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Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 181 records · Page 10Linked to original sources

Implications of host pancreatic hormones in the restart of grafted liver.

Regulatory roles of insulin and glucagon in hepatic metabolism and function are well described. However, little is known about implications of host pancreatic hormones in primary function of grafted liver. This study aimed to investigate it in relation to hepatic mitochondrial function. Insulin, c-peptide, and glucagon in peripheral blood were monitored for 2 days in clinical liver transplantation by a continuous sampling technique to avoid influences of hormonal oscillation. In grafts with immediate function (n = 10), smooth increase of arterial ketone body ratio reflecting hepatic intramitochondrial redox state was accompanied by increased c-peptide and decreased glucagon, resulting in the increase of c-peptide/glucagon ratio. In other functioning grafts (n = 20), where ketone body ratio was rather lower, increased glucagon level, observed also during anhepatic phase, resulted in the slower increase of c-peptide/glucagon ratio. There were accompanied by increased free fatty acid and ketone body levels. In primary nonfunction (n = 4), rapid increase of c-peptide accompanied by hyperglycemia resulted in the accelerated increase of c-peptide/glucagon ratio, but ketone body ratio did not show any increase. Insulin/c-peptide ratio also showed a rapid increase. These findings suggest that the increase of insulin/glucagon ratio in portal blood, potentially influenced by recipient condition, is associated with the recovery of mitochondrial energy metabolism in survived hepatic grafts. However, this relationship does not work in failed grafts, where irreversible impairment of energy metabolism is attributed to graft itself.

Adolescent↗

Allogeneic liver transplantation for hepatic veno-occlusive disease after bone marrow transplantation--clinical and immunological considerations.

Veno-occlusive disease (VOD) is a frequent complication early after bone marrow transplantation. In cases of severe liver failure treatment by allogeneic liver transplantation is possible. We report the clinical and immunological course of a patient after bone marrow transplantation for AML and subsequent allogeneic liver transplantation for severe hepatic VOD. After liver transplantation the patient recovered well clinically. Early after liver transplantation he had large numbers of liver donor T and NK lymphocytes in his circulation. He had no liver graft rejection, but he developed mild acute GVHD which was caused by liver graft-derived T lymphocytes. Two years after transplantation he had persistent microchimerism with donor liver cells detectable in his bone marrow. Now 36 months after transplantation, the patient has no evidence of recurrent leukemia, stable liver function, and no signs of graft-versus-host disease or bone marrow dysfunction.

Acute Disease↗

Different cellular patterns associated with hepatitis C virus reactivation, cytomegalovirus infection, and acute rejection in liver transplant patients monitored with transplant aspiration cytology.

Fine-needle aspiration biopsy (FNAB) is a routine diagnostic tool used for the monitoring of the graft during the first postoperative weeks after liver transplantation. The cellular pattern of acute liver rejection is typical in transplant aspiration cytology (TAC), documented and published by several authors. The lymphoid response associated with various viral infections may, however, provide differential diagnostic problems in the cytological monitoring. In this study, we have investigated in detail the cellular pattern of lymphoid response associated with hepatitis C virus (HCV) reactivation, and compared it with the pattern of cytomegalovirus (CMV) infection and with the typical diagnostic findings of acute cellular rejection. HCV reactivation was associated with rather mild total inflammation in the graft (4.5 +/- 1.5 CIU at the peak). The inflammatory infiltrate consisted mainly of small lymphocytes (3.1 +/- 0.2 CIU at the peak), with only occasional activated cells and without lymphoid blast response. No lymphoid activation was seen in the blood. CMV infection was associated with a mild immune response (3.9 +/- 0.4 CIU at the peak) recorded as a slight lymphoid activation and occasional blast cells both in blood and in the graft together with lymphocytosis in the graft (2.4 +/- 0.7 CIU at the peak). The typical findings of acute rejection were easily distinguished from the cellular pictures of both viral infections. The rejections were lymphoid blast (3.6 +/- 3.4 CIU at the peak) and activated lymphocyte (3.5 +/- 2.6 at the peak), dominated by a high peak of total inflammation (9.3 +/- 7.0 CIU). No blast cells and only a few activated cells were seen in the blood during rejection episodes. Thus, the cellular patterns of HCV reactivation and CMV infection differed slightly from each other, but significantly from that of acute liver allograft rejection monitored with the FNAB cytology.

Antibodies, Viral↗

Prostaglandin E plus famciclovir--a new concept for the treatment of severe hepatitis B after liver transplantation.

New concepts for the treatment of hepatitis B in immunocompromised patients are urgently needed. We describe our first experience with the new antiviral agent famciclovir in combination with a short course of prostaglandin E in a patient with severe hepatitis B after liver transplantation. Initial treatment with prostaglandin E reduced the inflammatory activity, as measured by transaminase activities, but did not affect viral replication. Consecutive long-term treatment with famciclovir further normalized liver function and profoundly suppressed viral replication. HBeAg and HBV-DNA -PCR all became negative and only HBsAg persisted. Histology documented marked reduction of cellular infiltration. The patient completely recovered and is back to regular work as a teacher.

2-Aminopurine↗

Patterns of donor-type microchimerism after heart transplantation.

Allogeneic microchimerism of donor-type has been demonstrated in stable patients in the long-term after organ transplantation. We have analysed microchimerism in skin and blood of 47 heart-transplanted patients after transplantation with polymerase-chain-reaction amplification specific for donor HLA-DRB1. Microchimerism was detectable in 50% of the patients in the first 6 months, in 100% between 6 months and 2 years, and in 58% in the third postoperative year or later. The state of chimerism was not related to acute or chronic rejections. Patterns of microchimerism after heart transplantation may be dynamic, but any association with clinical and immunological variables remains to be elucidated.

Gene Amplification↗

Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Antibodies, Monoclonal↗

[Symptomatic compression of the vena cava caused by a small liver hemangioma].

Occasioned by a recurrent urinary infection, ultrasonography was performed on a 41-year-old otherwise healthy woman. There were no abnormal renal findings, but a 4.5 x 4.5 cm space-occupying lesion with the echo-typical pattern of an haemangioma was found in the right lobe of the liver. Magnetic resonance imaging and dynamic computed tomography demonstrated compression of the vena cava by the tumour which was localized to the caudate lobe. The T2-weighed pictures suggested a cavernous haemangioma which extended from the vena cava at the diaphragm to the portal vein bifurcation. Obstruction to flow became evident 10 months later as oedema of the lower legs, giving the indication for surgical removal of the haemangioma. The benign tumour was enucleated under total vascular occlusion without significant blood loss pre- and post-operatively. The patient was discharged symptom-free on the 13th postoperative day.

Adult↗