Rising health care costs in general and prescribed medicine costs in particular continue to be a concern for U.S. policymakers and consumers of care. Breaking down total prescription drug costs into therapeutic classes and subclasses provides decision makers and the public with an understanding of the costs and extent to which specific therapeutic classes and subclasses of drugs are contributing to the upturn in total costs. This Brief provides trends for one therapeutic subclass of prescribed drugs--dermatological agents. This Brief presents trends in utilization and expenditures for outpatient prescription dermatological agents for the years 1999 and 2008. The estimates are for the U.S. civilian noninstitutionalized population and are derived from the 1999 and 2008 Household Component of the Medical Expenditure Panel Survey (MEPS-HC).

关键词：卫生保健支出;皮肤;皮肤病;药物;平民人口管控

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The definition of a medical device, as reported by Council Directive 93/42/EEC and subsequent amendments and additions, and the definition of medicinal products covered by the amended Directive 2001/83/EC of the European Parliament and of the Council, highlight how these types of products can have a therapeutic effect on humans. It is possible to identify the applicable Community legislation taking into account the main mechanism of action by which the products ensure the activity that determines the therapeutic effect. In the case of a medicinal product the mechanism of action should be pharmacological, immunological or metabolic, while for a medical device the main mechanism of action should not be the same, but it may be assisted by the above mentioned mechanisms. Evaluation of some elements, which help to define what is meant by pharmacological, immunologic and metabolic mechanism of action, is a criterion of discernment for the correct regulatory position of products that have a therapeutic effect on humans.

关键词：医疗设备;药物;评估;边缘产品;指令;欧洲;评价;立法;法规;治疗;药用产品

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This Statistical Brief provides descriptive statistics on expenditures for the top five therapeutic classes of outpatient prescription drugs, ranked by total expenses in 2009 for Medicare beneficiaries age 65 and older in the U.S. civilian noninstitutionalized population. Prescription drug therapeutic classes are defined according to the Multum Lexicon therapeutic classification system (see Definitions). In 2009, 18 broad therapeutic classifications were identified. The estimates presented are derived from the Household and Pharmacy Components of the 2009 Medical Expenditure Panel Survey (MEPS). Expenditures include payments for Medicare beneficiaries ages 65 and older from all sources (e.g., out of pocket, private, and public insurance sources) for outpatient prescription drug purchases during 2009. Insulin and diabetic supplies and equipment are also included in MEPS prescribed medicines estimates. Over-the-counter medicines are excluded from these estimates as are prescription medicines administered in an inpatient setting or in a clinic or physicians office. All differences discussed in the text are statistically significant at the 0.05 level or better.

关键词：处方药;门诊;治疗;成年人;费用;人口;家庭;药物

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Background: Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality. Methods: We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel. Results: Cumulative mortality was 5, 10and 18at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years PY) in those with 8804;50 CD4+ cells/mm3 before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with 8805; 500 CD4+ cells/mm3).

关键词：人类免疫缺陷病毒;抗体;背景;临床医学;咨询;死亡;血红蛋白

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The Center for Medicare Management at the Centers for Medicare and Medicaid Services (CMS) requested this report from the Technology Assessment Program (TAP) at the Agency for Healthcare Research and Quality (AHRQ). AHRQ assigned this report to the ECRI Institute Evidence-based Practice Center (EPC) (Contract Number: HHSA 290-2007-10063).

关键词：创伤和伤害,皮肤(解剖);替代品;治疗;临床医学;治疗;技术评估;组织培养;慢性伤口

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Androgen ablation, or androgen deprivation therapy (ADT), is the mainstay of treatment for patients with locally advanced or metastatic prostate cancer. This therapy is only temporizing, however. Within 3-4 years, the vast majority of patients develop androgen independent prostate cancer (AIPC). Though several new treatments have recently been approved, once a patient develops AIPC, options are less effective, with first line chemotherapy providing only 13-15 month survival.(1) The shift from androgen sensitive prostate cancer (ASPC) to AIPC is a seminal event in disease progression and thus it has been extensively studied. At the center of much of this research is the androgen receptor since many believe that the overexpression, mutation and/or constitutive activation of this receptor play a critical role in the progression from ASPC to AIPC. The chaperone proteins heat shock protein-90 (Hsp90) and Hsp40 are necessary for the correct formation of AR s tertiary structure. Subsequently a second co-chaperone, Cterminal Hsp interacting protein (CHIP), was characterized and found to bind HSP 70 and 90. CHIP contains E3 ligase activity which targets proteins for proteosomal ubiquitination and can also directly bind to a highly conserved portion of AR which increases degradation. In cells where CHIP is overexpressed, AR synthesis is decreased and much of the AR produced has a defective tertiary structure which prevents degradation. The addition of proteosomal inhibitors to the cells, does not restore AR levels to normal, indicating that AR degradation/suppression is occurring by non-proteosomal pathway(s) as well. The role of this study is to better characterize the interaction of CHIP and the androgen receptor and assess its role in disease progression.

关键词：前列腺癌雄激素;基因治疗;;化疗;芯片(电子);缺陷(材料)

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The disproportionate incidence and mortality of prostate cancer (CaP) among African Americans (AA) in comparison to Caucasian American (CA) are not well understood. It is believed that high circulating androgens reported in AA men may account for such racial disparities. It has been shown that metastatic tumors maintain functional androgen receptor signaling, suggesting that local (intracrine) androgens may contribute to the outgrowth of castration- adapted tumors under androgen deprivation therapy (ADT). Evidence exists for direct correlation between increased obesity and body-mass-index (BMI), which is significantly higher in AA-men, and the risk for aggressive CaP. Active steroidogenic pathways are active in adipocytes and adipose-derived mesenchymal stem cells (ASCs) are often recruited to tumor-stroma. Our goal will be to exploit the tumor-tropism of normal ASCs to deliver androgen inactivating genes to tumor microenvironments and enable an effective treatment strategy against CRPC. This will be achieved by: (a) investigate if intracrine production of testosterone by osteotropic ASCAA modulates growth and metastatic potential of CaP cells under ADT in vitro and in vivo; (b) determine if HSD-expressing osteotropic ASCCont will nullify the ADMSCAA-mediated CaP cell growth and metastasis in vitro; and (c) examine the efficacy of therapeutically engineered ASCCont to target and inhibit CaP tumor growth under CRPC in vivo. The proposed work will be innovative, because it capitalizes on an adjuvant approach for ADT by tumor-site specific inactivation of androgens. Considering the aggressive nature CaP, the outcome of our study is expected to have a positive impact on establishing preventive and/or therapeutic intervention strategies to reduce or circumvent PC, especially among AA-men.

关键词：非裔美国人;雄激素;转移;前列腺癌;死亡率;肿瘤

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Histone demethylases are a newly discovered class of non-heme iron enzymes that play an important role in regulating transcription and epigenetic inheritance. We have successfully expressed and purified highly active histone demethylases (HDMs), including the cancerrelevant JMJD2C (GASC1). A detailed enzyme kinetic and inhibition analysis of these HDMs was achieved through a range of fluorescence assays, mass spectrometry, and oxygen consumption measurements. An interesting case of cosubstrate inhibition is observed for these HDMs, with direct relevance to the potential role of alpha-ketoglutarate and HDMs in cancer cells. We have also employed an enzyme-templated approach for specific inhibitor design that takes advantage of the enzyme s substrate specificity. Finally, while the initially tested compounds do not seem to inhibit JMJD2C in MCF7 breast cancer cells, we believe that second generation compounds will be active HDM inhibitors in vivo. The developed specific inhibitors could lead to novel breast cancer therapeutics and can also be used as tools for studying the role of histone demethylases in breast cancer cell proliferation.

关键词：乳腺癌;组蛋白;细胞(生物学);化学试剂;酶;体内分析

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Breast cancer is the most common cancer in women and the second deadliest. There is a great need to finding new targeted therapies and to improve the efficacy of existing therapies. The TNF Related Apoptosis Inducing Ligand (TRAIL) pathway is part of the body s natural tumor surveillance program, preventing formation of tumors and metastasis while sparing normal cells. The TRAIL pathway has been exploited in clinical trials but resistance to TRAIL is common, limiting the efficacy of therapy. The mechanisms underlying TRAIL resistance are largely unknown and there is of yet not a good way to screen for TRAIL sensitivity. We have found that the gene Six1, which is overexpressed in over half of all breast cancers and in as much as 90of metastatic lesions, confers resistance to TRAIL. In addition, by screening a genome wide shRNA library we have identified 4 novel TRAIL resistance gene including the solute carrier family 26 (sulfate transporter), member 2 (SLC26A2). The role of these genes in TRAIL resistance and metastatic spread are being investigated, with the ultimate aim of identifying TRAIL resistance and circumventing it through targeted combination therapies.

关键词：乳腺癌;凋亡;基因;基因;转移;耐药性;治疗

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The overall objective of this project is to develop targeted therapy tools directed against the breast cancer vasculature. We aim to bypass many obstacles in the field by developing a treatment based on the targeting of tumor blood vessels with T cells bearing chimeric immune receptors (CIRs). We have constructed and tested first generation CIR lentiviral vectors targeting hTEM1, which were derived from a panel of scFvs of varying affinity. These constructs signal through CD3 but can be augmented by the addition of costimulatory molecules (CD28 and 4-1BB). In vitro, only T cells bearing the scFv78 CIR were activated upon co-culture with recombinant hTEM1 protein. However, no activation was observed when scFv78 CIR bearing T cells were co- cultured with cells expressing hTEM1 on the surface. Additional strategies, including hinge elongation and the utilization of loadable CIR bearing T cells, also failed to elicit a response against the hTEM1 bearing target cells. We engineered a new yeast-display scFv library from patients with ovarian cancer to isolate a second generation of anti-TEM1 scFvs. We validated a panel of multivalent antibodies for binding to recombinant proteins by ELISA assays.. We have generated CIRs against PSMA using scFv (PZ1) and T cells bearing PZ1 and CD28 produce a robust polyfunctional repertoire of cytokines. A tumor vascular mouse model expressing human TEM1 was developed and PET imaging with (124I)- MORAb-004 indicated TEM1-specific accumulation of antibody. We have established optimized HSV-tk as extra safety and tracer for PET imaging.

关键词：乳腺癌;T淋巴细胞;血管;心血管系统;疾病载体

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