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Biomedical subjects

E Z Rabin

Publications and source records attributed to E Z Rabin.

13 recordsLinked to original sources

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Blood Pressure

Analytical problems encountered during high-performance liquid chromatographic separation and coulometric detection of bopindolol metabolites in human plasma.

Good clinical control of hypertension is achieved with low doses of the potent beta-blocker bopindolol. Pharmacokinetic evaluations therefore require an analytical technique of high sensitivity. Analysis of plasma by high-performance liquid chromatography (HPLC) using electrochemical detection provides this sensitivity. This article describes the development of an analytical procedure and presents a reversed-phase HPLC method with coulometric detection suitable for plasma analyses during pharmacokinetic investigations of bopindolol therapy.

Adrenergic beta-Antagonists

Can plasma catecholamine levels be a useful index of sympathetic nervous system activity?

The hemodynamic responses of the sympathetic nervous system to the Valsalva maneuver were related to changes in circulating levels of catecholamines, aldosterone and plasma renin activity. Fourteen healthy normotensives (aged 27 +/- 8 years) took part. A catheter was inserted in the forearm then the subject was rested quietly (supine) for 30 mins. The Valsalva maneuver was performed (duration 40 s, intrathoracic pressure 40 mmHg) with continuous recording of supine heart rate. Blood was sampled before the maneuver (basal state) and at the bradycardic post maneuver phase for measurement of plasma noradrenaline, adrenaline, renin activity and aldosterone. In six subjects the procedure was repeated for durations of 10, 20, 30 and 40 s with a 30-min rest between each maneuver. Plasma catecholamines increased consistently (P less than 0.001) from pre- to post bradycardic phases of the maneuver. No changes in plasma renin activity or aldosterone were observed. The maximum tachycardia observed during each maneuver and the increments in catecholamine concentrations were each linearly related to the duration of straining but there was no overall correlation between the tachycardia and catecholamine concentrations. In conclusion under controlled conditions, plasma catecholamine concentrations can be useful indices of the stimulation of the sympathetic nervous system; the Valsalva maneuver does not appear to affect significantly the peripheral renin-angiotensin system; and the heart rate response to the Valsalva maneuver does not appear to be mediated solely by the sympathetic nervous system.

Adult

The renal handling of human urinary ribonuclease by rat kidneys.

The purpose of the study was to find out how poly(C)-avid human urinary ribonuclease is handled by the kidney. Purified human urinary ribonuclease (molecular weight 33 000) was radiolabelled with 125I. The enzyme was injected intravenously into dogs and monkeys with and without kidneys. The disappearance rate from the animals without kidneys was markedly prolonged. In the dog and monkey with kidneys, the radiolabelled enzyme which was infused was recovered in the urine unchanged. No large molecular weight fragments were found. When 125I-labelled ribonuclease was infused into rats the material recovered in the urine was primarily identical with the material infused. A very small fraction of the material recovered was found to contain some fragments which had chromatographic characteristics of monoiodotyrosine and diiodotyrosine. Two other fragments were detected but could not be identified. Autoradiographic studies of the rat kidneys also showed some reabsorption of the radiolabelled ribonuclease, particularly in the proximal tubules. With electron microscopy the radiolabelled material could be seen in the lysosomes. These observations corroborate findings discovered for other low molecular enzyme such as lysozyme (molecular weight 14 000) and suggest that the human ribonuclease is mainly excreted by the kidneys unchanged and that a minor amount may be reabsorbed by the proximal tubules and metabolized in the lysosomes.

Animals

Malignant hypertension.

Malignant or accelerated hypertension is a life-threatening disease whose complications may be prevented by rapid reduction of the blood pressure. Diazoxide is presently regarded as the preferred therapeutic agent, but drugs such as trimethaphan, sodium nitroprusside, phenoxybenzamine and hydralazine may be useful in particular situations. Treatment is best carried out in an intensive care unit, where appropriate monitoring and study of the patient can be done. Since the introduction of antihypertensive agents the life expectancy of these patients, even those with renal insufficiency, has increased.

Antihypertensive Agents

Ribonuclease activity in human serum, cerebrospinal fluid, and urine.

Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal fluid and urine of humans. Purified human urinary ribonuclease was used to produce a monospecific antibody in rabbits. The antibody was capable of: (i) inhibiting the enzyme activities in the serum, CSF, and urine; (ii) reacting with antigens in the serum and CSF. The antigens in the serum, CSF and urine were found to be immunologically identical. Immunoelectrophoresis data suggested that the urinary and CSF RNAase are chemically identical. Succesful renal transplantation reduced elevated serum RNAase to normal levels. The data suggest that the most likely source of both urinary and CSF ribonuclease activity is the blood stream.

Humans

Ribonuclease activity in renal failure: evidence for toxicity.

The normal level of serum or plasma poly C-avid ribonuclease activity is 1047 +/- 247 U/mL. Serum levels increase proportionately with elevations in serum creatinine, reaching levels of 9,500-35,000 in patients undergoing dialysis. The levels can be normalised by successful renal transplantation but not by dialysis. Purified human urinary ribonuclease, a glycoprotein enzyme similar to the serum ribonuclease, was capable of: 1) inhibiting the incorporation of 3H-thymidine into mitogen-stimulated lymphocytes; 2) inhibiting the proliferation and growth of bone marrow red cell colonies; and 3) adversely affecting the growth and viability of precursor fat cells.

Cell Division

Ribonuclease activity of human cerebrospinal fluid.

The ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal level was 269 +/- 95 units/ml. Consistent elevations above 550 units/ml were found in: 1. Chronic cerebrovascular disease; 2. Spinal cord compression; 3. Tumors. The molecular weights of the ribonucleases in the cerebrospinal fluid are approximately 33,000; 21,000 and 15,000; the major species is the one with m.w. 33,000. Although the increase in the CSF ribonuclease activity is not disease specific, the measurement has provided corroborative help in cases when the CSF protein is normal. The increase in CSF RNAase is not due to red or white blood cells and the immunologic data suggest that the CSF enzyme activity is derived from the blood stream. Further studies are necessary to rule out a nerve cell origin of the CSF ribonuclease activity.

Cerebrospinal Fluid

Correlation of left ventricular hypertrophy and its regression by lisinopril with salt-induced hypertension.

The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors