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Biomedical subjects

J W Eschbach

Publications and source records attributed to J W Eschbach.

At least 55 records · Page 3Linked to original sources
PubMed1985

Erythropoietin kinetics in normal and uremic sheep.

Homologous erythropoietin (Ep)-rich plasma was infused into sheep to determine the kinetics of this hormone in a large animal model. Ep levels after infusion were measured by radioimmunoassay using a sheep standard. Twenty-seven infusions into normal (14), subtotally nephrectomized (11), and anephric (two) animals were analyzed according to a single-compartment model. The volume of distribution was also calculated, and compared with values obtained indirectly from measurement of chromium 51-labeled red blood cells. The data showed that the t1/2 of the infused hormone was approximately 9 hours and was independent of renal function. After multiple infusions, the t1/2 appeared to shorten. The volume of distribution for this hormone corresponded to the plasma volume of the animals. These studies suggest that Ep, if administered to patients with chronic renal failure, could be given infrequently with little dependence on renal function.

Anemia↗
PubMed1984

The anaemia of chronic renal failure in sheep: studies in vitro.

The presence of inhibitors which accumulate during uraemia has been postulated as a significant factor in the development of anaemia in chronic renal failure (CRF). To determine whether factors in uraemic serum depress erythropoiesis, samples were obtained from sheep prior to and after surgical induction of CRF. The sera were tested in vitro for their effect on erythroid colony growth. The sheep sera were substituted for fetal calf serum (30% concentration) in cultures of serotype-matched or autologous sheep marrow cells at optimal doses of erythropoietin (Ep). Forty-two paired sera from five animals were tested against normal (22) and uraemic marrow (20). In 7/42 random pairs, erythroid colony growth was decreased by 20% in the presence of uraemic serum when compared to a normal sample from the same animal. In the remainder of the cultures, uraemic sera stimulated or supported erythroid colony growth as well as normal sera. When the results were analysed individually, serum from only one of five animals showed minimal (10%) in vitro inhibition of erythroid colony growth. This study, performed in a prospective manner utilizing compatible target cells, disputes the hypothesis that uraemic toxins significantly inhibit in vitro erythropoiesis. These data correlate with the in vivo response to Ep in this sheep model, and suggest Ep would be effective in treating the anaemia of CRF.

Anemia↗
PubMed1984

The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo.

The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma may contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

Anemia↗
PubMed1983

A hemodialysis orientation unit.

A separate dialysis unit was created within an existing large dialysis unit for the purpose of segregating all new hemodialysis patients into an environment that would provide optimum instruction about self-care. An educational curriculum was presented to each patient during each dialysis over the first 2 months of dialysis. Depending upon medical condition and response to the curriculum, patients were transferred either to the home hemodialysis training unit with or without a helper, to the limited care facility, or to the general dialysis area for medically unstable patients. An orientation unit not only improves patient participation in self-care, but appears to increase the number of patients interested in dialyzing at home.

Adolescent↗
PubMed1980

Physiologic studies in normal and uremic sheep: I. The experimental model.

A model of chronic renal failure was created in nine adult sheep by two-stage, subtotal nephrectomy. Carotid-jugular cannulas provided clot-free access for 72 to 274 days without exit-site infections. All sheep became uremic and anemic. Median survival, while uremic, was 145 days (72 to 327 days), although three were sacrificed. Five required dialysis within the first week of uremia, and median survival on dialysis was 70 days (41 to 177 days). Sheep that maintained adequate nutrition survived the longest on dialysis. Mean creatinine and BUN levels in the stable uremic and dialyzed sheep were 4.8/95 and 7.8/59 mg/dl, respectively. The other serum chemistries remained unchanged (mean values) from normal, although one sheep died of hypercalcemia (17.8 mg/dl). Renal blood flow correlated to GFR in both normal and uremic states. GFR fell more than serum creatinine rose, suggesting extrarenal excretion of creatinine.

Animals↗
PubMed1980

Physiologic studies in normal and uremic sheep. II. Changes in erythropoiesis and oxygen transport.

Red cell production and survival, cardiac output (CO), renal blood flow (RBF), serum erythropoietin (ESF), oxygen (O2) consumption, 2,3-diphosphoglycerate (2,3-DPG), P50, and circulating hemoglobin (HbC) were measured in normal sheep and in animals made chronically uremic and anemic by subtotal nephrectomy. The erythropoiesis characterizing uremic anemia was hypoproliferative as quantitated by ferrokinetics, but was still subject to normal feedback control in that erythropoiesis in normal and uremic animals increased with phlebotomy and was suppressed with transfusion. ESF levels were only measurable when the hematocrit fell below 25 in normal animals and were undetected in most stable uremics (hematocrit, 18 to 10%). HbC correlated with ESF. CO increased linearly with progressive anemia in normal and uremic states but, despite this increase, relative RBF decreased; the percent of the CO going to the kidney fell with severe anemia. Venous O2 extraction increased linearly in normal and uremic states as anemia progressed, resulting in no difference in O2 utilization between the study states. There were no correlations between 2,3-DPG, P50, or hematocrit, under any conditions. These results confirm the mechanism of anemia in chronic renal failure and demonstrate that the O2 delivery ESF erythroid marrow feedback mechanism persists in the uremic state over a wide range of hematocrits.

Animals↗
PubMed1978

Uremic neuropathy: evidence of middle molecule toxicity.

Ten dialysis patients were followed in a prospective study to determine the neurotoxicity of metabolites in the middle molecule (MM) molecular weight (mol wt) range of 500-200 daltons/molecule. In the absence of readily available direct serum measurements of MM concentrations, a theoretically calculated dialysis index, D1(MM), which included the combined effects of dialysis and residual glomerular filtration rate (GFR) on MM removal was used to estimate changes in their predialysis concentrations. The ten patients were dialyzed on protocols which yielded a D1(MM) less than 1.0. Evidence of uremic neuropathy developed in six of these ten patients, and five of these six also developed a progression in their anemia. Two additional patients with no signs of neuropathy developed a progression in their anemia. One patient developed pericarditis with tamponade. A total of eight patients developed complications. One additional patient developed increased weakness, tiredness and general malaise without change in objective findings. When the dialysis therapy to reduce MM concentrations by increasing the D1(MM) above 1.0 was instituted, the complications were reversed. Our data support the findings of others, namely, that there are toxic substances in the MM mol wt range of 500-2000 daltons/molecule. However, a synergism between elevated concentrations of small molecules and MM cannot be ruled out.

Blood Urea Nitrogen↗
PubMed1977

Iron balance in hemodialysis patients.

Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.

Ferritins↗
PubMed1977

14C cyanate as a tag for red cell survival in normal and uremic man.

14C cyanate was employed as a red cell tag. Incubated cells were washed before reinjection to remove free cyanate. Neither early or late elution was observed, and the mean red cell life span of 10 normal subjects was 115+/-12 days. In nine uremic subjects the mean life span corrected for blood loss was 73 days with a mean red cell turnover of about 0.79 times basal. Survival curves in normal subjects were similar to those observed with DF32P and in uremic subjects to those with 51Cr corrected for elution. These observatios show the reliability of 14C cyanate as a nonelutable red cell tag.

Carbon Radioisotopes↗