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Biomedical subjects

G Otto

Publications and source records attributed to G Otto.

At least 91 records · Page 5Linked to original sources
PubMed1996

First clinical realization of continuous monitoring of liver microcirculation after transplantation by thermodiffusion.

To date, no method is available for the continuous long-term monitoring of liver microcirculation in patients. Experimentally, thermodiffusion has been validated in the quantification of hepatic perfusion. In an attempt to investigate the practicability of thermodiffusion technology in patients after liver transplantation thermodiffusion probes were inserted into the graft in seven patients during liver transplantation. Continuous monitoring started intraoperatively and was performed until day 7, when the probes were extracted transcutaneously. No probe-related complications (i.e., hemorrhage, infection) were observed. In four patients with normal graft function, liver perfusion recovered within 12 h from the intraoperative reduction to a range between 85 and 93 ml/100 g per min. In contrast, primary graft failure (n = 1) was characterized by a constant decrease of hepatic perfusion (< 50 ml/100 g per min). In prolonged reperfusion injury (n = 1), a second peak of transaminases was paralleled by an impairment of liver microcirculation. In one patient, R2 rejection on day 7 was preceded by a drop in hepatic perfusion 48 h earlier. Thus, thermodiffusion is a safe and reliable method for the continuous quantification of liver microcirculation after transplantation in patients. Measurements are reproducible for at least 7 days. Changes in hepatic perfusion during postoperative complications can be detected. The characteristics of microcirculatory disorders will have to be defined in a larger number of patients.

Adolescent↗
PubMed1996

Two-year data from the European multicentre tacrolimus (FK506) liver study.

To provide a more definitive assessment of the efficacy and safety of tacrolimus therapy in comparison with cyclosporin, the extended follow-up of the European multicentre study is reported. Two-year Kaplan-Meier estimates indicated significant reductions in acute (tacrolimus 45.4%, cyclosporin 55.8%; P = 0.006), refractory (1.2% versus 6.4%; P = 0.003) and chronic rejection (2.0% versus 6.9%; P = 0.015) despite significantly lower steroid usage in patients receiving tacrolimus therapy. Patient and graft survival rates (80.6% versus 74.8% and 74.5% versus 70.0%, respectively) were also superior, although these failed to reach statistical significance. Safety profiles were comparable for most major categories (including renal, neurological and glucose metabolic disorders) and in certain aspects were more favourable for tacrolimus. Hypertension (28.0% versus 39.6%, P < 0.01) and cytomegalovirus infection (14.8% versus 22.3%, P < 0.01), two events with important long-term clinical consequences, were reported significantly less frequently. Hirsutism (0.0% versus 8.7%, P < 0.01) and gum hyperplasia (0.0% versus 2.3%, P < 0.05) were absent in patients receiving tacrolimus. Tacrolimus appears to provide effective and safe long-term immunosuppression.

Adolescent↗
PubMed1996

Prolonged allograft survival by the inhibition of costimulatory CD2 signals but not by modulation of CD48 (CD2 ligand) in the rat.

The CD2 receptor is an important costimulatory molecule in T cell activation. Its ligand CD48 in rodents is supposed to be a homologue of human CD58, because of its similarities in structure and distribution. We evaluated the immunosuppressive activity of CD2/CD48-directed therapy in vitro and in vivo for the efficacy in prolonging rat heart allograft survival in a high responder transplant model. CD2-directed monoclonal antibody (mAb) therapy significantly prolonged median survival time to 45 days (P < 0.001). Suppression was mediated by down-modulation of CD2 below 20% on lymph node cells without considerable cell depletion. In contrast, CD48 mAb could not prolong graft survival. Rejection occurred in the presence of complete CD48 modulation and, therefore, despite disruption of the CD2-CD48 interaction. CD48 mAb failed to inhibit lymphocyte activation via a mitogenic pair of CD2 mAbs and inhibited mixed lymphocyte reaction (MLR) only by an unspecific mechanism. In conclusion, our results suggest a negative regulatory signal transduction by inhibitory CD2 mAbs and argue against a pivotal role of mere disruption of the CD2-CD48 interaction in CD2-mediated immunosuppression.

Animals↗
PubMed1996

Aspergillus endocarditis, myocarditis and pericarditis complicating necrotizing fasciitis. Case report and subject review.

A patient with Aspergillus endocarditis, myocarditis and pericarditis is described. A 55-year-old man developed necrotizing fasciitis of the lower abdominal wall, pelvis and right thigh. Despite aggressive surgical débridement and antibiotic coverage, the patient died of multisystem organ failure. Autopsy revealed Aspergillus thromboulcerative endocarditis, myocarditis and pericarditis, acute necrotizing fungal bronchopneumonia and mycotic dissemination to brain, kidney and thyroid gland. A review of the literature showed that in the absence of open-heart surgery Aspergillus endocarditis and myocarditis are very uncommon.

Aspergillosis↗
PubMed1996

Allograft survival following immunization with membrane-bound or soluble peptide MHC class I donor antigens: factors relevant for the induction of rejection by indirect recognition.

T cells recognize foreign antigens in the form of peptide fragments resulting from antigen processing by antigen-presenting cells. In contrast to this indirect recognition, MHC molecules of foreign cells can be directly recognized by T cells. Direct recognition has for a long time been considered the only mechanism responsible for transplant rejection. Recent studies have provided evidence of a role of indirect recognition in rejection. In the current series of experiments, we studied the influence of indirect alloactivation, induced either by donor MHC class I peptides or by membrane-bound MHC I molecules, on heart allograft rejection in rats. Recipients were immunized before transplantation with synthetic donor MHC I peptides. The animals developed antibody and T-cell responses. Depending on the rat strain, peptide pretreatment either had no effect on graft survival (DA-->PVG; untreated controls 8.5 +/- 0.6 days, treated rats 9.5 +/- 0.6 days) or led to accelerated rejection (DA-->LEW; untreated controls 7.5 +/- 0.3 days, treated rats 5.1 +/- 0.2 days; P < 0.0002). Importantly, sensitization by indirect activation induced acute rejection in a donor-recipient combination (LEW.1A-->LEW.1WR2) in which neither direct nor indirect recognition led to rejection (untreated controls > 400 days, pretreated rats 15 +/- 4.2 days). Another group of animals was immunized with allogeneic or congenic erythrocytes carrying the MHC I antigen from which the peptides were derived. Although the immunization elicited a measurable immune response, it did not lead to accelerated rejection. We conclude that sensitization by indirect recognition is able to initiate an acute rejection even in recipients in which neither direct nor indirect recognition is effective, and that this effect is strain-dependent. The form in which the donor antigen is administered is decisive for the induction of rejection by indirect activation.

Animals↗
PubMed1996

Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion?

The CD95 (APO-1/Fas) system is an important mediator of T-cell cytotoxicity. We investigated this system in 22 hepatocellular carcinomas (HCCs) from patients. All HCCs had partially or completely lost the expression of the CD95 receptor constitutively expressed by normal liver cells and might thus evade CD95-mediated killing. We also considered a new mechanism of immune evasion, namely, the active destruction of T-lymphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messenger RNA and protein could be detected in the HCCs. In coculture experiments, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatment with cytostatic drugs, killed CD95+ Jurkat lymphocytes. Our data suggest that tumor cells can evade immune attack by down-regulation of the CD95 receptor and killing of lymphocytes through expression of CD95L.

Antimetabolites, Antineoplastic↗
PubMed1996

Kinetics of primary bile acids in patients after orthotopic liver transplantation.

Administration of cyclosporin A (CsA) may induce cholestasis, and this effect has been attributed to impaired hepatocellular uptake, transport, secretion and intestinal absorption of bile acids. Disturbances of the enterohepatic circulation may affect metabolism of bile acids. To test whether liver transplantation and treatment with CsA alters pool sizes or synthesis and turnover rates, we determined kinetics of primary bile acids in patients after orthotopic liver transplantation on CsA. Two male and four female patients were studied 6-20 months after transplantation. They had no overt signs of cholestasis, graft dysfunction or rejection. Kinetics of cholic acid (CA) and chenodeoxycholic acid (CDCA) were simultaneously determined after oral administration of [24-13C]-CA and [24-13C]-CDCA on the basis of isotope dilution in a single pool of bile acids. Ten healthy volunteers served as controls. After orthotopic liver transplantation, pool sizes, fractional turnover rates and synthesis rates of both primary bile acids, CA and CDCA were not significantly different from control subjects. In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids.

Adult↗
PubMed1996

[Liver transplantation and diagnostic radiology: socioeconomic aspects].

PURPOSE: For calculating cost-effectiveness in the context of diagnosis related groups (DRG) we analysed all radiological examinations for 56 consecutive liver transplantations during the primary stay in the surgical department (1052 chest x-rays, 296 ultrasonographies, 216 colour coded duplex sonographies, 72 cholangiographies, 35 CT, 23 angiographies, one MRI and one embolisation). METHODS: For calculation we used the reimbursement that the surgical wards received per patient day and the special fee for liver transplantation. We compared this with the refunds received by the department of radiology. RESULTS: The hospital was reimbursed a total of 143785.80 DM per patient. The diagnostic and interventional procedures that were requested for the 56 patients amounted to a total of 225118.63 DM and 4019.96 DM per patient, respectively. CONCLUSIONS: This means that only 2.8% of all the costs during and after liver transplantation were caused by the radiological examinations. This represents only a small portion of the expenses during the time in hospital, taking into account especially that patients after liver transplantation are at high risk for developing complications.

Adolescent↗
PubMed1996

A rapid and highly specific technique to detect hepatitis C RNA in frozen sections of liver.

AIMS: To develop a polymerase chain reaction (PCR) based technique that would permit the rapid and highly specific detection of hepatitis C virus (HCV) RNA extracted from frozen liver tissue. METHODS: Samples of liver tissue from 18 patients undergoing orthotopic liver transplantation were studied. Nine patients were HCV positive. Total RNA was extracted from between one and 10 sections, 10 microns thick, from each tissue sample. HCV RNA was amplified by (1) conventional, multistep reverse transcription PCR (RT-PCR) and by (2) combined, single step RT-PCR using coupled oligonucleotide primers based on the sequence of the 5' untranslated region of the viral genome. Positive results were confirmed by dot blot analysis using a digoxigenin labelled oligoprobe (Alx 89). RESULTS: HCV RNA was detected in the nine HCV positive patients by both conventional and combined RT-PCR. HCV RNA was not detected in the HCV negative patients. As little as 500 ng total RNA was needed as the template to yield detectable amounts of amplified cDNA. The digoxigenin labelled oligoprobe hybridised with HCV RNA positive specimens only. CONCLUSIONS: The combined, single step RT-PCR is a rapid and sensitive technique for detecting HCV RNA in frozen liver tissue.

Base Sequence↗
PubMed1996

Oxygenation of dog liver transplants as an early indicator of graft failure.

This study examines the potential value of liver oxygenation as a predictor of early graft function. pO2 measurements were performed on 10 pairs of beagle (donor) and foxhound (recipient) dogs during pentobarbital anesthesis. Two different explantation techniques were used: complete preparation and dissection before perfusion and explantation (group A) or rapid perfusion and explantation with detailed preparation of the liver and dissection of vessels ex situ after explantation (group B). In both groups, the technique of liver perfusion with 1,000 ml arterial and 500 ml portovenous application of ice-cold UW solution was equal. Local oxygen partial pressure values were obtained polarographically with miniaturized needle electrodes. The liver oxygenation directly after laparotomy was comparable in both groups (median values around 54 mm Hg). Prior to the infusion of UW solution, a reduction of the tissue oxygenation values to 24 mm Hg was observed in group A (p < 0.01 compared to postlaparotomy values). In group B, limited preexplantation surgical dissection resulted in a reduced pO2 decline to 42 mm Hg (n.s.). After transplantation, the reduced tissue oxygenation persisted in the livers of the dogs which were completely dissected in situ (group B) as compared to the preexplantation recipient and the donor liver before instrumentation (p < 0.01). In contrast, rapidly perfused livers again exhibited only an insignificant reduction of tissue oxygenation following transplantation. Survival correlated linearly with the liver oxygenation within the observation time after transplantation (p < 0.01). A significant survival advantage was found for the rapid perfusion technique (p < 0.05). We conclude that the tissue oxygenation might provide valuable information on early graft function.

Animals↗
PubMed1996

Image reconstruction with acoustic measurement using distorted Born iteration method.

The distorted Born iterative method (DBIM) is applied to solve electromagnetics and ultrasonics inverse scattering problems. First, we use the DBIM to process the data, which are the scattered fields from two-dimensional cylinders with arbitrary cross section. From this simulation, we confirmed that the first-order Born approximation can be applied to larger objects as long as the phase change of a wave passing through the object due to its presence is smaller than a limit. Then we applied DBIM to process the ultrasonic measurement data. Images for a balloon and an egg that are immersed in water have been reconstructed and compared with those from the first-order diffraction tomography (DT).

Humans↗
PubMed1996

Complete reversal of FK 506 induced diabetes in a liver transplant recipient by change of immunosuppression to cyclosporine A.

We report the case of a 41-year old patient who underwent orthotopic liver transplantation because of decompensated liver cirrhosis due to chronic HCV-infection. Severe acute allograft rejection was insufficiently controlled by cyclosporine A, steroids and a 6-day regimen of OKT 3 monoclonal antibody therapy. As a consequence immunosuppressive therapy was switched to FK 506 in a dose of 3 mg bid. The FK 506 concentration in whole blood consistently ranged between 5.1 and 7.8 ng/ml. Seven weeks after the onset of FK 506 therapy the patient developed severe diabetes mellitus with fasting blood glucose levels up to 640 mmol/l. The C-peptide was elevated reflecting a higher than normal insulin secretion. Intravenous insulin therapy with application of up to 85 units regular insulin per day was initiated. Because of the severe diabetes immunosuppression was changed back to cyclosporine A. After six weeks the patient did no longer require insulin and showed an entirely normal glucose tolerance test, C-peptide and Hb A1-level. This case shows that the diabetogenic side effect of FK 506 is more pronounced than that of cyclosporine A. We propose to change immunosuppressive therapy to cyclosporine A in cases of FK 506 induced severe diabetes mellitus, since long-term prognosis of many transplant recipients may depend on side effects of the immunosuppressive agents.

Adult↗
PubMed1995

Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of > 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus-related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.

Antibodies, Monoclonal↗