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Biomedical subjects

W Flamenbaum

Publications and source records attributed to W Flamenbaum.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1985

Monotherapy with labetalol compared with propranolol. Differential effects by race.

The antihypertensive effect of oral labetalol and propranolol were evaluated in 65 black and 75 white patients with mild to moderate hypertension (standing diastolic blood pressure (StDBP) of 90-115 mmHg) in a double-blind multicenter clinical trial. Following a 4-week placebo phase, labetalol (n = 70) or propranolol (n = 70) was randomly assigned. During a 5-week titration phase, labetalol could be increased from 100 mg BID to 600 mg BID to achieve a StDBP of less than 90 mmHg and a decrement of greater than or equal to 10 mmHg. Propranolol could be titrated from 40 to 240 mg BID. A 3-month maintenance phase was followed by an optional 8-month maintenance phase. Hydrochlorothiazide (HCTZ) could be added at any time during the maintenance phase. Supine and standing blood pressures were measured at each visit. Statistical analysis revealed significant (ANOVA, p less than 0.05) treatment by race effects. Therefore, the treatment groups were stratified retrospectively by race. This study demonstrated that labetalol is equally effective in white and black patients, whereas, propranolol is significantly (p less than 0.05) more effective in white than in black patients. Moreover, labetalol is significantly more effective than propranolol in lowering the standing systolic/diastolic blood pressure of black patients (p less than 0.02/p less than 0.001). These blood-pressure effects were accompanied by a significantly greater (p less than 0.04) reduction in heart rate with propranolol. Furthermore, significantly more (p less than 0.05) black patients treated with propranolol compared to those treated with labetalol required the addition of a diuretic for control of their blood pressure.

Adult↗
PubMed1985

Cis-diamminedichloroplatinum (II)-induced acute renal failure in the rat. Correlation of structural and functional alterations.

Studies were undertaken to examine the relationship between renal morphologic and functional alterations during the development of cis-diamminedichloroplatinum (II) (CDDP)-induced acute renal failure (ARF). Control and CDDP-treated rats (10 mg/kg, intraperitoneally) were housed in metabolic cages for the purpose of renal function determinations. Renal morphology was studied by light and electron microscopy at 6, 24, 48, 72, and 96 hours following treatment. Six hours following CDDP administration, morphologic alterations consisting of nucleolar segregation, ribosome dispersion, and the formation of aggregates of smooth endoplasmic reticulum were observed throughout the P3 portion of the proximal tubule located in the outer stripe of the outer medulla and medullary rays. These changes became more frequently observed throughout P3 during the course of the study. At 24 and 48 hours, focal changes were also observed involving the P1 and P2 segments of the proximal tubule which make up the pars convoluta. ARF, indicated by a reduced creatinine clearance, was first apparent 48 hours following CDDP administration. The development of ARF was associated with focal, primarily sublethal, cell injury throughout the proximal tubule. By 72 and 96 hours necrosis primarily affecting P3 became widespread, and renal function progressively worsened. The establishment of ARF prior to the development of tubular necrosis suggests that the processes of tubular obstruction and/or tubular fluid backleak are not involved in the initiation of ARF in this model. Instead, the alterations involving P1 and P2 appear to be most important during the early stages of CDDP-induced ARF. The severity of the convoluted tubular injury at 48 hours showed a significant correlation with the degree of renal function impairment. The tubular injury affecting P3 did not correlate with the loss of renal function at any of the time points studied. However, tubular injury in P3 did appear responsible for some degree of renal function impairment at 72 and 96 hours, probably as a result of tubular obstruction and/or tubular fluid backleak.

Acute Kidney Injury↗
PubMed1983

Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies.

The antihypertensive effects of intravenous labetalol were evaluated in 59 patients with hypertensive crises or severe hypertension in need of rapid lowering of blood pressure in a multicenter study. Patients appearing with a supine diastolic blood pressure 125 mm Hg or greater, or a supine systolic blood pressure of more than 200 mm Hg received an initial mini-bolus injection (20 mg) of labetalol. This was followed by repeated incremental doses of 20 to 80 mg given at 10 minute intervals to achieve a supine diastolic blood pressure of less than 95 mm Hg or decrease 30 mm Hg or greater, or a satisfactory decrease in systolic blood pressure. Patients were stratified into those who had taken antihypertensive medication within 24 hours and those who had not. The initial mini-bolus injection caused rapid but not abrupt reduction in blood pressure; the baseline mean blood pressure decreased 23/14 mm Hg. Further injections were needed in the majority of patients (mean: 197 mg). The blood pressure reduction after the last dose of labetalol was 55/33 mm Hg. In pretreated patients and in those who had no medication for 24 hours prior to the intravenous labetalol, the response was similar. Heart rate decreased 10 beats per minute in the total population. In patients pretreated with beta-adrenergic blockers, blood pressure response was similar to that in the total group (59/35 versus 55/33 mm Hg), but heart rate remained essentially unchanged. The dose required to achieve the therapeutic effect was less in pretreated patients than in untreated patients, but the duration of action was shorter. No serious adverse effects were encountered even in patients with concomitant diagnoses of acute left ventricular failure, myocardial infarction, stable congestive heart failure, atrial fibrillation, angina pectoris, acute stroke, transient ischemic attack or encephalopathy. Labetalol is a safe and effective treatment for a rapid blood pressure reduction in hypertensive emergencies.

Adrenergic beta-Antagonists↗
PubMed1983

Cis-diamminedichloroplatinum (DDP) induced acute renal failure (ARF): attempts at amelioration.

Nephrotoxicity is a dose limiting feature of cis-diamminedichloroplatinum (DDP) cancer chemotherapy. We have previously developed a model of DDP induced acute renal failure in the rat, which is characterized by non oliguric progressive azotemia. Protocols have been established in humans to prevent or diminish DDP associated renal alterations during the course of cancer chemotherapy. The present studies were designed to evaluate the effect of prior diuretic therapy, with furosemide, and enhanced solute diuresis, using dextrose and water as the sole source of drinking fluid, on DDP induced acute renal failure in the rat. As compared to water drinking controls neither the diuretic nor the enhancement of osmotic excretion effected DDP associated mortality. The courses of the acute renal failure observed in all three study groups were similar; however, there was a suggestion in the surviving animals that these maneuvers may have contributed to a more rapid return in renal function among rats not dying of DDP induced acute renal failure.

Acute Kidney Injury↗
PubMed1983

Metabolic consequences of antihypertensive therapy.

The availability of pharmacologic agents has contributed to a reduction in the morbidity and mortality of hypertensive cardiovascular disease. However, antihypertensive agents are associated with changes that may adversely affect patients receiving therapy. Nutritional and metabolic consequences of antihypertensive therapy may be associated with enhanced atherosclerosis. The abnormalities in lipid metabolism, carbohydrate tolerance, and changes in the renin-angiotensin-aldosterone axis are reviewed. The mechanisms by which antihypertensive therapy causes these complications are unknown and their exact role in hypertensive cardiovascular disease remains to be elucidated. Appropriate selection of therapeutic agents and dietary manipulations may minimize the metabolic and nutritional consequences of antihypertensive therapy.

Antihypertensive Agents↗
PubMed1982

Tubuloglomerular feedback response after hypotensive hemorrhage.

The tubuloglomerular feedback (TGF) response was studied in control rats and after either hypotensive hemorrhage or aortic clamping (AC). TGF was assessed both by differences in proximally and distally determined single nephron glomerular filtration rate (SNGFR) and by proximally determined SNGFR responses to orthograde microperfusion at 0 or 36 nl/min. Hypotensive hemorrhage was induced by the removal of blood equivalent to 0.5-1% of body weight. In control rats, proximal SNGFR was 29.74 +/- SE 0.87 nl/min and distal SNGFR was 28.64 +/- 0.82 nl/min, values not significantly different from each other. After moderate hemorrhagic hypotension (MH: BP = 86 +/- 1 mm Hg) or AC (BP = 70 +/- 4 mm Hg), both proximal and distal SNGFR decreased, with no significant differences between the values in either group. After severe hemorrhagic hypotension (SH; BP = 70 +/- 1 mm Hg), proximal SNGFR was 25.23 +/- 2.07 nl/min and distal SNGFR was 19.69 +/- 1.50 nl/min, values significantly different from each other and consistent with an enhanced feedback response. Using orthograde microperfusion, a significant reduction in SNGFR at a perfusion rate of 36 nl/min was observed under all circumstances. However, with SH hypotension the percent change in SNGFR at the two perfusion rates was significantly increased to 35.0 +/- 5.5%, compared to 21.6 +/- 6.6% in controls. In contrast, AC with reduction in renal perfusion pressure to a degree comparable to SH hypotension did not augment the relative decrease in SNGFR, the percentage change being 22.2 +/- 7.2%. Neither was TGF enhanced after MH hypotension when similar volumes of blood were removed but a similar decrease in BP was not obtained. These results suggest that some factor related to severe systemic hypotension enhanced the TGF response.

Animals↗
PubMed1982

The renin angiotensin system in conscious Brattleboro strain rats.

Plasma renin activity (PRA) was measured in conscious Brattleboro strain, vasopressin (AVP)-deficient diabetes insipidus (DI) and heterozygous rats with the aid of chronically implanted catheters. Baseline, dehydration-stimulated, and hemorrhage-stimulated levels of PRA were elevated in DI rats, as compared to levels in heterozygous controls. Replacement therapy with either AVP or the nonpressor AVP analog dDAVP reduced PRA to control levels. The high level of PRA in DI rats was associated with the lack of endogenous antidiuretic activity per se and not the pressor activity associated with the vasopressin molecule. Thus, elevated PRA in the chronic absence of AVP (in DI rats) most probably results indirectly from the chronically reduced plasma volume reported associated with hypothalamic diabetes insipidus.

Animals↗
PubMed1982

A comparison of ticlopidine and heparin on hemodialysis in dogs.

The efficacies of low-dose heparin and low-dose heparin plus ticlopidine as anticoagulants during hemodialysis in acutely uremic dogs were compared and evaluated. Heparin was administered as a bolus at a dose of 100 U/kg. In preliminary experiments it was determined that dogs dialyzed with ticlopidine alone demonstrated gross clotting of the artificial kidney within 2.5 hr. Ticlopidine was administered by gavage at a dose of 50 mg/kg/day starting 72 hr prior to hemodialysis and continuing throughout the period of hemodialysis (4 days). Each dog was dialyzed four times with either heparin alone or heparin plus ticlopidine. Each hemodialysis lasted 3.5 hr. Parameters followed included dialysis clearance of urea and creatinine, ultrafiltration rate, residual blood volume, gross clotting episodes, platelet count, and levels of fibrinogen and thromboxane B2. A lesser degree of hemodialysis-associated thrombocytopenia, a lower residual blood volume, fewer episodes of gross clotting, no reduction in fibrinogen levels, and no increase in thromboxane B2 levels were observed in the heparin plus ticlopidine group as compared to the heparin group alone. Although ticlopidine at the dosage employed should not be used as the sole anticoagulant for hemodialysis, it may be useful when added to low-dose heparin. The salutary effects demonstrated in this study suggest clinical benefits of the combination.

Animals↗
PubMed1981

A comparison of prostacyclin and heparin on hemodialyses in dogs.

A comparison of the efficacy of prostacyclin and heparin as anticoagulants during hemodialysis in uremic dogs was evaluated. Prostacyclin was infused continuously into the arterial limb of the dialyzer (100 ng/kg/min) while heparin was administered as a 5000 unit bolus at the beginning of dialysis. Prostacyclin and heparin were alternated and a total of 4 dialyses/dog were performed. Parameters followed to assess the efficacy of dialyses included: dialysance (ml/min) of urea, creatinine, ultrafiltration rate (ml/hr), residual volume and platelet count (% of baseline). A lesser degree of hemodialysis associated thrombocytopenia, and a higher ultrafiltration rate were observed with prostacyclin. These studies demonstrate that prostacyclin can be used alone as an anticoagulant in a uremic dog model, and in contrast to heparin it maintains the platelet count and improves the ultrafiltration rate during hemodialysis.

Animals↗
PubMed1980

Renal renin responses to changes in volume status and perfusion pressure.

The effects on juxtaglomerular apparatus (JGA) renin activity of maneuvers known to acutely alter renin secretory rates were studied in rats. Five groups of rats were studied: group I: control; group II: 1% volume expansion; group III: 10% volume expansion; group IV: hypotensive hemorrhage; and group V: aortic clamping. Superficial (S) JGA renin activity was decreased in group II and further decreased in group III. Deep (D) JGA renin activity did not change. After hypotensive hemorrhage both S- and D-JGA renin activity increased. Similar results were seen after aortic clamping, although the increase in D-JGA renin activity was significantly less. These results indicate that S- and D-JGA renin activity may be under the control of different stimuli and may vary independently. They also support the concept that acute changes in renin secretion may be related to changes in renin synthesis.

Animals↗