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Biomedical subjects

W Flamenbaum

Publications and source records attributed to W Flamenbaum.

At least 19 recordsLinked to original sources
PubMed1992

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult↗
PubMed1989

Hypertension, changes in high-density lipoproteins and antihypertensive therapy.

The risk for development of coronary heart disease (CHD) is related to a number of factors. Among these, both hypertension and various lipid abnormalities have been shown to play an important role. A clear inverse relation between high-density lipoprotein (HDL) cholesterol and CHD has been observed in numerous observational and short studies. Pharmacologic treatment of hypertension has been shown to reduce dramatically some of the sequelae of high blood pressure--renal failure, cerebrovascular accidents and congestive heart failure. However, a consistent reduction in associated CHD has not been demonstrated, and the dissociation between reducing blood pressure and reduction in CHD has not been definitively explained. One of the suggested explanations relates to alterations in blood lipid levels that may be induced by certain antihypertensive agents. Changes in HDL cholesterol levels or other lipid alterations due to antihypertensive therapy could modify the beneficial effects achieved by the direct reduction of blood pressure. If so, antihypertensive agents could be subclassified as atherogenic or antiatherogenic depending on the associated changes in lipid levels. Therefore, the antihypertensive agents of choice for patients whose cholesterol levels are a concern would be those that reduce the CHD risk factor of hypertension without compromising the risk factor associated with a patient's lipid profile.

Antihypertensive Agents↗
PubMed1989

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Antihypertensive Agents↗
PubMed1989

Beta-blockers and hypertension.

While there is general agreement on the natural history, pathology, and pathophysiology of hypertension, there continues to be controversy over the selection of specific antihypertensive agents. All antihypertensive agents will, by definition, lower blood pressure, and factors beyond side effects and other difficulties associated with therapy form the basis of selecting specific agents. One of these factors is the effect of a given drug on core organ function. Propranolol was the first beta-adrenoceptor-blocking agent introduced for the treatment of hypertension. Initiation of therapy with propranolol may result in a decline in blood pressure more at the expense of cardiac function due to a concomitant rise in total peripheral resistance. Furthermore, propranolol may result in a decline in both glomerular filtration rate (GFR) and renal blood flow (RBF). In contrast, cardioselective beta-blockers or those with intrinsic sympathomimetic activity may not adversely affect renal function. It had been predicted that nadolol, a noncardioselective beta-blocker without intrinsic sympathomimetic activity, should result in decreased renal function. In contrast, observations demonstrated a preservation or improvement in both RBF and GFR, suggesting the presence of an alternative effective mechanism. Recent additions to the beta-adrenolytic group of antihypertensive agents include drugs with concurrent beta-blockade and vasodilation. This vasodilatation may be achieved through agonist properties resulting in lesser increases in vasomotor tone and smaller, if any, decreases in cardiac output. Alternatively, vasodilation may be achieved by concomitant alpha-adrenoceptor blockade, such as with labetalol. This agent preserves GFR and RBF during therapy of hypertension, in patients with normal as well as diminished renal function and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Epoprostenol (PGI2, prostacyclin) during high-risk hemodialysis: preventing further bleeding complications.

The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatments in each of which prospective bleeding risk was assessed. PGI2 was associated with up to 50% overall reduction in the frequency of bleeding, particularly in the highest risk circumstances. PGI2 also allowed successful completion of the full, prospectively prescribed hemodialysis time in the most treatments (82% versus 93% with heparin). Furthermore, the efficiency of hemodialysis using PGI2, as indicated by the reduction in concentration of blood urea nitrogen and serum creatinine, was equal to that using heparin, even though there was a tendency toward modest reduction in residual volume of the hollow fiber dialyzer and slightly more frequent early termination of treatment from dialyzer clotting with PGI2. No severe vasodilatory side effects of PGI2 were observed during these studies. Hypotension was equally frequent during hemodialysis with heparin as with PGI2. The current results suggest that PGI2 should be considered as a substitute for heparin during high-risk hemodialysis because PGI2 may reduce the incidence of dialysis-associated bleeding without severe adverse side effects.

Adolescent↗
PubMed1987

Treatment of hypertension in the elderly.

The objective of treating the elderly patient with hypertension should be to reduce blood pressure to safe levels (systolic blood pressure less than 180 mm Hg), while minimizing adverse effects and changes in life-style. If the clinician considers the unique physiologic, pharmacologic, and psychosocial characteristics of this population, he will be successful in attaining these goals.

Aged↗
PubMed1986

Diuretic use in the elderly: potential for diuretic-induced hypokalemia.

The more potent "loop" diuretics are being used with increasing frequency. The elderly constitute a growing portion of the population undergoing treatment with diuretics. The alterations in renal function and pharmacokinetics in the elderly (over 60 years of age) may result in the development of certain adverse effects. In patients over 70 years old, there is a progressive decline in overall renal function, resulting in a more than 50% decrease in glomerular filtration rate. Most of the pharmacokinetic changes in the elderly consist of alterations resulting in enhanced plasma levels of any given drug; diminished hepatic drug extraction, detoxification/metabolism or prodrug conversion; decreased renal excretion of drug; and diminished volume of distribution of drug. Adverse reactions to diuretics may be grouped into metabolic changes (e.g., hypokalemia), physiologic alteration (e.g., volume contraction), toxic manifestation (e.g., interstitial nephritis) and allergic or idiosyncratic phenomena (e.g., rash or thrombocytopenia). There is general agreement that significant hypokalemia, particularly among elderly patients receiving digitalis glycosides, is significant and requires therapy. Diuretic-associated hypokalemia reflects the potency and duration of action of a diuretic, factors modulating potassium balance including dietary intake and concurrent medical processes. The short duration of action and greater natriuresis relative to kaliuresis characteristic of loop diuretics may result in a lesser degree of hypokalemia than that seen with traditional thiazide diuretics.

Aged↗
PubMed1986

Obesity and hypertension. Demonstration of a "floor effect".

Weight loss has a role in the treatment of essential hypertension. With the use of a medically supervised protein-sparing supplemented fast and a behavioral program, the changes in blood pressure as a result of weight loss in 135 obese hypertensive subjects were examined. Subjects' weight, blood pressure, and antihypertensive medication intake were recorded at baseline, at conclusion of supplemented fast, and at follow-up. Significant weight loss accompanied by decrements in blood pressure occurred in all subjects. Reductions in the number of antihypertensive medications also occurred. Although the correlations between changes in weight and blood pressure were significant, their moderate size suggests the amount of weight loss accounted for a relatively small part of the blood pressure reduction. Given the large weight losses in the majority of subjects, there appears to be a degree of weight loss beyond which further decrements in blood pressure will not occur ("floor effect"). Maintenance of blood pressure reductions at realimentation/follow-up suggests that weight loss, and not the supplemented fast, results in decreased blood pressure and medication level.

Adult↗
PubMed1986

Isolated hypoaldosteronism and abnormalities in renin, kallikrein, and prostaglandin.

To further define the pathophysiology of the syndrome of acquired isolated hypoaldosteronism, we determined plasma concentrations of active and inactive renin and urinary kallikrein and prostaglandin E2 excretion rates in 11 patients with the syndrome, 12 patients with similar serum creatinine levels, but without hyperkalemia, and in 12 normotensive patients with normal renal function and low plasma renin activities (PRA). Ten of 11 patients with the syndrome had low baseline PRA, and, unlike the control groups, six of 11 failed to double their PRA after furosemide stimulation. There were also consistent abnormalities in the percentage of inactive renin, no patient having a value less than and no control subjects having a value greater than 65%. Seven of 11 patients had prostaglandin E2 excretion rates lower than either control groups. Urinary kallikrein excretion rates in the patients with isolated hypoaldosteronism were significantly lower than in the control groups, but increased in response to therapy with fludrocortisone.

Adult↗
PubMed1985

Effect of zinc supplementation on hyperprolactinaemia in uraemic men.

Zinc and prolactin levels were measured in 32 male haemodialysis patients; 12 were receiving 50 mg zinc per day as zinc acetate and 20 were not. Zinc-treated patients had significantly higher plasma zinc levels (134 +/- 10 micrograms/dl v 88 +/- 2 micrograms/dl) and lower serum prolactin levels (11 +/- 4 ng/ml v 29 +/- 7 ng/ml) than untreated patients. Plasma zinc and serum prolactin were inversely related in zinc-treated and untreated patients (r = -0.79, p less than 0.001).

Adult↗
PubMed1985

The changing spectrum of heroin-associated nephropathy.

Thirty-five renal biopsies were performed on heroin abusers at our institution between January 1977 and June 1983 as part of the evaluation of unexplained heavy proteinuria. Twenty-eight patients (80%) had histopathologic diagnoses of either focal segmental glomerulosclerosis or renal amyloidosis. Patients having a diagnosis of renal amyloidosis were older (P = 0.025), had a longer history of heroin abuse (P = 0.05), and 13/14 demonstrated clear evidence of chronic subcutaneous suppurative lesions. The remaining seven patients demonstrated a spectrum of disease similar to that seen in the nonaddicted population. We compared the clinical and biopsy characteristics of patients evaluated between 1977 and 1980 with those seen between 1981 and 1983. The relative incidences of renal amyloidosis and focal glomerulosclerosis changed significantly (P = 0.025). Whereas 29% of patients in the early series had renal amyloidosis and 57% had focal glomerulosclerosis, the relative incidences in the later series were 48% and 29%, respectively. The development of renal amyloidosis in our patients appears to be related to a longer duration of heroin abuse with increased incidence of subcutaneous injection of the narcotic. Chronic, suppurative skin ulcerations tend to occur at the site of injection, resulting in a persistent acute-phase inflammatory state important for the initiation and potentiation of secondary amyloidosis.

Adult↗
PubMed1985

Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat: enzyme histochemical studies.

Enzyme histochemical techniques were utilized to examine the progression and extent of proximal tubular injury during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure. Acute renal failure was induced in male rats by the intraperitoneal administration of 10 mg CDDP/kg body weight. At 6, 24, 48, 72, and 96 hr following treatment, renal function was assessed and tissue was collected for renal morphologic and enzyme histochemical studies. The enzymes examined were gamma-glutamyl transpeptidase, alkaline phosphatase, sodium-potassium ATPase (nitrophenyl phosphatase), acid phosphatase, glucose-6-phosphatase, succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase. By 24 hr, the activity of acid phosphatase was reduced throughout the proximal tubule, with the greatest decrease occurring in the P3 segment of the proximal tubule located in the outer stripe of the outer medulla. Changes in the histochemical staining of the remaining enzymes were not consistently observed until 48 or, in some cases, 72 hr. These alterations involved all portions of the proximal tubule with the most severe changes involving P3. The results of the enzyme histochemical studies along with the morphologic findings indicating that the initiation of CDDP-induced acute renal failure, first apparent at 48 hr in this model, is associated with cell injury throughout the proximal tubule. The majority of the histochemical changes did not become apparent until late in the course of tubular injury. This suggests that most of the changes in enzyme activity represent nonspecific effects of CDDP-induced tubular injury, as opposed to direct enzyme inhibition by the drug.

Acid Phosphatase↗
PubMed1985

Safety and efficacy of guanabenz in hypertensive patients with moderate renal insufficiency.

Eight hypertensive patients with moderate renal insufficiency were treated with gradually increasing oral doses of guanabenz acetate to a maximum dose of 8 mg BID. Patients' medications were titrated over 8 weeks. Once blood pressure control was achieved (seated diastolic blood pressure, 90 mmHg, or decrease of 10 mmHg from baseline values), drug dosages were maintained for up to a 12-week total treatment phase. Patients had significant reductions of blood pressure during treatment with guanabenz as compared to that during pretreatment levels. No changes in body weight or creatinine clearance were evident, as compared to baseline values. Our data suggest that guanabenz, in relatively small doses, can be used as safe and effective monotherapy of essential hypertension in patients with moderate renal insufficiency.

Blood Urea Nitrogen↗