (a

cura di) D. Scafoglio. Salerno. Marlin

Editore, 2007.

9. Cersosimo, G., Rauty, R.: Riflessioni

sul controllo sociale: dalla normalità

della devianza alla normalità della

malattia. Keiron, n. 5, 2001, pp.

128-139.

10. Ciacci, M., Gualandi, V. (a cura di):

La costruzione sociale della devianza.

Bologna. Il Mulino, 1977.

11. Clarke, A. E., Mamo, L., Shim, J. K.,

Fishman, J.R., Fosket, J. R.:

Technoscience and the New

Biomedicalization: Western Roots,

Global Rhizomes. In: Sciences

sociales et santé 18, 2000, 2, 11–42.

12. Conrad, P.: Medicalization, Etiology

and Hyperactivity: A Reply to Whalen

and Henker. In: Social Problems 1977,

24:596-98.

13. Conrad, P.: The medicalization of

Society: On the Transformation of

Human Conditions into Treatable

Disorders. Baltimore. Jhons Hopkins


14. Conrad, P., Schneider, J. V.: Deviance

and Medicalization: From Badness to

Sickness. St. Louis: Mosby, 1980.

15. Dupuy, J.P., Karsenty, S. : L’invasion

pharmaceutique, Paris. Seuil, 1974.

16. Duster, T.: Medicalisation of race.

Lancet, 2007, 369:702-04

17. Giannotti, G. et al.: Anziani e giovani

nel Salento. Un contributo per le

politiche e le attività sociali educative

del territorio, Lecce.Piero Manni,

1996.

18. Goffman, E.: Asylums: Essays on the

Social Situation of Mental Patients

and Other Inmates. Torino. Einaudi,

1968.

19. Goffman, E.: Stigma. Bari. Laterza,

1970.

20. Goode, W.J.: The teorical limits of

professionalization, In: A. Etzioni (a

cura di), The Semi-Professions and

Their Organization: Teachers, Nurses,

Social Workers. New York. The Fre

Press, 1969.

21. Illich, I.: Limits to Medicine. Medical

Nemesis: The expropriation of Health.

London. Calder & Boyars, 1975.

22. Jennings, D.: The Confusion between

Disease and Illness in Clinical

Medicine. In: Can. Med. Ass. J., 1986,

135, 865-870.

23. Kickbush, I, Maag, D.: Lo sviluppo

della Health Literacy nelle moderne

società della salute, in Ingrosso M. (a

cura di) (2007), op.cit.

24. Leccardi, C.: Crescere nel

Mezzogiorno. Giovani e adulti in una

comunità calabrese degli anni

novanta. Rubbettino, Soveria

Mannelli, 1994.

25. Luhmann, N.: Sozale Systeme:

Grundrisz einer allgemeinen Theorie.

Frankfurt am Main. Suhrkamp, 1988

[tr. it., Sistemi sociali. Fondamenti di

una teoria generale. Il Mulino,

Bologna, 1990].

26. Luhmann, N. : Soziologie des Risikos.

Berlin-New-York, 1993 [tr. it.,

Sociologia del Rischio, Mondadori,

Milano, 1996].

27. Luhmann, N.: Tautology and Paradox

in the Self- Descripition of Modern

Society. In: Sociological Theory, 6,

1988, p. 36.


194

28. MCLellan, F.: Medicalisation: a

medical nemesis. In: Lancet, 2007,

369:627-8.

29. Mead, G.H.: Mind, Self and Society.

The University Chicago Press, 1932.

30. Merico, M., Rauty, R.: Giovani a

Montoro Inferiore tra modernità e

tradizione. Forino. Phorograf, 1999.

31. Metzl, J.M., Herzig, R.M.:

Medicalisation in the 21st century:

introduction. Lancet, 2007, 369:697-8.

32. Parsons, T.: Profession. In:

International Encyclopedia of the

Social Sciences, 1968, p. 536.

33. Rauty, R. (a cura di): Una tranquilla

estraneità. Caratteri della condizione

giovanile ad Avellino. Mercogliano.

Tipografia Grappone, 1999.

34. Rose, N.: Beyond medicalisation. In:

Lancet, 2007, 369:700-702.

35. Sandoz, T.: L’homéopathie comme

rituel de conjuration. In: Medicina e

Storia. Rivista di Medicina e Storia

della Sanità, 1, 2001, pp. 73-98.

36. Seppilli, T.: Medicine e magie.

Milano. Electa, 1989.

37. Siebert, R.: Cenerentola non abita più

qui. Uno sguardo di donna sulla

realtà meridionale. Torino.

Rosemberg & Sellier, 1999.

38. Trigilia, C. (a cura. di): Cultura e

sviluppo. L’associazionismo nel

Mezzogiorno. Roma. Meridiana Libri,

1995.

39. Velimirovic, B., Velimirovic, H.:

Therapeutischer Pluralismus? In:

Curare, vol. 5, 1, 1982.

40. Williams, S. J., Bendelow, G.: The

Lived Body. Sociological Themes,

Embodied Issues. London & New

York. Routledge, 1998.

41. World Health Organization: Self-help

and Health in Europe. Ginevra. Who-

Oms, 1983.

DILEMMAS AND FACTORS INVOLVED IN

PROMOTING MEN’S HEALTH

IN BRASOV COUNTY

L. ROGOZEA

1 A. BĂLESCU

1

J. DOMARADZKI2 E. WIERZEJSKA

3

M. BARITZ4 L. CRISTEA

4

Abstract: This study of the gender profiles of the health care populations in

Brasov County fills a gap in the research literature by presenting the

relationship existing between morbidity and gender data. There are also used

the experiences developed in 2 universities - Transilvania University of

Brasov and Poznan University of Medical Science, in understanding the

importance of health promotion for different kind of people and there are

compared these data with the data from Poland, especially in the field of

human behaviour and in the health promotion topics.

Key words: morbidity, gender, health promotion.

1 Transilvania University of Brasov, Dep Fundam. and Prophylactic Disciplines. 2 Poznan University of Medical Sciences, Chair of Social Sciences. 3 Poznan University of Medical Sciences, Chair of Preventive Medicine. 4 Transilvania University of Brasov.

1. General Context

Men's health is poor compared to

women's, according to a range of

measures, and varies according to ethnicity

and to the socio-economic class. [6]

For a good understanding of the gender-

based approach in health promotion, it is

important to know the local context and the

correlation with the other data from another

county, including from another country.

In the second half of the 20th century the

number of human beings increased by 3.5

billion, which is over 140%. This growth

was over one billion higher than the number

of people at the beginning of that period. [2]

In the year 2000, the United Nations

Organization estimated that the number of

people has increased dramatically, as it has

reached 6 billion 56,7 millions.

It is estimated that the number of the

elderly will still grow from 600 millions in

the year 2000 to 2 billions in the year

2050. [1]

Another important change is the

increased number of the so called “old-

old” (age 75 years and beyond) in relation

to the so called “young-old” (those

between 65 – official WHO’s age for the

beginning of the old age – and 74 years of

age).

In that context, we mention that in

Romania the ratio between female and man

is: 1.05 and the structure is: urban: rural

53.4 : 46.6 and life expectancy is: 67 for

males and 75 for females, which means

that the health promotion programme must

be focused on male life style.

Developing a health promotion

programme needs to identify the risk


196

factor, the main diseases which affect the

men and to do health promotion activities

according to that study.

Even if there is usually considered that

men have a higher status (social,

economic), accessibility to community and

society resources and that they are more

involved in decision taking, the life

expectance is lower for men. [3]

Likewise, the expectance for men and

women is different, which leads to a

different behaviour.

For example, traditional norms for

GIRLS include: working at home, taking

care of elderly people or babies, reading

love poems, watching love films,

following the fashions, crying when are

sad or hurt, playing dolls and

housekeeping, cooperating and looking for

help when it is needed, taking care of their

look and health, depending on the others.

By contrast, BOYS are expected to:

repair a machine, read detective and crime

stories, not care much about a tear in their

clothes, return blows when attacked, drive

a car, use strong expressions in their

speech, show no emotions and tears, play

with guns and cars, be independent in all

situations.

2. Local Context

The most frequent measures of health in

relation to sex are: higher mortality for

males and higher life expectancy for

females.

Males live shorter than females. Females

live longer and mortality is much higher

within male population in all age groups

including the foetuses and newborns. [4]

The population in Brasov County could

be show in the table 1

Brasov County Population Table 1

Brasov County 2003 2004 2005 2006 2007

Masculine 290.413 290.537 289.982 290.034 288.778

Feminine 305.364 305.603 305.229 305.724 305.150

Total population 595.777 596.140 595.211 595.758 593.928

Masculine 216.974 215.844 214.949 214.355 211.961

Feminine 231.496 230.778 229.937 229.898 228.584

Total urban 448.470 446.622 444.886 444.253 440.545

Masculine 73.439 74.693 75.033 75.679 76.817

Feminine 73.868 74.825 75.292 75.826 76.566

Total rural 147.307 149.518 150.325 151.505 153.383

According with these data, the ratio between females and males in 2007 is female: male

1.05, like in graphic 1.

Population of Brasov County in 2007

288.778;

49%305.150;

51%

masculine feminine

Graphic 1

Dilemmas and Factors Involved in Promoting Men’s Health in Brasov County 197

The life expectances in Brasov are presented in the next table (table 2), where we can

estimate that the females from Braşov live with 6 year more than men.

Table 2

Brasov County 2003 2004 2005 2006 2007

Masculine 68,61 69,11 69,38 69,43 69,82

Feminine 76,07 76,60 76,61 76,79 76,98

Total population 72,26 72,80 72,97 73,08 73,38

The probability of early death within

males is connected with their jobs and,

some researchers in social fields think that

males are less able to do all the housework

(cooking, cleaning) and consequently, after

the death of their partner, males live in

worse life conditions and die sooner.

It is unusual for males to go to a

psychologist (the same result was

established in Brasov and Poznan), which

is often seen as a weakness, typical of

females. In difficult life situations, males

seek help and support only from their wife.

Males cope with stress in a way that is

dangerous for their health and life. They

drink alcohol, use drugs, commit accidents

or devote themselves totally to their jobs.

[7]

The principal diseases that affect the

population of Brasov county are: circu-

latory disease and tumours, but also a high

morbidity from respiratory digestive disea-

se, or accidents was found (Graphic 2).

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

M F M F M F M F M F

2003 2004 2005 2006 2007

Accidents

Genito-urinary disease

Digestive System Disease

Respiratory Disease

Circulatory disease

Nervous System Diseases

Mental Disease and

Behaviour Disorders

Endocrine, Nutrition and

Metabolism Disease

Blood, Hematopoetic and

Imunitary Disease

Tumours

Infection and Parasite

Disease

Graphic 2


198

Males more often define themselves as healthy (both physically and mentally) even

when they are ill. [8]Graphic 3

3114

2696

3065

2679

3127

2736

3230

2734

3015

2720

0

500

1000

1500

2000

2500

3000

3500

2003 2004 2005 2006 2007

Morbidity by Gender

male female

Graphic 3

Although for most males health is a very

important value, they are ready to sacrifice

it in favour of other goals. They treat

health as ‘instrumental value’ and not as a

value in itself like females do. [5]

Males have higher rates of most chronic

disorders (among females, acute diseases

are dominant) such as: cancer, emphy-

sema, heart diseases, higher blood

pressure, diabetes, and coronary diseases.

[9]

tumours

677 696 712759 763

514 512553 570 555

0

100

200

300

400

500

600

700

800

900

2003 2004 2005 2006 2007

num

ver o

f case

s

Masculin Feminin

Graphic 4


Male ‘style’ of smoking is much more

dangerous: more males than females

smoke a lot, stronger cigarettes, inhale

deeper breaths with the smoke.

According to that and to their reduced

preoccupation for control of their health,

including by auto-palpation for preventing

the prostate cancer, the morbidity and

mortality in men is higher. Graphic 4

Circulatory disease

1736 17311657

1488

1707

1708

166715981519

1563

1350140014501500155016001650170017501800

2003 2004 2005 2006 2007

Feminin Masculin

Graphic 5

Even if males are less able to cope with

stress and if in stressful situations males

resort to such risky behaviours as: alcohol,

drugs, cigarettes, women eat more fat

aliments and the morbidity from cardio-

vascular disease is therefore higher for

women than for men, maybe according to

the fact that men make more sport and are

more active. (Graphic 5)

respiratory disease

206191

166196

113 113 103 94

218

166

0

50

100

150

200

250

2003 2004 2005 2006 2007

Masculin Feminin

Graphic 6


200

Men are more likely than women to be

respiratory ill and they are in greater risk

of lung cancer, pneumonia or other

infections, including silicosis or respiratory

chronic disease; men in routine and manual

jobs are more likely to smoke and have

chronic health problems than other men.

Graphic 6

Accidents

237266276

273264

71937462

79

0

50

100

150

200

250

300

2003 2004 2005 2006 2007

Masculin Feminin

Graphic 7

Usually, males dedicate themselves to

professions where they are more exposed

to dangerous materials, to a higher number

of accidents in the working place. They

have also much a more dangerous life and

they caused four - five times more car

accidents than females because males drive

more dangerously than females. They drive

faster, and after alcohol and drugs. Males

are also less eager to accept road safety

rules. Graphic 7

Conclusions

As Rokeach M said: “Fair and respectful

health policy and practice require an

understanding of the values that underlie

our choices. Values are enduring beliefs

that provide guidance for choice and

action”. [5]

While males get ill less frequently but

more seriously, the life of females is full of

less dangerous illnesses and disabilities,

which impair social functioning but do not

threat their lives and do not lead to death.

Most of our behaviours as males and

females are not a function of biology but

rather of learning. It is culture that

determines what we understand by health

and illness just as by masculinity and

femininity. [1, 2]

Focusing only on lifespan can prolong

morbidity and suffering without

commensurate human benefit. On the other

hand, gender may be used as a

discriminatory or exclusionary criterion,

but analysing the trends in developing

disease we are sure that the male morbidity

could raise some socio-economic

problems, especially in countries with low

standards of life. [6]

Developing a health promotion

programme must be based on the next

scheme (diagram 1):


Risk factors Disease Prevention Protective

Smoking

Alcohol

Dangerous

work places

Stress

Age

Sport

activities

Educational

Protective

behaviour

Health

promotion

programme

Tumours

Accidents

Cardio-

vascular

disease

etc

factors

Diagram 1

When the health professionals take a

decision, they make their judgements

based on “quality of life”; quality of life is

an all-encapsulating term which attempts

to describe a uniquely personal perception

reflecting feelings about one’s personal,

physical and spiritual well-being (diagram

2)

Diagram 2

Individual

health status

Population

health status

Economics

pressure

Particular

male

problems

Financial

dilemmas Personal

priorities

Biological

resources

Cultural,

behaviour

background


202

References

1. Keene, J., Li X.: Age and gender

differences in health service

utilization. In: Journal of Public

Health, VoI. 27, No. 1, pp. 74–79,

Advance Access Publication 6 January

2005.

2. Leishman, J: Around the world with

men's health and women's health

organisations. In: J Men's Health Gend

2005, 2:133-134.

3. Men's Health Forum Scotland: Razing

men's health awareness. [http://www.

mhfs.org.uk/mhfs/index.php]

4. Meryn, S., Jadad, A.R: The future of

men and their health. Are men in

danger of extinction? In: Brit Med J

2001, 323:1013-1014.

5. Rokeach, M.: The nature of human

values. New York. The Free Press,

Collier MacMillan; 1973.

6. Taylor, R. J., Smith, B. H., van

Teijlingen, E. R: Health and illness in

the community. Oxford: Oxford


7. Thom, B.: Smoking, drinking and drug

use: a privilege and a burden. In: J R

Soc Health 2004, 5:207-209.

8. Vasianovich, A., van Teijlingen, E. R,

Reid, G., Scott, N. W.: Key health

promotion factors among male

members of staff at a higher

educational institution: A cross-

sectional postal survey. In: BMC

Public Health 2008,

8:58doi:10.1186/1471-2458-8-58.

9. Wyllie, A, Casswell, S.: Gender focus

of target groups for alcohol health

promotion strategies in New Zealand.

Health Promotion International, Vol.

12, 141-149, Oxford University Press.

1 Research Assistant (Human Sciences), Transilvania University, Brasov. 2Theodor Aschenbrandt, "Die physiologische Wirkung und die Bedeutung des Cocains," Deutsche

medizinische Wochenschrift (December 12, 1883) în vol. Ernest Jones, The Life and Work of Sigmund Freud,

Volume I (1856-1900) (New York: Basic Books, 1953), p. 80. 3 In 1883, Freud was 27 years-old 4 Ernest Jones, Life and Work of Sigmund Freud, 1, 81

A DECADENT AGE - 1900.

FREUD AND COCAINE

Andrada FĂTU-TUTOVEANU

1

Abstract. In 1883-1884, Sigmund Freud was a young neurologist in search

for a brilliant medical discovery to launch his scientific career. After

studying some American papers on the subject, but also the results Dr.

Theodor Aschenbrandt had obtained on German ground, Freud has become

interested in cocaine. A less familiar drug at the time (in comparison with the

opiates), cocaine would prove impressive effects - during experiments – on

fatigue, pain and many other medical problems. Freud was both interested

in the substance as a cure for different diseases and as an intellectual

stimulant (as he could notice trying the drug himself). As Freud becomes

involved at various levels (at scientific, clinical, personal level and so on),

the study analysis the stages of his interest in cocaine, also the part he has

played in the scientific research regarding cocaine and last but not least, his

relation with the ‘decadent’ world around the year 1900.

Key words: cocaine, Sigmund Freud, 19th

century, panacea, opium,

medicine, hallucinogens

In 1883, Dr. Theodor Aschenbrandt

obtained a dose of pure cocaine from the

Merck Company of pharmaceutics and

gave it, with positive results (subsequently

published) to the Bavarian soldiers during

the fall manoeuvres.2 Freud was at the

time3 a young neurologist, confronted

himself with neurotic symptoms due to

exhaustion/ chronic fatigue and financial

problems. Cocaine seemed to be a solution

to all his problems, providing him with the

energy and high spirits for his intellectual

work, but also promising to be an

extremely important discovery in his

research career: “If it goes well [Freud had

already tried cocaine himself and also

prescribed it to two patients] I will write an

essay on it and I expect it will win its place

in therapeutics by the side of morphium

and superior to it. I have other hopes and

intentions regarding it. I take very small

doses of it regularly against depression

and against indigestion, and with the most

brilliant success.... In short it is only now

that I feel I am a doctor, since I have

helped one patient and hope to help more.

If things go on in this way we need have

no concern about being able to come

together and to stay in Vienna.”4


204

His enthusiasm and also the conviction

in the positive, even spectacular effects of

cocaine (which seemed to embody the

medical ideal of the 19th century, a

scientific panaceum universalis) made

Freud share the “magic” medicine with his

group of friends, his fiancée, his sisters,

colleagues and patients, which seems

particularly dangerous if regarded from the

point of view of subsequent medical

discoveries5. Freud’s letters on cocaine

continue in the same enthusiastic voice,

nourished by the observations provided by

his own experiences: In my last severe

depression I took coca again and a small

dose lifted me to the heights in a wonderful

fashion. I am just now busy collecting the

literature for a song of praise to this

magical substance.”6 At the 21

st of April

1884, Freud expresses in a letter towards

Martha his interest for a promising

therapeutic project, having acquired the

product for the purpose of some

experiments on heart and neurological

diseases. Also, on the 18th of July, he ends

his first paper7 (Über Coca

8), on the plant

of coca and cocaine (the derivative of the

former), which would be published a

month later. As a researcher, he was

interested in the common simulative

qualities of these substances, with effects

in the treatment of neurasthenia and also

providing the energy for a continuous good

rhythm in the intellectual work, free from

any sensation of hunger or thirst. The

article combines scientific methodology

(historical account, scientific description of

the plant of coca, chemical formula,

clinical observations and so on) with

subjective accents, suggesting personal

5 “looked at from the vantage point of our present

knowledge, he was rapidly becoming a public

menace.", Ernest Jones, on

http://www.druglibrary.org/schaffer/library/studies/c

u/CU35.html 6 Ernest Jones, Life and Work of Sigmund Freud, 1,

84 7 Cocaine, the alkaloid produced from leafs of coca 8 Sigmund Freud, ‘Über Coca’, Centralblatt für die

ges. Therapie, 2, pp. 289–314, 1884

involvement and unrestrained enthusiasm.9

It is most obvious that so far all the

premises were supporting Freud’s

professional ambitions regarding the

discovery of the Cure, the absolute

remedy. It is a common concern to the 19th

century scientists, an idea belonging to the

ambivalent area between medicine/ science

and magic, still present while science itself

was building its separate identity. The

magical/religious implications from the

letters are also to be found in the article

Über Coca (1884), even beyond the choice

of terms from this semantic area. Freud

makes references to saga from the

Peruvian mythology, where the plant of

coca is mentioned as a gift from the gods

offered to men in order to ‘satisfy the

hungry, fortify the weary, and make the

unfortunate forget their sorrows”10

. The

clinical observations of Freud’s own

symptoms refer to the action of cocaine

over depression and the restoration of high

spirits of a person in perfect health, also to

the increased work capacity (both physical

and mental) and finally, to the absence of

any sensation of addiction recorded in the

absence of the drogue, which was a

particular aspect in Freud’s own case.

Even more, one of the main causes of the

generalized use of cocaine at the end of the

19th century was the opinion (based upon

Bentley’s 1878 idea11

and afterwards,

among others, upon Freud’s studies on the

9In statements such as 'the most gorgeous

excitement', and administering an 'offering' of it

rather than a 'dose' , see also


u/CU35.html 10 “the mythical saga of how Manco Capac, the

Royal Son of the Sun-God, had sent it as 'a gift from

the gods to satisfy the hungry, fortify the weary, and

make the unfortunate forget their sorrows.' " Ernest

Jones, în


u/CU35.html 11 Dr .Jaffe (1965),


u/CU35.html

www.psikeba.com.ar/articulos/RAcocaina.htm

A Decadent Age – 1900. Freud and Cocaine

205

subject) regarding the capacity of cocaine

to cure morphine addiction.

Some of these observations were

confirmed by the subsequent research

(such as the effects of euphoria,

diminished sensations of hunger, pain or

tiredness and even increase of mental

capacity12

. This recognition was visible not

only at the scientific level, but also in

representations such as the early Coca-

Cola advertisements, which focused

precisely these qualities of the drink, as it

had contained coca until the beginning of

the 20th century. Still, there is more than

one element suggesting Freud’s later

acknowledgement of what cocaine actually

meant in its negative aspects (its strongly

addictive characteristics, the lethal danger,

its psycho-pathological implications and so

on), recognition equivalent to a powerful

deception towards this chemical solution

for all pains and especially for nervous

diseases. After an obvious descent in his

enthusiastic attitude (as in a 1887 study,

actually his last on the subject), next to a

diminishing use of the substance, from

1925 an even more radical cleavage takes

place, as cocaine is now referred to by the

use of the term allotrion (which in the

medical language of the time was

designating, in a pejorative manner, an

object which was foreign from the

scientific field)13

.

Some of those who have research

Freud’s biography go even further, by

admitting that the disenchantment and

mistrust regarding pharmaceutical

solutions (originated, as it seems, in the

“cocaine episode”) are the source of his

option for an alternative psychotherapy,

the psychoanalysis. More than that, it

seems that the latter emerges “historically

precisely in the moment when the medical

12 V. Denis Richard, La coca et la cocaïne, Presses

Universitaires de France, Paris 1994, p. 28 13 V. Rosa Aksenchuk, Freud y la cocaína:

¿experimentos con uno mismo?, în

www.psikeba.com.ar/articulos/RAcocaina.htm

practice meets its limits.”14

Among these,

Pierre Eyguesier15

regards this cocaine

“moment” as a gate to the psychoanalytical

stage, equally important as the self-

analysis16

, while the abandonment of the

substance, others say, overlaps the

discovery in the relation to dependence

between hysterical episodes and language

facts, which have eventually led to therapy

through words17

.

Analysing the historical moment of the

late 19th century, the moment cocaine is

obtained and gains field in the medical

conscience, one important aspect observed

is that at the time the prohibition and

opprobrium (which are nowadays related

to the notion of drug) were not present, as

they appeared as the effect of certain

historical and medical experiences and

moved towards the field of legislation and

sociologically involved campaigns18

. In

the 1880s, Vienna records an increasing

interest for the effects cocaine has in

achieving anaesthesia. “Sigmund Freud,

having discovered these researches and

noticing that many American doctors were

already using the product, convinces an

ophthalmologist friend of his, Königstein,

to try it; the latter would obtain miraculous

results”19

. From now on, many successful

interventions and not only ophthalmologic

ones, take place. The new discovery

becomes the subject of many discussions

and articles and “the medical environment

is literally enflamed towards the

miraculous alkaloid to the point that its

price becomes exorbitant”20

.

14 Ibid. 15Pierre Eyguesier, Comment Freud devint drogman.

Etude sur coca et la cocaine a la Belle Epoque,

Nevarin Editeur, Diffusion Seuil, Paris, 1983 16 Rosa Aksenchuk, op.cit., în

www.psikeba.com.ar/articulos/RAcocaina.htm 17 Ibid 18 Roland Jaccard, Freud, Presses Universitaires de

France, Paris, 1996, p. 31 19 Denis Richard, p. 13 20 Ibid.


206

Freud was interested in the studies

American researchers had made (and those

of surgeon Hammons, particularly) and

was interested himself in it clinically

“verifying the observations of the

Americans and developing new indications

on the product and searching, under this

pretext, the means to better understand the

origins of mental pathologies: from a

certain point of view, cocaine was one of

the cornerstones of the reflection on

psychoanalysis. On the 30th of April 1884

he would use the alkaloid upon himself”21

.

Soon he starts taking it regularly, as he was

convinced of the qualities cocaine

possessed22

and particularly enthusiastic

about its antidepressant and stimulation

effects, hoping that from all these points of

view cocaine would “launch” his career.

One of the ardent problems of the moment,

morphine addiction (stimulated mainly by

the generalized use in hospitals and

especially during crisis moments such as

wars, as doctors needed its powerful effect

on pain and initially ignored its addictive

character) seemed to submit to cocaine

treatment. Of course, it was another form

of addiction replacing the older one, but

this aspect became obvious only later. In

this context, Freud recommends the

magical treatment to one of his friends, Dr.

Ernst von Fleischl-Marxow (who was

addicted to morphine, due to a painful

nervous disease), but the results are tragic,

as the latter dies eventually from a cocaine

overdose. Subsequently, Freud would

recognize, as well as Lewin23

, the negative

effects of the medicine becoming more and

more aware of the side effects cocaine

implied.

21 Freud et la cocaïne, in Denis Richard, op.cit., p. 15 22Psycho-stimulation characteristics. Freud’s

prescriptions :

”physical and mental stimulation, indigestion, ;

indigestie; caşexie22; morfinism şi alcoolosm [s.n.];

astm; impotenţă; anestezie locală; sângerări nazale.

Aceste indicaţii vor dispărea la începutul secolului

XX, cu excepţia celei de anestezic.”, Denis Richard,

op.cit., p. 14 23 See above

There are some stages of his research, the

first study being Über Coca (1884) where

“Freud proves to be a brilliant

pharmacologist, by pertinently observing that

the treatment of various mental diseases by

chemical substances could prove possible.

Despite the failure Morselli and Buccola had

registered in the use of the alkaloid24

for the

treatment of severe nervous breakdowns, he

[Freud] underlined that because of «the

efficiency of coca25

in the cases of mental

and physical frailness research should be

continued». He also asserts that cocaine could

exert an antidepressant action especially in the

benign and neurasthenic cases”26

.

A second study, from 1885, Contribution

to the Knowledge of the Effect of Cocaine,

brought to the fore positive conclusions

and being followed by some others (all

these, proofs of his constant interest on the

subject) and also by his lecture in 1885,

Freud to the Viennese Psychiatric Society.

In 1887, his last article from what was later

called “the Cocaine papers”, Cocaine-

mania and Cocaine-phobia, besides his

response to the attacks some of his

colleagues had laid upon his previous

work, one can perceive also a certain

reticence of the author himself (such as

that referring to cocaine injections) and

some shifts on some older ideas. Despite

these changes in his scientific perspective

and although he significantly had

developed no addiction whatsoever, Freud

continued using the drug until 1895, with

some discontinuities. His personal interest

is still related to continuous research but

also to the stimulant benefits he was

recording in his program of intense work.

A loss of interest occurs gradually, as he

becomes more and more aware of the

complex dangers cocaine involves (after

the Fleischl episode27

, of cocaine-maniac

24 Cocaine 25 Here, the plant 26 Denis Richard, p. 16 27 Fleischl consuma după un an un gram de cocaină

pe zi, adică de dou-zeci de ori mai mult decât lua

Freud însuşi, însă mult mai sporadic, v. Edward M.


207

psychosis, then death, he would warn

Martha, to whom he was sending it

regularly): addiction, tolerance28

, which

was leading to a continuous growth of the

dose etc. Another factor, influencing this

decrease, is the constant criticism rising

from different directions. The chemist

Erlenmeyer29

, the first to criticize the

method (1885) describes, for instance, the

acute intoxication with cocaine, almost

simultaneously with Freud’s positive

theory. In De la quête de la morphine

(1887), the former speaks of “a third

plague of human kind” after alcohol and

morphine (his area refers especially to the

19th century main addictions). He also

demonstrates that there was confusion (in

the treatment of morphine addiction by

cocaine) between morphine withdrawal

symptoms and the psychotic episodes

produced by overdoses of cocaine.30

In

1886, a friend of Freud’s, Obersteiner, who

had initially promoted the use of cocaine,

changes his mind and becomes a critic of

it, after experimenting some nervous

disorders similar to delirium tremens. An

important critic is Louis Lewin, the author

of a famous toxicological classification in

the volume Phantastica and author of

various studies31

on the consequences of

cocaine use32

.

Brecher, The Consumers Union Report on Licit and

Illicit Drugs. 35. Cocaine,


u/CU35.html 28

Drug tolerance occurs when a subject's reaction to

a psychoactive drug (such as a painkiller or

intoxicant) decreases so that larger doses are

required to achieve the same effect. Drug tolerance

can involve both psychological drug tolerance and

physiological factors,

http://en.wikipedia.org/wiki/Drug_tolerance 29 Richard August Carl Emil Erlenmeyer (28 June

1825 – 22 January 1909), German chemist 30 Denis Richard, op.cit., p. 20 31 „Über Morphium-Intoxication," in "Deutsche

Zeitschrift für Praktische Medizin," 1874, No. 26;

"Experimentelle Untersuchungen über die

Wirkungen des Aconitin auf das Herz," in

"Centralblatt für die Medizinische Wissenschaft,"

1875, No. 25; "Über die Verwerthung des Alkohols

in Fieberhaften Krankheiten," in "Deutsches Archiv

In its first stage (the last decades of the

19th century), cocaine belongs mostly to

the medical environment, the consumers

being mainly doctors, pharmacists or

morphine-addicted patients, while the fin

de siècle/ turn of the century period (circa

1900) is the moment when it extends to all

social classes, as an individualized

attraction. Edward M. Brecher asserts that

Fleischl's experience was not “unique;

subsequent observations were to reveal

that repeated use of large doses of cocaine

produces a characteristic paranoid

psychosis in all or almost all users, and

that the tendency to overuse is widespread.

A peculiar characteristic of this psychosis

is ‘fornication’– hallucinations that of, or

insects, or (as in Fleischl's case) snakes,

are crawling along the skin or under it”33

.

Despite all these, as we have already

mentioned Freud himself does not

experience any “tolerance” or addiction,

continuously taking very small doses34

,

without feeling any withdrawal symptoms

whenever he interrupts the habit. Ernest

Jones, psychoanalyst and biographer, tries

to offer an explanation for this unexpected

für Klinische Medizin," 1876; "Über Maximale

Dosen der Arzneimittel," in "Transactions of the

International Medical Congress," ninth session,

Washington, 1887; "Über Allgemeine

Hautvergiftung Durch Petroleum," in Virchow's

"Archiv," cxii., 1888; "Über Anhalonium Lewinii

und Andere Cacteen," in "Archiv für Experimentelle

Pathologie und Pharmakologie," 1894; "Die

Behandlung der Lepra," in "Deutsche Medizinische

Wochenschrift," 1898; "Die Untersuchungen von

Blutflecken," ib. 1899; "Die Vergiftungen in

Betrieben," ib. 1890 (also translated by Pannier in

"Bulletin Général de Thérapeutique," 1902); "Über

die Behandlung der Lepra," ib. 1900. "Die

Nebenwirkungen der Arzneimittellehre," Berlin,

1881, 2d ed. 1893 (translated into Russian);

"Lehrbuch der Toxicologie," Vienna, 1885, 2d ed.

1897 (translated into French by Pouchet, Paris,

1902); "Über Piper Methysticum (Kawa Kawa),"

Berlin, 1886; "Über Areca Catechu, Chavica Detle,

und das Betelkauen," Stuttgart, 1889. 32 Denis Richard, p. 21 33 Edward M. Brecher, op.cit., în


u/CU35.html 34 30-50 miligrams of injectable product


208

absence of reaction through the criteria of

“addictive personality", as a factor for the

establishment of an addiction (still, the

author observes that in the case of cigars,

the addiction did exist)35

. Actually, Freud

himself was writing in 1887 that no

chemical product establishes addiction

entirely by itself, a psychic or emotional

predisposition being actually involved.

Some other explanations, of a

pharmaceutical nature, also suggest that on

one hand, there could be some biochemical

differences between individuals in what

concerns addictions and on the other hand

that quantity and frequency of use could

also prove decisive (in Freud’s particular

case – which functions somehow as an

exception - there are small doses, taken

from time to time, without the need to

increase the amount).

Until 1890 the psychosis and addiction

related to cocaine had become already a

medical certainty, fact which does not imply

a lessening in its popularity, especially in the

absence of a legal prohibition or even

involvement for the two following decades.

In the USA, cocaine was being used as an

ingredient for Coca-Cola, for tonic drinks or

very popular medicines in the treatment of

catarrh36

, which involved nasal aspiration of

the substance, procedure which seems to be

at the origin of this type of use of the

substance. The new (American) philosophy

surrounding this substance was focused on

the idea of high spirits and wellbeing, in

opposition to pessimism or melancholy, this

mal de siècle of the 19th century: “don’t lose

your time, be happy! If you feel pessimistic

or depressed ask for cocaine!” was one of the

formulas promoting the substance at the

end of the 19th century.

35 See Ernest Jones, The Cocaine Episode in Life

and Work of Sigmund Freud, Volume I (1856-1900)

(New York: Basic Books, 1953) 36“catarrh: inflammation of a mucous membrane in

humans or animals; especially : one chronically

affecting the human nose and air passages”,

http://medical.merriam-webster.com/medical/catarrh

As we have already mentioned Freud

admits at a certain moment that both these

side effects cocaine use involve (addiction,

physical disorder/ paranoia) as well as its

therapeutic failure (it had proved unable,

as well as psychoanalysis, to cure

morphine addiction). Yet, his scientific

observations (often experienced by

himself) represent a rigorous and important

part of turn of the century research on the

subject. In 1899 (though post-dated as

1900 by the publisher), The Interpretation

of Dreams (Die Traumdeutung)37

was

published, symbolizing a fundamental

switch of perspective, Freud having

discovered a solution beyond the “infernal

chemistry” of drugs, by going inside the

secret mechanisms of psychic and

language representations. Michael Pollak

observes that to use dreams as a basis for a

scientific paper meant a legitimate a

manner of writing and conceiving life,

already used by many writers, writing

becoming a space of self-reflection38

. With

a passion for archaeology and Greek and

Roman Antiquity39

, Freud develops, under

the inspiration of the former, a system

which investigates the inaccessible areas of

the mind (as he believed - William M.

Johnston asserts –at least until 1914 in a

level of invisible order under the chaos of

emotions and that bringing the hidden

conflicts to the light would disperse

them40

). From the Antiquity, Freud takes

37 „Freud considera Interpretarea viselor atât cea

mai semnificativă lucrare ştiinţifică a lui, piatra de

temelie a intregii sale creaţii, cât şi lucrarea care i-a

adus echilibrul pe plan individual, o sursă a forţei de

a ţine din nou piept unei existente agitate”, Carl E.

Schorske, op.cit., p. 175 38 Michael Pollak, op.cit., p. 124 sqq. 39 William M. Johnston, op.cit., p. 262: „ca în multe

case vieneze, sala de aşteptare a lui Freud avea pe

jos covoare orientale groase, iar pe pereţi

reproduceri după Lecţia de anatomie a lui

Rembrandt şi Coşmarul lui Johann Heinrich Füssli.

În biroul său se aflau nişte vitrine pline cu obiecte de

artă provenind din Grecia antică şi Egipt şi câteva

basoreliefuri egiptene în mărime naturală [...] Freud

venera Antichitatea greco-romană [266] 40 William M. Johnston, p. 265


209

over some essential structural patterns and

symbols, in a system which would

influence essentially the next century, as

William M. Johnston observes41

.

There is one more perspective describing

Freud’s relations to the cultural key-

moment of 1900 – less obvious - and that

is what Charles Bernheimer called

“Freud’s decadence”. This is affiliated

with the theories of the moment, on

decadence and the way in which a society

obsessed by degeneration can affect the

study of mental pathologies. Bernheimer

observed that, despite his biographers

having noticed Freud’s despise for Max

Nordau when the two meet in Paris in

1886, “Freud’s diagnosis of fin de siècle

decadence is not at all different from

Nordau’s”42

. In his study, ‘Civilized’

Sexual Morality and Modern Nervous

Illness, 1908, “Freud starts out by citing

just the sort of medico-psychiatric

authorities that Nordau repeatedly invokes

to give his cultural analysis the stamp of

scientific validity”43

, one of the quoted

studies, that of Wilhelm Erb44

, having

focused on the same influence of modern

literature and life on the growing number

of patients suffering from nervous

diseases. Yet, Freud considers that the

main factor of this expansion is sexuality,

more precisely the “’harmful suppression

of the sexualized life of civilized people’

by their own morality”45

and the

encouragement, by transforming this into a

taboo, of a constant feeling of guilt,

maintained mainly in the subconscious and

less motivated objectively (“the price we

pay for our advance in civilization is a loss

of happiness through the heightening of the

sense of guilt”46

, Freud writes). Although

the conclusion would be that of a mutual

41 Ibid., p. 417 42 Charles Bernheimer, Decadent Subjects, The John

Hopkins University Press, 2002, p. 163 43 Ibid. 44 Über die wachsende Nervosität unserer Zeit, 1893 45 See Charles Bernheimer, pp. 163-164 46 Ibid., p. 168

exclusion between civilization and sexual

health (having psychological implications),

he suggests the idea that a normal sexual

behaviour is useful to civilization, as the

concept of normality is related to that of

repression. One more concept comes to mind

in this context, that of “perversion”,

obsession of the fin de siècle “decadent”

society. It stands in relation to neurosis (both

considered as forms of deviance), as the

latter is understood as a perverse complex of

tendencies, impulses in a state of repression.

Civilization, Freud observes, implies a series

of restrictions stronger than the ability to

tolerate, as it places satisfaction in the field

of prohibition: “normalcy is being

constructed as a ‘modern nervous illness’.

Deviation from the norm is the norm.”47

Despite the context of successful theories of

degeneration at the turn of the century, an

essential observation Freud makes is that at

the basis of inheriting, transmission of

“perversion” from an individual to another

there is no biological determinism or

hereditary degeneration, but a psychological

and conduct transfer of the maternal

dissatisfaction from mother to child.

“Decadence sets in when individuals begin

to put their own pleasures first.”48

, as

becomes obvious that in order to assume

what society forbids and sanctions and

“break” the limit. There has to exist an

excess of constraint and despair or a moment

of crisis, allowing this excessive outburst. Later, Freud moves the centre of debate

from the socio-historical to the psychoanalytical area, speaking about normality as a utopia: “a normal ego…is, like normality in general, an ideal fiction. Every normal person, in fact, is normal on the average”

49. Neurosis seems to be more

of social illness, at a larger scale, than an individual problem. “Decadence is resolutely antiteleological and antimetaphisical, yet it cannot do without the illusion of a telos, the mirage of truth.

47 See Charles Bernheimer 48Bernheimer, p.167 49 Ibid., p. 166


210

[…] Freud has little sympathy with the decadent traits that he diagnoses in contemporary civilization. Perverse sexualities, regressive fixations, nervous exhaustion, impotence – Freud finds none of the creative potential in such negative states that decadent writers extol. […]Yet Freud’s antidecadence, like Nietzsche’s

has a decadent dimension: the place of judgment is not immune to contamination from below”

50 and a proof in this respect is

precisely his episode of fascination for the “magical” substance of the fin de siècle

medicine, cocaine.

References

1. Aksenchuk, R.: Freud y la cocaína:

¿experimentos con uno mismo?, from www.psikeba.com.ar/articulos/RAcocaina.htmwww.psikeba.com.ar/articulos/RAcocaina.htm

2. Bachmann, C., Coppel, A.: Le dragon

domestique. Deux siècles de relations

étranges entre occident et la drogue. Paris. Edition Albin Michel, 1989.

3. Bernheimer, Charles: Decadent

Subjects. Baltimore. The John Hopkins University Press, 2002.

4. Brecher, E. M.: and the Editors of Consumer Reports Magazine, The

Consumers Union Report on Licit and

Illicit Drugs. 35. Cocaine, 1972. from http://www.druglibrary.org/schaffer/library/studies/cu/CU35.html

5. de Liedekerke, A.: La Belle époque de

l'opium, [suivi d'une] Anthologie littéraire de la drogue de Charles Baudelaire à Jean Cocteau. avant-propos de Patrick Waldberg. Paris. Éditions de la Différence, 1984.

6. Eyguesier, P.: Comment Freud devint

drogman. Etude sur coca et la cocaine

a la Belle Epoque. Paris. Nevarin Editeur, Diffusion Seuil, 1983.

7. Freud, S.: Introducere în

psihanaliza: prelegeri de

psihanaliza: psihopatologia vieţii cotidiene. Traducere, studiu introductiv si note: Leonard Gavriliu.

50 See Charles Bernheimer

Bucureşti. E. D. P. 1980. 8. Greenslade, W.: Degeneration,

Culture and the Novel. 1880-1940. Cambridge. Cambridge University Press, 1994.

9. http://dexonline.ro/http://en.wikipedia.org 10. http://fr.wikipedia.org/ 11. http://fr.wikipedia.org/wiki/Exposition

s_universelles_de_Paris#Exposition_universelle_de_1900

12. http://www.observator.mednet.md/droguri/consum/

13. http://www.webwritingthatworks.com/ 14. Jaccard, R.: Freud. Paris. Presses

Universitaires de France, 1996. 15. Johnston, W. M.: Spiritul Vienei. O

istorie intelectuala si sociala 1848-

1938, Traducere de Magda Teodorescu. Iaşi. Editura Polirom, 2000, [1972].

16. Jones, E.: The Life and Work of

Sigmund Freud, Volume I. New York. Basic Books, 1953.

17. Le Rider, J. : Jurnale intime vieneze, Traducere din limba franceză şi prefaţă de Magda Jeanrenaud. Iaşi. Editura Polirom, 2001, [2000].

18. Milner, M. (ed.): Littérature et

pathologie. Vincennes. Presses Universitaires Vincennes, 1989.

19. Milner, M.: L'imaginaire des drogues: de Thomas de Quincey à Henry Michaux. Paris. Gallimard, 2000.

20. Pichot, P.: Un siècle de psychiatrie.

Paris. Synthélabo, 1996. 21. Porter, R. (ed.): Drugs and Narcotics

in History. Cambridge. Cambridge University Press, 1996.

22. Richard, D.: La coca et la cocaïne. Paris. Presses Universitaires de France, 1994.

23. Schorske, C. E. : Viena fin de siècle.

Politică şi cultură, Traducere de Claudia Ioana Doroholschi şi Ioana Ploeşteanu. Iaşi. Ed. Polirom,1998 [1961].

24. Sfez, L.(ed.) : L’utopie de la santé

parfaite, Presses Universitaires de France, Paris, 2001.

25. Vidal, B.: Histoire de la chimie, Presses universitaires de France, Paris, 1985.

26. Yvorel, J.-J.: Les Poisons de l’esprit.

Drogues et drogués au XIXe siècle. Paris. Quai Voltaire, 1992.

AUTHORS INDEX

A

Afzal, N. 89

Agache, I. 55

Alexandrescu, D. 93, 157

Alexandru, R. 119

Anghel, M. 47

Arghir, O. 93

B

Badea, M. 21, 29, 37

Ballabio, C. 37

Banuta, I.A. 1

Baritz, M. 195

Baum, E. 163

Bălescu, A. 169, 195

Bobescu, E. 81

Boda, D. 75

Bold, C.L. 1

Burtea, V. 107, 111, 115

Buzescu, M. 127

C

Caruso, D. 37

Cersosimo, G. 175

Chefneux, E. 169

Ciurea, C. 75

Colombo, M. L. 37

Coman, G. 21

Comşa, F. 151

Cristea, A. 47

Cristea, L. 195 Cucu, A. 133

D

Datcu, G. 81

Diaconu, S. 9

Domaradzki, J. 195

Durach, L. 133

F

Falup-Pecurariu, C. 99, 119

Falup-Pecurariu, O. 99, 119

Fanea, R. 145

Fătu-Tutoveanu, A. 203

Fleancu, A. 1, 9

Fleancu, C. 1

G

Galajda, Z. 81

Giavarini, F. 37

Goron, M. 93

Greavu, M. 17

Grecu, A. 1

H

Hussain, S. 89

I

Idomir, M. 43

Ifteni, G. 61

Ifteni, P. 111

K

Kohen, I. 89

L

Lazoriec, L. 21

Leaşu, F. 169

Lupu, A.M. 139

Lupu, S. 139

M

Man, M. A. 93

Manu, P. 89

Marty, J.-L 29

Medel, M.-L. 29

Mişarcă, C. 133

Moleavin, I. 43, 47

Monescu, V. 119

Moro, E. 37

Moşoiu, C. 107, 115

Munteanu, M. 21

Bulletin of the Transilvania University of Braşov � Vol. 1 (50) � Series VI 212

N

Nan, M. 75

Neculoiu, D. 47

Nedelcu, I. 67

Nemet, C. 43

Noguer, T. 29

Nunes, G.S. 29

O

Onisâi, L.L. 1, 17, 139

Oros, C. 145

P

Pamfil, G. 61, 119

Pascu, A. 43

Peri, G. 17

Persico, A. 37

Pop, M. 93

Postelnicu, A. 119

R

Râjnoveanu, R. 93

Rădoi, M. 61, 75, 81

Răşină, A. 99

Restani, P. 21, 37

Rogozea, L. 169, 195

Rus, H. 61, 75

S

Scârneciu, C. 67, 139

Scârneciu, I. 17, 67, 139

Scârneciu, V. 67

Scârneciu, V. D. 139

Sechel, G. 1, 9

Suta, C. 75

T

Ţurcanu, M. 9

U

Uberti, F. 37

V

Voroneanu, M. 145

W

Wierzejska, E. 195

bulletin - unitbv

Documents