tbuckley/cabot-search huggingface dataset:
Revalidation: swallow hard
Authors: Geoff Wong
Journal: BMJ (2004)

EDITOR—Sometime in 2005 (but who knows exactly when), all the 100 000 or so doctors in the United Kingdom will be subject to revalidation.1–3

Despite the gravity of this change in the licensing of medical practitioners, there has been and still is little debate on this matter. Read through, for example, van Zwanenberg's references and you will have read just …
Peripheral Arterial Disease in Patients With End-Stage Renal Disease
Authors: Sanjay Rajagopalan, Santo Dellegrottaglie, Anna L. Furniss, Brenda W. Gillespie, Sudtida Satayathum, Norbert Lameire, Akira Saito, Takashi Akiba, Michel Jadoul, Nancy Ginsberg, Marcia Keen, Friedrich K. Port, Debabrata Mukherjee, Rajiv Saran
Journal: Circulation (2006)

Background— Patients with end-stage renal disease are at high risk for cardiovascular morbidity and mortality. The aims of the present study were to describe the prevalence of peripheral arterial disease (PAD) and its effects on prognosis and health-related quality of life (HRQOL) in an international cohort of patients on hemodialysis. Methods and Results— Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, international, observational study of hemodialysis patients (n=29 873), were analyzed. Associations between baseline clinical variables and PAD were evaluated by logistic regression analysis. Cox regression models were used to test the association between PAD and risk for all-cause mortality, cardiac mortality, and hospitalization. PAD was diagnosed in 7411 patients (25.3%) with significant geographic variation. Traditional cardiovascular risk factors including age, male sex, diabetes, hypertension, and smoking were identified, together with the duration of hemodialysis, as significant correlates of PAD. Diagnosis of PAD was associated with increased all-cause mortality (hazard ratio [HR]=1.36; P &lt;0.0001), cardiac mortality (HR=1.43; P &lt;0.0001), all-cause hospitalization (HR=1.19; P &lt;0.0001), and hospitalization for a major adverse cardiovascular event (HR=2.05; P &lt;0.0001). HRQOL questionnaires revealed physical health scores that were significantly lower in PAD compared with non-PAD patients ( P &lt;0.0001). Conclusions— PAD is common in hemodialysis patients and is associated with increased risk of cardiovascular mortality, morbidity, and hospitalization and reduced HRQOL.
Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial
Authors: Lajos Pusztai, Jong-Hyeon Jeong, Yun Gong, Jeffrey S. Ross, Chungyeul Kim, Soonmyung Paik, Roman Rouzier, Fabrice Andre, Gabriel N. Hortobagyi, Norman Wolmark, W. Fraser Symmans
Journal: Journal of Clinical Oncology (2009)

Purpose We assessed Tau protein expression in primary breast cancer specimens of patients included in the National Surgical Breast and Bowel Project (NSABP) -B 28 clinical trial. Expression levels were correlated with disease-free survival (DFS) and overall survival (OS). Interaction between this marker and paclitaxel efficacy was also examined. Methods Tissue microarrays were available for 1,942 patients (63% of all trial participants) who were randomly assigned to receive either four courses of doxorubicin and cyclophosphamide (AC) or AC followed by four courses of adjuvant paclitaxel chemotherapy. All patients who were hormone receptor positive received adjuvant endocrine therapy. Immunohistochemistry was used to measure Tau expression at M. D. Anderson Cancer Center blinded to clinical outcome. Correlation between Tau and OS and DFS was performed by the NSABP Biostatistical Center. Results Forty-three percent of patients were Tau positive. Tau positivity correlated with estrogen receptor (ER) -positive status (P &lt; .0001), lower histologic grade (P &lt; .001), and lack of human epidermal growth factor receptor 2 (HER2) expression (P &lt; .0001). In univariate analyses, Tau- and ER-positive status were both associated with better DFS and OS (P &lt; .0001) whereas greater tumor size, high grade, lymph node- and HER2-positive status were each associated with worse DFS and OS (P &lt; .0001). In multivariate analysis, the same variables except HER2 remained significant. There was no significant interaction between Tau expression and benefit from paclitaxel in the total population or among ER-positive or -negative patients. Conclusion High Tau protein expression is associated with better prognosis in patients treated with adjuvant anthracycline and paclitaxel chemotherapy and endocrine therapy, but there was no significant interaction between Tau expression and paclitaxel benefit.
Workshop on Partial Breast Irradiation: State of the Art and the Science, Bethesda, MD, December 8-10, 2002
Authors: P. Wallner, D. Arthur, H. Bartelink, J. Connolly, G. Edmundson, A. Giuliano, N. Goldstein, J. Hevezi, T. Julian, R. Kuske, A. Lichter, B. McCormick, R. Orecchia, L. Pierce, S. Powell, L. Solin, F. Vicini, T. Whelan, J. Wong, C. N. Coleman
Journal: JNCI Journal of the National Cancer Institute (2004)

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments.
Circulating Nitric Oxide Is Suppressed in Obstructive Sleep Apnea and Is Reversed by Nasal Continuous Positive Airway Pressure
Authors: MARY S. M. IP, BING LAM, LAI-YEE CHAN, LING ZHENG, KENNETH W. T. TSANG, PETER C. W. FUNG, WAH-KIT LAM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. The recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases, and we postulate that nitric oxide may be one of the mediators involved. This study investigates the levels of circulating nitric oxide (NO), measured as serum nitrites and nitrates, in the early morning in OSA subjects compared with control subjects, and the effect of overnight nasal continuous positive airway pressure (nCPAP) in OSA subjects. Thirty men with moderate to severe OSA (age = 41.9 ± 9.0; apnea-hypopnea index, AHI = 48.0 ± 18.1) were compared with 40 healthy men (age = 40.6 ± 5.4; AHI = 1.4 ± 1.2). Serum nitrite/nitrate levels were significantly lower in OSA subjects (OSA = 38.9 ± 22.9 μ M, control subjects = 63.1 ± 47.5 μ M, p = 0.015). There was significant negative correlation between serum nitrites/nitrates and the following parameters: AHI (r = − 0.389, p = 0.001), oxygen desaturation time (r = − 0.346, p = 0.004), and systolic blood pressure (BP) (r = − 0.335, p = 0.005). Stepwise multiple linear regression with systolic or diastolic BP as the dependent variable identified serum nitrites/nitrates as the only significant correlate. Twenty-two OSA subjects had measurements of serum NO at baseline and after an overnight application nCPAP. There was significant increase in serum NO after nCPAP (baseline = 30.5 ± 14.4 μ M, after nCPAP = 81.0 ± 82.1 μ M, p = 0.01). This study demonstrates, for the first time, that circulating NO is suppressed in OSA, and this is promptly reversible with the use of nCPAP. The findings offer support for nitric oxide being one of the mediators involved in the acute hemodynamic regulation and long-term vascular remodeling in OSA.
Targeting of the Tumor Suppressor GRHL3 by a miR-21-Dependent Proto-Oncogenic Network Results in PTEN Loss and Tumorigenesis
Authors: Charbel Darido, Smitha R. Georgy, Tomasz Wilanowski, Sebastian Dworkin, Alana Auden, Quan Zhao, Gerhard Rank, Seema Srivastava, Moira J. Finlay, Anthony T. Papenfuss, Pier Paolo Pandolfi, Richard B. Pearson, Stephen M. Jane
Journal: Cancer Cell (2011)
ASSOCIATIONS BETWEEN HIGH-SENSITIVITY C-REACTIVE PROTEIN AND ANKLE BRACHIAL INDEX IN ASYMPTOMATIC OLDER ADULTS
Authors: Jang Hoon Lee, Kyun Hee Kim, Won Suk Choi, Sun Hee Park, Myung Hwan Bae, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae
Journal: Journal of the American College of Cardiology (2012)
Presence of foam cells containing oxidised low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis.
Authors: P G Winyard, F Tatzber, H Esterbauer, M L Kus, D R Blake, C J Morris
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVE--Increased concentrations of lipid peroxidation products have been described in the serum and synovial fluid from patients with rheumatoid arthritis. A large proportion of the unsaturated lipids in human extracellular fluids is a component of low density lipoprotein (LDL). The oxidative modification of LDL, and its subsequent uptake by macrophages, has been implicated in the pathogenesis of atherosclerosis, but not of rheumatoid arthritis. This study aimed to assess whether oxidatively modified LDL was present in the rheumatoid synovium. METHODS--A polyclonal antiserum raised in rabbits against oxidised LDL (o-LDL) was used to perform an immunohistochemical study of a series of synovial biopsy specimens from patients with rheumatoid arthritis. RESULTS--Collections of positively stained macrophages, arranged in a linear fashion and with the morphological characteristics of foam cells--that is, 9fatty streaks9, were identified around blood vessels within the intimal connective tissue. In addition, scattered, positively stained foam cells were present in association with deposits of fibrin. These staining patterns were absent from control synovial membranes (traumatic knee injuries). CONCLUSIONS--The findings in all rheumatoid patients studied suggest that atherosclerosis and rheumatoid arthritis have analogous pathogenetic features.
Immortal ALT+ Human Cells Do Not Require Telomerase Reverse Transcriptase for Malignant Transformation
Authors: Beicheng Sun, Meizhen Chen, Christina L. Hawks, Peter J. Hornsby
Journal: Cancer Research (2005)

Abstract Many human cancer cells lack telomerase activity but nevertheless maintain telomeres via a process termed “alternative lengthening of telomeres” (ALT). Despite being immortal and having a telomere maintenance mechanism, ALT+ human fibroblasts require telomerase reverse transcriptase (hTERT) for tumor formation in immunodeficient mice when tested by s.c. injection. Here we show that three ALT+ human SV40-immortalized fibroblast cell lines require only oncogenic RasV12G to be converted to a fully tumorigenic state. When cells were implanted beneath the kidney capsule of immunodeficient mice, they invaded the kidney and neighboring organs and metastasized to the lungs. RasV12G-expressing ALT+ cells remained completely telomerase negative. Introduction of hTERT conferred strong telomerase activity but did not appreciably change the malignant properties of the cells. However, when cells were tested by s.c. injection, RasV12G-transduced ALT+ cells did not form tumors, and in this site, hTERT was required for tumorigenicity. These data show that when the s.c. injection method is used as an assay for tumorigenicity, hTERT may be artifactually scored as an oncogene; the subrenal capsule assay shows that ALT, as a telomere maintenance mechanism, is equivalent to hTERT in neoplastic transformation of human cells by oncogenes.
Biological Mechanisms Linking Obesity and Cancer Risk: New Perspectives
Authors: Darren L. Roberts, Caroline Dive, Andrew G. Renehan
Journal: Annual Review of Medicine (2010)

Body mass index, as an approximation of body adiposity, is associated with increased risk of several common and less common malignancies in a sex- and site-specific manner. These findings implicate sex- and cancer site-specific biological mechanisms underpinning these associations, and it is unlikely that there is a "one system fits all" mechanism. Three main candidate systems have been proposed-insulin and the insulin-like growth factor-I axis, sex steroids, and adipokines-but there are shortfalls to these hypotheses. In this review, three novel candidate mechanisms are proposed: obesity-induced hypoxia, shared genetic susceptibility, and migrating adipose stromal cells. While public health policies aimed at curbing the underlying causes of the obesity epidemic are being implemented, there is a parallel need to better understand the biological processes linking obesity and cancer as a prerequisite to the development of new approaches to prevention and treatment.
Weight-for-age distribution and case-mix adjusted outcomes of 14,307 paediatric intensive care admissions
Authors: Nicholas J. Prince, Katherine L. Brown, Teumzghi F. Mebrahtu, Roger C. Parslow, Mark J. Peters
Journal: Intensive Care Medicine (2014)

To determine whether the paediatric intensive care (PIC) population weight distribution differs from the UK reference population and whether weight-for-age at admission is an independent risk factor for mortality. Admission weight-for-age standard deviation scores (SDS) were calculated for all PIC admissions (March 2003–December 2011) to Great Ormond Street Hospital: this is the number of standard deviations (SD) between a child's weight and the UK mean weight-for-age. Categorised into nine SDS groups, standardised mortality ratios (SMR) and logistic regression were used to assess the relationship between weight-for-age at admission and risk-adjusted mortality. Out of 12,458 admissions, mean weight-for-age was 1.04 SD below the UK reference population mean (p < 0.0001). Based on 942 deaths, risk-adjusted mortality was lowest in those with mild-to-moderately raised weight-for-age (SDS 0.5–2.5) and highest in children with extreme under- or overweight (SDS < −3.5 and SDS > +3.5). Logistic regression indicated that age, gender, ethnicity and weight-for-age are independent risk factors for mortality. South Asian and 'other' ethnicities had significantly increased risk of death compared to children of white and black ethnic origin. The PIC population mean weight-for-age is significantly lower than the UK reference mean. The extremes of weight-for-age are over-represented, especially underweight. Weight-for-age at admission is an independent risk factor for mortality. A U-shaped association between weight and risk-adjusted mortality exists, with the lowest risk of death in children who are mild-to-moderately overweight. Future studies should determine the impact of malnutrition on risk-adjusted mortality and investigate the aetiology of risk disparities with ethnicity.
Improved adherence to CPAP by telemetric support in newly diagnosed OSAS patients
Authors: Otto Schoch, Florent Baty, Jolanda Niedermann, Jochen Ruediger, Martin Brutsche
Journal: European Respiratory Journal (2013)

Introduction : Acceptance of positive airway pressure therapy (PAP) within the first month is predictive for long term adherence. Telemedicine is a novel tool to supervise PAP use at patient's home. We report 30-day results of a pilot study, comparing PAP use in telemetrically supervised vs. conventionally treated patients (pts).

Methods : Between 1/2012 and 12/2012, of 293 newly diagnosed OSAS pts, 170 started PAP with a telemetric 3G-device (ResTraxx OnlineTM, ResMed) and 123 conventionally. For telemedicine pts, hours of PAP use and leak flow were checked on a protected online data depository 3 d/week. Phone calls were triggered by  0.4L/s for 2 consecutive nights. After 30 days, PAP use/night and number of nights without PAP were compared.

Results : At baseline, OSAS severity (ESS, AHI, ODI) was not different between groups, but telemedicine pts were younger and more often outpatients.

View this table:

Baseline characteristics of the study population





Within the first 30 days telemedicine pts used PAP 48 minutes/night longer (5.2 [3.5-6.3] vs 4.6 [2.6-6.1] h/night, p=0.05) and for more nights (28 [23-30] vs 26 [18-30], p<0.001). After adjusting for age and proportion of outpatients, the telemedicine effect was stronger (p=0.02).

Conclusion : In this non-randomised pilot study, a telemetric support for the first month of PAP was technically feasible and increased PAP adherence. To determine the direct effects of telemedicine on medium and long-term PAP use, a randomised prospective study is necessary.
S102 The Effect of Influenza Infection on Bleomycin Induced Pulmonary Fibrosis
Authors: A Stavrou, L Jolly, A Habgood, A John, T Hussell, A Blanchard, G Jenkins
Journal: Thorax (2012)

<h3>Introduction</h3> Transforming Growth Factor-beta (TGFβ) promotes anti-proliferative and pro-apoptotic pathways in lung epithelial cells, both of which have been implicated in the pathogenesis of IPF. TGFβ must be activated before it can mediate these events. Acute exacerbations of IPF are characterised by widespread epithelial cell apoptosis. The precise cause of these exacerbations is not known. The Influenza A virus is a single-stranded segmented RNA virus that infects epithelial cells leading to cell death and injury, and can also activate TGFβ. The role of infection in acute exacerbations of IPF is unclear. The aim of this study is to investigate the effect of influenza infection on bleomycin-induced pulmonary fibrosis and TGFβ activation in vivo. <h3>Materials and Methods</h3> 60 U of bleomycin was instilled into the lungs of 6–8 week old male C57Bl/6 mice. After 28 days mice were exposed intranasally with 10, 20 Units of influenza virus ‘x31’ or PBS, and the lungs harvested 5 days later. Bronchoalveolar lavage (BAL) was performed and lung tissue harvested for mRNA analysis, histology and hydroxyproline levels. All animal studies were ethically reviewed and carried out in accordance with Animals (Scientific Procedures) Act 1986 and the GSK Policy on the Care, Welfare and Treatment of Animals. <h3>Results</h3> Mice exposed to bleomycin and infected with influenza lost less weight compared with saline-exposed influenza-infected animals. However, the lungs from bleomycin-exposed, influenza-infected mice showed increased lung damage with more matrix deposition on trichrome staining than saline-exposed, influenza-infected mice. Saline-exposed, influenza-infected mice demonstrated the anticipated dose dependent increase in BAL lymphocytosis as well as apoptosis staining in histological TUNEL assessment. However, in bleomycin-exposed mice, influenza infection did not promote enhanced BAL lymphocytosis or apoptosis. However, influenza appeared to enhance the fibrotic response demonstrated by an increase in matrix deposition on masson’s trichrome and increased lung hydroxyproline levels in influenza infected bleomycin exposed mice, as early as 5 days post infection. <h3>Conclusions</h3> These data suggest that influenza infection may exacerbate lung fibrosis by promoting epithelial apoptosis.
Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years
Authors: Mette K. Andersen, Virve Lundgren, Joni A. Turunen, Carol Forsblom, Bo Isomaa, Per-Henrik Groop, Leif Groop, Tiinamaija Tuomi
Journal: Diabetes Care (2010)

OBJECTIVE We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at &amp;gt;35 years of age (T1D&amp;gt;35y; n = 257) or &amp;lt;20 years of age (T1D&amp;lt;20y; n = 158), and type 2 diabetes. RESULTS Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D&amp;gt;35y patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS LADA patients differed genetically and phenotypically from both T1D&amp;gt;35y and type 2 diabetic patients in a manner dependent on GADA levels.
Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal cancer
Authors: D.Y. Zang, B.H. Lee, H.-C. Park, H.H. Song, H.J. Kim, J.Y. Jung, J.H. Kim, H.Y. Kim, J.H. Kwon, S.W. Hwang, S.R. Park, C.H. Park, K.O. Kim, M.-J. Kim, K.M. Jang
Journal: Annals of Oncology (2009)
Costs, Effectiveness, and Workload Impact of Management Strategies for Women With an Adnexal Mass
Authors: Laura J Havrilesky, Michaela Dinan, Gregory P Sfakianos, Lesley H Curtis, Jason C Barnett, Toon Van Gorp, Evan R Myers
Journal: JNCI Journal of the National Cancer Institute (2014)

We compared the estimated clinical outcomes, costs, and physician workload resulting from available strategies for deciding which women with an adnexal mass should be referred to a gynecologic oncologist. We used a microsimulation model to compare five referral strategies: 1) American Congress of Obstetricians and Gynecologists (ACOG) guidelines, 2) Multivariate Index Assay (MIA) algorithm, 3) Risk of Malignancy Algorithm (ROMA), 4) CA125 alone with lowered cutoff values to prioritize test sensitivity over specificity, 5) referral of all women (Refer All). Test characteristics and relative survival were obtained from the literature and data from a biomarker validation study. Medical costs were estimated using Medicare reimbursements. Travel costs were estimated using discharge data from Surveillance, Epidemiology and End Results–Medicare and State Inpatient Databases. Analyses were performed separately for pre- and postmenopausal women (60 000 "subjects" in each), repeated 10 000 times. Refer All was cost-effective compared with less expensive strategies in both postmenopausal (incremental cost-effectiveness ratio [ICER] $9423/year of life saved (LYS) compared with CA125) and premenopausal women (ICER $10 644/YLS compared with CA125), but would result in an additional 73 cases/year/subspecialist. MIA was more expensive and less effective than Refer All in pre- and postmenopausal women. If Refer All is not a viable option, CA125 is an optimal strategy in postmenopausal women. Referral of all women to a subspecialist is an efficient strategy for managing women with adnexal masses requiring surgery, assuming sufficient capacity for additional surgical volume. If a test-based triage strategy is needed, CA125 with lowered cutoff values is a cost-effective strategy.