tbuckley/cabot-search huggingface dataset:
Thymidylate Synthase Gene Polymorphism Predicts Toxicity in Colorectal Cancer Patients Receiving 5-Fluorouracil-based Chemotherapy
Authors: Thierry Lecomte, Jean-Marc Ferraz, Franck Zinzindohoué, Marie-Anne Loriot, David-Alexandre Tregouet, Bruno Landi, Anne Berger, Paul-Henri Cugnenc, Raymond Jian, Philippe Beaune, Pierre Laurent-Puig
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The target enzyme for 5-fluorouracil (5-FU) is thymidylate synthase (TS). The TYMS gene encoding this enzyme is polymorphic, having either double (2R) or tri-tandem (3R) repeats of a 28-bp sequence in the promoter region and a 6-bp variation in the 3′-untranslated region (3′-UTR). TS expression predicts response to 5-FU-based chemotherapy, and the expression seems to be determined by the TYMS gene promoter. The aim of this study was to investigate the utility of determining these two TYMS gene polymorphisms to predict the toxicity and efficacy of 5-FU treatment in patients with colorectal cancer. Experimental Design: The determination of TYMS genotypes was performed in tumor and normal tissues by PCR amplification from 90 patients with colorectal cancer who were treated with adjuvant or palliative 5-FU-based chemotherapy. Associations between polymorphisms in the TYMS promoter and in the 3′-UTR gene and clinical outcome of these 90 patients treated with 5-FU based chemotherapy were evaluated individually. The linkage between TYMS promoter and TYMS 3′-UTR region polymorphisms was evaluated and a haplotype analysis was performed. Results: Individuals who were homozygous for the double repeat in the TYMS promoter region had more severe side effects to 5-FU. Patients with a 2R/2R, a 2R/3R, or a 3R/3R genotype had a grade 3 or 4 toxicity rate of 43, 18, and 3% respectively (P &amp;lt; 0.01). The TYMS promoter and TYMS 3′-UTR polymorphisms were in linkage disequilibrium, and the haplotype 2R/ins 6-bp was significantly associated with a high risk of severe side effects to 5-FU. The TYMS promoter and TYMS 3′-UTR polymorphisms were not associated with a response to 5-FU and survival of patients who received palliative 5-FU-based chemotherapy. Conclusions: This study demonstrated that TYMS genotyping could be of help in predicting toxicity to 5-FU-based chemotherapy. TYMS genotyping might make it possible to individualize treatment for patients with colorectal cancer.
Prevalence of pulmonary hypertension and right ventricular dysfunction in patients with mixed types of ILD
Authors: Charlotte Andersen, Søren Mellemkjær, Ole Hilberg, Ulf Simonsen, Jens Erik Nielsen-Kudsk, Elisabeth Bendstrup
Journal: European Respiratory Journal (2011)

Pulmonary hypertension (PH) defined by a mean pulmonary artery pressure (MPAP) > 25 mmHg worsens the prognosis of ILD and can compromise right ventricular function. This study investigates the prevalence of PH and right ventricular dysfunction in ILD patients.  Patients with a diagnosis of ILD based on HR-CT scan and lung function parameters were screened by echocardiography to detect signs of PH. A tricuspid pressure gradient (TI) ≥ 40 mmHg, dilatation or decreased tricuspid annular plane systolic excursion (TAPSE) indicated PH on echocardiography. If possible, right heart catheterisation (RHC) was performed in patients with PH on echocardiography to confirm the diagnosis. NT-proBNP was measured in all patients.   Results  (mean±SEM): 206 ILD patients were included. These had a diagnosis of IPF (17%) NSIP (12%), DIP (5%), allergic alveolitis (6%), ILD associated to collagenosis (18%), sarcoidosis (8%) or other/unclassifiet ILD (33%). Mean Dlco and TLC was, respectively, 44±1% and 69±1% of expected. Mean NT-proBNP levels were 496±111 ng/l.  30 patients (14.5%) had signs of PH on echocardiography (TI = 59±3 mmHg, NT-proBNP 2209±657 ng/l). RHC data were obtained in 19 patients, and in 18, the diagnosis of PH was confirmed (MPAP = 39±2 mmHg). Nine patients (5%) had PH confirmed on RHC (MPAP = 42±3 mmHg) and had dilatation of the right ventricle, decreased TAPSE (mean 1.38±0.14 cm) and markedly increased values of NT-proBNP (mean 5599±1557 ng/l).   Conclusions:  The estimated prevalence of PH in the present cohort of ILD patients was 15%. 5% of patients had verified severe pulmonary hypertension compromising right ventricular function.
Association between<i>FOXP3</i>polymorphisms and vitiligo in a Han Chinese population
Authors: P. Song, X.-W. Wang, H.-X. Li, K. Li, L. Liu, C. Wei, Z. Jian, X.-L. Yi, Q. Li, G. Wang, C.-Y. Li, T.-W. Gao
Journal: British Journal of Dermatology (2013)

Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4(+)CD25(+) regulatory T-cell (Treg) dysfunction was involved in the pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) - a master regulator of Treg development and function - were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.In this hospital-based case-control study of 682 patients with vitiligo and 682 vitiligo-free age- and sex-matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene - rs2232365, rs3761548 and rs5902434 - by performing polymerase chain reaction with sequence-specific primers (PCR-SSP).Significantly increased vitiligo risk was associated with the rs2232365 GG [odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17-2·39, P = 0·004] and rs3761548 AA (OR 1·82, 95% CI 1·10-3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2-6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08-1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases.FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.
Staphylococcus aureus nasal carriage in rheumatoid arthritis: antibody response to toxic shock syndrome toxin-1.
Authors: D Tabarya, W L Hoffman
Journal: Annals of the Rheumatic Diseases (1996)

To determine the prevalence of Staphylococcus aureus nasal carriage and to compare antibody responses to two superantigens, staphylococcal toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), in rheumatoid arthritis patients and normal subjects.88 rheumatoid arthritis patients and 110 control subjects were cultured for nasal carriage of S aureus; 62 isolates were bacteriophage typed. Twenty five patients and 11 spouses were tested for antibodies to TSST-1, SEA, and sonicate extracts of Bacteroides fragilis and Escherichia coli; 19 patients were HLA-DR typed.50% of patients and 33% of normal subjects were S aureus carriers. Bacteriophage typing of isolates suggested significant differences between strains isolated from the two groups. Patients showed higher IgG (P = 0.0025) and IgA (P = 0.0372) antibody levels to TSST-1 than normal spouses and these responses were not related to rheumatoid factor titres or HLA-DR type.When compared to normals, rheumatoid arthritis patients more often carry S aureus in their nasal vestibule, carry a distinct subpopulation of S aureus strains, and have higher average antibody levels to TSST-1.
Difficulty matters: Unspecific attentional demands as a major determinant of performance highlighted by clinical studies
Authors: Mario Bonato, Marco Zorzi, Carlo Umiltà
Journal: Behavioral and Brain Sciences (2013)

Abstract The cognitive impairments shown by brain-damaged patients emphasize the role of task difficulty as a major determinant for performance. We discuss the proposal of Kurzban et al. in light of our findings on right-hemisphere–damaged patients, who show increasing awareness deficits for the contralesional hemispace when engaged with resource-consuming dual tasks. This phenomenon is readily explained by the assumption of unspecific depletable resources.
Prophylactic cranial irradiation can reduce symptomatic brain metastasis in extensive SCLC.
Authors: Ahmed Fahim
Journal: Thorax (2007)

▴ Slotman B, Faivre-Finn C, Kramer G, et al . Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357 :664–72.

Survival rates for extensive small cell lung cancer (SCLC) have not improved dramatically in the past 3 years. Brain metastases are common in this disease and indicative of …
Abstract P6-01-03: Change of HER2 status following neoadjuvant systemic therapy in primary breast cancer patients
Authors: Atsushi Yoshida, Naoki Hayashi, Hiroshi Yagata, Koyu Suzuki, Seigo Nakamura, Hideko Yamauchi
Journal: Cancer Research (2015)

Abstract Background: The incidence of change in HER2 status in primary breast cancer after neoadjuvant chemotherapy (NAC) and whether the prognosis is affected by the change in HER2 status is not well known. Patients and Methods: Five hundred and eighty-eight patients who were treated with anthracycline- and/or taxane-based NAC and had non-pathologic complete response between 2001 and 2008 in our hospital were enrolled. Human epidermal growth factor receptor-2 (HER2) status was assessed in specimen by needle biopsy before NAC and on the residual tumor of surgical specimen. We determine the impact of change in HER2 status on recurrence-free survival (RFS). Twenty-eight patients had received trastuzumab with NAC, and 57 patients had received trastuzumab as adjuvant therapy. HER2-positive was defined as 3+ by immunohistochemistry and/or amplification by fluorescent in situ hybridization. Association between change in HER2 status after NAC and clinicopathologic factors, including age, clinical T stage, estrogen receptor (ER), progesterone receptor (PR), Nuclear grade (NG), lymphovascular invasion (LVI) and Trastuzumab usage (NAC and Adjuvant setting) were determined. Result: A median follow-up period was 57 months (range, 3 to 131 months). Four hundred eighty-nine of the 588 patients (83.1%) had HER2-negative tumors and 99 patients (16.8%) had HER2-positive tumor before NAC. In 11 of the 489 patients (2.2%) HER2-negative changed to HER2-positive.In 33 of the 99 patients (30%) HER2-positive changed to HER2-negative. In clinicopathologic factors, ER and PR positive before NAC were associated with incidence of change in HER2 status after NAC. Receiving trastuzumab was not correlated with incidence of change in HER2 status. In terms of RFS, there was no difference between patients with and without change in HER2 status in both of the 489 patients with HER2-negative tumors and 99 patients with HER2-positive tumors before NAC (p=0.26, p=0.23, respectively). Conclusion: We herein reported the incidence of change in HER2 status after NAC with the largest sample size. However, change in HER2 status did not seems to affect prognosis. Further prospective study is needed to confirm the prognostic impact of change in HER2 status. Citation Format: Atsushi Yoshida, Naoki Hayashi, Hiroshi Yagata, Koyu Suzuki, Seigo Nakamura, Hideko Yamauchi. Change of HER2 status following neoadjuvant systemic therapy in primary breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-03.
Suicide within 12 months of contact with mental health services: national clinical survey
Authors: L. Appleby, J. Shaw, T. Amos, R. McDonnell, C. Harris, K. McCann, K. Kiernan, S. Davies, H. Bickley, R. Parsons
Journal: BMJ (1999)

To describe the clinical circumstances in which psychiatric patients commit suicide.National clinical survey.England and Wales.A two year sample of people who had committed suicide, in particular those who had been in contact with mental health services in the 12 months before death.Proportion of suicides in people who had had recent contact with mental health services; proportion of suicides in inpatients; proportion of people committing suicide and timing of suicide within three months of hospital discharge; proportion receiving high priority under the care programme approach; proportion who were recently non-compliant and not attending.10 040 suicides were notified to the study between April 1996 and March 1998, of whom 2370 (24%; 95% confidence interval 23% to 24%) had had contact with mental health services in the year before death. Data were obtained on 2177, a response rate of 92%. In general these subjects had broad social and clinical needs. Alcohol and drug misuse were common. 358 (16%; 15% to 18%) were psychiatric inpatients at the time of death, 21% (17% to 25%) of whom were under special observation. Difficulties in observing patients because of ward design and nursing shortages were both reported in around a quarter of inpatient suicides. 519 (24%; 22% to 26%) suicides occurred within three months of hospital discharge, the highest number occurring in the first week after discharge. 914 (43%; 40% to 44%) were in the highest priority category for community care. 488 (26% excluding people whose compliance was unknown; 24% to 28%) were non-compliant with drug treatment while 486 (28%; 26% to 30%) community patients had lost contact with services. Most people who committed suicide were thought to have been at no or low immediate risk at the final service contact. Mental health teams believed suicide could have been prevented in 423 (22%; 20% to 24%) cases.Several suicide prevention measures in mental health services are implied by these findings, including measures to improve compliance and prevent loss of contact with services. Inpatient facilities should remove structural difficulties in observing patients and fixtures that can be used in hanging. Prevention of suicide after discharge may require earlier follow up in the community. Better suicide prevention in psychiatric patients is likely to need measures to improve the safety of mental health services as a whole, rather than specific measures for people known to be at high risk.
Movements of the Mitral Valve
Authors: ROBERT F. RUSHMER, BLISS L. FINLAYSON, ALDEN A. NASH
Journal: Circulation Research (1956)

Cinefluorographic analysis of mitral valve motion in intact dogs provided evidence that the motility of the valve cusps is restrained by tension exerted through the chordae tendineae throughout the cardiac cycle, except for the rapid filling phase. At the onset of ventricular systole, early contraction of the papillary muscles may play an important role in approximating the mitral valve cusps. During ventricular ejection, the mitral cusps and valve ring move toward the apex of the heart. During diastole, separation of the valve cusps is remarkably slight. The valves were observed to fling wide during rapid ventricular filling when the heart was much smaller than normal, immediately after surgery.
Left ventricular dynamic geometry in the intact and open chest dog.
Authors: K R Walley, M Grover, G L Raff, J W Benge, B Hannaford, S A Glantz
Journal: Circulation Research (1982)

No approach to describing the heart's dynamic geometry has been widely adopted, probably because all require questionable assumptions of chamber shape, symmetry, or placement of the measuring devices. In other words, these approaches require assumptions about shape to reach conclusions about shape. We present an analysis that avoids such assumptions and provides an objective description of how the left ventricle deforms and rotates during the cardiac cycle. We only assume that the deformation of the left ventricular cavity is homogeneous, and explicitly validate this assumption. Our analysis yields the following new information about the contracting left ventricle: three principal directions of deformation and the relative length change alone these directions: the axis and angle of rotation, and relative volume. All these changes are referenced to the ventricle's configuration at end-diastole. We instrumented 13 dogs with tantalum screws without opening their chests. During systole, the three principal directions of deformation essentially are aligned along apex-base, anterior-posterior, and septum-free wall directions. There is little length change in the apex-base direction. The anterior and septal principal directions do not remain fixed with respect to the heart's anatomy during systole. During isovolumic relaxation and early filling, systolic shape changes are reversed. During slow filling, only small shape changes occur. Opening the pleura or performing a sternotomy and pericardiectomy makes the heart change orientation within the chest, but does not alter the magnitude of shortening, relative to the left ventricle's end-diastolic configuration.
Analgesic and nonsteroidal anti-inflammatory use in relation to nonmelanoma skin cancer: A population-based case-control study
Authors: Dorothea C. Torti, Brock C. Christensen, Craig A. Storm, Joan Fortuny, Ann E. Perry, Michael S. Zens, Therese Stukel, Steven K. Spencer, Heather H. Nelson, Margaret R. Karagas
Journal: Journal of the American Academy of Dermatology (2011)
P210 The national lung cancer audit--year 5 completeness and outcomes
Authors: P. Beckett, I. Woolhouse, R. Stanley, M. D. Peake
Journal: Thorax (2010)

<h3>Introduction</h3> The National Lung Cancer Audit aims to record outcomes in lung cancer on a large scale and through case-mix adjustment, start to explain the wide variations noted. Although Wales and Scotland also submit data to the audit, this abstract presents results for England only. <h3>Results</h3> In Year 5, participation has again increased and the number of cases submitted has risen from 10 920 cases in 2005, to 16 922 in 2006, to 20 639 in 2007 to 25 757 in 2008, and to 30 155 in 2009. Completeness of data on individual cases has also improved—recording of PS has risen to 88%, stage to 80% and treatment to 89% of cases. Results suggest that the quality of care is improving, with annual increases in the proportion of patients being discussed in an MDT, proportion of patients receiving anti-cancer treatment, and in the surgical resection rate (see Abstract P210 Table 1). Data also show that the degree of variation across organisation is reducing year-on-year. <h3>Conclusions</h3> These results once again highlight the considerable achievement of the National Lung Cancer Audit in collecting data and are a testament to the hard work of lung cancer teams across the country in achieving such high quality data on such a large scale. The results suggest that care for lung cancer patients is slowly improving, although some of the apparent improvement is likely to reflect the rise in data quality. However, wide variations in outcomes still persist between organisations, which need to be the focus of on-going service improvement work.
Radiation enteritis with malabsorption.
Authors: H I Tankel, D H Clark, F D Lee
Journal: Gut (1965)

EDITORIAL SYNOPSIS The clinical, biochemical, and radiological features, with the operative findings and relevant histology, in three cases of radiation damage to the small bowel which led to varying degrees of malabsorption, are described.There was no direct correlation between the severity of the mucosal changes and the severity of malabsorption.
Coordinated Regulation of Cell Cycle Transcripts by p53-Inducible microRNAs, miR-192 and miR-215
Authors: Sara A. Georges, Matthew C. Biery, Soo-yeon Kim, Janell M. Schelter, Jane Guo, Aaron N. Chang, Aimee L. Jackson, Michael O. Carleton, Peter S. Linsley, Michele A. Cleary, B. Nelson Chau
Journal: Cancer Research (2008)

Abstract Cell cycle arrest in response to DNA damage is an important antitumorigenic mechanism. MicroRNAs (miRNAs) were recently shown to play key regulatory roles in cell cycle progression. For example, miR-34a is induced in response to p53 activation and mediates G1 arrest by down-regulating multiple cell cycle–related transcripts. Here we show that genotoxic stress promotes the p53-dependent up-regulation of the homologous miRNAs miR-192 and miR-215. Like miR-34a, activation of miR-192/215 induces cell cycle arrest, suggesting that multiple miRNA families operate in the p53 network. Furthermore, we define a downstream gene expression signature for miR-192/215 expression, which includes a number of transcripts that regulate G1 and G2 checkpoints. Of these transcripts, 18 transcripts are direct targets of miR-192/215, and the observed cell cycle arrest likely results from a cooperative effect among the modulations of these genes by the miRNAs. Our results showing a role for miR-192/215 in cell proliferation combined with recent observations that these miRNAs are underexpressed in primary cancers support the idea that miR-192 and miR-215 function as tumor suppressors. [Cancer Res 2008;68(24):10105–12]
Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism
Authors: J C Fang, I Sarosiek, Y Yamamoto, J Liu, R K Mittal
Journal: Gut (1999)

Atropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR).To compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD.Oesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 microg/kg bolus, 4 microg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period.Atropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0. 55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0. 15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8. 1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0. 60)) (p>0.05).In contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade.