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Tom Gallucci - Merrill Lynch - Analyst On the sale margin statement that it was actually up year-over-year, is that adjusted for any sort of a mix or is that just pure cell margin applesto-apples? John Hammergren - McKesson Corporation - Chairman, President, CEO Well, there's always mix in all of our ratios and so that clearly has some mix in it, but I would say if anything, our mix is always working a little bit against us because our largest segment is probably less profitable than our slower growing smaller segments, and so we're always battling against growing our warehouse business or growing our large chain business which is frankly a drag on those ratios. Tom Gallucci - Merrill Lynch - Analyst Okay, thank you. John Hammergren - McKesson Corporation - Chairman, President, CEO Yes. Operator Next question comes from Ricky Goldwasser from UBS. Your line is open, ma'am. Ricky Goldwasser - UBS - Analyst Yes, good evening. 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Research Support ongoing or completed during last three years ; : 5-K23-HL03996-03 Margolis ; 6 1 99-5 NIH Mentored Patient-Oriented Research Career Development Award K-23 ; This award aims to encourage research-oriented clinicians to develop independent research skills, and gain experience in advanced methods and experimental approaches towards conducting patient-oriented research. The title of the award is "Program to Improve the Treatment and Control of Hypertension". Ongoing work in a managed care organization has addressed the following areas relevant the feasibility of conducting a clinical trial: 1 ; Determining knowledge, attitudes and beliefs among primary care physicians regarding hypertension management; 2 ; Conducting focus groups and interviews with primary care physicians, clinic managers and patients to identify appropriate interventions; 3 ; Testing the ability to identify patients with hypertension through data systems; and 4 ; Validating methods for comparing hypertension control between study arms. N01-WH-3-2101 Margolis ; 3 1 94-8 NIH Women's Health Initiative WHI ; This is a study of post-menopausal US women age 50-79 with randomization to hormone replacement, dietary intervention, and calcium vitamin D supplementation. Role: Principal Investigator ; Margolis ; 6 1 96-5 Wake Forest Univ. School of Medicine. Dissolution Assays From Slabs Figure 2 shows the DIL.HCl released at 37C and pH 7.2 as a function of the time from the whole range of copolymer composition. All of them have almost the same initial drug 4.

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25 platelet-derived growth factor PDGF ; , which is also involved in the growth of gliomas and other forms of cancer e.g., small-cell lung cancer ; . Laboratory research has supported the importance of this similarity in that gleevec has been shown to strongly inhibit glioma growth, with the result that gleevec currently is being studied in clinical trials involving gliomas. Because it has approval for its usage for leukemia, the drug is also available outside of clinical trials. There now have been a number of studies reporting its use with high-grade gliomas. When used as a single agent it appears to have minimal activity, as one study reported a PFS-6 value of only 11%, accompanied by an increased risk of intracranial hemorrhaging 72 ; , although another study, using different dosage levels, did report a number of tumor regressions, which they reported occurred very gradually over time 73 ; . More promising results have been reported when gleevec is combined with hydroxyurea, an older drug that at one time was believed to be a radiation sensitizer among other functions. In the initial trial 74 ; with this combination, performed in Germany, 5 of 14 patients with recurrent glioblastomas had tumor regressions, another 5 had stable disease and 4 had disease progression. A more recent study 75 ; confirmed this activity and reported a PFS-6 value of 32%, with 4 of 30 patients alive without evidence of tumor progression over two years after the initiation of treatment. Yet another study, done in the USA, 76 ; produced a PFS-6 value of 27%. This level of efficacy is superior to that of temodar when used in the setting of recurrent tumors, although there has been no direct comparison of the different protocols for patients receiving their initial treatment after diagnosis It is possible that hydroxyurea is not the ideal chemotherapy agent to combine with gleevec. An alternative would be daily low-dose temodar, which has impressive efficacy in its own right as a single agent. An interesting variation in the use of gleevec has been to begin its use for patients whose tumors have stabilized from prior treatment. Thirty patients whose tumors had been stable for 6 weeks received the gleevec hydroxyurea combination 77 ; , which produced a PFS-6 value of 60% and an 18-month overall survival rate of 53%. A second variation in the use of gleevec was to restrict its usage for patients with recurrent tumors who tested positive for overexpression of the plate-derived growth.
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The aqueous leaf extract of Pyrenacanthia Staundtii 100.0 400.0 mg kg, i.p ; . exhibited a significant and dose-dependent analgesic activity in the acetic-acid induced writhing activity in mice Table 1 ; . The possible effect of P. staundtii was evaluated by its effect on paw licking induced by formalin. The test possesses two distinct phases, reflecting different types of pain Elisabetsky et al., 1995 ; . The early phase reflects a direct effect of formalin on nociceptors neurogenic pain ; whereas the late phase reflects tissue injury or inflammatory pain Hunskar and Hole 1987, Elisabetsky et al., 1995 ; . The extract produced significant anti-nociceptive effect in both phases Table 2 ; . This probably suggests or indicates that the extract exerts its analgesic effect through both peripheral inhibitory actions on released prostagladins inflammatory pain ; and central activity relates to antagonistic action of the nociceptors neurogenic pain ; . Goodman and Gilman 1996 ; The extract was further tested for anti-convulsant activity and potentiation of hexobarbitone induced sleep. Pretreatment of animals with 400 mg kg of the extract and injection of strychnine 3 mg kg i.p ; showed 40% protection against strychnine-induced convulsion Table 3 ; . However, treatment with pictrotoxin 10 mg kg i.p ; did not afford any protection Table 4 ; . Strychnine has been shown to induce convulsion by modulation of action of glycine on inhibitory neurotransmitter Zbinderg and Randall 1967, Curtis et al., 1971, Ryall 1975, Gnyther and Curtis 1986 ; . However, the extract blocked the convulsion induced by strychnine indicating the involvement of glycinergic transmission. Picrotoxin is reported as GABA receptors antagonist Costa et al., 1975; Macdonald and Maclean, 1982 ; inducing convulsion, but the extract failed to block the convulsion induced by this agent. This indicates that the extract is not facilitating the GABA-ergic transmission. Treatment of animals with extract caused potentiation of hypnotic effect produced by hexobarbitone Table 5 ; . Sedation in animals with extract increases with the dose. Thus, on. Founded by William J. Gies in 1919. Official publication of the International Association for Dental Research and all of its Divisions. The Journal is owned and managed by the American Association for Dental Research, liii Fourteenth St., NW, Suite 1000, Washington, D.C. 20005. Telephone 202 ; 898-1050. FAX 202 ; 789-1033. The Journal of Dental Research is dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry and to the oral cavity and associated structures in health and disease. Editor All manuscripts and manuscript correspondence should be addressed to: The Editor, Dr. C. Dawes, JOURNAL OF DENTAL RESEARCH, Dept. of Oral Biology, Faculty of Dentistry, University of Manitoba, 780 Bannatyne Ave., Winnipeg, MB, Canada R3E 0W2, Telephone: 204 ; 788-6614. FAX 204 ; 783-9551. Articles are accepted only if they are contributed solely to this Journal. For current "Instructions to Authors", refer to the December, 1990, issue of the.

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