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1.
Edward J. Holland Walter O. Whitley Kenneth Sall Stephen S. Lane Aparna Raychaudhuri Steven Y. Zhang 《Current medical research and opinion》2016,32(10):1759-1765
Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED. 相似文献
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Aparna Gangopadhyay 《Nutrition and cancer》2020,72(8):1438-1442
AbstractBackground: The prognostic nutritional index (PNI), a marker of immune-nutrition balance, has predictive value in the survival and prognosis of various cancers. However, the impact of PNI on response to chemoradiation is poorly understood.Materials and Methods: A total of 583 women with locally advanced cervical cancer from two centers were clinically assessed for complete response after chemoradiation. The baseline PNI was individually recorded, and the significance of association between PNI and complete response was analyzed using logistic regression. ROC (receiver operating characteristics) curves were analyzed to determine the cutoff value of PNI that significantly predicted complete response.Results: Logistic regression analysis demonstrated that the PNI was significantly associated with complete response following chemo radiation (p?<?0.0001). Analysis of the ROC curve for PNI demonstrated an optimal cut off value of 44.8 (p?<?0.0001, sensitivity 66.7, and specificity 88.5); the area under the ROC curve was 0.813 (Youden’s index J, 0.7519).Conclusions: The PNI is significantly associated with clinical complete response to chemoradiation in locally advanced cervical cancer. Low baseline PNI may lower the likelihood of complete response after chemoradiation. In particular, those with PNI values below 44 should be carefully monitored during treatment; nutritional interventions may offer benefit in these women. 相似文献
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目的探讨肝、肺细胞因子基因表达与腹腔吞噬细胞上清液、循环血中细胞因子含量的关系,为临床诊治多细菌感染引发的炎症提供实验依据.方法将30只小鼠分为假手术对照组(sham组)和盲肠结扎组(CLP组).采用RT-PCR法检测肝脏和肺脏肿瘤坏死因子α(TNF-α)和白细胞介素10(IL-10)的基因表达情况,采用ELISA法检测腹腔巨噬细胞上清液和循环血液中相应细胞因子含量.结果CLP组的TNF-α、IL-10基因表达和腹腔巨噬细胞上清液、循环血液中的相应细胞因子含量均高于sham组.CLP后18h组与4h组比较,TNF-α在腹腔巨噬细胞上清液、循环血液中的活性均有显著性差异(P<0.05),在肝、肺中基因表达有非常显著性差异(P<0.01);IL-10在腹腔巨噬细胞上清液和循环血液中的含量无显著性差异,而在肝、肺中基因表达有显著性差异.结论发生多细菌感染性炎症时,肝、肺参与细胞因子的表达;血液中细胞因子含量不能完全代表组织器官内的基因表达情况;多细菌感染性炎症治疗应考虑靶器官细胞因子的表达状态. 相似文献
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M.R.C. Naidu D.R. Reddy K.V.R. Sastry P.K. Reddy 《Clinical neurology and neurosurgery》1987,89(4):265-267
Osteomyelitis of the skull is an uncommon disease in the present days, mainly due to the advent of modern and more effective antibiotics. Hematogenous osteomyelitis is very rare. Osteomyelitis of the skull is usually not associated with sclerosis which is commonly seen in the rest of the skeleton. There are only few occasional case reports of condensing osteomyelitis wherein there was sclerosis of the bone associated with osteomyelitis of the skull and epidural abscess. An unusual case of diffuse condensing osteomyelitis of the skull producing unilateral proptosis is reported. The clinical, radiological features and microbiological aspects are presented. The proptosis was treated by excision of the bone behind the eyeball and thus relieving the proptosis and the impaired vision. The patient was given broad spectrum antibiotics for a period of two months. Further management problems are discussed. 相似文献
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A study was undertaken to assess the health, nutrition and psychosocial profile of Institutionalized children in four States--Uttar Pradesh, Andhra Pradesh, Karnataka and West Bengal. A sample of 3,822 children from 70 institutions in 6-18 years age group formed the subjects of the study. It was observed that the destitute children were mainly taken care of in three types of institutions, viz, Voluntary, Government Aided and Government run institutions. Calorie deficiency and deficiency of Vitamins and minerals characterized the diets of these children. In general, there was no deficit of protein in their diets. Growth wise, these children were retarded both in height and weight compared to standards. However, they fared better in comparison to their age and sex counterparts in the rural and urban poor. Psychosocial profile of these children indicated that the prevailing environment in the institutions is less conducive for intellectual stimulation but not so for the development of skills of self-help, locomotion, socialization and imagery. 相似文献
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We have previously hypothesized that an effective vaccine against HIV should elicit cell-mediated immunity without antiviral antibody production. As a first step towards this goal we have identified potential T-cell epitopes, without B-cell activity against the native protein, from the first and second conserved sequences, and from three functionally important regions of the HIV-1 envelope protein gp160. For this approach, short peptide sequences selected by established computer programs were synthesized and chemically modified to generate either polymers with disulfide bonds, or micelles with two palmitic acid residues attached to the amino-terminal lysine. In both configurations several peptides were immunogenic without the need for coupling to carrier molecules. Of the 19 peptides we tested in our present studies, seven induced good T-cell proliferative response in mice representing four major histocompatibility complex haplotypes. None of these seven peptides produced antibodies that could recognize the envelope protein gp160. 相似文献
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Dai Z Weichenhan D Wu YZ Hall JL Rush LJ Smith LT Raval A Yu L Kroll D Muehlisch J Frühwald MC de Jong P Catanese J Davuluri RV Smiraglia DJ Plass C 《Genome research》2002,12(10):1591-1598
Knudson's two-hit hypothesis postulates that genetic alterations in both alleles are required for the inactivation of tumor-suppressor genes. Genetic alterations include small or large deletions and mutations. Over the past years, it has become clear that epigenetic alterations such as DNA methylation are additional mechanisms for gene silencing. Restriction Landmark Genomic Scanning (RLGS) is a two-dimensional gel electrophoresis that assesses the methylation status of thousands of CpG islands. RLGS has been applied successfully to scan cancer genomes for aberrant DNA methylation patterns. So far, the majority of this work was done using NotI as the restriction landmark site. Here, we describe the development of RLGS using AscI as the restriction landmark site for genome-wide scans of cancer genomes. The availability of AscI as a restriction landmark for RLGS allows for scanning almost twice as many CpG islands in the human genome compared with using NotI only. We describe the development of an AscI-EcoRV boundary library that supports the cloning of novel methylated genes. Feasibility of this system is shown in three tumor types, medulloblastomas, lung cancers, and head and neck cancers. We report the cloning of 178 AscI RLGS fragments via two methods by use of this library. 相似文献