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Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 199 records · Page 11Linked to original sources
PubMed1994

Liver transplantation for Budd-Chiari syndrome--palliation or cure?

This report documents two cases of Budd-Chiari syndrome (BCS) with essential thrombocytosis and antithrombin (AT) III deficiency as underlying etiological factors. Orthotopic liver transplantation was successfully performed in both patients but with different therapeutic intention. In the patient with essential thrombocytosis, hepatic transplantation only relieved the symptoms of the predisposing thrombogenic condition; it did not cure the underlying disorder. Prophylactic long-term anticoagulation, as well as adjuvant therapy for the causative disease, remained necessary. On the other hand, in the patient with AT III deficiency, liver transplantation was curative, resulting in complete reconstitution of serum AT III activity with resolution of the hypercoagulable state postoperatively. Thus, depending on the underlying etiology, liver transplantation for BCS can be considered as palliative, necessitating long-term adjuvant therapy, or as curative, with correction of a metabolic defect.

Adult↗
PubMed1994

The use of plasma levels for FK 506 dosing in liver-grafted patients.

FK 506 plasma levels were analyzed in 89 liver-grafted patients under FK 506-based immunosuppression. Plasma levels were found to be influenced by the patients' liver function: compared to patients without major liver dysfunction, those with cholestasis had higher plasma levels and these plasma levels were able to differentiate between rejection and toxicity. In patients with stable liver function, no clear difference was observed with regard to the plasma levels detectable during toxicity or rejection. We conclude that plasma levels can be used to determine the FK 506 dose but only in patients with cholestasis (i.e., during the early post-transplant course, or in patients with cholestatic rejection). In patients with stable liver function, plasma levels are only of limited clinical relevance.

Cholestasis↗
PubMed1994

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma.

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n = 57) and hereditary (n = 25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P < 0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P < 0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Adolescent↗
PubMed1994

Resting energy expenditure and nutritional state in patients with liver cirrhosis before and after liver transplantation.

Resting energy expenditure (REE), body composition, and the biochemical parameters of liver function were measured in 26 patients before and 432 days (range: 103-1022 days) after liver transplantation (LTX). PreLTX REE was variable (mean: 1638 +/- 308 kcal/day, range: 1220-2190 kcal/day or +10 +/- 11% of Harris Benedict = HB prediction, range: -19 - +33%) and was closely related to body cell mass (r = 0.66, p < 0.0003). PostLTX REE was variable (mean: 1612 +/- 358 kcal/day, range: 1010-2490 kcal/day or +5 +/- 15% of HB prediction, range: -20 - +37%) and was closely related to body cell mass (r = 0.65, p < 0.0006). When compared with preLTX values only small changes in mean REE (-71 +/- 43 kcal/day) and a close correlation between pre and postLTX REE (r = 0.82, p < 0.001) were observed. In contrast to REE, changes in body weight were highly variable (-16.5 - +32.7 kg/year). This variance was not explained by the number of postoperative complications, pre and postLTX liver function, possible graft rejection and/or hepatitis reinfection. Pre-operative hypermetabolism (i.e. REE >+20% of HB prediction) was associated with postoperative hypermetabolism and a reduced liver function before and after LTX. Hypermetabolic patients had a poorer nutritional outcome after LTX (weight change: 0 +/- 8.4 kg/year) when compared with normometabolic controls (weight change: +5.7 +/- 7.4 kg/year; p < 0.05). There was no significant association between deviations in pre and postLTX REE and changes in body weight. When corrected for changes in the nutritional state our data provide evidence for the persistence of resting energy expenditure in liver transplant patients.

Journal Article↗
PubMed1994

Indications for liver transplantation in hepatobiliary malignancy.

Our personal experience with 172 patients, the results from the European Liver Transplant Registry and a review of the recent literature are summarized and discussed to define present indications for liver transplantation in hepatobiliary malignancy. The following conditions should be considered contraindications: advanced primary liver tumors with any extrahepatic spread, cholangiocellular carcinoma, hemangiosarcoma and liver metastases from nonendocrine primary tumor. Currently, "favorable" indications include uncommon tumors such as fibrolamellar carcinoma, epithelioid hemangioendothelioma, hepatoblastoma and metastases from endocrine tumors. Further indications may be nonresectable hepatocellular and proximal bile duct carcinoma in tumor stage II. Borderline indications are hepatocellular and proximal bile duct carcinoma in tumor stage III. In advanced tumors confined to the liver, transplantation should be restricted to multimodality treatment protocols. Although there are strong arguments for transplantation in early resectable hepatocellular carcinoma with underlying cirrhosis, it remains an open issue requiring further investigation in a controlled study using the same tumor classification. With regard to limited resources of donor organs, split-liver transplantation permits transplantation in tumor patients without neglecting those with benign diseases.

Bile Duct Neoplasms↗
PubMed1994

Strategies in the surgical treatment of gastric carcinoma.

Surgical therapy still represents the treatment of choice for patients with primary gastric adenocarcinoma, but surgery may have reached its limits concerning the rate of resectability, postoperative mortality and survival rates. Resectability is as high as 80%, mortality after resection ranges between 3% and 5% and the best survival data can be achieved if potentially curative tumor-free (R0-) resection including systematic lymphadenectomy can be performed. Significant prognostic benefits are to be expected in tumor stages II and IIIA. Most gastric carcinomas, however, are diagnosed in far advanced tumor stages (i.e., stage IIIB and IV) and the survival rates in these patients remain disappointing. Multimodality treatment, consisting of preoperative chemotherapy and surgery, may be an encouraging alternative strategy. By endoscopic ultrasonography and staging laparoscopy it may be possible to identify patients with locally advanced tumors, so that these patients should be subjected to multimodal therapy to improve their prognosis. Primary surgical treatment should be exclusively performed in patients with tumor stages up to IIIA and those who are not eligable for aggressive chemotherapeutic regimens, while the concept of multimodality therapy needs to be investigated in the other cases within controlled prospective clinical trials.

Antineoplastic Agents↗
PubMed1994

Comparison of different assays for the quantitation of FK 506 levels in blood or plasma.

In a prospective study, we evaluated the analytical performance of different assays for the quantitation of FK 506 in blood and plasma. The new whole blood IMX assay was compared with four modifications (liquid/liquid or solid/liquid extraction of blood or plasma respectively) of the standard enzyme-linked immunosorbent assay (ELISA). Both assays utilize the same monoclonal antibody for detection of FK 506. Using isolated FK 506 metabolites generated in vitro, this antibody was shown to recognize not only the unmodified parent drug but also FK 506 metabolites. In stable liver-grafted patients, sensitivity of both modifications of the whole blood ELISA was adequate. In contrast, in some stable patients, plasma ELISA was not able to detect FK 506; this was observed mainly after liquid/liquid extraction of FK 506. Sensitivity of the IMX assay was also low; in six of 10 stable liver-grafted patients, IMX levels were below the limit of detection. In all assays, FK 506 levels were found to be elevated during episodes of liver dysfunction; a possible explanation for this effect would be that of accumulation of cross-reacting FK 506 metabolites. As FK 506 metabolites are known to be less immunosuppressive than the parent drug, liver function should always be taken into account if IMX or ELISA levels are used for drug monitoring.

Antibodies, Monoclonal↗
PubMed1994

Urodilatin: a new approach for the treatment of therapy-resistant acute renal failure after liver transplantation.

A pilot study was performed in patients after liver transplantation (Ltx) to examine the effect of continuous intravenous urodilatin (URO, CDD/ANP-95-126)-infusion as an alternative therapy of acute renal failure (ARF) resistant to conventional therapy. Eight patients who developed ARF after liver transplantation and fulfilled requirements for haemodialysis/haemofiltration were treated. After URO infusion was started, renal function improved and all patients developed a strong diuresis and natriuresis within 2-4 h. The extracellular expansion due to sodium and water retention in anuric/oliguric ARF lead to an increased central venous pressure (CVP) and elevated blood pressure. During the URO infusion CVP declined and systolic, as well as diastolic, blood pressure were stable. In six patients where haemodialysis/haemofiltration could be avoided, serum creatinine (SC) and blood urea nitrogen (BUN) declined during URO treatment and creatinine clearance (CC) also improved significantly. Fluid and electrolyte disturbances changed promptly and normalized. This was in concordance with renal excretion of electrolytes. Two patients still required haemodialysis/haemofiltration. The six patients who did not require haemodialysis/haemofiltration after URO treatment normalized concerning their renal function and did well in a control period of 12 weeks. The study shows that continuous low dose URO infusion may present a new concept for treatment of postoperative acute renal failure resistant to conventional therapy.

Acute Kidney Injury↗
PubMed1994

Focus on intractable rejection: 6-month results of the European multicentre liver study of FK 506 and cyclosporin A.

The incidence of intractable rejection was evaluated during the course of a multicentre, randomised, parallel-group study comparing the efficacy and safety of FK 506 and conventional cyclosporin A-based immunosuppressive regimens in patients undergoing primary liver transplantation. A diagnosis of intractable rejection was made if there was histological evidence of unchanged or worsening acute rejection, or chronic rejection after two discrete courses of antirejection therapy. Antirejection regimens were specific to each centre. Patients who experienced intractable rejection could be withdrawn from the study. Patients who were withdrawn from the cyclosporin A treatment group could subsequently receive FK 506 therapy and vice-versa. Intractable rejection was diagnosed in 32/540 patients (5.9%): 7/267 patients (2.6%) in the FK 506 treatment group and 25/273 patients (9.2%) receiving cyclosporin A therapy (P < 0.01). Of these 32 patients, 25 were withdrawn from the study: 3 and 22, from the FK 506 and cyclosporin A treatment groups, respectively. All three patients withdrawn from the FK 506 treatment group are alive: two having undergone retransplantation. Of the 22 patients withdrawn from the cyclosporin A group and converted to FK 506 therapy, 6 were retransplanted, 4 of whom subsequently died. A further two patients died without retransplantation. Thus, in 14 of the 16 patients who were still alive at 6 months, the liver graft was saved after conversion to FK 506 treatment. The reduced incidence of intractable rejection in patients receiving treatment with FK 506, together with the successful rescue of patients developing intractable rejection while receiving cyclosporin A, suggests that FK 506 is an effective immunosuppressive agent following orthotopic liver transplantation.

Adolescent↗
PubMed1994

Corticosteroids and concomitant medication in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.

The steroid-sparing effect and the use of concomitant medication during the treatment of liver transplant patients with the novel immunosuppressant FK 506 were evaluated within the European multicentre, randomized, parallel-group study in liver transplantation. Patients undergoing primary liver transplantation were randomized to treatment with FK 506 (n = 267) or with a cyclosporin-based immunosuppressive regimen (n = 273). The total cumulative steroid usage was significantly reduced in the FK 506 treatment group, which is likely to have resulted from the lower incidence of acute rejection in these patients. The number of patients receiving antidiabetic, diuretic and antihypertensive therapy did not differ between the two treatment groups, even though the incidence of diabetes mellitus and oliguria was significantly higher in the FK 506 group. It can, therefore, be assumed that in a number of such cases the severity of these events was very mild necessitating no specific therapy.

Adrenal Cortex Hormones↗
PubMed1994

Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicentre study.

From September 1990 to January 1992, 545 liver transplant patients were randomised to treatment with either FK506 and prednisolone or a conventional cyclosporin-based immunosuppressive regimen (CBIR). Eight European centres participated in the study. Adverse events were reported as defined by each centre. Hyperglycaemia was reported as an adverse event in 30.7% of patients receiving FK 506 compared with 20.5% in the CBIR group (P < 0.01). Diabetes mellitus was reported in 17.2% of patients treated with FK 506 and 9.5% of CBIR-treated patients (P < 0.05). Treatment with insulin was required in 12.0% of patients in the DK 506 treatment group and in 5% in the CBIR group at 6 months. Initially, higher doses of FK 506 were used. During the study, the protocol was changed to allow a lower dose of FK 506. When the early and late cohorts of patients were compared, the incidence of diabetes mellitus fell from 23.9% to 10.5% in FK 506-treated patients but remained relatively constant in the CBIR group (10.4% to 8.7%). The median cumulative doses of i.v. and p.o. corticosteroids were significantly greater in the CBIR group. Thus, in the overall series, the incidence of diabetes mellitus was significantly greater in the FK 506 group as compared with the CBIR group. However, when a lower FK 506 dose was used during the second half of the study, the difference in the incidence of diabetes mellitus disappeared.

Adolescent↗
PubMed1994

Renal complications and development of hypertension in the European study of FK 506 and cyclosporin in primary liver transplant recipients.

We examined the occurrence of renal complications and hypertension in 540 primary liver recipients entered into the European liver trial comparing primary FK 506 to a cyclosporin A based immunosuppression regimen (CBIR). No difference in serious renal impairment or mean creatinine levels was observed with similar rates of "kidney failure" (FK 506 9.4% vs. CBIR 7.3%) and dialysis requirements (FK 506 12% vs. CBIR 11%). "Abnormal kidney function", a less serious parameter of renal impairment, was reported in 89 recipients (33%) in the FK 506 group versus 58 (21%) in the CBIR group (P < 0.01). Development of this complication was associated with elevated intravenous FK 506 dosing schedules, with the mean cumulative dose 43% higher than treated patients with unaffected kidney function. In a later cohort of patients where intravenous dosing was lower, no significant difference in renal complications was detectable. The 6-month prevalence rate of systemic arterial hypertension was noted to be lower in the FK 506-treated patients compared to the CBIR group [33 (17.2%) vs. 47 (25.7%)].

Adolescent↗
PubMed1994

Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.

Neurological complications were examined in a multicentre, randomized, parallel-group study of 545 patients undergoing primary liver transplantation to compare the efficacy and safety of FK 506- and cyclosporin A-based immunosuppressive regimens (CBIR). In an additional analysis, patients were divided into early and late randomized cohorts to detect the influence of protocol amendements that allowed for FK 506 dose reductions. Initial follow-up was for 6 months. Tremor, headache and insomnia were the most frequently reported adverse events involving the neurological system. Whereas these neurological symptoms were observed significantly more often in FK 506-treated patients (P < 0.05 vs. CsA for the overall population), this was no longer the case for the late FK 506 and CBIR cohorts. The risk of FK 506-treated patients developing tremor was related to the initial i.v. dose, the rate of administration of the i.v. dose and the daily dose (P < 0.01). Headache was significantly correlated with the FK 506 dose (P < 0.05), and insomnia was not related to any dosing variable. Major neurological symptoms, including psychosis, convulsion, coma, aphasia and intracranial haemorrhage, were reported with a low frequency (0.4-5.2%), and differences between both treatment groups were neither significant for the overall population nor for the early and late cohorts of FK 506 and CBIR. Data from the late cohorts showed no differences in the overall incidence of neurological adverse events between FK 506- and CBIR-treated patients.

Cyclosporine↗
PubMed1994

Optimal FK 506 dosage in patients under primary immunosuppression following liver transplantation.

In a retrospective study, we analysed the FK 506 dosage used in primary liver graft recipients enrolled in the European FK 506 multicenter trial conducted from September 1990 to January 1992. In addition, a second cohort of patients treated more recently in a single centre was investigated. The impact of different dosing strategies on the clinical course of the patients was analysed with special emphasis on the incidence of rejection episodes and FK 506 side-effects. Among the patients enrolled in the European FK 506 multicenter trial, those patients enrolled during the "early" phase of the study received a higher oral FK 506 dose [mean oral dosage on day 7 = 0.19 mg/kg body weight (bw) per day, n = 134] compared to patients enrolled during the "late" period of the study (mean oral dosage on day 7 = 0.14 mg/kg bw per day, n = 133). This lower dosage was the result of several protocol amendments performed to reduce the incidence of FK 506 side-effects. Lowering of the FK 506 dosage was accompanied by a reduction in the long-term prevalence of side-effects such as diabetes (n. s.) or hypertension (P < 0.05), while patient survival and rejection frequency remained constant. Patients treated in centres with online FK 506 blood level monitoring experienced significantly less hypertension, less episodes of diabetes and less rejection episodes compared to patients treated in centres without. The clinical course of those patients enrolled in the multicentre trial was compared with the course of a cohort of liver-grafted patients treated with FK 506 more recently in a single centre. These patients had a further reduction in the FK 506 dosage (0.10 mg/kg bw per day p.o. or less according to whole blood levels, with no intravenous FK 506 administration). When compared to patients enrolled in the multicentre trial, these patients experienced less side-effects (nephrotoxicity, hypertension, serious early neurotoxicity) while adaequate immunosuppression was maintained.

Administration, Oral↗
PubMed1994

FK 506 primary immunosuppression following emergency liver transplantation for fulminant hepatic failure. European FK 506 Study Liver Group.

The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirements and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.

Adolescent↗
PubMed1994

Expression of cell-matrix molecules and integrin receptors in human liver grafts during chronic rejection.

The inflammatory response of immune cells to target cells and cell-matrix molecules is regulated by several receptor-ligand molecules. As fibrosis develops in ongoing chronic rejection after liver transplantation, it is of interest to analyze patterns of integrin receptors and cell-matrix molecules in order to study the relation between immune cells and the stromal and parenchymal cells. In the present study, we demonstrated the expression of these molecules in chronic rejected human liver grafts using immunohistochemical techniques. The results showed a differential expression and induction of integrin receptors and cell-matrix molecules on resident liver cells, especially on sinusoids, reflecting a state of chronic inflammation and a specific interaction between integrin receptors and cell-matrix molecules. The patterns of induced integrin receptors on graft-infiltrating cells was closely related to the local production of cell-matrix molecules and reflected the final sequence of a stepwise progress of the inflammatory reaction.

Bile Ducts↗
PubMed1994

Ileal and colonic fatty acid profiles in patients with active Crohn's disease.

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.

Acute Disease↗