Talma Rosenthal

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.

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.

Hypertension in women

Hypertension in women has received less attention than hypertension in men, and the major controlled trials of antihypertensive therapy have been carried out in populations made up predominantly of and have emphasised outcomes in men. Recently it has been recognised that women develop high blood pressure, particularly systolic hypertension, at an increased rate as they age, and that this age-related blood pressure increase is exaggerated by the menopause. The age-related rise in blood pressure, particularly systolic blood pressure and pulse pressure, contributes substantially to the age-related increase in risk of heart attack, heart failure, and stroke in middle-aged and elderly women. This article reviews aspects of hypertension epidemiology, pathophysiology, diagnosis and treatment that are important to women’s health with particular emphasis on important concomitant cardiovascular disease risk factors such as type 2 diabetes and the menopause. The role of ovarian hormones and their withdrawal in the pathogenesis of hypertension and related target organ damage is considered, as are the results of drug treatment of high blood pressure in women. Blood pressure in pregnancy is discussed in a separate article by Broughton-Pipkin and Roberts.

Device-guided breathing exercises reduce blood pressure: ambulatory and home measurements.

Slow breathing practiced routinely using an interactive device has demonstrated a sustained reduction in high blood pressure (BP). We reevaluated the BP response of hypertensives (n = 13) to this daily treatment for 8 weeks using 24-h ambulatory, home, and office BP measurements. A clinically significant BP reduction of similar magnitude was observed in all BP monitoring modalities during the daytime. Greater BP reductions were found for older patients and higher baseline BP. The results provide additional support for the efficacy of the device as an adjunctive lifestyle modification for treating hypertension.

Epinephrine pharmacokinetics and pharmacodynamics following endotracheal administration in dogs: the role of volume of diluent

OBJECTIVE to define the optimal volume of dilution for endotracheal(ET) administration of epinephrine (EPI). DESIGN prospective, randomized, laboratory comparison of four different volumes of dilution of endotracheal epinephrine (1, 2, 5, and 10 ml of normal saline). SETTING large animal research facility of a university medical center. SUBJECTS AND INTERVENTIONS epinephrine (0.02 mg/kg) diluted with four different volumes (1, 2, 5, and 10 ml) of normal saline was injected into the ET tube of five anesthetized dogs. Each dog served as its own control and received all four volumes in different sequences at least 1 week apart. Arterial blood samples for plasma epinephrine concentration and blood gases were collected before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 and 60 min after drug administration. Heart rate and arterial blood pressure were continuously monitored with a polygraph recorder. MEASUREMENTS AND MAIN RESULTS higher volumes of diluent (5 and 10 ml) caused a significant decrease of PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of diluent (1 and 2 ml), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects persisted for over 30 min. Mean plasma epinephrine concentrations significantly increased within 15 s following administration for all the volumes of diluent. Mean plasma epinephrine concentrations, maximal epinephrine concentration (Cmax) and the coefficient of absorption (Ka) were higher in the 5 and 10 ml groups. The time interval to reach maximal concentration (Tmax) was shorter in the 5 and 10 ml groups. Yet these results were not significantly different. Heart rate, systolic and diastolic blood pressures did not differ significantly between the groups throughout the study. CONCLUSIONS Dilution of endotracheal epinephrine into a 5 ml volume with saline optimizes drug uptake and delivery without adversely affecting oxygenation and ventilation.

Contribution of Nitric Oxide to the Beneficial Effects of Enalapril in the Fructose-Induced Hyperinsulinemic Rat

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.

The effect of antihypertensive drugs on the fetus.

A critical review of the literature on the effects of antihypertensive drugs on the fetus in pregnant women is presented. The survey covers the alpha-adrenergic receptor agonists, beta-blockers including topical eye medications, alpha-beta blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. The lack of data on angiotensin II receptor blockers is noted although effects are considered to be similar to those reported with ACE inhibitors and therefore to be avoided. Analysis of the literature underscores that some antihypertensive drugs can be used safely at certain stages of pregnancy, while others are suspect and to be avoided at all costs. The lack of placebo-controlled studies on the treatment of severe hypertension in pregnancy due to ethical considerations is discussed against the background of the pressing need to treat these women despite the possible deleterious effects of antihypertensive drugs

Effects of Enalapril, Losartan, and Verapamil on Blood Pressure and Glucose Metabolism in the Cohen-Rosenthal Diabetic Hypertensive Rat

We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.

Effect of a mineral salt diet on 24-h blood pressure monitoring in elderly hypertensive patients

The influence of a mineral salt on 24-h ambulatory blood pressure (BP) monitoring was studied in 20 elderly hypertensive subjects residing in an old peoples home. Ordinary table and cooking salt was substituted with a special Na-reduced, K-, Mg-, and l-lysine HCl-enriched mineral salt (Pansalt®) for 6 months. Antihypertensive therapy was uninterrupted. An ambulatory BP monitor (Suntech Accutracker) measured BP every 20 min during the day and every 30 min at night, before and 6 months after starting the diet. Nine patients (45%) decreased both systolic and diastolic BP significantly: systolic BP fell from 154.92 ± 33.67 mm Hg to 143.45 ± 53.1 mm Hg (P ⩽ 0.01) during the daytime from 6 am to midnight; and from 139.80 ± 32.84 mm Hg to 137.87 ± 31.17 mm Hg (P ⩽ 0.01) from midnight to 6 am. Diastolic BP fell from 85.34 ± 24.85 mm Hg to 70.29 ± 18.31 mm Hg (P ⩽ 0.01) during the daytime from 6 am to midnight; and from 77.1 ± 22.92 mm Hg to 67.76 ± 15.63 mm Hg (P ⩽ 0.01) at night. Blood pressure in the other 11 subjects showed no improvement. Heart rate also fell in the subjects, from 69.44 ± 21.62 beats per minute (bpm) to 66.94 ± 11.51 bpm (⩽0.01) during the day, and from 61.28 ± 12.82 bpm to 60.43 ± 10.33 bpm (P ⩽ 0.01) during the night. It is concluded that decreased intake of Na and increased intake of both K and Mg can be useful in controlling high BP.

Peripartum cardiomyopathy occurring in a patient previously treated with doxorubicin.

We present a 28-year-old primigravida woman in whom congestive heart failure developed 3 months after delivery of a neonate. The patient underwent doxorubicin treatment 10 years previously. The combined cardiotoxicity of prior doxorubicin treatment and pregnancy is considered, and the importance of careful follow-up of cardiac function during pregnancy and postpartum in patients previously treated with doxorubicin is stressed.

Takayasu arteritis in Israel

Chaim Sheba Medical Center is a national referral center and treats approximately 75% of the patients with Takayasu arteritis in Israel. A total of 50 cases have been seen to date, including the first series of 22 patients hospitalized at Sheba from 1965-1973 and reported by Deutsch [1] in 1974, and the 28 cases reported here. All cases were confirmed by arteriography, since clinical findings and plain film chest roentgenogram may indicate the presence of the disease but confirmation of the diagnosis and determination of the extent and type of lesion can be obtained only by angiographic studies. Vascular lesions may involve the aortic arch and brachiocephalic vessels as well as the abdominal aorta and its main branches. The angiographic features are narrowing and dilatations due to loss of elasticity of the vessel wall. Takayasu arteritis has been reported among Jewish ethnic groups almost exclusively in the Oriental and Sephardic communities. This is in contrast to Burgers disease which affects mainly Ashkenazic Jews [2]. A few words are required here about the Jewish communities of Israel, which divide roughly into 2 groups of differing origins. Sephardim are descendants of the Jews who were expelled from Spain in 1492 during the Inquisition and settled mainly in the then Turkish Empire; their descendants can be found in Greece, Turkey, Bulgaria, and other Mediterranean countries, as well as in North Africa. Ashkenazim are the descendants of the German Jews who populated Eastern Europe and form the majority of the present day Jewish communities of North and South America, England, and South Africa [1]. Of the 22 patients in Deutschs series, 9 were Arabs or Bedouins, 8 were Oriental Jews, and 5 were