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Biomedical subjects

A R Nissenson

Publications and source records attributed to A R Nissenson.

At least 19 recordsLinked to original sources
PubMed1992

Epoetin and cognitive function.

The uremia of chronic renal failure (CRF) can alter brain electrophysiology and cognitive function, even in the well-dialyzed patient. The effect of uremia on brain function can be assessed by electrophysiologic techniques such as electroencephalogram (EEG), sensory-evoked potentials (EPs), and cognitive event-related potentials (ERPs), and through a series of neuropsychologic tests. Five tests have been used clinically to measure the speed and efficiency of cognitive functioning and include the following: Number Cancellation, Trailmaking Test, Symbol Digit Modalities Test, Rey Auditory Verbal Learning Test, and Controlled Oral Word Association Test. Test performance by patients with CRF is often below that of healthy controls. Auditory ERPs, a sensitive indicator of subtle changes in central nervous system (CNS) function in uremia, result in the generation of a P300 component wave that varies in amplitude and latency with patient variables such as attention and effort. Although dialysis tends to normalize P300 latencies, the waves remain somewhat prolonged in most patients. The anemia often observed in patients receiving chronic dialysis appears to aggravate uremic encephalopathy. This effect can be reversed when anemia is corrected following administration of recombinant human erythropoietin (epoetin). Improvement in P300 amplitudes, and, in some cases, decreases in P300 latencies correlated well with epoetin-induced increases in hematocrit levels. With the correction of anemia, that component of brain dysfunction not attributable to retention of uremic toxins can largely be reversed.

Anemia↗
PubMed1991

Recombinant human erythropoietin and renal anemia: molecular biology, clinical efficacy, and nervous system effects.

Anemia (hematocrit less than 25%) predictably accompanies chronic renal failure and is present in over 90% of patients on chronic dialysis. Relative erythropoietin deficiency is the proximate cause. Recombinant human erythropoietin recently became available for research and clinical use. Erythropoietin production is regulated by a single copy gene located on chromosome 7; its expression has been shown in the kidney, liver, and macrophages. It is glycosylated protein of 166 amino acids with a molecular weight of 34,000 D. When given to patients with the anemia of renal failure, erythropoietin causes a dose-dependent rise in hematocrit to the normal range within 8 to 14 weeks. Complications of this response are minimal except for a significant incidence of hypertension. When the anemia is corrected, the patient's quality of life, cognitive function, and brain electrophysiology improve dramatically. Recombinant human erythropoietin represents a major breakthrough in the treatment of patients with chronic renal failure. Current reimbursement constraints limit its full application.

Anemia↗
PubMed1991

Cognitive function, mood and P3 latency: effects of the amelioration of anemia in dialysis patients.

Attention difficulties and psychomotor slowing associated with depressed mood affect the ability of individuals to perform on most neuropsychological tests. It has been suggested that latency of the P3 (P300) component of the event-related EEG potential is an index of neurocognitive status which is not affected by mood. Dialysis patients, who experience diminished dysphoric mood with the reversal of anemia when treated with recombinant human erythropoietin (rHuEPO), were tested for neurocognitive performance, mood and latency of P3. Prior to rHuEPO treatment mood was dysphoric, and neurocognitive testing showed mild deficits, but P3 latency was normal. After treatment, mood improved and neurocognitive test performance was normal. P3 amplitude increased over frontal areas, while P3 latency remained unchanged. Thus, in the case of dysphoric mood, P3 latency may provide a more accurate index of cognitive capacity (as opposed to level of functioning) than neurocognitive test measures.

Affect↗
PubMed1991

rHuEPO treatment improves brain and cognitive function of anemic dialysis patients.

Twenty-four patients with chronic renal failure, stabilized on hemodialysis, were treated with recombinant human erythropoietin. Before treatment, all patients were anemic (mean Hct = 23.7%). Hematocrits reached normal levels (36.5%) after three months of treatment. Brain event-related potentials and neuropsychological tests were used to assess changes in brain and cognitive functions associated with the correction of anemia. Assessments were done prior to and after three and twelve months of rHuEPO treatment. The P3 component of the event-related potential increased in amplitude significantly with treatment, while its latency was unaffected. Of the four neuropsychological tests administered, scores on two improved significantly with treatment, and the other two approached significance. Taken together, these findings suggest that the correction of anemia to hematocrits near normal in uremic patients by rHuEPO treatment improves brain and cognitive function by raising levels of sustained attention, thus increasing speed and efficiency of scanning and perceptual-motor functions and enhancing learning and memory. These findings also suggest that anemia, either directly or indirectly, may impair brain function.

Anemia↗
PubMed1991

National cooperative rHu erythropoietin study in patients with chronic renal failure: a phase IV multicenter study. Report of National Cooperative rHu Erythropoietin Study Group.

Initial experience with recombinant human erythropoietin (rHuEPO, epoetin alfa) was gained through research protocols in which patient selection and management were tightly controlled. When epoetin alfa was approved for use by the Food and Drug Administration (FDA) these constraints were removed. The present study was designed to examine the medical and social impact of epoetin alfa therapy, as well as to document its safety and efficacy as it is used in clinical practice. From 1,000 to 2,000 patients at 100 to 200 centers will be enrolled and monitored for 1 year. Two groups of patients are being studied--those already receiving epoetin alfa at study entry and those new to epoetin alfa therapy. Demographic data are collected initially and detailed outcome data are collected monthly. This interim report presents data from 68 participating dialysis centers on 447 enrolled patients. To date, 89% of the patients are on in-center hemodialysis, while 9% are on home dialysis (79% continuous ambulatory peritoneal dialysis [CAPD], 14% continuous cyclic peritoneal dialysis [CCPD]). Preliminary analyses suggest this population is similar in age and cause of chronic renal failure to the overall US dialysis population, although whites and males are somewhat underrepresented. Of those already on epoetin alfa at study entry, 62% were receiving 3,000 to 9,000 U/wk. In addition, those already on epoetin alfa had better self-rated general health than those new to therapy. Outcomes and epoetin alfa usage patterns are currently being fully analyzed. Three-month follow-up data on a cohort of patients new to epoetin alfa indicate that the average dose in these patients is less than 100 U/kg/wk; two thirds of the doses were administered intravenously. Hematocrit levels increased over the 3 months from a level of 25.1% at entry to 30.6% by month 3. The percentage of cohort patients who were transfusion-independent increased from 85.1% at study entry to 95.7% by month 3. No increases in the incidence of adverse events occurred in the cohort group and no changes in the safety profile were indicated. These preliminary findings suggest that low doses of rHuEPO are being used in general, with a resultant low mean hematocrit. Thus, patients do not seem to be realizing the full potential beneficial effects of this remarkable agent.

Adolescent↗
PubMed1990

Peritoneal dialysis in the geriatric patient.

Elderly patients on chronic peritoneal dialysis (CPD) from two large chronic peritoneal dialysis programs were compared with younger patients in regard to peritonitis rates, catheter problems, hospital days, transfers to other forms of therapy, and mortality. Peritonitis rates and organisms were similar in younger and older patients. Catheter replacements were less common in the elderly. Differences in hospital days were attributable to hospitalization for vascular disease. The elderly were more likely to have the first episode of peritonitis, to die and to change dialysis modalities at all times after the first year of continuous ambulatory peritoneal dialysis (CAPD) treatment, although other than increased mortality, differences between the two groups were small. CPD appears to be an acceptable form of renal replacement therapy in the elderly.

Aged↗
PubMed1990

Outcome of end-stage renal disease in patients with rare causes of renal failure. III. Systemic/vascular disorders.

This multicentre national study has provided demographic and outcome data on over 1700 patients with rare systemic/vascular diseases as a cause of ESRD. Except for those with Henoch-Schönlein purpura, polyarteritis nodosa and Wegener's granulomatosis, women predominated. On the other hand, black patients seem less susceptible to these illnesses than white patients except for SLE. Recovery of renal function sufficient for dialysis to be discontinued was more likely in each of these diseases except for SLE than for any of the other 'rare' diseases described by us, the usual causes of renal failure as reported by the EDTA Registry or our control patients. Overall survival was quite good except in those patients with progressive systemic sclerosis whose outlook was poor.

Adult↗
PubMed1979

Variations in serum complement following inulin infusion in man.

Complement levels were determined in 12 normal human volunteers while receiving intravenous infusions of inulin for determination of standard inulin clearances. Significant decreases in beta IC globulin and total hemolytic complement activity were observed when inulin was infused, but not following infusion of saline as a control. These effects were noted only when steady-state inulin levels were greater than 26 mg%, suggesting a dose-dependent response. No evidence of increased coagulation was noted as measured by fibrinogen and fibrin degradation products. Since C4 levels remained largely unchanged following inulin infusion, it was concluded that the results most likely occurred through activation of the alternate complement pathway.

Adult↗
PubMed1979

Poststreptococcal acute glomerulonephritis: fact and controversy.

Poststreptococcal acute glomerulonephritis is prototypic of the immunologic glomerulonephritides. It most commonly follows streptococcal infection of the pharynx or skin. The diagnosis is usually not difficult when a nephritic clinical presentation (with such manifestations as hematuria, edema, and hypertension) is associated with serologic evidence of recent streptococcal infection and a depressed serum complement concentration. Currently, however, the nephritogenic antigen(s) has not been identified and has not been shown to be the same antigen for all nephritogenic streptococci; it may not even be a part of the infecting organism. The development of a vaccine to prevent this illness from occurring is therefore still not possible. Whether poststreptococcal acute glomerulonephritis progresses to chronic renal failure is still uncertain. Painstaking laboratory research together with careful, prospective long-term follow-up studies of patients with poststreptococcal acute glomerulonephritis may provide some of the answers to these critical questions.

Acute Disease↗
PubMed1979

Hemodialysis in the treatment of psoriasis. A controlled trial.

We have treated seven patients with severe psoriasis with sham or true hemodialysis. Three patients received one 24-h course of true hemodialysis over 4 d followed by an identical 24-h course 4 weeks later. Four patients received one 24-h course of sham diaglysis over 4 d followed by a 24-h course of true dialysis 4 weeks later. Significant subjective improvement was noted by both groups after the first series of treatments but not after the second. No objective improvement in skin disease was found at any time. We were unable to confirm the many uncontrolled reports on the efficacy of dialysis in ameliorating severe psoriasis. Neither the heparin used for anticoagulation, the acetate present in the dialysis bath, nor the removal of a "psoriatic factor" seemed to affect the skin disease in these patients.

Acetates↗
PubMed1979

Mannitol.

Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.

Acute Kidney Injury↗