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Biomedical subjects

M Burnier

Publications and source records attributed to M Burnier.

At least 73 records · Page 4Linked to original sources
PubMed1999

Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists.

Use of angiotensin (Ang) II AT1 receptor antagonists for treatment of hypertension is rapidly increasing, yet direct comparisons of the relative efficacy of antagonists to block the renin-angiotensin system in humans are lacking. In this study, the Ang II receptor blockade induced by the recommended starting dose of 3 antagonists was evaluated in normotensive subjects in a double-blind, placebo-controlled, randomized, 4-way crossover study. At 1-week intervals, 12 subjects received a single dose of losartan (50 mg), valsartan (80 mg), irbesartan (150 mg), or placebo. Blockade of the renin-angiotensin system was assessed before and 4, 24, and 30 hours after drug intake by 3 independent methods: inhibition of the blood pressure response to exogenous Ang II, in vitro Ang II receptor assay, and reactive changes in plasma Ang II levels. At 4 hours, losartan blocked 43% of the Ang II-induced systolic blood pressure increase; valsartan, 51%; and irbesartan, 88% (P<0.01 between drugs). The effect of each drug declined with time. At 24 hours, a residual effect was found with all 3 drugs, but at 30 hours, only irbesartan induced a marked, significant blockade versus placebo. Similar results were obtained when Ang II receptor blockade was assessed with an in vitro receptor assay and by the reactive rise in plasma Ang II levels. This study thus demonstrates that the first administration of the recommended starting dose of irbesartan induces a greater and longer lasting Ang II receptor blockade than that of valsartan and losartan in normotensive subjects.

Adult↗
PubMed1999

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice.

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

Adult↗
PubMed1999

A mouse model for Liddle's syndrome.

Liddle's syndrome (or pseudoaldosteronism) is an autosomal dominant form of salt-sensitive hypertension, due to abnormal sodium transport by the renal tubule. To study the pathophysiology of salt sensitivity, a mouse model for Liddle's syndrome has been generated by Cre/loxP-mediated recombination. Under normal salt diet, mice heterozygous (L/+) and homozygous (L/L) for Liddle mutation (L) develop normally during the first 3 mo of life. In these mice, BP is not different from wild type despite evidence for increased sodium reabsorption in distal colon and low plasma aldosterone, suggesting chronic hypervolemia. Under high salt intake, the Liddle mice develop high BP, metabolic alkalosis, and hypokalemia accompanied by cardiac and renal hypertrophy. This animal model reproduces to a large extent a human form of salt-sensitive hypertension and establishes a causal relationship between dietary salt, a gene expressed in kidney and hypertension.

Animals↗
PubMed1999

Comparative safety and tolerability of angiotensin II receptor antagonists.

Hypertension is a very common disease and represents a major risk factor for cardiovascular adverse events such as stroke and heart failure. In recent years, a big effort has been put into detecting and treating patients with hypertension. Several classes of drugs acting by different pharmacological mechanisms can be chosen for the treatment of hypertension. However, the long term use of all anti-hypertensive agents is sometimes limited by the occurrence of adverse effects. Thanks to continuous pharmacological research, new compounds are regularly developed and become available in clinical practice. Recently, several new, nonpeptide, orally active angiotensin II receptor antagonists have reached the market. Today, these substances represent the most specific way to block the renin angiotensin system. Numerous studies have now demonstrated that these angiotensin II antagonists are as effective as ACE inhibitors, calcium antagonists, beta-blockers or diuretics in lowering blood pressure in patients with hypertension. Given the increasing use of angiotensin II receptor antagonists in the treatment of hypertension, it is important to review their safety and tolerability. Based on the actual level of knowledge, the striking feature of this class of agents is their favourable safety and tolerability profile which appears to be equivalent to that observed with placebo. Indeed, so far, no clear class-specific adverse effect has been attributed to the angiotensin II receptor antagonists. Thus, if angiotensin II antagonists prevent target organ damage and reduce the morbidity and mortality of patients with hypertension, they may well become a first-line treatment of hypertension.

Angiotensin II↗
PubMed1999

Comparative antihypertensive effects of angiotensin II receptor antagonists.

Blockade of the renin-angiotensin system is recognized as an effective approach for the treatment of hypertension and congestive heart failure. It is possible to antagonize the effects of angiotensin II (AngII) by blocking its receptors, using nonpeptide receptor antagonists. Six angiotensin receptor blockers (ARB) have been approved for the treatment of hypertension: losartan, valsartan, irbesartan, candesartan, telmisartan, and eprosartan. These new drugs are highly selective for the AT1 receptor subtype and induce dose-dependent inhibition of the BP response to exogenous AngII. Numerous double-blind, placebo-controlled studies have demonstrated that ARB are efficacious for treating mild, moderate, and severe hypertension. When compared with other classes of antihypertensive agents, ARB are as effective as angiotensin-converting enzyme inhibitors, calcium antagonists, thiazide diuretics, and beta-blockers. One advantage of ARB as a class is their excellent tolerability and side effect profile. Several large clinical trials of ARB are now under way to demonstrate their benefits in hypertension, heart failure, and type II diabetic nephropathy.

Angiotensin II↗
PubMed1998

Uricosuric effect of the angiotensin II receptor antagonist losartan in heart transplant recipients.

BACKGROUND: The angiotensin II receptor antagonist losartan is an effective antihypertensive agent with unique uricosuric properties. This study evaluates the uricosuric effects of losartan in 10 hypertensive heart transplant patients with hyperuricemia. METHODS: The patients were randomized to receive losartan 50 mg once daily and enalapril 20 mg once daily for 4 weeks according to a double-blind crossover design. Office blood pressure, plasma uric acid levels, and urinary uric acid excretion were monitored throughout the study. RESULTS: Plasma uric acid levels decreased significantly after 4 weeks of treatment with losartan (P<0.05) but not with enalapril. On day 1 and after 1 month of treatment, a significant increase in uric acid excretion was observed only with losartan. Significant decreases in office systolic and diastolic blood pressures were obtained with enalapril but not with losartan. CONCLUSIONS: Losartan effectively lowers plasma uric acid levels in hyperuricemic heart transplant patients.

Adult↗
PubMed1998

Circadian variations of renal sodium handling in patients with orthostatic hypotension.

BACKGROUND: Sodium wasting during the night has been postulated as a potential pathophysiological mechanism in patients suffering from orthostatic hypotension due to severe autonomic deficiency. METHODS: In this study, the diurnal variations in creatinine clearance, sodium excretion and segmental renal tubular handling of sodium were evaluated in 18 healthy subjects and 20 young patients with orthostatic hypotension (OH). In addition, 24-hour ambulatory blood pressure and the neuro-hormonal response to changes in posture were determined. The patients and their controls were studied on a free sodium intake. In a second protocol, 10 controls and 10 patients were similarly investigated after one week of a high salt diet (regular diet + 6 g NaCl/day). RESULTS: Our results demonstrate that, in contrast to normal subjects in whom no significant changes in glomerular filtration, sodium excretion and segmental sodium reabsorption were observed throughout the day, patients with OH were characterized by a significant increase in glomerular filtration rate during the nighttime (P = 0.03) and significant increases in urinary lithium excretion (P < 0.05) and lithium clearance (P = 0.05) during the night, suggesting a decreased proximal reabsorption of sodium. On a high sodium diet, the symptoms of orthostatic hypotension and the circadian variations in sodium reabsorption were significantly blunted. CONCLUSIONS: These results suggest that, while the patient is in a supine position the effective blood volume of those with OH becomes excessive due to the increased venous return. Hence, the kidney responds with an increase in glomerular filtration and a relative escape of sodium from the proximal tubular segments. These circadian variations in renal sodium handling may contribute to the maintenance of the orthostatic syndrome.

Adolescent↗
PubMed1998

Effect of indomethacin on the renal response to angiotensin II receptor blockade in healthy subjects.

BACKGROUND: Non-steroidal anti-inflammatory drugs are known to promote sodium retention and to blunt the blood pressure lowering effects of several classes of antihypertensive agents including beta-blockers, diuretics and angiotensin converting enzyme (ACE) inhibitors. The purpose of the present study was to investigate the acute and sustained effects of indomethacin on the renal response to the angiotensin II receptor antagonist valsartan and to the ACE inhibitor enalapril. METHODS: Twenty normotensive subjects maintained on fixed sodium intake (100 mmol sodium/day) were randomized to receive for one week: valsartan 80 mg o.d., enalapril 20 mg o.d., valsartan 80 mg o.d. + indomethacin 50 mg bid and enalapril 20 mg o.d. + indomethacin 50 mg bid. This single-blind study was designed as a parallel (valsartan vs. enalapril) and cross-over trial (valsartan or enalapril vs. valsartan + indomethacin or enalapril + indomethacin). Renal hemodynamics and urinary electrolyte excretion were measured for six hours after the first and seventh administration of each treatment regimen. RESULTS: The results show that valsartan and enalapril have comparable renal effects characterized by no change in glomerular filtration rate and significant increases in renal plasma flow and sodium excretion. The valsartan- and enalapril-induced renal vasodilation is not significantly blunted by indomethacin. However, indomethacin similarly abolishes the natriuresis induced by the angiotensin II antagonist and the ACE inhibitor. CONCLUSIONS: This observation suggests that although angiotensin receptor antagonists do not affect prostaglandin metabolism, the administration of a non-steroidal anti-inflammatory drug blunts the natriuretic response to angiotensin receptor blockade.

Adult↗
PubMed1998

Angiotensin II receptor antagonists in hypertension.

Blockade of the renin-angiotensin system is now recognized as an effective approach to the treatment of hypertension and congestive heart failure. Today, it is possible to antagonize the effects of angiotensin II more specifically by blocking its receptors by using nonpeptide receptor antagonists. These compounds that first have been used to recognize the various subtypes of angiotensin II receptors are now available clinically. Four of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as ACE inhibitors, calcium antagonists and beta-blockers in lowering blood pressure in hypertensive patients. When compared to ACE inhibitors, they appear to have comparable favorable effects on systemic and renal hemodynamic properties. One of the major characteristics of angiotensin II receptor antagonists as a class is the excellent tolerability with an incidence of side effects that is generally similar to that of placebo. Large clinical trials are now underway to demonstrate the long-term benefits of these agents in hypertension, heart failure and type II diabetic nephropathy.

Angiotensin Receptor Antagonists↗
PubMed1998

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

Adult↗
PubMed1998

Pharmacology of valsartan, an angiotensin II receptor antagonist.

Valsartan is the second orally-active, non-peptide angiotensin II receptor blocker to reach the market in Europe and the USA for the treatment of hypertension. Preclinical studies have demonstrated that this blocker is specific for the AT(1) receptor and has no affinity for the angiotensin II AT(2) receptor. Experimentally, valsartan dose-dependently inhibits the vasoconstriction induced by angiotensin II and lowers blood pressure in renin-dependent models of hypertension. Pharmacologically, oral valsartan is characterised by a low bioavailability but a rapid absorption and distribution with a half-life in keeping with once-daily administration. Thus, after oral administration, the maximal plasma concentration is reached 2 h after dosing and the elimination half-life is about 6 h. Clinically, several dose-finding and comparative studies have demonstrated that valsartan is an effective and well-tolerated antihypertensive drug in patients with mild to moderate hypertension. Valsartan has also been shown to be effective in severe hypertension. Valsartan is at least as effective as ACE inhibitors, diuretics, beta-blockers and calcium antagonists. However, none of the side-effects observed with these latter agents, including cough and lower limb oedema, has been observed with the administration of valsartan. Three large clinical trials are now underway to demonstrate whether valsartan can reduce morbidity and mortality: one in hypertensives with a high cardiovascular risk profile (VALUE), one in patients with heart failure previously treated with an angiotensin-converting enzyme inhibitor (VAL-HeFT) and one in post-myocardial infarct patients (VALIANT). These studies will further define the place of valsartan beyond the treatment of hypertension.

Journal Article↗
PubMed1998

Estimation of glomerular filtration rate by sinistrin clearance using various approaches.

Two protocols for the determination of glomerular filtration rate (GFR) from sinistrin clearance are considered: a bolus injection and a bolus followed by infusion. On both occasions, serial blood and urine samplings are scheduled up to 6 h. Four calculation methods are compared for estimating GFR from the data obtained during each protocol: classical UV/P (ratio of urinary excretion rate over plasma concentration) after bolus or bolus plus infusion; 2-point (log-linear slope multiplied by apparent volume of distribution); D/AUC (ratio of dose over area under the curve) after bolus; and Rin/P (ratio of infusion rate over steady-state concentration) during infusion. Some refinements of the calculations are devised. Data are simulated by running a bicompartmental pharmacokinetic model with renal elimination, and contaminating the values with an array of random errors. The statistical performance of the respective calculation methods is assessed by graphical means. The UV/P method performs poorly during 2 hours following the bolus; on both bolus and infusion data, it suffers from imprecision on the urinary volume. The 2-point method is acceptable between 1 and 4 h after bolus; later, the estimates become much less precise. The D/AUC method appears highly reliable when integrating the concentrations up to 3 h after bolus; it requires extrapolation towards infinity. The Rin/P method is satisfactory if applied later than 3 to 4 h after the loading dose. The advantages and drawbacks of each methods must be evaluated in relation with the particular clinical setting in which GFR is to be estimated. D/AUC represents the most advisable approach for snapshot renal testing in subjects or patients without important renal impairment.

Chromatography, High Pressure Liquid↗
PubMed1998

Electronic monitoring of adherence to treatment in the preventive chemotherapy of tuberculosis.

SETTING: Non-adherence to treatment is a frequent problem in the preventive chemoprophylaxis of tuberculosis. OBJECTIVE: To evaluate the usefulness of the Medication Event Monitoring System (MEMS) for following and improving patient adherence to 6-month treatment with isoniazid. DESIGN: Three methods of monitoring compliance, MEMS, pill count and a urine test for isoniazid, were compared prospectively in 30 patients. The efficacy of a combined intervention by the physician and the pharmacist was evaluated in non-compliant patients. RESULTS: According to the MEMS data, overall adherence to isoniazid therapy was 91.5%, and 86% of the patients were considered compliant throughout the period of observation. The pill count and the urine test tended to overestimate the overall compliance when compared to the MEMS. The combined intervention of the physician and pharmacist allowed drug adherence to be enhanced in non-compliant patients, but the effect was only transient if this was not repeated every month. CONCLUSION: Our results suggest that the MEMS system is a useful approach for monitoring and improving compliance with preventive chemotherapy for tuberculosis.

Adolescent↗
PubMed1997

A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism.

Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (alpha, beta, and gamma). In human, autosomal recessive mutations of alpha, beta, or gammaENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of alphaENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of alphaENaC driven by a cytomegalovirus promoter in alphaENaC(-/-) knockout mice [alphaENaC(-/-)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na+ transport in renal, colonic, and pulmonary epithelia. At days 5-9, however, alphaENaC(-/-)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult alphaENaC(-/-)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na+ absorption in this transgenic mouse results in a mouse model for PHA-1.

Amiloride↗
PubMed1997

[Differentiation between glomerular and non-glomerular erythrocyturia: what is the value of differential microhematuria diagnosis?].

A few years ago, a new and simple method has been proposed to help guiding the investigation of microhematuria. This method which consists in quantifying the percentage of deformed polymorphous erythrocytes in the urinary sediment using phase contrast microscopy allows to distinguish glomerular from non-glomerular erythrocytes. In this paper, we have reviewed the recent literature concerning this approach and have discussed the conclusions according to our own experience based on the analysis of 147 patients presenting with microhematuria. Our results demonstrate that this technique is still limited by the difficulty to obtain well-defined cut-off values which effectively differentiate renal from urologic diseases. Thus, only extreme results showing either the total absence or the presence of a very high percentage of dismorphic erythrocytes appear to be helpful for the physician. Despite the introduction of this new method, many patients with microhematuria are insufficiently investigated.

Diagnosis, Differential↗
PubMed1997

[Renal manifestations of viral diseases].

Like bacterial diseases viral diseases may also be accompanied by functional renal disorders or abnormalities of the urinary sediment. Thus, to find a hematuria or an isolated proteinuria in the context of influenza or hepatitis is not rare at all. In certain cases viral affections may even be accompanied by a nephrotic syndrome. This article aims at the discussion of multiple renal disorders appearing in the context of hepatitis B and C and AIDS.

AIDS-Associated Nephropathy↗