Cardiac tamponade, constrictive pericarditis and pericardial resection in rheumatoid arthritis.

Four patients with rheumatoid constrictive pericarditis and two patients with rheumatoid cardiac tamponade are presented, and 60 previously reported cases with these two complications are reviewed. Rheumatoid arthritis was moderate to severe in 84% of the patients with cardiac tamponade and in 74% of the patients with constrictive pericarditis. However, both these complications were also seen in patients who had only mild arthritis and in two previously reported cases constrictive pericarditis actually preceded the onset of rheumatoid arthritis. The duration of rheumatoid arthritis had no bearing on the development of these complications. In 75% of patients with cardiac tamponade, and in 66% of cases with constrictive pericarditis, subcutaneous nodules were present. In those cases where the rheumatoid factor was measured it was positive in 92% with cardiac tamponade and in 84% with constrictive pericarditis. In 63% of patients with cardiac tamponade and in 70% of cases with constrictive pericarditis a history of pericardial type of pain was obtained and/or a pericardial rub heard. The diagnosis of cardiac tamponade and constrictive pericarditis was made clinically and in doubtful cases confirmed by cardiac screening and intracardiac pressure recordings. The low sugar content in the pericardial fluid in the absence of infection or malignancy was an important clue to the rheumatoid etiology of the effusion. In the majority of the cases histological appearances of the pericardial tissue showed non-specific fibrous reaction and infiltration with plasma cells and lymphocytes. Only in five of the cases, including one from the present series, were typical rheumatoid granulomatous lesions demonstrated. Treatment with corticosteroids neither prevented the occurrence nor led to amelioration of either cardiac constriction or tamponade. Pericardial resection was life saving, producing both symptomatic and objective involvement of the cardiac function. In the present series of six cases two patients developed aortic incompetence. In one of these it was due to rheumatoid granulomatous valve disease and in the other due to non-specific aortic valvulitis. The combination of constrictive pericarditis and granulomatous aortic valve disease has not been previously recorded.


Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment.

Arginine-induced insulin and glucagon secretion preceding and following clofibrate treatment was studied in 13 patients with endogenous hypertriglyceridemia. A positive correlation was demonstrated between fasting insulin and triglyceride levels and between the fasting insulin/glucagon molar ratio and triglyceride levels. In patients with endogenous hypertriglyceridemia, anginine infusion induced a significantly increased glucagon response with respect to that found in controls. No correlation was found to exist between glucagon and free fatty acids (FFA) or between glucagon and triglyceride levels. The same lack of correlation was found in normal subjects rendered hypertriglyceridemic by means of Intralipid infusion, which did not modify the fasting glucagon-like immunoreactivity (GLI) or the GLI response to arginine. Clofibrate treatment induces a triglyceride reduction (incrementTG) which is correlated with the reduction in the insulin/glucagon molar ration (incrementI/G). After clofibrate treatment there is also a significant reduction in fasting GLI levels and in the insulin response to arginine, and an increase in the glucagon response. Clofibrate could exercise its hypolipidemic effect by modifying the relationship between insulin and glucagon levels.


Metabolism of 3-methylhistidine in man.

The metabolism of L-3-methylhistidine was studied in man using intravenously administered ((14)C)3-methylhistidine. Analysis for expired (14)CO2 for periods up to 2 hr following a single intravenous injection revealed no radioactivity, indicating that this compound is not oxidized in man. Analysis of urine samples for total radioactivity showed that 75% of the administered dose was excreted in 24 hr and 95% in 48 hr. Ion-exchange chromatography of urine samples with monitoring of the column eluated by a flow liquid-scintillation technique showed the presence of only two radioactive peaks. The time taken to elute these peaks was compatible with the major excretory component (95.5%) being ((14)C)3-methylhistidine, accompanied by a small amount (4.5%) in the form of N-acetyl-((14)C)3-methylhistidine. The plasma disappearance curves of ((14)C)3-methylhistidine suggested a half-life of approximately 130 min. The inability ot oxidize 3-methylhistidine and its quantitative excretion as the original compound as well as its N-acetyl derivative is similar to its metabolic fate in the rat and therefore suggests that 3-methylhistidine excretion may provide a reliable measure of actin and myosin turnover in the whole animal or in human subjects.


Studies of thyroid-stimulating hormone binding to bovine thyroid plasma membranes.

131I-TSH prepared by the lactoperoxidase method was used to study the binding of hormone to bovine thyroid plasma membrane. Specific binding was obtained using as little as 0.12 mU/ml 131I-TSH. Half-maximal binding occurred with 17.1 plus or minus 3.5 mU/ml and saturation at approximately 40 mU/ml. Scatchard plot analysis revealed two classes of binding sites, with association constants of 1.1 plus or minus 0.06 x 10(8) M(-1) and 1.4 x 10(7) M(-1) for the high- and low-affinity sites, respectively. Binding of 131I-TSH was linearly related to the amount of thyroid plasma membrane protein. Other polypeptide hormones and prostaglandin E1 did not inhibit specific TSH binding. Identical results were obtained using two TSH preparations of different biologic specific activity. 12.5 mU/ml unlabeled TSH decreased 131I-TSH binding 50%, and 156 mU/ml caused complete inhibition. After equilibrium of 131I-TSH binding was established, maximal displacement was achieved by 120 min using about 300 mU/ml TSH. However, only about one-half of the 131I-TSH was displaced. Although GTP potentiated the stimulation of adenylate cyclase by TSH, it inhibited binding of 131I-TSH. Binding of TSH correlated very well with activation of adenylate cyclase.


Hypercalcemia and tumor-prostaglandins: the VX2 carcinoma model in the rabbit.

The VX2 carcinoma produces profound hypercalcemia (17-22 mg/100 ml) in the rabbit about 3-4 wk after transplantation. A bone resorption-stimulation factor (assayed in vitro with mouse calvaria in culture) has been extracted with diethyl ether from the tumor tissue and from the medium of a clonal strain of VX2 cells grown in culture. Serologic methods reveal that the tumors contain 294 plus or minus 51 ng/g fresh weight (mean plus or minus SE, 25 tumors) of prostaglandin E2 (PGE2), a potent bone resorption-stimulating agent. VX2 cells in culture produce 0.5-3.0 mug PGE2 per mg cell protein per 24 hr. The production of bone resorption-stimulating activity and PGE2 by VX2 cells in culture were both inhibited by indomethacin (100 ng/ml). Tumors from normocalcemic, indomethacin-treated rabbits (10-40 mg/rabbit/24 hr) contained little or no bone resorption-stimulating activity nor PGE2. Tumor-bearing rabbits receiving indomethacin continuously did not develop hypercalcemia, however, following cessation of indomethacin administration, hypercalcemia developed rapidly and was again reversed by reinstitution of indomethacin feeding. In untreated, hypercalcemic, tumor-bearing rabbits, initiation of indomethacin treatment was followed by a rapid return of the plasma calcium to the normal range. Systemic venous plasma from hypercalcemic tumor-bearing plasma contained higher concentrations of PGE2 than plasma from normocalcemic control rabbits. Venous drainage of the tumor contained even higher plasma PGE2 concentrations than systemic venous plasma in hypercalcemic animals; plasma PGE2 concentrations locally and in systemic plasma were unmeasurable (less than 70 pg/ml) in normocalcemic, indomethacin-treated, tumor-bearing rabbits. We conclude that PGE2 is a bone resorption-stimulating factor produced by VX2 tumor cells, and that secretion of PGE2 by the tumor in vivo may well be responsible for the hypercalcemia observed in tumor-bearing rabbits.


Relationship between pacemaker fibrillation thresholds and electrode area.

Energy thresholds for electrical pacing of the heart are lower with small electrodes than with large. Because pacing of the heart during the vulnerable period may produce ventricular fibrillation, it is also pertinent to know if fibrillation threshold is affected by the electrode size. Electrodes of different surface area but of the same material were implanted in 40 dogs and the pacing thresholds were recorded. Ventricular fibrillation was electrically induced by discharging a 2-msec d.c. cathodal pulse of progressively increasing energy into the vulnerable period. It was found that small electrodes required more energy to produce ventricular fibrillation than large electrodes, and the ratio of fibrillation to stimulation threshold was higher for the small-surface-area electrode. The difference between the thresholds and ratios obtained with the various electrodes was statistically significant. A similar experiment was performed in animals with chronically implanted electrodes, producing comparable results. The results indicate that, in regard to pacing and fibrillation thresholds, small electrodes are preferable to large.


Long-term in vivo behavior of a platinum endoauricular-magnesium hybrid battery.

A hybrid bioelectric battery designed for pacemaker feeding was developed and implanted in 15 dogs for a period of 18 or more months. The smooth platinum cathode, set on an intra-cavitary pacing lead, is located in the bloodstream of the right auricle. The anode of pure (99.9 percent) Domal magnesium is placed in the subcutaneous tissue, which is then consumed by a uniform corrosion process. The theoretical consumption for a current output of 200 muA was evaluated according to Faraday's law at 7 g in 9 years; however, the real consumption, taking into account the corrosion phenomenon, is estimated at 14 g in 9 years. This histological tolerance to the magnesium is excellent. The fundamental characteristic of this platinum-magnesium battery is the great reproducibility of the output parameters (voltage, power) and the excellent stability with time, for any chosen platinum surface or load resistance. For an output current of 200 muA, the battery provides an available output power of 100 muW at a reproducible and stable voltage of 0.5 v. This stability is demonstrated in a long-term study on 15 beagles.


The impedance of electrodes used for ventricular defibrillation.

This study has shown that the apparent impedance of both electrode-electrolyte interfaces is small at the current levels used for transchest ventricular defibrillation, making it clear that the appearent impedance appearing between the electrode terminals is largely that of the subject. In addition, it has been shown that for measurement of the impedance of the subject, with low-intensity sinusoidal current, the electrode-electrolyte impedance becomes negligible above 10 kHz and is only slightly affected by the magnitude of the current used to make the measurement.


Instrumentation and examination procedures for a clinical vascular laboratory.

Instrumentation and examination procedures used in the clinical vascular Laboratory of the Massachusetts General Hospital are outlined and recommended for use in other similar laboratories. The arterial system is studied by the analysis of blood flow direction, segmental plethysmography, and systolic pressure measurements obtained at rest and following a measured exercise stress. The effect of induced reactive hyperemia on systolic pressure, obtained by direct intra-arterial measurement, is used to demonstrate the hemodynamic importance of stenotic lesions within the aorto-iliac system. Maximum venous outflow studies are combined with analyses of venous Doppler signals for purposes of screening patients with suspected deep venous thrombosis. The laboratory contributes important objective physiologic information to the examination of the arterial and venous systems. Experience obtained through the evaluationof more than 2500 patients resulted in the development of this recommended program.


An all-plastic double-lumen catheter for continuous blood sampling.

The all-plastic double-lumen catheter described in this paper represents a significant improvement over previously reported catheters. It is used routinely for continuous blood withdrawal in two clinical investigation units and one experimental laboratory in Toronto. No experiments have been terminated due to catheter failure or clot formation and no maximum time limit of its use has been established. In clinical use with adult patients (4), the outer cannula has been kept open overnight with a slow saline drip after 18 hours of use. The same cannula has then been reused the next day for another 16 hours with a new adapter precut to size. Its design enzures that: (1) heparin is mixed with the blood at the site of blood sampling. (2) Blood is never brought into contact with glass or metal. (3) The blood channel is a uniform polyethylene tube with no discontinuities and no junctions, except where it is introduced into the peristaltic pump tube. The overall manufacturing process is simple, and percutaneous insertion is straightforward. Through its use, clotting in the blood withdrawal line and thrombus formations in the blood analyzer are no longer problems to limit the use of techniques requiring continuous blood withdrawal.


A method for measurement of frequency, modulation characteristics and timer accuracy of ultrasonic therapy equipment.

A method is described for measuring the ultrasonic frequency, modulation data, and exposure time of ultrasonic therapy equipment be detection and analysis of the ultrasonic radiation rather than direct measurement of the electrical rf signal. The equipment used in performing these measurements consists of a receiving piezoelectric transducer, ana electron counter/timer designed to accept and process the detected ultrasonic signal, and an oscilloscope.


Rationalization of standards for medical devices--Part 2.

Current practices for preparing standards in general--and standards for medical devices, instruments, and products in particular--are too slow, too expensive, and too cumbersome. There is a need, therefore, for establishing administrative mechanisms to expedite standards preparation. This paper addresses some administrative, conceptual, and methodological aspects of standards preparation and suggests actions that might contribute to improvements in the effectiveness of standards and in the methods of their preparation.


A family with an unusual occupational hazard.

Pneumoconiosis from the carbon-copper-silica rods of film projector arc lamps is a relatively rare disease. There follows a description of a family in which the father and two sons developed radiographic changes after many years working as projectionists in New South Wales.


Cholecystostomy for acute cholecystitis.

During the period from 1963 to 1970, 318 patients were subjected to early operation for acute cholecystitis. Cholecystostomy was performed in 25 cases (7.8 percent). Despite advanced age and associated serious illnesses, cholecystostomy was an effective and definitive method of treatment. Many of these patients are likely to succumb from intercurrent disease before they develop further stones or cholecystitis. A planned cholecystostomy may be the operation of choice for poor-risk patients with acute cholecystitis.


A high-speed hydroplane accident.

This report records the investigation into a high-speed hydroplane accident in which the driver died. He was ejected head first into the water at 117 to 126 ft/sec (80 to 85 mph), suffering brain damage and a fractured skull. Suggestions are made to minimize the effects of these inevitable crashes.


Ruptured abdominal aortic aneurysms presenting to a general hospital.

Fifty-six patients with a ruptured abdominal aortic aneurysm presented to an acute general hospital over six years from 1968 to 1973. Twelve patients died before operation, while 19 of 44 patients (43%) survived replacement of the aneurysm with a Dacron graft. Patients aged under 70 years and not shocked on admission to hospital had the best chance of survival. It is suggested that survival rates can be significantly raised only by a decrease in the time between the onset of symptoms and an operation. A correct diagnosis may be made more often if it is remembered that the classical clinical triad of pain, shock and an abdominal mass is seen is less than half of the cases presenting to hospital.


The detection of glucose-6-phosphate dehydrogenase deficiency in mediterraneans by comparative quantitative enzyme electrophoresis.

Glucose-6-phosphate dehydrogenase (G6PD) can be easily isolated from haemolysates by cellulose acetate electrophoresis, and heterozygous (as well as hemizygous and homozygous) G6PD deficiency can be readily detected if the activity of the enzyme is determined densitometrically after electrophoresis and expressed as a ratio of the activity of a second enzyme, 6-phosphogluconate dehydrogenase (6PGD), which is isolated at the same time and whose activity is similarly determined. A method is presented here, together with the results of a recent survey in which 400 babies of Greek origin were tested for G6PD deficiency by the method. An overall incidence of 4-3% was found in the group; 2-9% of the males were completely G6PD deficient and 5-2% of the females were heterozygous for the deficiency.


A newly reported toxic Australian frog (genus Heleioporus).

Attention is drawn to an indigenous poisonous frog which, preliminary toxicity experiments indicate, can cause pronounced distress to some species, including man.


Eosinophilic meningitis (angiostrongylosis): a probable case.

A probable case of eosinophilic meningitis is described. This report is thought to be the first of a case of this disorder diagnosed in New South Wales, although infection probably occurred in Queensland. The life cycle of the parasite Angiostrongylus cantonensis is outlined briefly and the clinical manifestations of this disease are discussed. Treatment with thiabendazole seems to have been beneficial to this patient.


Keratoconus and the Ehlers-Danlos syndrome: a new aspect of keratoconus.

Hypermobility of the joints is a frequent finding in patients who have keratoconus. Twenty-two of 44 patients (50%) presenting in 1973 were found to have hypermobility of joints (mainly Ehlers-Danlos syndrome II or mitis type). The significance of this finding is discussed in relation to biochemical defects recently found in corneas with keratoconus. The hypothesis is presented that keratoconus is often a part of a generalized heritable disorder of connective tissue due to a biochemical defect causing a weakness in its structure.


Establishment of the Melbourne mobile intensive care service.

As the majority of deaths after infarction occur in the first hour, a mobile intensive care ambulance service has been instituted in Melbourne to enable adequate care and early monitoring facilities.  Initially the service was manned by doctors and ambulance officers, but currently each ambulance is manned by two specially trained officers. Over a 27-month period 52 patients have been resuscitated from ventricular fibrillation or ventricular standstill. Half of the patients had sustained a definite acute myocardial infarction and another 16 had probable but not proven myocardial infarction.  Of the 52 patients, 31 survived to leave hospital and all patients known to be alive are leading active and useful lives.  In spite of an initial fear that medical treatment might be overused or misused by the officers, this has not been the case, and only about 13% of patients have received drugs from the officers.  This paper deals with the setting up, staffing and training of the ambulance service and reviews its results.


Pre-hospital coronary care: review of a system in its fifth year.

The present "coronary" ambulance service in Sydney is poorly utilized, covers a small fraction of the city's population and operates at a cost which is less than 0-25% of the hospital care of patients admitted with suspected cardiac emergencies. A survey suggests that such a service could with benefit be replaced by a general emergency ambulance service, staffed by well trained paramedical personnel, strategically located throughout the city and responding to all emergency calls.


Elevation of blood viscosity, aggregation of red cells, haematocrit values and fibrinogen levels with cigarette smokers.

A study of blood viscosity factors was carried out on male smokers and non-smokers (125 volunteers) in the age group 45 to 55 years. The smoker's group exhibited elevated haematocrit values, fibrinogen levels and blood viscosity (P less than 0-025), and increased aggregation of red cells and plasma viscosity (P less than 0-005). Especially in the dependence of aggregation of red cells on the level of fibrinogen, the smokers of blood group O showed higher values than smokers of blood group A (P less than 0-01). Elevation of blood viscosity factors and functions in smokers suggests that pathways to ischaemia and thrombosis, to which smokers are more prone than non-smokers, may move through the blood high-viscosity syndromes.


Acute renal failure due to leptospirosis with hyponatraemia.

Severe forms of leptospirosis causing acute renal failure are uncommon in Australia. Reported here is one such case, with marked hyponatraemia, which was treated with peritoneal dialysis. Biopsy findings are presented. It is believed that the infection was acquired in suburban periodomestic surroundings.


[Treatment of obesity with low-carbohydrate diets (author's transl)].

Therapeutic problems with low-carbohydrate diets in the weight reduction of the obese are summarized presenting results of the literature and results of the own group. The small number of patients and the short periods of treatment do account to the controverse results observed by other authors with low-carbohydrate diets. Also studies performed under ambulant conditions should be interpreted carefully. The therapeutic effect of the low-carbohydrate formula diet tested, satisfied even in comparison with a diet discribed in other studies. Concentrations of plasma triglycerides and cholesterol elevated in part turned to normal during therapy. There were no side effects of the gastro-intestinal tract. Hypocaloric diets with reduction of carbohydrates are discussed to have a good therapeutic effect for the following reasons: High value of satiety and increase of the metabolic rate.


[Serum bilirubin in an obvious healthy population (author's transl)].

An unselected sample of a population aged between 15 and 45 years shows an average level of serum bilirubin of 0,624 plus or minus 0.251 mg p. c. in 1862 test persons. The distribution graphes are slightly inclined to the left and their peaks are for both sexes and in all age groups between 0.50 and 0.69 mg p. c. The results are independent of the age (between 15 and 45 years). Male persons on an average show a significant higher level of serum bilirubin than female persons (0.677 : 0.566 mg p. c.). In 93.5 p. c. of all men and in 97.1 p. c. of all women the level of serum bilirubin is under 1.1 mg p. c. In the sample 6.0 p. c. of the test persons show a level of serum bilirubin above 1.09 mg p. c. Serum bilirubin levels of 1.1 mg p. c. and higher are defined as hyperbilirubinemia. These patients have to be controlled carefully, because in the fifth part of them it is found an organic cause and in the major part of the rest there is indication for a functional distrubance in bilirubin metabolism.


[Treatment of severe digitalis-intoxication in suicidal attempt (author's transl)].

4 patients tried to commit suicide by ingestion of 45 to 100 tablets of digoxin (Lanicor 0,25 mg) and acteyldigoxin (Novodigal 0,2 mg) respectively. In all patients cardiac arrhythmias occurred including 3 rd degree av-block, tachyarrhythmias and ventricular fibrillation which was lethal in two patients. After a short period hyperkaliaemia a rapid decrease of potassium in the serum was observed 3-12 hours after administration of digoxin. This loss of potassium was due to an increased excretion of potassium and sodium in the urine. It is thought that a reversible tubular leakage is responsible for the loss of electrolytes by the kidney rather than an inhibition of the ATPase in kidney tissue. From our observations the following therapy scheme for digitalis-intoxication is recommended: 1. Gastric lavage and administration of absorbents (charcoal, cholestyramin) in order to decrease the absorption of the glycosides and to interrupt the enterohepatic circulation. 2. Substitution of electrolytes by infusions and by oral route to balance sodium and potassium levels in the serum. 3. Administration of diphenylhydantoin for treatment of cardiac arrhythmias. 4. Implantation of a temporary pacemaker for treatment of cardiac arrhythmias especially for the management of bradycardias. 5. Plasmapheresis to lower the glycosid concentration in the heart muscle and in other tissues.


[Osteoporosis- more than a bone disease (author's transl)].

Neither the bone-matrix theory of osteoporosis established by Albright in the 1940's nor the lack-of-calcium theory of the 1960's especially represented by Nordin, due to experimental tests and clinical results could be maintained. Here a new theory of osteoporosis is introduced, explaining osteoporosis not to be primarily a disfunction of calcium- or bone metabolism, but as a part-symptom of disfunction of the whole sustentaculum -bones, marrow, nucleus pulposus and musculation. Osteoporosis is predisposed by amyothenia respectively in activity and is initiated by reduced blood circulation of the sustentaculum. Certain relevant conclusions for prophylaxis and therapy of osteoporosis can be deduced without neglecting already the presently only effective therapy using sodium fluoride.


Nuclear magnetic resonance (NMR) relaxation spectroscopy in tissues.

Nuclear magnetic resonance (NMR) techniques have been used to study several in vivo and stabilized tissue samples. The results show that a multicomponent behavior characterizes the magnetization relaxation of all investigated samples. Various specimens were allowed to undergo necrotic processes and then they were examined with the same techniques used in in vivo tissue. A marked approach toward a single-exponential magnetization-decay behavior was observed in these necrotic samples. In addition, large and sometimes irreversible temperature variations have been observed in the relaxation parameters of several preserved and stabilized tissue samples. The most dramatic changes observed throughout these experiments relate to the long-lived magnetization components, and are not observed in in vitro experiments performed solely on necrotic tissues. Meaningful differentiation between normal and neoplastic tissue by NMR techniques is virtually useless unless the roles of the temperature and necrosis on the different magnetization-decay components are well understood.


Mathematical method for determining kVp from x-ray attenuation measurements.

A mathematical analysis of the shape of x-ray attenuation curves is presented that suggests a new method of determining the kVp of bremsstrahlung beams. The main result is a simple analytic formula which gives an excellent approximation to the attenuation curve for large thickness of high-Z absorber. From this, a graphical procedure is derived which yields a straight line whose slope is related to the mass attenuation coefficient evaluated at the peak energy. Included are corrections for aluminum filtration, ion-chamber energy dependence, and coherent scattering. The method is limited to beams generated by a constant potential and with negligible characteristic photons in the filtered spectrum. Numerical data are given for using copper absorber below 70 kVcp and tin above 90 kVcp.


Experimental test of a new method for kVp measurements.

We present the results of an experimental test of a new method for measuring the kVp of a diagnostic x-ray beam. The method involves measuring x-ray attenuation in copper or tin absorbers and plotting the attenuation curve in a new way. Our measurements were done at 60, 90, 100, and 120 kVp on a 3-phase, 12-pulse diagnostic generator. The kVp was measured with a calibrated voltage divider-oscilloscope system. Except at 90 kVp, excellent agreement was found, with precisions on the order of plus or minus 1%. The 90-kVp point appeared to be somewhat affected by characteristic tungsten radiation and gave agreement with a lower value of precision.


Series of high-sensitivity TL phosphors made from divalent-metal sulfates.

A systematic survey of the thermoluminescence (TL) of rare earth activated sulfates of the form MeSO4:RE was made, where Me denotes a divalent metal and RE the rare earth. SrSO4:Tb(3+) and BaSO4:Eu(2+) exhibit very high TL efficiency following gamma irradiation, comparable to that of the most sensitive phosphors currently available for TL dosimetry. Due to their relatively high Z, these phosphors could prove useful as quality indicators for personnel dosimetry or for detecting very small exposures of low-energy X rays of a known quality.


Mechanism to facilitate the fine adjustment of sidelights.

A simple optical mechanism is presented for the fine adjustment of sidelights. The characteristics of the device are that large angular displacements are required to achieve small lateral motions of a light beam. For this reason, the mounting mechanism may be made to quite coarse tolerances.


Binding of histamine- and other ligand-conjugated macromolecules to lymphocytes.

The presence of histamine receptors on lymphocyte membranes was investigated using conjugates of histamine and macromolecules tritiated or iodinated with I-125. Histamine-RSA conjugate binds to lymphocytes and causes patching and capping of the bound conjugate. It was found, however, that free histamine did not inhibit the binding of histamine-rabbit serum albumin to mouse lymphocytes, nor did His-RSA interfere with the binding of free histamine. In addition conjugates between RSA and other small molecules, such as ethylamine, ethanolamine, tyramine and glycine, were found to bind to the same sites on lymphocyte membrane as did His-RSA. Ethylamine-RSA like His-RSA when coupled to Sepharose, was capable of removing antibody producing cells from spleen cells of mice immunized against sheep red blood cells. In addition, when spleen cells from such immunized mice were passed through ethylamine or histamine-RSA-Sepharose and the unbound cells were subsequently injected into X-irradiated mice, a 1.8 fold increase in the immunological response was noted. We conclude that the selective binding to lymphocytes of the various ligand-macromolecular conjugates may be due to some general properties of the cell membrane and not to any specific receptors. Nevertheless, these conjugates can be used as a tool to remove selectively antibody producing cells as well as some regulatory cells.


Induction of mutation to streptomycin resistance in Micrococcus radiodurans.

No detectable induction of mutation to streptomycin resistance could be used in wild-type Micrococcus radiodurans and its radiation-sensitive and super-resistant mutants by ionizing or UV-radiation. N-methyl-N'-nito-N-nitrosoguanidine (NTG) was mutagenically active. The results suggest that repair of radiation-damaged DNA in Micrococcus radiodurans is mutation-proof.


Cytological studies on onion root-tip cells treated with water-soluble extract of tobacco smoke condensate from commercial cigarettes.

The effect of water-soluble extract of tobacco smoke condensate (TSC) from two commercially available cigarettes with dirrerent types of filters was studied on the cytology of root-tip cells of onion (Allium cepa). One of the cigarettes had a 2-cm cellulose acetate filter, and the other had a filter comprised of 1 cm of cellulose acetate and 2 cm of activated charcoal. TSC from these cigarettes induced mitotic abnormalities. To investigate whether these two commercial filters could retain cigarette smoke component (s) responsible for mitotic irregularities, the cigarettes were defiltered, and TSC was prepared and tested on the young roots of onion. Observations revealed that the cytological effect of TSC from defiltered cigarettes was not significantly different from the effect of TSC from cigarettes with filters. Thus, the filters utilized in these cigarettes do not retain compound(s) responsible for mitotic irregularities in the root-tip cells of onion. With increasing concentrations (0.01% ot 0.1%) of TSC from cigarettes with filters and defiltered, precent mitotic abnormalities increased. These abnormalities included scattering, stickiness, lagging, condensation, and breaking of chromosomes during metaphase. Bridging and lagging of chromosomes were observed during anaphase.


Relationship between experimental results in mammals and man. I. Cytogenetic analysis of bone marrow injury induced by a single dose of cyclophosphamide.

The extrapolation of experimental results to man was studied by cytogenetic bone marrow analysis and micronucleus test in mice, rats and Chinese hamsters. Furthermore, the frequency of chromosomal aberrations was compared with the frequencies of polychromatic erythrocytes containing micronuclei. Cyclophosphamide (CY) was given intraperitoneally at the doses of 5, 10, 20, 40 and 80 mg/kg b.w. to ICR mice and Wistar rats and at the doses of 10, 20, 40, 80, 120 and 160 mg/kg b.w. to Chinese hamsters. Five patients with various types of malignancies until then medically untreated, were i.v. administered 40 mg CY/kg b.w. Bone marrow cells were examined 24 h after the administration. CY induced in all rodents a clear-cut dose-effect relationship in the frequency of breaks, abnormal metaphases as well as in the frequency of micronuclei in polychromatic erythrocytes. When comparing the results in rodents and man at the dose of 40 mg CY/kg b.w., the sensitivity pattern of species was mice greater than rats greater than Chinese hamsters greater than man. From this aspect the possible differences in the metabolism of CY in analysed species are discussed. The presented results tend to a conclusion that micronucleus testing may be a very suitable method used for screening purpose, however, the method of classical cytogenetic analysis, especially the evaluation of breaks, still remains the most exact and reliable technique.


Measures of clinical efficacy. Cost-effectiveness calculations in the diagnosis and treatment of hypertensive renovascular disease.

The sensitivity and specificity of the hypertensive intravenous pyelogram and the iodohippuran renogram have been determined for the diagnosis of renovascular disease, and cost-effectiveness calculations have been made for the diagnosis and surgical treatment of patients with renovascular hypertension. When the intravenous pyelogram alone is used to screen representative hypertensive population, 78 per cent of patients with renovascular disease are located, but at the same time an equal number of patients without renovascular diasease have abnormal pyelograms. The renogram, on the other hand, is associated with varying true-positive and false-positive ratios. These data can be plotted in the form of a receiver-operating-characteristic curve. The cost of finding a patient with renovascular disease is about $2,000, and that of a surgical cure is about $20,000. The number of deaths for 100 surgical cures is approximately 15. The dollar cost of screening and treating the total American renovascular hypertensive population is of the order of 10 to 13 billion dollars.


Measures of clinical efficacy. The value of case finding in hypertensive renovascular disease.

An attempt was made to discover the difference in outcomes between treating all patients with essential and renovascular hypertension by drug therapy independent and ignorant of etiologic classification and identifying the patients with renovascular disease and operating on them. Outcomes were categorized as well without complications of hypertension, alive but suffering from a related morbid illness such as coronary or cerebral arterial disease, and dead from the complications of diagnosis, surgery or high blood pressure. The identification and surgical treatment of hypertensive renovascular disease resulted in an incremental benefit in morbidity over blind antihypertensive medical therapy only when the compliance with medical treatment was about  50 per cent or less (the rate suggested for most patient populations). The study underscores the extent to which the quantitative efficacy of diagnositc and therapeutic procedures depends not only on the inherent risks and benefits but also on related social and medical factors.


What do we gain from the sixth stool guaiac?

The six sequential stool guaiac protocol has been advocated for screening of colonic cancer. Analysis of the expenditures involved in such a program shows that the cost of detecting cancer rises exponentially so that the marginal cost of the sixth test may be 20,000 times the average cost. The marginal cost is decreased with lower test sensitivity and increased with lower prevalence of colonic cancer. This result shows that even an inexpensive test can become quite costly in terms of cases detected. The marginal cost per case detected depends on the prevalence of the condition in the population screened and the sensitivity of the test applied.


Therapeutic decision making: a cost-benefit analysis.

To help the physician decide whether or not to treat a patient who may or may not have a disease, a method has been developed for calculating a therapeutic threshold. If the probability of disease in a given patient exceeds the threshold, the preferable course of action is to treat; if the probability is below the threshold, the preferable course of action is to withhold treatment. This method is applicable in many medical and surgical settings in which some diagnostic uncertainty exists after all appropriate studies have been carried out. The technic not only exposes some of the basic principles of therapeutic decision making in the face of diagnostic uncertainty but also forms a convenient framework for analyzing the impact of "soft" clinical data on the decision-making process.


Protecting the medical commons: who is responsible?

The resources for medical care are clearly finite, but demands on those resources are growing rapidly. Of particular concern are the demands on those resources for medical practices of three kinds: those that pose conflicts between the interests of the individual and those of society; those of no value or of undetermined value; and those for potentially preventable conditions. Such practices must be evaluated in terms of social and medical priorities, and this requirement will become more urgent with the establishment of national health insurance. Who will make decisions is less clear, but it is not likely to be physicians alone. It is imperative that physicians and other health providers work closely with professionals from many fields, and with consumers, to ensure the availability and dissemination of information that will permit decisions that are in the best interests of society.


Rights and health care--beyond equity and efficiency.

Economic analysis in general has difficulty accommodating the concept of rights. The economic analysis of health care in particular proposes triage as the model of a rational delivery system, with no place for traditional ethical limits and obligations. Familiar arguments based on resource constraints do not prove that rights cannot reasonably be recognized. Nor are rights in general and rights in medical care in particular adequately respected by attending to considerations of just distribution or equity. Rights in medical care are different from rights to medical care, and must be respected in any decent, advanced society. That such rights may be overridden in emergencies does not mean that respect for rights is not a constraint upon the pursuit of equity and efficiency.


Saprophytic occurrence of Trichophyton mentagrophytes and Microsporum gypseum in the coats of healthy laboratory animals. (Preliminary report).

A group of 199 healthy laboratory animals, comprising 63 guinea pigs; 58 white mice. 47 rats and 31 rabbits, was sampled for the presence of pathogenic dermatophytes. T. mentagrophytes, var. granulare, was isolated in 10% (5-guinea pigs, 6 mice, 6 rats and 2 rabbits) and M. gypseum was found in 7 animals (3 guinea pigs, 3 mice and one rat). No ringworm lesions were observed in the respective animals. This is the first report on such findings in Israel.


Scanning electron microscopy of ascospores of Debaryomyces and Saccharomyces.

Ascospores from species of Debaryomyces and the Torulaspora-group of Saccharomyces were examined by scanning electron microscopy. Ornamentation on ascospores of D. hansenii varied from short to long interconnected ridges or broad based, elongated conical protuberances. A spiral rigde system was detected on the ascospores of D. marama, but wart-like protuberances occurred on those of D. cantarelli, D. castellii, D. coudertii, D. formicarius, D. phaffii, D. vanriji and D. yarrowii. Ascospores of D. halotolerans did not have protuberances and the species appears to be identical with Pichia farinosa. Wart-like protuberances also were found on ascospores of S. delbrueckii, S. microellipsodes, S. rosei, S. inconspicuus, S. fermentati, S. montanus and S. vafer, but the ascospore surface of S. pretoriensis was covered by fine ridges. Short tapered ridges covered the ascospores of S. kloeckerianus.


Mycotic flora of the interdigital spaces of the human foot: a preliminary investigation.

A qualitative and quantitative study of the mycotic flora of the interdigital spaces of 27 male volunteers yielded 1,291 moulds and 598 yeasts. Concurrently, a study of garden soil was conducted in order to obtain data concerning the transient-resident status of the fungi recovered from the feet. Of the 120 genera and species of fungi isolated, 51 were recovered from the volunteers, 53 from the soil, and 16 from both categories. The most commonly recovered fungi from the toewebs, in order to occurrence, were Torulopsis candida, Mycelia Sterilia, T. maris, Rhodotorula rubra, Cryptococcus albidus, and species of Aspergillus and Penicillium. Without sign of infection, Cryptococcus neoformans was isolated from 5 volunteers. Candida albicans was not recovered from any subject. Trichophyton mentagraphytes was recovered from 7 volunteers and T. rubrum from one.


Existence and possible roles of transcriptional barriers in T7 DNA early region as shown by electron microscopy.

Transcription of T7 DNA in vitro by Escherichia coli RNA polymerase in the absence or presence of termination factor rho has been studied extensively using electron microscopy. It is demonstrated that sequences located between the early genes behave as transient transcriptional barriers in the absence of rho and are recognised both as rho-dependent terminators and as RNaseIII cleavage sites.


Cardiac action potential and inotropic effect of noradrenaline and calcium.

1. Noradrenaline biphasically affects the duration of the action potential (AP) of guinea-pig cardiac ventricular muscle. Low concentrations (10-7M) prolong the AP duration, while high (10-5M) concentrations shorten it after an initial prolongation. The extent of the AP-prolonging effect is more marked at low (0.3 and 0.6 mM) than at high (2.4 or 4.8 mM) extracellular calcium concentrations. When the concentration of noradrenaline is cumulatively increased, the AP duration is always transiently prolonged, even if the AP is shortened in the second phase of the preceding noradrenaline effect. 2. The AP-prolonging effect begins immediately after the addition of noradrenaline. The positive inotropic effect does not appear until the maximum of the AP-prolonging phase has been reached. Its continued rise and amximum always occur during the subsequent phase of AP-shortening. 3. In essential aspects the effect of noradrenaline on AP duration and contractile force resembles the effect of an increase in [Ca-2+]o:AP duration is changed biphasically by noradrenaline in the same way as by an increase in [Ca-2+]o: in both cases an increase in force of contraction is related only to the AP-shortening effect. - But, unlike noradrenaline, calcium at concentrations higher than 1.2mM produces no transitory initial prolongation of AP duration. And, whereas higher concentrations of calcium shorten the plateau-phase of the AP in particular, noradrenaline has the most pronounced shortening effect on the late rapid repolarisation-phase of the AP. 4. The similarity of some of the effects of noradrenaline and calcium (i.e., prolongation of AP at low [Ca-2+]o: parallelism of positive inotropic effect and AP-shortening effect) indicated ahat at least part of the noradrenaline effect on the AP is the expression of an enhancement of calcium influx. For the effect of noradrenaline which is unlike that of calcium (i.e., prolongation of the relative plateau duration and transient prolongation of AP duration at high [Ca-2+]o), an additional influence on the membrane property must be assumed.


Response of nigral dopamine neurons to actue and prolonged morphine treatment: effect of exposure to cold, physostigmine and nicotine.

The effects of morphine and acute exposure to cold on nigral dopamine (DA) neurons and possible interactions with cholinergic systems were studied by histochemical microfluorimetry in normal and partially morphine-tolerant mice. Morphine (40 mg/kg), cold (4 degrees C), nicotine (1 mg/kg) and physiostigmine (0.25 mg/kg) elicited a rapid rise and subsequent decrease in the fluorescence intensity of DA nerve cells with certain differences in time course. Fastest changes with a peak at 5 min, a marked subsequent drop below control levels and return towards control  intensity after 40 min were seen after physostigmine. Antagonisms between various treatments were noted. DA responses correlated well with the time course of behavioural effects, especially after physostigmine. After 3 1/2 days of morphine treatment, the locomotor and analgesic effects of the drug were reduced. At this stage, the initial increase in fluorescence intensity after morphine and the biphasic pattern caused by physostigmine were delayed without any change in response magnitude. Responses to cold and nicotine remained unaltered both in magnitude and time course. Thus, partial tolerance affected the response of nigral DA neurons to some but not all funtional conditions and thereby markedly changed the interaction with cholinergic systems. The difference between physostigmine and nicotine suggests that neuronal circuits including mustcarinic mechanisms are possibly more susceptible to alteration.


Ontogenetic development of a 5-methyltetrahydrofolate requiring enzyme in rats and mice.

Developmental characteristics of 5-methyltetrahydrofolate requiring N-methyltransferase (5 MT-NMT) have been studied in rats and mice and compared to the development pattern of marker enzymes. In rat and mouse brain, the 5 MT-NMT activity expressed in units per mg protein, was found to decrease rapidly during the first five days after birth and then more slowly, whereas two other enzymes, dopa-decarboxylase and histamine N-methyltransferase increased gradually during maturation. In kidney, the ontogenetic development of 5 MT-NMT was first characterized by an increasing activity from birth until a different age, depending on the species, and then followed by an abrupt decline. In contrast to this, histamine N-methyltransferase activity in mouse kidney was about 60 times higher at maturity than at birth. When the enzyme activities are expressed in units per g tissue, the changes in the course of the development of 5 MT-NMT were less apparent, but in any way differed markedly from those of dopa-decarboxylase and histamine N-methyltransferase. The results suggest that 5 MT-NMT does not behave as a synaptosomal or perhaps even as a neuronal enzyme. Although its physiological role remains to be elucidated, it must have a more general function in the cellular economy than merely N-methylating biogenic amines.


In vivo rates of tyrosine and tryptophan hydroxylation in regions of rat brain at four times during the light-dark cycle.

The in vivo rates of tyrosine and tryptophan hydroxylation were studied in three regions of young adult rat brains at 4 times the light-dard cycle. The procedure utilized was to analyze the accumulation of Dopa and 5-HTP after injection of a centrally effective L-amino acid decarboxylase inhibitor, NSD 1015. Monoamine levels were also determined in all control animals and some treated animals. The reate of tyrosine dydrosylation in the telencephalon was significantly higher 7 hrs after dard onset than at the other three times tested. Smaller variations in tyrosine and tryptophan hydroxylation rates as a function of time of day were also observed. 5-HT levels were significantly higher during the light phase than the dark in the telencephalon with the same trend occurring in the diencephalon and brainstem. NA was stable in the telencephalon but reached lower levels in the light and higher levels in the dark in the other two regions. In the telencephalon DA reached high levels early in the light and in the dark phases, showing a biphasic variation. Of particular interest was the apparent lack of carrelation between cyclic changes in the monoamine levels and the changes in hydroxylation rates. Rates of hydroxylation can be considered indicative of rates of monoamine synthesis. This observation is discussed in relation to feedback and other mechanisms regulating synthesis and release of monoamines.


A micropuncture study of the effect of isoprenaline on renal tubular fluid and electrolyte transport in the rat.

To explain the mechanism of the isoprenaline induced antidiuresis the effect of this substance on fluid and electrolyte reabsorption in various nephron segments of the rat kidney has been studied using micropuncture techniques. Isoprenaline (1.5x10-9mol/kg-min i.v.) decreased GFR of superficial nephrons and increased fractional proximal fluid, sodium and potassium reabsorption. However, the fractions of filtered fluid and electrolytes, which had been reabsorbed up to early distal tubule were unchanged after isoprenaline. This indicated that the increased fractional proximal reabsorption has been completely compensated by decreased reabsorption from Henle's loops. In the distal convoluted tubules an increase in the fractional fluid and sodium reabsorption could be established using a recollection technique. Given directly into the distal tubular lumen isoprenaline stimulated the isotonic fluid reabsorption, which was measured by the Gertz split oil droplet method. From these results it is concluded that the decrease in superficial GFR and the increased distal tubular fluid and sodium reabsorption lead to the decrease in urine volume and in urinary electrolyte excretion after isoprenaline.


Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats.

The influence of pretreatment with spironolactone (84 mg/kg at 3 days, twice per day) on the tritium levels in plasma, urine and feces of female SD-rats (n=9) was investigated at various time periods after oral administration of 25mug/kg -3H-digitoxin. In plasma, the concentrations of total radioactivity are reduced in pretreated animals to about 20% of tritium levels in control rats, while the half-life of radioactivity in both groups is almost identical, 2.9 days in pretreated rats and 2.8 days in controls. The lower plasma levels of tritium in pretreated rats coincide with a six-fold decrease in the urinary -3H-elimination and a corresponding increase in the fecal excretion. This is due to a higher biliary clearance of tritiated products in the early phase of elimination. The separation of the excretion products by TLC shows that spironolactone pretreatment enhances the splitting of the glycosidic bonds of digitoxin. The amount of digitoxigenin-bis-digitoxoside and of digitoxigenin-mono-digitoxoside excreted in urine and feces within 96 hrs is four and ten times greater than that recovered in control animals, respectively. The formation of the hydroxylation products digoxin and digoxigenin-bis-digitoxoside is decreased from 50% of the total excreted radioactivity in control to 15% in pretreated rats. The conjugation reactions with glucuronic and sulfuric acid are increased after pretreatment with spironolactone. Thus, the effect of spironolactone on digitoxin kinetics is apparently related to an enhancement of the hepatic excretory mechanism as well as to an enhanced metabolism.


Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin.

In the eye of rats the long-lasting specific desensitization induced by local or systemic capsaicin treatment is characterized by three phases: 1. complete insensitivity, 2. decreased sensitivity and a tendency to rapid adaptation, 3. normal initial sensitivity with a tendency to rapid adaptation to chemical pain stimuli. A low density of nicrovesicles and swollen mitochondria were found after local capsaicin treatment in certain nerve endings of the cornea of rats, but no signs of axonal degeneration or alteration in fine structure of non-neural elements were seen. Systemic capsaicin desensitization induced selective mitochondrial swelling in B type of neurons of the trigeminal ganglion which was demonstrable even 60 days after the pretreatment. Actinomycin-D, 8-azaguanine, 6-azauracil, aminopterin, mannomustin or cycloheximide in high doses did not alter the desensitizing effect of systemic capsaicin treatment. However, pretreatment of rats with colchicine or vinblastine prolonged the desensitizing effect of local capsaicin application, probably by inhibiting the axonal flow. It is concluded that capsaicin is a specific sensory neuron blocking agent having a practically irreversible effect in rats and guinea-pigs.


Differences between (+)- and (-)-amphetamine in effects on locomotor activity and L-dopa potentiating action in mice.

The L-Dopa-potentiating effects of the two optical isomers of amphetamine, as well as the effects of their own, were investigated in mice, using locomotor activity as test parameter. The study was performed in three steps. First, the time-course were studied for the effects of (+)- and (-)-amphetamine and L-Dopa. Second, dose-response relationships were established for the amphetamine enantiomers. Third, the L-Dopa-potentiating effects, of a few, selected doses of the amphetamine isomers were investigated by establishing dose-response curves for L-Dopa with and without the amphetamines. All animals given L-Dopa were pretreated with an inhibitor of extracerebral aromatic amino acid decarboyxlase.  (+)-Amphetamine, 0.5-8 mg/kg, caused a dose-dependent stimulation of locomotoractivity, whereas (-)-amphetamine, 1-4 mg/kg, caused a dose-dependent depression. Doses higher than 8 mg/kg of the laevo-isomer caused stimulation of the activity. (+)-Amphetamine, 0.25 mg/kg, and (-)-amphetamine, 0.5 mg/kg, i.e. doses without any effect on locomotor activity of their own, caused virtually the same shift to the left of the dose-response curve for L-Dopa. (-)-Amphetamine, 4 mg/kg which per se caused depression of locomotor activity, caused a marked potentiation of the L-Dopa-induced stimulation of motor activity. Thus, there does not exist a close correlation between the L-Dopa-potentiating action of the amphetamines and their stimulating properties per se.


Uptake of dopamine into fractions of pig caudate nucleus homogenates.

Homogenates of the caudate nucleus of the pig were submitted to differential centrifugation. The 20000 g and 80000 g fractions were isolated and a part of them was osmotically shocked. The highest dopamine content per mg protein was found in the intact 80000 g fraction. Incubation experiments with the intact and the osmotically shocked fractions at 25 degrees C revealed that the particles of the intact 20000 g fraction took up dopamine, the influx of the amine was not enhanced by addition of ATP and magnesium to the incubation medium. On the other hand after osmotic shock the uptake of dopamine into the particles of this fraction was greatly enhanced by addition of ATP and magnesium. The uptake of dopamine into the particles of both intact and osmotically shocked 80000 g fractions was likewise enhanced by ATP and magnesium. The uptake in all fractions was not influenced by ouabain. The influx of dopamine into the particles of the intact 80000 g fraction was competitively inhibited by reserpine  (Ki0.96 x 10-8M) and prenylamine (Ki1.74 x 10-8M). It is concluded that the intact 20000 g fraction contains intact synaptosomes; the uptake of dopamine is independent of the presence of ATP and magnesium. The shocked 20000 g fraction and the 80000 g fractions contain synaptic vesicles; the uptake of dopamine into these vesicles is enhanced by ATP and magnesium.


Uptake of serotonin, gamma-aminobutyric acid and histamine into synaptic vesicles of the pig caudate nucleus.

Dopamine-containing vesicles were isolated from the caudate nucleus of the pig by differential centrifugation and incubated with 14-C-serotonin (14-C-5-HT), 14-C-gamma-aminobutyric acid (14-C-GAGA), 14-C-dopamine or 14-C-histamine. At 25 degrees C the uptake of 14-C-5-HT and 14-C-GABA was enhanced by ATP and magnesium. The Km for the uptake of 14-C-5-HT in the presence of ATP and magnesium was 0.67 x 10-6M, that of 14-C-GABA 1.33 x 10-4M. 14-C-Histamine was also taken up into the vesicles but its uptake was not incluenced by ATP and magnesim. The ATP-magnesium-dependent uptake of 14-C-5-HT and 14-C-GABA was abolished at 0 degrees C. At 37 degrees C the accumulation of 14-C-GABA in the presence of ATP and magnesium reached a steady state after 20 min, while the accumulation of 14-C-5-HT reached a maximum after 2.5 min of incubation and then gradually declined. Osmotic lysis of the vesicles followed by sonication abolished the enhanced uptake of 14-C-GABA, 14-C-5-HT and 14-C-dopamine in the presence of ATP and magnesium. Determination of the endogenous contents of the vasicles revealed 14.6 pmoles per mg protein for 5-HT and 22.7 nmoles per mg protein for GABA. It is concluded that the caudate nucles preparation used in this study contains not only dopamine-storing vesicles able to take up biogenic amines but also GABA-containing vesicles which take up GABA by an ATP-magnesium-dependent process.


Effect of calcium on the relationship between frequency of stimulation and release of noradrenaline from the perfused spleen of the cat.

The sympathetic nerves of the cat spleen were stimulated electrically (20 v, 1 msec, 7 sec) with increasing frequencies (1-30 Hz) during perfusion of the spleen with normal or low-calcium Krebs solution. Noradrenaline (NA) output per stimulus was measured. In spleens perfused with normal Krebs solution, the NA output per stimulus at 5Hz was barely detectable, while the output at 30 Hz was about 5-fold greater than at 5 Hz. Reduction of the calcium concentration in the Krebs solution to 0.2-0.5 mM, while reducing outputs at both frequencies, resulted in an output at 30 Hz that was nearly 8 to 10 times that at 5 Hz. In spleens pretreated with phenoxybenzamine (PBZ) the NA output was increased at all frequencies, and the maximal output occurred at 5 Hz, whereas the output at 30 Hz was only one-third of the maximal output. Reduction of the calcium concentration of the perfusion solution to 0.5 mM, while reducing outputs from PBZ-treated spleens, increased the output at 30 Hz by about 5-fold over the output at 5 Hz. The muscarinic inhibition of stimulation-evoked release of NA by acetylcholine was much more pronounced at low than at high frequency of stimulation. The increase in the release of NA per stimulus with increase in the frequency of sympathetic nerve stimulation is explained on the assumption that the specific entry of calcium ions required for transmitter release is also frequency-dependent.


Influence of isoprenaline and salbutamol on the threshold of electrically induced ventricular fibrillation in anaesthetized guinea pigs.

Fibrillation threshold and heart rate were measured after increasing doses of (-)-isoprenaline and (plus or minus)-salbutamol. The initial values of 212 plus or minus 10 muA (x plus or minus SEM) and 211 plus or minus 10muA were decreased to 74 plus or minus 10 muA by low doses of (-)-isoprenaline (10-11- to 10-10 moles/kg i.v.), and to 89 plus or minus 11 muA by (plus or minus)-salbutamol (10-9- to 10-8- moles/kg i.v.). Higher doses, paradoxically, increased fibrillation threshold to initial values, (-)-isoprenaline: 2x10-9- moles/kg; (plus or minus)-salbutamol: 2x10-6- moles/kg. A linear increase in heart rate per 10-fold increase of either drug was observed, (-)-isoprenaline: 25 beats - min-1-; (plus or minus)-salbutamol: 14 beats - min-1-. The apparent beta2-selective property of salbutamol is documented by its low potency in changing fibrillation threshold and heart rate.


The effect of D-penicillamine of the skeletal development of rat foetuses.

Rats received 20, 50 or 100 mg/animal D-penicillamine i.p. twice daily on days 15, 16, 17, 18, and 19 of gestation, i.e. a total dose of 200, 500 resp. 1000 mg/animal. At all dosages the number of fetal resorptions did not increase significantly. Weight of the 20 day old embryos as well as length of the long bones in the extremities in the 100 mg-group showed a significant decrease. Numerous skeletal alterations could be observed in the 1000 mg-group such as absence, deformations or incomplete mineralisation of bones. Light microscopic examinations revealed an inhibition of the ossification as well as a decrease of number and size of the trabecula and of the thickness of the perichondrial bone sheath. A swelling of the collagenous fibrils can be demonstrated with the electron microscope. The first apatite crystals aggregate in collagen-free areas. The fusion of these aggregates to homogenously mineralized trabecula is inhibitied. In contrast to bones from untreated embryos, mineralized areas show varying content of collagen and apatide crystals. A regular spatial relationship between apatite crystals and collagenous fibrils does not develop. These findings show that even after the so-called "critical period" malformations can be pproduced by substances which disturb synthesis and maturation of the mesenchymal intercellular substance.


Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by alpha-Adrenoceptors in the isolated rabbit papillary muscle.

Under the conditions of different stimulation frequencies the inotropic effects of the alpha-adrenoceptor stimulationg agents, methoxamine, naphazoling and oxymetazoline were studied on the isolated rabbit papillary muscle. 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10(-5)M caused a significant and dose-dependent positive inotropic effect. At 10(-3)M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5--1--1.5Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10(-6)M), in contrast ot that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10(-5)M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect. 2. The positive inotropic effect of metoxamine (10(-4)M) as well as of naphazoline (10(-5)M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10(-6)M). Methoxamine (10(-4)M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD2-value was 7.76. 3. In the presence of methoxamine (10(-4)M) the developed tension in the lower range (0.05--1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (greater that 1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10(-6)M). 4. Papaverine (2x10(-5)M) did not affect the positive inotropic effect of methoxamine. 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via alpha-adrenoceptor in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.


Absence of muscarinic modulation of vasopressin release from the isolated rat neurophypophysis.

1. Isolated rat neurohypophyses were incubated in Locke solution at 37 degress C and the vasopressin output into the medium determined by bioassay. 2. Potassium chloride 60 mM caused a 9-fold increase in the rate of vasopressin release that was abolished when calcium chloride was omitted from the Locke solution. 3. Acetylcholine 5.5x10-4M neither alone nor in the presence of atropine 2.9x10-6M changed the "resting" release of vasopressin. 4. Neither acetylcholine 5.5x10-4M oxotremorine 10-4 and k3x10-4M altered the vasopressin release evoked by potassium chloride 60 mM. 5. In contrast to the peripheral adrenergic nerve fibres, the secretory terminal fibres of the neurohypophysis do not appear to contain muscarinic inhibitory or nicotinic excitatory receptors.


Concentration of digoxin, methyldigoxin, digitoxin and ouabain in the myocardium of the dog following coronary occulsion.

26 mongrel dogs were given a single dose of 0.03mg/kg tritium-labelled digoxin, beta-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion. Examination of the epicardial ECG was performed by moving from intact to ischemic or necrotic zones. 60 min after glycoside administration the animals were sacrificed and tissue samples from the marked heart muscles areas and from the skeletal muscle were analysed for glycoside content. The early glycoside uptake in acute ischemic or necrotic myocardium was diminished independently of the physicochemical properties of the glycoside. Significantly higher glycoside concentrations (ng/g wet weight) were measured in the injured myocardium 3 hrs after coronary occlusion than 96 hrs afterward (p less than 0.005). The values in acute ischemic myocardium varied considerably. This nonhomogeneity of glycoside uptake in the acute ischemic heart muscle may partly explain the increased sensitivity to glycosides in myocardial infarction. The decline of glycoside concentration correlates with the alterations in the epicardial ECG. The cardiac effects of cardenolides 60 min after intravenous administration was caused by the unchanged glycoside. In contrast to the myocardium, glycoside accumulation could not be found in the skeletal muscle. The concentrations of digoxin, beta-methyldigoxin and digitoxin in the skeletal muscle were significantly higher than the concentration of ouabain, which was rapidly eliminated via the urine.


Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. II. Determination of phospholipids at maximum of potentiation.

A monosynaptic reflex pathway was used to produce a post-tetanic potentiation (PTP). in ten experiments (cats) one side was tetanized (via N. gastrocnemius) whereas the other one was taken as control. Tissue was punched out of the ventral horn area of the spinal cord (segment height L7/S1) for the analysis of the phospholipid content. The results demonstrate that PTP significantly increases phosphatidyl-inositol in the potentiated alpha-motoneurone area. Phosphatidylserine showed a trend towards a decrease; sphingomyelin, phosphatidylcholine and phosphatidylethanolamine remained almost unchanged. The effect of a different tetanizing time on the phospholipid content is discussed as is the intention of the present experiments.


Serotonin binding proteins from human blood platelets. An experimental model system for studies on properties of synaptic vesicles.

Serotonin uptake, binding and release were studied in human blood platelets. The uptake showed marked individual differences while the loss of 5-HT during resuspension of the 5-HT loaded platelets was constant. The existence of 5-HT binding proteins was demonstrated by equilibrium dialysis, gel filtration on a column equilibrated with 5-HT, affinity chromatography on a 5-HT-Sepharose column and polyacryl-amide disc gel electrophoresis experiments. After incubation of the platelet extract in the presence of [14-C]5-HT, electrophoretic and autoradiographic analysis demonstrated the presence of three 5-HT binding proteins, two of which were soluble glycoproteins specific for serotonin.


Postnatal growth of nerve fibres in the pyramidal tract of the rabbit.

The postnatal growth in diameter of corticospinal nerve fibres was studied in the medullary pyramid of the rabbit in order to make comparisons with the development of functional properties, which has been demonstrated by previous workers. During the first postnatal days the as yet unmyelinated fibres underwent a distinct increase in size. The first signs of myelin ensheathment were seen in 5-day-old animals, the ensheathed fibres varying between 0.4 and 0.7 mu in diameter. The growth in size of the largest myelinated fibres was more rapid during the second week and thereafter continued at a slower rate to a final size of 4--5 mu. The number of myelinated pyramidal fibres increased most rapidly during the first postnatal month and reached around 90,000 (unilaterally) in the adult. The vascular density initially increased, reaching a peak at 3 weeks and thereafter decreased. Comparison with physiological data showed that the initiation of myelination does not coincide in time with any striking decrease in response latency but rather seems to allow for a continued steady decrease. At a size of 3.5-4 mu the fibres appear to have attained the capability to follow rapid rates of stimulation.


Disruption of copulation in male rats after hypothalamic lesions: a neuroendocrine analysis.

Electrolytic lesions of the hypothalamic medial forebrain bundle (MFB) produced substantial deficits in the copulatory behavior of male rats, but no changes in testicular, seminal vesicle, ventral prostate or penis weights. Radioimmunoassay of serum from lesioned and control animals revealed a small but statistically insignificant reduction in testosterone and LH levels, and no change in FSH levels of lesioned males. In a second experiment, androgen levels were maintained in castrated males by subcutaneous implants of silastic capsules containing crystalline testosterone; this procedure failed to prevent the copulatory deficit which accompanied subsequent MFB lesions. We have concluded that the behavioral deficit produced by such lesions is not a direct result of pituitary-gonadal dysfunction.


Effects of dexamethasone before and after puberty on the daily corticosterone rhythm.

Female Sprague-Dawley-derived rats were injected at 25 days of age (prepubertal) or 60 days of age (adult) with 1 mug dexamethasone/100 g b.w. either before the beginning of the daily rise in serum corticosterone (at 10.00 or 12.00 h in adults and 10.00 h in prepubertal rats) or after the daily rise had begun (at 14.00 h in adults, and 12.00 or 14.00 h in perpubertal rats). Blood samples were collected by decapitation at 16.00, 20.00 and 24.00 h on that day and 04.00, 08.00 and 16.00 h the following day. In adults, dexamethasone (DEX) given at 10.00 shifted the corticosterone (B) peak to 04.00. In prepubertal rats, DEX given before the B rise did not shift the subsequent peak and the patterns of B did not diverge from controls. DEX given at 12.00 or 14.00 shifted the peak to 24.00 h. At 08.00 the next day, B was depressed in adults but normal in prepubertal rats. At 16.00 h, both age groups showed depressed B in comparison to controls. Prepubertal rats appear to respond differently to dexamethasone than do adults.


Neurosecretory activity within suprachiasmatic neurons of the female rabbit following castration.

The effects of ovariectomy on the ultrastructure of neurons within the SCH nuclei of the rabbit were investigated. All SCH neurons of the intact controls were similar in that they showed no morphological evidence of enhanced neurosecretory activity. In contrast, two distinct types of neurons were present within the SCH nuclei of the ovariectomized animals. The small, Type I neurons were ultrastructurally identical to the SCH neurons of the intact controls. The larger, Type II neurons, on the other hand, clearly presented structural evidence for elevated intraneuronal synthesis. To ensure that the changes which characterized the Type II neurons were due, at least in part, to the removal of ovarian steroids following ovariectomy and not to surgical stress alone, the SCH nuclei of laparotomized rabbits were also studied. Although the same two neuron types were observed, the number of Type II neurons in the laparotomized controls was significantly smaller (p smaller than 0.001) than the number in the ovariectomized group. These findings suggest that Type II neurons probably represent a functional state of the smaller, non-active neurons of the intact controls. In addition, the ultrastructural features that distinguish type II neurons are positively related to the endocrine state of the rabbit and, therefore, may represent the hypothalamic synthesis of the releasing hormones that control is gonadotropic activity.


Effect of ether inhalation by adrenalectomized pregnant rats on the adrenal corticosterone concentration in norma, decapitated, and encephalectomized fetuses.

The influence of decapitation or encephalectomy (total removal of the brain leaving the pituitary in place) on the adrenal corticosterone concentration of the 20-day-old rat fetus has been studied in normal pregnant rats, in adrenalectomized pregnant rats, and in adrenalectomized pregnant rats subjected to the stress conditions of inhalation of ether for 40 min. Decapitation or encephalectomy of the fetus always results in a drop in adrenal corticosterone concentration within 4 h which is prevented in 15 min by injecting 3.2 mU of hog ACTH into the decapitated fetus. In mothers adrenalectomized in order to avoid a negative feedback reaction of maternal corticosteroids on the fetal pituitary-adrenal system, ether inhalation causes an important rise in adrenal corticosterone concentration in normal fetuses but not in decapitated or encephalectomized ones. Thus ether, which crosses the placental barrier, is a stressor agent for the fetal rat.


Blockage of progesterone-induced release of LH by intrabrain implants of actinomycin D.

Implants of cocoa butter (CB) or CB and actinomycin D (AD) were placed in the hypothalamus, amygdala, or anterior pituitary gland of testosterone-pretreated ovariectomized rats. The animals were then given an injection of 2.5 mg progesterone (P) at 11.00 h and sacriviced at approximately 16.30 h. Serum LH was determined by radioimmunoassay. Implants of AD placed in or near the arcuate nucleus and in other sites in the ventromedial hypothalamus blocked p-induced LH release, but those placed in the preoptic area or ventrolateral hypothalamus were only partially effective. Implants of AD in the amygdala or anterior pituitary gland had no detectable effect on LH release. Approximately 70 percent of the radioactivity in implants of 3H-AD diffused from the implant site within 8 h. of that recovered, most was found within 1 mm of the implant site. These results suggest that the ventromedial hypothalamus is one site at which AD acts to block P-induced LH release.


Neurons in the subependymal layer of the rat median eminence.

A considerable number of small and medium-size neurons are described in the subependymal layer of the caudal part of the middle portion of the rat median eminence. They are arranged mainly in rostro-caudally oriented rows. Fine structure of these nerve cells is similar to that of the arcuate neurons. Small axon terminals establish synaptic contacts with these cells. The possible functional significance of these neurons is discussed.


Radioimmunoassayable avt and avp in adult mammalian brain tissue: comparison of normal and brattleboro rats.

Arginine vasopressin (AVP) and vasotocin (AVT) were measured by radioimmunoassay in extracts of cerebral cortex, cerebellum, brain stem, pineal, hypothalamus, and neurohypophysis from normal Long-Evans rats. AVP was present in expected concentrations in pituitary and hypothalamus and there was no evidence of its accumulation elsewhere. AVT was not detectable in these tissues (within the limits imposed on our assay by the presence of excessive amounts of AVP) but was easily detectable in pineal tissue with a concentration of 22.4 plus or minus 6.6 muU/gland. Extracts of neurohypophysis and pineal glands from homozygous Brattleboro rats (rats with hereditary hypothalamic diabetes insipidus) revealed the total absence of AVP and AVT. We conclude that the Brattleboro rat is incapabel of synthesizing biologically active neurohypophyseal peptides which contain arginine in position 8.


The pineal gland of the blind-anosmic female rat: its influence on medial basal hypothalamic lrh, pif and/or prf activity in vivo.

25-day-old female rats were left intact, or rendered either blind-anosmic or blind-anosmic-pinealectomized. Five weeks later, blind-anosmic animals were found to possess significantly depressed body, anterior pituitary, uterine and ovarian weights. The pituitary levels of LH were elevated while pituitary prolactin was depressed in the dual sensory-deprived rats. Blind-anosmic animals also had significantly depressed plasma levels of LH and elevated plasma levels of prolactin. The effects of blinding and anosmia were effectively reversed by pinealectomy. Ovariectomized, estrogen and progesterone-treated (OVX, EP-treated) rats that received an intracarotid injection of a medial basal hypothalamic (MBH) extract from intact or from blind-anosmic-pinealectomized female rats exhibited a marked rise in plasma LH to a peak at 10 min after injection. This peak was followed by a steady decline in plasma LH concentration. Animals injected with MBH extract from blind-anosmic rats also demonstrated a rise in plasma LH with the levels remaining more or less constant for the 10 and 20-min samples. Rather than declining, the plasma LH levels in 3 out of 4 rats exhibited a further increase until the 40-min sample. The injection of either cortical extract or saline had no effect on plasma LH levels. OVX, EP-treated rats receiving either MBH extracts from intact or blind-anosmic rats or cortical extract exhibited a depression in plasma prolactin titers 5 min following injection. This response was followed by a slight increase in plasma prolactin at 10 and 20 min with a subsequent decrease. Each of the OVX, EP-treated recipients injected with MBH extract from blind-anosmic-pinealectomized rats responded with an obvious increase in plasma prolactin levels within 5 min after injection, followed by a decrease. It was concluded that the MBH of the blind-anosmic rat was high in LRH activity while PIF appeared to predominate over PRF activity. On the other hand, in the MBH of the blind-anosmic-pinealectomized rat, LRH activity was lower while PRF appeared to predominate over PIF activity.


Neurohypophysial electrical activity in the anesthetized cat.

The spontaneous electrical activity of the neural lobe of the cat hypophysis has been recorded. We have observed two types of activity: (1) 0.5-1.0 mV in amplitude and 4-6 msec in duration, and (2) 0.03-0.07 mV in amplitude and 1-2 msec in duration. The discharge rates of both types of activity are affected by osmotic stimuli known to influence vasopressin release. Nevertheless, only the smaller potentials were studied because they were easier to obtain. The typical response to injections of hypertonic saline was an increase in the discharge rate characterized by two peaks in the frequency-time curve. This activity seems to correspond to the unit activity described by several authors for neurosecretory hypothalamic units. Hypotonic injections cause, in about 45% of the injections, a 50% decrease in the firing rate. Injections of isotonic saline did not alter the discharge rate by the neurohypophysis. We conclude that elements in the neural lobe of the pituitary are electrically excitable and respond to stimuli known to cause vasopressin release.


Effect of adrenocortical hormones on activity of the serotoninergic system in limbic structures in rats.

A single dose of corticosterone (1 mg/kg b.w.i.p.) increased the 5-hydroxytryptamine (5-HT) content in the mesencephalon, amygdala and hypothalamus. The maximum was observed at 15 min following administration. The 5-HT level returned to normal between 60 and 180 min. The 5-hydroxyindoleacetic acid (5-HIAA) content decreased in the mesencephalon and hypothalamus at 15 min, and then increased to the maximum at 30 min in the mesencephalon and at 45 min in the hypothalamus and amygdala. There were no changes in the septum and hippocampus either in 5-HT or in 5-HIAA content following corticosterone administration. Desoxycorticosterone administration (1 mg/rat i.p.) was ineffective. Tritiated 5-HT uptake did not change in the hypothalamus and mesencephalon tissue in vitro after corticosterone or desoxycorticosterone treatment. Adrenalectomy caused a decrease in the 5-HT content in all brain areas studies. 5-HIAA decreased only in the hypothalamus. Corticosterone administration normalized the 5-HT and 5-HIAA content in the hypothalamus and mesencephalon in adrenalectomized rats. Tritiated 5-HT uptake was lower in the hypothalamus and mesencephalon in adrenalectomized rats. Corticosterone administration increased the activity back to normal in the hypothalamus, however desoxycorticosterone was ineffective. The data suggest that the plasma corticosterone level plays a role in the regulation of the activity of the serotoninergic system in certain limbic brain structures.


Adrenal cortical activation induced by hypothalamic stimulation and stress in pigeons bearing ectopic pituitary autografts.

Adrenocorticotropic abilities in basal and stress conditions, and the responsiveness of ectopically-transplanted pituitaries to hypothalamic stimulation were investigated in adult red Carneau pigeons. In birds with pituitary autografts, both electrical stimulation of the hypothalamus and restraint stress elicited a significant increase in the plasma corticosterone level, however these adrenal cortical responses were not so important as those in intact pigeons. Ether stress, which was a very effective stimulus of adrenocortical activity in controls, did not result in any plasma corticosterone elevation in pigeons that had been operated on. Such a decrease in the functional abilities of ectopic adrenocorticotropic cells was interpreted as the result of an impaired hypothalamic control acting via the systemic bloodstream. This hypothesis was corroborated by a moderate reduction in diurnal variations of the plasma corticosterone level in birds with autografts with respect to intact pigeons. Adenohypophysectomized controls did not show any adrenocortical response either to hypothalamic stimulation or to stress application.


Catecholamine-modulated field potentials in the hypothalamus.

Average evoked responses (AERs) were recorded simultaneously from 3 hypothalamic nuclei of freely behaving rats. Permanent semi-microelectrodes were implanted 6-8 days before experiments were begun. The amygdaloid AER to 32 successive stimuli consisted of large amplitude potentials made up of 3 components (P1, N1 and P2) with short latencies. The neuronal recovery function (NRF) was short. However, the acoustic AER to 32 successive acoustic stimuli in anterior hypothalamus (AH), ventromedial hypothalamus (VMH), and arcuate nucleus (AN) consisted of large amplitude potentials of long duration made up of 5 components (P1, N1, P2, and P3) with long latencies. The NRR was long. Intraperitoneal administration of L-dopa heightened the amplitude of the acoustic AER and shortened the NRF in VMH and AN. Reserpine administration 2 h after L-dopa maintained the phenomena in VMH and AN without alteration of the AER and NRF in AH. When reserpine was administered first, enhancement of the acoustic AER and shortening of the NRF was again obtained only in VMH and an L-dopa injection after reserpine treatment maintained these phenomena. Low doses of pentobarbital after L-dopa and reserpine and vice versa caused a marked increase in the acoustic AER and a shortening of the NRF in all recording sites. The amygdala AER and NRF, however, were not altered by any treatment or in any recording sites.


Prolactin release induced by electrical stimulation of the hypothalamic preoptic area in unanesthetized sheep.

The hypothalamic preoptic area (POA) was electrically stimulated through permanently implanted electrodes in 4 unanesthetized sheep. Initiation of POA stimulation was followed witin 10-20 min by large increases in plasma levels of prolactin (PRL). The stimulation-induced discharges of PRL were consistently observed in both untreated and estradiol-treated castrated animals using 0.1 to 0.7 mA of applied current. Since behavioral modifications were only sometimes associated with electrical stimulation of the POA, the response appears unrelated to the stress-induced release of PRL.


Effect of exposure to continuous light on estrogen-induced precocious sexual maturation in female rats.

Immature female rats, raised in either cyclic light (LD; 14 H LIGHT/10 H DARK) Or constant light (LL) were divided into 4 groups and given daily injections of estradiol benzoate (5, 10, or 25 ng) in 0.1 ml sesame oil starting at 24 days of age. Control animals received oil only. Injections were continued until vaginal opening (V.O.). Half of each group of animals was killed and dissected 1 day after V.O. Results indicate that both LL exposure and EB treatment accelerated sexual maturation (as indicated by the day of V.O.) with a significant interaction between the 2 treatments. Thre greatest difference in age at V.O. between LD and LL rats was observed at a dose of 10 ngEB/day. Body weights and uterine weights decreased with higher doses of EB, apparently reflecting the younger age at the time of V.O. No significant differences in ovarian weights were observed. Results are interpreted to indicate that increased exposure to light may change the sensitivity of the hypothalamic-pituitary axis to the positive feedback of estrogen.


Altered growth of hormone secretory pattern following prolonged sleep deprivation in the rhesus monkey.

Plasma concentrations of growth hormone (GH) were determined in samples obtained sequentially at 15-min intervals during the last 4 h in monkeys deprived of sleep for 76 h and the first 8 h of ensuing recovery sleep. Electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activities were recorded. Stages 3-4 sleep occurred rapidly after sleep onset and were of long duration. Plasma GH secretion was markedly elevated during sleep recovery, without apparent relationship to stage of sleep.


Reduced depletion of neurohypophysial hormone stores by vasopressin administration in rats drinking 2% NaCl.

The food and fluid intake, the fecal weight and weight of urine voided, urinary and plasma osmolality and neurohypophysial content of vasopressin and oxytocin were measured in groups of rats injected with oil and vasopressin (0.5 IU Pitressin tannate in oil daily, i.m.) before, during and after substitution of a 2% solution of NaCl for drinking water for 3 days. Before 2% NaCl was substituted for the drinking water, vasopressin treatment significantly decreased food and water intake (p smaller than 0.05) and daily weight gain (p smaller than 0.01), but no significant effect on plasma osmolality or on neurohypophysial content of vasopressin and oxytocin could be demonstrated. Vasopressin treatment did not significantly reduce the intake of the 2% NaCl solution when this was substituted for drinking water but did reduce the resulting neurohypophysial depletion of vasopressin (p smaller than 0.01). Furthermore, on the first day of NaCl drinking, the neurohypophysial content of vasopressin in vasopressin-treated rats was increased above the control value (p smaller than 0,05). These results suggest the existence of a negative feedback of vasopressin on its own release.


[Use of glucagon in the treatment of acute pancreatitis].

Personal experience with glucagon in 15 cases of acute pancreatitis is reported. Complete remission of pain within 2-3 hr after infusion of the drug was noted in 85% of the series, together with normalisation of blood amylase within 48-72 hr. Glucagon inhibits pancreatic secretio&n. Vairous theories concerning its mechanism of action are examined.


[A case of follicular carcinoma of the thyroid gland, with uptaking metastases, treated with surgery and isotope therapy].

A short review of the relevant literature is followed by the presentation of a case of follicular cancer of the thyroid with uptaking spinal metastases. Five months after almost total thyroidectomy for right macrofollicular goitre and left follicular cancer, a 131-I scintiscan showed uptake in the right lobe of the thyroid and IX and X dorsal vertabrae. Resection of the remainder of the thyroid was followed by the administration of 100 and then 150 mC of 131-I. The result at 10 months was satisfactory, though not final; no uptake at the Xth vertebra, reduced uptake at the IXth, disappearance of subjective and objective symptoms of spinal pain.


[Treatment of cancer of the lung. Considerations on a current problem].

In spite of its limitations, surgery is still the only effective means of treating lung cancer, particularly in cases where an early diagnosis has been made. Reference is made to various points associated with diagnosis, indications and treatment. It is felt that surgical management should be conducted on a radical basis, provided the patient is left with an acceptable degree of respiratory function.


[Intralobar pulmonary sequestration in lymphoid and vascular hamartia].

A case of intralobar pulmonary sequestration observed in a young women subjected to right lower lobectomy is described. Reference to the relevant literature is made in outlining the anatomical and clinical picture of this form. Emphasis is laid on certain particular features: rarity, congenital origin, difficulty of interpreting the clinical picture, the need for careful angiographic examination to ensure positive diagnosis, and the indispensability of surgical management.


[Surgical trend in the treatment of chronic venous insufficiency and in the post-phlebitis syndrome].

Experience in the management of the complications of varicose diseases is described. The series consists of 173 patients with chronic venous insufficiency (including 30 with post-phlebitis syndromes). In 90% of cases, interruption of the communicating vessels according to Linton gave final cure of ulcere and eczematous dermatitis.


[Surgical treatment of cardiospasm].

Results obtained with Heller's operation in the management of 27 cases of cardiospasm are presented. The probable causes of oesophageal achalasia leading to dilatation and elongation of the wall are examined. These, in association with nervous changes, form the most marked features of the syndrome. The soundness of the operation employed is confirmed by the results achieved. These are most satisfactory when the disease is at the initial stages and dilatation is not excessive.


[Klobusitsky's hemocoagulase in plastic surgery].

Klobusitzsky haemocoagulase, a haemostatic drug obtained from snake poison, was administered prior to surgery in 35 cases of harelin, cleft palate, hypospadias and deviation of the nasal septum. Treatment was carried out from 2 to 6 days, doses and i.m. or i.v. administration being determined on the basis of age. Objective and subjective results were good, particularly in cases of cleft palate and septum deviation. In all cases, there was a significant shortening of bleeding time after treatment with the drug.


[A case of intestinal duplication. Clinical study].

Reference to the relevant literature is followed by the presentation of a personal case of ileal duplication, in which pain led to an a mission diagnosis of appendicitis, whereas surgery revealed a second ileum, rising about 6-7 cm from the caecum and running for 35 cm into the sigmoid colon. The aetiopathogenesis of this abnormality is discussed. Pain, as in the present case, is evaluated with respects to its interpretation in preoperative diagnosis.


[Effects of slowly progressive constriction on the proximal pancreas of the rabbit].

Slow, progressive constriction with cellophane tape was experimented on the proximal segment of the rabbit pancreas. Histological examination of the distal segment over a period of 10-30 days showed the appearance of morphological changes reminiscent of chronic pancreatopathy in man. Stress is laid on the need for an experimental model suitable for the provocation of chronic forms, particularly if similar results can be obtained on animals of larger size.


[Use of modified heterologous arterial prostheses in reconstructive arterial surgery].

Results with modified heterologous artery prostheses in reconstructive artery surgery.


[Anorectal fistulous abscesses. Long-term follow-up of the 1st operation, in 287 cases].

A review of a series of 287 operations for peri-anal fistulous abscess in patients admitted for the first time, to the 1st Surgical Division of the Fatebenefratelli Hospital, Milan, is reported. Surgical management adapted as far as possible to the anatomy of the anal canal and to the aetiopathogenesis of the fistula, resulted in a recurrence rate of only 13%. There were no instances of faecal incontinence. Two cases of partial gas incontinence were observed.


[Spironolactone combined with chlorthalidone in the treatment of essential arterial hypertension].

The antihypertensive effect and the tolerance of the association of spironolactone and chlorthalidone were evaluated clinically and by numerous laboratory examinations in a group of 18 patients affected with non-complicated essential hypertension. All the patients were treated for 30 consecutive days with chlorthalidone (100 mg/day) and then for another 30 days with the two drugs administered contemporaneously (100 mg/day of spironolactone + 100 mg/day chlorthalidone). The balanced combination of the two drugs showed to be significantly more active than the treatment with just chlorthalidone and the margin of safety wider; the therapeutic activity showed to be independent from the variations of the plasma renin activity.


[When cholangiocholecystography should and should not be performed].

Little-know contraindications for i.v. cholangiocholecystography with water-soluble hexaiodated contrast media are presented. Particular reference is made to suspected cholecystic lithiasis and dysprotidaemic patients or those undergoing treatment with sulphamides, salicylic acid, barbiturates, etc. Lastly, reference is made to the suitability of cholegraphy in suspected acute cholecystitis. Here, in fact, this method is preferable to oral cholecystography.


[Urinary kallikrein excretion in hepatic cirrhosis].

Measurements of urinary kallikrein using an esterolytic assay revealed higher levels in patients with liver cirrhosis than in a control population. The range of excretion in 33 patients with cirrhosis was from 18.68 to 85.20 E.U. per 24 hours with a mean excretion of 39.42 plus or minus 2.84 E.U. Kallikrein excretion in the control group ranged from 13.20 to 39.50 E.U. per 24 hours with a mean of 24.44 plus or minus 1.66 E.U.


[On the hypouricemic action of an alkaline mineral water in the aged].

The importance of loading tests, particularly venous loading with fructose, in the determination of changes in purine metabolism is stressed. Such changes may well be present even if basic uricaemia is within the limits of normal. Fructose loading was used to determine the hypouricaemising and uricosuric effects of a mediomineral water in aged subjects following daily administration. A hypouricaemising effect was noted and there was an improvement in loading curve patterns. This effect is considered to be primarily due to the uricosuric activity of the water itself. Sugar tolerance and the insulin response to loading, on the other hand, were not altered by the treatment.


[Clinical and epidemiological repercussions of bacterial resistance].

Following the observation of a high percentage of bacterial resistance to antibiotics, the mechanisms of the establishment and transmission of such resistances on an extra-chromosomal basis (R factors) are examined in detail. After noting that the increased incidence and spread of bacterial strains resistant to chemotherapeutic substances and antibiotics is caused by the widespread use of antibiotics in the zootechnical field, the use of antimicrobic substances for food conservation, the increasing use of broad spectrum antibiotics and the rapid selection of resistant Gram-negative strains in hospitals, the clinical and epidemiological effects of antibiotic resistance in the Enterobacteriaceae are considered. The situation in Italy is looked at in particular where multiresistance to antibiotics promoted by R factors, already widespread in northern Italy, is being presently extended to southern Italy. It is hoped that physicians will realise the immediate and future epidemiological effects of the indiscriminate employment of broad spectrum antibiotics as this inevitably leads to the establishment of multiple resistance factors in Gram-negative bacterial populations.