Missed diagnosis of acute arthritic gout in kidney transplant recipients.
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Biomedical subjects
Publications and source records attributed to E A Friedman.
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Left ventricular size and function were evaluated in 15 anemic chronic hemodialysis patients before and after the administration of recombinant human erythropoietin (rHuEPO). All patients were studied with two-dimensional and M-mode echocardiographic examinations before the initiation of rHuEPO (T1) and at 28 +/- 7 weeks of rHuEPO therapy (T2). The two-dimensional targeted M-mode echocardiographic measurements obtained were: end-diastolic dimension (EDD); end-systolic dimension (ESD); stroke dimension (SD); dimensional shortening (SD/EDD); systolic posterior wall thickness (PWs); diastolic posterior and interventricular septal thickness; end-systolic wall stress (ESWS); and left ventricular mass. Mean hematocrit in these patients increased almost 50%. The EDD decreased from a mean value (+/- SEM) of 6.41 +/- 0.33 to 4.93 +/- 0.21 cm (p less than 0.05). ESD decreased from a mean value of 4.16 +/- 1.2 to 2.77 +/- 0.06 cm (p less than 0.05). The calculated mean SD decreased slightly but not significantly from 2.21 +/- 0.69 to 2.19 +/- 0.60 cm. The calculated SD/EDD increased from a mean 0.35 +/- 0.09 to 0.44 +/- 0.07 (p less than 0.05). ESWS fell from 59.2 +/- 12.2 to 37.6 +/- 9.3 gm/cm2 (p less than 0.01), and left ventricular mass fell (p less than 0.05) from 347 +/- 15.2 to 227 +/- 59 gm. There was no significant difference in resting heart rate or systolic blood pressure between T1 and T2. The increase in dimension shortening reflects afterload reduction, as indicated by the fall in end-systolic wall stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma viscosity (PV), apparent whole blood viscosity (WBV), relative blood viscosity (RV) and erythrocyte deformability (filterability) (EDF) were determined in 13 New Zealand White (NZW) rabbits with alloxan induced-diabetes (AID) and 8 normal NZW rabbits, matched for age, sex and weight. AID rabbits were divided into two groups depending on the duration of hyperglycemia (long-term, greater than 6.0 months (n = 7), and short-term, less than or equal to 3.0 months of hyperglycemia, n = 6). Comparing long-term AID rabbits to normal animals, we found significant increases in WBV (P less than 0.001, 0.005 for high and low rates of shear, respectively), and a marked reduction in EDF (P less than 0.001). There was no significant difference in PV between long-term AID and normal rabbits. Conversely, PV was significantly increased in rabbits with short-term diabetes (P less than 0.01) while there was a concurrent significant increase in WBV measured at high and low rates of shear (P less than 0.001, 0.001, respectively). No difference was detected in EDF between normal and short-term AID rabbits. Furthermore, in long-term AID rabbits there was a strongly positive correlation between RV and reduced erythrocyte deformability (r = 0.94, P = 0.006) while WBV strongly correlated with PV (r = 0.92, P = 0.004) in the short-term AID subgroup. We conclude from these data: (1) elevated blood viscosity in long term AID rabbits is associated with reduced erythrocyte filterability; and (2) elevated WBV in short-term AID rabbits is associated with increased PV.
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Pseudohyperkalemia, defined as serum to plasma potassium difference of more than 0.4 mmol/l, occurs when platelets, leukocytes or erythrocytes release intracellular potassium in vitro, leading to falsely elevated serum values. Pseudohyperkalemia has been observed in myeloproliferative disorders [1], including leukemia [2] and infectious mononucleosis [3] as well as in rheumatoid arthritis [4]. We present 2 patients with renal disease and thrombocytosis in whom pseudohyperkalemia was recognized only after common therapeutic measures and/or dialysis failed to effect a decrease in serum potassium. In patients with renal disease and thrombocytosis, plasma as well as serum potassium should be routinely measured prior to instituting aggressive therapy or altering dialysis prescription in order to avoid potentially dangerous overtreatment with resulting hypokalemia.
We prospectively followed the course of eye disease in patients with diabetic end-stage nephropathy from the time of initial referral by the renal unit. A total of 31 patients (62 eyes)--9 of whom had functioning renal transplants and 22 of whom were on maintenance dialysis--were consecutively evaluated for 6-24 months (mean follow-up of 18 months). Visual acuity and diabetic retinopathy stabilized or improved in all 18 eyes of the transplant patients and in 41 of 44 (93%) eyes of the dialysis patients. When first evaluated, economically useful vision (20/200 or better) was present in 11 of 18 (61%) eyes in the transplant group and in 25 of 44 (57%) eyes in the dialysis group. At the most recent evaluation, economically useful vision was present in 13 of 18 eyes (72%) in the transplant group versus 28 of 44 eyes (64%) in the dialysis group. Ambulatory vision (counting fingers or better) was present in 15 of 18 eyes (83%) in the transplant group versus 37 of 44 eyes (84%) in the dialysis group.
Diabetic nephropathy is currently the leading cause of new patients requiring dialysis in the United States. Management of the diabetic patient with ESRD is complicated by the frequent coexistence of complications affecting other organ systems, including retinopathy, cardiovascular disease, peripheral neuropathy, or autonomic neuropathy, manifested as gastroparesis, diarrhea or obstipation, cystopathy, or orthostatic hypotension. Associated clinical syndromes must be followed and treated, if possible, while preparing the patient to receive renal replacement therapy. Both the clinical condition and the psychosocial environment are key factors in choice of ESRD therapy for an individual patient. Rehabilitation data are best for patients who undergo kidney transplantation, but these data are confounded by the fact that the healthiest patients are referred for this treatment modality. Living, related kidney transplant is the preferred initial choice for the diabetic patient with kidney disease. At most centers, both in the United States and abroad, the cadaveric transplant is the second choice for uremia therapy. At the appropriate institution, the patient with type I diabetes may also be considered for a simultaneous cadaveric pancreas transplant. While awaiting cadaveric transplantation, or if contraindication to transplantation is present (chronic infection, recent malignancy, or severe cardiac disease), diabetic patients with severe impairment of the glomerular filtration rate (less than 10-15 ml/min) are referred for vascular access placement and/or insertion of a peritoneal catheter. The decision regarding the choice of CAPD vs. hemodialysis must be made on an individual basis. Rehabilitation and survival data for these therapies are similar, although technique survival rates for CAPD decline dramatically as time progresses because of infectious complications. In-center hemodialysis has the worst survival and rehabilitation profile, but the sickest, most debilitated patients with the highest number of comorbid conditions tend to be referred for that therapeutic modality. Most studies of rehabilitation were performed before use of recombinant human erythropoietin, and comparison between ESRD treatment modalities will have to be reevaluated now that the drug is routinely used.
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BACKGROUND: Glucose reacts nonenzymatically with proteins in vivo, chemically forming covalently attached glucose-addition products and cross-links between proteins. The excessive accumulation of rearranged late-glucose-addition products, or advanced glycosylation end products (AGEs), is believed to contribute to the chronic complications of diabetes mellitus. METHODS: To elucidate the relation of AGEs to diabetic complications, we used a radioreceptor assay to measure serum and tissue AGEs in diabetic (Types I and Type II) and nondiabetic patients with different levels of renal function. Serum AGEs were measured as a low-molecular-weight (less than or equal to 10 kd) peptide fraction and a high-molecular-weight (greater than 10 kd) protein fraction. RESULTS: The mean (+/- SD) AGE content of samples of arterial-wall collagen from 9 diabetic patients was significantly higher than that of samples from 18 nondiabetic patients (14.5 +/- 5.2 vs. 3.6 +/- 1.5 AGE units per milligram, P less than 0.001). Moreover, diabetic patients with end-stage renal disease had almost twice as much AGE in tissue as diabetic patients without renal disease (21.3 +/- 2.8 vs. 11.5 +/- 1.9 AGE units per milligram, P less than 0.001). The AGE levels in both serum fractions were elevated in the patients with diabetes, and the levels of AGE peptides correlated directly with serum creatinine (P less than 0.001) and inversely with creatinine clearance (P less than 0.005), suggesting that levels of AGE peptides increased with the severity of diabetic nephropathy. In six patients with diabetes who required hemodialysis, the levels of AGE peptides were five times higher than in eight normal subjects (82.8 +/- 9.4 vs. 15.6 +/- 3.4 AGE units per milliliter, P less than 0.001). In another group of diabetic patients the mean serum creatinine level, which decreased by 75 percent during a session of hemodialysis, whereas the level of AGE peptides decreased by only 24 percent. Serum levels of AGE peptides were normal in two patients with normal serum creatinine levels after renal transplantation. CONCLUSIONS: AGEs accumulate at a faster-than-normal rate in arteries and the circulation of patients with diabetes; the increase in circulating AGE peptides parallels the severity of renal functional impairment in diabetic nephropathy.
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When the infectivity of the influenza virus is determined by means of titration on chicken embryos, calculating the infection titre according to Reed and Muench, the course of inactivation with beta-propiolactone shows an anomaly - the fraction of infected embryos in a batch initially increases and then decreases as the degree of dilution of the virus-containing sample is increased. This anomaly occurs because a slight dilution lowers the agent concentration insufficiently so that inactivation goes on after the dilution of the sample before and/or after the inoculation of the solution into the embryo. The anomaly can be avoided either by neutralizing or removing the agent prior to titration or by starting titration from high dilutions.
The kinetics of inactivation of the infectivity of the influenza virus by beta-propiolactone have been studied. Rate constants have been determined for inactivation of the A/Leningrad/385 (H3N2) and B/Leningrad/489/80 influenza virus under the action of beta-propiolactone on a virus-containing allantoic fluid and on a purified viral suspension. The data obtained allow calculation of the time required for inactivation of the influenza virus infectivity to a given extent in virus-containing solutions at any initial concentration of beta-propiolactone.
Despite mounting experimental evidence that cyclosporine inhibits pancreatic islet cell function, clinical data on posttransplant diabetes mellitus (PTDM) in renal allograft recipients in the cyclosporine era are scarce. Between June 1983 and December 1988, 39 of 337 (11.6%) cyclosporine-treated adult renal transplant recipient whose grafts survived longer than 1 year developed PTDM. Of these, 43.6% and 74.4% were diagnosed by 3 and 12 months posttransplant, respectively, and 51.3% were insulin-dependent. Incidence of PTDM was highest in blacks (19.8%) and Hispanics (21.3%) and in those with HLA-A 30 and Bw 42 antigens. Older recipients and those that received cadaveric kidneys were more likely to develop diabetes than those who received living related allografts (14% vs. 5.3%, P less than 0.05). The rate of PTDM appeared to be independent of the type of induction, immunosuppressant therapy, incidence of rejection, total steroid and cyclosporine dose, percentage of body weight gain in the first posttransplant year, and serum creatinine concentration. Actuarial 5-year, decaying from 100% at 1 year, patient and graft survival rates were 87% and 70%, respectively, in the PTDM group compared with 93% and 90%, respectively, in controls. Causes of graft failure among the diabetics included chronic rejection (6), patient death (3), noncompliance with immunosuppressants (2), and sepsis (1). The incidence of infectious complications was significantly higher in the PTDM group compared with the control group (53% vs. 16%, P less than 0.05), with all 5 deaths among the diabetics being sepsis-related.
To assess the effect of substantial increases in blood hemoglobin (Hb) caused by treatment with recombinant human erythropoietin (rhEPO) on exercise capacity in maintenance hemodialysis patients, we evaluated 10 patients (7 men and 3 women) at a mean age of 44.3 +/- 8.4 years on maintenance hemodialysis for a mean of 29.7 +/- 30.2 months by treadmill exercise to exhaustion. The patients were tested before administration of rhEPO and after a minimum 1 g/dl rise in Hb. With a change in Hb from 7.1 +/- 1.4 to 9.8 +/- 2.1 g/dl, peak oxygen consumption (VO2 peak) with exercise increased 50.3 +/- 9% (T1 = 15.1 +/- 5.3, T2 = 22.7 +/- 4.6 ml O2/kg/min, p less than 0.05). Respiratory exchange ratio (RER) at a given submaximal exercise level (3 mph, 6% of elevation) decreased significantly (T1 = 1.13 +/- 0.24, T2 = 0.92 +/- 0.08, p less than 0.05). The rhEPO-mediated increase in Hb was associated with an increased VO2 peak--an improvement of the peak exercise capacity and a reduced submaximal RER--reflecting a reduction in anaerobic metabolism at activities of daily living.
It has been reported that patients with azotemia have reduced red blood cell (RBC) deformability. Since this is a major determinant of whole-blood viscosity (WBV) and rigid RBCs increase WBV disproportionately relative to the level of hematocrit, it is conceivable that sustained improvement of hematocrit with recombinant human erythropoietin (rhEPO) therapy in azotemic patients might result in abnormally raised WBV. To address this concern, WBV and plasma viscosity (PV) were measured in 9 adult patients (4 men, 5 women) with anemia (mean hematocrit 29.2 +/- 2.7%) and azotemia [mean serum creatinine concentration 339.85 +/- 102.44 mumol/l (3.8 +/- 1.1 mg/dl)] before and after 6 months of treatment with rhEPO (50-175 U/kg given intravenously thrice weekly). Baseline and post-treatment hematocrit, WBV and PV were compared to values derived in 50 normal adult subjects with normal renal function [25 women, 25 men; mean serum creatinine concentration 79.56 +/- 8.84 mumol/l (0.9 +/- 0.1 mg/dl), mean hematocrit 42.4 +/- 3.7%]. To compare rheologic factors at subnormal hematocrits, blood from subjects with normal renal function was diluted with autologous plasma to achieve a range of hematocrits from 20 to 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To study the incidence, outcome, and possible etiopathogenic factors involved in posttransplantation diabetes mellitus in cyclosporine-treated black renal allograft recipients. RESEARCH DESIGN AND METHODS: One hundred thirty-eight nondiabetic black renal transplant recipients whose grafts survived greater than 1 yr were studied retrospectively. RESULTS: Twenty-eight (20.3%) patients developed posttransplantation diabetes mellitus, 46 and 75% were diagnosed by 6- and 12-mo posttransplantation, respectively, and 46% were insulin dependent. Diabetes was more frequently encountered in older recipients and recipients of cadaveric kidneys but was independent of sex, number of transplants, incidence of acute rejection, percentage of body weight gain, steroid or cyclosporine dose, and use of beta-blockers and/or diuretics. Renal function was similar in the diabetic group compared with the control group. Actuarial 5-yr graft survival was 82% in the diabetic cohort compared with 78% in the control group, with chronic rejection accounting for all graft losses within the diabetic group. CONCLUSIONS: Twenty percent of black cyclosporine-treated renal allograft recipients developed diabetes mellitus in the posttransplantation period. However, its presence did not appear to influence intermediate-term graft or patient survival.