[Evidence-based medicine in routine clinical practice].
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Evidence-Based Medicine↗
Biomedical subjects
A Pechère-Bertschi
Publications and source records attributed to A Pechère-Bertschi.
[Evidence-based medicine and arterial hypertension: reasonable or unreasonable marriage?].
Rational medical decisions should be based on the best possible evidence. Yet clinical trial results may not reflect conditions in actual practice. In hypertension, for example, the evidence-based approach to medical care involves the explicit use of evidence on the magnitude of the effects of interventions to influence treatment decisions. Evidence-based medicine is a paradigm challenging our medical practice, as foundation it uses proofs originating from scientific research and controlled randomized trials, more than intuition, clinical experience and pathophysiologic rationale. In this article, we analyze two clinical problems in hypertension generating current questions. We try to use this method in order to obtain pertinent answers for a given patient. We observe that the application of EBM has some limitations. Very restrictive inclusion criteria in some studies make the sample of patients studied not comparable with the individuals in front of us. On the other hand, for other sub-groups of patients, results obtained from EBM are very useful and give valuable information. For a good application of this paradigm critical reading of literature is essential, in order to balance its importance.
Antihypertensive Agents↗
Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle.
The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.
Adult↗
[Does constitutional hypotension exist?].
Orthostatic hypotension is frequently related to severe insufficiency of the autonomic nervous system associated with neuropathy or systemic disease like diabetes. Inversely, pre-syncopal orthostatic symptoms associated with mild drop in orthostatic blood pressure is quite often a reason to seek medical care, but is relatively unrecognized in the literature. Recently a syndrome of mild orthostatic intolerance has been defined, and seem to be quite common among young subjects, characterized by frequent orthostatic presyncopal symptoms associated with orthostatic tachycardia and high plasma catecholamines levels. In the paper, we will review different causes of orthostatic hypotension, and mention some physiopathological mechanisms linked to renal sodium handling. In particular, alterations in renal proximal segmental handling of sodium might generate and play a pathophysiological role in maintenance of the orthostatic hypotension. Finally, we will evoke some therapeutical aspects.
Adult↗
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↗
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↗
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↗
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↗
Determination of the polyfructosan sinistrin in biological fluids by HPLC with electrochemical detection.
A sensitive HPLC method with electrochemical detection was developed for the determination of the polyfructosan sinistrin in human plasma and urine. Proteins and interfering components such as glucose were removed from plasma and urine samples by solid phase extraction on C18 cartridges. Chromatographic separations were achieved at 85 degrees C on a 300 mm x 7.8 mm i.d. column, using ion moderated partition chromatography with distilled water at a flow rate of 0.6 ml min-1. After post-column addition of NaOH 0.3 M (0.6 ml min-1), the electrochemical detection of the eluate was performed with a sequence of three potentials (0.05 V, -0.8 V, 0.6 V) of specific pulse duration 300, 100 and 100 ms respectively. Xylose was used as internal standard for the quantitative determinations. The calibration curves were linear (r2 > 0.992) over the working range 5-300 micrograms ml-1. This method has been characterized, validated and applied successfully in a study comparing two modes of glomerular filtration rate determination in healthy volunteers (bolus vs. constant rate infusion of sinistrin).
Chromatography, High Pressure Liquid↗
Studies of the renal effects of angiotensin II receptor blockade: the confounding factor of acute water loading on the action of vasoactive systems.
The acute renal tubular effects of two pharmacologically distinct angiotensin II receptor antagonists have been evaluated in normotensive volunteers on various salt diets. In the first study, the renal response to a single oral dose of losartan (100 mg) was assessed in subjects on a low (50 mmol Na/d) and on a high (200 mmol Na/d) salt intake. In a second protocol, the renal effects of 50 mg irbesartan were investigated in subjects receiving a 100 mmol Na/d diet. Both angiotensin II antagonists induced a significant increase in urinary sodium excretion. With losartan, a modest, transient increase in urinary potassium and a significant increase in uric acid excretion were found. In contrast, no change in potassium and uric acid excretions were observed with irbesartan, suggesting that the effects of losartan on potassium and uric acid are due to the intrinsic pharmacologic properties of losartan rather than to the specific blockade of renal angiotensin II receptors. Assessment of segmental sodium reabsorption using lithium as a marker of proximal tubular reabsorption demonstrated a decreased distal reabsorption of sodium with both antagonists. A direct proximal tubular natriuretic effect of the angiotensin II antagonist could be demonstrated only with irbesartan. This apparent discrepancy allowed us to reveal the importance of acute water loading as a possible confounding factor in renal studies. The results of the present analysis show that acute water loading per se may enhance renal sodium excretion and hence modify the level of activity of the renin-angiotensin system expected from a given sodium diet. Since acute water loading is a common practice in clinical renal studies, this confounding factor should be taken into account when investigating the renal effects of vasoactive systems.
Adult↗
[Essential cryoglobulinemia].
The diagnosis of cryoglobulinemia relies on an in vitro artefact, i.e. the precipitation of immunoglobulins induced by a drop in temperature. Cryoglobulinemia has been described in association with neoplasia, infectious and connective tissue diseases. They are classified into two major groups: monoclonal or mixed (more than one type of immunoglobulin). In many patients the mixed type has been described as essential because of the absence of an associated disease. Recent evidence suggests, though, that more than half and probably up to 90% of mixed 'essential' cryoglobulinemias are in fact associated with chronic liver disease due to hepatitis C virus infection. This observation would be in accordance with the clinical response of half of these patients to interferon-alpha therapy; however, more prospective studies are required to confirm the possible beneficial effect of interferon alpha.
Adrenal Cortex Hormones↗
Hepatitis C: a possible etiology for cryoglobulinaemia type II.
Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.
Adult↗
[Comparison of the efficacy and tolerance of recombinant human erythropoietin between intravenous and subcutaneous administration in chronic hemodialysis. Prospective multicenter study].
The efficacy and tolerance of intravenous and subcutaneous administrations of recombinant human erythropoietin (r-HuEPO) have been compared in 50 maintenance hemodialysis patients. A 2 month course of intravenous r-HuEPO given at stable dosage was followed by a 6 month course of subcutaneous r-Hu EPO. We reduced r-HuEPO dosage by 50% when starting subcutaneous administration and regularly adapted the dosage to achieve hematocrit levels between 30 and 35%. At the end of the study, mean r-HuEPO dosage was 82 +/- 8 (mean +/- SEM) IU/kg/week, which represented 70 +/- 7% of intravenous r-HuEPO dosage. Mean hematocrit value was 32.9 +/- 0.5% when starting subcutaneous administration and also at the end of this study. Arterial blood pressure remained stable over the whole trial period as did most biological blood tests which were not influenced by the route of administration. In 98% of cases, patients expressed either pain-free (50%) or slight to moderate pain (48%) at the injection site. This trial confirms a substantial dosage economy when using r-HuEPO by subcutaneous route rather than by intravenous route. Moreover, objective and subjective tolerance was excellent on r-HuEPO subcutaneous administration.
Adolescent↗