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Biomedical subjects

D Brown-Cartwright

Publications and source records attributed to D Brown-Cartwright.

8 recordsLinked to original sources

Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis.

Using radiopaque markers, we evaluated gastric emptying in 10 male patients with end-stage renal disease on continuous ambulatory peritoneal dialysis and in 15 normal men. Dialysis patients were studied twice, once without peritoneal dialysate in the abdomen (drained) and once with 2 L of dialysate in the abdomen (full). Each normal man and 9 of 10 dialysis patients, when drained, emptied all 10 markers by 6 h after a test meal. In contrast, 5 of the 10 dialysis patients, when full, had delayed emptying of radiopaque markers. Thus, continuous ambulatory dialysis may delay gastric emptying of indigestible solids.

Adult

Effect of high-dose etodolac on renal function.

Previous studies from our laboratory have demonstrated transient effects on renal function by etodolac, 200 mg b.i.d. The current study assessed the effects of a larger dose of etodolac (500 mg b.i.d.) to explore the time course of its renal effects and to determine whether the transient effect would become more prolonged with a larger dose. We studied 10 normal subjects and nine patients with renal insufficiency, examining the effects of the first 500 mg dose of etodolac as well as 4 days of b.i.d. administration. In both groups, etodolac transiently decreased fractional excretions of sodium and chloride and urinary prostaglandin E2. In patients, etodolac also transiently decreased inulin and para-aminohippuric acid clearances and urinary 6-keto-prostaglandin F1 alpha. Chronic administration caused no changes in renal function in either group. In summary, in this relatively small group of patients, high-dose etodolac caused only transient, fully reversible effects on renal function, the cumulative effect of which was negligible.

6-Ketoprostaglandin F1 alpha

Reversible acute decrease in renal function by NSAIDs in cirrhosis.

The effects of sulindac were compared with those of ibuprofen or naproxen on creatinine clearance and urinary prostanoids in patients with severe alcoholic cirrhosis. Sulindac caused acute declines in all renal parameters in four of five patients. The effect occurred with serum concentrations of the active sulfide metabolite comparable to those in patients with no hepatic impairment. The patient who was not affected had less effects on urinary PGE2 and TxB2 and no effect on 6-keto PGF1 alpha. In this patient, dosing with ibuprofen caused pronounced declines in all urinary prostanoids and a decrease in creatinine clearance. Two other patients treated with ibuprofen and one treated with naproxen also suffered decrements in all parameters. In conclusion, sulindac had suppressant effects on renal prostanoids associated with declines in creatinine clearance in these patients with cirrhosis, indicating a need for similar cautions with its use as with other NSAIDs.

Acute Disease

Effects of nonsteroidal antiinflammatory drugs on renal function in patients with renal insufficiency and in cirrhotics.

We have assessed the effects of acute and chronic administration of etodolac, ketoprofen, and indomethacin on renal function in patients with mild to moderate chronic renal insufficiency (CRI). We studied 18 normal volunteers and 24 patients with CRI due to hypertension and/or diabetes mellitus with creatinine clearances between 19 and 83 mL/min/1.73 m2. Clearance studies were performed with the first dose of nonsteroidal antiinflammatory drug (NSAID) to compare acute effects of the agent with a no-drug control. Subjects then received the NSAID for three to five days and, on the last day of study, underwent another clearance study to assess the effects of a single dose of NSAID superimposed on chronic dosing. With each dose of each NSAID, inulin and paraaminohippurate (PAH) clearances and fractional excretion of NA+ decreased. However, the baseline control collections after chronic dosing did not differ from the no-drug control periods. Hence, the decline in renal function with each dose is transient, and no overall adverse effect on renal function occurred with chronic dosing. In five patients with cirrhosis, we assessed the renal sparing effects of sulindac. After equilibration on a fixed sodium intake, they received a 200-mg dose of sulindac. In one patient, no adverse effect occurred; the remaining patients suffered declines in creatinine clearance of 29%, 87%, 37%, and 37%, respectively. This effect was transient and returned to control values six to eight hours after sulindac administration. At the time of maximal depression of renal function, serum concentrations of sulindac sulfide were comparable to those in subjects with normal hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Response to furosemide in chronic renal insufficiency: rationale for limited doses.

Patients with renal insufficiency often undergo therapy with large doses of loop diuretics. We tested the hypotheses that remaining nephrons respond normally to amounts of diuretic reaching them, and that more limited doses than are commonly used are sufficient to reach effective portions of the dose-response curve. In eight patients with creatinine clearance less than 20 ml/min/1.73 m2, the amount of diuretic causing half-maximal response was identical to that in normal subjects, but the maximal response expressed as fractional excretion of sodium was increased approximately 60%. The upper plateau of the dose-response curve was attained with single intravenous doses of furosemide, 120 to 160 mg. In conclusion, remnant nephrons appear to demonstrate an exaggerated response to furosemide. Because maximal response was attained with single intravenous doses of furosemide of 120 to 160 mg, there appears to be no need to administer larger single doses in such patients.

Adult

Effects of acute and chronic dosing of NSAIDs in patients with renal insufficiency.

Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to patients with chronically impaired renal function has been reported to cause abrupt and sustained reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), and solute and water excretion in association with decreased renal prostanoid production. However, the time course of these acute effects and whether they are sustained during chronic exposure to the NSAIDs are unknown. Accordingly, using standard clearance and balance techniques, we investigated the effects of acute (zero to four hours) and chronic (five days) oral administration of two different NSAIDs on renal function in patients with stable, mild to moderate chronic renal insufficiency (CRI) and in normal subjects. In patients, acute oral administration of ketoprofen (K) and indomethacin (I) resulted in significant decreases in GFR (K: from 36 +/- 3 to 20 +/- 4 ml/min, P = 0.001; I: from 37 +/- 6 to 30 +/- 7 ml/min, P = 0.032; in RPF (K: from 194 +/- 21 to 146 +/- 21 ml/min, P = 0.002; I: from 222 +/- 33 to 147 +/- 18 ml/min, P = 0.016); and in urinary PGE2 excretion (K: from 0.60 +/- 0.25 to 0.08 +/- 0.02 ng/min, P = 0.05; I: from 0.34 +/- 0.06 to 0.18 +/- 0.06 ng/min, P = 0.042). Fractional excretion of sodium chloride and fractional free water clearance (CH2O/CIn) also decreased significantly after both agents. In normal subjects, GFR and RPF were not significantly decreased after acute dosing, whereas urinary PGE2 and fractional excretions of NaCl and free water decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of doxepin on basal gastric acid and salivary secretion in patients with duodenal ulcer.

We compared the effect of 50- or 100-mg doses of oral doxepin or a placebo on basal gastric acid secretion, salivary flow, and pulse rate in seven asymptomatic patients with chronic duodenal ulcer disease. Acid secretion and salivary flow were measured for four 1-hour periods beginning at 3.5, 5.5, 7.5, and 9.5 hours after medication, with plasma sampling for measurement of doxepin at the midpoint of each collection period. Compared to placebo, the 50- and 100-mg doses of doxepin reduced mean basal acid output by 46% and 37%, respectively. There was no significant difference in the effect of the 50- or 100-mg dose on acid secretion even though mean plasma concentrations of doxepin were higher with the 100-mg than with the 50-mg dose (p less than 0.01). Salivary flow was reduced by 62% and 84% with the 50- and 100-mg doses, respectively, whereas doxepin had no effect on mean pulse rate.

Adult

Effect of etodolac in patients with moderate renal impairment compared with normal subjects.

Twenty subjects (10 with normal renal function and 10 with moderate renal insufficiency) participated in an 8-day study to assess the effects of acute and chronic etodolac dosing on renal function. Subjects and patients were hospitalized and followed a controlled diet (150 mEq sodium, 60 to 80 mEq potassium) during the study. A 3-day drug-free period was followed by 4 days of etodolac, 200 mg b.i.d. Sodium balance and body weight remained unchanged in both groups. Modest reductions in renal function as measured by clearances of inulin and p-aminohippurate occurred acutely only in the patients with renal impairment. Chronic therapy resulted in no decrements in daily creatinine clearance. In an average effective anti-inflammatory dose, etodolac did not produce a sustained effect on renal function in either normal subjects or patients with moderate renal insufficiency.

Acetates