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Biomedical subjects

F Dumler

Publications and source records attributed to F Dumler.

At least 37 records · Page 2Linked to original sources
PubMed1992

Clinical experience with short-time hemodialysis.

After at least 6 months on conventional hemodialysis (cellulosic dialyzers, acetate dialysate, and a 3- to 4-hour treatment time), 56 patients were changed to short-time hemodialysis (less than 180 minutes) using polysulfone dialyzers and bicarbonate-containing dialysate. Treatment time decreased (191 +/- 5 v 147 +/- 5 min; P = 0.001), while Kt/V (1.22 +/- 0.04 v 1.29 +/- 0.06; P = NS) and normalized protein catabolic rate (pcr) (1.10 +/- 0.05 v 1.10 +/- 0.07 g/kg/d; P = NS) remained constant. When compared with the conventional period, 30 months of short-time hemodialysis resulted in no changes in predialysis blood pressure (BP) (151 +/- 2/84 +/- 1 v 151 +/- 2/86 +/- 1 mm Hg), postdialysis BP (144 +/- 2/81 +/- 1 v 143 +/- 3/84 +/- 1 mm Hg), interdialytic weight gain (2.4 +/- 0.1 v 2.7 +/- 0.2 kg), or blood urea nitrogen (BUN) (26.1 +/- 0.71 v 25.3 +/- 1.07 mmol/L [73 +/- 2 v 71 +/- 3 mg/dL]). Shorter treatment times were not associated with an increase in intradialytic complications. Actually, the frequency (%) of dialysis treatments associated with nausea (5.94 +/- 1.33 v 2.21 +/- 0.52), vomiting (3.12 +/- 0.87 v 0.54 +/- 0.14; P less than 0.05), headaches (5.60 +/- 1.13 v 2.03 +/- 0.52; P less than 0.05), and back pain (0.91 +/- 0.25 v 0.05 +/- 0.05; P less than 0.05) was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1992

Mesangial cell killing by leukocytes: role of leukocyte oxidants and proteolytic enzymes.

Mesangial cells from human and rat kidney were examined for sensitivity to killing by neutrophils. Cells from both species were sensitive to killing by phorbol myristate acetate-stimulated neutrophils. Catalase was highly protective while superoxide dismutase was less protective and a number of protease inhibitors were not protective. Strong protection was also observed with the iron chelators, deferoxamine and phenanthroline, and with the hydroxyl radical scavengers, dimethylthiourea and 5,5-dimethyl-1-pyrroline N-oxide. Pretreatment of the mesangial cells with deferoxamine followed by washing also provided protection. Mesangial cells were also killed by reagent hydrogen peroxide (H2O2) but were much less sensitive to injury by direct application of proteolytic enzymes. The ability of H2O2 to injure mesangial cells was prevented by pre-incubation of the H2O2 with human leukocyte myeloperoxidase. These data suggest that killing is due primarily to the generation of H2O2 by the stimulated neutrophils and its further reduction in an iron-catalyzed reaction. The hydroxyl radical may be the reduction product that actually mediates lethal injury but lack of scavenger specificity prevents definitively concluding this. Mesangial cell killing by activated neutrophils could be significantly inhibited by monoclonal antibodies to CD11/CD18 molecules, suggesting that close contact between the target and effector cells is required for cytotoxicity. Although qualitatively similar to endothelial cells, the mesangial cells appeared to be quantitatively more oxidant sensitive than previously examined human and rat endothelial cells. Taken together, these data show that mesangial cells from rat and human are sensitive to leukocyte-induced injury and that injury results via an oxidant pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.

Animals↗
PubMed1992

Age-related changes in glomerular volume and hydroxyproline content in rat and human.

Total 4-hydroxyproline content and volume were measured in the same sample of microdissected glomeruli obtained fro rat and human outer or inner cortex. Glomerular volume was determined by computer-assisted image analysis, and 4-hydroxyproline was measured by a highly sensitive gas-liquid chromatographic method. Results were expressed as weight of basement membrane material by comparison with the amount of 4-hydroxyproline in purified basement membrane/mesangial matrix preparations. Microanalyses were possible in samples containing as few as eight human glomeruli. Rat glomerular size increased sevenfold between 5 wk and 2 yr of age, with volume being consistently 36 to 45% greater in inner than in outer cortex glomeruli. Basement membrane material content per glomerulus markedly increased with age (12-fold); however, when expressed per unit volume, this change was greatly reduced (2-fold). Expressed per volume, inner and outer cortex glomerular content of basement membrane material was always similar, regardless of age. Therefore, a greater glomerular size, in itself, does not accelerate the rate of basement membrane material deposition. Glomerular size distributions (measured by skewness and kurtosis) did not change, indicating that, although glomerular volume increases with age, aging does not appear to cause the emergence of distinct glomerular populations within an age group. Basement membrane material accumulation is probably a generalized change. Human glomeruli increased sevenfold in size from infancy to adulthood and then declined during senescence. Contrary to that in the rat, glomerular basement membrane material content appeared to closely follow size changes, thus, varying little from infancy to senescence if expressed per unit of glomerular volume.

Adolescent↗
PubMed1992

Single center success with a high risk peritoneal dialysis population.

A large end stage renal failure population treated by chronic ambulatory peritoneal dialysis (CAPD) was examined for rates of infection, CAPD modality failure and patient survival (N = 347). Nearly half were considered high risk for survival for reasons of age (39% older than 60 years), diabetes mellitus (33%), hemodialysis access failure (10%), poor cardiopulmonary reserve (16%) or technical challenges (30% had morbid obesity, history of abdominal aortic aneurysm repair or multiple abdominal surgeries). Hence, CAPD was often initiated by default rather than choice in the 347 patients studied (mean age: 51 +/- 17 years). Infections greatly outnumbered technical failures as grounds for cessation of CAPD. Over 5521 patient-months, 51% of patients developed infection with peritonitis predominating (80%) when compared to exit site infections (20%). The frequency of infections was 1.9 mean episodes per patient; however, 55% of these patients had only one episode of peritonitis. A rate of 0.75 infections per patient per year was seen with an average interval of 16 months between infections. Technique and patient survival rates at 4 years were 50% and 61% respectively. High risk status does not preclude successful CAPD and should not preclude its implementation.

Adolescent↗
PubMed1992

Renal malignancy in peritoneal dialysis patients with acquired cystic kidney disease.

A known complication of long-term hemodialysis, acquired cystic kidney disease (ACKD) has been reported infrequently in association with chronic ambulatory peritoneal dialysis (CAPD). The duration of end stage renal failure (ESRF) is thought to correlate with the development of ACKD. Renal cell carcinoma has been reported in 4-10% of patients with ACKD. Two patients on CAPD for more than 6 years without prior hemodialysis treatment developed renal malignancy in the setting of ACKD. Flank and abdominal pain was the presenting symptom in both patients neither of whom had hematuria. Renal ultrasound detected cystic lesions consistent with ACKD; malignant masses were ultimately identified by CT scan. Both patients underwent flank radical nephrectomy, resumed CAPD early in the postoperative period and continue on CAPD 9 and 4 months after surgery. One patient has since developed hepatic metastasis. ACKD is an important risk factor for the development of renal cell carcinoma not only in maintenance hemodialysis patients but also in the CAPD population. A high index of suspicion and serial ultrasound screening for ACKD is warranted in patients with long-term dialysis-dependence.

Carcinoma, Renal Cell↗
PubMed1992

Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance.

A threat to survival in renal failure, malnutrition in continuous ambulatory peritoneal dialysis patients (CAPD) is often occult as CAPD patients often gain weight masking actual protein malnutrition. Bioelectrical impedance (BEI) accurately assesses body composition in CAPD patients and uncovers subtle changes in lean body mass (LBM) that escape indirect anthropometric detection. Segregating parameters of body composition is crucial to nutritional management of CAPD patients in whom fat may account for overall weight gain. While both skin-fold methods and BEI correctly distinguished thin and overweight patients in terms of fat mass, only BEI accurately segregated these patients by LBM (P = 0.007). Serial weights of 39 CAPD patients followed longitudinally for three or more months did not correlate with BEI-measured changes in LBM. LBM was lost in 49% of patients as determined by BEI, while serial weights detected a loss of LBM in 36% of these patients. Strikingly, by serial weights, 64% of patients demonstrated weight gain; however, in 24% of these an actual loss of LBM was demonstrated by BEI. BEI provides specific quantitation of LBM in CAPD patients with changing body habitus and unrecognized nutritional derangement.

Adult↗
PubMed1992

Enhanced peritoneal dialysis delivery with PD-PLUS.

We prospectively studied the effects of enhanced continuous ambulatory peritoneal dialysis (CAPD) on the normalized protein catabolic rate (NPCR) and Kprt/V of two patients with zero residual renal function and marginal or below minimal HCFA values on urea kinetic modeling (Kprt/V = 0.21). Predictable increases in NPCR (from 0.61 to 0.76 and from 0.73 to 0.81 gm/kg/day, respectively) were seen after two weeks of enhanced CAPD achieved by the addition of a fifth nighttime exchange by a portable, easily operable, automated device (PD-PLUS).

Creatinine↗
PubMed1992

Effect of diet composition on renal morphology in diabetic rats.

Streptozotocin-induced diabetic rats were fed rodent diets with standard (4.5%) or high (10%) polyunsaturated fatty acid content for up to 12 months. Diabetic rats fed a standard diet developed thickening of glomerular basement membrane (GBM) when compared to similarly fed controls (285 +/- 21 vs. 243 +/- 18 nm, respectively; p = 0.0003). No differences in GBM thickening were observed between control and diabetic rats fed high-fat diets (188 +/- 23 vs. 195 +/- 21 nm, respectively; p = n.s.). Regardless of diabetes, all rats fed high polyunsaturated fat diets had decreased GBM thickness compared to standard-fed rats (p = 0.0001). Glomerular and mesangial volumes were similar in control and diabetic rats fed standard or high fat diets. Diets high in polyunsaturated fatty acids prevent GBM thickening in diabetes and reduce GBM thickness in control rats.

Animals↗
PubMed1992

Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients.

Although malnutrition poses a significant risk to the well-being of chronic hemodialysis patients, their nutritional assessment is usually empirical. We studied body composition by bioelectrical impedance (BEI) prospectively in 39 patients followed for 5-12 months. BEI correctly discriminated between underweight and overweight patients in terms of fat mass (21 +/- 5 vs. 34 +/- 10%; p = 0.002), lean body mass (78 +/- 4 vs. 67 +/- 10%; p = 0.004) and total body water (57 +/- 3 vs. 49 +/- 7%; p = 0.002), respectively. Serial body weights did not correlate with changes in lean body mass (LBM) as measured by BEI. While 28% of patients lost weight, 41% lost LBM. Most striking is the contrast between the patients who showed no change in LBM by BEI and those whose body weight remained neutral (3 vs. 28%). BEI is a most sensitive clinical tool for assessing changes in LBM in hemodialysis patients.

Body Composition↗
PubMed1991

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.

Bacterial Infections↗
PubMed1990

Relationship between values of bioelectrical impedance and creatinine clearance.

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.

Adult↗
PubMed1989

Effect of cyclosporine on the rate of renal function recovery after renal transplantation.

To assess the effect of cyclosporine therapy on the rate of renal function recovery after renal transplantation, patients with no clinical evidence of rejection and who were treated with either cyclosporine or azathioprine in addition to steroid therapy were studied (n = 74). Of the patients with immediate renal function (n = 57), those receiving organs from living, related donors had a faster recovery rate of glomerular filtration than patients with cadaveric grafts (azathioprine, 15 +/- 2 versus 7 +/- 1 mL/min/day, P = 0.0001; cyclosporine, 14 +/- 3 versus 6 +/- 1 mL/min/day, P = 0.001). Recipients of cadaveric grafts with delayed renal function (n = 17) had a decreased recovery rate of allograft function when treated with cyclosporine as compared to those treated with azathioprine (4 +/- 2 versus 6 +/- 1 mL/min/day, respectively; P = 0.026). Patients on azathioprine achieved better renal function (P = 0.01) than those on cyclosporine (recipients of organs from living, related donors, 59 +/- 5 versus 52 +/- 3 mL/min; recipients of cadaveric grafts, 52 +/- 5 versus 40 +/- 2 mL/min). Thus, even in this early period, cadaveric-graft recipients treated with cyclosporine demonstrate an apparent reduction in creatinine clearance when compared to patients treated with azathioprine.

Adult↗
PubMed1988

Uracil ribonucleotide metabolism in rat and human glomerular epithelial and mesangial cells.

Uridine diphosphosugars (UDP-sugars: UDP-N-acetylglucosamine, UDP-glucose, and UDP-glucuronic acid) are essential coenzymes for the synthesis of glomerular basement membrane and mesangial matrix (GBM-MM). This study has characterized UDP-sugar metabolism in rat and human glomerular cells in tissue culture. Culture of rat mesangial cells in medium containing dialyzed fetal calf serum resulted in UTP loss (28 +/- 4 nmol.mg DNA-1.h-1); the addition of 2 microM orotate to this medium resulted in net UTP accretion (5.42 +/- 0.06 nmol.mg DNA-1.h-1). Rat mesangial cells demonstrated 16- and 29- to 46-fold greater UTP and UDP-sugar pools, respectively, than whole glomeruli. In human mesangial cells, 6-azauridine (500 microM) decreased UDP-sugar pools by 48% (P less than 0.05), whereas uridine (50 microM) produced a 2.5-fold increase. Human and rat mesangial cells had greater (1.8- to 6.1-fold) UDP-sugar pools than epithelial cells and 1.7-3.4 times greater labeled precursor incorporation into UDP-sugars. In conclusion, glomerular cells utilize both exogenous orotate and uridine for ribonucleotide synthesis, and the extracellular concentration of these precursors markedly influence the formation and cellular content of UDP-sugars. Prominent differences exist between separate glomerular cell populations in their metabolism of UDP-sugars. This may represent diverse activity of glycosylating reactions.

Adenosine Triphosphate↗
PubMed1988

Glomerular uracil nucleotide synthesis.

The biosynthesis of basement membrane material requires the sugar derivatives of uridine 5'-triphosphate (UTP) for protein glycosylation. Uridine and orotate utilization for the biosynthesis of uracil ribonucleotides was studied in isolated rat glomeruli incubated in vitro. At a 1 microM concentration total orotate utilization was 9.6 +/- 1.8 pmol.min-1.mg DNA-1 (1 mg DNA approximately 0.175 X 10(6) glomeruli), 51% of the total amount metabolized was used in ribonucleotide formation, and there was a significant UTP accretion. Except at a high initial concentration (50 microM), exogenous uridine failed to increase the UTP pool due to rapid uridine breakdown by a cytosolic phosphorylase. Inhibition of this enzyme with benzylacyclouridine resulted in increased biosynthesis and accretion of UTP, and in a 17-fold higher concentration of uridine, primarily produced from performed sources of nucleosides. Continuous addition of exogenous uridine to maintain its concentration at 1 microM resulted in a total uridine utilization of 550 +/- 30 pmol.min-1.mg DNA-1. Uridine salvage for ribonucleotide biosynthesis was only 3% of the total metabolized. In contrast to uridine, and presumably due to UTP pool compartmentation, orotate incorporation into uridine 5'-diphosphosugars was prominent. The metabolism of exogenous orotate was not decreased by the presence of large amounts of uridine and by an expanded UTP pool. It is concluded that when exogenous orotate is present, it is an important precursor for glomerular uracil ribonucleotide biosynthesis. Due to its rapid rate of catabolism, uridine cannot maintain ribonucleotide biosynthesis at a rate sufficient to result in UTP accretion unless it is provided continuously in substantial quantities.

Animals↗
PubMed1988

Glomerular uracil nucleotide synthesis: effects of diabetes and protein intake.

The biosynthesis of uridine 5'-triphosphate (UTP), uridine 5'-diphosphohexoses, and 5'-diphosphohexosamines (UDP-sugars) was studied in isolated rat glomeruli 48 h after streptozotocin-induced diabetes. Compared with control, diabetic glomeruli demonstrated an increase in the following: exogenous orotate utilization, orotate incorporation into UTP and UDP-sugars, UTP accretion rate, and UDP-sugar pool size. Since these phenomena were not associated with enhanced biosynthesis of orotate de novo, the increased glomerular UDP-sugar bioavailability in diabetes is due to enhanced utilization of exogenous orotate. Plasma concentrations of orotate and uridine were measured in control, sham operated, and unilaterally nephrectomized rats receiving 5, 20, or 60% protein diets. The concentration of pyrimidine precursors correlated directly with protein intake, with doubling at the 60% dietary protein level. In conclusion, glomerular uracil ribonucleotide biosynthesis may be modulated by the quantity of dietary protein. Because UDP-sugars are necessary for basement membrane material formation, an increase in their bioavailability may be part of the metabolic change responsible for diabetic glomerulosclerosis. Diets with high protein content could augment this metabolic alteration.

Animals↗