Study on the insulin-binding capacity of blood serum by a cellulose adsorption method.

The cellulose adsorption method was used for the quantitative study of the insulin-binding capacity of blood serum. The results support the view that anti-bodies to insulin are of exogenous origin and that may be responsible for insulin resistance in individual cases. While the insulin requirement of patients was found to be related to the serum antibody level, the latter was unaffected by the duration of insulin treatment even though the number of cases exhibiting normal values decreased with the length of treatment.


[Course of disease and prognosis of diabetes mellitus].

In potential diabetics, environmental factors, especially overweight, appear to be more significant for the prognosis than genetic factors. The frequency of overt diabetes is higher in females than in males. Mean life expectancy amounts to about 70%, compared with the whole population. Mean survival after manifestation is more than 18 years. Diabetic coma has almost disappeared as cause of death. Today, approximately 75% of diabetics die from vascular complications, mainly from coronary heart disease. The coronaries are affected with same frequency in diabetic males and females. Renovascular complications are the leading cause of death only in young diabetics. Diabetic macro- and microangiopathy is correlated with the duration, not with the severity of diabetes. It should be imperative to physicians to control diabetes very strictly, especially during the first years following manifestation, in order to reduce frequency and/or severity of vascular complications.


[Demonstration of arterial vascular occlusions using 125 I-fibrinogen].

In 10 patients with arterial occlusions, 125-I fibrinogen was injected intravenously. In all patients with acute embolic or thrombotic arterial occlusions verified surgically and/or angiographically, a significant accumulation of radioactivity in the affected region was observed. The use of 125-I fibrinogen in this manner obviously is a valuable means for the detection and localization of acute arterial occlusions.


[Clinical study of the normothymic effect of dipropylacetamide].

On the basis of his results, obtained during a long term study of 32 patients presenting cyclic variations of mood with a known frequency, the author concludes that dipropylacetamide permits to stabilise mood in about 70% of all cases through a supression of relapses or by reducing significantly their frequency. No biological changes were observed and the clinical tolerance of the drug was excellent in most cases. This drug constitutes a variable alternative to lithium treatment, and lacks the well known lithium side effects and limitations.


The lipid metabolism of the arterial wall and its abnormalities in diabetes.

Arteries are not simply conduits for the transport of blood, but consist of metabolically active tissue which has the capacity to synthesize all the components of the atherosclerotic lesion. The smooth muscle cell appears to be the most important metabolically active cell in the arterial wall. There is little information on arterial metabolism in human diabetes. Experimental diabetes depressed all aspects of arterial lipid metabolism and this effect is reversed by insulin. Insulin promotes changes in arterial metabolism which are similar to those an atherosclerosis. Thus the relationship of human diabetes to the metabolism of the arterial wall is complex and little understood.


R factors derived from Shigella flexneri strains.

Of 2492 Shigelle flexneri strains isolated from dysenteric patients in Hungary in the years 1972-1974, 767 (30.8%) were resistant to 1-5 antibiotics. Resistance was due to R factors in 79.2% of the strains. Fertility inhibition experiments with F specific phages showed R factors to be fi+ in 12.9% and fi- and 87.1%. Of the antibiotic markers, the chloramphenicol-tetracycline resistance determinant was the most common (46.4%). Chloramphenicol resistance determinants were carried out by fi- R factors.


Restriction and modification of Shigella flexneri phages by R factors.

Out of 420 R factors derived from Shigella flexneri strains, 50.8% restricted Escherichia coli and S. flexneri phages. Phage restriction was produced both by fi- and fi+ R factors. The R factors were divided into nine groups on the basis of the efficiency of plating of S. flexneri phages. Changes of phage types were produced by transferring R factors of different restrictive types. The changes offered some information concerning the evolution of phage types. Studies on phage modification supported the grouping of R factors determined on the basis of restriction. R factors of different restrictive types were type-specific except for types VII and IX. Modified phages proved to be highly practical for epidemiological purposes. The use of modified phages, as an additional phage-set besides that basic phage-set, was suggested to trace the source of strains which changed their phage types as an effect of R factors.


A double blind study of pimozide versus chlordiazepoxide in anxiety neuroses.

Eighteen patients diagnosed as anxiety states were treated under double blind conditions for a four week trial period with pimozide and chlordiazepoxide after randomisation. No significant differences could be demonstrated between chlordiazepoxide and pimozide as far as therapeutic efficacy or toxicity were concerned. Pimozide administered in a single daily dose was as effective as chlordiazepoxide administered in divided daily doses for the relief of anxiety symptoms.


Endotoxin-induced non-specific resistance in rats examined by Trypanosoma equiperdum challenge.

In rats weighing 100 g, intravenously administered Trypanosoma equiperdum organisms started logarithmic growth immediately, whereas in rats weighing 150-300 g growth started after a lag phase of 0.7-3.1 hr. The lag phase lasted for 15-17 hr when the rats were pretreated serially with endotoxins and this time course was not modified by changes either in the host's body weight or in the germ count of the inocula. Maximum resistance to infection was achieved with gradual doses of the endotoxin given at 48 hr intervals on 6 occasions. The total dose of endotoxin was fourfold of its LD50. Additional doses failed further to increase the resistance. Serial passages of the strain in rats pretreated with endotoxin disclosed that the trypanosomes growing after the lag phase had developed resistance to the factor responsible for the lag phase. Thus the method does not allow a quantitative estimation of resistance induced by serial endotoxin treatment, yet it represents a rapid and simple procedure in every case in which qualitative assessment is sufficient.


[Treatment of chronic psychoses with oral clopimozide].

A longterm investigation containing three distinct studies has been carried out in order to clarify efficacy and inocuity of clopimozide in the maintenance treatment of chronic psychotics. Twelve patients took part in the pilot study (Study I) during which the optimal weekly dose was established to be 24 mg. These patients were then subdivided into two groups for a controlled study with placebo (Study II). This double-blind evaluation has clearly established the superiority of cloprimozide over placebo. Patients were evaluated at the start and completion of the study with three scales. During the surveillance period (Study III), clopimozide was administered daily with a mean dose of 2.5 mg. Results were equally satisfying as those obtained during weekly treatment. The appearance of side-effects, mostly akatsia and dyskinesia, was only noted during the weekly administration. They could be efficiently controlled with dexetimide.


Antibodies to nuclear antigens in patients undergoing long-term hemodialysis.

Free nuclei of damaged leukocytes adhere to hemodialysis membranes. To see if the incidence of antibodies to nuclear antigens is increased in patients receiving hemodialysis, serums from 77 patients undergoing long-term dialysis for one to 66 months were assayed for antibodies to extractable nuclear antigen and native deoxyribonucleic acid (DNA) by hemagglutination technics. Serums from 300 other hospital patients (who did not have diseases known to be associated with antibodies to nuclear antigens) were assayed concurrently. Of the 77 dialysis patients, serums from 19 (25 per cent) were positive for one or both antibodies.  Serums from only three (1 per cent) of the 300 other patients had detectable antibodies. The incidence was significantly higher (p less than 0.001) in dialysis patients suggesting the possibility of sensitization to nuclear antigens during hemodialysis.


Desquamative interstitial pneumonia following long-term nitrofurantoin therapy.

Two patients with diffuse interstitial lung disease after long-term nitrofurantoin therapy were characterized clinically by exertional dyspnea and basilar rales, roentgenographically by diffuse interstitial infiltrate and physiologically by a restrictive lung defect. Pathologically, light microscopy revealed desquamative interstitial pneumonia. In one patient electron microscopy was characteristic of desquamative interstitial pneumonia. Immunofluorescent studies of one biopsy specimen showed specific fluorescence of interstitial cells with immunoglobulin E and third component of complement. In in vitro studies, nitrofurantoin therapy failed to induce lymphoblast transformation or histamine release. Treatment consisted of discontinuing the administration of nitro=furantoin and adding corticosteroids. Both patients felt better and showed clinical improvement. Our findings suggest that in some cases desquamative interstitial pneumonia may be drug related.


Obstructive polyuric renal failure following renal transplantation.

In a previously nephrectomized patient with a well functioning renal allograft, acute renal failure with massive polyuria and hypertension developed. Relief of a periureteric obstruction resulted in rapid correction of all three. Pathogenesis of hypotonic polyuria is thought to be a defect in the collecting duct permeability to water, stimulating nephrogenic diabetes insipidus. Normal urinary dilution and acidification suggest intact function of the ascending loop of Henle and distal convoluted tubules. The quick reversal of polyuria and renal failure after obtaining relief of the obstruction suggest that both the decrease in the glomerular filtration rate and tubular dysfunctions are due to functional changes in the nephron rather than to organic damage, a possibility also borne out by the findings in a renal biopsy specimen showing normal glomeruli and intact tubular epithelial cells. Ureteric obstruction should be considered in any patient with renal failure and polyuria; it may be a correctable cause of hypertension.


Iso-renin of extrarenal origin. "The tissue angiotensinogenase systems".

Enzymes, similar to kidney renin, are present in extrarenal tissue of most mammals; they hydrolyze angiotensinogen to form angiotensin I. We suggest that these enzymes be called angiotensinogenases. Angiotensinogenase concentrations in extrarenal tissue can exceed those in the kidney. The enzyme has been obtained in pure crystalline form. Angiotensinogenases are part of a complex enzyme system which leads to local production of angiotensin. Results indicating a biologic role of the angiotensinogenase system in brain, adrenal gland, uterus and tissue culture are discussed.


The renal circulation in hypertensive disease.

The pivotal role of the kidney in sustaining hypertension from any source or etiology is becoming increasingly clear. The possibility that the renal vasculature participates not only in the pathogenesis of renal vascular hypertension, but also in that of essential hypertension, has been the subject of continuing interest for 40 years. Evidence that a functional abnormality resulting in increased renal vascular tone is present in about two-thirds of patients with uncomplicated essential hypertension is reviewed, along with more circumstantial evidence that sympathetic nervous system activity operating on the renal vasculature is responsible. Two additional groups of patients in whom a characteristic abnormality of the renal vasculature is present have also been identified. In one group there is severe hypertension which is resistant to most forms of antihypertensive therapy but which is especially responsive to propranolol. In these patients renal blood flow and glomerular filtration rate are reduced, renin secretion rate is increased and the renal vessels are resistant to vasodilators, suggesting the presence of advanced organic arteriolonephrosclerosis, as a complication of long-standing, severe hypertension. The renal lesion, in turn, contributes to the increasing severity of the process. In a second group of patients, generally young and with uncomplicated hypertension, renal blood flow is inappropriately increased. In these patients a number of observations on their renal vasculature, renin and aldosterone responses to a volume challenge suggest an abnormality in the perception of extracellular fluid volume. A perfectly normal renal arterial tree, free of organic abnormality or an increase in tone due to active vasoconstriction, is distinctly unusual in essential hypertension.


Role of prostaglandins in the pathogenesis of Bartter's syndrome.

Increased renal prostaglandins activated by beta-catecholamines could produce renal tubular sodium wasting and angiotensin pressor resistance observed in Bartter's syndrome. We therefore measured plasma renin activity (PRA), aldosterone and prostaglandin A (PGA) by radioimmunoassay, and body composition by isotope dilution prior to and following beta-adrenergic blockade with propranolol (200 mg/day for 4 days) and prostaglandin synthesis inhibition by indomethacin (200 mg/day for 4 days) in a patient with Bartter's syndrome on a 250 meq sodium diet. After the administration of propranolol, body weight increased 3 kg, daily urine sodium decreased within 24 hours from 230 to 64 meq, and urine potassium from 102 to 45 meq, but PRA and the aldosterone level remained elevated. With the administration of indomethacin, body weight increased 5 kg, daily urinary sodium decreased within 24 hours to 11meq and urine potassium to 16 meq, PRA (normal less than 3 ng/100 ml/hour) decreased from 55 to 4.3 ng/ml/hour, plasma aldosterone (normal less than 8 ng/100 ml) from 74.1 to 3.6 ng/100 ml, and whole blood PGA (normal 546 +/- 307 pg/ml) decreased from 1,390 and 945 to 86 pg/ml. After the administration of propranolol or indomethacin, exchangeable sodium, total body water, extracellular volume and plasma volume all increased from less than to greater than predicted, and pressor resistance to angiotensin was normalized. These results suggest that Bartter's syndrome results from beta adrenergic and prostaglandin-mediated proximal tubular rejection of sodium leading to increased distal sodium-potassium exchange.


Renal prostaglandins and the regulation of blood pressure and sodium and water homeostasis.

In addition to its well known prohypertensive role in various states of experimental and human hypertension, the kidney has also been shown to exert an antihypertensive "endocrine" function. According to this hypothesis, certain forms of experimental and human hypertension might not solely be the result of an excess in the activity of such renal pressor systems as the renin-angiotensin system and the sympathetic nervous system, but might also result from an absolute or relative deficiency of intra-renal vasodilator antihypertensive factors which might allow pressor systems to act unopposed to produce peripheral arteriolar vasoconstriction and sustained hypertension. At least four factors have been characterized in the kidney of various animal species and man which might be responsible for such an antihypertensive function. These are (1) the renomedullary prostaglandins (PGs), (2) the renomedullary antihypertensive neutral lipid, (3) antirenin phospholipid and (4) the renal kinins. This review is restricted to an examination of the possibility that the vasodepressor renomedullary prostaglandins (PGA and/or PGE) may, at least in part, mediate the so-called antihypertensive function of the kidney and participate in the regulation of renal blood flow and natriuresis by physiologic antagonism of various renal vasoconstrictor stimuli such as the renal renin-angiotensin and the sympathetic nervous systems.


Angina pectoris among 10,000 men. II. Psychosocial and other risk factors as evidenced by a multivariate analysis of a five year incidence study.

The major independent role played by anxiety and severe psychosocial problems (especially family ones) is demonstrated by this multivariate analysis of a five year prospective study of the development of new angina pectoris among almost 10,000 adult men (average annual incidence = 5.7/1,000). The independent effect of these two variables is considerably augmented by the other significant risk factors of age, total serum cholesterol, systolic or diastolic blood pressure, certain electrocardiographic abnormalities and diabetes mellitus. The presence of all seven risk factors (at a high level) increases the probability of angina pectoris developing within five years to 289/1,000 from 14/1,000, when these factors are low or absent. The wife's love and support is an important balancing factor, which apparently reduces the risk of angina pectoris even in the presence of high risk factors. The implications of these findings to the pathophysiology and prevention of angina are stressed.


Notes from "Pavlov's Wednesdays": Gestalt relationships as conditioned stimuli.

When A.O. Dolin's dog Ger was trained to differentiate between metronomic frequencies of 60 (positive) and 120 (negative) per minute, its conditioned salivary reaction to the positive stimulus was attenuated immediately after a test on a more positive stimulus (30 per minute) and that to the negative stimulus was augmented immediately after a test on a more negative stimulus (200 per minute). Pavlov and his colleagues considered explanations based on the relationship between the test and trained stimuli, on reciprocal induction, and on gradients of generalized excitation and inhibition à la Spence. This was just before Pavlov's death, but his last words on the topic leaned in the Gestalt relational direction.


[Chemotypes of "Shigella flexneri" R mutants and related phage receptors. II. -- Localization of phage receptors (author's transl)].

Receptor sites for phages FP3, V, P1kcvir, H+, C21, T4, T3, T7 and 6SR have been investigated, by comparing the lytic activity of these phages on R mutants of strain F6 (F6R) and of various serotypes (FH) of Shigella flexneri with their inhibition by the lipopolysaccharides isolated from these mutants. The results suggest the following localizations for the receptor sites: phage FP3: lipid A-KDO; phage V: heptose or glucose; phage C21: heptose-glucose; phages H+, P1kcvir, T4 and T3: glucose; phage T7: glucose-galactose; phage 6SR: complete core structure.


[Chemotypes of "Shigella flexneri" R mutants and related phage receptors. I. -- Chemical study of the lipopolysaccharides (author's transl)].

The F6R rough mutants isolated from Shigella flexneri F6S, serotype 5b, and the FH rough mutants, derived from other serotypes of S. flexneri, were chemotyped according to the chemical analysis of their lipopolysaccharides. Further, the following stages of lipopolysaccharide core biosynthesis in S. flexneri have been established: --(KDO)3--heptose--heptose--glucose--galactose; the last three stages are: either --glucose--glucosamine--glucose, or --glucosamine--glucose--glucose. The results of the chemical study of the R lipopolysaccharides are compatible with the assumption of the existence of a similar core in all considered S. flexneri serotypes.


[Compatibility groups of metabolic plasmids (author's transl)].

The compatibility groups of eleven plasmids determining metabolic characters used in taxonomy and isolated from naturally-occurring strains were examined. Seven of these plasmids determined lactose fermentation. Two were fi+: one of these belonged to group FI and the other to a novel group. Of the remainder, which were fi-, one (which also determined chloramphenicol resistance) belonged to group H; the others were compatible with representative plasmids from every group so far recognized. Two plasmids determined sucrose fermentation. Both were fi-: one belonged to group H, the other was compatible with plasmids of every group. Two plasmids determined haemolysin production. One was fi+ and belonged to group FIII; the other was fi- and belonged to group I2. Plasmids belonging to known compatibility groups and determining metabolic characters only should prove particularly useful in the classification of plasmids determining antibiotic resistance.


[Variation of pyrolysis products from Salmonella typhi-murium during subculturing (author's transl)].

Consecutive subculturing of the same bacterial strain over a period of time resulted in variations of relative concentration of pyrolysis products. It is recommended that judicious care should be taken in the choice of these products used for taxonomic purposes.


[Experimental pyelonephritis in rats: value in the comparison of antibiotics (author's transl)].

The author discusses the conditions which an experimental pyelonephritis must fulfill to provide therapeutic results which will allow the assessment of new therapeutic agents. He subjects the chosen model to the therapeutic effect of four antibiotics and three antimicrobial drugs. A numeric value is given to the bacteriuria recession slope observed during the experiment. A comparison of the results being obtained with the bacteriological and pharmacological data normally evaluated, the author demonstrates the value of the present study. The analysis of the results collected during the tests shows that comparison between antibiotics are of greater value when they are of the same family. Nevertheless, the experimental pattern, when applied to antibiotics as different as kanamycine and cephalosporins, give a very good correlation particularly when the overstepping coefficient, as proposed by Canetti, is calculated on the results expressed as free products.


The design and analysis of experiments for the assessment of drug interactions.

It was pointed out that all fields of biological research have one feature common: inherent variability. Since this is the case and since it is not feasible to examine the entire population one is interested in, the experimenter is forced to give probability statements concerning any treatment differences observed. In order to do this, it is necessary for the experiment to be designed in such a way that a statistical analysis of the data will yield a valid answer to the question, "What is the probability that the differences observed could have occurred by chance?" The importance of randomization in the selection of the samples was emphasized. The problem of determining the sample size was discussed in relation to Type I (rejecting the null hypothesis when it is true) and Type II (accepting the null hypothesis when it is false) errors. It was suggested that too little attention is given to the possibility of Type II errors in biological research. It was emphasized that the specific question, or questions, one is asking should be precisely formulated prior to the design of the experiment, since hazily formulated ideas are difficult to discuss and virtually impossible to test for correctness. Once the experiment has been designed, both the questions and the design should be critically and logically evaluated for any fallacies. If the investigator has any doubts about the design or the manner in which the data will be analyzed, a statistician should be consulted before the experiment is conducted. A statistician cannot extract meaningful results from data collected with a faulty design. It was emphasized that it is important to know both the dose effect and time effect of each substance on the responses to be measured, in order to provide a rationale for the doses used in the interaction studies and the time after dosing at which the effect is to be measured. The design of drug  interaction experiments is based, in part, on whether or not both substances when given alone affect the response. If both substances are active, one determines the potency of one substance relative to the other in affecting the response. This can be done for either quantitative or quantal data. Once the relative potency has been determined, subsequent studies involve combining fractional doses of the substances and comparing the results against those obtained using standard doses of the substances individually. Doses of the combination and the single substances are picked such that equivalent responses should be obtained if the effect of the two together is additive. The null hypothesis is that the two compounds behave as though they were different forms of the same substance, one of which  is possibly (depending on the potency ratio) diluted with an inert substance. Equivalence of response can be tested using such parametric tests as Student's t or analysis of variance (or their nonparametric equivalents) for quantitative data. Additivity is inferred if the null hypothesis is accepted...


The combined effect of marihuana and dextroamphetamine.

The studies in mice indicated that locomotor activity could be stimulated THC and that this would enhance the effect produced by MAMP. We have previously shown that when 3, 6, or 9 mug/kg THC were administered to young adult males by MJ smoking, a dose-related impairment in standing steadiness (WB) and attentive motor performance (PM) resulted, although DAF and subjective evaluations were insensitive to these treatments. These same testing procedures after d-AMP 5, 10, and 15 mg/70 kg revealed no important performance effect. Systolic blood pressure was elevated with 15 mg/70 kg d-AMP, and subjective detection was positive and dose related. A combination of 25 mug/kg THC delivered by smoking an appropriate MJ cigarette and 10 mg/70  kd d-AMP taken orally produced subjective effects and psychomotor performance decrements not different from those with the MJ alone. The doses used were modest, yet most subjects believed their driving performance, a representative motor and metal skill, would be impaired. This judgment is supported by the laboratory measurements made. It is reasonable that realistically higher doses may not only have adverse psychological and cardiovascular effects but increase an accident potential.


[Role of the individual sensitivity to various cytostatic agents in children with neuroblastomas].

Primary plasmic cultures of 33 tumors of the sympathic nervous system of children (27 neuroblastomas and 6 ganglioneuromas) were used for determination of their individual sensitivity to vincristin, vinblastin, dactinomycin, mithramycin, olivomycin, cyclophosphant bruneomycin and adriamycin. Most of the tumors were sensitive to vincristin, rubomycin an adriamycin. The data obtained in vitro and in the clinic were compared with respect to 12 cases (treatment with vincristin, combination of olivomycin with cyclophosphan, vincristin with rubomycin or cyclophosphan). Coinsidence of the results was observed in 8 cases. The method of primary plasmic cultures may be successfully used for determination of individual sensitivity of children with neuroblastomas to various cytostatics.


[Substantiation for the kanamycin treatment of certain diseases, taking into account its concentration at the sites of localization of the causative agent (an experimental study)].

Kanamycin concentration in the inflammatory foci was studied on experimental models of pneumonia, maxillary sinusitis and acute dysentery. The kanamycin levels in the sites of the pathogen localization were lower than those in the same tissues of healthy animals. The antibiotic dose should be chosen with the account of its concentration in the focus of the pathogen localization rather than in the blood serum.


[Interprétation of the gonadtropin response after LHRH in adult (author's transl)].

The response to LHRH is never characteristic of a given hypothalamo-hypophysial gonadal axis except in the cases of severe gonadal disturbances, but reflects the functional states which can be observed under various circumstances. The same functional state may be found in different diseases and in contrast one disease can evolve through different functional states with time.


[Preliminary results of a cooperative clinical study of the new antitumor antibiotic, carminomycin].

The clinical trials of karminomycin, a new Soviet antitumor antibiotic in treatment of different malignant tumors showed that the drug had a pronounced antitumor activity against the soft tissue sarcomas of various histogenesis, lympho- and reticulosarcoma, acute leukemia and some other neoplasms.


[Clinical evolution of LH-RH reactivity in gynecology (author's transl)].

Impaired LH response to LH-RH has been found in 2/4 cases of primary amenorrhoea, in 2/8 cases of psychogenic secondary amenorrhoea, in 2/4 cases of secondary  amenorrhoea associated to a pituitary tumour and in 1/5 cases of iatrogenic secondary amenorrhoea post hormonal contraception. Therefore, this test appears not to differentiate these pathologic conditions.


[Fucidin, its basic properties and place in the modern therapy of suppurative and inflammatory processes].

Sodium fusidin prepared at the All-Union Research Institute of Antibiotics was studied experimentally and clinically. High antibacterial activity of fusidin especially against methicillin-resistant staphylococci was found. The clinical trials showed high efficacy of fusidin in treatment of perichondritis, osteomyelitis, pyodermia, pseudofurunculosis, multiple abscesses of the skin because of its satisfactory penetration into the skin and cartilage tissues, skin and subcutaneous cellular tissue. The tolerance of the drug by most of the patients was satisfactory.


[Incomplete testicular feminisation syndrome by testosterone insensitivity (author's transl)].

Male pseudo-hermaphroditism by partial testosterone sensitivity, without steroido-genesis abnormality, without apparent 5 alpha reductase deficit - Empty complete scrotum and hypospadias surgically normalized. At 39, scrotal testis 32 X 15 mm right, 23 X 10 mm left. Infantile penis and prostata. Gynoid scapulo-pelvic proportions, adipo-muscular ratio and fat distribution. Bilateral gynecomastia. Caryotype 46 XY - 17 ks 26 mg. After intravenous 100 ng LH RH: plasma (pl) LH increased 105 to 285 ng/ml, pl testosterone 5 ng/ml unchanged, pl oestradiol 115 to 135 pg/ml. 48 h after intra muscular 300 mg testosterone propionate: pl testosterone increased, 13 to 39 ng/ml, androstenedione 1,5 to 3,04 ng/ml, dihydrotestosterone 0,85 to 1,45 ng/ml, OEstradiol 52 to 110 pg/ml. No effect of 29 g testosterone oenanthate in 2 years.


[Microflora and its antibiotic sensitivity in chronic pharyngitis treated by cryotherapy].

Antibiotic sensitivity of the pharynx mucosa microflora in patients with chronic pharyngitis subjected to cryotherapy was studied. Examination of 36 patients showed that cryotherapy at a temperature of -1950 markedly decreased the number of the grown colonies, their qualitative characteristics being changed. In 10 days both the quantitative and the qualitative characteristics of the flora completely reduced. The cryotherapy did not change the virulence of the flora and its sensitivity to antibiotics.


[Experimental study of the effect of a number of chemotherapeutic preparations on the intracellular growth of dysentery bacteria, and their interaction with epithelial cells].

The effect of some chemotherapeutics on intercellular growth of Sh. sonnei and their capacity for penetration into cells Hep-2 and primarily triptinized cells of the monkey kidneys was studied. By the character of their effect the drugs were divided into 3 groups. The drugs of the first group, i.e. furazolidone had no effect on intracellular growth of Shigella. The drugs of the second group, i.e. neomycin, monomycin, kanamycin, polymyxin M, ampicillin, negram and 5-NOK induced a rapid decrease in the number of the specimens located inside the cells. The drugs of the third group, i. e. enteroseptol, streptomycin and tetracycline promoted a decrease in the intracellular growth of Shigella by the 3rd-4th day. None of the drugs could be detected inside the cells in the concentrations corresponding to the minimal bacteriostatic ones with respect to Shigella. The activity of the drugs of the second group was connected with their cytotoxicity.


[Comparative activity of 6 cephalosporin antibiotics against the causative agents of surgical infection].

Activity of 6 cephalosporanic antibiotics, such as cephaloridin, cephalotin, cephradin, cephacetry1, cephamezin and cephalexin was studied on 200 strains of microorganisms causing purulent infections in surgical patients (Staphylococcus, E. coli, Proteus and Ps. aerugionsa, 50 strains of each organism). The studies showed significant differences in the activity of the above antibiotics against definite species of the pathogenes. The highest activity of the cephalosporins was observed with respect to the clinical strains of staphylococci resistant to such drugs as benzylpenicillin, tetracycline, erythromycin, kanamycin, lincomycin. A significant part of the clinical isolates of gramnegative organisms, i.e. E coli and indol-negative Proteus was characterized by sensitivity to cephalosporins. Among the cephalosporins tested cephaloridin was most active against Staphylococcus, cephacetryl and cephaloridin were most active against E. coli. With respect to the indol-negative Proteus no pronounced advantages of the separate drug were noted. All 6 cephalosporins had low activity against the indol-positive strains of Proteus and all strains of Ps. aeruginosa.


[Effect of R-factors on the sensitivity of Shigella sonnei to nalidixic acid].

Bacteriostatic effect of nalidixic acid was studied by the method of serial dilutions in nutrient agar using 36 antibiotic sensitive strains of Shigella Sonnei and their conjugated substrains carrying separately the following R-factors: R1(TcCmSm) fi-, R2(TcCm) fi+, R3(CmSm) fi-. The above R-factors were isolated from clinical strains of Shigella Sonnei and transferred to the strains studied by means of an intermediate donor of E. coli MF-Nr. The bactericidal effect of nalidixic acid was studied on 9 antibiotic sensitive strains of Shigella Sonnei and their conjugated substrains carrying separately the following episomes: R1(TcCmSm) fi- and R2(TcCm) fi+. It was studied by determination of the number of alive bacteria 24, 48 and 72 hours after their interaction in Hottinger broth with nalidixic acid (400 gamma/ml). It was found that the R-factors did not change the sensitivity of Shigella Sonnei to the bacteriostatic effect of nalidixic acid: the MIC for the R- strains was 4+/- 0.14 gamma/ml, for the substrains with episomes R1(TcCmSm) fi-, R2(TcCm) fi+ and R3(CmSm) fi- it was 4.22 +/- 0.21, 3.88 +/- 0.25 and 4.16 +/- 0.27 gamma/ml respectively. The differences were not statistically reliable (P greater than 0.05) when estimated according to both Student criterion t and Wilcockson criterion for the wto-by-wto conjugated variants. The R-factors inreased the Shigella sensitivity to the bactericidal effect of nalidixic acid: the death rate of the R+-bacteria during the first day was 4--130 times higher than that of the two-by-two conjugated strains of the R-bacteria (P less than 0.01).


[Antibacterial activity of the derivatives of cholic acid (author's transl)].

The synthesis of derivatives of cholic acid with L-lysine and Lysil-lysine with antibacterial activity, is here described. Derivatives with one molecule of lysine show antibacterial activity at 100 mug/ml concentration, while lysil-lysine derivatives, particularly Col-Lys-Lys-NH2-2HCl, are effective also at 25 mug/ml.


[Experimental studies on the pathogenesis of coli enterotoxemia in swine. 3. Effect of coli enterotoxin in weaned piglets following intragastric administration].

The following results were obtained from experiments with 23 clinically intact weaned piglets, aged between five and six weeks (18 animals) or eight weeks (five animals), which had received three intragastric applications of crude enterotoxin (culture filtrate supernatant of Escherichia coli O149:K91(B)K88(L):. 1. Twelve animals (52 per cent) responded to enterotoxin application by temporary outbreaks of diarrhoea (1-8.5 hours) following differentiated latencies (2.5-10 hours). No diarrhoea was recorded from eleven piglets (48%) which had received the same doses of enterotoxin. 2. No signs of a systemic disease were clinically recordable after enterotoxin administration from 22 (96%) animals, no matter whether diarrhoea had developed or not. Respiration, temperature, heart rate, and haematological values were unchanged. Feed and water intake were normal. No exsicosis was observed. All animals exhibited lively behaviours and activity. The conclusion drawn regarding the pathogenesis of the gastrointestinal form of coli-enterotoxaemia, with reference to the authors' own earlier findings, is that in this disease parenteral endotoxin effects (following endotoxin resorption) seem to coincide with enteral enterotoxin effects.


[Effect of acetylsalicylic acid on experimentally induced endotoxin reactions in swine].

The time and severity of clinical responses to endotoxin depend on dosage, Administration of acetylsalicyclic acid and Indometacin prior to endotoxin application may delay or moderate the clinical phenomena that are likely to result from certain endotoxin amounts.


[On the salmonellosis. Data, considerations and operative indications (author's transl)].

The Authors expose data of 14317 proofs on the salmonellosis and propose a new method of struggle and a concentration of the data by provice laboratories.


[In vitro culture of human tumours and individual antineoplastic drug sensivity (author's transl)].

The paper summarizes preparations of cell suspensions (mechanical, fermentative, by chemical agents) and from explant cultures. Several techniques of cell and tissue culture and determination of cell damage are described. The use of these techniques and the evaluation for individual testing of antineoplastic drug sensitivity are discussed.


[Antibacterial activity of the derivatives of dehydro-and deoxy-colic acids (author's transl)].

The synthesis of derivatives of dehydro-and deoxy-colic acids with L-lysine and Lysil-lysine with antibacterial activity, is here described. Results show no antibacterial activity of dehydrocolic acid derivatives, while deoxycol-lys-OH-HCl, and particularly deoxycol-lys-NH2-2HCl, seem to be very effective on Gram-positive bacteria at 5 mug/ml, and on Gram-negatives at 25 mug/ml.


[A simplified micromethod for the measurement of leukocyte candidacidal activity (author's transl)].

A technicall simple micromethod for the assessment of leukocyte candidacidal activity is described. It is based on the alterations in Giemsa staining characteristics which Candida albicans cells develop when ingested by glass-adhering phagocytes. This method, which requires small quantities of whole blood and produces reliable results, may be of promising clinical usefulness for detecting primary and secondary phagocyte candidacidal defects in patients with chronic or recurrent localized and systemic candidiasis.


The distribution of nerves in human deciduous and permanent teeth.

Human permanent teeth without caries, obtained from 10-16 year old males and females and noncarious human deciduous teeth in which roots remained intact or were only poorly resorbed, were studied histologically. The distribution of sensory nerves in deciduous teeth were compared with that in permanent teeth by means of the silver-nitrate technique. 1. In radicular pulp, the sensory nerve fiber bundles accompany blood vessels in the axial area and several nerve single-fibers occur in the peripheral area of the pulp. 2. The subodontoblastic nerve plexus is formed in or beneath the cell-rich zone of the coronal pulp, and further, the marginal nerve plexus is built up near the pulpo-predentinal border. 3. The nerve fibers entering the predentin can be classified into 3 types by their courses. In the first type, nerve fibers pass directly toward the calcification front along the dentinal tubules in the predentin. In the second type, nerve fibers run obliquely or transversely in the predentin. The transversal fibers form a plexus-like structure by dividing and interlacing at various levels of predentin. The third type nerve fibers pass along the dentinal tubules in the predentin and, after reaching the predentino-dentinal border, reverse the odontoblast layer, thus forming a looped course. 4. There is no essential difference between the nerve supply in the deciduous and in the permanent teeth, but the nerves in the deciduous teeth are less dense in distribution and lower in amount than in the permanent teeth. Moreover, a typical marginal nerve plexus, which occurs constantly in the permanent teeth, is only occasionally found in the deciduous teeth; and no nerve fiber was observed to penetrate into the calcified dentin in the deciduous teeth. This finding seems to account for the fact that the deciduous teeth are less sensitive than their permanent successors.


[Relationship between the epithelium and the stroma of the small-intestinal mucosa during antigenic stimulation].

The state of cells and intercellular structures, as well as the pattern of interaction between the epithelium and the stroma of the small intestine mucosa following their exposure to microbic toxins were studied in experiments on rabbits using histological, histochemical and immunofluorescent methods. It was established that the immuno-barrier function of the intestine was implemented by the brush border, epithelial cells, their basal membrane, fibres and cells of lamina propia of the mucosa. Damage of the epithelial lining of the mucosa was accompanied by intensification of immunological processes in its stroma, which in the preliminary immunized animals contributed to an increase in the resistance of the epithelial lining to damaging factors of the lumen of the intestine. The lymphoid infiltration of the epithelium of the intestine mucosa represented a manifestation of immunological processes constantly proceeding therein. The epithelial basal membrane which fixed on its surface immunoglobulins coming from lamina propia, retained antigens passing through it from the lumen of the intestine into the thickness of the mucosa's stroma.


[Diabetic fetopathy].

Studies of the endocrine system, internal organs and vessels of the microcirculatory bed were carried out in infants whose mothers suffered from diabetes mellitus. It was established that late diabetic fetopathy was essentially fetal diabetes developed against the background of relative insufficiency of insulin due to overstrain and depletion of the insular apparatus of the fetus. Fetal diabetes was characterized by generalized microangiopathy in the development of which a leading role belonged to hypercorticoidism.


[Comparative study of the effect of inhibitors of monoamine oxidase and ftorafur on the growth of de-differentiated astrocytoma].

To evaluate the possible antitumour effect of intensified deposition of serotonin in the region of localization of the tumour caused by a pharmacological preparation studies of the effect of inhibitors of monoamine oxidase transamine and N2N2-dibenzylhydrazide of DL-malic acid on rat's cerebellum tumour de-differentiated by astrocytoma (strain No 101/12) were carried out. The effect of inhibitors of monoamine oxidase was compared with that of antiblastic preparation of phthorafur. Differences in the mechanisms of action of pharmacological agents referred to above are shown. It was established that inhibitors of monoamine oxidase administered against the background of the developing tumour caused a considerable reduction in its weight and prononced dystrophic and necrotic changes.


[Interpretation of the results of various histochemical reactions used in pathological anatomy].

Some approaches to correct interpretation of indices of histochemical reactions most often used in pathologo-anatomic investigations are analysed on the basis of the author's personal observations and literature data. It is shown that direct interpretation of results of histochemical reactions according to the conventional scheme (negative reaction--the absence of the substrate in question, low-positive reaction--a low content, and highly positive reaction--a high content) is not always justifiable. One and the same histochemical phenomenon may have different meanings and reflect various functional states of the structure under study. To be able to reveal mechanisms underlying the changes in histochemical indices in experimental material and to determine the significance of this fact in every specific case, one should use a specially selected set of various histochemical and other research methods allowing the possibility of checking and correcting the indices obtained with the help of each of them.


Reaction of human smooth muscle autoantibody with foetal glial cells and their precursors.

Tissue culture monolayers of dissociated human and rat embryonic brains were examined by indirect immunoflurescence with human serum containing smooth muscle antibody. Flat, epithelioid cells showed staining of a fine, filamentous network in the cell body while multipolar cells showed diffuse cytoplasmic fluorescence of the cell body and processes. Both cell types were identified as glial cells by silver stains. Specificity of the immunofluorescent staining reaction was established by failure to obtain staining with normal serum, with smooth muscle antibody serum neutralized by homogenates of smooth muscle or by extracts contining actin-like protein derived from smooth muscle. Reacitivity of of embryonic glial cells with smooth muscle antibody indicates the presence of actin-like proteins which are probably located in cytoplasmic microfilaments.


Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in pateints with essential hypertension.

Plasma renin activity (PRA), supine, erect and post-frusemide (1 mg/kg IV) was studied in 51 patients with previously untreated essential hypertension and their age- and sex-matched normotensive controls. Supine PRA, and the rise in PRA in response to the erect posture and frusemide, were significantly less in hypertensives compared to controls. When the hypertensives were arbitrarily divided into lower, mid, and upper subgroups according to supine PRA, the renin responsiveness was similar in each subgroup but significantly less in hypertensives compared to controls, subdivided in the same way. This does not support the existence of a separate "low renin" subgroup. The low supine PRA and reduced response to stimulation appears to be a feature of patients with essential hypertension. Thirty-nine of these hypertensives entered a double-blind cross-over drug trial of oxprenolol, methyldopa and spironolactone. All three drugs were equally effective in lowering the systolic and diastolic blood pressures in all three renin subgroups. Spironolactone caused a greater fall in systolic pressure in the lower renin group than in the other groups. Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side-effects compared to 13% on spironolacone and 29% on methyldopa.


Thermal inactivation of cholera phages.

Thermal inactivation of seven cholera phages have been tested over the temperature range between 50 degrees to 70 degrees C. It was found that the phages vary widely in their heat sensitivity, Mukerjee's phages III being the most sensitive of the whole group. With all the phages over the temperature range studies, the inactivation curve seem to follow the pattern of virus thermal inactivation in general, the inactivation proceeding initially at a rapid rate, which in about 15 minutes time, gradually changes to a slower rate, each component tending to follow kinetics of the first order. The difficulty of explaining this phenomenon on the basis of population heterogeneity has been discussed.


Double-blind comparison of clozapine with chlorpromazine in acute schizophrenic illness.

Double Blind comparative trial of a new dibenzodiazepine derivative Clozapine (Leponex) with Chlorpromazine was conducted in the treatment of acute schizophrenic illness over a 6 week period. Factor Analysis of ratings in 9 matched pairs indicates that Clozapine, at 300 mg. per day, is comparable in efficacy to Chlorpromazine in all factors except "Irritability" for which Clozapine appears to be superior. Illness severity and Global Change ratings in all patients showed that Clozapine is more effective in producting a shift towards improvement at the end of 6 weeks. Major side effects reported in Clozapine confirmed sedation and hypersalivation as consistent problems and presence of rigidity and tremor (extra-pyramidal) being at variance with other studies.


Adhesion of cholera phage to glass surfaces at high inactivation temperatures.

Decimal dilutions of cholera phage heated in test tubes at the temperature range of 65 degrees to 70 degrees showed an erratic behaviour in that the residual counts had no relationship to the quantity of phage originally present in the tubes. If the contents of the heated tubes were decanted off and the empty tubes washed repeatedly with broth, the recovery of phage from successive washings of the tubes was much higher than what would be expected on the basis of the simple dilution effect of washings. The data presented indicate that the heating causes loose adhesion of phage to the wall of the glass tubes from where they can be detached by washing or shaking. The facts that E. coli phage T1 and also cholera phages tested with two different broths have given similar results, suggest that some general property of the phage itself is responsible for the phenomenon observed. The phenomenon appears to be different from the adsorption of phage to glass filters at lower temperature range described by earlier workers.


Evaluation of a cooperative clinical study of the cytostatic agent ifosfamide.

In cooperative studies performed in 21 German clinics, the new cytostatic agent 3-(2-chloroethyl)-2-[(2-chloroethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (ifosfamide; trade name: Holoxan) was administered as massive-dose treatment. The studies aimed at confirming the results obtained in pharmacological and Phase I clinical trials with a fractionated administration of ifosfamide on a large scale. The study was carried out in 390 patients suffering from various malignant conditions. The majority of patients had had pretreatment without response or were admitted at an advanced stage of disease. Despite this negative selection, 25.5% of the patients showed an initial full remission and 42.3% partial remission; in 32.2% of the patients, reduction of the tumour signs by at least 50% was not attained. After an average observation period of 6 1/2 months, 53.8% of the patients were still alive. The study clearly shows the superiority of fractionated administration of ifosfamide when compared to its use as a single administration. In addition, the rates of remission and survival, and of survival times, were clearly dependent on dosage, independent of the tumour type. A daily dosage of 50 to 60 mg/kg ifosfamide on 5 consecutive days produced the best results. In spite of the fact that ifosfamide was not always given at optimum dosage, it proved to be definitely superior to conventional chemotherapy in testicular tumours, particularly teratomas and also in hypernephromas. Retrospective comparison with results of conventional chemotherapy for ovarian, bronchial and mammary cancer has shown ifosfamide to produce the same therapeutic effect in these tumour types. In this study group, leukopenia was not regarded as a limiting factor to the administration of ifosfamide. Side effects in the efferent urinary tract, particularly cystitis, were controlled with adequate preventive measures.


Effect of ethyl apovincaminate on the cerebral circulation. Serial angiography and regional cerebral circulation studies in neurosurgical patients.

The effect of ethyl apovincaminate (RGH-4405, Cavinton) on the cerebral circulation has been studied with two methods in a series of neurosurgical patients. Regional circulation was studied with the H2 clearance method in five patients in whom deep electrodes were lodged in various cerebral structures with stereotactic surgery performed for the underlying disease. In connection with serial angiography of 25 patients 10 mg Cavinton was injected i.v.; circulation time of the contrast medium, arterial circulation time, changes of normal and pathological filling were appraised. Registered 15 min after administration, regional circulation showed significant increase, but slight increase was demonstrable in every structure investigated. The change was more marked in two elderly patients over 60 years. In eight cases of serial angiography marked difference was seen in filling by normal and pathological vessels on Cavinton effect; arterial circulation time changed in three cases, contrast medium circulation time did not in any of the cases. The most marked changes occurred in three cases of cerebral vascular disease. In two cases of glioma vascularization of the tumour was visualized by Cavinton.


Radiocirculographic study of the effect of ethyl apovincaminate on the cerebral circulation.

The effect of ethyl apovincaminate (RGH-4405, Cavinton) on cerebral circulation has been studied with radiocirculography (rc) in 12 healthy individuals and 17 patients suffering from cerebrovascular diseases. It was shown that acute Cavinton effect produced prolongation of circulation time both in healthy individuals and in more than half of our patients. Shortening of circulation time was observed in one case. On long-term Cavinton treatment circulation time was prolonged in 7 cases, not changed in 7, while in 3 cases it was shortened. The circulation times measured by rc did not reflect changes in the clinical picture.


[The 32P-incorporation into nucleic acids and adenosine phosphates of the rat brain after acute and chronic influence of meclofenoxate (author's transl)].

Beta-Dimethylaminoethyl-p-chlorophenoxyacetate hydrochloride (meclofenoxate, Helfergin) was adminstered orally in dosages of 300 mg/kg 3 times during an 18-h period. The incorporation rate of the total and cytoplasmic RNA as well as of ATP, ADP and AMP decreased. Contradictory results were obtained after a 16-day treatment with orally 300 mg/kg per day: while the 32P-incorporation rate of the cytoplasmic RNA and the 3 adenosine phosphates increased, the nuclear RNA showed a correspondent diminishing. No changes of the ATP content could be observed in any group. The differences between the acute and chronic experiments could be explained by a different excitation of the animals and by the very different dosages. The increased 32P-incorporation into the cytoplasmic and into the adenosine phosphates in the chronic experiments are explained by a stimulation of the pentose phosphate shunt which yields mainly the phosphate group for the synthesis of AMP.


[Treatment of hyperlipemia and hyperuricemia with 2-acetamidoethyl-(4-chlorophenyl)-(3-trifluoromethylphenoxy)-acetate (halofenate), a derivative of clofibrate].

23 patients with hyperlipidemia and hyperuricemia received acetamidoethyl-(4-chlorophenyl)-(trifluoromethylphenoxy)-acetate (halofenate), a clofibrate derivative, and probenecid or probenecid and placebo over 36 weeks following a placebo period of 6 weeks. Halofenate compared with probenecid lowered elevated serum uric acid levels satisfactorily to a therapeutic level between 5 and 6 mg/100 ml. Serum triglyceride levels were not always lowered sufficiently, serum cholesterol levels were not influenced.


[Treatment of irritable colon. A multicenter placebo-controlled double-blind study in general practice].

The effect of Asa foetida (0.1% alcoholic dilution) and a combination of Asa foetida and Nux vomica (0.01% alcoholic dilution) was tested in a multicenter placebo-controlled double-blind trial. Both groups with active medication differed trivially but showed a marked superiority to the placebo group. The differences, however, just miss the conventional 5%-level of statistical significance. For the interpretation of this result it must be considered that only about half of the total of patients could be reached who in the planning phase of the study had been regarded necessary for a statistical confirmation of a therapeutic effect. The diagnosis "Colon irritabile" is discussed in its historical context and the psychological structure of the patient sample is described by means of the scores of a standard personal inventory test (FPI). The trial shows that it is possible to obtain objective results on the basis of the patients' judgment (rating scales with low information content).


The effect of dioxyphenylalanine (DOPA), amides and some potential sources of energy on the multiplication of Mycobacterium leprae.

The multiplication of 2 out of 3 M. leprae strains on a medium containing substances from digested non-acid-fast microorganisms or even free of them was significally promoted to D-3,4-dihydroxyphenylalanine (DOPA). The following organic substances exerted growth-promoting effects on several strains: 0.02-0.10% concentrations of succinate greater than fumarate greater than alpha-ketoglutarate and acetate greater than glycerol; 0.2% concentrations of citrate and pyruvate greater than isonicotinamide and benzamide greater than lecithin. 0.5% concentrations of oleate greater than citrate greater than pyruvate greater than acetate greater than fumarate greater than succinate; 5.0% concentrations of butanol and butandiol greater than propanol greater than sorbitol greater than ethanol. However, these effects were variable and strains of various origins acted differently. On media containing DOPA, malachite-green (MG) and at least 0.12 x 10(6) microorganisms/ml the following oxidation-reduction reaction was observed: DOPA was oxidized to a brown compound and malachite-green reduced to an almost colourless product. Consequently, the blue-colour of the cultures turned from blue to brown. This DOPA-MG reaction and the inability to grow on conventional media were used for the identification of 10 cultures (inocula directly from patients) as M. leprae, while a DOPA-MG negative patient-strain grew on media employed for cultivable mycobacteria and was not identical with M. leprae, as proved by the foot-pad test in mice.


Isoantibodies to human exocrine pancreas and endothelium.

A cytoplasmic immunofluorescence of some human pancreatic exocrine cells was obtained in 19.2% of 270 patient undiluted sera and confirmed in 20.4% of 98 healthy controls. No relation was found with clinical disorders or autoantibodies. This reaction was always associated with human endothelial antibodies and both were clearly related to high titre "incomplete" IgG anti-A group isoagglutinins.


[Modifications of B lymphocyte membrane markers in patients with osteosarcoma].

A study was performed on the B lymphocyte membrane markers in patients with osteosarcoma. The findings obtained would indicated apparently normal cell function conditions (intracytoplasmic membrane immunofluorescence, PWM lymphocyte blastogenesis) and a marked cytotoxic lymphocyte drop ("killer" lymphocytes: EA rosettes).


Leukocyte inhibiting factor (LIF) production from human lymphocytes stimulated by bacterial lipopolysaccharides.

Leukocyte inhibiting factor (LIF) release from lymphocytes cultures stimulated by bacterial lipopolysaccharides (LPS) has been investigated. Human lymphocytes cultured in the presence of E, coli or S. enteritidis LPS were able to release in the supernatants a substance with the following properties: a) same elution pattern of Bovine Serum Albumin (MW 69000) when filtered on Sephadex G-100; b) it migrates on disc electrophoresis a an albumin; c) not dialyzable; d) not cytotoxic; e) inhibition of polymorphonuclear cells migration in agarose plates; f) heat stability at 56 degrees C for 30'. This substance could be likely identified as LIF.


Platelet-endotoxin interaction: a review.

The studies reviewed in the present manuscript outline the effects of bacterial endotoxins on human and animal platelets. In animals the endotoxin administration is followed by thrombocytopenia, presence of platelet aggregates in the blood vessels of several organs, appearance of appreciable quantities of serotonin in plasma and increased platelet factor 3 availability. These in vivo effects can readily be explained by the in vitro demonstration that endotoxin aggregates platelets, induces release of vasoactive amines and adenine nucleotides and activates platelet factor 3. There is substantial evidence suggesting that the mechanism of this animal platelet-endotoxin interaction is immunological and complement dependent. In humans thrombocytopenia is frequently observed in endotoxemia as encountered during Gram-negative sepsis indicating that platelets are involved in some of the biological effects endotoxin. In vitro experiments demonstrate that several endotoxin preparations significantly enhance a weak procoagulant activity of human platelets different from platelet factor 3.


Hepatitis B infections in renal transplantied patients.

Multiple serum samples collected from ten renal transplanted patients were examined by means of radioimmunoassay procedures in order to check and quantitate both hepatitis B surface antigen (HBs Ag) and antibody to it (anti-HBs). The anticomplementary activity of serum, levels of serum immunoglobulins and other laboratory parameters were also tested and related to the clinical followup of patients in the pre- and post-operative period, during which they underwent immunosuppressive treatment with azathioprine, methyl-prednisolone and antilymphocyte globulin. The results obtained provided evdence that all subjects under examination either were currently infected or had been previously exposed to hepatitis B virus. Five basic situations could be detected: state of persistent HBs Ag carrier (I) or of persistent positivity for anti-HBs (II) or reinfections (IV) and presence of HBs Ag/anti-HBs immunocomplexes (V). All HBs Ag and anti-HBs-positive sera were ayw subtype, which is typical for hepatitis B virus circulating in Italy.


Respiratory mechanics with constant flow inspiration. A comparison of two measurement techniques.

Resperatory compliance and resistance were measured during positive pressure ventilation in anaesthtized, paralysed dogs. Airway pressures measured during constant-flow inspiration allowed the calculation of pulmonary and chest-wall resistances, and static and non-static compliances. Contiguous studies of dynamic compliance and resistance allowed comparison of the two techniques, and the level of agreement was reasonalble. Cconstant-flow inflation of the lungs allows a simple means of measuring respiratory mechanics, and should be valid for the observation of short-term changes in the apnoeic patient.


[Chloroplast ribosomes].

A brief review of modern concepts on the structure and properties of chloroplast ribosomes is given. An attention is paid to the similarity of 70S chloroplast ribosomes, 80S cytoplasmic ribosomes and ribosomes of prokaryotic type which is interesting from the viewpoint of the origin and evolution of plastids. Problems of rRNA and ribosomal proteins biosynthesis, of biogenesis and functions of chloroplast ribosomes are also considered.


[Simple method for isolation of three DNA-polymerases from E. coli using chromatography on DNA-cellulose].

A simple method for isolation of three DNA-polymerases from E. coli is developed; it is based on properties of the enzymes to bind with single-stranded DNA, fixed on cellulose. DNA-polymerases I, II and III were identified by their relation to templates, ionic strength, heat denaturation and inhibition of the activity with agents which blocked sulfhydryl groups. After purification which included chromatography on DNA-cellulose as well as fractionation with phosphocellulose and gel-filtration through Sephadex G-100, the enzymes were free the endonucleases contamination.


[Biospecific chromatography of acid proteinases. The role of ionic and hydrophobic interactions].

Pepsin chromatography was studied on peptide ligand sorbents, differing in the length of the polypeptide chains, ionogenic groups and the nature of hydrophobic side groups. Pepsin sorption was found to be dependent of a specific interaction of the substrate analogs with the enzyme and ionic interactions with the matrix and ionogenic groups of the ligand. Non-specific hydrophobic interactions of the enzyme and the ligand have little effect on the sorption. Efficient methods for the isolation of pepsin and separation of the mixture of bovine chymosin and pepsin are described.


Ultrastructural localization of IgA globulins in normal and coeliac intestinal mucosa using immunoenzymatic methods.

Using peroxidase-labelled antibodies, the ultrastructural localization of IgA immunoglobulins in duodenojejunal biopsies from children with active coeliac disease was investigated. Satisfactory penetration of conjugates was achieved by 20 hour-fixation in 4% formaldehyde and 8 hour-incubation of thick frozen sections in the presence of peroxidase-labelled anti-human alpha heavy chain antibody under continuous mild agitation. In normal duodeno-jejunal mucosa, deposits of IgA were observed at the ultrastructural level in the rough endoplasmic reticulum and the perinuclear space of plasma cells and on lateral cell membranes of villous and crypt epithelial cells. In coeliac mucosa, immuno-electron microscopic studies confirmed the increased cell density of IgA immunocytes and revealed heavy deposits of IgA on the basement membrane of surface epithelial cells and the wall of neighbouring blood vessels.


[Use of autologous bone marrow taken from a shielded area at different times after irradiation].

It was shown that in X-irradiation of rats in the absolute lethal dose (850 R) shielding of the shank saved 32% of the animals from death. Bone marrow autotransplantation from the shielded portion immediately after the irradiation augmented the shielding effect considerably. Such protective action of autotransplantation persists if conducted in the course of the first 5 days after the irradiation, but it decreases later (on the 7th-10th day).


[Nature of rec+ revertants isolated from E. coli K-12 cultures mutant with regard to gene rec A].

The nature of Rec+ revertants isolated from the E. coli K-12 AB 2463 recA13 defective strain cultures was ascertained by transduction of the recA gene region into the cells of the JC 2915F- strain with the aid of P1 vira phage. Then the recombination capacity of the transductants was tested by crossing with the JC 158 Hfr strain, and the UV sensitivity of the transductants was determined. Besides, the response of the transductants to the suppression phages was examined. As revealed, the REc+ revertants were characterized by differences in the recA gene. In a number of Rec+ revertants phenotype Rec+ appeared as a result of reverse mutation in this gene from rec- to rec+, whereas in other revertants Rec+ phenotype was due to indirect suppression.


[Isolation of high molecular DNA of plasmids FBI and FBI drd from serologically typed strains of E. coli (AP1 and AP2)].

The authors elaborated a method of isolation of high molecular DNA from the plasmids FB1 and FB1drd of the conditionally pathogenic E. coli strains. Molecular weights of the isolated plasmid DNAs were determined by means of electrophoresis of the DNA fragments in agar gel and sedimentation in the neutral gradient of glycerine concentration.


[Immunohistochemical study of protein S-100 in the neurons and glia of the grape snail (Helix pomatia)].

Indirect Coons' method was used to study the localization of the brain-specific S-100 protein in the neurons and the glia of Helix pomatia. This protein was demonstrated to be present in the cytoplasm of the nerve and glial cells, in the nuclei and the outer membrane of the neurons.


[Cyto-immunological studies of the gonadotropic cells of the human fetus].

The immunicytological analysis of PAE fixed semi-thin sections of pituitary cells (of human fetuses aged 6 to 26 weeks) using immunesera directed against the human total glycoproteic hormones, HCG, LH, FSH and TSH or made specific for the LH, FSH, and TSH beta subunits shows: -- the presence up to the 12th week of only the subunit of the glycoproteic hormones revealed indifférently by our anti total hormones immunesera; -- the apparition of the betaTSH subunits at the 13th week, characterizing the differentiation of the thyrotrophs; -- the apparition of betaLH and betaFSH subunits on the one and same gonadotropic cell population at the 15th week.


[Immuno-cytologic study of LH-RH cells and fibers in the human fetus].

The application of immunofluorescence and immunoenzymology techniques with an anti LH RH I.S. permitted to reveal neurons and fibers in the human fetal hypothalamus from the 13th week up to birth. The morphology and dispersion areas of the neurons in the mediobassal, premammillary and anterior hypothalamus (lamina terminalis and its surroundings and the septum) as well as the direction and the destination of the immuno-reactive fibers of the hypothalamo infundibular tract have been described. These fibers are in contact with the capillaries of the Mantelplexus before and after the apparition of the intra-eminential loops at the 16th week. The general topography of the LH RH peptidergic system in the human fetus can be compared with the topography of other adult primates. The role of this system in the maturation and the control of gonadotropic cells is evoked.


[There is only 1 type of A cells in the islands of Langerhans of the pancreas].

Differences of A cell reactions in Langerhans islets can be explained by variations of the activity of a same cell. Resting of this cell by injection of glucagone or glucose makes it argyrophilic and abolishes tryptophan reaction. Stimulation of A cells by fasting or injection of insulin suppresses argyrophilism and makes the tryptophane reaction positive. A1 and A2 cells cannot be opposed. Variations of glucagone production explains diversity of the reactions in A cells.


Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer.

Tamoxifen (NSC-180973), a synthetic antiestrogen, was studied for efficacy and toxicity in patients with metastatic breast adenocarcinoma. Two dose levels were used, 10 mg bid and 15 mg/m2 bid, in separate groups. In the 10-mg bid dosage group, 30 of the 31 patients were considered evaluable for efficacy. Five complete and 11 partial responses were recorded, for an overall response rate of 53%. In the 15-mg/m2 bid dosage group, 44 of the 45 patients were considered evaluable for efficacy. Three complete and 16 partial responses were recorded, for an overall response rate of 43%. All 76 patients were evaluated for toxicity. Side effects were generally mild, consisting mostly of hot flushes, transient leukopenia, transient thrombocytopenia, nausea, and fluid retention. A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the test as a means to select patients for tamoxifen treatment. The conclusion from this study is that tamoxifen used as a single agent is an effective drug with minimal toxicity for treatment of metastatic breast adenocarcinoma.


The enzyme-linked immunosorbent assay (ELISA).

The enzyme-linked immunosorbent assay "ELISA" developed in recent years represents a significant addition to existing serological tools. Encouraging preliminary results obtained through its application to a number of parasitic diseases during the last two years indicate the value of further investigations and trials which will permit a true evaluation.Although the technique is easy to perform and quite sensitive, there are certain problems to be solved before it becomes widely usable. In the present Memorandum the technical details are given and the advantages and shortcomings of the procedure are discussed. Present applications and future prospects are reviewed.


Parallel evaluation of serological tests applied in african trypanosomiasis: a WHO collaborative study.

Previously, the most commonly used serological tests for the indirect diagnosis of African trypanosomiasis were the indirect fluorescent antibody test, immunodiffusion test, and the determination of IgM levels in serum and cerebrospinal fluid. Recently, the capillary passive haemagglutination test and the enzyme-linked immunosorbent assay (ELISA) have been used in diagnosing trypanosomiasis. However, a parallel evaluation was needed to indicate the comparative diagnostic value of these various serological tests. A double-blind study conducted by WHO with the collaboration of three European and four African laboratories using well-documented serum samples provides a reasonable basis for determining in parallel the sensitivities of the various techniques.


Preliminary studies of artificial immunization of rats against Plasmodium berghei and adoptive transfer of this immunity by splenic T and T + B cells.

Protective T lymphocyte and T+B lymphocyte responses in rats artificially immunized against P. berghei have been demonstrated by adoptive transfer. The techniques used could be developed for detailed analysis of protective lymphocyte responses generated by various methods of immunization, and their relationship to immunity.


Comparative study of reactions and serological response to cholera vaccines in a controlled field trial conducted in the USSR.

This article presents the results of a comparative study of the reactogenicity and the serological response induced by a number of cholera vaccines. Conducted in the USSR on 998 adults aged 18 years and over, the study covered whole-cell heat-killed and formalin-inactivated cholera vaccines, whole-cell heat-killed El Tor vaccine, and a new partially purified toxoid preparation proposed for the immunoprophylaxis of cholera-all administered by hypodermic syringe or jet injector. The most marked reactions were found to occur with the formalin-inactivated cholera vaccine and the least marked with the partially purified toxoid. It was also established that the toxoid was no less effective than the whole-cell vaccine in inducing the intense production of antibodies to the Inaba serotype and, in somewhat lesser degree, to the Ogawa serotype of the El Tor vibrio. It was the only preparation to give rise to intense production of specific antitoxins in 95-98% of cases. The reactions to and immunogenic properties of the cholera vaccines did not show any statistically significant difference whether administered by hypodermic syringe or by jet injector.


Present knowledge of immunization against tuberculosis.

This is a selective review, which, after recalling some immunological aspects, analyses the present knowledge on the protective efficacy of BCG vaccination, the vaccination reactions and complications that may be observed, and current methods of vaccine production and control. As regards the application of BCG vaccination, particular attention is given to dosage and vaccination techniques, direct and simultaneous vaccination, and revaccination. Finally, the evaluation of BCG vaccination programmes is briefly discussed.


The epidemiology of infertility: a review with particular reference to sub-Saharan Africa.

The problem of infertility, with particular reference to Africa south of the Sahara, is reviewed. In many areas, up to 40% of women are reported to have completed their reproductive years without bearing a child. The condition is widely distributed, but also often localized in pockets corresponding to geographical or tribal units. Most available demographic data provide estimates of childlessness but it is not sufficient to define the problem in terms of primary and secondary infertility, pregnancy wastage, and infant and child mortality. The major underlying cause for the high levels of infertility appears to be the sequelae of Neisseria gonorrhoeae infection in both men and women, manifested as obstructive azoospermia and tubal occlusion. Other infections, such as those that may follow abortion or delivery, or systemic infections, may be important in some areas. The available data suggest that different patterns of infertility and pregnancy wastage, and different etiological agents and processes, contribute to the problem of infertility in the different areas. The need for a systematic, standardized research approach in several areas is clearly indicated.


Hitler: a neurohistorical formulation.

It is hypothesized that Adolf Hitler suffered from a constitutional left-side weakness that allowed his cerebral hemisphere to exert a strong influence on his thought and behavior. Physical characteristics such as trembling of the left extremities, lack of a left testicle, and tendency to exhibit leftward eye movements are interpreted as supportive of the hypothesis. Right hemisphere dominance is consistent with a number of Hitler's personal traits such as praise of the irrational, automatic speech, auditory hallucinations, hypochondriasis, uncontrolled rages, and spatial and musical interests. Right hemisphere dominated thought may also have formed a basis for his two basic political policies: Lebensraum and anti-Semitism.


[Heidegger and modern research].

The unity of thought content and its corresponding object in reality - an unsolved problem till now - is explicated in a gestaltqualitative-neurobiological way. This gives the opportunity of analyzing Heidegger's concepts of truth as "lichtendes Bergen", of "Gestimmtheit" and "Angst", of life and death and "Dasein" in an actualgenetic framework. In opposition to Heidegger's postulation of the non-thinking modern science it results that Heidegger's conceptualization of thought contents is emphasizing primarily the aspects of unity and constancy versus division of unity and complexity by the modern science.


Is the antioxidant butylated hydroxytoluene a depigmenting agent in man?

Because of the allegation that butylated hydroxytoluene produced depigmentation in man, a prospective study was performed. Sixteen adult darkly pigmented males received daily occlusive applications for 60 days. Depigmentation was not observed.


Etiological factors in the denture sore mouth syndrome: an investigation of 24 patients.

A total of 24 patients, 19 women and 5 men, complaining of denture sore mouth, were studied. In 18 persons complaints had started with the wearing of the first prosthesis. In 12 patients complaints started within the first half-hour of contact. Several prostheses had been manufactured for most patients without any beneficial result. The following investigations were performed: a. Mechanical factors were evaluated; b. Temperature was measured beneath the prosthetic denture; c. Yeast cultures were made; d. Patch tests with possible allergens were performed on the buccal mucosa and on the skin of the back. In all these investigations, there were no significant differences with the results obtained in a control group. Finally, the influence of possible psychosomatic factors is considered.


Severe slowly resolving heroin-induced pulmonary edema.

Severe heroin-induced pulmonary edema occurred in three previously healthy young men. Adequate arterial PO2 could only be achieved with the use of positive endexpiratory pressure (PEEP). Recovery was characterized by the gradual clearing of the pulmonary infiltrates and a gradual lessening of the severe restrictive ventilatory defects over many weeks. Concomitant aspiration of gastric acid was thought to be the explanation for the severity of these cases. In cases such as these, initial vigorous therapy, including PEEP for hypoxia, corticosteroids for possible aspiration and volume replacement for hypotension, is recommended.


Medical treatment for spasticity in children with cerebral palsy.

Dantrium and Valium were compared in 22 children manifesting various degrees of spasticity. Treatment brought definite improvement in spasticity and in activities of daily living in 20 of the 22 patients. The two-part double-blind study showed that Dantrium was most effective in nine and Valium in seven cases. In four cases the drugs appeared to be equally beneficial. The combination of Dantrium and Valium appeared to be more effective in eight patients than either medication along, the greatest effect being seen in the upper extremities and about the hip joints. Patients on placebo showed no significant change. Side effects of lethargy and drowsiness on the combination were not bothersome after a short period of acclimation. The results indicate that the spasticity of cerebral palsy can be relieved significantly, and that the combination of peripherally and centrally acting agents is more beneficial than either medication alone.


[Early changes in transplants of lung organ cultures treated with several polycyclic hydrocarbons].

The authors examined the early changes in transplants from lung organ cultures treated with 64/ml of 3,4-benzpirene and 4 mg/ml of 20-methylholantrene. The bronchial cycst represented the most significant changes on the control transplants. In the transplants treated with two cancerogens there were several kinds of changes increasing with the advancement of the course of the transplantation-hyperplasia of lymphocytes, hyperplasia of the bronchial epithelium, gland-like structures and bronchial cysts. Besides this there were also tumours at the end of the third month in the transplants, treated with 20-methylcholantrene--in one of the transplants there was adenom and in another-carcinoma.


[Development of delayed hypersensitivity in rats with streptococcal myocarditis and arthritis].

The authors induced streptococcal myocarditis and arthritis in rats by means of three methods. They proved the development of late hypersensitivity in the experimental animals by determining skin sensitivity and by transfer of lymphocytes and leucocytes from animals with myocarditis and arthritis of healthy recipients. The maximal percentage of animals with late hypersensitivity was obtained in the groups, in whom leucocytes from rats with arthritis were transfered. The arthritis was caused by administration of alive streptococcal culture (at 14 days intervals) three times. Recipients of leucocytes from rats with adjuvant arthritis and streptococci were next. The smallest percentage of successful transfer of late hypersensitivity was obtained in recipients of leucocytes, isolated from animals with streptococcal arthritis and myocarditis, induced after single contamination with alive streptococcal culture.


[Acute diazepam poisoning in experimental animals and the effect of centrophenoxine on it].

The author carried out studies on 20 white rats (weight of 150 gm) and 40 white mice (weight of 20 gm), equal number of both sexes administering oraly respective doses of diazepam in a dose of 650 mg/body weight and 620 mg/body weight, having in mind the LD50 determined by him (730 mg/body weight for rats and 535 mg/body weight for mice). In this way he induced acute intoxication especially gravely manifested in mice. After two hours, when the rats were in a comatous state, he introduced oraly centrophenoxine in a dose of 50 mg/body weight in half of the animals, but the other animals remained as controls. Mice succumed to coma after two and a half hours. In half of them he administered oraly centrophenoxine in a boose of 50 mg/body weight, which dose was repeated after two hours, but the remaining animals remained as controls. All rats, treated with centrophenoxine, remained alive and recovered quickly from the intoxication while four of the control animals died, but in the remaining alive animals the recovery was very slow. Only four of the mice treated with centrophenoxine died, but in the remaining alive mice the signs of intoxication disappeared quickly. Twelve of the control animals died, but the remaining animals recovered very quickly. The obtained results corresponded to the favourable effect of centophenoxine, observed by us, in treatment of persons, intoxicated by diazepam.


Some aspects on pituitary function in human and rat anovulatory cycles.

To investigate the anterior pituitary function of human anovulatory cycles, hormonal environments were analyzed in an animal experimental model and women with anovulatory cycles. A specific antiserum to hypothalamic luteinizing hormone-releasing factor (LH-RF) was prepared in rabbits. Intravenous injection of 1.0 ml of this antiserum to 4-day cycling female rats on the proestrous day blocked ovulation in the following cycles without changing regular estrous cycles on vaginal smear. Thus experimental anovulatory cycles were induced in antiLH-RF serum-treated rats. In this experimental model, LH surge on the proestrous evening was blocked but LH and FSH were maintained at the basal levels. In human anovulatory cycles, serum LH and FSH levels were also not significantly reduced except during the period of LH surge, and blood estradiol-17beta levels were similar to the levels of women with normal ovulation. Serum progesterone levels were higher in the normal women after the expected day for ovulation. These data may indicate that the anterior pituitary is able to secrete its gonadotropins without stimulation by LH-RF and this tonic discharge of gonadotropins would maintain the basal levels of ovarian secretion of steroids.


Lack of release of human chorionic gonadotropin by gonadotropin-releasing hormone.

The effects of either single injection or continuous infusion of synthetic Gn-RH on plasma hCG levels were studied in 5 pregnant women (14-38 week gestation). No definite increase of hCG level was seen in all the cases studied. In view of large dosages of Gn-RH used in this study in comparison with its minimum effective dose for the pituitary gonadotropin release, Gn-RH seems unlikely to play a role in hCG secretion during human pregnancy.


Prolactin release by synthetic luteinizing hormone-releasing hormone (LHRH) in thyroidectomized-androgenized adult rats.

Synthetic LHRH, at a dose of 5 mug/kg, induced a marked increase in the serum LH level but a marked decrease in the serum prolactin level when injected iv to normal adult female rats on the day of estrus. In adrogenized adult rats which had been showing persistent estrous vaginal smears, a less marked increase in the serum LH level was shown following injection of LHRH. Prolactin level decreased only slightly in these animals. Control level of serum prolactin in normal estrous and androgenized rats were 4.95 +/- 0.35 and 5.42 +/- 0.65 mIU/ml, respectively. Thyroidectomized-normal cycling rats responded to LHRH with a slight decrease in the serum prolactin level when injected on the day of diestrus. Prolactin level increased, however, 5 min after LHRH injection in thyroidectomized-androgenized adult rats, which were thyroidectomized at the age 4, 6 or 10-12 weeks and have retained a low prolactin level similar to that in the diestrous stage of normal cycling rats thereafter. The present results suggest that regulatory system of prolactin secretion became labile by androgenization and this status led to the release of prolactin by LHRH treatment after thyroidectomy.


Heterozygous effects on cell yield and generation time in Saccharomyces cerevisiae.

The data obtained analyzing generation time, cell yield and their variability in different culture media in diploid strains of Saccharomyces cerevisiae demonstrate the existence of a biochemically determined heterotic effect, that could be of some relevance for the study of yeast population genetics, as well as for the improvement of microbial fermentation processes.


Inhibited hormonal induction of hepatic phosphoenolpyruvate carboxykinase in poly I: treated mice, an endotoxin-like glucocorticoid antagonism.

Corticosteroid induction of mouse hepatic phosphoenolpyruvate carboxykinase was inhibited by prior injection of poly I:C. Mice challenged with a lethal dose of endotoxin 4 h after administration of poly I: C could not be protected by a concurrent injection of hydrocortisone.


Columnar cells of the parietal layer of Bowman's capsule and their relationship with the sexual cycle in normal female mice.

The tubule-like cells (TLC) are present also in the parietal layer of the Bowman's capsule of the renal corpuscles in normal female mice kidney. These cells are morphologically similar to the cells of the proximal convoluted tubule. Further, significant variations of the TLC were present according to the phase of the sexual cycle.


Staphylococcus epidermidis in the circulating blood of normal and thrombocytopenic human subjects: immunological data.

Immunological studies, performed with human sera and rabbit antisera upon some strains of Staph. epidermidis carried in the circulating blood of normal and thrombocytopenic subjects, indicate that the reactivity is very low and almost completely related to antigenic properties common to Staph. aureus.


[A study on serum luteinizing hormone response to luteinizing hormone-releasing hormone iny hyper- and hypothyroidism (author's transl)].

In order to study the mechanism of gonadal dysfunction in patients with abnormal thyroid function, the pituitary luteinizing hormone (LH) response to 200 mug of luteinizing hormone-releasing hormone (LH-RH) was investigated in 20 untreated and 18 treated hyperthyroid patients and in 21 untreated and 8 treated hypothyroid patients in addition to 29 matched control subjects. Serum LH levels were measured by double-antibody radioimmunoassay technique with HLH kit Daiichi. In untreated hyperthyroid men, the slightly elevated mean basal level and the exaggerated mean response to LH-RH of LH were observed, and in treated hyperthyroid men, both values were found to be similar to those of matched control men. Furthermore, in these patients, the maximal increments and the net increments of responses to LH-RH of LH were correlated with serum thyroxine levels and Thyopac-3 values. In most untreated and treated hyperthyroid premenopausal women with and without menstrual disturbances, the basal levels and the responses to LH-RH of LH were similar to those of matched control premenopausal women. In untreated hyperthyroid postmenopausal women, the mean basal level of LH was elevated, although the mean LH response to LH-RH was similar to that of matched control postmenopausal women, and in treated hyperthyroid postmenopausal women, the mean basal level and the mean response to LH-RH of LH were similar to those of matched control postmenopausal women. Furthermore, in these patients, the basal levels were correlated with serum thyroxine levels. In untreated and treated hypothyroid men, the mean basal level and the mean response to LH-RH of LH were similar to those of untreated and treated hyperthyroid postmenopausal women. In most untreated and treated hypothyroid premenopausal women with and without menstrual disturbances, the basal levels were observed to be inconsistent, and the LH responses to LH-RH were similar to those of matched control premenopausal women. In untreated and treated hypothyroid postmenopausal women, the mean basal level and the mean response to LH-RH of LH were similar to those of matched control postmenopausal women. These data indicate that the ability of the pituitary to secrete LH in patients with abnormal thyroid function was augmented in hyper- and hypothyroid men, and augmented in hyper-, but normal in hypothyroid postmenopausal women. Therefore, it is concluded that the cause of gonadal dysfunction at least in the premenopausal women with abnormal thyroid function lies not inside but outside the pituitary gland.


[Orally administered nitroderivates: efficacy and duration of the effects of isosorbide dinitrate (author's transl)].

The effects of 20 mg of orally administered isosorbide dinitrate on 10 patients with stable angina pectoris were studied by means of exercise tests. First, the reproducibility of the angina threshold of each patient was controlled; then the effects after 60, 150 and 210 minutes after administration of the drug and of a placebo, given in a random sequence, were studied. No significant changes of the parameters examined were observed after the placebo. A significant increase of duration of exercise and total amount of work performed before appearance of angina were observed after the drug. These changes were maximal in tests made 60 minutes after administration of the drug, declining thereafter; nevertheless, statistically significant differences from placebo were also observed in tests performed after 150 and 210 minutes. The appearance of ischemic ST changes was retarded by the administration of the drug. Disappearance of pain after interruption of exercise was significantly quicker when compared with the observations made after placebo.


[Evaluation and comparison of five antianginal treatments by means of a bicycle ergometer exercise test (author's transl)].

The antianginal effect of three drugs (isosorbide dinitrate-nifedipine-oxprenolol) and of two drug associations (isosorbide dinitrate-oxprenolol; nifedipine-oxprenolol) was studied in six patients, by means of a bicycle ergometer exercise test. The study was double blind; placebo was also included in the test. Treatments were administered according to the sequence of a 6 X 6 "balanced" latin-square design. After treatment with isosorbide dinitrate and nifedipine a significant delay in the appearance of angina and of signs of electrocardiographic positivity was observed while after treatment with oxprenolol a significant delay was noticed only in the time of appearance of electrocardiographic positivity. On the contrary, placebo did not determine significant changes in the studied parameters. The best results were achieved with the associations oxprenolol-isosorbide dinitrate and oxprenolol-nifedipine. With these treatments, angina appeared during the exercise test in only two patients while the others had to stop the test because of muscular exhaustion; electrocardiographic signs of ischemia did not appear in one patient. The favourable results of the associations oxprenolol-isosorbide dinitrate and oxprenolol-nifedipine can be explained by the pharmacologic effect of these drugs and by their complementary action.


Immunotherapy of human lung cancer with BCG cell-wall skeleton.

Effect of BCG cell-wall skeleton (BCG-CWS) on the recovery of responsiveness of lymphocytes and the survival period was studied in patients with lung cancer. (a) Responsiveness of lymphocytes as demonstrated by proliferative response to phytohemagglutinin (PHA) or microcytotoxicity test with cultured cells of a bronchogenic carcinoma was depressed in the patients at later stages of cancer and it was restored by treatment with BCG-CWS in many of such patients. (b) Survival period of the patients at later stages such as III or IV was prolonged by treatment with BCG-CWS. Such an effect was detected even in the patients with carcinomatous pleuritis. (c) A close correlation was found between the reactivity such as PHA response or cytotoxicity and clinical course of the patients given BCG-CWS. Assay system with PHA response and microcytotoxicity test appears to be reliable in anticipating the prognosis and in following clinical course after the BCG-CWS treatment.


Current clinical problems of intensive husbandry.

The author performs an examination of the concept of pathocenosis, diseases of groups, and the consequences of the continually increasing unification of microbial populations on a world level. Then the current problems of veterinary assistance on intensive farms are examined and discussed with particular reference to the clinical and control aspects.


Vibrio parahaemolyticus: aetiological agent of food poisoning.

After mentioning the principal morphological, cultural, physiological, biochemical, enzyme and serological characteristics of Vibrio parahaemolyticus (a facultative halophilic bacterium and the aetiological agent of food poisoning caused by the consumption of fish products) a description is given of its ecological aspects, geographical distribution, and potential enteropathogenicity for man, with general information on its isolation and identification.


Machine milking: experimental observations on the life of teat-cup liners.

The useful life of neoprene teat-cup liners used in milking machines was determined by physico-mechanical, optical and microbiological studies. The various tests showed that after more than 1,000 hrs' use, that is the milking time plus disinfection time, there were physico-mechanical and biological changes that could have an adverse effect on the health of the udder as a result of a loss of elasticity and a dissemination of mastitis-producing microorganisms (S. agalactiae, S. aureus) which settle in cracks in the surface of the rubber.


Massive homogenous osteo-articular bone grafts. Long term results.

The authors present a long term review of thirty cases of massive homogenous bone grafts carried out at the Istituto Ortopedico Rizzoli between 1967 and 1971. Thirty one of these were either complete or partial diaphyseo- articular grafts. The lesions for which the operations were performed were: twelve giant cell tumours; one Ewing's tumour; two reticulosarcomas; eight osteosarcomas; six chondrosarcomas; one loss of bone substance from trauma, one echinococcosis of the femur and one aneurysmal bone cyst. In some of these cases amputation or disarticulation had been advised but refused by the patient. Follow up three and a half to five years after operation showed complete incorporation of the graft in eight cases, partial incorporation in live, and resorption in four. In the remaining fifteen cases the follow up was terminated by early death, recurrences, infection or intolerance with rejection. In conclusion, the authors recommend that massive osteoarticular homogenous grafts should be confined to the substitution of unicondylar lesions as these offer greater contact with the host bone and therefore a greater possibility of incorporation. The same indications exist in cases involving only diaphyseal substitution where osteogenetic invasion of the graft can occur from both ends. In all the other cases, they recommend either resection arthrodesis or prosthetic replacement.