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Periprosthetic osteolysis is one of the main reasons for revision of arthroplasty. The osteolytic reaction is influenced by the dose, size and shape of the wear particles. For arthroplasty, a low number and biologically less active particles are required. This is the first study which analyzes the impact of different knee designs, combined with crosslinked polyethylenes (sequentially irradiated and annealed as well as remelted techniques), on the amount, size and shape of particles. Overall, six material combinations, four of them with crosslinked polyethylene (XPE) and two of them with ultra-high molecular weight polyethylene (UHMWPE) inserts, including fixed and mobile bearings, were tested in a knee joint simulator. After isolation nearly 100,000 particles were analyzed in size, shape and number by scanning electron microscopy and image analysis. For all the designs, the wear was predominantly smooth and granular with few fibrillar particles. The Scorpio design with the X3 insert, the Natural Knee II design with the Durasul insert and the LCS design, also combined with a crosslinked polyethylene insert, generated statistically significant (P0.05) lower particle numbers. The particle size was independent of the radiation dose. The wear generated by the LCS knee design (XPE and UHMWPE) had a higher percentage fraction of particles1microm in size (equivalent circle diameter). The NexGen design, tested with the Prolong insert, showed a high number of particles in the biologically active size range compared with the other crosslinked designs, which could be a predictor for higher biological reactivity.

High-fidelity simulation uses simulators that combine all of the physiological and pharmacological responses of a human in a manikin. These simulators change and respond to the users and trainees. Using simulators for teaching sedation in the field of gastroenterology unifies all the advantages of manikins. To understand the pharmacological and pharmacodynamical principles of drugs used for sedation in different clinical scenarios, such as cardiopulmonary diseases, a high-fidelity simulator is extremely useful. Respiratory complications and airway problems are the main side effects when using sedatives. To overcome these problems, exercise of precautionary measures are highly demanded to avoid hazards. High-fidelity simulation is increasingly being used for the development of crisis resource management. There are still limitations in using simulators for education and training. At present, applying simulation for teaching is expensive. The start-up costs and the expenses for instructors and technicians are high. Moreover, no direct evidence has demonstrated that simulation training improves actual patient safety outcome and, therefore, a lot of research in this field remains to be done. Even so, confidence is growing in the validity of medical simulation as the training tool of the future.

Peroxisome proliferator-activated receptor gamma (PPARgamma), a fatty acid-activated nuclear receptor, is implicated in adipocyte differentiation and insulin sensitisation. In view of the association of dietary fat intake and bowel disease, the expression of PPARgamma in rodent and human intestine was studied. Expression of PPARgamma mRNA was examined by Northern blot hybridisation, RNase protection, and/or competitive RT-PCR assays, whereas PPARgamma protein levels were evaluated by immunoblotting and immunohistochemistry. PPARgamma mRNA and protein were abundantly expressed in colon relative to the small intestine both in rodents and in man. Interestingly, expression of PPARgamma was primarily localised in the more differentiated epithelial cells in the colon. The level of expression of PPARgamma in colon was similar to the levels seen in adipose tissue. Expression of PPARgamma increased from proximal to distal segments of the colon in man. In Caco-2 and HT-29 human adenocarcinoma cells, PPARgamma expression increased upon differentiation, consistent with PPARgamma being associated with a differentiated epithelial phenotype. High-level expression of PPARgamma was observed in the colon, but not in the small intestine, suggesting a potential role of this nuclear receptor in the colon.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of insulin resistance (IR), and IR is associated with an increased risk of colorectal carcinoma (CRC). Increased echogenicity suggesting NAFLD is a frequent incidental finding on ultrasound examination. We aimed to systematically evaluate whether NAFLD is an independent risk factor for colonic neoplasia.One thousand two hundred and eleven patients (603 males, 60.6 ± 9.6 years; 608 females, 61.1 ± 10.3 years) who underwent screening colonoscopy according to national screening recommendations for CRC were evaluated in a cross-sectional study. Colorectal adenomas were classified as tubular adenoma, advanced adenoma (villous features, size ≥ 1 cm or high-grade dysplasia) or carcinoma. NAFLD was diagnosed by increased echogenicity on ultrasound examination after serological exclusion of infectious, immunological, hereditary or alcoholic aetiology.Nonalcoholic fatty liver disease was diagnosed in 367 (60.8%) males and in 265 (43.5%) females. The total rate of adenomas was increased in subjects with NAFLD (243/367 vs. 107/236 in males, P = 0.010; 94/265 vs. 78/343 in females; P = 0.014). In particular, more tubular adenomas (127/367 vs. 56/236; P = 0.006), adenomas of the rectum (40/367 vs. 8/236; P = 0.004) and more cancers (6/367 vs. 1/236; P0.001) were observed in males with NAFLD. In females with NAFLD, more tubular adenomas (59/265 vs. 48/343; P = 0.011) and adenomas of the proximal colon (51/265 vs. 40/343; P = 0.041) were observed. Multivariate regression analyses demonstrated an independent association of colorectal adenomas with hepatic steatosis after adjustment for age, sex, body mass index and glucose intolerance (OR 1.47; 95% CI 1.079-2.003; P = 0.015).Patients with NAFLD undergoing screening colonoscopy reveal significantly more CRC precursor lesions and early CRC compared with subjects without NAFLD. This elevated risk is independent from other manifestations of IR. These findings suggest that detecting fatty liver on ultrasound should heighten the awareness for referral to screening colonoscopy.

Methods: We studied 157 patients in accordance with the inclusion criteria, who underwent paired liver biopsies from 1994 to 2012. Ninety-three patients had treatment failure (TF) and 64 patients were treatment-naive (TN). Annual fibrosis progression rate (FPR) was calculated and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow-up. Because of the differences in baseline biochemical and histological features, multiple regression analyses with backward elimination were performed to find out independent predictors of SFP and FPR. Results: Demographic characteristics and duration between paired liver biopsies were similar in TF and TN-groups. Baseline ALT and GGT levels (82±48 vs. 45±20 and 60±45 vs. 36±27, respectively), baseline mean fibrosis stage (2.9±1.1 vs. 1.9±0.8) and histologic activity index (6.7±1.9 vs. 4.3±1.6) were higher in TF-group compared to TN-group (p < 0.001). According to regression analyses strongest independent predictor of fibrosis progression was GGT level (OR: 1.03, 95%CI 1.01–1.5, p < 0.001). Treatment experience (OR: 4.55, 95%CI 1.27–16.2, p = 0.02) and follow-up ALT levels (OR: 4.20, 95%CI 1.41–12.5, p = 0.01) also appeared independent predictors of FPR and SFP. Conclusion: Failed interferon-based treatment against CHC may lead to accelerated FPR in long-term compared to natural course.

To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders.304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months.Virological response at end of treatment and 6 months thereafter.University hospitals and tertiary referral centres.At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA.A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.

Sera of 223 dyspeptic patients with endoscopic findings of nonulcer dyspepsia (72%), gastric ulcer (15%) and duodenal ulcer (13%) were tested for antibodies against Helicobacter pylori with an enzyme immunoassay and an immunoblot technique using lysates of Helicobacter pylori cells as antigen source. One hundred and fifty-one (68%) sera were found to be positive for Helicobacter pylori IgG with both methods; 5% of the positive results in the enzyme immunoassay were false-positive due to cross-reactions mainly of proteins with a molecular mass of 43-66 kDa. Since cross-reactivity not only reduces the diagnostic value of the immunoassay but also complicates evaluation of the immunoblot results, an attempt was made to overcome these problems by using specific purified recombinant proteins instead of the crude cell preparations as antigens. Of the commonly recognised immunogens of Helicobacter pylori, antibodies against a cell surface protein of 26 kDa, the small urease subunit (29 kDa) and the cytotoxin-associated protein (130 kDa) were identified as highly sensitive serological markers for inclusion in a recombinant antigen mixture for Helicobacter pylori screening. Only the cytotoxin-associated protein was confirmed to be an indicator immunogen for ulcerogenic strains. To assess the reliability of recombinant fragments of this protein in serological screening, the reactivity of antibody to purified fragments of the cytotoxin-associated protein was compared with that to the natural protein. A C-terminal recombinant fragment of 58 kDa showed results identical to those obtained with the natural protein and was thus considered to be an appropriate component of an antigen mixture for serological detection of Helicobacter pylori.

prevalence and potential effect of graft vs recipient IL28B genotype on early HCV-RNA kinetics after liver transplantation (LT). Objective and Methods: Retrospective-prospective assessment of IL28B-SNP rs12979860 by PCR-RFLP (Forward – TTATCGCATACGGCTAGGC; Reverse – ACAATTCCCACCACGAGAC; BstUI) in a cohort of HCV subjects undergoing LT between Jan 2001-November 2010, and evaluation of the impact of graft vs recipient IL28B genotypes on week 4 HCV-RNA decay. Results: IL28B was performed in 89/171 consecutive HCV-LT subjects (52%): both graft/recipient 55 (62%), only recipient 17 (19%), only graft 17 (19%), 77 HCV G1/4 (86.5%). The overall distribution of IL28B genotypes in graft (n = 72) was: C/C 38% (n =27), C/T 54% (n =39), T/T 8% (n =6), and in recipients (n = 72): C/C 33% (n =24), C/T 46% (n =33), T/T 21% (n =15). When both samples were available (n = 55), concordance was observed in 26 (47%): C/C 47%, C/T 58%, T/T 25%), with no differences according to HCV genotype (56% G2/G3, 46% G1/G4, p = 0.72). 61 patients (36%) started peg-IFN/RBV after LT, 54 HCV-G1/4 (88.5%), with median HCV-RNA 6.9 log10 IU/ml (5.15–8.3), and IL28B available in 60 (98%): both samples 38 (63%), graft 13 (22%), recipient 9 (15%). In HCV G1/4 subjects, HCV-RNA decay at week 4 was strongly influenced by recipient (C/C −1.85 log10 IU/ml vs C/T −0.95 log10 IU/ml and T/T −0.76 log10 IU/ml, P = 0.053; C/C −1.85 log10 IU/ml vs nonC/C −0.88 log10 IU/ml p =0.017), but not by graft IL28B genotype (C/C −1.05 log10 IU/ml, C/T −1.11 log10 IU/ml, T/T −0.09 log10 IU/ml, P = 0.31; C/C −1.21 log10 IU/ml vs non-C/C −0.93 log10 IU/ml p =0.4), effect not observed in HCV G2/3 subjects: graft (p = 0.37), recipient (p = 0.55). Conclusions: In LT subjects, C/T was the most prevalent IL28B genotype, both in graft and recipients, with a high concordance rate. Only in patients with HCV G1/4, recipient but not graft IL28B genotype significantly affected week 4 HCV-RNA decay on pegIFN/RBV.

P. Ferenci 1 , U. Bergholz 1 , H. Laferl 2, T.M. Scherzer 1 , A. Maieron 3, M. Gschwantler 4, H. Brunner 5, R.R. Hubmann 6, C. Datz 7, M. Bischof e, R. Stauber 9, R Steindl-Munda 1 . 1Department of Internal Medicine IE Medical University of Vienna, Allgemeines Krankenhaus, Wien, Austria," 2Kaiser Franz Josef Hospital, Wien, Austria," 3 Krankenhaus der Elisabethinnen, Linz, Austria," 4 Wilhelminenhospital, Wien, Austria," 5 Krankenhaus Lainz, Wien, Austria," 6General Hospital, Linz, Austria," 7Krankenhaus Oberndorf 8Krankenhaus Rudolj~'tiftung, Wien, Austria," 9Department of Internal Medicine, Medical University of Graz, Austria