Studies on intra-arterial cushions. I. Morphology of the cushions at the origins of intercostal arteries in mice. The origins of intercostal arteries in mice are surrounded by cushions which project into the aortal lumen. A boat-like structure, whose bow is directed against the blood stream, is formed by the cushions. The shape of this formation depends on the dilatation of the aortal wall, becoming flatter when the aortal wall is stretched. Grooves direct the blood into the initial segment of the branching artery which is narrowed in moderately distended or relaxed states of the aorta. The cushions are covered by an endothelial layer which continues to the endothelium of the aorta and of the branching artery. Ramified smooth muscle cells are found in the stroma of the cushions, while connective tissue are absent. Ramifications of the lamina elastica interna project into the stroma and faint elastic fibres reach the apical margins of the cushions. Basement membranes of ramified smooth muscle cells form a three-dimensional network which is connected with the basement membrane of the endothelium. Contacts between processes of endothelial cells and those of ramified smoot; muscle cells occur. Collagen fibrols are absent or extremely rare. In the interstitial space clusters of electron dense granules (mean diameter 500 A) are found which might be secreted by the specialized ramified smooth muscle cells. This peculiar morphology characterizes the intraaortal cushions as autonomous formations and excludes their being regarded as simple retroextension of the branching artery.


Effects of guanethidine on paraganglionic cells in the superior cervical ganglion of the rat. Paraganglionic cells in the rat superior cervical ganglion were investigated by fluorescence and electron microscopy following treatment with guanethidine for 5-30 days. Control animals received saline and guanidine. Fluorescence cytophotometric measurements revealed a general decrease in the catecholamine content of paraganglionic cells in guanethidine-treated animals. However a few cell clusters showed focal increases. Similarly by electron microscopy there was a general decrease of cell clusters showing increases. -- guanethidine -- as well as guanidine--treated animals showed non-specific cytological alterations such as mitochondrial swelling and increase of cytoplasmic glycogen. However no changes of catecholamine contents and of dense core vesicles were noted in control animals. These results confirm the conception that in rat paraganglionic cells the dense core vesicles are the main storage site of catecholamines. The marked difference in the response of some cell culsters to the experimental treatment can be considered as evidence of functional heterogeneity of this cell population in the rat superior cervical ganglion.


Tuberculosis care in general hospitals: Arizona's experience. In June 1973 the state of Arizona transferred all in-hospital care of patients with tuberculosis from the State Sanatorium to general hospitals. Eleven general hospitals, 2 extended care facilities, and 30 physicians are under contract; the state pays billed charges after payment from any third-party insurers. Admission to the Tuberculosis Hospitalization Program is controlled by the state and requires real evidence of need for hospital care; there are no residency or indigency requirements. During the first 2 years of the program, 279 patients were admitted for hospital care. The average length of stay was 23.6 days; a marked decrease from the 93-day average in the sanatorium in 1971-1972. Of the 274 patients discharged during the first 2 years, 232 had a final diagnosis of tuberculosis; 105 of these were discharged with sputum smears positive for acid-fast bacilli. Although the cost per patient day was higher than in the sanatorium, the average cost of hospitalization per patient was lower because of the decrease in length of stay. Thirty-five per cent of the patients had some insurance coverage and/or Medicare. An employee skin testing program was required in all hospitals participating in the program. Although there was a 3.5 per cent conversion rate among all hospital employees, there were only 5 converters among employees exposed to patients with tuberculosis under the program. None of the employees was found to have tuberculosis. Of 70 patients with active tuberculosis who have been followed 12 to 24 months, 65 are bacteriologically negative. The general hospital program has been well accepted by patients, physicians, hospitals, and the public.


Skin testing: a comparison of the jet injector with the Mantoux method. Employees in a large industry in Baltimore were tested with 5 TU of purified protein derivative (PPD)-S and PPD-B using both jet injector and Mantoux methods. Wheal sizes tended to be larger among men than women and larger among blacks than whites, regardless of the technique used. Within any given race-sex group, and also within subjects, considerable systematic and nonsystematic variations in wheal size occurred when the jet injector was used. On the contrary, there was little variation in wheal size within race-sex groups when the Mantoux method was used. Mean wheal sizes elicited with the jet injector tended to be smaller than those elicited with the Mantoux method. There were also considerable differences in the reactions elicited by the 2 techniques. The Mantoux method elicited more and larger reactions than the jet injector, which suggests that the 2 injections are in some way qualitatively or quantitatively different. For jet injector tests, the frequency of reactions of different size tended to be related to the size of the wheal measured immediately after injection. This was not true for the Mantoux method. On the basis of these findings, it is suggested that the jet injector method is inferior to the Mantoux method in tuberculin skin testing.


Active transport of Na+ and Cl- across the canine tracheal epithelium in vitro. The flow of water across the tracheobronchial epithelium is likely to be an important determinant of the efficiency of mucociliary clearance. Because bulk water flow has been shown to be coupled to net ion flux in several epithelia, experiments were performed to determine whether ions are transported actively by the canine tracheal epithelium. Electrical potential difference, short circuit current, and the unidirectional fluxes of positive sodium ions (Na+) and negative chloride ions (Cl-) were measured using an in vitro preparation of the posterior membranous portion of canine trachea. The values of the electrical parameters were potential difference, 30.7 +/- 2.7 mV (SE; n = 30), lumen negative to submucosa; short circuit current, 108 +/- 8 muA per cm2 (SE; n = 30). Bidirectional fluxes of Na+ and Cl- were measured both with and without continuous short circuiting of the epithelium. Under short circuit conditions there was a unidirectional flux of Cl- toward the lumen of 7.4 +/- 1.2 muEq per cm2 per hour (SE; n = 6) and toward the submucosa of 4.7 +/- 1.1 muEq per cm2 per hour (SE; n = 6), resulting in a calculated net flux of Cl- of 2.7 +/- 0.6 muEq per cm2 per hour toward the lumen. The unidirectional flux of Na+ toward the lumen was 1.3 +/- 0.5 muEq per cm2 per hour (SE; n = 8) and toward the submucosa was 2.1 +/- 0.7 muEq per cm2 per hour (SE; n = 8). This resulted in a calculated net flux of Na+ of 0.8 +/- 0.2 muEq per cm2 per hour toward the submucosa. These fluxes are consistent with active transport and together they account for the entire short circuit current. Under open circuit conditions, the calculated net fluxes of Cl- and Na+ were not significantly different from zero.


A case of primary alveolar hypoventilation associated with mild proximal myopathy. A 34-year-old man presented with clinical features of primary alveolar hypoventilation, but was found additionally to have an adult onset myopathy caused by acid maltase deficiency. This was not severe, as judged clinically, and was initially overlooked. His vital capacity and sprint maximal ventilatory volume were only slightly reduced, and the ventilatory response to CO2 was virtually absent. There was, however, a mild impairment  in the ability to decrease Pco2 to normal by voluntary hyperventilation. The relation of myopathy and alveolar hypoventilation is discussed, and it is proposed that the primary muscle disease predisposed the patient to the development of the ventilatory abnormality.


"Bad breath": presenting manifestation of anaerobic pulmonary infection. Three patients are described in whom a putrid breath odor was the only or fist manifestation of anaerobic infection of the lung. Fever, productive cough, and pleuritic pain, common findings in anaerobic pulmonary infection, were not initally present. "Bad breath" may be an early due to the presence of anaerobic pulmonary infection.


Diagnosis and management of major vascular injuries: a review of 200 operative cases. In a series of 250 civilian vascular injuries, 85 per cent were due to firearms and 50 per cent involved the torso, both of which represent an increased frequency of occurrence over other reports. There were 40 deaths, 31 of which occurred during operation or in the recovery room and were due to irreversible shock or coagulopathy. Of the nine late deaths, failure of the vascular repair was responsible for only three. In 124 extremity artery injuries, there were 12 leg amputations (10%) with shotgun wounds responsible for nine and popliteal artery injuries involved in seven. In gunshot wounds of the aorta and iliac arteries, there were five suture line disruptions in nine primary repairs and no disruptions in 11 patients repaired by grafts. The evidence indicates that an antibiotic soaked dacron graft is the method of choice to repair gunshot wounds of the aorta and iliac arteries at this time.


Hydroxychloroquine sulfate in prevention of thromboembolic phenomena in surgical patients. Hydroxychloroquine sulfate appears to be a safe drug with no apparent hemorrhagic or other complications when used pre- and postoperatively in the manner described. With the criteria for thromboembolism of abnormal impedance plethysmography and confirmatory clinical signs, protection seems to have been afforded by hydroxychloroquine sulfate. Since these studies support prior extremely favorable results, further clinical trial with parenteral hydroxychloroquine sulfate seems indicated.


Evaluation and management of solitary pulmonary nodules. The incidence of malignancy in solitary pulmonary nodules found on routine chest roentgenographic survey is unknown but may be as high as 20 per cent. The greatest dilemma confronting most physicians involved in the primary care of patients with solitary pulmonary nodules is sorting out those nodules that can be safely watched from those that should be surgically removed. Certain roentgenographic features of these nodules have been found to be helpful in diagnosis. The only two features that can indicate benign lesions are the presence of dense or concentric calcifications and the stability of the lesion over a period of more than two years. The final decision to operate or not may depend on comparison with old films. Pulmonary nodules present for more than two years without any change in size can be safely followed without operation. Operation is indicated in most newly discovered noncalcified nodules larger than 4 cm and for lesions causing obstructive symptoms.


[Retention of noradrenaline by the rat endometrial epithelium. Action of estradiol]. The application of the cytochemical fluorescence method on uterine samples obtained from spayed rats, injected with ascorbic acid, oestradiol, norspinephrine and oestradiol plus norepinephrine, permits the visualization of an extraneuronal uptake of norepinephrine by the luminal and glandular epithelium of the rat endometrium. The enhancing of the oestradiol uptake exerted by norepinephrine could be explained in this case by a direct action of norepinephrine on the target cell.


[Importance of urinary 3-O methyldopamine in the metabolism of adrenergic tumors]. Urinary 3-O methyldopamine has been found highly increased in all cases of malignant tumours, as well of sympathetic nature (sympathoblastoma) as of chromaffin type (pheochromocytoma) but at a lesser extent in benign sympathetic tumours (ganglioneuroma). On the other hand, 3-O methyldopamine excretion is normal in benign pheochromocytoma. The ratio of this compound in the dopaminergic block is increased in sympathoblastoma, decreased in ganglioneurona and unchanged in pheochromocytoma. This kind of analysis has not been made for the case of malignant pheochromoblastoma. This ratio of 3-O methyldopamine in the whole dopaminergic and noradrenergic metabolism is increased only in sympathoblastoma. In the other cases (ganglioneuroma and pheochromocytoma) this ratio is decreased. Comparative analysis of urinary 3-O methyldopamine and the two other methoxylated amines (norepinephrine and metanephrine) shows that the methoxylated derivative of dopamine, when compared to normal subjects values, increased at the greatest extent in sympathoblastoma, while in ganglioneurona and chromaffin tumours, normetanephrine is with a variable degree, the predominant compound.


[Circadian plasma LH changes in young bulls]. Six young postpubertal bulls (1 year of age) were blood sampled on one to three occassions each, at hourly intervals for 25 hours. One of them was sampled on a separate occasion every 10 minutes for 2 hours. They were managed in similar conditions since they were 8 days old. LH was measured by radioimmunoassay. There was not a circadian periodicity of LH levels. Peak frequencies or magnitudes varied widely not only between bulls but also between days.


[Male hypogonadotropic hypogonadism. Success of treatment of sterility with HMG plus HCG]. Ten typical cases of male eunuchoidism (two with anosmia) are reported. After administration of clomifene citrate to five patients, there is no change in blood levels of gonadotrophins in four cases; in the fifth, a small and transitory increase of LH is noted. The intravenous injection of LHRH (100 mug) to five patients induces an increase of serum LH in all cases and serum FSH in three cases. The initial site of the dysfunction is possibly hypothalamic with secondary gonadotrophic pituitary insufficiency. Among six patients anxious for paternity, prolonged treatment (for 36 to 98 weeks), with HCG (250-1 000 I.U. daily) +HMG (65-120 I.U. FSH daily) results in appearance of spermatozoa in the seminal fluid in five cases and a pregnancy was obtained in four cases. Comments are done upon methods of treatment.


[Testosterone metabolism in isolated cells of rat and ram seminiferous tubules]. Aspermatogenic seminiferous tubules were obtained from adult Wistar rats treated with Busulfan at the 20th day of foetel life. The isolated tubules converted 14C testosterone (T) into androstenedione (delta4), 3,5%) 5 alpha-dihydrotestosterone (DHT), (1%) ANd 5 alpha-androstane-3 beta, 17 beta-diol at unit gravity and incubated with 14C-T. Only delta was produced (2%). Using a similar technique the same result was obtained when pure preparation of round spermatids and primary spermatocytes from ram testis were incubated with 14C-T. From these experiments, we conclude that 5 alpha-reductase activity is present only in Sertoli cells.


[Role of guanidylic nucleotides in the adenylate cyclase activity of the rat liver]. Glucagon and adrenaline exert their action upon the liver via the cyclic AMP synthetizing system located in the plasma membrane. The enzyme adenylate cyclase is further regulated by guanyl nucleotides. It has been recently shown that the rat liver plasma membrane system could respond to GTP by simultaneous increase in the cyclase activity in response to glucagon and by the dissociation of this hormone from its binding sites (1). Unambiguous relationship between the activating effect of GTP upon the cyclase and its action upon glucagon binding has not been determined yet (2). This problem was approached using the in vitro action of epinephrine as a model. When 1 to 100 muM GTP or DGP were added to rat liver plasma membranes isolated from adrenalectomized animals, they increased markedly the response of the cyclase system to epinephrine. These effects could be observed in the absence of an ATP-regenerating system and were mimicked by 5'-guanylyl diphosphonate; GTP and GDP were the most active compounds followed by ITP, CTP and by a series of guanyl derivatives. UTP, as well as guanosine, GMP, cyclic GMP and ppGpp were inactive. Guanyl nucleotides did not increase the affinity of the cyclase system for the activating hormones, but enhanced the affinity for ATP-Mg and also the Vmax of the reaction. Finally, GTP, ATP, CTP, UTP but not GDP displaced epinephrine bound to plasma membranes by a mere chelation phenomenon. It is concluded that 1) guanyl nucleotides do not act primarily by influencing the binding of hormones to the membranes; 2) they act directly upon the catalytic subunit of the cyclase; 3) the low concentrations of GTP required for its action strongly suggest that this nucleotide plays a role in the physiological regulation of the intrahepatic cyclic AMP level.


[Experiments concerning the enhancement of clostridial growth (Clostridium butyricum 1672 A McClung) by means of the anaerobic metabolism of Ehrlich ascites carcinoma cells of the mouse (author's transl)]. Ehrlich ascites carcinoma cells stimulate the vegetative growth of Clostridium butyricum in a modified Parker medium under N2 atmosphere. The enhancement of clostridial growth depends on the number of tumour cells added. The Ehrlich ascites carcinoma cells keep the ordinary transplantability after anaerobic incubation with the vegetative forms of Clostridia. Further means for the manometric investigations of the tumour clostridium phenomenon are discussed.


[Contribution of radioimmunologic determination of parathyroid hormone (PTH) to the diagnosis of hyperparathyroidism (HPT) (38 cases]. The P.T.H. radioimmunoassay was done in 38 cases of suspected H.P.T. In confirmed primary H.P.T., the dosage was in positive correlation in 75% of cases; the classic metabolic exploration was in good correlation in 81% of cases. The specificity of the dosage is good but the defect of correlation comes from the antiserum utilised which recognizes the NH2-terminal region of human P.T.H.


[A transplantable myeloid hamster leukemia with high peripheral leukocyte counts and C-particles. I. Transplantation experiments, pathogenesis, and electron-microscopic observations (author's transl)]. In this article is reported a generalized leukemia of the myeloproliferative system of golden hamsters capable of cellular transmission. Cellfree transmissions to 83 golden hamsters after a 6-month latency period, have so far yielded the same result in three cases. After cellular transplantation leukocyte counts of 180,000 on the average occured abruptly in the end-phase of the disease. Latencies were between 4 and 10 days. Electronmicroscopically, oncorna-viruses were demonstrated in hamsters inoculated with either the cellular or the cellfree preparation that bear close resemblance to the murine C-particles.


Comparative studies on the behaviour of the plasmatic clotting system and platelet function in surgically treated cancer patients. By measuring 18 functional parameters of blood coagulation the dynamic pattern of pre- and postoperative blood coagulation was studied in a total of 43 patients with primarily operable solid tumours. The results were compared with those obtained in patients having benign diseases in the same anatomical regions. Results were discussed preferably from the tumourbiological point of view. Changes of blood coagulation occuring in operated cancer patients with benign diseases. Compensatory processes operating in the haemostatic system provide a well balanced coagulation even in cancer patients. Patients with gastric cancer having low adenine nucleotide levels in platelets had a significantly higher risk to die postoperatively than those with normal levels. This indicates metabolic disorder on cellular levels than haemostatic dysfunctions.


[Radioimmunological determination of calcitonin (TCT) in the course of thyroid tumor pathology (84 cases)]. The dosage of calcitonin was done in 13 thyroid carcinoma and 71 begnin thyroid tumors. In one case, the preoperative diagnosis of medullary thyroid carcinoma (M.T.C.) was alloved; in one another case of M.T.C. the repeatted dosage allows the evolution survey and the exploration of the family; in a third case, the dosage allows to doubt the diagnosis of M.T.C. in post-mortem. In 71 cases of begnin thyroid tumors, the calcitonin immunoassay is in the normal range. The interest and limits of the preoperative dosage was drawn of this experience.


[Histologic structure and spread of malignant neoplasms within the urinary bladder (author's transl)]. In 96 out of 250 cases of bladder cancer, neoplastic tissue was found by biopsy in areas within the bladder but remote of the primary and unsuspiciously looking mucosa. Neither the histologic type of the tumour nor the degree of infiltration of the primary allow predictions regarding remote cancerous lesions within the bladder. It must be concluded: In bladder cancer, indication and choice of treatment must take into consideration that the neoplastic process involves the urinary bladder as a whole.


[Beta-glucuronidase activity and morphological alterations in the nervus trigeminus of the rat after application of the neurotropic carcinogen ethylnitrosourea (author's transl)]. Newborn rats were given subcutaneuously 85 mg ethylnitrosourea/kg body weight. The trigeminal nerves of the grown up and of infantile animals were histologically examined and their beta-glucuronidase activity biochemically determined. These activities were compared with those of untreated control animals of the same age. More than 50% of the enzyme values of the experimental animals were significantly higher than those of the controls. Most of the elevated activities were encountered in the central part of the nerve and consisted mainly of the pooled soluble and bound fraction of the enzyme. There is a positive correlation between the level of the enzymatic activity and the degree of morphological changes. An increased enzymatic activity was found in almost 100% of the tumor bearing nerves. Moreover such increased activities were found in a considerable number of histologically tumor free nerves. Ruling out other causes, for instance inflammation, it may be assumed that the increased activity of beta-glucuronidase in the trigeminal nerve of the rat after application of ethylnitrosourea is an expression of its carcinogenic effect and precedes the histologically visible alterations.


Cell proliferation, differentiation and transformation in the rat submandibular gland during early postnatal growth. A quantitative and morphological study. The development of the submandibular gland of the rat was studied between days 2 and 55 of the postpartum. Besides confirming previous ultrastructural findings wer observed at the electron microscope that the architecturally complex terminal tubules, proacinar, acinar and striated duct cells retained mitosis the major ultrastructural features they exhibited in interphase. The ultrastructure of cells that were in the S period of the proliferative cycle was evaluated in high resolution autoradiographs from rats injected with thymidine-H3. All cell types were thus studied and no obvious cytoarchitectural modifications could be detected in these cells preparing for dividion. We obtained ultrastructural evidence that between days 20 and 30 some terminal tubule cells undergo transformation into acinar cells. The intercalated duct cells showed the highest rate of proliferation and the lowest daily increment in number. This suggests that cells from the intercalated ducts migrate to the neighboring morphological compartments. Quantitative data on the rate of cell proliferation and accumulation in the straited duct indicated that cells from the intercalcated ducts should differentiate into straited duct cells. Differentiation of intercalated duct cells into the terminal tubule cells was observed with the electron microscope.


Electron microscopic study of early formation of the tooth enameloid of a fish (Hoplognathus fasciatus). I. Odontoblasts and matrix fibers. An electron microscope study was made on the tooth germs of Hoplognathus fasciatus in early developmental stage. Special attention was given to the odontoblasts, enameloid matrix fibers, calcification of enameloid and the hitherto controversial origin of the enameloid. 1. The ameloblasts and the odontoblasts are demarcated by a single layer of basement membrane which persists until immediately before the calcification of the enameloid matrix. 2. This histogenesis of the enameloid matrix begins with the formation of non-striated fibers 140-180 A thick. They are arranged in a direction vertical to the basement membrane and parallel to the sides of odontoblasts. Fibers with regular cross striations of 640 A periodicity later appear and the entire enameloid matrix is formed by these fibers. 3. Along with the formation of the enameloid, the odontoblasts assume a high columnar form, with a marked increase in cell organelles which show marked polarity suggesting active protein synthesis. Numerous odontoblastic processes are noted in the enameloid matrix. Granules, representing precurosors of enamleoid matrix fibers occur in the odontoblasts. Based on these findings, the enameloid matrix fibers must be of mesodermal origin. 4. Deposition of crystals of small size, needle and tube in shape, occurs in the circumference of the fiber bundles. As calcification progresses, crystals appear in the central portion of the bundles. Later, large crystals of rod and platelet shapes become intermingled. In addition to this, small crystals are fused, forming aggregates.


Scanning electron microscopy of tannin-osmium treated and resin-embedded specimens. A demonstration of transmural passage of blood cells in the bone marrow. Tissue pieces were made conductive by osmium impregnation (revised tannin-osmium method of MURAKAMI, 1974) and embedded in hydroxy ethyl methacrylate. The resin-embedded specimens were cracked and observed with neither elimination of resin nor metal containing, the scanning electron microscope. Using the bone marrow of the rat femur, it was shown that this resin-embedding preserved the delicate tissue-elements without undesirable dislocation and breakage and assured the effective scanning observation as high as X 10,000 at 25 kV accelerating voltage. Passage of blood cells through the sinus wall was thus clearly demonstrated.


Electron microscope study on endocrine cells and tumor cells in the glandular stomach of Praomys (mastomys) natalensis. Endocrine cells in the normal glandular stomach and gastric carcinoids of mastomys were observed by electron microscopy and at least five types of endocrine cells, EC, G, D-like, R (round-granule) and ECL cells were identified. Of these, four types excepting G cells were recognized in the fundic mucosa. Characteristic in mastomys was a scarcity of endocrine cells in the fundic mucosa, where ECL and R cells were predominant types. Silver impregnation methods including SEVIER-MUNGER's argyrophil reaction of our own modifications were applied to tissue sections and the endocrine cells were examined by electron microscopy. Only EC cells revealed argentaffin granules under the light and electron microscope. R, ECL and some of the G cells were non-argentaffin and argyrophil in reaction and D-like cells and the rest of the G cells failed to show even an argyrophil reaction. Granules of mastomys carcinoid cells, as noted in the previous reports, were non-argentaffin but faintly argyrophil. Mastomys gastric carcinoids were studied by the same method, with special reference to the parent cells of this particular neoplasia. Noteworthily, mastomys gastric carcinoids arise mostly from the fundus, the area where R and ECL cells mainly occur in normal animals. The neoplasms are composed of cells containing granules resembling partly those of R cells and partly those of ECL cells. ECL cells and neoplastic cells in the present investigation have a similar reactivity to SEVIER-MUNGER's method. Considering the generally accepted fact that neoplastic cells may not fully duplicate their parent cells in cytological features, it seems reasonable to presume that R and/or ECL cells might be the parent cells of the mastomys gastric carcinoids. In connection with this assumption histamine has been demonstrated to be produced both in mastomys carcinoid cells and normal ECL cells.


Permeability characteristics of brain adjacent to tumors in rats. The brain immediately surrounding 9L sarcoma and Walker 256 carcinosarcoma was evaluated, using radioactive water, albumin, red blood cells, urea, and sodium to quantitate isotopic exchange and permeability in the brain adjacent to tumor (BAT), normal brain, and, to a lesser extent, tumor. Exchange between blood and BAT for 14C-urea and 22Na averaged 53% of that for comparable regions of normal brain. This reduction in exchange is not explainable by differences in capillary surface area for transcapillary exchange in the BAT. This reduction in capillary permeability in the BAT could be detrimental to the delivery of watersoluble and rapidly binding drugs.


Homovanillic acid and 5-hydroxyindoleacetic acid cerebrospinal fluid levels. A study with and without probenecid administration of their relationship to the state of consciousness after head injury. Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured in the lumbar cerebrospinal fluid of 98 patients after closed head injury. The HVA levels decreased in patients, whether or not they were given the drug probenecid, which inhibits the active transport of these acids from the brain. The decline of HVA was more notable in patients with the longest duration of unconsciousness. The HVA levels showed no correlation with the state of consciousness at the moment of the lumbar puncture. The 5-HIAA levels were below normal in the conscious patients, but paradoxically, at about normal levels in unconscious patients. The overall results suggest a decreased cerebral dopamine and serotonin metabolism after head injury.


Ultrastructure of aneurysms.

Ultrastructure of aneurysms. The fine structure of five cerebral aneurysms, four early aneurysmal changes, and three arteriovenous aneurysms (two cerebral and one spinal) were investigated from surgical and autopsy specimens. Each lesion was characterized by thickening, lamination, redundancy, and separation of basement membranes, abundant cellular debris, and a paucity or absence of elastica. In several instances, extracellular lipid and lipophages were present. These vascular lesions were remarkably similar to one another and also to the degenerative changes in experimental arteriovenous aneurysms, thus substantiating the concept that they, too, are essentially degenerative in nature.


Reversible vacuolar myopathy of type II fibers. A 23-year-old ex-bicycle racer with vague gastrointestinal symptoms had an acute weight loss of 13.6 kg (30 lb). During the period of maximal weight loss, he experienced muscle weakness, dysphagia, bradycardia, and T wave changes on the electrocardiogram. His skeletal muscle biopsy showed a severe vacuolar myopathy devastating the atrophic type II fibers. Without treatment, he recovered completely and has remained well. This may be an exaggerated or acute form of type II atrophy not previously reported, or it may represent an acute muscular degeneration.


Effects of shock on the pancreatic acinar cell. Cellular and subcellular effects in humans. Pancreatic tissues from 22 patients with a wide variety of types of shock were obtained within minutes of somatic death for light and electron microscopy and for cytochemical studies. By light microscopy, it was difficult to ascertain any differences between the shock groups; however, electron microscopy disclosed subcellular alterations that could be correlated well with the type, severity, and duration of shock. Mild cases of shock or shock of short duration showed mild cell damage, while extreme cases of hemorrhagic or septic shock showed cell death and necrosis. No morphological evidence for lysosomal initiation of damage was seen, but it is clear that the pancreas can undergo severe cell injury during shock that could result in release of further damaging enzymes, most probably from zymogen granules rather than from lysosomes.


Glomerular lesions in Hodgkin disease.

Glomerular lesions in Hodgkin disease. Three cases of Hodgkin disease with renal manifestations were studied with electron microscopy and immunofluorescence. The first patient had lipoid nephrosis that disappeared after chemotherapy for Hodgkin disease. Immune-complex nephritis was observed in the second patient who also had Sjogren syndrome. The third patient developed amyloid nephrosis five years after the onset of Hodgkin disease. Apparently, diverse lesions and mechanisms are involved in the development of the nephrotic syndrome in Hodgkin disease and the diagnosis can only be established by appropriate studies of kidney specimens.


Acute calcium nephrotoxicity. An electron microscopical and semiquantitative light microscopical study. Rats were infused for three hours with doses of calcium gluconate to elevate serum calcium level and were killed either immediately after infusion or after 24 hours. Necrosis of proximal tubular cells was observed when serum calcium level was 16.0 mg/dl or higher. Above 16.0 mg/dl, an additional 5% of renal tubular profiles contained damaged cells for each 1 mg/dl in serum calcium. No difference in extent of damage was found in rats killed immediately or after 24 hours. Initial changes were formation of granular dense bodies in mitochondria, cell swelling, rupture, and extensive mitochondrial calcification. Renal tubular basement membrane changes appeared to be initiated by protrusion of cytoplasmic buds, forming ovoid bodies, which became embedded in the basement membrane. These ovoid bodies then appeared to serve as a nidus for further extensive basement membrane calcification.


D-serine nephrotoxicity. The nature of proteinuria, glucosuria, and aminoaciduria in acute tubular necrosis. Administration of D-serine to rats induced acute necrosis of the proximal straight tubules, proteinuria, glucosuria, and aminoaciduria. Proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by new epithelium. Our findings suggest (1) that abnormal loss of protein and glucose in urine is due to diffusion of these substances from interstitium to tubular fluid across the denuded permeable basement membranes of the necrotic tubules, and (2) that tubular cells normally are a barrier to diffusion of certain solutes betweeen interstitial and tubular fluids. Amino-aciduria preceded the onset of tubular necrosis and increased excretion of some amino acids persisted after tubular repair. Thus, D-serine-induced aminoaciduria may be due to impaired reabsorption of amino acids by the injured proximal straight tubules, as well as by backward diffusion of amino acids from the interstitium.


Oncocytic change in mucoepidermoid carcinoma of the parotid gland. Among the morphological features of an oncocytic mucoepidermoid carcinoma of the parotid salivary gland in a 78-year-old man, the oncocytes had granular eosinophilic cytoplasm that was characterized ultrastructurally by large numbers of mitochondria that displayed minimal abnormalities. Complex cell-to-cell relationship, well-developed junctival complexes, and microvillous-like surface projections suggestive of ductal differentiation were present; epidermoid features in the form of dense focal aggregates of cytoplasmic fibrils were also seen.


Elastic tissue in pseudoxanthoma elasticum. Ultrastructural study of endocardial lesions. A 56-year-old woman had pseudoxanthoma elasticum (PXE). Ultrastructural findings in the endocardium showed increased collagenogenesis and elastogenesis. The newly formed elastic fibers appeared morphologically normal, but showed a notable propensity to become calcified. The internal structure of the calcified areas was essentially similar to that of the adjacent uninvolved portions of the elastic fibers. Some of the heavily calcified fibers showed loss of internal structure and fragmentation. These findings support the concept that in PXE, calcification involves morphologically unaltered elastic fibers that subsequently may undergo secondary degenerative changes, such as loss of internal structure and fragmentation.


[Characteristic electrolyte changes in the hereditary myopathy and cardiomyopathy of the Syrian golden hamster (strain BIO 8262) (author's transl)]. In hamsters of differing ages suffering from a hereditary myopathy and cardiomyopathy (strain BIO 8262), the electrolytes sodium, potassium, calcium, and magnesium in serum, and several tissues were compared with appropriate controls. The determinations of the electrolytes were performed by atomic absorption spectrophotometry. An enormous accumulation of calcium in the necrotizing heart and skeletal muscle was the noticeable feature besides pronounced elevation of the sodium content in the myopathic skeletal muscle. While the latter refers mainly to an interstitial edema which is a consequence of the myopathy, the calcium accumulation is assumed to be an essential part in the cycle of pathologic events occurring in the hereditary disease: it seems to induce the necrotization.


[Spontaneous changes in blood pressure and aortal pulse wave velocity in normotensive subjects (results of a long term study in 183 men) author's transl)]. The changes in the aortal pulse-wave velocity (PWV) occurring in connection with and dependent on spontaneous fluctuations of blood pressure has been recorded at intervals over the years in 183 normotensive men, who were aged from 17-74 at the beginning of the long term study. An essential condition was that the diastolic blood pressure should not exceed 95 mm Hg and the systolic 145 mm Hg. In order to eliminate the effect of age on the PWV between 2 measurements, and so to obtain a "pure" PWV-mean pressure relationship (c-p relationships), 7 cm/sec per year was subtracted from the c-value of the second measurement before the age of 55 and 9 cm/sec per year after that age. The differences quotient delta cp as a standard for the change of c with the mean pressure p was obtained from the difference between two c values (c1-c2) taken at different times, converted to a pressure change of 10 mm Hg, and divided by the difference of the mean pressure levels belonging to them (p1-p2). In applying the appropriate age correction to c2, the time factor had no statistically recognisable effect on delta cp. In 78% of the cases in our long term study, c rose and fell with p, in 22%, the changes of c were at variance with the changes of p. Taking into consideration all the test subjects, delta cp averaged 0.40 m/sec. Before the age of 55, delta cp is smaller (0.30 m/sec) than above that age (0.55 m/sec). The age difference of delta cp is significant ( = 0.05). When the concordant c-p relationships alone were calculated, delta cp was 0.70 m/sec and scarcely differed from the delta cp values of hypertensives published earlier (0.60 m/sec: also concordant c-p relationships only). The generally lower delta cp values from group cross sections (in contrast to the longitudinal investigations) are explained by an unrecognisable admixture of discordant c-p relationships. In a range of pressure from 90-170 mm Hg, delta cp was shown to be independent of the level of the initial pressure. Also the magnitude of the (spontaneous) mean pressure variation (5-70 mm Hg, normotensives - hypertensives) seems to have no effect on the statistical mean value of delta cp. delta cp is, however, dependent on the direction of the pressure change in normotensives (just as with hypertensives), even when age is taken into account. If the pressure is reduced, c is higher and delta cp (p = 0.05) is greater than when the blood pressure is increased. The c-p relationship traverses a kind of loop (counterclockwise). In the discussion, an attempt is made to point out the effect of the vascular musculature on delta cp, which threads conspicuously through the comparison of the physiological delta cp values with the delta cp values in arteriosclerosis (hypertension; diabetes) and in endurance training. From this it can be deduced that normal values for c and delta cp in arteriosclerosis indicate that the musculature is still capable of maintaining a normal elastic function even with considerable regressive changes in the vessel wall.


[Organization of experimental thrombi in arteries and veins. A comparative study (author's transl)]. Thrombi were produced in 62 female white rats (Sprague-Dawley) by injection of thrombin in the right common carotid artery and in the left vena iugularis as well. Partly the vessels were ligatured proximal and distal of the thrombus, partly they were closed with one ligature. In this latter group (one ligature) the thrombus was exposed to the blood-pressure, while in the first group the thrombus was protected against the blood-waves. After 2, 4, 6, 8, 10 and 14 days as after 4 and 6 weeks the rats were sacrificed and the thrombosed vessel-segments were studied by light-microscope. In the arterie we found occlusive thrombi. In the veins the thrombi were higher in fibrin content than in the arteries. Between the thrombus and the endothelium of the vein-wall there was a sinus which became wider with aging of the thrombus. In the first days the progression of thrombus-organization was more rapid in veins than in arteries; endothelial cells, fibroblasts and capillary buds invaded the thrombus more extensive. In veins there was no difference in composition and organization of the thrombi of the two groups. In the thrombosed veins often small capillaries could be seen running through the vessel wall into the tissue of the organized thrombus but not in arteries. 6 weeks after thrombus-formation wide capillaries recanalized the veins, but the arteries were obturated by fibrous tissue with only a few small capillaries. Elastic fibres could be seen in the organized arterial thrombi earlier and more extensive than in the venous. In double ligatured arteries the organization of thrombi was more rapid than in arteries, in which the thrombus was influenced by the pulsating blood-pressure. In this latter group with only one ligature the organization-process was pronounced in the proximal part of the thrombus, which was higher in fibrin content. Next the ligature the thrombus was composed mainly of erythrocytes and hematoidin-needles. In this part of the thrombus the organization-process started with delay. From our findings we may conclude that the composition of a thrombus, the influence of the blood-pressure and the structure of the vessel-wall are important factors to explain the different temporal course and morphological pattern of thrombus-organization.


Effect of the carotid sinus nerve stimulation on nutritive myocardial blood flow in regional cardiac ischaemia. The authors have studied the local blood flow regulation of the heart under the influence of the stimulation of the carotid sinus nerve in segmental myocardial ischaemia. The experiments were carried out on 38 dogs. By ligating the mid-portion of the left anterior descending coronary artery, a small artificial infarction has been produced. Circulatory examinations were made after 24 hours following the coronary ligation. In 18 dogs the circulatory investigations were done during the electrical stimulation of the carotid sinus nerve while 20 dogs were used as control. The local nutritive blood flow of the heart was measured by the administration of 86 rubidium in the intact zone, in the ischaemia (necrotic) zone and at the border zone of the heart. According to the experimental data, under the influence of the carotid sinus nerve stimulation the blood flow of the intact zone does not change considerably while the necrotic and border zones increases to a great extent. Reflex redistribution of the myocardial blood flow probably plays a decisive role in the antianginal effect of carotid sinus nerve stimulation.


Genetic variation of an intestinal leucine arylaminopeptidase (Lap-1) in the mouse and its location on chromosome 9. Electrophoretic variation for an intestinal enzyme that cleaves L-leucyl-beta-naphthylamide has been discovered among inbred mouse strains. Several strains including related strains C57BL/6J, C57BL/10J, C57BR/cdJ, C57L/J, and C58/J demonstrate an electrophoretic band of this enzyme that is absent in other strains and stocks thus far observed. The enzyme is tentatively being called leucine arylaminopeptidase (LAP) and the variant genetic locus Lap-1. The presence of the band is determined by an allele designated Lap-1a. Homozygotes for the alternate allele, Lap-1b, are without the band and heterozygotes are, under our electrophoretic conditions, indistinguishable from Lap-1a homozygotes. Data from recombinant inbred lines and a B6D2F1 X DBA/2J backcross established linkage of Lap-1 to dilute (d) and supernatant malic enzyme (Mod-1) on chromosome 9 in the following order: Lap-1-d-Mod-1. The Lap-1 to d map distance was estimated to be 21.3 +/- 4.6 cM from backcross data and 8.1 +/- 4.8 cM from recombinant inbred lines.


[Intramyocardial pressure at various depths, during aortic constriction and myocardial ischemia in the dog (author's transl)]. Systolic intramyocardial pressure (IMP) is measured with a modification of the "closed perfusion technic" in 3 different layers of the myocardium in 8 anesthetized mongrel dogs. In the subendocardium IMP exceed left ventricular pressure (LVP) by about 30% whereas it is 30% lower than LVP in the subepicardium. Under resting conditions the level of isobaric balance of IMP and LVP is at a distance of 57% from the epicardium. During thoracic aortic constriction the ratio of IMP/LVP increases in the subepicardium but decreases in the subendocardium. Occlusion of the left circumflex coronary artery for 30 seconds results in a decrease of IMP and IMP/LVP in the ischemic region. In 25% of all cases, however, an increase of these parameters is found.


Mitochondrial malate dehydrogenase (Mor-1) in the mouse: linkage to chromosome 5 markers. Malate dehydrogenase is present in most mammalian tissues in both supernatant and mitochondrial forms. Although genetic variation for the supernatant form has not been observed in the mouse, electrophoretic variants caused by alleles at the mitochondrial locus (Mor-1) have been previously described. We have located this locus 11.0 +/- 2.9 cM from the beta-glucuronidase structural gene, Gus, on chromosome 5. The gene order is Hm-Pgm-1-rd-bf-Gus-Mor-1. Thus Mor-1 is presently the most distal marker on chromosome 5. Three different nuclear loci for mitochondrial enzymes (Mod-2, Got-2, and Mor-1) have now been mapped in the mouse, all on different chromosomes.


Collateral vessel formation: isolation of a transferable factor promoting a vascular response. Collateral vessel formation to the kidney was induced by renal artery stenosis or embolization in six dogs. Extracts from control and collateral-forming kidneys were assessed for their ability to promote a vascular response in the hamster cheekpouch. The highly significant response evoked by particulate and soluble fractions of cytoplasm from collateral-forming kidneys suggests a humoral element in collateral vessel formation.


Genetic control of acid phosphate isozymes in Arabidopsis thaliana (L.) heynh. Starch gel electrophoresis in a discontinuous buffer system has enabled us to study two acid phosphatase systems (AcPh-1 and AcPh-2) in Arabidopsis thaliana. The AcPh-2 bands are much more prominent than those belonging to AcPh-1. Among the 17 geographic races, one variant for AcPh-2 was detected. A study of F1 hybrids and F2 segregating progenies showed that AcPh-2 variants are controlled by two codominant alleles (AcPh-2N and AcPh-2F) at one locus. The heterozygotes are characterized by an intermediated hybrid band in addition to the two parental ones, thus showing that these proteins are at least dimeric structures.


Linkage of the locus for serum albumin in the house mouse, Mus musculus. An electrophoretic variant for serum albumin in Mus musculus has been used to map the structural gene for this protein to chromosome 5.


Influence of the sympathomimetic activity of oxprenolol on haemodynamics in the anaesthetized dog. In anaesthetized, artificially respirated mongrel dogs, the intravenous infusion of oxprenolol (0.3 mg and 1 mg/kg over 10 minutes) led to an increase in heart rate and cardiac output. Blood pressure in the pulmonary capillaries and right atrium, and vascular resistance were reduced. The pressure in the aorta was transiently decreased. Infusion of propranolol in the same doses was followed by a decrease in heart rate and cardiac output. The calculated peripheral resistances, pulmonary capillary pressure and right-atrial pressure increased slightly. Pressure in the aorta diminished slightly. In the light of the present results, it is evident that the intrinsic sympathomimetic activity of oxprenolol has a significant bearing on its haemodynamic effects in the anaesthetized dog.


Deficiency of toxin-binding protein activity in mutants of sugarcane clone H54-775 as it relates to disease resistance. Three mutants selected from a population of sugarcane clone H54-775 that had been irradiated with 3 kR gamma-radiation all lacked toxin-binding protein activity. This activity previously had been shown to be essential for eye spot disease susceptibility and was demonstrated in the susceptible parent clone H54-775. In one mutant, the biochemical, immunochemical, and electrophoretic mobilities of the toxin-binding protein were all modified.


The phosphorylase kinase deficiency (Phk) locus in the mouse: evidence that the mutant allele codes for an enzyme with an abnormal structure. Female (I/St X C57BL/St) F1 mice heterozygous at the sex-linked phosphorylase kinase deficiency locus (Phk) have phosphorylase kinase activities averaging 86% that of mice homozygous for the wild-type allele (C57BL/St), i.e., 72% greater than the sum of one-half the activities of the parental strains. Approximately one-half the phosphorylase kinase activity in the (I X C57BL) F1 muscle extracts had a stability at 42.5 C similar to that of the activity in C57BL extracts (t1/2 = 13.2 min); the other half of the activity in the F1 extracts was more labile (t1/2 = 3.9 min). Two species of phosphorylase kinase activity in F1 muscle extracts were also differentiated with an antiserum prepared in guinea pigs against purified rabbit skeletal muscle phosphorylase kinase. This anti-serum cross-reacted with phosphorylase kinase in C57BL muscle extracts but did not cross-react with skeletal muscle extracts of mice hemi- or homozygous for the mutant allele (I/LnJ). The guinea pig antiserum precipitated 52% as much protein from (I X C57BL)F1 muscle extracts compared to those of C57BL. However, an antiserum prepared against purified rabbit skeletal muscle phosphorylase kinase in the goat cross-reacted with the mutant phosphorylase kinase. The ratio C57BL:(I X C57BL)F1:I of immunoprecipitated protein from skeletal muscle extracts with this antiserum was 1:0.97:1.08. Polyacrylamide gel electrophoresis of the immunoprecipitates in the presence of 0.1% sodium dodecylsulfate showed three subunits for mouse phosphorylase kinase with molecular weights of 139,000, 118,000, and 41,000; these values are similar to the ones obtained with purified rabbit skeletal muscle phosphorylase kinase. These three subunits were also observed in immunoprecipitates from I/LnJ muscle extracts. These results offer substantial evidence (1) that in skeletal muscle extracts of mice heterozygous at the Phk locus the mutant phosphorylase kinase is active, (2) that the gene product of the mutant allele is an enzyme with an abnormal structure, and (3) that the phosphorylase kinase deficiency in I/LnJ skeletal muscle extracts is not the result of the absence of phosphorylase kinase or one of its subunits.


The status of ribosomal RNA genes during nuclear DNA reversion in flax. Heritable changes in plant weight and nuclear DNA content may be induced in certain varieties of flax by different fertilizer environments. The large stable form (L) has 16% more nuclear DNA that the small stable form (S). In subsequent generations in particular environments the nuclear DNA difference disappears, although the plant weight differences remain, while in other environments both DNA and plant weight differences are maintained. The large stable form has 56-70% more rRNA genes than the small stable form. The majority of this difference in rDNA is maintained in types where the nuclear difference has reverted. It is suggested that the expression of the flax genome may be susceptible to a reduction in the multiplicity of rRNA genes which limits the availability of protein synthetic machinery needed for growth.


High genetic variability in an ecologically variable vertebrate, Bufo viridis. Allozymic variation in proteins encoded by 26 loci was analyzed electrophoretically in 517 specimens of green toads from 11 populations from Israel and one population from Vis Island in the Adriatic Sea. Genetic variation in this toad is the highest yet reported in any vertebrate. All three genetic parameters, mean number of alleles per locus (A), mean proportion of loci polymorphic per population (P), and mean number of heterozygous loci per individual (H), are very high (A = 1.65, range 1.38-2.04; P = 0.423, range 0.346-0.615; H = 0.133, range 0.108-0.159). Central and marginal mainland populations are only slightly more variable than desert isolates, but much more variable than the Vis Island population. Genetic similarity is very high between mainland populations  (S = 0.951, range 0.93-0.97). Frequencies of two alleles (Icd-lc and Tfa) are correlated with an ecological gradient of increasing aridity. Regulatory enzymes appeared to contribute more to overall polymorphism than non-regulatory enzymes. The genetic variation observed suggests that selection for heterozygosity as an adaptive strategy is operating in the ecologically variable environment in which green toads live.


Variation in the isozymes of flax (Linum usitatissimum) genotrophs. Peroxidase, esterase, and acid phosphatase isozymes of environmentally induced L and S genotrophs, nuclear DNA reversion types, and the orginal plastic (Pl) type of the flax variety Stormont Cirrus have been compared by polyacrylamide gel electrophoresis. Differences were observed in particular line was not correlated with the nuclear DNA amount. The relationship between the isozyme pattern and the phenotypes of the lines in which they are expressed is discussed.


Two factors affecting the heat stability of xanthine oxidase in extracts of mouse intestine. The heat stability at 56 C of xanthine oxidase (Xox) from mouse intestine was found to be affected by two factors: (1) Xox which had been partially digested by trypsin was less heat stable than Xox which was protected from digestion by the presence of soybean trypsin inhibitor and phenylmethylsulfonyl fluoride; (2) Xox was less heat stable in glass tubes than in polystyrene tubes and siliconized glass tubes resembled polystyrene tubes in this respect.


Gel isoelectric focusing of mouse lactate dehydrogenase: heterogeneity of the isoenzymes A4 and X4. LDH of mouse organs (including testis) was investigated by isoelectric focusing in polyacrylamide gels. The number of LDH bands in this pattern considerably exceeds the five (six in testis) of the standard electrophoretic pattern. An attempt was made to identify these bands as tetrameric isoenzymes formed by random association of different subunits. This included isoelectric focusing of purified LDH A, B, and X, two-dimensional separation of LDH, urea treatment of LDH, staining with specific substrates, and comparison of different organs. Further experiments were performed to exclude artifacts possibly produced by the isoelectric focusing technique. Different strains of mice were also investigated. The results demonstrate that in addition to the common five LDH bands (A4-B4) one set of five bands is formed by LDH A (A41-A42) and another one by LDH X (X 41-X42). Moreover, an unusual band was found which has a lower molecular weight and no affinity to the other isoenzymes. The data suggest that the heterogeneity of the LDH pattern revealed by isoelectric focusing arises from post-transcriptional events rather than from a number of additional genes.


Evaluation of rosette inhibition test by antisera to hl-a system. Specific antisera to HL-A antigens may inhibit spontaneous rosette formation by HPL bearing the corresponding antigen. This rosette-inhibiting activity is removed by absorption with lymphocytes carrying the specific antigen. The rosette-inhibition test may be acceptable as a cross-matching procedure for detecting tissue sensitization in the field of transplantation.


The c 1 fixation and transfer test for studying immunity in melanoma patients. Sera from 27 melanoma patients and from 30 healthy persons were investigated for humoral immunity by C 1 fixation and transfer test. The number of C 1 molecules fixed to serum treated, sensitized tumor cells and C 1 molecules fixed to these cells in vivo were calculated and the quotient of these values was determined. On the basis of the quotient the patients could be divided into four groups. In Group 1 the serum treatment of cells decreased the C 1 fixation; in these cases the presence of blocking factors can be supposed. In Group 2 the serum treatment did not cause any difference: the patient serum does not contain humoral antibody. In Groups 3 and 4 the C 1 fixation rose slightly and significantly respectively. Work is in progress to find a possible relation of the results with the stage of the disease.


Radioimmunoassay for the simultaneous detection and quantitation of hepatitis B surface antigen and of the homologous antibody. A solid-phase radioimmunoassay procedure is presented, which allows the simultaneous detection and quantitation of HB, Ag and of anti-HBs. This procedure involves short preliminary incubation of test sera and of negative controls with a standard HB, Ag. The standard HBs Ag is diluted, according to preliminary assays, in order to yield a count ratio to negative controls of 10 to 1. Therefore, a value of 10 is ascribed to the counts of positive controls (standard HBs, Ag + HBs-negative serum) and counts of all test sera are proportionally related. The values obtained are denominated HBs Units. Test sera are considered to be positive for HBs Ag or anti-HBs when the corresponding HBs Units are significantly higher or lower, respectively, than the average value of standard antigen controls. Including the reference standard HBs Ag controls in each set of assays ensures the quantitative reproducibility of results among different assays and among different laboratories. Titres of serum HBs Ag and anti-HBs can be expressed as end-point dilutions, simply by plotting the corresponding HBs Units on a nomography. This was drawn according to the indications emerging from analysis of the radioimmunoassay kinetics. Laboratory assays and the practical application of the combined procedure over several thousands determinations showed that the binding capacity of the solid-phase substrate used (small antibody-coated polystyrene tubes) is extremely homogeneous. Such homogeneity accounts for a very high accuracy and reproducibility of quantitative results.


Studies on hydrolysis and synthesis of fats in staphylococcus aureus and candida lipolytica. Hydrolysis of triglycerides via di- and mono-glycerides has been obtained from washed cells and crude lipolytic enzyme from Staphylococcus aureus and Candida lipolytica. The same strains were unable to synthesize triglycerides starting from oleic acid and glycerol, while synthesis was obtained starting from mono- and di-oleate.


Effect of L-histidine and various buffers on colony size and morphology of a T-strain of mycoplasma. The incorporation into agar medium of either histidine or various buffers affects the colony size and the type of superficial outgrowth (fried egg), stabilizing the initial low pH of the medium.


[Evaluation of the lysozyme and DNAase activity for the identification of pathogenic staphylococci]. The sensitivity of two tests recently proposed for the classification of pathogen staphylococci were evaluated: --production of DNA-ase with the modified method of Lachica et al.; --production of lisozyme. The two above tests were studied with other six tests on 1,000 strains of staphylococci showing a very high specificity. The Authors propose that the DNA-ase production and the lisozyme production, also for their very simple execution, should become routine tests to identify the strains of pathogenic staphylococci.


[Effect of phytohemagglutinin (PHA) on rosette formation by human peripheral lymphocytes]. Treatment of human perypheral blood lymphocytes with phytohaemagglutinin (PHA), for 30 min and for 72 h, increases their ability to form E-rosettes. Possible interpretations of the phenomenon are discussed.


Oral influenza vaccination with live attenuated viruses. 1. Acceptability, immunogenicity and transmissibility. 151 subjects were vaccinated by oral route with live attenuated influenza virus vaccine, bivalent A and B, prepared in the U.S.S.R. Each subject received two vaccine doses with a 10-day interval. Vaccination did not bring about any important clinical manifestation and the incidende of the symptoms after vaccination was not significantly different in comparison with what observed in the non vaccinated cohabitants. The vaccine showed good immunizing activity: among the subjects who before vaccination, had a HI antibody titer lower than 1/16, 91% responded for A type, and 70% for B type. Several subjects with starting low antibody titers also responded to vaccination. Among the cohabitants of the vaccinated no influenza virus infections were serologically ascertained, thus showing that no transmission of the virus from the vaccinated to the cohabitants occurred.


Oral influenza vaccination with live attenuated viruses. 2. Protective efficacy during a type A(H3N2) epidemic. 151 subjects, orally immunized with live attenuated influenza virus of the Institute for Viral Preparations of Moscow (bivalent A(H3N2) England 72 and B vaccine) and 66 non vaccinated cohabitants were studied during an epidemic caused by strains similar to A/Port Chalmers/73. 5 cases of disease were virologically or serologically ascertained among the vaccinated (morbidity 3.3%) and 8 among the non-immunized cohabitants (12.1%). The difference turned out statistically significant. By comparing the incidence of the disease in the two groups the protection resulting from vaccination was 72.6%.


Immunological investigation and immunotherapy approaches in cancer patients. The Authors report the preliminary results of a two-step far-reaching investigation carried out on cancer patients to study: 1) the immune conditions of the patients and establish, by a thorough immune monitoring, employing tests of humoral immunity (tetanus toxoid response), of delayed immunity (BCG test, PHA-lymphocyte blastogenesis, MIF release, skin window) and macrophage immunity (skin window), the chemotherapy effects on the immune conditions and the most suitable time to carry out immunotherapy; 2) the immunotherapeutic results which can be obtained with three different immunogens (BCG, C. parvum and ribonucleotides). The results obtained in the first part of the investigations pointed out the usefulness of the tests adopted to follow up the evolution of the immunological reactivity in patients submitted to chemotherapy, while the results of the immunotherapeutic trial show a preliminary character and, at present, do not allow definitive conclusions. Carefully planned and randomized studies are at present under way to establish, more thoroughly, the optimal modalities and the real possibilities of the immunotherapy performed with C. parvum and ribonucleotides in cancer patients.


Beta-glucuronidase activity of lymphocytes in the premature infant with special reference to the fetal maturation stage. Activity of beta-glucuronidase (GR) was determined cytochemically by the Hayashi et al. method on peripheral blood lymphocytes of 50 premature infants, born between 21st and 37th week gestation. The subjects studied were subtyped into group I (21st to 28th week), group II (29th to 33rd week), and group III (34th to 37th week). Absolute count of enzyme-positive lymphocytes was lower in group I, when compared with group II and III as a whole. Absolute count of GR-positive lymphocytes exhibiting granular reaction type was significantly lower in group I, when compared with other groups. Absolute counts of GR-positive cells, with both granular and diffuse, or diffuse enzymatic reaction did not differ in groups I, II and III. The results obtained indicate ontogenetic development of lysosomal granules containing GR in the lymphocyte cytoplasm in premature infants related to their fetal age.


[Cellular lysis and dissociative phase of the genus Bacillus]. The sensitivity of the dissociative variants "R", "RS" and "S" of the spore-forming bacilli to some lytic agents (lysozyme, sodium lauryl sulphate, lipase, trypsin and some of their associations) has been studied. The research has been carried out on 32 strains: 14 "R", 14 "RS" and 4 "S" of different species of the genus Bacillus. The results have shown that the sensitivity to the studied lytic agents is strictly correlated, not to the species, but to the dissociative phases: these results are in accordance with those obtained in previous researches, carried out by the same Authors, on other characters, both morphological and biological, of the same variants. Thus, also through this way, it is possible to reach the conclusion that within this genus, there is more similarity among the different species of the same dissociative phase than among different dissociative variants of the same species. The results obtained in the present study allow to advance hypothesis, based also on the data of the literature, about the composition of the cell walls of the three above mentioned dissociative variants of the strains belonging to the genus Bacillus.


[Anti-mycoplasmatic activity of 2 antracyclinic antibiotics]. The antimycoplasma activity (bacteriostatic and bactericidal) of daunomycin and adriamycin has been tested on 14 strains in liquid and solid medium. The minimal inhibitory concentration (MIC) values of daunomycin and tetracycline have resulted of the same greatness, while those regarding adriamycin are lightly greater.


A study of complement functions in a family with hereditary angioneurotic edema. A study of some complement functions was performed in two patients affected with hereditary angioneurotic edema (HAE) - mother and daughter - from a Southern Italy family (Apulia) and in three of their relatives. A decreased level of the C1 esterase plasma inhibitor was found in both the patients, who were treated with tranexamic acid with a slight, but definite improvement. However, the disease could not be traced beyond two generations in the pedigree and a couple of ascendants was found who were free from HAE both from the clinical standpoint and from that of the laboratory evaluation of complement functions. The possibility that HAE arose in the family through a mutational event is discussed.


A paramagnetic method for measuring the carbon dioxide concentration of a gas. A paramagnetic method of carbon dioxide analysis enables the simultaneous analysis of carbon dioxide and oxygen to be made at 2-min intervals. The method depends upon observing the change of oxygen concentration in a gas mixture before and after absorbing the carbon dioxide component. The carrier-gas in the experiments reported was nitrogen. The output of the paramagnetic meter was measured both by a digital voltmeter and by a chart recorded and the carbon dioxide concentrations calculated from these observations (Y1% and Y2% respectively) were compared with those obtained by Lloyd-Haldane (x%) gas analysis, for carbon dioxide concentration of 2-20% in a range of oxygen concentrations of about 9-90%. The agreement between paramagnetic and Lloyd-Haldane carbon dioxide analysis is shown in the following linear regression equations: Y1=0.996x-0.001 (r=0.9999+/-0.04 SEM of estimate; P less than 0.001); Y2=0.997x-0.006 (r=0.9999+/-0.06 SEM of estimate; P less than 0.001). Carbon dioxide in nitrogen was measured by the prior addition of an arbitrary concentration of oxygen, to a gas sample. The method is applicable to the measurement of carbon dioxide and oxygen, when the carrier-gas may have characteristics which preclude the use of katharometer, infra-red or Haldane analysis.


A method for the gas chromatographic analysis of inhalation anaesthetics in whole blood by direct injection into a simple precolumn device. A simple heated precolumn device constructed from standard gas chromatographic components is described and evaluated. The device permits the analysis of concentrations of anaesthetic agents by direct injection of whole blood containing a suitable internal standard. A method is described for the analysis of halothane, chloroform, trichloroethylene, and methoxyflurane. The procedure is rapid and of acceptable accuracy.


The uptake and elimination of halothane in dogs: a two- or multicompartment system? I: Gas chromatographic determination of halothane in blood and in inspired and end-tidal gases. The gas chromatographic determination of volatile organic anaesthetic agents in blood and in respiratory gases is described. The analysis in blood is based on a head space technique. Sampling of inspired and end-tidal gases is carried out by means of a system including a gas sampling valve.


Effects of althesin anaesthesia and surgery on plasma concentrations of luteinizing hormone and testosterone in man. This study was undertaken to investigate the effects of Althesin and surgery on plasma concentrations of luteinizing hormone (LH) and testosterone in 10 male patients. Plasma LH concentrations increased markedly during Althesin anaesthesia given alone over a period of 45 min. The high concentration lasted for 30 min after the start of surgery and was followed by a gradual decrease, although the concentration remained significantly greater than the control value. Plasma testosterone concentrations decreased during Althesin anaesthesia, and a further decrease was noted during the period following surgery.


The use of a digital computer for the on-line real-time assessment of neuromuscular blockade in anaesthetized man. A computer program written mainly in a high level language (ALGOL), but with the sampling routine and certain calculations written in assembly language (SIR), has been developed to assess neuromuscular blockade in anaesthetized man by means of an Elliott 903 digital computer. The program allows the on-line real-time analysis of a range of variables including twitch height, maximum slope of twitch and twitch pulse widths, peak height of tetanic contraction, end-height of tetanic contraction, the tetanic tension ratio and the percentage tetanic transmission. The program has been used to investigate the pattern of action of neuromuscular blocking drugs and has particular value in the study of the pharmacokinetic action of these drugs.


Muscle hypertonus after intravenous suxamethonium: A clinical problem. Hypertonus of masseter and chest wall muscle in one patient following intravenous suxamethonium is reported. Subsequent investigations including electromyography and muscle biopsy with in vitro pharmacological testing failed to reveal any abnormality to account for the response. The clinical problems presented to the anaesthetist when suxamethonium-induced hypertonus occurs are discussed. The relationship between a hypertonic reaction to suxamethonium and neuromuscular disease (including myotonic disorders and the malignant hyperpyrexia myopathy) is considered.


Pulmonary damage from a Swan-Ganz catheter. A patient developed pulmonary damage following the insertion of a Swan-Ganz catheter into the pulmonary artery. Suggestions are made on how to avoid this complication.


Accidental subdural analgesia: A case report, possible clinical implications and relevance to "massive extradurals". A continuous obstetric epidural is described, in which an abnormally extensive block and hypotension resulted. The catheter was subsequently shown to enter the subdural space. As this case resembles a "massive epidural", it is suggested that subdural injection may explain the phenomenon.


The changing pattern of bronchial carcinoma. 1. The age incidence of bronchial carcinoma in England and Wales is rising. 2. In one series the proportion of the patients operated on over the age of 65 years rose from 12% in 1950-5 to 37% in 1970-4. 3. Thes change reflects the national figures in both men and women. 4. The proportion of the population in the ages at risk has risen substantially, particularly amongst men, in the last 20 years, but this does not nearly account for the rise in the incidence in the older age groups. 5. The rate continues to rise in the patients over 65 years of age, but is now falling in all groups of men below that age. It is still rising in all age groups of women. 6. As time has passed the rate has begun to fall in men of older age groups. 7. The sex ratio continues to fall. 8. The process described has been going on for at least 50 years, and it is suggested that the decline in the younger age groups represents the natural history of bronchial carcinoma in the community. 9. The timing of the change in mortality is different in different parts of the world and in the two sexes. 10. It is predicted that the number of men with broncial carcinoma fit for surgery may shortly start to fall in this country.


Failure of resolution in pneumonia.

Failure of resolution in pneumonia. An account is given of the clinical, radiological and pathological features of 50 cases of pneumonia in which resolution was incomplete. This phenomenon occurs mainly in middle-aged and elderly men with chronic bronchitis and may simulate bronchial carcinoma. It most frequently affects the right upper lobe. Fibrosis and inflitration by chronic inflammatory cells are the characteristic histological abnormalities. Serious long-term sequelae are uncommon.


Patterns of response to isoprenaline in asthmatic patients. Six asthmatic patients whose airway obstruction improved significantly during a trial of prednisone have been studied in detail. Serial measurements of forced expiratory volume in 1 second (FEV1) were made at specific times each day before and after isoprenaline, for 8 days. Peak response was at 5 minutes in the majority of tests. In contrast to previous studies no clear pattern of response emerged in relation either to type of asthma, length of history or initial FEV1.


Confluent lymphoreticular aggregates in the bronchi of children--'mural bronchitis'. A study of a random series of 503 lungs from children of all ages and comprising a cross-section of almost all deaths in children in Sheffield shows that 'mural bronchitis' is not seen at birth but increases progressively with post-natal age. These lesions bear no relationship to unexpected death in infancy. They are probably a normal component of children's lungs, and an indication of bronchus associated lymphoid tissue. There is a positive correlation between the presence of prominent lesions and long-standing history of respiratory symptoms.


The effect of angrod on the delayed hypersensitivity response in rats. Delayed hypersensitivity was induced in rats by means of sheep erythrocytes and bovine serum albumin-lipid conjugate. Administration of heparin to rats sensitized to either antigen resulted in diminution of the delayed hypersensitivity reaction. Administration of ancrod, however, failed to inhibit the delayed cellular reaction to either antigen. Granuloma formation remained unaffected when rats were injected with either heparin or ancrod. The lack of ancrod effect, in contrast to heparin effect, on delayed hypersensitivity is discussed.


Protection by carbon tetrachloride against the toxic effects of dimethylnitrosamine in mice. A single intraperitoneal dose of carbon tetrachloride (CCl4), from 0-004 to 0-5 ml/kg, protected male mice against the toxic effects of dimethylnitrosamine (DMN). The LD20 of DMN was increased by a factor of about 4-2 with the highest dose of CCl4 and by a lesser factor with lower doses. The increase in LD50 correlated with a decrease in DMN-demethylase activity in the liver of CCl4 treated mice. These effects commenced within 10 min of administration of CCl4, increased very rapidly for 12 h to a high level which was maintained for up to 60 h, after which the LD50 of DMN and the level of DMN-demethylase returned slowly to normal only in 5 or 6 days. The administration of CCl4 reduced the acute hepatonecrotic action of DMN.


En face organ culture of vascular endothelium. A simple technique is described for maintaining in organ culture segments of blood vessel in such a way that the endothelium can be studied en face. The behaviour of such cultures throws further light on the interaction between endothelium and intravascular clotting.


The resolution of thermal oedema at various temperatures under coumarin treatment. The treatment of thermal oedema with coumarin (a benzopyrone) has been found to be most effect when fast moving air of 20 degrees was blown over the burnt animals. Coumarin has two main effects: one is to cause vascular injury thus allowing extra protein and fluid into the tissues; the other is to stimulate phagocytosis, enzyme production and thus proteolysis and a subsequent removal of protein and fluid from the injured tissues. At lower temperatures the injurious nature of coumarin is prominent. At medium range temperatures the proteolytic actions of coumarin outweigh its injurious nature. Resolution thus proceeds much more rapidly. At high temperatures resolution is slowed. This is a consequence of the antioxidant effect of coumarin on adrenaline and ambient temperature on peripheral dilatation. The results obtained tie in well with those obtained by workers using water of equivalent temperature.


The induction of renal papillary necrosis in Gunn rats by analgesics and analgesic mixtures. Homozygous members of the mutant Gunn strain of Wistar rats genetically lack the enzyme uridine diphosphate glucuronyl transferase. "High" and "low" dose gavage feeding for 18-34 days of an analgesic mixture containing aspirin, phenacetin and caffeine (APC) confirmed the previously reported susceptibility of these animals to analgesic induced renal papillary necrosis. Heterozygotes do not share the gross enzyme deficiency of homozygotes and, when treated with APC under identical conditions, failed to develop renal papillary necrosis. Groups of homozygotes were dosed by gavage with aspirin, phenacetin and paracetamol for 4 weeks. Renal papillary necrosis was produced by all 3 drugs, the lowest frequency of lesions occurring with phenacetin. It is postulated that the enzyme deficiency of homozygous Gunn rats influences the metabolism of analgesics to favour the excretion of nephrotoxic metabolites. The renal papillary necrosis appearing in these experiments is essentially an acute lesion, differing both in natural history and morphology from the renal papillary necrosis of analgesic nephropathy, suggesting that the pathogeneses of the experimental and human lesions differ.


The response of the rat liver to alterations in total portal blood flow. In attempting to isolate the various components involved in the stimulus induced by partial hepatectomy, the effect of sudden increased portal flow to the whole liver has been studied. The technique involved the construction of a portacaval anastomosis and after a week, reconstitution of the original portal vein, allowing resumption of portal blood flow. The effects of increased portal flow in this experiment were to induce hypertrophy of hepatocytes and a minor degree of DNA synthesis.


Studies on the mechanism of shock. The importance of central catecholaminergic neurons in the response to injury. Destruction of central catecholaminergic nerve terminals and axons by the injection of 6-hydroxydopamine (6-OHDA) into a lateral cerebral ventricle lowered the resistance of rats to 4-h bilateral hindlimb ischaemia. Although treatment with 6-OHDA alters food intake and growth rate its effect on the resistance of rats to this injury could not be attributed to differences in the size of the limbs which were made ischaemic or in nutritional state. It was not seen after peripheral chemical sympathectomy produced by the intravenous injection of 6-OHDA. Pretreatment with intraventricular 6-OHDA affected the core temperature changes during and after the limb ischaemia and impaired the blood pressure response after removal of the tourniquets. The lesions in the hypothalamus associated with these changes were examined with fluorescence histochemistry and found to be severe and widespread. It was concluded that the catecholaminergic fibres innervating the hypothalamus and other parts of the brain concerned in homoeostasis play a beneficial role in the defence against injury.


Reduction of carbon tetrachloride toxicity by prior administration of a single small dose in mice and rats. Mice were given progressively smaller doses of carbon tetrachloride (CCl4) and at intervals later the LD50 of a second dose was determined. The LD50 was greater than in previously untreated mice as soon as 10 min after the first dose, increased to a maximum between 12 and 24 h that was maintained for about 3 or 4 days, after which the LD50 returned to normal by the 7th day. The maximum LD50 reached was dependent on the first dose, but even a minute first dose, 0-004 ml/kg, had a significant effect. The same phenomenon was confirmed in rats. Administration of promethazine before doseing with CCl4 did not have this effect, nor did an ether anaesthetic.


Haematological changes and iron metabolism in rats after administration of Corynebacterium parvum. Administration of 1-4 mg of C. parvum to rats caused a transient and mild normochromic and normocytic anaemia with reticulocytosis. There was also an immediate and marked fall of plasma iron concentration and a moderate increase of total iron binding capacity of plasma. Despite increased clearance of 59Fe from the plasma there was no significant change of the plasma iron turnover rate. At later intervals after administration of C. parvum an increased incorporation of iron into red blood cells and the spleen was observed. These changes in iron metabolism have been explained in terms of increased retention of iron in the mononuclear phagocyte system during the first few days after C. parvum and enhanced erythropoiesis at later intervals. Other haematological parameters remained normal, with the exception of the absolute number of lymphocytes, which initially fell sharply but soon returned to, and even exceeded, control levels. Liver and spleen weights increased greatly after administration of C. parvum, reaching a maximum at the end of the first week, and both these organs contained mononuclear cell infiltrates, granulomata and giant cells.


Natural antibiosis among skin bacteria as a primary defence against infection. Antibiotic-producing bacteria were present on the healthy intact skin of 77 of 340 people but predominated in only 38-9% of these. In contrast, antibiotic-producers which occurred in the lesions of 51 out of 263 dermatological patients predominated in 78-4%. The presence of inhibitory commensals in skin lesions was associated with a significantly low incidence of secondary infection both on admission and during hospital stay; there was, however, a small excess of Gram-negative infections on admission in skin lesions containing antibiotic producers. Among ninety surgical patients, also, the presence of inhibitory skin bacteria was associated with a relatively low rate of wound colonization by pathogenic bacteria. The ecological implications and practical applications of the findings are discussed.


The significance of a positive cutaneous immunofluorescence test in systemic lupus erythematosus. Direct cutaneous immunofluorescence microscopical examination of uninvolved skin is an important diagnostic test in systemic lupus erythematosus. Its prognostic significance is undetermined. In twenty-four patients there was an increased incidence of leukopenia, hypocomplementaemia, and LE cells in patients with positive skin immunofluorescence. Positive cutaneous immunofluorescence of uninvolved skin was correlated with the most severe forms of lupus renal disease, membranous glomerulonephritis, and diffuse proliferative glomerulonephritis.


In vitro assay of immunity to human wart antigen. The cell-mediated and antibody responses to human wart antigen have been studied in patients with warts and in controls. Most patients show a positive cell-mediated response at or about the time of resolution of their warts but the detectable immunity is short-lived. The majority of patients with warts have antibodies and the percentage rises both with resolution of the warts and with increase in the duration of the infection. No correlation between the presence of antibodies and the development of cell-mediated immunity was found.


Cell-mediated immune responses in patients with warts. Competence of cell-mediated immunity in patients with warts was assessed by measuring in vitro response to PHA and PPD. Patients with warts were found to be less responsive as compared with a control group and this deficiency was related to the length of history of the wart infection.


Nickel hypersensitivity. Nickel binding to amino acids and lymphocytes. The nature of a protein hapten conjugate which could effect lymphocyte transformation in nickel hypersensitivity was investigated by subjecting the culture media employed to radiochromatographic analysis. Autoradiographic studies with 63Ni demonstrate direct binding of nickel salts to the lymphocyte cell surface. This occurs with a proportion of lymphocytes both from nickel sensitive and from control subjects and so binding is not of itself the stimulus for transformation.


Comparative bio-availability and activity of proprietary topical corticosteroid preparations: vasoconstrictor assays on thirty-one ointments. Thirty-one proprietary corticosteroid ointments were evaluated for vasoconstriction using an occluded blanching test. The results were expressed as three parameters: (1) area under the blanching curve, (2) summed % total possible score, and (3) square root transformation of sum of scores divided by number of volunteers. Experiments were performed to (a) compare the bio-availability and activity of the ointments, (b) determine the effect of antimicrobial additivies, and (c) assess the retention of steroids in the skin. Scores for the additivie-containing and 'plain' preparations were within 90% except for Locorten-Vioform/Locorten (58%). A steroid reservoir in the skin was demonstrated lasting for 8-14 days. Selected preparations were re-tested by a non-occluded method. The results for the ointments were compared with those previously obtained using the corresponding creams.


Hodgkin's disease in a patient with follicular and dermal mucinosis and spontaneous ooze of mucin (mucinorrhoea). A patient with follicular and dermal mucinosis is described. Although the skin histology was of a benign nature the patient died from an associated underlying reticulosis. Spontaneous mucinorrhoea subsided with therapy for Hodgkin's disease.


Leprechaunism. Case report in a black African child. A case of leprechaunism is described. This is thought to be the first reported in a black child.


Multiple keratoacanthomas: association with deficient cell mediated immunity. A case of multiple keratoacanthomas associated with deficient cell mediated immunity in a 44-year-old male Caucasian is presented. Many attempts to restore the lymphocyte function (transfer factor, levamisole) have failed but the treatments may have had a curative effect on the development of new lesions. The significance of impaired cellular immune defense mechanisms is discussed.


The simulated tutorial. Method for assessing medical school applicants. The simulated tutorial is a method for selecting medical students by their performance in a small problem-solving group, currently being tested at McMaster University. Four hundred and thirty-two applicants were randomly allocated to groups consisting of 5 or 6 members, assigned a group leader, and asked to work through two unstructured problem situations in a 50-minute session. Assessors, seated behind a one-way mirror, evaluated applicants according to their abilities to relate to their peers, to function in the group, and to define issues in the problem situations. Feedback from the assessors and applicants suggests that the simulated tutorial is potentially useful as a selection tool. All assessors thought they were able to evaluate the 5 or 6 applicants in the group in the time provided. Nearly 80% of the applicants who anonymously returned questionnaires felt they were able to express themselves during their simulated tutorial. The data also suggest that applicants with experience in small groups and applicants previously rated as having outstanding 'personal qualities' are given higher ratings than other applicants. A validation study of the simulated tutorial, comparing individual's scores with evaluations of performance in tutorial groups in the undergraduate M.D. programme, is currently in progress.


Entry to medical schools with 'A' level in mathematics rather than biology. The majority of British medical schools now accept for their shortest courses students who have mathematics at A level in place of the former requirement of biology A level. Only a small fraction of the entry, less than one-fifth, enters this way, in spite of statements by most medical schools that they make no distinction between those with mathematics and those with biology when making conditional offers of places. There is no evidence that those without biology are at a disadvantage in the courses. If the prospects of entry without A level biology were better publicized medical schools would have a wider field of possibly abler entrants, and pupils entering sixth forms could defer for a year a choice between a medical (or dental) career and one involving physical science, engineering, or other mathematics-based university education.


Comparative study of Hebrew University-Hadassah Medical School participation in education council ofr foreign medical graduates (ECFMG) examination. The achievements of the 874 (55%) medical graduates of Hebrew University-Hadassah School who took the ECFMG examination from 1962, when it was introduced in Israel, to 1972, were compared with those of candidates from other schools during the same period. The achievement level of candidates was high: usually above the 90th percentile rank position; 80 to 85% of its candidates passed the examination (compared to about 40% from all other schools); and the frequency distribution of ECFMG examination scores of HUHMS candidates in 1965 revelas a similarity to the achievements in American medical schools. The difference between the percentage of candidates passing the ECFMG examination from year to year supports the contention that the level of difficulty of the examinations varies. Candidates taking the examination after several years of clinical experience do not perform better. Since only 19% of all HUHMS graduates have gone abroad for postgraduate training, and only 11% have remained abroad for 4 or more consecutive years, participation in ECFMG has not been reflected in an increase in 'brain drain'.


Teaching psychological diagnosis and management. Teaching experiences have been described which illustrate the medical student's tendency to isolate what is learned in psychiatry from clinical work in general medicine. This tendency can be minimized by presenting diagnosis as the complete assessment of a patient, rather than exclusively as a search for disease. Early experience in patient care helps the student broaden his or her concept of clinical assessment. An important goal of psychiatric teaching in medical school is to help students learn to evaluate the psychological status of the general medical patient. Attention is focused upon this evaluation by use of the problem-orientated record. Since the data base is derived largely from the medical history, objectives for the interview are presented in detail. Students are encouraged to consider the relations between the patient's psychological status and other aspects of the medical problems. Only after they have learned to make evaluations of general medical patients, are the psychiatric syndromes introduced. An example is presented of a programme in which psychiatric teaching is carried out in a surgical ward of a general hospital. Success of such programmes depends upon explicit description of goals and methods, and upon collaboration with colleagues in other departments who share similar goals.


Parental attitudes to a clinical examination in paediatrics. A selected group of parents, whose children were patients in a recent clinical examination, declared, with one exception that this experience was not disturbing to them or their child. The overall impression given was of interest in the proceedings and of satisfaction that this was a tangible method of expressing their gratitude for the care their children had received. Complaints were few and related to organization rather than to the examiners or candidates.


Case methods in teaching organization of medical care. This paper describes the use of case methods in teaching the organization of medical care on the two year masters course in social medicine at the London School of Hygiene and Tropical Medicine. The basic characteristics of the subject and of case methods are related and the teaching implications of their similarities discussed. Terminology and different kinds of case methods are introduced and the objectives of using them on the course are outlined. A brief specimen case report is given to illustrate the use of the case methods approach in practice. It is emphasized that the effective development and use of case methods requires suitable materials, preparation, and teaching skills, and a list of the basic requirements is given. It is concluded that case methods of teaching have generally achieved their objectives on the course and have been well received by the students.


A survey of interests in teacher training of health science faculty. Interests in teacher training. In excess of 1000 members of the faculty at the University of Illinois Medical Center completed and returned an 'Educational Needs Inventory'. In general, respondents displayed a willingness to pursue several educational topics, through short-term seminars and workshops, an interest that was unrelated to present time commitments. Questionnaire results also documented that nearly 50% of the faculty had educational training in the past and perceived this training as valuable and useful to people in instructional roles.


Survey of biochemical topics used by clinicians in teaching and practice. In a pilot survey of biochemical topics, implied and overt, one of us (M.K.) attended 14 clinicians in 7 London medical schools during 4 half-day sessions, chosen at random, and recorded the activities and their relation to biochemistry. The sample was not intended to be representative but aimed at reasonable comprehensiveness. A list of twenty 'biochemical and related' topics was derived from these records, sent to the clinician for approval and comment, and used for rating the incidence of topics during the sampled sessions. Ratings by the two authors independently and the clinicians were combined. Collaboration between biochemist and clinicians was found crucial for the interpretation of clinical events in biochemical terms. Extension of this survey, using a questionnaire embodying the 20 biochemical categories, is to serve as a basis for defining objectives in biochemistry teaching for medical students.


Home bases for private work and study. Are multidisciplinary laboratories the best answer? Since 1970 we have measured the use of our multidisciplinary laboratories as home study bases for out-of-hours private work, and find that our students make little use of them in this way, preferring to work in study-bedrooms or libraries. We consider that there is no need to incorporate private study areas in the design of multidisciplinary laboratories, with the result that uncluttered areas with free sight lines can be used for a variety of purposes; we suggest that multidisciplinary laboratories will evolve in the future along this multi-purpose, multifunction line.


Influence of personality on achievement of medical students. In this study second year medical students completed a battery of psychometric tests which measured both cognitive and non-cognitive personality traits. Personality profiles obtained have been compared with reported norms from some other published sources. The scores obtained from factor analyses of these tests were used as predictors of total achievement in cellular biology and physiology over two years. In agreement with reports by other authors we found that the most important trait contributing to achievement was introversion/extra-version with introversion correlating with high achievement particularly in multiple choice tests. Emotional maturity was also a major factor especially as a predictor of success in essay tests. General mental ability, verbal skills, and reading comprehension appeared as significant predictors of achievement, and these were apparently of comparable importance in both kinds of test. Students of foreign origin whose first language was other than English tended to perform better in essay than multiple choice tests but their overall performance was lower than would have been expected from their other personality traits including their verbal skills. On the other hand, students resident in college halls tended to have better overall performance than expected.