Modulation of airway hyperresponsiveness by thiols in a murine in vivo model of allergic asthma

OBJECTIVE AND DESIGN: Since oxidative stress contributes to the pathogenesis of asthma, this study addressed the question whether supplementing the endogenous antioxidant, glutathione (GSH), would alleviate features of allergic asthma in the mouse. MATERIAL AND METHODS: Ovalbumin-sensitized mice received aerosols of the GSH-donors, glutathione-ethyl ester (GSEt) or N-acetylcysteine, before or during respiratory allergen challenges, or during methacholine challenges given one day after the last allergen challenge. Lung GSH levels were measured shortly after allergen or methacholine challenge. In addition, the effect of GSH supplements on airway hyperresponsiveness and inflammatory cell numbers in the airway lumen was assessed. RESULTS: GSEt decreased allergen-induced airway hyperresponsiveness when given in combination with methacholine. However, when given before or during allergen challenge, both GSH-donors failed to decrease the methacholine-induced airway contractility, change cell numbers in the airway lumen, or increase lung GSH levels. In addition, allergen challenges of sensitized mice did not decrease lung GSH levels. CONCLUSION: In contrast to guinea pigs and humans, allergen challenges in mice does not lead to acute oxidative stress.     

Differentiation of malignant and benign proximal bile duct strictures： The diagnostic dilemma

AIM： To identify the criteria for the differentiation of hilar cholangiocarcinoma （HCCA） from benign strictures. METHODS： A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These findings were analyzed to obtain the final diagnosis. RESULTS： Histological examination of the resected specimens confirmed HCCA in 58 patients （85%, group Ⅰ） whereas 10 patients （15%, group Ⅱ） were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients （79% group vs 60% group Ⅰ, P = 0.23）. Laboratory findings showed greater elevation of transaminase levels in group Ⅰ compared to group Ⅱ. The various imaging modalities showed vascular involvement exclusively in the malignant group （36%,P 〈 0.05）. Brush cytology was positive for malignant cells in only 50% patients in group Ⅰ whereas none in group Ⅱshowed malignant cells. CONCLUSION： Despite improvements in imaging techniques, 10 patients （15%） with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.     

A comparative study of intraductal papillary neoplasia of the biliary tract and pancreas

Intraductal papillary mucinous neoplasm of the pancreas is a rare but well-established entity in contrast to intraductal papillary mucinous neoplasm of the biliary tract. The aim of this study was to compare the clinicopathologic features of intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas. Twenty patients who underwent resection for intraductal papillary mucinous neoplasm of the biliary tract were compared with 29 cases resected for intraductal papillary mucinous neoplasm of the pancreas. Clinicopathologic characteristics and resection specimens of all patients were reassessed and immunohistochemically screened for expression of a distinct set of tumor markers. Median ages of patients with intraductal papillary mucinous neoplasms of the biliary tract and of the pancreas were 66 and 62 years, respectively (P < .05). Twelve patients with intraductal papillary mucinous neoplasm of the biliary tract (60%) had neoplasms with infiltrating carcinoma, compared with 6 patients with intraductal papillary mucinous neoplasm of the pancreas (21%, P < .05). Cytokeratin 7 and 20 expressions were equal in biliary and pancreatic intraductal papillary mucinous neoplasms. Cytokeratin 20 expression was mainly found in intestinal-type tumors. Gastric, pancreaticobiliary, and oncocytic subtypes were all observed in the intraductal papillary mucinous neoplasm of the biliary tract group. The distribution was significantly different from the intraductal papillary mucinous neoplasm of the pancreas group. The 3-year overall survival rate of malignant biliary and pancreatic intraductal papillary mucinous neoplasm was 63% and 65%, respectively (P = .798). Positive lymph nodes and a high expression of membranous mucin were associated with a significantly shorter overall survival in patients with malignant intraductal papillary mucinous neoplasm. Finally, p53 and Ki67 proliferation index were both associated with the carcinogenesis of intraductal papillary mucinous neoplasm, whereas DPC4 and CDX2 were not. Clinicopathologic features of intraductal papillary mucinous neoplasm of the biliary tract largely resemble those of intraductal papillary mucinous neoplasm of the pancreas, although intraductal papillary mucinous neoplasm of the biliary tract was associated with a higher malignancy rate at the time of surgical treatment. The level of membranous mucin expression and positive lymph nodes are significant prognosticators in patients with malignant intraductal papillary mucinous neoplasm.     

Embolization for Hemoptysis in Chronic Thromboembolic Pulmonary Hypertension: Report of Two Cases and a Review of the Literature

Hemoptysis is a known complication in patients with bronchial artery hypertrophy due to a variety of chronic pulmonary disorders. Bronchial artery hypertrophy is observed in most patients with chronic thromboembolic pulmonary hypertension (CTEPH), but surprisingly little is known about the incidence of hemoptysis in these patients. In this paper, we report on 2 patients with CTEPH and recurrent severe hemoptysis, who were treated by bronchial artery embolization. One patient recovered and 1 patient died as a consequence of the bleeding. A systematic review revealed 21 studies on the underlying pathology in 1,844 patients with moderate to severe hemoptysis. CTEPH was reported to be the cause of bleeding in 0.1% (n = 2), pulmonary arterial hypertension without chronic thromboembolic disease in 0.2% (n = 4), and acute pulmonary embolism in 0.7% (n = 12) of the patients. In contrast to this, 5 patients (6%) in our own series of 79 CTEPH patients suffered from moderate to severe hemoptysis requiring medical intervention. Severe hemoptysis appears to be an uncommon, but possibly underreported, life-threatening complication in CTEPH patients. As most CTEPH patients require life-long anticoagulants a therapeutic dilemma may ensue. Therefore, we propose that even mild hemoptysis in CTEPH patients warrants prompt evaluation, and treatment by embolization should be offered as first choice in CTEPH patients.     

Staging of cholangiocarcinoma: the role of endoscopy

The main question for staging is resectability, which is reliant on vascular, longitudinal, and metastatic spread. Today, accurate staging of perihilar tumors is achieved by non-invasive diagnostic investigations. Direct cholangiography has been the gold standard as a diagnostic procedure in recent decades. Endoscopic retrograde cholangiopancreaticography (ERCP) often only shows the ducts below the obstruction, and visualization of an obstructed part of the biliary tree is often not possible. Direct cholangiography reveals no information about local tumor extension, lymph nodes, or vascular involvement. Because of the given limitations, potential complications (cholangitis, sepsis) associated with direct cholangiography and reduction of the accuracy of subsequent cross-sectional imaging studies, these invasive techniques should only be used in the case of palliative interventions. Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) can be used to assess the nature of biliary strictures and to derive information about the extent of periductal disease and the presence of lymph node metastases. In a study by Fritscher-Ravens, 44 patients with hilar strictures underwent EUS-FNA. The overall diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were 91% (95% CI, 78.4-96.3%), 89% (95% CI, 73.3-96.8%), 100% (95% CI, 63.1-100%), 100% (95% CI, 88.8-100%), and 67% (95% CI, 34.9-90%), respectively. The planned surgical approach was changed in 27 of 44 patients. In 15-20% of cholangiocarcinoma, patients with unremarkable abdominal imaging studies have metastatic lymph node involvement according to EUS evaluation. Due to the risk of peritoneal seeding, however, EUS with FNA is not recommended in patients still with a potential curative tumor.     

Impact evaluation of a Dutch community intervention to improve health-related behaviour in deprived neighbourhoods

This study investigates the impact of a 2-year community intervention on health-related behaviour among adults aged 18-65 years living in deprived neighbourhoods in Eindhoven, The Netherlands. The intervention is evaluated in a community intervention trial with a quasi-experimental design in a longitudinal cohort survey (n=1926 and attrition rate: 31%) using postal questionnaires. In the 2-year implementation phase, more than 40 intervention activities were planned and delivered by intersectoral neighbourhood coalitions. Outcome measures were fruit consumption, vegetable consumption, physical activity, smoking, alcohol consumption and intermediate outcomes of behaviour (i.e. attitudes, self-efficacy, awareness, knowledge and stages of change). The intervention demonstrated no evidence for an impact on vegetable consumption, physical activity, smoking and alcohol consumption and weak evidence for a small impact on (intermediate) outcomes of fruit consumption.