Identification and chromosome mapping of loci predisposing to colorectal cancer that control Wnt/beta-catenin pathway and progression of early lesions in the rat

Sporadic colorectal cancer (CRC) is a major health concern worldwide. Epidemiologic evidence suggests a polygenic predisposition to CRC, but the genes responsible remain unknown. Here, we performed genome-wide scanning of male (ACI/SegHsd x Wistar-Furth)F2 (AWF2) rats to map susceptibility genes influencing the evolution of early colorectal lesions to adenocarcinoma following 1,2-dimethylhydrazine administration. Phenotypic analysis revealed higher incidence/multiplicity and lower size of adenomas in ACI/SegHsd (ACI) and (ACI/SegHsd x Wistar-Furth)F1 (AWF1) than Wistar-Furth (WF) rats and higher incidence/multiplicity of poorly differentiated adenocarcinomas in WF than ACI rats, with intermediate values in AWF1 rats. Linkage analysis of 138 AWF2 rats identified three loci on chromosomes 4, 15 and 18 in significant linkage with lesion multiplicity that were identified as rat Colon cancer resistance (rCcr) 1, rCcr2 and rCcr3, respectively. Seven other loci on chromosomes 5, 6, 15, 17, 18 and 20 were in suggestive linkage with adenoma/adenocarcinoma multiplicity/surface area. Six of them were identified as rCcr4-9 and a locus on chromosome 5 was identified as a susceptibility locus, rCcs1. Significant interactions between rCcr3 and rCcr6, rCcr6 and rCcr8 and rCcr5 and rCcr9, and four novel epistatic loci controlling multiplicity/size of colorectal lesions were discovered. Apc, located at rCcr3, did not show functional promoter polymorphisms. However, influence of susceptibility/resistance genes on Wnt/beta-catenin pathway was shown by defective beta-catenin inactivation in WF but not in ACI and AWF1 rat adenocarcinomas. These data indicate that inheritance of predisposition to CRC depends on interplays of several genetic factors, and suggest a possible mechanism of polygenic control of CRC progression.     

The elderly with synchronous non-small cell lung cancer and solitary brain metastasis: does palliative thoracic radiotherapy have a useful role?

We evaluated the prognosis associated with advanced age by comparing the clinical features of individuals 65 years of age and older to those of younger patients with single metastasis to the brain alone (SMBA) and simultaneous non-small cell lung cancer (NSCLC), and the potential role of palliative thoracic radiotherapy in this cohort of patients. Our 23-year experience included 72 consecutive (22 elderly and 50 non-elderly) people. Older patients predominantly presented with N0-N1 stage disease and coexisting illness. Univariate analysis showed that younger age (p=0.04) and operative removal of SMBA (p=0.01) were predictive of better survival. However, with multivariate analysis, resection of SMBA remained the sole predictor of prognosis. The application of NSCLC radiotherapy for palliation did not favorably alter outcome. In conclusion, elderly patients with simultaneous NSCLC and SMBA seem to fare less well than their younger counterparts. Moreover, the concurrent application of radiotherapy for palliation of the lung neoplasm was not prognostically advantageous.     

Epidemiology of hip fractures in northwestern Italy: a multicentric regional study on incidence of hip fractures and their outcome at 3-year follow-up

Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003 in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship. Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was 2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons for giving information to patients and their relatives.     

Panniculitis: another clinical expression of gout

Gouty panniculitis is an unusual clinical manifestation of gout, characterized by the deposition of monosodium urate crystals in the lobular hypodermis. Its pathogenesis is poorly understood but is associated with hyperuricemia, and the clinical presence of indurate subcutaneous plaques, which may precede or appear subsequently to the articular clinical expression of tophaceous gout. The aim of this report is to describe the clinical characteristics and potential risk factors for the development of lobular panniculitis secondary to chronic tophaceous gout. This is a retrospective clinical review of 6 patients with gouty panniculitis seen at the rheumatology service at the National University of Colombia. All cases fulfill diagnostic criteria for gout. The presenting clinical characteristics of each case were analyzed. All 6 patients were men, with an average age of 26 years. Two patients initially presented with cutaneous manifestations, and in the remainder 4 joint involvements preceded the cutaneous manifestations. Articular involvement first developed in lower extremities, of intermittent nature, and subsequent occurrence of polyarthritis of upper and lower extremities. A positive family history of gout was observed in half of the patients. Smoking and high alcohol intake were relevant risk factors. On physical examination, all exhibited the presence of erythematous, irregular surface, deep indurate subcutaneous plaques. Biopsy of skin and deep dermis including panniculus revealed the presence of granulomatous inflammatory changes with deposition of amorphous eosinophilic material surrounded by palisading histocytes and lymphocytes. Characteristic negative birefringent monosodium urate crystals were observed in the synovial fluid of patients with arthritis. All patients exhibited high levels of serum uric acid and were non-complaint to treatment with allopurinol, NSAIDs, and colchicine. Gouty panniculitis should be considered in the differential diagnosis of panniculitis, especially in the presence of high levels of uric acid. It is usually observed in the third decade of life and may appear prior to the inflammatory articular manifestations of tophaceous gout.     

Prognostic Influence of Loss of Blood Group A Antigen Expression in Pathologic Stage I Non-Small-Cell Lung Cancer

IntroductionIn the scientific literature, contradictory results have been published on the prognostic value of the loss of expression of blood group antigen A (BAA) in lung cancer. The objective of our study was to analyze this fact in our surgical series.Patients and methodsIn a multicenter study, 402 non-small-cell lung cancer (NSCLC) patients were included. All were classified as stage-I according to the last 2009-TNM classification. We analyzed the prognostic influence of the loss of expression of BAA in the 209 patients expressing blood group A or AB.ResultsThe 5-year cumulative survival was 73% for patients expressing BAA vs 53% for patients with loss of expression (P=.03). When patients were grouped into stages IA and IB, statistical significance was only observed in stage I-A (P=.038). When we analyzed the survival according to histologic type, those patients with adenocarcinoma and loss of expression of BAA had a lower survival rate that was statistically very significant (P=.003). The multivariate analysis showed that age, gender and expression of BAA were independent prognostic factors.ConclusionsThe loss of expression of blood group antigen A has a negative prognostic impact in stage I NSCLC, especially in patients with adenocarcinoma.     

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.     

A longitudinal study of peripheral sensory function in vibration-exposed workers

Purpose  

To investigate prospectively the relation between vibration-induced sensory dysfunction and measures of daily exposure to hand-transmitted vibration (HTV).