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Biomedical subjects

R Bernard

Publications and source records attributed to R Bernard.

At least 19 recordsLinked to original sources

Effects of TGF beta 1 on the proliferation and differentiation of an immortalized astrocyte cell line: relationship with extracellular matrix.

The astrocyte cell line (C.LT.T.1.1.), which is immortalized and has retained a normal density-dependent regulation of growth, is a suitable model for studying the relationships between proliferation, differentiation, and the production of extracellular matrix. The growth factor TGF beta 1 was used to modulate these processes. When added to proliferative cells, it inhibited growth and caused morphological changes. It also suppressed the growth arrest at confluence, so that the cells formed multilayers of parallel spindle-shaped cells. Whereas untreated control cells expressed progressively the glial fibrillary acidic protein (GFAP) after arrest of multiplication, the addition of TGF beta 1 to proliferative cells prevented GFAP expression and accumulation of its mRNA. Concomitantly, it increased the amounts of laminin, fibronectin, and collagens synthesized during the growth phase and greatly altered the composition and the structure of the matrix deposited at confluence. In contrast, when added after cell differentiation had begun, TGF beta 1 did not alter the appearance of the matrix whereas it still stimulated, but to a lesser extent, extracellular matrix components production. The results show that TGF beta 1 prevents the transition from the proliferating to the differentiating state and correlatively alters the composition and structure of the extracellular matrix.

Animals

Effect of blocking angiotensin II receptor subtype on rat sympathetic nerve function.

This study examined effects of nonpeptide angiotensin II (Ang II) receptor subtype antagonists on the interaction of sympathetic function and Ang II in pithed rats. Effects of spinal cord stimulation (0.5-4 Hz) and norepinephrine (0.3-3 micrograms/kg i.v.) on mean arterial pressure (recorded with a carotid arterial catheter), cardiac output (measured with an electromagnetic flowmeter and flow probe around the thoracic ascending aorta), total peripheral resistance, and heart rate were determined. The subtype 1-selective Ang II receptor antagonist losartan (previously known as DuP 753) at 10 mg/kg i.v. blocked the hemodynamic responses to Ang II at 1 microgram/kg i.v. It inhibited mean arterial pressure and total peripheral resistance responses but not cardiac output and heart rate responses to spinal cord stimulation. In contrast, it reduced mean arterial pressure and cardiac output responses but not total peripheral resistance and heart rate responses to intravenous norepinephrine. Given at 100 mg/kg i.v., the subtype 2-selective receptor antagonist PD123177 did not reduce hemodynamic responses to intravenous Ang II, spinal cord stimulation, and intravenous norepinephrine. These results suggest that endogenous Ang II facilitates the release of norepinephrine from sympathetic nerve terminals in the vasculature of pithed rats. Similar to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor in pithed rats appears to be of subtype 1.

Angiotensin Receptor Antagonists

Pyruvate dehydrogenase activity is stimulated by growth hormone (GH) in human mononuclear cells: a new tool to measure GH responsiveness in man.

Human peripheral mononuclear cells (PMC) were used to examine the effects of hGH and insulin on the activity of the pyruvate dehydrogenase (PDH) complex. Incubation of PMC with 10(-7) mol/L hGH or insulin increased basal PDH activity. Hormonal effects were maximal (50-60% above control values) at 15 min. Later on, activation progressively decreased and was no longer detectable at 30 min. Total PDH activity was unaffected by hormonal treatment. PMC were subfractionated into lymphocytes and monocytes to assess the sensitivity of each cell types to the hormones. hGH significantly increased basal PDH activity in lymphocytes and monocytes (38% and 70% above control values, respectively), whereas insulin increased basal PDH activity only in monocytes (151% above control value). PMC from healthy subjects aged 1-45 yr were incubated for 15 min with 10(-7) mol/L hGH or insulin before PDH measurement. An increase of enzyme activity higher than 20% was observed in 26 patients out of 29 with hGH, and in 15 out of 18 with insulin. In conclusion, hGH is able to stimulate PDH activity of human mononuclear cells. This hormonal effect allows rapid evaluation of the cellular responsiveness of hGH in various pathophysiologic situations.

Adolescent

[Value of serum immunoglobulin assays in early myocardial infarction].

Serum immunoglobulin (Ig) levels were assayed in 672 patients admitted for acute myocardial infarction with onset within 24 hours of hospitalization. Supranormal Ig levels (A > or = 300, G > or = 1,200) or subnormal Ig levels (M < 40 mg/100 ml) were seen in patients with one or several risk factors (diabetes mellitus, alcohol abuse) or a history of previous myocardial infarction. Patients with one or more Ig anomalies were more likely to exhibit unfavorable outcomes, including early death, suggesting that increased viscosity due to aggregation of Ig molecules may occur.

Acute Disease

Influence of upright exercise on pulmonary hemodynamics in left heart failure.

Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill-exercise test in severe heart failure patients.

Adult

[Activity of the sympathetic nervous system and of the renin-angiotensin system in the acute stage of myocardial infarction].

We studied sympathetic and renin-angiotensin systems activity in a series of 175 patients suffering from acute myocardial infarction. These two systems were both overactivated especially in the cases complicated by hemodynamically documented left heart failure. The response of these systems to acute heart failure was in the same range for patients younger or older than 65 years and the witness (norepinephrine and plasma renin levels) of sympathetic and renin-angiotensin activities were good independent prognostic factors of in-hospital mortality.

Acute Disease

[Refractory arterial hypoxemia and interatrial right-left shunt in myocardial infarction of the right ventricle].

The authors report the case of a 63 year old woman who developed refractory arterial hypoxemia due to a right-to-left interatrial shunt through a patent foramen ovale during the acute phase of right ventricular infarction. The precarious haemodynamic condition of the patient contra-indicated surgical intervention and so the effects of the shunt were reduced by obstructing the atrial septal defect with the balloon of a Swan-Ganz catheter. The management of this type of shunt is discussed based on the degree of hypoxemia and the patient's haemodynamic status with reference to this particular case and a review of the literature.

Catheterization, Swan-Ganz

[Thrombolysis in the acute stage of myocardial infarction].

The authors recall the conditions in which intravenous thrombolysis is justified, and the mode of action of the various thrombolytic products. They show the efficacy and the utility of thrombolysis and also its complications. The success of this treatment is closely linked to the time interval after thrombosis, which should be reduced as much as possible.

Fibrinolytic Agents

[Development of fetal semiology in North America].

A survey of the emergence of fetal semiology in the 17 editions of the Williams' Textbook of Obstetrics used by North-American medical students since 1900 was carried out. Three periods were identified: 1906-1950: the fetus, seen as a part of its mother, is ignored until birth and is of no interest to the obstetricians. From the fifties', the decrease in maternal mortality and progress in physiology and therapeutics permitted to study the fetus and a greater attention given to the care of the sick newborn. Since 1970, the availability of ultrasonography has contributed in making the fetus the second patient for obstetricians. It is now possible to study its growth, integrity, health, and well-being. Furthermore, the fetus is now accessible to establish a prenatal diagnosis.

Embryonic and Fetal Development

[Hemodynamic impact of pressotherapy].

We study the hemodynamic effects of pressotherapy in 11 patients (mean age : 68 +/- 10 years) with uncomplicated acute myocardial infarction (n = 6) or with chronic ischemic heart failure (n = 5). We measure the right auricular pressure (RAP), the mean pulmonary arterial pressure (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (T 20 min) and 30 minutes after the end of pressotherapy (T 30 min). We use five-chambered leg garments with 80 mm Hg pressure during 20 minutes. The wavelike action (from the bottom to the top) is intermittent: the compression time is 10 second (sec); compression is maintained during 60 sec; deflation time is 15 sec. After 20 minutes pressotherapy (t 20) the 3 variables increase: RAP: from 3.6 +/- 5 to 7 +/- 7 mm Hg (P less than 0.001), MPAP: from 25 +/- 14 to 29 +/- 17 mm Hg (p less than 0.01) and the PWP from 10 +/- 8 to 17 +/- 11 Hg (p less than 0.01). This rise is particularly important in heart failure patients: from 18 +/- 8 to 29 +/- 8 mm Hg for the PWP, with cough in one patient. At T 30 these 3 variables decrease and return nearly to initial values: respectively 2.7 +/- 4.7 (RAP), 24 +/- 14 (MPAP), 12 +/- 8 mm Hg (PWP). In conclusion pressotherapy increases RAP and pulmonary pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Short- and long-term prognosis of myocardial infarct. Contributions and limitations of the clinical aspects and non-invasive technics].

Clinical variables and those obtained by non-invasive techniques were recorded in a series of 306 patients discharged from hospital after an acute myocardial infarction. We studied the prognostic value at 2 and 12 months of these variables (alive/dead). The results of simple clinical data were as discriminant as those from more elaborated techniques. When the prognostic value of the same data at 12 months was studied in those surviving for two months, most of the predictive variables lost their discriminant power. The study shows that the predictive value of many of the predischarge variables usually taken into account in the assessment of long term risk, does not extend beyond the first two months.

Echocardiography

Dexamethasone treatment of amiodarone-induced thyrotoxicosis (AIT) with or without persistent administration of the drug.

Treatment of amiodarone-induced thyrotoxicosis (AIT) with thionamide, lithium or radioactive iodine is ineffective. This particular form of hyperthyroidism is long-lasting because of the slow elimination of amiodarone. Therefore, an alternative therapy is necessary, especially for patients who need to continue permanent administration of the drug. We report 2 cases of AIT: in one case, amiodarone was interrupted; in the other case, amiodarone was continued because of recurrent ventricular tachycardia resistant to classical antiarrhythmic drugs. Both patients were successfully treated with propylthiouracil (PTU) and dexamethasone (DXT).

Amiodarone

Pimobendane (UD-CG 115 BS) in the treatment of severe congestive heart failure. An acute haemodynamic cross-over and double-blind study with two different doses.

1. We compared the effects of two doses (5 and 10 mg) of oral pimobendane (UD-CG 115) on haemodynamics in eight patients suffering from chronic congestive heart failure. The two doses were given according to a randomized cross-over double-blind protocol; haemodynamics and plasma levels of pimobendane and its main metabolite UD-CG 212, were determined 1, 2, 3, 5, 7, 9, 11 and 12 h after each dose. 2. Both doses significantly improved the left and right ventricular functions of these patients, with a peak action 3 h after drug intake and long duration (more than 12 h). A significant dose-effect relationship was observed only for pulmonary wedge pressure and right atrial pressure. Significant correlations were found between UD-CG 212 plasma levels and cardiac index (r = 0.54, P less than 0.05), and pulmonary wedge pressure (r = 0.74, P less than 0.001); no correlation was found between these haemodynamic variables and pimobendane plasma levels. 3. One patient developed a transient drop in blood platelets together with a cutaneous rash, while three others had a transient and mild decrease of thrombocytes. 4. In conclusion, pimobendane improved right and left ventricular functions in severe heart failure. Both doses (5 and 10 mg) were effective. The higher dose induced marked improvement of the haemodynamic variables but the difference between doses was only significant for right atrial and pulmonary wedge pressures.

Aged

Pimobendane (UD-CG 115 BS) in chronic congestive heart failure. Short-term and one-month effects of a new inotropic vasodilating agent.

We studied the effects of oral administration of pimobendane on hemodynamics, blood gas levels, the renin-angiotensin system, and plasma catecholamines in 11 patients who were affected by severe chronic congestive heart failure. Following the administration of 5 mg, the cardiac index increased from 2.0 +/- 0.2 to 2.5 +/- 0.2 L/min/m2 (p less than 0.01), and the pulmonary wedge pressure decreased from 28 +/- 3 to 17 +/- 4 mm Hg (p less than 0.01). The maximal changes were noted five hours after intake of the drug. In spite of a significant decrease in arterial oxygen pressure (PaO2) (from 81 +/- 4 to 67 +/- 5 mm Hg; p less than 0.05), a significant increase in the oxygen delivery index was seen (from 322 +/- 32 to 436 +/- 38 ml/min/m2; p less than 0.01). The patients who were submitted to long-term treatment (5 mg twice daily) and who were reassessed after at least one month exhibited an improved cardiac index from 1.9 +/- 0.2 to 2.5 +/- 0.1 L/min/m2 (p less than 0.01), as well as a decreased pulmonary wedge pressure from 26 +/- 2 to 14 +/- 4 mm Hg (p less than 0.01). The norepinephrine levels were significantly reduced after one month (from 1,496 +/- 185 to 678 +/- 95 pg/ml; p less than 0.01), whereas the plasma renin activity was not. One patient died suddenly during the one-month follow-up period. With the exception of one case, which was also treated with heparin, a transient cutaneous rash and a drop in the level of blood platelets were observed, pimobendane was well tolerated. This new inotropic and vasodilating drug thus seems to have promise for the treatment of chronic congestive heart failure.

Administration, Oral