Biomedical subjects

R M Hoffmann

Publications and source records attributed to R M Hoffmann.

At least 19 recordsLinked to original sources

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↗

PubMed1992

T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-gamma upon mitogen stimulation.

Primary biliary cirrhosis (PBC) is considered an autoimmune disease characterized by destruction of small intrahepatic bile ducts by lymphocytes. Altered functions of these lymphocytes might reflect an abnormal immune response leading to tissue damage. We investigated lymphokine secretion by mitogen-stimulated T lymphocytes from the liver biopsies of patients with PBC and for comparison also peripheral blood. In PBC, diminished synthesis of lymphotoxin (TNF beta), tumor necrosis factor (TNF alpha) and interferon-gamma (IFN gamma) was found both in T-cell lines from liver tissue and in peripheral blood. The reduction was most prominent for TNF beta in early histological stages of PBC, and appeared to be a stable phenomenon when T cells were tested after long-term tissue culture. Analysis of mRNA levels indicates a possible link between reduced TNF beta production and a defect in interleukin-2 transcription. The data suggest that diminished lymphokine production in patients with PBC may play an important role in the immunopathogenesis of this disease.

Adult↗

PubMed1992

The use of UW solution in clinical transplantation. A 4-year experience.

The development of the University of Wisconsin (UW) cold storage solution has extended safe preservation of the liver and pancreas from 6 to 24 hours or more. From May 1987 until November 1991, 288 livers and 163 simultaneous pancreas/kidney transplants were performed using UW solution. The mean preservation times were: liver, 12.7 +/- 4.4 hours, pancreas 17.2 +/- 4.4 hours, and kidney, 19.2 +/- 4.3 hours. Included in this series were 35 reduced-sized liver transplants, 7 cluster transplants, and 132 combined liver/pancreas retrievals. No differences in allograft function or graft-related complications were seen in organs preserved for less than or longer than 12 hours or in grafts from combined liver/pancreas retrievals. All pancreas/kidney transplants and most liver transplants were performed semi-electively. Actuarial 1-month patient and graft survival after liver transplantation was 91.4% and 80.2%, and at 4 years was 74.0% and 62.0%, respectively. After pancreas/kidney transplantation, the actuarial patient survival at 1 month and 4 years was 99.4% and 90.5%, respectively, whereas pancreatic and renal allograft survival at 1 month was 97.5% and 96.8%, and at 4 years was 83.0% and 83.4%, respectively. The ability to extend preservation times with UW solution has many advantages; however, the most important contribution of UW solution to clinical transplantation has been the increased utilization of scarce donor organs for more recipients because the previously imposed constraints on preservation time have been removed.

Adenosine↗

PubMed1992

The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant recipients.

We retrospectively analyzed 526 primary cadaver recipients transplanted at a single center to identify pretransplant variables that predict long-term survival with multivariate analysis. All recipients received at least three random blood transfusions and were treated under a quadruple-therapy protocol consisting of ALG, azathioprine, prednisone, and cyclosporine. Of 526 consecutive transplants, 86 grafts were lost from acute or chronic rejection. Thirteen grafts were lost for nonimmunologic reasons and 35 recipients died with a functioning graft. A total of 273 patients (52%) experienced at least one episode of acute rejection. Donor age ranged from 3 to 64 years, with 62% of donors less than 30 years of age and 9% of donors over 50 years of age. Donor age was not predictive of long-term graft survival and neither was the difference between donor and recipient age. Recipient age was predictive of subsequent immunologic graft less, with younger recipients at greater risk (P = 0.011). The rate of first rejection was also inversely related to recipient age, with younger recipients rejecting earlier (P = 0.0001). The degree of DR mismatch was the only other significant predictor of long-term graft success (P = 0.013). Transplant survival correlated with the degree of DR mismatch: 2 DR mismatch was the worst, 1 DR mismatch was intermediate and 0 DR mismatch was the best (P = 0.02). A, B, AB, and BDR did not influence long-term graft outcome. In our center, donor age does not predict graft failure. Younger recipients have a higher rate of early rejection and, combined with a poor DR match, are at higher risk for long-term graft failure.

Adult↗

PubMed1991

Analysis of the interchangeability of a dental articulator.

A series of Dentatus ARL articulators and gauge blocks were tested for the reliability of the system to reproduce articulator mountings. Points of occlusal contact were measured at several locations on a set of casts. Analysis of the data indicated that the location of the occlusal contacts and the gauge block used were critically related to the results. Further studies to quantify the measurement error and to carefully explore where this system could be used are needed.

Analysis of Variance↗

PubMed1991

The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation.

Methods of accurately assessing the suitability of donor livers prior to transplantation are required if the incidence of primary nonfunction (PNF) is to be reduced. This study evaluated the ability of donor liver biopsies to predict the development of primary nonfunction after transplantation. From June 1987 until May 1990, 170 liver transplants were performed in 147 patients. A total of 124 donor liver biopsies were obtained and divided into three groups. Group 1 biopsies (n = 77) were obtained after revascularization of the liver, group 2 biopsies (n = 19) were obtained prior to donor hepatectomy but examined only after implantation, and group 3 biopsies (n = 28) were obtained as in group 2, but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as having normal histology developed primary nonfunction, while one of 26 (3.8%) biopsies interpreted as having a minimal or moderate amount of fatty infiltration developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A fourth liver with hydropic degeneration and poor function ultimately failed requiring retransplantation 8 weeks later. Analysis of liver function revealed progressive elevation in aspartate-aminotransferase, alanine-aminotransferase, lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty infiltration. Donor age and weight was also found to be significantly higher in livers with fatty infiltration. This study suggests that donor liver biopsies demonstrating normal histology or minimal-to-moderate fatty infiltration function adequately, but that donor livers with severe fatty infiltration or hydropic degeneration function poorly and should not be transplanted.

Biopsy↗

PubMed1991