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Biomedical subjects

J Menard

Publications and source records attributed to J Menard.

At least 55 records · Page 3Linked to original sources

Benefits of a computer-assisted education program for hypertensive patients compared with standard education tools.

ISIS (Initiation Sanitaire Informatisée et Scénarisée), a French computer-assisted hypertension and cardiovascular risk education program, was developed to provide patients at cardiovascular risk with a modern interactive educational tool combining rigorously scientific information with the aesthetic attractiveness of multimedia communication. To test the impact of this tool on patient health information retention, 158 hypertensives hospitalized for initial work-up (day hospital) or therapeutic adjustments (3 days) were randomized into control (n = 79) and ISIS (n = 79) groups. Both groups received cardiovascular education through standard means: physicians, nurses, dietitians and pamphlets. In addition, ISIS patients underwent a 30- to 60-min session on the computer with the ISIS program. Cardiovascular knowledge was tested by the same investigator administering a standardized 28-item questionnaire before and 2 months after education. Retesting was made by telephone. At the time of first assessment, all patients were aware that they would be retested. A total of 138 completed questionnaires (69 from each group) was analyzed. Overall mean cardiovascular knowledge score before education improved significantly after education. This improvement was greater in the ISIS than the control group. These results confirm the potential of computer-assisted education in hypertensives from a specialized center.

Adult↗

Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man.

We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Feasibility study of N-of-1 trials with blood pressure self-monitoring in hypertension.

The objective of this study was to assess individual responses to antihypertensive treatment by N-of-1 trials using blood pressure self-monitoring in 79 patients of both sexes referred to a hypertension clinic. Thirty-five patients who remained untreated (study 1) and 44 N-of-1 trial participants (study 2) were consecutively selected if their clinic blood pressure was between 160/95 and 220/115 mm Hg and there were no hypertensive complications. Blood pressure was measured daily at home for 21 days (three consecutive measures, morning and evening). Each N-of-1 trial was a single-blind treatment consisting of two successive 10-day treatment pairs, each pair comprising 5 days of placebo followed by 5 days of 20 mg enalapril once daily in the morning. Study 1 showed no significant blood pressure regression toward the mean over 20 days and justified the choice of 5-day treatment periods in study 2. In study 2, blood pressure fell significantly 12 hours after the first administration of enalapril and rose within 24 hours of the end of the 5-day active treatment period. Using evening blood pressure values (12 hours after enalapril intake) from the first treatment pair, 33 patients were classified as responders (diastolic blood pressure fall > or = mm Hg). In 16 of these 33 patients, the fall in blood pressure above 6 mm Hg was not maintained in the morning, 24 hours after drug intake. Response reproducibility was tested by comparison with the second treatment pair: the observed agreement was only 0.71 (chance-corrected agreement: 0.34) when defined according to both evening and morning values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Recent advances in pediatric HIV.

Pediatric human immunodeficiency virus (HIV) infection is a disease of mother-to-infant transmission. The World Health Organization estimates there will be ten million HIV-infected children by the end of this century. It is now thought that both intrauterine and intrapartum transmission of HIV occurs. Infants infected in utero develop clinical signs and symptoms at an earlier age than those who are infected at the time of delivery. We describe two cases that demonstrate early-onset and late-onset pediatric HIV disease, respectively. Recently, it was determined that perinatal transmission of HIV can be significantly reduced by the administration of the antiretroviral drug, zidovudine (ZDV), to HIV-positive pregnant women and their newborns, making HIV screening of pregnant women more desirable than ever. A program of universal voluntary HIV testing for pregnant women has been successfully implemented at the University of Arkansas for Medical Sciences. Details of this program are described herein.

Fatal Outcome↗

Do physicians estimate reliably the cardiovascular risk of hypertensive patients?.

For hypertension management, it is increasingly recommended to individualize treatment according to the individual patient's characteristics. However, the ability of physicians to predict the patient's risk in the absence of a computer aid is unknown. Our aim was to determine if senior hypertension specialists were able to assess reproducibly cardiovascular disease (cvd) risk in hypertensive patients. The records of 100 patients were selected at random from the ARTEMIS database. The group comprised 53% of males, mean age was 43.7 (15), blood pressure 160 (25) / 99 (12) mmhg and serum cholesterol 5.6 (1.1) mmol/l. The records were summarized on a standardized form. Nineteen items were devoted to general characteristics and medical history of patients, 15 to clinical examination and 7 to biological tests. These items have been chosen because they were used in the framingham cvd risk prediction equation and/or had decisional value in a bayesian program designed for secondary hypertension diagnosis. Six physicians, twice at one month intervals, assigned each patient to one of the three categories of risk (low, moderate, high). The order of cases was randomized. Chance corrected agreement (intra-physician agreement) between the two estimations was only moderate except for one expert (kappa values: 0.658, 0,543, 0.439, 0.363, 0.328 and 0.207 for each expert, respectively). The proportion of patients assigned by each physician to each category ranged from 22.7% to 77.3% for the low risk, and from 4.5% to 43.9% for the high risk category. One physician overestimated risk, one underestimated it and the three others were in keeping with framingham predictions. Bias and lack of reproducibility influence physician judgment in assessing cvd risk of hypertensive patients. Application of computer aids could result in more rational assessments and better decision making.

Adolescent↗

Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension.

Angiotensin II (AII) is a vasoconstrictive peptide with hypertrophic and mitogenic effects on many cell types. Previous studies have shown that in vivo administration of AII in rats results in proliferation of, and phenotypic changes in, many renal cell populations, but in doses also causing hypertension. Thus, it was not possible to differentiate nonhemodynamic from hypertensive effects of AII. Therefore, we studied rats with renin-dependent, AII-mediated hypertension (the two-kidney, one-clip Goldblatt model; mean systolic blood pressure 238 +/- 48 v 140 +/- 6 mm Hg in sham-operated controls). The unclipped kidneys, which were exposed to high blood pressure, developed significant glomerular and tubulointerstitial injury, tubulointerstitial cell proliferation, dense focal interstitial monocyte-macrophage influx, increased deposition of types I and IV collagen, as well as increased cellular expression of desmin and actin, in tubulointerstitial areas when examined at 11 weeks. In contrast, clipped kidneys, protected from hypertension but with high local renin expression, had minimal abnormalities. These studies suggest that in this model increased renin, and presumably AII, does not mediate significant proliferative or phenotypic changes in the kidney in the absence of hypertension at 11 weeks.

Angiotensin II↗

Renin-secreting tumors.

An analysis of the renin-secreting tumors published in the literature suggests the diagnosis of JGC tumor should be evoked systematically in a young patient with severe hypertension and hypokalemia in whom a renovascular lesion has been eliminated by arteriography. A very high PRA usually is observed and blood pressure drops during converting enzyme treatment. Under acute administration of captopril, plasma renin may or may not increase, showing the inconsistency of the secretory autonomy of the tumor. The most useful examination for the localization of the tumor is the CT scan. Excessive renin production may provoke vascular lesions, left ventricular hypertrophy, and impairment of renin function that all disappear after surgical treatment, at the time when blood pressure returns to normal. Primary reninism has great physiologic importance for the hypothesis that favors the essential role of the kidney in determining the level of blood pressure. It can be considered as a unique, purely renin-dependent form of hypertension. This syndrome has no experimental equivalent and is the most caricatural form of other renin-dependent hypertension, such as renovascular disease, and probably some other forms of essential hypertension. The discovery of a renin-secreting tumor therefore constitutes a life-saving diagnosis for the patient, a subject of reflection for the specialist, and a useful tool for studies of the general mechanisms involved in enzyme biosynthesis and tumoral endocrine cell function.

Adenocarcinoma↗

Accuracy and reproducibility of left ventricular mass measurement by subcostal M-mode echocardiography in hypertensive patients and professional bicyclists.

In some patients, left ventricular (LV) mass cannot be evaluated by M-mode echocardiography because the parasternal long-axis view is not available. The aim of this study was to determine whether the subcostal view obtained by M-mode echocardiography under 2-dimensional guidance allows accurate and reproducible LV mass determination. Using the cube formula, LV mass was calculated, from parasternal and subcostal views in 96 subjects: 73 hypertensives and 23 professional bicyclists, covering a wide range of LV dimensions. M-mode tracings were read by 2 experienced echocardiographers and the interobserver variability was evaluated. With use of the subcostal view, the interobserver reproducibility, expressed as observer 1-observer 2, was excellent: -0.3 +/- 1.3 mm for LV diastolic diameter, -0.1 +/- 1.0 mm for ventricular diastolic septal thickness, 0.2 +/- 0.6 mm for diastolic free wall thickness and 0.03 +/- 16.7 g for LV mass. In 96% of cases, the difference in LV mass between the 2 observers did not exceed 30 g. With use of the parasternal and subcostal approaches, LV mass was not statistically different (202.6 +/- 2.2 g and 206.5 +/- 2.0 g, respectively) and the difference was < 52 g (clinically significant threshold) in 91 of 96 cases. It is concluded that, using the cube formula, LV mass calculation based on the subcostal view was accurate and not statistically different from that provided by the usual parasternal approach.

Adult↗

Anxiogenic stimuli in the elevated plus-maze.

Untreated rats normally avoid the open arms of the "elevated plus-maze," preferring instead the closed arms, whereas rats treated with antianxiety drugs (e.g., diazepam) show far less open-arm avoidance. Although it has often been assumed that rats avoid the open arms because of novelty, height, or open space, the anxiogenic role of these stimuli in the plus-maze has not been systematically examined. In Experiment 1, rats were repeatedly exposed to the elevated plus-maze with the expectation that their "fear" of the open arms would habituate over trials. Instead, open-arm avoidance actually increased on the second trial and showed no evidence of habituating after 18 trials. In Experiment 2, three 30-min sessions of confinement to the open arms ("flooding") failed to decrease rats' open-arm avoidance. Instead, rats that had received flooding avoided the open arms significantly more than control rats during the first test. Experiment 3 showed that although diazepam-treated rats avoided the open arms less than vehicle-controls on the first test this difference dissipated across test trials. Further, diazepam had no carryover effect on rats' subsequent avoidance of the open arms in a nondrugged state. In Experiment 4, plus-maze height was varied from 50 to 6 cm, but rats did not display more open-arm activity as maze height decreased. In Experiment 5, height cues were manipulated by placing a "floor" 8 cm beneath one open arm while leaving the floor of the other open arm at 50 cm. Rats did not avoid the "low" open arm less than the "high" open arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effects of blocking the angiotensin II receptor, converting enzyme, and renin activity on the renal hemodynamics of normotensive guinea pigs.

The effects of three renin-angiotensin system (RAS) antagonists, DuP 753, a nonpeptide angiotensin II (Ang II) receptor antagonist, MK 521, an inhibitor of converting enzyme, and Ro 42-5892, a human renin inhibitor, on renal function and hemodynamics were investigated in anesthetized, ventilated normotensive guinea pigs. This species was selected because this human renin inhibitor inhibits guinea pig renin. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by [3H]inulinmethoxy and [14C]aminohippuric acid clearances. Animals were perfused with isotonic saline at 0.2 ml/min. After a stabilization period of 1 h, drugs were given as an intravenous (i.v.) bolus (DuP 753, 1; MK 521, 0.1; Ro 42-5892, 1 mg/kg), followed by continuous infusion (DuP 753, 3; MK 521, 0.3; Ro 42-5892, 3 mg/kg/h). These doses have been used to induce slight but significant and similar decreases in mean arterial blood pressure (MABP). The mean changes during 1-h treatment showed similar decreases in MABP: vehicle, -2 +/- 1% (n = 10); DuP 753, -13 +/- 2% (n = 10); MK 521, -15 +/- 2% (n = 10); Ro 42-5892, -13 +/- 3% (n = 10), p < 0.001. Diuresis was unchanged in the four groups. GFR (vehicle, -0.2 +/- 8.4%; DuP 753, +10.7 +/- 6.4%; MK 521, +13.2 +/- 8.6%; Ro 42-5892, +37.2 +/- 7.5%, p < 0.01) and RBF (vehicle, -0.7 +/- 6.6%; DuP 753, +10.5 +/- 6.8%; MK 521, +16.4 +/- 6.8%; Ro 42-5892, +37.9 +/- 7.8%, p < 0.01) increased in parallel with the three drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Calcium antagonists-ACE inhibitors combination therapy: objectives and methodology of clinical development.

The practical objectives of a combination therapy are to obtain a better control of blood pressure (BP), and/or to improve tolerability through the use of lower doses of existing component. The prescription, in a single pill, of an angiotensin-converting enzyme (ACE) inhibitor and a calcium blocker has the theoretical and practical advantages of improving compliance by reducing the number of pills that have to be taken daily and the number of boxes the patient must carry. It also has a pharmacologic rationale mainly based on the buffering by ACE inhibitors of the calcium-blocker-induced stimulations of the renin-angiotensin system and the sympathetic nervous system, and on the reinforcement of the ACE inhibitors antihypertensive effect by the calcium-blocker-induced negative sodium balance. As an argument for such combinations, the neutralization of some dihydropyridines side effects, such as palpitations and edemas, must be addressed. The choice of each component dose is to provide a safe first-line indication and effective and flexible stepped-care treatment. It can only be the result of a complex development program, where BP effect measured at peak and at trough is investigated by the coherent utilization of parallel-group, cross-over, and factorial study designs. Safety studies in high-risk patients enrolled in special controlled trials are necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Clinical significance of the metabolic effects of antihypertensive drugs.

Data from the Hypertension Treatment Trials do not indicate that the metabolic effects of the medications used, namely diuretics in all and beta-blockers in some, are of great clinical significance. Effects on lipids are mainly short-term (about one year) and the increased incidence of significant hyperglycaemia and/or diabetes in treated compared with control or placebo subjects is < 1% in most trials. The use of these drugs has improved the prognosis of subjects with both severe and less severe hypertension. Despite these findings, it is possible that medications such as the calcium blockers, ACE inhibitors, or multiple-action drugs, e.g. the alpha-beta-blockers which have no negative and possibly have some positive effects on lipids and glucose metabolism, will improve outcome still further. We must await additional long-term trials to determine this. It is possible that combinations of small doses of two different agents from different classes of drugs will prove to be the ideal approach to hypertension management in the future: efficacy is improved and any adverse metabolic effects are minimised.

Adult↗

Decreased renin release and constant kallikrein secretion after injection of L-NAME in isolated perfused rat kidney.

A possible role of the endothelial L-arginine/NO pathway in the control of renal hemodynamics, renin release and kallikrein secretion was studied in an isolated rat kidney model perfused in a closed-circuit. NG-nitro-L-arginine methyl ester (L-NAME, 1-50 microM), an inhibitor of nitric oxide biosynthesis, caused a dose-dependent increase in perfusion pressure (PP) and a dose-dependent decrease in renal perfusate flow. Renin release was inhibited independently of a rise in PP. L-NAME did not change the urinary kallikrein secretion. These results confirm the intervention of the L-arginine/NO pathway in the vasodilation of this isolated perfused kidney model and demonstrate the inhibitory effect of L-NAME on renin release. They suggest that nitric oxide synthesis plays a role in stimulating renin release and is not involved in the regulation of urinary kallikrein secretion.

Analysis of Variance↗

The effects of fadrozole hydrochloride on aldosterone secretion in healthy male subjects.

The aim of this double blind placebo-controlled cross-over study was to evaluate the effects of fadrozole, a new oral nonsteroidal aromatase inhibitor, on basal and stimulated cortisol and aldosterone secretion at a daily dosage of 4 mg given for 14 days to eight healthy men. After 2 weeks of treatment, fadrozole, compared with placebo, effectively suppressed plasma estrogen levels (P less than 0.05 at 0800 h), but did not affect glucocorticoid secretion either under basal conditions or after stimulation with ACTH. Basal plasma aldosterone levels were not significantly different with fadrozole treatment compared to those after placebo treatment. However, compared with pretreatment values, basal aldosterone secretion appeared impaired (P less than 0.05). A statistically significant blunting of the responses of plasma aldosterone to ACTH (P less than 0.01) and upright posture (P less than 0.01) after fadrozole compared with placebo treatment further indicated that fadrozole impaired basal aldosterone secretion. This attenuation of aldosterone secretion was accompanied by a rise of PRA in the basal condition (P = 0.05) and after stimulation by 40 mg furosemide (P less than 0.01) and upright posture (P less than 0.01). An increase in deoxycorticosterone was observed after fadrozole treatment compared with pretreatment values (P less than 0.01) and after stimulation with ACTH compared with placebo (P less than 0.05). This study confirms that fadrozole given in daily doses of 4 mg is an effective aromatase inhibitor which does not affect glucocorticoid secretion. However, this dose may induce an impairment of aldosterone secretion which is modest and revealed mainly under specific stimulatory conditions, and does not lead to clinical symptoms of hemodynamic dysregulation or a relevant disturbance of serum electrolytes.

Adult↗

[Control of vascular tone by the endothelium: the coupling active vasodilation in the kidney to renin secretion].

The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics.

Animals↗