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Biomedical subjects

T W Gehr

Publications and source records attributed to T W Gehr.

33 records · Page 2Linked to original sources
PubMed1994

Hormonal, blood pressure, and peritoneal transport response to short-term ACE inhibition.

OBJECTIVES: To evaluate the hormonal, blood pressure, and peritoneal transport effects of intraperitoneal enalaprilat and oral enalapril. DESIGN: A nonrandomized, nonblinded, prospective clinical trial was performed. SETTING: The study was conducted at the Clinical Research Unit at the Medical College of Virginia, a tertiary care center. PATIENTS: Six continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension were enrolled in the study. All 6 patients received intraperitoneal enalaprilat. Five of the patients also received oral enalapril. INTERVENTIONS: Hormonal, clinical, and transport parameters were investigated in patients given intraperitoneal enalaprilat and oral enalapril. Standardized 2-L exchanges were performed during a control period, following 2.5 mg intraperitoneal enalaprilat and after a week of oral enalapril. Inulin, blood urea nitrogen (BUN) and creatinine clearances, and glucose absorption were determined during these exchanges. RESULTS: After intraperitoneal enalaprilat, both systolic and diastolic blood pressure significantly declined, reaching maximal decreases of -21.7 +/- 14.2% at 95 +/- 92 minutes, and of -23.3 +/- 15.4% at 105 +/- 105 minutes, respectively. Plasma angiotensin converting enzyme (ACE) activity was suppressed below detectable limits at four hours following intraperitoneal enalaprilat, and remained suppressed throughout all sampling time points following oral enalapril treatment. There was no significant change in drain volumes, glucose absorption, or BUN, creatinine, or inulin clearances, whether enalaprilat was administered intraperitoneally or enalapril orally. CONCLUSION: This study demonstrates that intraperitoneal administration of enalaprilat is a rapidly effective route of administration of this ACE inhibitor. There were no changes in peritoneal transport characteristics demonstrated.

Administration, Oral↗
PubMed1994

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone.

Administration, Oral↗
PubMed1993

The pharmacokinetics and pharmacodynamics of fosinopril in haemodialysis patients.

The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium (a new angiotensin-converting enzyme (ACE) inhibitor), were investigated in six haemodialysis patients. Intravenous 14C-fosinoprilat (7.5 mg), oral 14C-fosinopril sodium (10 mg) and oral fosinopril sodium (10 mg) were administered in an open-label, randomized study. Mean maximum concentration (Cmax), clearance (CL), volume of distribution at steady-state (Vss), mean residence time (MRTiv), and t1/2 values after IV administration of 14C-fosinoprilat were 2,042 micrograms.ml-1, 11.3 ml.min-1, 11.0 l, 16.3 h and 28.3 h, respectively. Following oral administration of 14C-fosinopril, mean Cmax, time to maximum plasma concentration (tmax), and fosinoprilat bioavailability values were 197 ng.ml-1, 5.2 h and 29.2%. Para-hydroxy fosinoprilat and fosinoprilat glucuronide comprised approximately 15% and 2% of radioactivity recovered in faeces. Four hours of haemodialysis only cleared approximately 1.5% of the administered dose. The maximum effect (Emax) model was fitted to the percentage inhibition of serum ACE activity vs. fosinoprilat concentration data in three patients. Emax ranged from 95.3 to 102.5%, and IC50 (the fosinoprilat concentration required to produce 50% of Emax) ranged from 2.6 to 4.2 ng.ml-1. Pharmacokinetic variables of the patients were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dosing following dialysis are unnecessary.

Administration, Oral↗
PubMed1993

The peritoneal equilibration test in children.

Eight children, aged 15 months to 17 years 9 months, maintained by continuous ambulatory peritoneal dialysis (CAPD)/continuous cycling peritoneal dialysis and nine adults, aged 20-59 years, managed by CAPD were compared using a standardized peritoneal dialysis protocol, the peritoneal equilibration test (PET). The peritoneal glucose concentration tended to equilibrate with the serum glucose more rapidly in children, but the percentage of the glucose load absorbed was not different between the two age groups. There was an inverse trend between the percentage of glucose absorbed and age in children. Peritoneal creatinine clearance scaled to surface area in children was significantly less than that of the adults; however, the clearances became similar when adjusted for body weight. Peritoneal creatinine clearance scaled to surface area bore a positive and significant relationship to age which, when expressed per kilogram body weight, disappeared. Children had a significantly higher dialysate/plasma (D/P) creatinine ratio after the first 2 h of the PET, but this ratio approached unity by 4 h and was not different from adults. The fractional change in the creatinine D/P ratio during the PET was not different between the two age groups. Drain volume adjusted to surface area was significantly less in children than adults. This difference was reversed when drain volume was factored by weight. Similarly drain volume scaled to surface area demonstrated a significant and positive relationship to age, which disappeared when drain volume was expressed per kilogram body weight. Ultrafiltration, whether factored by weight or scaled to surface area, did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

External-standard high-performance liquid chromatographic method for quantitative determination of furosemide in plasma by using solid-phase extraction and on-line elution.

A rapid and simple external-standard high-performance liquid chromatographic (HPLC) method has been developed for the determination of the concentration of furosemide in plasma. The analyte is extracted with a C-2 ethyl sorbent. On-line elution of the analyte into the HPLC system is accomplished with an advanced automated sample processor (Varian). Furosemide is quantified by fluorescence detection within a linear range of 25 to 1000 ng/mL (average correlation coefficient, 0.9998), with a limit of detection of 1.8 ng/mL. Both internal- and external-standard procedures were evaluated, and the external-standard procedure demonstrated superior characteristics. The external-standard procedure was precise to within a relative standard deviation of 8% and accurate with less than 3% error throughout the concentration range studied. The external-standard HPLC method was used to analyze the concentration of furosemide in greater than 1000 plasma samples obtained from patients with either normal kidney function or renal failure who had received furosemide either orally or intravenously in an experimental setting.

Aged↗
PubMed1991

Fosinopril pharmacokinetics and pharmacodynamics in chronic ambulatory peritoneal dialysis patients.

The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng.ml-1, 4.8 h, and 3.19 micrograms.h.ml-1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng.ml-1, tmax of 9 h, and AUC of 18.1 micrograms.h.ml-1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml.min-1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.

Adult↗
PubMed1991

Metolazone pharmacokinetics and pharmacodynamics in renal transplantation.

Metolazone pharmacokinetics and pharmacodynamics were investigated in five renal transplant patients and five creatinine clearance matched controls. Whereas the time to peak metolazone excretion was similar in both groups (with the exception of one renal transplant patient who subsequently was found to have chronic rejection), the percent of the administered dose excreted over 48 h was significantly less in renal transplant patients (8% in renal transplant patients vs 24% in controls). Diminished bioavailability of metolazone or tubular secretion likely accounted for this disparity in metolazone excretion. Both groups developed diuretic tolerance as indicated by hysteresis in the dose response relationship. Cumulative sodium excretion over three successive 12-h time intervals did not differ between groups. Despite this comparable natriuresis, potassium excretion was significantly less in the renal transplant patients during the first day of the study. Accordingly, metolazone administration may provide a means to "unmask" subclinical, tubular secretory dysfunction in the transplanted kidney, as exemplified by defects in metolazone secretion and potassium excretion.

Adult↗
PubMed1989

Triamterene and the kidney.

Triamterene (TA) is a mild 'potassium-sparing' diuretic usually employed in combination with other more potent diuretics in the treatment of hypertension. TA pharmacokinetics and pharmacodynamics in normal volunteers, elderly subjects and in patients with renal and hepatic dysfunction are reviewed. A variety of adverse renal effects, such as abnormalities in urinary sediment, nephrolithiasis, interstitial nephritis and acute renal failure, has been reported to occur and is also reviewed. Of particular concern with the increased availability of 'over-the-counter' nonsteroidal anti-inflammatory medications (NSAID) is the adverse interaction between TA and NSAID which may culminate in acute renal failure. Although a rare occurrence, the clinician should be aware of potential adverse reactions associated with the use of TA.

Humans↗
PubMed1988

Furosemide pharmacokinetics and pharmacodynamics in renal transplantation.

Furosemide was administered intravenously to four patients who had undergone renal transplantation in the past and four creatinine clearance--matched control subjects. Both patients who had undergone renal transplant and control subjects displayed similar pharmacokinetic and pharmacodynamic behavior, as assessed by drug delivery to the urine and sodium excretion, respectively. Despite similar degrees of natriuresis, patients who had undergone renal transplantation demonstrated a clear defect in urine potassium excretion. This defect in potassium excretion was not related to altered responsiveness of the renin-angiotensin-aldosterone axis because plasma renin activity increased in a normal fashion after furosemide in both control and transplant subjects. Although the plasma aldosterone response to increases in plasma renin activity was sluggish in patients undergoing renal transplantation, normal increases in plasma aldosterone levels were achieved in both groups, suggesting that there may be an intrinsic defect in distal tubular potassium secretion that can be unmasked by furosemide.

Adult↗
PubMed1987

Case report and review of the literature: ureteral endometriosis.

Endometriosis is a common disorder affecting women of all ages. Although urinary tract involvement is not uncommon, ureteral obstruction is an infrequent complication of endometriosis. A case is reported of acute renal failure caused by bilateral ureteral obstruction resulting from extensive pelvic endometriosis. All reported cases of ureteral endometriosis are reviewed with special emphasis on bilateral ureteral involvement. Physicians need to be aware of this reversible complication of endometriosis.

Acute Kidney Injury↗
PubMed1978

New hydrophilic copolymers for biomedical applications.

New hydrophilic copolymers with controlled number of surface hydroxyl groups were prepared using gamma-irradiation. The method involved the copolymerization of 2 monomers of varying feed ratio, using gamma-irradiation from a Cobalt60 unit, followed by partial or full hydrolysis (methanolysis), which leads to linear copolymers of simple structure with surface hydroxyl groups. These surfaces were further heparinized using covalent bonds through acetal bridges between heparin and surface hydroxyl groups. In systems of VAc and NVP, the feed ratio varied between 0.1--0.5 and the irradiation dose between 1--5 megarads. The copolymers obtained by this method were analyzed for nitrogen to establish their chemical structure. The reactivity ratios (r1 and and r2) were determined as 0.322 and 3.26, respectively, and curves of copolymer composition versus feed ratio were constructed. Upon hydrolysis swelling ratios of up to 24 were determined and reported as a function of copolymer hydroxyl composition. These hydrogels of PVA copolymers were heparinized by covalent binding of heparin on the hydroxyl groups and elution of heparin in flow was studied.

Heparin↗
PubMedDate not supplied

Direct vasodilators and their role in hypertension management: minoxidil.

Minoxidil is a direct vasodilator that has been in use for over two decades. It is used primarily to reduce blood pressure in hypertensives who have been poorly controlled on various multidrug regimens. Although minoxidil is extremely effective, its usefulness is limited by its tendency to increase the pulse rate and to trigger salt and water retention. The latter may be incapacitating in some patients. Therefore, minoxidil is typically administered with both a diuretic and an agent that can control the pulse rate, such as a beta blocker. Minoxidil has several other side effects that may limit its use, including hypertrichosis, aggravation of myocardial ischemia and/or left ventricular hypertrophy, and (infrequently) pericardial effusions. If a patient's hypertensive pattern is sufficiently severe to warrant contemplation of minoxidil therapy, referring the patient to a hypertension specialist should be strongly considered. (c) 2001 by LeJacq Communications, Inc.

Humans↗
PubMedDate not supplied

Replacement of amino acid and protein losses with 1.1% amino acid peritoneal dialysis solution.

OBJECTIVE: Losses of nutrients into dialysate may contribute to malnutrition. Peritoneal dialysis (PD) patients are reported to lose 3-4 g/day of amino acids (AAs) and 4-15 g/day of proteins. The extent to which one exchange with a 1.1% AA dialysis solution (Nutrineal, Baxter, Deerfield, IL, U.S.A.) offsets these losses was investigated in a 3-day inpatient study in 20 PD patients. DESIGN: Simple, open-label, cross-over study on consecutive days in a clinical research unit. On day 1 all patients were given a peritoneal equilibration test (PET). On day 2 they received 1.5% dextrose Dianeal (Baxter) as the first exchange of the day and their usual regimen thereafter. On day 3, the first exchange of the day was the 1.1% AA solution in place of 1.5% Dianeal and the usual PD regimen thereafter. On days 2 and 3 all dialysate effluent was collected and analyzed for AAs and proteins. Patients were maintained on a constant diet. RESULTS: Losses of AAs and total proteins on day 2 were 3.4 +/- 0.9 g and 5.8 +/- 2.4 g, respectively, totaling 9.2 +/- 2.7 g. The net uptake of AAs on day 3 was 17.6 +/- 2.6 g (80 +/- 12% of the 22 g infused). Mean gains of AAs on day 3 exceeded losses of proteins and AAs on day 2, p < 0.001. Losses of total proteins, but not losses of AAs, and the net absorption of AAs from the dialysis solution were correlated directly with peritoneal membrane transport characteristics, obtained from the PET. CONCLUSION: Daily losses of AAs and proteins into dialysate are more than offset by gains of AAs absorbed from one exchange with 1.1% AA-based dialysis solution. Net gains of AAs exceeded losses of proteins and AAs in all patients studied. The difference was relatively constant across a wide range of membrane transport types. Net AA gains were approximately two times the total AA and protein losses.

Adult↗