W. Flamenbaum - Academia.edu (original) (raw)
Papers by W. Flamenbaum
American Journal of Physiology-Legacy Content, 1973
The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from ... more The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
Kidney international. Supplement, 1976
Kidney International, 1975
Active and passive immunization to angiotensin in experimental acute renal failure. A number of s... more Active and passive immunization to angiotensin in experimental acute renal failure. A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin 11, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (CIN) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, CIN of one
Kidney International, 1972
Effect of renin immunization on mercuric chloride and glycerolinduced renal failure. The effect o... more Effect of renin immunization on mercuric chloride and glycerolinduced renal failure. The effect of immunizing rats with hog renin, inactivated renin, or crude renin-depleted renal substance on the development of mercuric chloride (4.7 mg/kg body wt, subcutaneously) or glycerol-induced (10 mI/kg body wt of 50% glycerol in water) myohemoglobinuric acute renal failure was studied. Rats exposed to these various immunization procedures were evaluated on either a routine diet or after dietary sodium loading. Effective renin immunization was determined by the demonstration of a suppressed pressor response to the infusion of exogenous hog renin. Additionally, serum from renin-immunized animals neutralized the pressor activity of hog renin injected into a normal rat and also inhibited angiotensin generation from the reaction between sheep renin substrate and either hog or rat renin. Saline loaded rats, regardless of immunization procedure, demonstrated significant amelioration of both mercuric chloride and glycerol-induced acute renal failure. Renal renin concentration was decreased only in saline loaded rats. Despite plasma renin activity depression to the level obtained with saline loading alone, renin immunization did not protect against the development of experimental renal failure. If the renin-angiotensin axis is etiologically related to the development of experimental acute renal failure, it appears that renal renin acting via a local intrarenal mechanism, rather than circulating renin, is the vasoactive mechanism. Effet de l'immunisation par la rénine sur l'insuffisance rénale induite par le chlorure mercurique ou le glycerol. L'effct de l'immunisation de rats par Ia rénine de porc, la réninc inactivée ou de l'extrait non purifié de rein ddplété dc réninc sur le développement de l'insuffisance rénale aigue induite par le chlorure mercurique (4,7 mg/kg poids corporel) ou dc celle, myohémoglobindetermine whether immunization against renin would serve to prevent rats from developing mercuric chloride or glycerol-induced acute renal failure and to further examine the role played by the renin-angiotensin axis in the developmental and sustained phases of acute renal failure in the rat. Methods
Journal of Clinical Investigation, 1971
concentration of serum albumin in proximal tubule fluid of normal rats and animals with aminonucl... more concentration of serum albumin in proximal tubule fluid of normal rats and animals with aminonucleoside nephrosis was studied using renal micropuncture techniques. Albumin was quantitated by an ultramicrodisc electrophoresis method capable of measuring 3 X 10'" g of albumin, in 10 nl volumes. With this sensitivity., only small samples of tubule fluid were required for analysis. Collectifn times could be kept short, therefore decreasing the opportunity for sample contamination with extraneous serum albumin. The measured mean concentration of albumin in proximal tubule fluid (1 mg/100 ml in females and 0.7 mg/ 100 ml in males) was somewhat lower than values reported by others, but even these values are apt to have been artifactually high as a result of animal preparation and trace contamination of samples during micropuncture. Rats injected with aminonucleoside of puromycin 4 days earlier, showed a significant increase in tubulefluid albumin concentration coincident with a fall in serum albumin concentration and a 43-fold increase in urine albumin concentration. Tubular absorption of albumin was small relative to that of water. Although albumin filtration was significantly increased over that in normal animals, the glomerular basement membrane still served as a highly efficient barrier to albumin transfer.
Journal of the National Medical Association, 1987
The Journal of laboratory and clinical medicine, 1982
The efficacies of low-dose heparin and low-dose heparin plus ticlopidine as anticoagulants during... more 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 re...
Clinical pharmacology and therapeutics, 1975
The effect of propranolol therapy on plasma renin activity and blood pressure control was evaluat... more The effect of propranolol therapy on plasma renin activity and blood pressure control was evaluated in 35 uremic patients receiving intermittent center-based outpatient hemodialysis. Patients were determined to be either compliant or noncompliant with therapy based on the steady-state predialysis plasma propranolol concentration. Noncompliance occurred with remarkable frequency and was associated with persistent hyperreninemia and poorly controlled hypertension. Blood pressure control was significantly better in compliant patients, in whom plasma renin activity was generally, but not universally, suppressed. Propranolol can be effectively used in the management of hypertensive dialysis patients, but steady-state plasma propranolol levels should be measured to assess compliance in patients apparently refractory to treatment.
Pharmacotherapy
Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop&qu... more Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop" class of diuretics. Since it is rapidly and almost completely absorbed after oral administration, oral and parenteral formulations have a similar pharmacokinetic profile. Peak plasma levels are achieved approximately 30 min after oral administration. The apparent half-life is 1.2-1.5 hr, and the volume of distribution is about 25 liters. Plasma clearance is 228-255 ml/min. Bumetanide is promptly and almost completely eliminated by metabolism of the butyl side chain and urinary excretion of the parent drug and its metabolites. The principle renal site of action is the ascending limb of the loop of Henle, with a minor effect on the proximal tubule. The drug causes decreases in both free water clearance (during water diuresis) and solute free water reabsorption (during hydropenia), increased fractional delivery of sodium chloride to the distal tubule and a natriuresis approaching 20% of...
The Orthopedic clinics of North America, 1978
Journal of Human Hypertension
Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, ... more Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of clinical hypertension, 1985
The antihypertensive effect of oral labetalol and propranolol were evaluated in 65 black and 75 w... more 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 stu...
The American journal of physiology, 1976
Previous studies of heavy metal salt-induced acute renal failure demonstrated abnormalities of fl... more Previous studies of heavy metal salt-induced acute renal failure demonstrated abnormalities of fluid and solute transport by nephron segments and alterations in glomerular filtration rate and renal hemodynamics. To determine the direct effects of uranyl nitrate (UN) or HgCl2 on ion transport, their effects were studied on the isolated urinary bladder of the turtle. Unidirectional 24Na+ and 36Cl- fluxes were measured across short-circuited bladders. The addition of 0.1 mM UN to the mucosal solution resulted in a 69.9 +/- 4% (SEM) decrease in short-circuit current (SCC) without change in transepithelial resistance. Net Na+ flux (7.95 +/- 0.81 mueq/h per 8 cm2) decreased by the same magnitude as the SCC, primarily due to a 5.75 +/- 0.76 mueq/h per 8 cm2 decrease in the mucosal- (M) to-serosal (S) Na+ flux. Net Cl- flux decreased also primarily due to a decrease in M-to-S Cl- flux. Addition of 0.4 mM UN to S did not measurably affect the SCC or ion fluxes. The addition of 10 muM HgCl2 i...
Journal of human hypertension, 1994
Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, ... more Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respecti...
Journal of human hypertension, 1994
One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension... more One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP...
Transactions - American Society for Artificial Internal Organs, 1984
Kidney international. Supplement, 1976
The American journal of physiology, 1979
The present studies examined the role of the renin-angiotensin system as a modifier of the renal ... more The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal...
Nephron, 1978
The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a signi... more The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.
American Journal of Hypertension, 1989
American Journal of Physiology-Legacy Content, 1973
The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from ... more The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.
Kidney international. Supplement, 1976
Kidney International, 1975
Active and passive immunization to angiotensin in experimental acute renal failure. A number of s... more Active and passive immunization to angiotensin in experimental acute renal failure. A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin 11, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (CIN) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, CIN of one
Kidney International, 1972
Effect of renin immunization on mercuric chloride and glycerolinduced renal failure. The effect o... more Effect of renin immunization on mercuric chloride and glycerolinduced renal failure. The effect of immunizing rats with hog renin, inactivated renin, or crude renin-depleted renal substance on the development of mercuric chloride (4.7 mg/kg body wt, subcutaneously) or glycerol-induced (10 mI/kg body wt of 50% glycerol in water) myohemoglobinuric acute renal failure was studied. Rats exposed to these various immunization procedures were evaluated on either a routine diet or after dietary sodium loading. Effective renin immunization was determined by the demonstration of a suppressed pressor response to the infusion of exogenous hog renin. Additionally, serum from renin-immunized animals neutralized the pressor activity of hog renin injected into a normal rat and also inhibited angiotensin generation from the reaction between sheep renin substrate and either hog or rat renin. Saline loaded rats, regardless of immunization procedure, demonstrated significant amelioration of both mercuric chloride and glycerol-induced acute renal failure. Renal renin concentration was decreased only in saline loaded rats. Despite plasma renin activity depression to the level obtained with saline loading alone, renin immunization did not protect against the development of experimental renal failure. If the renin-angiotensin axis is etiologically related to the development of experimental acute renal failure, it appears that renal renin acting via a local intrarenal mechanism, rather than circulating renin, is the vasoactive mechanism. Effet de l'immunisation par la rénine sur l'insuffisance rénale induite par le chlorure mercurique ou le glycerol. L'effct de l'immunisation de rats par Ia rénine de porc, la réninc inactivée ou de l'extrait non purifié de rein ddplété dc réninc sur le développement de l'insuffisance rénale aigue induite par le chlorure mercurique (4,7 mg/kg poids corporel) ou dc celle, myohémoglobindetermine whether immunization against renin would serve to prevent rats from developing mercuric chloride or glycerol-induced acute renal failure and to further examine the role played by the renin-angiotensin axis in the developmental and sustained phases of acute renal failure in the rat. Methods
Journal of Clinical Investigation, 1971
concentration of serum albumin in proximal tubule fluid of normal rats and animals with aminonucl... more concentration of serum albumin in proximal tubule fluid of normal rats and animals with aminonucleoside nephrosis was studied using renal micropuncture techniques. Albumin was quantitated by an ultramicrodisc electrophoresis method capable of measuring 3 X 10'" g of albumin, in 10 nl volumes. With this sensitivity., only small samples of tubule fluid were required for analysis. Collectifn times could be kept short, therefore decreasing the opportunity for sample contamination with extraneous serum albumin. The measured mean concentration of albumin in proximal tubule fluid (1 mg/100 ml in females and 0.7 mg/ 100 ml in males) was somewhat lower than values reported by others, but even these values are apt to have been artifactually high as a result of animal preparation and trace contamination of samples during micropuncture. Rats injected with aminonucleoside of puromycin 4 days earlier, showed a significant increase in tubulefluid albumin concentration coincident with a fall in serum albumin concentration and a 43-fold increase in urine albumin concentration. Tubular absorption of albumin was small relative to that of water. Although albumin filtration was significantly increased over that in normal animals, the glomerular basement membrane still served as a highly efficient barrier to albumin transfer.
Journal of the National Medical Association, 1987
The Journal of laboratory and clinical medicine, 1982
The efficacies of low-dose heparin and low-dose heparin plus ticlopidine as anticoagulants during... more 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 re...
Clinical pharmacology and therapeutics, 1975
The effect of propranolol therapy on plasma renin activity and blood pressure control was evaluat... more The effect of propranolol therapy on plasma renin activity and blood pressure control was evaluated in 35 uremic patients receiving intermittent center-based outpatient hemodialysis. Patients were determined to be either compliant or noncompliant with therapy based on the steady-state predialysis plasma propranolol concentration. Noncompliance occurred with remarkable frequency and was associated with persistent hyperreninemia and poorly controlled hypertension. Blood pressure control was significantly better in compliant patients, in whom plasma renin activity was generally, but not universally, suppressed. Propranolol can be effectively used in the management of hypertensive dialysis patients, but steady-state plasma propranolol levels should be measured to assess compliance in patients apparently refractory to treatment.
Pharmacotherapy
Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop&qu... more Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop" class of diuretics. Since it is rapidly and almost completely absorbed after oral administration, oral and parenteral formulations have a similar pharmacokinetic profile. Peak plasma levels are achieved approximately 30 min after oral administration. The apparent half-life is 1.2-1.5 hr, and the volume of distribution is about 25 liters. Plasma clearance is 228-255 ml/min. Bumetanide is promptly and almost completely eliminated by metabolism of the butyl side chain and urinary excretion of the parent drug and its metabolites. The principle renal site of action is the ascending limb of the loop of Henle, with a minor effect on the proximal tubule. The drug causes decreases in both free water clearance (during water diuresis) and solute free water reabsorption (during hydropenia), increased fractional delivery of sodium chloride to the distal tubule and a natriuresis approaching 20% of...
The Orthopedic clinics of North America, 1978
Journal of Human Hypertension
Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, ... more Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of clinical hypertension, 1985
The antihypertensive effect of oral labetalol and propranolol were evaluated in 65 black and 75 w... more 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 stu...
The American journal of physiology, 1976
Previous studies of heavy metal salt-induced acute renal failure demonstrated abnormalities of fl... more Previous studies of heavy metal salt-induced acute renal failure demonstrated abnormalities of fluid and solute transport by nephron segments and alterations in glomerular filtration rate and renal hemodynamics. To determine the direct effects of uranyl nitrate (UN) or HgCl2 on ion transport, their effects were studied on the isolated urinary bladder of the turtle. Unidirectional 24Na+ and 36Cl- fluxes were measured across short-circuited bladders. The addition of 0.1 mM UN to the mucosal solution resulted in a 69.9 +/- 4% (SEM) decrease in short-circuit current (SCC) without change in transepithelial resistance. Net Na+ flux (7.95 +/- 0.81 mueq/h per 8 cm2) decreased by the same magnitude as the SCC, primarily due to a 5.75 +/- 0.76 mueq/h per 8 cm2 decrease in the mucosal- (M) to-serosal (S) Na+ flux. Net Cl- flux decreased also primarily due to a decrease in M-to-S Cl- flux. Addition of 0.4 mM UN to S did not measurably affect the SCC or ion fluxes. The addition of 10 muM HgCl2 i...
Journal of human hypertension, 1994
Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, ... more Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respecti...
Journal of human hypertension, 1994
One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension... more One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP...
Transactions - American Society for Artificial Internal Organs, 1984
Kidney international. Supplement, 1976
The American journal of physiology, 1979
The present studies examined the role of the renin-angiotensin system as a modifier of the renal ... more The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal...
Nephron, 1978
The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a signi... more The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.
American Journal of Hypertension, 1989