Challenge to conventional treatment for myocardial failure-mechanical assist. Use of a prosthesis for temporary or permanent circulatory support in left ventricular failure has been investigated by our group for over 12 years. Experiences with both a U-shaped mechanical auxiliary ventricle (MAV) and the intraaortic balloon pump showed that in-series devices can stabilize the failing circulation. Studies with a MAV based on the balloon pump, the dynamic aortic patch (DAP) indicated that this system too is hemodynamically effective. In addition, data from extensive in vivo studies indicated that when its intravascular surface is made of Electrolour (Dacron velour backed by polyurethane with a negative electrical charge), the frequency of thromboembolism is greatly diminished. Following initial activation of the DAP in a patient with advanced chronic congestive failure, his hemodynamic parameters rapidly approached normal values: mean pulmonary artery and end-diastolic pressures were reduced, cardiac output increased, and myocardial metabolism changed from anaerobic to aerobic. The patient's cardiac function gradually improved, allowing his return to his home. The patient died on the 96th postoperative day after three months of improved cardiac function. Autopsy disclosed the DAP to be functional. A stable fibrin layer had formed on its intravascular surface; there were no signs of embolization. The DAP represents a promising approach to long-term ventricular support. For more than twelve years, our group has been interested in the possibility of using a mechanical prosthesis, not for total heart replacement, but rather for partial temporary or permanent circulatory support. In the first several years of work following this approach, we concentrated on the development of a permanently implantable system for in-series ventricular assistance. This work led to the study of several configurations of a mechanical auxiliary ventricle which gave effective circulatory support in laboratory and clinical studies [1,2]. The problem of achieving satisfactory interaction between blood and prosthesis was not resolved in these studies, but we were sufficiently encouraged by the hemodynamic effects to look into the possibility of working with the temporary support system initially proposed by Moulopoulos, Topaz, and Kolff [3].


An intra-abdominal chamber for continuous long-term observation of the sheep ovary. Rupture of the ovarian follicle (ovulation) is a clinically important event in reproduction, and its prediction or detection has been the object of many investigations. Direct observation is presently the only conclusive concurrent evidence of ovulation and is, therefore, necessary in investigations on the validity and precision of signals hypothesized to be time-related to ovulation. For this purpose, an ovary observation chamber, with a kink-resistant polyvinyl chloride viewing conduit, has been fabricated from resin-reinforced fibreglass, further coated with a silicone elastomer. The chamber is implanted surgically in ewes with the ovaries placed in the distal section of the chamber. The rigid fibreglass construction can withstand the normal physical activity of the animal, while the flexible portion of the chamber allows movement of the flank musculature with minimum impairment of blood supply at the ovary pedicle. A glass window permits continuous external observation and photography of both ovaries with their follicles. Both ovaries of each of 8 sheep were mounted in a chamber and, after an initial swelling, presented relatively normal morphology for 2-9 weeks. The tissue in contact with the chamber showed no adverse reaction. No infection was observed as long as the tissue-biomaterial interface near the abdominal skin was intact. In 6 of the 8 sheep implanted with the device, components of normal cyclic development have been identified by histological, photographic, or hormonal evidence.


Tissue factor activity of cultured human lymphocytes. Potent procoagulant activity develops in human lymphocytes during mixed culture, preceding the cell multiplication. This activity has the same characteristics as that of tissue factor. The membrane support of the activity binds factor VII, leading to the formation of factor X activator. The same observation is made when lymphocyte culture is made without antigenic stimulation, demonstrating that "in vitro" culture alone is able to endow lymphocytes with tissue factor activity. The mechanism of this non-specific stimulation remains to be elucitaded.


Phalangeal acroosteolysis associated with Down syndrome. This report described a case of acroosteolysis of phalangeal type associated with regular Down syndrome. The findings of the present case overlapped those of familial or idiopathic acroosteolysis previously reported by others. Study of the patient's family uncovered consanguineous marriage of the parents and affection of his brother, suggesting affection was the result of homozygosity for an autosomal recessive gene. Similarities of findings of the digits among acroosteolysis, pyknodysostosis and Down syndrome were discussed.


[The role of renal acid mucopolysaccharides in the mechanism of reabsorption of osmotically free water]. The authors compared the histochemical characteristics of acid mucopolysaccharides (MPS) of the medulla of the kidney with functional indices of the latter in dogs under conditions of water, osmotic diuresis and in polyuria caused by the administration of heparin. There was seen a correlation between the changes in the MPS staining and the intensity of reabsorption of osmotically free water. On the basis of the results obtained a supposition was put forward that the change in the physico-chemical properties of the MPS served as one of the most significant factors determining the permeability of the medulla structures for the passage of water from the tubular lumina into the interstitium.


[The effect of 1-adamantyl radicals on curare-like activity]. In the series of polymethylene bis-ammonium salts R(CH3)2N(CH2)NN(CH3)2R . 2I--(R=CH3 or Ad) a study was made of the significance of hydrophobic 1-adamantyle radicals (1--Ad) for curare-like activity. Administration of 1-ad radicals into the cation groups of depolarizing agents (n-9--11) altered their mechanism of action and diminished their activity. Attachmeni of 1-Ad radicals to the both quarternary nitrogen atoms of the antidepolarizing agents (n=5 and 6) sharply increased their curare-like activity. The data obtained pointed to the presence of hydrophobic zones in the cholinoreceptors of skeletal muscles.


[The effect of sodium and potassium ions on serotonin absorption by lung tissue]. Experiments were conducted on the isolated perfused lungs of albino rats; there was shown a dependency of serotonin (ST) absorption on the Na+ and K+ concentration in the perfusate. Which high Na+ concentrations in the perfusate ST was absorbed by the lung tissue cells in great quantities, but when Na+ concentrations were low - ST absorption showed a sharp reduction. K+ concentration in the perfusate had a lesser influence on the ST absorption; the maximal absorption was seen with the K+ concentrations of from 5 to 20 mM. A reduction or an increase in the K+ concentration inhibited the ST absorption. Strophanthin K, a powerful Na, K-dependent ATPase inhibitor, markedly inhibited the ST absorption in a concentration of 10(-4)-- 10(-3) M. It is supposed that there was an association of the ST transport through the cell membrane with the Na+ transport.


[Characteristics of contact activation of rabbit blood (kallikrein and plasmin systems]. In vitro experiments showed that caoline-induced contact activation of the kallikreine-kinine system and streptokinase-induced activation of plasmin could possibly occur in rabbit blood plasma. Preliminary short-term treatment of plasma with chloroform removed the factor, inhibiting the two mentioned activation processes. The results obtained provided an indirect evidence for the existence of a functional relationship between the kallikreine and plasmin systems of the blood at the level of the initial step of their activation, i.e. the Hageman factor.


[Changes in fibrinolysis components during short-term adaptation to high altitude]. In studying hemocoagulation in dogs under conditions of Frunze (760 m above the sea level) and Tuya-Ashu (3200 m above the sea level) it was shown that in the "emergency" phase of adaptation (the first three days) there was seen activation of fibrinolysin and profibrinolysin with depression of antifibrinolysins and inhibitors of profibrinolysin activators. The concentration of plasma fibrinogen at that period decreased by 100 mg%, which could promote an increase in the vascular permeability and improvement of oxygen approach to the tissues. Later, along with elevation of fibrinolysin and profibrinolysin activators there was a marked increase in the level of fibrinolysis inhibitors. Correlation of all the fibrinolysis components was established at a new level.


Detection of soluble intermediates of the fibrinogen-fibrin conversion using erythrocytes coated with fibrin monomers. The presence of minimal amounts of fibrinogen-fibrin intermediates in human plasma was visualized by an agglutination reaction of glutaraldehyde-treated human erythrocytes coated with purified fibrin monomers. A degree of monomer coating was established which produced erythrocytes not agglutinated by normal plasma but by plasma containing minimal amounts of soluble complexes of fibrinogen with fibrin monomers. Under standardized conditions of coating, erythrocyte concentration, temperature, pH, and incubation time, the agglutination time varied with the ratio of soluble fibrin to fibrinogen in plasma. The test was sensitive down to a soluble fibrin concentration of 0.675% of the plasma fibrinogen concentration. Early fibrinogen and fibrin degradation products (FDP) in the plasma led to a prolongation of the agglutination time at a concentration of more than 16 mg/100 ml. Late FDP in a concentration of 100 mg/100 ml did not convert a positive test to negative. The test was not affected by heparin and protamine at concentrations of up to 12.5 and 50 NIH units/ml, respectively.


[Vectorcardiography].

[Vectorcardiography]. The principle of vectorcardiography is first discussed. The setting out in space is very instructive. An over-valuation of slight vectorcardiographic changes can lead to wrong conclusions. The changes in right hypertrophy may in many cases be important for diagnosis. This is true for cases of intraventricular conduction disturbance and incomplete right bundle branch block. In certain cases of myocardial infarction, the vectorcardiogram can be valuable as additional diagnostic method. Finally the diagnostic possibilities of vectorcardiography in pacemaker patients, contour irregularities of the vector loops, congenital valvular heart disease and ventricular extrasystole, and the question of standardisation are discussed.


Stimulation of pathologic electrocardiograms: the role of Durrer layers in the normal, the hypertrophied and the ischemic heart. A mechanism is described which explains the electrocardiographic manifestations of cellular hypertrophy and acute ischemia. This mechanism arises from neighboring cells having different transmembrane action potentials, and it has been called the "contiguity effect". The contiguity effect of adjacent "Durrer layers" (defined in the paper) gives rise to the T-wave distortions in hypertrophy and is also responsible for the polarity of the normal T-wave. This mechanism has been incorporated in a computer model of electrical heart activity which generates high fidelity 12-lead electrocardiograms. It is shown that the increase in R-wave amplitude and in ventricular activation time, and the flattening and/or polarity reversal of the T-wave in hypertrophy is due to an increase in the size of myocardial cells, and the S-T segment shift in acute ischemia is produced by the contiguity effect between normal and ischemic cells. For a lesion of given size, the S-T segment shift is linearly proportional to the "severity"; i.e., the reduction in electrical activity, of ischemic cells, and fora lesion of given severity, the S-T segment shift is a measure of the area, not the volume, of ischemic tissue. Therefore, a direct correlation does not necessarily exist between volume measuring tests (such as serum enzyme values in the case of necrosis) and S-T segment shifts in acute ischemia.


New long-stay patients in a hospital for mental handicap. Better Services for the Mentally Handicapped (1971) forecasts a diminution in the number of beds in hospitals for mental handicap. It can be achieved only by the admission of fewer new long-stay patients. This paper considers 50 new long-stay cases admitted to a hospital for mentally handicapped in the five years 1970 to 1974. Of these admissions 42% were children, and of all the admissions 54% had Wechsler intelligence quotients under 25. Further, 62% of the admissions were for behaviour problems and 38% were for physical infirmity and helplessness. It is concluded that there are some mentally handicapped people who have problems with which only a hospital can cope. The high nursing dependency and the profound mental retardation of a majority of the new long-stay patients present a formidable challenge.


The medical model of the disease concept. According to the medical model of the disease concept, a class of patients is homogeneous only when it is characterized by manifestations which have their ultimate intra-organismic origin in a particular kind of physio-pathological cause. Most patient classes are still heterogeneous because we are still ignorant of that cause. The medical model can be applied to the subdivision of all classes of patients, including classes of non-organic psychiatric patients. However, the successful application of the medical model depends on the acquisition of knowledge of relevant physiopathological facts. It is argued that the dimensional model of evaluating psychological abnormalities is not likely to help in acquiring that knowledge.


Local hyperalimentation of open wounds.

Local hyperalimentation of open wounds. After débridement of necrotized and devitalized tissue in deep burns and large traumatic soft tissue defects, the raw surfaces were covered with separate sheets of viscose cellulose sponge (VCS), each moistened by continuous slow infusion of one of the following solutions: (a) 0-9 per cent NaCl; (b) 10 per cent glucose; (c) Rheomacrodex (dextrane hydrolysate in 0-9 per cent NaCl); (d) 7 per cent Levamin (a mixture of essential amino acids and glycin in 5 per cent sorbitol; (e) a combination of two solutions containing amino acids (Le-7402 A) and glucose, electrolytes and vitamins (Le-7402 B). The cellulose sponges were removed or changed 3-7 days later. Macroscopically, histologically and enzyme histochemically, the most active granulation tissue formation was found under the VCS moistened with amino acid solutions, especially when accompanied by glucose and vitamin supplementation. The results strongly suggest that local cellular hyperalimentation of open raw wound surfaces is possible, permitting a new kind of nutritional support in these patients.


Outpatient laparoscopic sterilisation.

Outpatient laparoscopic sterilisation. One-hundred consecutive laparoscopic sterilisations were carried out on an outpatient basis without serious operative complications. All patients were discharged home on the day of operation. Two patients subsequently required emergency admission to hospital. Most patients were completely satisfied with the day-case service.


Bony symptoms in secondary syphilis.

Bony symptoms in secondary syphilis. Aching bony pains were prominent in six of 144 cases of secondary syphilis. These pains included headache, backache, aching pains in the limbs, and chest pains. The cause of some of these pains is not clear, but it is important to recognize that secondary syphilis may present with a variety of pains.


Isolation and characterization of myosin from cloned rat glioma and mouse neuroblastoma cells. Myosin has been isolated from the clonal lines of murine neuroblastoma and rat glioma cells. Partial characterization of the two cellular myosins indicates that both possess the following properties: (1) the same elution position as rabbit skeletal muscle myosin by Sepharose 4B chromatography; (2) the presence of heavy (molecular weight about 200,000) and light subunit polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis; (3) EDTA and Ca2+ activated but Mg2+-inhibited ATPase activity in 0.6 M KCl; and (4) binding to rabbit skeletal muscle F-actin which is inhibited by Mg2+-ATP. For both mouse neuroblastoma and rat glioma cells, approximately 0.5-1.5% of the total cell protein is present as myosin. Cellular myosin appears to be indistinguishable in quantity and biochemical properties regardless of whether it is isolated from monolayer or suspension neuroblastoma cells.


The preparation and characterization of synaptic vesicles of high purity. Very pure preparations of synaptic vesicles have been obtained from guinea pig cerebral cortex and from the electromotor synapses of Torpedo marmorata by density gradient centrifugation in a zonal rotor followed by chromatography on columns of glass beads of controlled pore size. Markers for soluble cytoplasm (lactate dehydrogenase), plasma and endoplasmic membranes membranes (Na-K-ATPase; acetylcholinesterase, NADPH-cytochrome c reductase], mitochondrial membranes [cytochrome oxidase] and lysosomes [acid phosphatase] were used to assess contamination and were undetectable. The only enzymes detected in the highly purified preparations from guinea pig cerebral cortex were Mg- and Ca-activated ATPases, but their content relative to acetylcholine fell  on chromatography suggesting that they may be constituents of non-cholinergic vesicles. Lipids analyses of the highly purified vesicles confirmed earlier results and showed that glycolipids and lysolecithin are present in negligible amounts; this suggests that lysolecithin is not required for exocytosis of synaptic vesicles. A discussion of the probable limiting concentration of acetycholine in cerebral cortical vesicles derived solely from cholinergic terminals suggests that from 13 to 56% of the vesicles isolated are cholinergic, depending on the assumptions made.


[Production of aldosterone by the regenerated adrenal gland after neonatal autograft in the normal, and the sodium deprived rat]. The suppression of the adrenal medulla by bilateral neonatal autograft in Sprague-Dawley male rat involves important changes in plasma aldosterone concentration: it falls of about 50% in animals with control diet; on the contrary, it is doubled in sodium depleted rats. Changes in adrenal aldosterone level are slight and non significant. The mechanism of effect of adrenal medulla on aldosterone production is discussed.


[Comparative morphometric data on the epiphysis, the subfornical organ, and the anterior pituitary gland in 2 groups of pure strain Wistar female rats, SPF or conventional]. In SPF female rats, the pineal gland is less voluminous and its cell-nuclei are smaller than those of conventionnal female rats. This confirms (with the voluminous adrenals previously reported) the stressing action of the absence of pathogenic germs on these animals. The anterior lobe of the hypophysis is slightly smaller and subfornical organ a little larger than in conventionnal female rats.


[Nycthemeral variations of mitotic activity in the adrenal cortex of the rat]. Working on histologic sections 7 microns thick in the equatorial part of male rat adrenal cortex, we found two high mitotic activity periods. The first one stays at midnight and shows an average number of 42 mitoses per section; the second one occurs at 5 a.m. with an average number of mitoses of 70,1 per section. If we except these particular points, the mitotic activity is low, the average number of mitoses being 13,2 per section.


[Physicochemical study of platelet aggregation by 3 polylysines]. The action of polylysines of various molecular weight on platelet behaviour is studied with the help of 3 techniques: photometric test, screen filtration pressure on PRP and electrophoretic mobility. Polylysines, which are polybasic substances, produce a platelet aggregation studied by photometry after a short period of latency. Aggregation, depending on the doses of poly-lysine and chiefly on the optic density, shows a "plateau" with the dose of 100 gamma/ml for poly-lysine L, of molecular weight 17000. The screen filtration pressure increases continuously in the presence of the polylysines studies. Finally, the platelet charge decreases. The results depend on the concentration of poly-lysine, and the optimal concentration which involves the more marked alterations is inversely proportional to the molecular weight of the polylysine studied.


[Influence of the oxygenation state of the culture media on the level of non esterified fatty acids and of cholesterol in heart cells of the newborn rat]. The uptake of non esterified fatty acids (NEFA), from a medium supplemented with 10% of calf serum, by rat myocardial cells cultured during 8 days, without renewal of the medium, was identical whatever the values of partial pressures of oxygen in the medium. Cellular cholesterol level was reduced when air or oxygen (+5% CO2) was blown into culture bottles; it was enhanced by gassing with nitrogen 24 h later. Cellular NEFA level was reduced by air, but not by oxygen blowing; it was enhanced by gassing with nitrogen 24 h later. The variations observed may originate from pertubations of NEFA beta-oxidation.


[Modification of potassium current by 4 aminopyridine. Case of the isolated giant axon of the cockroach (Periplaneta americana)]. Action of 4-aminopyridine has been studied under voltage-clamp on the isolated giant axon of the cockroach. Our results show that 4-AP reduces K+ currents (inward or outward currents).


[Estimation of the level of blocking antibodies in patients suffering from reagin allergy]. We have studied the level of blocking antibodies in patients consulting for reagin-mediated allergies. This determination is, in our opinion, important to follow the course of treatment and the natural history of reagin-mediated diseases, treated by immunization.


[Action of testicular graft on the ovary of chick embryo having undergone a partial decapitation]. The absence of the hypothalamo-hypophyseal complex had neither influence on the ovarian atrophy, nor on the mullerian retrogression induced by an embryonic testicular graft in the female embryo. So, the hormone responsible of the mullerian retrogression had an inhibiting action on the embryonic ovary of the chick which is independant of the hypothalamo-hypophyseal complex.


[The normal reaction of sinocarotidian origin in the rabbit]. Spontaneous changes of respiratory rate and blood pressure in the slightly anesthetized rabbit, contemporaneous with hippocampal synchronization, might be related with abrupt changes of the alertness. Registration of arousal reaction in hippocampal, thalamic and cortical leads, elicited by Hering nerve stimulation, shows that baro- and chemosensitive afferences may induce activation of areas which are usually involved in conditioning process.


[Influence of somatostatine on plasma level of calcitonin in the calf and the swine]. In young calves receiving intraveinously a small dose of calcium to stimulate calcitonin release, intraveinous infusion of somatostatin did not significantly modify the jugular veinous plasma calcitonin levels measured by radioimmunoassay, using a porcine system which cross-reacts with bovine calcitonin. In piglets, intraveinous infusion of somatostatin also did not change the jugular veinous plasma calcitonin concentration.


[Interrelationship between adrenal cortex and genital apparatus of the male rat]. Interactions between gonadal hormones and adrenocortical function have been studied in the male rat. After injection (im) of testosterone, the accessory reproductive organs are more stimulated in the castrated rats than in the castrated adrenalectomized rats. Gonadectomy increases lipids, cholesterol and corticosterone in adrenal glands and plasma corticosterone levels. Testosterone reverses these effects.


[Isolation and electrophoretic characteristics of 3 lymphocyte populations of normal human blood]. Cell electrophoresis allows separation of normal human blood lymphocytes into two main groups which are a function of their relative rates of migration, with regard to the reference speed (1 mum.sec.-1V-1.cm): the lymphocytes which have a greater mobility than this value seem to be T-lymphocytes (80,1 per cent for 42 healthy adults); on the contrary, B-lymphocytes have an inferior mobility (19,9 per cent). Two known methods are used for the selection of the lymphoid populations: spontaneous rosetting with sheep's red blood cells, which are characteristic of T lymphocytes, and adherence to nylon wool columns, which is dominant in the case of B-lymphocytes. This method confirms the fact that T-lymphocytes have a rapid migration and B-lymphocytes a slow migration. We have isolated a third population, having neither the T markers, nor the B markers. It has a very homogeneous migration, centered on the two classes 1,05 and 1,10 mum.sec.-1.V.-1.cm.


[Influence of moderate normoxic hypercapnia on the autoregulation of the cerebral circulation in the unanesthetized rabbit]. In the unanesthetized rabbit autoregulation of cerebral blood flow was evaluated by continuous recording of local cerebral blood flow during progressive hypotension induced by exsanguination. Under hypercapnia induced by CO2, 8 per cent in air, autoregulation was not suppressed but an increase of the threshold under which autoregulation disappears was noted.


[Effect of heating in the presence or absence of glucose on digestive and metabolic utilization of amino acids of casein]. The effect of heating casein with and without glucose was studied with growing rats. Apparent digestibility of dry matter, organic matter, crude protein and amino acids was recorded. The utilization of amino acids was studied by estimating food consumption, growth and blood and muscle free amino acids. Heating casein with glucose at 90 degrees C during 24 hours resulted in significant loss of lysine and affected food intake, protein efficiency ratio and protein digestibility. Threonine and lysine availabilities were lowered.


[Radiological study of LSD-25 effects on the  amphibian Pleurodeles waltlii Michah. Comparison between controls and subjects issued from males treated with LSD-25]. LSD treated males were mated with untreated females and their progeny examined by S-R. The incidence of morphological anomalies in the offsprings of control animals appears to be important but is doubled in the progeny of LSD treated males. Our observations are limited to the limbs, the vertebrae, the ribs and the pelvic girdle.


[Influence exerced by the season on the modifications of lipid metabolism induced by an increase of the ambiant temperature in the rat]. A fast increase of 10 degrees C (from 24 degrees C up to 34 degrees C) of the ambient temperature alters the male rat lipid metabolism differently if the experiment takes place in autumn or in spring. Generally to this change of temperature, the rat seems to react more in spring than in autumn.


[Effects of normebaric and hyperbaric hyperoxia on digestive motricity of the awake rabbit. I Antropyloric motricity]. The effects of normobaric and hyperbaric hyperoxia (short and long time) have been studied on the pyloric antrum motility of the rabbit. The results show the absence of effect of normobaric oxygen in short application (twenty to thirty minutes), but its inhibiting effect on the pyloric antrum motility in long time application. The hyperbaric hyperoxia slows down the frequency of the pyloric antrum contractions so much more the pression is higher. This effect is independant of the speed to which the pression is set up, and also of the moment of day where the experiment is done.


[Exploration of the sodium pump of the erythrocyte by 22 Na and 42 K. II Effect of triamterene]. The study of the effect of triamterene on the movements of sodium and potassium shows: the absence of influence of triamterene on sodium movements, and the decrease of the entry of potassium in red blood cells when the solution contains triamterene. This effect of triamterene might be one of those explaining the potassium-sparing effect of this product.


[Pressure-volume relationship in the right ventricle]. The curve of the pressure-volume relationships of the right ventricular cavity is not a mono-exponential one. It can be characterized by the presence of two successive segments: linear and exponential. The points that constitute the first of them could not be subjected to Starling's law. This is material for the physiopathology of the tamponade.


[Tension-volume relationship of the wall of the isolated right ventricle]. The variations of tension on the wall of the isolated right verticle have been observed on 18 dogs. The Tension/Volume curve we got can be superimposed to that obtained by pressures. The wall of the right ventricle itself (the radius of the curve in the cavity and the wall-thickness) seems to vary only with the changes in its tension in a rather small part of the curve.


[Consequences of the chronic administration of phenformine on the blood thiamine level in the dog]. The chronic oral administration of phenformin (20 mg/kg daily during 8 days) to the normal concious dog provokes a decrease in the fasting thiamine levels of plasma and erythrocytes. During intragastric loading tests with thiamine hydrochloride (30 mg/kg), carried out during the chronic treatment with the biguanide, the curve of plasma hyperthiaminemia is increased. The authors suggest an explanation for these apparently contradictory results.


[Action of glibenclamide on glucagon and insulin secretions studied on isolated and perfused pancreas of the rat]. Glibenclamide stimulates the insulin secretion by the isolated and perfused rat pancreas, but does not inhibit glucagon secretion when the perfusion liquid contains 1.5 g/I glucose. In the absence of glucose in the perfusion medium, glibenclamide stimulates both insulin and glucagon secretions.


[Effect of mitomycin C on the structure of human chromosomes observed in metaphase after labelling by moderate thermal denaturation]. Mitomycin C induced chromosome rearrangements were analysed in cultured human leukocytes by reverse banding technique. Breaks and chromosomal exchanges involved preferentialy the entromeric region of some chromosomes (1, 5, 9, 16, and 20). Associations between acrocentric chromosomes was not found to be increased. But acrocentric associations with centromeric regions were frequently present. The differences between the mechanism of exchanges and breaks are discussed. The part of heterochromatin in post replication DNA repair is considered.


[Polygraphic recording in the rat by a miniaturized radiotelemetric technic]. The authors describe the results obtained on rats by a method of four channel telemetric recording system. The transmitter with a range of a few meters, has a pass band from 0,3 to 400 Hz, weighs 4 grams and can operate autonomously for a minimum of 10 days.


[Postimperative negativity of the contigent negative variations: a critical index of a stress reaction in the normal subject?]. 21 subjects were recorded during two experimental sessions: 1st session: 2 CNVs in control conditions; 2nd session: 1) control CNV, 2) CNV and arithmetic calculation, 3) CNV and labyrinthine stimulation, 4) CNV, arithmetic calculation and labyrinthine stimulation, 5) control CNV. The results obtained show a post-imperative extension of the CNV in the situation 2: arithmetic calculation (P less than 0.025) and 4: double interference (P less than 0.05).


[Incidence of early excision of the retina on the development of the optic pedicle in the chicken]. The retina cutting of 4 days old chick embryos determine the disappearing of the pedicle optic cells. Absence of the optic fibers result in a absence of the glial cells differentiation.


[Tetratospermia and chromosome abnormalities]. Human semen in two chromosomal abnormalitie cases presents one important increase of small, large and double head spermatozoa. Findings of this type of abnormal sperm morphology must be include chromosome analysis in the subfertile couple investigations.


[Various effects of insulin on in vitro dental differenciation]. The authors have studied the effects of insulin at various concentrations on in vitro cultivated dental rudiments. They observed histologic lesions generated by edema, neither anticipated cellular differentiation nor stimulation of collagen secretion, decrease of mitotic activity, but stimulation of thymidine 3H incorporation after short contact times.


[Effects of insulin on the protein metabolism of carp liver]. Studies on protein metabolism in carp liver under influence of insulin injections have been carried out. Protein turn-over is significantly reduced by insulin; in fact, half-life of tritiated proteins is increased to twice the controls value. Furthermore, electron microscopic studies of nucleolus suggest an enhancement of proteosynthesis. Our findings, similar to those generally described in mammals are in good accordance with the rise of protein amount. With regard to the strong drop of carpe liver glycogen after insulin injection, which had been previously reported, these data could thus indicate that such a paradoxical effect of the hormone is limited to the glycogen metabolism.


[Role of the season and of the nutritonnal state on the distribution of tissular fatty acids in the hibernating dormouse (Eliomys quercinus L.)]. Seasonal changes were observed in fatty acid composition of plasma, liver and cardiac muscle. During hibernation unsaturated fatty acids levels increase in plasma cholesterol esters (CE), glycerides (GL) and phospholipids. After spring arousal, the oleic acid content decreases in total fatty acids of liver and cardiac muscle. In summer fasting induces lipid changes similar to that occuring in natural hibernation. Desaturation observed in winter can be explained by the accumulation of unsaturated GL and CE in the tissues.


[Cecal motricity and ceco-iliac transit in the horse]. Electrical spiking activity of the caecum is increased eight-fold and the rate of passage of digesta is increased four-fold when the volume of caecal contents is doubled. The role of caecal motility in regulating the volume of caecal contents is discussed.


[Comparative diffusion of 14C-ethionine and 14C-methionine in rat tissue]. The pancreas is the tissue which traps the most intensively the trace-dosis injected ethionine -14C; 30 min after the injection, the pancreas fixes the labelled product twice more than the liver and five times more than the stomach. This trapping might explain the pancreatic modifications occuring during the intoxication. In the same experimental conditions, the pancreas fixes the ethionine -14C twice less than methionine. Urinary excretion of ethionine is faster and more important than that of methionine.


[Electromyographic analysis of motor perturbations linked with gastrointestinal strongyloidiasis]. The effects of experimental infection of lambs with third stage Trichostrongylus larvae are described. Preceding diarrhea, disturbances in the motility of the reticulum, abomasum and jejunum were observed by electromyography. Disappearance of the migrating myoelectric complexes occurred about 24 h before diarrhea and was accompanied by a decrease in both the frequency of reticular contractions and of contractions propagated through the antro-duodenal junction. The significance of these findings is discussed and compared with natural infestation in the field.


[Influence of thioacetamide on nucleolar apparatus of the liver. Cytophotometric study]. The nucleolus associated chromatin in Feulgen-stained liver cells of TAA treated rats is studied using the Lison cytophotometer. The results indicate that the increase in nucleolar volume in these hepatocytes is accompanied by an increase in Feulgen-DNA contents of the nucleolar apparatus, both in rats treated with a normal standard diet and with a Miller and Price diet. This increase is maximal 2 days after a single dose of 10 mg/100 g body weight and reaches 50 and 25% respectively. These results are discussed with consideration to mitosis, distributional error and the metabolic DNA hypothesis.


[Electroretinogram in the nocturnal Prosimian Perodicticus potto]. There is histological evidence for the presence of cones in potto's retina: about 1 cone for 300 rods. The ERG of the dark adapted animal resembles that of the night monkey. In the potto's retina some red sensitive elements respond to wavelenghts beyond those which affect visual purple. The ERG evoked by these long wavelenghts differs from that produced by white light, suggesting a duplex character of the retina. These red sensitive receptors dark adapt faster than the others. However their fusion frequency is low, if compared with that in other species with a duplex retina. Nevertheless in potto the critical fusion frequency is higher for red light than for blue light.


[Relationship between the release of hypophyseal LH under the influence of LRH and the plasma testosterone level in women]. There is a direct significant correlation (r = 0,49, p less than 0,01) between cumulative LH response to i.v. injection of 25 mug LRH and testosterone blood level in 17 women with an excess of endogenous androgens (plasmatic testosterone and/or urinary androsterone and etiocholanolone). The relation also exists if the patients are divided in two groups according to the origin of the dysfunction: polycystic ovaries (n = 9, r = 0,62, p less than 0.05) or hypercorticism (n = 8, r = 0,53, p less than 0.1). In the same patients there is no correlation between LH release and the sum of androsterone and etiocholanolone 24 hours urinary excretion (r = 0,21, p: NS); there is no correlation between basal testosterone blood levels and urinary metabolites (r = 0,19, p: NS). Our data suggest that testosterone (or a closely related metabolite) acts at the hypophyseal level to inhibit the spontaneous LH discharge hence increasing the pituitary hormonal stores. This action could be responsible for menstrual abnormalities often found in hirsut women.


[Release of neurophysins during suckling in the lactating woman]. Using radioimmunoassay for total immunoreactive blood neurophysins (I.R.Neur.) we demonstrate a significant increase 30' after the onset of suckling in 26 normal carefully studied lactating women. On the first day postpartum a constant increase is only observed in 12 patients whilst a significant increase is clearly shown for all patients from the 2nd to the 6th day. These variations are similar to those observed for prolactin blood levels; there is however no relation between basal, suckling stimulated, or ergocryptin inhibited prolactin blood level on the one hand and I.R.Neur. blood level on the other hand.


[Kinetic study of the hepatic regeneration in the rat after exeresis of the left lobe only (Hepatectomy of a third of the mass)]. Regeneration is induced after exeresis of the left liver lobe lone (i.e. 1/3 of the normal liver mass). Cell divisions are less numerous than after the usual 2/3 hepatectomy; they appear later and the slope of the first labelling and mitotic indices is much less steep. However, the same circadian rhythm of divisions is also observed and the duration of the cell cycle phases (G2, S and M) are the same whatever the size of the hepatectomy.


Subunit studies of coupling factor 1 of bean chloroplasts. A bean chloroplast coupling factor (CF1) with latent Ca2+-dependent ATPase activity was studied. Immunodiffusion of bean (Phaseolus vulgaris) chloroplast and etioplast coupling factors and spinach coupling factor against antiserum to spinach coupling factor showed partial identity of the bean coupling factor with that of spinach. An immunoelectrophoretic comparison, under dissociating conditions, of bean leaf extracts and spinach extracts containing CF1 subunits (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) gave identical results for both extracts. At least six distinct polypeptide species were found. The major species had molecular weights of 42 000, 59 000 and 63 000 daltons. Amino acid analysis of electrophoretically purified bean CF1 gave results similar to those published for spinach CF1.


Comparative study of the lipid composition of rabbit and lobster sarcoplasmic reticulum. Sarcoplasmic reticulum (SR) membranes isolated from rabbit and lobster muscles have similar phospholipid classes, but they differ in plasmalogen content. The plasmalogenic species are mostly distributed among phosphatidylethanolamines (PE's) and make up about 62% of the total in rabbit SR and about 46% in lobster membranes. Lobster SR phospholipids contain large amounts of polyunsaturated fatty acids which are present in low amounts in rabbit membranes. The total unsaturated fatty acids of phosphatidylcholines (PC's) represent about 53% and 73% of the total fatty chains for rabbit and lobster SR, respectively. The values found for PE's were about 56% and 64%, respectively. Furthermore, lobster membranes contain significant amounts of PC and PE molecular species with unsaturated fatty acids in positions 1 and 2, whereas rabbit SR contain low amounts.


Marlex mesh for repair of abdominal wall defects. The best synthetic material available for repair of abdominal wall defects associated with an insufficiency of tissue is Marlex mesh. Among 14 patients with large hernias and 3 who underwent tumour resection only 2 manifested recurrence of the defect. In three of these patients infection developed, but its control made it unnecessary to remove the Marlex. In another three with gross infection of the abdominal wall, Marlex was used successfully to provide abdominal wall closure.


Plasma hormone levels in different ethnic populations of women. It has been suggested that the urinary hormone profile is subject to environmental changes, such as urbanization and Westernization, and that the composition of the hormones can be used as a discriminate in determining the patient at risk for breast cancer. In this study, a comparison of the plasma hormone levels in Bantu and Japanese women, low-risk populations, and Caucasian women, a high-risk population, showed a higher level of 17 beta-estradiol in prepubertal girls and young Bantu and Japanese women. The higher estrogen level in the Bantu was evident in the early luteal and late follicular phases of the menstrual cycle. The difference in the dehydroepiandrosterone and testosterone levels in Bantu young women and prepubertal Bantu girls, suggests differences in adrenal activity between Bantu and Caucasian women. A fall in the plasma androstenedione was evident in postmenopausal Bantu and Japanese but not Caucasian women. Data suggest that the hormone profile is different among the 3 ethnic groups in both the pre- and postmenopausal women. Since the daily life-style of the women is comparable, it is suggested that the composition of the hormone profile is partially dependent on dietary on dietary factors.


Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. A single application of various hepatocarcinogens to rats results in the formation of islands of enzyme-deficient liver cells, which are mainly irreversible and very probably represent the first cellular stage involved in the process of liver cancer formation. Comparison of the island-size distributions obtained for different carcinogens indicated that proliferation is a common property of islands that is independent of the inducing carcinogen and does not need any further presence of carcinogen or other stimulating factors. Toxic doses resulted in all cases in an enhanced island size. The number of islands induced by a single dose of carcinogen was enhanced by a prior partial hepatectomy only in the case of the dialkylnitrosamines, dimethylnitrosamine, and diethylnitrosamine. Dose-response relationships measured with diethylnitrosamine, the carcinogen with the lowest toxicity as compared with the carcinogenic action, indicated that island formation is due to a one-hit process, i.e., that one specific alteration in the target cell is responsible for the precancerous transformation. These kinetics and the low probability of transformation might indicate that the crucial hit is scored at the genetic level. The irreversible action of carcinogen (memory effect) and the influence of time on cancer formation (time effect) are discussed in terms of induction and proliferation of irreversible cell populations serving as precursor of the cancer cell. The number of specific alterations (hits) involved in the development of the malignant cancer cell is also briefly discussed.


Ultrastructural and cytochemical studies on hyperbasophilic foci with special reference to the demonstration of cell surface alterations in hepatocarcinogenesis. Following the formation of hyperplastic nodules at a late stage of azo dye hepatocarcinogenesis, some areas of parenchyma show an intense RNA staining, and such hyperbasophilic foci apparently develop hepatomas. Radioautographic analyses with [3H]thymidine labeling indicate the foci to be areas of continued cell proliferation, and the hepatocytes are morphologically distinguishable from the surrounding tissue. The increase of basophilia occurs simultaneously with histochemically demonstrable decreases in bound cations and concomitant increases in pyroantimonate-precipitable free cations. Thus, the phenomenon of hyperbasophilia and the ensuing alteration of cell cycle appears to be associated with changes in intracellular homeostasis. Ultrahistochemical localizations of adenosine triphosphatase and alkaline phosphatase suggest topographic alterations of membrane enzyme activities in the foci and the persistence of altered patterns during tumor progression. The developmental feature of surface adenosine triphosphatase activity has been further studied with subcultures of epithelial cells, which were derived from normal and precancerous livers. The enzyme activity of nontumorigenic cells is minimal, while a considerably high activity is detectable in situ at the outer surface of plasma membranes of tumorigenic cells. A Ca2+- Mg2+-dependent adenosine triphosphatase is identified at the cell surface, and the ectoenzyme would be a useful marker for detection of malignant liver epithelial cells.


Decreased ability of blood leukocytes from patients with tumors of the urinary bladder to act as stimulator cells in mixed leukocyte culture. Blood leukocytes from patients with active neoplasms of the urinary bladder were found to have a decreased ability to stimulate in one-way mixed leukocyte culture (MLC). The ability of the patients' leukocytes to act as stimulator cells in one-way MLC was assessed by simultaneous comparison to the ability of leukocytes from normal individuals to stimulate. In addition, the ability of the patients' leukocytes to act as responder cells in the one-way MLC was evaluated. Cells from 31 (56%) of 55 patients with active disease exhibited subnormal stimulatory activity in the MLC while 26 of these 31 patients (84%) had normal responsiveness. Cells from 9 of the 55 failed to respond normally. Poor stimulation occurred with both early and advanced disease, and the stimulatory activity increased after tumor removal in 12 of 15 patients who had previously shown subnormal stimulation. Six patients without active disease at the time of testing, in addition to the 55, exhibited normal levels of stimulation and responsiveness. This defective stimulatory activity is suggestive of an acquired, disease-related phenomenon and is not necessarily associated with decreased blood leukocyte responsiveness.


Muscle spindle supply to the snout musculature in moles (Talpidae). To define the anatomical background of the neuromuscular mechanism involved in the movement of the snout of the moles (Talpidae) the present histological study was carried out on the snout muscles of this family including the Japanese shrew-mole (Urotrichus talpoides), Japanese lesser shrew-mole (Dymecodon pilirostris) and Temminck's mole (Mogera wogura). The snout musculature consists of five muscles: A) Zygomaticus major, B) Levator labii superioris, C) Levator alae nasi superioris, D) Levator alae nasi inferioris and E) Zygomaticus minor, the former two of which are the possessor of the muscle spindles and the latter three of which are not so, with the exception of the Zygomaticus minor having one spindle in the Japanese shrew-mole. Seventy-three spindles were counted on one side of the snout musculature in the Dymecodon pilirostris (12 g in weight), 120 spindles in the Urotrichus talpoides (19 g in weight) and the Mogera wogura (100 g in weight). The snout musculature was 0.015 g, 0.02 g and 0.1 g in weight, respectively. The number of spindles per milligram weight of the muscle was 4.9 in the Dymecodon, 6 in the Urotrichus and 1.2 in the Mogera. The density of the spindle distribution was much higher in the former two than in the latter one. Since the Dymecodon and Urotrichus actually search for food by moving their long snout vigorously over the ground and the Mogera, being a subterranean, searches for food by moving his snout not so vigorously under the ground, the pattern of the snout movement seems to be coincident with the morphological differentiation of the snout musculature and the density of the muscle spindle distribution in the moles (Talpidae).


Topological distribution of muscle spindles in the human tongue and its significance in proprioception. In order to obtain numerical data concerning the lingual muscle spindle distribution, the muscle spindles were histologically surveyed on the serial frontal and horizontal sections (stained by hematoxylin-eosin) from the apex to the radix of the tongue. On one side four hundred and sixty-six muscle spindles were counted in seven muscles, the superior longitudinal muscle containing 159 spindles, the genioglossus 80, the transverse 79, the styloglossus 75, the hyoglossus 37, the inferior longitudinal 22 and the vertical 14. The chondroglossus and the palatoglossus are devoid of the spindles. The question of whether the proprioceptive impulses from the lingual spindles lie in the hypoglossus nerve or in the lingual nerve has remained unsolved. This histological confirmation of the pathway and primary cell station of the lingual proprioceptive afferents is the subject in which the authors are greatly interested.


Modulation of Ca2+ control of dog and rabbit cardiac myofibrils by Mg2+. Comparison with rabbit skeletal myofibrils. Increases in free Mg2+ from 0.04 to 10.0 mM with constant pH 7.0 TO 0.10 M ionic strength, and 2 mM MgATP2- caused a rightward shift of the free Ca-relative ATPase relation for both cardiac skeletal myofibrils. The specific activity of cardiac myofibrillar ATPase over a wide range of free Ca2+ was, however, depressed in 0.04 vs. 1.0 mM Mg2+, whereas a similar decrease in free Mg2+ slightly enhanced skeletal myofibrillar ATPase. Lowering free Mg2+ from 1.0 to 0.04 mM caused similar increases in cardiac and skeletal myofibrillar bound calcium, which were largely attributable to increased calcium binding to myofibrillar myosin. Raising free Mg2+ from 1.0 to 10.0 mM caused only a slight decrease of skeletal myofibrillar bound calcium, and this change was attributable to myofibrillar myosin. The same increase in free Mg2+ caused cardiac myofibrils to bind increased amounts of calcium and this change was not attributable to myofibrillar myosin. By subtracting calcium bound to myofibrillar myosin, we were able to estimate calcium binding by myofibrillar troponin. The transition between basal and maximal ATPase in 1.0 and 10 mM Mg2+ was found to be assocciated with binding of an additional 2 mol/mol of either skeletal or cardiac myofibrillar troponin.


Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit. We studied hearts from sham-operated and uninfected catheterized rabbits as well as from rabbits at early and late stages of cardiomyopathy and failure after 3 and 6 days of infection with Streptococcus viridans. No ultrastructural abnormalities or biochemical changes in membrane and myofibrillar activities were seen in 3-day uninfected hearts. In 6-day uninfected hearts there were decreased sarcolemmal M2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding and uptake, and myofibrillar Ca2+-stimulated ATPase as well as increased mitochondrial calcium uptake. Slight ultrastructural changes also were apparent in 6-day uninfected hearts. At both early and late stages of infective cardiomyopathy and failure there were varying degrees of depression in sarcolemmal Mg2+ ATPase, Na+-K+ ATPase, adenylate cyclase and calcium binding, microsomal calcium binding, calcium uptake and basal ATPase, and myofibrillar Ca2+-stimulated ATPase activities. However, sarcolemmal Ca2+ ATPase and myofibrillar Mg2+ ATPase activities were decreased only after 6 days of infection. Mitochondrial calcium binding and uptake were increased in early stages but decreased in late stages of disease. Furthermore in infected hearts there were defects in mitrochondrial respiration and phosphorylation. Generalized severe myocardial cell damage involving myofibrils, mitochondria, and the sarcotubular system was seen only in late stages of infection. The results demonstrate impairment of different membrane and contractile protein functions as well as ultrastructural abnormalities in bacterial cardiomyopathic hearts which were absent or of lesser magnitude in hearts with only hypertrophy. The findings reported here suggest to use that there is an association between heart failure and changes in function of cellular components during bacterial infective cardiomyopathy.


The significance of the left atrial appendage in rheumatic heart disease. The possible diagnostic value of an enlarged left atrial appendage (LAA) on the posterior-anterior or right anterior oblique chest film as a means of implicating a rheumatic etiology for mitral valve disease in children was investigated. Chest films were examined without prior knowledge of clinical or laboratory data, and the results were later correlated with this information in 113 children and adolescents. The clinical and laboratory data included application of the modified Jones criteria for the diagnosis of acute rheumatic fever, streptococcal antibody titers and clinical and cardiac catheterization findings. In children with mitral valve disease, our data suggest that as enlarged LAA, especially in the presence of pulmonary venous obstruction, is characteristic of rheumatic heart disease. This finding appears to be particularly useful, in conjunction with streptococcal antibody studies, in distinguishing rheumatic from nonrheumatic patients with mitral insufficiency.


Echocardiography in mechanical alternans. With a note on the findings in discordant alternans within the left ventricle. We described the echocardiographic manifestations of mechanical alternation of left ventricular (LV) contraction during regular sinus rhythm. Chronic LV dilatation and failure existed in all our four cases. Alternation was observed with respect to the following echocardiographic variables: amplitude and rate of increase of amplitude of systolic excursions of the LV posterior wall and ventricular septum (VS); reciprocal changes in the duration of LV ejection and pre-ejection periods (on the aortic valve echo) such that the total duration of LV electromechanical systole remained constant; reciprocal changes in the duration of RV ejection and pre-ejection periods (on the pulmonic valve echo) such that the total duration of RV electromechanical systole remained constant; systolic anterior excursion of the aortic root as a whole; steepness of the mitral EF slope; septal and LV posterior wall diastolic position; and end-systolic LV diameter. In two patients, discordant alternans of the motion of the LV posterior wall and the VS was observed.


Local nasal desensitization provoking systemic illness with proteinuria. We report a case of allergic rhinitis with systemic illness and proteinuria, which was repeatedly provoked by nasal exposure to allergen. Local nasal desensitization resulted in remission of both rhinitis and systemic illness. The disease was associated with systemic complement fixation via the classical pathway.


White cell function in Down's syndrome.

White cell function in Down's syndrome. Neutrophil function was studied in 25 patients with Down's syndrome at a mental subnormality hospital and compared with 26 normal controls. In vitro killing of Candida albicans was significantly lower in the Down's group, but there was no difference in the percentage of cells actively involved in phagocytosis or in the phagocytic index. The spontaneous nitroblue tetrazolium reduction was increased in 10 patients, but no abnormality of peroxidase activity or leucocyte alkaline phosphatase activity was found.


Congenital, irreducible, permanent lateral dislocation of the patella. This is a report of 6 cases (one bilateral) of congenital irreducible, permanent lateral dislocation of the patella, ages 5 to 14; 2 patients were normal and 4 were mongoloid. The dislocation was reduced by means of a newly-devised surgical reconstruction of anterior attachments of nearly all of the para-articular bone and ligamentous structures. The 2-year follow-up results are satisfactory.


Degenerative spondylolisthesis: surgical treatment. Degenerative spondylolisthesis occurs most frequently at the 4th lumbar vertebra in aging females. It does not occur before the fifth decade or in conjunction with neural arch defects. The amount of slipping does not exceed 30 per cent. The forward slipping occurs as a result of forward remolding of the z-a joints secondary to localized degenerative arthritis of these joints. The degenerative arthritis results from instability of L4 in spines which are unduly stable at the lumbosacral level. The degenerative changes and the forward slipping combine to produce localized spinal stenosis which may compress the nerve roots and cauda equina. The cardinal symptom is pain in the low back and/or lower extremity. It is characterized by remissions and is usually not incapacitating. Ten per cent of patients have sufficient pain and disability to require surgical decompression which is best accomplished by excision of the distal half of the laminae and spinous process of the slipped vertebra and the proximal half of the laminae and spinous process of the slipped vertebra. The medial half of each z-a joint is also excised to complete the decompression. If the decompression is adequate lasting relief of pain can be expected, but some low back symptoms due to instability may be noted postoperatively. These symptoms diminish with the passage of time.


Spondylolisthesis: indications for lumbar nerve root decompression and operative technique. Pain mechanisms attributable to spondylolisthesis are discussed with particular regard to the anatomic relationships at the site of nerve root impingement where the exiting lumbar nerve root is noted to pass anterior to the pseudoarthrosis mass in the pars interarticularis portion of the posterior element of the vertebral body. Clinical findings support the fact that nerve root impingement is a definite factor in producing the pain and associated symptoms in root impingement further supports this hypothesis. The incidence of lower motor neuron deficit is determined by a combination of muscle testing and electromyography. Postoperative results are evaluated in terms of patients having arthritic changes associated with the spondylolisthesis and in those patients with absence of arthritic change. These changes distinguish the patients who might respond best to simple decompression of the nerve root impingement from those patients who might better benefit from spinal fusion. Operative techniques should include adequate decompression of the exiting lumbar nerve root by means of total laminectomy approach. Exision of the pseudarthrosis mass attached to the pedicle side of the pars interarticularis of the vertebra is necessary to relieve pressure on the shoulder of the exiting nerve root.


Therapy of spondylolisthesis by repositioning and fixation of the olisthetic vertebra. A new method for reduction of the slip and stabilization in spondylolisthesis is presented. A detailed description of the operative technique is given. Of special importance to repositioning of the olisthetic vertebra is sectioning of the ilio-lumbar and ilio-transverse ligaments. It is also most important to remove a portion of the superior surface of S1 in those cases with greater than 30 per cent olisthesis. A distinction in the technique of surgery is drawn between cases with less than 30 per cent of slip and those with greater than 30 per cent. In those with less than 30 per cent 2 bone grafts taken from one iliac crest are placed between the repositioned body of L5 and the body of S1. In those with more than 30 per cent slip grafts are not necessary. In these a portion of the superior surface of S1 is removed in such a way that the body of S1 fits snugly against the under surface of the repositioned body of L5. A special traction apparatus with wires through the spinous processes of L3 and L4 is used to accomplish reduction of the olisthetic vertebra. This apparatus is spring-loaded and is mounted on a modified Milwaukee brace. The patient remains in bed while this is worn. When it is believed that there is enough solidity in the fusion between the bodies of L5 and S1 the traction apparatus is removed and the patient allowed up.


Technique of anatomical reduction of lumbar spondylolisthesis and its surgical stabilization. This is a report of a method for treatment of spondylolisthesis based upon: (1) preoperative reduction of the olisthesis by plaster casts; (2) fixation of the reduction by posterior arthrodesis, accompanied by a system of instrumentation which has been developed by the authors. The treatment of severe spondyloptosis in six children and of spondylolisthesis in 14 adults is considered separately, because of the somewhat different problems in the two different age groups.


Chemonucleolysis: a double blind study comparing chemonucleolysis with intra discal hydrocortisone: in the treatment of backache and sciatica. This paper attempts to answer the controversial question, namely, how effective is chemonucleolysis in the treatment of discogenic back pain and sciatica? By using a type of double-blind study, a comparison has been made between 20 patients who were treated with chemonucleolysis and 20 who were treated with intra-discal hydrocortisone. The 2 year post-injection survey by an independent observer, demonstrated that chemonucleolysis produced 9 good, 3 fair, and 8 unimproved results in 20 patients. In contrast, hydrocortisone produced 3 good, 8 fair, and 8 unimproved results in 20 patients - one patient dying from unrelated causes. Although not statistically significant, the data suggest that chemonucleolysis was superior to intra-discal hydrocortisone in this series.


Acute back pain associated with a calcified Schmorl's node: a case report. This is a case report of a 56-year-old woman with an unusual acute attack of back pain associated with a calcified intervertebral disk and herniation into the 10th dorsal vertebral body.


Spondylolysis in the female gymnast.

Spondylolysis in the female gymnast. In a roentgenographic analysis of the lumbar spine of 100 young female gymnasts engaged in high-level competition, the incidence of pars interarticular defects was 11 per cent; 6 per cent had spondylolisthesis. This is 4 times higher than their non-athletic female peers. It appears that the female athlete may have the same incidence of pars interarticularis defects as the male performing similar activities. Pars defects developing in association with athletic activities may be distinct from those developing in early childhood. A negative lumbosacral roentgenographic series does not completely rule out a developing pars defect. Bone scintography offers an additional tool for evaluating early stress reaction in the pars, and suggests that if the athlete restricts vigorous activity, some will heal without progressing to roentgenographically detectable defects. Low back pain in the young gymnast should be a warning sign. Close scrutiny of pars interarticularis in these young athletes will reveal a high incidence of developing defects.


Conservative treatment in spondylolisthesis. Spondylolisthesis occurs mainly at the L5-S1 interval, thus involving the dynamic segment. The general incidence is between 2 and 5 per cent, but about half of these patients are asymptomatic. The conservative therapy for the asymptomatic patients includes preventive measures such as correction of poor posture, elimination of stressful occupational requirements, avoidance of certain spine movements, and special sport activities. The mild to moderate low back pain syndrome requires alleviation of anxiety, analgesics and muscle relaxants, deep heat and relaxation and range of movement exercises. The severe low back pain which may prevent neurological deficit as well, should include a brief period of bed rest with strong analgesics and then gradual mobilization. In most instances, corsets are not required. Paravertebral blocks may be administered in special recalcitrant cases.


Loading and conventional dose therapy with phenytoin in children: kinetic profile of parent drug and main metabolite in plasma. Epileptic children were given phenytoin (DPH) in loading (four doses of 4.4 to 6.3 mg/kg/dose given 8-hourly and then 6 mg/kg/day) or conventional (5 to 9 mg/kg/day) doses. Plasma levels of DPH and its main metabolite (p-OH-DPH) were measured by a mass fragmentographic technique. Plasma DPH levels of more than 10 mug/ml were achieved within 16 to 38 hr in the children given loading doses and within 5 days in the conventionally dosed children. No immediate side effects were noted, but within 8 to 10 days 9 of 13 children developed a generalized skin rash. Plasma p-OH-DPH (free or conjugated) paralleled DPH during the accumulation phase but not during DPH elimination. The ratio of metabolite to DPH in plasma showed both an interindividual variation and an inverse relation to the level of DPH. Identical twins in the study had a similar ratio and plasma level-time course profile. It is concluded that the loading dose regiment achieves an appropriate plasma level of DPH rapidly, that saturation kinetics are operative for p-OH-DPH formation, that the ratio of metabolite to DPH in plasma is an individual characteristic in children, and that further studies on the delayed toxicity are needed before the loading dose regimen can be recommended.


Plasma growth hormone concentrations in Huntington's chorea. 1. Growth hormone secretion was assessed in nine control subjects and nine patients with Huntington's chorea. 2. Early-morning fasting plasma samples from patients with Huntington's chorea contained abnormally high concentrations of growth hormone. 3. The suppression of growth hormone after oral glucose in choreic patients, unlike the control subjects, occurred at irregular intervals after the glucose was given and was followed, again at irregular intervals, by an exaggerated rebound phase. 4. The response to intravenous insulin was not markedly abnormal in choreic patients. However, there was a significant increase in the rate of rise of growth hormone concentration in the first half and hour after the insulin injection when compared with control subjects.


Rat hepatic sodium plus potassium ion-dependent adenosine triphosphatase after treatment with digoxin and thyroxine. 1. The effect of treating rats with digoxin and thyroxine for 45 days has been studied. 2. Animals fed with digoxin gained significantly more weight than the control animals. 3. Treatment with digoxin, thyroxine or both produced a similar significant increase in the amount of Na+ + K+ -dependent adenosine triphosphatase in liver without an additive effect. 4. It is suggested that digoxin resistance in thyrotoxicosis may be related to this similarity in action.


[Liver metastases: diagnostic value of blood tests, scintiscanning, and laparoscopy (author's transl)]. In 90 patients with known extra-hepatic malignancy the liver was examined for metastases. The diagnostic value of clinical information, blood examinations, 99mTc scintiscan, and laparoscopy for the diagnosis of the liver metastases was evaluated. Clinical data (age, sex, time since onset of symptoms and localisation of primary tumor) are of no diagnostic value. The most reliable blood tests are alkaline phosphatase (AP) and GOT. The probability of liver metastastases rises with increasingly abnormal values of AP and GOT. However, the probability is not much greater in cases with highly abnormal values than in cases with only moderate elevation of AP and GOT. Diagnostic accuracy of AP is optimal by using a cutoff point of 76 U/l (sensitivity 79%, specificity 64%). Bilirubin, prothrombin time, haemoglobin and blood sedimentation rate are of very little value. Combinations of AP with these blood tests does not improve diagnostic accuracy. Therefore, it is not useful to determine more blood tests than AP alone. Informed reading of liver scans has a specificity of 75% and a sensitivity of 91%. Blind reading of scans has a sensitivity of 94% and a specificity of 95%. This diagnostic accuracy cannot be improved by additional blood tests. Laparscopy has a sensitivity of 85% and a specificity of 95%. Scanning and laparoscopy are complementary methods. When optimal diagnostic accuracy is required both methods should be used.


[Enzymatic changes in the mucous membrane of the small intestine in tetrachlormethane-induced experimental liver cirrhosis]. The author examined the enzymatic activity in the intestinal mucosa under the conditions of rat liver cirrhosis, experimentaly induced by carbon tetrachloride. There was a correlative connection between liver damage and the functional activity of the intestines, manifested by the inhibition of the activity of the membrane enzymes-alkaline phosphatase and aminopetidase as well as the activity of acid phosphatase and succinic dehydrogenase.


Selective effect of androgens on LH and FSH release in anterior pituitary cells in culture. A possible direct effect of androgens at the pituitary level on gonadotropin release was studied using rat anterior pituitary cells in primary culture. The preincubation of cells with 3 X 10(-9)M testosterone (T) for 40 h increased the concentration of luteinizing hormone-releasing hormone (LHRH) required for half-maximal stimulation (ED50) of LH release from 3 X 10(-10)M to 1 X 10(-9)M. In the same experiment, the LHRH ED50 for FSH release (3 X 10(-10)M) was not affected by preincubation with T, while a slight stimulatory effect of the androgen was observed on balal FSH release and on the maximal FSH response to LHRH. Time-course experiments showed that the inhibitory effect of T on the LH response to LHRH was maximal after about 48 h of incubation and that 54 h after the removal of T, only 50% of the inhibition was reversed. 5 alpha-Dihydrotestosterone (DHT) and T led to the same maximal inhibition (15-20% of control) of the LH response to 10(-10)M LHRH. DHT was, however, about 3 times more potent than T, their ED50 values being 1.6 X 10(-10)M and 5 X 10(-10)M, respectively. In contrast to the effect on LH, the FSH response to 10(-10)M LHRH was only slightly, but not significantly, inhibited by increasing concentrations of DHT or T. The finding that total LH (medium + cell content) remained constant after incubation with T or DHT clearly indicates that the inhibition of the LH response to LHRH is really due to changes in the sensitivity of the releasing mechanisms in the LH-secreting cells. Androgens did, however, lead to increased total FSH. The present data indicate an independent control of LH and FSH secretion by a direct action of androgens at the pituitary level.


Cholinergic and serotonergic neural links and the inhibitory effects of hippocampus, lateral amygdala and central gray matter on gonadotropin release. Effects of electrical stimulation of the hippocampus (HPC), lateral amygdala (1-AMYG) and midbrain central gray matter (CG) on the release of ovulatory gonadotropin were examined using proestrous Wistar rats with or without pretreatment with reserpine, atropine or p-chlorophenylalanine (PCPA) at such dosage that had been confirmed not to block ovulation. Electrical stimulation of the HPC, 1-AMYG or CG under light ether anesthesia just before the critical period prevented a rise in serum LH, FSH and prolactin levels at 18:00. Pretreatment with atropine (200 mg/kg body wt, sc) was effective to abolish this inhibitory effect of the HPC stimulation on the release of LH and FSH, whereas reserpine treatment (1mg/kg body wt, ip) did not affect the effect. The inhibitory effect of the 1-AMYG or CG stimulation on LH and FSH release was abolished by treatment with PCPA (150 mg/kg body wt, ip), while neither atropine nor reserpine had any effect. The inhibitory effect of the HPC stimulation on the release of these hormones was also blocked by PCPA treatment. In regard to the prolactin release, it was inhibited by the stimulation of the HPC, 1-AMYG or CG in both the non-treated rat and in the atropine or PCPA-treated one, while in the reserpine-treated rat it was not inhibited but rather was facilitated by these stimulations. It was assumed that the normal maintenance of both cholinergic and serotonergic neural links for the expression of the HPC inhibition on ovulatory LH, FSH and prolactin secretion and that of serotonergic link for the expression of the 1-AMYG or CG inhibition are needed. The inhibitory action on prolactin release changed into facilitation under the depletion of monoamines, but the mechanism is unknown.


Mutagenicity assays on fluorescent whitening agents using microorganisms. Six fluorescent whitening agents (FWAs) have been re-examined for their activity as inducers of cytoplasmic petite mutants and mitotic gene conversion in diploid yeast Saccharomyces cerebisiae and reversion from auxotrophy to prototrophy in Neurospora crassa, Escherichia coli and Salmonella typhimurium. The results provide no indication that the FWAs examinded produce mutagenic changes or any other alterations in the gene material. In a recent re-examination with Salmonella using the method of Ames et al., the four examined compounds failed to elicit a mutagenic response in the presence of rat liver postmitochondrial supernatant and cofactors.


The identification of myosin in rabbit hepatocytes. A myosin-like protein was identified in isolated rabbit liver cells. It was extracted with high-ionic-strength buffer containing ATP, and purified by gel filtration in the presence of iodide. The myosin polypeptide was indistinguishable in size from the heavy chain of muscle myosin as determined by electrophoresis on polyacrylamide gels and gel filtration in the presence of sodium dodecyl sulfate. The hepatic myosin had an amino acid composition similar to that of muscle myosin, but lacked 3-methylhistidine. The Mg2+ -ATPase of the myosin was not activated by muscle actin. At low ionic strength, in the presence of Mg2+, the protein aggregated to form bipolar filaments 0.3 mum in length. A protein which resembled muscle actin in size and amino acid composition was extracted along with the myosin. Based on scans of stained sodium dodecyl sulfate polyacrylamide gels, the myosin content was estimated as 0.3% to 0.4% of the cell protein. The actin-like component was present in approximately ten-fold excess by weight. This ratio suggests that the organization and function of myosin in the hepatocyte is very different from that in the muscle cell.


A comparison of the influence of potassium and ammonium ions on the phosphofructokinases from rabbit muscle and rat erythrocytes. Phosphofructokinases from rat erythrocytes and rabbit muscle have been compared in their kinetic behavior with respect to monovalent cation activation and ATP inhibition. Both ammonium and potassium ions affect the muscle enzyme in a two-fold manner: they act both as activators and effectors. On the other hand only ammonium exerts the two-fold effects on the erythrocyte enzyme, while the potassium ions activate without affecting cooperativity. The lower ATP inhibition of muscle phosphofructokinase may be partially explained by the action of potassium ions on the cooperative behavior of the enzyme. The differences between the phosphofructokinases from erythrocytes and muscle in the potassium type-II activation and ATP inhibition represent an organ specifity. Furthermore, the inhibition constants for 2, 3-bisphosphoglycerate differ by 10-fold between the two enzymes.


(Na+, K+)-activated adenosinetriphosphatase of axonal membranes, cooperativity and control. Steady-state analysis. 1. The ATP sites. Homotropic interactions between ATP sites have been studied in a very large range of Na+ and K+ concentrations. The ( Na+, K+)-activated ATPase displays Michaelis-Menten kinetics for ATP under standard concentration conditions of Na+ (100 mM) and K+ (10 mM). The steady-state kinetics behavior changes at very low concentrations of K+ where negative cooperativity is observed. The existence of a high affinity and a low affinity site for ATP was clearly demonstrated from the study of the ATP stimulated hydrolysis of p-nitrophenylphosphate in the presence of Na+ and K+. The ratio of apparent affinities of high and low affinity sites for ATP is 86 at pH 7.5. 2. The Na+ sites. The binding of Na+ to its specific stimulatory sites (internal sites) is characterized by positive cooperativity with a Hill coefficient n(H(Na+))=2.0. Homotropic interactions between Na+ sites are unaffected by variations of the K+ concentration. 3. The K+ sites. (a) Binding of K+ to the (external) stimulatory site of the ATPase has been analyzed by following the (Na+, K+)-ATPase activity as well as the p-nitrophenylphosphatase activity in the presence of Na+ and K+ (with or without ATP). Binding is characterized by a Hill coefficient of 1.0 and a K(0.5(K+))=0.1 to 0.8 mM. The absence of positive or negative cooperativity persists between 5 mM and 100 mM Na+. (b) The analysis of the p-nitrophenylphosphatase or of the 2, 4 dinitrophenylphosphatase activity in the presence of K+ alone indicates the existence of low affinity sites for K+ with positive homotropic interactions. The characteristics of stimulation in that case are, K(0.5)=5 mM, n(H)=1.9. The properties of this family of site(s) are the following: firstly, saturation of the low affinity site(s) by K+ prevents ATP binding to its high affinity internal site. Secondly, saturation of the low affinity sites for K+ prevents binding of Na+ to its internal sites. Thirdly, this family of sites disappears in the presence of ATP, p-nitrophenylphosphate or of both substrates, when Na+ binds to its internal sites. Na+ binding to its specific stimulatory sites provokes the formation of the high affinity type of site for K+. 4. Mg2+ stimulation of the (Na+, K+)-ATPase is characterized by a Hill coefficient n(H(Mg2+))=1.0 and a K(0.5(Mg2+))=1 mM stimulation is essentially a V effect. Heterotropic effects between binding of Mg2+ and substrate to their respective sites are small. Heterotropic interactions between the Ms2+, Na+ and K+ sites are also small. 5. The fluidity of membrane lipids also controls the (Na+, K+)-ATPase activity. Phase transitions or separations in the membrane hardly affect recognition properties of substrates, Na+, K+ and Mg2+ for their respective sites on both sides of the membrane. Only the rate of the catalytic transformation is affected.


Comparison of Frank's and McFee's lead systems using multivariate statistics. Two widely used orthogonal corrected 3-lead system - the Frank and the McFee systems - were studied in order to evaluate whether a significant difference in diagnostic performance could be observed; in the case of a positive answer, we would be able to advocate one system instead of the other. No such overall difference was noticed. Although +/- 17% discrepancies were found on the individual classification level (a patient correctly classified with system A and missed with system B and conversely), the practical implication is negligible since each system is responsible for +/- half of these discrepancies. Multivariate analysis, as already largely proved by Pipberger's group, drastically ameliorates the diagnostic results. Special caution has been given to the number of selected discriminators in order to enhance repeatability of the results; the reproducibility, using the approach developed by Cornfield, was found excellent. Some particular features as to the choice and location of the best discriminators were found somewhat puzzling by the autors but no deterministic explanation could be offered: the selection of the variables, indeed, rested on statistical bases and not on the (sometimes fragmentary) knowledge of what is going on in the heart and how these events relate to surface waveform patterns.


Angiocardiographic/pathologic correlations in congenital mitral valve anomalies. The angiocardiographic findings were reviewed in 21 patients with congenital mitral valve disease in whom the exact anotomic diagnosis was known independently. Patients with discordant (1)transposition and simple atrioventricular canal defects were excluded. No precise diagnosis was made in five patients (24%), all of whom had a cleft anterior leaflet or congenital short chordae. In the remainder, the specific diagnosis could have been made by injection of constrast medium downstream to the mitral valve alone in 15 (71%). Upstream injection was performed in 13 of these but would have made the precise diagnosis in only three (23%). In one patient both upstream and downstream injections were necessary. Anomalies giving characteristic angiocardiographic appearances were parachute valve, atresia, annular hypoplasia, dysplasia, anomalous arcade and anomalies associated with subaortic stenosis. Thus injection downstream to the valve is preferable to upstream injection, because it gives information about its patency, competence, tensor apparatus, and annular dimensions.


Cardiac NaK ATPase activity during positive inotropic and toxic actions of ouabain. In order to define pharmacological actions of ouabain in the dog heart, ouabain uptake and subcellular distribution and its effect on NaK ATPase (MG2+ dependent, Na+-K+-activated adenosinetriphosphate phosphohydrolase, E.C. 3.6.1.3), have been investigated in 21 open-chest dogs. A continuous infusion of ouabain (0.036 mug/kg/min) after a loading dose (20 mug/kg) produced a relatively constant plasma concentration of approximately 10(-8) M (6 ng/ml) ouabain, which induced a sustained positive inotropic response for the 300 min experimental period. In these hearts much greater binding of ouabain was noted in the NaK ATPase and microsomal fractions than in other myocardial fractions. No statistically significant inhibition of NaK ATPase activity was noted. Doubling the loading and infusion doses of ouabain raised the plasma level of ouabain to approximately 3 X 10(-8) M and produced various types of arrhythmia within an hour, which persisted for the rest of the 5 h experimental period. Under this experimental protocol there was a significant inhibition of NaK ATPase activity and increased binding of ouabain to this enzyme. This study does not support the hypothesis that there is a causal relationship between inotropic response to ouabain and NaK ATPase inhibition. It was concluded that NaK ATPase inhibition might be causally related to the development of ouabain toxicity.


Increase in the (Na+ + K+)-ATPase activity in heart muscle after chronic treatment with digitoxin or potassium deficient diet. In guinea pigs, administration of digitoxin (0.3 mg/kg s.c. for 7-24 days) causes an increase in activity of the (Na+ + K+)-ATPase of the heart. The plasma K+ level and the K+ content of the heart muscle of these animals remains unchanged and there is no significant alteration in the digitoxin toxicity compared to controls. In guinea pigs with potassium deficiency produced by a potassium deficient diet for 12 days, there is a related increase of the (Na+ + K+)-ATPase. The plasma K+ level of these animals is diminished while the K+ content in the heart muscle remains unchanged the toxicity of digitoxin is enhanced. In both test groups the increase in the (Na+ + K+)-ATPase activity is limited to enzymes from heart muscle, those from brain or kidney remaining unaffected. This increase in activity seems to be the result of an adaptive enzyme induction.


Diphenylhydantoin effects on salivary secretion and microsomal calcium accumulation and release. Diphenylhydantoin inhibited calcium uptake into dog submandibular microsomes at concentrations of 0.05 mM and greater but did not affect calcium release; mesantoin and hydroxyphenyl-phenylhydantoin were without effect. Diphenylhydantoin (20 mg/kg) given i.v. significantly reduced, and mesantoin slightly reduced secretion from submandibular and parotid glands, but hydroxyphenyl-phenylhydantoin was without effect. These data suggest that the reduced secretory volume produced by diphenylhydantoin may be related to its effect on transmembrane calcium movements.


Immunohistological investigation of N-acetylserotonin in the rat cerebellum after parachlorophenylalanine treatment. The amount of N-acetylserotonin (NAS) in the granule layer of the rat cerebellum was investigated using immunolohistologic double antibody technique. After 5 days of treatment with parachlorophenylalanine (PCPA) an increase of NAS was observed. The possibility of a differential effect of PCPA on serotonin synthesis in the neurons and the nerve terminals is discussed.


[Action of some bis-quaternary derivatives of fluorene and related compounds on the skeletal muscles of vertebrates]. In experiments with skeletal muscles of cats, rats and frogs bis-trimethylammonium derivatives of fluorene are shown capable of being strong muscle relaxants of the depolarizing type of action and that the presence of sulfamide or ester groups in the chain between nitrogen atoms is not indispensable for their high activity.


[Role of the hydrophobicity of monoquaternary ammonium compounds in the mechanism of their curariform action]. The lengthening of the alkyl radical at the quaternary nitrogen atom (from -C2H5 to -C20H41) in the series of alkyltrimethylammonium compounds was found to lead to a gradually growing hydrophobicity of the compound. A change in the mechanism responsible for the myoparalytic action of the compound is due to a mounting degree of hydrophobicity. With the methyl group in the molecule of tetramethylammonium replaced with polyalicyclic radicals (bornyl, adamantyl) the compound, acting after a non-depolarizing type, possess a greater degree of hyrophobicity than do substances of the depolarizing type.


[Cholinomimetic activity of acetylcholine and sebacinyldicholine derivatives with differing cationic group structures]. The intrinsic alpha activities and the D2 (frog, m, rectus abdominalis) concentrations were estimated for different acetylcholine and sebacinylcholine derivatives. So were also the A2 values for antagonists and the affinity constants Kc for some partial agonists. The results obtained disprove Paton's "rate-theory". The relationship between the cholinergic activity and the volume of cationic groups was studied and it could not possibly be explained by the steric hindrance alone. It is suggested that certain hydrophobic radicals of the cationic groups contact the receptor surface outside the anionic centre. Such contacts prevent the cholinoreceptor to change its conformation and thus inhibit the depolarization of the membrane. An approximate estimation of the anionic site dimensions is given.


[Pharmacological characteristics of a new curariform compound from a series of naphthalene-peri-tetracarboxylic acid derivatives]. Experiments staged with rabbits, cats, frogs and chicken have proved tetracarboxylic acid dibenzosulphoethylate-bis (para-piperidinophenol)-diimidonaphthalene-1, 4, 5, (see article) to be capable of totally blocking the neuro-muscular conduction in a dose of 0.5 mg/kg and to block 20 per cent of it in a dose of 0.3 mg/kg. The action of the compound on the arterial pressure is half as great as that of d-tubocurarine. A pharmacological analysis conducted on the musculus rectus abdominus of the frog and chicken points to an antidepolarizing type of action. The durarolike effect of (see article) can be averted or abolished by introduction of nivalin (galanthamine), proserine and pimadine. The author deems it expedient to make clinical trials of the drug.


Effect of dexamethasone and clomiphene citrate on peripheral steroid levels and ovarian function in a hirsute amenorrheic patient. A 22-year-old infertile woman with amenorrhea and mild hirsutism failed to experience uterine bleeding following withdrawal of progestin therapy and failed to ovulate or menstruate following treatment with clomiphene citrate in doses up to 200 mg/day for 5 days. Clomiphene citrate, 200 mg/day, plus 10,000 IU of human chorionic gonadotropin given on day 13 also failed to induce either ovulation or menses. Serum androgen levels were: cortisol, 186 ng/ml; dehydroepiandrosterone sulfate, 6400 ng/ml; dehydroepiandrosterone, 17.92 ng/ml; androstenedione, 4.68 ng/ml; testosterone, 1.28 ng/ml; and dihydrotestosterone, 0.75 ng/ml. Upper limits of normal values for these androgens in our laboratory are, respectively: 140, 2500, 8.0, 2.3, 0.5, and 0.35 ng/ml. The dexamethasone (Dex) suppression test indicated predominantly an adrenal source of the hyperandrogenism. Except for androstenedione the levels of all androgens measured returned to normal following treatment with 0.5 mg of Dex/day. Four months of this treatment had a beneficial effect on the hirsutism but failed to induce ovulation or menses. Clomiphene citrate, 100 mg/day for 5 days, given concurrently with Dex therapy resulted in ovulation and conception. Adrenal androgen excess has been postulated to be a cause of ovarian dysfunction. Our data support this postulate.


Nutrition in the practice of pediatric dentistry. Nutrition is an important aspect of the total environment of a growing child. The dentist should evaluate the nutrition of pediatric patients from the physical parameters of the child including growth, general appearance, posture, muscle control, oral findings, and dietary history. Some common malnutrition problems of the pediatric age group include deficiencies of iron, calcium, vitamins A, C, and D, protein and/or calories, and excess ingestion of calories. The causes of and means of preventing nursing-bottle syndrome are easily preventable in this form of dental caries which has many dental, systemic, and economic consequences. The use of group dynamics as an effective and enjoyable method of teaching preventive dentistry is discussed.


Staphylococcal scalded skin syndrome in an adult. The staphylococcal form of toxic epidermal necrolysis or staphylococcal scalded skin syndrome (SSSS) is exceptionally seen in an adult patient. We report a case of SSSS in a 21-year-old male who suffered from a fulminant pneumopathia due to a phage group II Staphylococcus aureus. The onset of that clinical picture in an adult patient is unusual and could be due to a deficient immunity, as previous case reports have emphasized. Unfortunately, the sudden death of our patient did not allow us to investigate his immunological defences.


Hyperlipoproteinemia in streptozotocin-treated rats. In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal dose of streptozotocin was 45 mg/kg body weight for the sucrose-fed rats. With this dose, plasma glucose reached a maximum of over 600 mg/100 ml., and plasma insulin was reduced by 60 per cent. Plasma triglycerides rose in the sucrose-fed rats to over 1,000 mg/100 ml. two days after the streptozotocin was given and then decreased to over 770 mg./100 ml. 12 days after treatment and then to 585 mg./100 ml. 10 weeks after induction of diabetes. With this dose, ketonuria did not occur nor did any of the animals die, as occurred with higher doses. In the chow-fed rats, plasma triglyceride levels were elevated with the induction of diabetes to levels of approximately 300 mg./100 ml. The concentration of all the plasma lipoproteins increased with the induction of diabetes. The concentration of very-low density lipoprotein (VLDL) protein in the sucrose-fed diabetic increased fivefold, the low-density lipoprotein (LDL) protein increased, and especially striking was the increase in high-density lipoprotein (HDL) protein concentration, which became more pronounced with the duration of the diabetes. The diabetes produced by streptozotocin administration to sucrose-fed rats, thus, provides a useful model for the study of the hyperlipoproteinemia of diabetes.


Nutrition and somatomedin. II. Serum somatomedin activity and cartilage growth activity in streptozotocin-diabetic rats. Since diabetes mellitus is a condition in which poor growth occurs despite elevation of plasma GH, we have attempted to determine if poor growth in diabetes, as in malnutrition, could be associated with a decrease in somatomedin activity. Young male rats were rendered diabetic with intravenous streptozotocin (STZ). The growth activity of their cartilage was estimated by 35SO4 incorporation in vitro, and somatomedin (SM) activity in their serum was determined by the stimulation of SO4 incorporation by cartilage from hypophysectomized rats or normal young pigs. Cartilage growth activity was significantly decreased 24 hours after STZ and fell to hypopituitary levels after 48 hours. The decreased growth activity could not be attributed to decreased cartilage responsiveness to SM, since incubation of diabetic cartilage with normal rat serum (normal SM) resulted in significant stimulation of cartilage SO4 incorporation. SM in diabetic serum decreased to hypopituitary levels 24 hours after STZ, and decreased further after 48 hours. The decrease in SM and cartilage growth activity was not prevented by the administration of high doses of bovine GH. The fall in bioassayable SM appeared to be due in part to the presence of an SM inhibitor in the diabetic serum, since addition of diabetic serum to normal serum decreased to measurable SM in the normal serum. Administration of insulin to diabetic rats 48 hours after STZ led to significant increases in SM and cartilage growth activity, and insulin therapy 24 hours after STZ prevented the decreases in SM and cartilage growth activity which occurred without insulin. Thus, acute STZ-induced diabetes in rats was associated with a significant decrease in both serum SM and cartilage growth activity; these changes were not ameliorated by administration of GH, and insulin therapy could both prevent and reverse the fall in SM and cartilage growth activity. From these observations, we conclude that (1) that fall in somatomedin activity and cartilage growth activity associated with STZ-induced diabetes appears to be due to insulin deficiency and (2) growth failure in diabetes, as in malnutrition, may be due to decreased somatomedin activity.


Studies on streptozotocin diabetes.

Studies on streptozotocin diabetes. Both alloxan and streptozotocin produce beta-cell necrosis in the rat. Previous studies have shown protection against alloxan toxicity by D-glucose, D-mannose, and the nonmetabolized analogue 3-0-methyl-D-glucose and removal of this protective effect by D-mannoheptulose. The effect of several agents (i.v. infusion) against the beta-cell toxic effect of streptozotocin (60 mg./kg. i.v. in 24-hour-fasted 200-gm. male rats) was studied. Protection was determined by plasma glucose concentrations 24 and 48 hours later and, in certain experiments, by histologic examination of the islets. D-glucose and D-mannose provided no protection. Similarly, D-galactose, D-fructose, alpha-methyl-D-glucoside, D-L-glyceraldehyde, D-xylose, and D-glucosamine had no effect. However, 3-0-methyl-D-glucose administered immediately before streptozotocin resulted in progressive inhibition of beta-cell toxicity with complete protection at 0.83 mMoles per rat. The protective effect of 3-0-methyl-D-glucose was not altered by mannoheptulose. 2-Deoxy-D-glucose, which has no effect against alloxan, provided nearly complete protection against streptozotocin at 2.2 mMoles per rat. The effects of 3-0-methyl-D-glucose and 2-deoxy-D-glucose were additive and were not altered by glucose. Furthermore, the 3-0-methyl-D-glucose as well as 2-deoxy-D-glucose protective effects were still present, albeit attenuated, when these agents were given following the administration of streptozotocin. This is in contrast to alloxan, against which 3-0-methyl-D-glucose provides protection only when given before alloxan. 3-0-Methyl-D-glucose is the only carbohydrate protective against both streptozotocin and alloxan in the rat. However, several silent differences seem to exist between the mechanisms of beta-cytotoxic effects of these two diabetogenic compounds.


Handicapped children under National Health Insurance. This paper describes the services for the care of handicapped children and young people in the United Kingdom and Sweden--two countries which have a system of a national health service and national health insurance. The author discusses the implications for the United States, which is now moving towards a national health insurance scheme. The future of existing programmes, the need for a national plan, and the choice of priorities are considered.