bulgarian medicine

bulgarian medicine

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Филип Куманов Philip Kumanov (главен редактор) (Editor-in-chief)

Дроздстой Стоянов Drozdstoj Stoyanov (научен секретар) (Scientific Secretary)

Боян Лозанов Boyan Lozanov

Добрин Свинаров Dobrin Svinarov

Георги Кирилов Georgi Kirilov

Григор Велев Grigor Velev

Кънчо Чамов Kancho Tchamov

Маргарита Каменова Margarita Kamenova

Михаил Боянов Mihail Boyanov

Членове на Международния International Advisory Board редакционен съвет

Андрю Майлс Andrew Miles (Лондон, Обединено Кралство) (London, UK)

Ашок Агарвал Ashok Agarwal (Кливланд, САЩ) (Cleveland, Ohio, US)

Гюнтер Стала Günter K. Stalla (Мюнхен, Германия) (München, Germany)

Хуан Е. Месич Juan E Mezzich (Ню Йорк, САЩ) (New York, USA)

Кенет Уилиам Фулфорд Kenneth William Fulford (Уоруик, Оксфорд. Обединено Кралство) (Warwick, Oxford, UK)

Самуел Рефетоф Samuel Refetoff (Чикаго, САЩ) (Chicago, Illinois, US)

Стенли Прузинър, Нобелов лауреат Stanley B. Prusiner, Nobel Laureate (Сан Франциско, САЩ) (San Francisco, USA)

ISSN 1314-3387

Съдържание

Оригинални статии

Диагностика на автоимунния хепатит ............................................. 4Деница Дукова, Искрен Коцев

Образователни тенденции и реализация на управленските кадри в сферата на здравните грижи и общественото здраве ............................. 13Мариана И. Льочкова, Ванина Кр. Михайлова-Алакиди, Мариета Т. Тодорова, Екатерина Л. Райкова

Оценка на надеждността на скалата на Ф. Ланг за качество на живот в България .............................. 21Златослав Арабаджиев, Калоян Харалампиев, Христо Давидов, Владимир Божилов

Хроника / chronicle

Рита Леви-Монталчини: глобалната кралица на невронауката Un tributo per Rita ....................................................................................... 25Доц. д-р Георги Чалдъков, д.м.

Изисквания към авторите

Съдържание

Original papers

Diagnostics of Autoimmune Hepatitis .................................................... 4Denitsa Dukova, Iskren Kotzev

Educational trends and realization of the management personnel in the field of health care and public health ............................................................. 13Mariana I. Lyochkova, Vanina Kr. Mihaylova-Alakidi, Marieta T. Todorova, Ekaterina L. Raykova

Evaluation of the reliability of P. Lang’s quality of life scale in Bulgaria ................................................................ 21Zlatoslav Arabadzhiev, Kaloyan Haralampiev, Hristo Davidov, Vladimir Bozhilov


Rita Levi-Montalcini: The global queen of neuroscience Un tributo per Rita ....................................................................................... 25Assoc. Prof. George Chaldakov, MD, PhD

author’s guidelines

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Bulgarian medicine vol. II № 1–4/2012 Bulgarian medicine vol. II № 1–4/2012

Диагностика на автоимунния хепатит

Деница Дукова, Искрен Коцев Клиника по хепатогастроентерология, УМБАЛ „Света Марина“, гр. Варна

Diagnostics of Autoimmune Hepatitis

Denitsa Dukova, Iskren Kotzev Clinic of Hepatogastroenterology, University Hospital „St. Marina“, Varna

Оригинални статии / Original papers

РЕзюМЕ

Диагнозата автоимунен хепатит (АИХ) чес-то представлява клинично предизвикателство. Клиничният спектър на заболяването е доста широк. АИХ може да засегне пациенти от всички възрастови групи, двата пола, всяка раса и ре-гион. Ходът на заболяването може да варира от безсимптомно повишени чернодробни ензими до фулминантна чернодробна недостатъчност. Други пациенти се представят много късно с картината на чернодробна цироза. Автоанти-телата са отличителна характеристика на АИХ, но не са специфични за заболяването, нито пък задължителни за диагнозата. SLA/LP антитела-та са единствените антитела специфични за АИХ, но са налице само при около 10–30 % от случаите. Най-честата характеристика на всич-ки пациенти с АИХ е повишаване на стойно-стите на IgG обикновено селективно или силно преобладаващо в сравнение с IgA и IgM. Все пак, при някои пациенти относителното покачване на стойностите на IgG може да е в нормални гра-ници. Хистологията може да покаже типични белези като богатство на плазматични клетки и интерфейс хепатит, но разграничаването от други възпалителни чернодробни заболявания, включително медикаментозно индуцирано чер-нодробно увреждане може да бъде трудно. Тази

ABSTRAcT

Diagnosis of autoimmune hepatitis (AIH) often represents a clinical challenge. The clinical spectrum of disease is quite wide. AIH can affect patients of all age groups, both sexes and any race and region. The course may range from asymptomatic elevation of aminotransferase levels to fulminant hepatic failure. Other patients present very late with the picture of cryptogenic cirrhosis. Autoantibodies are a hallmark of AIH but they are neither specific, nor required for the diagnosis. SLA/LP-autoantibodies are the only antibodies specific for the diagnosis of AIH, but they are only present in 10–30% of cases. The most char-acteristic finding is a selective elevation of IgG with normal levels of IgA and IgM. The diagnosis of AIH should not be made without a liver biopsy showing necroinflammatory changes. Histology may show typical features such as enrichment of plasma cells and piecemeal necroses, but distinction from other inflammatory liver disease including drug-induced liver injury may be difficult. The heterogeneity of the clinical presentation can make it difficult to di-agnose AIH and even in very experienced hands the diagnosis at times may remain uncertain. Diagnosis rests primarily of high index of suspicion and should be considered in any patient with elevated liver en-zymes and in any patient with cirrhosis. The present-ing scoring systems can aid in the diagnosis of AIH.

хетерогенност прави трудно диагностициране-то на АИХ и дори в много опитни ръце, диагно-зата понякога остава неясна. Диагнозата почи-ва преди всичко на висок индекс на съмнение. За АИХ трябва да се мисли при всеки пациент с повишени трансаминази и при всеки пациент с цироза. Представените точкови системи могат да помогнат при диагнозата на АИХ.

Ключови думи: автоимунен хепатит, диа-гноза, точкови системи

Autoimmune hepatitis (AIH) is inflammatory liv-er disease, characterized by hypergammaglobu-linemia, autoantibodies, interface hepatitis and a usually favorable response to corticosteroid ther-apy (9). AIH arises in all races and in all regions. The few data available suggest a prevalence of at least 1:10 000 both in Caucasians and in Japa-nese. However, the subclinical character of the disease in a considerable proportion of patients makes it likely that the true frequency is consid-erably higher. Both sexes are affected, but women develop AIH much more frequently (ratio 3,6:1) (11, 19). AIH occurs in all age groups. The pa-tients commonly are young or middle-aged, but approximately 20% of adults with AIH present after the age of 60 years (8). The universal occur-rence of AIH, the very wide age range of primary disease manifestation and the involvement of both sexes means that AIH needs to be consid-ered in the differential diagnosis of any patient with laboratory evidence of liver disease (19).

clinical presentationaIH has diverse presentations and it is important to diagnose it during the early stages of disease (6). The most frequently occurred symptoms are: fatigue, jaundice, upper abdominal discom-fort, pruritus, anorexia, myalgia, diarrhea, fevеr, and the described physical findings are: hepa-tomegaly, jaundice, spider naevi, cocommitant immune disease, splenomegaly, ascites, enceph-alopathy. The laboratory features includея ele-vated aminotransferase level, hypergammaglob-

ulinaemia, increased immunoglobulin G level. The frequently met immunoserologic markers are: SMA, ANA or anti-LKM1, atypical pANCA, anti-ASGPR, anti-actin, antichromatin, anti-liver cytosol 1, anti-soluble liver antigen.

About the third of the patients present with an acute icteric hepatitis, occasionally even with fulminant hepatic failure (19). Acute AIH is char-acterized by newly developed, severe inflamma-tion in the liver or a spontaneous exacerbation of a previously unsuspected chronic disease (9). The majority of patients have milder and even subclinical disease. They may come to clinical attention because of non-specific symptoms such as fatigue, arthralgia, fever, anorexia, upper abdominal pain. Some patients experience jaun-dice and even pruritus (2, 19). In 25% to 34% of patients the disease has an asymptomatic course and is diagnosed as a chance finding in the context of routine investigations by detect-ing raised liver enzymes (11, 17). It is important to identify and treat AIH at its earlier stages, be-cause 49% of untreated patients with mild dis-ease progress to cirrhosis within 15 years (9). At least a third of patients have already cirrhosis at presentation, indicating that the disease has gone unrecognized for a considerable period of time prior to diagnosis (11). Even in the group of patients presenting with acute disease, liver biopsy often show signs of advanced fibrosis or cirrhosis (19). As many as 38% of patients with AIH have concurrent immune diseases, which may mask the underlying liver disease – auto-

Key words: autoimmune hepatitis, diagnosis, scoring systems

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immune thyroiditis, Graves’ disease, ulcerative colitis, type 1 diabetes mellitus, vitiligo, celiac disease (19). The identification of AIH in diverse clinical situations is critical since prompt insti-tution of corticosteroid therapy can be life-sav-ing (6). Examination findings may be normal or comprise jaundice, hepatomegaly, splenomegaly and signs of liver cirrhosis (2).

The forms of AIH are: classic, fulminant, asyptomatic, mixed (overlap syndromes) and hereditary.

Diagnosis

The definite diagnosis of AIH requires exclusion of other hepatic diseases, presence of elevated aminotransferases, serologic markers for auto-immunoreactivity and pathohistologic data for interface hepatitis. The diagnosis of AIH may be probable if clinical findings are compatible with AIH but insufficient for definite diagnosis.

Biochemical findings

On biochemistry, patients with AIH are generally found to have a hepatitis enzyme pattern with elevated aminotransferases (ALAT, ASAT, γGT). Since AIH usually has a very fluctuating course, the transaminases may range from normal levels to up to 50 times the normal at the time of diagnosis. Alkaline phosphatase (AP) is also frequently elevated, but to a lesser extent compared with the aminotransferases. A greatly elevated AP (over 3 to 4 times the normal level) makes the presence of AIH less likely (29). The most characteristic finding of AIH is a selective elevation of IgG with normal levels of IgA and IgM. As the range for normal IgG levels is wide, difficulty arises in those AIH patients who physiologically have low baseline levels of IgG. These patients usually have significantly increased IgG levels during phases of disease activity, but the increase may remain within the normal range (20).

Autoantibodies

The suspected diagnosis of AIH is generally confirmed by the demonstration of

autoantibodies are not specific for AIH and the titers can vary considerably in the course of the diseases. LKM-1 antibodies can be detected in up to 5% of patients with HCV infection. From clinical perspective, it is important to identify HCV patients with LKM antibodies since they can have a flare of the disease during interferon therapy (29). Anti-LKM1 are detected by indirect immunofluorescence, but because they may be confused with antimitochondrial antibody (AMA) using this technique, they can be assessed by measuring antibodies to cytochrome P4502D6, the major molecular target of anti-LKM1, using commercial enzyme-linked immunosorbent assays (ELISA) (21). Immunofluorescence testing is considered the gold standard for the detection of serologic markers. In this way ANA, SMA, AMA, anti-LKM and anti-LC1 antibodies can be detected. In addition some antibodies, especially those where the specific antigens are known, can be detected by ELISA or Western blot (29).

Serological overlap

Up to 35% of AIH patients are found to have anti-mitochondrial antibodies (AMA), which are highly specific for primary biliary cirrhosis (PBC). The demonstration of AMA can be evi-dence of an overlap syndrome but many patients

characteristic autoantibodies (Table 1) (21, 29). The autoantibodies that can be found in AIH patients are antinuclear antibodies (ANA), smooth muscles antibodies (SMA), antibodies against liver kidney microsome 1 (anti-LKM-1), antibodies to liver cytosol antigen 1 (anti-LC1), liver membrane antibodies (LM), antibodies to soluble liver antigen/liver pancreas (anti-SLA/LP) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) (often atypical: perinuclear antineutrophil antibody (pANNA)). The difference in antibody patterns has led to the discrimination between two subtypes of AIH (21). Significant titers (≥1:40) of ANA and/or SMA are present in 70–80% of patients (AIH type 1). Anti-LKM is detected in 3–4% of AIH cases (AIH type 2) along with anti-LC1, but typically in the absence of ANA and SMA (2). But even the finding of high autoantibody levels is not in itself sufficient to prove the diagnosis of AIH and the serological parameters should always be interpreted in context with the other clinical, biochemical and histological findings. A small proportion of AIH patients are not found to have antibodies or antibodies only occur at a later stage in the disease so that AIH cannot be ruled out based on the absence of or low levels of autoantibodies (29). Autoantibody negative AIH is important to recognize because these patients can respond well to corticosteroid therapy (12, 14). Their diagnosis can be supported by testing for the non-classical autoantibodies, including anti-SLA or atypical pANCA (4). Some corticosteroid responsive patients remain seronegative throughout their disease and they may await discovery of their signature autoantibody (4, 6). Confidence of the diagnosis of autoantibody-negative AIH can be strengthened by applying the comprehensive scoring system of the International Autoimmune Hepatitis Group (IAIHG) (1). Seronegative patients can frequently be categorized as having AIH by this method (5). Of all the antibodies only SLA/LP-autoantibodies are disease-specific and therefore of high diagnostic value. However their prevalence is only between 10% and 30% (19). The remaining

do not subsequently develop biliary changes typical of PBC in the long-term follow-up and the disease course and treatment response are the same as those of AMA-negative AIH („sero-logical overlap“) (22, 24–26). AMA may persist for as long as 27 years in the absence of PBC (26); they may disappear spontaneously (24); or they may appear late in the course of the dis-ease without apparent clinical relevance (24). Severe inflammatory activity may result in mod-ification of the mitochondrial antigens through oxidative stress and facilitate the production of AMA which in turn can disappear when the in-flammatory stress subsides (18). Importantly, most of the antibodies may also be detected in patients with other liver diseases. Serological findings of AIH have been recorded in patients with alcoholic and non-alcoholic steatohepatiits and in viral and drug-induced hepatitis. Drugs, in particular, such as minocycline, diclofenac, infliximab, propylthiouracil, atorvastatin, nitro-furantoin, methyldopa and isoniazid can induce AIH-like changes, but are generally reversible after the medication has been stopped (21).

Histology

In establishing the diagnosis of AIH, the histo-logical findings together with the serological

Table 1. Autoantibodies in liver diseases

Antibody Target antigen(s) Liver disease Importance for AIHANA Multiple nuclear antigens AIH, PBC, PSC, drug -induced hepati-

tis, HBV, HCV, NASHDiagnosis of AIH

SMA Actin, vimentin, desmin As for ANA Diagnosis of AIHLKM-1 Cytochrome P450 2D6 Type 2 AIH, HCV Diagnosis of type 2 AIHLKM-3 UDP glucuronosyl transferase

type 1Type 2 AIH, HDV Diagnosis of type 2 AIH

SLA tRNP AIH, HCV Diagnosis of AIH/ Prognosis/dis-ease course

LC-1 Formiminotransferase cyclode-aminase (FTCD)

Type 2 AIH, HCV Diagnosis of AIH/ Prognosis/dis-ease course

pANNA, pANCA

Perinuclear antigens AIH, PSC Diagnosis of AIH

ASGPR Asialoglycoprotein receptor AIH, PBC, drug-induced hepatitis, HBV, HCV, HDV

Prognosis/ disease course

LM Cytochrome P450 1A2 Drug-induced hepatitis, APECED hepatitis

Diagnosis of APECED (autoim-mune polyendocrinopathy candidi-

asis ectodermal dystrophy syn-drome) hepatitis

8 9


and clinical findings are of great importance. A definite diagnosis of AIH cannot be established without a liver biopsy. Here, the morphology is important not just in order to confirm AIH but also to differentiate from other liver diseases, which sometimes are also accompanied by an increase in the AIH-typical serological changes (29). There are some histological features that are highly suggestive of the diagnosis, but like hypergammaglobulinemia and autoantibod-ies (except for SLA/LP probably), histology is not diagnostic in itself (19). Characteristic fea-tures suggestive typical AIH include interface hepatitis, portal and periportal inflammation, presence of plasma cells, resetting of hepato-cytes and emperipolesis (19). However, none of the histological findings are specific, and in particular, interface hepatitis can be part of the disease spectrum of other hepatic dis-orders (2). Histological spectrum may include centrilobular zone 3 necrosis (suggestive of an acute viral or toxic injury) and coinciden-tal changes (bile duct injury or loss) (7, 10, 15, 27). Centrilobular zone 3 necrosis is probably an early form of AIH that is detected mainly in patients with an acute onset (15). It can transform to interface hepatitis as the disease evolves and its presence early in the disease should not delay the diagnosis or therapy (15, 27). Concurrent biliary changes, including isolated destructive cholangitis may also be found in patients with otherwise classical AIH (7, 10). These patients do not have a choles-tatic clinical or laboratory profile and succes-sive tissue examinations have not disclosed persistence of progression of the biliary injury (7). The histological features can overlap with those of primary sclerosing cholangitis (PSC) or PBC (9).

Fatty changes may also be present at ac-cession or after corticosteroid therapy. Non-al-coholic fatty liver disease is a common finding in the general population, and it may be asso-ciated with autoantibodies and hypergamma-globulinemia. Both conditions can co-exist and corticosteroid therapy can ameliorate the auto-

immune hepatitis and intensify the NAFLD. The presence of coincidental fatty change should not discourage the diagnosis or treatment of AIH, but it compels an accurate diagnosis. Wors-ening of the laboratory indices during therapy justifies liver tissue examination and reassess-ment of the treatment strategy. Progressive fatty change can be a cause of treatment failure (6, 23).

Scoring system

the diagnosis of AIH requires demonstration of the characteristic clinical and biochemical find-ings and the exclusion of other diseases that may be the cause of chronic hepatitis or cirrho-sis (29).

Due to the absence of a specific diagnostic test, the IAIHG formulated diagnostic criteria in 1993 (16) and subsequently revised these in 1999 (Table 2) (1). However the criteria are complicated and not useful in everyday practice. They were designed as a scientific tool by which to ensure the comparability of study populations in clinical trials. The re-vised scoring system is useful in assessing patients with few or atypical features of the disease (5).

In 2008, the IAIHG produced a simplified system for the diagnosis of AIH which is less complex and easier to use in clinical practice (13). This system takes into account only 4 pa-rameters: autoantibodies, IgG concentration, exclusion of viral hepatitis and histological cri-teria (Table 3) (13). This score has a sensitiv-ity of 88% and a specificity of 97% at a cut-off of ≥6 points as well as a sensitivity of 81% and a specificity of 99% at a cut-off of ≥7 points (13). The simplified scoring system is useful in excluding AIH in patients with other condi-tions and concurrent immune features (5). The simplified scoring system detects fewer cases of AIH than the original system (lower sensitiv-ity 95% vs 100%), but it has higher specificity (90% vs 73%) (5).

Table 2. Revised original scoring system of the IAIHG

Parameter ValueSex

Female + 2Male 0

Ratio of alkaline phosphatase to aminotransferase> 3,0 – 21,5 – 3,0 0< 1,5 + 2

Increase in total serum globuin, γ-globulin or IgG in relation to the upper limit of normal

> 2,0 + 31,5 – 2,0 + 21,0 – 1,5 + 1< 1,0 0

Conventional autoantibodies (ANA, SMA, LKM-1)> 1:80 + 31:80 + 21:40 + 1< 1:40 0

Autoantibodies in cholestatic liver disease (АМА)Positive – 4Negative 0

Detection of unconventional autoantibodiespANCA, anti-LC-1, anti-SLA/LP, anti-ASGRP

+ 2

Viral markers (HAV, HBV, HCV)Negative + 3Positive – 3

Medicine and drug historyNegative + 1Positive – 4

Mean alcohol consumption< 25 g/day + 2> 60 g/day – 2

Genetics (HLA-DR3 or -DR4)Present + 1

Other autoimmune diseasesDetectable + 2

Чернодробна хистологияInterface hepatitis + 3Predominantly lymphocytic infiltrates + 1Rosetting of hepatocytes + 1None of the above findings – 5Changes in architecture of bile ducts – 3Other changes – 3

Response to therapyComplete remission + 2Recurrence of hepatitis + 3

Pretreatment aggregate score: definite diagnosis > 15; probable diagnosis 10–15

Post treatment aggregate score: definite diagnosis >17; probable diagnosis 12–17

Table 3. Simplified scoring system

Parameter ScoreAutoantibodies ANA or SMA ≥ 1:40

ANA or SMA ≥ 1:80 or LKM > 1:40

or SLA/LP positive

12

IgG (or gamma globulins)

Upper normal limit>1,1 times normal limit

12

Liver histology Compatible with AIH 1

Typical for AIH 2

12

Absence of viral hepatitis

YesNo

20

Definite AIH ≥ 7; probable AIH ≥ 61 Compatible: Chronic hepatitis with lymphocytic infiltration

without features considered typical 2 Typical: (1) Interface hepatitis, lymphocytic/ lymphoplas-

mocytic infiltrates in portal tracts and extending in the lobule; (2) emperipolesis; (3) hepatic rosette formation. Atypical: Showing signs of another diagnosis like NAFLD.

Absence of viral hepatitis was generally thought to be a prerequisite for making a diag-nosis of AIH but in a few patients viral and AIH may co-exist. This is particularly relevant in countries with a high prevalence of viral hepa-titis, where a diagnosis of AIH may be entirely overlooked in viral hepatitis infected patients. However, both chronic hepatitis B and hepa-titis C virus infection may induce elevation of IgG and development of autoantibodies. Crite-ria for AIH in these patients should therefore be very strict. The revised simplified scoring system allows the diagnosis of AIH in these patients only in the presence of high IgG levels and high titer autoantibodies as well as s typi-cal histology (19).

In clinical practice, the differentiation be-tween drug induced liver injury and AIH may be challenging. Severe drug-induced hepatitis usually responds to high dose steroids in the same fashion as severe acute AIH and thus the differential diagnosis may be not so relevant if immunosuppression is started without delay. The course of the disease will later allow differ-entiation between AIH and drug-induced dis-ease: patients with drug-induced hepatitis will not relapse after withdrawal of corticosteroids (in the absence of the offending drug), while AIH patients will relapse (30).

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OVERLAP SYNDROMES

Some patients within the spectrum of au-toimmune liver disease present with clinical, laboratory and/or histological features of both a cholestatic liver disease (i.e. PBC or PSC) and AIH. These conditions may be difficult to clas-sify and are commonly designated as „overlap syndromes“. As internationally agreed criteria defining overlap syndromes are lacking, a vari-ety of definitions have been applied (2).

Overlap between PBc and AIHThe exact prevalence of an AIH/PBC over-

lap syndrome is difficult to establish given the lack of generally recognized diagnostic criteria, but approximately 10% of adults with AIH or PBC may belong in this overlap category (28). In 1998, Chazouillères et al. defined an AIH/PBC overlap syndrome in PBC patients if at least two of each of 3 of the following features of both diseases were present (3) (Table 5). In PBC patients features of AIH have also been de-scribed to develop in sequential manner.Table 4. Diagnostic criteria of PBC-AIH overlap syndrome

PBC criteria

• AP > 2х ULN or γGT > 5х ULN• АМА ≥1:40• Liver biopsy with florid bile duct damageAIH Criteria

• ALAT > 5х ULN• IgG >2х ULN or SMA positive• Liver biopsy showing moderate or severe periportal or

periseptal lymphocytic piecemeal necrosis

At least 2 of 3 criteria for PBC and AIH respectively should be present

PSc/AIH overlap syndrome

The prevalence of the overlap syndrome of AIH and PSC shows considerable variation in the lit-erature and at 1–10% in adulthood is much less than in childhood (30–50%). In adult patients with confirmed PSC, after calculating the modi-fied AIH score, there was found to be definite AIH in approximately 2% of cases and prob-

able AIH in approximately 10% of PSC patients. Conversely, in one study, PSC-typical bile duct changes on MRCP were described in 10% of AIH patients (29). The absence of characteris-tic cholangiographic changes does not preclude the diagnosis of PSC because small-duct disease may be present. The occurrence of intrahepatic biliary changes in patients with predominant features of AIH could represent coincidental bile duct injury or an overlap syndrome with small-duct PSC or AMA-negative PBC (4). As in the case of AIH-PBC overlap, there may be many years between the two diagnoses. In AIH patients it is important to consider an overlap syndrome early on if pruritus, chronic inflam-matory bowel disease, bile duct changes, a cholestatic enzyme pattern or poor response to glucocorticoids occur. In PSC patients, the fol-lowing signs can suggest an overlap syndrome: an elevation of IgG, positive ANA and/or SMA and interface hepatitis on liver biopsy (29).

AIH/HcV overlap syndrome

Depending on the definition, the co-occurrence of AIH and viral hepatitis is included among the overlap syndromes. Low titers of antibodies are a regular phenomenon in patients with chronic hepatitis. On the other hand, anti-HCV tests pro-duce false positive results in 4% of AIH patients and thus always require demonstration of HCV RNA to confirm diagnosis of hepatitis C. The concomitant presence of hepatitis C and AIH is probable if, in addition to demonstration of HCV RNA, there are high antibody titers (>1:320) and other findings suggest AIH. The histology can in particular provide information as to which liver disease requires priority and thus primary requires therapy. While plasma cell in-filtrates of the portal fields, lobular inflamma-tion and interface hepatitis suggest AIH to be dominant, the histology if hepatitis C is domi-nant typically shows dense portal lymphocytic infiltrates and frequently mild macrovesicular fatty degeneration of the liver. In the treatment of AIH-HCV overlap syndrome, there is the fun-damental problem that antiviral therapy can

make the autoimmune liver disease worse and conversely, immunosuppressant therapy can exacerbate the viral hepatitis (29).

cONcLUSION

AIH needs to be considered in the differential diagnosis of any patient with elevated liver en-zymes and in any patient with cirrhosis. In AIH it is essential that affected patients should re-ceive adequate immunosuppression and the di-agnosis should neither be delayed nor missed. There are no pathognomonic features of AIH. It is the combination of laboratory features and histological assessment that makes the diag-nosis, it is only the response to immunosup-pression that really confirms the diagnosis and saves the patient. Two scoring systems have been developed by the IAIHG and they can aid in the diagnosis of AIH.

References

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9. Czaja, A.J., M.P. Manns. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology, 139, 2010, 1, 58–72 e54.

10. Czaja, A.J., P. Muratori, L. Muratori, et al. Diagnos-tic and therapeutic implications of bile duct injury in autoimmune hepatitis. Liver Int, 24, 2004, 4, 322–329.

11. Feld, J.J., H. Dinh, T. Arenovich, et al. Autoimmune hepatitis: effect of symptoms and cirrhosis on nat-ural history and outcome. Hepatology, 42, 2005, 1, 53–62.

12. Gassert, D.J., H. Garcia, K. Tanaka, et al. Corticos-teroid-responsive cryptogenic chronic hepatitis: evidence for seronegative autoimmune hepatitis. Dig Dis Sci, 52, 2007, 9, 2433–2437.

13. Hennes, E.M., Y.H. Oo, C. Schramm, et al. Mycophe-nolate mofetil as second line therapy in autoim-mune hepatitis? Am J Gastroenterol, 103, 2008, 12, 3063–3070.

14. Heringlake, S., A. Schutte, P. Flemming, et al. Pre-sumed cryptogenic liver disease in Germany: High prevalence of autoantibody-negative autoimmune hepatitis, low prevalence of NASH, no evidence for occult viral etiology. Z Gastroenterol, 47, 2009, 5, 417–423.

15. Hofer, H., C. Oesterreicher, F. Wrba, et al. Centri-lobular necrosis in autoimmune hepatitis: a histo-logical feature associated with acute clinical pres-entation. J Clin Pathol, 59, 2006, 3, 246–249.

16. Johnson, P.J., I.G. McFarlane. Meeting report: Inter-national Autoimmune Hepatitis Group. Hepatol-ogy, 18, 1993, 4, 998–1005.

17. Kogan, J., R. Safadi, Y. Ashur, et al. Prognosis of symptomatic versus asymptomatic autoimmune hepatitis: a study of 68 patients. J Clin Gastroen-terol, 35, 2002, 1, 75–81.

18. Leung, P.S., L. Rossaro, P.A. Davis, et al. Antimito-chondrial antibodies in acute liver failure: impli-cations for primary biliary cirrhosis. Hepatology, 46, 2007, 5, 1436–1442.

19. Lohse, A.W., G. Mieli-Vergani. Autoimmune hepati-tis. J Hepatol, 55, 2011, 1, 171–182.

20. Lohse, A.W., C. Wiegard. Diagnostic criteria for au-toimmune hepatitis. Best Pract Res Clin Gastroen-terol, 25, 2011, 6, 665–671.

21. Manns, M.P., A.J. Czaja, J.D. Gorham, et al. Diagno-sis and management of autoimmune hepatitis. Hepatology, 51, 2010, 6, 2193–2213.

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Образователни тенденции и реализация на управленските кадри в сферата на здравните грижи и общественото здраве

Мариана И. Льочкова, Ванина Кр. Михайлова-Алакиди, Мариета Т. Тодорова, Екатерина Л. Райкова Катедра по Управление на здравните грижи, ФОЗ, МУ – Пловдив

Educational trends and realization of the management personnel in the field

of health care and public health

Mariana I. Lyochkova, Vanina Kr. Mihaylova-Alakidi, Marieta T. Todorova, Ekaterina L. Raykova

Department of Healthcare Management, Faculty of Public Health, Medical University – Plovdiv

РЕзюМЕ

Въвеждането на европейските стандарти в подготовката на здравни кадри с управленски функции, както и повишаване на образовател-ната степен при обучението им с оглед постига-не на равнопоставеност и пълноценно присъст-вие на страната ни в европейските структури е причина за разкриване на специалностите упра-вление на здравните грижи и здравен менидж-мънт в Медицински университет – Пловдив.

ЦЕЛ на настоящия труд е да се установят осигуреността и реализацията от управлен-ски кадри за ръководители по здравни грижи и здравни мениджъри за лечебни структури в Южна България.

Материал и методи. Проследен е броят на кандидат-студентите и приемът от създаване-то на специалността Управление на здравните грижи (1997 г.) до настоящата учебна година

ABSTRAcT

The implementation of the European stand-ards in the training of health specialists with man-agement functions, as well as the increase in the educational degree of their training with a view to achieving equality and full-value presence of our country in the European structures preconditions the opening of the university subjects Healthcare Management and Health Management at the Medi-cal University of Plovdiv.

The objective of the present work is to deter-mine the procurement with and realization of man-agement personnel for healthcare and health man-agers for medicinal structures in Southern Bulgaria.

Material and methods. The number of candi-date students and the admittance since the intro-duction of the university subject Healthcare Man-agement (1997) until the present academic year (2010/11) was tracked out, as well as the average

22. Mishima, S., K. Omagari, K. Ohba, et al. Clinical im-plications of antimitochondrial antibodies in type 1 autoimmune hepatitis: a longitudinal study. Hepatogastroenterology, 55, 2008, 81, 221–227.

23. Montano-Loza, A.J., H.A. Carpenter, A.J. Czaja. Fea-tures associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease. Hepatology, 46, 2007, 4, 1138–1145.

24. Montano-Loza, A.J., H.A. Carpenter, A.J. Czaja. Fre-quency, behavior, and prognostic implications of antimitochondrial antibodies in type 1 autoim-mune hepatitis. J Clin Gastroenterol, 42, 2008, 9, 1047–1053.

25. Nezu, S., A. Tanaka, H. Yasui, et al. Presence of anti-mitochondrial autoantibodies in patients with au-toimmune hepatitis. J Gastroenterol Hepatol, 21, 2006, 9, 1448–1454.

26. O’Brien, C., S. Joshi, J.J. Feld, et al. Long-term fol-low-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology, 48, 2008, 2, 550–556.

27. Okano, N., K. Yamamoto, K. Sakaguchi, et al. Clin-icopathological features of acute-onset autoim-mune hepatitis. Hepatol Res, 25, 2003, 3, 263–270.

28. Rust, C., U. Beuers. Overlap syndromes among au-toimmune liver diseases. World J Gastroenterol, 14, 2008, 21, 3368–3373.

29. Vogel, A., M.P. Manns. Autoimmune Hepatitis. UNI-MED-Verlag AG, 2010.

30. Weiler-Normann, C., C. Schramm. Drug induced liver injury and its relationship to autoimmune hepatitis. J Hepatol, 55, 2011, 4, 747–749.

Адрес за кореспонденция: Adressfor correspondance:

Проф. Искрен Коцев, д.м.н.

Клиника по хепатогастроентерология, УМБАЛ „Св. Марина“ ВарнаУл. „Христо Смирненски“ №1, Варна [email protected]

Prof. Iskren Kotzev

Clinic of Hepatogastroenterology, University Hospital „St. Marina“ Varna

Hristo Smirnenski Str., Varna 9010

[email protected]

Оригинални статии / Original papers

14 15


Material and methods

The number of candidate students and the ad-mission since the introduction of the university subject Healthcare Management (1997) until the present academic year (2010/11) has been tracked out, along with the average number of candidate students for one place.

A survey was carried out through consulta-tion with managers of health establishments on the territory of the region, which included in-formation on the following criteria: total num-ber of healthcare (HC) specialists; number of specialists with educational and qualification degree (EQD) in the subject Healthcare Manage-ment (HCM); number of full-time positions for healthcare managers; number of occupied posi-tions for senior managers with EQD in Health-care Management; number of „rank“ specialists with EQD in Healthcare Management; number of specialists in the subject with bachelor’s and master’s educational and qualification degrees; number of specialists with master’s degree in Health Management (HM).

(2010/11г.), както и средният брой кандидат-студенти за едно место. Проведено бе и гнездо-во проучване чрез допитване до управители здравни заведения на територията на региона, включващо информация по определени крите-рии. Паралелно се осъществи уточняващо теле-фонно интервю с главните медицински сестри и управители на здравни заведения.

Резултати и анализ. Установи се, че две години преди изтичане на гратисния период (приключващ 2009 г.) едва 1/5 от длъжности-те за ръководители по здравни грижи са заети от дипломирани специалисти по управление на здравните грижи. През 2011 г. обезпечеността на тези места с дипломирани бакалаври и ма-гистри надхвърля вече половината (56, 92%). Понастоящем липсва закон за заемане на уп-равленски длъжности от магистри по здравен мениджмънт, въпреки че те се предпочитат при провеждането на конкурси.

заключение. Специалностите управление на здравни грижи и здравен мениджмънт про-дължават да бъдат атрактивни и търсени, по-твърждаващо се от конкурентостта в приемни-те изпити по ново обществено здравеопазване и здравен мениджмънт.

Ключови думи: осигуреност с кадри, ви-сше мениджърско образование, управление на здравните грижи, здравен мениджмънт

number of candidate students for one place. A study was carried out through consultation with manag-ers of health establishments on the territory of the region which included information on certain crite-ria. Parallel to that a clarifying telephone interview was conducted with chief nurses and managers of health establishments.

Results and analysis. It was found out that two years prior to expiration of the grace period (end-ing 2009) only 1/5 of the positions for healthcare managers were occupied by specialists graduated in healthcare management. In 2011 more than half of these positions (56.92%) were occupied by garadu-ate specialists with bachelor’s and master’s degrees. Currently there are no legal provisions with respect to occupation of management positions in health management by specialists with master’s degree although they are given preferences when competi-tions are conducted.

conclusion. The university subjects Healthcare and Health Management continue to be attractive and demanded which is evidenced by the competi-tion during the entry examinations in new public health and health management.

Key words: procurement with personnel, high-er management education, healthcare management, health management

Introduction

The health reform imposes before the educa-tion in the field of Public health the require-ment for its development and improvement in line with the contemporary European educa-tional tendencies. The implementation of Euro-pean standards in the training of the specialist in Healthcare Management (HCM) and Health Management (HM), as well as the establish-ment of hierarchical educational system, in-cluding through implementation of pedagogical innovations and methodological technological solutions in educational management is the fi-nal objective directed towards improvement of healthcare and increase in the management culture of the personnel.

In a national plan a number of studies have been conducted, treating mainly the manage-ment and organizational aspects of the training in these topical university subjects, as well as the creation of a project for permanent train-ing quality management system, the motivation for training of students in the system of public health, as well as the necessity of expand the contents of the educational degree in this field [3,4,5,6,9].

The OBJEcTIVE of the present work is to find out the procurement with and realization of management personnel for healthcare and health managers for medicinal structures in Southern Bulgaria.

Parallel to that a clarifying telephone inter-view was conducted with the chief nurses and managers of health establishments.

Results and analysis

The first three years following the introduction of this university subject (Healthcare, in 2006 renamed to Healthcare Management) are dis-tinguished for considerable inrush of candidate students, in the academic year 1999/2000 be-ing 360 persons for 58 places. In the same year the state quota for admission of students for bachelor’s degree varying between 30 and 50 persons was reduced (Fig. 1). The competition for the discussed period (calculated using the index average number of candidate students for one place) is illustrated on Fig.2, which shows that it is the highest for the year discussed – 6,21. The initial levels (for the first two years of existence of the subject) are also satisfactory (over 3,50 – applicants for one place).

As a result of the positive Program accredi-tation in 2004 and the propagation campaign

050

100150200250300350400450

1997/98уч.г.

1998/99уч.г

1999/00уч.г.

2000/01уч.г.

2001/02уч.г.

2002/03уч.г.

2003/04уч.г.

2004/05уч.г.

2005/06уч.г.

2006/07уч.г.

2007/08уч.г.

2008/09уч.г .

2009/10уч.г.

2010/11уч.г .

приети обучаваниAdmitted students Trained students

Fig. 1 Admittance of students in Healthcare Management for the period 1997/98 – 2010/11 academic year

01234567

1997/98 уч.г.

1998/99 уч.г

1999/00 уч.г.

2000/01 уч.г.

2001/02 уч.г.

2002/03 уч.г.

2003/04 уч.г.

2004/05 уч.г.

2005/06 уч.г.

2006/07 уч.г.

2007/08 уч.г.

2008/09 уч.г.

2009/10 уч.г.

2010/11 уч.г.

Fig. 2 Average number of candidate students for one place for the period 1997/98 – 2010/11 academic year

16 17


of the Healthcare Management Department, advertising the perspective of the specialty in the medicinal establishments in Southern Bul-garia, the interest in it increased. A peak was marked in the academic year 2005/06 com-pared with the preceding year and the rate of increase in the number of students willing to be trained in it became 1,66 which reflected on the competition – the index being 3,45 (Fig. 2). The index for the academic year 2006/07 marks a downward trend again; it comes as a result of Ordinance 248 (State Gazette 95/22 November 2005) according to which nurses and midwives graduate with bachelor’s edu-cational and qualification degree [7]. It is very likely that the ordinance has a misleading im-pact on part of the potential candidate stu-dents who do not take into consideration that this bachelor’s degree has the nature of basic training only for ordinary and not for manage-ment positions.

The index 1.07 for the academic year 2007/2008 is the lowest. This is so because of the fact that the Ministry of Education and Sci-ence granted a state quota for admittance to the Medical University of Plovdiv for 90 students for bachelor’s degree (60 full-time and 30 by correspondence) in Healthcare Management. This coincided with the first admittance of stu-dents for master’s degree in HCM – 107 places, which caused withdrawal from the bachelor’s educational and qualification degree. Of all stu-dents admitted to both courses for Master’s degree, 62 were subject to item 2 of the Uni-fied State Requirements (with training period of three semesters), the places being filled by students graduated from Medical Colleges who have acquired bachelor’s degree in the follow-ing subjects: social activities, social pedagogy, social management and health management; a large part of them have already occupied senior management positions in medicinal establish-ments which should be defended by law with the acquisition of the specialty Healthcare Man-agement. Forty five students with Bachelor’s degree in Healthcare Management were admit-

ted for a Master’s degree in Healthcare Man-agement with duration of the course of studies two semesters, (at that time both courses for Master’s degree were at the Faculty of Medicine (2009) and the merging of the specialty Health-care Management with it for the purpose of stabilizing its image, is the reason for the dou-bling of the number of candidate students for one position for the academic year 2009/2010. The global number of students trained by us in Healthcare Management (both for Bachelor’s and Master’s degree) for the period 1997–2011 is 1008.

Together with the first admission for Mas-ter’s degree in Healthcare Management the ad-mission for Master’s degree in Health Manage-ment took place (both for medical and non-med-ical students), initiated by the Healthcare Man-agement Department and to the credit of the future Dean of the yet not established Faculty of Public Health and the Head of the Department of Health Management, Economy of Health and General Medicine – Prof. Dr. Zhelyazko Hristov, MD. This gives incentive the positions for man-agers of health establishments, heads of wards and other management positions (with Region-al Health Inspectorates, National Health Insur-ance Fund, National Insurance Institute) in the health-related spheres in Southern Bulgaria to be occupied by persons who, apart from Mas-ter’s degree in medicine or dental medicine, also have qualification in health management, preferably certified by a Diploma for master’s degree in Health Management. The results from the survey undoubtedly indicate that the lead-ing position is occupied by the Multi-profile Hospital for Active Treatment „St. Pantheley-mon“– Plovdiv. Medical students who have ac-quired master’s degree in Health Management occupy management positions in the medical institutions, including graduated economists and lawyers, i.e. a large number of students with the relevant educational and qualification degree in Health Management, being ahead of the differentiation of this requirement into a law. University Multi-profile Hospital for Active

Treatment „St. George“ has a stable statute and most of the structures are headed by manag-ers (23 in number, with an upward trend), who have acquired master’s degree in Health Man-agement at the Faculty of Public Health, Medi-cal University of Plovdiv. The non-medical stu-dents with higher education in Health Manage-ment (economists, lawyers, psychologists, etc.) also represent a considerable share. It is worth noting that by academic years the inrush of students with master’s degree in medicine and dental medicine also increases, including from the circle of those not occupying management positions (mainly from our higher institution), willing to acquire such education. We should not ignore the fact that a certain part of the stu-dents have the prevailing desire to obtain a di-ploma in Health Management. Very indicative is the fact that the interest in the taught subjects increases (evidenced by questionnaires), main-ly in the sphere of socio-medical knowledge and its structural branches.

Taking into account the discordance be-tween the high qualification of the managerial medical personnel represented by those having a master’s degree in medicine and the compara-tively unsatisfactory level of patient servicing, we attach great importance to the operational management carried out by the healthcare managers, who have acquired the specialty Healthcare Management. In this connection the realization of management personnel in Health Care is a decisive factor of special importance.

The procurement of specialists with bach-elor’s and master’s degrees in Healthcare Man-

79,75%20,25%

Diplomaed managers in Healthcare Management

Non-diplomaed managers in Healthcare Management

56,92%43,08%

Diplomaed managers in Healthcare Management

Non-diplomaed managers in Healthcare Management

Fig. 3. Procurement of managers in healthcare diplomaed in the specialty Healthcare Management in Southern Bulgaria (2006 and 2011)

agement for this region of the country is reflect-ed on Fig. 3.

It is worth noting that while three years prior to expiration (2006) of the ten-year grace period (SG 62/9 July 1999) only 1/5 (20.25%) of the positions for chief and senior managers were occupied by certified bachelors in the re-quired specialty, two years after the expiration of this period (2011) the procurement exceeds half of them and amounts to 56,92% (P<0,001), i.e. it almost triplicates, which we assess as a favorable tendency. However, in a considerable large part of the cases (43.08%) specialists in Healthcare who have graduated from the Medi-cal Colleges at the Medical Universities were appointed without the necessary management and educational qualification.

Therefore the structural changes launched should be consolidated – the vacated positions for senior managers should be occupied after a contest or by rank specialists in the relevant health establishments who have acquired bache-lor’s or master’s degree, failing which, by external persons having such educational qualification.

At the same time it should be noted that a considerable part (43.51%) or the specialists graduated and working in the specialty Health-care Management in health establishments have a master’s degree acquired mainly at the Faculty of Public Health (FPH) at the Medical University of Plovdiv.

Although the ratio between the number of students trained by us for bachelor’s or mas-ter’s degree admitted 10 years after introduc-tion of the specialty (2007) is 2/3:1/3 it is obvi-

18 19


ous that the realization of those with master’s degree is considerably better (Fig. 4).

It is due to the fact that part of the bach-elors occupying management positions have obtained a higher educational and qualification degree (master of Healthcare Management). Apart from that, their management position motivates them for higher educational degree compared with the „clinical“ bachelors appoint-ed parallel with them. The described results form a tendency (P>0.05) since the system is not capsulated. Some of them (though single cases) are trained at the Medical University of Plovdiv but are appointed in cities outside Southern Bulgaria and vice versa, students graduating from other higher institutions occupy manage-ment positions in Healthcare Management in medical establishments in Southern Bulgaria. Apart from that a small number of the students occupying management positions (under the established state of affairs), mostly bachelors of Healthcare Management in a number of cases continue their education for master’s degree in the same specialty.

Recognize as weaknesses ensuing from De-cree No: 215 of 18 August 2006 (SG 70, 2006) of the Uniform State Requirements – the training of masters pursuant to Article 6, Subpar. 1 and 2 to be performed under one and the same cur-riculum [7]. The exclusively clinical classifica-tion of nurses and midwives (SG 95/2005), so called „clinical bachelors“ on the one part and the considerably stable management training of those graduated from Medical Colleges and additionally acquired the specialties Healthcare

Management, Social Activities, Social Pedagogy and Social Management requires differential approach to the training for master’s degree in Healthcare Management [6]. Their differen-tiation in separate courses with different cur-riculums could moderate this discrepancy. The dissatisfaction of the personnel having certain management qualification will also be over-come (under item 2).

The procurement (in number and relative share) of specialists with bachelor’s/master’s degree in Healthcare Management at the posi-tions of senior and chief manager (nurse, mid-wife, rehabilitation therapist, radiographer, etc.) in 26 health establishments in Southern Bulgaria, 22 of which multi-profile hospitals for active treatment. It is obvious that a number of medical institutions of low entry level have a high rate of procurement with personnel in Healthcare Management occupying manage-ment positions in healthcare (Table 1).

The highest degree of procurement with personnel having the required educational and qualification degree is observed at MPHAT „St. Kirilovich“ – Haskovo (90%), followed by MPHAT „St. Pantheleymon“ – Plovdiv (78.57%), increased by 58% at P<0.001. The third posi-tion is occupied by MPHAT „St. Pantheleymon“ – Yambol (77.78%). The fact that in a number of health establishments the positions for chief and senior managers are not occupied by per-sons having the required educational degree is disturbing. Among them are: MPHAT – Madan, MPHAT – Dimitrovgrad, MPHAT – Panagy-urishte, MPHAT – Smolyan. Immediate solu-

tions of the management in the relevant health establishments are necessary in order to ensure the procurement with managers in healthcare in compliance with the legal requirements.

We can mark as significant the increase in the relative share of procurement for the peri-od 2006–2011 for MPHAT „St. George“ Plovdiv from 30% to almost 70% [8] and MPHAT Plov-div JSC from 16.67% to 60.61%, i.e with increase rate 2.33 and 3.63 respectively. The reaction of the management of the above mentioned health organizations is timely and in compliance with the Medical Establishments Act (SG 62/1999), namely: within ten years as of effectiveness of the Act (until July 2009) they have appointed persons with the required educational degree at these positions.

The amendments quoted in SG (59/2007) are even more categorical – the following text has been nullified: „persons with educational and qualification degree lower than bachelors can be appointed if no applicant meeting these statutory requirements appears“. The nullified text is „…senior nurse (midwife, laboratory as-sistant, rehabilitation therapist) may be a person having bachelor’s or master’s educational and qualification degree in Healthcare Management“. This statutory requirement should immediately provoke the conduct of competitions in the re-maining medical institutions for the purpose of appointing persons at the discussed positions only with the above indicated educational de-gree. The mandatory provision that the position of chief nurse should be occupied by certified

Bachelor’s degree Master’s degree Bachelor’s degree

Specialists occupying management positions

Master’s degree

43,51%

56,49%

33,63%

66,37%

Trained specialists Fig. 4. Ratio between trained and realized specialists with bachelor’s and master’s degrees in Healthcare Management

Table 1. Procurement of specialists with bachelor’s and master’s degree in Healthcare Management at the position of manager in healthcare in some medical establishments in Southern Bulgaria for 2006 and 2011

№ Medical Establishments

Procurement of managers in

Healthcare/relative share/

2006 г.

Procurement of managers in

Healthcare/relative share/

2011 г.

Increase rate

1 Multi-profile hospital for active treatment “St. Kirilovich”– Haskovo 7,40% 90% 12,162 MPHAT “Bratan Shukerov”– Smolyan 4% 34,62% 8,663 MPHAT – Asenovgrad 8,33% 66,67% 84 MPHAT “Sveti Mina” – Plovdiv 8,33% 61,54% 7,395 MPHAT – “Velingrad” Ltd – Velingrad 10,52% 70% 6,656 MPHAT “St. Pantheleymon” – Plovdiv 20% 78,57% 3,937 MPHAT “Plovdiv” JSC 16,67% 60,61% 3,648 MPHAT – Pazardzhik JSC 11,11% 37,03% 3,339 MPHAT – Burgas 14,70% 42,42% 2,8910 MPHAT “Prof.Dr. Asen Shopov” – Zlatograd 28,57% 71,43% 2,5011 UMPHAT “St. George” – Plovdiv 30,49% 68,67% 2,2512 MPHAT ”Dr. Ivan Seliminski” – Sliven 30,86% 65,51% 2,1213 MPHAT “Prof. Dr. Stoyan Kirkovich”– St. Zagora 35,30% 73,53% 2,0814 MPHAT “Devin” Ltd – Devin 28,57% 50% 1,7515 MPHAT “Aytos” Ltd – Aytos 25% 28,57% 1,1416 MPHAT “St. Ekaterina” – Dimitrovgrad 16,66% 18,18% 1,0917 MPHAT “Prof. Dr. Konstantin Chilov” – Madan 0% 10% –18 MPHAT “St. Pantheleymon” – Yambol 0% 77,78% –19 MPHAT ”Dr. At. Dafovski” – Kardzhali 0% 44% –20 MPHAT “Sabo Nikolov” – Panagyurishte 20% 11,11% –

21Military Medical Academy Hospital Base for Active Treatment Plo-vdiv

– 53,85% –

22 Diagnostic and Consulting Centre “St. George” Ltd – Plovdiv – 11,76% –23 Oncological Disease Centre – Haskovo – 100% –24 Complex Oncological Centre – Plovdiv Ltd – Plovdiv – 30,77% –25 Centre for Mental Health – Smolyan – 100% –26 MPHAT “Esculap” – Pazardzhik – 0% –

20 21


personnel with master’s degree in Healthcare Management should be enacted. The high num-ber of ordinary specialists with educational and qualification degree in the specialty (bachelor’s and master’s degree) considerably exceeding half of the total number of students graduated with this degree, mostly in the largest medical institutions in Plovdiv is a certain reserve ena-bling immediate way out of this unusual situa-tion. When competitions are held, a diploma for bachelor’s / master’s degree in Healthcare Man-agement should be presented, along with the professional qualification „Healthcare Manager and Practical Trainer“, issued by the Faculty of Public Health at the higher medical schools [1,2].

conclusion

the tendency of procurement graduate spe-cialists in Healthcare Management for the man-agement positions in healthcare is consolidated. At the same time certain discordance is available – almost half of the positions for the studied re-gion are occupied by persons lacking the statuto-ry required educational and qualification degree and a large part of those graduated the relevant management specialty continue to perform the functions of ordinary healthcare personnel.

The introduction of stimuli, differentiating the statute of the graduates in Healthcare Man-agement from the personnel without any man-agement qualification – nurses and midwives with bachelor’s degree in healthcare and pro-fessional bachelors. It is indicative that the spe-cialty continues to be attractive and demanded which is confirmed by the increasing number of candidate students for one place in the entry examinations in social medicine and organiza-

tion of health, developing into a competition for new public health, in compliance with the new conceptual approaches.

References

1. Medicinal Establishments Act, SG 62/1999, § 72. Law on amendment and supplement of the Medici-

nal Establishments Act, SG 59/2007, § 10 and § 113. Lyochkova, M., G. Petrova, M. Todorova, M. Lesinska,

R. Karadzhova, R. Masaldzhieva. A project for per-manent educational quality management system in Healthcare, Nursing Science Magazine, 2003, booklet 2, page 3–8.

4. Milcheva Hr., Role of the academic motivation for studying in the training process, Contacts Maga-zine, booklet 3, 2007, page 63–65

5. Hristov, J., DS. Stoyanov., B. Tornjova., D.Dimitrova. Bulgarian Person-centred Public Health Project: towards the introduction of the person-centred care model in global medical education politics. The International Journal of Person Centred Med-icine, Volume 1 Issue 1, 2011 pages 101–104.

6. Ordinance of the Council of Ministers № 248 of 22.11.2005 on enactment of a Decree for Unified State Requirements for acquisition of higher ed-ucation in the specialties Nurse and Midwife for Bachelor’s educational and qualification degree, SG 95/2005.

7. Ordinance 215 of 18 August 2006 on enactment of the Unified State Requirements for Bachelor’s and Master’s degree in Healthcare Management, SG 70/2006.

8. Project for opening of a Faculty of Public Health at the Medical University of Plovdiv, Provisional as-signor – Rector, G. Paskalev, Assoc. Prof. MD, Re-search project director – M. Lyochkova, 2007, p. 79.

9. Lyochkova. M., V. Mihaylova-Alakidi, M. Todorova, E. Raykova. Procurement of personnel with higher education in management in the sphere of health-care. Academic Journal Management and Educa-tion, 2011, 7, Vol. 3, p. 373–378.

corresponding authors:

Vanina Mihaylova – Alakidi, MDMedical University of Plovdiv

Faculty of Public Health „Prof. Dr. T. Zahariev“Healthcare Management DepartmentOffice tel.: 023 602 323; 032 602 355

e-mail: [email protected]

Оценка на надеждността на скалата на Ф. Ланг за качество на живот в България

Златослав Арабаджиев*, Калоян Харалампиев**, Христо Давидов#, Владимир Божилов## * МУ Пловдив, Катедра Психиатрия и медицинска психология ** СУ Св. Климент Охридски, Катедра Социология # ПУ Паисий Хилендарски, ПФ ## Болница Св. Едмънд

EVALUATION OF THE RELIABILITY OF P. LANG’S QUALITY OF LIFE ScALE IN BULGARIA

Zlatoslav Arabadzhiev*, Kaloyan Haralampiev**, Hristo Davidov#, Vladimir Bozhilov##

* Medical University Plovdiv, Department of Psychiatry and Medical Psychology, ** Sofia University „St Kliment Ohridski“ Department Of Sociology, Faculty of Philosophy

# Plovdiv University „Paisii Hilendarski“ Faculty of Psychology ## BMI Hospital Bury St Edmunds

ABSTRAcT

Quality of life has been exciting people as long as the world turns. It stands for how much better do people thrive compared to the others or how much better is „today“ compared to „yesterday“.

The conceptualized interest in quality of life in its contemporary sociological aspect, studying and evaluating quality of life as an integral indicator of the state of being, achievements and success of the individual, and those of his/hers family, community and society, as those of certain political (governmental) circles has had, though not centennial, but prolific enough traditions.

The last had been institutionalized in the mid 60’s, initially in the US when an extensive, nationwide program had been presented. It encompassed the

РЕзюМЕ

Качеството на живот вълнувало хората от-както „свят светува“. То е мерило доколко те са по- добре от други, доколко днес са по-добре от вчера. Kонцептуализираният интерес към „ка-чеството на живот“ в съвременния социологи-чески смисъл, изучаването и измерването на ка-чеството на живот, като интегрален показател на състоянието, постиженията и успеха на ин-дивида, неговото семейство, общността и обще-ството, както и на дейността на различни нива в управлението, има не дълголетни, но богати традиции. Последните се институционализират към средата на 1960-те години, първоначално в САЩ, където и когато стартира широка общо-национална програма за изработване и въвеж-

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Introduction

Quality of life as a notion emerged in the US and Japan in 50’s and 60’s of the last century. The rapid economical development after World War Two had been contributing to the increase in people’s wealth and they had begun reflecting on a way to evaluate it and compare it to the others.

It was reckoned then that a family was as happier as the bigger was the number of long term utilization items in their possession. That’s why the first quality of life conceptions and research make us smile nowadays. Never-theless these were taken quite seriously at their time-family income growth had been calculated dynamically along with the rate of increase of the number of families possessing TVs, vacuum cleaners, living room furniture, etc.

Meanwhile the conceptions changed and gradually it was realized that such an evalua-tion of quality of life is applicable in a complete-ly stable situation only, provided that:

– First of all, everybody must believe that material wealth provides „obligatory“ happiness

– Financial/material stratification within the population should be minimal and the highest levels of wealth (where happiness was supposed to begin) should be stable and achievable for the majority of the population.

Contemporary man is deprived of such illu-sions. Due to the rapid and impetuous develop-ment of the technologies, we are no more able to define how much we need to be ultimately satisfied and happy. Constant information flow makes us realize that there is always something missing and thanks to the advertisement we feel constantly deprived of something. Our environ-

ment is getting evermore material and people tend to be more and more dependent on their passion of buying new items, new hi-tech gadg-ets, new estate. We end up in a race of being up to date with every new technologies and new employment requirements.

The existential need of man to measure how much today was better than yesterday and to plan how much tomorrow would be better than today has existed for long, long time ago. In regard to the actual reality this could be in-terpreted as quality of life. World Health Organ-ization (WHO) suggests a definition of quality of life within the following axes:

1) Physical – the general somatic condition of the individual and his/hers ability to independently satisfy his routine, daily requirements

2) Psychological – regarding psychological well being, one’s inner world and way of interpreting reality

3) State of independence – everyday activity, fitness to work and dependence on treatment (medicines)

4) Interpersonal contacts – social, friendly relations, experiencing social acceptance and realizing one’s own social importance. There are included here intimate (sexual) life, family, friendships, professional realization, leisure activities, etc.

5) Environment – household, safety, information access

6) Spirituality and personal beliefs – defined by the specific ethnic traditions

The above mentioned aspects of quality of life are well interconnected and change in any of them necessarily changes the others.

Quality of life: definition

That is a generalizing term, suggesting the pres-ence of sufficient data about how people live and how do they envision and evaluate their own living. Quality of life is people’s well being in the society, considering every individual’s in-volvement in a variety of life situations micro and macro perspectively.

Doctor Phillipp Lang’s scale of quality of life is a self evaluation scale, containing 78 ques-tions grouped in 15 domains. The total score of all questions ranges between 0 and 212 points. Generally speaking the scale might be divided into domains evaluating the positive aspects of quality of life (1–3), psychological domains (4–13), and domains concerning the personal features disharmony.

− domain 1 – measures every day physical activity− domain 2 – it is related to the social functioning

evaluation− domain 3 regards to the economical status− domain 4 regards to the impulsive/antisocial

behavior− domain 5 regards to the psychoactive

substances abuse− domain 6 measures anxiety− domain 7 defines the affective oscillation

between depressive and maniacal state− domain 8 evaluates the presence of hyperactivity

or over excitement− domain 9 regards to the ability to test reality− domain 10 measures intellectual functioning− domain 11 is the self assessment of the need of

hospital admission− domain 12 self awareness− domain 13 self assessment of overall

psychosocial functioning

Last two domains are in a relation with the presence of disharmonic features of the differ-ent individuals that might be grouped in clus-ters A, B or C of personal disorders

Objectives of the study

Our objective was to define the validity and reli-ability of quality of life scale in Bulgarian popu-lation.

252 individuals who do not fulfill the DSM-4 and IDC-10 criteria for mental disorder/so-matic decease participated in that research. The population studied aged between 17 and 76, of which 126 men and 126 women. They have dif-ferent marital and social status (students, un-dergraduates, employees and retired).

Method of the study

A self assessment questionnaire was presented twice for a period of 7 days to the same people and data from the first test has been compared to the re-test results in a week time.

Data

At our perusal are the 15-domain and 4-social/demographic results of the 252 participants, who have constituted the control group

The same questionnaire has been used twice in a 7 day period. Paired-Samples T Test is used for the comparison.

Results

The results of the test and the re-test are illustrated in the table bellow (table 1)Table 1

Domains Mean difference

Standard deviation

physical functioning 0,052** 0,270social functioning 0,000 0,000economical functioning 0,012 0,189impulsive/antisocial behavior 0,000 0,000Abuse 0,000 0,000Anxiety 0,000 0,000Dysphoric mood 0,000 0,000Hyperactivity 0,000 0,000reality awareness 0,000 0,000intellectual functioning 0,000 0,000need of hospital admission 0,000 0,000Insight 0,000 0,000overall psychological functioning 0,000 0,000clusters A+B 0,000 0,000cluster C 0,000 0,000TOTAL SCORE 0,063** 0,363

** The difference is significant at the 0, 01 level (2-tailed)

After the statistical processing of the re-sults of both the test and the re-test, there was

дане на „социални индикатори“, във връзка със социалните следствия за гражданите от косми-ческата програма на НАСА. Самият този факт достатъчно говори за мащабите на концентра-цията на научния и практически интерес, за зна-чението, което се отдава на тази проблематика от самото начало.

establishment and implementation of certain social indicators that had influenced the community after NASA space program had been launched. This fact alone is sufficient in favor for the extent and concentration of scientific and practical interest and impact attributed to that kind of research since its very beginning.

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an absolute concurrence in 13 of 15 domains. As for the economical functioning domain the mean difference is not significant. It was only the physical functioning domain where a statis-tically significant mean difference was present (at 1% level). This significant mean difference actually determines the overall significance of mean difference in the total score.

Results achieved are shown in table 2Table 2

Statistical indicators ValueMean 0,052Median 0,000Mode 0,000standard deviation 0,270Skewness 5,724Kurtosis 34,382Minimum 0Maximum 2

The mode value of 0,000 shows that the most common difference was 0, meaning there most frequently was a concurrence between the test and the re-test. This result is confirmed by the enormously high kurtosis (34,382) mean-ing that the concentration in the 0 is really con-siderable.

That is clearly evident within the distribu-tion itself.Table 3

difference Frequency Percent0 242 96,01 7 2,82 3 1,2

total 252 100,0

According to the results shown in Table 3, 96.0% of all differences are 0, i.e. in 96.0% there was a total concurrence of the test and re-test results.

Another argument in favor of the fact that mean difference, even significant, is sufficiently low was the high value of the correlation coef-ficient between the two paired samples, regard-ing the physical functioning domain.

The value of the coefficient of correlation it-self was 0.971 (and squared is 0,955), i.e. 95.5% of the variance in re-test scores is affected by primary test scores.

conclusions

Considering the high rate of concurrence between the results of the test and the re-test of the scale we might well conclude that it pos-sesses the reliability needed and might be ap-plied amongst the Bulgarian population for evaluation of the quality of life.

It might be useful either for a single, snap shot evaluation or for a prolonged follow up of treatment progress and change in one’s condi-tion in time.

On the other hand the scale evaluates the quality of life in accordance to all the axes of definition as suggested by the World health Or-ganization.

References

1. Аmerican Psychiatry Association – . Diagnos-tic And Statistical Manual Of Mental Disorders , Fourth Edition, Text Revision. 2005. 297–344; 345–428.

2. Stoyanov, DS, PK Machamer and KF Schaffner, Rendering clinical psychology as evidence-based scientific discipline: a case study, Journal of Evalu-ation in Clinical Practice, 18: 149–154

3. Elms, D., Rodigert, H., Kentawts. B – Experimental Psychology Ninth Edition 2009. 83–102; 353–284

4. Goodwin, C. 2010. Research in Psychology. Meth-ods and Design. 6th Edition. Wiley, pp. 247–253

5. Kraghaed, E., Nemenrof, Ch., – Encyclopedia Psy-chology and Behavioral Science, Second Edition 2008. 1166- 1173; 1256–1270

6. Long, D. M.D. – Scale Of Quality Of Life 20037. Seaman Jh, Kenrik D – Psychology – Second Edi-

tion. 13/ 433–452; 15/ 505–5348. Pallant, J. 2011. SPSS Survival Manual. 4th Edition.

Allen & Unwin, pp. 243–2479. Гоев, В. 1996. Статистическа обработка и ана-

лиз на информацията от социологически, мар-кетингови и политически изследвания със SPSS. Университетско издателство „Стопан-ство“, стр. 105–107


РИТА ЛЕВИ-МОНТАЛЧИНИ: ГЛОБАЛНАТА КРАЛИЦА НА НЕВРОНАУКАТА Un tributo per Rita*

Доц. д-р Георги Чалдъков, д.м. Лаборатория по клетъчна биология, Медицински университет, Варна

RITA LEVI-MONTALcINI: THE GLOBAL QUEEN OF NEUROScIENcE

Un tributo per Rita*

Assoc. Prof. George Chaldakov, MD, PhD Laboratory of Cell Biology, Medical University, Varna, Bulgaria

E-mail: [email protected]

* Тази статия е посветана на 103-ия рожден ден – 22 април 2012 – на професор Рита Леви-Монталчини, Лауреат на Нобелова награда. This article is dedicated to the 103-rd birthday – 22 April 2012 – of Rita Levi-Montalcini, Laureate of Nobel Prize

curriculum Vitae

Име: Рита Леви-МонталчиниРодена: 22 април 1909 г. в Торино, Италия.1930–1936: учи медицина в родния си град.1940–1945: италианският фашизъм забранява на евреите да работят в университети. Изследва-

нията в областта на невроембриологията провежда в една стая в къщата си в Торино, по-късно – във Флоренция.

1946–1977: работи в Washington University in St. Louis, Сейнт Луис, Мисури, САЩ.1961–1969: Ръководител на италианския Национален научен съвет (Consiglio Nazionale delle

Ricerche).1968: член на Националната академия на науките на САЩ.1972: член на Американската асоциация за изкуство и наука.1961–1977: основател и директор на Института по клетъчна биология и невробиология, Нацио-

нален съвет за наука, в Рим. Работи шест месеца в годината в Рим, шест месеца – в Сейнт Луис, Мисури.

1986: получава Albet Lasker Award for Basic Medical Research – предвестник за Нобелова награда за медицина.

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1986: получава Нобелова награда за медицина за откриването на растежен фактор за нерви (nerve growth factor, NGF). С нобеловите долари основава Фондация за подкрепа на млади учени и European Brain Research Institute – в Рим.

2001: Публикува Cantico di una vita („Песен на един живот“) – около 200 писма, писани на майка й, когато работи в Сейнт Луис, Мисури. Рита прибавя фамилията на майка си към тази на баща си Адамо Леви, и така става известна на света като Рита Леви-Монталчини.

2001: президентът на Италия Карло Чампи избира Леви-Монталчини за пожизнен сенатор в Се-ната на Италианската република.

Il corpo faccia quello che vuole. Io non sono il corpo: io sono la mente.(Тялото може да прави каквото си пожелае. Аз не съм тяло: аз съм душа.)

Рита Леви-Монталчини

Рим, 21 април 2009: симпозиум, тържества, гала вечеря в чест на 100-годишната възраст на професор Рита Леви-Монталчини – живата интелектуална легенда на Ита-лия. И на невронауката в света. Като се върнах във Варна написах: „21–23 април 2009: пак се срещнах с РЛМ“ – нещо като „Днес видях ДГ“, написано от Иван Вазов за Дора Габе. Днес със своите centotre anni (103 години), събрали огромен опит, ерудиция и мъдрост на учен, учител и сенатор, Леви-Монталчини продължава да участва в научния, полити-ческия и обществения живот на Италия.

Рим, 21 април 2009. Луиджи Алое, Рита Леви-Монталчини и Георги Чалдъков. „Нейният стогодишен живот изгради научен мост между два века и две хилядолетия – път, по който преминават много генерации от учени“ – така е написано на дипломата за Почетен член на Българското дружество

по клетъчна биология, която тя получи от българския лектор; вижда се дипломата, която тя държи в ръката си.

Евристичният трафик: Торино-Сейнт Луис-Рио Де Жанейро-Стокхолм

През 1946 г. Рита Леви-Монталчини получа-ва първите резултати от изследванията си на пилешки ембриони, направени в домаш-ната ѝ лаборатория в Торино, която нарича „Робинзон Крузо“. Тя публикува резултати-те си в едно италианско списание. Статията е впечатлила професор Виктор Хамбургер – известен невроембриолог и ръководител на Катедра по зоология във Вашингтонския университет в Сейнт Луис, Мисури. Хамбур-гер кани Леви-Монталчини да работи в не-говата лаборатория. На 19 септември 1946 г. тя отплува от Генуа за Ню Йорк с полския кораб Sobieski и емигрира в САЩ заедно със състудента си Ренато Дулбеко. Той отива в Блумингтън, щата Индиана при третия им състудент от Торино – Салвадор Луриа. (Защо някои квазиродолюбци се притесня-ват от емигрирането на талантливи бълга-ри в напредналите страни!) Леви-Монтал-чини гостува на Луриа и той я представя на генетика Херман Мюлер, който през ок-томври 1946 г. е получил Нобелова награ-да за медицина. Лурия представя Рита и на младия си сътрудник Джеймс Уотсън, който през 1962 г. ще получи Нобелова награда за медицина за структурата на ДНК. Тази сре-ща в Блумингтън остава известна в исто-рията на биомедицинската наука като сре-ща на „Един нобелист с четирима бъдещи нобелисти“. Тримата от тях са ученици на Джузепе Леви (1872–1965) – професор по хистология от Торино: Рита Леви-Монтал-чини (1909) за NGF, Салвадор Лаура (1912–1991) и Ренато Дулбеко (1914) за открития в генетиката.

„Да предскажеш непредсказуемото“ – пише Рита Леви-Монталчини през 1987 г. в автобиографичната си книга In Praise of Imperfection. Откритието на NGF е резултат на научна логика, интуиция и шанс – ком-бинация, която се „усмихва на гениите“ (пе-рифраза по Луис Пастьор). От тумор на миш-ки, присаден на пилешки ембриони, през

змийска отрова и слюнни жлези на плъхове да откриеш молекула (NGF), която стиму-лира растежа на нервни клетки, е блестящ пример за евристика. Поставено е начало-то на нова парадигма в биомедицинската наука: растежът и функциите на клетките се контролират от специфични протеино-ви молекули, наречени растежни фактори – днес техният брой е повече от 50. Досега – 20 април 2012 г. – за NGF има публикувани 11 584 научни статии според библиограф-ските източници на Pubmed; 17 от тях са на автора с колеги от Институт по клетъчна биология и невробиология в Рим.

Когато към нервни клетки in vitro (в кул-тура) се прибави NGF, те излъчват израстъ-ци (аксони и дендрити) – това невротрофно явление е наблюдавано с микроскоп от Ле-ви-Монталчини през 1952 г. в Института по биофизика на Херта Маер в Рио Де Жанейро (фиг. 1). И в следващите години е концеп-туализирано като невротрофна теория (гр. trophos – хранене, в случая – фактори, под-държащи растежа и функцията на неврони) (фиг. 2).

– NGF + NGFФигура 1. Микрофотографията във вляво (– NGF) – лишени от NGF, нервните клетки не формират израстъци и умират. Вдясно са показани нервните клетки, които се „радват на добро здраве“ и образуват много израстъци, защото към тях е прибавен растежен фактор за нерви (+ NGF) – тази „графика“ стана класическа в историята на NGF. Леви-Монталчини я нарече NGF Hallo. Днес този ореол е емблема на Института по клетъчна биология и невробиология в Рим.

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Фигура 2. Схематич-но представяне на не-вротрофната теория на Леви-Монталчини. Ефекторната (тар-гетна) секретира ра-стежен фактор за нер-ви (NGF) и го предоста-вя – по ретроградния аксонален път – на тя-лото на неврона, къде-то NGF стимулира екс-пресията на гени, чии-то протеини оказват трофично действие за неврона. Когато невро-

нът „огладнее“, секретира невротрансмитерни мо-лекули, които стимулират секрецията на NGF.

неврон

трансмитер NGF

таргетнаклетка

На 13 октомври 1986 г. в телефонен раз-говор от Стокхолм Леви-Монталчини на-учава, че е удостоена с Нобелова награда за медицина. Така 35 години след откриването на NGF, на 8 декември 1986 г. в Каролинския институт в Стокхолм, шведският крал Карл

XVI Густав връчва Нобеловата награда на Рита Леви-Монталчини. Наградата е поде-лена със Стенли Коен – биохимикът, който работи с нея в Сейнт Луис през 1953–1959, и по-късно открива епидермалния растежен фактор, за което получи наградата.

Екстраневронални ефекти на NGF

Днес се знае, че NGF действа не само на нервни, но и на други клетки и съответно участва в патогенезата не само на нервно-дегенеративни, но и на сърдечнометабо-литни болести (атеросклероза, хипертония, обезитас, диабет тип 2, метаболитен синд-ром), бронхиална астма, рак на гърдата, рак на простатата и кожни болести. Важно кли-нично приложение, въведено от д-р Луиджи Алое – сътрудник на Леви-Монталчини по-вече от 40 години – е, че NGF, приложен ло-кално, действа лечебно на рани на кожата и на корнеята на окото, както и на ретинопа-тия.

Открит като фактор, стимулиращ рас-тежа на определени популации от неврони (симпатикови и сензорни нерви и холинер-гични неврони в мозъка), т.е. NGF e невро-трофен фактор, NGF има трофични ефекти и върху мастоцити, лимфоцити, еозинофи-ли и макрофаги, т.е. NGF e и имунотрофен фактор. Други екстраневронални ефекти на NGF са стимулиране пролиферцията на кератиноцити, васкуларни ендотелни клет-ки и ентероцити, т. е. NGF e и епителиотро-фен фактор. И също така метаботрофен фактор, тъй като подобрява хомеостазата на глюкоза и липиди. Посочените трофични ефекти се медиират и от други невротрофи-ни (BDNF, NT-3, NT-4/5).

Стокхолм, 10 декември 1986 г.: шведският крал Карл XVI Густав връчва Нобеловата награда на Рита Леви-Манталчини. Фотографията е от личния архив на Рита Леви-Монталчини и е подарена на автора.

Благодарности

Благодаря на Луиджи Алое, Марко Фиоре, Вивиана Трика и Луиджи Манни от Института по клетъчна биология и невробиология в Рим и на Петър Генев, Антон Тончев, Марияна Христова и Веселка Николова от Медицински университет-Варна за съвместната научна работа през последните 15 години.

Книгопис

1. Levi-Montalcini R. The nerve growth factor thirty-five years later. Science 1987; 217: 1154–1162.

2. Aloe L, Chaldakov GN, editors. Nerve Growth Fac-tor in Health and Disease. Biomed Rev 1999; 10: 1–113.

3. Aloe L, Calza L, editors. NGF and Related Molecules in Health and Disease. Prog Brain Res 2004; 146: 3–527.

4. Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, Ghenev PI, Aloe L. Neu-rotrophin presence in human coronary athero-sclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 146: 279–289, 2004.

5. Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol 102: 169–171, 2005.

6. Fiore M, Chaldakov GN, Aloe L. Nerve growth factor as a signaling molecule for nerve cells and also for the neuroendocrine-immune systems. Rev Neuro-sci 2009; 20:133–145.

7. Sornelli F, Fiore M, Chaldakov GN, Aloe L. Adipose tissue-derived nerve growth factor and brain-derived neurotrophic factor: results from experi-mental stress and diabetes. Gen Physiol Biophys 2009;28:179–183.

8. Chaldakov G. The metabotrophic NGF and BDNF: an emerging concept. Arch Ital Biol 2011;149:257–263.

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Изисквания към авторите / author’s guidelines

Bulgarian Medicine is the official Journal of the Bulgarian Academy of Science and Arts, Science Division, Research Center for Medicine and Health Care and is published in 4 issues per year. It ac-cepts for publication reviews, original research articles, case reports, short communications, opinions on new medical books, letters to the edi-tor and announcements for scientific events (con-gresses, symposia, etc) in all fields of basic and clinical medicine. The journal is published in Eng-lish with exceptional reviews on significant topics in Bulgarian. The detailed abstracts and the titles of the articles, the names of the authors and insti-tutions as well as the legends of the illustrations (figures and tables) are printed in Bulgarian and English.

The manuscripts should be submitted in two printed copies, on standard A4 sheets (21/30 cm), double spaced, 60 characters per line, and 30 lines per standard page or as attached files to the e-mail given bellow.

The size of each paper should not exceed 10 pages (up to 5 000 words) for original research articles, 12 pages for reviews (7 500 words), 3 pages for case reports, 2 pages for short com-munications, 4 pages for discussions or corre-spondence on scientific events on medical books or chronicles. The references or illustrations are included in this size (two 9x13 cm figures, photo-graphs, tables or diagrams are considered as one standard page).

The abstracts are not included in the size of the paper and should be submitted on a sepa-rate page with 3 to 5 key words at the end of the abstract. They should reflect the most essential topics of the article, including the objectives and hypothesis of the research work, the methods, the main findings and the principal conclusions. The abstracts should not exceed one standard type-written page of 200 words.

The basic structure of the manuscripts should meet the following requirements:

Списание „Българска медицина“, издание на Българската Академия на Науките и Изку-ствата, Отделение за наука, Научен център по медицина и здравеопазване, излиза в четири книжки годишно. В него се отпечатват ориги-нални научни статии, казуистични съобщения, обзори, рецензии и съобщения за проведени или предстоящи научни конгреси, симпозиуми и други материали в областа на клиничната и фундаменталната медицина. Списанието изли-за на английски език с подробни резюмета на български и английски. Изключения се правят за обзорни статии по особено значими теми. Заглавията, авторските колективи, а също над-писите и означенията на илюстрациите и в таблиците се отпечатват и на двата езика.

Материалите трябва да се предоставят в два еднакви екземпляра, напечатани на ком-пютър, на хартия формат А4 (21 х 30 см), 60 знака на 30 реда при двоен интервал между редовете ( стандартна машинописна страни-ца). Освен това могат да бъдат изпратени като прикачени файлове по електронната поща на адресите, посочени по-долу.

Обемът на представените работи не тряб-ва да превишава 10 стандартни страници за оригиналните статии (или 5000 думи според стандарта на англосаксонските издания) 12 страници (7 500 думи) за обзорните статии, 3 страници за казуистичните съобщения, 4 страници за информации относно научни про-яви в България и в чужбина, както и за научни дискусии, 2 страници за рецензии на книги (монографии и учебници). В посочения обем се включват книгописът и всички илюстра-ции и таблици. В същия не се включват резю-метата на български и английски, чийто обем трябва да бъде около 200 думи за всяко. Ре-зюметата се представят на отделни страници.Те трябва да отразяват конкретно работната хипотеза и целта на разработката, използва-ните методи, най-важните резултати и заклю-

Title page

The title of the article, forename, middle initials (if any) and family name of each author; institu-tional affiliation; name of department(s) and in-stitutions to which the work should be attributed.

Text of the article

Titles and subtitles should be standardized.The original research reports should have the

following structure: introduction (states the aim, summarizer the rationale for the study), subjects and materials, methods (procedure and appara-tus in sufficient detail, statistical methods), re-sults, discussion, conclusions (should be linked with the aims of the study, but unqualified state-ments not completely supported by research data should be avoided). These requirements are not valid for the other types of manuscripts. Only of-ficially recognized abbreviations should be used, all others should be explained in the text. Units should be used according to the International System of Units (S. I. units). Numbers to biblio-graphical references should be used according to their enumeration in the reference list.

Illustrations

Photographs should be presented both in the text body to indicate their location and in separate files as saved in jpeg, tif or bitmap formats.

The figures, diagrams, schemes, photos should be submitted in a separate file with: con-secutive number (in Arabic figures); titles of the article and name of the first author. The explana-tory text accompanying the figures should be pre-sented along with the respective number of the figure in the main text body with space left for insertion of the figure.

References

The references should be presented on a separate page at the end of the manuscript. It is recom-mended that the number of references should not exceed 20 titles for the original articles and 40 ti-tles for the reviews; 70 % of them should be pub-lished in the last 5 years. References should be listed in alphabetical order, English first, followed by the Bulgarian ones in the respective alphabetic order. The number of the reference should be fol-

чения. Ключовите думи (до 5), съобразени с „Medline“, трябва да се посочат в края на всяко резюме.

Структурата на статиите трябва да отго-варя на следните изисквания:

Титулна страницаа) заглавие, имена на авторите (собствено име

и фамилия), название на научната органи-зация или лечебното заведение, в което те работят. При повече от едно заведение име-ната на същите и на съответните автори се маркират с цифри или звездички;

б) същите данни на английски език сеизписват под българския текст.

Основен текст на статията

Заглавията и подзаглавията следва да бъдат уеднаквени и различими.

Оригиналните статии задължително тряб-ва да имат следната структура: увод, материал и методи, собствени резултати, обсъждане, за-ключение или извод.

Методиките следва да бъдат подробно описани (включително видът и фирмата про-изводител на използваните реактиви иапара-тура). Същото се отнася и за статистическите методи.

Тези изисквания не важат за обзорите и другите видове публикации. В текста се допус-кат само официално приетите международни съкращения; при използване на други съкра-щения те трябва да бъдат изрично посочени в текста. За мерните единици е задължителна международната система SI. Цитатите вътре в текста е препоръчително да бъдат отбелязва-ни само с номерата им в книгописа.

Илюстрации и таблици

Снимките – освен в Word, за да се знае мeсто-положението им, следва да бъдат предоставе-ни и като отделни файлове във формат jpg, tif или bitmap.

Илюстрациите към текста (фигури, гра-фики, диаграми, схеми и др. черно-бели копия с необходимия добър контраст и качество) се представят на отделни листове (без обясни-телен текст), в оригинал и две копия за всяка от тях. Текстът към фигурите със съответната

32 33


lowed by the family name of the first author and then his/her initials, names of the second and other authors should start with the initials fol-lowed by the family names. The full title of the cited article should be written, followed by the name of the journal where it has been published (or its generally accepted abbreviation), volume, year, issue, first and last page. Chapters of books should be cited in the same way, the full name of the chapter first, followed by“In:“ full title of the book, editors, publisher, town, year, first and final page number of the cited chapter.

Examples:

Reference to a journal article:1. McLachan, S. , M. F. Prumel, B. Rapoport. Cell

Mediated or Humoral Immunity in Graves’ Oph-thalmopathy? J. Clin. Endocrinol. Metab., 78, 1994, 5, 1070–1074.

Reference to a book chapter:2. Delange, F. Endemic Cretenism. In: The Thyroid

(Eds. L. Braveman and R. Utiger). Lippincott Co, Philadelphia, 1991, 942–955.

Submission of manuscripts

The original and one copy of the complete manu-script should be submitted together with a cover-ing letter granting the consent of all authors for the publication of the article as well as a state-ment that it has not been published previously elsewhere and signed by the first author. The pro-cedure should be complemented via electronic submission.

Manuscripts of articles accepted for publica-tion will not be returned to the authors.

Peer-review process

Following the international standards in the field, the Editorial board has adopted double-blind peer-review policy assigned to independent ref-erees.

Following acceptance for publication the au-thors are charged 5 euros per page for language editing and corrections.

Ethical regulations: reports with experi-ments on human subjects should specify whether the procedures were conducted in accordance

им номерация (на български и на английски език) се отбелязва вътре в основното тексту-ално тяло на статията под съответния номер на мястото, където трябва да се разположи при предпечатната подготовка. Таблиците се представят с готово написани обяснителни текстове на български и на английски, които са разположени над тях; номерацията им е от-делна (също с арабски цифри).

Използвана литература:

Книгописът се представя на отделен лист. Бро-ят на цитираните източници е препоръчител-но да не надхвърля 20 (за обзорите до 40), като 70 % от тях да бъдат от последните 5 години. Подреждането става по азбучен ред (първо на латиница, после на кирилица), като след поред-ния номер се отбелязва фамилното име на пър-вия автор, след това инициалите му; всички ос-танали автори се посочват с инициалите, пос-ледвани от фамилното име (в обратен ред) до третия автор, последвани от съкращшението et Al. Следва цялото заглавие на цитираната ста-тия, след него названието на списанието (или общоприетото му съкращение), том, година, брой на книжката, началната и крайната стра-ница. Глави (раздели) от книги се изписват по аналогичен начин, като след автора и заглави-ето на главата (раздела) се отбелязват пълното заглавие на книгата, имената на редакторите (в скоби), издателството, градът и годината на издаване, началната и крайната страница.

Примери:

Статия от списание:1. McLachlan, S., M. F.Prumel, B. Rapoport. Cell

Mediated or Humoral Immunity in Graves’ Ophthalmopathy? J. Clin. Endocrinol. Metab., 78, 1994, 5, 1070–1074.

Глава (раздел) от книга:2. Delange, F. Endemic Cretenism. In: The Thyroid

(Eds. L. Braveman and R. Utiger). Lippincott Co, Philadelphia, 1991, 942–955.

Адрес за кореспонденция с авторите

Той се дава в края на всяка статия и съдържа всички необходими данни (вкл. електронна поща) на български език за един от авторите, който отговаря за кореспонденцията.

with the ethical norms if the responsible commit-tee on Human experimentation (local or regional) and/or with the Helsinki Declaration, as revised in 2000. Respective guidelines for animal experi-mentation should be considered.

Address for sending of manuscripts and other editorial correspondence

1431 Sofia, Zdrave str. 2, University Hospital for EndicrinologyAnd the next electronic addresses:Prof. Dr Philip Kumanov, Editor-in-chief: [email protected]

With copy for the scientific secretary –Assoc. Prof. Drozdstoj Stoyanov: [email protected]

Всички ръкописи трябва да се изпращат с придружително писмо, подписани от автори-те, с което потвърждават съгласието си за от-печатване в сп. „Българска медицина“. В пис-мото трябва да бъде отбелязано, че материа-лът не е бил отпечатван в други научни списа-ния у нас и в чужбина. Ръкописи не се връщат.

Процедура по рецензиране:

С оглед спазване на международните стандар-ти, редакционната колегия е приела процеду-ра по ‘двойно сляпа’ рецензия от независимио референти.

След положителна рецензия и одобрение на редколегията, авторите на статията дъл-жат заплащане в размер на 10 лв. за всяка стандартна машинописна страница, с оглед на покриване разноските по ангийска езикова редакция на текста и коректури.

Етически съображения: всички трудове, които отразяват експерименти с хора следва да бъдат съобразени с етическите норми и регулации, въведени от съответния местна или регионална научна комисия и/или с Де-кларацията от Хелзинки, ревизия от 2000г. Експериментите с животни следва да бъдат също така съобразени със съответните норми и правила.

Всички материали за списанието се изпра-щат на посочения адрес на редакцията:

1431 София, ул. Здраве 2, УСБАЛЕИли на следния електронен адрес:Проф. Д-р Филип Куманов, главен редактор: [email protected]С копие до научния секретар –Доц. Д-р Дроздстой Стоянов: [email protected]

www.iztok-zapad.eu www.iztok-zapad.eu

bulgarian medicine vol. ii № 1–4/2012

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