[Acute infectious endocarditis after valvular replacement surgery. I. Clinical and etiological study of 949 operated patients].
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Biomedical subjects
Publications and source records attributed to R Franco.
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Substance P is present in intrinsic nerves in the intestine and in some extrinsic sensory nerves. It can be released from these nerves to act on the muscle layers and on other enteric neurons. Immunohistochemical studies show that the enteric substance P neurons are short and branch profusely to supply all intestinal layers. Pharmacological studies indicate that enteric substance P neurons receive inputs from enteric cholinergic interneurons. This suggests that these neurons are part of multineuronal nerve pathways in the intestine. The substance P neurons are not essential for the enteric reflexes which subserve peristalsis but they appear to modulate these reflexes.
In soluble rat brain fraction, the specific activities of purine nucleoside phosphorylase, guanine deaminase, 5'Nucleotidase and adenosine deaminase, decrease in their mentioned order. A kinetic parameter comparison between these enzymes shows that 5'Nucleotidase with AMP has the lowest KM and the greatest Vmax values, while purine nucleoside phosphorylase has its lowest KM and its greatest Vmax values with guanosine and with inosine, respectively. The enzymes activity is not modified by the metabolic intermediates differently from their own reaction products which behave as competitive inhibitors.
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Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.
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The desensitization of receptors for substance P in the longitudinal muscle of the guinea-pig ileum has been studied. Receptors for substance P in the muscle became desensitized in the presence of relatively large concentrations of synthetic substance P; a desensitizing concentration of substance P of 7.5 x 10(-9) M shifted the concentration-response curve for substance P about 20-fold to the right, while a desensitizing concentration of 7.5 x 10(-8) M shifted the curve about 300-fold to the right. This desensitization appeared specific; concentration-response curves for carbachol, DMPP, 5-HT and bradykinin were not significantly affected by substance P, 7.5 x 10(-8) M. Furthermore, substance P in concentrations up to 7.5 x 10(-8) M did not modify transmission from either cholinergic nerves or enteric inhibitory nerves when these were stimulated electrically. However, hyoscine-resistant contractions produced by stimulation of nerves in the ileum at 10 Hz were abolished by exposure to concentrations of substance P of 7.5 x 10(-9) M or greater, suggesting that these nerves release a substance similar to or identical with substance P. DMPP evoked small hyoscine-resistant contractions of the ileum. These contractions were also antagonised by desensitization of receptors for substance P. Immunohistochemical studies showed substance P-like immunoreactivity in nerve terminals of both the myenteric and submucous plexuses.
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Hyporeninemic hypoaldosteronism was diagnosed in a young woman with glomerulonephritis who was receiving indomethacin therapy. Despite only mildly abnormal renal function, serum K+ was elevated to 6.2 meq/L, and plasma renin activity (0.12 ng/mL h) and aldosterone (4.4 ng/dL) failed to respond to the combined stimuli of furosemide and posture. Urinary prostaglandin E2 (PGE2) was suppressed (70 ng/24 h). When indomethacin was withdrawn, significant kaliuresis occurred, accompanied by normalization of serum K+ and PGE2 and a supranormal rebound in renin and aldosterone levels. Challenge with indomethacin resulted in antikaliuresis and resuppression of PGE2, renin, and aldosterone. This case study documents for the first time that indomethacin can cause the syndrome of hyporeninemic hypoaldosteronism, probably by inhibiting prostaglandin biosynthesis.
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1 Desipramine and protriptyline were administered to anaesthetized rats by two consecutive intravenous infusions in order to obtain a peak level (first infusion) followed by lower steady state concentrations (second infusion) (Wagner, 1974). Theoretical plasma level time courses were confirmed experimentally.2 Desipramine and protriptyline were measured in atria and ventricles. Increasing infusion rates led to proportional increases in plasma and atrial concentrations. The tissue/medium ratio ranged from 57 to 21 for desipramine and from 43 to 11 for protriptyline according to the time of determination during infusions.3 Heart rate changes, deviation of the electrical axis of the heart and prolongation of atrioventricular conduction were recorded at fixed times during infusion.4 Positive chronotropic effects were noted at plasma concentrations ranging from 0.035 to 0.1 mug/ml for desipramine and from 0.04 to 1.2 mug/ml for protriptyline. At higher plasma concentrations the positive chronotropic effect decreased and bradycardia developed. Both drugs induced right rotation of the electrical axis of the heart. Threshold plasma levels giving 40 degrees rotation were 1.35 mug/ml (desipramine) and 1.75 mug/ml (protriptyline). Atrioventricular conduction was prolonged at threshold plasma concentrations of 2.2 mug/ml for desipramine and 3.6 mug/ml for protriptyline.5 Desipramine is more cardiotoxic than protriptyline. This difference is discussed in relation to the plasma and heart concentration of the two drugs.
1. The relationship between plasma concentrations and cardiac effects of nortriptyline was studied in anaesthetized young and old rats. 2. Nortriptyline was administered by two consecutive intravenous infusions which resulted in a peak plasma concentration followed by steady state values. Increasing infusion rates were followed by proportional increases in the drug plasma concentrations ranging from 0.15 to 6.0 microgram/ml. 3. In young rats, nortriptyline induced an increase in the heart rate, a right rotation of the electrical axis and a prolongation of the PQ interval. Heart rate changes were not correlated with nortriptyline plasma concentrations, while significant correlations were found for the other two parameters. Plasma concentrations inducing 20% increase of the PQ interval and 40 degrees rotation of the electrical axis were 1.65 microgram/ml respectively. Arrhythmias occurred at concentrations higher than 5.2 microgram/ml. 4. Nortriptyline caused more severe cardiac effects in old than in young animals. However, plasma concentrations of nortriptyline in old rats were two to five times higher than those found in young rats at similar infusion rates. A higher concentration of the drug at its sites of action seems to be responsible for the more severe cardiac toxicity of nortriptyline observed in old rats.
Dialysable peptides (M. W. less than 12,000) were obtained by plasmin digests of purified bovine fibrinogen. The biological effects of these peptides were studied in rats in three different test systems: ADP-induced platelet aggregation, isolated atria contractility and vascular permeability. The effects induced by the peptides were: inhibition of ADP-induced platelet aggregation, increase in the frequency of isolated atria contractions and local increase in vascular permeability. All these activities were concentration dependent. Six micrograms of the peptides were still effective in increasing vascular permeability; in the in vitro systems the smallest effective dose ranged between 165 and 650 mug/ml. Following elution through a Sephadex G-25 gel with bidistilled water, four fractions were obtained. The second fraction (M.W. about 5,000) was the most active, followed by the first and then the third one; the fourth fraction was inactive. These data suggest that local accumulation of peptides in vivo may be of clinical relevancy.
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Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon.
Jourard's 40-item Self-disclosure Questionnaire was administered to 50 students in a training and selection program for a quasi-counseling position and 52 randomly selected students. Subjects indicated past disclosures to three target persons, parents, best friend, and stranger. Results indicated: highest disclosures were reported to best friends, lowest to strangers; subjects interested in the quasi-counseling position reported more disclosure than subjects not interested in this position; females reported more disclosure than males only to strangers.
The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.