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Biomedical subjects

F Dumler

Publications and source records attributed to F Dumler.

At least 55 records · Page 3Linked to original sources

Effect of dialyzer reprocessing methods on complement activation and hemodialyzer-related symptoms.

The effects of different dialyzer processing methods and of reuse on complement activation and dialyzer-related symptoms were studied in 96 maintenance hemodialysis patients. New dialyzers were either unprocessed (Group 1) or machine-washed with bleach and stored in formaldehyde (Group 2). Reused dialyzers were manually cleansed using the combination of bleach and formaldehyde (Group 3), or machine-washed in formaldehyde (Group 4) or peracetic acid (Group 5). Prewashed new dialyzers (Group 2) were associated with greater complement activation during dialysis when compared with unprocessed, new dialyzers (Group 1) (p less than 0.05). Reused, unbleached but formaldehyde-treated or peracetic acid-treated dialyzers (Groups 4 and 5) were associated with reduced complement activation (p less than 0.05). Complement activation was not reduced when bleach was used for reprocessing (Group 3). The percentage of patients without symptoms during dialysis was significantly greater with reused dialyzers than with new dialyzers (Groups 3 through 5 versus Groups 1 and 2; 39 versus 25%; p = 0.035). The severity of total symptoms correlated significantly (p = 0.0004) with complement activation. Our results suggest that total symptoms during dialysis are correlated with the degree of complement activation. However, trends in the data pertaining to chest pain suggest that factors other than complement activation may be important in the pathogenesis of some dialyzer-related symptoms.

Chest Pain↗

Effect on renal function of change from high to moderate protein intake in type I diabetic patients.

The effects on renal function of moderate restriction in protein intake were studied in 14- to 20-yr-old type I diabetic patients who had no clinical renal disease or hypertension; matched normal subjects served as controls. After assessment of protein intake and renal function, studies were conducted at the completion of each of two consecutive dietary periods of 1 wk. Diets containing 3.5 and 1.5 g X kg-1 X day-1 protein were provided during the first and second periods, respectively. Baseline protein intakes were substantial in both controls (1.86 g X kg-1 X day-1) and diabetics (2.17 g X kg-1 X day-1). Baseline creatinine clearance was increased in diabetics (P = .043). At the end of the high-protein intake period, both diabetics and controls showed similar high values of glomerular filtration rate (GFR) and renal plasma flow (RPF). GFR and RPF decreased markedly (P less than .001) and to a similar degree in both groups after normal protein intake. GFR and RPF in diabetics were not higher than in controls at this point, but filtration fraction was increased in diabetics. Albumin excretion rates were similar in both groups and not influenced by renal function changes. GFR and RPF values correlated significantly with the quantity of protein intake, as estimated from the urea nitrogen appearance rate in both groups. The results suggest that the functional response to variations in protein intake is not altered in the diabetic kidney. In addition, increased renal function in diabetics may be related partly to the excessive protein content in commonly prescribed diabetic diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Relationship between renal function and metabolic alterations in early streptozocin-induced diabetes in rats.

To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h after streptozocin injection, and significant hyperglucagonemia and acidosis were present at 36-48 h. Glomerular filtration rate (GFR), expressed per unit of body weight, first increased at 3 days of diabetes [1.35 +/- 0.07 (SE) (N = 14)] and was 18% greater than in controls [1.14 +/- 0.03 ml X min-1 X 100 g-1 (SE) (N = 38)] (P less than .005). Renal enlargement preceded GFR changes, so that GFR per unit of kidney weight was lower at 48 h in diabetics [1.31 +/- 0.06 (SE) (N = 16)] than in controls [1.54 +/- 0.04 ml X min-1 X g-1 (SE) (N = 38)] (P less than .01). Nucleotide and RNA metabolism was studied in the renal cortex after infusion of radio-labeled orotate or adenine. Rate of RNA synthesis, total cellular RNA, and the pools of ATP, UTP, and uridine 5'-diphospho-N-acetyl glucosamine were significantly increased 13-51% in 48-h diabetics. Nucleotide precursor incorporation was significantly increased only in uracil ribonucleotides. The increase in uracil ribonucleotide pool exceeded the degree of cell hypertrophy. Our studies indicate that renal hypertrophy and specific increases in uracil ribonucleotide synthesis precede functional changes in early diabetes. Renal metabolic changes may be the critical primary factors in diabetic nephropathy.

Animals↗

De novo pyrimidine nucleotide biosynthesis in isolated rat glomeruli.

Uracil ribonucleotide-sugars and aminosugars are required for glomerular basement membrane (GBM) biosynthesis. Since these nucleotides are metabolic derivatives of uridine 5'-triphosphate (UTP), we have studied the cellular pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphoglucuronic acid (UDPGA), uridine 5'-diphospho-N-acetyl glucosamine (UDPAG) and UTP, and measured UTP synthesis de novo in isolated glomeruli incubated in vitro. Improved techniques for nucleotide quantitation were established and the optimal conditions for glomerular isolation and incubation determined. Substantial quantities of uracil ribonucleotide coenzymes and an active utilization of orotate for the synthesis of pyrimidine nucleotides were demonstrated. UTP synthesis and the pools of UDPG and UDPGA varied markedly with changes in the experimental conditions. The adverse effects of suboptimal conditions were more apparent in glomeruli from diabetic animals than in controls. The use of suboptimal conditions could provide misleading information on GBM metabolism in isolated glomeruli since uracil ribonucleotide coenzyme availability might be reduced.

Animals↗

Effect of cooled dialysate on serum catecholamines and blood pressure stability.

In the current study dialysis at 34 degrees C resulted in improved vascular stability in a group of patients who developed hypotension on conventional dialysis at 37 degrees C. Side effects of dialysate cooling were not noteworthy. The stability of blood pressure during cool dialysis may at least in part be due to an increase in plasma norepinephrine concentrations not observed during warm dialysis. Although pathogenesis of dialysis induced hypotension has not been clearly elucidated, a reduced vasoconstrictor and catecholamine response may be an important mechanism.

Blood Pressure↗

Effects of early diabetes on uridine diphosphosugar synthesis in the rat renal cortex.

To assess the effects of streptozotocin-induced diabetes on the substrates utilized in the formation of glycoproteins, the pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphogalactose (UDP-GAL), uridine 5'-diphosphoglucuronic acid (UDPGA), and uridine 5'-diphospho N-acetyl galactosamine (UDPA-GAL) were measured in the renal cortex of control and over a 48-hr period in diabetic rats. In control rats these pools measured: UDPG, 256 +/- 23; UDP-GAL, 75 +/- 14; UDPGA, 147 +/- 16; UDPAG, 367 +/- 23; UDPG-GAL, 131 +/- 13 nmoles/mg DNA. In diabetic rats, except for UDP-GAL, all pools were increased 41 to 68%. The incorporation of radiolabeled orotate was increased in all pools, except UDP-GAL, in diabetic rats by 41 to 77% compared to control rats. The incorporation into UDPG and UDPAG was increased even after correction for the specific radioactivity of their immediate precursor, uridine 5'-triphosphate (UTP). Expansion of the UTP pool after orotate infusion was associated with an increase in the size of the UDPG and UDPAG pools in both control and diabetic rats. Depletion of the UTP pool after adenine infusion in controls was associated with a decrease in all pools. This study demonstrates that after the induction of diabetes there is a rapid increase in the bioavailability of substrates utilized in the synthesis of glycoproteins and glycosaminoglycans. It is theorized that this increase is necessary for the augmented synthesis of basement membrane-like material in the diabetic kidney.

Animals↗

Long-term alternate day steroid therapy in renal transplantation. A controlled study.

Seventy-six adult renal allograft recipients were allocated 5 months post-transplantation to daily or alternate day maintenance methylprednisolone therapy. All 15 recipients of living related kidneys and 23 recipients of cadaver kidneys were placed on the alternate day regimen, while 38 patients with cadaveric grafts remained on daily methylprednisolone. In patients on alternate day methylprednisolone, serum creatinine concentrations, frequency of acute rejection episodes, and prevalence of chronic rejection were similar to those of patients on daily steroids. Furthermore, no differences were noted in the rate of loss of graft function between recipients of cadaver kidneys on daily versus alternate day steroids. There were no differences in body weight, blood pressure, degree of hyperglycemia, or hyperlipidemia between patients on the daily or alternate day schedules. However, the prevalence of clinical osteonecrosis and the rate of infectious complications requiring hospitalization were significantly decreased in patients on alternate day methylprednisolone. We conclude that alternate day methylprednisolone therapy is as effective as daily steroids for the maintenance of graft function in renal transplant recipients. The decreased incidence of osteonecrosis and the lower frequency of infectious complications represent a strong argument in favor of alternate day steroid therapy.

Adult↗

Alterations in glomerular RNA in diabetic rats: roles of glucagon and insulin.

Incorporation in vivo of labeled orotate into RNA and total nucleotides was measured in isolated glomeruli and whole renal cortex. In 2-day diabetic animals, glomerular RNA was increased, and there was greater incorporation of orotate into total nucleotides and RNA as compared with controls. Insulin reversed the exaggerated incorporation at infusion rates that corrected hyperglucagonemia without reducing plasma glucose and with only minimal changes in insulin concentrations. The addition of glucagon to insulin infusions reproduced the increased incorporation observed in untreated diabetics. Similar changes occurred in renal cortex, where differences in orotate incorporation into nucleotide precursors seemed to be the main cause for alterations in RNA labeling. Isotope incorporation in glomeruli correlated positively with plasma glucagon, but not with insulin or glucose concentrations. Although in 7-month diabetic animals orotate incorporation into RNA was less than in controls, probably as a consequence of renal disease, 24-hour insulin infusion decreased it further. Our results confirm that in the diabetic kidney, abnormal uracil nucleotide metabolism and increased cellular content of RNA are demonstrable in glomeruli as in the renal cortex. These changes appear to be related directly to hyperglucagonemia.

Adenine↗