Search PubMed⌕ Search

Biomedical subjects

J Lefebvre

Publications and source records attributed to J Lefebvre.

At least 73 records · Page 4Linked to original sources
PubMed1995

Comparative assessment of antihypertensive efficacy of DL-nebivolol and D-nebivolol in patients with confirmed mild to moderate hypertension.

We compared the antihypertensive activity of DL- and D-nebivolol in patients with essential hypertension on clinic and 24-h ambulatory blood pressure (BP) and during dynamic exercise as well. After a 4-week placebo run-in period, 30 patients (mean age 48 years) were randomly allocated to double-blind treatment with either DL-nebivolol 5 mg or D-nebivolol 2.5 mg once daily for 4 weeks. After an interim single-blind placebo washout of 2-4 weeks, all patients crossed over double-blind to the alternative DL- or D-nebivolol treatment for 4 weeks. The results show that DL- and D-nebivolol produced similar reductions in clinic trough (delta systolic/delta diastolic BP (delta SBP/delta DBP): -10/-8 and -13/-9 mm Hg, respectively, all p < 0.0001 vs. placebo), 24-h ambulatory (-12/-11 and -13/-11 mm Hg, respectively, all p < 0.0001), and peak exercise BP (-13/-6, both p < 0.01; and -13/-7 mm Hg, both p < 0.0001, respectively) as compared with placebo (SBP/DBP clinic 147/99, ambulatory 147/94, exercise 211/103 mm Hg). Our results showing superimposable clinic and ambulatory BP profiles as well as exercise BP responses with DL- and D-nebivolol treatment do not confirm results of animal pharmacologic experiments in which the L-isomer potentiated the antihypertensive effect of the D-isomer.

Adolescent↗
PubMed1995

Evaluation of commercial antisera for Shigella serogrouping.

Shigella serogrouping antisera from six companies (Becton Dickinson, Denka, Difco, Murex, Roach, and Sanofi-Pasteur) intended for the slide agglutination test and those of the Wellcolex Colour Shigella latex agglutination test were evaluated to identify quality products for Shigella identification. Forty-six reference Shigella strains (one for each serotype and species), 50 clinical strains (21 S. flexneri, 21 S. sonnei, 4 S. dysenteriae, 4 S. boydii) representing the most prevalent species and serotypes encountered in Quebec, and 9 non-Shigella strains were tested according to the manufacturers' instructions. A 3+ reaction (> or = 75% agglutination) was considered positive for the slide agglutination tests. Sensitivity varied from 47% (Roach) to 94% (Difco). For the 105 strains tested, accuracy ranged from 53% (Roach) to 91% (Wellcolex). Specificity varied from 97 to 100% for group A antisera, from 96 to 100% for group B antisera, from 88 to 100% for group C antisera, and from 95 to 99% for group D antisera. The costs of reagents required to test one strain varied from $3.50 to $13.20 (in Canadian dollars). In conclusion, Roach reagents proved to be unsatisfactory for Shigella serogrouping. Among those from the remaining companies, the Denka, Difco, and Wellcolex reagents met a performance standard of 90% accuracy.

Agglutination Tests↗
PubMed1995

Modulation of the renin-angiotensin-aldosterone system and cough.

OBJECTIVES: To review the clinical features of the cough related to angiotensin-converting enzyme (ACE) inhibitor therapy, and to suggest from a prospective controlled study that angiotensin II (Ang II) receptor antagonists are not associated with this particular side effect to the same extent as observed with ACE inhibitors. DATA SOURCES: All pertinent data from reports published between 1972 and 1994 were identified through a comprehensive medical literature search. Additionally, results are presented from an international multicentre study examining the occurrence of cough in 135 patients with mild to moderate hypertension, with a history of ACE inhibitor-related cough, who were randomly given either losartan (a type I Ang II receptor antagonist), lisinopril (an ACE inhibitor), or hydrochlorothiazide (a thiazide diuretic). STUDY SELECTION: More than 500 articles were identified; those reporting frequency, characterization, mechanism and treatment of ACE inhibitor-induced cough were chosen. For the multicentre study, men and women with uncomplicated hypertension and a history of ACE inhibitor dry cough were eligible to enter, provided their cough had completely resolved. DATA EXTRACTION AND SYNTHESIS: Relevant information from published case reports, abstracts, postmarketing surveillance studies, hospital series and randomized controlled trials was examined and synthesized. In a recent multicentre study in which patients with a prior history of ACE inhibitor-related cough were randomized into three treatment groups, the percentage of patients with a dry cough was significantly higher in the lisinopril group (72%) than in the losartan (29%) or the hydrychlorothiazide (34%) groups. CONCLUSIONS: Ang II receptor antagonists are novel pharmacological agents that block the renin-angiotensin-aldosterone system at the level of tissue receptors, without affecting interdependant systems. Results from the prospective study reported in the present manuscript demonstrate that the higher specificity of the type I Ang II receptor antagonist losartan is associated with a significantly lower incidence of cough than seen with ACE inhibitors. Losartan thus represents a potential new treatment for hypertensive patients in whom ACE inhibition or Ang II receptor antagonists are indicated, but who develop cough with ACE inhibitors.

Angiotensin II↗
PubMed1994

1,25-dihydroxyvitamin D3 receptors in normal and malignant human colorectal tissues.

1 alpha,25-Dihydroxyvitamin D3, (1,25(OH)2D3), the active metabolite of vitamin D3, has important physiological effects on growth and differentiation in a variety of malignant and non-malignant cell types. In order to better understand the significance of 1,25(OH)2D3 receptors (VDR) in human colorectal cancer, we determined the levels of VDR in paired samples (malignant and adjacent normal tissues) of 24 colorectal cancer bearing patients. Our results demonstrated differences in the relative abundance of VDR between normal and transformed tissues according to the localization of the tumor. While colonic tumors exhibited significantly higher VDR values than their normal counterparts, the contrary seemed to occur in the rectal tumors. In colonic tumors, we found significant correlations between VDR levels and the absence of node involvement or a low Astler-Coller stage. The increased VDR values in colonic tumors as compared with the normal adjacent tissues, may warrant, at least in this type of cancer, the action of 1,25(OH)2D3 or its non-calcemic analogs, to help induce cell differentiation and growth inhibition.

Adult↗
PubMed1994

Effect of extracellular ATP on breast tumor cell growth, implication of intracellular calcium.

We studied the effects of purine nucleotides and particularly adenosine triphosphate (ATP) in two (one hormonosensitive, MCF7 and one hormonoinsensitive, MDA-MB 231) human breast tumor cell lines. As described in other cells, we observed that purine nucleotides produced transient elevations in intracellular calcium ions, [Ca2+]i, in both types of cells as determined from Indo-1 fluorescence of loaded cells. In the absence of external calcium the [Ca2+]i transients consisted of single narrow peaks while an extension of peak duration along with a biphasic appearance were observed in the presence of external calcium. The potency of different purine nucleotides in elevating [Ca2+]i was ATP > ADP >> AMP > adenosine (which was inefficient) proving the presence of P2 purinergic receptor subtypes. Suramin, a compound known to compete with ATP for its binding sites, nearly abolished the effect of ATP on [Ca2+]i increase. while verapamil, a calcium channel blocker, was unable to abolish such an an ATP-induced [Ca2+]i increase. The concentrations of ATP required to increase [Ca2%bdi ranged from 10(-7) M to 10(-3) M, the maximal effect being obtained with 10(-4) M ATP. At this latter concentration, ATP induced cell growth inhibition which was dose-independent as triggered only when maximal elevation of [Ca2+]i was attained. This ATP concentration also induced maximal apoptotic features in both types of cells. Together, our results highlighted an 'all or none' effect of ATP on breast tumor cell growth mediated by its effect on [Ca2+]i liberation from intracellular stores, the first rise of [Ca2+]i being further amplified by an influx of calcium from extracellular space. The attainment of sufficient [Ca2+]i level then triggers cellular events.

Adenosine Triphosphate↗
PubMed1994

Glucocorticoid inhibition of Na-Pi cotransport in renal epithelial cells is mediated by protein kinase C.

The effect and mechanism of action of glucocorticoids (GC) on Na-Pi cotransport were evaluated in opossum kidney cells. Dexamethasone (1-1000 nM) inhibited sodium-dependent Pi uptake in a time- and concentration-dependent manner. Inhibition was maximal after a 6-h incubation with dexamethasone and was prevented by cycloheximide and actinomycin D. The effect was related to a 37% decrease of the Vmax value after incubation with 100 nM dexamethasone. The effect of dexamethasone was mimicked by cortisol and blocked by GC receptor antagonists RU38486 and progesterone. GC affected neither glucose or alanine uptake nor Na/H exchange activity. Inhibition of Pi uptake persisted when Na/H was blocked by amiloride or dimethylamiloride. GC had no effect on basal or parathyroid hormone- and forskolin-stimulated intracellular cAMP content. Dexamethasone and extracellular cAMP, parathyroid hormone, or 3-isobutyl-1-methylxanthine had additive inhibitory effects on Pi uptake. Staurosporine, GF109203X, or calphostin C (three dissimilar inhibitors of protein kinase C (PKC)) and PKC down-regulation blunted the inhibitory effect of glucocorticoids on Pi uptake. GC increased both membrane-bound PKC activity and the membrane/cytosol PKC activity ratio. This is the first report of GC activation of PKC in renal cells, which appears to mediate the steroid inhibitory effect on Pi transport.

Aldosterone↗
PubMed1994

Calcium regulation of heparan sulfate proteoglycans in breast cancer cells.

Breast tumor cells have been shown to be responsive to calcium in that external calcium modifies cell calcium, shape and growth. In order to highlight some of the numerous mechanisms by which calcium is operating, we investigated its influence on the cell microenvironment and particularly its effect on membrane-associated heparan sulfate proteoglycans. The breast cancer cells MCF-7 were grown either at low (0.04 mM) or high (2.5 mM) calcium concentration. After 3 days of culture, cells were labeled with Na2(35)SO4 for 24 h and cell-associated proteoglycans extracted and purified. We showed that calcium enhances approximately twofold the synthesis of sulfated proteoglycans and, among these sulfated proteoglycans, chemical treatments indicated a specific two- to threefold increase of heparan sulfate proteoglycans. In view of the increasing implication of heparan sulfate proteoglycans in numerous mechanisms such as cell-cell contact, cell-matrix interactions and cell growth control, it appears that calcium may be a target for modulating metastatic and growth processes in breast tumor cells.

Breast Neoplasms↗
PubMed1994

Reproductive failure in sows following experimental infection with a Belgian EMCV isolate.

In this study, a transplacental infection with fetal death was demonstrated following inoculation of pregnant sows with a Belgian encephalomyocarditis virus (EMCV) isolate. Eight multiparus sows were inoculated between 60 and 92 days of gestation with this EMCV-isolate to investigate its ability to cause reproductive failure in sows. Virus persistence and antibody titre in their offspring were also studied. Only the two sows inoculated at 60 days of gestation showed premature farrowing, but all sows seroconverted to EMCV. Virus was recovered from the offspring of all sows at the time of farrowing, but not from every piglet born. One month after birth EMCV could be isolated from all the piglets examined. These results can help in a better understanding of the spread of the disease in piggeries.

Animals↗
PubMed1994

Treatment of ambulatory hypertensives with nebivolol or hydrochlorothiazide alone and in combination. A randomized, double-blind, placebo-controlled, factorial-design trial.

This placebo-controlled multifactorial design trial assessed the antihypertensive efficacy of nebivolol, a novel cardioselective beta 1-blocker with vasodilating properties, and hydrochlorothiazide monotherapy and in combination. After a 4-week placebo period, 240 white patients with a mean daytime ambulatory blood pressure of > or = 90 mm Hg were randomized to receive either placebo, nebivolol (1, 5, or 10 mg), hydrochlorothiazide (12.5 or 25 mg), or one of the six possible combinations of nebivolol and hydrochlorothiazide for 12 weeks. A dose-related reduction in clinic and ambulatory blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Nebivolol, 5- and 10-mg doses, showed a larger effect than hydrochlorothiazide doses on clinic blood pressure and over the 24-h interval. Moreover, the combination doses had substantial antihypertensive effects that were sustained over the entire 24-h profile with a greater effect observed with the higher dose combinations. The reduction in ambulatory blood pressure was further substantiated by the reduction of blood pressure loads (% of BP > 140/90 mm Hg awake and > 120/80 mm Hg asleep) to as low as 11.5% with 10 mg of nebivolol combined with 25 mg of hydrochlorothiazide. Nebivolol and hydrochlorothiazide were well tolerated. We provided evidence that nebivolol, given as monotherapy or in combination with low dose of hydrochlorothiazide, is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension. The results provided further evidence for the use of ambulatory blood pressure monitoring and factorial designs when investigating new antihypertensive agents.

Adolescent↗
PubMed1994

[11 beta-Hydroxysteroid dehydrogenase (11-beta-OHSD): physiology and lack of action in pathology].

The 11 beta OHSD is an ubiquitous enzyme which inactivates cortisol to cortisone by transforming the hydroxyl group at the 11-carbon to a keto group. Therefore, it confers to mineralocorticoid receptors their selectivity toward their ligand and may constitute an important mechanism of regulation tissue-specific of the access of ligand toward its receptors. More widely the 11 beta OHSD would modulate glucocorticoid activity to their own receptor. There is no possibility to measure directly this enzyme and its deficiency is indirectly evaluated by enhancement of the quotient (THF + alpha THF)/THE after analysis of urinary steroid metabolites. Such enzymatic deficits may be congenital and are observed in childhood where they give an apparent mineralocorticoid excess (AME) syndrome (type 1). Sometimes acquired and reversible, they are due to licorice intoxication, hypothyroidism, chronic alcoholism and may be involved in the genesis of some cases of hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Association between cough and angiotensin converting enzyme inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study.

BACKGROUND: A common adverse experience in hypertensive patients treated with angiotensin converting enzyme (ACE) inhibitors is a tickling dry cough. OBJECTIVES: The aim of the present study was to review clinical observations and mechanisms of cough associated with ACE inhibitors. In addition, since the AT1-type angiotensin II antagonists (represented by losartan, MK954, DuP753) are not expected to influence other systems (kinins, prostaglandins) affected by ACE inhibitors, we explored the hypothesis that antihypertensive therapy with these agents will not be associated with cough at a similar frequency or quality to that seen with ACE inhibitors. DESIGN AND METHODS: Patients with a history of an ACE inhibitor-associated dry cough confirmed by a second challenge with lisinopril were enrolled into an international, multicenter, randomly allocated, double-blind, parallel-group, controlled trial, to be treated with losartan, lisinopril or hydrochlorothiazide. The presence and severity of cough were assessed by a self-administered questionnaire and a visual analog scale, respectively. CONCLUSIONS: It is expected that the new class of antihypertensive agents, angiotensin II antagonists, will not be associated with the high incidence of dry cough associated with the use of ACE inhibitors. It appears that this cough is not related to alterations in the renin-angiotensin system but to kininase II effects.

Adult↗