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Biomedical subjects

D Brosh

Publications and source records attributed to D Brosh.

9 recordsLinked to original sources

Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study.

The role of lipoprotein oxidation in promoting atherosclerosis is gaining recognition as its spectrum of effects is being unveiled. Accelerated atherosclerosis is a major cause of morbidity and mortality in diabetic patients. Treatment with ACE inhibitors reduces oxidation of low-density lipoprotein (LDL-ox) in hypertensive subjects, however, their effect on LDL-ox in diabetic patients is yet obscure. To evaluate the effect of the ACE inhibitor enalapril and the calcium channel blocker nifedipine on LDL oxidation in normotensive type 2 diabetic patients. A randomized single blinded cross-over study was conducted on 24 nonobese, metabolically stable, normotensive patients with type 2 diabetes who were randomly allocated to receive either enalapril, 10 mg/day, or nifedipine, 30 mg/day, for 4 weeks followed by a 2-week washout period. They were then crossed over to a 4-week course with the alternate drug. The oxidation of LDL was evaluated by three methods: dialdehyde analysis using the thiobarbituric acid reactive substances assay with and without the addition of CuSO(4) as well as determination of conjugated dienes in the LDL lipid extract. The propensity of the serum to oxidize LDL was reduced by enalapril by 17-28% depending on the laboratory method used (P=0.0001). Treatment with nifedipine resulted in a rise in LDL-ox of 7-11% as compared to baseline (P<0.05). The difference between the effects of enalapril and nifedipine was statistically significant with all three laboratory methods used (P=0.0001). Both drugs were equally effective in reducing systolic and diastolic blood pressure without affecting HbA(1c) levels and lipid profile. The albumin excretion rate was significantly reduced during treatment with enalapril returning to baseline levels during the washout period and the nifedipine treatment course. Our findings suggest that oxidation of LDL is attenuated by ACE inhibition and augmented by some calcium channel blockers. This observation may contribute insight into the underlying mechanism of the therapeutic effects of ACE inhibition in diabetic patients.

Adult↗

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗

Effect of enalapril and nifedipine on orthostatic hypotension in older hypertensive patients.

OBJECTIVE: To compare the effect of enalapril with long-acting nifedipine on orthostatic hypotension in older patients. DESIGN: A prospective, double blinded, cross-over study. SETTING: The outpatient clinic of a university hospital. PARTICIPANTS: Thirty-nine patients aged 65 years or older with systolic blood pressure (SBP) of 140-190 mm Hg and diastolic blood pressure (DBP) of 90-110 mm Hg. INTERVENTION: Enalapril 5-20 mg od or nifedipine 30-90 mg od for 8 weeks, followed by 4 weeks washout and cross-over for a second 8-week period. MEASUREMENTS: Supine and standing 0-, 1-, and 5-minutes blood pressure was recorded before and at the end of each treatment period. RESULTS: At baseline, SBP was 158.8 +/- 8.7 mm Hg, and DBP was 97.1 +/- 5.9 mm Hg. There was a decline in SBP of 6.1 +/- 2.7 mm Hg and 8.4 +/- 4.1 mm Hg after 1 and 5 minutes of standing, respectively. Both agents caused a significant decline in supine blood pressure. Enalapril: supine SBP 158.8 +/- 8.7 to 143 +/- 7.3 mm Hg; supine DBP 97.1 +/- 5.9 to 85.1 +/- 5.1 mm Hg (P = .0001). The drop in SBP after standing for 5 minutes was only 2.4 +/- 1.6 mm Hg with no change in diastolic values. A > or = 10 mm Hg drop in SBP was observed in only three patients, and no patient experienced a decline of 20 mm Hg or more. Nifedipine: supine SBP: 160.3 +/- 9 to 145.3 +/- 8.1 mm Hg; supine DBP: 96.3 +/- 5.7 to 86.3 +/- 5.8 (P = .0001). Nifedipine induced an orthostatic decline in SBP values; there was an 8.7 +/- 4.8 mm Hg difference between supine and 5 minutes standing values (P = .0005) without change in diastolic values. An orthostatic decline in SBP of > or = 10 mm Hg occurred in 13 patients, and there was a drop of > or = 20 mm Hg in six patients. The cross-over of enalapril and nifedipine reproduced the hypotensive effect and reversed the postural effect. (P = .0002 nifedipine vs enalapril) CONCLUSIONS: Enalapril and nifedipine were equipotent in reducing supine blood pressure levels. Enalapril also reduced the number of orthostatic episodes significantly, whereas nifedipine aggravated this phenomenon.

Angiotensin-Converting Enzyme Inhibitors↗

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

OBJECTIVE: To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. DESIGN: The literature on the "congenital long QT" was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. RESULTS: Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were "pause dependent"; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (</= 3 years old) were not pause dependent, while female sex correlated with pause dependent torsade. Using multivariate analysis, age was the only independent predictor of the mode of onset of torsade de pointes. CONCLUSION: Available data suggest that the majority of spontaneous arrhythmias in the congenital long QT syndrome are pause dependent. Torsade de pointes that is not preceded by pauses appears to be limited to patient subgroups with severe forms of the disease, like symptomatic infants. These findings have important implications regarding the use of cardiac pacing for arrhythmia prevention.

Adult↗

Catheter-based ultrasound thrombolysis--a new promising thrombus-debulking device for the treatment of intracoronary thrombosis.

Angiographic suggestion of intercoronary thrombus is often seen in patients sustaining acute coronary syndromes (ACS). Even in the era of stenting and glycoprotein IIb/IIIa antagonists, the presence of thrombus-rich lesion during percutaneous coronary interventions portends an increased risk of adverse events. It has been hypothesized that reduction of clot-burden prior to PCI may reduce complications and enhance efficacy. Experimental and clinical data have shown that catheter-based ultrasound thrombolysis is capable of inducing an efficacious and safe thrombus-debulking. This article reviews the collective experience with this promising device solution for the treatment of thrombotic lesions in the setting of ACS.

Cardiac Catheterization↗

Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes. OBJECTIVE: To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes. DESIGN: Randomized, double-blind, placebo-controlled trial with 6-year follow-up. SETTING: Eight outpatient clinics coordinated by a department of medicine in a university hospital. PATIENTS: 156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion < or = 30 mg/24 h). INTERVENTION: Enalapril, 10 mg/d, or placebo. MEASUREMENTS: Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1c values. RESULTS: Enalapril therapy decreased albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal (< 107 mm Hg) in all patients. CONCLUSIONS: Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.

Adult↗

Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia.

BACKGROUND: The control of hyperglycemia is of major importance in the treatment of patients with type 1 diabetes mellitus. However, there is no consensus about the required degree of metabolic control in patients with type 2 diabetes mellitus and about the role of hyperglycemia in diabetic nephropathy and in the development of atherosclerosis in relation to other risk factors. PATIENTS AND METHODS: A prospective, long-term follow-up study was conducted on 574 patients, aged 40 to 60 years, with recent onset of type 2 diabetes mellitus. Patients were initially normotensive and had normal renal function and a normal urinary albumin excretion rate (<30 mg/24 h). The patients were followed up for 2 to 9 years (mean +/- SD, 7.8 +/- 0.9 years). Levels of hemoglobin A1c and plasma lipids, mean blood pressure, and body mass index (calculated as the weight in kilograms divided by the square of the height in meters) were determined periodically. Cigarette smoking and socioeconomic status were recorded. Renal status was evaluated by the logarithm of the final urinary albumin excretion rate and by the decline in reciprocal creatinine values. Definite clinical events including death, nonfatal myocardial infarction, angina pectoris, congestive heart failure, and peripheral vascular disease were recorded. RESULTS: At the end of the study the urinary albumin excretion rate remained normal (<30 mg/24 h) in 373 patients (65%), 111 (19%) had microalbuminuria (30-300 mg/24 h), and 90 (16%) had overt albuminuria (>300 mg/24 h). Logistic regression models demonstrated that the correlation between hemoglobin A1c levels and the risk of albuminuria is exponential. Multiple logistic regression analysis indicated that levels of total cholesterol, mean blood pressure, and hemoglobin A1c were the main factors associated with the decrease in renal function and with the increase in albuminuria. The combination of values higher than the 50th percentile of all 3 factors defined a high-risk patient population. These high-risk patients had an odds ratio of 43 (95% confidence interval, 25-106) for microalbuminuria and 15 (95% confidence interval, 9-25) for clinical events related to arteriosclerosis compared with the rest of the group. Low levels of high-density lipoprotein, body mass index, cigarette smoking, low socioeconomic status, and male sex were all significantly associated with diabetic nephropathy, as well as with the manifestations of arteriosclerosis. CONCLUSIONS: The combination of blood pressure values in the high-normal range with moderately elevated levels of total cholesterol and hemoglobin A1c defines a high-risk group for the progression to diabetic nephropathy and for clinical events related to arteriosclerotic cardiovascular disease.

Adult↗

Clopidogrel.

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Cardiac Catheterization↗