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Biomedical subjects

M Lebel

Publications and source records attributed to M Lebel.

At least 19 recordsLinked to original sources
PubMed1992

EMLA partially relieves the pain of EMG needling.

The aim of this study was to evaluate the efficacy of the topical analgesic cream EMLA in alleviating the pains caused by needling in electromyography (EMG). During the course of regular neurophysiology clinics, 34 Caucasian patients of both sexes, aged 21 to 69 yr (mean 38.5 +/- 11.4 SD), scheduled for electromyography, were studied. The EMLA was spread thickly on two EMG sites on each arm: E site, on the lateral dorsal aspect of the forearm and A site, on the thenar eminence. Randomization was pre-established. Whenever EMLA was applied blindly on one of the sites of the arm, the placebo was applied on the homologous site of the other arm. After at least 45 min of application (range 45-145 min, mean = 72.3 +/- 22.2), the needle was inserted into the skin and into the muscle. Then the electromyographist asked the patient to score his degree of pain on a visual analogue scale (VAS 1-10 cm) for each level of insertion. The results showed that on the skin of E site, the pain was less after EMLA than placebo (VAS = 0.75 +/- 1.36 vs 3.10 +/- 1.75, P = 0.0001). The untreated E site (placebo) was less sensitive than the untreated A site (VAS = 3.10 +/- 1.75 vs 6.09 +/- 1.96, P = 0.0001). Muscle insertion on E site was less painful on the EMLA sites than placebo (VAS = 2.83 +/- 2.45 vs 5.73 +/- 2.30, P = 0.0001). The VAS scores for skin and muscle insertion on A site were identical whether EMLA or placebo had been applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Endocrine sodium and volume regulation in familial hyperkalemia with hypertension.

The hormonal regulation of sodium and volume homeostasis was investigated in three patients (two related) with the syndrome of familial hyperkalemic acidosis and hypertension with normal glomerular filtration rate. Recumbent plasma renin activity was low during normal sodium intake (135 mmol daily), and the response to upright posture or to low sodium diet (10 mmol daily) was blunted. Recumbent plasma aldosterone levels were normal in two patients and high in one, and the standing values were elevated in one; responses to upright posture were brisk on low sodium diet. Angiotensin II infusion induced a marked increase in plasma aldosterone. Plasma atrial natriuretic peptide was at the upper limit of normal during normal sodium intake, decreased during diuretic therapy, and increased during sodium chloride infusion in one patient. Basal urinary prostaglandin E2, prostaglandin F2 alpha, and 6-ketoprostaglandin F1 alpha excretion rates were decreased, and thromboxane B2 was increased. Total blood and plasma volumes were subnormal, whereas extracellular fluid volume and exchangeable sodium values were close to or above (in one patient) the mean normal values. Chronic treatment with hydrochlorothiazide in two patients corrected the hyperkalemic acidosis and hypertension, but on its discontinuation (in one patient) all biochemical abnormalities promptly reappeared.

Adult↗
PubMed1991

Effect of short-term administration of cromakalim on renal hemodynamics and eicosanoid excretion in essential hypertension.

Cromakalim, a novel potassium channel-activating drug, was administered for a 3-day period in eight untreated hospitalized patients with established hypertension. The fixed and single dose of 1.5 mg/day produced a significant reduction in systolic and diastolic blood pressure with a small increase in heart rate. Glomerular filtration rate was unchanged and effective renal plasma flow was slightly increased with a concomitant small decrease in filtration fraction and in renal vascular resistance. No significant change was observed in urinary prostaglandin (PG)E2, PGF2 alpha, and thromboxane B2, while 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) rose from 189 +/- 6 to 368 +/- 115 ng/day. The renal excretion of 6-keto-PGF1 alpha correlates with the modification observed in renal plasma flow, suggesting a compensatory role for prostacylin in preserving renal hemodynamics during antihypertensive therapy with cromakalim.

Adult↗
PubMed1991

Arachidonic acid does not share the antihypertensive properties of linoleic acid and fish oil omega-3 fatty acids in a model of angiotensin II-induced hypertension in the rat.

Linoleic acid and fish oil omega-3 fatty acids, but not arachidonic acid, exerted antihypertensive effects in a model of angiotensin II-induced hypertension in rats. Indomethacin did not influence the systolic arterial pressure of arachidonic acid-treated hypertensive rats whereas compound L-641,953, a prostaglandin H2/thromboxane A2 receptor antagonist, caused a notable but statistically nonsignificant decrease in blood pressure in these animals. Although these results do not exclude entirely the possibility that the lack of antihypertensive effect of arachidonic acid may be due, in part, to the concomitant formation of vasoconstrictor prostanoids, they do not support it. These observations, as well as those of a previous study, indicate that linoleic acid and fish oil omega-3 fatty acids exert antihypertensive effects of their own, independently of the prostanoid system, and that these properties are not shared by arachidonic acid.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Renal eicosanoids and renal hemodynamics in early borderline hypertension.

To study the modulatory role of renal eicosanoids on renal hemodynamics and electrolyte excretion, pressor doses of norepinephrine (NE) were infused in 10 control subjects (mean age, 26 y) and 13 patients (mean age, 25 y) with borderline hypertension. The highest NE dose used (150 ng/kg/min) produced comparable increases in mean blood pressure in control subjects (20 +/- 2 mmHg) and in patients (23 +/- 3 mmHg). NE induced a significant increase in renal vascular resistance (p less than 0.01, both groups), with a smaller decrease in glomerular filtration rate resulting in a concomitant increase in filtration fraction (p less than 0.01, both groups). The renal hemodynamic changes tended to be more pronounced in borderline hypertension. NE infusion led to similar decreases in electrolyte clearances in the two groups. Urinary prostaglandin (PG)E2, PGF2 alpha (p less than 0.01), and 6-keto-PGF1 alpha increased with NE infusion. Urinary thromboxane (TX)B2 increased slightly in control subjects and decreased in borderline hypertension (p less than 0.05). The 6-keto-PGF1 alpha/TXB2 ratio, an index of vasodilation, was significantly increased (p less than 0.05) in borderline hypertension. These results demonstrate that in both groups pressor infusion of NE induced significant modifications in renal hemodynamics and in urinary electrolyte and eicosanoid excretion. The vasodilatory component of the renal eicosanoid system appears hyperresponsive in borderline hypertension, which may represent an early antihypertensive defense mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effect of captopril injection in patients with moderate to severe hypertension.

The effect of intravenous captopril was studied in 24 white patients who had moderate to severe hypertension. Patients received incremental doses of 1 to 10 mg delivered at 10 min intervals over 50 to 80 min. Blood pressure (BP) was lowered within 5 to 10 min after the initial dose was administered and continued to decline, reaching a maximum response after 20 min (2 to 4 mg). At this time group mean BP fell from 175 +/- 3/111 +/- 1 to 166 +/- 3/97 +/- 2 mm Hg (P less than 0.01). Additional dose increments to an average cumulative dose of 40 mg did not increase the initial effect. No adverse side effects or symptomatic hypotension occurred in any subject. There was a significant correlation between diastolic BP decreases observed in response to intravenous captopril and subsequent long-term oral captopril therapy. The addition of hydrochlorothiazide increased the proportion of patients reaching normotension. We conclude that small intravenous bolus injections of captopril appear to be effective rapidly and are well tolerated in moderate to severe essential hypertension. Short-term intravenous administration seems to predict the response to chronic oral captopril therapy.

Administration, Oral↗
PubMed1990

Prostanoids and aldosterone-induced mild experimental hypertension in rats.

The goal of this study was to determine the role of prostanoids in a new model of mineralocorticoid-dependent hypertension induced by the subcutaneous infusion of aldosterone (1 micrograms/hr) to normal male Sprague-Dawley rats. This regimen caused a mild and gradual increase in systolic pressure over a period of 4 weeks (113 +/- 1 vs. 137 +/- 3 mm Hg) and was associated with an increase in the in vivo formation of prostaglandins I2 and E2 and of thromboxane A2 in the kidney. High sodium intake induced a fall in the urinary levels of prostaglandin E2 and a rise in the arterial pressure of control rats (126 +/- 1 vs. 113 +/- 1 mm Hg) but did not influence aldosterone-induced hypertension. Indomethacin (3.0 mg/kg/day) caused a profound inhibition of the in vivo synthesis of prostaglandin I2 and thromboxane A2 without modifying the renal production of prostaglandin E2. Although indomethacin exerted no effect on aldosterone-induced hypertension in rats fed a normal diet, it caused a further rise in systolic pressure in aldosterone-treated rats fed a high sodium diet (157 +/- 6 vs. 140 +/- 4 mm Hg). The results of this study in a model of aldosterone-induced mild hypertension in the rat indicate that 1) aldosterone exerts a stimulatory effect on the renal synthesis of prostanoid, particularly prostaglandin E2; 2) thromboxane A2 and prostaglandin I2 do not seem to play a role in aldosterone-induced hypertension under conditions of normal dietary salt intake, whereas the role of prostaglandin E2 is unclear; 3) there is enough sodium in a normal diet to allow for the maximal expression of the hypertensive effect of aldosterone; 4) prostaglandin I2 seems to play a significant role in modulating the cardiovascular impact of a high sodium diet in aldosterone-treated rats; and 5) the renal biosynthesis of prostaglandin E2 is particularly resistant to the inhibitory effect of indomethacin in vivo.

6-Ketoprostaglandin F1 alpha↗
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↗