23

PROCEEDINGS OF THE TWENTY-FOURTH SCANDINA- VIAN CONGRESS FOR INTERNAL MEDICINE

1. B. Christensen, Copenhagen:

The thyroid function and the iodine metabolism.

A survey of the present knowledge of the connection between the thyroid function and the iodine metabolism is given. The various possibilities of using radio-iodine in function tests of the thyroid gland are discussed. The iodine uptake in and discharge from the gland is mentioned in connection with the urinary excretion. The possible value of the excretion of radio-iodine with the saliva is pointed out.

In concluding the auther points out that function tests with radioiodine is of some value in the diagnosis of questionable thyroid disordes. The final evaluation of the patient rests upon the clinician.

The protein-bound iodine in diagnosis is mentioned and i t is stressed that the convertion rate of inorganic to organically bound iodine expresses the rate of thyroid hormone formation or secretion.

2. B. Skanse, Malmo:

The diagnosis of disturbances of thyroid function.

The different laboratory procedures used for the appraisal of thyroid function were briefly surveyed. The chief objective of the present study was to evaluate the determination of the serum protein-bound iodine as a diagnostic procedure. Two different clinical materials were studied. The first material included 198

patients with proved or suspected disturbance of thyroid function. The analyses were carried out with Riggs and Man’s permanganate acid ashing method. The serum protein-bound iodine values gave a correct indication of the functional level of the thyroid in 92 per cent and a probably correct indication in a further 3 per cent of the cases. The second material comprised 208 patients in whom disturbances of thyroid function was present or suspected to be present. In this material the serum protein-bound analyses were carried out with Barker and Humphrey’s alkaliincineration technique. In 95 per cent of the patients the

serum protein-bound iodine values correctly indicated the functional activity of the thyroid and in two additional per cent of the patients the values probably gave a correct measure. On the basis of an analysis of 18 patients with hypothyroidism i t was demonstrated that the determination of serum protein- bound iodine before and after administration of thyrotropic hormone is a valu- able adjunct in the differential diagnoses between primary and secondary hypothyroidism.

The merits and shortcomings of the two different methods for serum protein- bound iodine analyses were discussed. The normal values for the two methods agreed well.

It was concluded that the determination of the serum protein-bound iodine is a valuable diagnostic aid in appraising the functional level of the thyroid.

3. H. Hortling, Helsingfors:

Nembutal basal mehbolism.

Abstract not received. The paper will be published in Scand. J. Clin. Lab. Chem.

4. G. Brante, S.-G. Sjoberg, 0. Groth, M. Svanstrom-Krogvig and H. Derblom, Eskilstuna : Radioiodlne diagnostics in a thyroid case material.

164 unselected adults in medical ward a t the hospitals of Eskilstuna (76) and Bollnas (88) were studied with 1'31. Reason for examination and grouping was clinical suspicion or diagnosis of altered thyroid function. Dose was 10 pC KIX3*. Regarding the Bollnlis material dose was sent from and samples returned to Eskilstuna. In all cases twelve-hour cumulative urinary I'31-excretion was analysed acc. to Nitowsky and Puck (J. Lab. Clin. Med. 39, 824, 1952). Usually total 24- and 48-hour excretion, and total and proteinbound in plasma at 4, 24 and 48 hours were also estimated. In many Eskilstuna cases external counting over the thyroid (ECT) was performed.

In the clinically verified group all hyperthyrosis (60) but 2, with or without goiter or complicating diseases, had KT values 220 %. All hypothyrosis (16) had KT values < 8 and 11 of them < 5. In the clinically not verified group 13 of 66 suspected hyperthyrosis had KT values > 20 and 6 < 5. 0 of 22 suspected hypothyrosis had >20 and 4 had c 5. Preparation and clinical grouping errors probably caused some, at least, of the obvious deviations from the rule. Plasma 113' and ECT results largely corresponded to KT results as did total 24 and 48 hours excretion values, but the values clearly showed less ovcrlapping

25

between groups. In many of our cases T values acc. to Frasser e t al. (Quart. J. Med. 22, 99, 1935) for urinary 113' excretion could be calculated. Their distri- bution agreed well with that of the KT values. Frasser's T-results agree closely with thyroidal I13*-clearance results (Ann. Rev. Biochem. 1954).

We conclude, that thyroid I13l accumulation (KT ) estimation by excretion analysis gives results of high significance in the diagnosis of altered thyroid function, normal KT limits placed at 5-20 %. In many cases of hyperthyrosis, however, a single early ECT (e. g. 1 hour after dose; upper normal limit 20 % of dose) or, when complicating kidney or heart diseases can be excluded, estima- tion of total urinary 1'31 excretion in 24 hours (lower normal limit = 30 %) can give sufficient information. Plasma 1'31 estimations, carefully judged, can give valuable support to diagnoses. Long-distance sending of dose and samples causes no disadvantages.

5. Arnold Holst Berg and I(. F. Stea, Bergen:

A clinical evaluation of the Ii31-excretion test.

In 200 patients 264 testa with 1'31-excretion in urine has been carried out. 78 patients had clinically certain thyrotoxicosis, and 69 of these had not been treated. 62 of these - 90 % showed abnormally high I-absorption, while the remaining were within the normal limits. In 12 patient8 with myxedema there was found a relatively high excretion, while a great deal were within normal limits.

As conclusion i t may be stated that the test with radioactive I is a valuable means within the diagnosing of thyrotoxicosis.

6. Hhkan Linderholm and Ivar Werner, Upsala:

On the effect of Propylthiouracil on the biological d cay rate of I,,, fr the thyroid gland in euthyroid and hyperthyroid.

D

The biological decay rate of I,,, from the thyroid gland in 8 euthyroid and 8 hyperthyroid patients was investigated before and during treatment with pro- pylthiouracil (PTU) in ordinary therapeutic dosage. The thyroid uptake and the urinary excretion of I,,, were observed to confirm diagnosis and to check the effect of treatment.

After an I,,, test and a fourteen day period for the determination of the decay rate, PTU treatment was started (0.05 g q. i. d.). Usually, after another 14 days, the I,,, test was again performed and the decay rate determined. In the hyperthyroid group PTU caused a decrease in BMR and improved general

26

condition but did not affect the biological decay rate of I,,, from the thyroid gland significantly. In the euthyroid group the biological decay rate increased about 3-4 times during treatment.

TSH is known to increase the biological decay rate of I,,, in euthyroid as well as in hyperthyroid individuals. The results thus seem to indicate that in the hyperthyroid individuals no increase in the TSH production occurs. In euthyroids such an increased secretion is well established. This is in agreement with the observation that prolonged treatment with antithyroid drugs in a dosage sufficient to maintain euthyroidism in Grave’s disease does not cause enlargement of the thyroid gland while larger doses do. With more potent dosage of anti- thyroid drugs an increased biological decay rate of I,,, in the thyroid gland has, in fact, been observed (Goldsmith et al., Solomon).

The results speak in favour of the concept of a disturbed interrelationship between the pituitary and the thyroid gland in hyperthyroidism.

7. R. Gordin and B.-A. Lamberg, Helsingfors:

Studies on the serum prothrombin level in thyrotoxicosis.

8. R. Grasbeck and B.-A. Lamberg, Helsingfors:

The electrophoretic lipoprotein pattern in disorders of thyroid function.

9. B.-A. Lamberg and R. Griisbeck, Helsingfors:

The paper electrophoretic serum protein pattern in disorders of thyroid function.

The changes in the serum prothrombin level, the lipoprotein and protein pattern in disorders of thyroid function were studied. A depression of the pro- thrombin level was seen in about 50 % of the cases in untreated thyrotoxicoois. During treatment a rise in the prothrombin values was seen in about 90 % of the cases including nearly all of those with initially low values and many of those with originally normal values. Administration of vitamin K or K, orally or parenterally induced a temporary rise in the prothrombin level similar to that seen in hepatitis. It is concluded that the decrease probably is attributable to imparied liver function.

In thyrotoxicosis the lipoprotein pattern showed no significant changes from the normal. In hypothyroidism a rise was seen in all fractions especially in the

27

chylomicrons and the beta lipoprotein. During treatment of thyrotoxicosis a rise occured in the total cholesterol, total lipid content and the chylomicrond and beta lipoprotein. During treatment of hypothyroidism an inverse reaction was seen including also the alpha lipoprotein.

The protein pattern in thyroxicosis revealed a decrease in the albumin and an increase in all the globulin fractions especially in the beta and gamma globulins. During treatment there was an increase in the albumin and the beta globulin along with a rise in the prothrombin level and a concomitant decrease in the gamma globulin. In hypothyroidism a depression of the albumin level and an increase in the beta globulin was seen. During treatment a further depression of the albumin level occurred along with a rise in the globulins especially in the alpha region.

The causes of these changes are discussed at some length. It is pointed out that the changes in the lipoprotein and the protein pattern in thyrotoxicosis do not necessarily implicate a hepatic damage in the sense of a decreased partial function but that actually an accelerated function may be involved. The findings of Rosenman, Byehr and Friedman (1952) with regard to the behaviour of the cholesterol in thyroid disturbances may support this view. In contrast with this concept the depression of the prothrombin level seems to be attributable to a decreased synthesis in the liver but i t is pointed out that the possibility of an increased break-down of this protein must also be taken into account. The value of the prothrombin level, the lipoprotein and protein pattern in clinical practice is discussed.

Disczcssiort to 1-9: L. G. Larsson, B. A. Lamberg, H. Castenfors, E. Bierring.

B.-A. Lambrg: A study on the clinical value of the serum proteinbound iodine (SPI) in thyroid disorders was presented (publ. in Nord. Med. 1954 :51:571 by B.-A. Lamberg, P. Wahlberg and P. I. Forsius). In Finland the thyroid disorders are predominantly connected with a multinodular goiter. The material included 60 cases of thyrotoxicosis, 9 cases of hypothyroidism and 93 control cases. A rather great overlapping between groups was seen about 30 per cent of the thyrotoxic patients showing values within normal range of distribution. The diagnostic value of SPI in Finland is thus limited at some extent. The great overlapping may be due to the multinodular character of the goiter.

A few cases illustrating the use of SPI as an index of thyroid activity after stimulation with thyrotrophin were shown (to be publ. in Acta Medica Scan. dinavica). The thyrotrophin test has been recommended for use in the differen- tial diagnoses between primary and pituitary hypothyroidism. Radioactive tech- nique is very convenient but is emphasized that use of SPI is valuable where radioactive facilities are not available. Whether all those cases which show a response to thyrotrophin treatment are really to be considered. as pituitary forms

28

of hypothyroidism cannot be assessed a t present. There remains the possibility of an underfunctioning thyroid gland which does not respond to actual phy- siological demands but may be well stimulated by a strong and specific stimulus as is the thyrotrophic hormone.

H. Castenfors & A. M. Allgoth: The most common test for determination of the thyroid gland is measurement of the 24 hour uptake and 24 hour excretion. The values are influenced by variations in the renal function. Therefore no sharp limit can be drawn between euthyroidism and thyrotoxicosis. The so-called thyroid clearance is indepedent of the renal function but is, acording to our observations, an irrelevant conception since rediffusion of iodine from the thyroid gland regularly occurs. Moreover, the method is circumstantial and not adapted to routine application. It sometimes occurs that particularly active thyrotoxicosis has already passed its maximum uptake after only a few hours with the result that the uptake values after 24 hours may be comparatively low. Patienta with renal damage have low excretion levels varying according to the degree of the renal damage. This may also distort the picture in the interpretation of a routine test. In order to preclude these errors in a simple manner we have instituted routine measurement of the 2 hour uptake in Medical Service I1 at St. Erik’s Hospital.

One important source of error in tests with tracer iodine is to be found in all the substances that depress the capacity of the thyroid gland to assimilate radio- active iodine. The most common of these is iodine present in cough medicine, intestinal antiseptics, toothpaste, and roentgen contrast mediums used in chole- cystography, myelography, pyelography and bronchography. Blocking of the radioactive uptake for up to one year after myelography and cholecystography has been reported. According to our experience the duration of the block is exceedingly variable and is dependent upon the rapidity with which the contrast medium is excreted in the individual case. It has long been known that thyroid preparations totally block the radioactive uptake and that the duration of the block may vary between one and six months after withdrawal of the preparation. Among the other substances affecting the uptake might be mentioned hormones (ACTH, cortisone, estrogens) and antithyroid substances with different points of attack (thiouracil preparations, thiocyanate, perborate, sulfa, P. A. S.). There are likewise a number of foodstuffs that are considered able to depress the uptake. These include turnips, cabbage, salt water fish, oysters and other items.

The table shows how after one week’s administration the ordinary iodine- containing intestinal antiseptic Enterovioform blocks the 24 hour uptake.

Because of all these sources of error we are of the opinion that the routine tracer iodine test should not alone be accepted as diagnostically decisive. On the contrary, here, as in all other cases, different laboratory tests should be used in correlation.

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10. A. Norgaard, Copenhagen:

Blood pressure in fully fit elderly persons.

The systolic and diastolic blood pressure waa measured in 2.269 fully fit persons aged 70 and over. Their fitness was evaluated on the ability to drive a car safely. In males between the ages of 70 and 82 the systolic blood pressure was found to be 156k30 mm and the diastolic 89k20 mm; females in the same age groups have mean value of 157189 mm. Males aged, from 83 to 91 showed 160183 mm. A slight rise waa observed in the systolic pressure and amplitude during the course of the years, but a slight fall in the diastolic pressure.

11. T. Hilden, A. R. Hrogsgaard and E. Gotiredsen, Ssborg:

Treatment of hypertension with Reserpine (Serpasil).

Reserpine is a crystalline Rauwolfia alkaloid, producing sedation, lowering of the blood pressure, bradycardia, and a tendency to increased intestinal function.

We have treated 30 outpatients suffering from essential hypertension with Reserpine. The duration of the treatment varied from 1 to 9 months.

Treatment was commenced with about Y2 mg of Reserpine daily, after which the dose was gradually increased to 1 or 2 mg daily in the course of some weeks. It waa later reduced to 1/2 or 1 mg daily in most cases. It was divided into 4 separate doses, the evening dose being the largest.

Results. - The treatment was instituted in 30 cases. It had to be discontinued in 8 owing to side-effects. Thus 22 patients continued the treatment. Ten of these were later given a combined treatment owing to insufficient effect on the blood pressure. This left 12 patients in whom treatment with Reserpine continued. In 10 out of these 12 patients a fall in systolic and diastolic blood pressure was obtained, from 20 to more than 60 mm Hg and from 10 to more than 30 mm Hg respectively. Thus only 10 out of 22 patients, or barely half the cases, responded with a certain fall in the blood pressure.

The changes in the fundus of the eyes showed only slight improvement. The electrocardiograms improved in 2 patients.

Many felt a subjective improvement. Headache was obviated in most cases, dizziness and angina pectoris subsided in a great number of the patients. We also saw subjective improvement without sufficient lowering of the blood pressure.

Side-effects were fatigue, sleepiness, depression, irritation of the mucous membrane of the nose, diarrhoea, cardialgia (in 2 patients with gastroduodenitis) , and increase of weight. In 8 cases, treatment had to be discontinued; in 3 of

these owing to nocturnal dyspnoea or oedemas, but these 3 patients had been given too large doses.

It is concluded that Reserpine can be used, in the treatment of outpatients owing to the harmless side-effects and the absence of orthostatic fall in the blood pressure. It cannot be decided to what extent the results are due to a sedative effect or a specific hypotensive action.

Discussion: S. HammarstrBm, H. Storm-Mathiesen, H. Lange.

12. A. Griiner, T. Hilden and A. R. Krogsgasrd, Ssborg:

Clinical investigations into the diuretic effect of Diamox (a carbonic an- hydrase inhibitor) and Asahydrin (3-chloromercuri-2-metoxypropyl urea).

Sulphonamides cause acidosis, increased excretion of salts, and a rise in the output of urine. This effect is due to an inhibition of the carbonic anhydrase in the tubules of the kidneys. The excretion of sodium, potassium and bicar- bonate is thus increased.

"Diamox" - 2-acetylamino- 1, 3, 4, 4hiodiazole 5-sulphonamide - exerts an especially strongly inhibitory effect om carbonic anhydrase, and can be used as a peroral diuretic in oedematous patients.

We have examined in hospitalized patients the diuretic effect of Diamox and, for comparison, that of a mercurial diuretic ("Asahydrin"), which is also administered by the mouth. The substances were administered for periods of fram 5 to 8 days, and the diuretic effect was expressed as the increase in the output of urine during the experiment in per cent. of the output during a prel- iminary period. In addition, the plasma levels of sodium, potassium, bicarbonate and chlorides were examined before and after the experiment.

108 experiments in all were performed in 87 oedematous patients. Diamox exerts a moderate diuretic effect. In about half the patients the output

of urine was increased by over 40 per cent. Larger doses are not more efficacious than small ones. One small daily dose (from 0.25 to 0.50 gm) is presumably the optimal dosage. The side-effects of Diamox - fatigue, paraesthesiae, dyspe- psia - become more pronounced with increasing dose.

Asahydrin becomes more effective with increasing dose; 6 tablets daily (= 60 mg Hg) exert the same effect as Diamox.

Diamox produces a fall in the bicarbonate level in the blood and a slight rise in the concentration of chlorides. The sodium concentration is not definitely altered, whereas the potassium level is lowered. Asahydrin causes a fall in the content of chlorides in the blood, but does not definitely influence the bicarbonate concentration. Large doses produce a slight rise in the plasma levels of sodium and potassium.

As Diamox expecially increases the excretion of sodium, and mercurial diuretics especially increase that of chlorides, i t has been attempted to combine the two diuretics.

Investigations of this nature are still few; in one series of experiments i t was considered that the effect of Diamox increased when it was combined with small doses of Asahydrin.

Discussion: S.-G. Sjoberg.

S.-G. Sjoberg: CMPU is also produced in Sweden under the name of Merilid (Pharmacia). I have used the drug in some forty cases of heart disease with oedema. I have compared i t with preparations of mercury for injection by giving alternately Hydrargan on one day a week and Merilid, 6 tablets (18 mg = 10 ml of Hg) on another day in the week (curves). The oral drug gave a distinct increase in the secretion of urine, which, naturally, is not comparable with that caused by the injected preparation (perhaps about one-fourth with the dosage used). Since the drug not seldom causes gastro-intestinal side-effects, the dosage is the crucical point. Four tablets is the minimum daily dose required to produce a diuretic effect. The curves show how this varies from case to case and that, as a rule, a t least 2 tablets 3 times daily have to be given. Dyspeptic symptoms occurred in nearly half of our cases, especially where a higher dosage was used, diarrhoea and nausea or vomiting rendering further treatment impossible in nearly one-fourth of these cases.

In the hope of eliminating side-effects but still maintaining an effective dosage we have recently started to givet intermittent doses (2 tablets 3 times daily for 4 days a week, if necessary increased to 2 tablets 4 times daily or 2 tablets 5 times daily for 4 days a week). This dosage seems to be effective, and up to now the results are promising.

CMPU, which should be further tried to establish the most suitable method of use, seems to have a satisfactory diuretic effect in the treatment of oedema of a not too acute or severe nature in heart diseases, and it is useful in such cases despite the risk of gastro-intestinal side-effects which possibly may be best avoided by using the above-mentioned intermittent dosage.

13. I. Edler, Lund:

The diagnostic use of ultrasound in heart disease.

As first discribed by Edler and Hertz (1) i t is possible to use ultrasonic reflectoscope for: 1. locating the boundaries between heart-wall and blood. 2. locating the heart-walls on living human beings.

33

Fig. 1. Section through the pulmonary artery from ox. The vessel is placed in water. The result is the same when blood is used instead of water. The quartz- crystal ( c ) above. The echogram to the left. O=outg&g pulse dgnal.

3. the continuous recording of the movements of the posterior wall of left ventricle and the anterior left atrial wall. Typical curves are obtained: Ultrasonic Cardiogram (UCG) . UCG and ECG are synchronized.

1. locate the boundaries between blood and vessel (Fig. 1) 2. differentiate pure mitral stenosis from mitral regurgitation (Fig. 2). During

the ventricular diastole there is a rapid inflow from left auricle in normal cases and in cases of mitral insufficiency. The refIecting surface of the left auricle makes a rapid movement in dorsal direction (Fig. 2 a). In cases of mitral stenosis the inflow from left auricle is slow and the left auricular wall makes a slow movement in dorsal direction during ventricular diastole. Plateau-curve (Fig. 2 b).

3. show the movements of the left auricular wall in a case of auricular flutter (Fig. 3).

4. diagnose thrombosis in the left auricle in cases of mitral stenosis (Fig. 4). 5. diagnose pericardial effusion (Fig. 5 ) .

Reference: Edler and Hertz: The Use of Ultrazonic Reflectoscope for the Continuous Recording of the Movements of Heart Walls. Kungl. Fysiografiska Sallskapets i Lund farhandlingar. Bd. 24. Nr 5. March 10. 1954.

In further investigations the author has been able to:

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35

Fig. 3. The rapid movements of the left auricular wall in a cwe of auricular flutter,

Fig. 4. Multiple echoes ( M ) f r o m the left auricular chamber. At ope- ration thrombosis were found in the left auricle. After operation the mul- tiple echoes were absent.

36

Fig. 5. Pericardial effusion. P = pericardium. AW = anterior heart wall. The distance between pericardium and anterior heart wall is

greater in sitting position than in recumbent position.

14. S. Helander, Stockholm:

Armchair treatment of myocardial infarction.

1949 the author reported an infarction material comprising 193 cases with a mortality of 30 per cent. On account of the desirability of comparing various materials in order to be able to judge different methods of treatment, a distri- bution into three groups was suggested, viz., mild, medium-severe, and severe cases, characterized by objective criteria. A classification of that material according to those principles showed that 56 of the 193 cases belonged to Group I (severe cases with shock and a fall in the blood pressure), with a mortality of 57 per cent, 116 to Group I1 with a 22 per cent mortality, and 21 to Group I11 without any fatalities.

Two other Swedish materials (published by Whllgren and Linden resp.) classi- fied according to the same principles, had a similar distribution of the death rates among the three different groups.

This material was treated with bed rest 4--6 weeks, but most of these patients were not treated with anticoagulants. As the difference of the prognosis in the various groups was obvious, the

patients in the milder grops 11 and 111 were allowed to leave the bed much

37

sooner than before, and since 1952, when Levine published his results with 81 cases treated in an arm-chair from the first days after the onset of the infarction, even the severe cases in Group I were allowed to rest in an arm-chair as long as they wanted.

The cases with severe shock were treated in bed excepting cases with heart insufficiency and dyspnae.

The results were encouriging. 71 cases were treated with a mortality of 9 per cent, 3 of 17 cases in Group I and 3 of 46 cases in Group I1 died (a mortality of 18 respectively 7 per cent). 8 cases in Group I11 survived without any compli- cations.

As the arm-chairtreatment seems to be a good prophylaxis against peripherial thrombosis the last 13 cases are not treated with any anticoagulants. No comp- lications are observed among these 13 cases. The author feels that the arm-chair treatment will reduce the mortality in Group I1 and possibly even in Group I, but probably the mortality in that group will be higher than 18 per cent when the material grows. The advantages of the arm-chair treatment are discussed.

Discussion: H. Bjerlov, H. Lublin, E. Warburg, E. Ask-Upmark, N. B. Krarup, H. Malmros, B. Ihre, C. Frumerie, P. J. Wising.

15. U. Carlborg, B. Ejrup, E. Gronblad and F. Lund, Stockholm:

The incidence of arteriosclerosis in pseudoxanthoma elasticum.

Considerable hemodynamic interest attaches to studies of the blood vessels in pseudoxanthoma elasticum, and indeed the disease may even come to be one of the manifold facets of research into the pathogenesis of arteriosclerosis.

The present series comprises 24 cases. Thirteen presented symptoms of effort angina type, remarkably enough without electrocardiographic signs of coronary insufficiency. Intermittent claudication occurred in ten, of whom six underwent exercise oscillography and showed pathologic inverse reactions. Oscillometry a t rest showed strikingly small deflections in 22 cases.

Arteriography was done in nine cases, five of which hade obliterations in one of the arteries of the legs. Roentgenograms disclosed pronounced calcifications in two, moderate in three, and very slight in three cases. The youngest patients in the three groups were aged 45, 27 and 36 respectively. No corresponding lesions were found in the arms.

With regard to the eyeground lesions, three stages can be distinguished: (1) the rupturing stage, leading to angioid streaks, (2) the "proliferation" stage, with disciform degeneration of the macula, and (3) the atrophic stage, with disappearance of the streaks.

The skin first shows small papules, then confluence of the papules in folds and increasing flaccidity, and finally atrophy with subsidence of the papules.

38

The vascular lesions appear to have corresponding stages : A rupturing stage followed by profilerations, which may produce more or less total obliteration of the lumen. Tre final stage, with atrophy, could lead to an improved passage, and explains the absence of any tendency to gangrene. - One of our cases showed a distinct improvement when reexamined by arteriography and exercise oscillography after six years.

Calcifications have been demonstrated in the skin, eyegrounds and vascular system. Arteriograms and general roentgenograms have revealed pictures similar to those in atheromatosis and arteriosclerosis obliterans. Whether these findings in pseudoxanthoma elasticum are due to medial calcifications bulging into the lumen of a flaccid vessel, or to secondary atherosclerosis, cannot be decided. - In one case, an exposed femoral artery when palpated was found to be unusually flaccid between the calcifications ; biopsy was not possible, - Focal calcifications of the media with normal intima have been described in the literature.

This paper is part of a bigger publication, which will be publised in Acta Med. Scand.

16. D. Dam, T. aeill, E. Lund and E. Sendergaard, Copenhagen:

Clinical experiences with various newer anticoagulants.

The following anticoagulants were examined : Dicumarol : 3,3'-methylene-bis-4-hydroxycumarin, G 25766 : 2-p-chlor-phenyl-l,3-indanedione,* G 23350 : 3- (a-p-nitrophenyl-P-acetylethyl) -bhydroxycumarin.* Marcoumar "Roche"3- ( 1' phenyl-prop yl- ) -4-oxycumarin.

A sterile aqueous transparent colloidal suspension of vitamin K, (1 %) con- taining "Tween" 80) (prepared by Dam and Ssndergaard) for intravenous administration, "Konakion", Roche (Trinkampullen) for oral administration, "K-vimin", Ido (menadiol sodium sulfate in sterile aqueous solution (0.5 % 1, Tablettae menadioni (Ph. Dan.) and Injectabile menadioni (Ph. Dan.) (Menadione sodium bisulfite.) All the above mentioned anticoagulanta were found suitable for clinical pur-

poses, but Marcoumar and G 25766 seemed to be preferable especially in long term treatment.

The superiority of vitamin K, over the simpler menadione derivatives in counteracting the anticoagulant effect was confirmed.

The vitamin K preparations tested were:

* From J. R. Geigy, Aktiengesellschaft, Baael.

39

In most cases intravenous administration of 10 to 20 mg vitamin K, incraesed prothrombin-proconvertin values below 10 % of the normal value to values within the therapeutic range (10-30 %) within 2 hours. Oral administration acted more slowly.

It is recommended to give 10 to 20 mg K, intravenously in cases with serious hemorrhage. Oral administration of a single dose of 2 to 2.5 mg K, or repeated daily doses of 1 mg may be used to raise undesired low prothrombin-proconvertin values without hemorrhages in order to counteract the latent bleeding tendency.

The use of larger doses of K, are dangerous by favoring the tendency to thrombosis and by incurring a temporary resistance to renewed anticoagulant treatment.

The simpler menadione derivatives should not be used for treatment of hemorrhages caused by anticoagulant treatment.

D k c u s h n : K. Korsan-Bengtsen, E. Lund.

We are aware of certain unpublished observations of pathologic changes following intravenous injection of large amounts of vitamin K, in colloidal solution. It is likely that these changes (pulmonary granulomas) were caused by the vehicle ("Tween" or similar substances) used as stabilizer. We are of the opinion that the small doses of "Tween" used in our cases are quite harmless.

We have examined the effect of menadione sodium bisulfite and vitamin K, during continuous dosage with anticoagulant. In all cases the effect of vitamin K, was evident, whereas no such effect could be found.after administration of menadione sodium bisulfite.

E. Lund (Reply to Korsan-Bengtsen) :

17. Kriistoffer Koraan-Bengtsen, Gothenburg:

Some aspects on the chemical nature of the proaccelerin.

Five series of experiments have been performed to study the supposed con- nection between the proaccelerin activity and the lipids in plasma.

In the first series of experiments cooled plasma was mixed with cold chloro- form and centrifuged a t 0°C. By this procedure 3 layers were produced, a plasma- layer, a chloroformlayer and a firm white interlayer which according to Folch consists of lipoproteins.

By this extraction the proaccelerin activity totally was removed from the plasma and was found in the white interlayer. The protrombin-proconvertin on the other side remained to its full extent in the plasmalayer.

When an oxalated plasma is stored for 3 days at 37°C. the proaccelerin activity is completely lost. In the second series of experiments it was found that only a comparative small amount of the lipids diaappeared during the same

time. Thus lipids per se do not seem to be responsible for the proaccelerin activity.

A stored plasma is always opalescent. According to McFarlane this opacity is due to lipids. Macheboeuf amongst others has shown that a lipoprotein to a large extent dissociates during storing. Thus i t would be of interest to estimate the proaccelerin activity in plasma after addition of agents known to influence the lipid protein linkage.

Chargaff has demonstrated that heparin is able to liberate the phospholipids from a high molecular lipoprotein (the trompoplastin from lungs). In own experiments the effect of heparin on the proaccelerin activity was studied. An addition of 0.01 mg heparin per ml plasma decreased the activity to less than 25 % within 2 minutes. The protrombin-proconvertin activity was unchanged. Is was observed by Machebouef and Tayeau that soap made the lipids in

plasma extractable by ether. This would indicate that soap in some way influ- ences the lipid protein complex.

In a fourth group of experiments it was found that potassium oleate, potassium stearate, and synthetic wetting agents rapidly diminished the proaccelerin activity to 25 %. In these experiments too the protrombin-proconvertin activity was unaltered.

Extraction of plasma by aceton-ether according to Blix removes practically all of the cholesterol and most of the choline phosphatides, but only a small part of the colamine and serine phosphatides. A plasma treated like this did not loose its proaccelerin activity.

From the results of these experiments may be concluded that the proaccelerin activity in some way is connected with an intact lipoprotein. It is probable that the lipid component is a cephalin.

18. N. Tornblom, Upsala:

Saddle embolism of the aortic bifurcation.

Published in extenso as: H. Lodin, P. Rudstrom and N. Tornblom: Saddle

Discussion: P. Kirketerp: 4 months ago my surgical colleague, Dr. Prip Buus had to operate

one patient twice for saddle-embolus. As this is probably a unique feat I will review the case history. The patient was a 33 year old woman with mitral stenosis who had a commisurotomy performed with digital widening of the very narrow mitral orifice. She had never hade emboli before and no thrombi were found in the auricle at the operation, From the 4th postoperative day she had auricular fibrillation and on the 9th day she suddenly developed symptoms of saddle- embolus. The embolectomy was difficult because aorta was anomalous with the

embolism of the aortic bifurcation: Acta Med. Scand. 1955.

41

bifurcature placed behind the transverse part of duodenum which had to be mobilised to make extraction of the big embolus possible. 3 days after the embolectomy the patient had a small pulmonary infarcation and anticoagulant therapy was started. In spite of this she 5 days later developed severe symptoms of a fresh saddle-embolus. The second operation through fleshy, friable and adherent tissues was extremely difficult but also the second embolus was succesfully removed and the patient could leave the hospital 4 weeks later with normal pulsations in both legs and with a much improved heart.

19. B. Ejrup, Stockholm:

Intermittent claudication in thrombosis of the aorta and iliac arteries.

Leriche’s syndrome (1940) consists of extreme fatigue and weakness in the lower extremities om walking, difficulties of erection, atrophy of the leg muscles bilaterally, abnormal pallidity, and absence of trophic disturbances.

De Wolfe et al. (Circulation, 1954) point out that lesions of high localisation are commonly associated with intermittent claudication referable to the gluteal and thigh muscles. Although I too would stress the importance of paying atten- tion to this syndrome, I nevertheless found among 31 cases (29 males and two females) a remarkably high number that, despite the high lesions, were distressed only by sural pain.

Aortography and arteriography of the iliac vessels were done in 22 cases, nine of which showed total occlusion and two partial occlusion distally in the aorta. Total occlusion was probable in a further two, making the total 13. The other 18 had lesions or total occlusion of an iliac vessel but no appreciable aortic changes. All showed pathologic exercise oscillograms.

One patient sought treatment for backache ; intervertebral disk degeneration was suspected and a jacket applied. The backache forced this patient to rest every 30 meters on his way to work. Penile erection was absent. There was total occlusion of the aorta. Diagnosis Leriche’s syndrome.

Another patient with total occlusion felt intense fatigue anteriorly in the thigh up to the groin, and in the calves too when walking. Numbness: walking distance 2-300 meters ; bilateral discomfort ; penile erection absent ; extremities thin. There was characteristic pallidity chiefly after exercise tests. Diagnosis : Leriche’s syndrome.

Three patients had symptoms from both the gluteal region and the thighs and calves; 13 mainly from the thighs, including eight with symptoms later from the calves too.

Of the 13 cases with thrombosis of the aorta, four were typical Leriche syndromes ; the remainder behaved like claudication cases.

,

42

The blood pressure exceeded 1601100 in four cases, including three with total

Cholesterin values above 300 mg per cent were found in seven cases, including

Discussion: P. Kirketerp.

occlusion of the aorta.

one with total occlusion.

20. K. Kjerulf-Jensen and P. Hruhaffer, Copenhagen:

Use of radioactive carbon monoxide in the determination of lung diffusion capacity in lung disease, with particular reference to emphysema.

Determination of the lung diffusion coefficient is undertaken in 20 patients with the aid of radioactive carbon monoxide (C14 0). Twelve of these patients suffered from chronic lung emphysema. Notwithstanding that the emphysema in the majority of the cases was pronounced, the DL C14 0 was not reduced by more than 50 per cent. From this observation the conclusion is drawn that the reduction of the diffusion might be of minor importance in the development of the arterial hypoxaemia in emphysema, while unequal distribution of the alveolar ventilation and perfusion is by fa r the most important factor.

In three cases of advanced pulmonary fibrosis the values for the DL C14 0 varied between one-third and one-fourth of normal. In lung diseases of this category a reduction of the lung diffusion capacity is consequently an important factor, although uneven distribution also plays a considerable rSle.

An attempt is made to evaluate the procedure of Riley and his associates in determination of the lung diffusion capacity (DL 02), and the contention is advanced that the determination of DL CO gives results that better reflect the actual condition.

Discussion: H. Colldahl, E. Roelsen.

21. 0. Storstein, Bode:

Respirator treatment of chronic pulmonary insufficiency.

In cases of total pulmonary insufficiency, where there is a failure both of oxygen uptake and of carbon dioxide elimination by the lungs, the only rational treatment is to increase the lung ventilation by means of artificial respiration.

This treatment has been given to two patients with chronic pulmonary emphysema as intermittent positiv pressure breathing, first by manual ventilation and then by &GA-respirator. After treatment for 9 and 2 weeks respectively, the hypercapnia was eliminated, a slight anoxemia still persisting in the first

43

patient. Two months after finishing the treatment, the carbon dioxide content of arterial blood was normal, while a slight anoxemia still persisted. Following respirator treatment there was an increase of the spontaneous lung ventilation.

Studies by cardiac catheterization showed a considerable fall of cardiac output during artificial ventilation, due to a hindrance of the venous return. At the same time there was a fall of the increased pressure in the pulmonary artery and a reduction to normal of the increased alveolar-arterial pO,-gradient.

Discussion: H. Colldahl.

22. S. Faine, Oxford, and W. J. Ealpainen, Helsingfors:

Experimental leptospirasis treated with erythromycin.

Several strains of Leptospira growing in Korthof's medium were found to be sensitive to erythromycin 0.001-0.01 gdml . A sensitive virulent strain of Lepto- spiru icterohuemorrhugiae killed untreated guinea-pigs (150-200 gm) in 4-6 days. Oral dosage with erythromycin begun during the first two days cured 80 % of the animals. Treatment for 6 days produced 10 9% renal carriers compared with 70 % carriers after 3 days treament.

Guinea-pigs did not tolerate erythromycin well. Some of the survivors and uninfected control animals treated with erythromycin developed anorexia, list- lessness and sometimes diarrhoea, and died, in both groups approx. 17 days after treatment began. Similar results of treatment were obtained in hamsters, which were as sensitive to the infection as guinea-pigs. Erythromycin was toxic for hamsters, some of which died similarly to the guinea-pigs approx. 13 days after treatment with erythromycin began.

Since toxicity of erythromycin has not been encountered in humans, these results suggest that treatment with erythromycin may be tried in human lepto- spirosis.

23. J. H. Solem, H. Kirkebye, H. Palmer and 0. Rameke, Drammen:

ACTH-treatment of acute hepatitis.

38 patients with acute hepatitis have been treated with intense stimulation with ACTH. In connection with the hormone therapy, there occurred a rapid drop in the serum index and a simultaneous rise to normal of prothrombin values. Parallel with this the dyspepsia and anorexia disappeared and made possible the adequate intake of food by the patients. No thromboembolic complications or signs of retention of fluid during the therapy were observed. It is emphasised that the patients must receive sufficient doses of ACTH and that the period of treatment must not be too short. It is stressed that the diet must be poor in salt. The authors discuss the value of the treatment.

44

24. Ph. Sandblom and 0.-A. Ekmm, Lund:

Surgical treatment of portal hypertension.

Portal hypertension with potentially fatal haemorrhage from oesophageal varices is usually due to a block of the efferent flow of the portal blood. This block may be extrahepatic - thrombosis in the lienal or portal veins (Banti’s disease), or intrahepatic - cirrhosis of the liver. In conservative treatment of cirrhosis of the liver with haematemesis the mortality is given as 50 to 80 per cent within one year after the first haemorrhage.

Surgical treatment is directed primarily against the potentially fatal haemorr- hages. Many methods have been tried with varying results. Attempts have been made to attack the oesophageal varices directly with sclerosing media, by means of multiple ligature or through dividing their afferent flow by partial oesopha- gogastrectomy. Portal hypertension has remained following these procedures, soon giving rise to new collaterals which have caused recurrent haemorrhage.

A decrease in the portal pressure is obtained either by decreasing the blood supply to the portal vein or by facilitating the efferent flow of the portal blood. Splenectomy decreases the afferent flow to the portal vein by about 30 per cent, to be sure, but is nevertheless a poor method since only temporary improvement is obtained. The best way to decrease the pressure in the portal system is to short-circuit or shunt the blood flow around the block in the portal vein or the liver to the cava system by creating an anastomosis either between the portal vein and vena cava or between the lienal and the left renal veins.

Our data are based on operative experience in 43 cases of portal hypertension (due to extrahepatic block in 19 and to intrahepatic in 24). Shunt operations were done in 36 of these cmes (15 of extrahepatic and 21 of intrahepatic block).

In the extrahepatic group the operative mortality was 0. However, recurrent haemorrhage occurred in eight cases, terminating fatally in six. Four of these six patients had previously undergone splenectomy. Therefore no satisfactory anastomosis could be obtained. Splenorenal anastomosis was done in nine cases. Seven of these patients are symptomfree 1% to 6 years after the operation.

In the intrahepatic group (21 cases) three patients died postoperatively. Haemorrhage recurred in only one case in this group. Twelve of the patients are living and symptom-free, and five died during the observation period (2 months to 5 years). Two of these deaths were caused by coma hepaticum; the others were due to intercurrent diseases.

We have not observed any noteworthy further deterioration of the hepatic function in consequence of the operative anastomosis.

Discussion : C.-A. Ekman and S. Bergstrand: In the choice of the shunt operation i t is

45

important for the surgeon to be oriented as to the localization of the efferent block and the suitability of the vessels for anastomosis. This information may be obtained through portal angiography. In 1951 Abeatici and Campi demonst- rated that percutaneous injection of contrast medium in the spleen resulted in rapid filling of the lienal and portal veins. With this method, which we have applied in 30 examinations, the anatomy and function of the portal system can be visualized easily and without great discomfort to the patient. In the investig- ation of cases of portal hypertension this examination reveals the degree of the portal hypertension, the localization of the efferent block and the degree of the cirrhosis of the liver. Moreover, portography is an excellent aid in testing the function of an anastomosis created between the portal vein and vena cava.

25. A. Svanborg, Gothenburg:

The cause of recidivating jaundice during pregnancy.

There are apparently two conditions in which jaundice in the pregnant woman is directly associated with the pregnancy. The first condition is the severe toxaemia of pregnancy. The second is that type of jaundice occurring in certain women, most frequently during the final third of the pregnancy] and regularly recurring in connection with repeated pregnancies. Seven patients with this type of jaundice were studied: two with jaundice in three successive pregnancies, two with jaundice in two pregnancies and three with jaundice exhibiting the characteristic course during one pregnancy.

The dominating subjective symtom is the itching of the skin that is accom- panied by dark urine, ligth-coloured faeces and jaundice. The symtoms appeared during the latter four months of pregnancy. The bilirubin increase rapidly reached its maximum, subsequently remaining a t a relatively constant level until the delivery and then disappearing within two to three weeks. A concurrent rise in the alkaline phosphatase activity in serum was demonstrated. This rise pro- gressed largely parallel to the bilirubin rise, but the biluribm rise disappeared somewhat more rapidly after delivery. Thymol turbidity tests and the Takata-Ara reaction showed normal results. In two patients with jaundice for the third time during late pregnancy electrophoretic plasma or serum protein investigations revealed only the protein changes typical of pregnancy. In no case were any changes demonstrated in the serum protein similar to those found in parenchymal liver disease. Nor were there any signs that the jaundice was of haemolytic origin.

This regularly recurring jaundice of pregnancy can best be explained in character and course as a disturbance in the bile flow, It is probable that milder disturbances of the dynamics of the biliary tract, with a rise in bilirubin, without

46

jaundice, but with retention of bile acid, accompanied by itching of the skin, are not unusual during pregnancy.

Biligraphy was performed in all cases after delivery. The bile ducts then had normal appearance and course. Discussion: H. Hult, E. Adlercreutz, W. Kerppola.

26. H. Colldahl, Stocholm

On nicotinic acid metabolism in the organism.

Earlier investigations (Colldahl, 1943 a. 1947) have shown that in animal expe- riments insufficient gas exchange caused by the respiration of a gaseous mixture of low oxygen tension and enhanced carbonic acid tension leads to reduced tissue respiration. This is partly due to the destruction of cozymase under such con- ditions (Colldahl, 1943). Later investigations (Grieg, 1944. Govier 1945) coincide with this assumption.

When i t is seen that insufficient gas exchange occurs in a number of different diseases, it is of interest to ascertain whether this condition results in changes of tissue metabolism similarly as in animal tests. Since cozymase can only be determined in the human organism with difficulty a thorough study of the nicotinic acid metabolism has been made instead, nicotinic acid being a part of the cozymase molecule.

Cayer and Cody (1948) studied nicotinamide methochloride in urine to gain closer knowledge as to the need of vitamin among patients with acute and chronic diseases. According to these authors their tests revealed no difference in the excretion in question. On the other hand, Cayer (1947), in cirrhosis of the liver, demonstrated that the rate of the excretion of nicotinamide methochloride after a test dose was considerably higher than is normal.

Leifer, Roth, Hogness and Corson (1951) were able to show that mice injected intraperitoneally with radioactive nicotinic acid revealed six different metabolites.

In this present work only nicotinamide methochloride has been determined. The study included a number of different diseases, as well as healthy persons, and the method was that of Huff and Perlzweig. The results are reproduced in fig. 1 and show the daily excretion of nicotinamide methochloride in the urine without test doses. The patients got the same hospital diet as is usually given in cases of this disease. No extra B-vitamines were administered. The only patients who displayed a regular increase of excretion of nicotinamide methochloride were those with liver parenchymal injury. In the majority of cases with obstructive jaundice the excretion of nicotinamide methochloride in the urin was normal. It is possible that this can be of significance in the differential diagnosis between hepatogenic and obstructive jaundice icterus,

47

Patient group

Investigations of the excretion of nicotinamide methochloride in the urin after test doses have shown that disturbance of the nicotinic acid metabolism not only occurs in hepatic parenchymal injury (see Table 1) but also in some cases of diseases with insufficient gas exchange, such as asthma bronchiale and cardial diseases with incompensation. Whereas the daily excretion of ulcus patients and healthy persons is fairly similar when investigated on different occasions, there is considerable dissimilarity of the excretion of asthmatic patients and patients with cardial incompensation, in regard to the same individual, on different occasions according to the state of the patients at the time of examination (Coll- dahl, 1955).

Complete elucidation of the problem in question presupposes investigation of all the metabolic products of nicotinic acid.

Excretion in 24 hours of nicotinamide metho- chloride in mg. after intravenous injection of

60 resp. 150 mg. of nicotinamide

Healthy persons . . . . . . . . . . . . Ulcus ...................... Hepatit. ac. . . . . . . . . . . . . . . . .

I KO mg I 150 mg.

10,O (1218 ) 29," (616) 11,2 (19110) 30,8 (514) 20,9 ( 3/3 ) 66,3 (312)

The bracketed figures refer to the number of determinations for the number

Discussion: 0. Lovgren, K. Kjerulf-Jensen, W. Kerppola. of patients. Thus 1218 indicates 12 determinations for 8 patients.

27. M. Faber, Copenhagen:

Medical treatment of patients after pancreahctomy for cancer of the pancreas.

To be published in extenso in Ugeskrift for Laege, 1955.

In surgical treatment of cancer of the pancreas rather extensive operations are carried out in some cases. For example, total extirpation of the pancreas may be done in combination with gastric resection. It is difficult to maintain the weight of these patients postoperatively. Several case histories illustrating this are presented, and the treatment is discussed. Balance experiments demon- strate how effective the postoperative medical treatment can be made. With a combination of dried pancreas and substances that decrease the intestinal motility the fa t loss in the faeces in successfully reduced by half.

48

28. E. Roelsen, Silkeborg:

Primary diffuse pulmonary carcinosis. Three cases of a charachristio clinical and pathologic-anatomical syndrome.

(To be published in extenso in Acta Med. Scand. 1955.)

Three cases of so-called malignant pulmonary adenomatosis are described. The patients were encountered within the last five years in a mediumsized medical department. This may be accidental, but the disease is supposed to be more common than generally accepted. So far, about 150 cases have been published. No doubt, several cases have not been published. All the cases took a subacute fatal course about five to nine months’ duration. The age of the patients was 49, 38 and 72; two were males, one female. The main symptoms were cough, increasing dyspnoea and cyanosis with pronounced tiredness, though surprisingly long-standing good general condition and normal sedimentation rate. In two cases the first diagnosis from the X-ray picture was diffuse sarcoidosis of both lungs, pulmonary tuberculosis could be ruled out. Only in one case was abundant sputum brought up, and only for the last weeks of illness. Two of the cases fulfilled the criteria set forth by Swan (1949), i. e., proliferation of the alveolarlining mem- brane by columnar cells, abscence of intrinsic primary bronchial tumour and absence of carcinome of any other organ. In the third case diffuse carcinomatous changes were found both in the lung tissue and in the bronchial tree. In all three cases the interalveolar septa were generally preserved, but carcinomatous invasion was obvious in all of them. Macroscopically the cut-surface of the lungs had the character of grey pneumonic hepatisation.

Discussion: T. Kahrs, S. Bjorkman, L. E. Warfvinge. L. E. Warfvinge: At Hallnas sanatorium since summer 1953 we have performed

paper electrophoretic investigations of sputum in different pulmonary and respiratory tract diseases. The results we obtained in one case of bronchiolar or alveolar cell carcinoma may be of some interest. The patient was a 60 year old man with massive opaque areas in both lungs. The diagnosis was established by means of aspiration biopsy. We were able to follow the case eight months, until the patient died of cor pulmonale.

Repeated paper electrophoretic sputum investigations showed identical pic- tures, with a dominant pure protein fraction which migrated towards the anode at the same rate as serum albumin (A), and with the commonly observed slowly migrating protein polysaccharide component (B) and a non-migrating component that took both protein and carbohydrate stains (A). In an extensive material, representing all common bronchial and pulmonary diseases and including two cases of bronchial cancer, all electrophoretic curves from sputum presented an entirely different appearance in that the A component - the pure protein frac- tion migrating like serum albumin - was only weakly indicated or was

49

frequently entirely absent. The phenomenon is most easily visualized in the accompanying photograph, in which the middle curve illustrates our case of bronchiolar cancer and the comparative curves above and below represent cases of bronchopneumonia, bronchial asthma, bronchiactasis and exudative pulmonary tuberculosis.

The characteristic change described in the sputum would appear to be of value in differential diagnosis inasmuch as sputum is a relatively early and constant symptom in this uncommon disease.

29. S.-G. Sjoberg, Eskilstuna:

Industrial disease caused by vanadium.

The metal vanadium is produced for the manufacturing of hard steel in the form of the pentoxide (V,O,, vanadium pentoxide). Vanadium-containing dust gives rise to irritation of the conjunctivae and the upper respiratory tract with rhinitis, pharyngitis, laryngitis and, as the most prominent symptom, bronchitis which is attended by a troublesome cough with many rhonchi and sometimes

50

leads to inability to work for weeks or months. Pneumonia may develop, and sometimes eczema. The condition is of an acute nature, but mild chronic changes in the mucous membranes may occur. Animal experiments support this opinion. The criteria for the diagnosis are contact with vanadium, typical complaints, and the detection of vanadium in the blood or urine, where this is not present normally.

Since vanadium occurs in most mineral oils derived from the enzymes of lower marine animals (Ascidiacea), it has in recent years become of increasing import- ance as a disease-producing agent in association with cleaning oil-fired boilers, in which V,O,-containing slag is deposited, especially in the large high-pressure boilers, but also in smaller ones. The writer has observed typical symtoms in men engaged on cleaning boilers of varous sizes. The prophylaxis is of great importance but is as yet at the experimental stage. By burning a mixture of pulverized coal and oil the formation of vanadium-pentoxide deposits can be eliminated and the symptoms thus prevented.

Literature: Sjoberg: Acta Med. Scand. 1950: 138; suppl. 238; Arch. Int. Hyg. & Occup. Med. 1951: 3: 631; Nord. Hyg. Tidskr. 1954: 3-4, 45; Arch. Inti Hyg. & Occup. Med.: In the press.

30. E. Lowgren, Stockholm:

On the mechanism of the benign postural proteinuria.

A short account of the definition and the synonyms is given. The older theories of the mechanism of this from the diagnostic and the prognostic point of view important form of proteinuria are reviewed, i. e., changes in the venous return from the kidney (stasis, pressure changes) and changes in the arterial circulation (blood pressure, pulse pressure, vasoconstriction, etc.) . It is emphasized that the appearence of the protein in the urine does not correlate to any changes in the renal blood circulation. Nor is there any correlation to the functions of the nephron, which all speaks in favour of the post-renal admixture of the pro- tein. This form of proteinuria has several features in common with the chyluria. And the factors (position of the body, a lordotic spine, intra- or extraabdominal pressure changes) wich are connected with the proteinuria should a t first hand influence the Zympatb circulation. Electrophoretical and ultracentrifugal urin- alaysis of the proteins are demonstrated, showing that big-molecular globulins are "excreted" in the same proportions as are albumins, their resp. "renal factors" being 1. This, together with the abscense of pathological form elements in these urines, seems to prove that the protein is in reality postrenal, i. e. added distally of the nephron. The renal lymphatic system is reviewed, with special refence to the renal pelvis and the fornix of the calyx.

51

To earlier reports by the author (Acta Med. Scand. 1952: 1944: 245; Nord. Med. in press) is referred. A thorough paper on this subject will appear as a supplement to this periodical.

31. M. Siurala, Helsingfors:

Gastric mucosal changes in some megaloblastic anemias.

The author has investigated the occurence and nature of the mucosal lesion in pernicious tapeworm anemia (PTA) and compared the findings with those in Addisonian pernicious anemia (APA) . Some PTA-patients were followed-up in order to eludicate the reaction of the mucosal lesion to specific treatment (expulsion of the worm).

The series consists of 57 cases with PTA and 18 untreated cases with APA. 66 tapeworm carriers without anemia acted as controls. The series and controls were divided into 3 age groups. Gastroscopy andlor biopsy (suction method) were performed in all cases.

Gastroscopically atrophy was found in all cases with APA and 46 out of 50 with PTA. When compared with controls the difference was statistically signific- ant in all age groups. - Histologically atrophy was found in all APA-cases, in 4 cases however partly normal mucosa or remnants of normal body glands were present. In the PTA-group atrophy was found in most cases (in 30 out of 34). When compared with controls this difference was significant in two age groups. The changes were lesser intense than those in APA. Thus total atrophy was present in 4 PTA-cases only. - The follow-up examinations are in progress and therefore only a preliminary report was given. Histologically atrophic changes improved in 7 cases, got worse in 3 and remained unchanged in 9 cases. The gastroscopical examination yelded approximately the same results.

Although the relatively high mean age of the PTA-patients may have cont- ributed to the high incidence of atrophic changes, it is concluded that the gastric mucosal changes like the neurological and haematological belong to the disease picture of PTA. In some cases the atrophy may have preceeded the anemia and contributed to its developement (cases with latent APA), in others howewer the histological picture and the reaction of the mucosa to treatment indicated that the mucosal lesion in some way may have been caused by the tapeworm infestation.

In APA the presence of some normal glands in 3 cases and locally even normal mucosa in one, seems to speek against the theory of the primary importance of the mucosal changes in the pathogenesis of pernicious anemia.

32. E. Hoff Jergensen and E. Landboe-Christensen, Copenhagen :

On the histotopographic localization of the vitamin B,, binding factor in the fundus, pylorus and duodenum.

In stomach and duodenum material from the hog successive layers of the gastric mucous membrane and duodenal wall have been separately assayed for vitamin B,, binding activity.

The material was obtained immediately after killing (shooting) of the animals (10 cases), or was removed during operation (3 cases).

Immediately after removal the samples to be examined were frozen on dry ice and sections were cut out. 1 mm thick from the fundic and pyloric (in a few cases also the cardiac) mucosa and from the duodenal wall. The frozen sections were then subdivided parallel to the surface in layers, usually 3 or 4, and extracts were made in 1 % sodium chloride of each separate layer using a Potter- Elvehjem disintegrator.

The B,, binding activity was assayed as previously described (Hoff-Jargensen and Landboe-Christensen, Arch. Biochem. and Biophys. 42, 474, 1953) and calculated per mg of (wet) tissue. The distribution of the binding activity was correlated with the histotopography of the various regions examined. The activity of the fundic and pyloric lamina muscularis mucosae and duodenal muscular coat was found to be nil. A slight to moderate activity was found in the deeper glandular layers of the fundic mucosa, whereas the superficial layers containing the pita and the surface mucus were but little active or not active a t all. The highest activity was found in the pyloric mucosa and was located chiefly within the deeper glandular layers. In the duodenum the Brunner gland layer was found to be more active than the mucosa, the former having from half to about the same activity as the most active part of the pyloric mucosa.

The binding activity of human material, fundic and pyloric mucosa and duod- enal wall (material removed surgically), was found to be markedly small compared with the activity of similar material from the hog.

Discussion: E. Forsgren. Case Case Case Case

7 8 9 10

Fundic supf. layer (fundic pits mucosa and surface mucus). . . . 0 3 0 4

glands) . . . . . . . . . . . . . . 11 6 4 9 12 14 3 7

middle layer (gastric

deep layer (lam. musc. muc. chiefly) . . . . . . . , 3 4 0 0

53

Pyloric mucosa

Duodenal wall

Cardiac mucosa

supf. layer (pyloric pita and surface mucus) . . 6

middle layers (pyloric glands proper chiefly). . 33

22

deep layer (lam. mum. muc. chiefly) . . . . . . . . 0

supf. layer (duod. villi and crypts. Surface muc- us) . . . . . . . . . . . . . . . . . . 12

middle layer (glands of Brunner) . . . . . . . . . . . . 16

0 deep layer (tunica musc. )

supf. layer . . . . . . . . . . . . deep layer . . . . . . . . . . . .

3

19 31

0

0 10

32 35 10 38

0 0

16 6 16

24 10 26

0 0 0

0 0 0 0

State of filling of stomach below empty below below medium medium medium

Table. Vitamin B,, binding effect of consecutive layers of fundus and pylorus mucosa and duodenal wall of the hog. Figures indicate mg of vitamin B,, bound per mg of tissue.

33. T. Siillstrom, Hlirnosand:

A study of thyrotoxicosis in the region served by Hamiisand central hospital.

The investigation includes the cases of toxic and nontoxic goitre treated at Harnosand Central Hospital from 1948 to 1953 in the outpatient department as well as during hospitalization. Comparison is made with an earlier study by the writer of the incidence of thyrotoxicosis in Sweden from 1925 to 1932 and with Hojer’s investigation of the distribution of nontoxic goitre in Sweden. The diagnosis of toxic and nontoxic goitre is discussed, and it is pointed out that the borderline between the different forms is frequently extremely difficult to establish. During the period studied the toxic goitre shows a clear rise in

incidence. proportionally more men are affected by the disease than shown by earlier-reported investigations. Nodular goitre is relatively common in the region served by the hospital, wich is situated in a coastal district (the ratio nodular: diffuse is 3: 4). The classic Basedow picture occours, but is not common (approximately 1: 10). There would seem to be some relation between endemic goitre and toxic in the region studied. The therapeutic results are discussed with reference to the different forms of goitre.

34. 5. Nordstrtim, Malma:

Flicker-fusion testa in rheumatoid arthritis treated with ACTH.

Using the flicker-fusion test in conjunction with evipan administered in toler- ance doses, Docent Ole Berg demonstrated earlier that active diffuse brain damage exists in approximately 30 per cent of the patients with rheumatoid arthritis.

A study of our polyarthritis material has confirmed his findings. Moreover, i t is demonstrated that the patients with rheumatoid arthritis who

have positive evipan testa will have negative evipan tests after a period on ACTH therapy. This indicates healing of an active, diffuse brain damage.

In addition, it has become apparent that the majority of the patients with rheumatoid arthritis show a clear rise in the flicker-fusion value during ACTH therapy, regardless of the results of tlie evipan test. This, too, may be interpreted as the healing of a diffuse brain damage.

Discmaion: K. Brcachner-Mortensen.

35. L. Hallberg, Gothenburg:

Effect of therapy on the total amount of hemoglobin and the concentration of csrboxyhemoglobin in pernicious anemia..

This is a preliminary communication about a part of an investigation in pernicious anemia. It is above all the hemolytic problem which is discussed, mainly on the basis of repeated determinations of the total amount of hemoglobin and the COHb-concentration (COHb) in the blood.

As has been shown by Sjostrand COHb is a relative measure of the degree of hemolysis in the body. In 23 untreated cases of pernicious anemia COHb was significantly increased in 21 cases. There was a certain correlation between COHb and the number of erythrocytes.

In connection with the institution of therapy there will be a considerable new- formation of erythrocytes during a short time. As the lifespan of erythrocytes

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under normal conditions is rather constant it might be expected that also the disintegration of these cells will take place during a rather short time. Thus after a certain t i e there will be an increased hemolysis and an increase in COHb too. In 8 cases hitherto followed for more than 5 months after the beginning of therapy an increase in COHb has regularly been observed. The measuring of the interval between the maximum of newformation and the maximum of COHb thus is a new method to determine the mean life span of erythrocytes in man, in point of principle analogous to the method of Hawkins and Whipple based on the bile pigment excretion.

In cases treated with vitamin B,, the mean life span was 110-130 days. In three cases treated with folic acid it was significantly less - 50 to 60 days.

If only normal cells are formed after the institution of therapy the earlier part of the COHb-curve represents the hemolysis of cells formed prior to therapy. By analysis of this part of the curve it could be concluded that in untreated cases of pernicious anemia there are probably different populations of erythro- cytes with life spans ranging from some day to 4 months.

However, in all cases, there was a rapid decrease in COHb in connection with therapy indicating for instance the disappearance of a population of erythrocytes with a life span of only some days.

36. L. E. Bottlger and 0. Hellstrom, Stockholm:

Erythroleucosis.

A short survey is given of the literature concerning di Guglielmos disease (erythremic myelosis) and its different variants. The name erythroleucosis is preferred and with this name is understood a primary malignant disturbance of the erythropoiesis, characterized by a therapy-resistent anemia and a bone- marrow hyperplasia of the erythropoiesis, generally with pathologic cells and a clinical course corresponding to that of myeloid leucemia.

A case of erythoblastomato~a, i. e. a tumorus variant of erythroleucosis, is described. A 73 year old woman was admitted to the hospital with signs of a severe anemia of essentially normochromatic type. No indications were found of hemolytic anemia, nor of any tumour or of myelofibrosis. Sternal punctate gave a pecualiar picture with a predominant erythopoiesis which was markedly pathologic with gigantoblasts, multinuclated erythroblasta and pathologic mitoses, but no signs of pernicious anemia. The patient did not respond to any treatment but blood transfusions, and died 1% year after the first anemic symptoms had appeared. Autopsy showed that the pathologic erythroblasts were found diffusely in the liver and the spleen and that they formed tumorous proliferations in the bone marrow, where they had destroyed spongiose bone tissue, thus showing the characteristics of a real tumour.

(The case will be published elsewhere in detail.) '