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Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.  相似文献   
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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects.  相似文献   
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The Forrest Report led to the introduction of the breast screening programme with the aim of reducing mortality from breast cancer. In 1989 a breast screening programme was introduced to the South Bucks District and now two cycles have been completed. The findings are of a high yield of good prognosis tumours 71% and 72%, respectively. These encouraging figures are reflected in a high response rate and with a fall in the incidence of non-screen-detected tumours.  相似文献   
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STUDY OBJECTIVES: This follow-up study examined the major complications among 4307 operative gynecologic laparoscopies. The overall complication rate and each individual category were compared with those of our previous study period. The clinical outcome and salvage procedures were correlated with the time of recognition and the severity of initial procedures in the individual injury type. DESIGN: Retrospective, comparative study based on medical record reviewing (Canadian Task Force classification II-3). SETTING: Tertiary teaching hospital, Chi Mei Foundation Hospital in southern Taiwan. PATIENTS: Records of women (n = 4307) aged 40.5 +/- 11.7 years (mean +/- SD [95% CI 40.1-40.5]) who underwent operative gynecologic laparoscopies from January 2000 through February 2006 were reviewed in this study. The complications were compared with those of our previous study based on 1507 laparoscopies performed between December 1992 and November 1999 for follow-up comparison. INTERVENTIONS: Gynecologic laparoscopic surgeries. MEASUREMENTS AND MAIN RESULTS: Thirty-four complications occurred in 31 patients requiring repair procedures, 3 of whom had multiple complications, with an overall complication rate of 0.72% (31/4307). There were 13 bladder injuries (0.30%), 7 bowel injuries (0.16%), 3 cases of internal bleeding (0.07%), 4 vaginal stump hematomas or abscesses (0.09%), 3 ureteral injuries (0.07%), 3 major vessel injuries (0.07%), and 1 trocar site hematoma (0.02%). In addition, there were 125 (2.88%) postoperative blood transfusions without additional operative intervention. The major complication rate decreased compared with that of the previous study (0.72% [95% CI 0.51%-1.02%] vs 1.59% [95% CI 1.07%-2.36%]; p = .005). The overall complication rates were not significantly different between laparoscopic hysterectomy (LH) group and non-LH group. However, bladder injury happened more frequently in the LH group, whereas bowel injury was more common in the non-LH group. In addition, the severity of the original injury, timing of recognition, and accompanying salvage procedures correlated with the clinical outcomes. CONCLUSION: The significantly decreased major complication rate, as compared with that of our previous study period, confirms the importance of experience accumulation and use of preventive maneuvers in reducing the complication rate. There were no significant differences among the individual injury category during these 2 study periods. The manifestations of bowel injury were highly variable and individualized. The accumulation of surgical experience with the aid of preventive maneuvers is helpful to reduce the complication rate significantly.  相似文献   
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