Discussing gene-gene interaction: warning--translating equations to English may result in jabberwocky

Interest in mapping susceptibility alleles for complex diseases, which do not follow a classic single-gene segregation pattern, has driven interest in methods that account for, or use information from one locus when mapping another. Our discussion group examined methods related to epistasis or gene x gene interaction. The goal of modeling gene x gene interaction varied across groups; some papers tried to detect gene x gene interaction while others tried to exploit it to map genes. Most of the 10 papers summarized here applied newly created or newly modified statistical methods related to gene x gene interaction, while two groups primarily examined computational issues. As is often the case, comparisons are complicated by little overlap in the data used across the papers, and further complicated by the fact that the available data may not have been ideal for some gene x gene interaction methods. However, the main difficulty in comparing and contrasting methods across the papers is the lack of a consistent statistical definition of gene x gene interaction. But despite these issues, two clear trends emerged across the analyses: First, the methods for quantitative trait gene x gene interaction appeared to perform very well, even in families initially ascertained as affected sib pairs; and second, dichotomous trait gene x gene interaction methods failed to produce consistent results. The difficulty of using (primarily) affected sib pair data in a gene x gene interaction analysis is explored.     

Shifting the Paradigm: Toward Integrative Research on Mothers and Children

The mother-child relationship has been examined extensively but most research has centered on maternal characteristics associated with poor childhood developmental outcomes or maternal response to stressors. The "maternal deficit" model has misdirected research and intervention. Research on maternal depression based on the maternal deficit model has resulted in research designs that do not adequately address maternal outcomes. Research must be conceptualized to address parent-child relationships and situational factors that influence them.     

The Relationship Between Social Support and Depression in Adolescents

In a non-clinical, adolescent sample, this correlational study tested the hypothesis that there will be an inverse correlation between perceived social support and depression. This hypothesis is consistent with the theoretical literature. The results suggest that perceived social support is associated with depression in adolescents.     

Adefovir dipivoxil: a new antiviral agent for the treatment of hepatitis B virus infection

BACKGROUND: Hepatitis B virus (HBV) infection is a major problem worldwide and an important cause of chronic liver disease and cirrhosis. Currently available treatments include interferon alfa-2b, lamivudine, and adefovir dipivoxil. Adefovir dipivoxil is an acyclic nucleotide analogue that was developed in part to improve on the limitations of earlier therapies. OBJECTIVE: This article is a review of available data on the clinical pharmacology, virology, efficacy, tolerability, and clinical use of adefovir dipivoxil. METHODS: A search of the English-language literature indexed on MEDLINE from 1966 to July 2003 was performed using the terms adefovir, PMEA, and Bis-POM PMEA. Pertinent abstracts from scientific meetings on infectious diseases and hepatology were also included. The manufacturer of adefovir dipivoxil provided additional information. These materials were supplemented by US Food and Drug Administration briefing documents and other unpublished materials. In vitro and preclinical studies were included in the review, as were Phase II and III clinical trials. RESULTS: In vitro, adefovir dipivoxil concentrations exceed those necessary to inhibit both wild-type and lamivudine-resistant isolates of HBV. In clinical trials, adefovir dipivoxil was clinically and virologically effective in patients in whom lamivudine therapy had failed due to the presence of lamivudine-resistant HBV. The drug was generally well tolerated. The risk of nephrotoxicity, the most notable adverse effect of adefovir dipivoxil at previously used higher doses, has been substantially reduced at the currently recommended dosage of 10 mg/d. CONCLUSION: Based on the data reviewed adefovir dipivoxil is an effective and well-tolerated alternative for the treatment of HBV infection, including disease that is lamivudine resistant.     

The Challenge of Ritualistic Child Abuse

Survivors of ritual abuse have endured physical and psychosexual trauma typically compounded by mind-altering drugs. Some abused children have never known a trustworthy adult to protect them from harm. Children often cope with the anxiety and terror of abuse through psychological defenses such as denial, self-hypnosis, and dissociation, but more extreme responses such as self-mutilation or multiple personalities may occur. Reports of ritual abuse of children are so shocking and bizarre that professionals initially respond with confusion and disbelief (Cozolino, 1989). Nurses need to assess clues and detect symbols of abuse in drawings or flashbacks, to build trust, and to monitor their attitudes and countertransference. Nurses are in a critical position to detect and begin healing wounds of ritual abuse.     

Soluble interleukin 2 receptor and soluble CD8 levels in previously treated human immunodeficiency virus-negative hemophiliacs multiply transfused with a monoclonal antibody-purified factor VIII concentrate

BACKGROUND : Serum levels of the soluble interleukin 2 receptor (sIL-2R) and soluble CD8 (sCD8) may be used as markers of T-cell activation. The course of serum levels of sIL-2R and sCD8 in hemophiliacs who were treated first with an intermediate-purity factor VIII concentrate and then with a monoclonal antibody (MoAb)-purified factor VIII concentrate are reported. STUDY DESIGN AND METHODS : Serum samples taken before the administration of the MoAb-purified concentrate and after 2 and 5 years of its administration to 20 human immunodeficiency virus-negative patients with hemophilia A were analyzed. Eighteen healthy age-matched men were used as controls. RESULTS : The sIL-2R and sCD8 levels were higher in patients treated with intermediate-purity concentrates than in controls (p = 0.006 and p = 0.0005, respectively). The sIL-2R levels showed a decrease after 5 years of treatment with the MoAb-purified concentrate (p = 0.018 for the difference between 2 and 5 years), to levels that were not significantly different from those in controls. Although sCD8 levels tended to decrease at 5 years (p = 0.09, for the difference between 2 and 5 years), they remained higher than those in controls (p = 0.0005 and p = 0.0016 at 2 and 5 years, respectively). The ratio of sCD8 and sIL-2R tended to increase between 2 and 5 years (p = 0.07). The sIL-2R and sCD8 levels were not related to the numbers of T-lymphocytes and HLA-DR-positive T-lymphocytes in peripheral blood. Nor was a relation demonstrated between sIL-2R levels and CD4-positive cell numbers or between sCD8 levels and CD8-positive cell numbers. Although a relation with chronic hepatitis C cannot be excluded, it seems more likely that changes in sIL-2R levels are due to the use of the MoAb-purified concentrate. CONCLUSION : Elevated levels of sIL-2R and sCD8 were found in multiply transfused human immunodeficiency virus- negative hemophiliacs. After treatment was changed to the use of a MoAb- purified concentrate. sIL-2R levels decreased. These findings suggest a change in immune stimulation that is remarkable, because signs of activation in the effector phase seem to have continued despite normalization in the proliferative phase.     

White cells protect donor blood against bacterial contamination

The possible beneficial role of white cells (WBCs) in donor blood has been investigated with respect to their capacity to remove bacteria. Preparations of buffy coat and whole blood, containing as well as reduced of WBCs, were inoculated with Staphylococcus epidermidis, S. aureus, Escherichia coli, Pseudomonas aeruginosa, and Propionibacterium species. Upon storage at room temperature, the presence of WBCs resulted in a reduction of the bacterial content. Units inoculated with S. epidermidis and E. coli were completely cleared of bacteria within 5 to 24 hours. On the other hand, S. aureus, after an initial reduction in number, started to multiply. In WBC-reduced units, the initial bacterial content remained unchanged for 5 hours, but the bacteria then exhibited vigorous growth within 48 hours in buffy coat and slower growth in whole blood. Propionibacterium sp. did not grow with or without WBCs. P. aeruginosa did not grow in buffy coat but showed a growth pattern similar to that of S. aureus in whole blood. The presence of WBCs in the donor blood during the first hours after collection thus seems to rid the blood of at least some species of bacteria. These results indicate that it would be favorable not to perform WBC reduction during blood collection and that several hours of contact can be needed to obtain sterility.