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Biomedical subjects

N W Levin

Publications and source records attributed to N W Levin.

At least 109 records · Page 6Linked to original sources

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↗

The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites.

The pharmacokinetics of ibuprofen and its two major metabolites, the hydroxy and carboxy derivatives, were studied in seven functionally anephric subjects undergoing hemodialysis therapy. Subjects received ibuprofen 800 mg tid for 14 days. Hemodialysis was performed three times weekly during this period. Arterial and venous blood samples were collected before dialysis and along with dialysate, and during the final dosing interval and dialysis session. No accumulation of ibuprofen plasma concentrations and an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly (mean plasma levels, carboxy 249 micrograms/mL and hydroxy 57 mu/mL); however, both were detected in dialysate. Mean extraction efficiencies were 0.16 (hydroxy) and 0.15 (carboxy). Dialysis clearance calculated by arterial-venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.

Adult↗

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↗

Contrast media for angiography: effect on renal function.

A total of 125 patients with severe peripheral vascular disease were examined with translumbar aortography. The mean dose of contrast medium injected was 65 ml of Angio Conray (containing 31.2 g of iodine). Forty patients were pretreated with mannitol, and 32 received furosemide. Thirty-eight patients (30%) had diabetes and, presumably, diabetic nephropathy. Eleven of them had significant azotemia (creatinine values greater than or equal to 4 mg/dl). Administration of contrast material did not significantly reduce renal function in any patient group. We conclude that acute renal failure following the injection of contrast material is uncommon, is reversible, and almost always occurs when avoidable complicating factors are present.

Adolescent↗

Repeated use of dialyzers is safe: long-term observations on morbidity and mortality in patients with end-stage renal disease.

In treating patients with end-stage renal disease, the dialyzer may be used on multiple occasions rather than once. Long-term effects of this practice are unknown. We report 259 and 1,059 successive patients from facilities practicing reuse in Cincinnati and Detroit, followed, respectively, for 535 and 2,209 patient years. The morbidity was relatively low, expressed by the number of hospital admissions (1.63 and 2.19/year) and by days in hospital (14.24 and 22.71/year), respectively. In Cincinnati the unadjusted case fatality rate was 70% of that in the Ohio Valley Renal Disease Network, in Detroit it was 96% of that in the Michigan Renal Network. There were no adverse long-term effects of multiple use of dialyzers.

Adult↗

Blood pressure response to changes in serum ionized calcium during hemodialysis.

The effect of an increasing serum ionized calcium concentration on blood pressure during hemodialysis was studied in a prospective cross-over trial. Twelve patients were dialyzed three times with a dialysate Ca concentration of 5.5 mg/dL and three times with one of 7.5 mg/dL. Dialysis with the high Ca dialysate was associated with less fall in the mean arterial pressure (p less than 0.001). No statistically significant changes occurred in serum osmolality, body weight, or heart rate after dialysis at the two dialysate Ca levels. Increasing the Ca concentration in dialysate may protect against intradialytic hypotension in some patients.

Adult↗

Sequential use of Minnesota antilymphoblast globulin and cyclosporine in cadaveric renal transplantation.

The use of Cyclosporine (CsA) immediately after renal transplantation may be associated with an increased incidence and duration of acute tubular necrosis (ATN) and permanent primary graft nonfunction. To avoid this potential interaction we treated recipients of primary cadaveric grafts initially with azathioprine (AZA), methylprednisolone (MP), and 5 daily doses of Minnesota antilymphoblast globulin (MAG) (postoperative days 3-7). AZA was discontinued and CsA started on day 6 if the graft was functioning by then. If ATN persisted beyond day 6, AZA and MAG (maximum 12 doses) were continued and CsA withheld until graft function was established (group 1-33 patients). This protocol is compared to our previous regimen of MAG (14 doses over the first 3 weeks), AZA and MP (group 2-68 primary cadaveric graft recipients). Improved one-year graft survival (81% vs. 60%, P less than 0.05) and patient survival (93% vs. 81%, P less than 0.05) were seen in group 1. The incidence and duration of ATN did not differ in the two groups. During the first year after transplantation more patients in group 1 were completely free of rejection episodes (40% vs. 20%, P less than 0.05) and the number of rejection episodes per patient was also lower in this group (1.0 +/- 15 vs. 1.6 +/- 49, P less than 0.05). The incidence of infections was not different in the two groups. No tumors have developed in either group. We conclude that in primary cadaveric renal transplantation the initial administration of a short course of MAG followed by CsA therapy results in excellent graft and patient survival while avoiding the potential adverse effect of CsA on an allograft already subjected to preservation injury.

Acute Disease↗

Nadolol in hypertensive patients maintained on long-term hemodialysis.

The pharmacokinetics, efficacy, and safety of nadolol were evaluated in hypertensive patients maintained on long-term hemodialysis. In nine patients the plasma elimination half-life of unchanged nadolol averaged 26 hours following a single 40 mg oral dose during the interdialytic period. Nineteen patients received nadolol once after each dialysis session. In addition, 12 of the 19 patients also received hydralazine and/or furosemide daily. Predialysis blood pressures and heart rates were significantly lower with nadolol than with combination or single therapy with conventional antihypertensive drugs, including other beta blockers. Nadolol administered only after each dialysis session (i.e., two or three times a week), in conjunction with hydralazine and/or furosemide, is an effective antihypertensive agent in hypertensive patients receiving long-term hemodialysis.

Adrenergic beta-Antagonists↗

Construct validity comparisons of three methods for measuring patient compliance.

A multitrait - multimethod design was employed to assess the construct validity of three commonly used methods for assessing patient compliance: physiological assessments (e.g., blood chemistries), ratings by health professionals, and patient self-reports. Subjects were patients receiving ambulatory hemodialysis treatments for end-stage renal disease, whose regimen required them to take medications, to follow dietary restrictions, and to limit fluid intake. Study findings indicated that of the three methods examined, the nurse rating approach was the most valid (although it contained only about 50 percent valid variance). Measures derived from physiological assessments contained a substantial proportion of residual error (over 70 percent), and the patient self-report method contained only about 12 percent valid variance (with about 18 percent method-effects variance, and 68 percent residual-error variance). These results make clear the need for additional research directed at developing valid methods for evaluating patient compliance behaviors.

Adult↗

Effects of hemodialysis on the cognitive and sensory-motor functioning of the adult chronic hemodialysis patient.

Twenty chronically dialyzed adults were administered a repeatable battery of 14 cognitive and sensory-motor tests on 3 consecutive days: immediately prior to their midweek dialysis, approximately 20 hr after their midweek dialysis, and again immediately prior to their end-of-the week dialysis. Serum electrolyte and methylamine analyses were performed at each test session. When compared to established norms, these patients scored within the normal range in a wide variety of areas. Limited impairments, probably due to peripheral neuropathy, were in evidence on the Grooved Pegboard, Finger Tapping (females), and Grip Strength (females) measures. Impairments suggestive of cerebral dysfunction were also noted on the Benton Visual Retention Test and on the Trail Making Test, Parts A and B, with particularly severe impairment noted on Part B. Despite significant daily changes in serum levels of toxic substances retained in uremia, there was little or no evidence to suggest that well-dialyzed patients undergo daily fluctuations in their cognitive and sensory-motor functioning.

Adult↗

Adult polycystic kidney disease: presymptomatic diagnosis for genetic counselling.

We evaluated 30 first degree relatives of 9 patients with end-stage renal disease secondary to adult polycystic kidney disease. The diagnostic accuracy of renal ultrasonography was compared with intravenous pyelogram with nephrotomography. In 27 patients the two tests were in agreement. In 3 patients both tests were abnormal but findings on IVP did not completely agree with ultrasonography. For early detection and genetic counselling, we recommend ultrasonography as the initial screening procedure for the evaluation of asymptomatic family members of a patient with APKD. IVP should only be considered if ultrasonogram is abnormal but not diagnostic of APKD.

Adolescent↗