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981.
Long‐term follow‐up of 123 patients with adenocarcinoma of the sinonasal tract treated with endoscopic resection and postoperative radiation therapy 下载免费PDF全文
982.
Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies. As a consequence, therapeutic decisions in these patients are usually complex and subject to uncertainties. In this article, we review the regulatory guidelines to study responses to drugs according to pharmacokinetic variability and the published information that is useful for guiding the dosage adjustment of frequently used drugs in patients with cirrhosis (antivirals, antibiotics, analgesics, etc.) to obtain the best risk-benefit ratio. 相似文献
983.
Tanret I Mangelings D Vander Heyden Y 《Journal of pharmaceutical and biomedical analysis》2008,48(2):264-277
Methacrylate-based monolithic stationary phases were evaluated for the analysis of drug molecules using capillary electrochromatography (CEC) as separation technique. The effect of the polymerization-mixture composition on the retention behavior of a small test set of mainly drug molecules was studied. Two factors were varied in a central-composite design-based approach: the ratio between the pore-forming solvents and the monomers on one hand, and the ratio within the pore-forming solvents on the other hand, resulting in nine different stationary phases. The central point of the design was chosen at 70% (m/m) pore-forming solvents (PFS) of which 30% (m/m) is 1,4-butanediol, i.e. 21% of the total polymerization mixture. Experiments were conducted using both a basic (pH 11.5) and an acidic (pH 3) mobile phase. Retention times, retention factors, peak asymmetry and number of theoretical plates are the responses used to evaluate the performance of the resulting monoliths. The best compromise between the different responses was found around 67% PFS and 18% 1,4-butanediol (relative to the total mass), i.e. rather close to the center point. At these conditions, retention times were generally below 15min and retention factors below 5. Asymmetry values between close to 1 were found, and theoretical plate numbers up to 10,900, which were improvements compared to the central point of the design. 相似文献
984.
GW Mirowski JF Hilton D Greenspan AJ Canchola LA MacPhail T Maurer TG Berger JS Greenspan 《Oral diseases》1998,4(1):16-21
OBJECTIVES: Mucocutaneous diseases are common in patients infected with human immunodeficiency virus (HIV). To identify cutaneous diseases for which HIV-infected people are at high risk, we sought those that are strongly associated with specific HIV-related oral lesions and with progression of HIV disease.
DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations.
RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/ju.l (range 0–950/pil), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS.
CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis. 相似文献
DESIGN: A cross-sectional study of HIV-positive outpatients referred to a university stomatology clinic for diagnosis and treatment of oral diseases. Each subject underwent both complete oral and cutaneous examinations.
RESULTS: Among 55 men, with a median age of 41 years and a median CD4 cell count of 125/ju.l (range 0–950/pil), 93% had active oral diseases or conditions, including candidiasis, hairy leukoplakia, ulcers, Kaposi's sarcoma (KS), and xerostomia, and 95% had skin conditions, including onychomycosis, dermatophytosis, seborrheic dermatitis, KS, folliculitis, xerosis, and molluscum contagiosum. Seborrheic dermatitis, xerosis, skin KS, and molluscum contagiosum were associated with oral HIV-sentinel lesions (oral candidiasis, hairy leukoplakia, and KS), with low CD4 cell counts, and with AIDS.
CONCLUSION: Our results suggest that xerosis and seborrheic dermatitis may be early harbingers of HIV disease progression. Their roles as predictors warrant further study, based on their associations with low CD4 cell counts and AIDS and strong co-prevalence with one of the most common HIV-related oral lesions, oral candidiasis. 相似文献
985.
Vitha T Kubícek V Hermann P Elst LV Muller RN Kolar ZI Wolterbeek HT Breeman WA Lukes I Peters JA 《Journal of medicinal chemistry》2008,51(3):677-683
Lanthanide complexes of DOTA derivatives 2a (BPAMD) and 2b (BPAPD), having a monoamide pendant arm with a bis(phosphonate) moiety, were comparatively tested for application in MRI, radiotherapy, and bone pain palliation. (1)H, (31)P, and (17)O NMR spectroscopy show that they are nine-coordinated, with one water molecule in the first coordination sphere of the Ln(III) ion. The bis(phosphonate) moieties are not coordinated to the lanthanide and predominantly mono- and diprotonated at physiological pH. The parameters governing the longitudinal relaxivities of the Gd complexes are similar to those of other monoamides of DOTA reported in the literature. Upon adsorption on hydroxyapatite, the relaxivities at 20 MHz and 25 degrees C of Gd-2a and Gd-2b were 22.1 and 11 s(-1) mM(-1), respectively. An in vivo gamma-ray imaging study showed that the (177)Lu complexes of 2a and 2b have a high affinity for bones, particularly for growth plates and teeth with a prolonged retention. 相似文献
986.
Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines 总被引:1,自引:0,他引:1
Otrubova K Lushington G Vander Velde D McGuire KL McAlpine SR 《Journal of medicinal chemistry》2008,51(3):530-544
We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating multiple drug-resistant colon cancers. 相似文献
987.
目的:通过一系列活体和体外实验来考察激光诱导间质热疗过程中血管及器官受高功率激光作用时的温度场发展规律。方法:实验性家兔1只,麻醉状态下应用波长为10.6mm的KD-Ⅲ型CO2激光器(北京科电微波电子有限公司生产)在不同功率激光照射其耳部不同部位,观察血管稀疏区与丰富区在激光照射下的反应。隔2d,将其麻醉处死,取出胃、肝、肺、肾、心等不同器官,进行激光照射。实验中引入红外成像仪来定量刻画被测对象表面的瞬态温度分布图像。结果:①当激光热量不足以完全切断血管时,血管丰富组织区的复温能力强于血管稀疏区;当激光准确作用于主血管并且达到一定能量时,不仅下游供血及加热可被切断,且上游供血也会受到影响。②在相同的激光频率、功率及作用时间下,胃部的穿透最深,肾部温度变化率最大。结论:①组织局部的血液灌注率会影响激光作用的效果。②不同器官由于热容量不同,且对激光的反射和吸收率存在差异,导致激光穿透厚度及组织温度变化的幅度不同。 相似文献
988.
目的:观察中药健骨二仙丸对体外培养人工关节假体周围界膜白细胞介素6表达的抑制作用,为健骨二仙丸防治人工关节假体周围骨溶解提供科学依据。方法:实验于2006-09/12在深圳市中医院中心实验室(国家级P2实验室)完成。①体外界膜组织培养:将备用的人工关节假体周围界膜(20g,取自右股骨颈骨折人工关节置换术后11年出现假体无菌性松动来深圳市中医院行翻修术患者,女性,74岁,对实验知情同意并经医院伦理委员会批准)放入Hank’s液中清洗后置于RPMI培养液中,然后将界膜标本用眼科剪剪成1mm3大小组织悬浮液。②含药血清制备:按每日中药健骨二仙丸生药12.0g/kg大鼠体质量灌胃(相当于临床剂量的6.25倍),每日固邦用量为1.04mg/kg体质量(相当于临床剂量的6.25倍)。2次/d,间隔5h,连续灌胃3d。末次灌药1h后,从腹主动脉取血,离心获取血清。③分组:取24孔培养板2块,分空白对照组、健骨二仙丸组、固邦组,各组又分别分100g/L,200g/L两个质量浓度亚组,共计6个组,每组8个培养孔。100g/L质量浓度组相应加入0.9mL组织悬液和0.1mL空白血清或健骨二仙丸、固邦含药血清。200g/L质量浓度组相应加入0.8mL组织悬液和0.2mL空白血清或健骨二仙丸、固邦含药血清。④实验评估:各组添加空白血清或含药血清后在体积分数为0.05CO2、37℃饱和湿度下培养72h,取上清液,用酶联免疫吸附法测定白细胞介素6的含量。上述界膜组织标本同时做细菌培养。结果:48个培养孔中的组织培养均成功,全部进入结果分析。①白细胞介素6水平:100g/L与200g/L空白对照组比较差异无显著意义[(97.113±11.989),(96.275±13.087)ng/L,P>0.05]。100g/L健骨二仙丸组[(92.288±10.397)ng/L]与空白对照组相比差异无显著性(P>0.05);200g/L健骨二仙丸组[(82.263±9.580)ng/L]低于空白对照各组(P<0.05)。100g/L与200g/L固邦组[(83.300±9.039),(79.338±11.118)ng/L]低于空白对照各组(P<0.05和P<0.01)。200g/L健骨二仙丸组与100g/L和200g/L固邦组比较,差异无显著性。②人工关节周围界膜组织细菌培养结果为阴性。结论:健骨二仙丸能够抑制磨损颗粒诱导的人工关节假体周围界膜细胞因子的分泌,进而阻止假体周围破骨细胞性骨溶解,对人工关节假体无菌性松动可能具有较好的防治作用。 相似文献
989.
BACKGROUND: Principal investigators have a responsibility to ensure and maintain the scientific integrity of their research studies and to protect the safety of the participants. Data and safety monitoring is required for all types of clinical trials, and the nature and degree of the monitoring must be related to the degree of risk involved. OBJECTIVES: This article aims to define the purpose of a data and safety monitoring board (DSMB), to describe the functions of a DSMB and distinguish them from the activities of an institutional review board, and to discuss the development and implementation of a DSMB plan. METHODS: The literature on data and safety monitoring is reviewed, and the process and key issues are illustrated with examples from the authors' clinical trial and others. RESULTS: The principal role of the DSMB is to monitor the data from the trial periodically, to review and assess the performance of its operations, and to make recommendations based on interim results (e.g., modification of the study protocol, or possible early termination of the study). Although the roles of a DSMB and institutional review board complement one another, the main focus of their responsibilities is different and carried out independently of one another. The members of a DSMB are selected on the basis of their methodologic, statistical, or clinical expertise. CONCLUSION: The multiple scientific, ethical, safety, recruitment, intervention, and budgetary responsibilities of a principal investigator can be complex. The role of the DSMB is crucial and offers independent evaluation to ensure participant safety and good science. 相似文献
990.
Sbastien Boutry Sophie Laurent Luce Vander Elst Robert N. Muller 《CONTRAST MEDIA & MOLECULAR IMAGING》2006,1(1):15-22
Targeting of the endothelial inflammatory adhesion molecule E‐selectin by magnetic resonance imaging (MRI) was performed with a superparamagnetic contrast agent in the context of in vitro and in vivo models of inflammation. The specific contrast agent was obtained by grafting a synthetic mimetic of sialyl Lewisx (sLex), a natural ligand of E‐selectin expressed on leukocytes, on the dextran coating of ultrasmall particles of iron oxide (USPIO). This new contrast agent, called USPIO‐g‐sLex, was tested, in vitro, on cultured human umbilical vein endothelial cells (HUVECs) stimulated to express inflammatory adhesion molecules, and in vivo, on a mouse model of hepatitis. In vitro, HUVECs were stimulated with the pro‐inflammatory cytokine tumor necrosis factor alpha (TNF‐α) and were then incubated with USPIO‐g‐sLex or ungrafted USPIO. In vivo, hepatitis was induced on NMRI mice by injection of concanavalin A (Con A). USPIO‐g‐sLex and ungrafted USPIO were injected intravenously. In vitro results showed an extensive retention of USPIO‐g‐sLex on TNF‐α stimulated HUVECs. Image intensity and R2 measurements performed on T2‐weighted MR images demonstrated a significantly higher binding of USPIO‐g‐sLex on stimulated HUVECs. In vivo, USPIO are known to pass through the fenestrae of the liver and to be captured by Kupffer cells, inducing a loss of signal intensity on T2‐weighted MR images. Unexpectedly, when injected to Con A‐treated mice, USPIO‐g‐sLex induced a significantly lower attenuation of liver signal intensity than USPIO or USPIO‐g‐sLex injected to healthy mice, or USPIO injected to Con A‐treated mice, suggesting that the specific contrast media is retained extracellularly by an interaction with E‐selectin overexpressed on the vascular endothelium. Both in vitro and in vivo results therefore indicate that USPIO‐g‐sLex is recognizing endothelial E‐selectin. USPIO‐g‐sLex is thus well suited for the MRI diagnosis of inflammation and for the in vitro evaluation of endothelial cells activation. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献