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Biomedical subjects

R M Hoffmann

Publications and source records attributed to R M Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed1996

The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C.

Since the discovery of hepatitis C virus it has become clear that chronic hepatitis C is a major health problem throughout the world. Because antiviral agents are of limited value in the treatment of chronic hepatitis C, research has focused on the antiviral immune response for the development of both a protective vaccine and effective immunotherapies for established chronic infection. Antiviral antibodies are present in almost all patients with chronic hepatitis C but do not seem to be virus neutralizing, probably due to the high mutational rate of viral envelope proteins. Studies on the antiviral T cell response have revealed the presence of virus-specific CD4+ helper and CD8+ cytotoxic T cells in a substantial proportion of patients with chronic hepatitis C. Recent studies describe an association between strong CD4+ T helper cell activity to certain hepatitis C virus antigens and a self-limited course of acute hepatitis C and possibly also a sustained response to treatment with interferon-alpha. Therapeutic manipulation of the virus-specific T cell response may thus develop into a new approach for prevention and treatment of hepatitis C virus infection.

Acute Disease↗
PubMed1996

Anergic TH1 clones specific for hepatitis B virus (HBV) core peptides are inhibitory to other HBV core-specific CD4+ T cells in vitro.

A strong and transient hepatitis B virus core (HBc)-specific CD4+ T-cell response has been shown to be associated with viral elimination in acute self-limited hepatitis B but to be absent in chronic hepatitis B. So far, little is known about immunological mechanisms involved in the regulation of the HBc-specific CD4+ T-cell response. We studied 28 patients with acute hepatitis B, and frequently a sudden decrease in the HBc-specific CD4+ T-cell response was found between 4 and 8 weeks after disease onset. Thirty-two CD4+ T-cell clones specific for amino acids 50 to 69, 81 to 105, 117 to 131, or 141 to 165 of HBc were isolated from a patient shortly before the peripheral blood mononuclear cell response to most HBc-derived peptides abruptly disappeared. TH1 clones, but not TH0 clones, could be anergized in vitro by stimulation with specific peptides even in the presence of costimulatory cells. Moreover, when anergic cells were mixed with responsive cells, the proliferation of HBc-specific TH1 or TH0 clones was inhibited antigen specifically by anergic cells. The unusual susceptibility of HBc-specific TH1 clones to anergy induction in vitro as well as their potential to inhibit other HBc-specific TH1 and TH0 clones suggests that anergy induction may be involved in the downregulation of the virus-specific immune response during acute hepatitis B in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1996

Preliminary experience with split liver transplantation.

BACKGROUND: The purpose of split liver transplantation is to alleviate the organ shortage for patients with end-stage liver disease. The procedure, however, has not gained wide acceptance. This is related not only to the complexity of the procedure but also to poorer results and the complications reported to be associated with the technique. STUDY DESIGN: We report 12 split liver transplantation procedures, seven in children and five in adults. Selection criteria were the same as those for whole-size liver transplantation. Patient and graft survival as well as complications were analyzed. Results were analyzed by Wilcoxon life tables. RESULTS: Patient and graft survival rates are 91.6 and 75 percent, respectively. One patient died at 2.5 months after transplantation because of lymphoproliferative disease. Another had acute vanishing bile duct syndrome and required retransplantation at 1.5 months. One patient had retransplantation because of hepatic artery thrombosis. Bile leaks occurred in two patients and hemothorax in one patient. CONCLUSIONS: Our results indicate that split liver transplantation has become a more acceptable method of hepatic transplantation and should be encouraged. Several guidelines can enhance success rates.

Adult↗
PubMed1995

Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection.

In acute hepatitis C virus (HCV) infection only 20-50% of patients spontaneously clear the virus. To characterise the immune reaction during that phase we studied the response of peripheral blood mononuclear cells (PBMC) to the recombinant HCV proteins core, non-structural protein 3 (NS3), NS4, and NS5 in 14 patients with acute hepatitis C. All eight patients with self-limited disease compared with two of six with evolving chronic infection showed an NS3- specific PBMC response (p = 0.015). Of 65 patients with established chronic hepatitis C, five showed a PBMC response to NS3. NS3-specific CD4 T-cell clones from patients with self-limited infection predominantly produced interferon-gamma and may thus support cytotoxic effector mechanisms important for viral clearance.

Acute Disease↗
PubMed1995

Successful extrarenal transplantation from non-heart-beating donors.

The current organ shortage has made utilization of organs from less-than-ideal donors more common. Although several transplant centers use kidneys from non-heart-beating donors (NHBDs), there has been reluctance to extend the use of these donors to extrarenal organs. Of the 130 donors referred to our organ procurement organization between January 1993 and May 1994, 16 (12.3%) were NHBDs. Organ retrieval from 10 of these resulted in extrarenal donation, 5 resulted in renal donation only, and 1 resulted in no retrieval as a result of prolonged warm ischemia (> 2 hr). A total of 39 organs were transplanted from these NHBDs. A rapid en bloc retrieval technique was used for extrarenal NHBDs. The mean warm ischemic time was 15.4 min; preservation times were similar for both NHBDs and heart-beating donors. After liver transplantation (n = 5), one episode of primary nonfunction that was technical in origin required retransplantation. Following simultaneous pancreas-kidney transplantation (n = 6), all patients were insulin independent and free of graft pancreatitis; one patient required hemodialysis (16.7%). After isolated renal transplantation (n = 21), 3 patients (14.3%) required hemodialysis. Three of 4 liver recipients are alive after a mean follow-up period of 12.7 months; all simultaneous pancreas-kidney and renal transplant recipients are alive after a mean follow-up period of 8.4 and 8.3 months, respectively. Three liver allografts, 5 pancreas and kidney allografts, and 19 renal allografts are functioning. The lung allograft was lost to rejection 81 days after transplantation; however, the recipient is alive 3 months after retransplantation. Our results demonstrate that in controlled situations, extrarenal organs can be utilized from NHBDs and can be expected to function similarly to organs retrieved from heart-beating donors. We increased the number of transplanted organs by 8.6% using NHBDs for both renal and extrarenal donation. Continued application of these techniques will likely further increase the number of organs retrieved for transplantation.

Heart↗
PubMed1995

Hepatitis C virus infection as a possible risk factor for ductopenic rejection (vanishing bile duct syndrome) after liver transplantation.

Irreversible ductopenic rejection (DR) after orthotopic liver transplantation (OLT) is a major cause of late hepatic allograft failure. A variety of risk factors for DR have been postulated, but they are controversial. All transplant recipients at our institution with graft survival of more than 1 month (n = 120) were examined retrospectively with a view to possible risk factors for DR. These factors included age, sex, underlying liver disease, hepatitis B and C infections, donor-recipient CMV status, post-OLT CMV infections, immunosuppressive regimen, ABO blood type, and HLA class I and class II mismatches. Statistical analysis was performed with the univariate chi-square test or the two-tailed Fischer's exact test. Ten patients (8.3%) developed DR. Seventeen patients had HCV infections after OLT. In this group, the incidence of DR was highest (4 of 17, or 23.5%). This was significantly higher than for all other OLT groups (6 of 103 patients, or 5.8%; P < 0.03). The other factors analyzed did not reach statistical significance, including those that other authors found important for the development of DR. It may well be that hepatitis C infection predisposes one to the development of DR after OLT.

Bile Duct Diseases↗
PubMed1995

Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection.

Overcoming hepatitis B virus infection essentially depends on the appropriate immune response of the infected host. Among the hepatitis B virus antigens, the core (HBcAg) and e (HBeAg) proteins appear highly immunogenic and induce important lymphocyte effector functions. In order to investigate the importance of HBcAg/HBeAg-specific T lymphocytes in patients with acute and chronic hepatitis B and to identify immunodominant epitopes within the HBcAg/HBeAg, CD4+ T-cell responses to hepatitis B virus-encoded HBcAg and HBcAg/HBeAg-derived peptides were studied in 49 patients with acute and 39 patients with chronic hepatitis B. The results show a frequent antigen-specific CD4+ T-cell activation during acute hepatitis B infection, a rare HBcAg/HBeAg-specific CD4+ T-cell response among HBeAg+ chronic carriers, and no response in patients with anti-HBe+ chronic hepatitis. An increasing CD4+ T-cell response to HBcAg/HBeAg coincides with loss of HBeAg and hepatitis B virus surface antigen (HBsAg). Functional analysis of peptide-specific CD4+ T-cell clones revealed a heterogeneous population with respect to lymphokine production. Epitope mapping within the HBcAg/HBeAg peptide defined amino acids (aa) 1 to 25 and aa 61 to 85, irrespective of the HLA haplotype, as the predominant CD4+ T-cell recognition sites. Other important sequences could be identified in the amino-terminal part of the protein, aa 21 to 45, aa 41 to 65, and aa 81 to 105. The immunodominant epitopes are expressed in both proteins, HBcAg and HBeAg. Our findings lead to the conclusion that activation of CD4+ T lymphocytes by HBcAg/HBeAg is a prerequisite for viral elimination, and further studies have to focus on the question of how to enhance or induce this type of T-cell response in chronic carriers. The immunodominant viral sequences identified may have relevance to synthetic vaccine design and to the use of peptide T-cell sites as immunotherapeutic agents in chronic infection.

Acute Disease↗
PubMed1995

Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection.

In acute and chronic viral disease the specific response of CD4+ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4+ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Patients of an ambulatory sleep center--critical variables of insomniacs].

The following study presents results of a broad diagnostical screening for 128 insomniacs, which includes polysomnography, sleep-wake diaries and psychosometrical testing. It was our special aim to investigate about critical but not classical variables for insomnia, which had been mentioned in sleep literature before. We therefore focused on hypotheses about the meaning of state 1 sleep (according to Zorick et al. 1984) and the number of REM-Non-REM Cycles (according to Rüther et al. 1985) for the diagnosis of insomnia. Statistical analysis (t-Test, p = 0.05) showed that patients with less than 3 REM-Non-REM Cycles consumed significantly more hypnotics during 6 months before the sleep examination. Moreover it was obvious (Chi-Square, p = 0.001) that more than 50% of insomniacs with organic causes presented less than 3 cycles, whereas the latter was true only for 1 patient with primary insomnia. Although results were not as strong for the "state-1 sleep variable", we find that these non-classical sleep variables should be sincerely regarded within the future context of the diagnosis of insomnia.

Adult↗
PubMed1995

[Sleep of sleep research personnel--results of the Munster Congress survey].

Due to different knowledge of sleep and sleep disorders (i.e. focussing) sleep quality of sleep-researchers may be better or worse than the sleep of other scientists. On the Münster Congress for Sleep-research and Sleep medicine in March 1994 we investigated this question using the Pittsburger Sleep Quality Index (PSQI). 46 sleep researchers, 52 practitioners and 103 scientists of other disciplines from the Münster University filled out the questionnaire. Results show no difference in overall sleep quality between the three groups, but only sleep quality in the group of sleep researchers shows a bimodal distribution suggesting a subpopulation with more serious sleep problems. 10 to 15% of the total academic population can be regarded as "poor" sleepers. Especially the group of practitioners, in which we found the highest values of daytime sleepiness, seems to be a risk-population for sleep disorders.

Adult↗
PubMed1994

Unusual coexistence of systemic lupus erythematosus and primary biliary cirrhosis.

Systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are distinct clinical disorders which rarely occur in the same patient. We report on a 65-year-old woman with coexistence of both conditions. Diagnosis of SLE was ascertained by the presence of seven ACR criteria (cutaneous lesions, photosensitivity, antinuclear and anti-double-stranded-DNA antibodies, pancytopenia, arthritis, oral lesions). PBC was disclosed by clinical investigation, liver histology and highly positive antimitochondrial M2 antibodies. The most important differential diagnoses of lupus hepatitis are PBC and autoimmune hepatitis. Diagnostic criteria for these conditions are discussed, and previous reports on overlap between SLE and PBC are reviewed.

Aged↗
PubMed1993

Risk factors for primary dysfunction after liver transplantation--a multivariate analysis.

In a retrospective analysis on 323 orthotopic liver transplant procedures performed between July 1984 and October 1991 the incidence of two forms of primary dysfunction (PDF) of the liver: primary nonfunction (PNF), and initial poor function (IPF) were studied. The incidence of PDF was 22% (73/323) with 6% PNF (20/323) and 16% IPF (53/323), while 78% (250/323) had immediate function (IF). Occurrence of both IPF and PNF resulted in a higher graft failure rate (P < 0.001), retransplantation rate (P < 0.001), and patient mortality (P < 0.003) within the first three months after OLTx. Univariate analyses of donor and recipient factors and their influence on PDF demonstrated that longer donor hospitalization (> 3 days), older donor age (> 49 years), extended preservation times (> 18 hr), and fatty changes in the donor liver biopsy, as well as reduced-size livers, younger recipient age, and renal insufficiency prior to OLTx, significantly affected the incidence of IPF and PNF. Multivariate analysis of potential risk factors showed that reduced-size liver (P = 0.0001), fatty changes on donor liver biopsy (P = 0.001), older donor age (P = 0.009), retransplantation (P = 0.01), renal insufficiency (P = 0.02), and prolonged cold ischemia times (P = 0.02) were independently associated with a higher incidence of IPF and PNF. No statistical correlation was found between PDF and etiology of ESLD, nutritional status of the recipient, UNOS status, and Child-Pugh classification in this study. We conclude that PNF and IPF are both separate clinical entities that have a significant effect on outcome after OLTx. Routine donor liver biopsies are recommended to decrease the rate of IPF and PNF. The combination of risk factors shown to be significant for PDF should be avoided--and, if that is not possible, the only variable that can be controlled, the preservation time, should be kept as short as possible.

Adolescent↗
PubMed1993

Long-term results of liver transplantation for biliary atresia.

BACKGROUND: Biliary atresia can be treated by portoenterostomy, which is primarily palliative, or by liver transplantation, which is primarily curative. The purpose of this study was to determine the long-term outcome of liver transplantation for the treatment of biliary atresia. METHODS: During an 8-year period, 45 patients who underwent liver transplantation for biliary atresia and 10 patients who were referred to our center for portoenterostomy were retrospectively analyzed. RESULTS: No patient with biliary atresia died awaiting liver transplantation. The waiting time for all patients was 36.7 +/- 42.8 days. Thirty-four patients (75.6%) required one transplant, whereas 11 patients (24.4%) required 17 retransplants. Twenty-two patients (48.9%) required 39 reoperations (1.8 per patient). There were 4.9 infectious episodes, 2.2 rejection episodes, and 4.4 readmissions per patient. However, 91% of reoperations, 80% of infections, and 78% of rejections occurred within 6 months of transplantation. The overall 7-year actuarial patient and graft survival for patients with biliary atresia was 86.2% and 62.7%, respectively. CONCLUSIONS: Our results indicate that long-term patient survival after liver transplantation for biliary atresia is excellent. However, portoenterostomy continues to have an initial complementary but limited long-term role in the treatment of infants with biliary atresia.

Biliary Atresia↗