Summary
Background
Barrett's surveillance is prone to sampling error.
Aim
To determine whether enhanced magnification endoscopy using acetic acid instillation improves diagnostic accuracy of ...specialized intestinal metaplasia/dysplasia in Barrett's oesophagus.
Methods
We examined the detection rate of the specialized intestinal metaplasia/dysplasia in 64 consecutive patients with Barrett's oesophagus using acetic acid to enhance mucosal pit patterns. Histology was compared with the previous findings at recent conventional surveillance in 62 patients. We also examined the inter‐/intra‐observer agreement in the assessment of the enhanced magnification endoscopy pit pattern findings.
Results
Histology revealed columnar‐lined oesophagus in six (9%) patients, specialized intestinal metaplasia in 49 (77%), low‐grade dysplasia in five (8%), high‐grade dysplasia in one (2%), and adenocarcinoma in three (5%). There was discordance between the histologic findings from conventional surveillance with random biopsy. Fifteen patients (24%) had a histological upgrade with enhanced magnification endoscopy. There was a high detection rate of specialized intestinal metaplasia even in short segment Barrett's oesophagus (74%), and additionally, there were two cancers, one with 2‐cm Barrett's oesophagus and one ultra‐short (1 cm). The mean kappa values for inter‐ and intra‐observer agreement in assessing the pit patterns were 0.571 (0.041) and 0.709 (0.038), respectively.
Conclusions
Enhanced magnification endoscopy allows clear visualization of the epithelial pit patterns within Barrett's oesophagus, and targeted biopsy results in a high yield of specialized intestinal metaplasia and dysplasia.
NSTX plasma operation with a Liquid Lithium Divertor Kugel, H.W.; Allain, J.P.; Bell, M.G. ...
Fusion engineering and design,
October 2012, 2012-10-00, 20121001, 2012-10-01, Letnik:
87, Številka:
10
Journal Article
Recenzirano
► NSTX 2010 experiments tested the effectiveness of maintaining the deuterium retention properties of a static liquid lithium molybdenum divertor surface when refreshed by lithium evaporation as an ...approximation to a flowing liquid lithium surface. ► Noteworthy improvements in plasma performance with the plasma strike point on the liquid lithium molybdenum divertor were obtained similar to those obtained previously with lithiated graphite. The role of lithium impurities in this result is discussed. ► Inspection of the liquid lithium molybdenum divertor after the Campaign indicated mechanical damage to supports, and other hardware resulting from forces following plasma current disruptions.
NSTX 2010 experiments were conducted using a molybdenum Liquid Lithium Divertor (LLD) surface installed on the outer part of the lower divertor. This tested the effectiveness of maintaining the deuterium retention properties of a static liquid lithium surface when refreshed by lithium evaporation as an approximation to a flowing liquid lithium surface. The LLD molybdenum front face has a 45% porosity to provide sufficient wetting to spread 37g of lithium, and to retain it in the presence of magnetic forces. Lithium Evaporators were used to deposit lithium on the LLD surface. At the beginning of discharges, the LLD lithium surface ranged from solid to liquefied depending on the amount of applied and plasma heating. Noteworthy improvements in plasma performance were obtained similar to those obtained previously with lithiated graphite, e.g., ELM-free, quiescent edge, H-modes. During these experiments with the plasma outer strike point on the LLD, the rate of deuterium retention in the LLD, as indicated by the fueling needed to achieve and maintain stable plasma conditions, was the about the same as that for solid lithium coatings on the graphite prior to the installation of the LLD, i.e., about two times that of no-lithium conditions. The role of lithium impurities in this result is discussed. Following the 2010 experimental campaign, inspection of the LLD found mechanical damage to the plate supports, and other hardware resulting from forces following plasma current disruptions. The LLD was removed, upgraded, and reinstalled. A row of molybdenum tiles was installed inboard of the LLD for 2011 experiments with both inner and outer strike points on lithiated molybdenum to allow investigation of lithium plasma facing issues encountered in the first testing of the LLD.
Abstract Objectives To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. Materials and methods The ...clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. Results and conclusions Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n = 12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p = 0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p = 0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.
BACKGROUND AND PURPOSE Nitrate tolerance, the loss of vascular responsiveness with continued use of nitrates, remains incompletely understood and is a limitation of these therapeutic agents. Vascular ...superoxide, generated by uncoupled endothelial NOS (eNOS), may play a role. As arginase competes with eNOS for L‐arginine and may exacerbate the production of reactive oxygen species (ROS), we hypothesized that arginase inhibition might reduce nitrate tolerance.
EXPERIMENTAL APPROACH Vasodilator responses were measured in aorta from C57Bl/6 and arginase II knockout (argII –/–) mice using myography. Uncoupling of eNOS, determined as eNOS monomer : dimer ratio, was assessed using low‐temperature SDS‐PAGE and ROS levels were measured using L‐012 and lucigenin‐enhanced chemiluminescence.
KEY RESULTS Repeated application of glyceryl trinitrate (GTN) on aorta isolated from C57Bl/6 mice produced a 32‐fold rightward shift of the concentration–response curve. However this rightward shift (or resultant tolerance) was not observed in the presence of the arginase inhibitor (s)‐(2‐boronethyl)‐L‐cysteine HCl (BEC; 100 µM) nor in aorta isolated from argII –/– mice. Similar findings were obtained after inducing nitrate tolerance in vivo. Repeated administration of GTN in human umbilical vein endothelial cells induced uncoupling of eNOS from its dimeric state and increased ROS levels, which were reduced with arginase inhibition and exogenous L‐arginine. Aortae from GTN tolerant C57Bl/6 mice exhibited increased arginase activity and ROS production, whereas vessels from argII –/– mice did not.
CONCLUSION AND IMPLICATIONS Arginase II removal prevents nitrate tolerance. This may be due to decreased uncoupling of eNOS and consequent ROS production.
This study investigated sonic hedgehog (Shh) signalling in gastric metaplasia in the insulin-gastrin (InsGas) hypergastrinaemic mouse +/- Helicobacter felis (H. felis) infection. Sonic hedgehog gene ...and protein expression was reduced in pre-metaplastic lesions from non-infected mice (90% gene reduction, P<0.01) compared to normal mucosa. Sonic hedgehog was reactivated in gastric metaplasia of H. felis-infected mice (3.5-fold increase, P<0.01) compared to pre-metaplastic lesions. Additionally, the Shh target gene, glioma-associated oncogene (Gli)-1, was significantly reduced in the gastric glands of InsGas mice (75% reduction, P<0.05) and reactivated with H. felis infection (P<0.05, base of glands, P<0.01 stroma of metaplastic glands). The ability of H. felis to activate the Shh pathway was investigated by measuring the effect of target cytokine, interleukin-8 (IL-8), on Shh expression in AGS and MGLVA1 cells, which was shown to induce Shh expression at physiological concentrations. H. felis induced the expression of NF-kappaB in inflammatory infiltrates in vivo, and the expression of the IL-8 mouse homologue, protein KC, in inflammatory infiltrates and metaplastic lesions. Sonic hedgehog pathway reactivation was paralleled with an increase in proliferation of metaplastic lesions (15.75 vs 4.39% in infected vs non-infected mice, respectively, P<0.001). Furthermore, Shh overexpression increased the growth rate of the gastric cancer cell line, AGS. The antiapoptotic protein, bcl-2, was expressed in the stroma of infected mice, along with a second Shh target gene, patched-1 (P=0.0001, stroma of metaplastic gland). This study provides evidence suggesting reactivation of Shh signalling from pre-metaplastic to advanced metaplastic lesions of the stomach and outlines the importance of the Shh pathway as a potential chemoprophylactic target for gastric carcinogenesis.
Background IgE antibodies, sequestered into tissues and retained locally by the high-affinity IgE receptor, Fc epsilon RI, on powerful effector cells such as mast cells, macrophages and eosinophils, ...may offer improvements in the therapy of solid tumours. The chimeric antibody, MOv18 IgE, against the human ovarian carcinoma antigen, folate receptor alpha (FR alpha ), is more effective than its IgG1 counterpart in xenograft models of ovarian cancer. Although MOv18 IgE binds to a single epitope on FR alpha and cannot cross-link IgE receptors on basophils, there remains a risk that components in the circulation of ovarian cancer patients might cross-link FR alpha -MOv18-IgE-receptor-Fc epsilon RI complexes on basophils to cause type I hypersensitivity. Objective To assess the propensity for MOv18 used in a therapeutic setting to cause Fc epsilon RI-mediated type I hypersensitivity. Methods As validated readouts of the potential for MOv18 to cause Fc epsilon RI-mediated type I hypersensitivity we measured release of a granule-stored mediator from a rat basophilic leukaemia cell line RBL SX-38 stably transfected with human tetrameric ( alpha beta gamma 2) Fc epsilon RI, and induction of CD63 on blood basophils from patients with ovarian carcinoma and healthy controls ex vivo. Results Serum FR alpha levels were increased in ovarian cancer patients compared with healthy controls. MOv18 IgE alone, or in the presence of its antigen recombinant human FR alpha , or of healthy volunteer (n=14) or ovarian carcinoma patient (n=32) sera, did not induce RBL SX-38 cell degranulation. Exposure to FR alpha -expressing ovarian tumour cells at target-to-effector ratios expected within tumours induced degranulation. MOv18 IgE did not induce expression of CD63 in blood basophils from either healthy volunteers (n=6), or cancer patients, despite detectable levels of circulating FR alpha (n=5). Conclusion and Clinical Relevance These encouraging data are compatible with the hypothesis that, when ovarian carcinoma patients are treated with MOv18, Fc epsilon RI-mediated activation of effector cells occurs within the tumour mass but not in the circulation mandating, with due caution, further pre-clinical studies. Cite this as: S. M. Rudman, D. H. Josephs, H. Cambrook, P. Karagiannis, A. E. Gilbert, T. Dodev, J. Hunt, A. Koers, A. Montes, L. Taams, S. Canevari, M. Figini, P. J. Blower, A. J. Beavil, C. F. Nicodemus, C. Corrigan, S. B. Kaye, F. O. Nestle, H. J. Gould, J. F. Spicer and S. N. Karagiannis, Clinical & Experimental Allergy, 2011 (41) 1400-1413.
Adjuvant BEP (bleomycin, etoposide, cisplatin) is effective treatment for high-risk clinical stage I (HRCS1) non-seminomatous germ cell tumours (NSGCT), but the known toxicities of etoposide, and the ...expansion of the HR group to any patient with vascular invasion (50% of patients), led the Medical Research Council to pilot the BOP regimen. Patients received two courses of BOP 14 days apart: cisplatin 50 mg m(-2) days 1 and 2, vincristine 1.4 mg m(-2) (max. 2 mg) days 2 and 8, bleomycin 30,000 IU days 2 and 8. Primary outcome was relapse rate; quality of life, fertility, hearing and lung function were assessed pre- and post-treatment. In all, 100 patients were required. A total of 115 eligible patients were registered, all received two courses of chemotherapy. Median follow-up is 70 months; two relapses have occurred and the 5-year relapse-free rate is 98.3% (95% confidence interval (CI) 95.5%, 99.9%). As assessed by clinicians during treatment, complete (reversible) alopecia was present in 20% of patients; World Health Organization (WHO) grade 1/2 neurotoxicity was present in 41%/5% of patients during treatment and 22%/1% at 6 months. However, 12% of patients reported 'quite a bit' or 'very much' pain/numbness/tingling in hands/feet 2 years after chemotherapy. Mature follow-up confirms high efficacy for two courses of cisplatin-based adjuvant chemotherapy in HRCS1 NSGCT. Substituting vincristine for etoposide decreases alopecia, but gives a low incidence of significant neuropathy. There are no clearcut advantages to 2 x BOP over 2 x BEP, except for patients who wish to maximise the chance of avoiding significant alopecia.
NKX2-5 is expressed in the heart throughout life. We targeted eGFP sequences to the NKX2-5 locus of human embryonic stem cells (hESCs); NKX2-5(eGFP/w) hESCs facilitate quantification of cardiac ...differentiation, purification of hESC-derived committed cardiac progenitor cells (hESC-CPCs) and cardiomyocytes (hESC-CMs) and the standardization of differentiation protocols. We used NKX2-5 eGFP(+) cells to identify VCAM1 and SIRPA as cell-surface markers expressed in cardiac lineages.
Bloodstream infections occurring in persons residing in the community, regardless of whether those persons have been receiving health care in an outpatient facility, have traditionally been ...categorized as community-acquired infections.
To develop a new classification scheme for bloodstream infections that distinguishes among community-acquired, health care-associated, and nosocomial infections.
Prospective observational study.
One academic medical center and two community hospitals.
All adult patients admitted to the hospital with bloodstream infection.
Demographic characteristics, living arrangements before hospitalization, comorbid medical conditions, factors predisposing to bloodstream infection, date of hospitalization, dates and number of positive blood cultures, results of microbiological susceptibility testing, dates of hospital discharge or death, and mortality rates at 3 to 6 months of follow-up.
504 patients with bloodstream infections were enrolled; 143 (28%) had community-acquired bloodstream infections, 186 (37%) had health care-associated bloodstream infections, and 175 (35%) had nosocomial bloodstream infections. Of the 186 patients with health care-associated bloodstream infection, 29 resided in a nursing home, 64 were receiving home health care, 78 were receiving intravenous or intravascular therapy at home or in a clinic, and 117 had been hospitalized in the 90 days before their bloodstream infection. Cancer was more common in patients with health care-associated or nosocomial bloodstream infection than in patients with community-acquired bloodstream infection. Intravascular devices were the most common source of health care-associated and nosocomial infections, and Staphylococcus aureus was the most frequent pathogen in these types of infections. Methicillin-resistant S. aureus occurred with similar frequency in the groups with health care-associated infection (52%) and nosocomial infection (61%) but was uncommon in the group with community-acquired bloodstream infection (14%) (P = 0.001). Mortality rate at follow-up was greater in patients with health care-associated infection (29% versus 16%; P = 0.019) or nosocomial infection (37% versus 16%; P < 0.001) than in patients with community-acquired infection.
Health care-associated bloodstream infections are similar to nosocomial infections in terms of frequency of various comorbid conditions, source of infection, pathogens and their susceptibility patterns, and mortality rate at follow-up. A separate category for health care-associated bloodstream infections is justified, and this new category will have obvious implications for choices about empirical therapy and infection-control surveillance.
During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for ...research of advanced epithelial ovarian cancer.
Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting.
One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.
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