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Biomedical subjects

J M Lazarus

Publications and source records attributed to J M Lazarus.

At least 19 recordsLinked to original sources
PubMed1992

Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis.

OBJECTIVE: To evaluate the utility of real-time, high-resolution ultrasound of the shoulder in the diagnosis of dialysis-related amyloidosis. METHODS: We performed a case series study of 2 groups of patients seen at a referral-based clinic in a tertiary care hospital. The shoulders of 13 patients with normal renal function and of 38 patients receiving long-term hemodialysis were studied by real-time, high-resolution ultrasound. All hemodialysis patients were evaluated clinically for the presence of dialysis-related amyloidosis. Surgical specimens of joints were available for all 13 patients with normal renal function and for 17 of the 38 hemodialysis patients. These specimens were evaluated for the presence of beta 2-microglobulin (beta 2m) amyloid by Congo red and immunohistochemical staining. RESULTS: Two ultrasonographic findings were selectively observed in the dialysis patients with clinical and histologic evidence of beta 2m amyloid in comparison with patients with normal renal function and no evidence of amyloid: rotator cuffs greater than 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff. The presence of at least 1 of these 2 findings corresponded to the presence of clinically and histologically evident beta 2m amyloid with a sensitivity of 79% and a specificity of 100%. When additional patients without surgical specimens for histologic confirmation of amyloidosis were included, the sensitivity of these 2 sonographic findings was 72% and the specificity was 97%. CONCLUSION: Real-time, high-resolution ultrasound is a relatively sensitive and highly specific noninvasive adjunct to the clinical diagnosis of beta 2m amyloidosis in patients receiving long-term hemodialysis.

Adult↗
PubMed1991

Reactive oxygen species production by monocytes and polymorphonuclear leukocytes during dialysis.

Intradialytic production of reactive oxygen species (ROS) by monocytes and polymorphonuclear leukocytes (PMNL) was examined separately in six hemodialysis patients. Samples obtained 15 minutes after initiation of dialysis with new cuprophane membranes demonstrated significantly increased (P less than 0.05) ROS production in both cell populations as measured by the fluorescence of a specific intracellular marker (2',7'-dichlorofluorescein diacetate [DCFH-DA]) assayed by flow cytometry. Granulocytes harvested during dialysis also showed decreased responsiveness to exogenous C5a and F-Met-Leu-Phe (FMLP) at 15, 30, and 60 minutes after initiation of dialysis (P less than 0.05). Our data suggest that hemodialysis with cuprophane membrane is associated with monocyte and PMNL activation as shown by production of ROS coincident with peak activation of the complement cascade; these granulocytes become refractory to further stimulation with C5a and FMLP during dialysis.

Adult↗
PubMed1991

Ten-year experience with cyclosporine as primary immunosuppression in recipients of renal allografts.

Cyclosporine has been used as primary immunosuppression in renal allograft recipients in our unit for the past decade. The overall clinical experience and long-term effects of the agent are reviewed. There were 461 consecutive recipients of kidney grafts; 379 received grafts from cadaver donors (CAD) and 82 from living related donors (LRD). Four separate clinical protocols were used sequentially using progressively decreasing doses of CyA; azathioprine was added in group 4 recipients of LRD grafts, and in patients receiving secondary CAD grafts (group 5). The patient mortality rate was less than 5%, with sepsis being the prime contributor. The majority of kidney grafts were lost within the first 2 months after operation; those that never functioned were found almost invariably to have been irreversibly rejected. During the subsequent years of follow-up, attrition of CAD grafts was significantly greater than LRD grafts. In contrast, the attrition rate of primary and secondary CAD grafts was the same after the first 3 months, emphasizing the importance of early immunologic graft destruction. Primary nonfunction occurred in 49% of CAD kidneys and 17% of LRD grafts; however 71% of initially nonfunctioning LRD grafts never functioned at all compared to 34% of CAD grafts, the majority of such organs undergoing fulminate rejection. Individual graft loss after 1 year was almost inevitably due to chronic rejection; there were no differences in long-term allograft function among the treatment groups. Although CyA has improved overall results of kidney transplantation, chronic rejection remains a major unresolved problem.

Adult↗
PubMed1991

Effects of recombinant human growth hormone in adults receiving maintenance hemodialysis.

Administration of recombinant human growth hormone stimulates protein synthesis, decreases urea generation, and improves nitrogen balance in individuals with normal renal function. However, little information is available concerning the effects of growth hormone in patients with renal disease. This pilot study evaluated urea kinetics and clinical/metabolic responses to short-term growth hormone administration in five clinically stable adult patients requiring maintenance hemodialysis for end-stage renal failure. The dialysis prescription, medications, and oral calorie and protein intake of each patient remained constant during an initial control week and a subsequent 2-wk growth hormone treatment period. During treatment, growth hormone (5 or 10 mg) was administered s.c. immediately after each dialysis session. Protein and calorie intake, vital signs, body weight, and other clinical parameters remained stable throughout the 3-wk study. BUN values fell significantly (approximately 20 to 25%) during growth hormone administration compared with control week values. Similarly, urea kinetic modeling demonstrated a significant reduction in urea generation and the protein catabolic rate during each week of growth hormone treatment. Plasma insulin-like growth factor I levels rose significantly, and serum phosphorus and intact parathyroid hormone levels fell significantly during growth hormone administration. Serum glucose and other blood values remained stable. This preliminary study suggests that growth hormone administration reduces urea generation and improves the efficiency of dietary protein utilization in stable adult hemodialysis patients. Growth hormone may be a useful adjunctive therapy to diminish body protein catabolism in this patient population.

Adult↗
PubMed1990

Extracorporeal removal of anti-HLA antibodies in transplant candidates.

We report on the results of a clinical trial in which 14 transplant candidates were treated with an extracorporeal immunoadsorption system using Protein A that selectively removes immunoglobulin from plasma; we also assessed the dynamics of anti-HLA antibody as a model of IgG removal and re-equilibration, as well as the clinical safety of the procedure. At the end of a treatment course, plasma IgG levels were reduced by 90% +/- 8% of control values (P less than 0.01). In contrast, albumin levels were reduced by only 15% (P less than 0.05). Specific cytotoxic anti-HLA antibody titers were reduced by approximately 18-fold. Panel reactivity was measured as the proportion of a 40-member cell donor panel killed by patients' serum in the presence of complement; in nine of the 14 patients, there was a significant reduction in this parameter (range, 23% to 87%). During the 4-week follow-up period, anti-HLA antibody titers returned to baseline levels. There were no remarkable changes observed in blood chemistries, nor were there any unanticipated adverse reactions seen in the patients treated. We conclude that selective extracorporeal immunoadsorption is a safe and effective way of removing IgG-type antibodies, with potential application to reduction of HLA antibodies in transplant candidates.

Adult↗
PubMed1990

Recombinant human erythropoietin and phlebotomy in the treatment of iron overload in chronic hemodialysis patients.

Five long-term hemodialysis patients with clinical iron overload were treated with 300 U/kg of recombinant human erythropoietin (rHuEPO) intravenously (IV) after each hemodialysis. The patients were phlebotomized after each hemodialysis at any time the predialysis hematocrit was 35% or greater. Over a period of 1 year, the average phlebotomy rate varied from 0.5 to 1.1 U/wk with a mean phlebotomy rate of 45.8 +/- 5.6 U/yr (range, 27 to 57 U). The mean serum ferritin decreased from 8,412 +/- 1,599 micrograms/L (ng/mL) to 3,007 +/- 1,129 micrograms/L (ng/mL), and the mean iron removal over this period was 9.5 g. Liver iron deposition, as measured by density on computed tomographic (CT) scan, improved, while skin color lightened significantly. Patients tolerated phlebotomy with no major symptoms or complications and exhibited no change in the hemogram or serum chemistries. In patients with severe iron overload, changes in serum ferritin with erythropoietin treatment alone may not reflect true change in iron burden. Use of high-dose erythropoietin and phlebotomy is an effective and safe (at least for 1 year) method of reducing iron overload in long-term hemodialysis patients.

Adult↗
PubMed1989

Progression of chronic renal failure.

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.

Creatine↗
PubMed1989

Reduced angiotensin receptors and pressor responses in hypotensive hemodialysis patients.

A sub-set of patients on chronic hemodialysis develop sustained hypotension (systolic pressure less than 100 mm Hg). To determine whether this hypotension could be due to altered production of, or sensitivity to angiotensin II (AII), we measured plasma renin (PRA), AII, and aldosterone in nine hypotensive and nine normotensive dialysis patients; we also assessed their sensitivity to infused AII and studied AII binding to their platelets as an indicator of AII receptors on vascular smooth muscle. All studies were performed just before dialysis when subjects were relatively volume-expanded. Hypotensives had higher PRA (5.7 +/- 2.4 vs. 2.1 +/- 0.8 ng AI/ml/hr, P less than 0.05). AII (56 +/- 15 vs. 31 +/- 3 pg/ml), and aldosterone (91 +/- 35 vs. 21 +/- 7 ng/dl, P less than 0.05) than did normotensives. During AII infusion at 1, 3, 10, and 30 ng/kg/min for 15 minutes each, hypotensives displayed a significantly blunted pressor effect across the range of AII doses. In parallel with this, hypotensives showed reduced AII receptors on their platelets compared to normotensives (0.8 +/- 0.4 vs. 3.6 +/- 1.0% 125I-AII specifically bound; P less than 0.03). Binding analysis revealed a single affinity state for the AII receptors which was similar in both groups (Kd = 3.2 +/- 1.1 for hypotensives vs. 3.8 +/- 0.7 x 10(-10) M for normotensives). The two groups had similar levels of plasma catecholamines, similar slowing of heart rate during AII infusion and no postural hypotension, indicating intact sympathetic nervous system pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Kinetics and efficacy of deferoxamine in iron-overloaded hemodialysis patients.

We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron-overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half-life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe-feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron-overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes.

Adult↗
PubMed1988

Biochemical parameters in chronic renal failure.

We analyzed biochemical data derived from 911 patients with renal insufficiency observed at our institution for periods up to 7 years. During early renal failure (RF) (creatinine less than 5 mg/dL), the rate of change of hematocrit, total CO2 (tCO2) and urea per unit change of creatinine was significantly higher than during moderate (creatinine between 5 and 10 mg/dL) or advanced (creatinine greater than 10 mg/dL) RF. For example, the rate of change of hematocrit (%, volume/volume [v/v]) was (mean +/- SEM) -2.15 +/- 0.15% for each 1 mg/dL increase in creatinine in the range of creatinine less than 5 mg/dL, whereas for the range of creatinine greater than 10 mg/dL, the rate of change was only -0.48 +/- 0.06% (P less than 0.001). Similarly, the rate of change of tCO2 was -1.68 +/- 0.09 mEq/L for each 1 mg/dL increment in creatinine concentration during early RF, and -0.19 +/- 0.09 mEq/L per unit increase in creatinine during advanced RF (P less than 0.001). Chloride concentration initially increased as a function of creatinine in early RF, but decreased in advanced RF, whereas the anion gap increased throughout the course of RF. Mean serum phosphate concentration also increased steadily, but remained below the upper range of normal (4.7 mg/dL) during early RF without the use of phosphate binders. These data suggest that different biochemical parameters change at different rates as a function of the severity of renal dysfunction, and that although phosphate retention may occur, hyperphosphatemia is not a hallmark of early RF.

Acid-Base Equilibrium↗
PubMed1987

Iron overload and mobilization in long-term hemodialysis patients.

Iron overload from repeated transfusions of RBCs in long-term hemodialysis patients is a problem of increasing clinical significance. We report on the prevalence of and diagnostic criteria for identification of hemodialysis patients with iron overload. In 150 unselected hemodialysis patients, 62 (41%) had ferritin levels greater than 2,000 ng/mL (normal = 10 to 360 ng/mL). In 16 of these patients, accurate transfusion histories were obtained and ferritin levels correlated with calculated transfusional iron burden (r = 0.553, P less than .05). These patients could be divided into two distinct groups on the basis of their response to a single dose (2 g, IV) of deferoxamine: "high" responders had twice the level of feroxamine (the chelated product of deferoxamine and iron) of the "low" responders (P less than .001). High responders also had significantly higher prevalence of the "hemochromatosis" alleles A3, B7, and B14 than a large group of dialysis patients awaiting transplantation (71% v 37%, P less than .001). In two patients with iron overload and clinically significant bone disease, bone histology revealed prominent iron staining at the calcification front. We conclude that transfusional iron overload is a significant clinical problem in long-term hemodialysis patients, that may also be associated with bone pathology.

Adult↗
PubMed1986

The effects of passive CO2 removal on breathing pattern in humans.

To determine the effects of nonventilatory CO2 transfer on breathing pattern, we monitored breathing in 7 patients with renal failure undergoing hemodialysis. A respiratory inductance plethysmograph was used to record ventilation before and during dialysis. The duration of inspiration (TI), the duration of each breath (TTot) and the duty cycle (TI/TTot) did not differ for the pre-dialysis and the dialysis periods. In contrast, for each patient the mean tidal volume (VT) fell significantly during dialysis (p less than 0.05), accounting for the reduction in minute ventilation (p less than 0.005). The mean inspiratory flow rate (VT/TI) also fell (p less than 0.01), demonstrating that nonventilatory CO2 loss via the dialysis bath is associated with reduced respiratory drive.

Adult↗
PubMed1985

Surgery for diverticulitis in renal failure.

Twenty-five patients were operated on at the Brigham and Women's Hospital for colonic diverticulitis complicating treated renal failure during the period 1951 to 1983. Twelve patients had functioning renal allografts (eight cadaver, four living-related); 13 were on dialysis therapy. Six patients had polycystic kidney disease. The majority of patients had acute abdominal pain. Four had histories of chronic abdominal pain; nondiagnostic exploratory laparotomies were performed on two of these patients, who developed localized tenderness. The overall mortality in this series was 28 percent, with sepsis being the most common cause of death. Six of seven patients who died had free colonic perforations at surgery. Mortality correlated with age, with six of 14 patients (43 percent) over age 50 dying, as compared with one of 11 patients (9 percent) under age 50. There was no correlation between survival rate and type of surgery performed, dose of prednisone or azathioprine used, or type of treatment received for renal failure.

Aging↗
PubMed1985

Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis.

We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required.

Acute Kidney Injury↗
PubMed1985

Effects of acetate and bicarbonate dialysate in stable chronic dialysis patients.

The effects of acetate and bicarbonate dialysate on the biochemical and clinical parameters of 16 stable chronic hemodialysis patients were investigated in a double-blind crossover study. A central delivery system was used for both types of dialysates with identical sodium concentrations (138 mEq/liter) and osmolality in a single-pass dialysate flow. The results indicate that dialysis with bicarbonate leads to significantly less hypoxemia (P less than or equal to 0.001) and hypotensive episodes (P less than or equal to 0.002) than with acetate. Pre- to post-dialysis blood pressure changes were also more marked during acetate dialysis. Older patients with recurrent hypotension on acetate benefit most from bicarbonate dialysate. This group of patients appears to metabolize acetate more slowly and has a significantly lower post-dialysis bicarbonate concentration (P less than or equal to 0.005) than asymptomatic patients during dialysis with acetate dialysate.

Acetates↗