Biomedical subjects
T Steinmüller
Publications and source records attributed to T Steinmüller.
Regulation of glucose tolerance in patients after liver transplantation: impact of cyclosporin versus tacrolimus therapy.
BACKGROUND: We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10). METHODS: We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT. RESULTS: Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P<0.05). Intravenous glucose tolerance [(K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time], insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P<0.05). Body mass index was the overall determinant of insulin sensitivity in all groups. CONCLUSIONS: Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.
Arterial complications after liver transplantation.
From September 1988 through April 1998, 1,000 liver transplantations were performed on 911 patients. During the postoperative control examinations of 837 patients, we found 23 (2.74 %) with hepatic artery thromboses, 27 stenoses of the hepatic artery (3.22 %), and 6 aneurysms of the graft artery. Seventeen patients underwent retransplantation because of arterial complications. Depending on the clinical symptoms, we treated both the local situation as well as the resulting complications of inadequate arterial graft flow. The aneurysms were primarily treated surgically. The first choice of treatment of stenoses was balloon angioplasty. Early postoperative artery thromboses were also treated surgically by thrombectomy in selected cases. For the resulting biliary and local septic complications we preferred endoscopic and drainage procedures. Our clinical experiences have led us to find pretransplantation angiography recommendable, especially in the case of splanchnic artery stenoses, for bypassing from the aorta for arterial perfusion of the graft.
Primary and secondary hepatic manifestation of neuroendocrine tumors.
BACKGROUND: In comparison with most other malignancies, in the treatment of metastatic neuroendocrine tumors one also has to consider endocrine symptoms and natural progression of disease. Since hepatic metastasis predominates and endocrine symptoms correlate with functional tumor mass, hepatic resection may improve prognosis or even cure patients. PATIENTS AND METHODS: We reviewed 41 consecutive patients with metastatic neuroendocrine tumors and four patients with primary hepatic disease presenting between 1989 and 1999. The neuroendocrine tumors were classified according to their origin, pattern of metastasis, endocrine activity, and histology. Operative therapy including hepatic resections of different extent, liver transplantation, and removal of the primary tumor was analyzed. The median survival after initial diagnosis and after hepatic resection were major parameters of outcome. RESULTS: There were 26 low-grade malignant, 12 high-grade malignant, 2 biphasically differentiated neuroendocrine carcinomas, and 5 pancreatic endocrine tumors. Hepatic resections were performed in 25 patients, resections of the primary tumor in 40 patients. The median survival after initial diagnosis was 49 months; 50.5 months in patients with hepatic resection versus 47 months in those with no liver surgery. CONCLUSION: Hepatic resection improved the outcome of patients with liver metastasis due to neuroendocrine tumors tendentiously but not significantly.
Evidence for impaired glucose effectiveness in cirrhotic patients after liver transplantation.
To evaluate the impact of acute and chronic liver disease and single immunosuppression (cyclosporine A [CSA] or FK506) on insulin sensitivity and glucose effectiveness in liver-grafted patients, we performed a frequently sampled intravenous glucose tolerance test (FSIGTT) in nondiabetic patients after orthotopic liver transplantation (OLT) with acute liver failure ([ALF] group, n = 9, with CSA therapy), in patients after OLT with chronic liver disease (CSA group, n = 8; FK506 group, n = 8), and in 9 healthy control subjects. Insulin sensitivity and glucose effectiveness were determined by analyzing glucose and insulin data from the FSIGTT with Bergman's minimal model technique for glucose. The intravenous glucose tolerance index ([KG] ie, the slope of the regression of the logarithm of blood glucose concentration) was not different between the ALF group (2.17 +/- 0.16 min(-1)) and controls (2.29 +/- 0.13 min(-1)), but was lower (P < .05) in both groups with chronic liver disease (CSA group, 1.46 +/- 0.1; FK506 group, 1.61 +/- 0.11 min(-1)) compared with the ALF group (P < .05). A positive relation for the KG and glucose effectiveness was found in all liver-grafted patients and controls. Insulin sensitivity was not different between all liver-grafted patients and controls. The body mass index (BMI) was the overall determinant of insulin sensitivity in all groups. Single immunosuppressive therapy does not impair insulin sensitivity in liver-grafted patients. The lower glucose effectiveness in liver-grafted patients with chronic liver disease but not in patients after ALF points to a defect in the regulation of glucose-mediated glucose uptake in peripheral tissue.
Impact of primary immunosuppression on the incidence of infectious complications after orthotopic liver transplantation.
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[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases].
BACKGROUND: Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively. PATIENTS AND METHODS: Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection. RESULTS: With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years. CONCLUSION: Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.
Prognostic factors in patients with differentiated thyroid carcinoma.
OBJECTIVE: To study the prognostic factors in patients with differentiated thyroid carcinoma. DESIGN: Retrospective analysis. SETTING: University hospital, Germany. PATIENTS: 139 consecutive patients who underwent surgery for follicular (n = 42) and papillary thyroid carcinoma (n = 97). MAIN OUTCOME MEASURES: Survival rate, type of operation (systematic lymphadenectomy or no lymphadenectomy). RESULTS: Median observation time was 72 months (range 1-203). The 5 and 10 year survival rates in patients with papillary carcinoma were 92% and 89% respectively, and in those with follicular carcinoma 88% and 80%, respectively. Prognostic factors for papillary carcinoma were distant metastases, age, and extrathyroidal growth, and for follicular carcinoma they were distant metastases, extrathyroidal extension, and multifocal growth. The Union International contre le Cancer and European Organisation for Research and Treatment of Cancer scores and the age, grade, extent and size score were all highly significant. The extent of lymphadenectomy, primary or secondary thyroidectomy, and partial or total thyroidectomy did not influence survival. CONCLUSION: Staging and score systems may be helpful in calculating prognosis in differentiated thyroid carcinoma, but the benefit of systematic lymphadenectomy remains controversial.
Preoperative contrast-enhanced MRI of the parathyroid glands in hyperparathyroidism.
RATIONALE AND OBJECTIVES: To evaluate the sensitivity of contrast-enhanced MRI in the preoperative detection of abnormal parathyroid glands in patients with clinical evidence of hyperparathyroidism. METHODS: Twenty-eight patients with biochemical evidence of hyperparathyroidism underwent contrast-enhanced preoperative MRI of the parathyroid glands. Two blinded readers assessed the MR images by consensus, and MR results were subsequently correlated with those from surgery (location, diameter, weight) and histopathology. RESULTS: MRI depicted 32 of 39 surgically proved abnormal parathyroid glands (sensitivity 82%; 95% confidence interval, 66%-92%), and 1 of 114 (0.9%) was incorrectly considered abnormal. All ectopic glands were correctly identified (2 mediastinal, 1 submandibular). Sensitivity was superior for adenomas but less for hyperplasia (adenomas 87%; 95% confidence interval, 67%-97%; hyperplasia 75%; 95% confidence interval, 47%-92%). Among all lesions, atypical signal characteristics on MRI were observed in 34% of lesions (9% hyperintense signals on T2- and T1-weighted images; 25% isointense signals on T2- and T1-weighted images), with improved lesion detection after contrast administration in 17% of lesions. CONCLUSIONS: MRI of the parathyroid glands presented a sensitive imaging modality, thus demonstrating its high potential to preoperatively detect abnormal glands. Moreover, in a minor proportion of patients with atypical parathyroid lesion characteristics, contrast administration may increase lesion detectability.
Complications associated with different surgical approaches to differentiated thyroid carcinoma.
INTRODUCTION: With the good prognosis associated with differentiated carcinoma, the morbidity and mortality of different surgical approaches are of crucial importance. METHODS: At the Department of Surgery (Virchow Klinikum Berlin), 139 patients who underwent surgery for differentiated thyroid carcinoma between 1979 and 1994 were reviewed, focussing on postoperative complications. In 113 and 18 patients, respectively, primary and completion thyroidectomy was performed. In five patients, less than total thyroidectomy and in three patients only palliative surgery was carried out. We performed thyroidectomy without systematic lymphadenectomy (LAD) in 70 patients (51.1%). In 15 patients (10.8%), lymphadenectomy of the lateral compartment and, in 53 patients (38.1%), central LAD was performed. LAD did not significantly influence survival time in either follicular (n = 42) or papillary carcinoma (n = 97). RESULTS: No patient died because of postoperative complications. Permanent laryngeal nerve palsy occurred in no patients after thyroidectomy without LAD, in one patient after central LAD (1.9%) and in one patient after lateral LAD (6.7%). Transient laryngeal nerve palsy was seen in ten patients [six (8.6%) after thyroidectomy only, two (3.7%) after central LAD and two (13.3%) after lateral LAD] (P = 0.19). Hypocalcemia was distributed equally within the LAD groups: total transient hypocalcemia could be recorded in 54 patients (38.8%), but permanent hypocalcemia occurred only in one patient (0.7%). Postoperative recovery was delayed in patients when a more radical approach was used (P = 0.03). CONCLUSION: The magnitude of the benefit of LAD in therapy for differentiated thyroid carcinoma is still controversial. This more radical approach is not necessarily accompanied, however, by higher morbidity and mortality.
Preemptive therapy in CMV-antigen positive patients after liver transplantation--a prospective trial.
OBJECTIVE: Preemptive therapy with intravenous ganciclovir and CMV-hyperimmunoglobulin in asymptomatic CMV pp65-antigen positive patients was compared with treatment of only symptomatic CMV-disease after liver transplantation in an open prospective study. PATIENTS AND METHODS: 48 out of 200 liver transplant recipients became positive during six weeks follow-up after transplantation. 17 out of these 48 patients who were already symptomatic at the time of positive antigen testing were successfully treated with ganciclovir and CMV-hyperimmunoglobulin. 31 asymptomatic antigen-positive patients were randomised to receive preemptive therapy or to receive therapy only at onset of clinical symptoms. RESULTS: Only two out of 15 patients in this latter group without preemptive therapy developed CMV-syndrome and were successfully treated with intravenous ganciclovir. 13 patients did not experience any clinical symptoms or disease and were therefore spared unneccessary toxicity and costs. The overall incidence of CMV-infection and -disease in the whole study population of 200 liver transplant recipients was 25% and 10%. As expected, CMV-negative patients who received an organ from a seropositive donor were at a higher risk of CMV-infection and -disease, but did not show more severe infections clinically. Patients with IL-2 receptor antibody induction therapy seemed to have a higher risk for CMV-infection and -disease.
Donor-recipient sex matching and posttransplant malignancies after induction therapy in hepatic transplantation.
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Treatment with PGE1 in patients after liver transplantation.
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Five-year follow-up of tacrolimus as primary immunosuppressant after liver transplantation.
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Contribution of early acute rejection episodes to chronic rejection in a rat kidney retransplantation model.
Chronic graft rejection represents the single most important risk factor for unsatisfactory long-term results after organ transplantation. In addition to various alloantigen dependent and independent factors, acute rejection episodes have been cited as a major immunological risk factor. However, the effects of acute rejection episodes on long-term graft outcome remains unknown. To examine the influence of a single early rejection event on ultimate graft outcome, acutely rejecting rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. LEWxBNF1 kidney allografts and LEW isografts were removed from their LEW recipients after three, four, five and seven days (N = 12/group/time period) and retransplanted into donor strain hosts. The grafts were followed functionally and harvested four, eight, and 32 weeks later. Urinary protein excretion was measured weekly. Kidneys were examined morphologically and immunohistologically using monoclonal antibodies (mAbs) against macrophages (ED-1), T cells and their subsets (CD5, CD4, CD8), MHC class II expression (OX3) and adhesion molecules (ICAM-1 and LFA-1alpha). The mean standard time +/- SD of non-retransplanted allografts was 14.5 +/- two days; isografts functioned indefinitely. At five and seven days, acutely rejecting allografts showed massive cellular infiltrates associated with extensive necrosis. These changes could not be reversed by retransplantation and the syngeneic recipients later died of renal failure. In contrast, most allografts retransplanted earlier in the process recovered completely when retransplanted after three (12 of 12 allografts) and four (7 of 12 allografts) days. During the subsequent follow-up period, urinary protein excretion was comparable in retransplanted allografts and isografts. The increased mononuclear cell infiltration in non-retransplanted allografts seen at three and four days was only occasionally observed during the follow-up period after retransplantation. Only a few sclerosed glomeruli (approximately 15%), mild arterial changes and minimal cellular infiltrates were observed by 32 weeks, which were similar to that seen in retransplanted isografts. A single acute rejection episode was completely reversible and did not progress to chronic rejection if retransplanted into syngeneic donors when the inflammatory changes are still early. Those results demonstrate the critical effect of alloantigen-dependent events on chronic graft deterioration, and indicate that prompt and aggressive treatment of initial acute rejection episodes are beneficial to protect against late deleterious changes in the graft.
Orthotopic liver transplantation for hepatic associated metabolic disorders.
Hepatic associated metabolic disorders represent 5% of the indications for orthotopic liver transplantation (OLTX) according to the European Liver Transplant Registry. We studied the outcome of this group at our institution after OLTX and combined liver/kidney transplantation. Between September 1988 and January 1997, 837 OLTXs were performed in 735 patients. Patient survival and graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr, range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7), hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n = 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1), ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering from primary hyperoxaluria type I received combined liver/kidney grafts. Survival rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant lymphoma 5 months after transplantation. One patient required retransplantation 2 months after OLTX following arterial thrombosis and ischemic type biliary lesion. One year after OLTX, all patients demonstrated good graft function, liver grafts (ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/- 15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX, respectively combined OLTX/NTX, represent a successful therapy for hepatic associated metabolic disorders. Survival rates and graft function are similar to those in liver graft recipients for established indications at our institution. OLTX seems to be an excellent treatment for hepatic based therapy resistant neurological disorders.