A regional EUS service using a collaborative network.

Endoscopic ultrasound (EUS) is increasingly used in the management of hepatobiliary lesions, allowing staging and tissue acquisition. It is operator-dependent, and fine needle aspiration (FNA) of solid lesions provides an auditable standard; high-volume centres have shown excellent results for solid pancreatic lesion FNA with sensitivities of 92%-97%. The British Society of Gastroenterology guidelines stress that clinical quality should determine service provision, with geographical accessibility a secondary consideration. We set up the Wessex EUS network, working from a single hepatobiliary (HPB) pancreatic multidisciplinary team, with EUS provided in four local centres providing agreed standards and audit. Pancreatic solid lesion FNA results showed a pooled sensitivity of 94%, comparable with high-volume single centres. This demonstrates a network with good clinical governance is a plausible solution to providing a specialist service such as EUS and may be a roadmap that other specialist services under pressure could follow.

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers. METHODS: Relevant articles were identified via Ovid medline 1946-2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis. RESULTS: A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15-3.79), CD3 (HR=0.51, 95% CI=0.32-0.70), CD8 (HR=0.55, CI=0.31-0.80) and EGFR (HR=1.65, 95% CI=1.14-2.16). DISCUSSION: Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.

Abdominal fat distribution in pre- and postmenopausal women: The impact of physical activity, age, and menopausal status.

Age-related increases in total body fat have been reported, but the impact of menopause on abdominal fat distribution is still unclear. The purpose of this study was to determine the impact of menopausal status on abdominal fat distribution using magnetic resonance imaging (MRI). In addition, we investigated the influence of abdominal fat distribution on blood lipid profiles and leptin concentrations. Twenty-three premenopausal (PRE), 27 postmenopausal (POST), and 28 postmenopausal women on estrogen replacement therapy (ERT) had measurements of regional abdominal fat, blood lipids, and serum leptin concentrations. The women were matched for body mass index (BMI) and total body fat mass. Age and menopausal status were not found to be significant predictors of total abdominal fat, visceral fat, or subcutaneous fat, while physical activity was a significant predictor (P <.01) for total abdominal fat (R(2) =.16), visceral fat (R(2) =.32) and percent visceral fat (R(2) =.25). There was a trend for a greater visceral fat content in the POST women compared with the PRE women (2,495.0 +/- 228.4 v 1,770.4 +/- 240.8 cm(2), respectively, P =.06). The percent visceral abdominal fat was significantly lower (P <.05) in the premenopausal women than in either postmenopausal group (PRE, 23.2% +/- 1.7%; POST, 28.9% +/- 1.8%; ERT, 28.9% +/- 1.6%). Menopausal status and age did not influence any of the blood lipid values. Abdominal fat distribution was a significant predictor of cholesterol concentrations and the cholesterol/high-density lipoprotein-cholesterol (HDL-C) ratio, but only accounted for approximately 15% of the variability in these levels. Total body fat and physical activity accounted for 47% of the variability in leptin concentrations, while abdominal fat distribution, age, and menopausal status were not significant predictors. In conclusion, in early postmenopausal women, the level of physical activity accounts for the variability in abdominal fat distribution observed, while menopausal status and age do not play a significant role. ERT was not associated with additional benefits in abdominal fat distribution compared with postmenopausal women not on ERT or in the blood lipid profile in these women.

Obesity attenuates the growth hormone response to exercise.

Resting serum GH concentrations are decreased in obesity. In nonobese (NonOb) individuals, acute exercise of sufficient intensity increases GH levels; however, conflicting data exist concerning the GH response to exercise in obese individuals. To examine the exercise-induced GH response in obese individuals, we studied 8 NonOb, 11 lower body obese (LBO), and 12 upper body obese (UBO) women before, during, and after 30 min (0800-0830 h) of treadmill exercise at 70% oxygen consumption peak. Blood samples were taken every 5 min (0700-1300 h) and were analyzed for GH concentrations with a sensitive (0.002 microg/L) chemiluminescence assay. The impact of 16 weeks of aerobic exercise training on the GH response to exercise was also examined in the obese women. In response to exercise, the 6-h integrated GH concentration was significantly greater (P < 0.05) in the NonOb women (1006 +/- 220 min/microg x L) than in either of the obese groups (LBO, 435 +/- 136; UBO, 189 +/- 26 min/microg x L). No differences were found between the LBO and UBO women. The increased integrated GH concentrations could be accounted for by a greater 6-h GH production rate [micrograms per L distribution volume (Lv)] in the NonOb women than in either of the obese groups (NonOb, 45.6 +/- 12.3; LBO, 16.9 +/- 1.2; UBO, 8.7 +/- 0.64 microg/Lv; P < 0.05). This increase was attributed to a greater mass of GH secreted per pulse in the NonOb women (NonOb, 10.8 +/- 2.5; LBO, 4.9 +/- 0.8; UBO, 4.0 +/- 0.5 microg/Lv; P < 0.05, NonOb vs. both obese groups). After 16 weeks of aerobic training, maximal oxygen consumption increased from 44.7 +/- 2.2 to 48.5 +/- 1.9 mL/kg fat-free mass x min; P < 0.05), but no significant change in body composition occurred in the 10 obese women who completed the training. No change was observed in the GH response to exercise after training (n = 10; pre, 379 +/- 144; post, 350 +/- 55 min/microg x L). In conclusion, the GH response to exercise was attenuated in the obese women compared to NonOb women. Short term aerobic training improved fitness, but did not increase the GH response to exercise.

Antibiotic effects on the photoinduced affinity labeling of Escherichia coli ribosomes by puromycin.

The effect of ribosomal antibiotics on the photoinduced affinity labeling of Escherichia coli ribosomes by puromycin [Cooperman, B.S., Jaynes, E.N., Brunswick, D.J., & Luddy, M.A. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 1974; Jaynes, E.N. Jr., Grant, P.G., Giangrande, G., Wieder, R., & Cooperman, B.S. (1978) Biochemistry 17, 561] has been studied. Although blasticidin S, sparsomycin, lincomycin, and erythromycin are essentially without effect, major changes are seen on addition of either chloramphenicol or tetracycline. The products of photoincorporation have been characterized by one- and two-dimensional gel electrophoresis and by specific immunoprecipitation with antibodies to ribosomal proteins. In the presence of chloramphenicol, protein S14 becomes the major labeled protein. In the presence of tetracycline, L23 remains the major labeled protein, but the yield of labeled ribosomes is enormously increased, and the labeling is more specific for L23. These results are discussed in terms of the known modes of action of these antibiotics and the photoreactivity of tetracycline.

Photoinduced affinity labeling of the Escherichia coli ribosome puromycin site.

The photoincorporation of puromycin into Escherichia coli ribosomes has been studied in detail. Incorporation into protein L23 as a function of puromycin concentration follows a simple saturation curve and is specifically blocked by structural and functional analogues of puromycin, thus demonstrating that such incorporation proceeds via an affinity labeling process. Incorporation into L23 becomes more specific as the light fluence is reduced, indicating that such incorporation takes place from a native rather than light-denatured puromycin site. L23 remains the major labeled protein using ribosomes prepared by several procedures, suggesting the conservative nature of the site. In addition evidence is presented for affinity labeling of S14 and of a site in the RNA fraction of the 50S particle. Specific incorporation appears to proceed with an anomalously high quantum yield. The detailed photochemical mechanism is not understood, although 8-alkylation of purine moiety has been excluded. Incorporation is largely inhibited in the presence of thiol reagents.

Photoincorporation of puromycin and N-(ethyl-2-diazomalonyl)puromycin into Escherichia coli ribosomes.

[3H]Puromycin and N-(ethyl-2-diazomalonyl)[3H]puromycin are incorporated into E. coli ribosomes on irradiation at 253.7 nm. Both compounds incorporate into both protein and nucleic acid. Two-dimensional gel electrophoresis of ribosomal protein shows that L23 is the major protein labeled by puromycin. Although incorporation is clearly a complex process, evidence is presented that L23 is labeled via an affinity labeling process, thus placing L23 at the aminoacyl-tRNA receptor (A) site. N-(ethyl-2-diazomalonyl)puromycin is a ribosomal ligand, as shown by its inhibition of two ribosomal assays, but it is not a good puromycin analog, and it is unclear whether its incorporation, which proceeds via both carbene-dependent and carbene-independent processes, results from affinity labeling.