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Biomedical subjects

E A Friedman

Publications and source records attributed to E A Friedman.

At least 109 records · Page 6Linked to original sources
PubMed1994

Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure.

In diabetes and ageing, glucose-derived advanced glycosylation endproducts (AGEs) cross-link proteins and cause vascular tissue damage. Elimination of circulating low-molecular weight AGE-modified molecules (LMW-AGEs) by the kidney is impaired in diabetic patients with end-stage renal disease, a group subject to accelerated atherosclerosis. We determined the effectiveness of current renal replacement treatments on elimination of serum LMW-AGEs in diabetic and non-diabetic patients with end-stage renal disease. Although diabetic patients receiving high-flux haemodialysis achieved 33% lower steady-state serum LMW-AGE than did those in conventional haemodialysis (p < 0.005), LMW-AGE concentrations remained 3.5-6 fold above normal, whether high-flux dialysis, conventional haemodialysis, or chronic ambulatory peritoneal dialysis were used. High-flux haemodialysis markedly reduced AGE during each treatment session (47.9% in the diabetic, p < 0.001 and 60.6% in the non-diabetic group, p < 0.001) but concentrations returned to pre-treatment range within 3 hours. In contrast, normal LMW-AGE concentrations were maintained in patients with functioning renal transplants. We found that LMW-AGEs with an apparent molecular weight of 2000-6000 circulate and retain strong inherent chemical reactivity--when exposed to collagen in vitro, up to 77% attached covalently to form AGE-collagen, and the AGE-crosslink inhibitor aminoguanidine completely inhibited this reaction. The results suggest that LMW-AGEs comprise a set of chemically-reactive molecules that are refractory to removal by current dialysis treatments. Through covalent reattachment onto vascular matrix or serum components, LMW-AGEs may exacerbate vascular pathology associated with end-stage renal disease.

Adult↗
PubMed1994

Dismal rehabilitation in geriatric inner-city hemodialysis patients.

OBJECTIVE: To assess the extent of functional and vocational rehabilitation achieved by elderly inner-city patients sustained on maintenance hemodialysis. DESIGN: Inception cohort study of elderly patients who have end-stage renal disease using a modified Karnofsky rating system. The need for a wheelchair, participation in household activities, and effect of comorbid conditions were noted. Current status was compared with patient's recollection of functional activity level 2 years before commencing maintenance hemodialysis. SETTING: Seven outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY. PATIENTS: One hundred four patients aged 65 years or older who were receiving maintenance hemodialysis for at least 6 months. MAIN OUTCOME MEASURES: A score of 76 or greater on a modified Karnofsky scale indicated independent function at a level that permitted participation in activities beyond those mandated by the hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed index correlated with severe debility. Employment status was also recorded. RESULTS: Present functional activity had deteriorated to a modified Karnofsky score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis. Diabetic patients had a lower score than nondiabetic patients. The mean comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within the diabetic subset, severe debility constrained 71 patients (68%) to limit all activity to their residence with the exception of travel to and from their dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81 diabetic patients (78%) had interests and activities that took them outside their homes (P < .001). Generalized weakness was the most common explanation given for the lack of outside activity by nine patients (9%) who were wheelchair bound. Erythropoietin, though regularly administered to 87 patients (84%) in the study group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05 (mean +/- SD). CONCLUSIONS: Maintenance hemodialysis does not return inner-city elderly patients to their predialysis level of functioning. Few elderly, diabetic hemodialysis patients conduct any substantive portion of their lives outside their homes. For nondiabetic patients, the modified Karnofsky score of whites (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4).

Activities of Daily Living↗
PubMed1994

Interdialytic weight gain correlates with glycosylated hemoglobin in diabetic hemodialysis patients.

Most of the excess mortality and morbidity in diabetic end-stage renal disease patients is ascribed to diabetes-associated cardiovascular disease, which is accelerated by uremia. We compared the interdialytic weight gain in 33 diabetic patients (group 1) undergoing maintenance hemodialysis in an ambulatory facility retrospectively over 3 months, with 25 randomly selected nondiabetic hemodialysis patients (group 2); in addition, we assessed glycemic control in the diabetic subjects using glycosylated hemoglobin (HbA1c). Interdialytic weight gain was expressed as a percentage of the immediately preceding postdialysis weight, and a mean was calculated for each subject. In all subjects, predialysis serum aldosterone, plasma renin activity, and the interdialytic change in serum sodium were measured. Both groups received an equivalent amount of dialysis using a cellulose membrane (mean +/- SD of thrice weekly dialysis: group 1 = 3.8 +/- 0.35 hours, group 2 = 3.86 +/- 0.3 hours; P < 0.5) and had similar predialysis serum creatinine, hematocrit, and serum albumin levels. Group 1 patients had a mean age of 56.5 +/- 11.4 years (age range, 30 to 71 years) and group 2 had a mean age of 55.8 +/- 15.4 years (age range, 29 to 76 years) (P < 0.84). Mean (+/- SD) duration on maintenance hemodialysis was 18.7 +/- 15.3 months (range, 2 to 84 months) for group 1 and 21 +/- 28.9 months (range, 3 to 156 months) for group 2 (P < 0.9). Interdialytic weight gain was 30% greater in group 1 (4.2% +/- 0.19%) than in group 2 (3.2% +/- 0.2%) (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Gouty arthritis in end-stage renal disease: clinical course and rarity of new cases.

We studied 201 end-stage renal disease (ESRD) patients sustained on maintenance hemodialysis (MD) (n = 164) and chronic ambulatory peritoneal dialysis (CAPD) (n = 37) to determine (1) the frequency of acute attacks of gouty arthritis (GA) in those ESRD patients who had GA before dialytic therapy, and (2) the incidence of new-onset GA in hyperuricemic long-term (> 12 years) ESRD patients on MD. The 2-month mean of predialysis serum uric acid levels was calculated for each subject and the prevalence of hyperuricemia ascertained. There were 25 patients on MD for more than 12 years, and this group was evaluated and analyzed separately from those patients on dialytic therapy for less than 12 years; the mean of each of their predialysis uric acid values was calculated for each subject for at least 60% of the time they have been on dialysis. Patients who had GA before or after initiation of dialytic therapy were identified, and the frequency of acute attacks of GA determined. The presence of treated hypertension in each subject was noted. Thirteen of 201 patients had clinically active GA before commencing dialytic therapy, and each recalled a minimum of two painful attacks of GA per year before the initiation of ESRD therapy. Mean duration of ESRD for these 13 patients was 25 +/- 3.8 months; painful attacks of GA have not recurred in nine patients (70%), and the frequency of attacks declined by 50% in the remaining four patients (30%), despite persistent hyperuricemia in all 13.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pervasive failed rehabilitation in center-based maintenance hemodialysis patients.

At its inception in 1972, the end-stage renal disease (ESRD) program was conceived with a set of assumptions about cost, rate of growth, and treatment outcomes in its client population. Despite the potential to correct anemia with recombinant erythropoietin (EPO) introduced in 1987 and improved survival, the level of physical activity among some segments of the hemodialysis population remains suboptimal. This study was undertaken, among other reasons, to identify correlates of poor functional status as measured by a modified Karnofsky scale. Using a modified Karnofsky scale, we measured the functional status of 430 patients who had been treated by hemodialysis for at least 1 year and some of whom were also receiving concomitant treatment with EPO. Patients studied were randomly selected from eight dialysis units in urban New York and suburban New Jersey. A Karnofsky score of less than 70 indicated frank disability--the subject was unable to perform routine living chores without assistance. In addition, current vocational activity was ascertained, and comorbid conditions were quantified. The necessity for wheelchair dependence was noted for each patient. The mean age (+/- SD) of the study population was 56 +/- 14 years (range, 21 to 92 years). Subjects had been on maintenance hemodialysis for 4.09 +/- 3.8 years (range, 1 to 23 years). The study group included 215 men and 215 women, of whom 65% were black, 27% white, 6% Hispanic, and 2% Asian; 36.5% had diabetes mellitus. Although 376 members (87%) of the study group were under treatment with EPO, the mean hematocrit of the study population was only 29% +/- 4.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1994

Partial absorption of hard exudates in patients with diabetic end-stage renal disease and severe anemia after treatment with erythropoietin.

BACKGROUND: Diabetic retinopathy improved in three patients with renal insufficiency after a rise in hematocrit induced by administration of recombinant erythropoietin. The change involved significant resorption of hard exudates in patients who were not eligible to receive laser treatment. METHODS: Three patients with diabetic nephropathy had the associated chronic anemia of renal insufficiency. In each patient, diabetic retinopathy with foveal/parafoveal hard exudates (but no clinically significant macular edema) was initially evaluated ophthalmoscopically. Fluorescein angiography demonstrated a low-grade diffuse leakage pattern. Treatment with subcutaneous recombinant erythropoietin (4000 IU twice weekly) was initiated within 1 to 3 months of initial evaluation. The resolution of hard exudates was observed on ophthalmoscopic examination and graded fundus photography (ETDRS seven standard field). RESULTS: Within 6 months of initiation of erythropoietin treatment, a substantial reduction of exudate was observed in all three patients, the hematocrit having increased from a mean of 21% to a mean of 33% (a mean increase of 33% in each patient). Visual acuity improved in two patients and stabilized in the other. Follow-up fluorescein angiographic examination demonstrated no change in the leakage pattern. CONCLUSION: Although no direct cause and effect relationship can be established, raising the red cell mass by treatment with recombinant erythropoietin may serve as adjunctive treatment of diabetic retinopathy in patients with diabetic renal insufficiency.

Absorption↗
PubMed1994

Salvage of clotted jugular vein hemodialysis catheters.

Jugular venous catheters (JVC) provide rapid, vascular access for both emergency and maintenance hemodialysis in both acute and end-stage renal disease. Clotting and occlusion of JVC is a common problem necessitating alternate vascular access. Urokinase will declot 80-90% of central venous catheters; however, recurrence of catheter occlusion is frequent. We successfully employed a guide wire insertion technique to salvage occluded JVC after failed urokinase infusion. In 24 patients JVCs, inserted for either temporary or permanent vascular access, clotted within 6-55 days of initiating hemodialysis. Urokinase (5,000 IU) instilled into both arterial and venous limbs of the catheter had been unsuccessful in restoring patency. In these patients, we inserted a soft-tipped guide wire into both lumina. In 21 of 24 patients (87.5%), guide wire insertion opened the occluded JVC, permitting immediate initiation of hemodialysis. We conclude that for clotted JVC unresponsive to urokinase infusion, guide wire insertion can salvage most catheters thereby facilitating hemodialysis.

Adult↗
PubMed1994

Cyclosporin A has divergent effects on plasma LDL cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] levels in renal transplant recipients. Evidence for renal involvement in the maintenance of LDL-C and the elevation of Lp(a) concentrations in hemodialysis patients.

Cardiovascular disease is the major cause of mortality in renal transplant recipients. Plasma levels of low-density lipoprotein cholesterol (LDL-C) are often elevated following renal transplantation, and the immunosuppressant cyclosporin A has been implicated as a predisposing factor for posttransplantation hyperlipidemia. Lipoprotein(a) [Lp(a)] is an LDL-like lipoprotein particle; elevated levels of Lp(a) provide an independent and significant risk factor for cardiovascular disease. Plasma concentrations of Lp(a) vary greatly among individuals, and the mechanisms that govern changes in their levels in transplant patients are unknown. The effect(s) of cyclosporin A on Lp(a) was studied in two groups of renal transplantation patients. In group I plasma lipoproteins including Lp(a) were measured before and after successful renal transplantation; this group received both prednisone and cyclosporin A for immunosuppression. Group II patients were studied after renal transplantation and received prednisone alone for immunosuppression. Following surgery, group I patients demonstrated increased plasma concentrations of LDL-C (mean +/- SEM range, 111 +/- 6 to 142 +/- 17 mg/dL; P < .005). In contrast, plasma Lp(a) levels for this group were markedly decreased after renal transplantation (median, 34.3 to 19.7 mg/dL). Patients not treated with cyclosporin A (group II) exhibited mean LDL-C and median Lp(a) levels (118 +/- 42 and 33.1 mg/dL, respectively) that were remarkably similar to those observed before renal transplantation (group I). These data confirm that hyperlipidemia following renal transplantation is associated with cyclosporin A therapy and show that this drug has opposing effects on plasma Lp(a) and LDL-C accumulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of early hyperlipidemia on graft and patient survival in cyclosporine-treated renal transplant patients.

Hyperlipidemia commonly occurs following renal transplantation. As hyperlipidemia has been postulated to contribute to renal dysfunction in animal models, the effect of early hyperlipidemia was studied in a cohort of 43 cyclosporine-treated renal transplant recipients over a 4-year follow-up period. Hypercholesterolemia occurred in 25 patients, with 18 patients remaining normolipidemic during the initial 3 months following transplantation. Prospective follow-up over a 4-year period was available for 16 of the 18 normolipidemic patients and 25 patients who developed hyperlipidemia, as well as 11 other hyperlipidemic patients who were not included in the initial analysis. Graft function was maintained in 11 (69%) of the patients with early normolipidemia and there has been one patient death (7%). Of the hypercholesterolemic group, two patients were lost to follow-up and 23 of the remaining 34 (68%) had persistent graft function. There have been two patient deaths (6%). No deaths from cardiovascular deaths have occurred in either group, all deaths resulting from infection/sepsis. Mean cholesterol values at 4-year follow-up were 202.0 +/- 11.2 mg/dL for the patients with early normolipidemia 282.9 +/- 14.3 mg/dL for the patients with early hyperlipidemia (p < 0.00001). The most recent cholesterol value was not associated with pretransplant cholesterol value, creatinine, or cyclosporine dose, but was associated with cholesterol value at 3 months both by regression analysis (P < 0.0001) and by Pearson R (r = 0.71, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗
PubMed1993

Dialytic therapy for diabetic patients with terminal renal failure.

Diabetes mellitus is the leading cause of irreversible renal failure in the United States, Japan, and industrialized Europe. Of those diabetic patients begun on uremia therapy, 80% are treated with hemodialysis and 12% with peritoneal dialysis. Continuous ambulatory peritoneal dialysis is proposed by some as appropriate primary therapy for many diabetics with end-stage renal disease (ESRD), but peritonitis is common at one episode per 11 to 21 patient-months. Cardiovascular disease is accelerated in patients with diabetic ESRD and is the most common cause of death in diabetic dialysis patients. Although survival of diabetic ESRD patients is lower than that of nondiabetic patients (1- and 5-year patient survival is 74% and 19%, respectively, in diabetics and 78% and 40%, respectively, in all ESRD patients), morbidity and mortality figures have improved steadily over the past two decades. When possible, renal transplantation is advised as the treatment most likely to effect rehabilitation and long survival.

Cardiovascular Diseases↗
PubMed1993

Correction of erythrocyte deformability defect in ALX-induced diabetic rabbits after treatment with aminoguanidine.

To test whether treatment with aminoguanidine, a drug known to prevent cross-linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and after 20 wk of treatment with aminoguanidine (100 mg.kg-1 x day-1). The key findings were as follows: 1) at 12 wk of treatment with aminoguanidine, mean erythrocyte deformability normalized and remained within the normal reference range throughout the period of aminoguanidine administration; 2) 10 wk after discontinuing aminoguanidine in a subset of diabetic rabbits, mean erythrocyte deformability deteriorated by approximately 50%; 3) blood glucose and total GHb did not vary significantly during treatment with aminoguanidine nor after its discontinuation.

Animals↗