Prevention of hypertension

Hypertension is a major risk factor for many cardiovascular diseases including stroke, coronary heart disease, cardiac failure, and endstage renal disease. Therefore, prevention of hypertension becomes an important goal in overall efforts to control blood pressure and reduce the incidence of hypertension-related cardiovascular and renal complications and outcomes. Many risk factors underlying hypertension have been identified including nonmodifiable factors such as age, gender, genetic factors, and race, as well as modifiable factors including overweight, high sodium intake, low potassium intake, alcohol consumption, and reduced physical activity. A number of studies have demonstrated that interventions aimed at changing these modifiable factors might decrease blood pressure and even prevent the development of hypertension. Thus, present national recommendations and guidelines include lifestyle modifications ranging from weight loss in case of obesity, engagement in regular isotonic physical activity, reduced sodium diet (<100 mmol/d), supplementation of potassium, and alcohol moderation (<1 ounce of ethanol or its equivalent per day).     

Use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous marrow transplantation for lymphoid malignancies

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following autologous marrow transplantation for lymphoid malignancies was explored in a phase I/II dose escalation study. rhGM-CSF given as a 2-hour infusion daily for 14 days was well tolerated at doses up to 240 micrograms/m2/day. When compared with 86 disease-matched and treatment-matched historical controls, patients receiving greater than or equal to 60 micrograms/m2/day rhGM-CSF recovered neutrophil and platelet counts more rapidly, had fewer days with fever, and were discharged from the hospital sooner.     

Quinaprilat increases total body vascular compliance in rats with myocardial infarction.

To test whether quinaprilat, a new angiotensin converting enzyme inhibitor, has any venous effect, its immediate effects were measured on mean circulatory filling pressure (MCFP), intravascular volume and total body vascular (i.e., venous) compliance in conscious rats with mild congestive heart failure induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-minute infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures by 8 mmHg and 0.7 mmHg, respectively (P less than 0.02); heart rate, MCFP, hematocrit and blood volume remained unchanged. Compared with control vehicle infusion, quinaprilat increased the total body vascular compliance (2.09 +/- 0.12 vs 2.69 +/- 0.23 ml/kg/mmHg; P less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs 28.53 +/- 2.55 ml/kg; P less than 0.02). These data suggest that quinaprilat produces possible venodilation through immediately improved total body vascular compliance thereby reducing cardiac preload in this rat model of chronic heart failure.

     

Hemodynamic comparison of two nifedipine formulations in patients with essential hypertension

The hemodynamic and humoral effects and trough-to-peak 24-hour blood pressure responses of 2 nifedipine formulations, capsules and continuous-release once-daily formulation tablets, were evaluated in 10 patients with mild to moderate essential hypertension. Both formulations reduced mean arterial pressure similarly from 120 +/- 3 (baseline) to 107 +/- 2 (p less than 0.005) and 105 +/- 2 mm Hg (p less than 0.005) and total peripheral resistance index from 65 +/- 9 (baseline) to 47 +/- 4 (p less than 0.05) and 45 +/- 3 U/m2 (p less than 0.05), respectively. Renal, splanchnic and total forearm (including skin and skeletal muscle) blood flows were maintained or even increased slightly associated with reductions in regional vascular resistances. Decreases in renal, total forearm and skeletal muscle resistances were significant (p less than 0.05) with the capsules, but the decrease was only significant in renal resistance with the long-acting tablets. Intravascular volume did not expand with reduction in arterial pressure. This antihypertensive effect was not related to baseline plasma renin activity levels or age. Nifedipine tablets provided a better control of mean arterial pressure (66%) than did capsules (44%).     

Refinements in method of evaluation and physical conditioning before and after myocardial infarction

A 54 year old white man with hypertension, obesity and an elevated serum cholesterol level volunteered for a physical training program. During the sixth week he became ill, and a repeated work-capacity test revealed physiologic evidences of myocardial insufficiency. The pre-exercise serum glutamic oxaloacetic transaminase level was elevated. A routine electrocardiogram four hours later revealed evidence of an acute inferoseptal myocardial infarction.

The course of the disease was uneventful and uncomplicated. Two months after infarction the patient resumed a physical activity program which provided for a slow increase in metabolic demands compatible with his capacity. Repeated work-capacity tests 20 and 23 weeks after infarction showed that he responded to training in exactly the same manner as has been observed in normal, healthy individuals. At that time he was normotensive, with a normal serum cholesterol concentration and near-normal body weight. The capacity for adequate cardiorespiratory adjustments to high metabolic demands was rated as “good.” This study illustrates how performance tests can be used in evaluating the work capacity and progress of a cardiac patient.     

Lecithin:cholesterol acyltransferase deficiency

Lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare familial disease inherited in an autosomal recessive pattern. It is characterized by a combination of plasma lipoprotein, corneal, erythrocyte and, in most patients, renal changes. The corneal changes consist of scattered stromal dots that are lipid deposits. Their composition is unique and suggests an intrinsic corneal metabolic defect. The corneal clouding is usually asymptomatic. Patients with the condition must be followed closely because renal failure may develop. We describe a patient with LCAT deficiency.     

Progressive systemic sclerosis: radionuclide esophageal scintigraphy and manometry

Radionuclide esophageal scintigraphy (RES) and manometry were used for prospective evaluation of esophageal involvement and disease severity in 11 patients (nine women and two men; median time since diagnosis, 1 year) with progressive systemic sclerosis (PSS). Quantitation of RES included calculation of the percentage of emptying at 30 seconds, while manometry provided measurements of proximal, distal, and lower esophageal sphincter (LES) pressures. The findings of both RES and manometry were abnormal in all 11 patients. There was a high correlation between the percentage of emptying and either distal esophageal pressure (r = .86, P less than .01) or LES pressure (r = .79, P less than .01). No significant correlation was found between the percentage of emptying and proximal esophageal pressure (r = .28, P = .39). RES is a safe, simple procedure that is readily accepted by patients and can be used in place of manometry for the detection and staging of esophageal involvement in PSS.