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Biomedical subjects

M Wiesel

Publications and source records attributed to M Wiesel.

At least 19 recordsLinked to original sources
PubMed2000

Atherosclerotic complications after renal transplantation.

Death with functioning graft, the most frequent cause being cardiac death, continues to be the most frequent cause of long-term graft loss. The risk of cardiovascular death in the transplanted patient is lower than in patients with other modalities of renal replacement therapy, but continues to be substantially higher than in the general population. Amongst the factors predicting patient and graft survival are hypertension, dyslipidemia, smoking and possibly hyperhomocysteinemia. It is concluded that lowering of blood pressure to levels far lower than levels accepted in the past, more widespread administration of statines, cessation of smoking and possibly administration of folate should reduce cardiovascular mortality and possibly also influence chronic allograft vasculopathy.

Arteriosclerosis↗
PubMed2000

Impaired bone metabolism following augmentation cystoplasties in growing rats.

OBJECTIVE: The aim of this study was to evaluate the possible risk of impaired bone metabolism following augmentation cystoplasties with different gastrointestinal segments. METHOD: 60 young rats underwent augmentation cystoplasties using gastric, ileal or sigma segments, or sham operations. An additional group undergoing sigma-cystoplasty received the bisphosphonate ibandronate to inhibit osteoclast-mediated bone resorption. Bone mass in the lumbar spine and tibia was analyzed monthly by in vivo densitometry. Bone turnover was assessed monthly using current bone metabolism markers for a period of 16 weeks. Bone ashing and serum analyses of the osteotropic hormones parathyroid hormone (PTH), and 25-OH vitamin D3 were performed at study conclusion. RESULTS: Following ileocystoplasty, reduced bone mineral density (BMD) was seen throughout the observation period; this was pronounced in the trabecular bone. The decline in BMD was associated with decreased serum 25-OH vitamin D3 levels. Following sigmacystoplasty, bone calcium content was significantly decreased; this could be prevented by ibandronate. No skeletal changes occurred in the gastrocystoplasty group. Serum pH was not altered in any group, and markers of bone resorption indicated normal bone resorption rates. CONCLUSION: There is a significant correlation between impaired bone metabolism and the type of segment used for bladder augmentation. While the use of the ileum (and probably the colon too) causes osteopenia, gastrocystoplasties seem to have little influence on bone turnover.

Absorptiometry, Photon↗
PubMed1999

[Radiodiagnosis following kidney transplantation].

Diagnostic imaging after renal transplantation is of high importance in the differential diagnosis of peri- and postoperative complications. Sonography with color duplex imaging is the method of choice in the diagnosis of acute transplant rejection. MRI is an additional method in the diagnosis of transplant dysfunction especially in diagnosis of perirenal fluid collections. MR angiography and MR urography are noninvasive diagnostic modalities with the potential to replace angiography and pyelography. Angiography, complemented by carbon dioxide angiography, still is the gold standard in the diagnosis of transplant artery stenosis.

Angiography↗
PubMed1999

P-glycoprotein expression is not a useful predictor of acute or chronic kidney graft rejection.

Because of the role of P-glycoprotein (P-gp) in multidrug resistance (MDR), it has been suggested that P-gp might play a role in acute and chronic rejection after organ transplantation. The purpose of the present work was to investigate a possible relationship between graft outcome and P-gp expression on peripheral mononuclear cells of renal transplant recipients. We determined P-gp expression in 27 patients with long-term, stable graft function (ST) and in 15 patients with chronic deterioration of graft function (CR). In addition, 40 patients were studied prior to, and at intervals after, transplantation with 21 healthy individuals serving as controls. P-gp values were highest in healthy controls and in ST patients. We found no correlation between P-gp values and acute rejection. CR patients tended to have lower levels of P-gp expression. Our results contradict the opinion that an overexpression of P-gp induces acute or chronic rejection by inhibiting the efficacy of immunosuppressive treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Role of color-coded Doppler sonography in the assessment of internal ureteral stent patency.

OBJECTIVE: To evaluate the role of color-coded Doppler sonography (CCDS) in the assessment of internal ureteral stent patency. PATIENTS AND METHODS: We compared micturating cystography (MC) and CCDS in 48 patients with internal ureteral stents. Forty-five of these patients had pyelocaliectasis on renal sonography. RESULTS: In all of the 48 patients, the distal end of the internal ureteral stent could be seen sonographically in the bladder. The color images of 30 patients showed typical flow from the distal holes of the stent. Micturating cystography demonstrated patency of the stents in 36 patients. The two procedures showed the same results in 42 of 48 patients. Six patients had no detectable flow by CCDS, but the MCs showed patency of the stents. CONCLUSION: The CCDS is a valid noninvasive method for the assessment of internal ureteral stent patency with a sensitivity of 100%, a specificity of 83%, a positive predictive value of 67%, and a negative predictive value of 100%.

Evaluation Studies as Topic↗
PubMed1999

Ureteral complications in renal transplantation with more than one donor ureter.

BACKGROUND: The purpose of this study was to evaluate the ureteral complications of renal transplant recipients with more than one donor ureter METHODS: Between 1967 and 1997, 19 patients (median age 34 years, range 6-62 years) received renal transplants from donors with more than one ureter. There were 18 donor organs with two ureters, and one patient underwent en bloc renal transplantation with four donor ureters. In nine patients, the ureters were implanted separately at the bladder dome according to the extravesical technique of Witzel, Sampson, Lich and Röhl. In 10 patients, we performed a modification of this extravesical technique according to Nghiem with a side-to-side anastomosis of the ureters before completing the ureteroneocystostomy. RESULTS: After a median follow-up of 55 months (range 2-218 months), no graft loss due to ureteral complications was noted. One patient died due to myocardial infarction, seven patients returned to dialysis without ureteral complications. There were two patients (one patient after side-to-side ureteral anastomosis, one patient with separate implantation of the two ureters) with ureteral obstruction of one donor ureter. Both patients underwent open surgical revision with temporarily placement of internal ureteral stents. CONCLUSIONS: The presence of multiple ureters from donor kidneys is associated with a higher complication rate in our patient population compared with donor kidneys with one ureter. There was no difference in the long-term outcome between the two implantation techniques used.

Adolescent↗
PubMed1999

Area under the plasma concentration-time curve for total, but not for free, mycophenolic acid increases in the stable phase after renal transplantation: a longitudinal study in pediatric patients. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Mycophenolate mofetil, an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy in pediatric renal transplant recipients. However, little is known about the pharmacokinetics of MPA in this patient population in the stable transplant phase, and dosage guidelines are preliminary. The authors therefore compared the pharmacokinetics of MPA, free MPA, and the renal metabolite MPA glucuronide (MPAG) in the initial (sampling at 1 and 3 weeks) and stable phases (sampling at 3 and 6 months) posttransplant in 17 children (age, 12.0 +/- 0.77 years; range, 5.9 to 15.8 years), receiving the currently recommended dose of 600 mg MMF/m2 body surface area (BSA) twice a day. Plasma concentrations of MPA and MPAG were measured by reverse phase HPLC. Because MPA is extensively bound to serum albumin and only the free drug is presumed to be pharmacologically active, the authors also analyzed the MPA free fraction by HPLC after separation by ultrafiltration. The intraindividual variability of the area under the concentration-time curves (AUC0-12) of MPA throughout the 12-hour dosing interval was high in the immediate posttransplant period, but declined in the stable phase, whereas the interindividual variability remained unchanged. The median MPA-AUC0-12 values increased 2-fold from 32.4 (range, 13.9 to 57.0) mg x h/L at 3 weeks to 65.1 (range, 32.6 to 114) mg x h/L at 3 months after transplantation, whereas the median AUC0-12 values of free MPA did not significantly change over time. This discrepancy can be attributed to a 35% decline of the MPA free fraction from 1.4% in the initial phase posttransplant to 0.9% (p < 0.01) in the stable phase. In conclusion, pediatric renal transplant recipients given a fixed MMF dose exhibit a 2-fold increase of the AUC0-12 of total MPA in the stable phase posttransplant and a 35% decrease of the MPA free fraction, whereas the AUC0-12 of free MPA remains unchanged over time. Because the latter pharmacokinetic variable is theoretically best predictive of the clinical immunosuppressive efficacy of MMF, these findings may have consequences for the dosing recommendations of MMF in renal transplant recipients.

Adolescent↗
PubMed1998

[Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new immunosuppressive agent. International Mycophenolate Mofetil Study Group].

1493 patients were enrolled in 55 centers in Europe, Canada, Australia and the USA comparing the efficacy of mycophenolate mofetil (MMF) in daily doses of 2 and 3 g with placebo/azathioprine (PLA/AZA) for the prevention of acute rejection in renal transplant patients. Acute rejections and graft loss and death at 1 year were measured per trial and these data were combined and analyzed in a pooled fashion. The three pooled treatment groups were well balanced regarding demographic characteristics and cause of renal failure leading to transplantation. At one year the graft survival rate was 90.4% and 89.2% in the MMF 2 g and 3 g groups compared with 87.6% in the PLA/AZA-group. MMF 2 and 3 g were significantly better than PLA/AZA in reducing biopsy proven rejection at one year: 40.8% placebo/aza vs. 19.8% in the MMF 2 g group and 16.5% in the MMF 3 g group.

Adult↗
PubMed1998

Impact of recurrent nephrotic syndrome after renal transplantation in young patients.

Recurrent disease is a frequent complication of patients transplanted for steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis. Its long-term prognosis has rarely been studied. We examined 39 patients aged 4-25 (mean 13.5) years at the time of first transplantation (TX). Twelve of these (30%) developed nephrotic syndrome after the first TX and 2 of 8 after the second TX. The mean observation period from first TX to last observation with a functioning graft or graft loss was 5.4 (0.1-19.3) years. We confirmed that recurrent disease is associated with older age at onset of the primary disease, shorter time from onset to end-stage renal disease, and diffuse mesangial proliferation in the initial kidney biopsy. Remissions occurred in all 3 children undergoing early repeated plasma exchange and in 1 adolescent following introduction of cyclosporin A 7 years after TX. At last observation 42% of relapsing and 48% of non-relapsing patients with a similar follow-up period had a functioning first graft. Median first graft survival was almost identical in the relapsing and the non-relapsing patients (4.3 vs. 4.2 years). Histological lesions of focal glomerulosclerosis were detected in the posttransplant biopsies of only 3 patients. In conclusion, young patients with nephrotic syndrome associated with focal segmental sclerosis have a similar graft survival with and without recurrence of the nephrotic syndrome.

Adolescent↗
PubMed1998

A placebo controlled study of mycophenolate mofetil used in combination with cyclosporine and corticosteroids for the prevention of acute rejection in renal allograft recipients: 1-year results. The European Mycophenolate Mofetil Cooperative Study Group.

PURPOSE: We performed a randomized, double-blind, multicenter, placebo controlled study to compare the efficacy and safety of 2 oral doses of mycophenolate mofetil with placebo for prevention of acute rejection episodes following first or second cadaveric renal allograft transplantation. MATERIALS AND METHODS: A total of 491 patients were enrolled in the study and randomly allocated to receive placebo (166), 1 gm. mycophenolate mofetil twice daily (165) or 1.5 gm. mycophenolate mofetil twice daily (160). Patients were given concomitant immunosuppression with cyclosporine and corticosteroids. Treatment with mycophenolate mofetil was initiated within 72 hours of transplantation and was continued for at least 1 year. RESULTS: The percentages of patients who experienced biopsy proved rejection or withdrew early from the trial for any reason were significantly reduced with 2 gm. (30.3%) and 3 gm. (38.8%) mycophenolate mofetil compared to placebo (56.0%) (p < 0.001). The biopsy proved rejection rates of the placebo, and 2 gm. and 3 gm. mycophenolate mofetil treatment arms were 46.4, 17.6 and 13.8%, respectively. There were fewer patients in the 2 gm. (28.5%) and 3 gm. (24.4%) mycophenolate mofetil groups compared to the placebo (51.8%) group, who received full courses of corticosteroids or antilymphocyte agents for treatment of rejection episodes in the first 6 months after renal transplantation. There was a greater incidence of gastrointestinal adverse events, leukopenia and opportunistic events in the mycophenolate mofetil treatment groups. CONCLUSIONS: Mycophenolate mofetil was shown to reduce significantly the number of patients who experienced biopsy proved rejection episodes or treatment failure during the first year after renal transplantation, and was well tolerated.

Acute Disease↗
PubMed1998

[MR tomographic monitoring of prostate carcinoma after cryotherapy: initial results].

PURPOSE: To assess the morphological changes in the prostate gland and adjacent tissue after cryosurgery by high resolution MRI in patients with histological proven prostatic carcinoma. METHOD: 15 patients (mean age 66 years) with histologically proven prostate carcinoma underwent T2- and contrast-enhanced T1-weighted high-resolution MRI examinations with fat suppression. Follow-up MRI with an identical imaging protocol were performed at different time intervals (24-72 h, 2-6, 12, 26-52 weeks). RESULTS: Mean prostate volume had decreased by 30% in all patients 12-52 weeks after cryosurgery. After cryosurgery, zonal differentiation was lost in all patients with abnormalities in the periprostatic tissue in all patients, and rectal wall thickening in 47% of patients. Cryosurgery-induced changes in the prostate could not be differentiated from tumour recurrence. CONCLUSION: High resolution MRI allows precise recognition of intraprostatic and adjacent tissue alterations after cryosurgery of prostatic carcinoma. However, reliable detection of tumour recurrence was impossible due to cryosurgically induced signal changes.

Aged↗
PubMed1998

Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.

Adolescent↗