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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
2.
3.
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.
Rajaram Gopalakrishnan Susan Simonton Michael D Rohrer Ioannis G Koutlas 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2006,102(6):773-777
Calcifying epithelial odontogenic tumor (CEOT) is a benign, locally aggressive odontogenic neoplasm characterized by sheets and nests of epithelial cells with deeply eosinophilic or occasionally clear cytoplasm, calcifications, and eosinophilic amorphous material that stains positive for amyloid. Although many cases of CEOT are associated with impacted teeth and occasionally appear radiographically as dentigerous cysts, a true cystic variant has not been previously reported. We report a 15-year-old white male with a large cystic maxillary lesion that filled most of the left maxillary sinus. It deformed the medial wall, the inferior orbital floor, and caused narrowing of the left inferior meatus. Histologically, the cystic lining showed characteristics of CEOT. An intraluminal component that featured histologic characteristics of CEOT was identified during surgery. The lesion was enucleated and the postsurgical course of the patient was uneventful. Because follow-up has been for less than 1 year, a meaningful long-term prognosis cannot be determined at present. However, the patient has not reported any symptoms or signs of recurrence during the follow-up period. 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
6.
K C Gopalakrishnan J Lewis 《The Journal of bone and joint surgery. British volume》1990,72(4):554-556
We report seven children in whom traumatic haemarthrosis of the hip had produced lateral subluxation of the femoral head, which is different from the apparent displacement seen in Perthes' disease. In all seven cases, aspiration of the haemarthrosis allowed reduction of the femoral head, and follow-up for a mean of 14 months revealed no evidence of avascular necrosis of the proximal femoral epiphysis. Traumatic haemarthrosis of the hip in children appears to be a clinical entity which can produce femoral head subluxation. Aspiration and traction is the treatment of choice and can cure the condition. 相似文献
7.
Calcium antagonizes the magnesium-induced high affinity state of the hepatic vasopressin receptor for the agonist interaction.
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H. Wang V. Gopalakrishnan J. R. McNeill P. V. Sulakhe C. R. Triggle 《British journal of pharmacology》1990,100(1):5-10
1. The present study describes the role of Ca2+ in the regulation of the hepatic vasopressin V1 receptor. With low concentrations of Ca2+, there was a small increase in [3H]-arginine vasopressin [( 3H]-AVP) binding, but above 10 mM, Ca2+ decreased the binding of this agonist. In contrast, low concentrations of Mg2+ were associated with a dramatic concentration-dependent increase in [3H]-AVP binding, reaching a maximal effect of 650% above control at concentrations ranging between 1-5 mM. At higher concentrations of Mg2+, the stimulatory effect of this cation was less pronounced, falling to 210% of control at 100 mM Mg2+. Strikingly, Ca2(+)-inhibited the stimulatory effect of Mg2+ in a concentration-dependent fashion. 2. Saturation binding data revealed that Ca2+ (2 to 10 mM) per se promotes the high affinity conformation of the V1 receptor for the agonist binding with the KD decreased from a control value of 2.3 nM to 0.5 nM in the presence of 10 mM Ca2+. This effect was attenuated with an increase in Ca2+ above 10 mM. With an increase in Ca2+ to 20 mM, however, the Bmax for [3H]-AVP binding was decreased. Ca2+ also decreased the high affinity/high capacity state (KD 100 pM) of the receptor induced by 1 mM Mg2+ for agonist interaction. 3. [3H]-V1 antagonist binding was inhibited by both Ca2+ and Mg2+. The IC50 values (mean +/- s.e. mean) for Ca2+ and Mg2+ were 32 +/- 8 and 53 +/- 9 mM respectively. Maximal inhibition achieved at 100 mM was 29% for Ca2+ and 42% for Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
Sunil Kumar Saxena S. Gopalakrishnan 《Indian journal of otolaryngology and head and neck surgery》2003,55(4):281-282
Despite the common occurrence of pleomorphic adenoma of major salivary glands, intranasal pleomorphic adenoma are rare. We
present a ease of pleomorphic adenoma of the nasal septum along with a brief review of literature. The histological nature
of this lesion in comparison to other salivary gland tumours and the importance of an accurate diagnosis has been stressed. 相似文献
9.
Hari Shankar Sharma N. K. Majumder V. Srinivas S. Gopalakrishnan 《Indian journal of otolaryngology and head and neck surgery》1988,40(3):105-106
Rarity of the carcinoid tumours in the larynx prompted us to report this case which has been successfully treated by partial laryngectomy. Oncogenesis of these tumours, mode of treatment and prognosis have been discussed. 相似文献
10.
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