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Biomedical subjects

B Ringe

Publications and source records attributed to B Ringe.

At least 127 records · Page 7Linked to original sources
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

Kidney transplantation in hepatitis B surface antigen carriers.

Chronic hepatitis B surface antigen (HBsAg) carriers run a high risk of developing chronic liver disease after renal transplantation. To determine the impact of liver disease on long-term morbidity and mortality of HBsAg carriers following kidney transplantation we analyzed 1977 patients, including 76 HBsAg carriers, who underwent renal transplantation during the period 1968-1992. Although the HBsAg carriers had a better 5-year patient and graft survival rate (94% and 83%) than HBsAg-negative patients (87% and 61%), the prognosis was poor after the tenth year of transplantation. Transplant loss is more frequently caused by death of the HBsAg carriers, in contrast to the total population (34% vs 17% for HBsAg-negative patients). Death occurs in 73% of cases due to complications of hepatitis B. In the HBsAg-negative patients, the predominant cause of death is cardiovascular failure (51% vs 11% in HBsAg carriers), whereas only 2% died of liver disease. Kidney transplantation in HBsAg carriers with normal liver function appears to be justified because of rare graft loss due to acute rejection, low early morbidity and mortality, and late onset of fatal hepatic deterioration.

Female↗
PubMed1994

[Combined lung and liver transplantation. Anesthesiologic management].

A 53-year-old man with alpha-1-antitrypsin deficiency had an 8-year history of progressive dyspnoea and two episodes of bleeding oesophageal varices with liver decompensation. After the diagnosis of terminal pulmonary emphysema (Fig. 1) and liver cirrhosis with progressive liver failure was made, he was accepted for combined lung and liver transplantation. METHODS. Anaesthesia was induced with thiopentone and fentanyl and maintained with fentanyl, midazolam, and isoflurane. After relaxation with succinylcholine, the patient's trachea was intubated with a left endobronchial double-lumen tube. Haemodynamic monitoring included arterial, central-venous, pulmonary-artery, and capillary-wedge pressures and cardiac output measurement. Ventilatory monitoring consisted of pulse oximetry, side-stream spirometry, and continuous measurement of arterial and mixed-venous blood oxygen saturation with fibreoptic catheters. A left single-lung transplantation was performed under one-lung ventilation without cardiopulmonary bypass. Prostacyclin was infused to reduce pulmonary vascular resistance. The transplant was ventilated separately with 50% oxygen and positive end-expiratory pressure of 8-10 cm H2O, and then liver transplantation was carried out. The institution of veno-venous bypass during the anhepatic phase failed because of portal-vein and axillary-vein thrombi. RESULTS. Total operation time was 6 h 30 min. Clamping of the left pulmonary artery lasted 45 min and the duration of the anhepatic phase was 92 min. Ventilation and oxygenation during lung transplantation caused no problems (Table 1). Clamping of the left pulmonary artery caused a slight increase in pulmonary vascular resistance (104 to 124 dyn.s.cm-5) and mean pulmonary artery pressure (25 to 27 mm Hg) without a decrease in cardiac index (Table 2). During the anhepatic phase with exclusion of the portal vein and inferior vena cava, a marked decrease in cardiac index (-27.2%) was seen (Table 4). The operation required substitution with 10 units packed red blood cells, 12 units fresh frozen plasma, and 5 platelet concentrates. The post-operative course showed normal liver graft function (Table 5). Acute pulmonary rejection on the 7th day was treated successfully with methylprednisolone. The patient's trachea has extubated 10 days after transplantation and he was discharged from the intensive care unit 2 weeks later. CONCLUSION. The management of this combined lung and liver transplantation was performed according to the experience with isolated lung and liver transplants in our hospital. Aggressive haemodynamic and ventilatory monitoring, including systemic and pulmonary arterial fibreoptic catheters, seems of particular importance in such high-risk procedures.

Anesthesia↗
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

Influence of gender on the monoethylglycinexylidide test in normal subjects and liver donors.

The objective of this study was to investigate the effect of gender on monoethylglycinexylidide (MEGX) formation in normal subjects and cadaveric liver donors. The study included 92 male and female healthy volunteers < 45 years of age and 98 age- and sex-matched liver donors from a previous study, whose livers were used for transplantation. Women < 45 years not taking contraceptives showed significantly lower MEGX concentrations 30 min after lidocaine administration than men [median (16-84th percentile)]: 59 micrograms/L (41-70 micrograms/L) versus 81 micrograms/L (58-98 micrograms/L)]. The lowest MEGX 30 min values were observed in women taking contraceptives: 39 micrograms/L (25-48 micrograms/L). Intraindividual variability of serial MEGX tests was moderate (median: 17.8%, n = 8) when measured in female subjects taking no contraceptives and males. Cadaveric liver donors showed significantly higher MEGX 15 and 30 min values compared with normal subjects (p < or = 0.0001). There was no statistically significant difference between MEGX values obtained in male and female cadaveric donors. The urinary excretion of MEGX was similar in male and female normal subjects. Our results suggest that sex-related differences in MEGX formation as well as the influence of contraceptives have to be taken into account when test results from living related liver donors and patients with less advanced chronic liver disease are evaluated. In cadaveric liver donors, however, sex-related differences do not affect MEGX formation.

Adult↗
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

Neurological examinations after liver transplantation concerning patients under corticosteroid immunosuppression and either FK 506 or cyclosporin.

To study the neurological sequelae in liver transplanted recipients, 25 patients were followed up between 5 and 30 months after transplantation and another 14 patients were seen before and after transplantation. Physical examination took special note of tremor and polyneuropathy; additionally, patients estimated concentration and memory, tremor, paraesthesias and sleep disturbances on a self-rating scale. Tremor was reported to be preexistent in 50% of the later FK 506 and cyclosporin group and only temporarily rose afterwards. Twenty-eight percent complained of tremor and 20% said that it interfered mildly with daily activity. Only 2 of 39 patients showed new signs of polyneuropathy. Concentration and memory improved significantly after transplantation. In the second group of patients, MRI, EEG, lumbar puncture and neuropsychological tests were done just before and routinely after transplantation, revealing numerous preexisting neurological deficits with only singular changes afterwards.

Adrenal Cortex Hormones↗
PubMed1994

Use of organotypical cultures of primary hepatocytes to analyse drug biotransformation in man and animals.

1. In conventional single-gel culture systems for primary hepatocytes, rapid loss of drug metabolizing capacities is a common feature and parallels general loss of function. An organotypical (double gel) culture technique for primary hepatocytes is established by enclosing the cells within two layers of extra cellular matrix. This serves to imitate the in vivo microenvironment within the space of Dissé. Using rat hepatocytes, this technique has been shown previously to maintain protein synthetic functions in vitro and to allow more efficient P450A-dependent biotransformation of drugs than a standard single-gel culture system. 2. The aim was to test the capacity of this organotypical culture model for primary rat and human hepatocytes to generate drug metabolites in a typical species-dependent pattern. 3. Urapidil, an antihypertensive drug, was used as a test compound, since it is metabolized in vivo in a species-dependent manner in rat and man. 4. Primary rat and human hepatocytes were cultured within two layers of collagen and exposed to 2.25 micrograms/ml urapidil for periods of 1-24 h at 3 days in culture. Urapidil metabolites were measured using hplc. 5. Metabolite M1 (hydroxylated product) was produced preferentially in human hepatocyte cultures, and metabolites M2/M3 (O-demethylated, N-demethylated product) were preferentially generated in rat cultures. This corresponded to the in vivo pattern found in man and rat, respectively. 6. Since in vitro urapidil metabolism by human and rat hepatocytes cultured in a double-gel system reflects that in vivo, it is suggested that information from such a system may be useful to predict the metabolic pathway of novel xenobiotics and to direct further toxicological evaluation.

Adult↗
PubMed1994

Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression.

By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

Drug Monitoring↗
PubMed1994

Spontaneous proliferation of peripheral blood lymphocytes as an indicator of intragraft immune activation in liver transplant patients.

The presence of activated lymphocytes in the blood of transplant recipients is considered to be a marker of an ongoing immune process. In this study, the clinical utility of spontaneous proliferation (SP) of peripheral blood mononuclear cells (PBMC) as a marker of in vivo activation was evaluated by in vitro [3H]thymidine incorporation in 22 patients in the 1st month after liver transplantation. Also immune activation in the graft was monitored by transplant aspiration cytology (TAC-A). In the study period, there were only 2 mild episodes of clinical acute rejection, where SP of PBMC was 1290 and 1541 cpm (vs. 99 cpm averaged in healthy controls). Though SP of PBMC was also increased in systemic infections, a significant positive correlation was observed between SP of PBMC and TAC-A score. In all episodes where TAC-A score was elevated to above 2, SP of PBMC was simultaneously increased to more than 1000 cpm. In 8 patients prophylactically treated with the anti-interleukin-2-receptor antibody, BT563, SP of PBMC was significantly lower compared to 7 patients treated with antithymocyte globulin. It is suggested that SP can be a reliable parameter of the in vivo activation of lymphocytes, which accompanies immune activation in liver graft, and is potentially useful as a sensitive, although rather non-specific, and non-invasive monitoring of intragraft alloresponse.

Adult↗
PubMed1994

The Budd-Chiari syndrome: clinical presentation and diagnostic findings in 45 patients treated by surgery.

We report on the clinical presentation and diagnostic findings in 45 patients with Budd-Chiari syndrome. The diagnosis was confirmed by histology at the time of liver transplantation (n = 37) or shunt surgery (n = 8). An underlying disorder could be established only in half of the patients, oral contraceptives as predisposing factor were known in 18 cases. Clinically, abdominal pain and distension as well as hepatomegaly and ascites were most frequent findings, whereas changes in laboratory data were more or less unspecific. By use of repeated ultrasound, a definite diagnosis of a Budd-Chiari syndrome could be confirmed in all cases by obligatory demonstration of obstruction or thrombosis of at least one major liver vein. Hepatic venography revealed only one false-negative result. Celio-mesenteric arteriography plus portography, cavography and preoperative liver biopsy did not present additional diagnostic information. These techniques may contribute to treatment planning of portosystemic shunt surgery or hepatic transplantation. In conclusion, the presence of hepatosplenomegaly, ascites, abdominal pain and distension, especially in combination with a known hypercoagulable state, should alert to the possibility of a Budd-Chiari syndrome. Ultrasound is the diagnostic tool of choice. Hepatic venography should only be performed if even repeated ultrasound is not conclusive.

Adolescent↗
PubMed1994

Quadrennial review on liver transplantation.

Within the last years, liver transplantation has definitely come of age, and evolved to the standard treatment of choice for patients with endstage liver disease, and after ineffective conventional therapy. This development became possible on the basis of intensive interdisciplinary scientific research and clinical experience, and is the result of a multiplicity of single factors related to patient selection, organ donation, the transplant operation, immunosuppressive therapy, and postoperative care of the recipient. Some of the most important aspects will be summarized in this article.

Humans↗