[Proceedings: The effect of beta receptor treatment with pindolol on the plasma renin activity and the left-ventricular dynamics in essential hypertension]. In 5 volunteers with essential hypertension (age between 32 and 48 years) plasma renin activity (PRA) was determined and right heart catheterization and femoral artery pressure measurements were carried out at rest and during isometric exercise by handgrip. Both investigations were repeated 88 to 98 days after continuous treatment with oral pindolol in increasing doses, the highest dose in all patients amounting to 45 mg/day. Following pindolol therapy arterial systolic cuff pressure decreased from 163 +/- 12 (1 SD) to 148 +/- 14 mm Hg (p less than 0,005). Diastolic cuff pressure decreased slightly but not significantly from 109 +/- 13 to 106 +/- 9 mm Hg. PRA varied in an inconsistent manner. Pulmonary capillary pressure (PCP), femoral artery mean pressure (FAM), cardiac output (CO) and systemic vascular resistance did not change significantly during treatment with pindolol. Stressing of the left ventricle by handgrip prior to and following pindolol elicited similar changes of heart rate, FAM, PCP, CO and stroke work. It is concluded (1) that pindolol produces only a small decrease in systolic cuff pressure, (2) that there is no correlation between changes in cuff pressure and PRA, and (3) that long-term treatment with pindolol is not accompanied by impairment of left ventricular function either at rest or during isometric exercise.


[Proceedings: The effect of volume manipulation (bloodletting or dextran administration) on pressure in the pulmonary circulation and on the hematocrit]. In a clinical survey the respective effects have been compared of venesection and of hypervolemic hemodilution on hematocrit and pressure in the pulmonary circulation. Whereas after venesection the pressure in the pulmonary circulation and the hematocrit decrease slightly, infusion of 1000 ml Macrodex is followed by marked hemodilution and a distinct increase in pressure in the pulmonary circulation.


[Proceedings: Frequency and form of arrhythmia and changes in ECG in juvenile healthy volunteers. Studies with long-term electrocardiography]. In 35 healthy volunteers with a mean age of 24 years an ECG recording for detection of arrhythmias and ECG changes was made by means of a Holter Avionics tape recording system for an average of 7.5 h. Ventricular and supraventricular premature contractions (VPC'S, APCs) were recorded occasionally in 31% and with greater frequency in 6%. Multifocal VPCs and serial VPCs were found in one person (3%). ST-depressions of greater than or equal to 0.1 mV were seen in 9% and a wandering atrial pacemaker in a further 9%. An intermittent increase in P-wave amplitude (greater than or equal to 0.25 mV) was observed in 17%. A surprising finding was frequent (49%) recording of a sinus arrest of short duration, usually followed by an atrial escape rhythm. In view of the frequency of this phenomenon it must be accepted as a normal variant in young people.


[Proceedings: Studies on myocardial perfusion by means of marked particles, injected selectively into the coronary system: an aid in preoperative evaluation of patients with coronary sclerosis]. Myocardial color scintigraphy using macroaggregates labeled with 99mTc and 131I were performed in patients with coronary heart disease. The particles were injected selectively into the coronary arteries. The scintigram was obtained using a color coded display system. The channel with the maximum counts was assigned the color red and each 10% change resulted in a different color. A count rate below 40% of the maximum was considered inadequate. 80 patients undergoing coronary surgery were evaluated postoperatively. Postoperative ventriculography documented improved contractions in 34 of 40 ventricular segments (85%) in which preoperatively an adequate perfusion was observed, whereas in only 13 out of 42 segments with preoperatively inadequate perfusion was an improvement in ventricular contractility observed.


[Proceedings: Diagnostic value of myocardial perfusion scintigraphy in coronary sclerosis]. Perfusion scintigrams with Technetium-labeled microspheres were performed in 60 patients undergoing selective coronary angiography. The scintigrams were analyzed semiquantitatively with the aid of a computer. In addition, angiograms were quantitated with regard to proximal obstructions as well as regional wall changes of the left ventricle (VCF). 1. A reduction of scintigraphic activity was already seen in narrowings of lesser degrees (50%); 2. scintigraphic activity followed the degree of obstruction rather than the contraction abnormality. Perfusion scintigrams are helpful in selecting patients for revascularization.


[Proceedings: Evaluation of the hemodynamic condition during the recuperative phase after the diagnostic isoproterenol test in a patient with coronary disease]. Previous investigations concerning isoproterenol infusion (PI) in the diagnosis of myocardial ischemia have shown that ischemic ECG changes are only significant if they persist or appear after discontinuing PI. In an effort to explain the mechanisms of this delayed response, hemodynamic parameters were measured in 10 patients with angiographically proven coronary disease before, during and after PI. It was found that the principal determinants of myocardial oxygen consumption (TTI and contractility) remain significantly elevated in the recuperation phase, but that aortic pressure and systemic arterial resistance, which diminish during PI, return to pre-infusion levels immediately after halting PI. The combined effects favor the late appearance of ischemic changes in the ECG. The coronary vasodilatation with resultant increased oxygen delivery to the myocardium seen during PI may be sufficient to meet the increased myocardial oxygen demand during PI but disappears immediately if PI is discontinued.


[Proceedings: Relaxation speed in the apex cardiogram. Comparison with criteria of myocardial function on the simultaneously registered left ventricular pressure]. A new apexcardiographic time parameter is described which is definable as the interval between the beginning of the aortic component of the second heart sound and the protodiastolic negative peak of the first derivative of the apexcardiogram and called A2-min dA/dt. There was a significant inverse correlation between the parameter in question and the simultaneous minimal and maximal rate of rise of the first derivative of left ventricular pressure in 20 patients (r = -0.79, p less than 0.001, r = -0.60, p less than 0.01 respectively).


[Proceedings: Left ventricular cineangiography and echocardiography in patients with the mesosystolic click-telesystolic sound syndrome]. Twenty-three patients with the syndrome of midsystolic click--late systolic murmur were investigated by right and left heart catheterization, cineangiography and echocardiography. Most of the patients had symptoms such as atypical chest pain and arrhythmias. Except in one patient, slight to moderate mitral incompetence was found at rest or during stress testing by infusion of aramine or rapid atrial pacing (2 patients). In all cases, an abnormal systolic mitral valve motion was found in left ventricular cineangiography. In 14 of 15 technically satisfactory echocardiograms a systolic prolapse of one or both mitral leaflets was observed. A minority of the patients had localized abnormal wall motion in the postero-basal area or moderate generalized hypokinesis.


[Proceedings: The specific ECG of the mesosystolic click-telesystolic murmur syndrome (So-called subvalvular mitral insufficiency). Zäziwil study. III]. For the diagnosis of small ischemic areas of the posterior wall of the heart, and particularly in the papillary muscles of the left ventricle, the 12 standard leads of the ECG are insufficient. The leads of Nehb and especially the new unipolar lead a VH (of the dorsal Nehb point D but with switch scheme of Goldberger) will be found more helpful. In all 33 patients with the clinical findings of midsystolic click--late systolic murmur syndrome a negative T in lead aVH was found; only 9 patients also showed ischemic signs in lead D of Nehb and only 6 patients in standard leads as well. These findings suggest that the midsystolic click--late systolic murmur syndrome is always caused by a papillary muscle lesion, even in young patients. A negative T in lead aVH (isolated or combined with signs of ischemic alterations on other leads) appears to point to the existence of a papillary muscle defect, even with a normal auscultatory finding. In this case the lesion will be too small to cause papillary muscle dysfunction. Usually, however, the typical auscultatory finding will be subvalvular mitral insufficiency (i.e. midsystolic click--late systolic murmur or a murmur called "pa-futt" by Huchard, in our opinion the same finding). In view of the fact that papillary muscles are vascularized by the finest ends of the coronary arteries, it seems obvious that a negative T in lead aVH could also signify the beginning of coronary heart disease.


[Proceedings: Surgical closure of an atrial septal defect in a patient of over 40 years of age]. Between 1961 and 1972, 354 patients with atrial septal defect were treated surgically. Of these, 80 patients were aged over 40 years at the time of operation. The hospital mortality was 5%; 2 patients had increased preoperative pulmonary artery systolic pressure (50-75 mm Hg), while the other 2 had mitral or tricuspid incompetence. At late follow-up 82% of patients were free of symptoms and 18% had slight clinical signs of breathlessness on exertion. The heart size decreased in 37 of 10 patients, the electrocardiographic signs of right ventricular hypertrophy receded in 23 patients. The operation had no effect on preexisting dysrhythmias. It is concluded that patients with atrial septal defect in this age group benefit from surgical closure of the defect.


[Proceedings: Experimental hemodynamic comparison of propranolol and oxprenolol]. In anesthetized dogs, differences in the haemodynamic effects of propranolol and oxprenolol were observed during normoxia, hypercapnia and hypoxia. These differences are presumably due to the sympathomimetic activity of oxprenolol.


[Proceedings: Animal experimental studies on the effect of revascularizing measures following acute coronary obstruction]. In a comparative study the degree of myocardial damage has been estimated following one hour coronary occlusion and following a permanent coronary ligation in pigs. With regard to infarct size, no significant difference could be detected between the two experimental groups; the extent of cellular injury as determined by a histochemical staining procedure and by serial serum enzyme studies in the surviving animal is of equivalent degree. Nevertheless, the development of a ventricular aneurysm can be prevented by early reperfusion. Reestablishment of coronary circulation appears to accelerate the proliferation of a more resistant granulation tissue into the infarcted myocardial area. Our hemodynamic findings suggest that the effect of reperfusion is unfavourable in the immediate phase; later on, however, coronary reperfusion appears to be beneficial to cardiac function.


[Proceedings: Results of early surgery in infectious endocarditis]. 23 patients with infective endocarditis have been treated surgically during the period 1965 to 1975. 20 patients underwent operation for intractable heart failure, complicated in 4 instances by systemic embolization and in 4 others by intractable infection. Two patients were operated upon only for intractable infection and one patient for severe hemolysis. There were 5 early deaths within 12 days and 2 late deaths 2 and 21 months after operation. Four months to 9 1/2 years after operation 16 patients were alive, only one of whom had mild heart failure. The best prognosis (1 death) was apparent in the 12 patients who underwent operation for intractable heart failure only.


[Lymphoproliferative diseases and paraproteinemias in Sjogren's syndrome]. Out of 8 cases of Sjörgren's syndrome observed by the authors between 1964 and 1974, 5 presented wit clinically as well as theoretically remarkable combinations of Sjögren's syndrome with lymphoproliferative disorders i.e. non-classifiable lymphoproliferative disease (case 1), Hodgkin's disease (case 2), reticulum cell sarcoma (case 3), and asymptomatic paraproteinemia of type IgM/K (cases 4 and 5). In case 1, manifestation of a lymphoproliferative disorder was preceded by autoimmune hemolytic anemia. In agreement with communications from several other authors, our observations confirmed the frequent occurrence of autoantibodies in patients with Sjörgren's syndrome. Forty-two more cases of lymphoproliferative disease in Sjögren's syndrome were found in the literature (Table 4). Pathologenetic problems arising from these nosological combinations are discussed.


[Korsakoff's syndrome and transitory cortical blindness following vetebral angiography]. Neurological complications of vertebral angiography are described with particular emphasis on memory and visual deficits. The material consists of 21 instances of such complications out of a total of 832 vertebral angiographies. A brief account is given of the posterior cerebral artery territory, which makes it possible to establish anatomo-clinical correlations. The pathogeny of the disorder is discussed.


[Heparin in intravascular coagulation].

[Heparin in intravascular coagulation]. 1. The diagnostic criteria of intravascular coagulation are critically reviewed. Before a potentially dangerous drug is administered, the diagnosis should be more securely established than has been the case in the past. In particular, fibrinogen loss from the circulation must be excluded whenever this protein shows unduly rapid rapid disappearance from the blood. 2. Even when the diagnosis is firmly secured, advocacy of heparin therapy should not be based on theoretical considerations or on the huge amount of accumulated case reports but on figures derived from controlled clinical trials, the essential data being nortality and bleeding complications and not the course of laboratory pattern.


[The scimitar syndrome: abnormal venous drainage of the hypoplastic right lung into the inferior vena cava in dextroposition of the heart]. Report on a 28-year-old female patient with classic "scimitar syndrome" (dextroposition of the heart, hypoplasia of the right lung and pulmonary veins opening into the inferior vena cava). The condition was diagnosed on the basis of chest X-ray findings in which the most striking feature was the scimitar-like course of the right pulmonary veins which gives the syndrome its name. The diagnosis was confirmed and the shunt volume determined by cardiac catheterization. Since in this case there were no additional deformities such as atrial septum defect, ventricular septum defect or patent ductus botalli and the shunt volume was small, surgical correction was not required.


[Successful treatment of a severe drowning accident after 20 minutes submersion]. Report on successful post-drowning cardiopulmonary resuscitation of a 2-year-old boy who had lain for 20 min in cold water at 5-7 degrees C. Because of severe pulmonary complications after primary resuscitation--e.g. pulmonary edema, repeated mediastinal and subcutaneous emphysema, pneumoperitoneum and bilateral pneumothorax--spontaneous respiration remained insufficient for 36 days. Under appropriate treatment the patient recovered completely except for slight muscular hypotrophy of the left thigh. 14 months after the submersion no other neurological or pulmonary sequelae could be detected.


[Evaluation of load tolerance in patients with coronary disease]. 12 patients with the diagnosis of coronary heart disease and angina pectoris underwent evaluation of heart rate as an indicator of tolerance of a given work load. A floating catheter in a pulmonary artery and a peripheral arterial catheter permitted measurement of blood pressures. Oxygen uptake per minute (VO2) was measured by Douglas bags and oxygen content of arterial and mixed-venous blood was determined at rest and during each minute of submaximal and symptom-limited maximal exercise on a treadmill. In the minute of exercise, in which 60-80% (mean 71.3%) of maximal heart rate (HF max) were attained, VO2 averaged 60.3% VO2 max, cardiac output (Q) 72.5% Q max and mean pulmonary arterial pressure (PAP) 26.6 mm Hg. With one exception, Q leveled off or dropped in the last minutes of exercise beyond 85% HF max. Heart rate (HF), oxygen difference between arterial and mixed venous blood (DavO2) and PAP reached their highest values in the last minute. It is suggested that heart rates up to 70% HF max, as individually determined in a symptom-limited maximal exercise test, are the tolerable limit during occupational activities. 85% HF max should not be exceeded during exercise training. Left ventricular function may be impaired beyond that limit because of acute coronary or myocardial insufficiency, and the regulation of cardiac output becomes uneconomical.


[The pharmacokinetics of doxycycline in kidney insufficiency in geriatric patients compared to younger adults]. In young adults i.v. injection of 200 mg doxycycline was followed by a rapid fall in serum levels in the first 30 minutes and than a slow decrease (serum concentration after 24 h on average 1.0 mug/ml). Biological half-life was 11.9 h, final distribution volume 50.0 litres and urine recovery 70%. After oral administration of 200 mg doxycycline the serum peaks measured were 3.4 mug/ml (2 1/2 h later). With repeated doses of 100 mg every 24 h serum peaks were 2.8 mug/ml and serum concentrations after 24 h 0.8-0.9 mug/ml (urine recovery 43%). The area under the curve was 25.5% less than after i.v. injection. In 7 adults with chronic renal failure the half-life of doxycycline varied between 10 and 24 h. With repeated oral administration of doxycycline (100 mg every 24 h) there was no accumulation of the drug in blood. During hemodialysis (Stuttgart kidneys, Rhône-Poulenc plates) doxycycline injected i.v. was eliminated as rapidly as before. In renal failure doxycycline may be given in the same dosage as where renal function is normal. In 12 geriatric patients without renal disease, serum levels of doxycycline after i.v. injection of 200 mg were not significantly different from those of young adults (distribution volume 46.2 +/- 16.2 litres). It can therefore be assumed that tissue penetration of the drug is similar in the elderly and in young adults.


[Modifications in the geometry of the alveolar capillaries and their role in the ventilation-perfusion ratio]. Alveolar capillary bed corresponds to a continuous space delimited at each side by the thin portion of the air/blood barrier. The thick portion crosses this space and constitutes structures referred to as "pillars". While the capillary space appears more or less regular in inflated rat lungs, it resembles a labyrinth in collapsed lungs. Such a change is due to the folding of the thin portion of the barrier into the capillary space. Another mechanism involved in the folding of alveolo-capillary membrane is the contraction of alveolar interstitial cells. Experimentally, hypoxia seems to stimulate these cells and to produce folding of the air/blood barrier. We have shown that the alveolar hematocrite increases in rat lungs when the animals are exposed to 4% O2 for 20 min. This increase is probably due to the trapping of red blood cells in the capillary spaces as a result of folding of the air/blood barrier. It is concluded that the relationships between alveolar and capillary configuration is an important factor in the autoregulation of V/Q ratio. The decrease in alveolar perfusion in collapsed areas and during hypoxia is due to the interference of alveolo-capillary membrane folds with the corpuscular circulation.


[Isolated endangiitis of the lung].

[Isolated endangiitis of the lung]. A case is reported of isolated endangiitis obliterans with interstitial fibrosis of the lung in a 44-year-old woman. It was characterized by rapid clinical progress with right heart failure: chest X-ray revealed only slight interstitial fibrosis of the lung. An exogenous noxa (by inhalation or ingestion, particularly of drugs) was ruled out. Histologic findings afforded evidence of a primary pathologic process involving the medium and small arteries of the lung. There was no evidence of primary multiple emboli of the lung.


[Sputum conversion and behavior of cavitations in the years 1967-1973]. The results of chemotherapy based on an intersanatorial study of 3306 patients with active pulmonary tuberculosis are presented. In 1967 sputum conversion was achieved in 93%; since 1970 the results have been better, with conversion in 96-97%. From 1967 to 1972 the cavitations disappeared in 51-57% of patients with cavitary disease, but in 1972 and 1973 only in 47% and 36% respectively.


[Low hemoglobin values in blood donors]. Out of 6000 regular blood donors at a regional blood donation service 135 women (5.44%) and 24 men (0.68%) were found to have low hemoglobin levels (borderline for females 12.4 g%, for males 13.2g%). In only half of these donors could the anemia be ascribed to iron deficiency or overt disease. In the other half no explanation was found for the low hemoglobin levels and iron therapy did not improve the situation. It is concluded that a small part of the healthy population persistently shows subnormal hemoglobin levels without presenting other pathology.


[The lung and the metabolism of vasoactive substances]. The lung is the site of a number of reactions affecting vasoactive substances: hydrolysis of angiotensin I, bradykinin and ATP, occurring at the surface of endothelial cell; uptake and intracellular metabolism of 5-hydroxytryptamine and norepinephrine; and intracellular oxidation of prostaglandins. Mediators, including prostaglandins, histamine and SRS-A (slow reacting substance of anaphylaxis), can also be released from the lung. The possible implications of these recent findings are analysed.


[The effect of combined respiration physiological measures on pulmonary gas exchange and ventilation]. The immediate effect of physiotherapy and the effect of IPPB-inhalations in 18 patients with chronic obstructive lung disease and global respiratory failure have been investigated and discussed. The procedures (physiotherapy or IPPB-inhalations) were tested singly and in combination. Better results are obtained when physiotherapy is performed before IPPB-inhalation. A significant decrease in pCO2 and a significant rise in VC and FEV1 are observed, with unchanged pO2.


[Pathogenesis of renal hypertension].

[Pathogenesis of renal hypertension]. Current pathogenetic concepts regarding renal hypertension are reviewed. Alterations of the renin-angiotensin-aldosterone system (RAA) on the one hand, and disturbances of NaCl and water metabolism on the other, represent the dominant factors in renal hypertension. The present view of the reactions within the RAA system and of its activators, inhibitors or antagonists is described schematically. The angiotensin II-antagonist 1-sar-8-ala-angiotensin II (Saralasin), when infused in a patient with angiotensinogenic hypertension, induces normalization of the blood pressure during the course of the infusion. The Saralasin infusion test may be of assistance in detecting cases with angiotensinogenic hypertension. The pressor(s) and the extracellular fluid volume appear to be the decisive pathogenetic factors in renal hypertension. As long as the functioning renal mass is sufficient to excrete water and salt normally or in excess, as is the case when the renal perfusion pressure in hypertension is elevated, the pressor is the dominating factor besides other, so far hypothetical mechanism such as the neurogenic. A critical reduction of the renal mass will enhance fluid and salt retention. Thus, an increase in extracellular fluid volume and blood volume will emerge as a major factor inducing hypertension. As a consequence of the volume gain and salt retention, renin secretion may slow down. The possibility is mentioned that the absence or ineffectiveness of renal depressor substances (prostaglandins) may be involved in renal hypertension. Finally, two hypotheses are presented which may explain the finding of LARAGH et al., who grouped their essential hypertensives into 'high, normal and low renin hypertensives'.


[The function of the diseased kidney].

[The function of the diseased kidney]. A few years ago the kidney in chronic renal failure was described as a mass of tissue "without significance, vanishing into the disparity of thousands of fantastically altered organs of strange design and anomalous behaviour". In order to refute this opinion, some of the morphological and pathophysiological evidence is summarized which points to the fact that even in chronic renal failure the remaining nephrons that contribute to renal function behave as a rather homogeneous population characterized by appropriate adaptations of glomerular and tubular functions and by a persistent responsiveness to the changing needs of the patient.


[Renal osteopathy].

[Renal osteopathy]. Bone histology and biochemical data indicate that hyperparathyroidism and abnormal metabolism of vitamin D are hallmarks of renal osteodystrophy. Early diagnosis is possible by means of bone biopsy. The clinical signs of renal bone disease include extraskeletal calcifications. Persistence of disease during hemodialysis treatment calls for treatment even of asymptomatic patients. Vitamin D3 and its metabolites or analogs play an important role in the suppression of hyperparathyreoidism and in combating osteomalacia.


[Clinical application of the radioimmunological measurement of the antidiuretic hormone]. A radioimmunoassay specific for arginine-vasopressin (AVP) developed in recent years has been applied to measurement of urinary AVP during physiological and clinical studies. Daily excretion of AVP was 34 +/- 10 ng (mean +/- SD) in 17 female normals and 69 +/- 45 ng in 17 male normals, this being a significant difference (p less than 0.01). After osmolar load (Carter-Robbins test) hourly excretion of AVP increased significantly in 7 males from 1.3 to 3.1 ng/h and in 6 females from 1.7 to 6.5 ng/h. Again the difference between male and female normals was significant. In both sexes a significant correlation between AVP excretion and either plasma osmolality or free-water clearance was found. When the osmolar load test was performed under constant angiotensin II perfusion in male subjects, their AVP excretion was significantly more elevated; this confirmed in man the hypothesis that angiotensin II is a stimulus to AVP secretion. Preliminary results of AVP excretion and response to osmolar load in diabetes insipidus are reported. Exceedingly high rate of excretion of AVP up to 55 330 ng/24 h have been found in cases of bronchial carcinoma with dilutional hyponatremia.


[Primary aldosteronism: diagnosis, laterality and regulation of hormone secretion]. In 16 patients with hypokalemic hypertension the combination of abnormally high and unsuppressible plasma aldosterone with low or undetectable renin activity led to the diagnosis of primary aldosteronism. To differentiate between aldosterone producing adenoma and idiopathic bilateral hyperplasia, determination of aldosterone concentration in both adrenal veins was performed in 12 patients. In 4 of these patients the two forms of primary aldosteronism could not be differentiated as in these cases only one of the two adrenal veins simultaneously showing an abnormally high aldosterone concentration could be canulated. Plasma aldosterone and plasma cortisol were determined overnight (20.00-8.00 h) at short time intervals in 8 patients with adenoma, 1 patient with carcinoma of the adrenal cortex and 3 patients with bilateral hyperplasis. In all patients with adenoma a significant correlation between aldosterone and cortisol was observed (p less than 0.05-0.001) whereas no correlation was seen in the patients with hyperplasia and carcinoma. The clinical importance of these findings is that in the presence of ACTH-dependent secretion of aldosterone the site of the adenoma can be predicted even when blood from only one adrenal vein is obtained.


[The euthyreotic hypotriiodothyroninemia]. In 33 patients with various, mainly severe diseases a subnormal triiodothyronine concentration (T3) and a normal thyroxin concentration (T4) were found. In addition to T3 and T4, the plasma TSH levels and T3 binding capacity were determined. In no case did the patient's history or clinical findings afford evidence of hypothyroidism. Diminished conversion of T4 to T3 is discussed as a possible cause of the inappropriately depressed T3 levels.


[Treatment of Paget's disease with phosphonates]. A group of 22 patients with Paget's disease of bone was treated with a diphosphonate (sodium etidronate; EHDP), a stable synthetic analogue of inorganic pyrophosphate. This substance was given during 3 months at the dose of 20 mg/kg body weight per day, and proved effective by reducing the raised urinary excretion of total hydroxyproline and by lowering the concentration of serum alcaline phosphatase. It also improved the disease-related osteo-articular pain in 60% of the patients. A rise in serum phosphate under EHDP therapy is due to the increase in renal tubular reabsorption of phosphate. Bone histology showed regression of disease activity and the appearance of lamellar structure in newly formed bone. Because of a transient increase of the amount of uncalcified osteoid, it is advisable to give the diphosphonate in courses not over 3 months or at a reduced daily dose.


[Treatment of the painful Paget's disease of the pelvis with salmon calcitonin in ambulant care. Studies in 2 cases during 26 and 19 months respectively]. Two patients with Paget's disease of the bones have been treated with salmon calcitonin for periods of 19 and 26 months. The results are good.


[Factors that intervene in adverse drug reactions]. Drug prescriptions and adverse reactions occurring during 2 periods of 3 months in a department of medicine were analyzed by computer programs. Among 148 reactions suspected, 130 were considered definite or probable by one physician (1.6 reaction per 100 drug prescriptions). The patients who suffered from an adverse reaction were older, were hospitalized for a longer period of time and received more drugs than the others. The data were submitted to two physicians who were asked to determine the degree of probability of each reaction independently. There were many discrepancies between physicians' judgements (52% of the reactions) if one of them had a brief summary of the case history and the other had all the data available. The discrepancies were far fewer (18.1%) if both physicians had all the data available, and were due to the drug(s) suspected (8.8%) or to the influence of the disease (9.3%).


[Thrombosis of the suprahepatic veins (Budd-Chiari syndrome) and polycythemia. A propos of 1 case]. A case is described of Budd-Chiari syndrome associated with polyglobulism in a 31-year-old subject. The connexion between Budd-Chiari syndrome and polyglobulism as a secondary symptom or a sign of a myeloproliferative syndrome is discussed.


[Pleural effusion: a symptom of acute and chronic hepatitis]. 3 cases of acute and 2 of chronic aggressive hepatitis associated with pleural effusion are presented. Pleural effusion in this setting is a rarity and always occurs in the early phase of acute hepatitis or during exacerbations of chronic aggressive hepatitis. It disappears with normalization of liver function tests. The exudate is rich in protein (3-4 g %) and contains lymphocytes as well as erythrocytes. In 2 cases Australia-antigen (HBs) could be documented. An immunological mechanism is suggested.


[First experiences with a new oral human pancreas function test with special emphasis on gastric voiding]. 1 g of N--benzoyl-L-tyrosyl-PABA was administered orally to 50 test persons, i.e. controls and patients with known pancreatic disease. In the presence of chymotrypsin, paraaminobenzoic acid (PABA) is split from the peptide and excreted in the urine. The amount of PABA excreted serves as parameter of exocrine pancreatic function. In the control group a mean of 59.2 +/- 6.2% of the peptide PABA was excreted over a period of 6 h. PABA excretion in exocrine pancreatic deficiency was significantly less (p less than 0.001) than in controls. No overlap of data was noted. Gastric emptying rate - estimated by using indium-113m microcolloid - did not appear to influence urinary PABA excretion.


[Evaluation of the Lundh test in the diagnosis of exocrine pancreas insufficiency]. The results of 611 Lundh-tests performed on 546 patients over a period of 4 1/2 years have been evaluated. The test was highly reliable in the diagnosis of exocrine pancreatic deficiency. False-normal results were seen in 2.04% and false-abnormal in 3%. The test does not differentiate between chronic pancreatitis and carcinoma. Extrapancreatic factors depressing duodenal tryptic activity are discussed.


[Treatment of ascites by ultrafiltration and reinjection of the proteins]. Report on 14 cases of ascites resistant to conservative treatment such as saltless diet, diuretics including spironolactone, and bedrest. 12 cases were due to alcoholic cirrhosis and a further 2 had malignant tumors (1 hepatoma, 1 adenocarcinoma of the pancreas). 14 patients underwent dialysis in which, after puncture of the ascites, the proteins are concentrated by filtration and then reinjected into the circulation. 16 dialyses were performed and all were well tolerated except in one alcoholic woman in very poor general condition who died from acute pulmonary edema. No significant clinical complications or technical problems were encountered. The dialysis-reinjection time lasted 3-28 h and the bodyweights diminished by 2.4-17 kg. Plasma volume, renal output and urinary concentration of electrolytes (Na) increased during dialysis. In 6 cases these effects persisted with spironolactone and low salt diet only, probably because of better renal perfusion and re-established sensitivity to the diuretic treatment. One year follow up revealed 4 cases out of 13 without relapse. Rapid emptying of the peritoneal cavity permitted two laparoscopies, which revealed the tumoral origin of the ascites in two cases, and one laparotomy for porto-caval shunt in bleeding esophageal varices at the earliest possible juncture. This method of treating cirrhotic ascites is simple and well tolerated. It considerably shortens the hospitalization and may rapidly improve general conditions of life in these chronic patients.


[Malignant lymphoma following years of hydantoin treatment for epilepsy]. The cases are presented of 4 hydantreated epileptic patients developing malignant lymphomas (1 Hodgkin's lymphoma). The duration of the hydantoin therapy ranged from 7 to 23 years. There was no evidence of an allergic drug reaction, with the exception of slight blood eosinophilia. Prior to the lymphoma one patient exhibited leukopenia and a second thrombocytopenia. Hydantoins were discontinued in 3 cases but the lymphomas never disappeared spontaneously and only once did tumor progression came to a stillstand. Two patients were successfully treated with either chemo- or radiotherapy. Possible correlations between the documented immunosuppressive action of hydantoin derivatives and tumor induction are discussed. Malignant lymphomas may be sequelae of long-term hydantoin therapy and are not always preceded by the well-known reversible hydantoin lymphadenopathy.


[Proceedings: Classification and anatomo-clinical correlations of glomerular nephropathies]. A number of classifications may be proposed according to whether glomerulopathy is defined from a morphological, clinical, etiological or pathogenetic point of view. However, glomerulopathies are now best defined according to histopathological criteria since from a practical point of view this is the only way in which prognosis can be evaluated. We propose a classification of glomeruloneyhritis essentially based on morphology as well as on the etiological circumstances in which the glomerulopathy is discovered. Four types of glomerular lesions (GL) may be disclosed: 1. The pathognomonic GL are rare and include thrombotic microangiography, amyloidosis, diabetic glomerulosclerosis, lupus nephritis with hematoxyphil bodies, etc. 2. The GL seen in primary glomerulopathies may be divided into 3 subgroups: minimal, focal (segmental and focal glomerulonephritis and focal glomerular sclerosis) or diffuse (membranous nephropathy and the various types of proliferative glomerulonephritis). The clinical presentation and course are studied for each of these varieties. 3. The GL seen in specific diseases (acute post-infectious glomerulonephritis, septicemia, systemic diseases, Goodpasture's syndrome, essential cryoglobulinemic glomerulonephritis, etc.) are in many ways similar to most of the lesions seen in primary glomerular diseases, but may have a different prognosis. 4. The GL seen in hereditary nephropathies (Alport's syndrome, nail patella syndrome, infantile mesangial sclerosis, partial lipodystrophy, amyloidosis of FMF, storage diseases, etc.) show, in most cases, specific morphological features. It is important for the clinican to know the natural history of these clinicopathologic entities in order to take appropriate decisions regarding possible treatment. Moreover, the fact that some of these glomerular lesions may recur on the grafted kidney is one more reason for identification of the underlying disease.


[Proceedings: Evolutive forms of glomerulonephritis and their prognosis]. The prognosis in patients with glomerulonephritis can now be established with some confidence. The major advance has been the use and interpretation of renal biopsies. The different histological varieties have their own evolution and prognosis. The clinical/pathological correlations assist the physician in determining the prognosis in patients with glomerulonephritis. On the clinical side, the most important observation is the simplest: proteinuria or hematuria may persist separately for many years without alteration of renal function. However, in patients with persistent proteinuria associated with hematuria the prognosis is poor, as the evolution is towards renal failure.


[Proceedings: Plasma hemoglobin in patients with intermittent hemodialysis with special reference to various dialysis procedures]. In the pathogenesis of anemia in patients on intermittent hemodialysis is a frequently mentioned factor. To evaluate the red blood cell trauma caused by the hemodialyser, free hemoglobin was determined in the plasma before and after various types of hemodialysis. We investigated 22 patients with chronic renal failure in the age range from 18 to 54 years who were hemodialysed with various types of shunt (Cimino, Scribner or Thomas shunt) and hemodialysers (Kiil or Rhone-Poulenc). Determinations of hemoglobin in the plasma before and after 8-h hemodialysis were performed by the method of RICHTERICH. A significant increase in the initial normal values for hemoglobin in the plasma were found, but without any correlation between rate of hemolysis and type of hemodialyser. The presumed mechanical destruction of erythrocytes during hemodialysis can be determined by the free hemoglobin in the plasma. The small extent of intravascular hemolysis does not correlate with the type of hemodialyser.


[Proceedings: Hematopoiesis in chronic pyelonephritis. Quantitative-morphological study]. Bone marrow biopsies from the iliac crest in 56 patients with chronic pyelonephritis were evaluated quantitively and correlated with renal function and peripheral blood values (n = 100). In proportion to increasing serum creatinine, mild marrow hypoplasia develops which mainly, and to a statistically significant extent, affects the percentage and amount of erythropoietic cells and megakaryocytes. The simultaneous reduction of erythrocytes and reticulocytes in peripheral blood is more pronounced and only slightly correlated to the marrow cells. There is no correlation between the number of peripheral granulocytes or the decrease in lymphocytes concomitant with uremia, and their respective precursors in the marrow.


[Proceedings: Familial hemolytic-uremic syndrome. Studies on pathogenesis in the survivors]. The findings are reported in 4 siblings in whom death was due to typical hemolytic-uremic syndrome. In one, successive treatment with heparin, dipyridamole and aspirin was unsuccessful. 125I-fibrinogen half-life was 2.1 days under aspirin and 1.9 days under combined aspirin/heparin therapy. The parents and 4 surviving sibs had normal renal function and normal platelet and fibrinogen survival. The mother and 3 sibs had an increased percentage of megathrombocytes. Two exhibited renal accumulation of 51Cr-platelet radioactivity which was suppressed by platelet inhibitors. In both, renal biopsy disclosed definite ultrastructural endothelial alterations. These changes are probably responsible for the local platelet sequestration and appear to be the primary defect in this family with hemolytic-uremic syndrome.


[Proceedings: Alkaline phosphatases in patients in chronic hemodialysis]. The alkaline phosphatases (AP) have been studied in 28 patients on chronic hemodialysis. Total AP averaged 49 IU/1 while 4 out of the 28 patients exhibited pathologic values (above 60 IU/1). Determination of iso-AP by acrylamide gel electrophoresis revealed the existence of an intestinal band in 50% of cases, thought this is not observable in a control population. The only relationship seen between the presence of the intestinal iso-AP and different parameters concerned the blood groups O and B. Significant increase of total AP is in all cases due to a bone iso-AP. During a hemodialysis session a mean increase of 30% in total AP has been noted. An increase in total AP is observed in only 2 cases out of 17.


[Proceedings: Evaluation of the plasma-phenolred test as a simple kidney function test]. The phenolsulphthalein 60/60 plasma test (PSP 60/60) was evaluated in 30 control subjects (mean value 51 micrograms/100 ml +/- 49 micrograms/100 ml) and 60 patients with chronic renal disease with varying degrees of renal insufficiency. PSP 60/60 proved to be superior to determination of serum creatinine and urea nitrogen. PSP 60/60 correlated well with endogenous creatinine clearance and 131I-iodohippurate clearance in over 80% of cases. Of various exogenous and endogenous factors interfering with the test, drugs influencing renal excretory mechanisms are most important. Due to its technical simplicity, PSP 60/60 is a useful screening test for evaluation of renal function, especially as an office procedure.


[Proceedings: Correlations between blood pressure, body sodium/blood volume state and plasma renin in patients with terminal kidney insufficiency]. Plasma renin activity was found to correlate inversely with exchangeable sodium or blood volume in both normotensive and hypertensive hemodialysis patients. However, in the hypertensive patients mean circulating renin for any given sodium/volume state was markedly higher than in normotensive patients or normal subjects. Blood pressure correlated more closely with the products of circulating renin and exchangeable sodium (r = 0.55; p less than 0.001) or blood volume (r = 0.43; p less than 0.001) than with the individual components (r less than or equal to 0.39); multiple regression analysis including duration of previous hypertension as a second independent variable further improved these correlations (r = 0.66 and r = 0.63 respectively). This suggests that the sodium/volume state, circulating renin and vascular changes resulting from previous hypertension may be important complementary determinants of blood pressure in hemodialysis patients.


[Proceedings: Experimentally induced effects on the plasma renin activity]. In dogs, plasma renin activity (PRA) was increased by anesthesia, by hypercapnia and by extreme hypoxia (paO2 47.6 mm Hg). Relatively moderate hypoxia (paO2 47.6 mm Hg) and artificial respiration had no appreciable influence on PRA. It appears that the sympathomimetic stimulus of CO2 has an important bearing on PRA.


[Proceedings: Studies on the digoxin resorption in patients with decompensated right cardiac insufficiency]. Digoxin absorption was investigated in 7 patients suffering from severe right cardiac failure. After successful treatment and disappearance of the symptoms of right cardiac failure, the study was repeated in the same patients. Tritium-labelled digoxin in a dose of 0.1 mg as a solution, and non-labelled digoxin as a 0.25 mg tablet, were given to the patients in the fasting state. Blood samples were taken at specified time intervals up to 120 h and the urine was collected during the same period. The concentrations of digoxin in plasma and urine were measured in a liquid scintillation counter. The unlabelled digoxin was estimated by radioimmunoassay. The concentrations obtained in the plasma and urine were used to compute pharmacokinetic parameters. There was no significant difference in the plasma concentration curves in severe right cardiac failure and after successful treatment, nor did the calculated pharmacokinetic parameters differ significantly. Inhibition of digoxin absorption in severe right cardiac failure therefore seems unlikely.


[Proceedings: Clinical value of serum digoxin and digitoxin determination in renal insufficiency]. Plasma digoxin and digitoxin determination has proven to have an important bearing, particularly in patients with renal failure. It permits early detection of digitalis intoxication in the absence of marked clinical and ECG evidence, and adjustment of dosage accordingly. Also, in patent intoxication it makes it possible to select the right moment for resumption of therapy. To illustrate the importance of the method some cases are cited involving plasma digoxin and digitoxin determination.


[Proceedings: The ankle arterial pressure during reactive hyperemia in healthy patients and patients with arterial occlusive disease]. In 8 healthy subjects and in 16 patients with arterial occlusions in the iliac or ilio-femoral region ankle blood pressure and blood flow velocity were measured by Doppler ultrasound during postocclusive reactive hyperemia. In the normal subjects the ankle blood pressure decreased significantly within the initial 30 sec after release of the occlusion. The pressure values showed a negative relation to the simultaneous increases in flow velocity (r = 0.67). In the patients the pressure decreased further and the reduction was prolonged with the protracted course of the reactive hyperemia.


[Proceedings: Pacemaker implantation bradycardia and cardiac insufficiency. Preliminary report]. The longterm effects of pacemaker therapy have been investigated in 337 patients with bradycardia and congestive heart failure with or without Adams-Stokes syncope. The cumulative survival rate in patients with Adams-Stokes seizures without congestive heart failure (group I) is markedly better than in patients with Adams-Stokes seizures and congestive heart failure (group II). The death rate is highest in patients with congestive heart failure as sole indication for pacemaker implantation (Group III). In the patients from group II (mainly with slight to moderate decompensation) there was a higher percentage of improvement than in those from group III (chiefly with severe congestive heart failure), in whom cardiac decompensation improved in approximately half the cases. These findings do not prompt excessive enthusiasm about the longterm results in patients with bradycardia and severe congestive heart failure. The indication subsists where there is resistance to drug therapy, or digitalis intolerance, or where treatment with a provisional pacemaker produces good results.


[Proceedings: Studies on mechanically induced hemolysis following prosthetic heart valve replacement]. Investigations into the problem of mechanical hemolysis were carried out in 28 patients with one or more prosthetic heart valve replacements. Signs of compensated intravascular hemolysis were demonstrated in all cases by determination of lactic dehydrogenase activity and free hemoglobin in the serum. We found no correlation between the type and number of prosthetic heart valves and the incidence of hemolysis.


[Proceedings: Experiences with isolation of leukemic patients]. Time to onset of infection has been used to evaluate isolation procedures in patients with acute leukemia. Comparing laminar flow unit with ordinary reverse isolation, no difference was found between these two methods. Both were performed without whole body decontamination or gut sterilization.


[Proceedings: Changes in the disease pattern of pulmonary tuberculosis]. Some 100 cases of active tuberculosis of the lung from each of the years 1953, 1963 and 1973 were studied to determine changes in the disease pattern. Chronologically a reduction in the distribution of multisegmental lesions and a diminution of the number of cavities was observed, with a marked tendency towards segments 1, 2 and 6. The number of new patients diminished and that of reactivated cases increased. Particularly noticeable was the observation of more highly productive tuberculoses.


[Proceedings: Lung lesions caused by "rare earths"]. Three reproduction photographers were found to have light patchy and reticular infiltrates on the chest x-rays. They had a 30-year history of inhaling "rare earths" and thorium deriving from the dust of the electric carbon arc-light. The diagnosis was confirmed by whole-body gamma-counting in all cases and by additional lung biopsy in one. This type of pneumoconiosis shows no definite disease progression and no serious functional deterioration.


[Telemetric ECG control of the heart during the rehabilitation of hemiplegics]. In hemiplegic patients of advanced age the incidence of cardiac disorders, frequently combined with heart failure, is 80%. To assess the effect of rehabilitation on cardiac status 25 patients underwent period telemetric ECG monitoring during the rehabilitation period. The rest forced upon the patient in the initial period following the stroke economizes cardiac effort. The increasing load in rehabilitation thus has a favourable effect on the heart and affords appropriate cardiac training in addition to its immediate purpose.


[Frequent and rare forms of vitamin B 12 and folic acid deficiency anemias]. The common and rarer causes of vitamin B12 and folic acid deficiency are discussed with special reference to pathophysiological aspects and conditions in Switzerland. The overall incidence of Addisonian pernicious anemia was found to be 80 per 100,000 patients, whereas the incidence of other B12 deficiency states was 18 per 100,000  patients. Folic acid deficiency was found in 23 of 100,000 patients, though this figure appears to be an underestimate. Nutritional (latent) folate deficiency seems to be the most frequent vitamin deficiency in Switzerland.


[The treatment of intestinal helminthiasis with mebendazole. 294 treated patients]. 294 patients with slight intestinal helminthic infections have been treated with mebendazole, a broad-spectrum antihelminthic of high effectiveness and remarkably low toxicity. The high cure rates (91-95%) obtained in cases of trichuriasis, ascariasis and ankylostomiasis are in agreement with the results as published by other investigators. For helminthiases, the present patient sample was too limited to permit accurate evaluation. Nevertheless, mebendazole may be considered the drug of choice for treatment of trichuriasis in particular and for intestinal helminthic polyparasitism in general.


Double branched flicker fusion curves from the all-rod skate retina. Electrical responses from the skate retina will only follow flicker up to frequencies of 5 hertz when intensities are below rod saturation. At greater luminances, the eye responds to rates as high as 30 hertz. As a result, a plot of critical flicker fusion as a function of intensity is a double branched curve. It seems that prolonged stimulation of skate rods, at high intensities, permits them to change their temporal response characteristics so that they follow high frequencies much as cones do in the duplex retina.


Lysergic acid diethylamide: effect on histone acetylation in rabbit brain. Lysergic acid diethylamide increased acetylation of histones in rabbit cerebral hemispheres and midbrain 30 minutes after intravenous administration of the drug at doses of 10 and 100 micrograms per kilogram of body weight. Evidence for the stimulation of acetylation in individual histone bands was obtained after separation by electrophoresis on polyacrylamied gels.


Mass recruitment by army ants.

Mass recruitment by army ants. A single army ant (Ecitoninae) can attract and direct scores of workers to prey by means of a chemical trial and momentary contact between the recruiter and workers on a raid column. Recruited workers, in turn, attract more ants, resulting in a continuous stream of recruits. While the recruitment mechanism is basically similar, the speed and the number of ants recruited are greater form army ants than for other ants.


Repair of small veins with absorbable collagen tubules. An experimental technique is presented for the repair of very small veins using a biodegradable collagen tubule as an internal splint. The technique is simple and the long-term results are excellent. Variable patency rates in the first two weeks are being investigated.


Effects of mobilization on tensile strength of partial tendon lacerations. Fifty-percent-lacerated unrepaired chicken tendons were studied. Free mobility resulted in tensile strength significantly increased over immobility when the free mobility was begun on the day of wounding or after 28 days of immobility.


The use of directly frozen cells in LDA assay. A method of direct freezing is described which requires a cryoprotective medium consisting of human AB serum and DMSO, an ultra-low temperature freezer and a liquid-nitrogen refrigerator. Fresh and directly frozen cells were compared in the LDA assay. Direct freezing is quite reliable for normal lymphocytes, PHA transformed lymphocytes or leukaemic blasts used as targets. However, a controlled freezing procedure may be necessary to preserve the effector cell activity.


Cross-reactions between the major histocompatibility system of man and mice (HL-A and H-2). Cytotoxic action of anti-H-2 sera on lymphocytes. Alloimmune congenic anti-H-2 sera, dependent on the combination of H-2 haplotypes of donor-recipient strains, exert a strong cytotoxic activity against human cells. While strong sera react with almost all samples of human cells, in serial dilutions pronounced differences in strength of reactions can be found with different human cell samples in correlation with their HL-A phenotype. The strongest associations of some anti-H-2f and anti-H-2p sera were found with HL-A2 (r = 0.70 - 0.80), HL-A7 (r = 0.45 - 0.55) and HL-A27 (r = 0.65 - 0.75) (with HL-A27 in groups of patients with high frequency of this antigen r = 0.80 - 0.90). Associations with HL-A9 were also indicated. The reaction pattern itself, as well as absorption and family studies, strongly indicates that for the individual sera the differences in reaction strength are, in essence, quantitative in nature. While it is basically unclear which part of both MHS systems is responsible for the observed cross-reactions, out of several alternatives the hypothesis indicating the polymorphism of common-part structures on H-2 and HL-A molecules seems to be the most plausible.


Increased frequency of HL-A8 in Sjogren's syndrome. The histocompatibility antigen, HL-A8, was found to be elevated in patients with Sjogren's syndrome. Among 24 patients, the frequency of HL-A8 was 58% compared to 21% among controls (P less than 0.001 after correction). With the addition of this disorder to the list of other autoimmune diseases associated with HL-A8, it now seems possible to postulate a single basis autoimmune defect gene in high linkage disequilibrium with HL-A8.


Studies on recombination within the mouse H-2 gene complex. III. Further serological analyses of the H-2t haplotypes. The five H-2t haplotypes are all intra-H-2 recombinants which have identical K and D regions, but differ in the central regions of the complex. Analyses of H-2, Ia and Ss-Slp types indicate that the crossover in H-2t1 took place between the K and I regions, in the H-2t2 between G and D, in H-2t3 and H-2t4 between the I-B and I-C subregions and in H-2t5 between I and S. The set of recombinants will be very valuable for studies of traits which map in the I and S regions.


[Ozone and gynecologic radiotherapy].

[Ozone and gynecologic radiotherapy]. A short survey is given of the historical development and the physical basis of ozone therapy. Ozone is used in medicine as well as in other spheres. Papers reporting good results of ozone treatment in carcinoma seemed of particular interest. The efficacy of ozone as an adjuvant to the irradiation of carcinosarcomas of rats was confirmed by us. On account of this fact ozone was introduced by us as an adjuvant to the irradiation of women with gynaecological cancer and appeared to give good results. The mechanism of action of ozone is not yet fully clarified and several theories are discussed. Investigations are currently being undertaken in respect to the behaviour of several substances in the organism during ozone therapy.


[A path to spatial irradiation planning. I. The problem of dose homogeneity within the area of crossing ray beams with different planes of incidence; basic examinations leading to an optimization procedure]. Under certain circumstances, foci within distinct regions of the body are optimally included by irradiation from different directions of the space. In practice, such plannings mostly fail from the difficulty to produce a sufficiently homogenous dose distribution within the target volume. The present considerations disclose the possibility to determine certain parameters or irradiation in an explicit form, based on a vectorial view of the dose distribution, thus obtaining homogeneity of the radiation dose. Part I of this paper is presenting the foundations of a procedure which aims at dose homogeneity in cross-fire techniques with different planes of incidence, utilizing simple mathematical correlations among the vectorial dose quantities.


Distribution and behaviour of isoselenium salts in organism. III. Radioprotective effect of selenium derivatives. Radioprotective properties of Se-2-aminoethylioselenouronium bromide hydrobromide, 2-aminoselenoazoline and of selenium analogue of mercaptoethylguanidine were followed. Radio-protective effectiveness comparable with classical thiol radioprotectiva was manifested by 2-aminoselenoazoline. In the other two compounds there was on the contrary found a synergism of toxicity and radiation.


Microbiological synthesis of 16alpha, 18-dihydroxydeoxycorticosterone. 16Alpha, 18-Dihydroxydeoxycorticosterone (16alpha, 18-dihydroxy-DOC) (1) and 1, 2-3H-16alpha, 18-dihydroxy-DOC (1,2-3H-16alpha, 18-dihydroxy-DOC) of high specific activity were obtained in good yield by microbiological hydroxylation of 18-OH-DOC and 1,2-3H-18-OH-DOC by Streptomyces roseochromogenus (ATCC 13400). The identity of the fermentation product to human adrenal produced 16alpha, 18-dihydroxy-DOC was established by chromatographic studies, derivative formation and gas-liquid chromatography. Yield of the product was about 30% of sutstrate and, allowing for losses in recovery, about 60% of the substrate 18-OH-DOC was converted to this product. A second product of fermentation isolated in lower yield appeared to be a dimer of 16alpha, 18-dihydroxy-DOC found in the acidic conditions of the fermentation. This method of synthesis of 16alpha, 18-dihydroxy-DOC is a practical way to make large quantities of the compound for further study of its possible role in human and experimental hypertension.


Metabolism of 2-3H- and 4-14C-17alpha-ethynylestradiol 3-methyl ether (mestranol) by women. A mixture of 2-3H and 4-14C-mestranol was administered orally to five women and 2-3H-mestranol alone to one woman. Reactions involving position 2 were extensive as judged by liberation of 3H into body water (14-45% of the dose). 17alpha-Ethynylestradiol, 2-hydroxy-17alpha-ethynylestradiol, 2-methoxy-17alpha-ethynylestradiol, 2-hydroxy-17alpha-ethynylestradiol 3-methyl ether and 16geta-hydroxy-17alpha-ethynylestradiol were measured in the "glucuronide" and pH1 fractions and mestranol, D-homoestrone-17a and D-homoestradiol-17abeta were also measured in the "glucuronide" fraction frum the urine to two of the women by reverse isotope dilution. Radioactive 2-methoxyestradiol accounted for less than 0.011% of the 14C dose in the "glucuronide" fraction of one of the women, consistent with the extent of de-ethynylation previously reported (Steroids, 25, 343 (1975).


Synthesis of the specific monosulfates of cholic acid. The three isomeric cholic acid-monosulfates were synthetized and characterized. Cholic acid-3-sulfate was obtained by reacting cholic acid for 2 min with chlorosulfonic acid in pyridine and chromatography of the resulting bile salt mixture on Sephadex LH-20. The 7- and the 12-monosulfate were prepared by sulfation of the corresponding monohydroxy-diacetates followed by removal of the acetyl groups by alkaline hydrolysis and purification by chromatography on Sephadex LH-20. On TLC in n-butanol-acetic acid-water (10:1:1, v/v) the Rf values were 0.59 for cholic acid-3-sulfate, 0.52 for cholic acid-7-sulfate and 0.48 for cholic acid-12-sulfate. The time required for complete solvolysis at 37 degrees C in acid methanol-acetone (1:9) was 3 h for cholic acid-3-sulfate, 12 h for the 12-monosulfate and 18 h for the 7-monosulfate.


Evidence for episodic secretion of testosterone in laboratory mice. The concentration of testosterone (T) in the peripheral plasma of laboratory mice is extremely variable. This variability is already evident at 20--25 days of age and is not eliminated by brief or chronic exposure to male or female mice, or by isolation. The variation in T levels in plasma samples collected from the same animals on different occasions is comparable to the variation between individuals bled on a single occasion. The concentration of T in the testis is as variable as that in the peripheral plasma. It is suggested that in the laboratory mouse T is produced and released in an episodic fashion, that elevations in T levels in peripheral plasma of mice are greater than those observed in other species, and that testicular secretory episodes are interspersed with periods of minimal steroidogenic activity.


Comparative ability of rat seminiferous tubules, interstitium, and whole testes to utilize cholesterol-1,5-3H as a substrate for testosterone synthesis and the intratesticular distribution of cholesterol side-chain cleavage enzyme. Homogenates of rat seminiferous tubules, interstitium and intact testis tissues were assessed for their ability to convert cholesterol -1,2-3H to testosterone in vitro. While 3H-testosterone synthesis was observed in incubates of interstitial and whole testis homogenates, no synthesis was detectable in homogenates of seminiferous tubules. To determine whether cholesterol side-chain cleavage enzyme (CSCCE) was deficient or absent in tubules, mitochondria from tubules, interstitium and whole testes were analyzed for CSCCE activity by measuring conversion of cholesterol -26-14C to 14C-isocaproate (+pregnenolone). Interstitial mitochondrial preparations from each of six testes were found to be approximately 200 times more active in CSCCE than the corresponding tubule mitochondria, and 1600-1800 times more active on a specific activity basis. Although caution is required in extrapolation of in vitro data to the in vivo state, these findings suggest rat seminiferous tubules may be incapable of de novo testosterone biosynthesis and that this lack of synthetic ability may be due to a deficiency of CSCCE.


The in-vitro and in-vito effects of diethylstilbestrol on testicular synthesis of testosterone. The effect of diethylstilbestrol (DES) on the percent conversion of a 14C-progesterone (14C-P) substrate to 14C-testosterone (14C-T) when added to incubates fo rat testicular homogenates has been measured. Similarly the effect of DES administered parenterally to intact adult rats at 9 dose regimens on such conversion has been evaluated. In addition, in the latter group serum luteinizing hormone (LH) levels were assessed simultaneously. DES added in-vitro significantly reduced T formation at every level. Only the large parenteral dose of DES affected T synthesis after 24 hours, while every parenteral dose significantly reduced T synthesis with 4 and 8 day regimens. Mean serum LH levels failed to reflect a significant decrease at the 1 and 4 day dose level, but did decrease significantly in 2 of 3 groups on the 8 day regimen. These results suggest that there is a direct effect of DES at a testicular level inhibiting T synthesis not associated with a simultaneous drop in mean serum LH levels. A measurable decrease in LH concentration does occur with continued treatment.


Attempts to transfer immunity to Trichobilharzia ocellata (Trematoda: Schistosomatidae) passively via lymphoid cells and/or serum. White Pekin ducklings were injected with serum, lymphoid cells, or both, derived from donor birds which were immune to reinfection by the schistosome trematode, Trichobilharzia ocellata. Ducklings receiving serum and/or cells from susceptible birds, and untreated ducklings, served as controls. One set of experimental and control ducklings was kept alive and all of these birds passed viable T. ocellata eggs by day 20 indicating that protective immunity had not been transferred. Another set was killed 3-5 days after exposure. The schistosomula which were recovered from these were measured and in most cases no difference between experimentals and controls could be seen. However, birds which had received the maximum dose of serum (8 ml.) did produce worms of different length, the immune serum recipients having shorter parasites than controls. A second experiment was performed in which up to 60 ml. of immune serum was injected, controls being recipients of normal serum or saline. Recipients of immune serum either failed to pass worm eggs entirely, or passed low numbers after delayed onset. Controls were variable but exhibited earlier patency and heavier infections. Schistosomula recovered from birds killed 4 days after exposure were measured. In 3 of 4 groups, experimentals were significantly shorter than controls, but no significant differences were detected between normal serum and saline controls.


Electrocardiographic changes in African trypanosomiasis caused by Trypanosoma brucei rhodesiense. The electrocardiographic findings in 40 patients with Trypanosoma brucei rhodesiense infection are reported. Using rigid diagnostic criteria 7 out of 18 patients (39%) had abnormal electrocardiograms before any form of therapy and 22 of the 40 patients (55%) had abnormal electrocardiograms at some stage of the disease or its treatment. The electrocardiographic abnormalities are described and discussed and the literature is reviewed.


Experimental maduromycosis. II. Experimental mycetoma in mice caused by repeated injections of Phialophora jeanselmei. Intraperitoneal and subcutaneous lesions were produced in 17 out of 22 mice, sensitized by repeated subcutaneous injections of P. jeanselmei in FREUND'S complete adjuvant. The lesions were essentially self-limiting as were those described by us earlier in cortisone-treated mice. Precipitating antibodies and cutaneous hypersensitivity could not be demonstrated.


A comparison of post-mortem analysis of helminths with faecal egg counts. Intestinal helminth infections are very common amongst residents of the Colombo area. Most common by post-mortem examination of 104 cases of sudden death were Trichuris trichiura (97.1%), Necator americanus (88.5%), Enterobius vermicularis (77.9%) and Ascaris lumbricoides (40.4%). Trematode and cestode infections were not encountered except a single case of H. diminuta infection. A comparison of the results obtained by the direct smear method for examining stools missed cases harbouring gravid females of up to 3 Ascaris lumbricoides, 29 Trichuris trichiura and 66 Necator americanus. The direct smear revealed all the helminths present except threadworms in only 30% of the cases. The correlation between worm loads calculated from ova counts and actual numbers harboured was fairly close in 19 out of 35 cases for Ascaris and 37 out of 78 cases for Necator americanus. Highly erroneous results were obtained in many instances when worm loads were calculated from the results of ova counts.


Radiological patterns of pulmonary tuberculosis in Nigeria. Two hundred and sixteen patients with pulmonary tuberculosis were reviewed. Childhood and adult patterns of tuberculosis as noted in other countries were recognised. However, some children were seen with an adult pattern most probably due to a reinfection. There were also adults with the childhood pattern most probably due to a failure in the localisation of the primary intra-pulmonary parenchymal lesions with subsequent haematogenous spread. The prognosis in children with the adult pattern, and in adults with the childhood pattern was poor. The lesions (noted in this study) were severe and widespread, and with a high incidence of complications such as adenopathy and exudative lesions. The high incidence of associated diseases such as measles and malnutrition would account for the severity of tuberculosis and the high percentage of negative tuberculin tests in these patients. No lobes were exempted from involvement. But the upper lobes especially the right were the most affected. Negative tuberculosis tests make repeated sputa examinations imperative in the diagnosis of tuberculosis in this environment. The high predominance of male patients among those with miliary tuberculosis in our study remains unexplained. The genotype distribution amongst our patients shows no statistical difference between them and that of the population.


Pulmonary tuberculosis in diabetes mellitus. In 217 patients with diabetes mellitus, 32 (14.7%) had also pleuropulmonary tuberculosis confirmed by bacteriologic or histologic means. Either unilateral or bilateral lower lobe involvement was seen in 20 patients (62.5%). Of these, 75% were febrile, the response to antituberculous drugs was slower than in patients with apical lesions. Confirmation of tuberculosis was also more difficult in patients with lower lobe disease. The prevalence of tuberculosis in diabetic patients must be considered and the disease should be especially suspected in diabetic patients with lower lobe lesions.


Appendicitis in an urban community of North Celebes, Indonesia. In a study of 220 cases of appendicitis among inhabitants of the city of Menado, no relationship could be established between incidence and any social class. This might be due to the uniformity in food habits, all classes consuming a fair amount of proteins, estimated at 1 g/kg bodyweight. There were no children in our study material; appendicitis in children is rarely met in the area. There was a high incidence among young women and women over 45 years. A short meso-appendix was found in 72% of the removed appendices, a retrocoecal position of the appendix in 60% of cases. In nearly all the acute forms of appendicitis, the appendix was eight cm or longer. Since histopathological signs of inflammation were present in 215 of the examined specimens, we think it justifiable to perform an appendectomy in cases with recurrent lower abdominal complaints.


Effect of the Aswan High Dam on prevalence of schistosomiasis in Egypt. An increase in the prevalence of schistomiasis in Egypt, as a result of the Aswan High Dam, has for long time been predicted because of reclamation of land and conversion of annual flooding (basin irrigation) into perennial irrigation in Upper Egypt. Two aspects, neglected in the predictions, have been investigated in the present study, and these are: the ecological changes, relevant to the transmission of the disease, in the Nile itself, and those in irrigation canals and drains in areas which had been under perennial irrigation before the constriction of the dam. The findings indicate that the Nile, at least in the Delta, has become a favorite habitat for breeding of the snail hosts of both urinary and intestinal schistosomiasis, a center for human activities and evidently for transmission, and that irrigation canals and drains now harbor throughout the year undisturbed and stable populations of these snail hosts. This has resulted from the elimination in these canals, of the so-called 'winter closure', because it is no more needed. Before the dam the closure was enforced for about 40 days, during which the canals were closed and dried up, and the silt deposited on their beds during the Nile flood dredged out together with the snails and aquatic weeds.


A new focus of onchoceriasis in the Sudan. A new focus of onchocerciasis is reported from Upper Atbara River area in the Sudan. This river is a known seasonal breeding place of Simulium damnosum. The area was sparsely populated in the past but now, following agricultural development, is inhibited mainly by immigrants from Northern Nigeria and Chad. Clinically the common features are skin changes of the legs, thighs buttocks, arms and trunk. Other features are corneal opacities and small often deeply placed subcutaneous nodules. Choroido-retinal degeneration, genital elephantiasis and hydrocoele, commonly associated with onchocerciasis in other parts of the Sudan, are absent.


Serum alkaline phosphatase activity during pregnancy and the post-partum period in Ghanaian women. Serum alkaline phosphatase activity was determined in 454 Ghanaian women at various stages of pregnancy and the eighteen months following delivery and compared with the levels found in 45 non-pregnant women who were not nursing babies. There was a statistically significant fall in mean enzyme activity in the second trimester, followed by a rise above normal in the third trimester. During the eighteen months following delivery, the mean serum alkaline phosphatase activities were significantly raised. Increase in plasma volume which occurs during pregnancy is suggested as the cause of the fall in serum enzyme activity in the second trimester whereas the rise in enzyme activity in the third trimester is attributed to the well-known increase in serum alkaline phosphatase of placental origin. The prolonged elevation of serum alkaline phosphatase activity in the post-partum months is most likely due to the traditional prolonged breast-feeding that practised in Ghana.


Mortality and morbidity pattern in measles in Tanga District, Tanzania. Two hundred and fifty children, suffering from measles were studied for morbidity and mortality in Tanga District Hospital in Tanzania. The highest incidence of measles was in the second half of the first year of childhood (40%). Mortality was directly related to the nutritional status and associated complications. Medical care at the health centre level by medical auxiliaries during the acute phase and the problem of poor weight gain on follow-up are discussed.


Salmonella weltevreden: a sero-type of increasing public health importance in India. Infection due to Salmonalla weltevreden in man in India was quite uncommon until 1970, constituting less than 4% of total human salmonellosis. The incidence of infection increase considerably since that year and in 1972 this serotype constituted 29.1% of total human and 22.4% of both human and and animal salmonellosis. This serotype ranks second among 47 and 83 Salmonella serotypes isolated from sewage and other water sources during 1958-1973. The public health importance of this serotypes is discussed.


Isolation of a 'saprophytic' leptospiral serotype andamana from carrier rats in Israel. The first isolation of two leptospira strains belonging to the serotype andamana from the kidney of Rattus norvegicus is reported. A strain of this serotype has never before been isolated in the Middle East, nor from any rodent in any other part of the world. Its epidemiologic significance and the classification of this serotype as part of the saprophytic Biflexa species is discussed.


Acute viral hepatitis in Papua New Guinea: results of hepatitis B antigen and antibody studies. Using sensitive haemagglutination techniques, both a group of non-medical Papua New Guinean and European patients with acute viral hepatitis were investigated for Hepatitis B antigen and antibody. The results are compared with similar studies in a control population. Although total exposure rates (obtained by combining antigen and antibody techniques) were similar in the European patient and control groups, there was a 10% increase in Hepatitis B antigen rate in the Papua New Guineans with clinical hepatitis as compared with the control group. It is concluded that viral Hepatitis B is proportion of the hepatitis occurring in Papua New Guineans is Type B. Normal pooled immunoglobulin should be of use in the management of focal or more widespread outbreaks of acute viral hepatitis in Papua New Guinea.


A sero-epidemiologic survey on arbovirus in Wuvulu Island. The authors present here the results of a serological survey on arbovirus infections, which was conducted on 116 out of 505 inhibitants of Wuvulu island, the westernmost island of the Bismarck archipelago, located 260 km north of Wewak, Papua-New Guinea. The islanders are divided in two communities of unequal size: the Wuvulian themselves, who are Micronesians, and the coconut workers who are Melanesians coming from the Sepik district. In addition to the presence of a group A virus, this survey shows a recent infection in the Melanesians by Dengue type 2 virus, probably during the 1971-72 epidemic. The virus did not reach Wuvulu island, as shown by negative results observed in the micronesian sera. A better knowledge of the potential dengue mosquito vectors would be useful in order to define the risk of an eventual introduction of the virus on the remote island.


The 1974 epidemic of Chikungunya fever in children in Ibadan. During an epidemic of Chikunguya fever in Ibadan 16 strains of Chikungunya virus were recovered from children reporting sick with fever at the University College Hospital and Oluyoro Catholic Hospital Outpatient Clinic. Twelve strains were obtained from children within the 1-4 year age group, two from 5-10 year group and one each from less than one-year age group, and 10-15 year age group. A retrospective survey for neutralising antibodies to Chikungunya shows a significantly higher proportion of children were positive for Chikungunya N antibodies just after the 1969 epidemic than in 1974 just before the epidemic, with resultant pooling of Chikungunya seronegative children who are susceptible to infection.


The effect of long term anticonvulsant therapy on serum calcium, phosphate and alkaline phosphatase in Nigerian epileptic patients. A survey of calcium metabolism in fifty-two epileptic patients on long term therapy with anti-convulsant drugs, showed that their total serum calcium levels were within normal limits. There was neither clinical nor radiological evidence of osteomalacia in any of them. It is postulated therefore that the osteomalacic effect of antivonculsant drugs reported among Caucasians does not appear to occur in African patients in a tropical environment most probably due to the abundance of vitamin D derived from the sun's ultra-violet light.


The traditional basis of neuropsychiatric practice among the Yorubas of Nigeria. The Nigerian, because of gross shortage of 'western-trained' health personnel, not infrequently resorts to traditional native medicine and the native herbalists. The training of these native doctors is an arduous one and lasts on the average of 8-10 years. The core of their practice is handed-down tradition learned by rote and memorised. Pharmacotherapeutics are based in part on observations tested through the ages, and not uncommonly on the cause and effect phenomena. They are excellent psychotherapists, and maintain good relationship with their patients. Neurology as practised among the Yoruba native doctors recognises several classical neurological diseases including epilepsy, cerebrovascular accidents, fever and headache, migraine and the tropical ataxic neuropathy. Several often compound prescriptions are available, but the scientific basis of most of the prescriptions is for the moment unknown to them or to modern medicine. It seems that further research into some aspects of traditional native medicine may yield some fruitful results.


[Comparative electron microscope studies on the labelling Leishmania donovani, Leishmania tropica and Leishmania braziliensis with ferritin (author's transl)]. The labelling of negative charges on the cell surface of the developing promastigote forms in Leishmania donovani, L. tropica and L. braziliensis was determined using cationized ferritin and electron microscopy. Ferritin deposits were seen exclusively on the pellicle, since they cannot penetrate the cell membrane. The ferritin particles were distributed in regular rows covering the whole cell surface. The mean diameter of the particles was 8.76 nm and at a magnification of 104.000 an average of 9.8 particles was detected on 1 cm cell surface. Only in the membrane of the proximal part of the reservoir labelling was frequently absent. The possible explanations for this observation were discussed. There was no difference in the pattern size of the ferritin particles or in their number per cm cell surface among the various strains of L. donovani on the one hand or between L. donovani, L. tropica and L. braziliensis on the other.


[Intravaginal infection of the rat with Trichomonas vaginalis and Candida albicans. An experimental model for chemotherapy (author's transl)]. Ovariectomised and oestrogen premedicated rats were infected intravaginally, with first C. albicans and then with T. vaginalis. Under these conditions infections with T. vaginalis could be established with more reliability than when using axenically-cultivated T. vaginalis alone. This mode of infection is easily reproduced, and it allows the performance of chemotherapeutic tests on small groups of laboratory animals. Such tests were carried out with Metronidazole, Tinidazole and Nifuratel.


[Glutathionestatus of Plasmodium vinckei parasitized erythrocytes in correlation to the intraerythrocytic development of the parasite (author's transl)]. The glutathione status of Plasmodium vinckei parasitized erythrocytes of mice was determined in correlation to the intraerythrocytic stage of maturation of the parasite. The different stages of blood schizogony were separated by discontinuous Dextran-density-centrifugation. The changes of protein content, glutathione concentration (reduced/oxidized and bound/free glutathione) and in the specific activities of the following enzymes: gamma-glutamyl-cysteine-synthetase (GC-synthetase), glutathione-reductase (GR), glucose-6-phosphate dehydrogenase (Gl-DH), glutathione-peroxydase (G-POD) and catalase were investigated in dependence of the intraerythrocytic stage of development. The following changes of the investigated metabolic parameters were observed during the schizogony: - the protein content decreased to about one half, - the glutathione concentration increased about 10-fold, while the relations reduced/oxidized and free/bound glutathione remained constant, - Gl-DH activity appeared and increased steeply, - the specific activities of GC-synthetase and of GR increased more than 2-fold, while G-POD remained almost constant, - and the activities of G-6-PDH and catalase  showed a significant, strong decrease to about 25% of the original values. It is tried to relate the observed changes to the growing parasite or to the host cell. The significance of the results for the metabolism of malaria parasites and for a possible adaptation to the mosquito by a GSH mediated protection of the malaria parasite against an enzymatic defence-reaction of the mosquito, is discussed.


Biochemical, immunological and genetic studies in leprosy. III. Genetic polymorphism of C3 and immunoglobulin profile in leprosy patients, healthy family members and controls. 148 members from 30 families (64 children) from Ethiopia, where one of more persons were affected with leprosy, were investigated for genetic polymorphism of C3, serum concentration of ss1C/ss1A-globulin and immunoglobulins A, G and M using high voltage agarose electrophoresis, immunoelectroassay and single radial immunodiffusion techniques respectively. The results are compared with related healthy controls. No association between C3 phenotypes and leprosy could be established through family studies. C3 concentration was, however, lower in leprosy patients. Difficulties and drawbacks of such studies with small families are discussed.


[Immunodiagnostic tests for bilharziasis. IV. Demonstration of antibody in blood and serum eluates collected on filter paper discs (author's transl)]. Serum and blood samples dried on filter paper discs and normal sera were collected from 142 Liberians with proven schistosomiasis and 25 Liberians without schistosomiasis. These samples were tested by the indirect hemagglutination test (IHA) employing lyophilized sheep erythrocytes sensitized with either cercarial or adult Schistosoma mansoni antigens. The following results were obtained: Out of the 142 sera collected from the schistosomiasis patients 130 (91.5%) reacted with the cercarial antigen and only 89 (62.6%) reacted with the adult S. mansoni antigen. None of the 25 sera from persons free of schistosomiasis reacted with either antigen. The sensitized lyophilized erythrocytes showed no loss of antibody activity after laboratory storage at 4 degrees C for 4 months which was interrupted twice for 16 hours each during shipment. Filter paper serum and blood samples were stored at -25 degrees C up to 84 days with 16 hours interruption during shipment. 77.6% of the eluates from blood showed the same antibody titer levels as in normal serum; 10% showed lower antibody titers and 11.5% had negative results compared with normal serum. Results obtained with eluates from dried serum were somewhat better. An additional storage of the dried blood specimens for ten days at room temperature resulted in a rise of the proportion of negative titers from 11.5% to 34.1%. This loss of antibody activity was found in two thirds of the samples with low antibody titers. The results indicate that blood and serum samples dried on filter paper platelets should be stored at low temperatures (-25 degrees C) to preserve the antibody response.


Reactions to subconjunctival inoculation of Onchocerca volvulus microfilariae in pre-immunized rabbits. Rabbits, pre-immunized by intravenous inoculations of live, or of freeze-killed microfilariae of Onchocerca volvulus, were later challenged by subconjunctival inoculation of live microfilariae. Those pre-immunized with live microfilariae showed a marked chemotic conjunctivitis and reactions in the cornea (stromal keratitis and limbal abscesses), starting within one day of challenge. They were classed as sensitized. Those pre-immunized with dead microfilariae produced minimal reactions also starting on day 1, and were classed as tolerant. Histologically the reactions were distinctly greater in sensitized than in tolerant animals. The predominant cells in the inflammatory exudate were polymorphonuclear leucocytes and lymphocytes. The immunological basis for the differences between sensitized and tolerant rabbits is discussed, together with its possible bearing on human onchocerciasis. The effects of long-term subconjunctival and sclerocorneal inoculation of microfilariae were compared in one sensitized, one tolerant, one previously exposed, and one sensitized control rabbit. The sensitized test animal showed lesions resembling the sclerosing keratitis of human onchocerciasis. Immature microfilariae taken from intra-nodular fluid showed little ability to penetrate the cornea of the rabbit, and were minimally pathogenic.


Factors influencing the passage of Onchocerca volvulus microfilariae into the urine. The effect of various substances on the output of Onchocerca volvulus microfilariae in the urine was investigated in volunteers infected with the Cameroon forest and Sudan-savanna strains of the parasite. Output of microfilariae in the urine tended to be higher during periods of normal activity than during sleep. During waking hours, the rate of output remained generally steady, but in some patients occasional showers of microfilariae appeared in the urine, possibly associated with the intake of food and drink. Drinking 1.2-2.5 litres water produced a shower of microfilariae in the urine of some subjects. This began within an hour of drinking and its onset preceeded that of the diuresis. Thiazide diuretics, acting on the convoluted tubules, produced no increase in microfilaruria. In savanna subjects intravenous injection of DT TAB vaccine caused pyrexia, and simultaneously large numbers of microfilariae appeared in the urine. There was no associated diuresis, and no increase in the concentration of microfilariae in the venous blood. In forest subjects DT TAB caused no increase in microfilaruria. In all subjects 25-50 mg diethylcarbamazine (DEC) caused large numbers of microfilariae to appear in the urine on day 0, within a few hours of the first dose; and there was an increased output of urine over the first 24 hours. Microfilaruria declined sharply on day 1 of treatment, but in subjects developing a high microfilaraemia, it rose again on day 2, and declined more slowly thereafter. Betamethazone, given in conjunction with DEC, appeared to slow the rate of destruction of microfilariae in the skin and lymph glands, and to prolong the duration of microfilaraemia and microfilaruria. The findings suggest that there is a reservoir of microfilariae in the glomerular capillaries, which fills slowly by accumulating microfilariae from the circulating blood. The microfilariae probably enter the urine by penetrating the glomerular capillary.


Visual impairment and incidence of blindness in Liberia and their relation to onchocerciasis. The results of the epidemiological survey of 10,860 inhabitants of 121 Liberian communities from 1969-1971 were analysed on the prevalence, incidence and risk of blindness associated with onchocerciasis infection. The overall prevalence of economic blindness in the population sample was 3.24%, the total rate of measured visual damage in both eyes was 5.37% (impairment of vision etc.). Onchocerciasis was prevalent in a very high proportion of those having visual defects. Causes of blindness as by frequency were cataract in 45%, lesions of the anterior segment, other than onchocerciasis-related in 14%, phthisis bulbi (9%) and optic atrophy (6%). The importance of onchocerciasis as a cause of blindness and as a public health problem in Liberia is examined by the comparison of 5 categories of village populations, classified by their adjusted onchocerciasis prevalence rates. The risk of exposure to onchocerciasis increases gradually from nil to 100%, providing one infection-free control population and increasing degrees of prevalence in the next categories, dependent on duration of exposure and intensity of transmission. The attempt to estimate the risk of blindness attributable to onchocerciasis from this data reveals a 3-fold risk in people exposed to the infection in their habitat, whereas a 2,5-fold risk is found from the evaluation of findings in people classified by mf-prevalence in their skins only. Considering a proportion of at least 65% of the rural population to be living under onchocerciasis exposure, the attributable risk amounts to more than 50%, which suggests that this population suffers from 50% more blindness than would be expected without exposure to onchocerciasis sometime in life.


On two filarioid worms, Setaria labiatopapillosa and Pseudofilaria giraffae n. sp., from the East African giraffe. A single, however gravid, female filarioid worm collected from the peritoneal cavity of a giraffe in East Africa was identified as Setaria labiatopapillosa. Further filarioid worms recovered from the subcutaneous tissue and the Ligamentum nuchae of the same giraffe were recognized a new species and were described as Pseudofilaria giraffae.


[Investigations on the filariidae of the cervidae in Southern Germany. 3. The filariidae of roe deer (Capreolus capreolus) and fallow deer (Dama dama) (author's transl)]. Roe deer in southern Germany are frequently infected with W. rugosicauda. The adult worms are found subcutaneously in the connective tissues of the back of the host. The microfilariae concentrate in a considerable distance near the nose, in smaller numbers also in the ears and in the skin of the legs. The vector is probably Ixodes ricinus. In fallow deer C. wenki are found intradermally and subcutaneously. The microfilariae remain in the skin near the site of the adult worms. Skin inhabiting microfilariae of another filariid worm are found which cannot be associated with the described species of Cervidae. The host specificity of the filariid forms of roe deer, fallow deer and red deer is indicated, the development of the microfilarial distribution patterns is discussed.


Use of larvivorous fish for vector control in the Malvides Republic. The paper reports on the use of three larvivorous fishes in the Maldives Republic: Poecilia reticulata (Poeciliidae), Mollienesia sphenops (Cyprinodontidae) and for the first time Kuhlia taeniurus (Kuhliidae), a sea fish adapted to life in wells, which are the only sources of water supply (with the exception of a few rain-water cisterns). The approximately 20 000 wells are the main and all-year-round breeding places for both Anophelines and Culicines. Due to this type of breeding places, Maldives are in a unique situation, that the fish can theoretically be used as the main control measure for filariasis. This requires an absolute minimum of work and no cost at all. There has been a reduction of the filariasis overall endemicity rates over the last 10 years although no specific measures have been carried out (except in the capital city of Male) nor have any ecological changes taken place, which could explain this decrease. With this decrease however there has been lately a marked reduction in the percentage of wells with fish in some atolls.


Determination of the acetylator phenotype in a Northern Nigerian population. The sulphadimidine method was used to determine the acetylator phenotype in tuberculosis patients and hospital workers at Ahmadu Bello University Hospital, Zaria, Nigeria. The method gave good discrimination between slow and rapid acetylators. The proportion of slow acetylators in the whole group was 49 per cent and this is similar to other results from Negro populations.


Determination of the acetylator phenotype using matrix isoniazid. The development of a simple method for classifying subjects as slow or rapid acetylators is reported. The method is based on determining the ratio of acetylisoniazid to acid-labile isoniazid in the urine 23-24 hours after an oral dose of a slow-release isoniazid formulation. The results obtained when this method was applied to phenotype over 200 East African tuberculosis patients are described. It is suggested that the method would be particularly suitable for classifying tuberculosis out-patients.


[Comparative study in structure of myoglobins in semiaquatic animals: Castor fiber, Ondatra Zibethica, Lutra lutra]. A degree of similarity in the structure of myoglobins in the semiaquatic animals (beaver, muskrat, otter) is shown by the finger-print method with the determination of amino acids content in peptides. It is established that about 2/3 of the acid sequence in the investigated myoglobins are invariable. An assumption is advanced that these regions of the structure are of most importance in the functional respect.


[Kinetics of thrombinogenesis and thrombin-fibrinogen reaction inhibition by lipoid anticoagulants]. Influence of the lipoid anticoagulant (phospholipid brain fraction) was studied as applied to thrombokinasogenesis, thrombinogenesis and on the thrombine-fibrinogene reaction with different concentrations of the substance under study and substrates of the corresponding processes. The lipoid coagulation was established to inhibit chiefly the transformation of prothrombine into thrombine and to a less extent--fibrinogene into fibrin. A graphic analysis of the inhibiton kinetics indicates that in the thrombinogenesis process the lopoid anticoagulant acts as an inhibitor which interacts with the substrate and the thrombine--fibrinogene reaction is supressed by it in the conjugate-checking manner.


[Effect of trypsin on endogenous RNA synthesis of cell nuclei]. The effect of trypsin on endogenous RNA-polymerase activity was studied in the rat liver and kidney cell nuclei. It is shown that the endogenic ability for RNA synthesis of the liver nuclei is higher than that of the kidney ones. Trypsin effect causing chromatin histone hydrolysis and deblocking of the genome-primer results in the above 4-fold stimulation of RNA synthesis in both types of nuclei. Ammonium sulphate causes an additional growth of nuclei transcription ability. On the basis of the data on determining the endogenic RNA-polymerase activity in the medium with MgCl2, on the one hand, and in the medium with MnCl2 and ammonium sulphate, on the other, a conclusion is drawn that caryoplasmatic form of RNA-polymerase in the kidney nuclei prevails as compared with the liver nuclei.


[Change in conformation of histones F 2a and F 2b in solutions of different ionic strength]. A change was studied in the differential absorption spectra and fluorescence quantum yield of histones F2a and F2b with the ionic strength varies. It is shown that the structure of the histone F2a molecule stops changing with an increase in the concentration of NaCl up to 0.5 M. In the histone F2b molecule the conformational changes occur with the NaCl concentration less than 1.0 M. The conformation change results in formation of hydrophobic areas on the histone surface, which intensifies the histone-histone interaction. The role of the histone conformational changes for regulation of gene activity is discussed.