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Biomedical subjects

M Burnier

Publications and source records attributed to M Burnier.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Endothelial factors and cardiac insufficiency].

The endothelium produces several vasodilating factors such as prostacyclin or nitric oxide and also vasoconstricting agents such as endothelin. These factors play an important role in the regulation of vascular tone and tissue perfusion. Several recent studies have evaluated the role of endothelin and NO in the pathophysiology of congestive heart failure. This paper reviews the data suggesting that endothelin and NO contribute to the neuro-hormonal compensatory mechanisms in patients with heart failure and that specific blockade of endothelin receptors could be an effective new approach for the treatment of patients with severe congestive heart failure.

Bosentan↗
PubMed1997

Sinistrin clearance for determination of glomerular filtration rate: a reappraisal of various approaches using a new analytical method.

Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6-hour infusion. A recently developed high-performance liquid chromatography method was used for the determination of sinistrin levels, enabling precise measurements in plasma and urine samples with high sensitivity. Blood and urine were sampled up to 6 hours. Four calculation methods for estimating GFR were applied: 1) classical ratio of urinary excretion rate over plasma concentration (UV/P); 2) two-point (log-linear regression slope times monocompartmental volume of distribution) after bolus; 3) ratio of dose over area under the curve (D/AUC) after bolus; and 4) ratio of infusion rate over steady-state concentration during infusion (Rinf/P). The results obtained by fitting a pharmacokinetic model to all the plasma and urine data served as the standard against which the performance of the respective calculation methods were examined. The UV/P method performed poorly on bolus data, mainly by underestimating GFR at late times; on both bolus and infusion data, it suffered from important imprecisions on the urinary volume. The two-point method appeared applicable only between 2 and 4 hours after the bolus dose. The D/AUC method with extrapolation to infinity was highly reliable when integrating the concentrations up to 3 hours or more after the bolus dose. The Rinf/P method was satisfactory if applied later than 2 to 3 hours after the loading dose. The advantages and drawbacks of each method have to be evaluated in relation to the particular clinical setting in which GFR is to be estimated.

Adult↗
PubMed1997

Clinically suspected primary acquired nasolacrimal duct obstruction: clinicopathologic review of 150 patients.

PURPOSE: The incidence of lacrimal sac pathology in patients with clinically suspected primary acquired nasolacrimal duct obstruction is unknown. This is an important issue when considering the potential risk of either conservative nonsurgical management or laser dacryocystorhinostomy, neither of which permits direct visualization and biopsy of the lacrimal outflow apparatus. METHODS: A total of 162 lacrimal sac biopsy specimens were obtained in 150 consecutive patients undergoing external or endonasal dacryocystorhinostomy for clinical primary acquired nasolacrimal duct obstruction from January 1992 to October 1994. RESULTS: A total of 147 patients (98%) had histopathologic findings consistent with inflammation or fibrosis of the lacrimal sac or both. In the remaining three patients, abnormalities included sarcoid granuloma (one patient), oncocytoma (one patient), and lymphoma (one patient). CONCLUSIONS: The incidence of significant pathology of the lacrimal sac in clinically suspected primary acquired nasolacrimal duct obstruction is low. However, these cases can be identified correctly only by routine biopsy of the lacrimal sac during dacryocystorhinostomy.

Adult↗
PubMed1997

Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans.

We have evaluated the efficacy of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist (arginine-vasopressin [AVP]), in the blockade of the vascular effects of exogenous AVP in healthy subjects. In preliminary experiments, two procedures to measure the V1 vascular effects of AVP were assessed. First, the AVP-induced changes in skin blood flow were investigated by the injection of increasing doses of AVP intradermally, with or without a previous local vasodilation with calcitonin gene-related peptide (CGRP). In a second protocol, AVP was infused intra-arterially, and the changes in radial artery diameter and blood flow were measured. The intradermal injection of AVP caused significant decreases in skin blood flow, and the use of CGRP increased the sensitivity of the method by a factor of 10(2) to 10(3). AVP infused intra-arterially caused dose-dependent decreases in the radial artery diameter and blood flow. In the main study, the potency and efficacy of SR 49059 to block the AVP-induced changes in skin blood flow were assessed in 12 healthy men with a double-blind, triple crossover study design. The subjects were randomized to receive a placebo orally and 30 mg and 300 mg of the antagonist at a 1-week interval. The subjects were then further randomized to evaluate the efficacy of the same doses of the antagonist to block the vasoconstriction of the radial artery induced by an intra-arterial infusion of AVP. SR 49059 inhibits, dose-dependently and significantly, the AVP-induced changes in skin blood flow, with a peak effect occurring between 2 and 6 hours after injection. In addition, the 300-mg dose of SR 49059 completely blocked the vasoconstriction of the radial artery induced by AVP. In conclusion, skin blood-flow measurement, after intradermal injection of AVP on a skin area vasodilated with CGRP, is an effective method to investigate the V1 vascular effect of AVP in humans. SR 49059 is a potent and specific antagonist of V1 receptors, which blocks the AVP-induced vasoconstriction.

Administration, Oral↗
PubMed1997

Angiotensin II receptor antagonists - antihypertensive agents.

Blockade of the renin-angiotensin system (RAS) is now recognised as an effective approach for the treatment of hypertension and congestive heart failure (CHF). Today, it is possible to antagonise the effects of angiotensin II more specifically by blocking its receptors using non-peptide receptor antagonists. These compounds, which at first were used to identify the various subtypes of angiotensin II receptors, are now available clinically. Some 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 angiotensin converting enzyme (ACE) inhibitors at lowering blood pressure in hypertensive patients, and appear to have similar systemic and renal haemodynamic properties in patients with CHF and renal diseases. Large-scale clinical trials such as the LIFE, the ELITE and the RENAAL studies are now underway to investigate the long-term benefits of one of these agents in hypertension, heart failure and Type II diabetic nephropathy. The major clinical advantage of AT1 receptor antagonists is that, in contrast to ACE inhibitors, they do not induce cough. With the more widespread use of AT1 receptor antagonists, two unresolved questions remains unanswered: what is the role of AT2 receptors? Are the unblocked effects of angiotensin II on AT2 receptor sites of any clinical relevance to the safety profile or efficacy of AT1 receptor antagonists? Another interesting question is whether the combination of an ACE inhibitor with an AT1 receptor antagonist is advantageous. Studies attempting to answer these questions are underway and will certainly enable researchers to define more precisely the role and the advantages of these new specific non-peptide AT1 receptor antagonists in the treatment of hypertension and heart failure.

Journal Article↗
PubMed1997

Heterogeneous vascular response to vasopressin: radial artery versus forearm blood flow.

BACKGROUND: Arginine vasopressin (AVP) administered intra-arterially to normal volunteers exerts a biphasic effect on forearm blood flow when the effect is extrapolated from plethysmographic measurements. OBJECTIVE: To assess whether the high-dose AVP-induced increase in forearm blood flow could be confirmed when calculating blood flow from continuous radial artery diameter and flow velocity recordings obtained by using a high-resolution echotracking device combined with a Doppler system. METHODS: Increasing doses (0.04-0.8 ng/kg per min) of AVP were infused into a brachial artery of seven normal male volunteers (aged 21-33 years). Forearm blood flow derived from venous occlusion plethysmography was assessed simultaneously with proximal radial artery blood flow calculated from luminal area and flow velocity measurements. RESULTS: Confirming previous reports, plethysmography showed an increase in global forearm blood flow by > 100% with AVP concentrations > or = 0.2 ng/kg per min. In contrast, direct measurements of lumen diameter and blood flow velocity in the radial artery revealed a marked dose-dependent vasoconstriction with a > 30% decline in blood flow at the highest AVP concentration. CONCLUSIONS: The discrepancy between the two measurements suggests that AVP has a dual effect on forearm haemodynamics. At high AVP concentration, the muscle blood flow increase predominates over the vasoconstriction in the skin circulation. Furthermore, this study strongly suggests a heterogeneity of the vascular response to vasomediators by showing that opposing responses exist not only between resistive and conduit vessels but also between conduit arteries of a common vascular bed.

Adult↗
PubMed1996

[Diagnosis and treatment of arterial hypertension in the elderly].

The incidence of hypertension increases with age and becomes very high in the seventh decade. The increase of the blood pressure may be systolic, diastolic or both. Various controlled studies have shown that the treatment of hypertension in the elderly reduces the incidence of myocardial infarction and of stroke. It appears today that also patients with isolated systolic hypertension benefit from antihypertensive treatment. All classes of antihypertensive agents, including beta-blocking drugs, may be used in the elderly.

Aged↗
PubMed1996

Squamous cell carcinoma of the conjunctiva in a patient with the acquired immunodeficiency syndrome.

PURPOSE: To alert ophthalmologists to the possibility of human immunodeficiency virus (HIV) infection in individuals with conjunctival squamous cell carcinoma. METHODS: We treated a 24-year-old patient with the acquired immunodeficiency syndrome who developed a limbal mass. The mass was excised and examined by routine histologic and immunohistochemical methods. RESULTS: The histopathologic examination disclosed infiltrating squamous cell carcinoma with features of spindle cell carcinoma. Frequent abnormal mitotic figures were present in this neoplasia. CONCLUSIONS: Squamous cell carcinoma with histologic features of aggressive behavior in a young individual should alert physicians to the possibility of HIV infection. Such patients may require frequent follow-up examination, even after complete excision of the tumor.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Determination of trace lithium in biological fluids using graphite furnace atomic absorption spectrophotometry: variability of urine matrices circumvented by cation exchange solid phase extraction.

A graphite furnace atomic absorption spectrometry method has been developed for the quantitative determination of submicromolar endogenous concentration of lithium in human plasma and urine using pyrolitically-coated graphite tubes in combination with ammonium nitrate matrix modification. This latter treatment could not completely abolish the interferences caused by the matrix, notably in urine samples. The variability of the urinary matrices required an additional standardization procedure by solid-phase extraction on strongly acidic cation exchange cartridges. Matrix-matched samples were used for the establishment of calibration curves with the addition-calibration method. Calibration curves were linear up to 0.72 mumol/l (1.0 > r2 > 0.99). The described method enables accurate measurements of trace-lithium in biological samples at concentrations down to 0.03 mumol/l with intra- and inter-day variabilities < 10%. The method was applied to the determination of trace-lithium levels in urine and plasma samples from healthy individuals enabling the calculation of its fractional excretion (FeLi) (median range 17.3%), a value which reflects the functional capacity of the kidney to reabsorb sodium and water at the proximal tubular portion of the nephron. This sensitive method can thus be used as an investigative and diagnostic tool in various renal pathophysiological conditions, in clinical research, and may also be applied to studies on the trace-lithium status of population in connection with psycho-affective disorders.

Cations↗
PubMed1996

Renal effects of angiotensin II receptor blockade in normotensive subjects.

Several new non-peptide, orally active, angiotensin II receptor antagonists have recently been developed which enable to block the renin-angiotensin system at the AT1 receptor site. In contrast to angiotensin converting enzyme (ACE) inhibitors, these antagonists do not interfere with the metabolism of kinins. The effect of these agents on renal function may thus potentially differ from those of ACE inhibitors. Therefore, the renal pharmacology of various angiotensin II receptor antagonists has been examined in normotensive subjects. In normotensive subjects, losartan and irbesartan have been shown to have no effect on glomerular filtration rate and to induce either no change or a modest increase in renal blood flow. These results were confirmed thereafter in hypertensive patients where losartan produced a renal vasodilation with no change in glomerular filtration. In healthy subjects, both losartan and irbesartan induce an acute increase in urinary sodium excretion. The natriuretic response to losartan is proportionally more important during salt-depletion. In contrast to other angiotensin II receptor antagonists, losartan has a unique property to increase uric acid excretion. In this paper we show that this property is due to the potent inhibitory effect of the parent compound of losartan on the urate/anion transport in the human renal proximal tubule.

Angiotensin Receptor Antagonists↗
PubMed1996

Isolated office hypertension: a prehypertensive state?

OBJECTIVE AND METHOD: Isolated office hypertension, defined as hypertensive blood pressure values in a medical setting but normal self-measured or ambulatory-recorded blood pressures, is frequently encountered in clinical practice. Yet, whether this condition represents a transient state in the development of a sustained ambulatory hypertension is still unknown as no long-term analysis of the evolution of ambulatory blood pressure has been carried out in patients with isolated office hypertension. To evaluate whether such patients should be considered as truly normotensive or hypertensive, we have studied the long-term changes in office and ambulatory blood pressures in 81 patients in whom isolated office hypertension was observed between 1982 and 1988. RESULTS: After a 5-6 year follow-up, 60 of the 81 patients had a mean 12 h daytime ambulatory blood pressure greater than 140/90 mmHg, suggesting an evolution towards ambulatory hypertension. The development of hypertension could not be predicted on the basis of the follow-up office blood pressures as these tended to decrease during the follow-up period. CONCLUSIONS: The results of this study suggest that patients with isolated office hypertension should not be considered as truly normotensive individuals. Hence, these patients require a careful medical follow-up. Office blood pressure readings alone, however, do not appear to provide a good indicator of the long-term outcome of isolated office hypertension.

Adolescent↗
PubMed1996

Genetic predisposition to coronavirus-induced retinal disease.

PURPOSE: Retinal inflammatory and degenerative processes in humans and animals frequently are associated with genetic factors. The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. The genetic constitution of the host and the virus serotype can be critical factors in determining the outcome of a virus infection. The purpose of this study was to evaluate the possible role of host genetics in murine coronavirus-induced retinal disease. METHODS: JHM virus was inoculated by the intravitreal route into BALB/c, CD-1, and A/J mice. At varying times after inoculation, eye tissues were evaluated histologically. Antibody responses to the virus were evaluated by neutralization assays. RESULTS: JHM virus induces a biphasic retinal disease in BALB/c mice. In the early phase, 1 to 7 days after inoculation, retinal vasculitis is observed. The second phase, characterized by retinal degeneration in the absence of inflammation, is seen by day 10 and progresses for several months. There is a similar biphasic disease process in JHM virus-infected A/J mice. However, retinal changes are less severe than those seen in BALB/c mice. Retinal tissue damage induced by JHM virus in CD-1 mice is different. Only the early phase of the disease, consisting of retinal vasculitis, was observed. These CD-1 mice do not develop the retinal degenerative disease. In fact, after day 10, the retina has a normal appearance. These differences in retinal tissue damage are seen over a wide range of infectivity of the virus inocula. Virus concentrations ranging from 10(1.4) to 10(4.4) TCID50/5 microliters were capable of inducing both inflammation and degeneration in BALB/c mice, whereas, the highest concentration of virus (10(4.4) TCID50/5 microliters) in CD-1 mice resulted in only the early inflammatory changes. CONCLUSIONS: The authors show that the genetics of the host can profoundly affect the nature of retinal tissue damage. These studies substantiate the concept that a virus can indeed trigger retinal degenerative processes in genetically susceptible hosts.

Animals↗
PubMed1996

Experience with angiotensin II antagonists in hypertensive patients.

1. The availability of orally active specific angiotensin receptor antagonists (AT1 antagonists) has opened new therapeutic choices and provided probes to test the specific role of the renin-angiotensin system in the pathogenesis of cardiovascular disease. 2. The data available so far suggest that the antihypertensive efficacy of angiotensin receptor antagonists is comparable to that of angiotensin-converting enzyme (ACE) inhibitors. This provides further evidence that this latter class of drugs exerts its effect mainly through blockade of the renin-angiotensin enzymatic cascade. As expected, the association of a diuretic exerts an equally strong additive effect to the antihypertensive efficacy of both classes of drugs. 3. The most common side effect of ACE inhibitors, dry cough, does not occur with AT1 antagonists, which confirms the long-held view that this untoward effect of the ACE inhibitors is due to renin-angiotensin-independent mechanisms. 4. Long-term studies with morbidity/mortality outcome results are needed, before a definite position can be assigned to this newcomer in the orchestra of modern antihypertensive drugs. Notwithstanding, this new class of agents already represents an exciting new addition to our therapeutic armamentarium.

Angiotensin II↗
PubMed1996

Renal effects of angiotensin II receptor blockade and angiotensin-converting enzyme inhibition in healthy subjects.

The evaluation of a new drug in normotensive volunteers can provide important information, as long as the compound has a specific mechanism of action which can be evaluated in healthy subjects as well as in patients. The purpose of the present paper is to review the renal effects of new specific angiotensin II receptor antagonists observed in normotensive subjects and to compare them to those of angiotensin-converting enzyme (ACE) inhibitors. Blockade of the renin-angiotensin system with ACE inhibitors and angiotensin II antagonists induces an expected increase in plasma renin activity and plasma angiotensin I levels. Plasma angiotensin II levels decrease with ACE inhibitors, whereas they increase with angiotensin II receptor blockade. So far, the expected decrease in plasma aldosterone levels has been difficult to demonstrate with most angiotensin II antagonists. In normotensive subjects, ACE inhibitors, as well as angiotensin II antagonists, cause no change in glomerular filtration rate and either no modification or an increase in renal blood flow. Both approaches to block the renin-angiotensin system are natriuretic, and the natriuresis is more pronounced in salt-depleted subjects. Finally, in contrast to ACE inhibitors and other angiotensin II receptor antagonist, losartan markedly increases uric acid excretion and lowers plasma uric acid levels. This unique property of losartan is due to a direct interference of losartan with the uric acid transport system in the proximal tubule. The data obtained in normal subjects therefore suggest that ACE inhibitors and angiotensin II receptor antagonists have comparable renal properties. Whether this is also true in hypertensive patients and in patients with proteinuria and chronic renal failure remains to be demonstrated.

Angiotensin Receptor Antagonists↗
PubMed1995

[Diagnosis and treatment of hypertensive emergencies].

In hospital as well as in the office, the physician is often confronted with clinical situations in which blood pressure values are very high. In each case, he will have to evaluate rapidly the degree of emergency and the need for immediate antihypertensive therapy. In the last few years, the therapeutic approach to some hypertensive emergencies has changed. The purpose of the present article is to review: 1) the clinical situations where immediate control of blood pressure is necessary, 2) the present therapeutic approaches and 3) the cardiac and cerebral risks linked to an excessive and too rapid fall in blood pressure.

Adrenal Gland Neoplasms↗
PubMed1995

[Emergency and hypertensive crisis: definition and treatment].

The opinions on how fast high blood pressure values should be lowered in emergencies have changed over the last years. It seems now more and more reasonable to lower high blood pressure values over several hours rather than several minutes. In some cases, however, a rapid reduction of elevated blood pressure may be necessary. In these cases the risks of a rapid decrease of blood pressure with respect to cerebrovascular circulation have to be considered.

Acute Disease↗
PubMed1995

Screening for excessive alcohol drinking. Comparative value of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume.

BACKGROUND: Screening medical patients for excessive alcohol drinking is important because minimal intervention by physicians is effective in reducing excessive consumption. Screening tests, such as biologic markers of alcohol consumption, should therefore be investigated to assess their validity to detect alcohol drinking. METHOD: Levels of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) were determined in 1202 consecutive patients (20 to 75 years old) seen at the medical emergency ward (n = 552) and the primary care center (n = 650) of a city and teaching hospital. Each eligible patient was administered a CAGE questionnaire (an acronym for questions regarding cutting down on drinking, annoyance at others' concern about drinking, feeling guilty about drinking, and using alcohol as an eye-opener in the morning), and for each CAGE-positive patient (score > or = 2) as well as for a random sex-matched sample of CAGE-negative patients, standardized data about the recent level of alcohol drinking, morbidities, drug therapy, and smoking were recorded. The operating characteristics of CDT, GGT, and MCV were determined according to alcohol consumption and the CAGE test. Sensitivities, specificities, and receiver operating characteristic curves were computed to compare the tests at different cutoff values. RESULTS: Levels of CDT were elevated in 21% of men and 7% of women. According to recent alcohol consumption in men (> 60 g/d), the respective sensitivity and specificity of the tests were 0.58 and 0.82 for CDT, 0.69 and 0.65 for GGT, and 0.27 and 0.91 for MCV. Overall, receiver operating characteristic curves demonstrated similar performance of the three tests for screening of excessive alcohol drinking or alcohol abuse. However, in young men (< 40 years of age) and in smokers, CDT was superior to GGT or MCV. CONCLUSIONS: The study suggests that CDT determination may be a useful test for screening programs of excessive alcohol drinking in young male medical patients.

Adult↗