[Histoautoradiographic study of thymidine-3H incorporation into the parenchymal nuclei of the kidneys and other organs in rats with nephrotoxic nephritis]. The features of changes in the index of thymidine-3H incorporation into the renal parenchyma in nephrotoxic nephritis are compared to other organs. In the kidneys the index of incorporation inthe epithelial cells of the renal cortex was 7.5-fold and in the brain cortex epithelium 15-fold as increased, respectively. The number of labeled glomerular cells was 2.5-fold as increased. In glomerulonephritis, the index of thymidine-3H incorporation in the epithelium of the adrenals, liver, goiter gland and small intestine lowered within 30-80% from normal.


[Autoradiographic analysis of the effect of potassium orotate on the intensity of uridine-5 3H and proline-3H incorporation into wound fibroblasts]. The intensity of uridine-53H and proline-3H incorporation into fibroblast nuclei and cytoplasm as well as into intercellular spaces was studied in wound healing of mice given potassium orotate and in the control animals. It was shown that proline-3H incorporation was more intensive than that of uridine-53H. At the same time a significant increase in RNA synthesis in fibroblasts under the action of potassium orotate, and a less pronounced rise in proline-containing protein synthesis were noted in similar conditioelationships correlate with the fibroblast ultrastructural changes in the process of their differentiation.


[Morphometric study of the blood-carrying capillaries during the administration of a liquid into the salivary gland]. The physiological saline was injected into the excretory duct of the cat parotid gland under the pressure of 30, 70 and 120 cm H2O. It was found with the aid of transmission electronic microscopy, morphometry and statistical analysis that the liquid injection into the gland produces compression of the blood capillaries weaving the acinus. The compression of the capillary tubes is shown by a significant reduction in space given to the lumen of the capillaries and their endothelial layer. The compression of the capillary tubes is combined with a two-fold lessening suggest that the additional blood volume entering the gland in response to its perfusion by the liquid does not reach the blood capillaries and is thrown off into the vein vessels through the shunt communications and that regulation of the blood volume getting into the cat parotid gland capillaries is likely to depend on the hydraulic and osmotic state in the interstitial space of glandular lobes.


[Dynamics of the nuclear DNA content in the liver, skeletal muscles and myocardium of the rat in the postmortem period (a microspectrophotometric study)]. A comparative microspectrophotometric analysis of changes in nuclear DNA in the liver, skeletal muscle and myocardium of noninbred male albino rats which had died of cerebrocranial injury was conducted during three days following death. A decrease in the content of nuclear DNA within an interval of 30-72 h can be depicted mathematically by regression curves of the type M(t) = e-at+b. The data obtained allowed one to mathematically show the postmortem changes in DNA of the test material.


[Characteristics of the development of acute toxic hepatitis in rats stimulated with prodigiozan]. Acute toxic hepatitis was induced in Wistar rats by means of a single injection of 40% CCl4 on a peach-kernell oil base (0.2 ml/100 g body weight). Under conditions of stimulation with the bacterial polysaccharide prodigiosan, the resistance of hepatocytes to CCl4 sharply increased, which was shown by diminished severity of hepatic parenchyma destruction.


[Structural and immunomorphological characteristics of the human thymus in embryogenesis]. The thymus glands from one hundred of 4--34-week-old human fetuses were studied by the histologic, histochemical, immunomorphologic and electron microscopic methods. The development of the organ is described from the standpoint of systemogenesis. The laying of the gland is defined at the 5th week of the fetus development, and it reflects the features of the epithelium of the head intestine organs. The differentiation of the reticuloepithelium, the population of the gland by lymphocytes and emergence of antigenic specificity on their surface state at the age of 7--8 weeks. The growth zone of the thymus reticuloepithelium, the significance of Hassal's bodies, the appearance and quantitative dynamics of two subpopulations of T-lymphocytes are described. From 11--12 till 34 weeks of fetal development the percentage of T-lymphocytes forming rosettes with sheep red blood cells virtually does not change (70--90%), while the percentage of lymphocytes forming rosettes with their own red cell increases during the same period from 23 to 70%.


[Reaction of the ganglia to stress effects in the maxillodental area]. Neurohistologic and histochemical study has been performed of the trigeminal and upper cervical sympathetic ganglia as well as of the nodose ganglion in 35 dogs whose 4 lower teeth were prepared for full metal crowns. It was established that in the polishing of dental hard tissue the ganglia on the prepared side show changes in some neurons, intraganglionic nerve fibers, synaptic endings, in the content and distribution of RNA, glycogen and hyaluronic acid. The maximal evidence of the reaction was noted 1--3 days after operation. The ganglia under study did not show any marked changes following 21--28 days.


[Electron microscopic and histochemical study of the localization of adenylate cylase and acetylcholinesterase in the synapses of the rat cerebral cortex and basal ganglia]. Synapses of the brain cortex and basal ganglia of the rat were studied by means of electron histochemical reactions to adenylate cyclase and acetylcholinesterase. Three types of synapses, viz. cholinergic, adrenergic and mixed, were identified. Typification was carried out on the basis of presynaptic terminal vesicle characteristics and localization of the mentioned enzymes of the synapse receptor area.


[Role of the catecholaminergic mechanisms and of the caudate nucleus in the development of generalized convulsions caused by the parenteral administration of penicillin]. In freely moving cats the behavioral and EEG-shifts, accompanied by myoclonic jerks with slow negative waves and spike-wave complexes in the cortexand caudate nucleus, were recorded following a single intramuscular injection of high penicillin doses. The stimulants of catecholaminergic transmission (L-DOPA and apomorphine) inhibited the development of such phenomena but facilitated origination of tonicoclonic cramps. The inhibitors of catecholaminergic synapses (aminazin and haloperidol) exerted reverse effects. The electrolytic injury to the caudate nucleus head also prevented formation of petit mal-like seizures while the threshold low-frequency stimulation of the nucleus increased penicillin effect.


[Restoration of motor functions in disruption of the spinal cord or cauda equina]. Eight patients with a rupture of the spinal cord at the level of middle thoracic vertebrae or cauda equina at the lumbar level showed partial recovery of motor functions. The development of the activity was revealed by electromyography in body muscles and M. gluteus media in all the patients who attempted voluntary movements. Appearance and development of the activity was also observed in the muscles of the femur and crus. The level of rehabilitation shown by the patients was high enough. They could walk in fixation apparatuses, returned to their occupational activities and could practice self-service. The motor functions recovered more rapidly at the low levels of injury; however, the same and possibly complete rehabilitation was attained in 2 patients with a higher level of injury. The mechanism of the function recovery is underlain by the compensatory development of activity in the muscles of the body and capacity of the distal strip of the spinal cord for elaboration of new motor reactions in which the muscles of the extremities participate.


[Primary response mechanisms of the adrenal cortex in dogs to pain stress]. The adrenal cortex of dogs shows a drop in the glucocorticoid content 10--15 sec after the pain action in the presence of the free cholesterol level increase and its esterified form drop. The concentrations of hormones in the blood falls chiefly at the expense of protein bound hydrocortisone. The subsequent phase of the reaction (after 30--60 sec) is characterized by a considerable accumulation of the hormones by the gland. The level of free glucocorticoids significantly increases, the initial ratio of hydrocortisone and cortisone restores, and transcortin depot is filled up. The role of the adrenal and transcortine depot in realization of feedback mechanisms under stress is discussed.


[Biogenic amine content and the pathomorphological shifts in different organs and tissues in a period of the hematogennic spread and fixation of botulin toxin]. In experiments on cats it was shown that 30 minutes after intravenous injection of botulinum toxin, type C, there was a fall in the catecholamine and histamine contents with a simultaneous increase of serotonin in various structures of the brain and spinal cord and in a number of inner organs as well. The metabolic changes in the biogenic amines were combined with certain pathomorphologic changes seen in the form of acute swelling, chromatolysis, destruction of some neurons of the spinal cord and brain, distrophic changes in inner organs, and an increased permeability of the blood-tissue barriers. Marked biochemical and pathomorphologic changes in the spinal cord and brain where the minimum concentration of toxin becomes manifest during its spreading allow a conclusion that botulinum neurotoxin shows its pathogenic action through a disturbed metabolism of biologically active substances.


[Effects of injurying and restoring the body of rats with microwave (2400 MHz) irradiation]. In experiments on 2072 rats the thresholds of power density (PD) and the duration of microwave irradiation were obtained with the effect of destruction not more than 0.1%. The speed ratio of formation processes of destruction and regeneration depends on power density of microwave radiation and interpolates the exponential function. Previously obtained (from experiments on mice) and now published data allow the eifference to be established between mice and rats as species. Mice are more sensitive from the standpoint of time of achieving equal effects of destruction, half and full period of regeneration, the speed ratio between destruction and regeneration depending on PD of microwave radiation.


[Effect of serotonin and histamine on the cellular contractile activity of the internal carotid artery]. In the experiments on isolated segments of the canine internal carotid artery it was shown that serotonin (5.10(-11)--5.10(-5) g/ml) activated the contractions. Histamine (5.10(-9) g/ml) induced dilation of isolated segments and its higher concentrations produced the contractile responses. Serotonin and histamine were shown to induce the contractions of the depolarized smooth vascular muscle. It is suggested that serotonin activates the inflow of extracellular calcium ions and histamine activates both the inflow of extracellular and the cut-flow of the intracellular calcium ions.


[Differences between dose-effect curves for ethanol on locomotion and rearings in mice of various strains]. Ethanol (1--5 g/kg, per os) dose-response curve for locomotion in male mice of 4 strains (SHR, BALB/c, C3HA and C57BL/6) is characterized by a gradual rise up to the top (at 3 g/kg for all strains except C3HA, in which it was attained at 5 g/kg) and by subsequent decline. The dose-response curve for rearings gradually and gently slopes down to zero. The stimulant effect of ethanol (1.5--3 g/kg) can therefore be measured by an increase in lovomoyion. However, the action of various drugs (or other factors) on this effect has to be evaluated simultaneously from locomotion and rearings since a decrease in locomotion as a result of the curve fracture may indicate both diminution and enhancement of the stimulant effect of ethanol. Simultaneous decrease or increase in the rate of rearings suggests potentiation or diminution of the effect of ethanol, respectively.


[Effect of adrenoblockaders on vascular reactions in sinocarotid baroreflexes]. Blood pressure in the common carotid artery, the tone of the cerebral and femoral vessels were recorded by resistography in acute experiments on nonanesthetized cats (local anesthetics, listenon) with artificial respiration. The increased pressure in isolated carotid sinuses was accompanied by a decrease in arterial pressure and in the tone of the cerebral and femoral vessels. In both cases the reaction of the cerebral vessels was less pronounced as compared to that shown by the femoral vessels. The blocking of alpha-adrenoreceptors with phentolamine reduced or abolished completely the reactions noted. After beta-adrenergic blockade with obsidan these reactions persisted. The role of carotid baroceptors in the regulation of cerebral circulation under orthostatic collapse is discussed.


[Effect of leucine-enkephalin on the neuronal activity of the cerebral cortex]. In the experiments on non-anesthetised, flaxedilimmobilized rats it has been shown that the injection of leucin-enkephalin (150 micrograms) into the lateral ventricle of the rat brain induces different changes in the activity of 21 test neurons of the sensomotor zone of the brain cortex. Spike discharges of 5 neurons decreased, while those of 11 neurons increased. Naloxone (2 mg/kg, i. v.) completely prevented both inhibiting and activating effects of leucin-enkephalin after repeated injections of this pentapeptide. Leucin-enkephalin failed to change the activity of 5 neurons.


[Role of calcium in the mechanism of the change in vascular reactivity under the action of reserpine]. Reserpine induces an appreciable reduction of the calcium content in the segments of the distal aorta and rabbit femoral arteries incubated in a saline. These changes develop simultaneously to those in the reaction pattern of the vascular segment to direct electric stimulation (decline of constrictor responses and their subsequent replacement by relaxation). It is postulated that the decreased calcium content in the vascular wall may be one of the causes of altered vascular reactivity.


[Reversible endocytosis apparatus of the blood platelets]. The functioning of ganules of blood platelets participating in the reversible endocytosis reaction was investigated in rabbits. Eczocytosis was shown to be initiated by inducers of two types: proteolytic enzymes and compounds accumulated by the granules (biogenic amines, dyes, anesthetics and phenothiazines). Heparin inhibits thrombin-induced eczocytosis. During eczocytosis produced by accumulation of compounds by blood platelet granules, the cells lose their capacity for maintaining the aggregation state. The nature of blood platelet granules participating in the reversible endocytosis reaction is discussed.


[Glycosaminoglycans of the aorta in avitaminosis]. It has been shown that pregnancy specific beta 1-globulin (SBG) is found in the rat blood serum on the 6--7th day of pregnancy. SBG reaches the maximum by the end of pregnancy and is not detected already at the 3d--4th day after delivery. The placenta is the site of the SBG snythesis. Other organs of the pregnant rat are not able to incorporate radioactive aminoacids into the protein in vitro.


[Effects of injurying and restoring the body of mice with microwave (2400 MHz) irradiation]. In the experiments on 2200 mice the thresholds of powder density (PD) and time of irradiation were defined, when the death level did not exceed 0.1%. Dependence between the speed ratio of the destruction/regeneration and PD approached the exponential function. The functional dependences obtained quantitatively characterize the adaptive abilities of the mouse organism exposed to microwave irradiation.


[Change in the activity of specific and nonspecific immunity mechanisms in vitamin B1 deficiency]. The effect of thiamin deficiency on the immune response and activity of some mechanisms of natural immunity was studied in experimental mature rats. Thiamin deficiency was simulated by a single injection of hydroxythiamin (thiamin antagonists). Hydroxythiamin markedly decreased the complement activity, phagocytic activity of peripheral blood leucocytes, serum bactericidal activity as well as antibody production in response to sheep red blood cells. On the contrary, lysozyme activity increased. Vitamin B1 deficiency reduced 14C-leucine incorporation activity in the liver proteins.


[Morphological study of the neurosecretory hypothalamo-hypophyseal system and thyroid gland in intestinal carcinogenesis]. Pathomorphology of the neurosecretory hypothalamo-hypophyseal system and the thyroid gland of 150 rats of both sexes was investigated in intestinal carcinogenesis induced by 1.2-dimethyl hydrazine. Inhibition of the neurosecretory activity of paraventricular and supraoptical nuclei as well as atrophic changes in th: thyroid gland were found to be associated with the latent period of carcinogenesis. The arising of the intestinal tumor is accompanied by hypertrophy of neurons and their nuclei, by a decrease in the neurosecretory substance content and the thyroid gland tendency to return to normal. The tumor spreading provoked neuron hypertrophy and the reduction of the neurosecretory substance as well and pronounced atrophic changes in the thyroid gland.


[Physiological and reparative regeneration of the mitochondria]. The ultrastructure of mitochondria of hepatocytes in normal and pathological conditions was studied. It was shown that the process of regeneration of the ultrastructure of swollen mitochondria with a lucent matrix up to the normal state was completed in hepatocytes of the rat and chick embryos within one day. It was established that one of the ways of intraorganoid regeneration of mitochondria in hepatocytes of chick embryos and of mice after injections of CCl4 twice a week for 5 months was clasmatosis of the destroyed mitochondria fragments and their removal through the partially disintegrated exterior membrane of mitochondria followed by the membrane restoration. The process of mitochondrial regeneration after clasmatosis of its fragments was shown to require two days in the chick embryo hepatocytes.


[Effect of repeated cooling on the state of the adrenals and corneal epithelial proliferation in white rats]. The effect of repeated cooling on the adrenal glands, on the mitosis and the number of DNA-synthesising cells in the corneal epithelium of albino rats was studied. The animals were cooled by the contact method to 28 degrees C and were exposed to this temperature for an hour daily within 5 days. Strong activation of the suprarenal glands was observed: 2-fold increase in the suprarenal weight, 3-fold decrease in cholesterol content, 4-fold growth of 11-hydroxy-corticosteroid level in the blood and enhanced adrenaline excretion. The average number of mitoses in the corneal decreases 2-fold. Depression was not associated with the change in mitosis rate but with the inhibition of the cell entrance into mitosis in interphase. The level of pathological mitoses did not change. Chronic stress was not accompanied by the change in the number of DNA-synthesising cells or intensity of DNA-symthesis.


[Interaction of mitogenic lectins with lymphocyte plasma membranes]. It is shown that mitogenic stimuli from concanavalin A and phytohemagglutinin are summed up in the time. Under given experimental conditions each of the mitogens used did not induce mitogenesis when the interaction with lymphocytes continued for 14 and/or 20 hours. The results obtained are discussed from the point of view of the cell-to-cell interaction between the lymphocytes. It is assumed that the ability of the stimuli to sum up in the time underlies the nonspecific mechanism of defense from tolerance.


[Effect of short-term cerebral ischemia on the microcirculation in the rat mesentery]. The effect of brain ischemia, produced by constriction of the common carotid arteries, on microcirculation in the mesentery was studied in experiments on rats. The spreading and intensity of microcirculatory disturbances were dependent on duration of ischemia and post-ischemia. The state of systemic hemodynamics and microcirculation in the mesentery was compared. Possible mechanisms of the microcirculatory disturbances are discussed.


[Effect of armin on the ultrastructure of the neuromuscular synapse]. Alterations induced by the cholinesterase inhibitor armin (5.10(-7) g/ml) in the ultrastructure of motor nerve endings of the rat phrenic diaphragmal preparations at rest or electric stimulation of the nerve were studied. It was shown that armin at rest induced ultrastructural lesions in the endings similar to those in the control preparations during nerve stimulation. Electric stimulation did not produce additional changes in the ultrastructure of the neuromuscular junction under armin action. It is suggested that the disorder of the nerve ending function may be of importance in the mechanism of the blocking action of armin on the neuromuscular transmission.


[Electron microscopic study of the process of the removal of autogenous blood erythocytes beyond the limits of the subdural space]. The internal plate of the dura mater and arachnoidea of the dob brain was studied by electron microscopy after introducing 0.3--0.5 ml of the autogenous blood into the subdural space. The arachnoidea of the excretory channels and structural elements of the internal plate of the dura mater (cells of the internal covering layer, the collagen fibril and microfibril layer, the wall of the blood capillaries of the internal capillary network) involve the morphological substratum of the liquor-blood barrier-I between the liquor and blood of the blood capillaries of the internal capillary network of the dura mater. It was established that red cells of the subdural space penetrate the thickness of the dura mater, where they concentrate around blood capillaries of the internal capillary network, rather than penetrate into the arachnoidea.


Neutrophil kinetics in chronic neutropenia. Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratios determined from marrow sections. Postmitotic pool turnover was derived from the postmitotic pool size and transit time, the latter determined from 3H-thymidine neutrophil emergence time. Blood neutrophil kinetics were studied with 32P-diisopropylfluoophosphate-labeled autologous neutrophils. Mitotic pool size was basal or below basal in 12 of the 16 patients. The turnover of the post-mitotic neutrophils was subbasal in 6, basal in 7, and above basal in 3 patients. Blood neutrophil turnover was within the normal range in 8 patients and decreased in 8. The degree of ineffective granulocytopoiesis was assessed by comparing the relative size of the mitotic pool, postmitotic pool turnover, and blood turnover. On this basis, 13 of the 16 patients showed appreciable degrees of ineffective granulocytopoiesis. Ineffective neutrophil production occurred both early and late in neutrophil development. These studies indicate that most patients with chronic neutropenia without splenomegaly lack a proliferative marrow response to the neutropenia and suggest that ineffective granulocytopoiesis is a common feature of this disorder.


ABO compatibility and platelet transfusions of alloimmunized thrombocytopenic patients. With data on 91 alloimmunized thrombocytopenic patients and 389 donor-recipient pairs matched or selectively mismatched for HLA antigens, it was observed that ABO incompatibility significantly reduced the effectiveness of platelet transfusions. The mean 24-hr recovery of platelets from histocompatible donors and from donors selectively mismatched for cross-reactive HLA antigens was decreased by approximately 23% if the donor typed for blood group A and/or B not found in the recipient. Thus, the reduction in platelet recovery associated with ABO incompatibility is not of a magnitude that would contraindicate transfusion of ABO-mismatched platelets.


A case of generalized amyloidosis associated with cyclic neutropenia. A case of generalized amyloidosis associated with cyclic neutropenia is presented. A 24-yr-old female with cyclic neutropenia died from intestinal obstruction caused by necrosis and perforation of the small intestine. Post-mortem examination revealed generalized amyloidosis involving almost all organs. Amyloid deposits were prominent, especially in the alimentary tract, kidneys, spleen, and small blood vessels. As has been suggested in gray collie dogs with congenital cyclic neutropenia known to develop secondary amyloidosis in adulthood, an increase of antigenic stimulation during the intermittent bouts of acute infections may be one of the factors responsible for the development of secondary amyloidosis in this case. Although the association of amyloidosis and cyclic neutropenia in man has rarely been described, it is probable that amyloidosis is not a rare complication of human cyclic neutropenia, considering that patients with this hematologic disorder are chronically exposed to excessive antigenic stimulation.


Membrane receptors and their redistribution in lymphoproliferative disorders. Lymphoid cells from 20 patients with lymphoproliferative disorders, including chronic lymphocytic leukemia, hairy cell leukemia, Sezary syndrome, lymphoma, and lymphadenitis, were studied for redistribution of surface membrane immunoglobulins (SmIg) and concanavalin A (Con-A) receptors. Fluorescein-labeled polyvalent goat anti-human immunoglobulin and fluoresceinated concanavalin A were used as ligands. Results were similar with both ligands. The highest percentage of capping of ligand-membrane receptors was noted in mononuclear cells from patients with "hairy" cell leukemia: from 24% to 90%. These cells showed moderate to marked fluorescein activity and were able to cap within 15 min at 4 degrees C. Chronic lymphocytic leukemia cells showed a weak fluorescein stain with a very low percentage of cells (0%--16%) capping. Lymph node cells from patients with lymphoma demonstrated moderate to strong fluorescein activity with only an average of 3% of the cells capping; while lymphoid cells from patients with lymphaedenitis showed an average of 27.5% capping and moderate fluorescein activity. Capping of Con-A receptors in mononuclear cells from patients with Sezary syndrome was poor (0%--14%) with moderate fluorescein intensity. This report demonstrates difference in density and mobility of binding sites for SmIg and Con-A on the surface membrane of lymphoid cells from various subclasses of lymphoproliferative disorders. These differences may assist in the differential diagnosis and classification of these conditions.


The effect of aggregation and release on platelet prothrombin-converting activity. Platelets provide a procoagulant activity for the conversion of prothrombin to thrombin during normal hemostatis. This activity designated as platelet prothrombin-converting activity (PPCA) was monitored as rate of thrombin production in a two-stage assay using gel-filtered bovine platelets, factor Xa, and prothrombin. Expression of PPCA was not associated with ADP-induced release or platelet shape change but was associated with aggregation. Release of the contents of dense bodies, measured by release of 14C-5-hydroxytryptamine, was not required for expression of PPCA during platelet aggregation. During the PPCA assay, 5-hydroxytrypamine was released, but only after onset of thrombin production. Furthermore, the release of 5-hydroxytryptamine was retarded during the assay by the addition of 2 mM theophylline and 100 nM prostaglandin E1 without a comparable reduction in PPCA. In addition, 125I-factor-Xa was bound in greater amounts to platelets (aspirin-treated) after ADP-induced aggregation (without detectable release) than to unactivated control platelets. Finally, the PPCA of the ADP-activated platelets was saturated with respect to factors Xa and Va at less than 1 nM concentrations, indicating that the aggregation induced by ADP leads to the exposure of specific procoagulant sites by some process other than dense body secretion.


Fetal erythropoiesis and hemoglobin ontogeny in tail-short (Ts/+) mutant mice. Mutant Ts/+ fetuses are developmentally retarded as compared to normal +/+ littermates. Mutant fetuses have less total hemoglobin than do normal fetuses of the same gestational age. However, when compared to +/+ fetuses of similar body weight, Ts/+ fetuses have the appropriate amount of total hemoglobin, suggesting that the apparent anemia observed in mutant fetuses is most likely the result of delay in growth and development. Changes in proportions of embryonic hemoglobins during fetal development are similar in Ts/+ and +/+ fetuses at day 12 and later of gestation. Moreover, adult hemoglobin is detected in circulating primitive nucleated erythrocytes in the developmentally retarded Ts/+ mutant fetuses at about the same chronologic age as their +/+ normal littermates.


The hemostatic imbalance of plasma-exchange transfusion. Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.


Antibody-mediated acquired sideroblastic anemia: response to cytotoxic therapy. A 5 1/2-yr-old child developed severe anemia with erythroid hypoplasia and 50% ringed sideroblasts in his bone marrow. A serum inhibitor of erythropoiesis was demonstrated, utilizing syngeneic and autologous bone marrow in a plasma-clot culture system. The IgG fraction of the patient's serum effected similar suppression of erythroid colony formation. Prednisone therapy was ineffective, but following treatment with cyclophosphamide, normal erythropoiesis was established, ringed sideroblasts disappeared, and his serum no longer inhibited erythropoiesis in vitro. Cyclophosphamide was discontinued, and the patient has remained hematologically normal. This patient is an example of antibody-mediated sideroblastic anemia successfully treated with a cytotoxic drug.


Immune suppression of erythropoiesis in transient erythroblastopenia of childhood. Serum and IgG from four children with transient erythroblastopenia of childhood (TEC) was tested to see what effect it would have on development of erythroid colonies from bone marrow mononuclear cells. Serum and IgG specimens obtained at the time of diagnosis uniformly suppressed erythroid colony development from CFU-E. Washed bone marrow mononuclear cells from a child with TEC failed to grow in the presence of his own serum, but grew normally in the presence of isologous serum. Serum specimens obtained from patients after recovery from TEC had no effect on erythroid colony development. The anemia of TEC appears to be due to transient immune suppression of erythroid colony development.


Leukopheresis therapy of leukemic reticuloendotheliosis (hairy cell leukemia). Intensive leukopheresis has been valuable in the short-term palliation of chronic lymphocytic and granulocytic leukemias. A 47-yr-old man with refractory leukemic reticuloendotheliosis (hairy cell leukemia) manifested by anemia, thrombocytopenia, elevated peripheral leukemia cell counts, generalized lymph node enlargement, and leukemic infiltrative skin disease was treated with serial leukopheresis. Removal of approximately 7 X 10(11) peripheral leukemia cells resulted in marked clinical and hematologic improvement with resolution of enlarged lymph nodes and clearing of skin infiltrates. At the time of this reporting, more than 400 wk since the last leukopheresis, the patient continues to do well. The improvement in all blood counts, reduction in lymph node size, and clearing of skin lesions paralleled the reduction of peripheral leukemia cell load by leukopheresis, suggesting mobilization of leukemia cells from marrow, lymph nodes, and skin. Removal of large numbers of leukemia cells in hairy cell leukemia has the potential of achieving sustained clinical improvement and may be a useful alternative therapy for these patients.


Improvement of the red blood cell O2 release capacity by lipid vesicle-mediated incorporation of inositol hexaphosphate. Fusion of unilamellar lipid vesicles with red blood cells has been used to deliver entrapped inositol hexaphosphate (IHP) to the cells. Incorporated IHP tightly bound to hemoglobin produces a significant and lasting "right-shift" of the O2-binding curve of red blood cells. The O2 release capacity of red blood cells is increased by this method up to 270% of the normal value. The Bohr effect is increased so that carbon dioxide transport is also enhanced. The fine structure of the erythrocytes does not seem to be altered by the lipid vesicle incorporation.


Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen. Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.


[Antibody screening of commercially available immunoglobulins. Erythrocyte-, HLA- and autoantibodies (author's transl)]. A great number of commercially available immunoglobulins was screened for erythrocyte-, HLA- and autoantibodies. Isoagglutinin titers were in general low, hemolysins were not detected. No preparation was found to contain detectable amounts of autoantibodies versus nuclei, mitochondria, smooth muscle or parietal cells. Yet 7 out of 22 immunoglobulin charges contained irregular red cell antibodies, aside of polyspecific albumin reactive types in 5 cases a distinct anti-D. Only the preparation examined in 1975 contained polyspecific HLA-antibodies. 1977/78 all preparations for intravenous use were free from undesired antibodies, while those for intramuscular application were contaminated with irregular red cell antibodies 1975 as well as 1978. Because of their low strength these antibodies imply no clinical risk. Nonetheless an improvement of the official rules for the production and control of immunoglobulin preparations is inevitable to avoid damage caused by exceptional charges with extremely strong antibodies of this type.


[Value and interest of fine needle aspiration cytology in the follow-up of irradiated breast cancers (author's transl)]. Between 1968 and 1975, the authors studied at the Institut Curie the value of fine needle aspiration cytology in the follow-up of breast cancers, which have been previously treated with definitive irradiation (182 cases) or lumpectomy and post-operative irradiation (20 cases). The cytologic results have been compared to the pathologic aspects of the surgical specimens. The cytologic procedure was made when the tumor decrease was incomplete or too slow, or when, after a free interval, was noted in the irradiated breast a tissue reaction clinically and radiologically indefinite. The post-therapeutic investigation interested 202 cases of breast carcinoma. Compared to the histologic result, the cytologic results proved to be: -- identical. . . . . . . in 170 cases (84%) -- false benign . . . . . in 4 cases (2%) -- false malignant . . . .  in 4 cases (2%) -- insufficient cell material in 24 cases (12%) The high rate of correct cytologic diagnosis and the very low rate of wrong results prove the value and interest of the fine needle aspiration cytology for residual tumor masses or for recurrences in irradiated breast cancers.


[Immunological aspects of interactions between mother and foetus (author's transl)]. The essential information about materno-foetal immunologic interactions is reviewed. After a brief description of placental tissue (decidual cells from uterine mucosa, trophoblast), evidence that immunisation can be achieved by introduction of antigen into normal uterus is presented, although grafts performed in uterus of pregnant females are prolonged. Throphoblast cells bear specific antigens but histocompatibility antigens are usually not detectable at their surface. Proteins and cells from the foetus enter the maternal circulation and vice-versa, resulting in the production of antibodies against cell-associated foetal antigens by the mother. Some regulatory process of the maternal immune response have been investigated including blocking antibodies, maternal and foetal suppressor T cells. The biological roles of trophoblast and that of sustained microchimerism are underlined. Immunologic damage to the foetus can be produced only by inducing a cytotoxic cellular response before pregnancy. Possible analogies between immune responses to foetal allografts and tumors are discussed.


[Placental metastasis (author's transl)]. Rarity of placental metastasis is only apparent, for only few placentas of cancerous mothers have been examined histologically. However, it may show biological and immunological conditions which are characteristics of foeto-placental unit. During metastatic spread of solid tumors or hematologic malignancies in the mother, tumor emboli may be localized in intervillous spaces, without being real placental metastasis. Rarely tumor emboli are able to invade the struma of chorionic villi and produce true placental metastases: twelve such observations have been published, seven of which were malignant melanomas. It is even more exceptional that metastatic spread reaches the foetus. In most of the cases, it is thus protected against maternal cancer. This historical observation holds true. The fear of transplacental graft to the foetus is not an argument favorable of terminating a cancer associated pregnancy and foetal metastasis of maternal origin are not among the causes of congenital cancers in children.


[Epithelial displasias of the uterine cervix during pregnancy and its evolution (author's transl)]. During the ten year routing study of smears in 12,300 pregnant women, 180 cases of atypias of the uterine cervix were detected (1.46%). However, only 106 of these had sufficient follow up to allow us to draw useful conclusions. The lesions detected included: 1 invasive carcinoma, 71 atypical epithelial lesions and 34 border lesions of which 20 (58%) showed improvement and 14 (41%) remained unchanged. A comparative sutdy of 11,090 sexually active women who were on high oestrogen combination pills, revealed a similar incidence of cervical lesions (1.27%). The lesions included: 2 invasive carcinomas, 100 epithelial atypias and 38 border lesions of which 44 per cent showed improvement and 55 per cent remained unchanged. Cervical lesions were detected in only 0.5 per cent of women on law oestrogen combination pills. These results indicate that it is almost impossible for the cytologist to arrive at a diagnosis of carcinoma in situ in the pregnant woman or in the woman on the pill. No morphologic guide exists to help establish a prognosis. Only follow up study of the cervical lesion is valuable in this regard. Any lesion remaining 6 to 12 months after the delivery should be removed.


[Fetal risk of cancer chemotherapy (author's transl)]. The risks of embryonic, fetal, gondal damage of cancer chemotherapy are reviewed. Contrasting with the numerous malformations seen in laboratory animals, the teratogenic risk is low in man. Methotrexate is really dangerous during the first trimester of pregnancy. In malignant haematological diseases and solid tumours, the prognosis of the disease is the essential target but the use of immuno-suppressive drugs in non-malignant diseases is hazardous before 40 years of age. All the investigations show that alkylating agents injure the gonads. Young women should be avised to use contraceptives. The future of children born after administration of anti cancer drugs is uncertain. Sterility, carcinogenic risk, mutation, teratogenetic effects in future generations cannot be ruled out.


[Fertility and the progeny of children surviving cancer treatment (author's transl)]. Little is known about the late effects of damage to the gonads in children treated for cancer. This investigation requires a prolonged surveillance. Radiotherapy sterilizes the ovaries above a dose of about 500 rads in an adult. Therefore, to protect at least one ovary in partial irradiation of a child's abdomen in mandatory whenever possible, either by restriction of the irradiated volume, or transposition of the ovary. Combined chemotherapies do not seem to inhibit endocrine function but it is too early to appreciate the effects of different combinations of drugs on reproductive function in girls. In boys, alkylating drugs cause an oligo or azoospermia, either temporary or permanently. The genetic risks in the descendants of children treated for cancer are still unknown.


[Invasive carcinoma of the uterine cervix associated with pregnancy (author's transl)]. In 4,396 invasive cervix carcinomas treated between 1934 and 1973, 52 occurred during pregnancy or within 3 months post partum. Stages I were more frequent among pregnant women (24%) than without pregnancy (8%) and stages II were as frequent (50%). Stages I and II were more frequent among pregnant women treated during 1963-1973 than 1934-1962. The 3 years' survival rate, all stages combined, for pregnant women (42%) was lower than for matched control non-pregnant women (62%). This difference was significant at P = 0.05, but at 5 and 10 years, the difference was not significant for patients treated between 1963-1973. At an equal stage, survival rate seemed lower for stages IIb and III (P = 0.02 for these two stages combined.) The lymph node involvement was not more frequent; the decrease of global survival rate could be associated to some factors and especially incomplete therapy and an under-estimation of the tumor extension because of the pregnancy. Our results are compared to the data literature and therapeutic schedules are discussed.


The development and evaluation of a small ready-reference library collection for a rural practice: a case study. A demonstration core collection of twenty-four ready-reference sources and five journals was selected cooperatively by a solo practitioner in rural Menifee County, Kentucky, and the University of Kentucky Medical Center Library Field Librarian to fit the ready-reference and current awareness information needs of a primary care solo rural practice in eastern Kentucky. The collection selections were systematically assessed by the physician to determine their utility in filling the practitioner's information needs with regard to his particular situation in terms of medical experience and level of training, available library and educational resources, and the type of health problems seen in his practice. This assessment showed that the Rural Demonstration Library Collection completely filled the information needs of the physician 66% of the time materials were consulted and filled his immediate information needs either completely or partially 82% of the time the collection was searched. This demonstration has shown that, under a specific set of circumstances, a librarian and a solo rural practitioner can effectively work together in identifying health sciences materials which fit the information needs of a solo rural practitioner. It suggests that cooperation between a librarian and a physician is important in meeting information needs.


Classification of support staff in a consortium medical library: a case study. A representative committee of Houston Academy of Medicine-Texas Medical Center Library staff and faculty, under the direction of the library administration, successfully redesigned a job classification system for the library's nonprofessional staff. In the new system all nonprofessionals are assigned to one of five grade levels, each with a corresponding salary range. To determine its appropriate grade level each job is analyzed and assigned a numerical value using a point system based on a set of five factors, each of which is assigned a relative number of points. The factors used to measure jobs are: education and experience, complexity of work, administrative accountability, manual skill, and contact with users. Each factor is described according to degrees, so that a job can be given partial credit for a factor. An advisory staff classification committee now participates in the ongoing administration of the classification system.


MLA Certification by examination under the 1964 code: a survey of 1975-1976 participants. The increased attention being given to an examination in the Medical Library Association certification process prompted a study of a group taking the examination under the old (1964 revision) code. Completed questionnaires were received from fifty-three of the sixty-five persons who took the examination in 1975 and 1976. Backgrounds of individuals varied, especially in years of experience. The majority of those responding had worked in both health sciences and other libraries. Experience in health sciences libraries was reported by 92% of those replying. A number of reasons for seeking MLA certification were given. Problems in being able to take MLA-approved courses prompted the choice of the examination process. Preparation for the examination was chiefly by self-directed study. Continuing education courses were considered as of greater value for professional development than as help on the examination. The examination was rated "moderately difficult" by 57% of those responding. Opinions were expressed on the skills and areas of expertise which were considered by this group to be important in an examination for professional competence.


Mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leucocytes. Hydrocortisone (10 microgram/ml) greatly inhibits the prostaglandin release by rat peritoneal leucocytes phagocytosing killed bacteria. The inhibition, which occurs after an initial latency of 30 min, is completely reversed by either actinomycin D (0.5 microgram/ml) or cycloheximide (1 microgram/ml). Since these antibiotics are known inhibitors of DNA-dependent RNA synthesis and protein synthesis respectively, it appears that the mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leucocytes involves stimulation of transcription and induction of protein synthesis.


The effect of intracerebroventricular administration of methionine-enkephalin on the stress-induced secretion of corticosterone in mice. Ether stress or intracerebroventricular (i.c.v.) administration of saline, met-enkephalin, or naltrexone raised plasma corticosterone levels in mice. The response to ether stress was abolished by a preceding ether stress or by pretreatment with i.c.v. saline or naltrexone. However, following i.c.v. met-enkephalin, plasma corticosterone was significantly elevated by ether stress, the effect being blocked by simultaneous injection of met-enkephalin and naltrexone. Met-enkephalin appears to prevent fast-feedback inhibition of the hypothalamus-pituitary-adrenal system.


Pharmacological effects of phosphatidylserine liposomes: regulation of gylcolysis and energy level in brain. 1 The accumulation of glucose in the brain produced by the administration of phosphatidylserine liposomes into mice has been studied by measurement of the cerebral contents of glycolytic intermediates and high-energy compounds. 2 With a normal supply of oxygen to the brain, inhibition of glycolysis is indicated mainly at the phosphofructokinase step. The ratio of glucose-6-phosphate to fructose-1,6-diphosphate increased, whereas the levels of pyruvate and especially lactate decreased. 3 Under conditions of cerebral ischaemia, the administration of phosphatidylserine delays glycogen mobilization and ATP use. As a consequence of decreased energy utilization, the brain adenylate energy charge remains at a high level. 4 It is concluded that the phosphatidylserine-induced glucose accumulation in the brain is due to reduced energy expenditure and therefore to a decrease in carbohydrate consumption. The inhibition of glycolysis by the high level of adenylate energy charge is probably the control mechanism explaining the decreased carbohydrate utilization.


Stimulation and inhibition of the sodium pump by cardioactive steroids in relation to their binding sites and their inotropic effect on guinea-pig isolated atria. 1 The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea-pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined. 2 The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain. 3 The increase of KCl concentration from 2.7 to 12 mM decreased Nai in untreated atria and displaced ouabain dose-effect curves to the right. 4 ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration. 5 The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively. 6 The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high-affinity sites whereas the capacity of the other sites remained unchanged. 7 The results confirm the existence of two specific binding sites for ouabain in guinea-pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.


Actions of prostaglandin precursors and other unsaturated fatty acids on conduction time and refractory period in the cat heart in situ. 1 The effect of arachidonic, dihomo-gamma-linolenic, linoleic, alpha-linolenic and oleic acid, given by intravenous infusion, on conduction time and functional refractory period have been studied in the cat heart in situ. 2 The prostaglandin precursors, arachidonic acid and dihomo-gamma-linolenic acid, prolonged the conduction time and the functional refractory period. Linoleic acid was also effective but to a lesser degree. alpha-Linolenic acid and oleic acid showed no or only a weak effect in thie respect. 3 Pretreatment was indomethacin diminished or abolished the actions of the three effective fatty acids but not those of prostaglandin E2. 4 The results suggest that the effects of prostaglandin prostaglandin precursors on conduction time and refractory period are responsible for their antiarrhythmic effectiveness and that these effects are attributable to their endogenous conversion into prostaglandins.


Characterization of ultraviolet light-induced relaxation of the isolated duodenum of the rat. 1 Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation. 2 The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences. 3 Changes in the ionic environment of the tissue showed that NA+ and Ca2+ were essential for the photorelaxation. K+ depolarized-tissue did not show the photoresponse. 4 The presence of the metabolic inhibitors, iodoacetic acid, 2,4-dinitrophenol, sodium fluoride, sodium azide or potassium cyanide, abolished the photorelaxation response. 5 It is proposed that the photorelaxation of the tissue resulted from the liberation of metabolic energy following NO2 ion-dependent absorption of u.v. light energy, which in turn, interfered with the Na+ ion movement across the cell membrane.


The effects of H1- and H2-receptor agonists and antagonists on total lung resistance, dynamic lung compliance and irritant receptor discharge in the anaesthetized dog. 1 The effects of histamine and 4 methylhistamine (i.v.) alone, and in the presence of chlorpheniramine or cimetidine, on total lung resistance (RL), dynamic lung compliance (Cdyn) and irritant receptor activity have been studied in dogs anaesthetized with chloralose. 2 Histamine produced dose-related increases in RL and irritant receptor activity with associated falls in Cdyn which were blocked by chlorpheniramine but unaffected by cimetidine. 3 4 Methylhistamine produced small insignificant changes in RL and Cdyn and small significant increases in irritant receptor activity which were reduced with chlorpheniramine but unaffected by cimetidine. 4 The results suggest that histamine increases irritant receptor activity, either directly or indirectly, via H1-receptors.


Effect of 5-hydroxytryptamine on protein synthesis in gastrointestinal and other tissues and on serum gastrin concentrations in rats. 1 The effect of 5-hydroxytryptamine (5-HT) on protein synthesis in the gastrointestinal tissues as well as in the liver, heart and brain was studied by measuring [3H]-leucine incorporation into total tissue protein in vivo in rats. 2 A single injection of 5-HT (10 mg/kg) produced a marked inhibition (45 to 65%) in protein synthesis in the stomach (oxyntic gland area), intestine (jejunum + ileum), colon and brain, but not in the liver and heart. 3 Dose- and time-dependent studies of 5-HT-induced changes in protein synthesis in the stomach of fed rats revealed that the maximal inhibition of about 65% occurred 1 h after a dose of 12.5 mg/kg. 4 Animals deprived of food for 24 h differed from their fed counterparts only in the degree of responsiveness, in that a greater inhibition (75%) of [3H]-leucine incorporation into total protein of the stomach was observed 30 min after 5-HT injection. 5 Pretreatment of animals with methysergide (0.25 mg/kg) essentially abolished the 5-HT-mediated inhibition of protein synthesis in the stomach. 6 Serum gastrin concentration in fasted animals remained slightly elevated during the initial period of 5-HT treatment (up to 1 h). 7 The results demonstrate that in certain tissues, 5-HT markedly inhibits protein synthesis. The inhibition in protein synthesis in the gastrointestinal tract cannot be attributed to changes in the concentration of gastrin.


Evidence for an indirect cholinergic regulation of blood flow in the hypothalamus of conscious rabbits. 1 The effects of methacholine, atropine and adrenoceptor blockade on hypothalamic blood flow (HBF) were measured in conscious rabbits. 2 A dose of 1 microgram methacholine increased HBF while smaller and larger doses had no significant effect. 3 The vasodilatation induced by methacholine was blocked by atropine and by chemical sympathectomy of the hypothalamus with 6-hydroxydopamine. 4 The vasodilatation was reversed by propranolol but was not affected by phenoxybenzamine. 5 These results suggest that the vasodilator action of muscarinic receptor agonists on hypothalamic resistance vessels depends upon the integrity of a noradrenergic system, and is mediated via beta-adrenoceptors.


Relationship between accumulation, storage and overflow of noradrenaline in the rat salivary gland after chronic treatment with guanethidine. 1 The effect of guanethidine on the endogenous noradrenaline (NA) content, accumulation and overflow of [3H]-noradrenaline ([3H]-NA) in the rat salivary gland was examined at various times after drug administration. 2 Twenty-four h after a single injection of guanethidine (1 or 10 mg/kg s.c.), the respective values for the endogenous NA content and for the accumulation and overflow of [3H]-NA were approximately 55, 85, 30%, and 15, 55, 10% of the controls. 3 Although [3H]-NA accumulation had returned to control levels within 48 h after the dose of 10 mg/kg guanethidine, the overflow of [3H]-NA evoked by electrical stimulation or excess potassium (K+) remained depressed. 4 After the low or the high dose of guanethidine, the NA content of the salivary gland was restored to about 50% of the normal value between 4 to 24 and 48 to 72 h, respectively. 5 The accumulation of [3H]-NA was inhibited by about 75% by cocaine. The same degree of inhibition was obtained 4 h after 10 mg/kg guanethidine. In these experiments phenoxybenzamine did not reduce the residual (25%) uptake. 6 The reasons for differential rates of recovery of the endogenous NA content and the storage of [3H]-NA after guanethidine are discussed.


Effects of beta 2-adrenoceptor stimulation on cardiac metabolism in the conscious dog. 1 The effects of the beta 2-adrenoceptor stimulant, salbutamol, on cardiac metabolism have been studied in conscious mongrel dogs. The potential effects of anaesthesia on the study of cardiac metabolism have been avoided by prior implantation of arterial (A) and coronary sinus (CS) catheters for blood sampling and a central venous catheter for infusion. Extraction of substrates for myocardial energy metabolism (CA-CS) was assessed 3 to 24 days post-operatively. A 100 micrograms bolus of salbutamol was given followed by an infusion of 3 micrograms/min for 1 h. 2 Although heart rate increased significantly from 106 to 165 beats/min, fractional extraction of oxygen tended to fall from 84% to 77%. Thus an increase in coronary blood flow rather than in oxygen extraction must have maintained an oxygen supply commensurate with the salbutamol-induced tachycardia. 3 Neither CA-CS glucose nor fractional glucose extraction altered significantly during salbutamol infusion despite increases in arterial concentration (CA) of glucose and arterial insulin immunoreactivity and a decrease in CA of free fatty acids (FFA). This suggests that an insulin-antagonistic action accompanies the infusion of salbutamol. 4 The fractional extraction of lactate increased during salbutamol infusion. In part, this may have been a reflection of a decreased myocardial extraction of FFA with salbutamol in this model.


Cardiovascular responses produced by the injection of dopamine into the cerebral ventricles of the unanaesthetized dog. 1 The injection of dopamine (100 to 500 microgram) into the cerebral ventricles (i.c.v.) of 10 unanaesthetized dogs produced a dose-dependent increase in arterial blood pressure and heart rate. The dogs licked, swallowed, sometimes vomited and became sedated. 2 Autonomic ganglion blockade with hexamethonium (10 mg/kg i.v.) abolished cardiovascular responses to i.c.v. dopamine, indicating that dopamine was exerting its effect within the central nervous system. 3 The dopamine receptor antagonists, haloperidol (500 microgram), chlorpromazine (200 micrograms) and ergometrine (500 micrograms), each given i.c.v., sugsequently abolished the cardiovascular responses to dopamine. 4 Pretreatment with either the beta-adrenoceptor antagonist, propranolol (600 microgram) or the alpha-adrenoceptor antagonist, phentolamine (1 mg) given i.c.v. had no significant effect on the response to dopamine. 5 It is suggested that dopamine injected into the cerebral ventricles of the unanesthetized dog causes hypertension and tachycardia by activating central dopamine receptors.


The effects of disopyramide phosphate on early post-coronary artery ligation dysrhythmias and on epicardial ST-segment elevation in anaesthetized dogs. 1 The antidysrhythmic, haemodynamic and metabolic effects of intravenously administered disopyramide phosphate (1 to 5 mg/kg) have been studied in greyhounds, anaesthetized with trichloroethylene. 2 In doses of 2.5 and 5.0 mg/kg, disopyramide significantly reduced the ventricular dysrhythmias that occur in the initial 30-min period following acute coronary artery ligation. None of the disopyramide-treated animals developed ventricular fibrillations. 3 The metabolic consequences of coronary artery ligation, assessed by local coronary venous sampling from the ischaemic area, were not modified by disopyramide except that K+ egress was prevented. 4 There was evidence for substantial disopyramide-induced myocardial depression (decreased cardiac output and left ventricular dP/drmax with elevated ventricular filling pressure and pulmonary oedema and shunting) and it is suggested that great care be taken when the drug is administered intravenously in conditions where cardiac function is already compromised. Disopyramide also reduced myocardial blood flow. 5 In chloralose-anaesthetized mongrel dogs, disopyramide (2.5 mg/kg) significantly reduced the ST-segment elevation (assessed from epicardial recordings) that resulted from short (3 min) coronary artery occlusions. This could indicate a reduction in the extent and severity of myocardial injury or simply reflect decreased K+ efflux (since locally administered K+ itself increased ST-segment elevation).


An analysis of the negative inotropic action of somatostatin. 1 Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea-pigs.2 SS was completely inactive in rat and rabbit auricles but exerted a dose-dependent, negative inotropic effect in guinea-pig auricles in concentrations between 1.5 x 10(-8) to 1.2 x 10(-6) M.3 The negative inotropic effect of SS (6.0 x 10(-8) and 3.0 x 10(-7) M) was not inhibited by a mixture of antagonists containing practolol (7.9 x 10(-6) M), phentolamine (3.5 x 10(-7) M), methysergide (2.8 x 10(-7) M), diphenhydramine (3.9 x 10(-5) M), cimetidine (4.0 x 10(-5) M) atropine (3.4 x 10(-7) M) and indomethacin (1.4 x 10(-5) M).4 The negative inotropic effect of SS was greatly potentiated by reduction in the Ca(2+) concentration of the medium from 5.0 to 1.25 mM.5 On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea-pig auricles.6 SS (6.0 x 10(-8) and 6.0 x 10(-7) M) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea-pig but not in rat auricles.7 The inhibitory action of SS against NT was independent of its negative inotropic action.8 These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea-pig atria. The interaction between SS and its receptor may cause a decreased Ca(2+) diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed.


The effect of some general anaesthetics on the surface potential of lipid monolayers. 1 This study sought to investigate the report by Ginsberg (1978) that 0.7 M ethanol brought about a + 100 mV change (DeltaDeltaV) in the surface potential of glyceryl monooleate (GMO) monolayers formed on KCl, although he predicted that a DeltaDeltaV of -10 mV should have been found.2 The effect of general anaesthetics such as n-alkyl alcohols and pentobarbitone on surface potential (DeltaV) and surface tension (gamma) of lipid monolayers formed on 145 mM KCl from either glyceryl monooleate (GMO) or phosphatidyl choline (PC) was examined with an Americium-241 air electrode assembly (DeltaV) and a platinized platinum dipping plate and force balance (gamma).3 It was found that, as predicted by Ginsberg (1978), addition of 0.7 M ethanol to the aqueous phase bathing either PC or GMO monolayers brings about a negative-going change in interfacial potential (DeltaDeltaV).4 The magnitude of DeltaDeltaV is dependent in a linear fashion on ethanol concentration.5 Longer chain length alcohols up to n-decanol also bring about a negative going change in DeltaDeltaV, and the dependence of DeltaDeltaV on anaesthetic activity, with respect to increasing chain length of anaesthetic, is consistent with Traube's law.6 Pentobarbitone added to the aqueous phase bathing the monolayer also elicits a negative DeltaDeltaV, a finding which rules out the possibility of adsorption of the volatile alcohols to the measuring electrode.7 The findings are discussed in terms of the proposition that increasing disorder in an array of fixed dipoles, such as might occur in a bilayer exposed to anaesthetic, would result in a lowering of the electrostatic barrier to the predominantly impermeable cation.


Responses to DL-ibotenic acid at locust glutamatergic neuromuscular junctions. 1 The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied L-glutamic acid and DL-ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.2 Iontophoresis of L-glutamate to junctional sites produced transient depolarizations. Ibotenate applied iontophoretically to these sites usually evoked small hyperpolarizations which probably resulted from the activation of glutamate H-receptors on the extrajunctional membrane surrounding the junctions. However, at a minority ( approximately 20%) of junctions, ibotenate iontophoresis evoked transient depolarizations.3 Iontophoretically applied glutamate desensitized the ibotenate receptors, and vice versa. In experiments performed at junctional sites at which ibotenate depolarizations were absent, ibotenate had no effect on the responses to glutamate.4 Glutamate and ibotenate junctional currents had similar reversal potentials, measured under voltage-clamp, suggesting that the ionic bases for these currents are identical.5 It is proposed that the excitation caused by ibotenate results from the activation of receptors for extended L-glutamate and that these receptors co-exist on the post-junctional membranes of locust excitatory nerve-muscle synapses with ibotenate-insensitive glutamate receptors activated by glutamate in partially folded conformation.


Decreased binding of drugs and dyes to plasma proteins from rats with acute renal failure: effects of ureter ligation and intramuscular injection of glycerol. 1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37 degrees C. 2 Acute renal failure induced by bilateral ligation of the ureters produced a greater than threefold increase in the unbound fraction of o-methyl red relative to normal rat plasma. Unbound dye concentration in plasma from sham-operated control rats was also significantly increased but to a lesser extent. 3 Glycerol-induced acute renal failure produced a significant increase in the unbound fractions of o-methyl red, methyl orange, bromocresol green (BCG), 2-(4'-hydroxybenzeneazo) benzoic acid (HABA), phenytoin and salicylic acid. A marginally significant increase in unbound warfarin concentration was observed. 4 Glycerol-induced renal failure had no effect on total plasma protein concentration and experiments with o-methyl red and salicylic acid indicated that a direct effect of glycerol was not responsible for the diminution of binding. 5 Glycerol-induced acute renal failure, which produced decreases in drug and dye binding similar to those reported for human uraemic plasma, provides a convenient non-surgical animal model for the investigation of this phenomenon.


Rapid absorption from the urinary bladder of a series of n-alkyl carbamates: a route for the recirculation of drugs. 1 The rate of loss of a series of n-alkyl carbamates from the lumen of the urinary bladders of female rats has been studied. 2 The rate of loss obeys first order kinetics and was not affected by water flux across the bladder wall nor by binding of the carbamates to it. 3 The rate of loss of octyl carbamate was reduced by about 76% by the presence of 5% Tween 80. Histological evidence indicates that this may be due to the formation of a thin luminal lining which may be adsorbed Tween 80 or mucopolysaccharide material. 4 The absorption rate of the carbamates was limited by their hydrophilicity but reached a plateau for the more lipophilic homologues with a half life for loss of approximately 10 min. 5 The implications of these results with regard to the recirculation of unmetabolized drugs and hydrolysed conjugates of drugs, the systemic absorption of intravesically applied cancer chemotherapeutic agents and bladder wall permeability to carcinogens are discussed.


Glutamate as the neurotransmitter of cerebellar granule cells in the rat: electrophysiological evidence. 1 Glutamate and the excitatory aminoacid antagonist, alpha-aminoadipic acid (alphaAA), have been applied by microiontophoresis to Purkinje cells in the rat cerebellum. 2 Glutemate produced excitation of Purkinje cells and alpha AA selectively reduced that excitation without affecting responses to acetylcholine or hydrogen ions. 3 Monosynaptic spikes were evoked in Purkinje cells by stimulating the parallel fibres. alpha AA had little effect on these spikes when applied alone. 4 When the Purkinje cell excitability was reduced by the iontophoresis of gamma-aminobutyric acid, alpha AA then produced railure of the monosynaptic spike on 10 of 13 Purkinje cells, in doses shown to be selectively antagonistic towards aminoacids. 5 These results support neurochemical evidence that glutamic acid may be the neurotransmitter released by granule cell parallel fibres.


On the distribution of [met5]- and [leu5]-enkephalins in the brain of the rat, guinea-pig and calf. 1 By means of a highly sensitive radioimmunoassay, the content of [met5]-enkephalin (ME) and [leu5]-enkephalin (LE) was measured in various regions of the rat, guinea-pig and calf brain. Provisions were made to differentiate ME from LE by the use of cyanogen bromide (CNBr) to destroy methionine, the carboxy terminal amino acid in the ME sequence. This allows for correction of possible errors due to the cross-reactivity of the ME to the LE antiserum. Evidence is presented to demonstrate that the specific radioimmunoassay combined with the CNBr technique is a valid method to measure LE and ME content in crude tissue extracts. 2 In all the species studied, enkephalins appeared to be highly concentrated in the striatum and hypothalamus while very low amounts were found in the cerebe-lum and hippocampus. 3 Although the ratio between ME and LE content varied from area to area, the ME content in every region of the rat, guinea-pig and calf brain was more than 4 fold greater than that of LE.


Effects of noradrenaline and carbachol on temperature regulation of cold-stressed and cold-acclimated rats. 1 Noradrenaline (20 micrograms) and carbachol (1 microgram) injected into the anterior hypothalamus of rats at an ambient temperature of 23 degrees C evoked significant falls in core temperature and increases in tail temperature. 2 When rats were cold-stressed (4 degrees C for 90 min) or cold-acclimated (4 degrees C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature. 3 Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non-esterified fatty acid (NEFA) concentrations in control, acutely cold-stressed and cold-acclimated rats. 4 Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4 degrees C for 1 to 28 days, glucose oxidation rate of both cold-stressed and cold-acclimated rats was significantly greater than in rats at 23 degrees C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.


Improved insulin receptor assay: effects of an antidiabetic sulphonylurea on liver membrane insulin receptors from obese hyperglycaemic mice. 1 A simple assay of liver membrane insulin receptors is described, under conditions which apparently stabilized the insulin-receptor complex. The receptor population was measured in the presence of physiological doses of radioactive hormone under conditions which minimized negative co-operativity effects. 2 Equilibrium between receptor and hormone was attained in vitro within 60 min of incubation time at 13 degrees C with no apparent loss of binding sites after 3 h of incubation. 3 Liver membranes from lean mice possessed 8.8 times the receptor number per mg membrane protein measured in membranes from obese hyperglycaemic (ob/ob) littermates. After treatment of ob/ob mice with ARDF-26 (Gliquidon; Boehringer Ingelheim Ltd) the concentration of liver membrane insulin receptors was increased 5 fold.


Relationship between inhibition of acetylcholinesterase and response of the rat phrenic nerve-diaphragm preparation to indirect stimulation at higher frequencies. 1 Rat isolated diaphragm preparations were stimulated indirectly either intermittently at 20, 50 or 100 Hz or continuously at 0.2 Hz.2 Addition of 1.8 muM paraoxon (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which undergoes slow spontaneous reactivation) for 5 min to the organ bath produced a failure of the muscle to maintain tetanic tension (tetanic fade, Wedensky inhibition) and potentiated the neuromuscular blocking activity of exogenous acetylcholine. The rates of recovery from both these effects were recorded.3 In a series of experiments with dyflos (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which does not undergo spontaneous reactivation) the relationship between functional acetylcholinesterase activity and neuromuscular blocking activity of exogenous acetylcholine was also determined.4 From the data obtained, the relationship between functional acetylcholinesterase activity and tetanic fade was calculated. These calculations show that (i) a considerable reduction in functional acetylcholinesterase activity is required before the diaphragm loses its ability to respond with a sustained tetanus to indirect stimulation at higher frequencies, (ii) the minimum (critical) level of functional acetylcholinesterase activity required for a normal tetanic response is directly related to the frequency of stimulation and (iii) once functional acetylcholinesterase activity has been reduced to the critical level, a very small further reduction leads to a complete tetanic fade.5 The meaning of functional acetylcholinesterase assays and of conclusions which can be drawn from them, is discussed.


Relaxant response of goat trachea to 5-hydroxy-tryptamine mediated by D-tryptamine receptors. 1 Goat isolated trachea contracted in response to carbachol, histamine and 2-pyridylethylamine (an H(1)-receptor agonist) and relaxed after application of isoprenaline. 5-hydroxytryptamine (5-HT) and phenylephrine.2 Mepyramine, a selective H(1)-receptor antagonist, blocked histamine- and 2-pyridylethylamine-induced contractions. In high doses it also exhibited some nonspecific antagonism to carbachol. After H(1)-receptor blockade, 4-methylhistamine and dimaprit (specific H(2)-agonists) relaxed the carbachol-contracted trachea.3 Propranolol, a beta-adrenoceptor blocker, antagonized relaxation in response to isoprenaline and phenylephrine. In high doses, it produced a reversal of the phenylephrine response.4 Indomethacin enhanced contractions in response to carbachol and histamine.5 Relaxation to 5-HT was not affected by propranolol, indomethacin, metiamide or cimetidine (H(2)-blockers). These findings appear to exclude the involvement of adrenergic, prostaglandinergic and H(2)-histaminergic mechanisms in the mediation of this response.6 Atropine potentiated 5-HT-induced relaxations. This suggests the participation of a ;masked' excitatory cholinergic mechanism.7 Methysergide, dibenamine and dibenzyline selectively antagonized or reversed 5-HT-induced relaxation. Dibenamine and dibenzyline enhanced relaxations to isoprenaline.8 This investigation showed (i) a relaxant response of goat trachea to 5-HT, mediated via D-muscular tryptamine receptors; (ii) a small population of excitatory M-neuronal tryptamine and alpha-adrenoceptors; and (iii) predominance of H(1)-histamine receptors in the goat trachea.


A study of the muscarinic receptor by gel electrophoresis. 1 Muscarinic receptors from the brain of rat, guinea-pig and frog have been labelled with tritiated propylbenzilylcholine mustard ([3H]-PrBCM). 2 After solubilisation and sodium dodecyl sulphate (SDS)-polycarylamide gel electrophoresis a single radiolabelled peak was seen which was completely suppressed when labelling was carried out in the presence of 10(-6) M atropine. The results suggest the presence of a single polypeptide chain with a molecular weight of similar to or approximately 80,000. 3 In the case of intestinal smooth muscle multiple labelled peaks were found. Precautions against proteolysis led to the identification of a major peak with a molecular weight in the region of 80,000.


Single pulse stimulation of guinea-pig vas deferens and the presynaptic receptor hypothesis. 1 The effect of phenoxybenzamine on the efflux of [3H]-noradrenaline and the mechanical response to single pulse excitation of superfused guinea-pig vas deferens was determined to examine the validity of the currently accepted hypothesis of a presynaptic negative feedback system on adrenergic nerve terminals. 2 The adrenoceptor antagonist enhanced both the outflow of tritium and the mechanical response to single pulse stimulation. The efflux of labelled material and the responses to 4 pulses were also enhanced, as expected. 3 Blockade of neuronal and extraneuronal uptake did not by itself increase nerve-induced outflow or the mechanical response nor dated within the framework of a hypothesis that proposes that the enhancement of response and tritium efflux by phenoxybenzamine results from blockade of a feedback system whereby noradrenaline released by previous impulses inhibits its own subsequent release.


Noradrenaline release in rats during prolonged cold-stress and repeated swim-stress. 1 Plasma noradrenaline concentration in rats was measured during prolonged cold-stress and repeated swim-stress. 2 Cold exposure for 6 h caused a rise in plasma noradrenaline which reached a peak at 4 h. 3 Administration of desmethylimipramine and normetanephrine to block neuronal and extra-neuronal uptake of noradrenaline raised plasma noradrenaline concentration without changing the pattern of the response to cold exposure. 4 Repeated cold exposure on subsequent days produced no change in the pattern of plasma noradrenaline concentration. 5 Five successive 1-min swims at 30-min intervals caused a rise in plasma noradrenaline concentration which was maximal after the third swim. 6 It is suggested that prolonged and repeated activation of sympathetic nerve terminals leads to a decline in noradrenaline release.


Effect of guanidine on release of noradrenaline from the perfused spleen of the cat. 1 Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected. 2 NA output was doubled at low concentrations (1 to 2 mM) of guanidine, but maximal effect was obtained at 4 mM. At 10 mM, spontaneous release was occasionally observed. 3 The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mM calcium-Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mM, but maximum output was obtained at 2.5 mM. 4 Guanidine had no effect on the recovery of intra-arterially infused NA. 5 The effects of guanidine and tetraethyl-ammonium (TEA) on NA release at 5 Hz were additive. 6 Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz. 7 Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation. 8 It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding of calcium.


The release of prostaglandin E2 from the skin of the plaice, Pleuronectes platessa L. 1 A fungal extract which produces a cutaneous hypersensitivity reaction in the plaice, Pleuronectes platessa L., was incubated in vitro with the skin of this teleost fish. Samples of incubation media were assayed for smooth muscle stimulating activity. 2 Prostaglandin E2 was identified by bioassay, thin-layer chromatography, ultraviolet absorption spectroscopy and gas chromatography--mass spectrometry. Release from challenged skin was maximum after 60 min incubation. 3 Analysis of the fatty acid composition of plaice skin showed that although arachidonic acid was present (3% of total fatty acids), the precursor of prostaglandin E3, eicosapentaenoic acid contributed 9% of total. 4 Indomethacin (50 mg/kg i.p) did not inhibit the erythema induced by the fungal extract, whilst a dose of 1 mg/kg maximally inhibited prostaglandin release from skin on incubation in vitro. 5 It is concluded that prostaglandins do not have an exclusive role in the mediation of the hypersensitivity reaction.


Backward walking and circling: behavioural responses induced by drug treatments which cause simultaneous release of catecholamines and 5-hydroxytryptamine. 1 The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+)-amphetamine (5 mg/kg) and either p-chloroamphetamine (2--5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.


Temperature coefficients of affinity and entropies of adsorption from enantiomeric pairs of compounds acting at muscarinic receptors in the guinea-pig ileum. 1 The affinities of a series of enantiomeric pairs of esters of phenylcyclohexylglycollic acid, of a pair of esters of alpha-methyltropic acid and of hyoscyamine methiodide have been measured for the muscarinic receptors of the guinea-pig ileum at 30 degrees and 37 degrees C and estimates have been made of their free energies, enthalpies and entropies of adsorption. 2 With (-)-S-hyoscyamine methiodide the enthalpy of adsorption is negative whereas with the (+)-R-enantiomer it is positive. 3 With the esters of phenylcyclohexylglycollic acid the size of the onium group appears to be as important as the stereochemical configuration in determining entropy. Large onium groups appear to be associated with an increase in entropy though this can only be measured approximately because of the narrow range of temperature which can be used.


Temperature coefficients of affinity constants for the binding of antagonists to muscarinic receptors in the rat cerebral cortex. 1 The temperature coefficients of binding of a series of muscarinic antagonists to their receptors in membrane preparations from the rat cerebral cortex has been examined. 2 At 37 degrees C the affinity constants agree with those determined by antagonism of acetylcholine-induced contractions of the guinea-pig ileum. 3 The temperature-dependence of the affinity constants is low; for the antagonists examined, the affinity constants at 0 degrees C differ by less than a factor of 3 from those measured at 37 degrees C. 4 There are qualitative similarities between the estimates of the temperature coefficient of binding of the antagonists to receptors in ileum strips and in the cerebral cortex.


Effects of methoxyverapamil on the stimulation by Ca2+, Sr2+ and Ba2+ and on the inhibition by Mg2+ of catecholamine release from the adrenal medulla. 1 Bovine adrenal glands were perfused with Ca2+-free Locke solution and catecholamine release was induced either by the introduction of Ca2+, Sr2+ or Ba2+ into the perfusion fluid or by the substitution of Na+ by an osmotically equivalent amount of sucrose. 2 Methoxyverapamil (D600) at a concentration of 3 X 10(-4) M blocked the release of catecholamines in response to Ca2+, Sr2+ or Ba2+ stimulation but failed to block the release evoked by the omission of Na+. 3 Mg2+ (10 to 20 mM) blocked the release induced by Na+-deprivation; however, this inhibitory effect of Mg2+ was not modified by D600. 4 D600 blocked the increase in the efflux of 45Ca from the perfused gland induced by the introduction of Ca2+ into the perfusion fluid and blocked the uptake of 45Ca into adrenal medullary slices induced by K+ depolarization. 5 The results suggest that Ca2+, Sr2+ and Ba2+ may enter the chromaffin cell through the same channel and that this channel is blocked by D600. Mg2+ may enter the cell through the same Ca2+ channel but with a high rate of permeation or it may enter through a channel which is resistant to D600. Alternatively, Mg2+ may exert this inhibitory effect at an extracellular site.


The effect of aminosteroid, ORG 6001, on hypothermia induced ventricular fibrillation in the cat. 1 The effect of the antidysrhythmic aminosteroid, ORG 6001, on hypothermia-induced ventricular fibrillation was investigated in cats anaesthetized with pentobarbitone. 2 ORG 6001 (total dose, 10 mg/kg, by intravenous injection) reduced both the incidence of fibrillation and the temperature at which it occurred. The number of animals that survived to 16 degrees C was increased. 3 This protective effect of ORG 6001 could not be explained by changes in respiratory acidosis, plasma concentrations of sodium and potassium, or by changes in the action potential of excised hypothermic ventricular muscle. The hypothermia-induced elevation of blood lactate was less in cats treated with the aminosteroid. 4 Over a limited temperature range, ORG 6001 prolonged the P wave and QRS duration and shortened the QTc interval. ST segment elevation was slightly reduced in the drug-treated group. J deflections were observed but were not correlated with the development of fibrillation. 5 The onset of fibrillation was not considered to be due to temperature differences between the myocardium and arterial blood or between localized areas of the left ventricular wall.


The energy cost of an 80 km run.

The energy cost of an 80 km run. Data was collected from two men who attempted an 80 km run. Measurements of aerobic power (VO2 max) and determinations of heart rate (HR) and submaximal oxygen consumption (VO2) during treadmill running were carried out one week before the run. Throughout the 80 km run, HR was recorded by telemetry and used together with the laboratory data to estimate VO2 as a percentage of VO2 max. One subject completed the 80 km distance at 58% of VO2 max, the other subject, operating at 74% of VO2 max, was obliged to retired after 55 km. The data in this and other studies indicate that the high energy costs reported for the marathon (70-85% of VO2 max) cannot be sustained over the 80 km distance but that about 60% of VO2 max can be continued for seven hours and longer.


Body composition of rugby union football players. The components of body composition were studied in 56 second class rugby union football players: 28 forwards and 28 backs. Fowards were found to have 19.5% TBF (TOTAL BODY FAT) and 80.5% LBM (LEAN BODY MASS); backs 12.2% TBF and 87.8% LBM. It was felt that greater attention should be given to the ratio of TBF to LBM in determining body weight and that there should be an increased emphasis of the LBM at the expense of TBF.


A study of maximum oxygen uptake and heart rate during work and recovery as measured on cycle ergometer on national Indian sportsmen. We have studied 73, top level Indian sportsmen for VO2 max and heart rates during work and recovery. High negative values of 'r' between VO2 max and heart rate during work and recovery have been observed. Absolute VO2 max, VO2 max/kg body wt/min and VO2 max/kg lean body mass/min are found to play an important role in influencing recovery of heart rate, more so in the initial phases. A similar trend has been observed while studying the influences of work heart rate on the recovery of heart rate after a standard exercise. Regression equations for the prediction of VO2 max from recovery pulse scores, have been worked out for Indian sportsmen.


Equestrian injuries--a one year prospective study. A one year prospective study of equestrian injuries was carried out in an area where horse riding is a popular pursuit. 115 persons suffered injury--eighty females and thirty-five males of whom sixty were under fifteen years of age. No fatalities were recorded and there were 0.2 injuries per 100 rides. Most injuries were minor and to the musculo-skeletal system. Visceral and cerebral injuries were not common but the former were life threatening in all cases. It is concluded that young riders should be supervised.


Chronic respiratory failure and physical reconditioning: case study of an elderly obese woman. A case is described of a 67 year old obese white woman who had a history of multiple medical problems and who was in chronic respiratory failure but responded poorly to intermittent positive pressure breathing, chest physiotherapy, and supplementary oxygen. She was treated successfully with a 600 k.cal diet and a 26-day physical reconditioning programme. Reconditioning techniques included free and treadmill walking, stair climbing, bench stepping, light calisthenics, and breathing retraining. Improvements were noticed in blood gases, spirometry, electrocardiogram, motor coordination, and physical working capacity.


The treatment of iliotibial band friction syndrome. Iliotibial band friction syndrome is a common cause of knee pain in long distance runners. The pain is caused by friction of the iliotibial band over the lateral epicondyle of the femur. Two hundred and twenty one cases were seen in a two year period. Tenderness over the lateral epicondyle associated with pain at 30 degrees of flexion on compressing the iliotibial band against the lateral epicondyle is diagnostic. Conservative treatment consisted of treating the cause, mostly training irregularities and the local inflammation mostly with steroid injections and rest. Nine cases failed to respond to conservative treatment and these were treated by surgical release of the posterior fibres of the iliotibial band.


Determinations of performance and mechanical efficiency in nordic skiing. Determinants of performance and mechanical efficiency of effort have been made on a group of ten male nordic skiers, all participants in the University of Toronto ski-team. The oxygen intake at the maximum attainable speed of skiing on a level course averaged 89.6 percent of the maximum oxygen intake observed during uphill treadmill running; the latter (average 63.9 ml.kg-1 min-1) may be compared with values greater than 80 ml.kg1 min-1 for international competitors. Maximum heart rates and respiratory gas exchange ratios were generally lower during skiing than running, and it is suggested that the maximum oxygen intake attained during skiing is limited by the individual's skill. In support of this the more experienced skiers were able to reach close to 100 percent of the treadmill maximum oxygen intake during level skiing. A multiple regression analysis indicated that the skiing speed sustained over a one-hour period was related to experience of skiing, maximum oxygen intake, and the percentage of body fat. Assuming a dynamic friction coefficient of 0.075, a drag area of 0.7 m2 and a drag coefficient of 1.0, the gross mechanical efficiency of the university-class skier averaged a little under 20 percent, with a net efficiency of 21.3 percent.


Physical efficiency tests in Indian urban adolescent boys and girls. Simple anthropometric measurements and physical efficiency tests were performed on adolescent Indian urban boys between 10-14 years and girls between 11-14 years of age. The similar height and weight of the subjects of both sexes were observed and was suggestive of higher growth rate in girls than the boys during only the initial phase of adolescent growth spurt. The vital capacity (total, ml/cm of height, l/m2 of surface area), Peak Expiratory Flow Rate (total, l/cm of height, l/kg of weight, l/m2 of surface area, l/year of age) and grip strength were observed to be insignificantly different between the sexes.


Fitness test profiles and trainng intensities in skilled race-walkers. A broad profile of national standard race-walkers was obtained. Subjects were taller and had more body fat than competitive runners of comparable distance as found in the literature. Pulmonary function, blood pressure and maximal heart rates were similar to normal sedentary values. The group's somatotype was 2.5 : 3 : 4, low mesomorphy being reflected in inferior strength measures. Haematological status corresponded to the runners of Brotherhood et al (1975). Predicted VO2 max (x = 70 ml kg min-1) was not related to performance. Time to exhaustion on a treadmill test correlated with 20 km race time (R = -.94; p less than .001). Multiple regression equations derived to predict race performance from combinations of 4 to 6 personality traits were non-significant. Mean heart rate in typical training regimes was 167 beats min-1 for interval training at 13 kmh-1 on the track and 134 beats min-1 over a 2.1 h road walk at 10.3 kmh-1. Physiological strain was greater in uphill than in level or downhill walking (P less than .001).


The radiological manifestations of metaphyseal dysplasia (Pyle disease). Pyle disease is a rare genetic skeletal disorder which is conventionally classified with craniotubular dysplasias. The radiographic manifestations in three affected adults included widening of the metaphyseal portions of the long bones which extended through a major portion of the diaphyses, with cortical thinning and mild cranial sclerosis. The femora presented the characteristic Erlenmeyer flask configuration. Pyle disease is clinically, radiographically and genetically distinct from craniometaphyseal dysplasia, a relatively common condition with which it has been confused.


Metaphyseal fractures in osteogenesis imperfecta. Forty-one children with osteogenesis imperfecta have been reviewed. A minority (7/41) showed small metaphyseal fractures, resembling those seen in non-accidental injury, but in all of these there was obvious generalized bone disease so that confusion with non-accidental injury did not occur.


A review of the radiological anatomy of the round window. Experimental studies on dried temporal bones in various projections combined with studies of the anatomical details marked with metal wires and/or barium paste have been performed to define the round window and its anatomical relation to surrounding structures. The exact plane of the round window was not found to be tomographically demonstrable and the term to describe the dehiscence in the lateral wall of the promontory below and posterior to that of the oval window should be the niche of the round window. Previous radiologically described pathological changes at the round window should be reviewed.


Intravenous cholangiography in childhood. Intravenous cholangiography (IVC) was performed on 102 children aged between one and 13 years. Eighty of the patients who were non-icteric were divided into four groups and received contrast medium containing either 53, 75, 106 or 150 mg iodine/kg body weight by intravenous injection over ten minutes. Complete demonstration of the common bile duct (CBD) was achieved in 85% of patients and in a similar proportion of all age groups. There was some delay in opacification of the CBD in young children but this was not of practical significance. The two higher dosage regimen gave significantly better results than the two lower dosages (p less than 0.001) and this improvement was evident in the young and older age groups. Nausea and vomiting occurred as side effects in 6%. In eight patients in whom there was inadequate demonstration by the standard IVC, an infusion technique over 3--8 hours was carried out. This improved the demonstration in three children with diagnostic results in two.


Traumatic para-mediastinal air cysts.

Traumatic para-mediastinal air cysts. Two cases of traumatic para-mediastinal air cyst are presented. The air and fluid collection develops between two layers of the pulmonary ligament following trauma to the lung and rupture of alveoli adjacent to the pulmonary ligament.