tbuckley/cabot-search huggingface dataset:
OC-011 Endoscopic therapy in barrett's oesophagus (be) with HGD (high grade dysplasia) and early malignancy; a prospective, single centre experience
Authors: H C McEwan, A J Morris, P Glen, J E Abela, J J Going, G Fullarton
Journal: Gut (2012)

<h3>Introduction</h3> There is increasing evidence that endoscopic therapy in BE with a combination of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) is an effective treatment of intramucosal cancer (IMC) and HGD. The widespread application of this therapy is yet to be assessed in the UK outside the trial setting. We present here the results of a single centre study from a large tertiary referral teaching hospital. We aim to assess the efficacy and safety of endoscopic therapy with EMR and RFA in the treatment of HGD and IMC. <h3>Methods</h3> 102 consenting patients with a mean age of 69 (range 42–89) with HGD or IMC were enrolled between July 2008 and September 2011. All pathology was reviewed by a pathologist with a particular interest in Barrett9s. The treatment protocol involved EMR of all nodular areas with subsequent RFA of all remaining Barretts epithelium. The RFA technique involved a combination of circumferential RFA (HALO 360) followed by subsequent focal ablation (HALO 90) of residual areas of Barrett9s tongues or islands. The UK protocol involved a maximum of two HALO 3609s and 3 HALO 909s. <h3>Results</h3> 102 patients have been recruited (30 with IMC and 72 with HGD). Fifty patients have completed the treatment protocol (median of 1 HALO 360 and 1 HALO 90) and of these, 52% had initial EMR. Median follow-up in this group was 9 months (range 3–41). Thirteen of these 50 patients had IMC (26%) with 37 patients demonstrating flat HGD only. Of the 102 patients recruited, nine patients (8.7%) have progressed to invasive malignancy after a median of 12 months. As a result, there were 59 patients who exited the protocol following an intention to treat. To date eradication of dysplasia was achieved in 49/59 patients (83%) and eradication of metaplasia in 40/59 patients (68%). Three patients died from unrelated causes, two from cardiorespiratory comorbidities and one from concurrent lymphoma. Eight patients (8%) developed mild strictures. One patient required readmission for retrosternal pain requiring analgesia. There were no serious complications or peri-procedural mortality. <h3>Conclusion</h3> This study demonstrates the efficacy of endotherapy with EMR and RFA in the treatment of IMC and HGD. Although further follow-up is required, these results suggest that such therapy should be offered to all patients as an alternative to surgery. <h3>Competing interests</h3> None declared.
The scars of time: the disappearance of surgery for pyloric stenosis
Authors: R. Hall, C. Royston, K. D. Bardhan
Journal: Gut (2011)

<h3>Introduction</h3> The changing pattern of both elective and emergency operations for peptic ulcer disease (PUD) has been well described but less is known about operations for pyloric stenosis (PS). <h3>Methods</h3> Data registration was started by the York surgeon, the late Arthur HC Visick. After his death his successors formed the York Peptic Ulcer Research Trust to continue data collection. The database was maintained after 1971 by Robert Hall who continues as its archivist. All patients undergoing emergency or elective definitive operations for PUD (i.e. with the intent of cure), were entered into the database. The first registered operation was in 1929 and the last in 1997. We examined the pattern of the 4248 definitive operations for PUD and the subset of 475 with PS. Early registrations were sparse hence data before 1940 are amalgamated. <h3>Results</h3> See Table 1. PS was found in 475/4248 (11%). Operation numbers steadily rose until 1974, declining rapidly thereafter until hardly any were carried out in the last decade. 2. Those born 1900-1909 had by far the highest proportion of PUD operations both overall and with PS, peaking in 1950-59. Later cohorts showed a similar pattern but with progressively lower peaks. <h3>Discussion</h3> 1. The decline in operation rates preceded the introduction of H2-receptor antagonists (H2RA) in November 1976, thus indicating it was independent of medical treatment. 2. By the time H2RA emerged those with severe disease had been operated upon and many of those born early in the 20<sup>th</sup> Century no longer survived. Thus this powerful new medical treatment was required by a decreasing PUD population who may have had milder disease. 3. We suggest that the falling numbers coming to operation even before the introduction of H2RA indicate a natural decline in the severity of PUD. The effect of H2RA has added to this. <h3>Conclusion</h3> Operation for PS has largely vanished in parallel with the decline in elective PUD operation. This dramatic reduction owes as much to a spontaneously changing natural history as it does to the evolution of modern medical therapy.
Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes.
Authors: G Isenberg, L Belardinelli
Journal: Circulation Research (1984)

We studied the effects of adenosine and isoproterenol on membrane currents of isolated bovine and guinea pig ventricular myocytes with a two-microelectrode voltage clamp technique. Adenosine (50 microM to 0.2 mM) alone had no effect on any of the membrane currents measured, but it antagonized the effects induced by 10 nM isoproterenol. Peak calcium membrane current was augmented by isoproterenol from a control of 4.8 +/- 0.6 to 8.6 +/- 0.8 nA and adenosine reduced it to 5.7 +/- 0.7 nA (mean +/- SEM of six cells). The inactivation time constant was not altered by isoproterenol alone or isoproterenol plus adenosine, and neither was the voltage dependence of peak calcium membrane current. Thus, the changes caused by isoproterenol could be described as an increase in maximal calcium conductance from 0.86 +/- 0.7 to 1.55 +/- 0.04 mS/cm2 and partially antagonized by adenosine to 0.97 +/- 0.04 mS/cm2. Isoproterenol also increased the non-inactivating component of calcium membrane current from 17 +/- 1 to 24 +/- 4%, and adenosine reduced it to 18 +/- 2% (n = 4). The steady state activation and inactivation variables remained unchanged. Consistent with these effects on calcium membrane current, adenosine completely antagonized the isoproterenol-induced increase of the slow action potentials obtained in sodium-free medium. Isoproterenol increased the steady state outward currents at potentials between -90 and -30 mV (i.e., probable iK1). Adenosine alone had no effect on potassium membrane current, but it antagonized the effects of isoproterenol. Slow action potentials in 25 mM potassium were enhanced by isoproterenol, but were only moderately attenuated by adenosine. Accordingly, in 25 mM potassium the isoproterenol-induced changes in membrane currents were not antagonized by adenosine. This lack of inhibition by adenosine of the isoproterenol effects in 25 mM potassium could not be mimicked by 1-minute-long conditioning prepulses to -45 mV. The results indicate that adenosine by itself (absence of isoproterenol) has no effect on maximal calcium conductance, that the isoproterenol-induced increase in cyclic adenosine 3',5'-monophosphate, which leads to an increase in maximal calcium conductance, is antagonized by adenosine, and that such action can account for the ability of adenosine to attenuate the stimulatory effects of isoproterenol.
The Structure of the CD4 and CD8 Genes
Authors: D R Littman
Journal: Annual Review of Immunology (1987)

The CD4 and CD8 glycoproteins are nonpolymorphic members of the immunoglobulin gene superfamily which are expressed on the surface of functionally distinct populations of T lymphocytes. These molecules, also known respectively as T4/Leu3 and T8/Leu2 in human, and as L3T4 and Lyt2/Lyt3 in mouse, appear to be essential for effective cell-cell inter­ actions, resulting either in target cell lysis or in activation of T lymphocytes. Expression of the CD4 and CD8 molecules correlates with the specificity of T cells for either class-II or class-I major histocompatibility complex (MHC) molecules on target cells (1-7). Thus, CD4 and CD8 may serve to increase the avidity of cell-cell interactions by directly binding to mono­ morphic determinants of the appropriate MHC molecule on target cells (2, 8, 9). The view that the CD4 and CD8 molecules act solely as avidity enhan­ cers has been challenged by recent findings which suggest that these mol­ ecules have a role in transmembrane signal transduction (10-14a). However, no experiments to date have directly tested the ability of CD4 or CD8 to bind ligand or to transduce physiologically relevant signals. It is also not known whether CD4 and CD8 perform analogous functions on separate populations of T cells. The basis for intra thymic selection of CD4+ and CD8+ cells that express appropriate MHC-restricted receptors likewise remains a mystery. The elucidation of these problems awaits functional experiments utilizing the newly isolated genes that encode the CD4 and CD8 glycoproteins (15-24). The emphasis of this review hence is on the isolation and structure of these genes and on the glimpses that the predicted structures of the glycoproteins give us into their potential
Completion of Adjuvant Chemotherapy and Use of Health Services for Older Women With Epithelial Ovarian Cancer
Authors: Kathleen M. Fairfield, Kimberly Murray, F. Lee Lucas, Heidi R. Wierman, Craig C. Earle, Edward L. Trimble, Laurie Small, Joan L. Warren
Journal: Journal of Clinical Oncology (2011)

Purpose This analysis identifies factors associated with completion of adjuvant chemotherapy for patients with ovarian cancer and subsequent use of health services. Patients and Methods We used the Surveillance, Epidemiology, and End Results (SEER) –Medicare database to identify 4,617 women age 65 years or older with ovarian cancer diagnosed from 2001 to 2005. By using multivariable analyses with completion of chemotherapy as the outcome of interest, we describe factors associated with completion of treatment, including age, race, marital status, comorbidities, and sociodemographic factors. Use of health services was captured from Medicare claims. Results Among 4,617 patients with untreated ovarian cancer, 1,329 (28.8%) received no chemotherapy, 1,139 (24.7%) received a partial course of chemotherapy, and 2,149 (46.5%) completed chemotherapy. Women age 75 years or older were at greater risk of incomplete chemotherapy versus women age 65 to 74 years (odds ratio [OR], 1.64; 95% CI, 1.33 to 2.04). Having two or more comorbidities was also significantly associated with incomplete chemotherapy (OR, 1.83; 95% CI, 1.34 to 2.50). Among women who received either a partial or complete course of chemotherapy, we did not find an increase in use of health services (hospitalizations, emergency department visits, or physician visits) for the oldest women (age 80 years or older) compared with younger women. Conclusion There is considerable room for improvement in helping older patients with ovarian cancer initiate and complete chemotherapy. The oldest women who completed chemotherapy in this study did not use health services more than younger women did. Treatment teams for older patients with ovarian cancer should include expertise in geriatric assessment, should carefully identify medical and psychosocial barriers to completing treatment, and should support patients throughout treatment.
Understanding Optimal Colonic Cancer Surgery: Comparison of Japanese D3 Resection and European Complete Mesocolic Excision With Central Vascular Ligation
Authors: Nicholas P. West, Hirotoshi Kobayashi, Keiichi Takahashi, Aristoteles Perrakis, Klaus Weber, Werner Hohenberger, Kenichi Sugihara, Philip Quirke
Journal: Journal of Clinical Oncology (2012)

Purpose Over recent years, patient outcomes after colon cancer resection have not improved to the same degree as for rectal cancer. Japanese D3 resection and European complete mesocolic excision (CME) with central vascular ligation (CVL) are both based on sound oncologic principles. Expert surgeons using both techniques report impressive outcomes as compared with standard surgery. We aimed to independently compare the physical appearances and quality of specimens resected using both techniques in major institutions in Japan and Germany. Methods A series of resections for primary colon cancer from one European and two Japanese centers were independently assessed in terms of the plane of surgery, physical characteristics, and lymph node yields. Results Mesocolic plane resection rates from both series were high; however, Japanese D3 specimens were significantly shorter (162 v 324 mm, P &lt; .001), resulting in a smaller amount of mesentery (8,309 v 17,957 mm 2 , P &lt; .001) and nodal yield (median, 18 v 32, P &lt; .001). The distance from the high vascular tie to the bowel wall (100 v 99 mm, P = .605) was equivalent. Conclusion Both techniques showed high mesocolic plane resection rates and long distances between the high tie and the bowel wall. The extended longitudinal resection after CME with CVL increased the nodal yield but did not increase the number of tumor involved nodes. Both series were oncologically superior to recently reported series from other countries and confirm the wide variation in colonic cancer surgery and the need for further standardization and optimization following the approach undertaken in improving rectal cancer outcomes.
Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis
Authors: Shilpi Pandey, Ashalatha Shetty, Mark Hamilton, Siladitya Bhattacharya, Abha Maheshwari
Journal: Human Reproduction Update (2012)

BACKGROUNDEarlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions.
Identification of <i>PDE4D</i> as a Proliferation Promoting Factor in Prostate Cancer Using a <i>Sleeping Beauty</i> Transposon-Based Somatic Mutagenesis Screen
Authors: Eric P. Rahrmann, Lara S. Collier, Todd P. Knutson, Meghan E. Doyal, Sheri L. Kuslak, Laura E. Green, Rita L. Malinowski, Laura Roethe, Keiko Akagi, Michelle Waknitz, Wei Huang, David A. Largaespada, Paul C. Marker
Journal: Cancer Research (2009)

Retroviral and transposon-based mutagenesis screens in mice have been useful for identifying candidate cancer genes for some tumor types. However, many of the organs that exhibit the highest cancer rates in humans, including the prostate, have not previously been amenable to these approaches. This study shows for the first time that the Sleeping Beauty transposon system can be used to identify candidate prostate cancer genes in mice. Somatic mobilization of a mutagenic transposon resulted in focal epithelial proliferation and hyperplasia in the prostate. Efficient methods were established to identify transposon insertion sites in these lesions, and analysis of transposon insertions identified candidate prostate cancer genes at common insertion sites, including Pde4d. PDE4D was also overexpressed in human prostate cancer patient samples and cell lines, and changes in PDE4D mRNA isoform expression were observed in human prostate cancers. Furthermore, knockdown of PDE4D reduced the growth and migration of prostate cancer cells in vitro, and knockdown of PDE4D reduced the growth and proliferation rate of prostate cancer xenografts in vivo. These data indicate that PDE4D functions as a proliferation promoting factor in prostate cancer, and the Sleeping Beauty transposon system is a useful tool for identifying candidate prostate cancer genes.
Angiotensin II Type 1 Receptor–EGF Receptor Cross-Talk Regulates Ureteric Bud Branching Morphogenesis
Authors: Ihor V. Yosypiv, Mercedes Schroeder, Samir S. El-Dahr
Journal: Journal of the American Society of Nephrology (2006)

Angiotensinogen-, angiotensin-converting enzyme-, and angiotensin II (Ang II) type 1 receptor (AT(1)R)-deficient mice exhibit a dilated renal pelvis (hydronephrosis) and a small papilla. These abnormalities have been attributed to impaired development of the ureteral and pelvic smooth muscle. Defects in the growth and branching of the ureteric bud (UB), which gives rise to the collecting system, have not been examined carefully. This study tested the hypothesis that Ang II stimulates UB growth and branching in the intact metanephros. Immunohistochemistry demonstrated that embryonic mouse kidneys express AT(1)R in the UB and its branches. Embryonic day 11.5 metanephroi were microdissected from Hoxb7-green fluorescence protein mice and grown for 48 h in serum-free medium in the presence or absence of Ang II. The number of green fluorescence protein-positive UB branch points (BP) and tips was monitored in each explant at 24 and 48 h. Ang II increased the number of UB tips and BP at 24 h (tips: 24.3 +/- 1.1 versus 18.3 +/- 0.7, P < 0.01; BP: 14.4 +/- 0.6 versus 11.7 +/- 0.6, P < 0.01) and 48 h (tips: 30.2 +/- 1.3 versus 22.9 +/- 0.8, P < 0.01; BP: 21.3 +/- 0.9 versus 15.7 +/- 0.6, P < 0.01) compared with control. In contrast, treatment of metanephroi with the AT(1)R antagonist candesartan inhibited UB branching, decreasing the number of UB tips and BP. Similarly, inhibition of EGF receptor (EGFR) tyrosine kinase activity abrogated Ang II-stimulated UB branching. A cross-talk between the renin-angiotensin system and EGFR signaling was elicited at the cellular level by the ability of Ang II to induce tyrosine phosphorylation of EGFR in UB cells and through abrogation of Ang II-induced UB cell branching using an EGFR tyrosine kinase inhibitor. These data demonstrate that Ang II, acting via the AT(1)R, stimulates UB branching morphogenesis. This process depends on tyrosine phosphorylation of the EGFR. Cooperation of AT(1)R and EGFR signaling therefore is important in the development of the renal collecting system.
Reported food intolerance and respiratory symptoms in young adults
Authors: RK Woods, M Abramson, JM Raven, M Bailey, JM Weiner, EH Walters
Journal: European Respiratory Journal (1998)

The aim of the study was to assess the ability of the European Community Respiratory Health Survey (ECRHS) questionnaire to provide data on the prevalence, type and reported symptoms associated with food intolerance from a group of young adults in Melbourne. Six hundred and sixty nine randomly selected subjects completed the questionnaire with 553 attending the laboratory for skin-prick tests, anthropometry, and ventilatory function tests. A further 207 symptomatic participants completed the questionnaire, with 204 of them attending the laboratory. Seventeen per cent of all respondents reported food intolerance or food allergy. A wide variety of food items was cited as being responsible for food-related illnesses. Those with current asthma did not report food-related illness more frequently than those without asthma. Respondents who reported respiratory symptoms following food ingestion were more likely to be atopic, to have used inhaled respiratory medications in the previous 12 months, reported less exposure to regular passive smoking over the past 12 months and weighed more. These associations between respiratory symptoms and food intolerance require further prospective investigation and verification. The importance of using appropriate dietary methodology in future studies for determining diet-disease relationships was highlighted by this study.
Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history
Authors: T R Orchard, B P Wordsworth, D P Jewell
Journal: Gut (1998)

Background —Peripheral arthropathy is a well-recognised complication of inflammatory bowel disease (IBD). Little is known of its natural history, but a variety of joint involvement has been described, from large joint pauciarticular arthropathy to a rheumatoid pattern polyarthropathy. Aims —To classify the peripheral arthropathies according to pattern of articular involvement, and study their natural history and clinical associations. Methods —The case notes of all patients attending the Oxford IBD clinic were reviewed, and information on general disease characteristics, extraintestinal features, and arthropathy extracted. This was confirmed by direct patient interview using questionnaires at routine follow up. Patients with recorded joint swelling or effusion were classified as type 1 (pauciarticular) if less than five joints were involved and type 2 (polyarticular) if five or more were involved. Patients without evidence of swelling were classified as arthralgia. Results —In total, 976 patients with ulcerative colitis (UC) and 483 with Crohn’s disease (CD) were reviewed. Type 1 occurred in 3.6% of patients with UC (83% acute and self-limiting) and in 6.0% of those with CD (79% self-limiting); 83% and 76%, respectively, were associated with relapsing IBD. Type 2 occurred in 2.5% of patients with UC and 4.0% of those with CD; 87% and 89%, respectively, caused persistent symptoms whereas only 29% and 42%, respectively, were associated with relapsing IBD. Conclusion —Enteropathic peripheral arthropathy without axial involvement can be subdivided into a pauciarticular, large joint arthropathy, and a bilateral symmetrical polyarthropathy, each being distinguished by its articular distribution and natural history.
The Changing Legal Climate for Physician Aid in Dying
Authors: David Orentlicher, Thaddeus Mason Pope, Ben A. Rich
Journal: JAMA (2014)

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