PubMed Health⌕ Search

Biomedical subjects

J M Lazarus

Publications and source records attributed to J M Lazarus.

At least 55 records · Page 3Linked to original sources
PubMed1996

Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease.

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.

Absorption↗
PubMed1996

Therapeutic plasma exchange in renal diseases.

Plasma exchange has been used extensively for over 2 1/2 decades to treat a variety of renal diseases. In this article, the scientific rationale for therapeutic plasma exchange in primary and secondary glomerulonephritis, thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, myeloma cast nephropathy, and allograft rejection are reviewed. The clinical studies that evaluate its efficacy are summarized, with special emphasis on the results of randomized controlled trials, when available. Consensus plasma exchange regimens are presented for diseases in which there is evidence to support its use.

Animals↗
PubMed1996

Multicenter clinical validation of an on-line monitor of dialysis adequacy.

Quantitation of hemodialysis by measuring changes in blood solute concentration requires careful timing when taking the postdialysis blood sample to avoid errors from postdialysis rebound and from recirculation of blood through the access device. It also requires complex mathematical interpretation to account for solute disequilibrium in the patient. To circumvent these problems, hemodialysis can be quantified and its adequacy assessed by direct measurement of the urea removed in the dialysate. Because total dialysate collection is impractical, an automated method was developed for measuring dialysate urea-nitrogen concentrations at frequent intervals during treatment. A multicenter clinical trial of the dialysate monitoring device, the Biostat 1000 (Baxter Healthcare Corporation, McGaw Park, IL) was conducted to validate the measurements of urea removed, the delivered dialysis dose (Kt/V), and net protein catabolism (PCR). The results were compared with a total dialysate collection in each patient. During 29 dialyses in 29 patients from three centers, the paired analysis of urea removed, as estimated by the dialysate monitor compared with the total dialysate collection, showed no significant difference (14.7 +/- 4.7 g versus 14.8 +/- 5.1 g). Similarly, measurements of Kt/V and PCR showed no significant difference (1.30 +/- 0.18 versus 1.28 +/- 0.19, respectively, for Kt/V and 42.3 +/- 15.7 g/day versus 52.2 +/- 17.4 g/day for PCR). When blood-side measurements during the same dialyses were analyzed with a single-compartment, variable-volume model of urea kinetics, Kt/V was consistently overestimated (1.49 +/- 0.29/dialysis, P < 0.001), most likely because of failure to consider urea disequilibrium. Because urea disequilibrium is difficult to quantitate during each treatment, dialysate measurements have obvious advantages. The dialysate monitor eliminated errors from dialysate bacterial contamination, simplified dialysate measurements, and proved to be a reliable method for quantifying and assuring dialysis adequacy.

Cross-Sectional Studies↗
PubMed1996

Performance characteristics of a dialysis-related amyloidosis questionnaire.

To evaluate the effects of beta-2 microglobulin amyloidosis on functional status, a 19-item self-administered questionnaire exploring two major domains-symptoms and disability-was developed as part of this study. Fifteen patients with dialysis-related amyloidosis (DRA) were identified and compared with 15 age-matched control subjects who had been on hemodialysis for less than 24 months. Demographic data, Charlson comorbidity scores, and other clinical and laboratory variables were recorded. Total dialysis-related amyloidosis questionnaire (DRAQ) score (52.1 +/- 16.3 versus 24.4 +/- 6.2, P < 0.0001) and the scores of the symptom (24.5 +/- 7.0 versus 11.5 +/- 2.3, P < 0.0001) and disability (27.5 +/- 10.8 versus 12.9 +/- 4.0, P < 0.0001) subscales were markedly increased among patients with DRA. Baseline characteristics among case and control subjects were similar, except for serum creatinine concentration, which tended to be lower among patients with DRA (8.9 +/- 2.6 versus 11.5 +/- 2.3 mg/dL, P = 0.07). Instrument reliability and internal consistency were high. With a total DRAQ score of 30 or more, the sensitivity and specificity of the instrument were 93% and 80%, respectively. The DRAQ is a reliable, internally consistent, and valid instrument that may be suitable for population screening and clinical practice.

Activities of Daily Living↗
PubMed1995

Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. METHODS: The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. RESULTS: The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. CONCLUSIONS: Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.

Acute Kidney Injury↗
PubMed1995

Intact parathyroid hormone levels in renal insufficiency.

To define the onset of the rise in intact parathyroid hormone (PTH) levels in renal insufficiency, we conducted a cross-sectional study of parameters of mineral metabolism in patients with varying degrees of renal impairment. Using an immunoradiometric assay to measure intact PTH levels, we found elevations in intact PTH levels as creatinine clearance approaches 60 ml/minute (serum creatinine near 1.8) and a significant inverse relationship between indices of renal function and intact PTH levels (r = -0.60, P < 0.001 for intact PTH and creatinine clearance.) Calcium and phosphate levels correlate less strongly with the degree of hyperparathyroidism (r = -0.39, P < 0.001 for total calcium; r = 0.31, P < 0.05 for phosphate). As a group, only patients with severe renal failure (creatinine clearance < 20 ml/minute) had 1,25-dihydroxyvitamin D levels below normal (11 +/- 4 [SEM] pg/dl, normal range 15-60). Intact and n-terminal PTH measurements correlate well in this patient population with varying degrees of renal insufficiency (r = 0.9, P < 0.001). Intact PTH can be elevated in patients with mild to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.

Adult↗
PubMed1995

Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients.

Hemodialysis patients were studied to determine whether the dose of recombinant human erythropoietin (Epoetin alfa; Amgen Inc, Thousand Oaks, CA) required to maintain a therapeutic hematocrit level changed when the route of administration was switched from intravenously (IV) three times per week to subcutaneously (SC) three times per week. Thirteen to 16 weeks after patients were changed from IV three times per week to SC three times per week treatment, the Epoetin alfa requirement was reduced by 18.5% +/- 3.8% (P < 0.001; n = 72), and after 21 to 24 weeks of SC treatment the mean dosage had decreased from the IV dose by 26.5% +/- 4.2% (P < 0.001; n = 41). Sixty-one percent (44 of 72) of patients experienced maintenance-dose reductions over 13 to 16 weeks of treatment and 80% (33 of 41) were maintained on lower weekly doses after 21 to 24 weeks of treatment than at baseline (IV). There was interpatient variability, however: 26% of the patients required greater doses SC than IV following 13 to 16 weeks of SC treatment, and 15% required greater doses SC than IV following 21 to 24 weeks. On completing the initial SC three-times-per-week stage of the study, patients were randomized to one of three SC dosing strategies for an additional 12 weeks: (1) once per week, (2) three times per week Epoetin alfa diluted 1:2 with bacteriostatic saline to mitigate stinging at the injection site, or (3) continued three times per week with undiluted Epoetin alfa. Patients who were switched to administration of SC once per week undiluted Epoetin alfa (n = 20) had their total weekly dose lowered by 18.0% +/- 9.4% (P > 0.05), but the mean hematocrit for this cohort also decreased, from 34.3% +/- 3.0% to 32.4% +/- 3.9% (P > 0.05), rendering dose comparison between the two schedules ambiguous. The maintenance dose for patients who received Epoetin alfa diluted 1:2 with bacteriostatic saline (n = 23) did not differ from the undiluted three times per week dose at the end of stage 1. The third cohort of patients (n = 24), who continued to receive undiluted Epoetin alfa on the same SC three-times-per-week schedule, did not require a significant change in dosage over the ensuing 12 weeks. Comparison of SC three times per week mean dosage after an average of 32 weeks following the switch from IV three times per week for this latter cohort revealed a decrease of 23.5% +/- 6.5% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Multifrequency bioelectrical impedance estimates the distribution of body water.

Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.

Body Composition↗
PubMed1995

Initiation of dialysis.

The decision to initiate dialysis in a patient with progressive renal disease often depends on the physician's assessment of the patient's subjective symptoms of uremia. There is an increasing need to identify objective criteria for such a decision. Recent evidence suggests that malnutrition at the initiation of dialysis is a strong predictor of subsequent increased relative risk of death on dialysis. In this context, the role of prescribed protein restriction as well as the influence of the progression of renal disease on spontaneous dietary protein intake is examined. It is proposed that the indices of malnutrition such as progressive weight loss, serum albumin levels below 4.0 g/dL, serum transferrin levels below 200 mg/dL, and spontaneous dietary protein intake (using 24-hr urinary nitrogen measurement) below 0.8 to 0.7 g/kg per day be considered as objective criteria for the initiation of dialysis. Studies that have examined the role of "early" versus "late" dialysis have consistently shown a better outcome in the patients starting dialysis early. Other studies also suggest that early referral to nephrologists results in improved morbidity and mortality as well as hospitalization costs. An adequate vascular access, as well as social and psychological preparation of the patient, is an important early step in the process.

Humans↗
PubMed1994

The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients.

Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.

Creatinine↗
PubMed1994

Role of bioincompatibility in dialysis morbidity and mortality.

This review examines the mechanisms by which bioincompatibility in dialysis systems may have an effect on morbidity and mortality in the dialysis population. Direct toxic effects of membrane materials and various chemical substances have been well demonstrated in the chronic dialysis population. Activation of the complement cascade and stimulation of cytokine production may have autocrine effects on leukocyte function with sequelae such as enhanced rates of infection and the development of B2-microglobulin amyloidosis. The variable effect of different membrane materials on each of these effector systems is examined. Bioincompatibility may effect the incidence of infection, malignancy, cardiopulmonary disease, and malnutrition as well as induce novel disease processes. All these confounding variables must be considered when evaluating the effect of dialysis on mortality and morbidity.

Biocompatible Materials↗
PubMed1994

Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study.

Hemodialysis (HD) vascular access thrombosis remains a major cause of morbidity, accounting for 17.4% of all HD patient hospital admissions in 1986. We initiated this prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded polytetrafluoroethylene (ePTFE) grafts in HD patients. Two patient groups were studied: Type I--with a new ePTFE graft; and Type II--with thrombectomy and/or revision of a previously placed ePTFE graft. One hundred and seven patients were followed for 18 months or until the first thrombotic episode. Actuarial analysis of Type I patients showed cumulative thrombosis rates (mean +/- SEM) of 21 +/- 9% on dipyridamole alone, compared with 25 +/- 11% on dipyridamole and aspirin combination, 42 +/- 13% on placebo, and 80 +/- 12% on aspirin alone. The relative risk of thrombosis with dipyridamole was 0.35 (P = 0.02) and that for aspirin was 1.99 (P = 0.18). In Type II patients, the rate of thrombosis was high in all study drug and placebo groups (overall 78% thrombosis) and actuarial analysis was not carried out because of the small number of patients enrolled. We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts. Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts.

Adult↗
PubMed1994

Sustained volume expansion and [Na,K]ATPase inhibition in chronic renal failure.

Hypotheses regarding the pathogenesis of volume-dependent hypertension have invoked an endogenous sodium pump inhibitor or digitalis-like factor (DLF) to link altered sodium homeostasis to the rise in blood pressure. Our goal was to develop a clinical protocol that achieved predictable, sustained volume expansion, with the premise that renal failure patients on peritoneal dialysis would increase intravascular volume, gain weight, and raise blood pressure (BP) in relation to measured increases in DLF. In a 5-day protocol, dialysis was kept constant but dietary NaCl and fluids were modified in 7 patients. DLF was measured as inhibition of [Na,K]ATPase. Likewise, the first 2 L of daily peritoneal dialysate (PD) was processed on HPLC and the eluate analyzed for DLF. The group achieved significant weight gain (WT) by day 3 (delta WT = 4.1 +/- 1.2 kg, P < .05). Likewise, mean arterial pressure (MAP) and plasma DLF activity increased significantly. All variables were highly correlated (DLF v WT: R = 0.88, P = .004; MAP v DLF: R = 0.82, P = .01; MAP v WT: R = 0.90, P = .003). Although a number of HPLC fractions contained agents that interacted with the assay, only one PD HPLC fraction (at 19.5 min) contained DLF activity that correlated with changes in MAP (R = 0.60, P = .002), and body weight (R = 0.67, P = .0003). We conclude that candidate DLF responds to sustained volume expansion and the relationship suggests that it could influence blood pressure. Moreover, the application of stringent criteria to the confusing array of factors in plasma that may affect assays for DLF appears to reduce the field dramatically, to a single candidate in this setting.

Adult↗
PubMed1993

The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

BACKGROUND: Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. METHODS: We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. RESULTS: As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. CONCLUSIONS: Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.

Diabetes Mellitus↗
PubMed1993

National Cooperative rHu Erythropoietin Study in patients with chronic renal failure--an interim report. The National Cooperative rHu Erythropoietin Study Group.

This second interim report of the National Cooperative rHu Erythropoietin Study presents data from 324 patients new to recombinant human erythropoietin (Epoetin alfa) who completed at least 12 months of study participation. Mean hematocrit levels increased to approximately 30% by month 3 in patients on hemodialysis (n = 293) and stabilized for the remainder of the study whether Epoetin alfa was administered by the intravenous (n = 250) or subcutaneous (n = 42) route. The intravenous dosage level ranged between 106.9 and 121.6 U/kg/wk; subcutaneous dosing ranged between 87.4 and 108.0 U/kg/wk; dosing levels in patients on peritoneal dialysis (n = 31) were similar, although there was a trend towards slightly higher hematocrit levels. Throughout the 12 months of the study, there was no relationship between blood pressure and either hematocrit level or Epoetin alfa dose. Approximately two thirds of the patients were receiving iron supplementation at any given time, and there was a trend towards the increased use of oral iron supplements. The incidence of adverse events in this cohort of patients was low throughout the study, and there was no relationship between the incidence of adverse events and either hematocrit level or Epoetin alfa dose. Based on an analysis of data from baseline to first follow-up, Epoetin alfa therapy resulted in improvement in several quality-of-life factors, most notable of which was vitality. Improvement occurred in all patient subgroups with some variability in the level and intensity of effect. Overall, these data demonstrate that Epoetin alfa therapy is safe and effective when used in a broad cross-section of patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗