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Biomedical subjects

Douglas R Labrecque

Publications and source records attributed to Douglas R Labrecque.

3 recordsLinked to original sources

Mental and physical symptoms associated with lower social support for patients with hepatitis C.

AIM: To systematically examine the impact of the hepatitis C virus (HCV) diagnosis on patients' level of social support in a large-scale study. METHODS: Patients evaluated and treated for HCV in a tertiary referral center were enrolled in a cross-sectional study. Demographic data, functional and emotional status as measured by the Hospital Anxiety and Depression Scale (HAD) and the Sickness Impact Profile (SIP), severity of liver disease, mode of acquisition, and physical and psychiatric comorbidities were collected from patients or abstracted from the medical record. All participants completed a semi-structured interview, addressing questions of social support. RESULTS: A total of 342 patients (mean age 45.2 years; 37% women) were enrolled. Ninety-two (27%) patients described lower levels of support by family and friends. Nearly half of the participants (45%) noted the loss of at least one relationship due to the disease. Fears related to transmitting the disease (25%) were common and often associated with ignorance or even discrimination by others (19%). Nearly one fifth of the patients did not share information about their disease with others to avoid being stigmatized. Lower levels of social support were significantly associated with living alone, being unemployed, being excluded from antiviral therapy, having psychiatric comorbidities, contracting HCV through intravenous drug use, having high levels of anxiety and depression as measured by the HAD and negative mood state as measured by the SIP. Patients reporting lower levels of social support also noted more physical symptoms as measured by the SIP. CONCLUSION: Patients with hepatitis C often face significant social problems, ranging from social isolation to familial stress. The most common concerns reflect a limited insight of patients and their relatives and friends about the disease, the risk factors for its spread, and about potential consequences. Our data suggest that educational interventions targeting support persons and the stressors identified in our findings may lessen or alleviate the social strains patients with hepatitis C experience.

Adult↗

Treatment of hepatitis C cryoglobulinemia: mission and challenges.

Mixed cryoglobulinemia (MC) is a syndrome resulting from cold-insoluble immunoglobulin complexes or cryoglobulins (CGs) that precipitate in the serum of 40% to 50% of patients with chronic hepatitis C virus (HCV) infection. The pathogenesis of cryoglobulinemia likely occurs due to chronic viremia and generation of rheumatoid factor following continuous presentation of antigen-immunoglobulin complexes to B cells. CGs are thought to be responsible for a variety of extrahepatic manifestations associated with HCV, including vasculitis, glomerulonephritis, arthritis, and neuropathies, which occur in approximately 10% of HCV patients with CGs. CGs also are a powerful predictive factor for progressive liver disease and the aggressive reoccurrence of liver disease in HCV-positive patients after liver transplantation. First-line therapy for MC due to HCV infection is antiviral therapy with pegylated interferon-alpha and ribavirin. Viral eradication usually produces marked reduction of physical complications and arrests end organ damage concomitant with clearance of CG. Additional prospective, controlled studies are necessary to determine whether CG influences patient virologic response and/or its durability to antiviral therapy. Immunomodulators such as corticosteroids and cyclophosphamide are efficacious for palliative treatment of the symptomatology of HCV cryoglobulinemia but may enhance viral replication. Consequently, prolonged therapy with immunomodulatory agents should be limited to severe vasculitis or aggressive glomerulonephritis in patients with MC due to HCV who have failed to respond to antiviral therapy. In acute, fulminant presentations, plasmapheresis may provide temporary relief and arrest the rapid progression of the disease so that additional therapy can be initiated.

Journal Article↗

GB virus type C NS5A sequence polymorphisms: association with interferon susceptibility and inhibition of PKR-mediated eIF2alpha phosphorylation.

GB virus type C (GBV-C) causes persistent infection in humans, although the mechanism by which the virus avoids clearance by the host is unknown. To determine if amino acid polymorphisms in the GB virus type C (GBV-C) NS5A and E2 proteins alter response to interferon (IFN) therapy, we studied the sequence of GBVC NS5A and E2 obtained from people receiving IFN therapy. In addition, we expressed recombinant GBVC NS5A protein to determine if it interferes with RNA-activated protein kinase (PKR) function in vitro. GBVC NS5A amplified from a person whose virus was cleared by IFN therapy (IFN sensitive) demonstrated unique amino acid changes occurring in the region that aligns with the hepatitis C virus (HCV) IFN sensitivity-determining region (ISDR) compared with NS5A sequences from individuals who did not clear GBV-C (IFN resistant). There were no differences in the E2 sequences obtained from IFN-sensitive and IFN-resistant isolates. Using a yeast genetic system, IFN-resistant NS5A inhibited PKR-mediated phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) in yeast, whereas IFN-sensitive NS5A did not inhibit PKR function. GBV-C NS5A amino acid polymorphisms appear to be involved in response to IFN therapy, and IFN-resistant GBV-C NS5A inhibited PKR-mediated eIF2alpha phosphorylation in a yeast genetic system, suggesting a mechanism by which GBV-C may evade clearance by naturally occurring host antiviral responses.

Amino Acid Sequence↗