Inflammatory ocular disease is an important cause of blindness and uveitis accounts for 1.0% of blind patients in Canada.¹ This disease can be particularly troublesome to treat, because the nature of the causal factor or factors and mechanisms of progressi n are usually unknown. Non-specific anti - inflammatory agents have been used orally and systemically with some success to treat uveitis, ²⁻⁸ but they may produce serious side effects both locally and elsewhere in the body.⁹̛¹²̛¹⁴ With prolonged use tolerance to these drugs may develop , making them ineffective. Recently a powerful immuno suppressive agent, Cyclosporine (Cy), used orally and systemically in the treatment of uveitis has shown promising results.¹⁶⁻¹⁹̛²⁸ However, its routine use is limited because of a narrow therapeutic index and renal toxicity. Several studies have shown that subconjunctival injection of a number of antineoplastic agents enhanced ocular absorption ²⁰⁻²⁴ in a traditional pharmacological sanctuary,¹³̛¹⁴ and circumvented the associated systemic side effects. Therefore, if Cy were administered subconjunctivally it might be possible to avoid the side effects associated with the oral and systemic routes, and at the same time provide higher levels of Cy to the eye. A protocol for the administration of Cy subconjunctivally was developed in New Zealand white rabbits, to study toxicity, ocular pharmacokinetics following equidose administration subconjunctivally and systemically and the effects of Cy on an animal model of uveitis. Subconjuntival administration of 5mg of Cy in O.lcc (Sandimmune I.V.(R) 50 mg/ml) weekly was found to be the maximum tolerated dose by the rabbitsˈ eye, and was superior to intravenous injection for ocular penetration while minimizing systemic exposure. The uveitis model showed that Cy was effective in reducing the inflammatory response and the earlier the application of Cy the milder the uveitis. The results from our study support the contention that local administration of Cy would lead to higher levels of Cy absorption and circumvent the side effects of systemic administration. This may facilitate the routine use of Cy in ocular inflammatory disease. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Orientadores: Andre Deeke Sasse, Carmen Silvia Passos Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T13:13:47Z (GMT). No. of bitstreams: 1 Duarte_IgorLemos_M.pdf: 729678 bytes, checksum: 3da7b8934fdc3f3c7776ad13bc0dbd2b (MD5) Previous issue date: 2015 / Resumo: Pacientes com câncer de mama localmente avançado são de alto risco para recidiva após ressecção cirúrgica com intuito curativo. Muitos estudos têm sido realizados na tentativa de se descobrir alguma intervenção adjuvante capaz de reduzir este risco. No entanto, há, na literatura atual, controvérsias no que tange a melhor estratégia terapêutica neste cenário. Discordância entre intensidade de dose e densidade de dose ainda permeiam o tema. O objetivo desta revisão sistemática foi avaliar o exato papel da quimioterapia em dose densa nas pacientes portadoras de câncer de mama local. Foram comparados os efeitos da quimioterapia em dose densa com quimioterapia convencional em pacientes com câncer de mama localizado ou loco-regionalmente avançado. Os desfechos clínicos avaliados foram sobrevida global (SG), sobrevida livre de doença (SLD) e toxicidades severas. A análise dos dados extraídos foi realizada no programa estatístico Review Manager 5.0 (RevMan 5; Cochrane Collaboration Software). As diferentes estratégias de tratamento adjuvante foram avaliadas em conjunto e separadamente. Quatro estudos (3418 pacientes) foram incluídos. A metanálise demonstrou que quimioterapia em dose densa pode melhorar a sobrevida livre de doença (3356 pacientes; HR 0,83; 95% IC 0,73-0,95; p 0,0005), independente do status de expressão hormonal. Não houve benefício em sobrevida global (3356 pacientes, HR 0,86; IC 95% 0,73-1,01; p 0,006), independente do status de receptor hormonal (SG no subgrupo hormônio positivo HR 0,94; 95% IC 0,74-1,21; SG no subgrupo hormônio negativo HR 0,78; IC 95% 0,62-0,99; p 0,28). Regimes em dose densa causaram pequeno aumento em mucosite, porem sem impacto em eventos cardíacos, leucemia ou mielodisplasia. Em conclusão, a quimioterapia adjuvante em dose densa pode melhora sobrevida livre de doença em pacientes com câncer de mama localizado com pouco impacto na segurança. Entretanto não há claro benefício em sobrevida global. Novas pesquisas podem indicar se há algum impacto em sobrevida global, não verificada atualmente em função do tamanho da amostra, e possivelmente qual grupo de pacientes teria maior benefício / Abstract: Patients with locally advanced breast cancer are at high risk for recurrence after surgical resection with curative intent. Many studies have been conducted in an attempt to discover some adjuvant intervention can reduce this risk. However, there is, in the current literature, controversies regarding the best therapeutic strategy in this scenario. Disagreement between dose intensity and dose density still permeate the theme. The aim of this systematic review was to assess the exact role of dose dense chemotherapy in patients with local breast cancer. The effects of dose dense chemotherapy with conventional chemotherapy in patients with localized breast cancer or loco-regionally advanced were compared. The clinical endpoints were overall survival (OS), disease-free survival (DFS) and severe toxicities. The extracted data was performed in Review Manager 5.0 (RevMan 5, Cochrane Collaboration Software) statistical program. The different strategies of adjuvant treatment were evaluated together and separately. Four studies (3418 patients) were included. The meta-analysis showed that dose dense chemotherapy in improvements can free survival (3356 patients, HR 0,83, 95% CI 0,73 to 0,95, p 0,0005), regardless of the status of hormone expression. There was no benefit in overall survival with chemotherapy dose dense (3356 patients, HR 0,86, 95% CI 0,73 ? 1:01, p 0,006), independent of hormone receptor status d (SG subgroup hormone positive HR 0,94, 95% CI 0,74 ? 1:21, SG in the subgroup negative hormone HR 0,78, 95% CI 0,62 ? 0.99, p 0:28). Regimes in dense dose caused small increase in mucositis, however no impact on cardiac events, leukemia or myelodysplasia. DD adjuvant chemotherapy may improve disease-free survival in patients with early breast cancer with little impact on safety. However there is no clear benefit in overall survival. New research may indicate whether there is any impact on overall survival, not currently seen as a function of sample size, and that group of patients will benefit most / Mestrado / Clinica Medica / Mestre em Clinica Medica

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This study investigated the influence of tobacco use on postoperative narcotic requirements of female patients following pelvic surgery. The history of tobacco use was taken by telephone survey, and the amount of postoperative narcotic used was obtained from a retrospective review of the patients’ hospital charts. Postoperative narcotic use for patients who never smoked was 10.9 mg/12 hr (n = 83, S.E. = 0.5), for former smokers was 13.0 mg/12 hr (n = 33, S.E. = 0.8) and for current smokers was 13.1 mg/12 hr (n = 53, S.E. = 0.7). Patients who never smoked used significantly less narcotic than former smokers (p =.02) or current smokers (p =.007). There was no difference between current and former smokers. Patients who have smoked required more narcotic for postoperative pain control. This effect was equally strong for former as for current smokers.

Purpose: To show the necessity of distinguishing several patterns of drug prescribing that may lead to co-medication. It is demonstrated how these different patterns can be investigated using large databases containing pharmacy data or reimbursement data. Methods: Two examples illustrate how the particular pattern of co-medication studied will influence the reported proportion of patients having co-medication, the use of antidepressants among people using anticonvulsants, and the use of antihistamines among people receiving penicittines. Results: Depending on definition and period considered, the percentage of anticonvulsant users co-medicated with antidepressants ranged from 5.8% (95%CI 5.0%, 6.8%) to 14.5% (95%CI 13.2%, 15.9%) in 2000. Comparing 2002 with 2000, the ratio of proportions ranged from 1.3 to 2.1. The percentage of people who received penicillines and were co-medicated with antihistamines ranged from 0.5% (95%CI 0.4%, 0.6%) to 9.7% (95%CI 9.3%,10.2%) in 2000. Comparing 2002 with 2000, the ratio of proportions ranged from 1.2 to 1.6. Conclusion: The co-medication patterns investigated yielded clinical as well as statistically significant different estimates. The estimates differed up to a factor 2.5 for the drugs usually prescribed for long periods, and a factor 12 for drugs prescribed for short periods. Hence, we propose to distinguish the patterns 'co-prescribing', 'concomitant medication,' and 'possibly concurrent medication.' The research question determines the co-medication pattern of interest, and the drug and disease under study determine the time window.

This review summarizes and updates data presented at recent annual Southern Medical Association conferences on postmenopausal osteoporosis. As part of any osteoporosis treatment program, it is important to maintain adequate calcium and 25-hydroxyvitamin D levels either through diet or supplementation. Among the available pharmacologic therapies, the bisphosphonates alendronate and risedronate have demonstrated the most robust fracture risk reductions- approximately 40 to 50% reduction in vertebral fracture risk, 30 to 40% in nonvertebral fracture risk, and 40 to 60% in hip fracture risk. Ibandronate, a new bisphosphonate, has demonstrated efficacy in reducing vertebral fracture risk. Salmon calcitonin nasal spray and raloxifene demonstrated significant reductions in vertebral fracture risk in pivotal studies. Teriparatide significantly reduced vertebral and nonvertebral fracture risk. Drugs on the horizon include strontium ranelate, which has been shown to reduce vertebral and nonvertebral fracture risk, and zoledronic acid, an injectable bisphosphonate that increased bone density with once-yearly administration.

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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18683号 / 医博第3955号 / 新制||医||1007(附属図書館) / 31616 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 岩田 想, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM