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Biomedical subjects

P J Scheel

Publications and source records attributed to P J Scheel.

34 records · Page 2Linked to original sources

Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine.

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.

Cyclosporine↗

Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy.

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.

AIDS-Associated Nephropathy↗

Disposal of dialysate in HIV-positive patients: an update.

One of the concerns with the use of peritoneal dialysis in human immunodeficiency virus (HIV)-positive patients is disposal of the peritoneal effluents. This article reviews survival characteristics of HIV in dialysate effluents and current disinfectant strategies.

Dialysis Solutions↗

HIV-1 survival kinetics in peritoneal dialysis effluent.

Viable and potentially infectious HIV-1 has been recovered from the peritoneal dialysis effluent (PDE) of patients with end-stage renal disease (ESRD) who are infected with the human immunodeficiency virus (HIV). No information had previously been available as to how long HIV-1 could survive in this environment, and no data were available as to how long HIV-1 could survive on peritoneal dialysis exchange tubing (PDET). Therefore, this study was designed to answer these questions. HIV-1 Mn was added to PDE and allowed to incubate at room temperature for 0 to 14 days. Following centrifugation, the cellular component of the PDE mixture was placed in co-culture with peripheral blood mononuclear cells (PBMC) from HIV negative donors. Aliquots from the co-cultures were removed after 14 days and assayed for the HIV-1-P24 antigen. High levels of HIV P24 antigen were recovered up to and including seven days of room temperature incubation. HIV could not be recovered from PDE that had been incubated at room temperature for 10 to 14 days. Ten milliters of HIV-PDE mixture was placed within PDET and incubated at room temperature for 10 minutes. The solution was then removed by gravity drainage. After drying times of 0 to 168 hours, the tubing was flushed with HIV culture medium and placed in co-culture with PBMCs from HIV negative donors. The culture supernatant was assayed for the HIV-1 P24 antigen as a marker of viral replication. High levels of HIV-1 P24 antigen were recovered from the PDET wash for up to and including 48 hours of drying time. No viable virus could be detected for drying times of between 72 and 168 hours. To determine if common disinfectants found in the dialysis unit could inactivate HIV, dilutions of Amukin 50% and household bleach were prepared at final concentrations ranging from 1:32 to 1:2048. These disinfectant solutions were incubated with PDE containing HIV for 10 minutes. The cellular fraction of the PDE was isolated by centrifugation, washed, and placed in co-cultures with peripheral blood mononuclear cells. HIV P24 antigen levels were assayed every three days for 28 days. Amukin 50% and a 10% household bleach solution were effective in killing HIV in PDE at dilutions up to and including 1:512. These results indicate that HIV can survive in PDE at room temperature for up to seven days. HIV can survive on peritoneal dialysis exchange tubing for up to 48 hours. Final dilutions of 1:512 Amukin 50% and 10% household bleach, after 10 minutes of exposure, are effective viricidal agents in disinfecting PDE.

Culture Media↗

Acute renal failure associated with immunoglobulin therapy.

Four cases of acute renal failure induced by intravenous immunoglobulin are presented, and the literature on the subject is reviewed. The clinical course varies from asymptomatic serum creatinine elevation to anuric renal failure occurring within days of the institution of therapy, followed by the rapid recovery of renal function after termination of therapy. The renal histology demonstrates severe tubular vacuolization with cellular swelling and preservation of the brush border. Glomerular endothelial, mesangial, and epithelial cells also may demonstrate swelling and vacuolization. There is no evidence for inflammatory or immune complex-mediated etiologies. The immunoglobulins or carbohydrate additives in the preparations appear to have a unique and reversible effect on the glomerular and tubular cell function.

Acute Kidney Injury↗

Percutaneous translumbar inferior vena cava cannulation for hemodialysis.

The purpose of this study was to evaluate the percutaneous translumbar approach for long-term hemodialysis catheter access. Seventeen double-lumen hemodialysis catheters were placed percutaneously from the right flank to the inferior vena cava in 12 patients. Catheter placement was successful in all patients. Adequate flow rates were obtained. Seven episodes of thrombosis-related access failure occurred (0.33 episodes/100 days at risk). Two catheters were removed and five catheters were managed with urokinase infusion. Six episodes of infection occurred (0.28 episodes/100 days at risk). Four required catheter removal. Two catheters were removed after defects developed in the catheter. Five catheters were removed electively because catheter hemodialysis was discontinued. Four catheters remained in place. Cumulative patency was 52% at 6 months and 17% at 12 months. Translumbar inferior vena cava hemodialysis catheters represent a valuable alternative in cases in which traditional catheter sites have failed.

Adult↗

Recovery of human immunodeficiency virus from peritoneal dialysis effluent.

Increasing numbers of HIV-infected patients who have ESRD are being treated with continuous ambulatory peritoneal dialysis (CAPD). To investigate the potential infectious nature of peritoneal dialysate (PD), the peritoneal dialysis effluent was studied in 14 patients on CAPD who were known to be HIV antibody positive. Peripheral blood mononuclear cells and the sediment of PD were obtained from each patient and subjected to a qualitative microculture assay using a coculture of patient cells or PD fluid with peripheral blood mononuclear cells from non-HIV-infected individuals. Samples from the coculture were collected twice weekly for HIV P24 antigen determination as a marker of viral replication. PD, white blood cell and red blood cell counts, and peripheral blood CD4 lymphocyte counts were also measured. All 14 patients developed a positive blood culture by Day 3. Twelve of the 14 patients developed a positive PD fluid culture. The mean CD4 count was 310 cells/mm3. No patient had clinical or cellular evidence of peritonitis at the time of fluid sampling. These data indicate that peritoneal dialysis effluent from patients who are HIV antibody positive is potentially infectious.

Adult↗

Thrombosed dialysis access grafts: percutaneous mechanical declotting without urokinase.

PURPOSE: To evaluate percutaneous declotting of dialysis access grafts with available catheters without urokinase. MATERIALS AND METHODS: Thirty-four clotted grafts were treated in 24 patients. Clot was macerated and pushed into the central circulation with balloon catheters. RESULTS: Successful mechanical declotting was performed in all but two patients (94%). The procedure was abandoned after successful declotting in four patients with poor venous outflow, resulting in a 24-hour success rate of 82%. Mean total procedure time was 116 minutes. Eight grafts clotted within 1 week. Using successful dialysis beyond 1 week as the measure of clinical success, the authors report a 59% clinical success rate with mean primary patency of 126 days (range, 16-322 days). Two complications, both emboli to the brachial artery, were successfully treated with urokinase. No symptomatic pulmonary emboli occurred. CONCLUSION: Mechanical thrombolysis of clotted grafts with currently available catheters yields results similar to those reported with mechanical devices and urokinase. The procedure is relatively inexpensive, safe, and well tolerated.

Adult↗

Clinical application of recombinant erythropoietin in renal dialysis patients.

The advent of erythropoietin (EPO) can be considered one of the major advances over the past 10 years in the treatment of end stage renal disease (ESRD) patients who are receiving chronic maintenance dialysis. Not only has it resulted in freedom from transfusion dependency and elimination of the attendant risks, but it also has led to a significant improvement in the quality of life these patients are able to achieve within the physical and emotional limitations imposed by the multiple metabolic abnormalities, concomitant medical problems of ESRD, and the dialysis process itself.

Drug Resistance↗

Cholestyramine-induced hyperchloremic metabolic acidosis.

Cholestyramine is a nonabsorbable anion exchange resin that is used predominantly for the treatment of hypercholesterolemia in adults and the management of acute diarrhea in children. The authors report two cases of severe hyperchloremic nonanion gap metabolic acidosis associated with the use of cholestyramine therapy. The authors recommend that patients taking cholestyramine who have concomitant renal insufficiency or who are volume depleted or who are taking spironolactone be monitored carefully for the emergence of a hyperchloremic metabolic acidosis.

Acidosis↗

Screening for dialysis access graft malfunction: comparison of physical examination with US.

PURPOSE: To test the reliability and performance of two physical diagnosis algorithms for use in physical examination of vascular access grafts. MATERIALS AND METHODS: Grafts were assessed in 39 patients by means of physical examination performed by four observers. Grafts were characterized as having a thrill, pulse, or indeterminate examination at three locations (arterial, midpoint, venous). Findings with this algorithm were compared with those from ultrasound (US) with volume flow measurements. RESULTS: Patients with a thrill at all three locations of the graft all had volume flows greater than 450 mL/min (negative predictive value = 100%). Of patients with a pulse at any of three locations, only 28% (positive predictive value) had a volume flow of 450 mL/min or less. CONCLUSION: Physical examination is a good screening test for ruling out the low flows associated with impending access graft failure, thereby eliminating the need for routine US for many patients.

Adult↗

Guide wire directed manipulation of malfunctioning peritoneal dialysis catheters: a critical analysis.

PURPOSE: To evaluate patency rates after guide wire directed manipulation of malfunctioning continuous ambulatory peritoneal dialysis (CAPD) catheters. MATERIALS AND METHODS: During a 58-month period, 23 patients underwent 34 outpatient guide wire directed manipulations of their CAPD catheter to improve function (n = 30) or reduce pain and improve function (n = 4) during dialysis. Catheter patency rates were subsequently determined by review of departmental, hospital, and dialysis center charts; procedural reports; and patient telephone interviews. RESULTS: Among 12 patients who underwent a single guide wire directed manipulation, long-term (> 30 days) catheter patency was achieved in seven (58%). With use of the Kaplan-Meier survival method, the 3-, 6-, and 12-month probability of patency after a single guide wire manipulation was 0.61, 0.54, and 0.11, respectively. The mean duration of patency achieved in this group was 131 days (range, 2-421 days). In those patients (n = 8) who underwent multiple catheter manipulations (n = 19), 11 (58%) procedures resulted in long-term patency, with each patient (100%) achieving at least one such period. The Kaplan-Meier survival method determined the probability of patency in this group at 3, 6, and 12 months to be 0.75, 0.69, and 0.54, respectively. The mean secondary catheter patency was 235 days (range, 2-646 days). Overall, 75% of patients followed up achieved at least one period of long-term catheter patency during the time of this study. One (3%) episode of postprocedure peritonitis occurred. CONCLUSION: Guide wire directed CAPD catheter manipulation is a relatively simple outpatient procedure that restores long-term catheter function for most patients with minimal risk for a major complication. Patients with nonfunctioning CAPD catheters who do not have peritonitis or sepsis will most likely benefit from at least one attempt at radiologic manipulation of their catheter.

Adolescent↗

Differential glucocorticoid responsiveness of dialysis patients' lymphocytes.

OBJECTIVES: To evaluate in vitro glucocorticoid responsiveness of phytohemagglutinin (PHA)-stimulated lymphocytes from peritoneal dialysis (PD) patients compared to hemodialysis (HD) patients. DESIGN: Cross-sectional study of prevalent PD and HD patients and concurrent control subjects. SETTING: Urban outpatient dialysis unit. PATIENTS: 20 HD, 14 PD, and 20 control subjects. MEASUREMENTS: Using standard lymphocyte culture techniques, the concentration of prednisolone (P) and methylprednisolone (MP) required to cause 50% inhibition (IC50) of the proliferative response to phytohemagglutinin (PHA) was determined from dose-response curves. RESULTS: There was considerable heterogeneity in the sensitivities of individual patients' PBMC to glucocorticoid inhibition, especially those of HD patients' cells to P. The mean +/- SD IC50 for MP was significantly (p < or = 0.001) lower than that for P in each cohort: PD 11 +/- 5 vs. 34 +/- 18 ng/mL; HD 22 +/- 14 vs. 89 +/- 43 ng/mL; control subjects 14 +/- 11 vs. 55 +/- 56 ng/mL. Interestingly, the IC50 for both P and MP was significantly higher in HD than in either PD or controls (ANOVA, P: F = 6.56, p = 0.003; MP: F = 3.77, p = 0.03), indicating decreased sensitivity of HD lymphocytes to both drugs. There were no significant differences in mean IC50 values for either P or MP between PD and controls. No correlations were found between IC50 for either P or MP and patient age, gender, duration of dialysis, serum creatinine, serum albumin, or parathyroid hormone level. CONCLUSIONS: In vitro glucocorticoid responsiveness of dialysis patients' lymphocytes appears to be influenced by dialysis modality, but the factor(s) involved remains to be determined. The greater sensitivity of PD lymphocytes to both P and MP might result in better immunosuppression and less severe rejection after renal transplantation. MP may be particularly advantageous following renal transplantation for any patient manifesting relative or absolute in vitro resistance to P.

Cross-Sectional Studies↗

Differential glucocorticoid responsiveness of hemodialysis patients' lymphocytes.

Acute allograft rejection remains a problem after renal transplantation, even in the cyclosporine era. Interindividual differences in the pharmacodynamic responses of the immune system to immunosuppressive agents might contribute to the vulnerability of some patients to rejection. Having previously demonstrated decreased sensitivity of hemodialysis patients' lymphocytes to glucocorticoid suppression of mitogen induced proliferation, the authors undertook a separate study to assess the suppressive effect of glucocorticoids on lymphocyte responsiveness to allogeneic cells and mitogenic stimulation. Lymphocytes were isolated from 32 hemodialysis patients in clinically stable condition for studies in both phytohemagglutinin (PHA) stimulated cultures and in one-way mixed lymphocyte (MLR) cultures. From the concentration-response relationships derived from stimulated cultures with 10 (-6), 10(-7), and 10(-8) M concentrations of prednisolone and methylprednisolone, the concentration of steroid required to achieve 50% inhibition (IC50) of lymphocyte proliferation was determined. A broad range of IC50 values was found in both PHA and MLR cultures, but within individual patients, the IC50 values for both steroids correlated significantly between PHA and MLR cultures. The inhibitory effect of methylprednisolone was significantly greater than that of prednisolone in both PHA and MLR cultures. These results demonstrate a heterogeneity of pharmacodynamic responsiveness to prednisolone and methylprednisolone that is consistent with individuals in two in vitro models of cellular immune response. Pretransplant evaluation by these methods may help identify patients at risk of suboptimal immunosuppression and assist in selecting the steroid component of the immunosuppressive regimen.

Adult↗