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Biomedical subjects

P J Scheel

Publications and source records attributed to P J Scheel.

At least 19 recordsLinked to original sources

Outpatient vancomycin use and vancomycin-resistant enterococcal colonization in maintenance dialysis patients.

BACKGROUND: Although outpatient vancomycin is widely used as empiric therapy for dialysis-associated infections, its relationship with vancomycin-resistant enterococcal (VRE) colonization is not established. METHODS: During a two-year prospective cohort study, rectal swabs obtained from patients at the start and finish of the study period and during interim hospitalizations were cultured for VRE. RESULTS: Ten of 124 patients initially grew VRE. Twenty-four of the remaining patients had no follow-up cultures because of patient death (62%), transfer to another dialysis facility (17%), patient's refusal (7%), and transplantation (4%), and were thus excluded. The remaining patients (N = 90) had a median age of 54.3 years and were 92% African American and 50% male. Fifty-eight percent were treated by hemodialysis. They received 403 g of intravenous vancomycin over 157.2 patient-years of follow-up, 73% as outpatients. Sixteen of 90 patients (17.8%) became colonized with VRE, an incidence rate of one case per 9.8 patient-years of follow-up. None of the 29 patients who did not receive vancomycin developed VRE compared with 26% of those treated with vancomycin (P = 0.001). The odds ratio (95% CI) for the association of outpatient vancomycin (g per year) with VRE colonization was 1.23 (1.05, 1.44, P = 0.008). The association remained significant following adjustment in separate logistic regression analyses for relevant demographic, clinical, antimicrobial (inpatient vancomycin, oral or intravenous cephalosprins, aminoglycosides, quinalones, or antianaerobics), and hospitalization exposures. The unadjusted relative risk of death in patients growing VRE was significantly higher than in those not colonized with VRE (P = 0.005). CONCLUSIONS: VRE colonization is a relatively common and under recognized problem among chronic dialysis patients. It is strongly and independently associated with the outpatient use of vancomycin, which should be avoided whenever possible.

Adult↗

Percutaneous radiologic placement of peritoneal dialysis catheters: long-term results.

PURPOSE: To evaluate the efficacy of percutaneous radiologic placement of peritoneal dialysis (PD) catheters. MATERIAL AND METHODS: Nineteen patients with end-stage renal disease were referred for percutaneous radiologic placement of a commercially available PD catheter. The patient group consisted of 11 men and eight women with a mean age of 58 years (range, 38-85 y). All procedures were performed on an outpatient basis with use of conscious sedation. Patients were followed up to determine technical success, complication rate, catheter survival (continuous patency without infection or mechanical dysfunction), and long-term outcome. RESULTS: The technical success rate for catheter placement was 95% (18 of 19). Complications included one (5%) failed attempt at catheter placement and one (5%) case of postplacement peritonitis. Mean and median catheter survival durations were 320 and 289 days, respectively (range, 33-823 d). A Kaplan-Meier survival analysis yielded 6-, 12-, and 24-month probabilities of catheter survival of 0.89 +/- 0.15, 0.81 +/- 0.20, and 0.81 +/- 0.20, respectively. Long-term outcomes included: continued PD, n = 9 (47%); death, n = 6 (32%; all related to comorbid disease); successful renal transplant, n = 2 (10.5%); and continued or resumed hemodialysis, n = 2 (10.5%). CONCLUSION: Percutaneous radiologic placement of PD catheters has a high technical success rate, low complication rate, and can be performed on an outpatient basis. Catheter survival is comparable to that achieved with surgical and percutaneous endoscopic methods of catheter placement.

Adult↗

Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia.

BACKGROUND: Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients. METHODS: Subjects with a mean three-month prestudy serum albumin of 3.8 g/dL or less and who demonstrated >/=90% compliance during a two-week run-in period were randomized to 3.6 g of essential amino acids (EAAs) or placebo three times daily with meals for three months. Randomization was stratified by dialysis modality and by severity of the hypoalbuminemia. The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up. RESULTS: Fifty-two patients were randomized; 47 patients (29 hemodialysis and 18 peritoneal dialysis) met the predetermined primary analysis criteria. The mean compliance rates averaged 75, 70, and 50% at months 1, 2, and 3, respectively, and were similar for EAAs and placebo. Serum albumin in the hemodialysis patients, EAA versus placebo, improved [(mean +/- SE) 0.22 +/- 0.09 g/dL, P = 0.02]. Changes in peritoneal dialysis patients were not significant (0.01 +/- 0.15 g/dL), but approached significance for the total study group (0.14 +/- 0.08 g/dL, P = 0.08). Patients in the very low albumin strata (<3.5 g/dL) improved more than those in the low albumin strata (3.5 to 3.8 g/dL, P < 0.01). There was a significant correlation (r = 0.83, P = 0.001) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin. Improvements were also seen in grip strength and SF-12 mental health score, but not in serum amino acid levels, SF-12 physical health score, or anthropometric measurements. CONCLUSIONS: Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects. Further study of their long-term effects on morbidity and mortality is warranted.

Administration, Oral↗

Cohort study of the treatment of severe HIV-associated nephropathy with corticosteroids.

BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) results in rapidly progressive azotemia. The effectiveness and safety of corticosteroids in the treatment of HIVAN, however, remains controversial. METHODS: We conducted a retrospective cohort study of patients with biopsy-proven HIVAN and progressive azotemia who were eligible for corticosteroid treatment and who had no clinical or histologic evidence of an alternative cause of acute renal failure. Selected patients were treated with 60 mg of prednisone for one month, followed by a several-month taper. RESULTS: Twenty-one eligible patients were identified. Thirteen subjects had received corticosteroid treatment, whereas eight had not. The mean serum creatinine was 6.2 and 6.8 mg/dL, respectively (P > 0.05). The relative risk (95% CI) for progressive azotemia with corticosteroid treatment at three months was 0.20 (0.05, 0.76, P < 0.05). This association remained significant despite adjustment in separate logistical regression analyses for baseline creatinine, 24-hour proteinuria, CD4 count, history of intravenous drug use, hepatitis B, and hepatitis C. In an additional logistic regression model, using backward stepwise selection of the previously mentioned covariates, only corticosteroid treatment (P = 0.02) and baseline serum creatinine (P = 0.10) were retained within the model. In the corticosteroid-treated group, the mean level of proteinuria decreased by 5.5 g/24 hour (P = 0.01). On long-term follow-up, there was no significant difference in the incidence of hospitalizations (1 per 2.1 vs. 1 per 2.3 patient months) or of serious infections (1 per 2.6 vs. 1 per 2.3 patient months), but there was a significantly longer duration of hospitalization in the corticosteroid-treated group (3.2 vs. 2 days per patient month). At six months, only one of the non-corticosteroid-treated patients but seven of the corticosteroid-treated group continued to have independent renal function (P = 0.06). Three of the corticosteroid-treated group continued to have independent function at two years of follow-up. CONCLUSION: A limited course of corticosteroid therapy in selected patients was beneficial and safe. Further research is required for the role of corticosteroids in the treatment of HIVAN.

AIDS-Associated Nephropathy↗

Relationship between lymphocyte and clinical steroid responsiveness in focal segmental glomerulosclerosis.

A remission in nephrotic proteinuria with steroid treatment appears to favorably alter the natural history of focal segmental glomerulosclerosis (FSGS). It is not known why some patients have a favorable response to steroid treatment whereas others do not. Considering the possibility that differences in the pharmacodynamic responsiveness to steroids among patients might be one factor, the authors examined the relationship between the pretreatment suppressive effect of steroids on lymphocyte proliferation (% inhibition) in vitro and the short- and intermediate-term responses of creatinine clearance (Clcr) and/or nephrotic proteinuria (urine protein/creatinine ratio = Up/c) in 13 patients with FSGS. There were significant correlations between % inhibition and the changes in Clcr at 3 (r = 0.92, p < 0.001) and 6 (r = 0.86, p < 0.01) months and the changes in Up/c at 3 months (r = -0.74, p = 0.02). Thus, the greater the pretreatment lymphocyte steroid sensitivity, the greater the increase in Clcr or decrease in Up/c. The changes in these parameters could not be accounted for on the basis of steroid dose or histopathology. The in vitro sensitivity of FSGS patients' lymphocytes to steroids may be of value in anticipating their clinical response to treatment.

Adult↗

Use of technetium Tc 99m sestamibi scintigraphy for recurrent tertiary hyperparathyroidism from a parathyroid forearm graft.

Technetium Tc 99m sestamibi scintigraphy is a sensitive technique for localizing recurrent parathyroid disease in the neck or mediastinum. We report the case of a 60-year-old woman with recurrent tertiary hyperparathyroidism after total parathyroidectomy. Technetium Tc 99m sestamibi images of the neck and mediastinum were negative; however, images of the right arm revealed a hyperfunctioning parathyroid autotransplant. Partial resection of the autograft resulted in prompt resolution of the hyperparathyroidism.

Arm↗

Forearm loop, upper arm straight, and brachial-internal jugular vein dialysis grafts: a comparison study of graft survival utilizing a combined percutaneous endovascular and surgical maintenance approach.

PURPOSE: To determine rates and duration of patency achievable in forearm loop, upper arm straight, and brachial-internal jugular (IJ) vein hemodialysis grafts utilizing a combined percutaneous endovascular and surgical maintenance approach. MATERIALS AND METHODS: A retrospective analysis of 74 hemodialysis grafts (forearm loop, n = 22; upper arm straight, n = 34; and brachial-IJ vein, n = 18) in 50 patients with end-stage renal disease was conducted. Operative notes, interventional procedural reports, and hospital records were used to construct a history for each of these grafts from the time of surgical placement until the time the graft was abandoned for an alternative method of dialysis. All procedures performed to maintain and/or restore patency during the usable lifetime of the grafts were documented. RESULTS: Survival analysis using the Kaplan-Meier method demonstrated the following probabilities of primary patency at 6, 12, and 16 months, respectively: forearm loop graft = .46, .26, and .26; upper arm straight graft = .39, .22, and .16; and brachial-IJ vein graft = .19, .06, and .06 (forearm loop vs upper arm straight grafts, P > .05; forearm loop and upper arm straight vs brachial-IJ grafts, P < .001, P < .001, respectively). The probabilities of secondary patency at 12, 24, and 48 months, respectively, were: forearm loop graft = .89, .30, and NA; upper arm straight graft = .52, .35, and .17; and brachial-IJ vein graft = .54, .42, and .21 (P < .05 for all three comparisons: forearm loop > brachial-IJ > upper arm straight). Six percutaneous and two surgical procedures were compared and no significant differences in utilization were determined among the three graft types (ANOVA, P range, .38-.88). CONCLUSION: Kaplan-Meier analysis determined the probability of primary patency for forearm loop grafts to be similar to that for upper arm straight grafts, and both were significantly greater than for brachial-IJ vein grafts. The secondary patency rates for forearm loop grafts are greater than for upper arm and brachial-IJ vein grafts, while that for the brachial-IJ vein graft is greater than the upper arm straight graft. Utilization of interventional and surgical resources required to maintain patency do not significantly differ among the three types of upper extremity hemodialysis grafts.

Arm↗

Lymphocyte suppression by glucocorticoids with cyclosporine, tacrolimus, pentoxifylline, and mycophenolic acid.

Methylprednisolone has been found to be significantly more suppressive than prednisolone (the pharmacologically active metabolite of prednisone) of mitogen-stimulated human lymphocyte proliferation. In this study, peripheral blood mononuclear cells (PBMC) from end stage renal disease patients were cultured with phytohemagglutinin (PHA) alone and with methylprednisolone and prednisolone individually, as well as each glucocorticoid (10(-7) mol/L) in combination with 300 ng/ml cyclosporine, 10 ng/ml tacrolimus, 25 microg/ml pentoxifylline, and 10(-7) mol/L mycophenolic acid. Under each experimental condition, the mean +/- SD % inhibition of PHA-stimulated 3H-thymidine incorporation was significantly greater with methylprednisolone than with prednisolone: methylprednisolone 55 +/- 17 versus prednisolone 28 +/- 14, p < 0.001; methylprednisolone + cyclosporine 76 +/- 18 versus prednisolone + cyclosporine 52 +/- 18, p < 0.001; methylprednisolone + tacrolimus 74 +/- 18 versus prednisolone + tacrolimus 50 +/- 20, p = 0.001; methylprednisolone + mycophenolic acid 69 +/- 14 versus prednisolone + mycophenolic acid 46 +/- 15, p < 0.001. These results confirm and extend previous observations and suggest that methylprednisolone might be more effective than prednisone in treatment protocols used to suppress allograft rejection.

Cells, Cultured↗

Lymphocyte suppression by rolipram with other immunosuppressive drugs.

Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phosphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the suppressive effect of rolipram alone and in combination with low concentrations of methylprednisolone and calcineurin enzyme inhibitors, compared to that of pentoxifylline on mitogen-stimulated lymphocyte proliferation. The percent inhibition of 3H-thymidine incorporation by both 10(-5) and 10(-8) mol/L concentrations of rolipram were significantly greater than that by both 10(-4) mol/L pentoxifylline and 10(-8) mol/L methylprednisolone. The percent inhibition by the combination of 10(-5), but not 10(-6), mol/L rolipram and methylprednisolone was significantly greater than that by 10(-4) mol/L pentoxifylline and methylprednisolone. Potentiation of the suppressive effects of cyclosporine and tacrolimus by rolipram was less consistent. Measurement of cell culture supernatant concentrations of interferon gamma and interleukin-10 indicate that one of the mechanisms underlying the immunosuppressive activity of rolipram is a significantly disproportionate inhibition of the proinflammatory cytokine, interferon gamma.

Adult↗

Pentoxifylline potentiates in vitro lymphocyte suppression by glucocorticoids and immunosuppressive drugs.

Pentoxifylline, which has immunomodulatory effects in addition to its better known rheologic effects, might potentiate the effectiveness of traditional immunosuppressive drugs. We therefore studied the suppressive effect of pentoxifylline in combination with clinically relevant concentrations of prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and mycophenolic acid on mitogen-stimulated lymphocytes from 29 patients with glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10(-7) and 10(-8) mol/L concentrations of the glucocorticoids and with 300 ng/mL cyclosporine was significantly increased when each was combined with 5, 25, or 50 microg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in combination with 10(-7) mol/L glucocorticoids was inversely proportional to the inhibitory effect of the 10(-7) mol/L concentration of glucocorticoid alone, suggesting that the less sensitive the patient's cells, the greater the potentiation by pentoxifylline. The greatest degree of potentiation by pentoxifylline occurred when combined with the lower (10(-8) mol/L) concentration of glucocorticoids. Pentoxifylline also significantly increased lymphocyte suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine, 5 ng/mL of tacrolimus, 2.5 x 10(-7) mol/L mycophenolic acid, and 10 ng/mL of rapamycin. These in vitro results suggest that pentoxifylline might have steroid-sparing effects and contribute to improved clinical outcomes from immunosuppressive treatment of renal diseases.

Adult↗

Laparoscopic renal biopsy.

BACKGROUND: Renal biopsy continues to be a pivotal tool and frequently indispensable diagnostic procedure in the clinical assessment of proteinuria and or unexplained renal disease. Laparoscopic renal biopsy has recently been reported as an alternative to open renal biopsy. METHODS: Thirty-two patients who had proteinuria and/or renal insufficiency underwent laparoscopic renal biopsy at our center. The indications for biopsy included failed percutaneous biopsy (N = 3), morbid obesity (14), solitary kidney (5), chronic anticoagulation/coagulopathy (6), religious consideration (refusal of potential blood transfusion) (2), multiple bilateral renal cysts and body habitus (1 case each). The kidney was approached via a laparoscopic retroperitoneal route (retroperitoneoscopy) using a two port technique. The lower pole of the kidney was localized using blunt dissection, laparoscopic cup biopsies were performed, and hemostasis was achieved using standard techniques. RESULTS: All biopsies were successfully completed laparoscopically with sufficient tissue obtained for histopathological diagnosis in all cases. Mean estimated blood loss was 25.9 ml (range 5 to 100). None of the patients required parenteral narcotics during the perioperative period. Operative time ranged from 0.8 to 3.0 hours (mean 1.5). Mean hospital stay was 1.7 days (range 0 to 7). Sixteen patients were treated as outpatients. Patients returned to normal activity at a mean of 1.7 weeks (range 0.3 to 3.0) postoperatively. In one patient, the spleen was inadvertently biopsied without consequence. An additional patient developed a postoperative 300 cc perinephric hematoma that resolved without the need for intervention. One postoperative mortality occurred on postoperative day seven secondary to a perforated peptic ulcer in a patient undergoing high-dose steroid therapy for lupus nephritis. CONCLUSION: Laparoscopic renal biopsy is a safe, reliable, minimally invasive alternative to open renal biopsy for patients in whom a closed percutaneous approach is either a relative or absolute contraindication, which can be performed on an outpatient basis.

Adolescent↗

Successful mycophenolate mofetil treatment of glomerular disease.

Eight patients with resistant and/or relapsing nephrotic syndrome or renal insufficiency were empirically treated with mycophenolate mofetil (MMF). The underlying glomerular diseases were membranous nephropathy (N = 3), minimal change disease (n = 2), focal segmental glomerulosclerosis (n = 1), and lupus nephritis (N = 2). Treatment with MMF 0.75 to 1.0 g twice daily, either as monotherapy or in combination with low-dose steroid treatment, resulted in substantial reductions in proteinuria or stabilization of serum creatinine. In relapsing patients following withdrawal from cyclosporin A, MMF achieved suppression of proteinuria equivalent to or better than that which occurred during cyclosporin A treatment. Steroids were successfully withdrawn in each of the non-lupus patients. MMF was well tolerated with no evidence of hematologic, hepatic, or other toxicity. These clinical anecdotes demonstrate the short-term clinical efficacy of MMF treatment. In addition, they suggest that MMF may have major steroid-sparing effects and might represent an alternative to cyclosporin A in appropriate patients.

Adult↗

Suppression of dialysis patients' lymphocyte IL-2R expression by glucocorticoids and cyclosporine.

Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found to be more sensitive to both glucocorticoids than those from patients on haemodialysis (HD). In order to begin to explore the cellular mechanism(s) underlying these observations, the differential suppressive effects of these drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen-stimulated PBMC from 23 PD and 30 HD were determined. The mean+/-SD concentrations (ng/ml) of steroid causing 50% inhibition (IC50) of cell proliferation was significantly lower for PD than HD PBMC with both P (94+/-93 vs 148+/-105, P<0.05) and MP (21+/-25 vs 35+/-31, P<0.05). MP was significantly (P<0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R expression was significantly (P<0.05) more suppressed by CsA alone and by 400 ng/ml CsA+10(-7) MP than was HD IL-2R expression. CsA+10(-7) M MP was significantly (P<0.001) more suppressive of IL-2R expression than the other drugs, alone or in combination, in both groups of patients. In conclusion, these results support the notion that at least one mechanism underlying the significantly greater efficacy of MP compared to P in suppressing PBMC proliferation is its significantly greater suppression of lymphocyte IL-2R expression, either alone or in combination with CsA. Thus, use of MP following allograft transplantation may result in more effective immunosuppression for many recipients.

Cells, Cultured↗

Lymphocyte responsiveness to glucocorticoids, cyclosporine, or both.

The reason why some patients with glomerular diseases respond to steroid treatment and others do not remains obscure, and it is not possible to prospectively evaluate the probability of response in individual patients. One factor that might contribute to the clinical response to treatment could be the relative sensitivity of a patient's immune system to the suppressive effects of steroids or other immunosuppressive agents. To evaluate this possibility, phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 16 patients with various biopsy-proven glomerulopathies were cultured with prednisolone or methylprednisolone in final concentrations of 10(-5) to 10(-8) mol/L. From the dose-response curves, the concentration of steroid required to cause 50% inhibition (IC50) of the PHA-induced proliferative response was determined. The PBMC from 10 patients also were cultured with 400 ng/mL cyclosporine both alone and with 10(-7) mol/L steroid, and the inhibitory effects were calculated. There was considerable heterogeneity in the sensitivities of individual patients to steroid inhibition, and the mean +/- SEM IC50 was significantly lower for methylprednisolone than for prednisolone. Cyclosporine caused 50% or greater inhibition in 6 of the 10 patients but had < 10% inhibitory effect in 2 patients. In most patients studied, cyclosporine plus steroid was significantly more inhibitory than cyclosporine alone, but the combination was usually no more effective than 10(-7) mol/L methylprednisolone alone. These results are consistent with the hypothesis that differences in the sensitivity of individual patient's immune systems to the immunosuppressive effects of steroids and cyclosporine might contribute to differences in their clinical responsiveness to treatment.

Adult↗

Suppression of lymphocyte interleukin-2 receptor expression by glucocorticoids, cyclosporine, or both.

Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously reported, suggesting that differences in the pharmacodynamic responsiveness of the immune system to these agents might be an important determinant of how well an individual patient responds to treatment. It also has been shown that methylprednisolone is significantly more suppressive than prednisolone. To identify cellular mechanisms by which these drugs act, a study of the suppressive effects of prednisolone, methylprednisolone, and cyclosporine on lymphocyte proliferation and the expression of the cell surface receptor for interleukin-2 (IL-2R) was conducted using phytohemagglutin-stimulated peripheral blood mononuclear cells (PBMCs) from 13 patients with glomerulopathy and 12 control subjects. Heterogeneity among individuals in both parameters of lymphocyte responsiveness to these drugs was again found, and the significantly greater suppressive effect of methylprednisolone was confirmed for both proliferation and IL-2R expression in patients and control subjects. Cyclosporine alone was moderately suppressive. For most individuals, the greatest degree of suppression occurred when cells were exposed to both cyclosporine and glucocorticoid. Further studies are being conducted to determine whether pretreatment assessment of in vitro lymphocyte responsiveness has any predictive value regarding therapeutic efficacy of each drug in individual patients and to identify of those patients likely to require a more intensive or multidrug immunosuppressive regimen.

Adult↗