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ACTG ; Mucosal Immunology Focus Group and is involved in the group's efforts to clarify the role of various compartments in HIV pathogenesis. Dr. Anton graduated magna cum laude from Harvard University in 1977 and received his M.D. from Case Western Reserve University in 1983. He did fellowship work at the Cholera Hospital in Bangladesh in 1983 and spent 1981 in a fellowship in pathology at Cleveland's Institute of Pathology. He performed his internship and residency in internal medicine at Bringham and Women's Hospital in Boston, Massachusetts. Dr. Anton began in his work at UCLA in 1986 with a Gastroenterology Fellowship and has been on faculty since 1989.
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652 METABOLISM-BASED DRUG-DRUG INTERACTIONS OF CANDIDATE ANTIMALARIAL DRUGS. Diaz D, Del Valle PL, Melendez V. Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD. The U.S. Army is evaluating analogs of the antifolate, biguanide, tryptanthrin, febrifugine, and artemisinin drug families for development as candidate antimalarial drugs. The objectives of this study were to implement a screening assay for the early assessment of metabolism-based drug-drug interactions DDI ; and determine the potential DDI for candidate drugs. The screening assay involves the use of commercially available human liver microsomes and employs a 96 well plate high-throughput format. It uses specific substrates that are markers for enzymatic activity of the five main CYP450 enzymes 1A2, 2C9, 2C19, and 3A4 ; . Fluorescence of the metabolic product was monitored and the 50% inhibition concentration IC50 ; calculated for each testing compound following the manufacturer recommendations. Criteria to qualify the inhibition results was established before hand; an IC50 lower or equal than 10 M was considered significant; an IC50 between 10 and 50 M was considered moderate; and an IC50 equal or higher than 100 was considered non-significant. A total of thirty-seven analogs from the different families under consideration by our Division were evaluated for metabolism-based DDI. Coefficient of variation was less than 15% for intra- and inter-day variation of the enzyme activity responses. Kinetic studies to explain significant and moderate interactions of selected candidate drugs are in progress. The assay is being used to rank-order analogs for each family of drugs based on their potential for DDI. Liver liabilities such as metabolism-based DDI should be evaluated early in the drug discovery and development process increasing the chance of better drugs to be developed from the beginning. This assay provides feedback for design improvements, optimization and selection of candidate compounds for further development.
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Water as the eluting solvent. The purified product was characterized by elemental analysis as well as by spectroscopic techniques such as, UV-VIS, FT-IR and 1H-NMR spectroscopy. The radiolabeling of the porphyrin derivative was achieved by adding 109Pd DMSO ; 2Cl2 solution to 4 mg of porphyrin derivative dissolved in 0.1 M ammonium acetate buffer pH~5 ; and incubating the resulting mixture at 80C for 15 min after adjusting its pH to ~8. The complex was characterized by paper chromatography PC ; using 25% aqueous acetonitrile and by UV-VIS spectroscopy. Several reaction parameters were varied extensively in order to achieve the optimum protocol for radiolabeling. To determine the tumor specificity of the radiolabeled porphyrin preliminary biodistribution studies were carried out in Swiss mice bearing fibrosarcoma tumors. Results: In PC using 25% aqueous acetonitrile, it was observed that, the 109Pd-porphyrin complex moved towards the solvent front Rf 0.8-1 ; while uncomplexed 109Pd did not move from the point of application Rf 0 ; . maximum complexation yield of ~97% was achieved under optimized conditions. The complex was observed to be stable upto 24 h at room temperature. Results of the biodistribution studies revealed good tumor uptake [ 2.800.57 ; % g] within 30 min post-injection and it remained almost constant till 24 h. Though initially the uptake in blood, liver, intestine and muscles were high, it decreased with progress of time. At 3 h post-injection the tumor blood and tumor muscle ratios were found to be 1.07 and 1.52, respectively which increased to 4.36 and 38.0 at 24 h postinjection. The complex showed predominately renal clearance [ 50.377.48 ; % at 30 min post-injection]. Conclusion: Present studies showed that the 109Pd labeled porphyrin prepared exhibited encouraging results and warrants further investigations. Key Words.
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DECISIONS INVOLVING EXTRAORDINARY MEANS The guardian retains the right to consent to or refuse extraordinary means, such as entry of "do not resuscitate orders" or removal of life support for a ward. To facilitate informed decisions the following information will be necessary: the attending physician's statement affidavit documenting that the ward's condition meets the criteria outlined in G.S. 90-322 and why extraordinary means should be discontinued or withheld; a second opinion from a non-attending physician in the form of a statement affidavit documenting concurrence with the attending physician's statement affidavit; evidence of any advance directives Living Will, Health Care Power of Attorney ; concerning the withholding or discontinuance of extraordinary medical procedures; summary of findings from face to face visit with the ward prior to refusal or authorization that extraordinary means be withheld or discontinued; and a statement or information from the ward's family members regarding the ward's wishes, if known, and their wishes for the ward, when possible and estradiol and diamicron, for instance, diamiron tablets.
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A forum in which a group of lay people put questions about a scientific or technological subject of controversial political or social interest to experts, listen to the experts' answers, then reach a consensus about this subject and finally report their findings at a press conference." Joss and Durant, 1994 ; The lay panel is the main actor in the process, determining the expert panel, determining the questions to be asked, and reaching consensus. The process consists of three steps: education and reception of information on the topic, so that the panel members can formulate specific questions to be explored; processing of information through panel discussions, hearings, and questioning of experts; and group deliberations and findings. Dienel and Renn, 1995; Sclove and Scammel, 1999 ; The process is facilitated by a neutral third party. Results are generally widely distributed in the media and are the basis for further local hearings. Consensus conferences generally address broader issues than normally addressed by experts, and they issue broader recommendations. A Norwegian lay panel on genetically modified foods, for example, found that such foods were not needed because the selection and quality of food was already sufficient and there was too much uncertainty about the potential impacts of these foods on health and the environment. Although cultural diversity and inequities may present challenges in this model, a U.S. consensus conference on telecommunications, convened by the Loka Institute demonstrated that a diverse group of individuals could ask detailed technical questions and issue far-reaching recommendations on highly complex issues. The consensus conference process is one in which "controversial and contested knowledge will be subjected to critical scrutiny, and through which lay citizens affected by a policy topic are provided a central role in framing and assessing the issue, and providing recommendations." Fixdal, 1997 ; Scenario workshops, community planning, and other models Other models for forward-looking decision-making are vehicles for the goal-setting and alternatives assessment that are so important to implementing the precautionary principle. In Europe, several governments have undertaken "scenario workshops" to develop future visions for a country or region. They involve different groups residents, government, academics, business, etc. ; in the assessment of possibilities and needs related to future technological developments. These workshops address broad "how" questions, such as how to develop a sustainable community or how to address toxic contamination. Often goals are set and strategies are developed to achieve those goals. In some European countries - particularly those where workplace co-determination is practiced - workers have been involved in production and workplace design issues. In the U. S., sustainable community planning exercises have been undertaken in various locations. Finally, other models exist such as the planning models of native cultures and groups such as the Amish, who have a long history of democratically choosing technologies. The Massachusetts Precautionary Principle Project is exploring using these and other methods on a statewide level to implement the precautionary principle in environmental health policy. The project is committed to establishing democratic decision-making processes for choosing the safest alternatives to meet our needs. It is building a large, diverse network of health professionals, academics, advocates, and victims of pollution and developing models for organizing toward fundamental environmental policy change. References.
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Using the Oral Analgesic Template This section presents an Oral Analgesic Template that can be used to support clinical decision-making for a variety of operative and non-operative cases. For each example, the template summarizes: 1 ; key variables for clinical decisionmaking and 2 ; oral analgesic regimens presented in stages from immediately after surgery or upon intake, through various in-hospital transition points, to discharge. Progress through these stages is based upon the patient's pain level and ability to tolerate oral medication. A column for Epidural IV Other analgesia is included only to illustrate the relationship between these methods and oral analgesia and to reflect the multimodal nature of acute pain management. Each case example also provides suggested considerations that can be useful in determining appropriate oral analgesia. These cases provide illustrations to help the reader understand the clinical decision-making process, and are not meant to suggest a particular analgesic recommendation for a specific operative or medical condition.
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References: 1 Watt, J.M. and Breyer-Brandwijk, M.G., 1962. The medicinal and poisonous plants of Southern and Eastern Africa. 2nd ed. Livingstone, London 2 Gross, H., Wright, A. D., Beil, W. and Konig, G. M., 2004. Two new bicyclic cembranolides from a new Sarcophyton species and determination of the absolute configuration in sarcoglaucol16-one. Organic Biomolecular and Chemistry, 2004, 2, 1133.
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