[Eulogy of Jean Cheymol (1896-1988)].
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Biomedical subjects
Publications and source records attributed to P Lechat.
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The effects of sodium butyrate (NaB), a potent growth inhibitory agent, on actin distribution, alkaline phosphatase (AP) activity and protein content were studied in rabbit articular chondrocytes in monolayer culture. When growth of randomly proliferating cells was arrested with NaB, actin stress fibers appeared; at the same time, vimentin-containing intermediate filaments and tubulin-containing microtubules were dispersed. Concomitantly, membrane AP activity and protein content were increased. Such effects support the hypothesis that NaB affects the expression of many proteins by modification of gene expression, probably at the transcriptional level.
We report 133 cases of strokes in patients aged 9-45 (male: 68, female: 65), mean age: 33.5 years. There were 112 arterial infarcts (84%), 9 venous infarcts (7%), 12 hemorrhages (9%). Among the arterial infarcts, 23 (20.5%) were due to a dissecting aneurysm, 17 (15%) to atherosclerosis, 13 (12%) to cardiac embolism. Echocardiography with contrast was performed in 69 patients showing a patent foramen ovale in 15. Mitral valve prolapse was present in 8, among which 5 had in addition a patent foramen ovale. Among 16 migrainous patients there were 7 dissecting aneurysms and 3 patent foramen ovale. Twenty two of 65 women were taking oral contraceptives at the time of the stroke. Strokes in patients taking oral contraceptives or during the puerperium accounted for 43% of the strokes in women. Ten cases (9%) have had no explanation. Venous infarctions were mainly due to puerperium and oral contraceptives. Hemorrhages were mainly due to arterial hypertension. No cause was found in 4/12 cases. The most useful investigations were angiography and echocardiography with contrast. This study confirms that extensive and early investigations are necessary in strokes in the young and particularly in women taking oral contraceptives, migraine patients and patients with mitral valve prolapse.
The cause of ischemic stroke in younger adults is undefined in as many as 35 percent of patients. We studied the prevalence of patent foramen ovale as detected by contrast echocardiography in a population of 60 adults under 55 years old with ischemic stroke and a normal cardiac examination. We compared the results with those in a control group of 100 patients. The prevalence of patent foramen ovale was significantly higher in the patients with stroke (40 percent) than in the control group (10 percent, P less than 0.001). Among the patients with stroke, the prevalence of patent foramen ovale was 21 percent in 19 patients with an identifiable cause of their stroke, 40 percent in 15 patients with no identifiable cause but a risk factor for stroke, such as mitral valve prolapse, migraine, or use of contraceptive agents, and 54 percent in 26 patients with no identifiable cause (P less than 0.10). These results suggest that because of the high prevalence of clinically latent venous thrombosis, paradoxical embolism through a patent foramen ovale may be responsible for stroke more often than is usually suspected.
The advent of vasodilator therapy and new cardiotonic agents has modified the medical treatment of heart failure. First-line treatment is no longer standard; its choice must take into account a number of individual factors such as patient's age, causative cardiopathy, severity of the disease, response to treatment, contra-indications and side-effects of drugs. The aim is to obtain an improvement not only in the patient's comfort but also in long-term prognosis. The prescription of digitalis compounds to heart failure patients with sinus rhythm has been questioned. Alternatives to the conventional therapeutic approach based on cardiac glycosides and diuretics are now available. They include the use at an early stage of vasodilator therapy, and notably angiotensin-converting enzyme inhibitors, in the hope of avoiding gradual reduction of cardiac performance.
Heart cells were cultured from newborn rats, and the contractile activity (CA) and beating frequency (BF) were recorded using an electrooptical technique. Myocardial cells were found to be highly sensitive to Prostacyclin (PGI2) since a 10(-11) M concentration increased the BF and CA. Increasing the concentration (2.7 x 10(-10) to 2.7 x 10(-8) M) resulted in a dose-dependent decrease in CA and BF. The stable product of the non-enzymatic degradation of PGI2 (6 Keto PGF1 alpha) was found to be completely ineffective, and the stable product of the enzymatic PGI2 metabolism (6 Keto PGE1) exerted only a dose-dependent (10(-6) to 10(-5) M) positive inotropic effect. PGI2 was also effective in the presence of serum instead of culture medium but the decrease in CA was less marked than in culture medium, probably due to protein-binding of the drug. When the CA was decreased by PGI2, perfusion with the intracellular calcium-releasing and phosphodiesterase inhibiting agent, caffeine, reversed the PGI2-induced negative inotropic effect. These results suggest that PGI2 participates in the regulation of the heart cell contractility. Its metabolite 6 Keto PGEI could also influence heart cell contractility but higher concentrations are needed. Moreover myocardial intracellular calcium availability seems to be influenced by PGI2.
Despite the benefits of chrysotherapy the responsible mechanism of action of gold compounds remains unclear. At a concentration of 5 x 10(-4) M, sodium aurothiopropanol sulfonate (SAS) modified the in vitro proliferation kinetics of articular chondrocytes by reducing growth, viability and plating efficiency. Flow cytometry analysis, using propidium iodide DNA staining, revealed slight but significant cell arrest in G2+M which, in fact, represents an increase in the proportion of binucleate cells. SAS did not induce any variations in chondrocyte phenotype stability as far as the biosynthesis of type II collagen was concerned, and no appreciable changes in overall mitochondrial activity reflected by rhodamine 123 incorporation.
The currently required surgical procedure for implantable defibrillator implantation is a limiting factor and several groups are therefore investigating transvenous approaches. Our electrode system consists of a nondistal right ventricular catheter electrode and two or three subcutaneously (SC) placed electrodes. An optimal location for these SC electrodes is important to obtain the lowest possible defibrillation threshold (DFT) by allowing a more homogeneous current distribution within the thorax. An empirical approach consists of placing randomly the SC electrodes to find out the lowest possible DFT. A mathematical approach is to calculate the SC electrode locations for an optimal electric field distribution by using magnetic resonance images of thorax cross-sections and a specially designed computer program. Our recent experimental results are based on a series of 15 pigs weighing between 60 and 102 Kg. DFT ranged between 10 and 26 joules. We conclude that an electrode system with a right ventricular electrode and two or three subcutaneous electrodes can be optimized to reach a DFT for pigs with human-near body weights which is compatible with the energy capabilities of our implantable device.
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Studies of changes in coronary blood flow during cardiac cycles may be a useful adjuvant to the measurement of coronary flow reserve to evaluate the hydraulic severity of coronary arterial stenoses. We used intracoronary pulsed Doppler velocimetry to measure phasic variations of blood flow in the anterior interventricular artery of 12 patients with angiographically identified stenosis of that vessel. The Doppler signal was obtained by means of a 20 MHz emission from a source placed at the tip of a catheter selectively positioned at the ostium of the anterior interventricular artery, upstream of the stenosis. The increase in severity of stenosis was paralleled by a relative decrease of diastolic blood flow velocity in relation to systolic blood flow velocity. The diastolic/systolic maximum velocities ratio was greater than 1 in 6 patients with a less than 70 p. 100 stenosis (group A) and inferior to 1 in 6 other patients with a 70 p. 100 or more stenosis (group B). In 5 patients of group B this ratio was reversed to normal after percutaneous transluminal angiography. Thus, measurement of intracoronary blood flow velocity may be helpful to evaluate the severity of stenosis, notably in the anterior interventricular artery where angiographic evaluation is difficult.
In heart of genetically obese (fa/fa) 12-week-old Zucker rats, ventricle contractility (4 mM KCl medium), amplitude and duration of slow action potentials (14 mM KCl medium) were less increased by isoprenaline than in heart of non obese (Fa/fa) rats. This difference could be related to a lower reactivity of beta-adrenoceptors in obese rat heart.
In order to study abnormalities of left ventricular diastolic function (LVDF) in heart transplant patients and their possible association with graft rejection, 21 patients who had recently undergone orthotopic heart transplantation were evaluated prospectively, on the day of endomyocardial biopsy, by pulsed and continuous Doppler echocardiography (DEC). Investigation of the LVDF consisted of pulsed DEC of the mitral valve in apical projection (4 cavities) with measurement of isovolumetric relaxation time (IVR), peak velocity of rapid ventricular filling (E), peak velocity of graft atrial contraction (A) and transmitral gradient decrease half-time (mitral T1/2). Each patients had 5 DEC examinations on average over a 2-month period. In patients with subsevere to severe rejection mitral T1/2 decreased significantly from 76.46 +/- 11.6 ms in the absence of rejection to 47 +/- 13.7 ms during rejection (P less than 0.001). When mitral T1/2 decreased by 25 p. 100 or more between two successive DEC, rejection was present in 89 p. 100 of the cases. It is concluded that Doppler echocardiographic studies of left ventricular diastolic function provide useful information in the follow-up of heart transplant recipients and offer hopes, in a not too distant future, of non-invasive detection of cardiac graft rejection.
Proton magnetic resonance spectroscopy of plasma indicates an alteration of proteolipid methyl and methylene resonances after heart transplantation. The intensity of these alterations is modulated by the transplant tolerance phenomena and allows the accurate detection of heart graft rejection. These results reinforce the analogy between the immunology of graft tolerance and the immunology of cancer or pregnancy where identical alterations have been identified.
Reproducibility of myocardial ischemia induced by atrial pacing (P) was investigated in 25 patients (pts) without previous anterior myocardial infarction and showing a positive exercise stress test. The second period of atrial pacing (P2) was exerted 20 minutes after the first (P1). During P2, a reduction in the parameters reflecting myocardial oxygen requirements (maximal left ventricular pressure, dp/dt max, TTI*HR values) was noted, while the signs of ischemia were less pronounced (ST depression decreasing from 2.3 +/- 1 mm to 1.6 +/- 1.0 mm; % of lactate extraction (%L) decreasing from - 6.4 +/- 25.5 to + 8.5 +/- 19.2; p less than 0.5). The 25 pts were divided into 2 groups according to the ejection fraction (EF greater than .55 16 pts Gr.F+; EF less than .55 9 pts Gr.F-). The distribution of coronary lesions was the same for the 2 groups. During P1 GR.F+ registered a negative % L as opposed to Gr.F-. During P2, the difference in the % L between the 2 groups was also significant (2.6 +/- 19.9% F+ vs 18.9 +/- 14.3% F-; p less than .05). Collateral circulation had no effect upon the results, neither for P1 or P2. This study shows that a second period of atrial pacing, 20 minutes after the first, induced lesser ischemia than the first period of atrial pacing. This phenomenon could explain the paradoxical improvement observed in certain patients after a first episode of angina. These results have implications as regards the necessity of double blind studies compared to placebo when using this technique in the evaluation of the effects of anti-ischemic drugs.
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Genetically obese Zucker rats share several abnormalities with obese patients: inheritance of the obesity, hyperinsulinemia, hypertriglyceridemia. Because alterations in membrane fatty acid composition and in prostaglandin synthesis can be involved in the genesis of the cardiovascular complications of obesity, cardiac prostaglandins and phospholipid fatty acid composition were compared in obese and lean animals. Obese cardiac tissues produced smaller amounts of prostacyclin, thromboxane A2 and PGE2 than lean (p less than 0.01). The cyclooxygenase pathway and the activation of phospholipase by the calcium ionophore A 23187 were not altered. Phospholipid fatty acid composition of obese tissues was abnormal: the amount of stearic, arachidonic, docosapentaenoic and cervonic acids was decreased, whereas the amount of linoleic acid, the precursor of arachidonic acid, was doubled. It is concluded that obesity in Zucker rats is associated with alteration of cardiac arachidonic acid metabolism and that the alterations associated with obesity can be studied in this rat strain.
H466-B and T47-D breast carcinoma cell lines were treated with recombinant gamma interferon (r gamma IFN) to study major histocompatibility complex (MHC) class I and class II antigen responses. Untreated H466-B cells released B2 microglobulin (B2M) into the culture medium and expressed B2M and class I heavy chain on 100% of the cells. The expression of class II antigens (DR) was limited to 8 +/- 4% of the cells. This subpopulation was isolated by cell sorting and labelled with 35S methionine. Protein extracts were immunoprecipitated with anti-DR antibody and subjected to two dimensional non-equilibrium pH gradient electrophoresis (2D-PAGE). A normal pattern of expression of invariant, alpha and beta chains was shown. The MHC antigenic expression of H466-B parental cell line was not modified by interferon treatment. Untreated T47-D cells did not release B2M into the culture medium, expressed B2M and class I heavy chain on 100% of the cells but did not express class II molecules using radio-immunoassay or 2D-PAGE. As early as 24 h after r gamma IFN addition, T47-D cells released B2M into the medium, B2M and class I heavy chain were significantly greater than that of untreated cells, and class II antigenic expression was found, all these in a dose dependent manner. 2D-PAGE analysis of class II antigens revealed the profile of human DR molecules but this expression seemed incomplete since only single alpha and beta spots were detected suggesting a possible defect in the sialilation of DR molecules. These results show a heterogeneity in MHC antigenic responses to r gamma IFN and suggest that synthetized class II molecules may be incompletely processed.