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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
4.
Palat Balachandran M.S. M.Ch. Shaleen Agarwal M.S. M.Ch. Narendra Krishnani M.D. Chandra M. Pandey Ph.D. Ashok Kumar M.S. M.Ch. Sadiq S. Sikora M.S. Rajan Saxena M.S. Vinay K. Kapoor M.S. 《Journal of gastrointestinal surgery》2006,10(6):848-854
The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer.
A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple
cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival
<24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status
(P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was
seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year
survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival
in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive
disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated
with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in
patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III
and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in
gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival
in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival. 相似文献
5.
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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Human immunodeficiency virus type 1 (HIV-1) isolates from asymptomatic homosexual men and AIDS patients were compared for their in vitro biologic and genetic properties. Most of the HIV-1 isolates from asymptomatic men, but not from AIDS patients, failed to infect CD4+ H9 cells and phytohemagglutinin-stimulated peripheral blood lymphocytes. In a longitudinal study, serial HIV-1 isolates obtained from men who seroconverted to HIV-1 and later developed AIDS were able to infect H9 cells. In contrast, longitudinal isolates from men who remained asymptomatic did not infect H9 cells. HIV-1 isolates from AIDS patients in general exhibited increased production of intracellular viral DNA, RNA, and protein as compared to isolates from asymptomatic men. Cells infected with HIV-1 isolates from asymptomatic men produced very little gp120, p24, and p55 proteins as compared to those from AIDS patients. The overall restriction patterns of HindIII, Sac-1, Pst-1, EcoR1, and BamH1 were very similar between HIV-1 isolates from asymptomatic men and those from AIDS patients. However, the restriction endonuclease pattern of BglII was quite distinct for isolates from asymptomatic men as compared to AIDS patients. Preliminary studies mapped a unique BglII site in the gag region of most of the isolates from asymptomatic men, approximately 2.0 kb from the 5' end. Thus, HIV-1 isolates from asymptomatic subjects and from AIDS patients have distinct biologic and genetic properties which may be related to the various clinical outcomes of HIV-1 infection. 相似文献
8.
Suppiah Balachandran Stuart Eason Lynn McGuire Suzanne Bernard Charles Boyd 《European journal of nuclear medicine and molecular imaging》1986,12(2):69-71
Summary In order to measure ejection fractions (EFs) from nuclear ventriculograms, we devised a semi-automated edge-detection technique based on a combination of inverse Fourier analysis and second-derivative techniques. Initial clinical studies showed that, for the left ventricle, our method gives EF values statistically identical with those obtained using a conventional isocontour technique. For the right ventricle, however, the values obtained using the two methods were somewhat more at variance. Despite requiring a longer processing time, the results obtained with our method are reproducible because less operator intervention is necessary. 相似文献
9.
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
10.
Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition 总被引:5,自引:0,他引:5
Pal PK Hanajima R Gunraj CA Li JY Wagle-Shukla A Morgante F Chen R 《Journal of neurophysiology》2005,94(3):1668-1675
We studied the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) on the excitability of interhemispheric connections in 13 right-handed healthy volunteers. TMS was performed using figure-eight coils, and surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor cortex (M1) followed by a test stimulus to the opposite M1 was used to study the interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles. After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049) and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre-RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly different. We conclude that 1-Hz rTMS reduces IHI in both directions but is predominantly from the stimulated to the unstimulated hemisphere. Low-frequency rTMS may be used to modulate the excitability of IHI circuits. Treatment protocols using low-frequency rTMS to reduce cortical excitability in neurological and psychiatric conditions need to take into account their effects on IHI. 相似文献