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Biomedical subjects

J F Maher

Publications and source records attributed to J F Maher.

At least 73 records · Page 4Linked to original sources

Prediction of radiographic severity of renal osteodystrophy by serum values.

Renal osteodystrophy, a frequent complication of chronic renal failure, is usually assessed by periodic X-rays of bone which are both poorly reproducible and expensive. Seeking a better screening test for osteodystrophy, we evaluated the usefulness of serum alkaline phosphatase as a predictor of bone disease and of hyperparathyroidism. Alkaline phosphatase, despite nonspecificity, correlates with the severity of osteodystrophy and with the increase in serum parathyroid hormone concentration. Serial measurements of alkaline phosphatase can predict changes in these parameters.

Adult↗

Effects of gastrointestinal hormones on transport by peritoneal dialysis.

Because the gastrointestinal hormones are known to dilate the splanchnic vasculature, their effects on transport of water and solutes during peritoneal dialysis were studied in an experimental model, the rabbit. In unanesthetized rabbits, dialysate volume was calculated by isotope dilution, and clearances were estimated by dialysate/plasma concentration ratio factored by minute volume. With isotonic dialysis solution, the mean increment in dialysate volume per minute of intraperitoneal dwell was 0.19 ml/kg/min, and mean clearances of creatinine and urea were 0.71 and 0.90 ml/kg/min, respectively. When administered intravenously, secretin significantly augmented osmotically induced water flux, but not when given intraperitoneally. Neither glucagon nor cholecystokinin affected dialysate volume. Intravenously, but not intraperitoneally, glucagon increased peritoneal clearances of creatinine and urea to more than 150% of control values. Neither cholecystokinin nor secretin augmented significantly peritoneal mass transport when given by either route. The data suggest that the site of acton is the endothelial surface of the membrane, that the mechanisms of augmenting transport involve increased permeability and/or surface area, and that agents which combine an increase in mass transport and capillary filtration coefficient may be clinically useful.

Animals↗

Divergent effects of catecholamines on peritoneal mass transport.

In rabbits, intravenous vasopressor doses of dopamine augmented peritoneal clearances of creatinine and urea, suggesting increased mesenteric blood flow and possibly augmented permeability. Intraperitoneal dopamine also accelerated peritoneal transport of urea. Solute transport across the peritoneum was decreased by intravenous infusion of 1-norepinephrine. Intraperitoneal administration of the alpha-adrenergic antagonist phentolamine partially abolished the augmentation of peritoneal clearances induced by intravenous dopamine. The results suggest that in patients undergoing peritoneal dialysis who require vasopressor therapy, dopamine should be preferred to norepinephrine.

Animals↗

Acceleration of peritoneal mass transport by drugs and hormones.

The major restrictions to the transport of solute and solvent across the peritoneum are the limited peritoneal blood flow, area and permeability. Recent investigations have demonstrated that several vasoactive drugs influence transport parameters. Isoproterenol, nitroprusside, dipyridamole and dopamine exemplify drugs that dilate the splanchnic vasculature, thereby augmenting transport, whereas vasoconstriction induced by l-norepinephrine decreases clearances. The tissue prostaglandins affect peritoneal mass transport in accord with their known vasoactive effects, suggesting a role in modulating peritoneal blood flow. The gastrointestinal hormones vasodilate the splanchnic circulation. Exposure of the endothelial surface to glucagon markedly increases peritoneal mass transport, while secretin increases the ultrafiltration rate significantly. These preliminary studies suggest the possible future clinical use of drugs and hormones to augment the efficiency of peritoneal dialysis.

Animals↗

Prediction of solute transport during peritoneal dialysis.

Solute transport, predominantly diffusion, across the peritoneum correlates inversely with molecular weight. Provided that the solute is water soluble, not protein bound, not of unusual density, not ionized, does not have a large hydration shell, and is transported from plasma to dialysate, the peritoneal clearance is predictable over the molecular weight range from 60 to 11,000 daltons. Transport reates that deviate from the predicted can be explained by known physical properties of particular solutes.

Animals↗

Therapy of iron deficiency anemia in patients on maintenance dialysis.

A controlled, prospective study compared the effectiveness of oral ferrous sulfate to intravenous iron dextran, each with and without concurrent intramuscular androgen for therapy of iron deficiency anemia in patients with chronic renal failure treated with maintenance hemodialysis. During the 12-week period of therapy, the patients who received oral ferrous sulfate and androgens showed an increment in their mean hematocrit of 16.3% and those who received oral ferrous sulfate alone had an increase of 8.3%. Patients treated with intravenous iron dextran androgens showed an increment in their mean hematocrit of 9.4% and those given iron dextran alone showed an increase of 3.5%. Serum ferritin levels increased with iron repletion but correlated inversely with the erythropoietic response. The serum ferritin assay provides a simple and reliable method to demonstrate iron repletion, and oral ferrous sulfate is the preferred method of iron repletion in compliant patients.

Administration, Oral↗

Inconsistency in radiographic evaluation of progressive renal osteodystrophy.

Five radiologists graded 49 series of bone X-rays of 20 patients with chronic renal failure treated by hemodialysis. There was a high incidence of osteodystrophy which progressed identifiably over intervals exceeding 12 months. The severity grade of osteodystrophy was poorly reproducible among patients, among radiologists, and even between interpretations by the same radiologist after an interval of 10 months. Although the severity of osteodystrophy correlated with serum alkaline phosphatase values, the latter was not an accurate predictor of the severity of the bone lesions. Radiographic reassessment at intervals of one year or less in the asymptomatic patient has less reproducibility than the anticipated changes. More sensitive and reliable techniques are recommended.

Alkaline Phosphatase↗

Augmentation of peritoneal mass transport by dopamine: comparison with norepinephrine and evaluation of pharmacologic mechanisms.

The effect of catecholamines on transport during peritoneal dialysis was studied in unanesthetized rabbits. Intravenous I-norepinephrine consistently decreased peritoneal clearances of urea and creatinine to 84% of control values or less but did not affect osmotically induced water flux. Comparable pressor doses of dopamine increased clearances of urea and creatinine to 145% of control values, whereas osmotic fluid flux increased only slightly. Dopamine also increased urea transport when administered intraperitoneally. The augmentation of solute transport by dopamine was unaffected by simultaneous administration of propranalol, was decreased by phentolamine, and was abolished by haloperidol. Dopamine may be preferable toI-norepinephrine when vasopressor therapy is required during peritoneal dialysis. The augmented transport with dopamine appears to depend on the action of dopamine receptors causing mesenteric vasodilation and in part on alpha-adrenergic receptors simultaneously increasing blood pressure while mesenteric blood flow is maintained.

Animals↗

Peritoneal dialysis in rabbits. A study of transperitoneal theophylline flux and peritoneal permeability.

Since vasodilators can restore toward normal the decreased peritoneal clearances associated with vascular disease, the influence of aminophylline on peritoneal solute transport was studied in unanesthetized rabbits. Mean control creatinine clearance was 0.56 ml/kg/min and urea clearance 0.80 ml/kg/min. Neither intraperitoneal nor intravenous aminophylline increased peritoneal clearances, nor did the ratio creatinine clearance/urea clearance change from the control value, 0.70. Bidirectional flux of theophylline occurred at clearances of 0.70 ml/kg/min efflux and 0.64 ml/min influx. The removal rate of theophylline was 0.05% min, allowing therapeutic removal of excess aminophylline and warranting supplemental therapy during dialysis if therapeutic theophylline concentrations are required. As the intraperitoneal aminophylline was well tolerated, this route can be considered for therapeutic administration.

Aminophylline↗

Augmented peritoneal mass transport with intraperitoneal nitroprusside.

Lightly restrained, alert New Zealand white rabbits underwent peritoneal dialysis by percutaneous instillation of standard dialysis solution with or without intraperitoneal nitroprusside. Corrected to a mean intraperitoneal dwell time of 36 minutes, mean clearances of creatinine and urea were 0.74 and 0.90 ml/kg/min in six rabbits. With intraperitoneal nitroprusside, 1.13 mg/kg clearances increased to 1.13 and 1.30 ml/kg/min (p less than 0.01) respectively. The 53% increment in creatinine clearance maintained the ratio clearance larger/smaller solute suggesting increased peritoneal permeability and/or area. Lower nitroprusside doses were less effective and not significantly above control. Nitroprusside also increased clearances during hypertonic peritoneal dialysis, but had no effect on osmotically induced water flux. Lavage studies demonstrated a persistent effect of nitroprusside after a single exposure and a sustained effect with repeated use.

Animals↗