Enhanced antiviral benefit of combination therapy with lamivudine and alpha interferon against WHV replication in chronic carrier woodchucks.

Cell culture studies in our laboratory previously demonstrated synergistic antiviral activity for the combinations of lamivudine and a novel recombinant hybrid human alpha B/D interferon (rHu alpha B/D IFN) against hepatitis B virus (HBV) replication. Based on these results, a study was designed to determine if an enhanced antiviral effect with this drug combination could be demonstrated in vivo using the woodchuck hepatitis virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers during previous studies by our laboratories.

Coping with neck and low back pain in the general population.

This study had 2 objectives: (a) to assess the psychometric properties of the Pain Management Inventory (PMI; G. K. Brown & P.

Antiviral activities of oral 1-O-hexadecylpropanediol-3-phosphoacyclovir and acyclovir in woodchucks with chronic woodchuck hepatitis virus infection.

Acyclovir triphosphate is a potent inhibitor of hepatitis B virus DNA polymerase, but acyclovir treatment provides no benefit in patients with hepatitis B virus infection. This is due in part to the fact that hepatitis B virus, unlike herpes simplex virus, does not code for a viral thymidine kinase which catalyzes the initial phosphorylation of acyclovir. We synthesized 1-O-octadecyl-sn-glycero-3-phospho (3-P)-acyclovir and found that it was highly active in reducing hepatitis B virus replication in 2.

Effect of oral administration of emtricitabine on woodchuck hepatitis virus replication in chronically infected woodchucks.

Emtricitabine [(-)FTC] [(-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (-)FTC against WHV replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against HBV, was examined in a placebo-controlled study. (-)FTC significantly reduced viremia and intrahepatic WHV replication in a dose-dependent manner that was comparable to the antiviral activity of lamivudine observed in previous studies conducted by our laboratories.

Treatment of chronic woodchuck hepatitis virus infection in the Eastern woodchuck (Marmota monax) with nucleoside analogues is predictive of therapy for chronic hepatitis B virus infection in humans.

The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a model of hepatitis B virus (HBV)-induced disease. Several published studies have used this experimental animal model system to demonstrate potential antiviral therapies for chronic HBV infections. However, there has been little comparative information available on compounds used in clinical anti-HBV studies in WHV-infected woodchucks, thereby making interpretations of the potential relative effectiveness of new antiviral agents in humans more difficult.

The factors associated with neck pain and its related disability in the Saskatchewan population.

Study Design: Population-based, cross-sectional mailed survey.

Objective: To identify factors associated with neck pain and its related disability in Saskatchewan adults.

Summary Of Background Information: Little is known about the etiology of neck pain and its related disability.

Enhanced antiviral benefit of combination therapy with lamivudine and famciclovir against WHV replication in chronic WHV carrier woodchucks.

Cell culture studies in our laboratory and others have previously demonstrated synergistic antiviral activity for combinations of 3TC (lamivudine) and penciclovir against Hepatitis B Virus (HBV) replication and the Duck Hepatitis B Virus (DHBV). Based on these results, a study was designed to determine if an enhanced antiviral effect with combinations of 3TC and famciclovir (FCV, oral prodrug of penciclovir) could be demonstrated in vivo using the Woodchuck Hepatitis Virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers in previous studies by our laboratories.

Effect of eliminating compensation for pain and suffering on the outcome of insurance claims for whiplash injury.

Background And Methods: The incidence and prognosis of whiplash injury from motor vehicle collisions may be related to eligibility for compensation for pain and suffering. On January 1, 1995, the tort-compensation system for traffic injuries, which included payments for pain and suffering, in Saskatchewan, Canada, was changed to a no-fault system, which did not include such payments. To determine whether this change was associated with a decrease in claims and improved recovery after whiplash injury, we studied a population-based cohort of persons who filed insurance claims for traffic injuries between July 1, 1994, and December 31, 1995.

Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent.

Preclinical aspects of a potent anti-hepatitis B virus (HBV) L-nucleoside, 1-(2-fluoro-5-methyl-beta-L-arabino-furanosyl)uracil (L-FMAU) are described. L-FMAU was prepared from L-ribose derivatives via either L-xylose or L-arabinose. L-FMAU shows potent antiviral activity against hepatitis B virus (EC50 5.

Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study.

Objective: Prolonged treatment with antiretroviral drugs results in the selection of HIV-1 variants with mutations conferring resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI) or to protease inhibitors (PI). There is serious concern about transmission of resistant viruses to newly infected persons. This study monitored the prevalence of resistant viruses in individuals undergoing primary HIV infection.

Is a lifetime history of neck injury in a traffic collision associated with prevalent neck pain, headache and depressive symptomatology?

The objective of this study is to determine whether independent associations exist between a history of neck injury related to a motor vehicle collision and: (1) graded neck pain in the past 6 months; (2) headaches in the past 6 months and; (3) depressive symptomatology during the past week. We used data from the Saskatchewan Health and Back Pain Survey, a population-based cross-sectional survey mailed to a stratified random sample of 2184 Saskatchewan adults aged 20-69 years. Fifty-five percent of the eligible population participated.

Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection.

Acute hepadnavirus infections either resolve or progress to chronicity. Factors that influence chronicity as an outcome of hepatitis B virus (HBV) infection in humans can be studied experimentally in the woodchuck model. Accordingly, several woodchuck hepatitis virus (WHV) inocula were characterized.

Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses.

Mutations in the dystrophin gene (DMD) and in genes encoding several dystrophin-associated proteins result in Duchenne and other forms of muscular dystrophy. alpha-Dystroglycan (Dg) binds to laminins in the basement membrane surrounding each myofibre and docks with beta-Dg, a transmembrane protein, which in turn interacts with dystrophin or utrophin in the subplasmalemmal cytoskeleton. alpha- and beta-Dgs are thought to form the functional core of a larger complex of proteins extending from the basement membrane to the intracellular cytoskeleton, which serves as a superstructure necessary for sarcolemmal integrity.

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus.

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus.

The Saskatchewan health and back pain survey. The prevalence of low back pain and related disability in Saskatchewan adults.

Study Design: Population-based, cross-sectional, mailed survey.

Objectives: To determine the lifetime, 6-month period, and point prevalence of low back pain and its related disability among Saskatchewan adults and to investigate the presence and strength of selective response bias.

Summary Of Background Data: There have been many reports of the prevalence of low back pain in different populations, and the estimates vary widely depending on case definition.

The Saskatchewan Health and Back Pain Survey. The prevalence of neck pain and related disability in Saskatchewan adults.

Study Design: Population-based, cross-sectional mailed survey.

Objective: To determine the lifetime, period, and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias.

Summary Of Background Data: In Europe, the lifetime and point prevalence of neck pain is almost as high as the prevalence of low back pain.

Antiviral activity and toxicity of fialuridine in the woodchuck model of hepatitis B virus infection.

Woodchucks were used to study the antiviral activity and toxicity of fialuridine (FIAU; 1,-2'deoxy-2'fluoro-1-beta-D-arabinofuranosyl-5-iodo-uracil). In an initial experiment, groups of six chronic woodchuck hepatitis virus (WHV) carrier woodchucks received daily doses of FIAU by intraperitoneal injection for 4 weeks. At 0.

Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope.

Patients receiving orthotopic liver transplantation (OLT) because of type D hepatitis frequently exhibit what appears to be an autonomous, or "isolated," hepatitis D virus (HDV) infection following the transplantation, with no evidence of hepatitis B virus (HBV) in the graft or in the serum. These observations have led to the hypothesis that HBV might not always be required for HDV infection, or that HDV could exist as a latent infection until rescued by HBV. Alternatively, an apparently autonomous HDV infection could be explained by coinfection of a small number of hepatocytes with both viruses following transplantation, with a very low level of HBV expression that supports low-level HDV propagation.

The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus.

The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region.

A study of the diagnostic accuracy and reliability of the Scoliometer and Adam's forward bend test.

Study Design: Study of the diagnostic accuracy and interexaminer reliability of scoliosis diagnostic tests.

Objectives: To estimate the sensitivity, specificity, and predictive value of the Scoliometer (National Scoliosis Foundation, Watertown, MA) and Adam's forward bend test in diagnosing scoliosis, and to determine the interexaminer reliability of the Scoliometer and Adam's forward bend test.

Summary Of Background Data: Exposure to diagnostic radiation in patients with adolescent idiopathic scoliosis may result in a small but significant increase in cancer rates.

Titration of recombinant woodchuck hepatitis virus DNA in adult woodchucks.

In vivo transfection of Eastern woodchucks (Marmota monax) with recombinant woodchuck hepatitis virus (WHV) DNA is effective in inducing virus infection for the study of replication, pathogenicity, and oncogenicity of wild-type and mutated WHV. The one drawback to this procedure is the need for preparation of large amounts of WHV DNA. Reduction of the amount of WHV DNA in the transfection protocol necessary to induce infection would save considerable time and resources.

Hepatic expression of the woodchuck hepatitis virus X-antigen during acute and chronic infection and detection of a woodchuck hepatitis virus X-antigen antibody response.

The expression and localization of the woodchuck hepatitis virus X-antigen (WHxAg) was examined and compared with other markers of a woodchuck hepatitis virus (WHV) infection using rabbit antisera generated against recombinant WHxAg produced in bacteria. Cellular fractionation studies showed that WHxAg was localized to the soluble and cytoskeletal fractions of the cell when assayed by immunoprecipitation of [35S]-met-cys labeled extracts derived from primary cultures of acute WHV-infected hepatocytes. Immunohistochemical examination of liver from chronic WHV-infected animals showed WHV core antigen (WHcAg) and WHxAg expression in non-neoplastic tissue.

The importance of atrial contribution: a case study of dual-chamber pacing in hypertrophic obstructive cardiomyopathy.

Beta blockers and calcium channel blockers are the mainstay of therapy for hypertrophic obstructive cardiomyopathy. Recent evidence suggests that dual-chamber pacing may also relieve symptoms in a subset of patients. Proper interval programming is critical to the success of this intervention-as well as maintenance of the atrial contribution to preserve left ventricular diastolic filling.

Cloning and characterization of partial cDNAs for woodchuck cytokines and CD3epsilon with applications for the detection of RNA expression in tissues by RT-PCR assay.

Immunologic reagents and methodology are essential to develop further the woodchuck and woodchuck hepatitis virus (WHV) as a model of immune response, inflammation, and immunotherapy in hepatitis B virus (HBV) infection. Partial cDNA clones for the woodchuck CD3epsilon marker of T cells (536 bp) and for selected woodchuck cytokines were developed, including IL-1beta (332 bp), IL-2 (249 bp), IL-4 (205 bp), IL-10 (476 bp), IFN-gamma (476 bp), and TNF-alpha (381 bp). This panel of markers includes sets to measure RNAs for T cells (CD3epsilon), immune response induction (IL-1beta, IL-2), TH subsets (TH1, IL-2/IFN-gamma vs.