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Biomedical subjects

A W Tucker

Publications and source records attributed to A W Tucker.

12 recordsLinked to original sources
PubMed1998

Cost-effectiveness analysis of a rotavirus immunization program for the United States.

CONTEXT: Rotavirus is the most common cause of severe diarrhea in children, and a live, oral vaccine may soon be licensed for prevention. OBJECTIVE: To estimate the economic impact of a national rotavirus immunization program in the United States. DESIGN: Cost-effectiveness was analyzed from the perspectives of the health care system and society. A decision tree used estimates of disease burden, costs, vaccine coverage, efficacy, and price obtained from published and unpublished sources. INTERVENTION: The proposed vaccine would be administered to infants at ages 2, 4, and 6 months as part of the routine schedule of childhood immunizations. MAIN OUTCOME MEASURES: Total costs, outcomes prevented, and incremental cost-effectiveness. RESULTS: A routine, universal rotavirus immunization program would prevent 1.08 million cases of diarrhea, avoiding 34000 hospitalizations, 95000 emergency department visits, and 227000 physician visits in the first 5 years of life. At $20 per dose, the program would cost $289 million and realize a net loss of $107 million to the health care system-$103 per case prevented. The program would provide a net savings of $296 million to society. Threshold analysis identified a break-even price per dose of $9 for the health care system and $51 for the societal perspective. Greater disease burden and greater vaccine efficacy and lower vaccine price increased cost-effectiveness. CONCLUSIONS: A US rotavirus immunization program would be cost-effective from the perspectives of society and the health care system, although the cost of the immunization program would not be fully offset by the reduction in health care cost of rotavirus diarrhea unless the price fell to $9 per dose.

Child↗
PubMed1997

Characterization of pigs transgenic for human decay-accelerating factor.

BACKGROUND: To prevent the central role played by complement activation in the hyperacute rejection of pig organs transplanted into primates, pigs transgenic for human decay-accelerating factor (HDAF) have recently been produced. The data presented here extend previous immunohistochemical findings by documenting the immunological characterization and the levels of expression of HDAF in these transgenic pigs. METHODS: Animals from 30 independently derived lines were included in this study. HDAF expression was characterized by immunoprecipitation and epitope mapping. Quantitative analysis was performed by radiometric assays followed by Scatchard analysis and by double-determinant radioimmunoassay. Deposition of iC3b on porcine aortic endothelial cells was determined by radioimmunoassay. DNA slot-blot analysis and densitometric scanning were used to evaluate HDAF transgene copy number. RESULTS: The integrity of HDAF expressed by these transgenic pigs could be demonstrated. HDAF was present in 72% of the organs analyzed, although considerable variation in expression occurred, both between animals and within the same pig. High levels of HDAF on porcine aortic endothelial cells resulted in iC3b deposition at levels as low as that detected on human endothelial cells. Twenty-six organs expressed levels of HDAF greater than those observed in the equivalent human tissue. HDAF expression did not correlate with the number of copies of the transgene incorporated into the porcine genome. CONCLUSIONS: Transgenic pigs, which express levels of functional HDAF even greater than those observed in humans, have successfully been produced. Pigs transgenic for human complement inhibiting molecules could represent a source of organs for future clinical xenotransplantation.

Animals↗
PubMed1995

Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs. A potential approach for preventing xenograft rejection.

Since complement-mediated hyperacute rejection of xenografts prevents the use of pigs as organ donors to man, the development of transgenic animals expressing species-specific complement inhibitors could provide a strategy for overcoming hyperacute rejection. The complement inhibitor, human decay-accelerating factor (hDAF), prevents the assembly of C3 and C5 convertases. In this article, the first histologic analysis of hDAF expression in pig tissues, specifically expression in endothelial cells of pigs transgenic for hDAF, is described. Twenty-seven transgenic pigs were categorized into 4 groups based on the expression patterns in endothelial, vascular smooth muscle, and squamous epithelial cells of skin biopsy specimens. Skin biopsy specimens permitted evaluation of the pigs without the need to kill them or to perform invasive procedures. Sixteen cases demonstrated endothelial cell staining. Complete necropsy evaluation, available in 14 of the 27 pigs, correlated with the skin biopsy specimen expression of hDAF. The immunoperoxidase data matched identically with the presence of the mRNA transcript in 25 of the 26 cases where RNA data were available. Also, the staining patterns of 6 transgenic pig founders and their 9 offspring (total of 9 founder-offspring pairs) correlated. Since transgenes are variably expressed in different cell types and since tissue lysates represent a melange of cell types, histologic evaluation for protein expression in tissues from transgenic animals will be critical if they are to be bred to become clinical organ donors. In addition to endothelial expression of hDAF, its expression on vascular smooth muscle cells may be important in preventing tissue damage when breaks in the endothelium occur.

Animals↗
PubMed1986

Report of the 1984 ASHA membership survey.

The results of the most recent American School Health Association (ASHA) membership survey, conducted by ASHA to retain its continuing education units provider status granted in 1981 by the American Nurses' Association are reported. Results of the 1984 survey are compared to two previous surveys, conducted in 1980 and 1982. Topics examined include membership demographics, attendance at national meetings, continuing education needs and preferences, maintaining professional competence, professional issues of importance to readers, and options for improving the usefulness of the Journal of School Health. Several membership trends are discussed and implications for future planning are noted.

Data Collection↗
PubMedDate not supplied

Complement activation, its consequences, and blockade by gene transfer.

The success of xenotransplanting vascularized pig organs into humans is limited owing to the immediate immune reaction, termed hyperacute rejection (HAR). This reaction is primarily mediated by naturally occurring xenoreactive antibodies binding to the graft and activating the complement system, resulting in organ dysfunction. Pig membrane-bound complement regulatory proteins efficiently control autologous complement only and are unable to protect against human complement-mediated damage. One line of current research to overcome HAR of pig organs involves the expression of human complement regulatory proteins by pig cells. In vitro data have demonstrated that pig endothelial cells expressing human regulators of complement activation (RCAs) are resistant to human complement-mediated attack, which has led to the successful production of pigs transgenic for human RCAs. Ex vivo perfusion studies using fresh human blood with organs from these animals has shown an improvement in graft function and survival through expression of human RCAs compared to that of nontransgenic pig organs. Similar results have been observed in primate models, where expression of human RCA proteins on the pig donor organ has resulted in protection against HAR and prolongation of graft survival. The initial complement-mediated immunologic barrier of HAR has been overcome through this genetic incorporation of human RCAs into pigs, and it is now possible to study the subsequent mechanisms of xenograft rejection in the pig-to-human combination.

Acute Disease↗