tbuckley/cabot-search huggingface dataset:
Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study
Authors: J. Coelho, L. Beaugerie, J. F. Colombel, X. Hebuterne, E. Lerebours, M. Lemann, P. Baumer, J. Cosnes, A. Bourreille, J. P. Gendre, P. Seksik, A. Blain, E. H. Metman, A. Nisard, G. Cadiot, M. Veyrac, B. Coffin, X. Dray, F. Carrat, P. Marteau
Journal: Gut (2010)

<h3>Background and aims</h3> Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines. <h3>Methods</h3> 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007. Physicians documented the following information from the women: last menstrual date, delivery term, details of pregnancy outcome, prematurity, birth weight and height, congenital abnormalities, medication history during each trimester, smoking history and alcohol ingestion. Data were compared between three groups: women exposed to thiopurines (group A), women receiving a drug other than thiopurines (group B) and women not receiving any medication (group C). <h3>Results</h3> Mean age at pregnancy was 28.3 years. 75.7% of the women had Crohn9s disease and 21.8% had ulcerative colitis, with a mean disease duration of 6.8 years at inclusion. Of the 215 pregnancies, there were 138 births (142 newborns), and the mean birth weight was 3135 g. There were 86 pregnancies in group A, 84 in group B and 45 in group C. Interrupted pregnancies occurred in 36% of patients enrolled in group A, 33% of patients enrolled in group B, and 40% of patients enrolled in group C; congenital abnormalities arose in 3.6% of group A cases and 7.1% of group B cases. No significant differences were found between the three groups in overall pregnancy outcome. <h3>Conclusions</h3> The results obtained from this cohort indicate that thiopurine use during pregnancy is not associated with increased risks, including congenital abnormalities.
Extent of lymph node dissection and overall survival in patients with uterine carcinosarcoma, papillary serous and endometrioid adenocarcinoma: A retrospective cohort study
Authors: Ioannis Alagkiozidis, Jeremy Weedon, Allison Grossman, Pengfei Wang, Benjamin Mize, Kirstie Wilson, Tana Shah, Katherine Economos, Ghadir Salame, Ovadia Abulafia, Yi-Chun Lee
Journal: International Journal of Surgery (2015)
Chemopreventive <b> <i>n</i> </b>-3 Polyunsaturated Fatty Acids Reprogram Genetic Signatures during Colon Cancer Initiation and Progression in the Rat
Authors: Laurie A. Davidson, Danh V. Nguyen, Regina M. Hokanson, Evelyn S. Callaway, Robert B. Isett, Nancy D. Turner, Edward R. Dougherty, Naisyin Wang, Joanne R. Lupton, Raymond J. Carroll, Robert S. Chapkin
Journal: Cancer Research (2004)

Abstract The mechanisms by which n-3 polyunsaturated fatty acids (PUFAs) decrease colon tumor formation have not been fully elucidated. Examination of genes up- or down-regulated at various stages of tumor development via the monitoring of gene expression relationships will help to determine the biological processes ultimately responsible for the protective effects of n-3 PUFA. Therefore, using a 3 × 2 × 2 factorial design, we used Codelink DNA microarrays containing ∼9000 genes to help decipher the global changes in colonocyte gene expression profiles in carcinogen-injected Sprague Dawley rats. Animals were assigned to three dietary treatments differing only in the type of fat (corn oil/n-6 PUFA, fish oil/n-3 PUFA, or olive oil/n-9 monounsaturated fatty acid), two treatments (injection with the carcinogen azoxymethane or with saline), and two time points (12 hours and 10 weeks after first injection). Only the consumption of n-3 PUFA exerted a protective effect at the initiation (DNA adduct formation) and promotional (aberrant crypt foci) stages. Importantly, microarray analysis of colonocyte gene expression profiles discerned fundamental differences among animals treated with n-3 PUFA at both the 12 hours and 10-week time points. Thus, in addition to demonstrating that dietary fat composition alters the molecular portrait of gene expression profiles in the colonic epithelium at both the initiation and promotional stages of tumor development, these findings indicate that the chemopreventive effect of fish oil is due to the direct action of n-3 PUFA and not to a reduction in the content of n-6 PUFA.
Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano
Authors: E. A. Herrera, R. V. Reyes, D. A. Giussani, R. A. Riquelme, E. M. Sanhueza, G. Ebensperger, P. Casanello, N. Mendez, R. Ebensperger, E. Sepulveda-Kattan, V. M. Pulgar, G. Cabello, C. E. Blanco, M. A. Hanson, J. T. Parer, A. J. Llanos
Journal: Cardiovascular Research (2007)

To study the nitric oxide (NO) and carbon monoxide roles in the regulation of the pulmonary circulation in lowland and highland newborn sheep and llamas. We used neonatal sheep (Ovis aries) and llamas (Lama glama) whose gestation and delivery took place at low (580 m) or high (3600 m) altitude. In vivo, we measured the cardiopulmonary function basally and with a NO synthase (NOS) blockade and calculated the production of carbon monoxide by the lung. In vitro, we determined NOS and soluble guanylate cyclase (sGC) expression, NOS activity, and haemoxygenase (HO) expression in the lung. Pulmonary arterial pressure was elevated at high altitude in sheep but not in llamas. Sheep at high altitude relative to sea level had significantly greater total lung NOS activity and eNOS protein, but reduced sGC and HO expression and carbon monoxide production. In contrast, llamas showed no difference in NO function between altitudes, but a pronounced increase in pulmonary carbon monoxide production and HO expression at high altitude. In the llama, enhanced pulmonary carbon monoxide, rather than NO, protects against pulmonary hypertension in the newborn period at high altitude. This shift in pulmonary dilator strategy from NO to carbon monoxide has not been previously described, and it may give insight into new treatments for excessive pulmonary vasoconstriction.
Presentation of Antigen by Endothelial Cells and Chemoattraction Are Required for Homing of Insulin-specific CD8+ T Cells
Authors: Alexei Y. Savinov, F. Susan Wong, Austin C. Stonebraker, Alexander V. Chervonsky
Journal: The Journal of Experimental Medicine (2003)

Activated insulin-specific CD8+ T cells (IS-CD8+ cells) home to the pancreas, destroy β cells, and cause rapid diabetes upon transfer into diabetes-prone NOD mice. Surprisingly, they also cause diabetes in mouse strains that are free of preexistent inflammation. Thus, we hypothesized that islet-specific homing may be in part dependent on IS-CD8+ cells' recognition of the cognate major histocompatibility complex (MHC)/peptide complexes presented by pancreatic endothelial cells, which acquire the antigen (insulin) from β cells. In fact, islet-specific homing was abrogated in mice that lack MHC class I expression, or presentation of the specific peptide, or have impaired insulin secretion. Moreover, we found that IS-CD8+ cells directly recognized pancreatic endothelial cells in islet organ cultures. Triggering of IS-CD8+ cells' T cell receptor (TCR) led to activation of integrins expressed by these cells. In addition, chemokines, particularly SLC (CCL21), were also required for IS-CD8+ cells' adhesion to endothelial monolayers and for successful homing in vivo. Thus, signaling through TCR and chemokine receptors work in concert to assure firm adhesion of T cells to the pancreatic endothelium. The antigen cross-presentation ability of endothelia may therefore contribute to the specificity of homing of activated T lymphocytes to the tissues where antigens are generated by other cell types.
Diagnosing chronic cough in children
Authors: M D Shields
Journal: Thorax (2006)

Resolving the controversies in Pseudomonas serology will depend on more research in PA-free and initially PA infected children with CF using improved serological methods applied longitudinally with greater frequency.Monitoring PA antibody titres in children with CF diagnosed through newborn screening offers many advantages:(1) they begin PA-free; (2) the titres are initially very low and constant; (3) seroconversion per se indicates PA infection with a host immune response and not colonisation.However, the greatest difficulty in studying young children with CF-that is, the problem of culturing lower respiratory secretions-will continue to plague these investigations.Although either nasopharyngeal/tracheal techniques or oropharyngeal techniques may be used, their sensitivity and reliability can always be challenged when standard microbiological culturing methods are employed.Consequently, interpretation of the data published in the two current papers and all the literature becomes very difficult.For these reasons, nonculture based methods such as serological tests or polymerase chain reaction require further research and evaluation.To discover the truth about the value of Pseudomonas serology in children with CF, we need to have more comprehensive research with better microbiological and serological techniques.We also need to identify an optimal panel of redundant complementary PA antigens that are clinically significant virulence factors.Ultimately, a combination of PA microbiology and serology will probably be used-serology will not replace microbiology.In the meantime, the implications of earlier studies 4-7 which are supported by the data of Kappler et al 9 as well as other publications 1 8 14 remain intriguing and interesting.
On the Mechanism of Antihypertensive Action of Hydrochlorothiazide in Rats
Authors: E. E. Daniel
Journal: Circulation Research (1962)

Hydrochlorothiazide significantly diminishes blood pressure in rats with DCA hypertension. Infusion with hypertonic saline or dextrose failed to reverse the blood pressure effects of hydrochlorothiazide. Infusion of hypotonic saline failed to restore blood pressure to the levels of hypertension in untreated controls in one experiment but tended to do so in another. There was no significant diminution of the inulin space accompanying the hypotensive action of hydrochlorothiazide, nor any relation between the expansion of the extracellular and cardiovascular volumes by various infusions and their effects on blood pressures of thiazide-treated rats. Plasma or extracellular fluid volume alteration was, therefore, not the primary action of hydrochlorothiazide in these rats. Analyses of the composition of plasma, aorta, stomach muscle, psoas muscle, or left ventricle did not support the theory that hydrochlorothiazide acts by decreasing the concentration of intracellular sodium or increasing the ratio of extracellular to intracellular sodium. Changes in composition of the left ventricle suggested that alterations in its function may have influenced some of the blood pressure changes noted. It is suggested that attention should be paid to the action of hydrochlorothiazide on other constituents in vascular and cardiac muscle.
Comparison of urinary glycosaminoglycan excretion in rheumatoid arthritis, osteoarthritis, myocardial infarction, and controls.
Authors: A J Chuck, J Murphy, J B Weiss, D M Grennan
Journal: Annals of the Rheumatic Diseases (1986)

Urinary glycosaminoglycan (GAG) excretion was measured in 24 patients with active rheumatoid arthritis (RA) before and after treatment with conventional second-line agents. Urinary GAG excretion was also measured in normal controls, patients with osteoarthritis (OA), and patients with acute myocardial infarction (MI). Total GAG excretion was increased in the RA group and fell after second-line therapy (p less than 0.01). More low than high molecular weight GAG was excreted in the active RA group, and this pattern was reversed after treatment. Excretion of total, high and low molecular weight GAG in the OA group did not differ significantly from controls. Total GAG excretion was increased in the MI group when compared with controls (p less than 0.02) and consisted mainly of high molecular weight GAG. The serial measurement of urinary GAG provides a further index of disease activity and may help to monitor response to treatment.
Methyl aminolaevulinate-photodynamic therapy for actinic keratoses, squamous cell carcinoma<i>in situ</i>and superficial basal cell carcinoma employing a square wave intense pulsed light device for photoactivation
Authors: A.M.R. Downs, C.B. Bower, D.A. Oliver, C.A. Stone
Journal: British Journal of Dermatology (2009)
Colorectal Cancer Survival Gains and Novel Treatment Regimens
Authors: Irfan Jawed, Julia Wilkerson, Vinay Prasad, Austin G. Duffy, Tito Fojo
Journal: JAMA Oncology (2015)

IMPORTANCEThe past 2 decades have witnessed progress in the management of metastatic colorectal cancer (mCRC) with more effective agents and better surgical, medical, and supportive care.While substantial progress has been made, much more must be achieved to prolong the lives of patients.OBJECTIVE To conduct a systematic review to ascertain what percentage of the life expectancy gain in locally advanced and mCRC over the past 2 decades is due to novel therapies vs improvements in supportive care or secular trends and to thus inform treatment development strategies. EVIDENCE REVIEWWe searched Cochrane Controlled Trials Register, Medline, Embase, CancerLit, and Healthstar electronic databases for trials covering the period 1993 to 2015, scanned reference lists of articles, and searched recent conference abstracts.Ninety-six phase 3 trials and large (>50 patients) phase 2 trials in mCRC were examined.Outcomes evaluated in the experimental arms (EAs) and control arms (CAs) included overall response rate, stable disease, progression-free survival (PFS), and overall survival (OS).FINDINGS Over the period covered by the studies, the OS in EAs increased at a mean (95% CI) rate of 0.80 (0.67-0.93) mo/y.Importantly, OS in the CAs improved 0.63 (0.51-0.75) mo/y, reflecting in part the use of experimental regimens in subsequent studies.Chemotherapy contributed only partly to the gains in OS, given that (1) mean (95% CI) improvements in PFS were only 0.31 (0.22-0.39) mo/y in the EAs and 0.23 (0.15-0.31) mo/y in CAs; (2) gains in survival not directly attributable to the protocol were greater than gains in PFS (0.46 [0.36-0.57]mo/y in EAs and 0.39 [0.29-0.49]mo/y in CAs; and (3) effects on OS were much lower in second-line trials (median [interquartile range] response rates, 8.6% [0%-11.0%] in EAs and 7.5% [3.8%-12.8%] in CAs) compared with first-line trials (39.5% [24.0%-50.2%]for EAs and 29.4% [16.4%-39.4%]for CAs). CONCLUSIONS AND RELEVANCEThe OS of patients with mCRC has improved gradually over the past 2 decades, with gains from chemotherapy occurring alongside gains from lead-time bias and improved locoregional approaches and supportive care.Gains from first-line therapies have been modest but consistent; however, gains from second-line therapies have been disappointing.We believe that future progress will be greater if emphasis is placed on enrolling patients in experimental trials to explore and develop alternative first-line regimens and better second-line therapies.
B Cell Phenotype in Patients with Common Variable Immunodeficiency (CVID) and its Relation to their Clinical Characteristics
Authors: A.M. Kahn, G. Luque, G. Gatti, M. Maccioni, J.J. Garcia, E. Cuestas, A. Basquiera, B. Ricchi, V.E. Rivero
Journal: Journal of Allergy and Clinical Immunology (2012)
Inactivation of Enhanced Expression of G <sub>i</sub> Proteins by Pertussis Toxin Attenuates the Development of High Blood Pressure in Spontaneously Hypertensive Rats
Authors: Yuan Li, Madhu B. Anand-Srivastava
Journal: Circulation Research (2002)

We have previously shown that the enhanced expression of G i proteins in spontaneously hypertensive rats (SHR) that precedes the development of high blood pressure may be one of the contributing factors in the pathogenesis of hypertension. In the present study, we demonstrate that the inactivation of G i proteins by intraperitoneal injection of pertussis toxin (PT, 1.5 μg/100 g body wt) into 2-week-old prehypertensive SHR prevented the development of hypertension up to 4 weeks and that, thereafter, it started to increase and reached the same level found in untreated SHR after 6 weeks. A second injection of PT after 4 weeks delayed the increase in blood pressure for another week. The PT-induced decrease in blood pressure in 6-week-old SHR was associated with a decreased level of G iα -2 and G iα -3 proteins in the heart, as determined by in vitro ADP ribosylation and immunoblotting. The decreased level of G i proteins was reflected in decreased G i functions. Furthermore, an augmentation of blood pressure to the same level in PT-treated SHR as found in untreated SHR was associated with enhanced expression and function of G i . These results indicate that the inactivation of G i proteins by PT treatment in prehypertensive SHR attenuates the development of hypertension and suggest that the enhanced levels of G i proteins that result in the decreased levels of cAMP and associated impaired cellular functions may be contributing factors in the pathogenesis of hypertension in SHR.
Diabetes and Vascular Disease in Different Arterial Territories
Authors: Binita Shah, Caron B. Rockman, Yu Guo, Jaclyn Chesner, Arthur Z. Schwartzbard, Howard S. Weintraub, Mark A. Adelman, Thomas S. Riles, Jeffrey S. Berger
Journal: Diabetes Care (2014)

The aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease (lower extremity peripheral artery disease [PAD], carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]).Prevalence of vascular disease was evaluated in 3,696,778 participants of the Life Line Screening survey between 2003 and 2008. PAD was defined as ankle-brachial pressure index <0.90 or prior revascularization, CAS as ≥50% stenosis or prior revascularization, and AAA as infrarenal aortic diameter ≥3 cm or prior repair. Odds ratios (ORs) and 95% CIs were assessed using logistic regression modeling.Diabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA was significantly higher (P < 0.0001) in participants with compared with those without diabetes. After multivariate adjustment for baseline demographics and clinical risk factors, a significant interaction existed between diabetes and vascular disease phenotype (P < 0.0001). Diabetes was associated with increased odds of PAD (OR 1.42 [95% CI 1.41-1.4]; P < 0.0001) and CAS (1.45 [1.43-1.47]; P < 0.0001) but decreased odds of AAA (0.86 [0.84-0.88]; P < 0.0001). The strength of association increased with increasing severity of disease in each vascular phenotype, and this association persisted in the population with asymptomatic vascular disease.In a large population-based study, the association between diabetes and vascular disease differed according to vascular phenotype. Future studies exploring the mechanism for these vascular-specific differences are needed.
The effect of antiallergic intranasal formulations on ciliary beat frequency of human nasal epithelium <i>in vitro</i>
Authors: J. Alberty, W. Stoll
Journal: Allergy (1998)

The nasal mucociliary clearance is an important defense mechanism of the upper respiratory tract. It is known to be influenced by many pharmacologic substances. We investigated the effects of three topical intranasal antiallergic formulations containing disodium cromoglycate (DNCG), dimethindene maleate (DMM), and azelastine‐HCL (AZL) on nasal ciliary beat frequency (CBF) in vitro. Nasal ciliated cells were harvested from 16 healthy volunteers. Cells were diluted 1:10 in culture medium and incubated with a placebo formulation (PLAC), containing 0,022% benzalkonium chloride, which was part of all formulations, a registered 2% formulation of DNCG, a 0.1% formulation of DMM, and a registered 0.1% formulation of AZL. After an incubation period of 20 min, CBF was registered by a photoelectric measurement device. Under control conditions (CONTROL), CBF was 11 4±1 3 Hz. PLAC reduced CBF to 9.7±2.3 Hz (NS). DNCG reduced CBF t o 9.7±2 Hz (NS). DMM reduced CBF to 7.2+1.7 Hz F&lt;0.O5 vs CONTROL, NS vs PLAC), and AZL reduced CBF to 0.9+1.8 Hz P ≤ 0.05 vs CONTROL, P ≤ O.001 vs DNCG, P &lt; 0.001 vs PLAC). In conclusion, a possible influence of antiallergic intranasal formulations on nasal ciliary function has to be considered in clinical application.
An I<sup>3</sup> Theory analysis of human sex differences in aggression
Authors: Eli J. Finkel, Erica B. Slotter
Journal: Behavioral and Brain Sciences (2009)

Abstract According to I 3 Theory, individuals enact aggressive behaviors when (a) instigating triggers are severe, (b) impelling forces are strong, and/or (c) inhibiting forces are weak. Archer's analysis of human sex differences in aggression could be bolstered by a careful analysis of male-female discrepancies in reactivity (or exposure) to instigating triggers, proneness toward impelling forces, and/or proneness toward inhibiting forces.
Point/Counterpoint: Is there a role for radiotherapy in the treatment of primary CNS lymphoma?
Authors: P. Y. Wen
Journal: Neuro-Oncology (2014)

Primary central nervous system lymphoma (PCNSL) is a relatively rare form of extra-nodal non-Hodgkin's lymphoma that accounts for approximately 4% of primary central nervous system tumors. Treatment with high-dose methotrexate-based chemotherapeutic regimens have resulted in response rates of 60-70% or higher and long-term survival in 15-30% of patients.1–4 While PCNSL is sensitive to radiation therapy, the duration of response is relatively short, and treatment is associated with delayed neurotoxicity, especially in the elderly.5 Increasingly, there is a debate regarding the value of radiation therapy in the initial treatment of patients with PCNSL. This is reflected in the two ongoing randomized studies of newly diagnosed PCNSL being conducted in the United States. One, sponsored by NRG Oncology, evaluates the value of adding radiation therapy to chemotherapy (NCT01399372). In contrast, a second study, conducted by the Alliance in Clinical Trials in Oncology Cooperative Group, eliminates radiation therapy completely and compares standard chemotherapy alone with chemotherapy followed by autologous stem cell transplantation (NCT01511562). In the subsequent articles, Dr. Lisa DeAngelis from Memorial Sloan Kettering Cancer Center discusses the data supporting a role for radiotherapy for the initial treatment of PCNSL, while Dr. Michael Weller from the University Hospital Zurich provides a counter-argument against the use of radiation therapy.
One hundred and ten sports related facial fractures.
Authors: S M Carroll, M A Jawad, M West, T P O'Connor
Journal: British Journal of Sports Medicine (1995)

In a 1 year period (1993) 332 facial fractures were treated in Cork Regional Hospital. Of these 110 (33%) were sports related. Males accounted for 94.5% of patients and 77% of patients were aged below 30 years. Nasal fractures were the most common fractures seen (56%). Almost half (49%) of sports related facial fractures occurred while playing Gaelic games. The incidence of hurling fractures has been more than halved over the last 20 years. Seventy eight percent of patients required operative treatment.