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Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Seven of nine depressed patients experienced a 4.3-fold increase in rated euphoria and activation following 30 mg d-amphetamine in a replicated dose, double blind study. d-Amphetamine was 2 to 2.3-fold more effective in producing activation, euphoria, and antidepressant effects than the same dose of l-amphetamine. Co-treatment with lithium carbonate produced a 60% (P less than 0.001) attenuation of the activation and euphoria responses to d-amphetamine. The responses to l-amphetamine were almost completely abolished by lithium. This study raises the possibility of lithium carbonate use as an adjunct in the treatment of amphetamine addiction.
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Some metabolic approaches to improving myocardial performance during cardiac hypoxia. Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested.
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Factors influencing tolerance of cardiac muscle to hypoxia. The effects of isoproterenol, glucose, and pH on the responses of isolated rat cardiac muscle to hypoxia (95% N2, 5% CO2) were examined while the muscles were contracting isometrically 12 times a minute at 28 degrees C. In the presence of 5.5 mM glucose, 10(-5) M isoproterenol and alkaline pH (7.8) improved the performance of cardiac muscle during early hypoxia. This was followed by a premature decline in developed tension, and contracture appeared. Recovery of function following reoxygenation with 95% O2 and 5% CO2 after a 60-min period of hypoxia was poor. Acid pH (6.8) resulted in an early decline of mechanical activity during hypoxia; but contracture did not appear, and full recovery of developed tension was seen upon reoxygenation after 60 min of hypoxia. When 22 mM glucose was used as substrate, the early responses to hypoxia were not altered; but late performance was improved, contracture did not appear, and full recovery after 60 min of hypoxia was seen. If additional glucose was added to the bath after 30 min of hypoxia (concentration 22 mM), little effect on developed tension was evident; but contracture diminished and recovery after 60 min of hypoxia was improved. Addition of 22 mM glucose allowed isoproterenol to exert its inotropic effect in the absence of late deleterious changes. The data support the concept that factors tending to increase the utilization of limited stores of anaerobic substrate during hypoxia facilitate deterioration. By increasing exogenous glucose, the support of inotropic activity without late adverse effects appears possible, and recovery is improved upon reoxygenation.
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Effects of pH and pCO2 on performance of ischemic myocardium. Contractile performance of ischemic feline myocardium was evaluated under conditions of selective changes in perfusate in pH and pCO2. A substantial increase in myocardial performance was noted when the pCO2 was lowered at constant pH, and depression of performance was noted when the pCO2 was increased at constant pH. Perfusate acidosis at constant pCO2 resulted in depression of performance and decreased performance only after 20 min of exposure. Alkalosis did not increase performance and decreased performance transiently during mild ischemia. These studies suggest that performance of myocardium during ischemia is closely related to tissue pCO2 and is minimally related to the level of extracellular pH.
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Effects of inhalation anesthetics on cardiac function and metabolism in the intact dog. In healthy, closed-chest dogs, dose-dependent depression of ventricular function was produced by the anesthetics halothane, methoxyflurane, and fluroxene, as evidence by decreases in left venticular stroke volume, stroke work, dP/dt, and an increased enddiastolic pressure. Myocardial blood flow and oxygen consumption decreased concomitantly and were correlated with aortic blood pressure decreases. There was no change in myocardial lactate extraction with halothane and methoxyflurane, suggesting that myocardial oxygenation was adequate in spite of the decrease in blood flow. However, even with marked increases in arterial lactate concentration during fluroxene anesthesia, extraction did not chance and, in fact, tended to decrease. The hemodynamic effects of halothane and methoxyflurane are similar to those previously reported in man, but those of fluroxene are different. Consequently, clinical speculation from these results is not justified at this time.
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Tissue water and pH in experimental primary cardiomyopathy induced by isoproterenol in frog. Acute aneurysms and other morphologically defined cardiac lesions were produced in frogs by isoproterenol (IPR) as previously described. Samples from lesions verified in vivo and from macroscopically normal ventricular areas, together with samples from nontreated control animals, were analyzed for total water content, inulin space, pHe, and pHi by using DMO-14C and inulin-3H. Total cardiac tissue water content was increased in all types of lesions after IPR injection. The highest content was found in bulging, noncontractile aneurysms. Inulin space was enlarged in all heart muscle specimens from IPR-treated animals, including those without macroscopically visible lesions. Those specimens with aneurysms showed the greatest degree of enlargement. The (pHe-pHi) did not differ between injected and noninjected animals, and the noncontractile samples from aneurysms did not differ from other lesions and macroscopically intact areas. In IPR-injected animals, there was no difference in pHi between macroscopically damaged and nondamaged segments of ventricle wall. On comparing these animals to controls, however, a slight shift to the alkaline side for both pHi and pHe was observed. The (pHe-pHi) was higher in skeletal muscle than in heart muscle in both IPR-treated and nontreated animals. Tissue water increased in skeletal muscle after IPR injection, reflecting a change of intracellular water as inulin space was maintained.
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Normal arterial blood gases during experimental hypertriglyceridemia in the rat. The possible effect of high concentrations of plasma triglycerides on arterial oxygen tension was investigated in rats by infusion of lymph chylomicrons or a soybean oil emulsion (Intralipid). Mean triglyceride concentrations were raised from 130 to 1454 mg/100 ml without statistically significant change in arterial oxygen tension, oxygen saturation, carbon dioxide tension, or pH. The small reduction in arterial oxygen tension, content, or saturation observed in earlier studies may have been due to inadequate stabilization of fat emulsion then available for intravenous use. The present data suggest that high concentrations of plasma triglycerides produced by infusion of chylomicrons or Intralipid do not affect arterial blood gases in the normal rat.
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Diagnosis of liver diseases by laboratory results and discriminant analysis. Identification of best combinations of laboratory tests. Patients with different liver diseases were studied by discriminant analysis. Groups of patients classified mainly on the basis of liver biopsy findings showed functional differences which permitted a consistent reclassification by discriminant functions using laboratory results. Optimal combinations of laboratory tests for the separation of liver diseases were defined. Different combinations were found, dependent on the subsets of liver diseases studied.
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Survival of rats subjected to acute anemia at different levels of erythrocyte 2,3-diphosphoglycerate. An experimental procedure was worked out in which rats were subjected to an exchange of erythrocytes, followed by acute anemia by means of hemodilution. One group of rats received erythrocytes with a high concentration of 2,3-diphosphoglycerate (DPG), and the other group was given erythrocytes with a low DPG concentration. The survival rate was equal in the two groups. Irrespective of DPG concentration, the rats whose hemoglobin concentration reached the lowest level died. The rats that died were also more acidotic than the others. The results indicate that the hemoglobin concentration and the pH value were more important determinants for survival than the DPG concentrations.
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The influence of bacterial superinfection on the clinical course of influenza. Studies from the influenza epidemics in Stockholm during the winters 1969-70 and 1971-72. During two epidemics of influenza A infection in Stockholm 1969-72, 249 cases were selected for a study on the effect of bacterial superinfection. Bacterial involvement was demonstrated through cultures and serologic reactions. The occurrence of C-reactive protein in increased amount in serum was significantly more common in the group which had the strongest indication of bacterial infection. An increased duration of fever, and a higher incidence of pneumonia, leukocytosis and erythrocyte sedimentation rate over 50 mm/l h was also the rule in cases with bacterial involvement. During both epidemics the bacteria most often involved were pneumococci.
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Evaluation of the antibiotic effect of treatment of maxillary sinusitis. As the effect of antibiotic treatment of maxillary sinusitis has been questioned, the elimination of bacteria from sinus secretions was studied during antibiotic treatment. Penicillin V, azidocillin, tetracycline or doxycycline was administered to 54 patients with maxillary sinusitis. Samples of sinus secretion were aspirated both before treatment and 2-3 days after the onset of treatment. When the antibiotic concentration was below the upper limit of MIC for sensitivity group 1, bacterial growth was present in practically all samples. When the antibiotic concentration equalled or was above this limit, there was no bacterial growth in about half of the samples. A prerequisite for antibiotic effect--elimination of bacteria--is that the antibiotic concentration is well above the MIC of the bacteria at the site of infection. The choice between bactericidal or bacteriostatic antibiotics appeared unimportant. Bacterial survival in the maxillary sinus despite a high antibiotic concentration in the sinus illustrates that MIC values determined in the laboratory do not always mirror the sensitivity of bacteria to antibiotics in vivo.
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Roentgenological findings in cryptorchidism. Intravenous urography of 78 cryptorchid boys revealed no clinically significant upper urinary tract anomalies. Two boys had a rotated kidney and 2 others a double renal pelvis. One boy had previously been operated upon because of hydronephrosis. There thus appears to be no reason for routine intravenous urography of cryptorchid boys. Forty-two per cent of the boys had spina bifida occulta in the lumbar and sacral spine. One case of asymptomatic congenital cardiac disease was discovered at routine chest X-ray.
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Semen cahracteristics before and after ligation of the left internal spermatic veins in men with varicocele. The semen from 20 men with varicocele was studied before and after surgical correction of the varicocele. The effect on sperm quality was only marginal and could not explain the fairly high conception rate (20%) after operation. The recommendation that varicocele in men with long-term infertility should be eliminated by ligation of the internal spermatic veins is still justified despite the absence of positive effects on sperm quality.
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Plasma potassium and insulin during extracorporeal circulation using a glucose-containing pump prime. In order to investigate the possible relationship between a glucose-containing pump prime and changes in plasma potassium during extracorporeal circulation, determinations were made of blood glucose and plasma insulin, potassium, and magnesium in 18 subjects undergoing open-heart surgery. In 6 of the patients, the same parameters had been measured during a pre-operative glucose tolerance test. It was found that the elimination of glucose was considerably impaired during extracorporeal circulation, in spite of high insulin levels. During the first minutes of extracorporeal circulation, plasma potassium fell more than during the glucose tolerance test, in spite of comparable insulin levels. It is concluded that changes in plasma potassium during extracorporeal circulation do not reflect insulin activity to any noticeable extent.
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Construction and evaluation of a simple membrane oxygenator for small organ perfusion. A simple membrane oxygenator for isolated organ perfusion is described. The membrane employed consisted of an ordinary silicone rubber tubing, 2 mm internal diameter, 0.3 mm wall thickness, the length of the tubing varying according to the required gas transfer. When describing the capacity of the oxygenator, it was found that the maximum gas transfer rate per unit membrane surface was an inadequate measure, since this would vary with both flow rate through the oxygenator and the gas binding capacity of the perfusate. The following formula for the function describing the relation between maximally possible change in gas concentration in the perfusate (C), flow rate (F) and actual change in gas concentration in the perfusate (U) was proposed: U=C-e(-bF), b being a constant specific for the gas and the membrane. This formula was tested by a series of in vitro experiments and proved to give a valid description of the capacity of the oxygenator. It was also found that carbon dioxide was always more easily transferred than oxygen, so that oxygen transfer capcity was the limiting factor in the use of the oxygenator. To facilitate the construction of the right size membrane, a nomogram was constructed for oxygen transfer.
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The influence of arm ischaemia and arm hyperaemia on subclavian and vertebral artery blood flow in patients with occlusive disease of the subclavian artery and the brachiocephalic trunk. A peroperative study. A peroperative study of blood flow and flow direction was performed in series of patients with occlusive disease of the subclavian artery. Particular attention was focused on the flow variations caused by arm ischaemia and postischaemic hyperaemia and on the effect of injection of a vasodilator into the distal subclavian artery. The effect on blood flow and flow direction was measured with the aid of an electromagnetic flowmeter. During arm ischaemia induced by an inflated cuff on the arm, the subclavian flow diminished, as did the vertebral artery flow when it was retrograde. If the vertebral artery flow was anterograde, it increased during arm ischaemia. The postischaemic hyperaemia caused an increase of the subclavian flow and of reversed vertebral flow. If the vertebral flow was anterograde, it diminished during the postischaemic hyperaemia. Similar findings were obtained with intra-arterial injection of a vasodilator. The large amount of blood flow passing through the vertebral artery, as well as the flow variations caused by reactive arm hyperaemia, emphasize the role of this artery as a collateral vessel to the upper limb in cases of the subclavian steal phenomenon.
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Spectroscopic observation of acid sulfate in atmospheric particulate samples. Infrared spectra of time- and size-classified atmospheric particulate samples collected with a inertial impactor reveal the presence of acid sulfate in the submicrometer-sized fraction. Although the degree of acidity is highly variable with time, the acidic nature of the particles is observed at all times of the day and may persist for several days in urban areas.
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Specific effects of neurotransmitter antagonists on ganglion cells in rabbit retina. Directionally sensitive ganglion cells in rabbit retina lose their directional sensitivity when picrotoxin, an antagonist of the inhibitory neurotransmitter gamma-aminobutyric acid, is infused into the retinal blood supply. Strychnine, an antagonist of glycine, does not produce this effect. Other receptive field types are affected by strychnine but not picrotoxin. Inhibitory transmitters therefore have specific functions in information processing in the retina.
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Vascular and brain dopamine beta-hydroxylase activity in young spontaneously hypertensive rats. Dopamine beta-hydroxylase activity was higher in mesenteric vessels, adrenal glands, and serum of 3-week-old spontaneously hypertensive rats but lower in the locus coeruleus than it was in the control Wistar-Kyoto rats. The results support the concept that the nervous system is an important regulator of blood pressure.
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Protein purification: adsorption chromatography on controlled pore glass with the use of chaotropic buffers. Chromatography on controlled pore glass in combination with chaotropic buffers makes possible, in a single step, protein purifications of several hundredfold. The new emphasis is on highly selective controllable adsorption. The method is useful for the purification and concentration of proteins from large volumes of complex media and for the purification of proteins that are poorly soluble or tend to aggregate in aqueous solution D-(-)-Beta-Hydroxybutyrate dehydrogenase, a mitochondrial membrane-bound protein, several soluble proteins, and staphylococcal alpha toxin, which can be purified directly from large volumes of culture medium, are used to illustrate the method.
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[Determination of barbiturates from biological material]. A trace quantitative analysis of barbiturates has been carried out in blood, urine, organs and in gastric and intestinal concents. The amount of sample required for analysis is very small [approximately 400 mul blood]. Extraction is carried out four times with the mixture of acetone and either 1:1]. The preparation of columns, packing and standards has been described. The device used for the analyses [Chrom 3] is furnished with an adjusted feeding block preventing the decomposition of samples in the doser. The column temperature is 190 degrees C, the column packing is Chromaton N-AW-DMCS coated with 3% NPGS and 0.75% trimer acid, detector FID.
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The mechanism of the inhibition of iron absorption by tea. Previous human studies have shown that drinking tea during meals significantly inhibits the absorption of both food iron and medicinal iron. This study provides evidence from experiments with rats that the tannins in the tea are responsible for the inhibition, probably by forming non-absorbable complexes with the iron within the intestinal lumen. The molar ratio of tannin: iron is dependent on the pH, being 1:1 at pH 2,0 2:1 at pH 5,5 and 3:1 at pH 8,0. Since tannins are present in many vegetable foods the formation of such complexes may be a factor in the poor availability for absorption of much food iron.
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An investigation into the hepatic cytochrome P-450 catalysed metabolism of the anaesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether). The role of the different cytochromes P-450 in the metabolism of the anaesthetic agent fluroxene, and the mechanism of production of toxic effects seen after pre-treatment of the animals with pehnobarbital prior to anaesthesia, have been investigated. Male rats were anaesthetized with fluroxene, or with 2,2,2-trifluroethyl ethyl ether, or with ethyl vinyl ether in an attempt to ascertain the in vivo toxic effects of the three anaesthetic agents. The resultant hepatic histology is reported. A study of the binding and metabolism of fluroxene by isolated rat hepatic microsomes was also made. We conclude that it is elevated levels of cytochrome P-450 which potentiate the toxicity of fluroxene anaesthesia in phenobarbital treated animals and that cytochrome P-448 does not bind or metabolize fluroxene. The potential toxicity of the fluroxene molecule is considered to reside in the trifluoroethyl moiety, while the vinyl group of fluroxene appears to play a role in the observed liver damage.
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Direct revascularization of acute myocardial infarction by implantation of left internal mammary artery into infarcted left ventricular myocardium. This is a preliminary report. Clearly, the internal mammary artery implanted into the infarcted anterolateral portion of the wall of the left ventricle has been of help in decreasing the size of the infarction and in maintaining the life of the dogs and normal function six hours after a large left ventricular wall myocardial infarction had been created. More animals need to be studied at the end of six hours, eight hours, and ten hours after implantation. More studies are needed to learn if ligation of the coronary veins at the same time as the arteries is beneficial or not. Two internal mammary arteries may act better than one when implanted side by side into a 5 by 5 centimeter infarction. In man, both internal mammary arteries and the right gastroepiploic artery could be used to revascularize acute myocardial infarctions in the posterior and anterolateral parts of the left ventricle.
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Chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate. Relationships between various types of chronic anemia, wound healing, and red cell 2,3-diphosphoglycerate (2,3 DPG) were examined in rabbits. Wound tensile strength and energy absorption were not affected by chronic iron-deficiency anemia, the chronic hemolytic anemia caused by intravenous water infusion nor by chronic hemolytic anemia caused by intravenous water infusion nor by chronic phenylhydrazine-induced anemia. Red cell 2,3 DPG levels were increased in the anemia of iron deficiency and were normal in the rabbits with chronic phenylhydrazine-induced anemia at the time of wound excision but were low following phynylhydrazine injection. The results show that chronic anemia per se does not affect the tensile strength and energy adsorption of wound healing. The findings suggest that the wound healing process may differ in certain types of anemia.
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Effects of beta-adrenergic stimulating and blocking agents on the adrenaline response and adenyl cyclase activity of leukocyte in monkey and human being. Using the method in which leukocyte suspensions were incubated with NaF or metaproterenol at 30 degrees C for 15-30 min to allow them to convert 3H-ATP (10 muCi) to 3H-cyclic AMP, followed by separation of the formed 3H-cyclic AMP by common chromatography, the leukocyte adenyl cyclase activity of monkeys and human beings was measured with high reproducibility. The oral administration of metaproterenol increased the leukocyte adenyl cyclase activity which was stimulated by NaF and decreased the count of peripheral eosinophils in some of the monkeys. In the beta-adrenergic blockade of the monkey which was made by administration of propranolol, the leukocyte adenyl cyclase activity significantly decreased. The leukocyte adenyl cyclase from patients with coronary heart disease also decreased after oral medication with propranolol.
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Human erythrocyte carbonic anhydrase B and C in chronic obstructive lung disease. The levels of carbonic anhydrase B and C isozymes in human red cells were determined using a quantitative immunological technique in patients with chronic obstructive lung disease. A significant increase in the level of carbonic anhydrase B was observed in these patients, while the level of carbonic anhydrase C did not change substantially. Positive correlations were found between the level of carbonic anhydrase B and arterial CO2 tension and plasma HCO3 concentration. A negative correlation was observed between the levels of carbonic anhydrase B and blood pH. These findings suggest that the synthesis or degradation of carbonic anhydrase B isozyme is affected by arterial CO2 tension or plasma HC03 concentration. The clinical significance was also discussed in relation to these isozyme levels in red cell.
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Hemodynamic effects of aerosol propellants. II. Pulmonary circulation in the dog. The inhalation of trichlorofluoromethane (FC11), dichlorotetrafluoroethane (FC114) and dichlorodifluoromethane (FC12) caused a reduction in mean aortic blood pressure but only FC11 and FC114 caused a reduction in mean pulmonary arterial pressure. The primary cause of the fall is a decrease in pulmonary blood flow. When blood flow to a lobe is kept constant and the adrenergic alpha receptors are blocked by injection of phentolamine, the inhalation of FC11 caused vasodilation. In the intact circulation, the vasodilation is masked by release of catecholamines which constrict the pulmonary blood vessels.
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Human placental delta5-3beta hydroxysteroid dehydrogenase activity (delta5-3beta HSDH): intracellular distribution, kinetic properties, retroinhibition and influence of membrane delipidation. Delta5-3beta HSDH activity has been assayed either by spectrophotometric method or by use of radioactive substrates. The enzymatic activity is equally distributed between mitochondrial and microsomal fractions verified by electronic microscopy. The specific activity is comparable in both fractions, as well as the optimal pH and the Km for NAD and for the substrates. The delta5-3beta Hut optimal pH, specific activity and sensitivity to the inhibitory action of various steroids are different when C19 and C21 steroids are used as substrates. Estrogens and cyclic AMP have also an inhibitory action on the oxidation of C21 steroids. Treatment of microsomal or mitochondrial membranes with phospholipase A releases fatty acids (mainly arachidonic) and decreases the enzymatic activity. "Adsorbtion" of the fatty acids on bovine serum albumin partially reactivates the delta5-3beta HSDH.
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[Hydrolysis of insoluble collagen of bull bones by Streptomyces griseus crystalline protease]. Hydrolysis of collagen was studied in the bull bone tissues by the Str. griseus crystalline protease. The amount of collagen hydrolyzed by it composed 6.6% and 16% after 4-hour and 6-hour hydrolysis, respectively. When the enzyme:substrate ratio is 1:50 hydrolysis proceeds most intensively; with a decrease in the ratio up to 1:1000 the average amount of peptides increase from 2.6 up to 4 amino acidic residua, respectively. Under conditions of denaturated collagen hydrolysis the content of hydroxyproline in solution as compared with the native one increases; in this case the links with the presence of imino-acids are easier to split, the more resistant being those formed by hydroxyproline. Within the limit of 20-45 degrees C hydrolysis of protein intensifies with a temperature rise. Within the pH range of 5.0-11.0 the maximal amount of alpha- NH2-groups and hydroxyproline is observed at pH 8.5, the minimal--at PH 5.0. Hydroxyproline in the composition of peptides appears at the beginning of hydrolysis whereas the free one of enzymes of the longer effect 24 h after the beginning of the experiment composes 12.2% of its total content in the solved products. In the insoluble part of the substrate after 3-hour hydrolysis tyrosine composes less than 25% of its initial amount in protein whereas phenyl alanine--over 70%. After 6-hour hydrolysis the solved part of the system contains about 30% of alanine and 8.9 and 6% of glycine, proline and hydroxyproline, respectively.
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Effect of heparin or saline dilution of blood on PCO2 and pH. The effect of different dilutions with heparin solutions or saline on blood PCO2, pH and standard bicarbonate was investigated. Blood was first equilibrated to give about 40 or 60 mmHg PCO2. The solutions were in equilibrium with room air. The effect on blood PCO2 etc. could be fully explained by the dilution with a medium having a much lower PCO2. Thus, correction of the heparin solution to pH 7.40 and PCO2 40 mmHg eliminated the effect on PCO2, pH and standard bicarbonate. With ordinary procedure for blood heparinization (about 2% dilution) the effect is practically negligible.
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[Specific p-nitrophenyl phosphatase of yeast Pichia guilliermondii]. The cells of yeast P. guilliermondii contain specific p-nitrophenyl phosphatase (pNPPase), the level of which depends on the cells supply with inorganic phosphorus. Partially purified enzyme is activated by ions Mg2+, Co2+ and somewhat weaker -- by ions Fe2+. With the presence of Mg2+ the enzyme activity is inhibited by ions Cd2+, Zn2+, f-, Be2+, Cu2+, Mn2+, Ca2+, MoO42-, Fe3+, Fe2+, inorganic phosphate as well as by EDTA. A mixture ions Be2+ and F- causes a complete inhibition of the activity. Ions K+ and Na+ inhibit to some extent the enzymic activity, ATP removes the inhibitory effect of monovalent cations. Km of pNPPase is equal to 3.3-10(-4) M, the molecular weight determined by the method of gelfiltration is 60 000. The enzyme is the most active at 50 degrees C and pH 9,5 PNPPase does not manifest the phosphotranspherase activity in tris-HC1-buffer.
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Diagnosis of renal tumor by gamma-glutamyltranspeptidase (EC 2.3.2.2). A urinary enzyme pattern and kidney tissue pattern were investigated simultaneously in 117 urologic patients. In contrast to all other renal disorders only the sixteen malignant tumors of the kidney showed a significant drop of gamma-GT in tumor tissue and urine. So far urinary enzymology has been used only as screening test. Measurement of gamma-GT in urine, however, permits the diagnosis of kidney tumors.
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Bilateral testicular seminoma in intra-abdominal testes. A seminoma of both intra-abdominal testes in a forty-five-year-old patient is reported. Discovery of the tumor was fortuitous during admission for upper lobe pneumonia. Of particular interest in this case is that seminoma was found in both undescended testes. Surgical extirpation of both degenerated testes along with prostatic utricle was performed. The patient refused radiotherapy.
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[Study of the amniotic fluid of sheep in the normal course of pregnancy and in abortion]. Cytologic, biochemical and immunoelectrophoretic studies were carried out of amniotic fluids in 100 ewes with normal pregnancy and 40 ewes that had miscarried. Each month of pregnancy a total of 20 and 8 animals of the two groups, respectively were studied. It was found that the biochemical and metabolic processes taking place in the fetus lead to changes in the amniotic fluids altering the pH value, the alkali reserve, the content of potassium, calcium, phosphorus, alkaline phosphatase as well as their bactericidal activity. More characteristic changes linked with pregnancy were observed in the cell composition of the amniotic fluids. With advancing in age the increase in cell count was accompanied (staining with Nile blue sulfate) with a rise of the "orange cell" content. The amniotic fluids of ewes with normal pregnancy were found to contain proteins which precipitated with hyper immune sera against blood serum and kidney, heart, and placenta proteins. In ewes that had miscarried the pH values of the amniotic fluids dropped in the months when abortions took place: 7.36, 7.11, 6.90, 6.80 and 6.90, as against 7.41, 7.36, 7.28, 7.17 and 7.18, respectively. Along with pH the alkali reserve also dropped to 37.9 in the first month and 14.20 in the fifth month. In ewes that had miscarried in the 2nd, 3rd, and 4th month these values were 18.90, 14.90, and 13.80 cu. cm, respectively. In cases of abortions the protein composition of the amniotic fluids showed higher levels of the alfa and beta globulins.
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[Adrenal-like Leydig cells (author's transl)]. Adrenal-like lipoid-rich Leydig cells, which could be found in a cryptorchid testis, were investigated by light and electronmicroscopy. There were nodular and diffuse proliferation of these adrenal-like cells in the interstitium of the testis. Electronmicroscopically these cells are fasciculated and characterized by large liposomes, many tubulovesicular mitochondria, and a large smooth endoplasmatic reticulum. But the presence of crystals of Reinke in these cells underlined their relationship to Leydig cells. The clinical history of this case is characterised by an extreme adipositas (167 kg) and high urinary estrogenexcretion. This excretion could be suppressed with dexamethasone and stimulated with HCG. After orchiectomy estrogen excretion decreased for 4 months and then increased again, after ACTH stimulation performed by reason of adrenal insufficiency. At this time there is no evidence of adrenal tumor; in the contralateral, scrotal testis, spermiogenesis and Leydig cells are without pathologic changes as revealed by biopsy.
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[Properties of partially purified ATP desaminase from Actinomyces N4 antibioticus]. Three active fractions of ATP desaminase from Actinomyces N4 of type Antibioticus were obtained by gel filtration through Sephadex G-200. Some properties of each fraction were studied: effect of pH and Mg2+, substrate specificity, effect of pH on Km. The enzyme studied could be used for preparation of ITP, IDP, IMP, inosine and hypoxantine.
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[Changes in the content of ribosomal RNA and the activity of ribosomal RNAase in the brain under natural physiological conditions]. Optimal activity of RNAase from brain ribosomal fraction was observed at pH 5.4 and pH 7.9. After alimentary and conditioned-alimentary stimulation content of rRNA was significantly increased in brain, but the RNAase activity was decreased more than two-fold. After conditioned-alimentary inhibition content of rRNA was slightly decreased as compared to experiments with alimentary and conditioned-alimentary stimulation, but it was distinctly higher than in control. As compared with alimentary stimulation in the conditioned-alimentary stimulation the RNAase activity was increased at pH 5.4 and decreased at pH 7.9.
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[Effect of the antibiotic D-cycloserine and its dimer on the activity of tyrosine aminotransferase in liver tissue of intact, adrenalectomized and hypophysectomized rats]. In a period of lowest day activity of tyrosine aminotransferase, within 6-8 days after bilatheral adrenalectomy, the enzyme activity was decreased by about 20% as compared with an adequate control. At the same time, within a day and seven days after hypophisectomy, in rat liver tissue the enzyme activity was increased, approximately two-fold as compared with the normal state. Within four hrs after intraperitoneal administration into intact fasting rats at a dose of 2-2.5 g per 1 kg of body weight D-cycloserine and its dimer caused an induction of tyrosine aminotransferase by 75% and 180%, respectively. Induction of the enzyme by D-cycloserine and its dimer was inhibited by actinomycin D; the phenomenon was not observed in adrenalectomized rats. Within a day after hypophisectomy D-cycloserine did not cause the induction of tyrosine aminotransferase in rat liver tissue; to the contrary, the dimer of D-cycloserine caused induction of the enzyme, comparable to the ACTH effect, in liver tissue of hypophisectomized rats.
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[Analysis of inhibition in pathways of NADP.H2 and NAD.H2 oxidation in liver tissue microsomes]. Microsomal complexes of electron transfer were resistant to typical inhibitors of mitochondrial pathway of electron transport. In oxidation of NADP.H2 there were at least three point of molecular O2 reduction: NADP.H2-specific flavoprotein, Fe2+ participating in reactions of peroxidation of unsaturated fatty acids and cytochrome P-450. Efficiency of cytochrome P-450 inhibitors could not be evaluated by polarography as in the pathway several sites of molecular O2 activation were observed. In oxidation of NADP.H2 estimation of the rate of electron transfer reactions was carried out by monitoring of velocity of O2 absorption in presence of EDTA (inhibitor of the reaction of peroxidation) because about 50% of the total oxygen were utilized only in the process where NADP.H2 was oxidized. NAD.H2 oxidation, inhibited with EDTA, was activated by addition of Ca2+.
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[The effect of hydrocortisone and insulin on the activity and isoenzyme of tyrosine-alpha-ketoglutarate transaminase in cytostructures of rat liver]. Single administration of hydrocortisone or insulin into rats (body weight 200 g) and also combined treatment of the animals with the hormones at large doses caused a distinct increase in activities of anode and cathode isoenzymes of tyrosine-alpha-ketoglutarate transaminase in soluble fraction; total activity of the enzyme was also increased in mitochondria of rat liver tissue.
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[Changes in cerebrospinal fluid lactate and pyruvate levels during brain surgery under fluotane anesthesia]. The lactate and pyruvate content in the arterial blood and CSF of 24 patients operated on the brain under fluothane anesthesia with artificial ventilation of the lungs was measured. Towards the end of the operation and anesthesia a sizably elevated lactate level and accumulation of its excess in the blood were noted, these shifts having been more marked with hypocapnic ventilation of the lungs. An increased concentration of lactate and pyruvate in the cerebrospinal fluid was not attended by accumulation of lactate excess.
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[Enterococcal survival in forcemeat preserved in polymer films and in cutlets made from it]. The available data suggest that at 2 degrees and 5 degrees with a 12-day long storage in unpacked and in polymeric film packed forcemeat there occurs no propagation of the enterococci. At 22-24 degrees the multiplication of Str. faecalis var. liquefaciens proceeded similarly both in packed and unpacked forcemeat. When the temperature in the central part of the cutlets prepared from the enterococci-contaminated forcemeat reaches 7-80 degrees the bulk of the Str. faecalis var liquefaciens cells perishes, but even at 80 degrees there survive individual heat-resistant cells.
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[Comparative study of Aujeszky's disease virus reproduction in a suspension of poultry embryonic cells and tissues (author's transl)]. Reproduction of Aueski disease virus in suspension cultures of trysinized cells and mechanically minced tissue of chick, duck and quail embryos was compared. The optimal conditions for cultivation of vaccine and virulent strains of virus in these systems were determined. The advantages and prospects of using suspension cultures of minced avian embryo tissue for preparation of virus materials with high biological activity and in large volumes in comparison with trypsinized cell suspensions were demonstrated.
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[Determination of GSH-DH activity (E.C.1.8.5.1) presence of the enzyme in different wheat varieties (author's transl)]. 2,6-dichlorophenol-indophenol is more stable in 75% ethanol than in aqueous solution and ascorbic acid reacts considerably faster in this media than glutathione. The activity determination of glutathione: dehydroascorbic acid oxidoreductase was based on these observations by a photometric measurement of the ascorbic acid resulting from the catalysis. Extracts from various types of wheat were tested and relatively high enzyme activities were found.
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[A pharmacologic analysis of preparatory mechanisms of stereotyped activity in dogs]. In dogs with elaborated rhythmic and mozaic stereotypes of secretory and motor situational conditioned reflexes specific features were revealed in the action of some neurotropic drugs (amizyl, amedine, diphacil, pediphene, chlorpromazine and sodium oxybutyrate) on preparatory (latent) conditions of excitation and inhibition, appearing in the stabilized systems of reflexes. Pharmacological analysis has pointed to the predominantly cholinergic nature of preparatory and trigger mechanisms of alimentary conditioned activity. The blockade of M-cholinoreceptors (by means of amizyl and amedine) weakens or eliminates the preparatory conditions appearing in a dynamic stereotype and disturbs the trigger reactions within three to ten days. A pediphene blockade of H-cholinoreceptors intensifies the preparatory states.
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[The distribution of benorylate in plasma, synovial fluid and synovial tissue in rheumatoid arthritis]. The authors report on the drug benorylate which is available in the Federal Republic under the name of Benortan (4-acetamidophenyl-2-acetoxybenzoat). Numerous examinations have shown that it is well tolerated by mouth and that it has beneficial clinical effects with few side effects. Benorylate is a neutral, fat-soluble, water-insoluble substance which upon absorption is almost completely hydrolyzed into salicylate and paracetamol. 6 patients with classical seropositive rheumatoid arthritis and with a highly active synovialitis of one or both knee joints not previously treated received 4 g of a 40% benorylate suspension orally twice daily over a period of 9-14 days. On different days at exactly determined times of drug administration blood, and on the day of synovectomy synovial fluid and synovial tissue, were taken and frozen to - 70 degrees C and subsequently examined as to the content of salicylate, paracetamol, and unchanged benorylate. The plasma levels of salicylate and paracetamol were generally distinctly higher than the concentrations of these metabolites in the synovial fluid. Benorylate which is practically not detectable in blood is found in the synovial tissue and is detectable in greatest quantities in the most inflamed synovial villi. Benorylate can probably penetrate into the synovial membrane like its metabolites salicylate and paracetamol; it remains, however, to be examined whether the metabolites are distributed differently in different synovial areas (active inflamed and unattacked synovial tissue, respectively) in the same way as benorylate per se.
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[In vitro effect of leukocytic and thymic histones and their fractions on the activity of the causative agent of meningopneumonia]. It was found in studying the antimeningococcus activity of the leukocytic and thymus histones and their fractions that both histones were capable of neutralizing in vitro the activity of the causative agent of meningopneumonia (MP). The neutralization effect was chiefly associated with the F3 fraction rich in arginine and depended on the duration of the histone fraction contact with the MP causative agent, the weight concentration of the histone and the pH of the incubation medium.
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[Immunological polyfunctionality of proteins and its meaning for the analysis of an allergen-active bacterial substrate]. It was shown with the aid of immunosorption of an allergen-active substrate of E. coli 020: K84 (No. 2-rII) that protein substances taking part in the phenomenon of cell hypersensitivity were active in the humoral immunity reactions. The allergenic and immunochemical activity served as functions of the same molecules of bacterial proteins, this substantiating the use of immunochemical analysis for the study of an allergen-active bacterial substrate. By protein denaturing it is possible to obtain immunochemical inert allergen-active preparations capable of detecting the cell hypersensitivity to crude bacterial proteins. The problem of immunological polyfunctionality of proteins is discussed from the aspect of nonhomogeneity of their antigenic determinant groups.
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[Some properties of the alpha-hemolysin produced by a hemolytic strain of E. coli]. It was found that alpha-hemolysin of E. coli P 678 HIy+ was maximally active against human erythrocytes at pH 6.5. The hemolytic activity is characterized in time by a distinct lag-phase and a phase of the greatest velocity of the reaction immediately following it. The duration of the lag-phase and also the rate of hemolysis depends on alpha-hemolysin concentration, whose increase is accompanied by a decrease of the lag-phase and acceleration of hemolysis. There is a definite limit below which the duration of the lag-phase remains unchanged with further increase of hemolysin concentration. There was noted a linear relationship between the amount of erythrocytes taken for the test and the rate of hemoglobin release and also a temperature activation of the hemolytic reaction.
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[An experimental study of the spectrum of individual psychotropic activity of clozapine (Leponex)]. An experimental analysis of the psychotropic activity of Leponex (in a chronic experiment on II cats) in conditions of a group interaction depicted that the preparation processes a definite tranquillizing and antipsychotic effect. In conditions of zoosocial interactions this drug promotes disappearance of neurotic reactions and a resocialization of animals in the zoosocial ierarchy. In tranquillizing doses the preparation has an antihypertensive effect and prevents the development of a long-term tonic hypertension due to emotional stress.
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Affinity elution of pyruvate kinase from phosphocellulose. Pyruvate kinase from ascites tumour cells can be eluted from phosphocellulose by very low concentrations of phosphoenolpyruvate, fructose 1,6-bisphosphate, adenosine 5'-diphosphate and pyrophosphate, respectively. The appropriate limiting conditions for "facilitated desorption" of the enzyme from phosphocellulose by these ligands have been elaborated for achieving maximum selectivity and recovery in the process of its purification. This method has been designated as "affinity elution chromatography" owing to the specific interactions between a ligand as a constituent of the eluting medium with the adsorbed enzyme, which causes its selective desorption from the ion-exchanger. Affinity elution with phosphoenolpyruvate has been found to be very effective for preparation of the M-types of pyruvate kinase. A specific activity of 420 for an almost homogeneous preparation of pyruvate kinase from ascites tumour cells has maximally been obtained.
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[Influence of temperature on enzyme activity determination in serum : L-aspartate aminotransferase isoenzymes]. The influence of temperature on activity assays of the isoenzymes of L-aspartic aminotransferase in described. For this purpose, isolated human isoenzymes were added to inactivated serum. Half-saturation constants were determined at 17.8 degrees C, 25 degrees C, 30 degrees C, and 37 degrees C, and the substrate saturation and pH curves were recorded. The cytoplasmatic (c) and mitochondrial (m) GOT showed temperature-dependent differences in the half-saturation constants for the substrates L-aspartate and 2-oxoglutarate. For both isoenzymes pH 7.4 is considered the optimum regardless of the temperature of measurement, and Tris-HCl is the optimal buffer. In the Arrhenius plot there is a bent at 27 degrees C for both isoenzymes. Thermal denaturation as a possible reason for this deviation from the linearity in the Arrhenius plot could be ruled out.
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[Studies of in vitro cultivated cells from the smooth muscle organs. 3. Effectiveness of some drugs on pulsation frequency of isolated smooth muscle cells of the chicken amnion]. The effects of some drugs on the beating frequency of isolated cells of the chick amnion cultivated on cover slips were investigated. Cholinergic and adrenergic agonists and antagonists, serotonine, antispasmodics, coronary dilatants and local anesthetics influenced the beating frequency significantly. The isolated chick amnion cells equal in their pharmacological behaviour the intact chick amnion and smooth muscle cells of mammals but differ from isolated beating heart cells.
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[Modification of the adjuvans arthritis by carrageenin, compound 48/80, histamine- and serotonin antagonists, non-steroid antiphlogistics as well as protease inhibitors and their possible relations to inflammation mediators]. 1. Injections of carrageenin (1,25 mg/kg i.v.) from the 1st to the 3rd day and then each 2nd or 3rd day inhibited paw swelling in adjuvant arthritis of the rat during the time of treatment. Injections from the 11th to the 15th day were ineffective. The level of plasma kininogen was slightly decreased but the total complement serum level was significantly lowered. 2,5 and 3 mg carrageenin/kg respectively were toxic after repeated injections. After a single administration the levels of plasma kininogen and of total serum complement were decreased by 50% although paw swelling was not affected. 2. Pentosane polysulfoester (25 mg/kg i.v.) did not influence paw swelling despite daily administration from the 1st to the 17th day. Heparin (10 000 IE/kg i.v.) was likewise ineffective. 3. Single or repeated injections of compound 48/80 (0,125-0,5 mg/kg i.v.; 1-5 mg/kg i.p.; 3-6 mg/kg s.c.), reserpine (0,2 mg/kg i.p.), cyproheptadine (5 mg/kg i.v.), bromolysergic acid diethylamide (2 x 2 mg/kg i.v.) or metiamide (10 mg/kg i.v.) were without effect on paw swelling. Neither did compound 48/80 effect the complement serum level. 4. Daily administration of chloropromazine (4-10 mg/kg p.o.) or of promethazine (10-15 mg/kg s.c. or p.o.) inhibited paw swelling in the first phase of adjuvant arthritis but not in the second one. 5. The soybean trypsin inhibitor (15 mg/kg i.v.) inhibited paw swelling significantly up to the 4th day, the Kunitz inhibitor (25 000 E/kg i.v.) was ineffective. 6. The content of prostaglandin E of the inflamed paws was increased threefold in both phases of arthritis. The results are discussed with regard to the putative role of mediators of inflammation (histamine, serotonin, kinins, prostaglandins, lysosomal enzymes, lymphokines, complement).
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Properties of plasma membranes from granulation tissue with reference to extracellular matrix. Treatment with neuraminidase decreased the activity of Na+,K+-activated Mg2+-adenosine triphosphatase in plasma membranes isolated from experimental granulation tissue but not that of 5'-nucleotidase or leucine-beta-naphthylamidase. A temporary lowering of the pH of the plasma membrane suspension to 2-3 inactivated all three enzymes, which remained inactive after the pH had been readjusted to 7.4. Addition of dextran preparations to the membrane suspension decreased the activity of adenosine triphosphatase. Ethanol (0.4%) had a similar effect. These marker enzymes of plasma membranes were not affected by additions of hyaluronate, chondroitin sulfate, protein polysaccharide or soluble collagen. Serotonin stimulated the adenosine triphosphatase activity slightly. About 10-20% of the protein in the plasma membrane preparation was extracted with EDTA. This "fuzzy coat" fraction yielded a distinct gel-electrophoretic protein pattern. Hyaluronidase was not helpful in cleaving this surface layer from the plasma membranes.
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Serum gastrin concentration before and after parietal cell vagotomy in man and dog. Serum gastrin concentrations were measured during fasting and after feeding in duodenal ulcer patients and in dogs before and after parietal cell vagotomy (PCV). Postoperatively, fasting serum gastrin concentrations increased significantly in man and insignificantly higher in dog. After feeding, serum gastrin reached higher values postoperatively in both man and dog. The percentage rise in food-stimulated serum gastrin after PCV was higher in dog than in man.
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[Comparative study of a new antihistamine, mequitazine, and placebos]. In a double-blind trial lasting 2 weeks, a new, long-acting antihistamine, Mequitazine, and a placebo, were compared. 115 allergic patients participated in this experiment (mequitazine n = 56, placebo n = 59). Therapeutic results and the effect on diurnal alertness were evaluated by means of a questionnaire filled in daily by the patients. Whether considering the day by day results or the results of the entire treatment period, statistically, Mequitazine (10 mg/24 hrs) is very significantly more active than the placebo. The daytime drowsiness induced by Mequitazine is statistically no greater than that induced by the placebo, whether analyzed on a day by day basis or over the entire treatment period (P = 0.23). The side effects, 8 for Mequitazine, 5 for placebo, are mild and did not lead to discontinuation of the treatment in the Mequitazine group.
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Beclomethasone dipropionate aerosol treatment of hay fever. A dose-response investigation. In a controlled, double-blind study 20 children and adults, suffering from summer hay fever, were treated intranasally with a daily dose of 200 mug, 300 mug or 400 mug beclomethasone dipropionate (Beconase, Becotide Nasal) or with placebo for 2 weeks during the hay fever season. No beneficial effect of the placebo treatment was observed. In patients treated with 200 mug and 300 mug beclomethasone dipropionate a day there was a moderate decrease in nasal symptom scores and in use of antihistamine tablets. As the results indicated 400 mug a day to have the most pronounced effect on nasal symptoms, this dosage is recommended for children as well as adults suffering from summer hay fever.
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Influence of changes in arterial PCO2 on cerebral blood flow and cerebral energy state during hypothermia in the rat. In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.
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Neurohistological and histochemical observations on the lung of Rattus rattus rufescens (Indian black rat). The intrinsic innervation of the lungs (right and left) has been studied by the cholinesterase technique, considering the effect of various pH, incubation periods and temperatures. Cholinergic innervation dominated. The peribronchial ganglia, large, medium-sized and irregular-shaped, rounded and small, showed a positive cholinesterase reaction. Maximum ChE activity was noticed in the bronchi and their branches and on the periphery of the alveoli.
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Response of the hypothalamic neurosecretory system of the female catfish, Heteropneustes fossilis (Bloch), to hypophysectomy. The effect of hypophysectomy on the hypothalamic neurosecretory system of the catfish, H. fossilis, was studied. Hypophysectomy resulted initially in an accumulation of NSM at the distal ends of the cut axons. The axons had grown and were reorganized into a neurohypophysis-like structure 3 weeks after hypophysectomy, and this persisted even more than 3 years post-hypophysectomy.
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Reactions of the arterial blood pressure in changed haemodynamic conditions and under the effect of bilateral carotid occlusion. In order to throw light on the problems related to the magnitude and the possibility of maintaining pressor response in the case of bilateral carotid occlusion (BCO), acute experiments were carried out on heparinized cats in chloralose-urethane narcosis and spontaneous respiration. The perfusion pressure in a hind leg autoperfused with a roller pump with a constant flow and the arterial blood pressure were recorded electromanometrically. A study was made of the changes taking place under the effect of BCO in the normal animal, in animals in a haemorrhagic state, after pharmacological alpha-adrenergic blockade, haemorrhage after alpha-adrenergic blockade, retransfusion of blood + alpha-adrenergic blocking agent and after local application of 0.01 papaverine. It was established that some of the factors determining the haemodynamic state of the organism, such as: blood volume, arterial pressure, vascular resistance, cardiac output, etc., are of great significance for the realization of the pressor response to BCO, but the haemodynamic state of the animal before the occlusion and the interactions between the abovementioned factors are decisive for the form, magnitude and maintenance of the pressor response in BCO.
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On the mechanism of the relaxing adrenaline effect on cat jejunum. The effect of propranolol, phentolamine, papaverine, theophyline and Ca++, administered in different combinations of their threshold doses, on the relaxing effect of adrenaline was studied on an isolated segment of proximal jejunum of male cats. It was established that phentolamine weakened the relaxing effect of adrenaline, while propranolol had no effect on it. Papaverine potentiated the relaxinf effects of adrenaline both when administered alone and in combination with propranolol or with phentolamine. Theophylline weakened the relaxing effect of adfrenaline and of the combination phentolamine-adrenaline. Ca++ increased the smooth-muscle tone. The interpretation of the results obtained leads to the fundamental conclusions that the relaxing effect of adrenaline on cat jejunum is more alpha- than beta-adrenergically determined and that the system of the cyclic AMP participates in its realization. At the smae time, however, the possibility of participation of other mechanisms is not excluded. The smooth-muscle effect of papaverine and theophylline is not determined only by their inhibitory effect on phosphodiesterase.
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A method for the continuous study of net water transport in the feline small bowel. A new perfusion technique has been developed for the study of net water transport across the intestinal epithelium in vivo. The lumen of an isolated intestinal segment is steadily perfused with a solution of known composition in a closed perfusion system with a reservoir large enough to prevent recirculation. The intestinal segment may be enclosed in a plethysmorgraph. Changes in the perfused volume is recorded by a volume transducer coupled to the recirculating system via a T-tube. If no motility occurs, the changes of the perfusion volume reflects net water transport across the intestinal epithelium. A quantitative comparison of this technique with the convention polyethylene glycol method revealed no significant difference. The plethysmorgraphic method also makes it possible to quantify the net water absorption via lymph and blood.
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Effect of bulbar acidification on basal secretion of acid and gastrin in dog. Dogs were provided with mucosal septal pouches of the stomach and of the duodenal bulb. In some dogs a drainage gastric cannula was inserted into the most dependent portion of the stomach. In dogs which were found to secrete acid spontaneously during a control period at the start of each experiment, the bulbar puches were perfused with 0.1 M HC1 for 5-120 min. Bulbar acidification rapidly and profoundly reduced the basal acid output. In dogs which did not secrete acid spontaneously during the control periodbulbar pouches were perfused with 0.1 M HC1 for 1 h. Bulbar acidification did not significantly influence the plasma gastrin concentration and no acid was secreted from the Pavlov pouches following such acidification. The present results support the hypothesis that reduction of the intrabulbar pH may contribute to the reduction of acid secretion during interdigestive periods. The physiological significance of of mechanisms in the upper intestine which induce acid secretion following a reduction of the intraluminal pH is questioned.
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Classification and biological distribution of histamine receptor sub-types. The distribution and classification of histamine receptors in mammalian and avian tissues have been summarized in Tables 1-4. It is evident that histamine receptors are present on a number of morphologically distinct cell types and the proportion of cells bearing H1- and H2-receptors varies not only with the species but also with the cell source. The pharmacological receptors mediating mepyramine-sensitive histamine responses have been defined as H1-receptors. Receptors mediating mepyramine-resistant, but burimamide or metiamide-sensitive histamine responses have been classified as H2-receptors. Histamine responses mediated via H2-receptors seem to involve the adenylcyclase system resulting in elevation of intracellular cyclic-AMP level, which is susceptible to burimamide blockade but insensitive to beta-adrenergic blocking agents. This mode of action of histamine involving H2-receptors and the adenyl cyclase system has been shown to stimulate the mammalian heart; promote gastric acid secretion; inhibit antigen-induced histamine release from leucocytes and inhibit lymphocyte-mediated cytotoxicity. It can further be concluded that both H1- and H2-receptors are widely distributed throughout the animal body in the gastro-intestinal, reproductive, respiratory and cardiovascular systems, nervous system and on mast cells and blood leucocytes. In these tissues, histamine receptors play an important role in physiological, immunological and immunopathological processes. Interaction of histamine with both H1- and H2-receptors in varying proportions modulates the overall manifestation of cardiovascular and respiratory syndromes during certain immunopathological conditions (e.g. inflammation, allergy and anaphylaxis). Histamine receptors also appear to play and important role in the development of immuno-competence and immunity.
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Differentiation of newly isolated strains of Trypanosoma (Schizotrypanum) cruzi by agglutination and precipitation reactions. Serological relationships between new isolates of Trypanosoma cruzi from a single locality have been examined by direct agglutination and immunodiffusion, and compared with established strains. The strains were divided into three groups according to the absorption properties of their precipitinogens. The three groups were defined by the same characteristics as those in which strains of wide-ranging provenance and long laboratory history have been placed by previous workers. A lack of correspondence between the antigenic constitutions of the groups as described here and as described previously was demonstrated using reference strains. Relatedness values were calculated from agglutination titres, which indicated a complex heterogeneity of antigens, and from which a scheme of relationships was drawn.
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Identification of T. brucei-subgroup strains isolated from game. Several T. brucei-subgroup strains isolated from game were investigated with the blood incubation infectivity test (BIIT) and in human volunteers. Original isolates and their clones derivatives were tested. In order to check the validity of the BIIT, volunteer tested clones were used under modified BIIT conditions. Inoculation of different trypanosome strains into volunteers yielded positive parasitaemia for original isolates from lion, hyaena, and Coke's hartebeest. Changing antibody titers during the course of infection in the volunteers were checked with the indirect fluorescent antibody test (IFT). The BIIT WAs reliable (consistently positive) for cloned T. b. rhodesiense. When testing T. b. brucei, the BIIT results depended on the number of incubated parasites and on the parasitaemia peak number the tested trypanosomes derived from. It was further shown that the in vivo part of the BIIT is actually essential for the complete neutralization of T. b. brucei induced by the action of human plasma. Tests with trypanosomes originating from experimentally mixed T. b. rhodesiense and brucei infections gave inconsistent results. On the other hand, pure populations mixed in vitro-prior to incubation for BIIT-revealed results depending on the proportion of the 2 species: up to 20% T. b. rhodesiense gave negative, higher concentrations consistently positive results.
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Studies on malaria and responses of Anopheles balabacensis balabacensis and Anopheles minimus to DDT residual spraying in Thailand. Studies on malaria and on A. b. balabacensis and A. minimus responses to DDT spraying were conducted in a forested hilly area in northern Thailand. In a first phase, base-line data were collected from July 1970 to March 1972. In a second phase, the study area received five round of DDT spraying over a period of two years and at the same time all malaria infections received radical treatment. During this two-year period of field operations, entomological and epidemiological observations were continued. The studies carried out in the second phase, showed that malaria transmission decreased under the applied optimum anti-malarial measures but was not interrupted. Human ecology and population movement inside the forest, especially during the dry season, contributed to a great extent to this result. The transmission occurring in the early part of the monsoon season clearly indicates the importance of the timing of DDT spraying. A. b. balabacensis appeared to be transmitting malaria all the year round in the deep forest but only in the monsoon season in the forest fringe. The vectorial capacity of both vectors was estimated separately for indoor and outdoor populations. The pre-spraying values obtained for A. b. balabacensis were much higher thaan for A. minimus. After DDT spraying A. b. balabacensis showed a decrease in vectorial capacity estimated at 31.5 times for the indoor population and 18 times for the outdoor population. A. minimus, on the other hand, showed a much smaller decrease, estimated at 6.8 and 1.9 times for the indoor and outdoor populations respectively.
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[Ecological study of Ixodes ricinus (Linné, 1758) (Acarina, Ixodoides) in southeastern France]. Ixodes ricinus (LINNE, 1758) is being surveyed in the northern Alp and the Jura mountains. This species, quite often found in the mesophilous forests of the hills, preferably takes root in the forest clusters, where there is a mull type mild humus often covered with an abundant litter. Such plant layers maintain a high degree of moisture, which beneficially affects this species. Examinations performed for three years in a southern Jura's resort allow for securing a preliminary approximation as regards the seasonal population variations.
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The micro-organisms of tsetse flies. Micro-organisms from tsetse fly mycetomes were maintained in culture, where they were more pleomorphic than in the mycetomes, but were in some cases very similar to those observed in ovaries by other authors. Agglutination tests on the cultured forms indicated in affinity to Rickettsia. They were sensitive to antibiotics introduced by feeding flies on hosts treated with Ampicillin; this reduced the longevity and fecundity of the tsetse flies and appeared to disturb normal digestion of bloodmeals.
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The histopathology of experimental disease produced in mice infected with Trypanosoma vivax. An acute form of trypanosomiasis (course of disease 4 to 8 days) was produced in mice experimentally infected with a strain of T. vivax. The features of the disease were: a parasitemia which appeared to increase exponentially from 23.8 to 243.6 times 10(6) trypanosomes per ml within the last 24 hours of the disease; anaemia was not severe in the disease in mice; the basic histological lesion was generalized fibrin thrombus formation in the blood vessels of the heart, lung, spleen and brain; trypanosome enboli were present in the brain, spleen and liver of infected mice. The disease in mice could prove a useful model in studies of the pathogenesis of acute trypanosomiasis and also in studies in the mechanism of generalized intravascular coagulation.
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Lipase and unspecific esterase activity in the fat body of Aedes aegypti L. In the fat body of Aedes aegypti a very high unspecific esterase activity and a low lipolytic activity was found. The electrophoretic isozyme patterns of the unspecific esterases show only few changes in the different physiological stages. The activity of the unspecific esterases as well as of the lipase is especially high in young sugar fed and in blood fed mosquitoes which points to special energy requirements in these stages. The role of the unspecific esterases is discussed.
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Effect of adsorbents on IgM and IgG measles antibodies. Sera from rabbits immunized with L-16 measles virus absorded with monkey blood cells; kaolin and blood cells; and MnCl2 and heparin were examined in haemagglutination inhibition (HI) and neutralization tests. Kaolin and MnCl2 adsorbed primarily HI IgM antibodies from the early immunization period. The adsorbents used had no influence on HI and neutralization IgG antibodies. Human convalescent serum gave similar results, i.e. only IgG antibodies were found and they were not affected by kaolin and MnCl2 with heparin.
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Correlation between molecular size and interferon- inducing activity of poly I:C. Electron microscopy showed that commerical poly I: C consisted of molecules varying in length from less than 0.05 nm to more than 5 nm and also in morphology . To clarify the relationship between its molecular size and interferon-inducing activity, poly I: C was sonicated or fractionated by sucrose density gradient centrifugation, and the molecular length distribution and interferon-inducing activity of each preparation was determined in vivo and in vitro. The results showed that (1) poly I : C molecules 0.1-0.3 nm long were the most effective for interferon induction; (2) sonication of poly I : C reduced its molecular length and also the interferon-inducing activity, the degree of reduction varying in different fractions; and (3) the interferon-inducing activity of poly I: C of 0.1-0.3 nm obtained by sucrose density gradient centrifugation was higher than that poly I: C of corresponding length prepared by sonication.
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Distribution of Lednice (Yaba 1) virus in the chick embryo. Distribution of Lednice (Yaba 1) virus antigen (LVA) was followed by immunofluorescene (IF) in chick embryos inoculated into the yolk sacs. Positive fluorescence of LVA was observed in neurons and neuroblasts of the developing brain, spinal cord and spinal ganglia as well as in skeletal muscles, heart muscle, vascular endothelium and lung mesenchyma. In the yolk sac, foci of specific fluorescence were occasionally seen in endothelium cells of vessels and in islands of extraembryonic haematopoesis. At sites corresponding to the occurrence of LVA, extensive oedema was accompanied by extravazation of erythrocytes and accumulation of white blood cells. The nature of tissues in which the virus replicates was discussed from the point of view of LVA distribution and the morphological lesions observed.
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Serological differences between some isolates of bean yellow mosaic virus. The degree of serological relatedness of three isolates of bean yellow mosaic virus (BYMV) was studied. One common antigenic group (m) was demonstrated in all 3 isolates. In addition, another antigenic group (a) was demonstrated in the isolate FvM1. This group was absent from the isolates TpM3 and TpM11, in which the antigenic group n was found. Antisera to the 3 isolates contained the corresponding antibody groups. The antibody group (M) shared by all 3 BYMV isolates was present in the FvM1 antiserum in a level only a little higher than the second antibody group (A). Antisera to TpM3 and TpM11 isolates showed only a low titre of M antibody, while the second antibody group (N) reached titres from 512 to 1024. Cross-absorption tests revealed serological identity of both isolates of the "necrotic type" (TpM3 and TpM11) and allowed to estimate the degree of their serological relatedness to representatives of the "mosaic type" isolates of BYMV (FvM1).
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Enhancement of the antigenic activity and virulence of the vaccine strain E of Rickettsia prow azeki by passages in cell culture. Changes in the biological properties of the vaccine strain E of Rickettsia prowazeki occurred upon cultivation of A1 (human amnion) cells infected with this strain. In the course of passages of these cells the antigenic activity and virulence of the rickettsia increased. The changes were observed in 10 out of 22 cell cultures examined: in 6 cultures there was an increase in the antigenic activity and in 4 both in the antigenic activity and in virulence. The time of the occurrence of these changes in the rickettsial populations varied from 12-18 to 53-102 days of passage of the infected cells.
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Immunization against Q-fever of naturally infected dairy cows. Dairy cows infected naturally with Coxiella burnetii as evidenced either by presence of phase II agglutinating antibodies in the blood or by shedding C. burnetii in the milk, were vaccinated subcutaneously with formalin-killed phase I C. burnetii organisms. Attempts to demonstrate C. burnetii in the milk of vaccinated dairy cows 47 days after vaccination were negative, while continuous shedding of C. burnetii in the milk of control non-vaccinated dairy cows was repeatedly demonstrated in the course of 123 days (period of investigation). No harmful systemic reaction following vaccination was observed.
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Characterization of Nigerian strains of West Nile virus by plaque formation. Seven strains of West nile virus isolated in Nigeria were investigated for their ability to form plaques in monkey kidney cell monolayers. Five strains antigenically related to one another produced plaques of about the same size 3 to 4 days after the addition of the overlay medium. The two other strains closely related to each other produced no plaques. Their inability to produce plaques was regarded as a significant characteristic of the intratypic group to which the two strains belong.
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Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation. Complement-requiring neutralizing antibodies to herpes simplex type 1 virus (HSV 1) in titres from 2 to greater than 16 were detected in the cerebrospinal fluid (CSF) of 47% senile patients with various forms of dementia, but in none of mentally retarded adolescents and adults suffering from various neurologidal diseases. Also the incidence of HSV 1 serum antibodies in elevated titres (larger than or equal to 512) was increased in senile demented patients (61%) as compared with persons in normal senium (31%), normal adults (15%), mentally retarded adolescents (17%) and prisoned felons with low IQ (45-47%).
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On the problem of oncogene of tumour viruses. The approach to the problem of oncogenesis of tumorigenic viruses is compared and analyzed from the position of the Altshtein-Vogt hypothesis and from that of the general theory of oncogenesis advanced by the present author. In contrast to the hypothesis of Altshtein-Vogt dealing mainly with the problem of oncogene origin, the general theory of oncogenesis not only defines concretely the origin of the oncogene and the essence of its product, but also makes it possible to understand why, when and how integration of the oncogene with the genome of the cell leads to the transformation of the cell into a benign cell and when into a malignant tumour cell. An analysis of the essence of the "oncogene position effect" from this standpoint shows that an integration, similar in its mechanism but differing in polarity, of the genome of other viruses with the cell genome should lead to the formation of a corresponding antiviral stable (life-long) immunity or also to the emergence of pseudoautoimmune disease of the type caused by "slow" viruses.
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Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.
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Nutrition education in the medical school curriculum: a proposal for action: a curriculum design. Nutrition has been traditionally taught in medical schools with emphasis on clinical management of disease states with modified diets. However, the science of nutrition can no longer be considered only in terms of the diagnosis and treatment of nutritional deficiency diseases. Prevention of disease-care rather than cure-must be emphasized. Using the nutrition concepts that evolved from the 1972 Williamsburg Conference encompassing the science and the sociology of nutrition, the author offers a proposal for action-a sequential nutrition curriculum design for years, I, II, and III of undergraduate medical education based on the experiences of the Nutrition Division, Department of Community Medicine, Mount Sinai School of Medicine-City University of New York.
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Management of life-threatening asthma with intravenous isoproterenol infusions. Thirty-four patients with life-threatening childhood status asthmaticus were treated with intravenous isoproterenol infusions. Twenty-seven responded favorably; seven failed to respond and underwent mechanical ventilation. Intravenously administered isoporterenol was a useful therapeutic adjunct in the treatment of these severe attacks. Complications in these cases were rare, but cardiac arrhythmia, rebound bronchospasm, and acute mobilization of secretions need to be considered. Further evaluation of the efficacy of intravenous infusions of isoproterenol in status asthmaticus would be valuable.
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Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes. To evaluate responses to medical therapy in ulcerative colitis, rectal biopsies of patients with active untreated disease, individuals with positive and negative sigmoidoscopic findings treated with salicylazosulfapyridine, prednisone and 6-mercaptopurine, alone and in combinations and noncolitis controls were compared histologically. Predominant histological observations were analyzed statistically. There were fewer crypt abscesses but more mucosal edema after all forms of therapy. Quantitative histopathological analysis failed to demonstrate that the response to one drug was significantly different from another.
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Biochemical and electrophoretic studies of erythrocyte pyridoxine kinase in white and black Americans. The mean PNK activity in red blood cells from black subjects was only about 40% of that in whites. Among 51 whites examined, one was found to have enzyme deficiency. The estimated gene frequencies for PNKH (the common allele in whites which codes for higher enzyme activity) and PNKL (the common allele in blacks which codes for lower enzyme activity) were .35 and .65, respectively, for black donors, and .81 and .19, respectively, for white donors, The variant enzyme in persons with enzyme deficiency was associated with an increased rate of degradation in red cells during aging. No other biochemical or electrophoretic differences were detected.
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Use of the latent image technique to develop and evaluate problem-solving skills. This project involved designing, developing and evaluating a simulation module, utilizing the latent image technique. The general topic chosen for this simulation was the laboratory characterization of anemias. Target learner populations included medical technology students, physician assistant students, and pathology residents. Members of all three groups participated in the evaluation of the module and responded to its use in varied settings.
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Development of a special electrode for continuous subcutaneous pH measurement in the infant scalp. Using a combined special glass electrode it is possible to monitor pH ratios and pH variation in the subcutaneous tissue of the infant scalp continuously. Tests on a normal sample of newborn babies immediately after birth showed a significant correlation between tissue pH and capillary blood pH, with the trend of pH variation being broadly similar in both measurement media.
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Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial. We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation.
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Effect of pH on ionic exchange and function in rat and rabbit myocardium. The effects of pH variation on ionic exchange and mechanical function were studied in the arterially perfused rat and rabbit septa. The pH and PCO2 of the control perfusate were 7.40 and 39 mmHg, respectively. In the rabbit septum a metabolic acidosis (pH equals 6.82, PCO2 equals 39 mmHg) caused a loss of 16% of control tension in 12 min. Na+ and K+ exchange were unaltered. A comparable respiratory acidosis (pH equals 6.81, PCO2 equals 159 mmHg) caused a 51% loss of tension in 2 min. Na+ exchange was unaltered but K+ efflux fell from 8.9 +/- 0.6 (mean +/- SE) to 4.9 +/- 0.3 mmol/kg dry wt per min (P less than 0.001, n equals 10). A net gain of K+ of 16.9 +/- 1.7 (n equals 14) mmol/kg dry wt occurred and was attributable to a delayed fall in K+ influx relative to efflux over 15 min. The net gain could not be mimicked by epinephrine administration or blocked by propranolol and was absent in the beating rat septum and the quiescent rabbit septum. These results suggest that the net uptake of K+, which appears to be dependent on a period of depolarization, and the changes of contractility are controlled by the H+ ion concentration at a cellular site whose exchange with the extracellular space is characterized by a considerable restriction of diffusion. Changes of contractility are not related to the net uptake of K+.
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Acid-base balance in amphibian gastric mucosa. It has been established that H+ secretion can be maintained in frog stomach in the absence of exogenous CO2 by using a nutrient bathing fluid containing 25 mM H2PO4 (pH approximately equal to 4.5) or by lowering the pH of a nonbuffered nutrient solution to about 3.0-3.6. Exogenous CO2 in the presence of these nutrient solutions uniformly caused a marked decrease in H+ secretion, PD, adn short-circuit current (Isc) and an increase in transmucosal resistance (R). Elevation of nutrient [k+] to 83 mM reduced R significantly but transiently without change in H+ when nutrient pH less than 5.0, whereas R returned to base line and H+ increased when nutrient pH greater than 5.0. Acidification of the nutrient medium in the presence of exogenous CO2 results in inhibition of the secretory pump, probably by decreasing intracellular pH, and also interferes with conductance at the nutrient membrane. Removal of exogenous CO2 from standard bicarbonate nutrient solution reduced by 50% the H+, PD, and Isc without change in R; K+-free nutrient solutions reverse these changes in Isc and PD but not in H+. The dropping PD and rising R induced by K+-free nutrient solutions in 5% CO2 - 95% O2 are returned toward normal by 100% O2. Our findings support an important role for exogenous CO2 in maintaining normal acid-base balance in frog mucosa by acting as an acidifying agent.
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Effect of sodium nitrate loading on electrolyte transport by the renal tubule. Effects of sodium nitrate were compared with sodium chloride loading on transport of electrolytes by the nephron. Maximal levels of free water clearance/clomerular filtration rate (CH2O/GFR) averaged 8.4% with nitrate loading and 14.4% with saline loading. Since ethacrynic acid and chlorothiazide exert their major natriuretic effect in the distal nephron, the increment in Na ad Cl reabsorbed beyond the proximal tubule. The administration of these agents resulted in an increase in fractional sodium excretion (CNa/GFR) of 21.1%, urinary sodium excretion (UNaV) of 1,126 mueq/min, and urinary chloride excretion (UClV) of 848 mueq/min during nitrate loading compared with an increase in CNa/GFR of 37.6%, UNaV of 2,362 mueq/min, and UClV of 2,397 mueq/min during saline loading. The smaller diuretic-induced increment in Na and Cl excretion in the nitrate studies suggests, as do the hydrated studies, that less Cl and Na are reabsorbed in the distal nephron during nitrate than saline loading. At every level of UNaV, fractional bicarbonate reabsorption was higher, urine pH was lower, and urinary potassium excretion (UKV) was higher in the nitrate studies. Thus, compared with saline loading, sodium nitrate decreases chloride and sodium reabsorption in the distal nephron. The higher hydrogen and potassium secretion in the nitrate studies may be consequent to the decreased ability of the distal nephron to reabsorb chloride.
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Coronary vascular and myocardial responses to carotid body stimulation in the dog. Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood.
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Oxygenation of frog gastric mucosa in vitro. We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2.
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Mechanisms of disposal of acid and alkali in rabbit duodenum. Stripped duodenal mucosa of rabbits was mounted in Ussing chambers containing a Ringer solution gassed with 100% O2. The disappearance of acid or alkali from the mucosal solution of short-circuited tissue was measured with a pH stat while the serosal pH was kept at 7.4. The duodenum rapidly disposed of both acid and alkali; neither property was altered by gassing with N2 while iodoacetate was in the perfusing solutions. Prevention of release of CO2 from the mucosal chamber obliterated the early rapid phase of acid disposal by the mucosa while a similar maneuver in the serosal chamber increased the appearance of serosal acid without altering the rate of acid disposal. Gut sacs of rabbit duodenum in vitro and in vivo showed a positive correlation between acid disposal and the rate of luminal CO2 production. While acid disposal progressively decreased with time for the in vitro gut sacs, the in vivo gut sac showed no fatigue in this respect. Luminal acidification in the Ussing chamber was associated with a profound reduction in short-circuit current (Isc), partially reversible by elevation of the mucosal pH but not by luminal glucose. Our data suggest that acid disposal occurs in part by intraluminal neutralization and in part by diffusion into the mucosa.
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Maintenance antipsychotic therapy: is the cure worse than the disease? The serious long-term complications of maintenance antipsychotic therapy led the authors to undertake a critical review of outpatient withdrawal studies. Key findings included the following: 1) for a least 40% of outpatient schizophrenics, drugs seem to be essential for survival in the community; 2) the majority of patients who relapse after drug withdrawal recompensate fairly rapidly upon reinstitution of antipsychotic drug therapy; 3) placebo survivors seem to function as well as drug survivors--thus the benefit of maintenance drug therapy appears to be prevention of relapse; and 4) some cases of early relapse after drug withdrawal may be due to dyskinesia rather than psychotic decompensation. The authors urge clinicians to evaluate each patient on maintenance antipsychotic therapy in terms of feasibility of drug withdrawal and offer practical guidelines for withdrawal and subsequent management.
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Task delegation to physician extenders--some comparisons. This study uses a task delegation questionnaire to compare 1973 physician extender practices in seven primary care-oriented sites with a physician attitude survey made in 1969. One additional site using no physician extenders was included as a control. The study involves both major types of physician extenders (physician assistants and nurse practitioners) in ambulatory practices with at least one year of experience in using such personnel. With minor exceptions, actual task delegation patterns conform with the 1969 attitudes of physicians as to which tasks "could and should" be delegated to physician extenders.
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Chest roentgenography as a window to the diagnosis of Takayasu's arteritis. The chest roentgenographic findings in Takayasu's arteritis include widening of the ascending aorta, contour irregularities of the descending aorta, arotic calcifications, pulmonary arterial changes, rib notching, and hilar lymphadenopathy. The single most important diagnostic sign is a segmental calcification outlining a localized or diffuse narrowing of the aorta. The other signs may be suspicious or suggestive, but the diagnostic accuracy increases when several findings are present simultaneously.
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