Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.
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We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality. (+info)
Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway.
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OBJECTIVE: Regulation of insulin release by glucose involves dual pathways, including or not inhibition of ATP-sensitive K(+) channels (K(ATP) channels). Whereas the K(ATP) channel-dependent pathway produces pulsatile release of insulin it is not clear whether the independent pathway also generates such kinetics. DESIGN AND METHODS: To clarify this matter, insulin secretion and cytoplasmic Ca(2+) ([Ca(2+)](i)) were studied in perifused pancreatic islets from ob/ob mice. Insulin release was measured by ELISA technique and [Ca(2+)](i) by dual-wavelength fluorometry. RESULTS: Insulin secretion was pulsatile (0.2--0.3/min) at 3 mmol/l glucose when [Ca(2+)](i) was low and stable. Stimulation with 11 mmol/l of the sugar increased the amplitude of the insulin pulses with maintained frequency and induced oscillations in [Ca(2+)](i). Permanent opening of the K(ATP) channels with diazoxide inhibited glucose-stimulated insulin secretion back to basal levels with maintained pulsatility despite stable and basal [Ca(2+)](i) levels. Increase of the K(+) concentration to 30.9 mmol/l in the continued presence of diazoxide and 11 mmol/l glucose restored the secretory rate with maintained pulsatility and caused stable elevation in [Ca(2+)](i). Simultaneous introduction of diazoxide and elevation of K(+) augmented average insulin release almost 30-fold in 3 mmol/l glucose with maintained pulse frequency. Subsequent elevation of the glucose concentration to 11 and 20 mmol/l increased the release levels. After prolonged exposure to diazoxide, elevated K(+) and 20 mmol/l glucose, the pulse frequency decreased significantly. CONCLUSIONS: Not only glucose signaling via the K(ATP) channel-dependent but also that via the independent pathway generates amplitude-modulated pulsatile release of insulin from isolated islets. (+info)
Trends in antihypertensive drugs in the elderly: the decline of thiazides.
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The last decade has seen the publication of different editions of guidelines for the pharmacological treatment of hypertension that were based on the results of large, randomised trials. Since these guidelines were meant to inform practitioners, we analysed the pattern of prescription of antihypertensive agents between 1988 and 1997 among older hospitalised adults. Because of the wealth of data supporting the use of thiazides diuretics, we focused on diuretic prescription, to identify independent predictors of their utilisation. To this end, we used the GIFA database that includes patients admitted to academic medical centres throughout Italy between 1988 and 1997. We studied 5061 patients over 65 years of age selected among a population of 28 411, based on the diagnosis of arterial hypertension at discharge. The use of ACE-inhibitors has been raising steadily through the years, and they are the agents most commonly used since 1996. Calcium channel blockers showed a similar trend and were the top prescribing drug until 1995; afterwards, the documentation of potentially severe side effects has resulted in a nearly 20% reduction of their use. Beta-blockers have remained unpopular throughout the decade. Instead, the prescription of diuretics as a class showed a biphasic trend; an initial decrease with a prolonged steady state and a more recent raise. However, at a separate analysis, it was a evident that a progressive increase of the use of loop diuretics since 1988 has been paralleled by a nearly 50% reduction of thiazides prescriptions. Loop diuretics were more likely to be prescribed to older individuals, those with cardiac heart failure, coronary heart disease and high creatinine level. In contrast, independent predictors of thiazides use were female gender, good functional status, preserved renal function, and absence of cardiovascular comorbidity. In conclusion, despite continued recommendations to use thiazides diuretics for the treatment of hypertension among older individuals, their use has been declining steadily between 1988 and 1997. A possible explanation is that the choice to prescribe a thiazides diuretic is influenced by age, functional status and comorbidity. (+info)
Diet and medication in the treatment of hyperuricemia in hypertensive patients.
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OBJECTIVE: To evaluate the effects of diet and medication, either isolated or associated, on serum levels of uric acid in patients with hyperuricemia. METHODS: We studied patients from the Hypertension Unit of the University of Goias who had hyperuricemia (men > or =8.5 mg/dL and women > or =7.5 mg/dL). We divided the patients into three groups: G1 (low purine diet), G2 (low purine diet + medication), and G3 (medication only). Patients received allopurinol, 150 mg/day titrated up to 300 mg/dL when necessary. Patients were evaluated with regards to their lifestyles (diet, smoking, physical, activity, alcohol consumption), uric acid, blood pressure, use of medication, body mass index, cholesterol, and triglyceride. Follow-up took place in weeks 0 (M1), 6 (M2), 12 (M3) during the intervention and in week 36 (M4) after the study was completed. RESULTS: Fifty-five patients participated in the study, 31 women, mean age 54.4+/-10.6 years, body mass index 28.6+/-3.9 kg/m2. A similar reduction (p<0.001) in uric acid levels occurred in the three intervention groups. In week 36 (M4), after 24 weeks without intervention, a tendency toward elevation of uricemia was noted in G2 and G3, and a continuous drop in uricemia was noted in G1. No significant modifications were observed in the other variables analyzed. CONCLUSION: Considering the cost x benefit relationship, a diet low in purine should be the 1st therapeutic option for controlling hyperuricemia in patients with similar characteristic to the ones presented in this study. (+info)
Correlation of AMPA receptor subunit composition with synaptic input in the mammalian cochlear nuclei.
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The composition of AMPA receptors in patches excised from somata and dendrites of six cell types in the mammalian cochlear nuclei was probed and compared electrophysiologically and pharmacologically with the rapid application of glutamate. Cells excited predominantly by auditory nerve fibers had AMPA receptors with exceptionally rapid gating (submillisecond deactivation and desensitization time constants). The nonlinear current-voltage relationship in the presence of spermine showed that few of these receptors had GluR2 subunits, and the insensitivity of desensitization to cyclothiazide indicated that they contained mostly flop splice variants. At synapses made by parallel fibers, AMPA receptors were slowly gating (time constants of deactivation and desensitization >1 msec) and contained higher levels of GluR2 and flip isoforms. However, receptors at auditory nerve synapses on cells that also receive parallel fiber input, the fusiform cells, had intermediate properties with respect to kinetics and contained GluR2 and flip isoforms. Given the diverse biophysical properties, patterns of innervation, patterns of electrical activity, and targets of each cell type in vivo, these data indicate that the kinetics and permeation properties of AMPA receptors are linked to factors associated with synaptic connectivity. (+info)
Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus.
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The mechanisms underlying the acute antidiuretic response to bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM glucose. One group in addition received i.v. replacement of urinary sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI, thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to sodium depletion. This contrasts the response in rats with central diabetes insipidus, where thiazides in addition increase distal water reabsorption. (+info)
Progress in hypertension research: 1900-2000.
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The author reviews the various factors (sodium, aldosterone, renin-angiotensin system, and norepinephrine; each of these factors being influenced by others) involved in the mechanism of human hypertension. A coherent picture is emerging, with the final pathway of these mechanisms converging on the renin-angiotensin system in the presence of a positive sodium balance and responsible for arteriolar resistance and responsiveness to pressor agents. This would correspond to the labile phase of hypertension, which leads with time to arteriolar restructuring and the increased media/lumen ratio, as demonstrated by Schiffrin and coworkers, and which can revert to normal structure with the administration of antihypertensive drugs such as converting-enzyme inhibitors, calcium-blocking drugs, and antagonists of the angiotensin II type 1 receptor. The author also presents the experience obtained in the Hypertension Clinic of the Clinical Research Institute of Montreal, which has been in existence since 1953; this experience is based on the observation of senior observers (clinical scientists, clinicians, and nurses) that the blood pressure of hypertensive patients can be controlled to normal levels in almost all cases for years and decades with a proper combination of the present antihypertensive drugs. (+info)
Tolerability and safety of a calcium channel blocker in comparison with a diuretic in the treatment of elderly patients with hypertension: secondary analysis of the NICS-EH.
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A randomized prospective controlled study, the National Interventional Cooperative Study in Elderly Hypertensives (NICS-EH), previously demonstrated that the preventive effect of the long-acting calcium channel blocker nicardipine on the cardiovascular endpoint was similar to that of the diuretic, trichlormethiazide. The present report is a sub-analysis in which we compare the tolerability and safety of the calcium channel blocker with that of a diuretic in the long-term treatment of elderly hypertensives. A total of 429 elderly patients with hypertension were assigned to the nicardipine group or the diuretic group by the double-dummy method and were followed up for 5 years. Two hundred four patients in the nicardipine group and 210 patients in the diuretic group were analyzed. The incidences of fatal and nonfatal cardiovascular (CV) events in the two groups were comparable, and there was no significant difference in the cumulative event-free rate. However, the total incidence of adverse reactions, including non-CV events and unfavorable BP changes, was 31 cases (15.2%) in the nicardipine group, which was significantly lower than the 47 cases (22.4%) in the diuretic group (log-rank: p=0.026, G. Wilcoxon: p=0.01). The total number of medical endpoints, including CV events, the withdrawal of the patient from the study, was 52 (25.5%) in the nicardipine group, which was significantly lower than the 65 (31.0%) in the diuretic group (log-rank: p=0.078, G. Wilcoxon: p=0.044). It was concluded that sustained-release nicardipine is better tolerated, as it exhibits a lower incidence of medical-related withdrawals such as adverse drug reactions, non-cardiovascular events and unfavorable BP responses during the treatment. (+info)