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Biomedical subjects

D Freedman

Publications and source records attributed to D Freedman.

At least 55 records · Page 3Linked to original sources
PubMed1989

Nicardipine and hydrochlorothiazide in essential hypertension.

Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.

Adult↗
PubMed1989

Acquired immunodeficiency syndrome.

A report entitled "Kaposi's Sarcoma and Pneumocytosis Carinii Pneumonia among homosexual men in New York City and California" in the MMWR in July 1981 alerted the world to the appearance of a completely new disease. The opportunistic infections and cancers occurring in these patients had previously only been seen in patients who were immunosuppressed. Homosexual men were the first as a major risk group to be identified. Others quickly followed. The pattern of occurrence clearly indicated an infectious agent as the likely cause, and within two years the virus had been identified in Europe and the USA. In Europe it was named Lymphadenopathy Associated Virus (LAV) by Montagnier its discover, and in the USA, Human T cell Lymphotrophic Virus III (HTLV III). It is now known as Human Immunodeficiency Virus (HIV).

Acquired Immunodeficiency Syndrome↗
PubMed1988

Vanadate down-regulates cell surface insulin and growth hormone receptors and inhibits insulin receptor degradation in cultured human lymphocytes.

Insulin is able to down-regulate its specific cell surface receptor in cultured human lymphocytes. The effect of vanadate, a known insulinomimetic agent, was examined to determine whether it could mimic insulin to down-regulate the insulin receptor. Exposure of cultured human lymphocytes (IM-9) to vanadate (0-200 microM) resulted in a time- and dose-dependent decrease in cell surface insulin receptors to 60% of control, while insulin (100 nM) down-regulated to 40%. The vanadate effect, in contrast to the rapid effect of insulin, was slow to develop (4-6 h). Surface receptor recovery after 18 h exposure was rapid after vanadate removal (20 min), but it required hours after insulin suggesting the presence of an intracellular (cryptic) pool of receptors after vanadate treatment. Insulin binding to Triton X-100-solubilized whole cells after 18 h treatment revealed that total cell receptors had decreased to 50% of control after insulin but increased to 120 and 189% of control after 100 and 200 microM vanadate, respectively. Furthermore, vanadate inhibited the insulin-mediated loss of total cell receptors from 50 to 28%. Removal of cell surface receptors by trypsin before cell solubilization revealed that 100 microM vanadate increased insulin binding to 321% of control indicating an accumulation of intracellular receptors. Labeling of cell surface proteins with Na125I and lactoperoxidase followed by immunoprecipitation of solubilized receptors with anti-receptor antibody after incubation for various times up to 20 h and quantitation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that, while insulin shortened t1/2 from 7.3 to 5.3 h, vanadate prolonged receptor t1/2 to 14 h. No effect of vanadate was detected on insulin receptor tyrosine kinase activity with up to 4 h incubation at the vanadate concentrations used in this study. Furthermore, human growth hormone surface receptors were similarly down-regulated by vanadate. We conclude that 1) vanadate has an apparent insulin-like effect to down-regulate cell surface insulin receptors in cultured human lymphocytes; 2) in contrast to insulin-induced down-regulation which is associated with receptor degradation vanadate causes an accumulation of intracellular (cryptic) receptors and inhibits insulin receptor degradation; and 3) these effects of vanadate may be exerted on other cell surface receptors.

Binding, Competitive↗
PubMed1988

The life history calendar: a technique for collecting retrospective data.

"This paper details the authors' selection, design, and use of a life history calendar (LHC) to collect retrospective life course data. A sample of nine hundred [U.S.] 23-year-olds, originally interviewed in 1980, were asked about the incidence and timing of various life events in the nine years since their 15th birthday.... The following aspects of the LHC are described: (a) the concept, uses, and advantages of the LHC, (b) the time units and domains used, (c) the mode of recording the responses and the decisions and problems involved, (d) interviewer training, and (e) coding. The following results attest to the accuracy of the LHC retrospective data: (a) only four of the calendars had missing data in any month; (b) the data obtained in 1980 about current work, school attendance, marriage, and children showed a remarkable correspondence to the retrospective 1985 LHC reports of these events; (c) the interviewers were positive about the LHC's ability to increase respondent recall."

Americas↗
PubMed1987

Design features of a controlled clinical trial to assess the effect of a calcium entry blocker upon the progression of coronary artery disease.

This report presents the design and methodological features of a double-blind, randomized, placebo-controlled, trial in 383 patients with coronary artery disease. The study's principal objective is to determine whether chronic treatment with a calcium entry blocker can retard the progression of coronary artery disease. The study population consists of patients with coronary artery disease and a baseline coronary arteriogram that qualifies them as being at high risk for disease progression. After satisfying all entry criteria, patients were randomized to receive either the calcium entry blocker nicardipine or placebo. All indicated concomitant medications except calcium entry blockers are permitted. Patients are being followed clinically for 24 months before undergoing a second coronary arteriogram. The effect of the treatments on a variety of clinical and angiographic parameters will be determined.

Adult↗
PubMed1986

Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial.

Nicardipine, a new calcium channel blocking drug of the dihydropyridine family, was administered to 63 patients at a dose of 30 or 40 mg 3 times daily in a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Nicardipine midly increased heart rate (HR) at rest and midly decreased the blood pressure (BP) at rest. When generally similar responses to the 30- and 40-mg doses were averaged, nicardipine produced a 7% increase in peak exercise HR, which was balanced by a 6% decrease in peak exercise BP. Thus, no change occurred in the exercise HR-BP product. With nicardipine, treadmill exercise duration increased 9%, time to angina increased 15%, time to 1-mm ST-segment depression increased 16%, and oxygen consumption at peak exercise increased 13%. Mean anginal frequency declined, as did mean weekly sublingual nitroglycerin consumption, but not significantly. There were more cardiovascular side effects with nicardipine than with placebo, with at least 3 patients having increased angina judged by investigators as probably related to the drug. Vasodilatory side effects were also more frequent with nicardipine, but were generally mild and well tolerated; the drug had to be discontinued in only 1 patient, because of vasodilatory effects. Nicardipine is effective and generally well tolerated in patients with chronic stable angina.

Adult↗
PubMed1986

Detection of an intracellular transforming protein (v-Ki-ras p21) using the flow activated cell sorter (FACS).

The transforming protein coded for by the Ki-ras oncogene, v-p21, localizes at the cytoplasmic face of the plasma membrane. A method is presented whereby the appearance of v-p21 in Kirsten murine sarcoma virus-transformed cells can be detected by flow cytometry, using a monoclonal antibody to v-p21 and methods modified from immunofluorescence microscopy. The method is sufficiently sensitive to differentiate between cellular and viral p21 levels, to detect small subpopulations of virus-transformed cells, and to monitor changes in p21 expression in response to physiologic variables. The method provides a rapid, quantitative means to investigate the expression of an intracellular transforming protein in heterogeneous cell populations.

Animals↗
PubMed1985

The metabolism and pharmacokinetics of nicardipine hydrochloride in man.

Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. After intravenous infusion of nicardipine at 5 mg-1 for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. Steady-state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration.

Administration, Oral↗
PubMed1985

Nicardipine for stable angina pectoris.

Nicardipine, 30 and 40 mg thrice daily, was administered to 66 patients with stable angina pectoris in a multicentre, randomised, double-blind, cross-over trial. With nicardipine therapy, duration of exercise and cumulative oxygen consumption increased, while times to onset of angina and 1 mm ST segment depression were prolonged. Anginal frequency and nitroglycerin consumption declined with use of nicardipine, but this did not reach statistical significance. Resting heart rate increased slightly and resting blood pressure decreased. Two patients on nicardipine and one on placebo sustained acute infarction. Otherwise, side effects were generally mild and transient.

Adult↗
PubMed1985

Short- and long-term treatment of stable effort angina with nicardipine, a new calcium channel blocker: a double-blind, placebo-controlled, randomised, repeated cross-over study.

This study evaluated 1 year the efficacy of therapy with nicardipine in patients with chronic stable angina pectoris. Twenty-five male patients were entered. After a placebo run-in phase, the patients received nicardipine 30 mg, nicardipine 40 mg, and placebo, three times daily given in random, double-blind manner for 8 weeks. A double-blind, cross-over study comparing nicardipine with placebo was then undertaken. After 5 months of open treatment with nicardipine 90 or 120 mg day-1, patients received either placebo or nicardipine for 3 weeks, each followed by the alternative treatment for an additional 3 weeks and further open-label treatment with nicardipine for another 3-5 months. There were no significant changes in the PR, QRS or QT intervals, or in the QRS pattern during the short-term and long-term studies. There were no significant differences in mean heart rate after nicardipine compared with baseline. During treatment with nicardipine 120 mg day-1, patients reported significantly fewer anginal attacks compared with placebo, and nitroglycerin consumption also decreased. Nicardipine increased treadmill time, time to onset of angina, and time to one mm ST segment depression. These effects were maintained after 6 months of continued nicardipine therapy. Adverse effects were minor and well tolerated and included headache, dizziness, gastrointestinal upset, flushing paraesthesia and pedal oedema. Abrupt withdrawal of nicardipine at the end of the study resulted in a rapid return of the original symptoms but without further deterioration from the baseline measurements. Nicardipine was effective in the treatment of stable effort angina pectoris; this benefit was maintained for the entire year of treatment.

Adult↗
PubMed1984

Pharmacokinetics of nicardipine following oral and intravenous administration in man.

The pharmacokinetics of nicardipine have been studied following oral and intravenous administration in man and the effects of food on nicardipine kinetics investigated. Following intravenous administration of nicardipine as an infusion plasma levels declined in a biphasic manner and plasma clearance values were of the same order as hepatic plasma flow. Following oral administration in the starved state nicardipine was rapidly absorbed but subject to presystemic elimination. Maximal plasma concentrations were achieved typically between 20 minutes and 2 hours after administration. The oral bioavailability of nicardipine determined by reference to a co-administered intravenous radiolabelled dose was found to be non-linearly related to dose. Bioavailability ranged from 15-45% approximately over the dose range 10-40 mg. Administration of nicardipine following a meal reduced the bioavailability of nicardipine.

Administration, Oral↗
PubMed1982

Glycosylated haemoglobin in chronic renal failure and after renal transplantation.

Haemoglobin A1 (HbA1) was determined by ion-exchange chromatography in 37 normoglycaemic patients with chronic renal failure (CRF) and 26 with successful renal transplants. Blood glucose concentrations in patients with CRF were similar to those in controls, and there was a significant correlation between fasting blood glucose concentration and HbA1 in these groups. HbA1 in patients with CRF was, however, significantly lower than that in control subjects. Concentrations of HbA1 in patients on haemodialysis, peritoneal dialysis, and those with steady state CRF prior to dialysis were not significantly different from each other. Whereas patients with successful renal transplants of greater than 3 months' duration had HbA1 concentrations indistinguishable from controls, HbA1 in patients with transplants of shorter duration were significantly lower. These observations are suggestive of a shortened erythrocyte survival in CRF per se. Furthermore, these results indicate: (a) the inadequacy of HbA1 in monitoring the quality of diabetic control in patients with CRF, and (b) the absence of a specific effect of dialysis on HbA1, and the restoration to normal HbA1 after successful renal transplantation.

Adolescent↗