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Biomedical subjects

F Guérin

Publications and source records attributed to F Guérin.

At least 37 records · Page 2Linked to original sources

[Primary leiomyosarcoma of the pulmonary artery. Apropos of a case. Review of the literature].

A 59-year-old woman hospitalised because of dyspnea and a heart murmur in a context of pyrexia was found to have evidence of obstruction of the pulmonary arterial system, clearly defined by ultrasonography, catheterisation and angiography and Imatron scan. The particular feature of this fifth reported case of pulmonary artery leiomyosarcoma is its documentation by transesophageal ultrasonography and tumor biopsy during catheterisation. Surgery with partial excision of the tumor was followed by survival for 6 months, bearing in mind the absence of chemo- or radiosensitivity of this type of tumor. Cases from the literature are reviewed.

Angiography↗

[Mechanism of cellular action of nitrate derivatives].

Nitrate derivatives have to undergo metabolic activation in the smooth muscle cell or in the plasma with a sulflydryl radical. This transformation results in the formation of nitric oxide and/or S-nitrosothiols. These products stimulate an enzyme, the soluble guanylate cyclase in the sarcoplasm of the smooth muscle cell; giving rise to the formation of intracellular cyclic GMP from GTP. The cyclic GMP activates a kinase protein which in turn activates a number of other protein enzymes involved in the recaptation of calcium by the sarcoplasmic reticulum and in the extrusion of calcium from the cell. In addition, cyclic GMP reduces the level of phosphorylation of the myosin light chain, thereby reducing the sensitivity of the contractile proteins to intracellular calcium. All these phenomena cause smooth muscle relaxation so explaining most of the vasodilator effect of nitrate derivatives.

Cyclic GMP↗

[Isosorbide dinitrate in the treatment of coronary insufficiency].

The improvement of our understanding of the pharmacology of nitrate derivatives has allowed rationalisation of their use in the treatment of coronary artery disease. The comprehension of the evolution of the sensitivity of the vessel wall to nitrate vasodilatation with time has enabled definition of a rhythm of administration which preserves therapeutic efficacy: a daily therapeutic window of 8 to 10 hours. The introduction of new galenic forms (slow release oral preparations and transdermal patches) facilitates the practical application of the "optimal" pharmacokinetic profile. A single daily dose of slow release ISDN is effective in controlled trials versus placebo in the treatment of chronic stable angina. Many clinical trials have also shown the synergy of the anti-anginal effects of ISDN and betablockers, both in single dose studies and during prolonged administration. These therapeutic windows are not adapted to the treatment of acute coronary insufficiency (unstable angina, myocardial infarction); however, it has recently been shown that the use of small, fixed doses of intravenous ISDN over a 3 day period is usually adequate for controlling acute coronary insufficiency and is not associated with the phenomenon of tolerance.

Adrenergic beta-Antagonists↗

[Evaluation of tolerance during intravenous administration of low dose of isosorbide dinitrate in the treatment of unstable angina].

The eventuality of tolerance was assessed in 19 patients with unstable angina treated by continuous intravenous infusion of 50 micrograms/min of isosorbide trinitrate (ISDN) in association with heparin and betablocker therapy. The tolerance phenomenon was evaluated by the hypotension produced by the ISDN infusion and by the amplitude of fall in blood pressure produced by an intravenous bolus of 1 mg of glyceryl trinitrate (GTN) according to the principle of crossed tolerance to the two nitrate derivatives. Under these conditions of administration, the authors observed partial attenuation of the blood pressure response to continuous ISDN infusion and absence of cross tolerance between ISDN and intravenous GTN. The co-prescription of intravenous N-acetylcysteine at a dosage of 10 g/24 hours in 10 of the 19 patients did not affect the blood pressure or the response to the GTN bolus compared with the 9 other patients who had received placebo after double-blind randomisation. The results of this study do not indicate if the maintenance of vascular sensitivity to nitrate derivatives at least for 72 hours, was related to the choice of a relatively low dose and/or the use of ISDN rather than another nitrate derivative, in particular glyceryl trinitrate. The use of intravenous ISDN at a low dose over a 3 day period in the usual conditions of prescription for unstable angina does not seem to induce a quantitatively significant phenomenon of tolerance.

Acetylcysteine↗

The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Animals↗

[Effect of sinorphan, an endopeptidase inhibitor on severe congestive cardiac insufficiency].

Sinorphan is a powerful inhibitor of enkephalinases or endopeptidases 24-11, enzymes implicated in the degradation of the atrial natriuretic factor (ANF). In healthy volunteers, it increases plasma concentrations of endogenic ANF and increases diuresis and natriuresis. In order to study the tolerance and biological effects of pharmacological increase of plasma concentrations of endogenic ANF in severe congestive cardiac failure, 12 patients (in functional Classes III or IV of the NYHA classification) were given a single oral dose of 10, 20 or 40 mg of Sinorphan. Sinorphan was clinically well tolerated. The diastolic blood pressure decreased slightly (- 10 +/- 9 mmHg) but significantly (p less than 0.05). Systolic blood pressure and heart rate were unchanged. Despite spontaneously high plasma ANF concentrations (on average 15 times higher than normal subjects), Sinorphan induced an additional increase of 80 to 100% of plasma ANF concentration compared to the initial values (p less than 0.01) with no dose-dependent response for the dosages used. The inhibition of plasma endopeptidase activity attained 47% at the 30th minute. Urinary cyclic GMP excretion increased by 30% at the second hour (p less than 0.05). In addition, a statistically non significant tendency to increase diuresis and natriuresis was observed. These results show that Sinorphan increases plasma ANF concentrations by inhibition of its degradation in severe congestive cardiac failure and that this increase seems to be associated with potentially beneficial biological changes. The concept of endopeptidase inhibition should constitute a new therapeutic approach in cardiac failure, a situation in which the ANF seems to exert a favourable effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Demonstration of abnormalities of myocardial mitochondrial oxygenation in cardiac graft rejection].

Abnormalities of myocardial metabolism during acute rejection may be due to ischemia to primary metabolic changes related to rejection. An experimental study of heterotopic cardiac transplantation in the rat was undertaken to study myocardial mitochondrial oxidation during acute rejection. The receivers were Lewis rats and the donors Fischer (FL: allograft) or Lewis (LL: isograft) rats. The oxygen consumption of the mitochondria (VO2m) isolated from the transplanted and native hearts was measured by oxygraphy six days after transplantation. Using maleate and glutamate substrates, the VO2m of transplanted hearts was significantly lower than that of native hearts in the two groups of rats (FL, p less than 0.01; LL, p less than 0.01). In addition, the VO2m of FL allograft transplanted hearts was significantly lower than in the LL rats (30 +/- 9 vs 100 +/- 15 nanoatoms of oxygen/min.mg/prot, p less than 0.01) as was the VO2m of the native hearts (FL: 106 +/- 23 vs LL: 164 +/- 26, p less than 0.02). The respiratory control ratio (RCR) was significantly lower in the transplanted than in the native hearts in both the FL and LL groups (p less than 0.05 and p less than 0.01 respectively). The comparison of the RCR in the two groups (FL vs LL) showed no significant difference for transplanted or native hearts. Electron microscopy of transplanted (rejected or not) and native hearts showed no morphological abnormality of the mitochondria. The lower VO2m of the allograft group indicates a disturbance in the mitochondrial respiratory pathway during acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Abnormalities of the skeletal muscle in hypertrophic cardiomyopathy. Spectroscopy using phosphorus-31 nuclear magnetic resonance].

There have been several reports of electromyographic and histological changes of striated skeletal muscle, especially of the type I oxidative fibres, in hypertrophic cardiomyopathy. In order to determine whether these anomalies also cause metabolic changes, a P-31 magnetic resonance spectroscopic study was undertaken at rest and on exercise in 5 pauci-symptomatic patients and 10 control subjects. The 5 patients had primary hypertrophic cardiomyopathy without alteration of systolic function or signs of congestive cardiac failure (Stages I or II). There were no clinical signs of myopathy. None of the patients were receiving betablocker therapy at the time of investigation. No significant difference was observed at rest. Intracellular acidosis was particularly pronounced in 2 of the 5 patients at the peak of exercise. In addition, the phosphocreatine recovery time (T1/2) was longer in the patient group (3.4 +/- 1.7 vs 1.6 +/- 0.9 mn; p less than 0.01) suggesting a mitochondrial metabolic oxidation abnormality. These results suggest that some patients with primary hypertrophic cardiomyopathy have abnormalities of mitochondrial oxidation in their striated skeletal muscle which can be demonstrated by P-31 magnetic resonance spectroscopy. This would suggest a global abnormality of striated muscle which, at a more advanced stage of the disease, could account for decreased effort tolerance in these patients.

Adult↗

[The function of beta receptors in chronic left ventricular insufficiency].

Hyperactivity of the noradrenergic sympathetic system is one of the essential "compensatory"mechanisms in chronic left ventricular failure. The ensuing stimulation of myocardial beta-adrenergic receptors results in an increase of heart rate and contractility which, to some extent, counterbalances the alteration of left ventricular function, but rapidly reaches its limits: the excessive shortening of diastoles and, mostly, the increase of myocardial oxygen demand neutralize the beneficial haemodynamic effect of beta-adrenergic stimulation, especially when ischaemia is the cause of the heart failure; the chronic exposure of adrenergic receptors to noradrenaline in high concentrations leads to desensitization, to a "down regulation" which primarily affects the beta 1 receptors and spares, at least partly, the myocardial beta 2 receptors which seem to play a quantitatively important inotropic role, particularly in chronic heart failure. These new data on the physiology of the cardiac noradrenergic system have major therapeutic consequences: in practice, the positively inotropic beta-stimulants can only be used for a short period in acute episodes of heart failure; - the use of beta-blockers in low doses is now considered in the treatment of some forms of heart failure; the mechanism of their therapeutic action remains controverted, and their long-term effectiveness in a large patient population is under study; - a new pharmacological class, beta-adrenoceptor partial agonists, seems to give satisfactory clinical and haemodynamic results in mode-rate heart failure, A wider clinical evaluation is needed to determine the therapeutic role of theses new pharmacodynamic agents.

Adrenergic beta-Antagonists↗

Pharmacodynamic effect of nicardipine on left ventricular function in systemic sclerosis.

Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients with systemic sclerosis. Resting gated, blood-pool images were obtained at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SEM) left ventricular ejection fraction significantly increased from 65.4 +/- 2.3% at baseline to 71.3 +/- 2.3% after nicardipine (p less than 0.005). The mean global defect score significantly decreased from 2.90 +/- 0.73 without nicardipine to 1.50 +/- 0.52 with nicardipine (p less than 0.01). The mean number of left ventricular sectors with severe hypokinesis significantly decreased from 0.80 +/- 0.24 at baseline to 0.20 +/- 0.09 after nicardipine (p less than 0.05). No significant side effects were observed with nicardipine. These results demonstrate short-term improvement in left ventricular function with nicardipine in patients with systemic sclerosis.

Adult↗

[Constrictive pericarditis and Whipple's disease].

The authors report the case of a 61 year-old patient treated by tetracycline for very probable Whipple's disease who developed constrictive pericarditis requiring pericardectomy. Although intestinal biopsy was negative, histological examination of the resected pericardium was very suggestive of a cardiac localisation of Whipple's disease, showing a fibrous pericarditis with a mononuclear infiltration including PAS-positive histiocytes. In addition, the same histological changes were found in a small fragment of myocardial biopsy. This case illustrates the prevalence and consequences of cardiac involvement in Whipple's disease.

Cineradiography↗

[Adrenergic betareceptors and cardiac insufficiency].

Noradrenergic sympathetic tone is always increased in chronic left ventricular failure of which it is one of the main compensatory mechanisms. Beta-1-adrenergic stimulation increases the heart rate and left ventricular contractility. However, the efficacy of this "compensatory" mechanism is limited on the one hand by the energetic cost of inotropic stimulation and, on the other hand, by the phenomenon of desensitisation and down-regulation of myocardial beta-1-receptors during intense and prolonged noradrenergic stimulation as observed in chronic cardiac failure. These physiopathological concepts raise the question of the indications of drugs affecting betareceptors in cardiac failure. Positive inotropic beta-mimetics can only be used during short periods of acute decompensation: low dose betablocker therapy protects the betareceptors from the phenomenon of desensitisation and seem to exert a beneficial action in this way in some cases of cardiac failure; these preliminary results require confirmation by large scale controlled therapeutic trials. Finally, a new pharmacological class of drugs, the beta-1 adrenergic partial agonists, seems to be useful in the management of moderate degrees of cardiac failure due to ischemic heart disease.

Adrenergic beta-Agonists↗

[The value of recording the pulmonary insufficiency flow by continuous Doppler for the evaluation of systolic pulmonary artery pressure].

Systolic, diastolic and mean pulmonary artery pressures can be evaluated by Doppler recordings of the maximal velocity of tricuspid regurgitation and early and late diastolic pulmonary regurgitant flow. The aim of this study was to assess the reliability of the calculation of systolic pulmonary artery pressure from pulmonary regurgitant flow by comparing the values with those obtained from the tricuspid regurgitant flow in the same patient. With this objective in mind, we investigated 70 patients with an average age of 45 +/- 34 years, in sinus rhythm, all of whom had tricuspid and pulmonary regurgitant jets which could be recorded with continuous wave Doppler. Systolic pulmonary artery pressure was calculated as follows: from tricuspid regurgitation: maximum pressure gradient + 10 mmHg; from pulmonary regurgitation: 3 x early diastolic gradient - 2 x late diastolic gradient + 10 mmHg. The systolic pulmonary artery pressures calculated from tricuspid and pulmonary regurgitation were: 42 +/- 16 mmHg and 43 +/- 17 mmHg respectively (r = 0.97) with an estimated standard error of 4.7 mmHg. These results show that the recording of pulmonary regurgitation by continuous wave Doppler allows accurate estimation of pulmonary artery pressures. The calculation by the two methods using tricuspid and pulmonary regurgitant jets increases the reliability of the results and provides a means of internal validation of the Doppler technique.

Adolescent↗

[Peripheral circulatory and metabolic changes in cardiac insufficiency. Therapeutic implications].

Many peripheral changes are observed in heart failure concerning regional blood flow, vasomotor tone and oxygen uptake by skeletal muscle. They contribute to the alteration of exercise capacity and have to be taken into consideration in adapting therapy. A regression of these peripheral abnormalities is often observed after prolonged treatment which implies evaluation of efficacy on effort tolerance after a sufficiently long period of administration.

Blood Circulation↗

[Dilated cardiomyopathy with deep, completely reversible dysfunction of the left heart in alcoholic patients. Report of 2 cases].

Two cases of dilated, hypokinetic cardiomyopathy complicated by cardiac failure, are reported in a 29 year old woman and a 55 year old man, with no etiological factors other than chronic major alcoholism (consumption of over 100 ml of alcohol per day for over 5 years). This was completely reversed 10 and 14 months after cessation of alcohol consumption. The isotopic left ventricular ejection fraction increased from 22 to 70 p. 100 and from 12 to 73% respectively. These cases are are and are evidence in favour of an alcoholic cardiomyopathy rather than alcohol being an aggravating factor in patients with cardiomyopathy.

Adult↗

Change in human cardiac rhythm induced by a 2-T static magnetic field.

The influence of a 2-T static magnetic field on the cardiac rhythm was studied with 24-hour electrocardiographic monitoring in 12 healthy volunteers for 1 hour before exposure, 1 hour during exposure, and 22 hours after exposure. Four other subjects were exposed to 1 T, and nine control subjects were exposed to 0 T. In the 2-T group, the mean cardiac cycle length (CCL) was 912 msec +/- 83 before exposure. A significant 17% increase in CCL was observed after 10 minutes of exposure. No further significant variation was observed during exposure, and the CCL was back to preexposure values 10 minutes after exposure. No other arrhythmogenic effect was noted during the 24-hour monitoring. No statistically significant change was observed at either 0 or 1 T. The magnetically induced blood-flow potentials superimposed on the T wave were observed. The CCL increase during exposure could reflect a direct or indirect effect of magnetic fields on the sinus node, which is probably harmless in healthy subjects. However, its safety in dysrhythmic patients remains to be determined.

Adult↗