tbuckley/cabot-search huggingface dataset:
Cutting to the chase: circumferential endoscopic mucosal resection for Barrett's neoplasia
Authors: G. W. Falk, G. G. Ginsberg
Journal: Gut (2010)

These are exciting times in the management of Barrett's oesophagus. The emergence of large multicentre consortia, along with new imaging and treatment modalities that utilise ever-improving study design are all welcome developments in the face of the continuing increase in the incidence of oesophageal adenocarcinoma. From a diagnostic, staging and treatment perspective, endoscopic mucosal resection (EMR) has emerged as a critical tool in the management of patients with both high-grade dysplasia and early carcinoma. Tumour staging with EMR is accurate when compared with surgical pathology following oesophagectomy: negative margins on EMR specimens correlate well with absence of residual disease at the time of surgery but submucosal involvement is associated with predictable rates of residual disease and/or lymph node metastases at the time of surgery.1 Furthermore EMR will change the diagnosis in approximately 50% of patients when compared to endoscopic biopsies, given the larger tissue sample available for review by the pathologist.2 Inter-observer agreement among pathologists is improved as well.

EMR is clearly a therapeutic option for high-grade dysplasia and intramucosal carcinoma with low risk characteristics that have been well described previously by the Wiesbaden group.3 However, EMR, when used as a standalone therapy for early neoplasia in Barrett's oesophagus, is limited by the subsequent development of metachronous lesions in approximately 21% of patients.4 A number of risk factors for recurrence have been identified with perhaps the most important being the lack of treatment of the residual at risk mucosa.4 There are currently two options to deal with the remaining at risk mucosa: focal EMR accompanied by endoscopic ablation of …
Randomized Trial of a Decision Aid for Patients with Cystic Fibrosis Considering Lung Transplantation
Authors: Katherine L. Vandemheen, Annette O'Connor, Scott C. Bell, Andreas Freitag, Peter Bye, Alphonse Jeanneret, Yves Berthiaume, Neil Brown, Pearce Wilcox, Gerard Ryan, Nancy Brager, Harvey Rabin, Nancy Morrison, Peter Gibson, Mary Jackson, Nigel Paterson, Peter Middleton, Shawn D. Aaron
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

We developed an evidence-based decision aid for patients with advanced cystic fibrosis considering referral for lung transplantation.To prospectively evaluate whether use of the decision aid increased knowledge about the options, improved realistic expectations, and decreased decisional conflict in adult patients.We performed a single-blind randomized controlled trial involving 149 adult patients with cystic fibrosis with an FEV(1) <or= 40% predicted from 14 Canadian and Australian centers. All participants received an education and counseling session from their cystic fibrosis team and were then randomized to receive the decision aid or usual care. The decision aid is available online at http://decisionaid.ohri.ca/decaids.html.The primary end points measured were participants' knowledge, realistic expectations, and decisional conflict evaluated 3 weeks after randomization. Patients randomized to the decision aid had greater knowledge about their options (P < 0.0001) and had more realistic expectations about the benefits and risks of lung transplantation (P < 0.0001) compared with those randomized to usual care. The total decisional conflict score was significantly lower in the decision aid group 3 weeks postrandomization compared with the usual care group (11.6 vs. 20.4; P = 0.0007). Decisions were durable; 88% of patients in the decision aid group and 75% in the usual care group maintained the same choice 12 months after randomization (P = 0.06).Use of a decision aid for patients with cystic fibrosis considering referral for lung transplantation, in addition to usual education and counseling, improves patient knowledge, realistic expectations, decisional conflict, and patient satisfaction. Clinical trial registered with www.clinicaltrials.gov (NCT00345449).
Important Therapeutic Targets in Chronic Myelogenous Leukemia
Authors: Hagop M. Kantarjian, Francis Giles, Alfonso Quintás-Cardama, Jorge Cortes
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Review the state-of-art knowledge of the biology and therapy of chronic myelogenous leukemia (CML). Experimental Design: A review of the literature was undertaken to summarize current information on the pathophysiology of CML and to update data of imatinib mesylate therapy, mechanisms of resistance, and in vitro and clinical data with the new tyrosine kinase inhibitors. Results: Imatinib, which targets the ABL kinase activity of BCR-ABL, has prolonged survival in CML. Despite the efficacy of imatinib, some patients in chronic phase and more in advanced phases of CML develop resistance, frequently as a result of BCR-ABL tyrosine kinase domain mutants that impair imatinib binding but retain enzymatic activity. New tyrosine kinase inhibitors inhibit BCR-ABL more potently than imatinib and maintain activity against an array of imatinib-resistant BCR-ABL mutants. The IC50 values of nilotinib and dasatinib are at least 10- to 100-fold lower for BCR-ABL compared with imatinib. Phase I-II trials of nilotinib and dasatinib showed high activity in imatinib-resistant CML and Philadelphia chromosome–positive ALL. Dasatinib also inhibits members of the Src family of kinases (SFKs); nilotinib does not. Whether SFKs have a critical role in imatinib resistance or BCR-ABL–mediated oncogenesis is unresolved. Agents that target signals downstream of BCR-ABL (e.g. Ras/Raf and phosphatidylinositol 3-kinase) are under investigation. Conclusions: Understanding the pathophysiology of CML and mechanisms of resistance has produced effective targeted strategies for imatinib-resistant CML.
Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group
Authors: Fernando Calais da Silva, Fernando Manuel Calais da Silva, Frederico Gonçalves, Américo Santos, Jan Kliment, Peter Whelan, Tim Oliver, Nicos Antoniou, Spiro Pastidis, Anton Marques Queimadelos, Chris Robertson
Journal: European Urology (2013)
Preparticipation injury complaint is a risk factor for injury: a prospective study of the Moscow 2013 IAAF Championships
Authors: Juan-Manuel Alonso, Jenny Jacobsson, Toomas Timpka, Ola Ronsen, Alma Kajenienne, Örjan Dahlström, Armin Spreco, Pascal Edouard
Journal: British Journal of Sports Medicine (2015)

To determine the health status of athletes before the start of an international athletics championship and to determine whether preparticipation risk factors predicted in-championship injuries.At the beginning of the 2013 International Association of Athletics Federations (IAAF) World Championships, all registered athletes (n=1784) were invited to complete a preparticipation health questionnaire (PHQ) on health status during the month preceding the championships. New injuries that occurred at the championships were prospectively recorded.The PHQ was completed by 698 (39%) athletes; 204 (29.2%) reported an injury complaint during the month before the championships. The most common mode of onset of preparticipation injury complaints was gradual (43.6%). Forty-nine athletes in the study reported at least one injury during the championships. Athletes who reported a preparticipation injury complaint were at twofold increased risk for an in-championship injury (OR=2.09; 95% CI 1.16 to 3.77); p=0.014). Those who reported a preparticipation gradual-onset injury complaint were at an almost fourfold increased risk for an in-championship time-loss injury (OR=3.92; 95% CI 1.69 to 9.08); p=0.001). Importantly, the preparticipation injury complaint severity score was associated with the risk of sustaining an in-championship injury (OR=1.14; 95% CI 1.06 to 1.22); p=0.001).About one-third of the athletes participating in the study reported an injury complaint during the month before the championships, which represented a risk factor for sustaining an injury during the championship. This study emphasises the importance of the PHQ as a screening tool to identify athletes at risk of injuries before international championships.
Isokinetic performance and shoulder mobility in elite volleyball athletes from the United Kingdom
Authors: Hsing-Kuo Wang, Alison Macfarlane, Tom Cochrane
Journal: British Journal of Sports Medicine (2000)

Objectives —To evaluate the differences in strength and mobility of shoulder rotator muscles in the dominant and non-dominant shoulders of elite volleyball players. Methods —Isokinetic muscle strength tests were performed at speeds of 60 and 120°/s, and shoulder mobility was examined in ten players from the England national men's volleyball squad. The subjects also completed a questionnaire that included a visual prompt and analogue pain scale. Results —The range of motion of internal rotation on the dominant side was less than that on the non-dominant side (p&lt;0.01). The average peak strength at 60°/s external eccentric contraction was lower than that of internal concentric contraction in the dominant arm, but was higher in the non-dominant arm. Six of the ten subjects reported a shoulder problem, described as a diffuse pain located laterally on the dominant shoulder. Conclusions —These elite volleyball players had a lower range of motion (internal rotation) and relative muscle imbalance in the dominant compared with the non-dominant shoulder.
Adjuvant radiotherapy delays recurrence following subtotal resection of spinal cord ependymomas
Authors: Michael C. Oh, Michael E. Ivan, Matthew Z. Sun, Gurvinder Kaur, Michael Safaee, Joseph M. Kim, Eli T. Sayegh, Derick Aranda, Andrew T. Parsa
Journal: Neuro-Oncology (2012)

Ependymoma is the most common glial tumor of the adult spinal cord. Current consensus recommends surgical resection with gross total resection (GTR) whenever possible. We performed a comprehensive review of the literature to evaluate whether adjuvant radiotherapy after subtotal resection (STR) has any benefit. A PubMed search was performed to identify adult patients with spinal cord ependymoma who underwent surgical resection. Only patients who had clearly defined extent of resection with or without adjuvant radiotherapy were included for analysis. Kaplan-Meier and multivariate Cox regression survival analyses were performed to determine the effects of adjuvant radiotherapy on progression-free survival (PFS) and overall survival (OS). A total of 348 patients underwent surgical resection of spinal cord ependymomas, where GTR was obtained in 77.0% (268/348) of patients. Among those who received STR, 58.8% (47/80) received adjuvant radiotherapy. PFS was significantly prolonged among those who received adjuvant radiotherapy after STR (log rank; P < .001). This prolonged PFS with adjuvant radiotherapy remained significant in multivariate Cox regression analysis (STR versus STR + RT group; hazard ratio (HR) = 2.26, P = .047). By contrast, improved OS was only associated with GTR (GTR versus STR + RT group; HR = 0.07, P = .001) and benign ependymomas (HR = 0.16, P = .001). Surgery remains the mainstay treatment for spinal cord ependymomas, where GTR provides optimal outcomes with longest PFS and OS. Adjuvant radiotherapy prolongs PFS after STR significantly, and OS is improved by GTR and benign tumor grade only.
The prevalence of common skin conditions in Australian school students: 1. Common, plane and plantar viral warts
Authors: None Kilkenny, None Erlin, None Young, None Marks
Journal: British Journal of Dermatology (1998)

Although viral warts are common, their exact frequency in the community is often underestimated and not well recorded. A random sample of 2491 students from schools throughout the State of Victoria, Australia were examined by dermatologists and dermatology registrars to record the prevalence of common, plantar and plane warts. The overall prevalence of warts adjusted for the age and sex of Victorian school children was 22% (95% confidence interval (CI) 20.1–20.7) varying from 12% (95% CI 9.4–15.7) in 4–6 year olds to 24% (95% CI 18.3–30.4) in 16–18 year olds. Common warts were the most frequent (16%) compared with plantar warts (6%) and plane warts (2%). There was no difference in the overall frequency of warts between males and females and there was no difference in frequency between those who had eczema and those who did not. Almost 40% of those found to have warts on examination had indicated on the survey questionnaire that they did not have any of these lesions. Of those who knew that they had warts, only 38% had used any treatment for them. These data, the first community-based prevalence data on warts ever published from Australia, confirm that warts are indeed common. They suggest the need for education programmes in schools on the nature of these lesions and the treatment available.
Improvements in insulin sensitivity and whole-body fat oxidation after a period of high-intensity interval training
Authors: S O Shepherd, M Cocks, K D Tipton, A J M Wagenmakers, C S Shaw
Journal: British Journal of Sports Medicine (2010)

Physically trained individuals exhibit high rates of whole-body fat oxidation and elevated insulin sensitivity. High-intensity interval training (HIT) has been suggested to induce similar metabolic adaptations in a more time efficient manner than traditional endurance training. To widen this claim the authors aimed to investigate whether 6 weeks of HIT improves whole-body fat oxidation and insulin sensitivity in young sedentary males. Eight participants (23±2 years; body mass index 24.5±1.5 kg/m 2 ; VO 2 peak 43.0±1.5 ml/min/kg) with normal glucose tolerance undertook 6 weeks of HIT consisting of between four and six 30-s Wingate tests separated by 4.5 min rest, performed three times per week. Insulin sensitivity (oral glucose tolerance test (OGTT)) and substrate metabolism during a 60-min steady state cycling trial (∼65% pretraining VO 2 peak) was assessed before and after HIT. Dual energy x -ray absorptiometry was also used to measure changes in body composition in response to training. VO 2 peak increased 18% (pre 43.0±1.5 ml/min/kg 2 , post 50.8±1.8 ml/min/kg 2 ; p&lt;0.05). A 5% reduction in relative fat content in the body was observed (pre 19.6±2.2%, post 18.8±2.1%, p&lt;0.05), which was attributed to a 6% decrease in relative fat content in the legs. Absolute carbohydrate oxidation was reduced after HIT (pre 1.75±0.11 g/min, post 1.49±0.11 g/min; p=0.04), while relative fat oxidation showed a tendency to increase (pre 35.2±5.7%, post 43.3±3.6%; p=0.078). Plasma glucose and insulin area under the curve in response to the OGTT was reduced by 17% and 31% (p&lt;0.05) posttraining, respectively, which corresponded with a 27% improvement in the Matsuda index of insulin sensitivity (pre 4.0±0.5, post 5.1±0.6, p=0.066). The results obtained for the first time provide evidence to suggest that HIT is also a time-efficient method to improve whole-body fat oxidation, body composition and insulin sensitivity in young, sedentary males.
Laennec: his medical history.
Authors: R Y Keers
Journal: Thorax (1981)

Critical study of the career of Théophile Laënnec, with particular reference to his medical history, gives cause to query the commonly accepted belief that his whole life was a constant battle against pulmonary tuberculosis. He developed respiratory symptoms almost immediately on his arrival in Paris but they were those of bronchial asthma and responded promptly and completely to a change of environment. It was only in the concluding years of his life and when he was worn out by overwork that the symptoms of tuberculosis appeared and thereafter the disease progressed rapidly to its fatal termination.
Discrepancy between Consensus Recommendations and Actual Community Use of Adjuvant Chemotherapy in Women with Breast Cancer
Authors: Xianglin L. Du, Charles R. Key, Cynthia Osborne, Jonathan D. Mahnken, James S. Goodwin
Journal: Annals of Internal Medicine (2003)

Although the efficacy of adjuvant chemotherapy in prolonging survival for women with breast cancer has been well documented, limited population-based information is available on the actual use of chemotherapy.To examine the relationship between age and chemotherapy use.Cohort study.New Mexico.5101 women 20 years of age or older receiving a diagnosis of stage I, stage II, or stage IIIA breast cancer from 1991 through 1997.Pattern of chemotherapy use by age; logistic regression analysis to generate the odds and probabilities of receiving chemotherapy; and sensitivity analysis to estimate potential effects of unmeasured confounders.Overall, 29% of women received chemotherapy. The rate of chemotherapy use for women with stage I, stage II, or stage IIIA breast cancer was 11%, 47%, and 68%, respectively. Across all tumor stages, the use of chemotherapy decreased substantially with increasing age (P < 0.001). Overall, 66% of women younger than 45 years of age received chemotherapy compared with 44% of women between 50 and 54 years of age, 31% of women between 55 and 59 years of age, and 18% of women between 60 and 64 years of age. The decreasing pattern of chemotherapy use with age continued after adjustment for prognostic factors and was relatively insensitive to changes in unmeasured factors.There is considerable discrepancy between the 1990 National Institutes of Health Consensus Conference recommendations for chemotherapy administration in women with breast cancer and the actual use of chemotherapy in the community. The decrease in use with age may relate to the decreasing efficacy of chemotherapy with age, as reported in clinical trials. Outcomes studies should address whether the recommendations are overly aggressive or whether practicing oncologists are too conservative in their use of chemotherapy.
Deletion of Calcineurin and Myocyte Enhancer Factor 2 (MEF2) Binding Domain of Cabin1 Results in Enhanced Cytokine Gene Expression in T Cells
Authors: Christine Esau, Marianne Boes, Hong-Duk Youn, Lisa Tatterson, Jun O. Liu, Jianzhu Chen
Journal: The Journal of Experimental Medicine (2001)

Cabin1 binds calcineurin and myocyte enhancer factor 2 (MEF2) through its COOH-terminal region. In cell lines, these interactions were shown to inhibit calcineurin activity after T cell receptor (TCR) signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions under physiological conditions was investigated using a mutant mouse strain that expresses a truncated Cabin1 lacking the COOH-terminal calcineurin and MEF2 binding domains. T and B cell development and thymocyte apoptosis were normal in mutant mice. In response to anti-CD3 stimulation, however, mutant T cells expressed significantly higher levels of interleukin (IL)-2, IL-4, IL-9, IL-13, and interferon γ than wild-type T cells. The enhanced cytokine gene expression was not associated with change in nuclear factor of activated T cells (NF-AT)c or NF-ATp nuclear translocation but was preceded by the induction of a phosphorylated form of MEF2D in mutant T cells. Consistent with the enhanced cytokine expression, mutant mice had elevated levels of serum immunoglobulin (Ig)G1, IgG2b, and IgE and produced more IgG1 in response to a T cell–dependent antigen. These findings suggest that the calcineurin and MEF2 binding domain of Cabin1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression probably through modulation of MEF2 activity.
Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development
Authors: Beate Lanske, Michael Amling, Lynn Neff, Jennifer Guiducci, Roland Baron, Henry M. Kronenberg
Journal: Journal of Clinical Investigation (1999)

Parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized.
Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux
Authors: M Solaymani-Dodaran
Journal: Gut (2004)

While patients with Barrett's oesophagus develop oesophageal adenocarcinoma more frequently than the general population, it has controversially been suggested that gastro-oesophageal reflux (GORD) itself is a more important determinant of risk. In order to assess the validity of this suggestion, we examined the risk of oesophageal cancer in patients with Barrett's and with GORD compared with the general population in a community based cohort study.Cohorts of patients with Barrett's (n = 1677), oesophagitis (n = 6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were selected from the General Practice Research Database. The last three cohorts were matched to the Barrett's cohort by general practitioner practice, age, and sex. Cox's regression analysis was used to calculate relative risks for oesophageal cancer. Standardised incidence ratio methodology was used to estimate the relative risks for oesophageal adenocarcinoma.A total of 137 oesophageal cancers were identified, of which 94 prevalent cases were excluded. The hazard ratios for oesophageal cancer were 10.6 (5.1-22.0), 2.2 (0.9-5.2), and 1.7 (0.7-4.5) in the Barrett's, oesophagitis, and reflux cohorts compared with the reference cohort, respectively. The corresponding relative risks for oesophageal adenocarcinoma were 29.8 (9.6-106), 4.5 (1.04-19.6), and 3.1 (0.6-14.2).Barrett's oesophagus increases the risk of oesophageal cancer approximately 10 times and oesophageal adenocarcinoma approximately 30 times compared with the general population. There is only a modestly increased risk of oesophageal cancer in patients with reflux who have no record of Barrett's oesophagus. Our findings therefore do not support the suggestion that gastro-oesophageal reflux disease itself predisposes to cancer.