Biomedical subjects

Michael P Curry

Publications and source records attributed to Michael P Curry.

6 recordsLinked to original sources

PubMed2005

The gallbladder and biliary tract in cystic fibrosis.

Chronic liver disease is a major complication of cystic fibrosis. Its incidence and severity are variable, and diagnosis relies on a combination of clinical evaluation, biochemical testing, and radiologic assessment. Identifying patients who have early disease is critical, and the administration of ursodeoxycholic acid appears to be beneficial. The pathogenesis is incompletely understood, and factors that contribute to the variability in incidence and severity are unknown. Fortunately, only a small proportion of individuals progress to advanced liver disease; however, in this population, there is significant morbidity and impairment in quality of life. Liver transplantation can be performed successfully in patients with end-stage liver disease. Future treatments involve targeted gene therapy and activation of mutant forms of the cystic fibrosis transmembrane conductance regulator.

Biliary Tract↗

PubMed2005

Use of growth factors with antiviral therapy for chronic hepatitis C.

Interferon (IFN)-based regimens for the treatment of chronic hepatitis C virus (HCV) infection have become increasingly effective and are able to eradicate virus in more than one half of treated individuals. Treatment strategies are complex and involve self-administration of injectable IFN and oral ribavirin medication, frequent office visits, and laboratory testing. Current therapies have significant side effects that may impair performance and quality of life (QOL), necessitating dose reductions or interruption of therapy. As a consequence of these dose reductions or treatment interruptions, patients may not achieve a sustained virologic response (SVR). Recent data suggest that aggressive management of side effects may improve QOL and therefore patient adherence to therapy. Use of antidepressant and anxiolytic medications and off-label use of hemopoietic stem cell growth factors are increasing in the daily management of HCV therapy. Although these therapies may improve QOL, prevent dose reductions, and increase the number of patients completing therapy, there are no data available to definitively show that such tactics are associated with improvement in SVR rates in individual patients.

Anemia↗

PubMed2005

Atypical radiological presentation of progressive multifocal leukoencephalopathy following liver transplantation.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain caused by JC virus (JCV), occurs following transplantation and other conditions associated with immunosuppression. On magnetic resonance imaging (MRI), PML lesions typically appear as hyperintense signal on T2-weighted and FLAIR images located in the subcortical white matter, which are devoid of contrast enhancement or mass effect. The prognosis is poor, but unusual inflammatory forms of PML characterized by contrast enhancement have been associated with a cellular immune response against JCV and a better prognosis. The authors report an atypical presentation of PML with contrast-enhancing lesions and mass effect on the MRI in a liver transplant recipient,who had a progressive course and fatal outcome.

Adult↗

PubMed2004

Hepatitis B and hepatitis C viruses in liver transplantation.

Liver transplantation (LT) for end-stage liver disease (ESLD) secondary to hepatitis viruses has evolved rapidly during the last two decades. ESLD secondary to hepatitis C virus (HCV) accounts for approximately 50% of LT in the United States and Europe. Despite the decrease in the number of new HCV infections, the prevalence of advanced HCV-related liver disease is steadily increasing. In light of the near universal recurrence of posttransplantation HCV infection and our limited ability to treat recurrent disease, transplantation is in danger of being overrun by viral hepatitis, unless effective strategies can be used to treat disease, expand the donor pool of available organs, and prevent disease recurrence. In the early 1980s, results of LT for chronic hepatitis B virus infection were hampered by recurrent infection and subsequent allograft failure. However, with the introduction of passive immunoprophylaxis with hepatitis B immunoglobulin and treatment with potent nucleoside analogs, there has been a resurgence of LT for hepatitis B virus-related ESLD. Despite the wide acceptance of LT as a therapy for ESLD, there is little consensus on the appropriate immunosuppressive regimens, and prophylactic and therapeutic treatments vary widely from one center to another. This review summarizes available data and highlights appropriate strategies to improve outcomes.

Hepatitis B↗

PubMed2003

Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver.

BACKGROUND/AIMS: Association of hepatitis C virus (HCV) with increased autoantibodies, mixed cryoglobulinaemia, non-Hodgkin's B-cell lymphoma and increased peripheral innate (CD5(pos)) B cells suggests a role for B-lymphocytes in the pathogenesis of HCV-infection. METHODS: Flow cytometry was used to estimate CD5(pos) B cell levels and CD81 co-expression in chronic HCV infection. Viral load was assessed using PCR. RESULTS: We demonstrate expansion of innate B cells in HCV-infected liver from patients with fibrosis score less than stage II (39%, % of total B cells, P=0.002) and end stage HCV cirrhosis (20%, P<0.05) compared with normal liver (8%). Expression of CD81, a signal transducing molecule and putative HCV receptor, was significantly increased on peripheral blood CD5(pos) B cells compared with conventional B cells (P=0.0001). Higher levels of CD81 on CD5(pos) B cells were more dramatic in the liver of HCV-infected individuals. However, no significant difference was observed in the viral load of CD5(pos)CD81(High) B cells and CD5(neg)CD81(Low) B cells. CONCLUSIONS: Increased expression of CD81 on innate B cells, a population that is expanded in the livers and peripheral blood of chronic HCV-infected patients, suggests a role in viral specific activation and clonal proliferation in chronic HCV infection.

Adult↗

PubMed2002

Decrease in hepatic CD56(+) T cells and V alpha 24(+) natural killer T cells in chronic hepatitis C viral infection.

BACKGROUND/AIMS: The intrahepatic immune system is likely to play a key role in determining the outcome of hepatitis C virus (HCV) infection. The hepatic lymphocyte repertoire is characterised by high CD8/CD4 T cell ratios and large numbers of gamma delta T cells, natural killer (NK) cells, NK T cells and NK receptor-positive T cells. It is not known which of these populations contribute to immunity against HCV or immune pathology. METHODS: To explore the relative contributions of lymphocyte subpopulations, we have compared the intrahepatic lymphocyte repertoires and cytokine expression in 13 patients with mild chronic hepatitis C infection, 14 with end-stage hepatitis C cirrhosis and five histologically normal livers by flow cytometry and immunohistochemistry. RESULTS: CD4(+) T cells bearing alpha beta T cell receptors (TCR) were significantly expanded in livers with chronic HCV infection while CD56(+) alpha beta T cells and V alpha 24 TCR-positive T cells were significantly depleted. Expanded CD4(+)T cells were predominantly Th1 cells, producing interferon-gamma but not interleukin-4. CONCLUSIONS: Failure to resolve HCV infection may be due to deficient innate and/or memory immune responses, while Th1 cells may mediate immune pathology.

Adult↗