"Practical suggestions on facial plastic surgery -- how I do it". Augmentation mentoplasty using polyamide mesh.

Augmentation mentoplasty, a cosmetic surgical procedure to reshape the contour of the mental area, usually is accomplished with the insertion of autogenous graft or alloplastic implant material. Obtaining autogenous graft material has been the major disadvantage of requiring an additional surgical procedure. Alloplastic implant material is wiedly perferred because of its ready availability, ease of sterilization, capability of being cut, carved, and shaped as desired, and the relatively few postoperative complications that ensue from its use. The possible complications are infection, rejection by the host, displacement (even many years later), and underlying mandibular bone resorption. The author's four-year experience using polyamide mesh placed supraperiosteally in 100 patients is reported and the technique is described. Results have been consistently good, no implant has had to be removed or replaced. Other advantages are ease of inserting the polyamide mesh, thus facilitating the surgical procedure, minimal postoperative morbidity or reaction, flexibility in conforming exactly to the shape of the mandible, ingrowth of fibrous tissue thus avoiding late displacement, and providing a natural feel to the reconstructed area. There has been no roentgenographically demonstrable evidence that suggests bone resorption.


[Operating room ethrane pollution (author's transl)].

Several surveys of ethrane pollution were made by the authors in operating rooms, either equipped or not with general ventilation systems, during operations where non-rebreathing anaesthesia devices were used. In operating rooms without general ventilation systems, but with simple air conditioning systems, ethrane pollution was found to be rather high and to attain 30-40 ppm at the fourth hour of operation. No statistically significant differences were elicited among levels found at the anaesthetist, surgeon and assistance personnel sites. The authors analyze the kinetics of ethrane pollution as a function of its consumption and of time and discuss the most suitable means for decreasig and preventing such pollution.


[Benzene acute aleukemic leukosis, with widespread leukemic parenchymal infiltration (author's transl)].

A case is reported by the authors of a progressive benzene hemopathy with a final leukemic evolution. The leukemic pattern was an autopsy ""surprise'', inasmuch as never, even in the hours just before death, could leukemic cells be detected in the blood stream. The authors discuss some pathogenic aspects, with particular emphasis on the systemic spreading of a malignant hemopathy from very few leukemic cells in bone marrow.


[Epidemiologic evaluation of isocyanate immediate irritative action: 'one day effect' control (author's transl)].

Nineteen MDI exposed workers showed ventilatory changes, after eight hour exposure, mainly involving upper respiratory airways; the changes reversed following a bronchodilator aerosol. An incomplete recovery of VC was found in some subjects; therefore, the possibility of changes in the lung elastic recoil forces was hypothesized. No statistically significant differences were found as to occupation and smoking habit, which suggests that even low MDI concentrations could be enough to give rise to acute effects. The greater impairment found in subjects who were already affected by morning time emphasizes the necessity that such subjects were not employed in their specific work.


[The medical management of carcinoma of the stomach (author's transl)].

Only a small proportion of patients with carcinoma of the stomach are suitable for radical surgery. For the remainder symptomatic treatment and radiotherapy alone or in combination with chemotherapy can be used to relieve distressing symptoms of pain, nausea and vomiting, and severe anemia. In the case of radiotherapy or chemotherapy, a degree of tumor regression can be expected. There have been encouraging results recently in palliating this disease with new radiotherapy techniques, notably fast neutron irradiation.


[Surgical management of gastric carcinoma (author's transl)].

The treatment of choice of gastric carcinoma is still radical surgery which has to be tried in all cases which are not proven to be untreatable by this method. During surgery the tumor as well as regional lymph nodes and neighboring structures have to be removed; in special cases subtotal gastrectomy carrying a lower risk at surgery does allow complete removal of the tumor. Replacing the stomach by interposition of a long loop of the small intestine has proven to yield good results. The overall bad results of management of gastric carcinoma cannot be improved to any considerable extent by surgical means, e.g. by lowering the risk of surgery or by increasing the number of patients operated upon. Early diagnosis is of outmost importance since patients with tumors of an early stage have a rather good chance of being completely cured.


[A new endoscopic method: the peroral choledocho-pancreatoscopy (author's transl)].

A new very thin glass fiber endoscope ("baby scope") has been developed, which can be passed through the channel of a modified duodenoscope ("mother scope") for catheterization of the choledochus or of the pancreatic duct. Peroral choledocho-pancreatoscopy (PCPS) was performed in 9 patients, the endoscopic results are presented. Other new auxiliary instruments for diagnostic or therapeutic purposes in biliary or pancreatic diseases are described: a brushing catheter, a special biopsy forceps, a retention probe and a balloon-tipped catheter.


[Endoscopy of the upper gastrointestinal tract with the new panendoscope f7 (author's transl)].

The Panendoscope F7 with a diameter of 9.5 mm, originally designed for pediatric endoscopy, was used in adults. First results are reported. The instrument has a shorter flexible tip facilitating biopsies in the esophagus. During exploration of the duodenal bulb tip of the instrument can be inverted in most cases allowing inspection of the pyloric region of the duodenum. The aboral part of a gastrojejunal anastomosis after partial gastrectomy can be visualized with the inverted tip of the panendoscope as well. The instrument does also facilitate endoscopic examination of the remaining stomach and of the afferent loop in patients partially gastrectomized. Emergency endoscopy can be done while a gastric tube removing blood during the examination may stay in position.


[Lymphangiosis carcinomatosa of the lung and cardiopulmonary shock as initial findings in gastric cancer (author's transl)].

A case is reported of a 34 year old woman, who was hospitalized because of cardiopulmonary shock of sudden unsuspected onset. X-ray examination revealed diffuse interstitial pulmonary infiltration. Intra-aortal counter-pulsation did improve the condition only for short time. On autopsy an adenocarcinoma of the stomach was found, as well as diffuse carcinomatous infiltration of pulmonary lymph and arterial vessels. Thus lymphangiosis carcinomatosa has to be taken into consideration in discussing the differential diagnosis of diffuse interstitial pulmonary infiltration in young patients. The presence of microangiopathic hemolytic anemia may help to establish the diagnosis.


[The pathogenesis of gastric carcinoma--epidemiologic pathology of precursor lesions (author's transl)].

An overview of the epidemiologic and pathologic significance of premalignant lesions of the stomach is presented, with correlations between cancer risk, prevalence of atrophic gastritis and environmental factors such as nitrate and food items. The protective role of lettuce and fresh vegetables is discussed. The diffuse type of gastric cancer appears to be less environmentally linked than the intestinal type, and it is hypothesized that the pathogenetic process may begin during the first decade of life. An analysis of precursor lesions and gastric cancer in various geographic regions of Columbia, South America is presented to illustrate these relationships.


[Experimental gastric cancer (author's transl)].

Methods have been established to produce gastric cancer in rats and dogs by administration of N-methyl-N'-nitro-N-nitrosoguanidine or of the ethyl derivate. The agent is administered in drinking water or by a pellet diet soaked in the carcinogen. Histologically well differentiated and poorly differentiated types of adenocarcinoma and signet-ring cell tumors are induced in several months with greath reliability. Metastases were observed in both rats and dogs with gastric carcinoma. The carcinogenic effect could be enhanced by surface active agents, sodium chloride, iodoacetamide, insertion of plastic beads into the stomach and gastroenteroanastomosis. Follow-up studies by radiologic, endoscopic and bioptic examinations are possible in the dog. There are similarities in these experimental tumors to those in man and thus they provide means for the investigation of histogenesis, prevention, and chemotherapy of gastric cancer. An adenocarcinoma of the glandular stomach of a Wistar rat was successively transplanted to new born rats of the same strain.


[Gastric cancer--an attempt to correlate experimental and clinical findings (author's transl)].

The correlation of induced gastric cancer in experimental animals with spontaneous gastric cancer in man may be based on several parameters. Malignant tumors have many properties, such as growth, heterotopia, anaplasia, unresponsiveness to extrinsic stimuli, and ability to evoke local and systemic reactions in the autologous host. Individually these properties do not characterise malignancy, but collectively they provide criteria for correlation of human and experimental gastric cancer. Accumulated data, particularly recent findings, attest to many similarities of induced animal and spontaneous human gastric cancer. However, the complexity of the disease is emphasized and data indicate a multi-causative etiology, with various factors interacting in a multi-coordinate manner.


Effects of beta-hydroxybutyrate, glycerol, and free fatty acid infusions on glucagon and epinephrine secretion in dogs during acute hypoglycemia.

The importance of glucagon in the regulation of carbohydrate metabolism is clearly established. However, the role played by this hormone in the regulation of the overall fuel economy is less certain, particularly with respect to such nonglucose fuels as free fatty acids, glycerol, and ketoacids. In order to elucidate glucagon's role with respect to the latter substrates, dogs were infused with solutions of these three fuels, and their A-cell responses to concomitant insulin-induced hypoglycemia were studied. In addition, epinephrine levels were also monitored. It was found that while these infusions failed to suppress glucagon release, the ketoacid infusion did significantly reduce epinephrine secretion during the insulin-induced hypoglycemic period. It was therefore concluded that glucagon secretion under these experimental conditions is not responsive to prevailing non-glucose fuel levels. Indeed, these data suggest that the sympathetic nervous system may play an important role in the regulation of the over-all fuel economy.


Alterations in proline metabolic enzymes with mammalian development.

Through the use of specific radioisotopic assays, the activities of enzymes degrading and synthesizing proline were examined in rat liver and kidney as a function of development. Proline oxidase (PO), the enzyme converting proline to delta 1-pyrroline-5-carboxylate (PC), undergoes 15- and eight-fold increases in liver and kidney, respectively, as rats mature from term-fetal to adult life (6-12 wk). The differences are not due to enzyme inhibitors or activators, and kinetic analysis reveals the change to be one of greater tissue content of the same enzyme. delta 1-Pyrroline-5-carboxylate dehydrogenase, which converts PC to glutamate, shows a two- to three-fold increase in both tissues, paralleling the changes in PO with development. delta 1-Pyrroline-5-carboxylate reductase (PCR), the enzyme which catalyzes the committed step in endogenous proline formation, undergoes oppositely directed changes, such that adult levels are only 20%-25% of fetal levels in liver and kidney. PO/PCR ratios are 25- to 50-fold greater in adult central tissues than they are in fetal tissues. Thus, the central tissues of adult rats appear to function as proline utilizers, whereas those of young rats are chiefly proline formers. This difference may relate to different rates of utilization of proline for protein synthesis in young and adult rats.


Insulin sensitivity of adipose tissue in vitro and the response to exogenous insulin in obese human subjects.

The effect of varying concentrations of insulin on 1-14C-glucose conversion to 14CO2 was measured in subcutaneous adipose tissue samples obtained from 16 obese human subjects (10 nondiabetic, 6 diabetic). An index of insulin sensitivity in vitro, Kins, was calculated as the concentration of insulin stimulating one-half maximal 14CO2 production. An index of insulin sensitivity in vivo, Kitt, was calculated as the rate constant for decrease in blood glucose after rapid intravenous administration of 0.05 U/kg insulin. There was, over-all, a significant correlation between Kins and Kitt, indicating that insulin sensitivity of 1-14C-glucose oxidation by adipose tissue in vitro reflects the general state of sensitivity of glucose metabolism to insulin in vivo in obese human subjects. The mean values for both Kins and Kitt in the nondiabetic subjects were significantly different from those in the diabetic subjects, indicating greater sensitivity to insulin in the former group. The nondiabetic group was also distinguished by a significantly greater plasma insulin:blood glucose ratio in the oral glucose tolerance test. These results support the view that tissue insulin sensitivity as well as pancreatic beta cell response play an important role in determining glucose tolerance in obesity.


Metabolic responses to dietary supplements of bran.

During a metabolic ward study, the addition of dietary fiber in the form of wheat bran biscuits to the diet of five volunteer subjects resulted in an increase in the stool wet weight and fecal solids. The excretion of fecal solids was highly correlated with the intake of unavailable carbohydrates, and fecal losses of water were similarly correlated with fecal excretion of these constituents. The major component of the increase in fecal solids was due to the noncellulosic polysaccharide fraction of dietary fiber. There was an increased fecal excretion of nitrogen fat and energy by most subjects when the supplement was eaten. However, the increased loss of energy in the feces was only 40-80 kcal/day, and therefore a large supplemental intake of dietary fiber had only minor effects on energy metabolism. Supplemental fiber is thus unlikely to induce a useful loss of calories in the management of obesity. The addition of dietary fiber caused an increased excretion of most inorganic constituents, particularly sodium and phosphorus; increased excretion of iron and magnesium was also found in two subjects.


The importance of the stomach in mediating histamine-induced hypocalcemia in the rat.

The effect of histamine on serum calcium homeostasis was studied in the rat. After the intravenous administration of 0.5-1.0 mg histamine base to fasted Holtzman rats weighing 80-100 g, a significant lowering of serum calcium (Ca) level occurred 30 min after injection (decrease in Ca, 1.4-1.9 mg/100 ml), but normocalcemia returned at 60 min. Repeat intravenous injections of histamine 1.0 mg resulted in repeated lowering of the serum Ca level. Hypophosphatemia did not accompany the hypocalcemia. Thyroparathyroidectomy (TPTX) did not eliminate the calcium-lowering effect of histamine in acute TPTX animals but did so in more chronic TPTX animals in which the mean serum Ca was 7.6 mg/100 ml or less. Gastrectomy, however, completely eliminated the calcium-lowering effect of histamine given in doses of up to 2 mg/rat (20 mg/kg of body weight), despite the presence of an intact thyroid gland. These studies support the role of a gastric factor and not the thyroid secretion of calcitonin in mediating this response in the rat.


[Biological and medical applications of the cathodoluminescence in the scanning electron microscope (author's transl)].

The light emission according to the excitation of solids and molecules by electrons--named cathodoluminescence--extends the analytical field of applications of the scanning electron microscope. This method can be applied in biological and medical research. It can be used for the investigation of marked specimens similar to the fluorescence microscopy. The autoluminescence of some substances can also be used for special applications. The cathodoluminescence in the scanning electron microscope has the advantage that more sensitive detector-systems can be used than with the fluorescence microscope. Moreover, in the scanning microscope it is possible to combine the cathodoluminescence mode with other imaging or analytical equipments.


[A coordinate and area recording microscope for the topographic analysis of particle size distributions (author's transl)].

A coordinate recording microscope equipped with a rolling disc planimeter is described. The application of the instrument for the analysis of cell size distribution in histologic preparations is demonstrated. The microscope stage is moved in x, and y directions by two digital micrometer spindles. The planimeter is equipped with a rotary encoder. The spindles and the rotary encoder are connected to digital counters which are input to a multiplexer. The multiplexer outputs the data to a teletype terminal both as hard copy and on paper tape. To avoid repeated measurements a video-acoustic monitoring system is provided. Processing of the data is carried out off-line with a IBM 1130 computer. Here the measured cells are displayed as points or circles on an oscilloscope. The distribution of cells of any size can be studied topographically in any region of the field of measurements.


Incoherent bar images formed by a polarizing microscope with crossed polarizers.

Diffraction images of incoherent bar objects formed by a polarizing microscope with crossed polarizers are studied. Expression for intensity distribution has been derived and the results in the form of curves have been plotted. The images which are of unusual shape, different from the patterns formed by the ordinary microscope are strongly dependent upon the size of the bar/coherence parameter. The line spread function can be obtained by taking a very narrow bar.


Dynamics of myocardial infarction--the role of critical closing pressure.

Pressure in the primary distributing network of a vessel on the surface of the heart is normally sufficient to prevent critical closure of its derivative vessels. It is proposed that acute occlusion of a major supply vessel or over activity of the heart in the presence of an impairment of the lumen of a major supply vessel may reduce transmural pressure in parts of the network. In consequence vasospasm, the result directly of critical closure, is postulated as the basis for myocardial infarction, together with maximal dilatation of vessels in which pressure did not fall to critical levels.


Ascorbic acid and diabetes mellitus.

Dehydroascorbic acid, the oxidized form of vitamin C, causes diabetes when injected into animals and has been reported to be present in increased amounts in the blood of patients with diabetes mellitus and even in prediabetics. One of the earliest changes in diabetes mellitus is electron-microscopic evidence of damage to the inner endothelial lining of the blood vessels. Certain bioflavonoids, which are natural non-toxic food substances from plants, like rutin from buckwheat, prevent the oxidation of ascorbic acid and seem to protect the endothelium when given with vitamin C; it is therefore suggested that all vitamin C tablets should be combined with these flavonoids.


On the potential usefulness of exchange plasmapheresis in the immunotherapy of cancer and of some chronic persistent infections.

In an individual sensitized to an antigen, Withdrawal of the corresponding antibody and of the accompanying antigen-antibody complexes stimulates antibody production: the end result is thus not unlike the effect of a booster dose of that antigen. Conversely, a sufficient concentration of antigen-antibody complexes will eventually shut off the antibody production to that antigen. The body is able to regulate through this mechanism the amplitude of the immune response, using the feed-back interaction of antigen-antibody complexes with the immune system. Without such a control system any antigenic stimulation would result in an uncontrolled out-pouring of antibodies, as is observed in myeloma. The regulation of cell mediated immunity is also indirectly affected by the concentration of circulating antigen-antibody complexes. Other mechanisms of immunoregulation are also at work, using the mediation of so-called suppressor cells, identified as sub-populations of T and B cells acting both specifically and non-specifically on immune effectors cells. It is likely that a major factor contributing to the pathogenesis of some persistent chronic infections such as syphilis, brucellosis, chronic viral hepatitis, leprosy, vaccinia, congenital cytomegalovirus infection persisting in childhood, and so on, and in conditions such as cancer, is an inadequate initial production of antibodies, further aggravated by the ensuing immunosuppression brought about by the formation of antigen-antibody complexes. Antigen-antibody complexes have indeed been identified as playing a prominent role in some of these diseases. It is also suggested that the magnitude of the initial antigenic dose may influence the ensuing immune response: while a large antigen dose could induce a "classic" and efficient immune response, a low antigen dose, such as an incipient neoplasm, could result in a minimal antibody response, further suppressed by the appearance of antigen-antibody complexes. Through this mechanism, a premature failure to eradicate the disease would follow. I suggest that a significant and sudden lowering of the concentration of relevant entibodies and antigen-antibody complexes through exchange plasmapheresis, would trigger a fully adequate and therapeutic immune response. This possibility is discussed.


On the evolution of X-chromosome inactivation in mammals and the clinical consequences to man--a hypothesis.

A clinical analysis of abnormal sex chromosome states in man suggests that Lyon's recent X-Y translocation hypothesis for the evolution of X-chromosome inactivation in mammals most likely would have lead to an evolutionary dead-end. Therefore, as an alternate I have hypothesized that: X-chromosome inactivation in somatic cells of mammals could have evolved by a complementary process of one by one heterozygous physical deletion in males and heterozygous inactivation in females of genes for "somatic" traits scattered throughout the genome whose effective output had become 50% excessive during prior evolution. However, this complementary process could occur safely only if the genes so deleted or inactivated first segregated by chance onto the evolving sex-chromosomes via a one by one reciprocal exchange for non-sex related genes already there. The complementary process thereby would allow slow evolution of the Y-chromosome in the male and X-chromosome inactivation in the female. Evolution of X-chromosome inactivation in this manner is compatible with Ohno's observation of "conservation" of the X-chromosome in mammals; and the occurrance of clinical "somatic" abnormalities in the abnormal X or Y chromosome states of man despite X-chromosome inactivation.


"Basal" palmar skin potentials and body fluid potassium.

When palmar eccrine sweat glands are inactive the potential difference between palmar skin and a prepared forearm site is a function of the ratio of external (electrode electrolyte) and internal (tissue fluid) potassium concentrations. Evidence indicates that this "basal" palmar skin potential changes systematically with changes in ECF K+, and may be used to monitor such shifts, as, for example, in stress.


Computer analysis of external counterpulsation by use of a nonlinear mathematical model of the cardiovascular system.

A pressure system externally applied to the limbs of a patient has been proven effective in assisting circulation in animal and clinical studies. In this study a nonlinear mathematical model of the cardiovascular system is utilized to determine the effectiveness of high-frequency components in the external pressure waveform. The development of the model, the method of analysis, and the results acquired with the model are presented in this report, demonstrating its suitability for the study of external counterpulsation.


Counterpulsation with a new pulsatile assist device (PAD) in open-heart surgery.

A new pulsatile assist device that converts roller pump flow to pulsatile flow has been developed and proven effective through clinical testing. The PAD is also a hemodynamically effective arterial counterpulsator both before and after cardiopulmonary bypass. The PAD has been found to be an important adjunct to the care of critically ill patients undergoing open-heart surgery. In addition, in selected patients, the PAD is a reasonable alternative to the elective use of intra-aortic balloon pumping.


Cortisol in physiological concentrations acts within minutes to modify effects of prolactin and growth hormone on prostaglandin secretion: importance of effect in modulating cellular responses to calcium and cyclic nucleotides.

We propose that intracellular prostaglandins (PGs) are essential for the final expression of the effects of second messengers in most cells. We suggest that the amounts of PGs required are very small (in the picomolar range) and are much lower than those used in most current PG studies. We suggest that while therapeutic levels of inhibitors of PG synthetase may be adequate to block the overflow of PGs from cells, they are in most cases unlikely to reduce intracellular PGs sufficiently to test the role of such PGs. We propose that there is a basal level of PG synthesis unaffected by hormones but that above this level PG synthesis is regulated by the interplay between physiological levels of cortisol, prolactin, growth hormone and thyroid hormones. For the most part prolactin seems to stimulate PG synthesis and cortisol to inhibit it: cortisol has, however, no inhibitory effect on basal PG synthesis. In reducing prolactin-stimulated PG synthesis cortisol is 1000-2000 times more potent than indomethacin on a molar basis. We suggest that the regulation of intracellular PG levels is the mechanism of the so-called "permissive" actions of these hormones. These concepts could prove important in the understanding of many aspects of physiology and pathophysiology including diurnal and seasonal changes in hormone responsiveness. They are also relevant to the use of established drugs and the design of new ones.


Physiologic profiles in circulatory support.

Measurements of hemodynamic, oxygen transport, and tissue utilization functions were incorporated into a physiologic profile assessment system in order to evaluate patients who are candidates for mechanical support of the failing heart. Circulatory function was assessed in patients with acute myocardial infarction associated with diminished peripheral perfusion and compared to an age-matched, normal patient group. Serial studies performed prior to and during intra-aortic balloon counterpulsation provide a means to assess circulatory status accurately and document the efficacy of therapeutic interventions.


Circulatory support with a left-heart assist device after intracardiac operation: design concepts and management techniques.

A simple left-heart assist device was developed to reduce left ventricular preload while simultaneously increasing total systemic blood flow. It consists of special cannulas connected to a simple extracorporeal tubing loop and roller pump, designed to permit bypass of as much as 5 liters of blood per minute from left atrium to ascending aorta. Employed in 15 patients with advanced heart disease who were in low cardiac output following repair, the system was proven effective. An asset of the device is the ability to subsequently separate the patient from the device without need to reenter the thorax or abdomen.


Return to work after a myocardial infarction: evaluation of planned rehabilitation and of a predictive rating scale.

This paper reports the first recorded controlled trial of cardiac rehabilitation after myocardial infarction in men of working age, viewed as a team intervention effort to facilitate the patient's return to normal work.  Our results show that this intervention is helpful in returning to jobs which they can handle successfully men who would otherwise be at risk of remaining unemployed. A previously developed rating scale for predicting return to work after myocardial infarction was used and reevaluated. Employment and occupational level at admission to hospital, work history, availability of the previous job, educational level, family and social stability, age at which regular cigarette smoking commenced, and level of anxiety and depression on a personality scale proved highly predictive.


Mobile laboratory for respiratory surveys in industry.

This paper describes the design and performance of a self-contained mobile respiratory laboratory used for the carrying out of complex lung function tests in epidemiological studies of respiratory disease in industry. The laboratory is equipped to perform all conventional lung function tests other than those involving arterial puncture or radioactive isotopes. It has been shown to have a high level of employee acceptability and technical accuracy.


Hemodynamic alterations with a reversed unidirectional intra-aortic balloon.

The hemodynamic effects of dual-chambered unidirectional balloon pumping in alternate directions were studied in 44 trials conducted on 8 dogs. Results indicate an increase in cardiac output in normal dogs with downstream pumping by unidirectional intra-aortic balloon, which may have important implications for the treatment of low output cardiac failure.


Medical manpower-the Australian scene.

Medical manpower projections indicate that by 1991 there will be one doctor to 500 population instead of the 1: 721 ratio in 1976. There are many variables; projections, while hazardous, are necessary for planning because of the long lead time. Productivity is equally important. There is no evidence that the rapidly rising female intake will reduce productivity in the next 15 years.


Primary oxalosis with myocardial involvement and heart block.

An unusual case is described of primary oxalosis with renal failure and cardiac involvement with complete heart block. Although cardiac involvement rarely occurs, it nevertheless requires evaluation because of the therapeutic implications.


The Windkesselventricle with guiding balloon as a new approach for assisted circulation.

A simple method was developed to aid the patient with low cardiac output syndrome following cardiac surgery. The concept was shown to be feasible in electric circulatory analog studies and verified in 20 dog experiments. A Dacron graft (end-to-side) through the right second intercostal space connects the ascending aorta to the subcutaneously implanted, ellipsoidal-shaped artifical ventricle. A spherical polyurethane balloon is positioned in the aorta distal to the Dacron graft via the femoral artery. The ventricle and balloon are pneumatically driven synchronously with the ECG. In natural systole the balloon is inflated, occluding the aorta, and the artificial ventricle sucks the entire stroke volume. In natural diastole the balloon deflates and the artificial ventricle ejects the blood into the peripheral arteries. With this system it is possible to maintain a normal systemic pressure and have high hemodynamic efficiency. The left ventricular systolic pressure is 85 percent unloaded. The systolic wave is turned 180 degrees to the natural. After treatment, the device can be removed without thoracotomy.


Intra-aortic balloon assist for cardiogenic shock and ischemic states at Massachusetts General Hospital.

Intra-aortic balloon pumping is used at MGH for the reversal of acute myocardial ischemia in those patients not responding to usual medical means. The survival rate of surgical intervention in patients in cardiogenic shock was significantly increased in patients who had been balloon-pumped prior to surgery. The use of the intra-aortic balloon assist early in the postoperative patient showing low cardiac output state not only served to improve hemodynamics but also led to the preservation of the myocardium and ultimate improved survival. The balloon assist was initiated to control the ischemic states in patients with severe unstable angina. Used in association with nitroprusside and propranolol, this method produced marked improvement and reduction of pain in patients. Indications are that intra-aortic balloon counterpulsation at the present time is the safest and most predictable means of controlling acute ischemia in patients who are resistant to standard medical intervention.


Anatomy of the lumbar spine.

The macroscopic courses of the posterior primary rami in the lumbar spine are described and illustrated from fresh cadaver dissections.


How did you guess? Or, what do multiple-choice questions measure?

Multiple-choice questions classified as requiring problem-solving skills have been interpreted as measuring problem-solving skills within students, with the implicit hypothesis that questions needing an increasingly complex intellectual process should present increasing difficulty to the student. This hypothesis was tested in a 150-question paper taken by 721 students in seven Australian medical schools. No correlation was observed between difficulty and assigned process. Consequently, the question-answering process was explored with a group of final-year students. Anecdotal recall by students gave heavy weight to knowledge rather than problem solving in answering these questions. Assignment of the 150 questions to the classification by three teachers and six students showed their congruence to be a little above random probability.


[Breast affections requiring surgery: diagnosis from the view-point of a radiologist (author's transl)].

Examinations by X-rays are the best method to detect early carcinomas of the breast and precancerous alterations. In many cases it is possible to avoid operations by pneumocystography. An unsuspected result by pneumocytostography permits to depart from the principle to remove every palpable tumor. Nevertheless the X-ray examinations have some limits. Therefore it is necessary for the radiologist to know exactly the clinical state. Furthermore there must be a very good cooperation between the radiologist, the surgeon and the histologist. Problems originated from the appearance of so-called suspicious microcalcifications visible in well made mammograms. The sooner the microcalcifications are excised the more it is possible to discover early carcinomas and precancerous alterations but also harmless variations. Pathological secretion from the nipple is an indication for galactography. If there are pathological alterations in the ducts it is necessary in order to avoid mistakes in diagnosis to excise and examine the specimen by very reliable methods. The results from thermographical and cytological investigations are sometimes of value for the decision to perform an operation but not for the decision to omit the histological examination.


[Vulvitis due to ancylostoma duodenale (author's transl)].

There is reported about a case of vulvitis, which was resistant to usual forms of therapy. Infections as such of Candida or of Trichomonas as well as diabetes could be excluded. But there could be proved an incidence of Ancylostoma duodenale, which is nowadays more often to be observed. Adequate therapy was successful.


Nervous signs in bovine coccidiosis.

In 2 outbreaks of coccidiosis due to E bovis and/or E zurnii infection in Canadian cattle, nervous signs included opisthotonos, medial strabismus, hypersensitivity, tetanic spasms, and convulsions. All of the affected animals died in convulsions after an illness of one to several days during which time they showed periodic nervous signs. Necropsy revealed a very severe enteritis with the most severe lesions in the spiral colon. Much of the intestinal mucosa in this area had been destroyed by the parasite. None of several suggested causes of such nervous signs was indicated by laboratory findings, but the possibility of toxins produced by the coccidia could not be ruled out.


Temperature-sensitive breakdown in vivo of polysomes with mutants of Chlamydomonas reinhardii.

Two temperature-sensitive mutants of Chlamydomonas reinhardii Dangeard which are defective in protein synthesis were examined. Both show breakdown of their polysomes at the restrictive temperature into monosomes which do not contain fragments of mRNA. Many of the ribosomes still contain nascent peptides able to react with puromycin. The polysome breakdown involves only cytoplasmic (80S) ribosomes and is prevented or reversed when ribosome translocation is inhibited with cyloheximide.


Recombination between mutants of Phycomyces with abnormal phototropism.

Sexual crosses were studied between mutants of Phycomyces blakesleeanus with abnormal phototropism (phenotype mad). Recombination frequencies were determined among five genes madA to madE. No clear evidence was found for linkage between any of the genes. Inconsistent results in crosses involving madC are attributed to nonisogenicity between the particular strains used. One mad strain was discovered to be a double mutant. A new gene, tentatively designated madG, was segregated from a cross involving that strain.


A proposal for a uniform nomenclature for the genetics of bacterial protein synthesis.

A new genetic nomenclature for the macromolecules involved in bacterial protein synthesis is proposed and explained. Genes for ribosomal proteins are designated rsp, rpl and rpm while genes for ribosomal RNAs are rrs and rrl. Protein synthesis factors and ribosome assembly and modification activities are also consistantly named.


The product of the ade1: gene in Schizosaccharomyces pombe: a bifunctional enzyme catalysing two distinct steps in purine biosynthesis.

The assignment of the known ade genes to steps in purine biosynthesis in Schizosaccharomyces pombe has been completed with the demonstration that an ade3 mutants lacks FGAR amidotransferase, ade1A mutants lack GAR synthetase and ade1B mutants lack AIR synthetase. A comparison of enzyme activity with map position for ade1 mutants shows that (1) complementing ade1A mutants lack GAR synthetase but posses wild type amounts of AIR synthetase, (2) complementing ade1B mutants lack AIR synthetase but posses variable amounts of GAR synthetase, (3) non-complementing mutants lack both activities. In wild type strains the two activities fractionate together throughout a hundred-fold purification. Hence the ade1 gene appears to code for a bifunctional enzyme catalysing two distinct steps in purine biosynthesis. The two activities are catalysed by two different regions of the polypeptide chain which can be altered independently by mutation. Gel filtration studies on partially purified enzymes from wild type and various complementing mutant strains, indicate that the bifunctional enzyme is a multimer consisting of between four and six sub-units of 40,000 daltons each. GAR synthetase activity is associated with both the monomeric and multimeric forms but AIR synthetase is only associated with the multimer. A comparison of enzyme levels between diploids and their original complementing haploid strains suggests that complementation is due to hybrid enzyme formation.


Lethal and mutagenic effects of nitrosoguanidine on synchronized Chlamydomonas.

The lethal and mutagenic effects of 5 mug/ml N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were maximal during the nuclear S-period of synchronously grown Chlamydomonas reinhardtii. This was revealed by a 50% drop in survival and a 50- to 100-fold increase in the recovery of slow-growth mutants (up to 40% of the survivors) which were first recognized as small colonies on agar medium. Partial characterization of these isolates revealed about 50% to be stable on subculture, and several were demonstrated to be either acetate-dependent, dark-lethal (light-dependent), or acetate-sensitive mutants. There was no significant increase of lethality or of slow-growth mutants correlated with treatment during the chloroplast DNA replication phase of the cell-cycle. The results of genetic analysis with 13 mutants induced during the nuclear S-period were consistent with their nuclear origin. These analyses were hampered by the high proportion of lethality among the progeny of most crosses. It is concluded that the enhanced mutant induction among nuclear S-phase cells may indicate preferential mutagenesis of replication fork DNA and induction of multiple-closely-linked mutations, as in some bacteria. Consequently, for C. reinhardtii, caution should be exercised in drawing relationships between abnormal behavioral and biochemical phenotypes in MNNG-induced mutants.


Genetic evidence of ribosomal antisuppressors in Podospora anserina.

Antisuppressors were screened for with the help of informational suppressors in Podospores anserina. Four mutations in the AS1 locus and two in the AS2 locus were isolated, using allele non specific suppressors supposed to be ribosomal ambiguity mutations. Four mutations in the AS3 locus and 45 in the AS4 locus were obtained, using a nonsense (t-RNA like) suppressor. All antisuppressors are partially dominant. Most mutations in the AS4 locus are lethal. The four mutants at the AS3 locus and 6 out of the 8 viable mutants at the AS4 locus are cold sensitive. Phenotypic properties and action spectra of the antisuppressors suggest that they are restrictive ribosomal mutations.


Insect cytochrome P-450.

Two approaches may be used to study the function of cytochrome P-450 in insects: (a) an evaluation of the spectral and catalytic properties of the hemoprotein while associated with microsomal membranes; (b) the solubilization, resolution and purification of the microsomal mixed-function oxidase system. The first approach has provided some understanding of the biochemical factors involved in the metabolism of a variety of compounds, including pesticides, drugs, hormones and many other xenobiotics. However, solubilization of the monooxygenase system allows the study of each of its components individually, providing a better insight on the sequence of events leading to the hydroxylation of a substrate, the type of intermediates formed, and the rate-limiting step(s). This report discusses studies carried out with the monooxygenase system associated with microsomal membranes, as well as procedures to solubilize and partially purify its components from housefly microsomes. The latter involves solubilization with either Triton X-100 or sodium cholate, followed by either ammonium sulfate fractionation, Sephadex G-200, DEAE-Sephadex A-50 column chromatography or by omega-amino-n-octyl-Sepharose 4B affinity chromatography. These procedures have shown that two cytochrome P-450 species (P-450 and P-450I) are present in microsomes isolated from a resistant housefly strain. Induction with either naphthalene or phenobarbital appears to increase cytochrome P-450I preferentially.


Modification of calf lens crystallins as determined by gel electrophoresis.

Variations in size and charge of calf lens proteins, particularly gamma crystallins, were studied by polyacrylamide gel electrophoresis. Exposure of gamma crystallins to near-UV light in the presence of L-tryptophan produces species of higher electrophoretic mobility and higher retardation. Treatment with urea and sulfonation also produced changes in the retardation co-efficient. The increase of retardation co-efficient of gamma crystallin is interpreted to be a result of conformational changes. Gamma crystallins are particularly sensitive to photo-modification, and this process may be associated with age-related changes in the lens.


Efficacy of law enforcement procedures concerning alcohol, drugs, and driving.

Fatality rates in autobomile crashes vary widely from nation to nation. For instance, in 1970 Japan reported a rate of 11.4 and the United States 2.6. Finland stood about midway with 6.2 fatalities per 100 million vehicle kilometers 1970 (OECD, 1974). These rates reflect all fatal crash causes. The alcohol rates are quite imprecise for many nations but a comparison of the Finnish and United States figures reveals some interesting facts. The United States rate of alcohol involvement in highway deaths is about 50% (of a rate of 2.6). The Finnish rate of alcohol involvement is 27% (of a rate of 6.2). Thus the alcohol rate for Finland is about 1.7, and for the United States 1.3. These percentages provide a guide for enforcement officials. The higher the percentage, the higher the priority. Moreover, the role of traffic deaths in overall mortality is important. For instance, in Japan each year 25 traffic deaths occur in each 100,000 of population, while in the United Kingdom the figure is 13 (1970 figures; OECD, 1974). Another factor is available countermeasures. Safety features on cars, quality of roads, driver training, and cultural attitudes toward cars all contribute. Driver behavior controlled by law enforcement is a very important factor. There is evidence that enforcement of drunken driving laws is extremely lax even in those nations claiming vigorous programs. An enforcement program that will screen the corporate whole of the driving population on an optimal basis will identify those drivers whose drinking is a problem for treatment ranging from punitive to therapeutic on the basis of their needs and at the same time bring about a general deterrence because of a perception of the high risk of being apprehended.


Characteristics of driving in relation to the drug and alcohol use of Finnish outpatients.

A questionnaire was administered to 765 rheumatoid arthritic, 715 tubercular and 1,050 psychiatric outpatients and to 587 control subjects concerning their use of drugs and alcohol, driving habits and traffic accident involvement. The driving populations of all groups were matched as to their age and area of residence. The results of the study show a relatively very small number of driving licence holders among rheumatoid and psychiatric patients whereas the tubercular group includes as many driving licences as the control group. Also, the annual driving experience of the rheumatoid arthritic and psychiatric patients was low. The main reason for driving was recreation, and the driving mainly took place on highways. Excluding the psychiatric patients, the patient groups had been involved less often in traffic accidents that the controls. The use of drugs correlated inversely with driving: the more you used drugs the less you drove. Also the consumption of alcohol increased in direct proportion to the number of kilometres driven: the greater the alcohol consumption per drinking session, the more you drove annually and were involved in accidents.


Alcohol and highway crashes. Closing the gap between epidemiology and experimentation.

It is frequently observed that alcohol-impaired drivers involved in certain types of crashes apparently 'couldn't stop in time'. However accurate this observation, it is simply a description and is not an adequate explanation. Therein lies the basis for the gap between epidemiology and experimentation. If alcohol actually does degrade a motorist's performance and increase the probability of his being responsible for a fatal crash, then alcohol-induced changes in driving behavior should be manifest and should be measurable. However, no controlled study has previously been conducted to obtain systematic but unobtrusive data on the actual influences of alcohol upon real-world driving behavior in its natural environment. One recently completed field study is reported which was designed to provide such data by means of unobtrusive electronic measures of nocturnal driving performance. In the present paper, to illustrate one approach to closing the gap between epidemiology and experimentation, one combination variable was selected which lends itself readily to comparison across the full spectrum of alcohol investigation: reaction time and braking performance. A review of the literature concerning this interrelated variable examined alcohol influences upon reaction time as investigated in laboratory, simulator, and instrumented car experiments, as well as alcohol influences upon braking performance in instrumented car experiments and in our recent field study involving unobtrusive electronic measures. The reviewed experiments were interpreted in terms of a conceptualization of the information-processing sequence which leads up to brake use. On the basis of the reviewed results, it was concluded that alcohol increases reaction time (both simple and choice) appreciably more in driving situations than in laboratory experiments. It was also concluded that a consistent alcohol impairment of the qualitative aspects of braking performance is manifest in driving situations, for example, as reflected by changes in brake-pressure modulation. More specifically, the braking performance of motorists and subjects at high BACs is abrupt, unsmooth, and less controlled than that of sober motorists or the same subjects with no alcohol. It was concluded that at least in terms of quality, alcohol impairs response implementation of the final stage of the information-processing sequence. It was hypothesized that the abrupt, lower quality braking performance observed at high BACs results--at least in part--from less time remaining available for stopping because the information-processing time has been increased by alcohol at some previous stage--apparently the response-selection stage. At the most general level, it was suggested that high BACs both increase the time necessary to begin applying the brakes, as well as reduce the degree of control in the actual use of the brakes during the course of stopping. These two factors in combination probably account for a large part of the alcohol contribution to highway crashes.


A case-control study on alcohol as a risk factor in pedestrian accident. A preliminary report.

Alcohol as a risk factor in pedestrian accidents was studied so that the BACs were measured by gas chromatography in 341 accident patients and by ASD-breathalyzers in 682 sex-, site-, and time-matched pedestrians not involved in accidents. Alcohol was found in the blood in 53% of the accident cases and in 15% of the controls. The RR, if 1.0 at zero BAC, was 0.59 at BAC 0.3-0.5, 2.2 at 0.6-1.0, 6.8 at 1.1-1.5, 13 at 1.6-2.0, and 29 at BACs of over 2.0 g/l.


Precision, accuracy and relevance of breath alcohol measurements.

The methods employed for evaluating the performance of some currently available breath alcohol devices are described. A program consisting of in vitro experiments, extensive in vivo laboratory studies, controlled field studies, and finally roadside random testing has been used. The importance of considering the underlying physiological mechanisms particularly with regard to the blood/breath partition ratio and its variability is emphasized. An important finding is that the relationship varies with the phase of alcohol metabolism in a regular and systematic way. Some statistical techniques are outlined for calculating the precision and accuracy of breath-testing instruments, which are important properties of a method to be used for medico-legal purposes.


X-ray-induced mutation to 6-thioguanine resistance in cultured human diploid fibroblasts.

X-ray induced mutation to 6-thioguanine (6TG)-resistance was studied in early passage cultures of human diploid fibroblasts. The appearance of phenotypic induced mutants in irradiated cell populations was linearly related to the number of post-irradiation cell doublings and to the duration of the growth period prior to mutant selection; the maximum yield of X-ray induced mutants was observed when cells surviving radiation had completed 3--4 douplings (6--7 days growth) in non-selective medium. The maximum induced mutation frequency was linearly related to X-ray dose and the mutation rate was estimated to be 3.1-10(-7) mutations per viable cell per rad. The data obtained for X-ray induced mutations in cultured human diploid fibroblasts were compared with (a) similar experimental data obtained with established cell cultures and (b) with theoretical predictions of X-ray mutation rates in human germ cells.


Inhibition of mouse testicular DNA synthesis by mutagens and carcinogens as a potential sample mammalian assay for mutagenesis.

Since mutagenic substances induce structural changes in DNA, studies were undertaken to determine whether substances would modify DNA replicative activity. DNA synthesis was quantitated 3.5 h after drug administration as uptake into DNA of a 30-min pulse of 10 muCi of [3H] thymidine. Combinations of methylurea (20000 mg/kg) and sodium nitrite (150 mg/kg) administered p.o. resulted in gastric synthesis of nitrosomethylurea and inhibited testicular DNA synthesis by 83%. Combinations of methylurea and sodium nitrite of 1000 and 100 mg/kg respectively inhibited DNA synthesis by 75%. With dimethylamine and sodium nitrite, a combination which results in gastric synthesis of dimethylnitrosamine, inhibitions of 65 and 57% were observed at 2000 mg/kg together with 150 mg/kg and 1000 mg/kg in combination with 100 mg/kg, respectively. In separate experiments, dimethylnitrosamine (50 mg/kg, p.o.) and diethylnitrosamine (100 mg/kg, i.p.) inhibited thymidine uptake by 30 and 89%, respectively. The mutagenic polynucelar hydrocarbon 3-methylcholanthrene (15 mg/kg) inhibited DNA synthesis by 95% and safrole (640 mg/kg), a mutagenic methylenedioxybenzene derivative, inhibited by 60%. Cadmium chloride (10 mg/kg), acetylaminofluorene (160 mg/kg) and dibutylnitrosamine (500 mg/kg) also induced statistically significant effects. Noncarcinogenic analogues of these substances (anthracene, 125 mg/kg; diphenyl-nitrosamine, 500 mg/kg; piperonyl butoxide, 640 mg/kg, and methylurea, 2000 mg/kg in combination with sodium nitrate) were inactive. Highly toxic substances (potassium cyanide, 2.5 mg/kg; 2,4-dinitrophenol, 20 mg/kg; and lead acetate, 150 mg/kg) were also inactive. This index of mutagenicity appears to have considerable sensitivity and therefore may have potential in drug evaluation.


Cytogenetic effects of mutagens/carcinogens after activation in a microsomal system in vitro I. Induction of chromosome aberrations and sister chromatid exchanges by diethylnitrosamine (DEN) and dimethylnitrosamine (DMN) in CHO cells in the presence of rat-liver microsomes.

A rat-liver microsomal system in vitro has been used to activate two indirectly acting carcinogens, DMN and DEN. On activation, both compounds were extremely potent in inducing chromosomal aberrations as well as sister chromatid exchanges in Chinese hamster cells. The implications of these findings and the potential utility of this technique to detect mutagens/carcinogens are discussed.


Replicative bypass repair of ultraviolet damage to DNA of mammalian cells: caffeine sensitive and caffeine resistant mechanisms.

Replicative bypass repair of UV damage to DNA was studied in a wide variety of human, mouse and hamster cells in culture. Survival curve analysis revealed that in established cell lines (mouse L, Chinese hamster V79, HeLa S3 and SV40-transformed xeroderma pigmentosum (XP)), post-UV caffeine treatment potentiated cell killing by reducing the extrapolation number and mean lethal UV fluence (Do). In the Do reduction as the result of random inactivation by caffeine of sensitive repair there were marked clonal differences among such cell lines, V79 being most sensitive to caffeine potentiation. However, other diploid cell lines (normal human, excision-defective XP and Syrian hamster) exhibited no obvious reduction in Do by caffeine. In parallel, alkaline sucrose sedimentation results showed that the conversion of initially smaller segments of DNA synthesized after irradiation with 10 J/m2 to high-molecular-weight DNA was inhibited by caffeine in transformed XP cells, but not in the diploid human cell lines. Exceptionally, diploid XP variants had a retarded ability of bypass repair which was drastically prevented by caffeine, so that caffeine enhanced the lethal effect of UV. Neutral CsC1 study on the bypass repair mechanism by use of bromodeoxyuridine for DNA synthesis on damaged template suggests that the pyrimidine dimerer acts as a block to replication and subsequently it is circumvented presumably by a new process involving replicative bypassing following strand displacement, rather than by gap-filling de novo. This mechanism worked similarly in normal and XP cells, whether or not caffeine was present, indicating that excision of dimer is not always necessary. However, replicative bypassing become defective in XP variant and transformed XP cells when caffeine was present. It appears, therefore, that the replicative bypass repair process is either caffeine resistant or sensitive, depending on the cell type used, but not necessarily on the excision repair capability.


Type B hepatitis: the infectivity of blood positive for e antigen and DNA polymerase after accidental needlestick exposure.

To determine the relation between the presence of donor DNA polymerase and e antigen, and recipient hepatitis, we tested, under code, serums from a controlled trial of hepatitis B immune globulin used to treat individuals accidentally inoculated with HBs Ag-positive blood. All recipients lacked antibody to HBs Ag. In 29 of 31 donors, both polymerase and e were in perfect agreement; both demonstrated a highly significant correlation with recipient hepatitis (P less than 0.001). DNA polymerase/e-negative blood did not cause hepatitis. Blood containing polymerase or e antigen did not cause hepatitis in six of 31 and four of 18 recipients, respectively. Hepatitis did not correlate with transaminase or duration of antigenemia in the donor. Polymerase and e appear to be indicators of the relative infectivity of HBs Ag-positive serum, particularly after small-volume exposure. They may be important determinants in assessing infectivity of chronic carriers of HBs Ag and in evaluating efficacy of hepatitis B immune globulin and hepatitis B vaccines.


Polycythemia vera: stem-cell and probable clonal origin of the disease.

Two women with polycythemia vera and heterozygosity (GdB/GdA) at the X-chromosome-linked locus for glucose-6-phosphate dehydrogenase were studied to determine the nature of the cellular origin of their polycythemia. In contrast to unaffected tissue, such as skin fibroblasts, which consisted of both B and A types, the glucose-6-phosphate dehydrogenase of the patients' erythrocytes, granulocytes and platelets was only of Type A. These results provide direct evidence for the stem-cell nature of polycythemia vera and strongly imply a clonal origin for this disease. The fact that no descendants of the presumed normal stem cells were found in circulation suggests that bone-marrow proliferation in this disorder is influenced by local (intramarrow) regulatory factors.


Doctors who perform operations. A study on in-hospital surgery in four diverse geographic areas (first of two parts).

The generous supply of surgeons in the United States stimulated a study of their operative work based on all operations performed by all physicians in hospitals of four geographic areas. Each operation was assigned a California Relative Value to permit work-load comparisons between specialties and practices. General practitioners constituted more than one quarter of physicians who performed operations but accounted for less than one tenth of total work. Surgical specialists, about half the physicians in the study, performed about 80 per cent of total operative work. Work loads of surgical specialists varied by certification, specialty, age and practice organization status. We conclude that far too many physicians perform surgical operations and that work loads of surgical specialists are modest. Calculations involving reallocation of operative work loads suggest that the total volume of operations in this study could have been handled by a substantially smaller cadre of busier surgical specialists.


Studies on the biological effects of deuteriated organic compounds. I. Antifungal activity of perdeuteriated fatty acids on dermatophytes in vitro.

The antifugal activity of some perdeuteriated fatty acids, with normal chain 11 to 18 carbon atoms, was investigated on common dermatophytes Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes and T. rubrum under in vitro conditions. These studies were performed by dilution technique and with respiratory measurements, Perdeuteriation of some fatty acids increases their inhibitory effect on the dermatophyte growth. Perdeuteriated n-hendecanoic acid proved to be the most active of the substances tested. Possible mechanisms behind the enhanced antifungal activity due to the perdeuteriation of fatty acids are discussed.


Studies on the biological effects of deuteriated organic compounds. II. Morphological changes of Epidermophyton floccosum exposed to perdeuteriated n-hendecanoic acid studied with interference contrast and scanning electron microscopy.

In order to visualise the morphological changes of Epidermophyton floccosum associated with exposure to perdeuteriated n-hendecanoic acid, the architecture of the dermatophyte was investigated by means of interference contrast and scanning electron microscopy. The morphology of mycelia grown on substrate containing perdeuteriated n-hendecanoic acid, or the unlabelled analogue, was compared. The perdeuteriated n-hendecanoic acid produced a characteristic undulant effect of the hyphae. The characteristic wave-like appearance of the mycelia looked similar to the curling effect occuring after treatment of dermatophytes with griseofulvin, but was not so pronounced. Perdeuteriated n-hendecanoic acid, unlike the unlabelled analogue, also seems to cause a reduction of the number of chlamydospores perforations of the macroconidia. The changes in the morphological structure of Epidermophyton floccosum exposed to pereuteriated n-hendecanoic acid have been investigated. Morphological examination of mycelia exposed to this substance by interference contrast microscopy demonstrated a picture of defect hyphae and macroconidia. By the aid of scanning electron microscopy we have attempted to obtain a better visualization of these changes at ultrastructural level.


Studies on the biological effects of deuteriated organic compounds. III. Antifungal activity of perdeuteriated fatty acids on dermatophytes in vivo experimental microsporie in guinea pigs.

Investigations on the antimycotic properties of perdeuteriated fatty acids were carried out on Microsporum cains infections in vivo. The study was performed on experimental microsporie in guinea pigs using four different methods, all based on the ability of M. canis to cause alopecia. Perdeuteriated n-hendecanoic acid showed in vivo a statistically significant enhanced antimycotic effect compared to its unlabelled analogue. This is in accordance with our previous observations in vitro conditions. The remaining perdeuteriated fatty acids (C12--C18) showed no statistically significant growth retarding effect on M. canis infections in guinea pigs when compared with their unlabelled analogues. The present study attempts to ascertain if some perdeuteriated fatty acids have any antifungal activity in vivo conditions. Our previous papers (3,4) concerning the evaluation of the antifungal activity of some perdeuteriated fatty acids on dermatophytes in vitro, demonstrated that the perdeuteriation of n-hendecanoic acid, lead to a pronounced antimycotic effect on common dermatophytes as e.g. E. floccosum, T. rubrum, M. canis and T. mentagrophytes. As our previous results indicate a decreasing of fungistasis with an increasing carbon-chain length of the perdeuteriated fatty acids, we have attempted to verify this observation in vivo conditions. A special interest was, of course, focused on the most promising compound, the perdeuteriated n-hendecanoic acid.


Kerion-like tinea capitis and barbae caused by Microsporum gypseum in Israel.

Four cases of hair invasion by Microsporum gypseum are reported. In three the scalp was involved and in one, the beard. All presented a kerion type of invasion. In 3 cases hair penetration was of the ectothrix type, while in one case the kerion of the scalp resembled the type of invasion seen in T. schonleini infection. None of the invaded hairs showed fluorescence in Wood's light. The soil was the source of infection in 3 patients, the fungus having been isolated from soil samples collected in the vicinity of the houses of these patients through the hair bait method. In one case the source of contamination was the family dog, in which scaly, alopecic, follicularlike lesions caused by the same agent were found.


Fungal degradation of anaerobically digested sewage sludge.

Fifty isolates of fungi were screened for their ability to grow on and degrade sludge. Cunninghamella elegans was selected for further study of degradation as affected by moisture, nutrients, time and temperature. Maximal sludge degradation (total dry weight basis) was 5.8% by Rhizopus oligosporus, 5.4% by C. elegans and 5.3% by Myrothecium verrucaria, representing approximately 11% degradation of the organic matter present. Added nutrients had little or no effect on sludge degradation. Maximal sludge degradation by C. elegans occurred in three weeks at 30-35 C or four weeks at 25 and 40 C.


Miconazole in the treatment of superficial mycoses.

Miconazole nitrate (2%) cream was evaluated in the treatment of superficial mycoses. Out of 116 patients having multiple clinical diagnoses, 66 cases were found to be positive by culture. Species of Trichophyton were the predominant etiological agents (in over 60%) followed by Candida species (20%) and Epidermophyton floccosum (15%). All the cases selected for study were followed up to a period of 4-18 months. A cure rate of 94.6 per cent was observed in all the cases where causal organisms were isolated. Significantly high cure rate (66%) was also seen in cases where causal organisms could not be isolated, including cases of tinea versicolor. Results of mycological examination were in confirmity with the clinical results.


Development of injectable microcapsules for use in the treatment of narcotic addiction.

Injectible microcapsules containing narcotic antagonists have been prepared with dl-poly (lactic acid) as the coating material. The encapsulation technology has developed to the point that high yields of less than 180 mu capsules can be prepared routinely. Such capsules with an initial payload of 50 wt. % naltrexone pamoate provide 60-90% antagonism to the action of morphine 28 days after injection into mice as a peanut oil/aluminum monostearate suspension at a dose level of 40 miligrams naltrexone pamoate/ kg. mouse.


Long-acting narcotic antagonist complexes.

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.


Sustained release of naltrexone from glyceride implants.

Solid dispersions of naltrexone in natural glycerides were used to form injectable implants which continuously release narcotic antagonists in vivo. The dispersions were formed and tested either as small cylindrical pellets, e.g. l x 3.0 mm in size, or as particles with diameters in size ranges between 125-250 mu, that are suspended in an aqueous methyl cellulose solution. Both types of implants delivered naltrexone to mice at rates that were effective in blocking the antiociceptive action of morphine for at least one month. The rate of naltrexone release was controlled by altering its concentration in the dispersion and by varying the glyceride composition. Degradation and absorption of the implants were found to depend on their composition, dimensions and location in the body. No appreciable tissue incompatibility was seen in mice, rats, rabbits, monkeys and swine, even when long-lasting preparations were removed a year after treatment.


Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.


Development of Chronomers tm for narcotic antagonists.

The object of this program is to prepare a bioerodable naltrexone delivery system which can be implanted subcutaneously in humans and which can relieve the narcotic antagonist over 1-6 months at relatively constant and sufficient rates to block the euphoric effect of morphine based drugs. The system is composed of naltrexone uniformly dispered in a solid hydropholic CHRONOMER TM matrix which undergoes predictable surface erosion when exposed to an aqueous medium. Kinetic studies in vitro have been carried out during the course of the program to determine the best composition for the system. Toxilogical studies conducted at ALZA during the past 2 years have not revealed limiting adverse effects of either the CHRONOMER TM materials or their hydrolysis products. The tail-flick test procedure was used to measure the effectiveness of naltrexone to antagonize the analgesis of morphine in rats. Naltrexone infused intravenously at doses of 4 and 16 ug/kg/hr resulted in, after 6 hours, 54 and 89% antagonism, respectively, against a 63.5% effective dose of morphine. Perliminary sterilization studies showed that no adverse effects to CHRONOMER TM/naltrexone systems occurred after exposure to 2.5 or 5.0 mrads of 60CO irradiation.


Analytical methods for the determination of cannabinoids in biological media.

A pharmacokinetic study of the blood plasma levels in man of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-tetrahydrocannabinol and cannabinol has been carried out by means of combined gas chromatographic-mass spectral analysis. In some cases comparison of the data was obtained on the same sample using thin layer chromatography of radiolabeled samples and electron capture gas-liquid chromatography. For the mass spectral studies appropriately deuterium labeled analogs of the previously named compounds were used both as internal standards and as a carrier for the relatively small amounts of nonlabeled drug present in plasma. Blood samples were obtainted at periodic intervals up to 24 hours from volunteers receiving 4-5 mg delta9-THC intravenously. After extraction and "clean-up" by Sephadex chromatography, the extracts were concentrated and subjected to glc-ms in the electron impact (ei) mode or alternatively with a chemical ionization (ci) source, in which case preliminary chromatography could be omitted. In all cases calibration curves were obtained from replicate analyses of spiked plasma containing the internal standard and various quantities of the cannabinoid under analysis. A typical biphasic elimination of the drug was observed with rapid elimination of delta9-THC from the blood over a period of 40 min followed by a much slower elimination up to 24 hours. The experimental data show that 11-hydroxy-delta9-THC is found in the plasma in quantities only about one-twentieth to one-twenty-fifth the values found for delta9-THC. Cannabinol was not found in significant quantities. Good agreement was obtained between the mass spectral analyses and the thin layer chromatography or electron capture gas-liquid chromatographic procedures.


Separation and sensitive assay of THC in biological fluids by HPLC and GLC.

HPLC systems were developed to permit quantitative separation of delta9-tetrahydrocannabinol from many of the heptane extractable lipoidal and other endogenous substances in biological fluids. These substances interfered with the quantification by flame ionization GLC of unmodified compound and by electron capture GLC of pentafluorobenzoylated compound. Reverse phase HPLC elution, with 47% acetonitrile in water, and normal phase HPLC with 25% chloroform in heptane, separated tetrahydrocannabinol from 11-hydroxy-delta9-tetrahydrocannabinol and other monohydroxylated tetrahydrocannabinols. These systems also purified stock solutions of tetrahydrocannabinol from accompanying contaminants. The various monohydroxylated tetrahydrocannabinols were resolved from each other in normal phase, 80% chloroform in heptane. The delta8 and delta9-tetrahydrocannabinols were separable in normal phase with 5% tetrahydrofuran in hexane. The GLC analysis of pentafluorobenzoylated tetrahydrocannabinol had a sensitivity of 1 ng/ml of plasma with an estimated 5% standard error of an assay with the extraction and GLC procedures given herein. Radiochemical analysis of the HPLC separated fraction had s sensitivity of 0.2 ng/ml of plasma with an estimated 2% standard error of an assay. There was no significant difference between the liquid scintillation and electron capture GLC assays of the HPLC separated delta9-tetrahydrocannabinol obtained from the plasma of dogs administered the drug. Radiolabelled compounds can be added to plasma samples as internal standards to determine the recovery efficiencies of the several procedures in the analysis of unlabelled tetrahydrocannabinol.


Rolling hairpin model for replication of parvovirus and linear chromosomal DNA.

A novel, quasicircular scheme is proposed for the replication of parvovirus DNA. Daughter strands are initiated after the copying and rearrangement of a terminal palindromic sequence, a process termed 'hairpin transfer'. Such a process may be involved in the replication of other viruses and host cell DNA.


[Atmospheric trace chemicals].

This paper deals with the important trace-materials in the natural and anthropogenetic influenced atmosphere. They exist as gases as well as solid and solid-fluid particles. They are significant for numerous physical processes in the atmosphere and have also a direct influence on our biological environment.


Atmospheric ozone and man-made pollution.

Atmospheric photochemistry and transport processes, related to the ozone layer, are discussed. Natural or man-made changes of the biosphere, variations of radiation, or general circulation as well as anthropogenic release of ozone-destroying catalysts are likely to alter the earth's ozone shield. The possible effects of ozone depletion caused by supersonic aircraft, nuclear weapons, nitrogen fertilizers, and chlorofluoromethanes are discussed.


Progress in biochemical engineering.

Biochemical engineering is one of the answers to some of the challenges of the present age: hunger, shortage in raw material and energy supply and contamination of environment. Its contribution to the solution of these problems is the industrial production of protein, the use of raw materials (incl. waste products) not used up to now, the accomplishment of chemical reactions at ambient temperatures as well as the degradation or utilization of widely different waste materials.


Evidence for a free-running circadian rhythm in pituitary-adrenal function in blinded adult female rats.

To study the eyes' role in maintaining the circadian rhythm in pituitary-adrenal function, 24-h patterns of corticosterone levels were compared in intact and blinded adult female rats. Rats were blinded by optic enucleation at approximately 80 days of age. Nonstress plasma corticosterone levels were determined fluorometrically in serial blood samples obtained from a tail vein at 4-h intervals for 44-h periods, 3 and 10 weeks after surgery. At 3 weeks after surgery, blinded and intact rats demonstrated comparable rhythms in corticosterone levels. At 10 weeks, steroid fluctuations in individual blinded rats still had an approximate 24-h periodicity. However, these fluctuations were no longer synchronized with the light-dark cycle or with those of other rats. These findings suggest that rats blinded as adults have a free-running pituitary-adrenal circadian rhythm.


Effect of variations in pituitary-adrenal activity on dopamine-beta-hydroxylase activity in various regions of rat brain.

Since noradrenergic neurons in the brain appear to inhibit ACTH secretion and dopamine-beta-hydroxylase (DBH) is found in noradrenergic neurons, the effect of variations in pituitary-adrenal activity on the activity of DBH in the brain stem, hypothalamus and hippocampus was determined. There was no significant circadian fluctuation in hypothalamic or brain stem DBH, as measured by the coupled radioenzymatic method of MOLINOFF et. al. [1971]. Pentobarbital and ether anesthesia, injection stress and surgical stress also had no acute effect. There was a decrease in anterior hypothalamic DBH 30 min after immobilization stress. Two days after adrenalectomy, there was a decrease in DBH in the hypothalamus and brain stem. A large dose of corticosterone (B) caused an increase in hypothalamic DBH. However, a smaller dose of B which increased plasma B to values comparable to those produced by endogenous secretion failed to have this effect. The data demonstrate an effect of the adrenal glands on brain DBH activity, but it is as yet uncertain whether this effect is mediated by glucocorticoids.


Hypophysectomy facilitates sexual behavior in female rats.

Lordosis was elecited in 49% of 87 hormonally untreated, hypophysectomized-ovariectomized (hypox-ovx) female rats in response to palpation of the flanks and perineum (vaginal stimulation was not applied). By contrast, only 12% of 113 hormonally untreated ovariectomized (ovx) rats showed lordosis in response to such stimulation. Subsequently, hypox-ovx and ovx-only rats were given daily injections of 1 mug/kg estradiol benzoate (EB) and tested for sexual receptivity with males. Teh estrogen-treated hypox-ovx females became sexually receptive significantly earlier, and exhibited higher lordosis quotients and more soliciting behavior, than the estrogen-treated ovx-only rats. The increased sexual responsiveness in the hypox-ovx rats could be due to increased LRH activity. To test this, we treated hypox-ovx rats with dihydrotestosterone propionate (DHT-P), which suppresses plasma LH levels but is relatively ineffective in inducing sexual receptivity, and found a significant depression of lordosis responsiveness. These experiments suggest that hypox-ovx females show a heightened responsiveness to hormonal and/or sensory factors that induce a lordosis response, possibly because of increased LRH activity.


Immobilization does not inhibit the post-coital ovulatory surge of luteinizing hormone in the rabbit.

Heparinized blood samples were obtained through an indwelling catheter in the central ear artery from sexually mature female New Zealand white rabbits after copulation. Immediately after 1 or 2 matings the female was transferred to a restraining cage; blood samples were taken at intervals while the animal was completely immobilized for 3-5 h or was only immobilized for blood withdrawal. Ovulation was detected by the presence of corpora lutea at laparotomy the following day. Plasma was analyzed for LH by established radioimmunoassay procedures. Immobilization did not inhibit ovulation or the pre-ovulatory surge of LH in either group. These data suggest that immobilization cannot inhibit the reflex release of LH in the female rabbit.


Cytoplasmic and nuclear metabolism of testosterone in the brains of neonatal and prepubertal rats.

The metabolism of testosterone (T) in neonatal rat brains was measured following in vivo and in vitro incubations with 3H-testosterone.Steroids associated with nuclear and cytoplasmic fractions of brain tissue from 4, 12, and 32-day-old male and female rats were identified. Although there are quantitative differences under different methods of incubation, in all cases more than 95% of the radioactivity was recovered and identified as T, or the 5alpha-reduced metabolities, DHT and 3alpha-androstanediol. Most of the metabolism of T occurred in the cytoplasm but 5alpha-reduced metabolities were also associated with purified nuclei. Reaction kinetics indicate that the metabolic sequence is T leads to DHT leads to 3alpha DIOL. DHT levels were similar in the cytoplasmic fractions from the neonates (4 and 12-day-old animals) and prepubertal animals (32-day-old animals), but 3alpha-androstanediol was significantly reduced in these fractions from prepubertal animals compared to those from neonates. Sex differences in the metabolism of T in the various subcellular fractions were not detectable.


[Acute plasma-cell leukemia. Report of a case].

A case of fatal, diffused plasmacytoma is presented. The picture also included leukaemia and is felt to be an example of plasma-cell leukaemia, as opposed to plasmacytoma in the light of the anatomical and clinical features of the onset and course: high and very pronounced plasma-cell leukocytosis, diffuse proliferation of the plasma cell series in the bone marrow, spleen and lymph nodes, infiltration of plasma cells in the parenchymal organs, extremely rapid progress with serious anaemia, haemorrhage, general organic involvement, high fever, and infection.


[Clinical applicability of an enzyme micromethod for the rapid determination of blood sugar].

The clinical applicability of an enzymatic micromethod for the fast determination of glycaemia is discussed. The method is based on the use of an optical reflectometer for the quantitative reading of the variation in colour intensity of specific reactive strips for the semi-quantitative evaluation of blood glucose. Thanks to the method's rapidity and simplicity, it can be used for mass screening and is also very useful for the routine investigations of Diabetologic Centres. It is also invaluable for the identification of emergency clinical situations.


[Medical treatment of arrhythmias in myocardial infarct. Results of the use of bunaftine].

After a short survey of the physiopathology of arrhythmia in myocardial infarction, especially at the initial stage, the results of using bunaphthine in 21 personal cases of myocardial infarction are reported and the fully satisfactory results described. This substance is held to be an effective, useful antiarrhythmia drug which can be usefully employed in the prophylaxis of arrhythmia in myocardial infarction.


[On a syndrome of immunopathic type with pleural and systemic localization observed in patients with intracavitary electrostimulators. Considerations on 4 cases].

The complications arising out of the installation of pacemakers are listed and classified and it is suggested that a syndrome characterized by recurrent pleural effusion recalcitrant to the usual medico-depletive therapies, observed in four patients with pacemakers, should be included among such complications. The clinical pictures of the syndrome is described in detail and particular attention is paid to its date of onset in relation to installation of the pacemaker, early symptomatology, the most typical symptoms, clinico-humoral development, prognosis and therapy. Some theoretical and practical remarks are also offered, specifically three pathogenetic suggestions are formulated on the basis of clinical and developmental features but mainly in relation to humoral and immunological findings. These suggestions stress alternative interpretations of the syndrome: A) as an autoimmune disease arising secondary to surgical denaturation of myocardial and/or endocardial autoantigens; B) as a systemic autoimmune disease due to congenital or acquired insufficiency of immunological homeostasis; C) as a monosymptomatic pleural form of systemic lupus erythematodes with late clinical outbreak. The fascinating pathogenetic, clinical, biological and therapeutic resemblances between the present syndrome and the post-infarctual syndrome of Dressler and Johnson's post-pericardiotomic syndrome are pointed out and it is suggested that complications of medical nature already described as being secondary to the installation of pacemakers, such as endocarditis and pericarditis, should be looked at from an autoimmune type of pathogenetic viewpoint. Finally, in the light of personal observations, the need for immunological study of high risk patients, namely relations of patients with autoimmune diseases, is stressed. All candidates for pacemaker installation should also be included. Routine screening of this type would take on enormous practical importance as it would enable preventive or curative treatment to be undertaken to modify the immunitary balance of those subjects in whom pacemaker installation is liable to trigger off critical, irreversible breakdown in immunitary homoeostasis of which the syndrome in question would seem to be the most dramatic, but perhaps no the only, clinical manifestation.


[Recording of the potential of the bundle of His through the veins of the arm].

A new technique for recording His bundle and right branch potential through the veins of the arm instead of by the femoral route is described. Recordings were carried out in 70 patients. In 10, His potential was recorded simultaneously by the femoral and brachial routes. Potentials proved to be similar as regards morphology and duration; A-V conduction time proved identical while there were slight variations in His node conduction time since the atriogram revealed varying intrinsic deflexions. It is thus possible to confirm that the recording of His potential by the brachial route offers various advantages: 1) it takes less time than the femoral route; 2) it is an excellent alternative if, for various reasons, the patient cannot be examined by the femoral route; 3) His potential can be monitored more easily because of the greater stability of the catheter and the provisional electrosimulation using the same catheter when necessary; 4) contemporaneous recording of right branch and His bundle potential is possible in association with the femoral technique with better results than those obtained using multipolar catheters; 5) it is without complications: i.e. the phlebitis, phlebothrombosis, a-v fistula, and pulmonary emboly which, however rarely, may occur when using the femoral route.


[Supravalvular aortic stenosis. 6 operated cases].

6 cases of aortic supravalvular stenosis with associated abnormalities are reported. An aetiopathogenetic, anatomopathological and clinical discussion follows and the excellent results obtained with the therapy employed are reported.


[Critical analysis of the diagnostic value of the flow-volume curve].

Changes in the flow-volume curve after administration of a bronchodilator were studied in reversible bronchial obstruction. The concept of isovolume is used in analysis of the curve indices, i.e. it is felt that the index (75, 60, 50, 25% FVC) after administration should be fixed on the curve at the same volume as on the basic curve to enable an indirect account to be taken of changes in flow in function of time, since, if resistance is reduced, the emitted volume varies in the same period even though the conditions promoting the flow are unchanged.


[Albers-Schoenberg disease in adults. Description of a case].

-- A benign form of Albers Schonberg disease (osteopetrosis) is described. The clinical and pathogenetical aspects are discussed and the findings compared with the literature. The diagnosis was made on the basis of radiological findings and histological results of bone biopsy.


[Effect of S-adenosyl-methionine (SAMe) on some endocrine parameters in normal adult subjects].

No changes in serum prolactin, TSH and LH were noted when the antidepressant s-adenosylmethionine was given i.v. to 7 normal adults of both sexes. It would thus appear that the drug's antidepressant effect is not mediated by TSH. The results obtained are not comparable with those observed by other workers in the rat.


[Chronic alcoholic pancreatitis and blood gastrin].

On the basis of some experimental observations of hypergastrinemia in animals chronically intoxicated with ethanol, both fasting and after meals serum gastrin were determined in patients affected by chronic alcoholic pancreatitis. A significant increase in serum gastrin levels was observed in patients with chronic pancreatitis compared with controls, both in basal conditions and following food stimulation. The physiopathological hypotheses and possible aetiopathogenetic implications suggested by such gastrin behaviour are discussed.


[Acute pancreatitis and hyperlipoproteinemia].

About 10 patients admitted with acute pancreatitis were also, found to have Fredrikson type V hyperlipoproteinaemia. Eight were males aged less than 45 yr. Awareness of the aetiopathogenetic and metabolic aspects of this increasingly common association and its clinical identification form the sine qua non in the prevention of recurrences via marked dietary restriction of fats.


[Changes in vitro of the electrolyte content and erythrocyte volume of the venous blood of patients with chronic pneumopathy subjected to tonometry in oxygen].

As previously observed in vivo, statistically significant variations characterized by increase in chlorine and diminution in sodium, associated with an increase in red cell volume, have been noted in vitro in samples of venous blood taken from patients undergoing tonometry under oxygen. These variations appear to be independent of the basic concentration of chlorine and do not occur if the blood samples are incubated with theophylline at the same time. These results confirm the hypothesis of a "non respiratory" plasmatic acidifying effect of oxygen therapy inhibited by the antiphosphodiesterasic action of theophylline.


[Changes in paO2 and of acid-base equilibrium of the arterial blood of hypoxemic polyglobulic patients subjected to acute blood depletion].

Partial respiratory gas tension and acid-base equilibrium patterns were examined in polyglobulic patients subjected to acute blood depletion. The increase in oxyhaemoglobin concentration and fall in haematocrit value already described were confirmed. It was also noted that: 1) pH increased significantly in all subjects; 2) urinary osmolarity increased in all subjects; 3) blood sodium and potassium concentration increased significantly in 14 patients (1st group), but fell in the 2nd group (8 subjects). It is suggested, therefore, that acute blood depletion changes renal reabsorption of the main electrolytes, i.e. increased values in cases where a fall in glomerular arteriolar pressure leads to increased renal medullary osmolarity, and decreased values where a fall in circulation leads to increased arteriolar pressure, hyperosmolarity of the medulla, and retainment of liquids as opposed to electrolytes.


[Gilbert's jaundice. Current clinico-nosographical, physiopathological and therapeutic aspects. Note II. The phenomenon of enzyme induction at the level of the liver].

After a brief survey of the various modifications that may be encountered by drugs through the work of systems that detoxify the liver cell, attention is given to the problem of enzymic induction. The latter is the result of derepression of a gene that codes for a given enzyme; at the molecular level, derepression takes place when the substrate, by changing the tertiary structure of the repressor, brings about its detachment from DNA: in this way, RNA-polymerase is made capable of synthesising the corresponding mRNA. The inducing activity of phenobarbitone, a drug employed classically in the management of Gilbertian forms, must be substantially attributed to an increase in the synthesis of microsomial proteins, as shown by studies with labelled amino acids.


[Secretion of GH and diabetic retinopathy].

Recently it has been studied a possible pathogenetic role of GH in diabetic angiopathy. The purpose of the present study was to verify whether the diabetic retinopathy is associated or not with a high plasma GH level. In an attempt to answer this question we did the dosage of plasma GH after a oral glucose load (110 g), Insulin (0,1 U/Kg) i.v., and arginin i.v. (25 g/30'). The plasma GH measurements were approximately the same as in normal patients. The Authors underline the importance of GH in pathophysiology of diabetic angiopathy and report all recent literature on this argument.


[Perforating plantar ulcers in alcoholic polyneuritis. Physiopathology; clinical and instrumental findings].

Notes on the anatomical and physiological features of the circulation are followed by a description of the main physiopathological aspects of the terminal circulation of the lower extremities. Reference is made to the pathogenesis and clinical and instrumental diagnosis of plantar ulcers in alcoholic polyneuritis, along with the symtoms constantly observed in a series of some 30 cases.


[Evaluation of the changes in some laboratory parameters in liver disease patients treated with Toxepasi Complex].

Toxepasi Complex (UDPG, glutathione and vitamin B12) was administered to patients with aggressive chronic hepatitis and a second group with severe cirrhosis. Changes in laboratory enzymological data indicative of the overall extent of liver damage due to cell necrosis, cholostasis and impairment of protein synthesis were evaluated. Decreases tending to normalisation were noted two weeks after the commencement of treatment, particularly in the first group. The results suggest that the complex may be usefully employed in the management of aggressive chronic hepatitis and cirrhosis of the liver.


[Intestinal absorption of radiocalcium after long-term treatment with sodium fluoride in senile osteoporpsis].

Prolonged administration of sodium fluoride (NaF) in patients suffering from osteoporosis or Paget's disease leads to a positive calcium balance together with positivization of the calcium balance may mean an ins, intestinal absorption of calcium was evaluated directly with the oral rrotic patients; 6 months treatment with NaF led to a significant imprt is difficult to say how this finding is connected with the drug's actide apatite crystals; the crystals' greater stability probably leads to greater resistance of fluorated bone to the action of parathormone, thus bring on hypocalcaemia which homeostatically stimulates parathyroid hyperiirect pointer to parathyroid hyperincretion. The therapeutic effectiveness of NaF in diffuse decalcifying osteopathies is, however, limited by the drug's toxicity.


[Trial of a combination of proscillaridin A, thioridazine and Cori ester in the ambulatory treatment of some cardiopathies, especially senile types].

The effect of an association of proscillaridin A, thioridazine and Cori ester in ambulatory management of certain heart diseases, particularly in aged subjects, was assessed. Satisfactory results were observed in 58.3% of cases, with significant improvement of cardiac erethism, psychomotor instability and sleep disturbances, as well as cardiac frequency and signs of myocardial insufficiency. It is felt that the association is of assistance in the treatment of certain heart diseases unaccompanied by frank signs of insufficiency, especially in aged subjects.