Immunogenicity in humans of an edible vaccine for hepatitis B

A double-blind placebo-controlled clinical trial evaluated the immunogenicity of hepatitis B surface antigen (HBsAg) expressed in potatoes and delivered orally to previously vaccinated individuals. The potatoes accumulated HBsAg at approximately 8.5 microg/g of potato tuber, and doses of 100 g of tuber were administered by ingestion. The correlate of protection for hepatitis B virus, a nonenteric pathogen, is blood serum antibody titers against HBsAg. After volunteers ate uncooked potatoes, serum anti-HBsAg titers increased in 10 of 16 volunteers (62.5%) who ate three doses of potatoes; in 9 of 17 volunteers (52.9%) who ate two doses of transgenic potatoes; and in none of the volunteers who ate nontransgenic potatoes. These results were achieved without the coadministration of a mucosal adjuvant or the need for buffering stomach pH. We conclude that a plant-derived orally delivered vaccine for prevention of hepatitis B virus should be considered as a viable component of a global immunization program.     

A survey of health care practitioners’ knowledge of the QT interval

OBJECTIVE: To assess health care practitioners' ability to correctly measure the QT interval, and to identify factors and medications that may increase the risk of QT-interval prolongation and torsades de pointes. DESIGN: A cross-sectional analysis of a survey administered between April 2002 and March 2003. PARTICIPANTS AND SETTING: Health care practitioners attending Grand Rounds Conferences at 6 academic institutions in the United States in internal medicine and psychiatry and at 6 community hospitals in the same geographical areas as the academic institutions. INTERVENTION: Anonymous, self-administered questionnaire that included 20 questions on the QT interval. MEASUREMENTS AND MAIN RESULTS: Of approximately 826 attendees, 517 (63%) completed the survey. Of about 608 attendees of internal medicine conferences, 371 (61%) responded, and of about 208 attendees of psychiatry conferences, 146 (67%) responded. Of a total number of 20 questions, the median number of correct answers for the whole group was 10 (interquartile range 7-13). The median number of correct answers for internists was 12 (interquartile range 9-13), for psychiatrists 10 (interquartile range 7-13), and for other specialists 10 (interquartile range 5-13). Respondents who graduated between 1990 and 1999 and academicians performed significantly better overall than other respondents. Of the 517 respondents, 224 (43%) measured the QT interval correctly. Physicians in training and academicians were more likely to measure the QT interval correctly. CONCLUSION: The majority of health care practitioners cannot correctly measure the QT interval and cannot correctly identify factors and medications that can prolong the QT interval. Our findings suggest that greater attention to the QT interval is warranted to ensure safer use of QT prolonging medications.     

Human immunodeficiency virus-infected monocyte-derived macrophages express surface gp120 and fuse with CD4 lymphoid cells in vitro: a possible mechanism of T lymphocyte depletion in vivo.

Monocyte-derived macrophages (MDM) infected in vitro with a macrophage-tropic strain of human immunodeficiency virus (HIV) fused with uninfected, CD4-expressing T lymphoblastoid cells, but not with a subclone of these cells lacking surface CD4. Infected MDM also fused with uninfected autologous and heterologous MDM. Recombinant soluble CD4 protein (rsCD4) (10 micrograms/ml) and full-length recombinant glycosylated gp120 (20 micrograms/ml) each inhibited fusion by 94-99%; the inhibition was dose-dependent. The N-terminal portion of gp120 did not inhibit syncytium formation. Fusion was also inhibited by a monoclonal antibody to an epitope which binds gp120 (S3.5), but not by antibody to an epitope not involved in gp120 binding (OKT4). HIV-infected MDM specifically bound fluorescein-conjugated rsCD4, and virus could be visualized budding from the surface of these cells. HIV-infected MDM express viral gp120 on their surface and fuse with CD4-bearing cells in a fashion similar to lymphoid cells. Macrophages may contribute to CD4 lymphocyte depletion in vivo by this fusion mechanism.     

Moving beyond randomized controlled trials in the evaluation of compulsory community treatment

Compulsory community treatment for people with severe mental illness remains controversial due to conflicting research evidence. Recently, there have been challenges to the conventional view that trial‐based evidence should take precedence. This paper adds to these challenges in three ways. First, it emphasizes the need for critiques of trials to engage with conceptual and not just technical issues. Second, it develops a critique of trials centred on both how we can have knowledge and what it is we can have knowledge of. Third, it uses this critique to develop a research strategy that capitalizes on the information in large‐scale datasets.     

Drawbacks of GENEHUNTER for larger pedigrees: application to panic disorder

Large pedigrees can pose a problem for GENEHUNTER linkage analysis software. Differences in two-point and multipoint lodscores were observed when comparing GENEHUNTER to other linkage software. Careful consideration must be given when selecting linkage analysis programs. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:781-783, 2000.     

Lipopolysaccharide induces biochemical alterations in chicks trained on the passive avoidance learning task

We have recently shown that activation of the immune system with lipopolysaccharide (LPS) results in memory-processing deficits for the passive avoidance learning task in the day-old chick. The current study examined two important issues in understanding the mechanisms underlying these memory deficits associated with immune system activation, namely, whether LPS (1) impairs Na(+)/K(+)-ATPase functioning and (2) increases corticosterone (CORT) concentrations in chicks trained on the task. As the effects of LPS on sickness behavior have only previously been characterized in older chickens, this study also tested whether LPS is able to produce similar alterations in day-old chicks. LPS decreased brain Na(+)/K(+)-ATPase activity and increased plasma concentrations of CORT in chicks trained on the passive avoidance learning task. These findings give an insight into some of the mechanisms that may be responsible for the LPS-induced memory-processing deficits. Consistent with previous research in older chickens, LPS increased body temperature in a dose-dependent manner, however, only the lowest dose of LPS tested significantly decreased food intake in the day-old chicks.     

Providing competency-based family medicine residency training in substance abuse in the new millennium: a model curriculum

Background  

This article, developed for the Betty Ford Institute Consensus Conference on Graduate Medical Education (December, 2008), presents a model curriculum for Family Medicine residency training in substance abuse.