PubMed Health⌕ Search

Biomedical subjects

C Broelsch

Publications and source records attributed to C Broelsch.

At least 19 recordsLinked to original sources
PubMed2006

Safety profile of concomitant use of caspofungin and cyclosporine or tacrolimus in liver transplant patients.

BACKGROUND: Caspofungin is the first substance of a new class of antifungal agents, the echinocandins that interfere with fungal cell wall synthesis by inhibition of glucan synthesis. Alanine aminotransferase (ALT) elevations were seen in phase I studies of patients receiving caspofungin and cyclosporine A (CyA). Actually, there is no information regarding hepatotoxicity in liver transplant patients treated concomitantly with caspofungin and immunosuppressant agents like CyA or tacrolimus (TAC). PATIENTS AND METHODS: We conducted a retrospective study in 12 liver transplant patients (9 patients Child C, 3 patients acute liver failure) to assess the hepatic safety of simultaneous administration of caspofungin with CyA or TAC. Caspofungin was administered as first-line agent to patients for a 2-week period with either proofed invasive fungal infection (IFI) (n = 4), IFI-probable (n = 4), and IFI-possible (n = 4). All patients received concomitantly CyA or TAC as immunosuppressant agent. RESULTS: Two patients died within the first 10 days after start of treatment, caused by gram-negative rods. All other ten patients completed the 14-day treatment period. No liver enzyme elevation was recorded in these patients and administration of caspofungin with CyA or TAC was well tolerated without hepatotoxicity. CONCLUSION: The concomitant use of caspofungin with CyA or TAC in liver transplant patients is safe and seemed to be without hepatotoxic effect.

Antifungal Agents↗
PubMed2006

Disseminated adenovirus infection with respiratory failure in pediatric liver transplant recipients: impact of intravenous cidofovir and inhaled nitric oxide.

Adenoviruses (AdV) are opportunistic pathogens that can lead to severe infections and respiratory failure (acute respiratory distress syndrome, ARDS) with high mortality in immunosuppressed patients. Cidofovir (CDV) has been used in adenoviral disease in bone marrow transplant recipients. Two pediatric liver transplant recipients with disseminated adenoviral disease and ARDS were treated with reduction of immunosuppression, CDV, and inhaled nitric oxide (iNO). CDV 1 mg/kg was given three times per week intravenously with intravenous hydration and oral probenecid. Viral suppression and clinical improvement was achieved. AdV hepatitis did not occur, and graft function was preserved, although acute rejection occurred in both patients. Adverse effects were mild and transient not requiring dose modification. Severe hypoxemia was reversed with iNO 10-20 p.p.m. CDV treatment of AdV infections in organ transplant recipients and other immunocompromised patients should be further investigated in prospective studies.

Adenovirus Infections, Human↗
PubMed2004

[Consensus-recommendations for sirolimus in liver transplantation].

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

Drug Therapy, Combination↗
PubMed2000

Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.

UNLABELLED: Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. OBJECTIVES: In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. METHODS: Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. RESULTS: After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (p<0.05) and leukopenia (MMF: 2/28; 7.1% versus AZA: 6/29; 20%) (p=0.14) were less often observed under MMF compared to AZA. The incidence of serious bacterial infections and cytomegalovirus infections was almost identical in both groups. These preliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.

Adult↗
PubMed1999

Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation.

BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.

Acute Kidney Injury↗
PubMed1996

One year of experience with extended application and modified techniques of split liver transplantation.

As organ donation rates decreased in Europe, the authors started a systematic approach of liver splitting in their center in 1994. During this 1-year experience, 73 cadaveric liver transplantations were performed in 66 patients. Sixteen of these transplantations were the result of split-liver transplantation (21.9% of grafts, 24.2% of patients). Patient and graft survival rates at 3 months were 81.2% and 75%, compared with 89.1% and 76.9 % for whole organs. Two modified techniques were developed, based on the technique of living related liver procurement, and applied in 10 cases. With these new techniques, patient and graft survival rates were 90% and 90%. This systematic approach allowed the total number of transplantations in our program to be maintained, despite the decrease in organ availability.

Graft Survival↗
PubMed1990

A psychological support concept and quality of life research in a liver transplantation program: an interdisciplinary multicenter study.

Considering the increasing number of liver transplantations with longer periods of transplant function, there is a growing need for quality of life research in the field. In addition to lethality, mortality and rehabilitation, parameters of 'quality of life' are to be evaluated: the patient's rating of his subjective physical symptoms, psychological condition (anxiety, depression and mental adjustment), social reintegration and life satisfaction. This paper describes our psychological support program that has been established at the Hamburg LTX center as well as the first results of the ongoing QoL research study. Using the methods developed by the Hamburg Study group on 'quality of life in surgery', 38 liver transplantation patients of the University of Chicago (cross-sectional study with control groups of patients with chronic liver disease as well as healthy individuals) and 29 patients of the University Clinic of Hamburg (longitudinal study with points of evaluation before and 2, 6, 12, 24 and 36 months after transplantation) have been evaluated. First results: (1) All successfully transplanted patients show a significant postoperative increase of their overall quality of life. (2) The psychological parameters of quality of life are only partly correlated with physical symptoms. (3) There is a high correlation between rejection crisis periods and the decrease of all quality of life parameters. (4) In both samples men have a lower quality of life than women, (5) Preoperative depression and lack of social support might be considered as being possible risk factors for long-term survival. (6) Long-term survivors rate their quality of life significantly higher than patients with chronic liver disease and--despite some persisting somatic restrictions--as high as healthy controls. (7) A psychotherapeutic support program increases the patient's compliance resulting a better adaption to the transplant procedure including rehabilitation.

Activities of Daily Living↗
PubMed1990

Hypoglycemic potency and metabolic clearance rate of intravenously administered human proinsulin and metabolites.

Since circulating proinsulin has been suggested to be important in the pathogenesis of noninsulin-dependent diabetes, and biosynthetic human proinsulin (HPI) may have a therapeutic role in patients with diabetes mellitus, the biological activity of proinsulin metabolites is of potential significance. Moreover, recent studies have suggested that the majority of circulating proinsulin immunoreactivity consists of metabolites. We, therefore, compared the blood glucose-lowering ability and MCR of the two proinsulin metabolites des-(31,32)HPI and des-(64,65)HPI with intact HPI in seven anesthetized dogs after an overnight fast. Intravenous bolus injections of 12.5 micrograms HPI/kg BW and equimolar amounts of des-(31,32)HPI and des-(64,65)HPI were given on three separate occasions. In addition to blood glucose, des-(31,33)HPI, des-(64,65)HPI, and HPI were measured using an insulin RIA and peptide-specific standard curves. Kinetic parameters were derived by fitting two exponentials to the respective decay curves. The MCR of HPI (3.3 +/- 0.1 ml/kg.min) was significantly lower (P less than 0.05) than that of des-(64,65)HPI (6.4 +/- 0.6 ml/kg.min), but was not significantly different from that of des-(31,32)HPI (3.8 +/- 0.4 ml/kg.min). The MCR of biosynthetic insulin (17.2 +/- 1.8 ml/kg.min), as measured in three of the dogs, was higher than that of HPI or the two metabolites. The blood glucose-lowering ability (defined as nadir glucose/fasting glucose, expressed as a percentage) of des-(64,65)HPI (49.3 +/- 5.0%) was significantly greater (P less than 0.05) than that of intact HPI (87 +/- 2.2%), and the glucose-lowering ability of des-(31,32)HPI (75.2 +/- 3.8%) was intermediate. In conclusion, HPI metabolites are more biologically active than intact HPI. The extent of in vivo conversion of proinsulin to metabolites may enhance the biological activity of proinsulin and, thus, have physiological, pathophysiological, and therapeutic significance.

Animals↗
PubMed1989

[Carbon tetrachloride poisoning in a swine model].

It was intended to establish a model for acute hepatic failure in order to test the function of isolated and auxiliary transplanted hepatocytes. 6 pigs (19.75-27.0 kg) were intoxicated with different dosages of CCl4 and ethanol. According to publications on acute hepatic failure induced in rats by CCl4, adequate dosages were applied in pigs. Three different regimens of CCl4 and C2H5OH applications were used: CCl4 was administered intragastrically alone (group 1) or combined with ethanol (group 2), and CCl4 was given intragastrically and ethanol intravenously (group 3). Animals of group 1 and 2 survived intoxication for the period of observation. Histological examination of the livers revealed central necrosis, ghost cells and swollen hepatocytes. The animals of group 3 died shortly after intoxication. Histological examination did not show any evidence for acute hepatic failure. CCl4 and C2H5OH intoxication in pigs causes effects that are different from those described in humans or laboratory rats. Therefore it should be necessary to use a large number of animals to establish a standardized model for acute hepatic failure in pigs that reflects the observations in humans.

Animals↗
PubMed1989

Right heart dysfunction, pulmonary embolism, and paradoxical embolization during liver transplantation. A transesophageal two-dimensional echocardiographic study.

In 16 adult patients, we performed continuous intraoperative two-dimensional transesophageal echocardiography (2DTEE) to help elucidate the mechanism of myocardial dysfunction that accompanies liver transplantation. In 4 of the 16 patients "paradoxical" motion of the interventricular septum consistent with right ventricular failure was seen. An additional three of the 16 patients showed right atrial enlargement and right-to-left deviation of the interatrial septum. Two patients showed evidence of paradoxical embolization (one of whom had right ventricular and right atrial enlargement), and a third patient (who had right atrial enlargement) embolized a large right atrial thrombus into the pulmonary circulation. Two-dimensional transesophageal echocardiography demonstrated that isolated right ventricular failure might account for some of the hemodynamic instability seen during liver transplantation. Venous, pulmonary, and paradoxical embolization of air and thrombi documented by transesophageal echocardiography likely contribute to right heart failure.

Adolescent↗
PubMed1988

Acetaminophen-induced acute hepatic failure in pigs: controversical results to other animal models.

To prove the function of isolated transplanted hepatocytes in acute liver failure we tried to establish a hepatic failure model in pigs which correlates to a clinical situation. In 12 pigs we administered 500-2000 mg acetaminophen/kg b.wt. after enzyme induction with pentobarbital. Seven animals receiving 500-1000 mg/kg survived the intoxication. Five animals receiving 1000-2000 mg/kg acetaminophen died within 6.5 h after intoxication because of methemoglobinemia. A close correlation between administered dosage of the drug, acetaminophen blood levels, and methemoglobinemia was found. Histology of surviving animals showed a dosage-dependent cell necrosis. A standardized hepatic failure model could not be established in pigs by acetaminophen intoxication because dosages of less than 1000 mg/kg were survived. In dosages higher than 1000 mg/kg a side-effect of the acetaminophen intoxication, i.e., methemoglobinemia, limited the life of the animals. Therefore, acetaminophen cannot be used to induce acute hepatic failure in pigs.

Acetaminophen↗
PubMed1981

Influence of a portacaval shunt on the distribution of 14C-chol-PC-DCP-liposomes and liposome entrapped 3H-methotrexate in the organs of rats.

The individual roles of hepatic parenchymal cells and non-parenchymal cells in the uptake of intravenously injected liposomes by the liver have not yet been clearly determined. Experimentally, it is suggested that a portacaval shunt reduces the phagocytic capacity of the liver RES. In our experiments a portacaval shunt does not influence the hepatic uptake of 14C-Chol-PC-DCP-liposomes and the liposome entrapped 3H-Methotrexate in rats. In normal rats and in rats with a portacaval shunt, most of the 14C- and 3H-radioactivity is found in the liver and the ratio between the amounts of free and liposome entrapped radioactivity 3 to 15 hours after i.v. injection is approximately 1:10. Therefore, it is concluded that the liver RES does not play an integral role in the enrichment of liposomes in the liver.

Animals↗
PubMed1980

Identification and partial characterization of glucocorticoid receptors in human liver.

In normal human liver from adult males and females cytoplasmatic components which bind dexamethasone specifically and with high affinity, were demonstrated via dextran-coated charcoal assay, agar gel electrophoresis, isoelectric focusing and sucrose gradient centrifugation. The apparent dissociation constant of the dexamethasone-binder complex was found to be 1.7 +/- 0.3 x 10-(8) mol/l. The binding capacity was limited to 67.5 +/- 5.3 fmol/mg of cytosol protein. The ligand specificity for binding to these components indicated the requirement for glucocorticoids. It was shown by means of agar gel electrophoresis that the dexamethasone-binding entities migrate to the receptor region of the gel. The isoelectric point of the binding components in human liver cytosol was found to be pH 6.3. Sedimentation in sucrose gradients revealed the bulk of these components to be in the 7S region. It is concluded that the specific dexamethasone-binding entities in human liver have all the properties of glucocorticoid receptors.

Adolescent↗