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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.
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
3.
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
4.
Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography 总被引:3,自引:0,他引:3
Anand D. Vijay Lim Eric Raval Usha Lipkin David Lahiri Avijit 《Journal of nuclear cardiology》2004,11(4):450-457
BACKGROUND: Electron beam tomography coronary calcium imaging is an evolving technique for the early detection of coronary atherosclerosis, and recent studies have established its prognostic value in asymptomatic individuals. The relationship of coronary artery calcium scores (CAC) to obstructive coronary artery disease (CAD) has been poorly studied but is clinically relevant because it determines which individuals are likely to benefit from revascularization procedures. Hence, we prospectively evaluated the prevalence of myocardial ischemia in asymptomatic patients with cardiovascular risk factors and subclinical atherosclerosis. METHODS AND RESULTS: We studied 864 asymptomatic patients with no previous CAD but with cardiovascular risk factors, referred for electron beam tomography coronary calcium imaging to our institution over an 18-month period. From this group, 220 consecutive patients (85% men; mean age, 61 +/- 9 years; age range, 31-84 years) with moderate to severe atherosclerotic disease (coronary calcium score > or =100 Agatston units) were prospectively evaluated by technetium 99m sestamibi single photon emission computed tomography (SPECT). Patients were followed up (mean follow-up, 14 months) and data regarding their subsequent clinical management recorded. Of the 220 patients, 119 had moderate atherosclerosis (CAC score of 100-400 Agatston units) and 101 had severe atherosclerosis (CAC score > or =400 Agatston units). Abnormal SPECT findings were seen in 18% of patients with moderate atherosclerosis (n = 21) and 45% of patients with severe atherosclerosis (n = 45). Increasing severity of atherosclerosis was related to increasing ischemic burden (summed difference score = 1 +/- 0.2 for CAC score of 100-400 Agatston units and 3.2 +/- 0.5 for CAC score > or =400 Agatston units). In a multivariate linear regression model incorporating risk factors, CAC was the only predictor of silent ischemia. CONCLUSION: In comparison to previously published data, we detected a higher prevalence of silent ischemia even in patients with moderate coronary atherosclerosis (18%). This may reflect the differing risk factor profile of our patient population. When coronary calcium screening is used to preselect asymptomatic patients with cardiovascular risk factors for myocardial perfusion imaging, the optimum coronary calcium score threshold will depend on the population prevalence of risk factors and asymptomatic obstructive CAD. 相似文献
5.
Prafulla Raval Howard H. T. Hsu H. Clarke Anderson 《Journal of orthopaedic research》1996,14(4):605-610
Implants of defatted, freeze-dried Saos-2 human osteosarcoma cells grown to confluency induce de novo bone formation in athymic mice. These cells are also richly endowed with bone morphogenetic proteins and express mRNA for bone morphogenetic proteins 1, 2, 3, 4, and 6, as well as for transforming growth factor-β1. Our aim was to study whether the ability to induce bone formation is related to the level of expression of bone morphogenetic protein. We studied the osteoinductive abilities and levels of expression of bone morphogenetic protein of Saos-2 cells both during the growth phase and after confluency was reached. Subconfluent cells were at least 70% less effective in their osteoinductive ability than confluent cells. Comparison of bone morphogenetic protein mRNA expression in confluent and subconfluent cells revealed that the latter had lower expression of all the mRNAs studied. The expression of bone morphogenetic protein-1, bone morphogenetic protein-2, and bone morphogenetic protein-6 mRNAs was 2, 3, and 6 to 10-fold lower, respectively, in subconfluent cells. These results suggest that the ability of Saos-2 cells to induce de novo bone formation may be correlated with the relative expression of these proteins; the expression of bone morpho-genetic proteins in Saos-2 cells also may be dependent on the cell cycle. 相似文献
6.
The effects of the calcium antagonists verapamil and nifedipine on blood glucose levels, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic effect of tolbutamide were studied in normal nondiabetic rabbits. Daily dosage of 40 mg/kg verapamil and 5 mg/kg nifedipine given orally up to 7 days did not affect blood glucose level, glucose tolerance, insulin secretion during glucose tolerance and hypoglycaemic activity of tolbutamide 250 mg/kg p.o. 相似文献
7.
A critically ill man suffered a respiratory arrest due to pulmonary air embolism after the exchange of central venous catheters over a guidewire. A pulmonary perfusion lung scan performed 90 min later demonstrated extensive perfusion defects which were interpreted as "high probability" for PTE. Pulmonary angiography 4.5 h later was normal. A second perfusion lung scan performed 24 h after the respiratory arrest was normal. Pulmonary air embolism can produce segmental (and larger) perfusion defects which may be indistinguishable from those caused by PTE. The rapid (24 h) resolution of the perfusion defects may help differentiate the two disorders. 相似文献
8.
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
9.
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
10.
A case of multiple myeloma diagnosed by fine-needle aspiration (FNA) biopsy and confirmed by laboratory studies in a patient with a history of renal-cell carcinoma is presented. The patient was diagnosed with renal-cell carcinoma of the right kidney and a radical nephrectomy was performed. Eighteen months after this diagnosis was made, the patient developed chest wall pain and was found to have osteolytic bone lesions of the ribs and vertebral bodies. FNA of an osteolytic rib lesion disclosed multiple myeloma. Additional laboratory studies confirmed the diagnosis of multiple myeloma. This case report demonstrates the value of FNA as a diagnostic tool for the follow-up of cancer patients, the subsequent discrimination between metatastic lesions and a second primary malignancy, and the cytology of multiple myeloma. 相似文献