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Biomedical subjects

J F Maher

Publications and source records attributed to J F Maher.

At least 55 records · Page 3Linked to original sources
PubMed1986

Contrasting effects of amphotericin B and the solvent sodium desoxycholate on peritoneal transport.

To distinguish amphotericin B effects on peritoneal transport from those of the solvent, sodium desoxycholate, dialyses in intact rabbits with either substance added intraperitoneally were compared to controls. Powered amphotericin B added to instilled dialysis fluid increased peritoneal ultrafiltration from 0.31 to 0.44 ml/kg/min (p less than 0.02), but did not affect mass transport (e.g. urea clearance changed from 0.86 to 1.04 ml/kg/min). In contrast, 10 mg of desoxycholate induced peritoneal irritation and raised clearances of urea (0.76-1.34 ml/kg/min), potassium, phosphate and dextrose, but did not affect ultrafiltration. Intraperitoneally, 1 mg/kg of desoxycholate changed clearances inconsistently, but lowered the ultrafiltration rate from 0.33 to 0.21 ml/kg/min. The dialysate-plasma dextrose gradient dissipated faster with 10 mg/kg of desoxycholate. Amphotericin B tended to raise ultrafiltration per osmotic gradient and mass transport of sodium. Selective increase in fluid flux results from amphotericin B, not its solvent.

Amphotericin B↗
PubMed1985

The mechanism of dextrose-enhanced peritoneal mass transport rates.

The mechanism whereby hypertonic dextrose affects peritoneal transport was investigated in a short-term model of peritoneal dialysis using alert intact rabbits. During control (1.5% dextrose) dialyses osmotic ultrafiltration was 0.28 mg/kg/min, the clearance of potassium was 0.98, urea 0.54, phosphate 0.32, and dextrose (reverse) 0.21 ml/kg/min. With 4.25% dextrose, the ultrafiltration rate increased to 0.73 ml/kg/min (P less than 0.02), but solute transport did not increase despite the added convective flux. The posthypertonic exchanges did not differ from control despite the effect of residual dialysate contaminating this peritoneal lavage. By indicator dilution residual volume averaged 12% of total dialysate volume. Acute volume expansion by intravenous dextrose after desoxycorticosterone acetate (DOCA) pretreatment increased the ultrafiltration coefficient, potassium and urea clearances significantly, and DOCA alone was ineffective. It is suggested that in uremic humans hypertonic dextrose dialysis increases peritoneal mass transport rates because the absorbed dextrose causes extracellular volume expansion that cannot be eliminated promptly. No evidence of a direct effect of dextrose augmenting peritoneal permeability was detected.

Animals↗
PubMed1984

Amphotericin selectively increases peritoneal ultrafiltration.

Because amphotericin B is known to affect transport rates across biologic membranes, the effects of this agent on transport parameters in an animal model of peritoneal dialysis were investigated. When amphotericin B in doses ranging from 0.5 to 25 mg/kg was instilled intraperitoneally with commercial dialysis solution, diffusive clearances of phosphate and urea did not differ from control values measured in the same animals, and only a modest increase in potassium clearance was detected. Ultrafiltration due to the osmotic gradient induced by the dextrose content of the dialysis solution increased significantly to 0.31 mL/kg/min with amphotericin B, compared with control values of 0.18 mL/kg/min. The drug did not affect dextrose transport and the osmotic gradient did not differ in the two groups. Hence, the ultrafiltration coefficient was higher with amphotericin B (14 microL/kg/min/mosm), than during control dialyses (6 microL/kg/min/mosm). Increased water flux was detected at the lowest dose and there was no dose relationship over the range studied. Amphotericin B may be the type of agent that will be clinically useful in patients with reduced peritoneal ultrafiltration capacity, and safer analogues should be explored.

Amphotericin B↗
PubMed1984

Ultrafiltration by hyperosmotic peritoneal dialysis fluid excludes intracellular solutes.

During peritoneal dialysis, progressive increments in the osmotic gradient increase ultrafiltration rate. Solute transport by convective flux is thereby raised but there is no preferential increase in potassium clearance. The data imply that ultrafiltrate derives from extracellular fluid alone. Mesothelial cells appear to resist solute and water flux in response to an immediately adjacent osmotic gradient.

Animals↗
PubMed1984

Pharmacokinetics in patients with renal failure.

Uremic patients manifest delayed elimination of many drugs prolonging the biological half-life, and impaired excretion of the metabolites of biotransformed drugs, some of which are toxic or biologically active. More subtle changes in bioavailability, distribution, metabolism and pharmacodynamics frequently occur, as well, rendering drug dosing hazardous, especially when the margin of safety is narrow. A review of the pharmacologic abnormalities of individual drugs exemplifies those that provide metabolic loads, those which can be eliminated by dialysis and those that can be used with the least risk. Restricting drugs use in uremic patients to unequivocal indications, limiting doses according to guidelines, restricting the duration of treatment, monitoring plasma drug levels, clinical observations and vigilant suspicion of toxicity would eliminate most toxicologic problems. Physicians must not, however, rely blindly on normograms and cookbook guidelines for dosing potentially toxic drugs.

Anti-Bacterial Agents↗
PubMed1982

Purification of bovine kidney and heart pyruvate dehydrogenase phosphatase on Sepharose derivatized with the pyruvate dehydrogenase complex.

Pyruvate dehydrogenase phosphatase has been purified to apparent homogeneity from mitochondrial extracts of both beef heart and beef kidney. An essential step in this three-step purification is affinity chromatography of a largely purified phosphatase fraction using Sepharose beads to which pyruvate dehydrogenase complex is covalently bound through the lipoic acid residues of the dihydrolipoyl transacetylase component of the complex. The purified phosphatase, which has a native relative molecular mass, Mr, of about 140000, is composed of two nonidentical subunits of Mr 89000 and 49000.

Animals↗
PubMed1981

Pathophysiology of renal hemodynamics.

The high blood flow rate/gram of kidney tissue supplies mainly the renal cortex. The net effect of the interaction of the renin-angiotensin system, the kallikrein-kinin system and prostaglandins is to autoregulate renal blood flow within a narrow range. Drugs and neurogenic factors also influence renal hemodynamics. The renal circulation responds to changes in extracellular fluid volume, and in cardiac output. Renal ischemia occurs readily as these parameters decrease and prompt correction of circulatory dynamics can restore renal blood flow and prevent tubular necrosis. With hypovolemia or heart failure, angiotensin II is a mediator of efferent arteriolar constriction promoting a proportionately greater fall in renal plasma flow than in glomerular filtration rate, thereby augmenting sodium reabsorption. With renal failure, glomerulotubular balance is affected conversely promoting sodium loss. Appreciating these distinctions allows recognition of inappropriate sodium retention or loss. With such data, prognosis can be estimated more accurately and attempts to restore circulatory dynamics can be guided.

Acute Kidney Injury↗
PubMed1981

Prediction of glomerular filtration rate by serum creatinine and beta 2-microglobulin.

The reciprocal of serum creatinine concentration (1/Cr) is often used to predict glomerular filtration rate (GFR). Serum creatinine also varies with age, size, and muscle mass, and so it may inaccurately estimate GFR. The reciprocal of serum beta 2-microglobulin (1/beta 2mu) has been proposed as an alternative estimator of GFR. This study compares 1/Cr and 1/beta 2mu as predictors of GFR as measured by 125I-iothalamate clearance (CIOT) and creatinine clearance (CCr) in 29 subjects with a wide range of age, size and kidney function, and including 12 chronic hemodialysis patients. 1/beta 2mu was a better predictor of CIOT (r=0.90) and CCr (r=0.87) than 1/Cr (r=0.50 and 0.78) was. In fact, in the nondialysis population, 1/beta 2mu predicted CIOT (r=0.86) about as well as CCr predicted CIOT (r=0.87). Beta 2mu was less dependent on body size than Cr and unlike Cr, was not influenced by dialysis and did increase as GFR decreased with age. Beta 2mu can be useful as an alternative clinical estimate of GFR, particularly when Cr is considerably influenced by factors other than renal function.

Adult↗