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Biomedical subjects

J Eisenburg

Publications and source records attributed to J Eisenburg.

At least 19 recordsLinked to original sources
PubMed1997

Depletion of CD8+ T lymphocytes by murine monoclonal CD8 antibodies and restored specific T cell proliferation in vivo in a patient with chronic hepatitis C.

Cellular immune mechanisms, especially those mediated by CD8+ T cells, are important in the pathogenesis and control of viral infections. On the other hand, as shown for chronic lymphocytic choriomeningitis virus infection in the mouse, CD8+ T cells may not only hinder the elimination of a virus, but make the host unresponsive to a second viral infection. In hepatitis C virus (HCV) infections, at least 50% of the patients become chronically infected, despite the detection of HCV-specific CTL and a specific proliferative response to HCV Ags in PBL and in lymphocytes isolated from the liver. To better understand the immunopathologic mechanisms of CD8+ cells in vivo and to search for a potential treatment, we applied murine CD8 mAbs to a patient with therapy-resistant chronic HCV. A drastic reduction of CD8+ circulating lymphocytes, a reduction of CD8 molecule density, and complement fixation on CD8+ cells were observed. The reduction of CD8+ cells was compensated partially by an elevation of CD4+ cells. High concentrations of neutralizing human anti-mouse Abs were induced. After the Ab infusions, the CD4/CD8 ratio in peripheral blood increased from 1.6 to values of about 3 during therapy, and gradually decreased to 2.3 1 yr after the last mAb infusion. A continuing decrease of serum aminotransferases and clinical improvement was observed. Interestingly, after initiation of treatment, a significant proliferative response to HCV-specific Ags became measurable.

Adult↗
PubMed1996

[Hepatic minimal encephalopathy. The most frequently overlooked, clinically occult "metabolic syndrome" on the cirrhosis patient].

The syndrome of minimal hepatic encephalopathy is used to describe discrete psychomental and neuro-psychological abnormalities in patients with chronic liver disease (cirrhosis) or portosystemic shunt, in whom classical clinical investigations reveal no evidence of mental or cerebro-neurological disorders, and who cannot be assigned to any of the usual stages of hepatic encephalopathy. Disorders of cerebral function, such as lack of concentration, impaired ability to think logically, loss of comprehension, impairment of space perception and the recognition of numbers and letters can be very reliably detected by simple psychometric tests (number-connection test, line-tracing test, handwriting), and are present in as many as 70% of cirrhotics. This may be expressed in everyday life by an impairment of driving ability, and at work by impaired ability to operate a machine. The use of established means of lowering blood ammonia levels (lactulose, ornithine-aspartate) results in a rapid improvement in the symptoms of encephalopathy.

Ammonia↗
PubMed1994

[Interferon or C virus-induced autoimmune chronic hepatitis? Report of personal observations and review of the literature].

Chronic persistent hepatitis C in a 35 year-old man treated for nine months with interferon, converted into autoimmune chronic hepatitis. Prior to this conversion, the laboratory cell-integrity parameters of C hepatitis had permanently returned to normal, and HCV RNA had become negative. Prior to the initiation of treatment with interferon, no autoimmune antibodies had been present. On the basis of reports in the literature, the possible pathogenesis of this conversion is discussed, with two major mechanisms being considered: 1. induction of the autoimmune process by interferon, and 2. the "unmasking" of a pre-existing autoimmune process in the later course of chronic virus C hepatitis.

Adult↗
PubMed1993

Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection.

CD8+ lymphocytes of the memory subset (= CD45R0+) encompass antigen-specific effector cells, which are believed to be decisive for virus elimination in several viral infections. To determine whether this can be extended to HBV infection naive and memory T cells were studied among CD(4+)- and CD(8+)-lymphocytes and used monoclonal antibodies in two-color flow cytometric analysis to quantitate functional T cell subsets in peripheral blood of patients with acute hepatitis B (n = 11), chronic hepatitis B (n = 24) and healthy individuals (n = 26). Compared to CD4+ populations of healthy individuals the number of total CD4+ lymphocytes in patients with both acute or chronic hepatitis was significantly reduced. In contrast CD8+ cells did not significantly change in either acute and chronic hepatitis. Analysis of naive and memory subsets demonstrated, however, a significant rise in CD45R0+ memory cells from 5 to 15% (70% of all CD8+ cells) in acute hepatitis. These changes within the CD8+ population were, however, restricted to the acute phase of hepatitis in that the frequency of CD8+CD45R0+ decreased within weeks post infection. Furthermore, patients with chronic hepatitis did exhibit normal values of CD8+ memory cells (30% of all CD8+ cells). These findings suggest that enrichment of CD8+CD45R0+ memory cells reflects an accumulation of functional effector cells, which may be specifically activated by viral antigens and determine the outcome of infection.

Acute Disease↗
PubMed1992

[Treatment of chronic hepatitis B. Part 2: Effect of glycyrrhizic acid on the course of illness].

AIMS: Testing of the therapeutic efficacy of Remefa S, a pharmaceutical comprising glycyrrhizinic acid, the major active substance of licorice, on the evolution of the disease in late chronic viral hepatitis B. METHODS: Prospective evaluation of the biochemical, virus-serological and histomorphological data (blind liver aspiration, laparoscopy) during and following 12 months of application (three times a week, short infusions) of Remefa S, and comparison with the course of the disease (12 months) prior to treatment. PATIENTS: Intermediate report on an ongoing multicentre study begun in 1989, with evaluation of 7 subjects receiving the preparation and 3 controls after 12 months of treatment and 10 months of follow-up. RESULTS: During or after treatment, 4 patients experienced a regression of biochemical disease activity. In 2 of the 4 patients, during treatment, an HBe-Ag seroconversion occurred for the first time and has persisted (to date 10 months); in another patient with no detectable HBe-Ag prior to treatment, HBe antibodies were formed under treatment, and have persisted to the present time. In 2 of these responders, histology also revealed an unequivocal reduction in disease activity. In contrast, HBs-Ag seroconversion was observed in none of the patients treated. Since in these three patients the virus genome was already integrated within the chromosome of the host cell (hybridization), this had not been expected from the start. CONCLUSIONS: Intravenous chronic application (12 months) of glycyrrhizinic acid in the form of Remefa S in patients with chronic viral hepatitis B, is capable of exercising a positive effect on the evolution of the disease. On the basis of the results obtained so far (30-40% success rate), a comparison with the results obtained with interferon suggests itself.

Adult↗
PubMed1992

[Treatment of chronic hepatitis B. Part 1: Critical overview of current results of studies].

AIMS: Critical appraisal of presently available results of studies on the treatment of chronic hepatitis B. MAIN POINTS CONSIDERED: Even the controlled studies on the treatment of chronic hepatitis B carried out in recent years, in particular involving the use of interferons, possibly in combination with glucocorticosteroids, real methodological shortcomings that, in part, are due to the characteristics of chronic hepatitis, such as variations in its evolution, inadequate information provided by individual evolution-related parameters and failure to take account of patient variables. Moreover, the spontaneous evolution of the disease is difficult to predict, and a definitive assessment of the results of treatment always requires longterm follow-up. CONCLUSIONS: Despite the shortcomings of the individual studies, treatment with interferon represents a great advance in the therapy of chronic hepatitis B. However, the high percentage of treatment failures makes the continued search for new therapeutic modalities necessary.

Combined Modality Therapy↗