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G Offermann

Publications and source records attributed to G Offermann.

At least 19 recordsLinked to original sources
PubMed2000

[Mycophenolate mofetil: a new immunosuppressive drug in dermatology and its possible uses].

Mycophenolate mofetil represents a new immunosuppressive drug. Several case reports have shown that mycophenolate mofetil has a good therapeutic effect in patients with psoriasis and autoimmune dermatoses. Mycophenolate mofetil is a morpholine ester of mycophenolic acid which was shown in the 1970s to be effective in patients with severe psoriasis. Mycophenolate mofetil has an increased bioavailability as compared to mycophenolic acid and thereby an improved therapeutic window. Currently, mycophenolate mofetil is indicated for the prevention of organ rejection in transplant patients. The mode of action and the pharmacology of mycophenolate mofetil are reviewed and the current clinical experience with this immunosuppressive drug for dermatological disorders is summarized.

Administration, Oral↗
PubMed2000

Computational analysis of blood volume curves and risk of intradialytic morbid events in hemodialysis.

BACKGROUND: Blood volume (BV) curves have been used to prevent intradialytic morbid events (IMEs) caused by hypotensive episodes in hemodialysis treatment. However, no standardized parameter is available to describe BV dynamics and to enable online interference with ultrafiltration rates in unselected patients. Moreover, only time-dependent BV reduction and absolute hematocrit threshold, but not BV variability, have been suggested as markers of pending hypotension. The present study therefore deals with a computer-aided analysis of indices characterizing both BV reduction per time and BV variability in treatments of nonselected maintenance hemodialysis patients. METHODS: The methodology uses indices obtained by mathematical analysis of BV curves and was designed to potentially enable automatic interference with ultrafiltration. RESULTS: In 46 out of 380 treatments (12.1%), IMEs occurred. In these treatments, the indices for long- and short-term variability and slope of the curves were significantly lower than in treatments without IMEs. Moreover, the last 10 minutes before an IME were characterized by additionally decreased variability and slope. In a risk analysis of long-term variability and IMEs, we established an index below 16 to be associated with the highest risk of IMEs. CONCLUSIONS: Using these kind of index thresholds and online analysis of BV curves, automatic management of ultrafiltration by BV dynamics could be a promising concept to avoid intradialytic morbidity.

Adult↗
PubMed2000

Fatal cytomegalovirus pneumonia after preemptive antiviral therapy in a renal transplant recipient.

Cytomegalovirus (CMV) infections occur with an incidence of up to 70% in renal transplant patients and mortality is low due to effective antiviral drugs. We report here the case of a patient who suffered from an uncommonly severe and therapy-resistant pulmonary CMV infection. During the disease course, CMV-PCR from alveolar cells and lung biopsy material was repeatedly negative despite high CMV pp65 antigenemia. CMV pneumonia was finally diagnosed from a biopsy obtained by open thoracotomy revealing positive CMV immunostaining of lung tissue. The patient died of respiratory failure though double-treatment using both ganciclovir and foscavir was administered. Post mortem, the clinically suspected resistance to both antiviral drugs, but not to cidofovir, could be proven by bioassay testing of in vitro growth responses using viral cultures. CMV pneumonia may thus not be diagnosed by standard PCR techniques in rare cases and may be resistant to the available antiviral therapy. Severe CMV pneumonia may benefit from novel antiviral drugs such as cidofovir, which is currently used in the treatment of CMV retinitis in HIV patients.

Antigens, Viral↗
PubMed1999

Monitoring dialysis efficacy by comparing delivered and predicted Kt/V.

INTRODUCTION: In Europe, especially in Germany, little is currently known about the relationship between delivered and predicted haemodialysis doses for patients on maintenance haemodialysis. We compared delivered and predicted Kt/V in patients of an outpatient dialysis centre in Berlin by calculating the ratio of delivered and predicted Kt/V, resulting in the efficacy quotient, QE. Moreover, we studied the influence of technical and anthropometric parameters on both delivered Kt/V and QE under routine clinical conditions. METHODS: Blood samples were taken after the long interval in a thrice-weekly regimen before and 10 min after ultrafiltration and 100 ml/min slow-pump method. Delivered Kt/V was computed using the Daugirdas III formula. Predicted Kt/V was estimated from the dialysis filter urea clearance given by the manufacturer, treatment time and the total body water (V) computed by the Watson formula and was corrected for real blood flow. As and when appropriate, bivariate and multivariate regression analyses were used to make comparisons. RESULTS: The mean quotient (QE) between delivered and predicted Kt/V was 1.02+/-0.20. Mean delivered Kt/V in 377 treatments of 128 patients was 1.28+/-0.27. Delivered Kt/V and QE were positively associated (P<0.001). QE was significantly associated with post-HD urea, body mass index (BMI) and sex, but not with session time. Significant positive predictors for delivered Kt/V were post-dialysis urea, sex, session time, blood flow and kind of vascular access. BMI was inversely related to delivered Kt/V. DISCUSSION: In this study, the relationship between delivered and predicted Kt/V (QE) was reproducible and close to the ideal value of 1.0. In contrast to delivered Kt/V, QE was not influenced by session time, and positively by BMI. Since QE gives a valid measure of technical dialysis efficacy we suggest the use of this parameter in addition to delivered Kt/V to monitor HD adequacy in clinical routine more comprehensively.

Body Mass Index↗
PubMed1999

Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.

Adult↗
PubMed1998

Familial hemolytic-uremic syndrome in three generations.

The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are complex entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and variable impairment of renal function, occasionally complicated by neurological symptoms. In both syndromes, rare instances of familial forms have been reported. We present the case of a family in which signs and symptoms of HUS/TTP appeared in three generations. We also briefly review the literature on inherited forms of HUS/TTP and discuss the outcome of renal transplantation in adult patients with this syndrome.

Adult↗
PubMed1998

Angiotensin-converting-enzyme insertion/deletion genotype and long-term renal allograft survival.

BACKGROUND: Increased activity of the renin-angiotensin system has been implicated in decreased long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, may be a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. The present study was conducted to determine whether the deletion variant of the angiotensin-converting-enzyme gene influences the long-term outcome in renal-transplant recipients. METHODS: We examined the relationship between recipient angiotensin-converting-enzyme genotype and clinical outcome in patients with a surviving allograft of at least 10 years (median survival 156 months, n= 86). Patients with an allograft survival of less than 3 years served as controls (median survival 10.4 months, n=87). RESULTS: Genotype distribution in long-term renal allograft survivors (II, 18; ID, 41; DD, 27; qD, 0.55) was similar to that in the control group (II, 12; ID, 53; DD, 22; qD, 0.56), and there were no significant differences between the genotypic groups in either cases or controls. Long-term survivors were more often female (58 vs 38%) and less often hypertensive (67 vs 77%). Both recipient and donor age were markedly lower in the long-term survivor group, whereas number of HLA mismatches and cold ischaemia time were comparable between cases and controls. CONCLUSIONS: This study does not support the hypothesis that the angiotensin-converting-enzyme insertion/deletion polymorphism is an important determinant of long-term transplant survival in Caucasian patients undergoing renal transplantation.

Adult↗
PubMed1998

Methylenetetrahydrofolate-reductase gene C677T variant and kidney-transplant survival.

UNLABELLED: BACKGROUND. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in haemodialysis and renal-transplant patients. As atherosclerotic lesions in hyperhomocysteinaemia resemble those of chronic allograft injury, we examined the hypothesis that the C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, which is linked to elevated plasma homocysteine levels in patients with renal failure, determines renal allograft survival. METHODS: DNA was prospectively collected from 336 patients undergoing renal transplantation in our clinic between 1988 and 1994 and their corresponding donors. Patient and allograft survival was analysed by blinded review of all case records over a follow-up period of 36 months. Additionally, we recruited 83 patients surviving with a functional kidney allograft for at least 10 years (mean: 156, range 120-240 months). MTHFR-C677T genotype was determined by a PCR-RFLP technique. The influence of genotype on transplant survival was analysed by Kaplan-Meyer life-table analysis and two-tailed global log-rank testing. RESULTS: Frequency of the MTHFR-C677T allele in the cohort group was identical in recipients (0.35) and donors (0.34), and comparable to that in the longterm allograft survivors (0.37). Furthermore, life-table analysis revealed a similar allograft survival over 36 months between the genotype groups (CC 74%, CT 69%, TT 75%). Other risk factors including donor and recipient age, hypertension, body-mass index, and number of rejection therapies were evenly distributed between the different genotype groups. CONCLUSIONS: These findings do not support the hypothesis that the C677T variant of the MTHFR gene is an important determinant of renal-transplant survival.

Adult↗
PubMed1997

IgA nephropathy in a patient with Behçet's syndrome--case report and review of literature.

A 25-yr-old Turkish patient who presented with oral and genital ulcers, erythema nodosum and peripheral arthritis was diagnosed as having Behçet's syndrome (BS). The patient had normal renal function, but persistent proteinuria with 3 g protein loss/day. Renal biopsy revealed glomerulonephritis (GN) with IgA deposits in the membrane. Co-occurrence of BS and IgA nephropathy (IgAN) has only been reported once to date. In contrast to the statements in most current textbooks on BS, the review of the literature presented here suggests that renal involvement is not infrequent, but serious kidney disease is a rather rare event in Behçet's disease.

Adult↗
PubMed1997

Angiotensin-converting enzyme genotype and renal allograft survival.

Increased activity of the renin-angiotensin system has been implicated in decreased, long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, is a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. To determine whether the deletion variant of the angiotensin-converting enzyme gene influences the long-term outcome in renal transplant recipients, the relationship between donor and recipient angiotensin-converting enzyme genotype and clinical outcome were examined over a follow-up period up to 30 mo in a cohort of 269 Caucasian patients undergoing kidney transplantation between 1988 and 1993. In a subsequent case control study, the frequencies of the angiotensin-converting enzyme genotype were compared in a group of Caucasian patients with a graft survival of less than 3 yr (mean survival, 11 mo; n = 328) with the frequencies in patients with a graft survival of at least 3 yr (mean survival, 65 mo, n = 461). Neither in the cohort nor in the case control study was there a significant effect of recipient or donor angiotensin-converting enzyme genotype on transplant survival. Furthermore, the frequency of the angiotensin-converting enzyme deletion allele both in recipients and donors was similar to that reported in Caucasian controls. This study, therefore, does not support the hypothesis that the recipient or donor angiotensin-converting enzyme insertion/deletion polymorphism is an important determinant of transplant survival in Caucasian patients undergoing renal transplantation.

Adult↗
PubMed1996

Severe calciphylaxis in a renal patient on long-term oral anticoagulant therapy.

The pathogenesis of calciphylaxis, a potentially life-threatening condition, is not well understood. Several factors such as end-stage renal disease (azotemia), hyperparathyroidism, hyperphosphatemia, hypercalcemia, a high calcium-phosphate product, and the use of steroids and cytotoxic drugs after kidney transplantation are believed to interact in calciphylaxis. Recently, hypercoagulability due to functional protein C deficiency has been suggested to play a pathogenic role in this condition. Here, we present a renal transplant patient, with secondary hyperparathyroidism and on long-term oral anticoagulant therapy, who developed calciphylaxis with severe skin necrosis of her legs. The patient's condition improved dramatically after total parathyroidectomy. Hypercoagulability, therefore, does not appear to have played a significant role in this case of calciphylaxis.

Administration, Oral↗
PubMed1996

Transplantation in autosomal dominant polycystic kidney disease without nephrectomy.

Some transplantation centers still suggest nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation at least in selected cases. We wanted to learn whether prior nephrectomy is beneficial. The outcome of kidney transplantation in 47 consecutive ADPKD patients without prior nephrectomy was compared with that in matched controls with respect to complications of ADPKD. Although ADPKD patients were older than controls (mean, 50.1 vs. 40.3 years), there was no statistically significant difference in 1- and 5-year allograft survival between ADPKD patients and controls: 76.6 and 68.0%, respectively, in ADPKD patients, and 83.9 and 56.3% in controls. After a mean follow-up of 66.5 months 3 patients with ADPKD had cyst infections and were managed with antibiotics. Two patients had episodes of hematuria; neither required invasive therapy. There was no renal malignancy and clinical sign of urolithiasis in any patient. No posttransplantation nephrectomy was required. With only few indications remaining, there is no rationale for routine pretransplantation nephrectomy in patients with ADPKD.

Adult↗
PubMed1996

Angiotensinogen-M235T genotype and post-transplant hypertension.

BACKGROUND: The angiotensinogen gene has been linked to the development of essential hypertension, and a M235T variant of this gene, associated with increased plasma levels of angiotensinogen, is more common in hypertensives than in normotensive controls in various populations. The present study was conducted to examine whether the M235T variant of the angiotensinogen gene may be a risk factor for the development of hypertension in patients undergoing renal transplantation. METHODS: DNA for genetic analysis was prospectively collected from 269 consecutive patients undergoing kidney transplantation between 1988 and 1993 and their corresponding donors. Presence of hypertension and graft survival was analysed by blinded review of all case records over a follow-up period up to 30 months. Angiotensinogen genotype was determined by a mutagenically separated allele-specific polymerase-chain-reaction technique. RESULTS: While post-transplant hypertension was present in 78% of all patients, no relationship was found between either donor or recipient genotype and the presence or severity of post-transplant hypertension. Furthermore, there was no relationship between angio-tensinogen genotype and graft survival during the course of the study. CONCLUSIONS: These findings do not support the hypothesis that the M235T variant of the angiotensinogen gene is a risk factor for the development of post-transplant hypertension.

Adult↗
PubMed1995

Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients.

Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.

Adolescent↗
PubMed1994

Impact of de novo membranous glomerulonephritis on the clinical course after kidney transplantation.

Besides rejection-induced transplant glomerulopathy de novo membranous glomerulonephritis (MGN) is the most frequent cause of nephrotic syndrome after renal transplantation. We evaluated 1029 renal transplantations (271 without and 758 with cyclosporine treatment), performed on 848 patients between 1970 and 1992, which resulted in 872 functioning grafts. De novo MGN was seen in 30 biopsy specimens from 21 patients (about 2%), of whom 10 had received immunosuppressive treatment without and 11 with cyclosporine. Taking into account the longer periods of observation of patients without compared with those with cyclosporine treatment (88 +/- 60 vs. 41 +/- 31 mo., respectively, P = 0.001), the two treatment groups did not differ significantly in prevalence of de novo MGN (4.0% vs. 1.5%). De novo MGN was diagnosed by biopsy 62.7 +/- 44.4 mo. after transplantation; its incidence increased significantly with time (from 0% to 5.3% over 8 years; 95% confidential interval: 1.7-8%). Proteinuria (mean, 3.2 +/- 2.9 g/L) was first observed 47.5 +/- 51.3 mo. after transplantation. Thirteen of the 21 patients (62%) were nephrotic (proteinuria, over 1.5 g/L). Steroid pulses were given to 12 patients with de novo MGN and high proteinuria, which did not decline after treatment. Signs of chronic viral infection (hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody) were found in 8 of the 21 patients (38%). Signs of vascular or interstitial rejection were seen in 17 and 12 of the 21 patients with de novo MGN, respectively, and cyclosporine arteriolopathy was diagnosed in four. Graft loss occurred in 14 of the 21 patients and was due to rejection in 13 and to de novo MGN in only one, who developed additional transplant vein thrombosis. Patients with de novo MGN did not differ significantly from the other 851 patients in graft survival (71.4 +/- 9.9% vs. 60.8 +/- 2.2% after 5 yr). De novo MGN is a late, often asymptomatic, complication of initially well tolerated grafts and is neither prevented by cyclosporine treatment nor reversed by further steroid medication. It is often associated with vascular changes caused by rejection or cyclosporine toxicity.

Adult↗