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Biomedical subjects

M Lebel

Publications and source records attributed to M Lebel.

At least 73 records · Page 4Linked to original sources
PubMed1989

Modulation of renal hemodynamics by renal eicosanoids during vasopressor infusions in man.

Pressor doses of norepinephrine (NE) (n = 8) and angiotensin II (A II) (n = 5) were infused in normal volunteers to determine whether the systemic administration of vasopressor hormones influence renal eicosanoid production and whether, in turn, the eicosanoids produced could modulate renal hemodynamics and electrolyte excretion. At the doses administered, both pressor substances induced the expected rise in blood pressure, a significant decrease (P less than 0.05) in renal blood flow and a proportionally smaller fall in glomerular filtration rate, resulting in a consistent augmentation in filtration fraction. Fractional sodium excretion was concomitantly reduced. NE infusion produced only slight modifications in urinary prostaglandin (PG)E2, 2,3-dinor-6-keto-PGF1 alpha and thromboxane (TX)B2, while urinary 6-keto-PGF1 alpha and PGF2 alpha were increased by 38% and 176% respectively. The increase in urinary 6-keto-PGF1 alpha (the non-enzymatic degradation product of PGI2, predominantly of cortical origin) was proportional to the level of circulating NE (r = 0.78, P less than 0.05) and to the renal vascular resistance (r = 0.85, P less than 0.01), suggesting an immediate compensatory role for PGI2 in response to the NE-induced pressor stimulus. The renal production of PGE2 and PGF2 alpha (predominantly medullary) was inversely correlated with the filtration fraction: the greater the increase in PGE2 and PGF2 alpha the lower the elevation in filtration fraction or the decline in renal blood flow upon NE administration. All infusion variably stimulated the renal eicosanoid production: PGE2, 41%; PGF2 alpha, 102%; 6-keto-PGF1 alpha, 38%; 2,3-dinor-6-keto-PGF1 alpha, 38%; and TXB2, 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Short-term monotherapy with the potassium channel activator BRL 34915 on endocrine sodium regulation in essential hypertension.

BRL 34915, a potassium channel-activating drug, was administered for a three-day period in eight untreated and hospitalized patients with established hypertension. The fixed and single dose of 1.5 mg/d produced a significant reduction in systolic and diastolic blood pressure with a small increase in heart rate. Plasma renin activity, plasma and urinary aldosterone, plasma atrial natriuretic peptide (ANP), and serum electrolytes were unchanged during the therapy. Urinary sodium and body weight remained similar throughout the study. These results indicate that short-term administration of an antihypertensive dose of BRL 34915 does not alter the renin-angiotensin-aldosterone and ANP systems. Blood pressure is lowered without secondary sodium retention.

Administration, Oral↗
PubMed1989

Increased hematocrit with normal red blood cell mass in early borderline essential hypertension.

Hematocrit, red blood cell mass, plasma volume and plasma renin activity were evaluated in 33 (15 women) young patients with borderline hypertension and in 30 (15 women) age- and sex-matched normotensive control subjects. Mean hematocrit values were slightly but significantly higher (P less than 0.05) at this early stage of hypertension and it correlated with the elevation of arterial hypertension (r = 0.39, P less than 0.05). Red blood cell mass was normal indicating normal bone marrow production. Plasma volume was significantly contracted (p less than 0.05) and it can account in part for the increased hematocrit and plasma renin activity. These results indicate that the alterations in circulating fluid components and in hematocrit described in moderate to severe forms of hypertension are also present in early borderline hypertension.

Adult↗
PubMed1988

Renal prostaglandins in postobstructive diuresis. Comparative study of unilateral and bilateral obstruction in conscious dogs.

An experimental model in conscious dogs was developed to investigate the role of prostaglandins (PG) in the obstructed kidney. Renal veins were separately catheterized. Urine flow was shunted to the skin by surgically implanted polyurethane loop ureterostomy so as to allow atraumatic manipulation with maintained continuous flow to the bladder between experiments. One week or more after surgery, renal function parameters as well as renal vein and urinary PGE2 and PGF2 alpha, and renal vein renin were studied during and after unilateral (UUO) and bilateral (BUO) ureteral obstruction. The release of ureteral obstruction produced a constant and marked elevation in urinary PGE2 and PGF2 alpha, two times higher after BUO than after UUO. A close correlation exists between PGE2 and sodium excretion in UUO and BUO. Increasing polyuria was observed only after chronic BUO. In BUO, renal vein renin concentration was augmented after 2 hours but was suppressed after 24 hours of BUO. Renal vein PG concentration was also elevated after chronic UUO and BUO but was in the normal range immediately prior to release of obstruction. The data obtained with the current experimental dog model indicate that the release of ureteral obstruction induces a striking increase in renal PGE2 and PGF2 alpha production which may mediate at least partly the phenomenon of postobstructive diuresis.

Animals↗
PubMed1988

Plasma bactericidal activity after administration of erythromycin estolate and erythromycin ethylsuccinate to healthy volunteers.

In a crossover design study, we compared the plasma bactericidal activities of erythromycin estolate (500 mg) and erythromycin ethylsuccinate (600 mg) after administration of a single oral dose to 12 healthy volunteers. Both erythromycin esters displayed very good plasma bactericidal activities against Streptococcus pneumoniae. The median bactericidal titers produced in plasma against Streptococcus pyogenes and Streptococcus pneumoniae were significantly higher with erythromycin estolate than with the ethylsuccinate ester at both 2 and 8 h after dosing (P less than 0.05 by Student's t test). Both erythromycin esters showed rather weak bactericidal activity against Branhamella catarrhalis; a further look at these results indicated that erythromycin estolate presented 50% of the plasma samples at 2 h with bactericidal titers superior or equal to 1:8, versus 11% for the ethylsuccinate ester. Of the 60 plasma bactericidal activity tests performed against Staphylococcus aureus, only 6 (10%) and 3 (5%) exhibited titers of 1:8 or greater for erythromycin estolate and erythromycin ethylsuccinate, respectively. Clinical trials are warranted in which these products are compared in infections other than Streptococcus pyogenes pharyngitis, for which the clinical superiority of erythromycin estolate has been demonstrated.

Adult↗
PubMed1988

Renin-producing ovarian tumor. A case report with immunohistochemical and electron-microscopic study.

A 39-year-old woman presented with arterial hypertension. Examination of the patient revealed elevated plasma renin activity, hyperaldosteronemia, hypokalemia, and a pelvic mass. Subsequently, an 11-cm right ovarian tumor mass with histologic features of an unusual stromal cell tumor was resected. Immunohistochemical studies demonstrated renin production by tumor cells. Organelles resembling mature renin granules were identified by electron microscopy. Although blood pressure normalized after the initial surgery, the hypertension resumed with later recurrence of the tumor. We believe the tumor originated from renin-secreting ovarian stromal cells, possibly granulosa cells.

Adult↗
PubMed1987

Pharmacokinetics in the elderly. Studies on ciprofloxacin.

In many ways, the elderly are a more heterogeneous group than the young, yet most pharmacokinetic studies of a new drug are carried out in healthy young volunteers. Based on a variety of age-related alterations in the gastrointestinal tract, one could postulate an a priori diminished absorption with age. In fact, absorption in old age is unchanged or even increased, as is observed with ciprofloxacin. Two comparative pharmacokinetic studies of oral ciprofloxacin found greater areas under the concentration-time curves and maximal serum concentrations in elderly than in young volunteers, which suggests better absorption (Ball et al, LeBel et al). Comparable results were also observed by Guay et al in an open study of 13 elderly patients. Smaller apparent volumes of distribution of ciprofloxacin were also noted in older than in younger volunteers. Several age-related changes in body composition may significantly affect the distribution of ciprofloxacin; the decrease in total body water plays a predominant role for this drug. For a drug that is mostly eliminated unchanged in urine, as ciprofloxacin is, the diminished glomerular filtration rate related to normal aging is the most significant factor to alter drug pharmacokinetics. A diminution of 55 to 60 percent in the total clearance of ciprofloxacin was noted in both studies comparing elderly and young persons. The decline in glomerular filtration rate observed with aging is well illustrated by the smaller renal clearance of ciprofloxacin obtained in this population. To prevent accumulation and eventual toxicity, it would seem appropriate to avoid dosage intervals shorter than 12 hours, especially in view of the lack of data concerning the effect that reduced glomerular filtration rate has on the elimination of metabolites of ciprofloxacin.

Adult↗
PubMed1987

Congenital malformations associated with maternal use of valproic acid.

Two children born with birth defects after intrauterine exposure to valproic acid are reported. The mothers took the drug throughout pregnancy as sole treatment for primary generalized epilepsy. The first baby showed facial dysmorphism, arachnodactyly and triphalangeal thumbs. The second had facial dysmorphism, severe laryngeal hypoplasia, tracheomalacia and an aberrant innominate artery that caused tracheal compression. A left superior vena cava, abnormal pulmonary lobulation, and unilateral hydronephrosis were also found at autopsy. Valproic acid has probable teratogenic potential in humans but the number of reported cases is few and the spectrum of anomalies is broad so it is not possible to delineate a definite fetal valproate syndrome.

Abnormalities, Drug-Induced↗
PubMed1986

Differential effects of diuretics on eicosanoid biosynthesis.

The selective influences of hydrochlorothiazide (HCT), furosemide (FUR), spironolactone (SPI) and indapamide (IND) on arachidonic acid (AA) metabolism were assessed in sheep seminal vesicle and in human platelet microsomes. All four compounds augmented the synthesis of prostaglandins (PGs) D2 (HCT,FUR), E2 (SPI) and I2 (FUR,IND), probably through facilitated reorientation of endoperoxide biotransformation. With the exception of HCT, the other drugs also suppressed the production of thromboxane A2 (IND greater than SPI greater than FUR); lipoxygenase formation of hydroxyeicosatetraenoic acid was also enhanced by SPI and IND. The antihypertensive efficacy of these diuretics could, in part, be related to their selective effects on AA metabolism which favor the net formation of depressor PGs.

Animals↗
PubMed1986

Erythema induratum of Bazin.

Erythema induratum of Bazin is a rare entity, the cause and treatment of which are topics of continuing controversy. This report documents the cases of two patients with ulcerating leg nodules. One patient had concurrent active pulmonary tuberculosis, and the other had a history of previous treatment for pulmonary tuberculosis. The treatment regimen for these patients is outlined. First described by Bazin, the rare entity of erythema induratum was thought to be of tuberculous origin or a tuberculid reaction. Opinion has varied, and some authors have classified this condition as a vasculitis involving subcutaneous vessels. Because of the rarity of this disorder and the controversy surrounding its cause and pathogenesis, we share our experience with two patients whose clinical and pathologic findings were consistent with the diagnostic criteria for erythema induratum and in whom there was a recent or remote history of tuberculosis.

Adult↗
PubMed1986

Abnormal renal prostaglandin production during the evolution of chronic nephropathy.

To investigate the role of renal prostaglandins (PGs) in the evolution of kidney parenchymal disease, PGE2 and PGF2a excretion rates were measured in 62 subjects (22 control subjects, 24 patients with different forms of nephropathy and varying degrees of renal failure, and 16 patients with end-stage kidney disease on chronic hemodialysis). Patients with kidney disease and severe renal failure (inulin clearance less than 25 ml/min) showed significant decreases in urinary PGE2 and PGF2a (p less than 0.05 for both PGs), and the values were markedly diminished in patients with end-stage renal failure on chronic hemodialysis. Conversely, in patients with nephropathy and normal renal function, urinary PGE2 was slightly elevated compared to age- and sex-matched control subjects. A significant correlation (r = 0.74, p less than 0.01) was found between inulin clearance and PGF2a in the group of 24 patients with chronic renal failure, both not between PGE2 and inulin clearance. These results indicate that except for patients at the early stage of kidney disease the renal excretion of PGE2 and PGF2a appears greatly diminished in parenchymal renal lesion with severe renal failure and in end-stage kidney disease. The latter phenomenon may be the consequence of diminished functional renal mass.

Chronic Disease↗
PubMed1985

Labetalol infusion in hypertensive emergencies.

The antihypertensive effects of labetalol infusion (2 mg/min; maximal dose 150 mg) were evaluated in 22 subjects requiring rapid lowering of blood pressure because of severe hypertension, a hypertensive crisis after surgery, or before angiographic examination. Overall systolic and diastolic blood pressures were reduced from 201 +/- 4 to 164 +/- 4 mm Hg and from 123 +/- 3 to 107 +/- 3 mm Hg, respectively. By the end of the infusion, diastolic blood pressure in 16 (73%) subjects was lowered to less than or equal to 110 mm Hg. No adverse effects were encountered, but one subject had a transitory hypotensive episode that did not require treatment. Intravenous labetalol appears effective and well tolerated in the control of blood pressure in hypertensive emergencies.

Adult↗
PubMed1984

Abnormal relation of extracellular fluid volume and exchangeable sodium with systemic arterial pressure in early borderline essential hypertension.

Interrelations between systemic arterial pressure, extracellular fluid (ECF) volume, exchangeable sodium (Na) and the renin-angiotensin-aldosterone system were studied in 38 young patients with borderline hypertension and in 37 age- and sex-matched control subjects. ECF volume and exchangeable Na were subnormal (not significant) in borderline hypertension. In normal subjects, volume data did not relate to arterial pressure; in contrast, negative correlations were observed between arterial pressure and ECF volume or exchangeable Na in patients with borderline hypertension (in hypertensive women, r greater than or equal to 0.7, p less than 0.01). Plasma renin activity was consistently elevated in borderline hypertension, mainly in the upright posture, and these values were inversely correlated with ECF volume and exchangeable Na. No correlation was observed between arterial pressure and plasma renin activity. These results show that slight elevation of arterial pressure in the early stage of hypertension induces a proportional decrease in ECF volume, suggesting that the phenomenon of pressure-natriuresis is operative in young borderline hypertensive persons. The renin-angiotensin system is activated in these patients, in part to preserve sodium homeostasis.

Adult↗
PubMed1984

Asynchronous pheochromocytoma in childhood.

A case of asynchronous pheochromocytoma in a 13-year-old boy is reported. Two years elapsed between excision of the right adrenal gland and the appearance of another tumour in the contralateral gland. Selective central venous sampling for plasma catecholamine measurement and adrenal phlebography were of diagnostic value. Excision of the tumour with partial adrenalectomy was the preferred surgical treatment in the remaining contralateral adrenal; no clinical or biochemical abnormalities were observed 2 years after removal of the second pheochromocytoma. This case stresses the importance of a closer follow-up in children for early detection of a second pheochromocytoma.

Adolescent↗
PubMed1982

Merits of adding a beta blocker (acebutolol) to a diuretic (hydrochlorothiazide) in the treatment of hypertension.

In a double-blind crossover study, the antihypertensive effect of hydrochlorothiazide alone and in combination with the beta blocker acebutolol was assessed in 18 patients suffering from mild to moderate hypertension. After a placebo period, the patients were placed on hydrochlorothiazide alone for four weeks at a dose of 50 mg daily. Acebutolol was than gradually titrated into the regimen until the optimum dose was established. The average dose was 555 mg per day, with the usual optimum dose 200 mg b.i.d. The patients then entered the crossover portion of the trial during which patients received either hydrocholorothiazide with acebutolol or hydrochlorothiazide with placebo. Each treatment period lasted six weeks. Blood pressure and heart rate were significantly lower with the combination treatment than with hydrochlorothiazide alone. At the end of each treatment period, the mean diastolic blood pressure (erect) was 90.5 mm Hg with hydrochlorothiazide-acebutolol but remained above 100 mm Hg with the diuretic alone. Neither hydrochlorothiazide nor acebutolol produced any significant changes in plasma renin activity or plasma aldosterone. There were very few side effects and no reports of bradycardia.

Acebutolol↗
PubMed1982

Angiotensin II effect on plasma steroids in selective hypoaldosteronism.

The effect of angiotensin II infusion on plasma pregnenolone, progesterone, corticosterone and aldosterone was investigated in 4 cases of established hypoaldosteronism, in 4 elderly controls in the same age range and in 6 young normals. In young and old normals, angiotensin II induced the expected dose response increase in aldosterone while corticosterone usually decreased progressively during the infusion. Progesterone levels were not significantly different in young and old subjects and no change was observed during angiotensin II infusion. Baseline pregnenolone levels were significantly lower in elderly controls and angiotensin II elicited a slight decrease in pregnenolone in the two control groups. In selective hypoaldosteronism, baseline plasma aldosterone concentrations were very low and the aldosterone response to angiotensin II was blunted. Plasma corticosterone and progesterone levels were in a comparable range to normals throughout the study. Contrary to control subjects, a dose dependent increase in pregnenolone was observed during angiotensin II infusion in the patient group. These results suggest that the anomalies of steroid biosynthesis found in selective hypoaldosteronism could be contributing factors to the hypoaldosteronism in some patients.

Adrenal Insufficiency↗