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Biomedical subjects

M Walser

Publications and source records attributed to M Walser.

At least 37 records · Page 2Linked to original sources
PubMed1994

Assessment of renal function and progression of disease.

Detection of early renal dysfunction remains a difficult problem because creatinine levels often do not become abnormal until glomerular filtration rate is severely reduced. Creatol, which also accumulates in renal failure, has been suggested as an alternative to creatinine. To measure glomerular filtration rate, a number of simplified techniques have been suggested; for the most part, however, they have not been validated in patients with severe chronic renal failure. Glomerular filtration rate can be estimated with fair precision from serum creatinine concentration with the use of improved equations, provided that the serum creatinine level is greater than 2 mg/dL. The use of cimetidine to reduce the discrepancy between creatinine clearance and glomerular filtration rate does not seem justifiable. In diabetic nephropathy, sequential biopsies may be preferable to sequential determinations of glomerular filtration rate for follow-up of patients with this disease.

Creatinine↗
PubMed1993

A crossover comparison of progression of chronic renal failure: ketoacids versus amino acids.

Rates of progression of chronic renal failure were compared in patients receiving alternately an amino acid supplement (AA) and a ketoacid supplement (KA) to a very low protein (0.3 g/kg), low phosphorus (7 to 9 mg/kg) diet. The first supplement was randomly chosen. Bias due to carryover effects was minimized by delaying the regression analysis until one month after starting or changing supplements. In order to minimize possible bias caused by initiating the two supplements at differing levels of severity, a multiple crossover design was used (ABA, BAB, ABAB, or BABA) with at least four GFR's in each treatment period (except for three GFR's in one instance). Sixteen patients completed the protocol; five dropped out. Average starting GFR's were nearly identical for the two supplements (15.4 and 15.9 ml/min). For each patient, mean progression on KA was compared with mean progression on AA. Thirteen out of 16 patients progressed more slowly on KA than AA. On the average, progression on KA was significantly slower (95% confidence limits = -0.36 to 0.09 ml/min/month) than on AA (-0.91 to -0.41 ml/min/month; P = 0.024). There was no significant difference in estimated protein intake, phosphate excretion, or mean arterial pressure between KA and AA periods. Serum triglyceride concentration was significantly lower on KA (P = 0.0026). 17-hydroxycorticosteroid excretion was also lower (P = 0.031). We conclude that KA slow progression, relative to AA, independently of protein or phosphorus intake, in patients on this regimen.

Adult↗
PubMed1993

Does prolonged protein restriction preceding dialysis lead to protein malnutrition at the onset of dialysis?

It has recently been suggested that prolonged protein restriction preceding dialysis may induce protein malnutrition and thus confer a poor prognosis during dialysis. We examined the records of all patients who were prescribed a very low protein diet (0.3 g/kg ideal body weight) plus supplemental essential amino acids and/or ketoacids for 6 to 72 months (median 26 months) preceding renal replacement, numbering 43. Hypoalbuminemia immediately preceding dialysis was present in only two patients. Final serum albumin averaged 4.1 +/- 0.4 (SD) g/dl. Final transferrin was subnormal in eight patients, but had been subnormal in six of these, without attendant hypoalbuminemia, for one to four years. Mean final transferrin was 241 +/- 56 mg/dl. Final serum cholesterol was below 150 mg/dl in six subjects, all of whom had normal levels of albumin (mean 4.0 +/- 0.2 g/dl) and a normal mean value for transferrin (211 +/- 22 mg/dl). In five patients who exhibited subnormal albumin and transferrin and high cholesterol concentrations at the beginning of dietary therapy, albumin and transferrin levels rose to normal or nearly normal, and hypercholesterolemia receded during the ensuing four months. Thus this predialysis dietary regimen, rather than causing protein malnutrition, prevents it; when protein malnutrition is present, this regimen corrects it.

Cholesterol↗
PubMed1993

Prediction of glomerular filtration rate from serum creatinine concentration in advanced chronic renal failure.

In 85 patients with established chronic renal failure, as manifested by serum creatinine concentration ([Cr]) > 0.177 mM (> 2 mg/dl), urinary clearance of 99mTc-DTPA (GFR) and [Cr] were determined one to four times and averaged. GFR was expressed per 3 m2 of height2 rather than in terms of 1.73 m2 of surface area because weight changes but height does not. GFR in these patients averaged 13 ml/min/3 m2 (range 2 to 37). The following equations were derived for predicting GFR from [Cr]-1 (mM-1), age (years) and weight (kg): males, GFR = 7.57 [Cr]-1 - 0.103 age + 0.096 weight - 6.66; females, GFR = 6.05 [Cr]-1 - 0.08 age + 0.08 weight - 4.81. These equations predict GFR in this series with a root mean square error of 3.0 ml/min and account for 89% of the observed variation in GFR. They are applicable only to patients with [Cr] > 0.177 mM (2 mg/dl). More precise estimates can be obtained by including a value for 24-hour urinary urea N, as a measure of protein intake. Less precise but simpler estimates can be obtained from [Cr]-1 alone: males, GFR = 7.58 [Cr]-1 - 4.29; females, GFR = 6.11 [Cr]-1 - 3.8. Expressing [Cr] in mg/dl, the latter equations become: males, GFR = 86 [Cr]-1 - 4.29; females, GFR = 69 [Cr]-1 - 3.8.

Adult↗
PubMed1993

Free and protein-bound tryptophan in serum of untreated patients with chronic renal failure.

In fasting sera from 46 untreated patients with chronic renal failure and in 22 normal subjects, non-protein-bound tryptophan, F, was separated by pH-controlled equilibrium dialysis. Total tryptophan, T, and F were measured by HPLC. Results in patients were related to gender, severity of chronic renal failure (as measured by radioisotopic glomerular filtration rate), protein intake (as measured by 24-hr urinary urea N excretion), and protein nutrition (as measured by serum concentrations of albumin and transferrin). T was subnormal in 59% of the patients. In seven hypoalbuminemic patients, F/T was markedly increased (approaching unity) but F was normal. In 39 non-hypoalbuminemic patients, F was again normal but F/T was often increased at glomerular filtration rates below 30 ml/min/3 m2 of height2, especially in females. T was significantly correlated with estimated protein intake (r = 0.54, P = 0.0004), even though neither F nor serum protein levels were correlated with it. We conclude that the serum level of free tryptophan is well-maintained in chronic renal failure, being uninfluenced by severity of renal insufficiency, voluntary protein intake, or serum protein concentrations. On the other hand, protein-bound tryptophan varies with protein intake, decreases markedly in hypoalbuminemic patients, and also decreases in many nonhypoalbuminemic patients (especially females) when the glomerular filtration rate falls below approximately 30 ml/min/3 m2 of height2.

Adult↗
PubMed1993

Ketoisocaproate infusion improves survival from experimental sepsis by an antioxidant mechanism.

Sepsis was induced in rats by cecal ligation and puncture. A nutrient mixture was infused that also contained either (A) sodium 2-ketoisocaproate (NaKIC) or (B) NaHCO3, at 18.75 mmol kg/day. In group A, 34 of 43 rats (79%) survived, while only 24 of 44 rats (55%) in group B survived (P < 0.02). In a second experiment, cecal ligation and puncture were performed 1 week after bilateral adrenalectomy or sham adrenalectomy. All adrenalectomized rats died within 2 days of CLP, whether corticosterone replacement level was low, normal, or high. Four of eight sham-adrenalectomized rats receiving NaHCO3 died, but none of seven receiving NaKIC died. Combining both experiments by ANOVA, the effect of KIC on survival in adrenal-intact animals is highly significant (P = 0.002). In NaKIC-infused rats, blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as blood levels of oxidized glutathione and ratio of oxidized/reduced glutathione were significantly lower. We conclude that KIC infusion improves survival of septic rats by an antioxidant mechanism, probably involving reaction with hydrogen peroxide.

Adrenalectomy↗
PubMed1993

Arteriovenous differences and tissue concentrations of branched-chain ketoacids.

According to previous reports, branched chain ketoacids (BCKAs) are undetectable in liver and brain. A procedure is described for HPLC analysis of tissue concentrations of BCKA that achieves 80% recovery of labeled 2-ketoisocaproate (KIC) added to frozen powdered liver. In normal overnight-fasted rats, substantial hepatic uptake was demonstrable in the order KIC > 2-ketoisovalerate (KIV) congruent to 2-keto-3-methylvalerate (KMV). All three BCKAs were very low in freeze-clamped liver. Liver concentrations were only 15% to 22% of the mean of portal vein, hepatic vein, and hepatic artery (aorta) concentrations. In view of the probable contribution to total liver content of extracellular BCKAs, the intracellular concentrations in liver tissue must be vanishingly low. Somewhat higher amounts were present in freeze-clamped kidney and heart tissue, and significant uptake of KIC and KMV by kidney was found. Brain released KIC. Muscle contained concentrations of BCKA that were 35% to 72% of concentrations in plasma, and it released all three BCKAs. Similar results were obtained from tissues in overnight-fasted dogs, except that even lower levels were found in freeze-clamped brain (sampled before circulation ceased) than were found in the liver. Plasma levels in dogs were similar to those of rats. In both species the tissue-to-plasma ratios were higher for KIV than for KMV or KIC. Remarkably low BCKA levels in liver and brain are unexplained, particularly in light of evidence that BCKAs gain access to cells in both organs.

Animals↗
PubMed1992

Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level.

The roles of the adrenal gland and of dietary protein level in ablative nephropathy in the rat were examined by comparing adrenalectomized rats, replaced with corticosterone at low physiological (1 and 2) or high physiological (3 and 4) levels with intact rats (5 and 6). All groups were subjected to 5/6 nephrectomy and followed 12 weeks on a regular diet (2, 4 and 6) or a reduced protein diet (1, 3 and 5). Groups 1, 2, 5 and 6 all grew at the same rate but groups 3 and 4 grew less, though food intake was nearly the same in all. Higher dietary protein, higher corticosterone maintenance level, and the presence of intact adrenal glands all increased proteinuria significantly. Extracellular fluid volume (82Br space) was identical in all groups at 8 and 12 weeks, because the animals were given a choice of water or saline to drink. Mortality was highest (50%) in Group 6 and lowest (11%) in Group 1, but these differences were not significant. Final inulin clearance was significantly improved by adrenalectomy when non-survivors were scored as having zero clearance, but not if the analysis was limited to survivors. It was not affected by diet or by corticosterone level. Renal histopathological scores were also improved significantly by adrenalectomy and by protein restriction, but were not influenced by corticosterone level. Thus adrenalectomy and dietary protein restriction independently ameliorate ablative nephropathy, but corticosterone replacement level has no effects, except on proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Effects of corticosterone administration on nitrogen excretion and nitrogen balance in adrenalectomized rats.

Adrenalectomized rats were implanted with pellets containing corticosterone in proportions varying from 0% to 100%, plus cholesterol. Stable concentrations of plasma corticosterone resulted, varying from subnormal (A) to physiologic (B) to supraphysiologic (C). When food was ingested ad libitum, weight gain was maximal in B at plasma corticosterone concentrations of 0.14-0.20 mumol/L; weight loss occurred in C, despite higher food intake. Even when rats had constant limited food intake, weight gain and positive nitrogen balance were significantly reduced in A compared with B because fecal nitrogen rose significantly and the retention of absorbed nitrogen for growth decreased. In C, weight decreased despite constant intake, and nitrogen balance became negative because urinary nitrogen increased markedly. We conclude that glucocorticoid insufficiency reduces nitrogen balance by impairing intestinal absorption of dietary protein and the utilization of absorbed nitrogen, whereas glucocorticoid excess reduces nitrogen balance by augmenting urinary nitrogen despite constant nitrogen intake.

Adrenalectomy↗
PubMed1992

Healing of intestinal anastomoses in adrenalectomized rats given corticosterone.

To determine the effect of physiological variations in glucocorticoid levels on wound healing, adrenalectomized rats, implanted with corticosterone pellets of varying concentrations, and sham-operated rats were subjected to ileal transection followed by end-to-end anastomosis. Adrenalectomized animals with plasma corticosterone levels less than 2.5 micrograms/dl suffered 25% mortality. In rats surviving 1 wk, bursting pressure of the anastomotic site was measured as an index of wound healing. At plasma corticosterone levels of 3.9-7.4 micrograms/dl, which approximate normal physiological levels, bursting pressure was not significantly different from that in sham-adrenalectomized animals. In adrenalectomized rats with lower or higher corticosterone levels, bursting pressure was significantly reduced. Thus a narrow range of plasma corticosterone is required for optimal wound healing in this model; higher values tend to impair healing, as do subnormal values, perhaps because of slower protein turnover; low values also lead to high mortality.

Adrenal Cortex↗
PubMed1992

Progression of chronic renal failure on substituting a ketoacid supplement for an amino acid supplement.

Twelve patients with severe chronic renal failure (average initial GFR, 13 mL/min) were monitored for 4 to 23 months while receiving an essential amino acid supplement and were then switched to a ketoacid supplement for 6 to 40 months, while continuously receiving a very low-protein (0.3 g/kg), low-phosphorus (7 to 9 mg/kg) diet. Urinary urea N excretion indicated that actual dietary protein intake averaged 0.46 g/kg. Progression, estimated as the linear regression slope of radioisotopically determined GFR on time, slowed from -0.46 +/- 0.31 (SD) to -0.24 +/- 0.15 mL/min/month (P = 0.029). Serum urea N, creatinine, phosphate, and uric acid rose significantly as GFR fell; blood pressure, plasma lipids, and urinary urea excretion were unchanged. Urinary 17-hydroxy-corticosteroid excretion decreased 18%, but this change was only marginally significant (P = 0.087). There was no change in plasma or urinary cortisol or urinary aldosterone. Viewed in light of previous evidence that progression seldom slows when treatment remains constant, the results suggest that this ketoacid supplement slows progression by approximately half, compared with an essential amino acid supplement, with no change in diet.

17-Hydroxycorticosteroids↗
PubMed1991

Effect of corticosterone administration at varying levels on leucine oxidation and whole body protein synthesis and breakdown in adrenalectomized rats.

Adrenalectomized rats were implanted with pellets containing corticosterone in proportions varying from 0% to 100%, plus cholesterol. Stable levels of plasma corticosterone resulted, varying from close to zero (I) to physiologic (II) to supraphysiologic (III). Whole body protein synthesis (S) was measured during fasting by a technique involving injection of [1-14C]-leucine, analysis of expired air for 14CO2, and measurement of urinary excretion of urea N plus ammonia N (C). Whole body breakdown (B) during fasting was calculated as the sum of S and C. C rose progressively from I to III, but fractional oxidation of 14C leucine was lowest in II. Both S and B were markedly reduced in I and maximal in II. In III, S fell but B remained high. Thus variations in glucocorticoid levels above and below physiologic exert profound effects on leucine oxidation and protein turnover, involving effects on both synthesis and breakdown.

Adrenalectomy↗
PubMed1991

Elevated 25-hydroxy and normal 1,25-dihydroxy cholecalciferol serum concentrations in a successfully-treated case of vitamin D3 toxicosis in a dog.

A 4-y old, 27 kg spayed female German Shepherd dog was observed to ingest one 1-oz package of a rodenticide containing cholecalciferol. An initial serum calcium concentration of 15.7 mg/dl was successfully reduced to normal during 10 d using calcitonin and prednisolone. During that time, the serum 25-hydroxy and 1,25-dihydroxy cholecalciferol concentrations ranged from 637 to 315 ng/ml (normal 32 +/- 6 ng/ml) and 64 to 29 pg/ml (normal 34 +/- 19 pg/ml), respectively. Serum mid-molecule parathyroid hormone concentrations (76 to 97 pcmol/L) were within the normal range (85-140 pcmol/L). These data indicate that hypercalcemia seen in dogs following field exposures to cholecalciferol-containing rodenticides may be associated with elevated 25-hydroxy rather than 1,25-dihydroxy cholecalciferol. Consequently, serum 25-hydroxy cholecalciferol concentrations may be the most conclusive method for diagnosing hypervitaminosis D3 toxicosis in the live dog.

Animals↗
PubMed1990

Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin.

PURPOSE: The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis). PATIENTS AND METHODS: Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations. RESULTS: At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued. CONCLUSIONS: It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis.

Adult↗