Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.

Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.

New perspectives in the use of ink evidence in forensic science: Part II. Development and testing of mathematical algorithms for the automatic comparison of ink samples analysed by HPTLC

In the first part of this research, three stages were stated for a program to increase the information extracted from ink evidence and maximise its usefulness to the criminal and civil justice system. These stages are (a) develop a standard methodology for analysing ink samples by high-performance thin layer chromatography (HPTLC) in reproducible way, when ink samples are analysed at different time, locations and by different examiners; (b) compare automatically and objectively ink samples; and (c) define and evaluate theoretical framework for the use of ink evidence in forensic context. This report focuses on the second of the three stages. Using the calibration and acquisition process described in the previous report, mathematical algorithms are proposed to automatically and objectively compare ink samples. The performances of these algorithms are systematically studied for various chemical and forensic conditions using standard performance tests commonly used in biometrics studies. The results show that different algorithms are best suited for different tasks. Finally, this report demonstrates how modern analytical and computer technology can be used in the field of ink examination and how tools developed and successfully applied in other fields of forensic science can help maximising its impact within the field of questioned documents.

Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: results of a multidisciplinary expert panel - EPACT II

Introduction: Many therapeutic decisions in the management of fistulizing and fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong scientific evidence. For this reason, explicit appropriateness criteria for CD fistula and stenosis treatment were developed by a multidisciplinary European expert panel in 2004 with the aim of making them easily available on the Internet and thus allowing individual case scenario evaluation; these criteria were updated in 2007. Methods: Twelve international experts convened in Geneva, Switzerland in December 2007. Explicit clinical scenarios, corresponding to real daily practice, were rated on a 9-point scale based on evidence from the published literature and panelists' own expertise. Median ratings were stratified into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1-3). Results: Overall, panelists rated 60 indications pertaining to fistulas. Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the mainstay of therapy for simple and complex fistulas. In the event of previous failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab were considered appropriate for complex fistulas. The panel also rated 72 indications related to the management of fibrostenotic CD. The experts considered balloon dilation, if the stricture was endoscopically accessible, stricturoplasty and bowel resection to be appropriate for small bowel fibrostenotic Crohn's disease, and balloon dilation and bowel resection appropriate for fibrostenotic colonic disease. In the presence of an ileocolonic or ileorectal anastomotic stricture of <7 cm, endoscopic balloon dilation, and bowel resection were considered appropriate. Conclusion: Antibiotics, azathioprine/6-mercaptopurine, and conservative surgery are the mainstay of therapy for fistulizing Crohn's disease. Infliximab is a therapeutic option in patients without prior response to immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon dilation, if feasible, or surgical therapy should be considered. These expert recommendations are available online (www.epact.ch). Prospective evaluation is now needed to test the validity of these appropriateness criteria in clinical practice. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Paraoxonase2 polymorphisms are associated with nephropathy in Type II diabetes.

AIMS/HYPOTHESIS: Paraoxonase is a member of a multigene family of three genes. Paraoxonase2 gene polymorphisms have been associated with coronary heart disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We tested the hypothesis of whether paraoxonase1 and paraoxonase2 polymorphisms were associated with diabetic nephropathy. METHODS: Our case-control study of 299 Swiss patients with Type II diabetes included 147 patients with confirmed diabetic nephropathy. RESULTS: In univariate analyses the two paraoxonase2 polymorphisms were associated with diabetic nephropathy. When subjected to multivariate analyses, both paraoxonase2 polymorphisms remained statistically associated with diabetic nephropathy independent of traditional risk factors (paraoxonase2-148: OR = 2.53, p = 0.003; paraoxonase2-311: OR = 2.67, p = 0.002). In addition, BMI interacted with paraoxonase2 polymorphisms as a risk factor of nephropathy. CONCLUSIONS/INTERPRETATION: The paraoxonase2 gene polymorphisms were significantly associated with diabetic nephropathy independent of traditional risk factors in Type II diabetic patients. The susceptibility to diabetic nephropathy was intensified by the degree of obesity. Pathophysiological pathways should be investigated and could be involved in insulin resistance or lipids metabolism or both.