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Biomedical subjects

B Chevalier

Publications and source records attributed to B Chevalier.

At least 109 records · Page 6Linked to original sources

Increased in-vivo insulin sensitivity but normal liver insulin receptor kinase activity in dwarf chickens.

The effects of the recessive and sex-linked dw gene on insulin sensitivity and liver insulin receptors were compared in normal (Dw-dw) and dwarf (dw-dw) brother or half-brother chickens. At 3.5 weeks of age, following an overnight fast, exogenous insulin (0-6.9 nmol/kg body weight) was slightly but significantly more hypoglycaemic in dwarf chickens. At 4 weeks of age, following an oral glucose load (2 g/kg), glucose tolerance was the same in both genotypes, whereas plasma insulin levels were greatly decreased in dwarf chickens. At 5 weeks of age, plasma concentrations of glucose and insulin were the same in both genotypes in the fasting state and decreased in the fed state in dwarf chickens. In liver membranes prepared from fasted chickens, insulin binding was increased in dwarf chickens, while the affinity of insulin receptors and the insulin-degrading activity of the membranes were the same in both genotypes. Following solubilization with Triton X-100, liver receptors were successively purified on lentil then wheat germ lectins. Autophosphorylation of the beta-subunit did not differ between either the genotype or the nutritional (fed or fasted) state. In the basal state (in the absence of insulin) the tyrosine kinase activity of the receptor towards artificial substrate poly(Glu, Tyr)4:1 was significantly decreased in dwarf chickens by fasting. However, the change in tyrosine kinase activity of the receptor in response to insulin was similar, irrespective of the genotype and the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

[Ventricular tachycardia during theophylline overdose. Apropos of a case of reduction by magnesium chloride].

The authors report a case of ventricular tachycardia (VT) induced by theophylline toxicity in a patient with ischaemic heart disease complicated by left ventricular failure and chronic asthma. Two episodes of VT were reduced by intravenous injection of magnesium chloride. The aggravating role of a moderate magnesium deficiency is suggested by the synergy of hypomagnesemia and theophylline on intracellular calcium fluxes contributing to an accumulation of intracytoplasmic calcium, a situation which has been shown experimentally to generate delayed after depolarisations. The respective roles of the correction of the metabolic deficiency and of the specific antiarrhythmic action related to the calcium blocking effect of magnesium salts at cellular level are discussed.

Drug Overdose↗

[Dynamic left ventricular obstruction increased by nitroglycerin in elderly patients with hypertension and concentric left ventricular hypertrophy].

Left ventricular outflow tract (LVOT) obstruction has been observed in elderly patients with concentric hypertrophic hypertensive cardiomyopathy (HHCM) and no significant valvular disease or regional wall motion abnormalities. In order to determine whether nitroglycerin (NTG) can increase the intraventricular obstruction, we performed echocardiographic (echo) and doppler studies, before and during administration of sublingual NTG (0.8 mg). Twenty patients (n = 20) with long-standing hypertension (19 women and 1 man, mean age 78 +/- 8 yr, mean duration of hypertension 13 +/- 10 yrs were examined. The clinical findings in 17 patients were: angina 5 (29%), dyspnea 9 (53%), syncope or malaise 4 (23%). Electrocardiographic criteria of left ventricular hypertrophy was present in 4 patients and an increased cardio-thoracic ratio (greater than 0.5) in 9 cases. The following echo parameters were determined using M-mode echocardiograms: LV end-diastolic (LVID) and systolic diameter (LVIS), fractional shortening (FS), ventricular septum thickness (IVST), posterior wall thickness (PWT) and the ratio ISVT/PWT (less than 1.3 in all patients). LVM could be calculated in 15 patients and was corrected for body surface area (LVMI). Pulsed and continuous wave Doppler study showed a characteristic late-peaking velocity waveform. We localized the elevated velocities in the LVOT and determined before and during administration of NTG: LVOT peak velocities (V) and peak intraventricular gradients (G) using simplified Bernoulli equation. Results were as follows: [table: see text] Mild mitral regurgitation was observed in 14 patients (70%) and mitral annular calcifications in 11 (55%). Systolic function, as assessed by FS, was normal in all patients. NTG induced a significant acceleration of the LVOT velocities in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Diminished toxicity of ouabain in the hypertrophied rat heart.

The responsiveness to ouabain of hypertrophied rat hearts has been investigated either in vivo using an isolated Langendorff rat heart perfused at various external calcium concentrations, or in vitro on purified sarcolemma vesicles. (i) The physiological study shows that at 0.25 mM CaCl2, the positive inotropic effect of 10(-5) M ouabain was diminished in hypertrophied hearts (p less than 0.02). At 0.5 mM CaCl2, the drug has no effect in controls, but it has a slight positive inotropic effect in hypertrophied hearts. At 2.50 mM CaCl2, ouabain has a negative inotropic effect accompanied by extrasystoles in controls, but in hypertrophied hearts it still has a positive inotropic effect and is not arrhythmogenic. (ii) After the pretreatment of the hearts with 2.5 mM CaCl2, the responsiveness of the (Na+, K+)-ATPase activity to ouabain was studied: the sarcolemma from hypertrophied heart contains half as many low affinity forms of (Na+, K+)-ATPase for ouabain (35% +/- 6) than in controls (80% +/- 2). Assuming that the low affinity forms are responsible for the toxic effect, these data correlate well with some of the physiological findings and suggest that the diminished toxicity for ouabain in hypertrophied hearts rather reflects a modification of the properties of the (Na+, K+)-ATPases than a change in the myocardial calcium metabolism.

Animals↗

Signal and adaptational changes in gene expression during cardiac overload.

Chronic cardiac overload stimulates various quantitative and qualitative mechanisms of adaptation, some of them being species-specific. The signals responsible for these changes in gene expression are still speculative, nevertheless early modifications of the microtubular network have been reported. Soon after overload an increased expression of various genes coding for regulatory proteins has also been observed, this includes various oncogenes and the genes of several heat-shock proteins. Hypertrophy only, is non species-specific and is adaptational because it both multiples the number of contractile units and it lowers wall stress. The slowing of the shortening velocity allows the heart to produce normal tension, at a lower cost, and has different biological explanations depending on the species. In small rodent ventricles, the main but probably not the unique, determinant of this physiological parameter is an isomyosin shift from a high ATPase activity form V1 to a low activity form V3, discovered in our laboratory in 1979. This shift has a transcriptional origin and also occurs in atria in every mammalian including humans; nevertheless it has not been evidenced in the ventricles of humans, dog, cat or guinea-pig. In these species it is necessary to take into account other mechanisms, namely those involved intracellular calcium movements. The number of total, and possibly active, calcium channels is normal in rat overloaded heart suggesting that their synthesis is activated commensurate to the development of hypertrophy. The situation is more complex for other sarcolemma proteins such as the beta-adrenergic system and the Na+, K(+)-ATPase. For the latter there is presently some evidence that an isoenzymatic shift is likely to occur, at least in rats.

Adaptation, Physiological↗

Beta-adrenergic system is modified in compensatory pressure cardiac overload in rats: physiological and biochemical evidence.

The beta-adrenergic system has been explored in cardiac hypertrophy (CH) by combining an in vitro study of the inotropic effect of isoproterenol (ISO) and of forskolin (FSK) and binding assays using radioactive pindolol. CH was obtained within 4-6 weeks by banding the abdominal aorta which results in an increase in left ventricular (LV) weight [743 +/- 14 and 1,098 +/- 24 mg in sham-operated (SH) and in CH, respectively, p less than 0.01] and in the LV wt/body wt ratio (2.14 +/- 0.05 and 3.24 +/- 0.05, p less than 0.001). The inotropic effect was evaluated on an isolated Langendorff heart preparation whose coronary flow was normalized per gram of tissue either by using different constant coronary pressures (75 and 110 mm Hg in SH and in CH, respectively) or different constant coronary flows (15 and 20 ml min-1 in SH and CH, respectively). Binding assays were performed using 125I pindolol, a rather crude preparation of sarcolemma and a LIGAND program for calculation. (i) The inotropic responsiveness to both ISO and FSK is depressed by approximately 30% in CH, at any drug concentration, without change in EC50 whatever the technique used to perfuse the tissue. The time course of the process is slower but, in the case of ISO, remains biphasic. (ii) Binding assays show a normal affinity (Kd 100 pM) while receptor density is depressed (32 +/- 3 and 25 +/- 2 fmol mg protein-1, p less than 0.05 or 3,287 +/- 312 and 2,000 +/- 163 fmol/g fresh tissue, p less than 0.01, in SH and CH, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A review of the renin-angiotensin system in the normal heart.

This review describes the vascular and cardiac tissue renin-angiotensin system (RAS), a so-called autocrine hormonal system as opposed to the circulating endocrine system. The existence of this autocrine system is suggested by the persistence of elevated concentrations of angiotensin II (Ang II) following binephrectomy. There is considerable evidence to support the concept of an autocrine RAS, but the functional aspects of such a system remain controversial: (a) Cultured endothelial cells from blood vessels can, for example, synthesize renin, but angiotensinogen messenger RNA (mRNA) is only present in perivascular adipocytes. (b) In the myocardium, there are obviously problems raised depending on the animal species considered: only rats apparently lack ventricular RAS, but tissue RAS is present in their atrial and conducting tissue system. In other species such as rabbit, the situation is quite different. In addition to the inotropic effect of Ang II, it has recently been demonstrated that this substance may determine the expression of the cardiac genome (oncogenes).

Animals↗

Screening of inotropic drugs on isolated rat and guinea pig hearts.

A technique is described for screening the effects of inotropic drugs on isolated rat or guinea pig hearts perfused at constant coronary pressure and at a frequency of 6 Hz. Their performances, including function curves, were recorded using an intraventricular balloon. Both preparations became either sensitive from initially having been insensitive, or more sensitive from having been slightly sensitive at the outset, to inotropic interventions, provided the external calcium concentration was reduced to 0.25 mM for the rat and 0.50 mM for the guinea pig. The inotropic effect of drugs such as isoproterenol, forskolin, and theophylline was only slightly altered by lowering [Ca]o. Amrinone, sulmazole, and beta agonists such as xamoterol, cicloprolol, pindolol, or RU 42173 almost never caused an inotropic effect at the serum calcium concentration of 2.50 mM, whereas they did provoke a positive response at low [Ca]o. Other compounds such as ouabain, salbutamol, and pimobendan were toxic at high [Ca]o, although at reduced [Ca]o their positive effect on contractility was quite evident.

Animals↗

Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and in humans.

In response to increasing demand, the cardiac muscle has developed several adaptational mechanisms. Gene expression is modified in a quantitative and a qualitative way since the heart hypertrophies and since its structure changes to improve the efficiency of the contraction. The sarcomere modifications are both species- and tissue-specific. An isoenzymic shift of myosin from high adenosine triphosphatase (ATPase) activity form V-1 to low activity form V-3 occurs in all conditions in which V-1 is initially predominant, i.e., in rat (and also rabbit) ventricles and the atria of other species, including humans. It was not observed in conditions in which V-3 was predominant, as in human ventricles (and also in those of cats and pigs). Another shift from creatine kinase (CK) monomer M to CK B, the form that predominates in the fetal heart, is also observed. The sarcolemma is also modified, at least in rats. The digitalis receptor was characterized by studying the inotropic effect of the drug on an isolated heart preparation and on a purified preparation of sarcolemma with a high Na+,K(+)-ATPase activity by binding [3H]ouabain and ouabain-induced inhibition of the enzymatic activity. In hypertrophied heart, both the recovery of normal contractility after ouabain infusion and the release of previously bound ouabain infusion and the release of previously bound ouabain were slowed, as for fetal hearts. Changes in other inotropic receptors have also been reported. From a practical point of view, this means that screening of new inotropic agents has to be done on hypertrophied hearts and not, as usual, on normal tissue.

Adult↗

[The late-life companion and the inanimate object of the person with senile dementia: an attempt at comprehension through a comparative study with phenomena encountered during childhood].

The thought of this work about the mad senile person's affective life concerns some almost permanent clinical establishments such as: on one hand, the existence of late-life companions and inanimate objects evoking some phenomena met during childhood: fancied companion, fetish objects. On the other hand, the existence of "behaviours" evoking those of the little child during his psycho-affective development. We have been led to study the notion of regression during the dementia process and ask ourselves about psychopathological mechanisms underlying this regression, regarded as a mechanism of narcissistic strengthening underlying the appearance of late-life companion or inanimate object. We underline in the conclusion that: on one hand, for these persons showing a deep disturbance of narcissistic economy, there is need to elaborate a relation with a narcissistic object, according to the somato-psychic deterioration level. On the other hand, the phenomena established during the dementia process, can't be assimilated to opposite distance covered by progressive movement.

Aged↗

Spontaneous electrodermal activity during sleep in man: an intranight study.

This study was designed to examine the intranight evolution of spontaneous electrodermal activity (EDA). Eight paid volunteer male students were recorded for 3 complete nights (after a habituation night). The results show that: during the first sleep cycle, EDA is significantly lower than during the rest of the night; rapid eye movement sleep evolves in a particular manner, which emphasizes the specificity of this sleep stage; and there is no internight habituation effect.

Adult↗

[Acetylation phenotype of isoniazid in Morocco. Preliminary study of 100 cases].

A preliminary study to determine the acetylator phenotype for Isoniazid was carried out for the first time on 100 patients. A correlation was shown between the blood and urinary methods; 59% were rapid acetylators and 41% slow acetylators, which were similar levels to those found in Black Africa. The predominance of rapid acetylators certainly explains the excellent tolerance of the high dose of INH (10 mg/kg) used in Morocco. If the determination of the acetylator phenotype could not be used systematically in our country, in view of the individual adaptation to the dosage--the dosage might, on the other hand be worked out in a prompt way before toxic signs appear at a dose of 10 mg/kg or under, of INH--thanks to the calculation of the index of inactivation estimated from a single sample.

Acetylation↗

[Breast cancer in males (author's transl)].

Breast cancer rarely occurs in males, and reliable epidemiological and aetiological studies are scarce. The condition is one hundred times less frequent than in females and usually develops around the age of 60, i.e. 8 years later on average than in women. Its incidence, however, is high in patients with Klinefelter syndrome. Clinical symptoms and paraclinical data are similar to those of female breast cancer. The overall prognosis is considered as being more severe, but the difference is reduced when the results are expressed as corrected survival rate. Treatment is predominantly surgical, radiation therapy being usually reserved to cases where surgery is contraindicated or used to complement surgery. Since breast cancer is hormone-dependent, patients with advanced stage of the disease may benefit from suppressive hormonal treatment.

Aged↗

Myocardial determinants in regulation of the heart rate.

Heart rate is a function of at least three factors located in the sinus node, including the pacemaker and the activity of the sympathetic and vagal pathways. Heart rate varies during breathing and exercising. The is far from being a purely academic question because, after myocardial infarction or in cardiac insufficiency, reduced heart rate variability (HRV) represents the most valuable prognostic factor. HRV is usually considered index of the sympathovagal balance and is explored using time domain analysis, such as spectral analysis. Nevertheless, methods such as the Fast Fourier Transformation are not applicable to small rodents which have an unstable heart rate with asymmetric oscillations. Nonlinear methods show chaotic behavior under some conditions. A time and frequency domain method of analysis, the Wigner-Villé Transform, has been proposed for the study of HRV in both humans and small rodents, as a compromise between linear and nonlinear methods. We developed a method to quantify both arrhythmias and HRV in unanesthetized rodents. Such a method allows study of the relationship between the physiological parameters and the myocardial phenotype. Ventricular premature beats are more frequent in 16-month-old spontaneously hypertensive rats than in age-matched controls. In addition, HRV is attenuated in spontaneously hypertensive rats, as in compensatory cardiac hypertrophy in humans, and such attenuation is considered a prognostic index. Converting enzyme inhibition reduces in parallel arterial hypertension, cardiac hypertrophy, and ventricular fibrosis; it prevents ventricular premature beats and normalizes heart rate variability. It can be demonstrated that the incidence of ventricular premature beats is linked to the myocardial phenotype in terms of both cardiac hypertrophy and fibrosis. The two factors act as independent variables. HRV is correlated with the incidence of arrhythmias, suggesting that the beneficial effects of converting enzyme inhibition are related to prevention of arrhythmias.

Animals↗

An evaluation of total parenteral nutrition in the management of steroid-dependent and steroid-resistant patients with Crohn's disease.

This study is an evaluation of short- and long-term benefits of total parenteral nutrition (TPN) in 20 patients with active Crohn's disease but without fistulae. TPN was done during 42 (14-80) days (median-range) after failure of medical therapy including patients with steroid-resistant (11 SR) or steroid-dependent (9 SD) active Crohn's disease. Efficacy of short-term TPN was demonstrated by nutritional repair and achievement of clinical remission in all but one patients. Follow-up was 28 (8-78) months in the 19 patients (10 SR, 9 SD) discharged improved after the end of TPN. At 1 yr, the cumulative recurrence rate was 26% (5/19). During the follow-up, three patients (2 SR, 1 SD) remained symptom-free, 13 (6 SR, 7 SD) had a partial remission defined as relapse controlled by medication, and only three patients (2 SR, 1 SD) had a relapse uncontrolled by medical therapy leading to surgery. Therefore in our selected population without fistula or abscess, after failure of medical therapy TPN was obviously an effective therapy which avoided surgery. Furthermore follow-up indicated that SD and SR were only transient events in the course of Crohn's disease patients.

Adrenal Cortex Hormones↗

[Medium-term follow-up after percutaneous aortic valvuloplasty in the elderly. Clinical study apropos of 102 cases].

Percutaneous transluminal balloon aortic valvuloplasty was introduced in 1985 and, owing to its sometimes dramatic short-term results, it has rapidly become a useful procedure in the management of aortic stenosis in elderly subjects. The purpose of this study was to determine its clinical results at medium-term and to identify possible prognostic factors in order to improve the selection of patients suitable for this technique. Between January 1986 and December 1987, 78 patients (30 men, 48 women, aged from 60 to 93 years, mean 80 +/- 6.7 years) totalling 85 procedures were selected among 102 dilatations on the basis of a primary success without complications. Dilatation was performed by a technique similar to that described by Cribier et al. The follow-up period was 10 +/- 5.7 months (range: 1 to 27 months). The aortic valve area increased from 0.47 +/- 0.15 cm2 to 0.77 +/- 0.23 cm2, i.e. from 0.29 +/- 0.09 cm2/m2 to 0.48 +/- 0.13 cm2/m2 as regards the indexed area. The hospital mortality rate was 3.3 p. 100. At the end of the follow-up period 55 p. 100 of the patients were in NYHA class I or II; 29 p. 100 had died, 10 p. 100 had undergone a second dilatation and 13 p. 100 had had aortic valve replacement. This distribution into functional classes and major cardiac events was not significantly different in the subgroup of patients with an aortic valve area greater than 0.9 cm2 or in the subgroup of primary failure. The patients who died for cardiac reasons were older (p less than 0.01), had a lower cardiac output before and after dilatation (p less than 0.001) and a lower ejection fraction after dilatation (p less than 0.05) or even before in case of early death (p less than 0.05). Mortality and morbidity therefore were high at medium-term and unrelated to the haemodynamic effect of dilatation. On the other hand, the left ventricular systolic function was determinant, mainly because it could improve or remain stable when initially altered. These results suggest that only patients for whom aortic valve replacement is truly contra-indicated and who have a limited alteration of left ventricular function should be selected for aortic valvuloplasty.

Aged↗