Experimental colitis in IL-10-deficient mice ameliorates in the absence of PTPN22.

Interleukin (IL)-10 plays a key role in controlling intestinal inflammation. IL-10-deficient mice and patients with mutations in IL-10 or its receptor, IL-10R, show increased susceptibility to inflammatory bowel diseases (IBD). Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) controls immune cell activation and the equilibrium between regulatory and effector T cells, playing an important role in controlling immune homoeostasis of the gut. Here, we examined the role of PTPN22 in intestinal inflammation of IL-10-deficient (IL-10-/- ) mice. We crossed IL-10-/- mice with PTPN22-/- mice to generate PTPN22-/- IL-10-/- double knock-out mice and induced colitis with dextran sodium sulphate (DSS). In line with previous reports, DSS-induced acute and chronic colitis was exacerbated in IL-10-/- mice compared to wild-type (WT) controls. However, PTPN22-/- IL-10-/- double knock-out mice developed milder disease compared to IL-10-/- mice. IL-17-promoting innate cytokines and T helper type 17 (Th17) cells were markedly increased in PTPN22-/- IL-10-/- mice, but did not provide a protctive function. CXCL1/KC was also increased in PTPN22-/- IL-10-/- mice, but therapeutic injection of CXCL1/KC in IL-10-/- mice did not ameliorate colitis. These results show that PTPN22 promotes intestinal inflammation in IL-10-deficient mice, suggesting that therapeutic targeting of PTPN22 might be beneficial in patients with IBD and mutations in IL-10 and IL-10R.

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Suprarenal aortic cross-clamping in elective abdominal aortic aneurysm surgery.

INTRODUCTION: this retrospective study was undertaken to evaluate whether suprarenal aortic cross-clamping increased the perioperative mortality and morbidity as compared to infrarenal clamping, in order to create the rationale for a more extensive application of this apparently more traumatic manoeuvre. MATERIALS AND METHODS: in a series of 734 elective aortic substitutions for abdominal aneurysm (AA), performed consecutively from January 1992 to June 1999, aortic cross-clamping was performed at a suprarenal level in 56 juxtarenal aneurysms, i.e. aneurysms extending to the lower edge of the renal arteries (8%, Group 1), and at an infrarenal level in 634 subrenal aneurysms (92%, Group 2). When analysing preoperative data, the diameter of aneurysms was larger in Group 1 than in Group 2 (p<0. 005). No significant differences were found between the two groups as regards age, sex, postinfarction cardiomyopathy, chronic obstructive pulmonary disease, chronic renal insufficiency and ASA classification of operative risks. RESULTS: the average time of renal exclusion in the juxtarenal aneurysms was 20 min (range 12-35 min). There is no difference between the two groups as regards the time of aortic clamping (mean 50 vs. 60 min) or the need for homologous blood transfusion (7% vs. 11% of patients). Perioperative (30 days) mortality did not differ: 3.6% vs. 1.9% (n.s.); nor did the incidence of acute myocardial infarction (3.6% vs. 2.3%). Renal function deteriorated in 8 (14%) vs. 0 (0%) (p<0.001) and 1 patient (2%) required permanent dialysis, as compared to 0% in Group 2. The incidence of ischaemic colitis was also significantly higher in Group 1 (7%) than in Group 2 (2%, p<0.01). CONCLUSION: this data shows that suprarenal clamping, which is necessary for the radical treatment of juxtarenal aortic aneurysms, can be performed with a low risk.

Hepatitis C infection in an Italian population not selected for risk factors.

AIMS/BACKGROUND: This study estimated the prevalence of HCV infection and relationship with viremia in a general population. The inhabitants of Albavilla town were personally invited to participate. METHODS: Out of 3997 inhabitants falling within the age range 18-85 years, 2403 (participation rate 60.1%) were examined for transaminases, HCVAb, HCVRNA, genotype and immunoblot assay. The following information was collected: sex, age, blood transfusions, surgery, use of glass syringes, drug addiction, alcohol consumption, tattoos and body mass index. RESULTS: 115 (4.8%) were HCVAb+, the prevalence being 1.2% under 40 years. Transfusion in the past was the only risk factor for HCV infection. Among the HCVAb+ subjects, 71 (61.7%) were HCVRNA+. 40.8% of the HCVAb+/HCVRNA+ group had normal ALT, compared with 68% of those with HCVAb+/HCVRNA-. The HCV genotypes in the 71 HCVRNA+ subjects were: 2a/2c in 58 (81.7%), 40% of them with normal ALT;1b in 11 (15.5%), none with normal ALT; genotype 3 in two (2.8%). CONCLUSION: The prevalence of HCVAb in this general population was 4.8%. About 3% were HCVRNA positive and of these genotype 2a/ 2c was present in 81.6%.

[The complications of pulmonary resection surgery: the experience of 200 consecutive cases]. / Le complicanze della chirurgia resettiva polmonare: esperienza su 200 casi consecutivi.

Postoperative complications observed in 200 patients after pulmonary resection (66 pneumonectomies--30%, 106 lobectomies--53% and 28 wedge resections--17%) are presented. Surgical operations were carried out in 86% of cases for cancer, in 16% for benign lesions. Major complications were: lobar atelectasis, bronchopneumonia, pulmonary embolism, respiratory insufficiency, bronchial fistula, ventricular tachyarrhythmia, altogether they concerned 21% of the cases. Their incidence was not significantly influenced by the extension of resection (the latter, on the contrary, influenced postoperative mortality as much as 4.5% after pneumonectomy, 2.8% after lobectomy and 0% after wedge resection), age of patients under or over 70 years, functional respiratory reserve, or associated cardiovascular diseases. On the contrary, the advanced stage of disease in neoplastic patients was significant for major complications. An adequate monitoring of minor respiratory and cardiac complications is recommended to reduce the incidence of major ones and their control when present. In authors' experience, in fact, postoperative mortality was overall 3% following such behaviour.

[Staging of lung cancer by computerized tomography: evaluation based on surgical experience]. / La stadiazione del cancro polmonare con tomografia computerizzata: valutazioni emergenti dall'esperienza chirurgica.

One hundred seventy patients with M0 bronchogenic carcinoma were preoperatively evaluated by CT staging whose results were correlated with surgical findings. A number of over and understaging were observed in assessing mediastinal nodes involvement, chest wall invasion, mediastinal pleura and vessels invasion as well as pulmonary vessels involvement. In conclusion, the Authors believe that no patient surgical indication should be excluded on the basis of CT evidence of intrathoracic invasion, in the light of the demonstrated potential for false-positive diagnoses.