HCV Infection of the Transplanted Liver: Changing CD81 and HVR1 Variants Immediately After Liver Transplantation

The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients. Clones of RT-PCR product were directly sequenced to identify HVR1 quasispecies variants. Explanted liver and serial allograft biopsies in recipients with HCV were examined by immunohistochemistry (IHC) for CD81 expression. Examination of HVR1 sequences demonstrated that only a fraction of the quasispecies variants recovered from each patient's blood sampled immediately prior to transplantation associated with and infected the allografts. Genetic diversity at HVR1 decreased with reperfusion but did not significantly decrease with infection. Expression of CD81 varied during the immediate post-transplant period. In conclusion, HVR1 quasispecies variants differentially associate with, and infect allografts, after liver transplantation. Additionally, allografts express variable amounts of CD81 after transplantation.     

The psychological adjustment of offspring of adults with obsessive-compulsive disorder: a brief report.

This study describes the prevalence of emotional and behavioural problems in the offspring of parents who are members of the Obsessive-Compulsive Neurosis Support Group in South Australia. The results suggest that the offspring of adults with obsessive-compulsive disorder do not have more problems than other children and adolescents in the community. The study also highlights potential benefits of collaborative research conducted by research groups and self-help organisations.     

What Determines Knowledge of Asthma Among Young People and Their Families?

In this analysis, we sought to determine factors that predicted the level of asthma knowledge in a sample of adolescents with asthma and their parents. Eighty-five young people aged 10-24 years attending tertiary care asthma clinics and 46 of their parents answered validated respiratory and asthma knowledge questionnaires. Older adolescents were more knowledgeable about asthma than were younger adolescents (r=0.36, p=0.001). Young people with severe asthma (p=0.015) scored higher on the asthma knowledge questionnaire than those with mild/moderate asthma. Asthma knowledge among young people was related to that of their mothers (r=0.47, p=0.014), however, only age and the asthma knowledge of fathers significantly predicted adolescent asthma knowledge. Adolescents develop increasing autonomy for asthma self-management as they mature, but parents remain an important source of information about asthma for young people.     

A sensitive and specific erythropoietin immunoprecipitation assay: application to pharmacokinetic studies.

Previous pharmacokinetic studies with radiolabeled erythropoietin have relied on results of nonspecific methods to derive pharmacokinetic parameters. Dependence on nonspecific protein precipitation or total radioactivity may result in falsely high determinations of plasma radiolabeled erythropoietin and erroneous determinations of pharmacokinetic elimination and distribution parameters. In the present study pharmacokinetic parameters were derived by using a specific, sensitive, and reproducible immunoprecipitation assay for biologically active iodine 125-labeled recombinant human erythropoietin (125I-rhEp) and compared with those obtained by using nonspecific protein precipitation with trichloroacetic acid (TCA). Tracer amounts of 125I-rhEp were administered by bolus injection to six newborn lambs. Plasma-precipitable radioactivity assayed by the immunoprecipitation method became progressively lower with time relative to those observed with the TCA method. Pharmacokinetic parameters derived from the immunoprecipitation assay demonstrated significantly more rapid plasma and elimination clearances, shorter terminal half-life, shorter mean body residence time, and shorter distribution time when compared with the TCA assay (p less than 0.01). Volume of distribution was not different. Comparison of immunoprecipitation and TCA assay results from gel permeation fractions of iodinated erythropoietin demonstrated that immunoprecipitation assay results provide a better evaluation of biologically active hormone as determined by comparisons with SDS-PAGE and erythropoietin radioreceptor data. We conclude that 125I-rhEp pharmacokinetic parameters derived by using the immunoprecipitation assay more accurately reflect physiologic conditions than do those derived by using TCA precipitation.     

Critical evaluation of three chest radiograph scores in cystic fibrosis.

BACKGROUND--A number of chest radiographic scores have been developed to assess the severity of respiratory disease in cystic fibrosis but critical statistical evaluation has been limited. In particular, the chest radiograph component of the National Institutes of Health (NIH) clinical score has not previously been validated. Three different chest radiograph scores have been compared and the association between them and lung function tests investigated. METHODS--The interobserver and intraobserver variation of the Brasfield, NIH chest radiograph, and the Royal Children''s Hospital (RCH) chest radiograph score was assessed by three observers--a paediatric radiologist, a junior and a senior respiratory physician--who independently scored, on separate occasions, 62 chest radiographs randomly selected from three age strata of patients ranging from 7 to 18 years. Lung function tests were available for 61 patients obtained within three months of the chest radiograph. Two way analysis of variance was used to estimate components of variation in scores. RESULTS--Results were similar for the Brasfield and NIH scores, both of which demonstrated greater precision than the RCH score, but the estimated repeatability of the Brasfield and NIH scores can be expected to differ by up to 20% of the maximum score. The reliabilities (intraclass correlation) are all reasonably high at 0.74, 0.73, and 0.61 for the Brasfield, NIH, and RCH scores, respectively. The estimated correlation between radiographic scores and lung function tests, adjusted for attenuation caused by measurement error, showed a similar correlation for all three scoring methods ranging from 0.55 to 0.78. Correlations were slightly greater with FEV1% than FVC%. These correlations are substantial but not high, indicating that a large proportion of the variability in radiographic scores cannot be explained by lung function measurements. CONCLUSIONS--The Brasfield and NIH chest radiograph scores have very similar statistical profiles and can be equally recommended if a chest radiograph score is to be used. The RCH radiographic score appears to be less reliable. The limitations of these scores need to be understood.