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Biomedical subjects

J F Maher

Publications and source records attributed to J F Maher.

At least 91 records · Page 5Linked to original sources
PubMed1977

Principles of dialysis and dialysis of drugs.

Consideration of the interactions of drugs and dialysis must include an understanding of the mechanisms of transport during dialysis, i.e., diffusion, ultrafiltration and membrane-protein binding effects. Clearance is a function of molecular size, blood and dialysate flow, membrane area and permeability, and dialyzer support geometry. Protein binding and hematocrit decrease the in vivo clearances in comparison to those measured in vitro with aqueous solutions. The effect on the serum half-life is also determined by the distribution space and clearance by other routes. Other factors such as metabolic alterations of dialysis can affect pharmacologic activity, and the clinical response is the end product of many determinants. Numerous drugs are effectively removed by hemodialysis or at a slower rate by peritoneal dialysis, which occasionally allows considerable influx. The influence of intestinal contents on elimination rates by peritoneal dialysis is unknown. Peritoneal dialysis can be influenced considerably by vasoactive drugs.

Animals↗
PubMed1977

Isoproterenol enhancement of peritoneal permeability.

As peritoneal dialysis is inefficient enouth to be time-consuming and sometimes clinically ineffective, we have evaluated pharmacologic enhancement of peritoneal permeability. Peritoneal dialyses were performed in New Zealand white rabbits by instillation of 50 ml/Kg of isotonic dialysis solution of standard composition. Mean peritoneal clearance of creatinine was 0.60 ml/Kg/min and urea was 0.80 ml/Kg/min, each decreasing as intraperitoneal dwell was prolonged (by .011 ml/Kg/min or less). With 0.04 micrometer/Kg of isoproterenol administered intraperitoneally, clearances increased to 0.91 and 1.30 ml/Kg/min (p less than 0.01). When isoproterenol was added to the dialysis solution one hour or more before instillation, the increment in clearances was less. Instillation of dialysis solution 24 hours after addition of a higher dose of isoproterenol (0.2 micrometer/Kg) did not increase clearances above control. No effect of isoproterenol on bulk flow of water, associated with the osmotic effect of dextrose, was demonstrated. As peritoneal clearances increased, the ratio creatinine clearance: urea clearance did not decrease, consistent with increased peritoneal permeability as well as blood flow.

Animals↗
PubMed1977

Effect of intraperitoneal diuretics on solute transport during hypertonic dialysis.

Hypertonic periotoneal dialysis in New Zealand white rabbits results in increased dialyzate volume, but the sodium content of net ultrafiltrate is 109.5 MEq/l, less than extracellular fluid sodium concentration. With intraperitoneal furosemide, mean net ultrafilrate sodium concentration increased significantly to 121.2 mE1/l while ethacrynic acid had no such effect and both drugs affected dialyzate volume very slightly. Hypertonic peritoneal dialysis increased urea clearance significantly above isotonic dialysis and the addition of ethacrynic acid increased clearances further (P LESS THAN.02). Added furosemide decreased urea clearances suggesting that the effect on sodium transport is not an overall permeability change. During isotonic peritoneal dialysis, furosemide increased peritoneal permeability, i.e. urea and creatinine clearances, but a significantly higher urea clearance resulted from intraperitoneal ethacrynic acid. Furosemide influx clearance average 0.31 ml/kg/min, a mean of 27 percent of the urea clearance. The data suggest that furosemide may be useful to prevent the hypernatremia that may complicate hypertonic peritoneal dialysis, but is not as efficacious as other vasoactive drugs in enhancing peritoneal permeability.

Animals↗
PubMed1976

The clinical spectrum of ascites associated with maintenance dialysis.

Among 197 patients being treated with maintenance dialysis, six were found to have ascites. Unlike previous reported series, the cause of ascites and the clinical course were variable. Two patients responded to definitive therapy directed against the specific cause. No consistent association was found with the etiology of renal disease or therapy of uremia including the duration of hemodialysis or prior peritoneal dialysis. Nonspecific therapy attempting to alleviate ascites was unsatisfactory. Severe hypertension was not characteristic and bilateral nephrectomy did not influence the course. An extensive diagnostic evaluation is recommended along with skepticism before declaring that idiopathic, refractory ascites exists signaling progressive deterioration.

Adult↗
PubMed1976

When should maintenance dialysis be initiated?

The present trend towared the use of maintenance dialysis in earlier stages of chronic renal failure, and more frequently in association with other morbid illness, raises the question of how well we understand the natural history and prognosis of chronic renal failure prior to total loss of renal function. Survival after serum creatinine exceeds 10 mg/dl is not necessarily very brief and is influenced by many variables. Morbidity and rehabilitation are poorly defined terms that should be approached as objectively and quantitatively as possible if the benefits of dialysis are to be assessed meaningfully.

Creatinine↗
PubMed1976

Detrimental effects of ultrafiltration on diffusion in coils.

Previous studies in dialysis coils have suggested decreases in diffusive transport with ultrafiltration. The present studies were designed to test whether increasing blood channel width, alterations in concentration gradients, or molecular sieving at high ultrafiltration rates might explain the phenomenon. Increases in blood channel width and molecular sieving can account only in part for the decreases in diffusion observed. The results suggest that ultrafiltration causes alterations in transmembrane concentration gradients from blood to bath presumably associated with solute accumulation on the bath side of the membrane or may alter bath flow kinetics. Increases in total dialysance with ultrafiltration would be even greater if decreases in diffusive transport could be prevented.

Diffusion↗
PubMed1976

Tin-protein binding kinetics in normal and uremic plasma and its effect on dialysis fluxes.

A high affinity of plasma protein for tin has been demonstrated by ultrafiltration studies. At physiologic concentrations, UF/P remained below 1%, consistent with more than 99% binding. Binding of tin was nearly complete despite a decrease in plasma protein concentration to 3.5 Gm% and an increase in plasma tin by 80 mg/L. This binding inhibits efflux of tin from plasma during dialysis while influx occurs readily. This may be a mechanism for accumulation of tin in patients undergoing maintenance hemodialysis. A mechanism for tin chelation could be clinically beneficial in the syndrome of dialysis dementia.

Blood Proteins↗
PubMed1975

Prognosis of chronic renal failure. III. Survival after one peritoneal dialysis.

Survival after serum creatinine exceeded 10.0 mg/100 ml was increased if one peritoneal dialysis was performed. After one peritoneal dialysis 'survival' of 62 patients to the present time, death or the next dialysis averaged 119 days; median survival was 28 days. Characteristics of prolonged survivors were persistent reduction of serum creatinine below the predialysis concentration, tubulointerstitial diseases, i.e. polycystic kidneys, pyelonephritis or obstructive nephropathy, potentially reversibel complications such as urinary tract infection or extracellular volume depletion, and high urine volume, and low blood pressure. Occasional pateints with survival exceeding 2 years suggest the possibility of prolonged benefit after a single dialysis at least in those wiht characteristics favoring longer survival.

Blood Pressure↗
PubMed1975

Influence of peritoneal dialysis on factors affecting oxygen transport.

To determine the effect of changing concentrations of uremic metabolites on factors affecting oxygen transport, without the effects of extracorporeal blood pumping, we studied five patients before, during and after peritoneal dialysis. Significant decreases in serum urea, creatinine and phosphate and increase in serum bicarbonate were not associated with changes in P50, a reflection of hemoglobin-oxygen affinity. High erythrocyte 2,3-DPG concentrations decreased only slightly. Arterial pO2 increased slightly as negative fluid balance was achieved. The slight changes in oxygen transport parameters with dialysis suggest an interplay of compensatory factors and do not warrant modifying dialysis to limit the correction on acidosis or hyperphosphatemia. Effects on hemoglobin and pO2 resulting from fluid loss can be the dominant influence of peritoneal dialysis on tissue oxygenation.

Creatinine↗
PubMed1975

NaHCO3 and NaC1 tolerance in chronic renal failure.

In patients with chronic renal failure, NaHCO3 therapy may correct or prevent acidemia. It has been proposed that the NaHCO3 required will not result in clinically significant Na retention comparable to that from similar increases in NaC1 intake. In each of ten patients with chronic renal failure, creatinine clearance (Ccr) range 2.5-16.8 ml/min, on an estimated 10-meq Na and C1 diet, electrolyte excretion was compared on NaHCO3 vs NaC1 supplements of 200 meq/day. Periods of NaHCO3 and NaC1 (in alternate order for successive patients) lasted 4 days, separated by reequilibration to base-line weight. Mean +/- SEM excretion (ex) of Na, C1, and HCO3 and deltaCcr and deltaweight (day 4-1) are compared below for the 4th day of NaC1 vs. NaHCO3 intake. Mean Ccr +/-SEM on day 4 of NaC1 and NaHCO3 were 10.8 +/-1.6 and 9.0 +/-1.4 ml/min, respectively (P less than 0.02). Mean systolic blood pressure (but not diastolic) increased significantly on NaC1 (P less than 0.05). No significant blood pressure changes were seen on NaHCO3. Net positive HCO3 balance occurred on NaHCO3 as indicated above and reflected a rise in mean serum HCO3 from 19 to 30 meq/liter (day 1 vs. 4) (P less than 0.01). Mechanisms for the greater excretion of Na on NaHCO3 may relate to C1 wasting as noted above on low C1 intake and limited HCO3 reabsorptive capacity. Thus, Na excretion by day 4 was greater on NaHCO3 than on NaHCO3 did Na excretion near intake (210 meq/day).

Adolescent↗
PubMed1975

Prognosis of chronic renal failure. II. Factors affecting survival.

After serum creatinine levels exceeded 10mg/100ml, median survival was 55 days (to death or dialysis) in a group of 112 patients with chronic renal disease. Renal failure was partially reversible in 29 patients, partially accounting for prolonged survival. Those with polycystic kidneys, pyelonephritis, or obstructive nephropathy survived longer,partially because of more frequent reversibility and a slower increase in serum creatinine concentration. Kiabetic nephropathy, myelomatous kidneys, and amyloidosis were associated with shorter survival, less frequent reversibility, and more rapid progression. Urinary infection and extracellular volume depletion often accounted for partially reversible renal failure and prolonged survival. Blood pressure and age were not prognostic variables, while coexistent heart failure shortened survival. Survival correlated significantly with sodium excretion.

Adult↗
PubMed1975

Dialysance and clearance measurements during clinical dialysis-a plea for standardization.

Mass transfer and dialysance measurements were determined using (1) whole blood solute concentrations with blood flow rates, (2) plasma solute concentrations with plasma flow rates, and (3) plasma solute concentrations with whole blood flow rates by standard formulas during 30 clinical hemodialyses. Resulting values by these three methods were compared for potassium, urea, and creatinine. The three techniques yield significantly different values and, accordingly, the type of measurement must be specified before such clinical measurements of solute transport are interpretable. Multiple mechanisms to account for the differences are suggested and include minimal or no immediate effect of a single coil blood transit on intracellular solute concentrations for all solutes studied.

Blood Flow Velocity↗
PubMed1975

Effect of hemodialysis on factors influencing oxygen transport.

Ten patients underwent 4 study hemodialyses, one with standard dialysis conditions, one with an isophosphate dialysate, one with simultaneous ammonium chloride loading, and other, after pretreatment, with sodium bicarbonate. Measurement of hemoglobin oxygen affinity (P-50), erythrocyte 2,3-DPG, blood-gasses, and serum chemistries revealed biochemically effective hemodialyses and slight changes in oxygen transport parameters. The P-50 (in vivo) values decreased slightly but significantly (p greater than 0.05) with dialysis. When corrected to pH 7.4, eliminating the Bohr effect, P-50 increased (p greater than 0.05). With unmodified dialysis elevated values of 2,3-DPG (in comparison to normal) decreased, a change that did not correlate with delta-p-50, delta-serum phosphate, or delta-serum creatinine. With standard and isophosphate dialyses Po-2 decreased significantly. The decrease correlated with delta-hydrogen ion concentration and did not occur with dialyses designed to maintain pH constant. Thus, hemodialysis influences many factors that affect oxygen transport in different and counterbalancing directions. These changes are not totally explained by alterations in 2,3-DPG, pH or serum phosphate. Maintenance of acidosis or hyperphosphatemia during dialysis is not recommended.

Adolescent↗