Biomedical subjects
Publications and source records attributed to T Rosenthal.
Takayasu disease in our Israeli series consists of 56 patients, and has been detected only in Sephardic and oriental Jews as well as in Arabs and Bedouin. Suspicion of Takayasu disease should be raised whenever renal artery stenosis and involvement of the aorta and its branches occur in patients from oriental origin.
We examined accumulating evidence of the positive contribution of nitric oxide to the pharmacological effects of converting enzyme inhibitors in 36 rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet. We studied the response of blood pressure, insulin, and triglyceride levels to inhibition of either converting enzyme-kininase II, nitric oxide synthase, or both. Two weeks of the converting enzyme inhibitor enalapril (20 mg/kg) reduced blood pressure from 137 +/- 2 to 105 +/- 7 mm Hg, insulin from 7.6 +/- 2.0 to 2.2 +/- 1.1 pg/mL, and triglycerides from 292 +/- 37 to 163 +/- 37 mg/dL. Treatment with NG-nitro-L-arginine methyl ester (100 mg/kg) raised blood pressure from 144 +/- 7 to 170 +/- 8 mm Hg without affecting the other parameters. Two weeks of concomitant treatment with both agents blunted the hypotensive and beneficial metabolic effects of enalapril; thus, final blood pressure (141 +/- 7 mm Hg), insulin (6.4 +/- 2.4 pg/mL), and triglyceride (231 +/- 51 mg/dL) values were no different from those of untreated fructose-fed rats. These data suggest that persistent synthesis of nitric oxide contributes to the vasodilator and metabolic effects of enalapril in the fructose-fed rat model.
Blood pressure (BP), glucose and lipid profile were examined in 108 adult Yemenite immigrants within a few weeks after their arrival in Israel. Mean systolic BP was 105.8 +/- 15.21 mm Hg and mean diastolic BP was 69.74 +/- 12.25 mm Hg. Glucose was 81.4 +/- 30.49 mg/dl; total cholesterol was 167.54 +/- 44.54 mg/dl and triglycerides 137.11 +/- 94.9 mg/dl, while the small size of the group preclude drawing definitive conclusions, it can be said that BP as well as lipids level in this group were lower than in Yemenite immigrants who stepped off the magic carpet more than 45 years ago.
The prevalence and awareness of hypertension among Israeli Arabs was evaluated by measuring blood pressure (BP), heart rate, height and weight in a group of 412 subjects, 176 women and 236 men, mean age 38.4 +/- 18 (range 12-87 years) residing in Northern Israel. All subjects completed a questionnaire that included medical and family history and habits. Hypertension was defined when the subject used antihypertensive treatment or measured systolic BP was > 140 mm Hg and/or diastolic BP was > 90 mm Hg. BP was related to age, body mass index, gender, place of living (urban or rural), tobacco use, and level of physical activity. It was not related to coffee and alcohol use, and dietary sodium. The prevalence of hypertension in this group was 26.7%, similar to that in the general Israeli population. Only 9.7% were aware of their hypertension. The level of unawareness was significantly higher in the urban dwellers than in rural dwellers: 20.7% vs 12.8% (P < 0.05). This especially high rate among urban dwellers should be taken into account in designing screening programmes to detect hypertension in this population.
The objective of the study is to compare fatal and nonfatal cardiovascular endpoints in hypertensive patients randomised to the calcium-channel blocker, nifedipine GITS or a thiazide diuretic, co-amilozide. A total of 6592 patients from nine countries (UK, France, Israel, Spain, Italy, The Netherlands, Sweden, Denmark and Norway) will be recruited, aged 55-80 and with a blood pressure (BP) > or = 150/95 or > or = 160 mm Hg (systolic). All patients will have at least one other major cardiovascular risk factor. Patients will be minimised by country and risk factors and randomised to double-blind treatment with either nifedipine GITS or diuretic. After a single dose titration, additional treatment will be atenolol or enalapril (where beta-blockade is contra-indicated). After achieving a target BP of 140/90 mm Hg patients will be followed for a total of 3 years. Primary endpoints are myocardial infarction, stroke, subarachnoid haemorrhage, heart failure and sudden cardiac death. The study has a power of 80% at 5% significance to detect a difference between 8% event rate over 3 years in diuretic-treated patients and 6% in those receiving nifedipine.
A total of 411 patients were recruited in the Israeli cohort of the Hypertension Optimal Treatment (HOT) Study, a multinational study conducted to assess the effect on cardiovascular morbidity and mortality in hypertensive patients of three levels of target diastolic blood pressure: < 90, < 85, and < 80 mm Hg. Initial treatment with felodipine in all patients was supplemented with other drugs as needed. When compared to the subjects in the rest of the world, the percentage of Israeli patients getting previous antihypertensive treatment was higher, reflecting a higher proportion of hospital-recruited patients. This accounted for the lower percentage of Israeli patients ending up with low-dose felodipine: 50% vs 56% in other countries. The percentage of patients getting high-dose felodipine plus additional drugs was also higher: 3.8% vs 2.9% for other countries. Felodipine was remarkably well tolerated, and most of the patients were able to continue this drug regimen.
The efficacy of felodipine and tolerance of this drug was examined in 52 patients, 23 men and 29 women, 18-76 years of age, in whom it either replaced previous therapies of nifedipine and other vasodilators, or was added to a constant dose of beta blockers and diuretics or another previous therapy, which was unchanged. Felodipine significantly reduced blood pressure (BP), from 192.3 +/- 31.9/114.3 +/- 18.0 to 155.7 +/- 19.5/93.8 +/- 11.5 mm Hg, with no change in pulse rate. There were no significant biochemical changes, renal deterioration or blood sugar disequilibrium. Adverse reactions including flushes and leg edema could be tolerated by most of the patients, however six patients dropped out. Orthostasis dictated a decrease in felodipine dosage. Felodipine appears to be a highly potent, well tolerated drug and offers a substitute treatment for severe hypertensives refractory to other vasodilators.
Diuretics are among the first drugs offered to the hypertensive patient. However, they can induce metabolic changes resulting in cardiovascular insult. Especially noteworthy are increased levels of glucose and lipids. Indapamide is a diuretic and vasodilator that does not raise blood glucose or lipid levels. We therefore investigated its use as a substitute diuretic in patients whose treatment had resulted in hyperglycemia and/or hyperlipidemia. In 24 hypertensives, Indapamide, 2.5 mg daily, replaced the diuretic therapy they were receiving. Blood pressure, blood glucose, hemoglobin A1C and lipid profile were measured before and every month during the 6 months of Indapamide treatment. Replacement of diuretics with Indapamide significantly reduced blood glucose from 148 +/- 53 mg/dl to 127 +/- 37, p = 0.05 HbA1C from 8.42 +/- 0.4 mg/dl to 7.7 +/- 2.0, p = 0.05; total cholesterol from 253 +/- 45 mg/dl to 228 +/- 43, p < 0.05; and triglycerides from 224 +/- 145 mg/dl to 176 +/- 91, p < 0.05. Blood pressure was better controlled with Indapamide than with previous medications. It was reduced from an average of 155 +/- 1 systolic and 89 +/- 8 diastolic (mm Hg), to 142 +/- 13 and 83 +/- 7, respectively, p < 0.05. We conclude that Indapamide is safe and effective in lowering blood pressure and contributes to better control of blood glucose and lipid levels in diabetic and dyslipidemic patients, compared to standard diuretics.
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Infection with human immunodeficiency virus type 1 (HIV-1) induces vigorous and persistent cytotoxic CD8+ T cell responses. CTL clones were derived from peripheral blood or cerebrospinal fluid of three HIV-1 patients, with depressed CD4+ T cell counts. When stimulated with HLA-compatible target cells (B-LCL) presensitized with cognate HIV-1 peptides, all clones produced GM-CSF, TNF-alpha, and IFN-gamma and most produced low amounts of IL2, IL3, and IL4. After nonspecific stimulation with a phorbol ester and calcium ionophore, the clones secreted cytokines at levels similar to those from CD4+ lines from an HIV-1 infected donor. The ability of supernatants from the stimulated CTL clones to support the formation of granulocyte-macrophage colonies in normal bone marrow suggests that the GM-CSF was biologically active. Release of cytokines by activated CTL may influence the immunopathogenesis of HIV disease.
The effect of 20 mg of enalapril with and without 12.5 mg of hydrochlorothiazide on glucose metabolism insulin sensitivity and lipids was evaluated in hypertensive non-insulin-dependent diabetes. Ten mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus were treated for 8 weeks with 20 mg enalapril once a day, and then divided into two groups of 5 patients each for a second 8 weeks of treatment with enalapril alone or in combination with hydrochlorothiazide, 12.5 mg once a day. Blood pressure, fasting plasma glucose, lipids and insulin, glycosylated hemoglobin, and insulin sensitivity were measured at baseline and after 8 and 16 weeks. Results were analyzed by the ANOVA test for repeated measures and all values are given as mean +/- SD. Diastolic blood pressure decreased significantly after the first and second period of enalapril and after the combination of enalapril and hydrochlorothiazide. Glycosylated hemoglobin dropped significantly after the first and second period of enalapril monotherapy. Plasma triglycerides and fasting plasma insulin decreased significantly after the 16 weeks of enalapril. Insulin-mediated glucose uptake increased significantly after 8 and 16 weeks of monotherapy with enalapril. No significant difference was observed in any of the metabolic characteristics, including insulin sensitivity, between the values after 8 weeks of enalapril alone and the final values of the enalapril-treated and the enalapril/hydrochlorothiazide-treated groups. It is concluded that enalapril improves some of the metabolic parameters, including insulin sensitivity, of hypertensive diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The expectation that training programs will place more of their physician graduates into primary care has caused internal medicine programs to explore different educational experiences for their residents. One proposal is to transfer the ambulatory training site for residents from the hospital clinic to a community academic practice (CAP) site. We discuss the theoretical aspects, the practical considerations, and our experience with one CAP site, including the problems that have been solved and the problems remaining.
PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.
Patients with diabetes mellitus are particularly vulnerable to cardiovascular disease. Although structural and functional myocardial complications are present in patients with diabetes alone, they are particularly severe in patients with both diabetes and hypertension. Considerable evidence--both in experimental animal models and in humans--points to hypertension as of critical importance in the pathogenesis of severe diabetic heart disease. In diabetic hypertensive cardiomyopathy, coronary artery disease as well as structural and functional abnormalities are more pronounced than would be expected from either process alone. The myocardial damage is attributed mainly to hypertension, whereas the myocellular dysfunction is attributed mainly to diabetes. Together, the consequences to the myocardium are devastating. Strict control of the hypertension and diabetes may have an ameliorative effect on the subsequent development of diabetic heart disease.
The lack of comparative studies of nifedipine and felodipine using 24-h blood pressure (BP) monitoring in the same patients led to the present study evaluating the antihypertensive efficacy and side effects of treatment with slow-release (SR) nifedipine (20 mg twice daily) and extended-release (ER) felodipine (10 mg once daily). In the double-blind study, subjects were randomly assigned to one of two treatment groups: 6 weeks of nifedipine SR (20 mg twice daily) followed by 6 weeks of felodipine (ER) (10 mg once daily with evening matched placebo), or vice versa. Twenty-four-hour ambulatory BP monitoring showed no significant differences in systolic BP (SBP) during the day. There were no significant differences in diastolic BP (DBP) throughout the 24 h, although the frequency of DBP recordings > 90 mm Hg was greater during nifedipine (33.1%) than felodipine (27.75%) treatment. The most common side effects were flushing, palpitations, headaches, and ankle edema; there were no adverse effect on lipid profile or glucose level.
PURPOSE: We document the incidence of complications associated with laparoscopic nephrectomy in a multi-institutional study. MATERIALS AND METHODS: The study included the initial 185 patients undergoing laparoscopic nephrectomy at 5 centers in the United States between June 1990 and July 1993. RESULTS: A total of 30 patients (16%) had 34 complications. There was no mortality. Access-related complications included 2 cases of hernia formation at the trocar site, 1 abdominal wall hematoma and 1 trocar injury to a hydronephrotic kidney. Intraoperative complications included 5 cases of vascular injury, 1 splenic laceration and 1 pneumothorax. Postoperative complications involved the gastrointestinal tract in 6 cases, cardiovascular system in 6, genitourinary tract in 4, respiratory system in 4 and musculoskeletal system in 2. Miscellaneous complications occurred in 3 patients. Open surgical intervention was required electively in 8 patients and on an emergency basis in 2. The incidence of complications decreased with experience: 71% occurred during the initial 20 cases at each institution. CONCLUSIONS: In our early experience the complication rate for laparoscopic nephrectomy was 12% in patients with benign renal disease and 34% in those with renal cancer. Based on this collective experience, recommendations for prevention, recognition and treatment of complications are made.
1. The effect of angiotensin-converting enzyme inhibitors (ACEI) enalapril, lisinopril and ramipril was studied on fructose-induced hypertensive and hyperinsulinaemic rats. 2. 60 Sprague-Dawley rats were fed a fructose-enriched diet for 5 weeks, which produced hyperinsulinaemia, hypertriglyceridaemia and hypertension. Beginning with week 3 of the diet, lisinopril (10 and 20 mg per kg per day), ramipril (5 and 10 mg/kg per day) and enalapril (20 mg/kg per day) were given daily in drinking water for 2 weeks to 10 rats in each drug group. Ten rats fed only the fructose-enriched diet served as control. 3. Systolic blood pressure was measured weekly by the indirect tail-cuff method. Plasma insulin level was determined using RIA. 4. Data indicate that ACEI improve insulin resistance induced by high-fructose intake in rats; that despite their equal hypotensive effect, ACEI differ in their ability to improve insulin resistance; and that improvement of insulin resistance by ACEI is dose-dependent.
1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.