The National Institute for Clinical Excellence (NICE)

In discussions on the development of the institutional framework for decisions on the benefit package of social health insurance in Germany, the English National Institute for Clinical Excellence (NICE) is considered as either a good or a bad example for reform. According to this study, the procedures and criteria applied by NICE for making health care coverage decisions are legitimate. Procedures are transparent and interest groups are broadly represented. Decision criteria include cost effectiveness of services - albeit only if information on cost effectiveness is available and highly evident. Furthermore, cost effectiveness is not the only criteria for coverage decisions. NICE very rarely induces strong direct rationing, but rather leaves room for discretion. However, the trade-off between maximising allocative efficiency and avoiding distributional consequences becomes apparent.     

Transdisciplinary collaboration as a basis for enhancing the science and prevention of Substance use and "Abuse"

Transdisciplinary scientific collaborations (TDSCs) have the potential to strengthen substance use and misuse research and prevention. Despite its growing prominence as a mode for scientific research, research on TDSC remains in a nascent form and its value to the field of substance use and misuse merits further exploration. The overarching purpose of this article is to examine the potential contributions of transdisciplinary science to research and prevention using conceptualizations, methods, and evidence from a case study of two university-based research centers. The article provides (a) a discussion of the societal context and historical developments that have prompted increasing interest in TDSC; (b) a definition and conceptualization of TDSC; (c) a methodological approach for studying TDSC; (d) initial findings from the case study that reflect instances of transdisciplinary intellectual integration and it examines implications of these methods and findings for future research and policy development relevant to substance use and misuse.     

EUS-guided fine needle aspiration of idiopathic abdominal masses

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) has significantly increased the diagnostic capability of EUS. FNA can also be helpful in the diagnosis of non-GI disorders. The role of EUS-FNA in the diagnosis of idiopathic abdominal masses has not been determined. This study evaluated the diagnostic accuracy of EUS-FNA of abdominal masses of unknown cause and its impact on subsequent evaluation and therapy. METHODS: Thirty-four patients from 5 tertiary referral centers (21 women, 13 men; mean age 54 years, range 27-72 years) with idiopathic abdominal masses underwent EUS-FNA. Presenting symptoms included the following: pain (29 patients), weight loss (15), altered bowel habits (7), nausea/vomiting (6), abnormal liver function tests (4), palpable mass (4), and urinary retention (1). Four patients had a history of intra-abdominal cancer (2 cervical, 1 ovarian, 1 colon). A final diagnosis by EUS-FNA, surgery, autopsy, or long-term follow-up was available in all patients. Abdominal masses were classified into 3 disease categories: infectious, benign/inflammatory, and malignant. RESULTS: Final diagnosis included infectious (5), benign/inflammatory (6), and malignant (23) abdominal mass. Overall, EUS-FNA established a tissue diagnosis in 29 of 34 patients (85%) in all 3 categories (infectious, 80%; benign/inflammatory, 67%; malignant, 91%). EUS-FNA was instrumental in directing subsequent evaluation in 29 patients (85%) and therapy in 26 (77%). The number of fine needle passes for adequate tissue sampling was lower for nonmalignant (2.2-3.2) versus malignant diseases (4.6). One complication occurred (perirectal abscess) and was treated successfully with antibiotics. CONCLUSIONS: EUS-FNA of idiopathic abdominal masses is safe and accurate and helps to guide subsequent evaluation and therapy in the majority of patients. The most common and promising area seems to be EUS-FNA of malignant abdominal masses. Transluminal EUS-FNA provides minimally invasive tissue sampling and obviates the need for exploratory laparotomy.     

KOC is a novel molecular indicator of malignancy

The detection of malignant cells in fine-needle aspirates (FNA's) using marker genes is hampered by the fact that these markers are only expressed by certain malignancies or lack sensitivity and/or specificity. Here we report the results of a prospective pilot study examining the expression of KOC (KH-domain containing protein over expressed in cancer), a novel onco-foetal gene, in 76 patients who underwent fine-needle aspiration for further diagnosis of abdominal lesions, aszites, cysts or cerebrospinal fluid. Aspirates were examined by cytology and by a KOC RT-PCR assay. KOC expression was a highly sensitive and specific indicator of malignancy. The KOC assay could be useful to facilitate screening for malignant disease and to improve the diagnostic accuracy of FNAs.     

Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer

Claudin-4 has been identified as an integral constituent of tight junctions and has been found to be highly expressed in pancreatic cancer. The aim of the present study was to elucidate the effect of claudin-4 on growth and metastatic potential in pancreatic cancer cells, as well as the regulation of claudin-4 by oncogenic pathways. Claudin-4 was stably overexpressed in SUIT-2 pancreatic cancer cells, and its effect on invasion and growth in vitro was examined by using two-chamber invasion assays, soft agar assays, and fluorescence-activated cell sorter analysis. Claudin-4 localization was characterized by light and electron microscopy, and pulmonary colonization was analyzed in vivo after injection of claudin-4 overexpressing cells into the tail vein of nude mice. Overexpression of claudin-4 was associated with significantly reduced invasive potential in vitro and inhibited colony formation in soft agar assays. In vivo, tail vein-injected claudin-4 overexpressing cells formed significantly less pulmonary metastases in comparison with mock-transfected cells. These effects were not caused by changes in proliferation, cell cycle progression, or matrix metalloproteinase gelatinolytic activity, but were paralleled by increased cell contact formation. Moreover, proinvasive transforming growth factor beta was able to down-regulate claudin-4 in PANC-1 cells. Inhibition of Ras signaling by using dominant-negative Ras and specific inhibitors of both downstream effectors mitogen-activated protein/extracellular signal-regulated kinase kinase and phosphatidylinositol 3'-kinase also decreased claudin-4 expression. Our findings identify claudin-4 as a potent inhibitor of the invasiveness and metastatic phenotype of pancreatic cancer cells, and as a target of the transforming growth factor beta and Ras/Raf/extracellular signal-regulated kinase pathways.     

Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin

BACKGROUND & AIMS: Recently, several members of the claudin family have been identified as integral constituents of tight junctions. Using expression profiling, we previously found claudin-4 to be overexpressed in pancreatic cancer. Because claudin-4 has been described as a receptor for the cytotoxic Clostridium perfringens enterotoxin (CPE), we investigated the effect of CPE on pancreatic cancer cells. METHODS: Expression of claudin-4 was analyzed by Northern blots. In vitro toxicity of CPE was determined by trypan blue exclusion and the (86)Rb-release assay. The in vivo effect of CPE was studied in claudin-4-expressing nude mouse xenografts of the Panc-1 cell line. RESULTS: Expression analyses showed that claudin-4 was overexpressed in most pancreatic cancer tissues and cell lines and several other gastrointestinal tumors. CPE led to an acute dose-dependent cytotoxic effect, restricted to claudin-4-expressing cells and dependent on claudin-4 expression levels. Furthermore, transforming growth factor beta was identified as a negative modulator of both claudin-4 expression and susceptibility to CPE. In vivo, intratumoral injections of CPE in Panc-1 xenografts led to large areas of tumor cell necrosis and significant reduction of tumor growth. CONCLUSIONS: Our findings suggest that targeting claudin-4-expressing tumors with CPE represents a promising new treatment modality for pancreatic cancer and other solid tumors.     

A prospective evaluation of the incidence of bacteremia associated with EUS-guided fine-needle aspiration

BACKGROUND: Endoscopic ultrasound (EUS)--guided fine-needle aspiration (FNA) is frequently performed for diagnostic evaluation of lesions in or near the gastrointestinal (GI) tract. Little data exist concerning possible infectious complications associated with EUS-guided FNA. This prospective evaluation was undertaken to determine the frequency of bacteremia and infectious complications associated with EUS-guided FNA. METHODS: All patients undergoing EUS-guided FNA for any indication were enrolled in this study. Patients who required antibiotic prophylaxis as per the American Heart Association or American Society for Gastrointestinal Endoscopy guidelines were excluded from the study as were patients with cystic lesions, patients with advanced liver disease/ascites and those with human immunodeficiency virus/acquired immune deficiency syndrome. Blood cultures were obtained 30 and 60 minutes after the EUS-FNA. Patients were monitored for evidence of infection after procedure including telephone follow-up of each subject 1 week after procedure. RESULTS: One hundred patients underwent EUS-FNA of 108 lesions. All blood cultures were negative except in 6 patients in whom 1 of 2 bottles were positive for coagulase negative Staphylococcus, which was considered a contaminant. There were no complications of acute febrile illness, abscess or other infections. CONCLUSION: EUS-guided FNA was not associated with bacteremia or infectious complications.     

唐古特大黄提取物不同成分泻下作用的比较研究

目的：研究唐古特大黄提取物不同成分的泻下作用。方法：采用炭末推进方法、酚红排空方法进行肠推进实验,观察大黄提取物各成分(15 g·kg^-1)对小鼠小肠推进和肠水分吸收、大鼠大肠运动的影响。结果：唐古特大黄提取物不同成分与对照组相比,对小鼠小肠推进和肠水分吸收、大肠推进作用均有显著性差异(P<0.01)；与大黄水煎液、醇提液相比,泻下活性存在一些差异。结论：唐古特大黄提取物不同成分均有显著的泻下作用,但与大黄水煎液和醇提液相比有一些差异。