tbuckley/cabot-search huggingface dataset:
Vagus nerve stimulation protects against ventricular fibrillation independent of muscarinic receptor activation
Authors: Kieran E. Brack, John H. Coote, G. André Ng
Journal: Cardiovascular Research (2011)

The role of the vagus in the ventricle is controversial, although the vagus can protect against ventricular fibrillation (VF) via nitric oxide (NO). This study aims to determine whether the mechanisms involved are dependent on post-ganglionic release and muscarinic receptor activation. For this purpose, NO release and electrophysiological effects of vagus nerve stimulation (VNS) were evaluated in relation to acetylcholine and vasoactive intestinal peptide (VIP). In addition, the role of the coronary endothelium and afferent nerves was tested. Using the isolated innervated rabbit heart, we measured ventricular NO release using 4,5-diaminofluorescein (DAF-2) fluorescence and ventricular fibrillation threshold (VFT) during VNS after muscarinic, ganglionic, and VIP inhibition [atropine, hexamethonium, and VIP (6–28), respectively] and after Triton-X endothelial functional dysfunction. The vagal-mediated increases in NO and VFT were not significantly affected (P> 0.05) during (i) atropine perfusion [increase in NO: 196.8 ± 35.2 mV (control) vs. 156.1 ± 20.3 mV (atropine) and VFT 3.1 ± 0.5 mA (control) vs. 2.7 ± 0.4 mA (atropine)], (ii) VIP inhibition—increase in NO: 243.0 ± 42.4 mV (control) vs. 203.9 ± 28.5 mV [VIP(6–28)] and VFT 3.3 ± 0.3 mA (control) vs. 3.9 ± 0.6 mA [VIP(6–28)], or (iii) after endothelial functional dysfunction [increase in NO: 127.7 ± 31.7 mV (control) vs. 172.1 ± 31.5 mV (Triton-X) and VFT 2.6 ± 0.4 mA (control) vs. 2.5 ± 0.5 mA (Triton-X)]. However, the vagal effects were inhibited during ganglionic blockade [increase in NO: 175.1 ± 38.1 mV (control) vs. 0.6 ± 25.3 mV (hexamethonium) and VFT 3.3 ± 0.5 mA (control) vs. −0.3 ± 0.3 mA (hexamethonium)]. We show that the vagal anti-fibrillatory action in the rabbit ventricle occurs via post-ganglionic efferent nerve fibres, independent of muscarinic receptor activation, VIP, and the endothelium. Together with our previous publications, our data support the possibility of a novel ventricular nitrergic parasympathetic innervation and highlight potential for new therapeutic targets to treat ventricular dysrhythmias.
Form variation in Escherichia coli K1: determined by O-acetylation of the capsular polysaccharide.
Authors: F Orskov, I Orskov, A Sutton, R Schneerson, W Lin, W Egan, G E Hoff, J B Robbins
Journal: The Journal of Experimental Medicine (1979)

The chemical basis for the alternating antigenic change called form variation noted for the Escherichia coli K1-capsular polysaccharide has been shown by 13C nuclear magnetic resonance to be a result of random O-acetylation of C7 and C9 carbons of the alpha-2-8-linked sialic acid homopolymer. A serologic method (antiserum agar) was developed to identify and isolate the form variants. The O-acetyl positive and O-acetyl negative K1 polysaccharides had unique biochemical and immunologic properties. The O-acetyl-positive variants resisted neuraminidase hydrolysis in contrast to the susceptibility of the O-acetyl negative variant to this enzyme. In addition, O-acetylation altered the antigenicity of the O-acetyl polysaccharides. When injected as whole organisms, O-acetyl positive organisms produced anti-K1 -antibodies in rabbits specific for this polysaccharide variant. O-acetyl negative organisms were comparatively less immunogenic; however, antibodies induced by these organisms reacted with both K1 polysaccharide variants. Burros, injected with either variant, produced antibodies reactive with both K1 polysaccharides.
Mullerian-Inhibiting Substance Induces Gro-β Expression in Breast Cancer Cells through a Nuclear Factor-κB–Dependent and Smad1-Dependent Mechanism
Authors: Vandana Gupta, Giminna Yeo, Hirofumi Kawakubo, Vivek Rangnekar, Preethi Ramaswamy, Tetsu Hayashida, David T. MacLaughlin, Patricia K. Donahoe, Shyamala Maheswaran
Journal: Cancer Research (2007)

Abstract Mullerian-inhibiting substance (MIS), a transforming growth factor-β family member, activates the nuclear factor-κB (NF-κB) pathway and induces the expression of B-cell translocation gene 2 (BTG2), IFN regulatory factor-1 (IRF-1), and the chemokine Gro-β. Inhibiting NF-κB activation with a phosphorylation-deficient IκBα mutant abrogated MIS-mediated induction of all three genes. Expression of dominant-negative Smad1, in which serines at the COOH-terminal SSVS motif are converted to alanines, suppressed MIS-induced Smad1 phosphorylation and impaired MIS-stimulated Gro-β promoter-driven reporter expression and Gro-β mRNA. Suppressing Smad1 expression using small interfering RNA also mitigated MIS-induced Gro-β mRNA, suggesting that regulation of Gro-β expression by MIS was dependent on activation of NF-κB as well as Smad1. However, induction of IRF-1 and BTG2 mRNAs by MIS was independent of Smad1 activation. Characterization of κB-binding sequences within Gro-β, BTG2, and IRF-1 promoters showed that MIS stimulated binding of p50 and p65 subunits to all three sites, whereas phosphorylated Smad1 (phospho-Smad1) protein was detectable only in the NF-κB complex bound to the κB site of the Gro-β promoter. Consistent with these observations, chromatin immunoprecipitation assays showed recruitment of both phospho-Smad1 and p65 to the Gro-β promoter in vivo, whereas p65, but not phospho-Smad1, was recruited to the BTG2 promoter. These results show a novel interaction between MIS-stimulated Smad1 and NF-κB signaling in which enhancement of NF-κB DNA binding and gene expression by phospho-Smad1 is dependent on the sequence of the κB consensus site within the promoter. [Cancer Res 2007;67(6):2747–56]
Thrombospondin-1 in pulmonary arterial hypertension: what ails NOS?
Authors: W. P. A. Chan, J. D. Horowitz
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Activated CD47 promotes pulmonary arterial hypertension through targeting caveolin-1’ by P.M. Bauer et al ., doi:10.1093/cvr/cvr356. 

Pulmonary arterial hypertension (PAH) is a debilitating progressive disease with a poor prognosis. The median survival for idiopathic pulmonary hypertension was 2.8 years: advances in specifically targeted therapeutics have improved the prognosis significantly, but mortality remains high.1 Irrespective of the cause of PAH, there is evidence of severe vascular endothelial dysfunction within the pulmonary circulation with characteristic findings of vascular medial hypertrophy and intimal fibrosis, occasionally with luminal narrowing. This leads to increased pulmonary vascular resistance, persistent vasoconstriction, and eventually right ventricular hypertrophy and dysfunction.

The crux of the conceptual problem limiting the current understanding of the pathophysiology of PAH is whether there is a specific single primary cause underlying the pharmacologically diffuse phenomenon of pulmonary endothelial dysfunction. Indeed, the current therapeutic approaches to the management of pulmonary hypertension represent a ‘blunderbuss approach’ to pulmonary vascular reactivity, with both a number of targeted pathways [endothelin,2 nitric oxide (NO),3 prostacyclin]4 modulated as well as the non-specific approach of treatment with L-type calcium antagonists.5 Even in circumstances where a single mutation underlies the development of PAH,6 there has been no corresponding ‘targeting’ of therapy.

While there are multiple potential synergistic interactions …
Comparison of the asthma control test and % predicted FEV1 in relation to correlation with physicians assessment of asthma control and treatment decisions
Authors: Uruj Hoda, Bogusia Kasternow, Succony Laura, Corrigan Chris
Journal: European Respiratory Journal (2011)

Background: The Asthma Control Test (ACT) is a 5-item questionnaire for the assessment of asthma control. An ACT score of <20 correlates with poorly controlled asthma.

This study compared whether ACT or FEV1 correlated better with physicians assessments of asthma control and treatment decisions made by clinicians.

Method: Serial visits were reviewed to a specialist Asthma Outpatients Clinic. All subjects completed the Asthma Control Test and performed same day spirometry. Clinicians made their own assessment of the patients' asthma control and made appropriate treatment decisions. The clinicians were not blinded to the results of spirometry or ACT.

Results: 

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In the group defined as having controlled asthma (as defined by ACT <20), 88.4% of patients were also classified as controlled by clinicians. However, in the group with% predicted FEV1 < 0.8, only 53.7% of patients were classified as controlled by clinicians.

Conclusion: The results of our study show that an ACT score of <20 had a strong association with the physicians assessment of asthma control and correlated better with treatment decisions than did the severity of asthma as defined by FEV1. The ACT could serve as a useful in the assessment and management of asthma by guiding physicians with regards to asthma control.
Three-Year Trials of Personal Therapy Among Schizophrenic Patients Living With or Independent of Family, I: Description of Study and Effects on Relapse Rates
Authors: G E Hogarty, S J Kornblith, D Greenwald, A L DiBarry, S Cooley, R F Ulrich, M Carter, S Flesher
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: The study of individual psychotherapeutic approaches to the treatment of schizophrenia has yielded equivocal findings, partly because of methodologic problems. Further, the ability of psychosocial treatments to prevent psychotic relapse appears to lessen over time. The authors' goal was to develop and test a demonstrably effective individual therapy for schizophrenia. METHOD: Using a study design that addressed previous methodologic issues, the authors evaluated personal therapy specifically designed to forestall late relapse in patients with schizophrenia. They evaluated the effectiveness of personal therapy over a period of 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder diagnosed according to Research Diagnostic Criteria. The patients were randomly assigned to receive either personal therapy or contrasting therapies in one of two concurrent trials. One trial studied patients who were living with family (N=97); the other studied patients who were living independent of family (N=54). RESULTS: All of the patients had extensive psychiatric histories, but only 44 (29%) experienced recurrent psychotic episodes over the 3-year study period, and only 27 (18%) prematurely terminated the study; most of those who left the study were in the no-personal-therapy conditions. Among patients living with family, personal therapy was more effective than family and supportive therapies in preventing psychotic and affective relapse as well as noncompliance. However, among patients living independent of family, those who received personal therapy had significantly more psychotic decompensations than did those who received supportive therapy. CONCLUSIONS: Personal therapy had a positive effect on adverse outcomes among patients who lived with family. However, personal therapy increased the rate of psychotic relapse for patients living independent of family. The application of personal therapy might best be delayed until patients have achieved symptom and residential stability. (Am J Psychiatry 1997; 154:1504–1513)
Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead
Authors: Véronique Minard-Colin, Laurence Brugières, Alfred Reiter, Mitchell S. Cairo, Thomas G. Gross, Wilhelm Woessmann, Birgit Burkhardt, John T. Sandlund, Denise Williams, Marta Pillon, Keizo Horibe, Anne Auperin, Marie-Cécile Le Deley, Martin Zimmerman, Sherrie L. Perkins, Martine Raphael, Laurence Lamant, Wolfram Klapper, Lara Mussolin, Hélène A. Poirel, Elizabeth Macintyre, Christine Damm-Welk, Angelo Rosolen, Catherine Patte
Journal: Journal of Clinical Oncology (2015)

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse.
Inadequate Donor Size in Cadaver Kidney Transplantation
Authors: Bertram L Kasiske, Jon J Snyder, David Gilbertson
Journal: Journal of the American Society of Nephrology (2002)

There have been conflicting reports that kidneys from small donors may be at increased risk for late graft failure if they are transplanted into large recipients. Data from the United States Renal Data System was used to study all first cadaver kidney transplantations performed during the years 1994 to 1999. Donor and recipient body surface area (BSA) combinations were included along with other patient and transplant characteristics in a Poisson analysis of factors associated with early (in the first 4 mo) and late (> or =4 mo) graft failure. The numbers of large (BSA >2.2 m(2)) and medium size (BSA 1.6 to 2.2 m(2)) recipients that received kidneys from small (BSA <1.6 m(2)) donors are less than expected (chi(2) = 118.09; P < 0.0001), suggesting that transplant centers may be refusing some kidneys on the basis of donor-recipient size differences. Large recipients who received kidneys from small donors made up 1.5% of the population and had a 43% (95% CI, 17 to 75%; P = 0.0004) increased risk of late graft failure compared with medium-size recipients who received kidneys from medium-size donors (53.4% of the population). Medium-size recipients who received kidneys from small donors made up 12.0% of the population and had a 16% (95% CI, 6 to 26%; P = 0.0012) increased risk of late graft failure. Disparities in recipient and donor size had similar adverse affects on mortality. Effects of recipient obesity (body mass index) and donor gender on late graft survival were no longer statistically significant after the effects of donor and recipient body size were taken into account. In conclusion, the relative size of the donor and recipient should possibly be taken into account when choosing kidneys for transplantation.
Controlled Study of Fatigue, Quality of Life, and Somatic and Mental Morbidity in Epithelial Ovarian Cancer Survivors: How Lucky Are the Lucky Ones?
Authors: Astrid H. Liavaag, Anne Dørum, Sophie D. Fosså, Claes Tropé, Alv A. Dahl
Journal: Journal of Clinical Oncology (2007)

There are few studies of somatic and mental morbidity in epithelial ovarian cancer survivors (EOCSs). The aim of this controlled, cross-sectional study was to explore fatigue, quality of life (QOL), and somatic and mental morbidity in EOCSs.Among 287 EOCSs treated according to protocols at The Norwegian Radium Hospital between 1977 and 2003, 189 patients (66%) participated. Information was collected by a questionnaire containing demographic and morbidity items and self-rating scales. Internal comparisons of various subgroups of EOCSs were performed, and EOCSs were compared with age-adjusted controls from the general population.Minimal differences were observed relating to somatic and mental morbidity, fatigue, and QOL between EOCSs with and without relapse, long or short follow-up time, and prognostic index status. Chronic fatigue was found in 22% (95% CI, 16% to 28%), and only body image was significantly associated with chronic fatigue in multivariable analyses. EOCSs showed significantly more somatic and mental morbidity, somatic complaints, use of medications, and use of health care services than controls. The levels of anxiety and fatigue were also significantly higher in EOCSs than in controls, whereas the levels of depression and of several QOL dimensions were lower. The prevalence of chronic fatigue was 12% among controls.EOCSs had more somatic and mental morbidity, more fatigue, poorer QOL, and used more medication and health services than controls. Minimal differences were observed between various EOCS subgroups. Health care professionals should try to improve and be attentive to the health of EOCSs.
ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention—Summary Article
Authors: Sidney C. Smith, Ted E. Feldman, John W. Hirshfeld, Alice K. Jacobs, Morton J. Kern, Spencer B. King, Douglass A. Morrison, William W. O’Neill, Hartzell V. Schaff, Patrick L. Whitlow, David O. Williams, Elliott M. Antman, Sidney C. Smith, Cynthia D. Adams, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Jonathan L. Halperin, Loren F. Hiratzka, Sharon Ann Hunt, Alice K. Jacobs, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel
Journal: Circulation (2006)
Intrathoracic infections due to Eikenella corrodens.
Authors: S Javaheri, R M Smith, D Wiltse
Journal: Thorax (1987)

Eikenella corrodens, a fastidious facultative anaerobic Gram negative bacillus,' is part of the normal human oral flora.Although it has been implicated as the sole causative agent for certain infections, I-its pathogenetic importance remains uncertain.E corrodens has been isolated in respiratory tract infections, including pneumonia, abscess, and empyema, where detailed bacteriological investigations have been performed, but only in association with other microbes.2356 It was recently isolated by transtracheal or percutaneous aspiration from seven patients with pneu- monia or lung abscess,5 but in each case several other organisms were cultured.The present report shows that E corrodens can be the sole cause of respiratory tract infection.The organism has an unusual antibiotic sensitivity and the therapeutic importance of this is illustrated by our case his- tories. Case reports CASE 1A 52 year old man complained of a flu like syndrome, cough with purulent green sputum, chills, and fever one week after a syncopal episode.The respiratory rate was 28, temperature 37°C, and blood pressure 94/80 mmHg.He had extensive periodontal disease.Cardiopulmonary and abdominal examination showed nothing abnormal.His white blood cell
Randomized Phase II Trial of Erlotinib or Standard Chemotherapy in Patients With Advanced Non–Small-Cell Lung Cancer and a Performance Status of 2
Authors: Rogerio Lilenbaum, Rita Axelrod, Sachdev Thomas, Afshin Dowlati, Leonard Seigel, Donald Albert, Karsten Witt, David Botkin
Journal: Journal of Clinical Oncology (2008)

A multicenter randomized phase II trial to evaluate two treatment strategies in the first-line management of advanced non-small-cell lung cancer (NSCLC) patients with a performance status (PS) of 2.Patients were assigned to erlotinib 150 mg orally daily until progression or to carboplatin (area under the curve [AUC] 6) and paclitaxel (200 mg/m(2) day 1 every 3 weeks) for up to four cycles. Patients who experienced progression or did not tolerate or refused further chemotherapy were allowed to cross over to erlotinib. The primary end point was progression-free survival (PFS). Secondary end points were response, survival, quality of life (QOL), and a retrospective molecular correlation.Fifty-two patients were randomly assigned to erlotinib and 51 to chemotherapy. Partial responses were 2% and 12%, respectively. Median PFS was 1.9 months in the erlotinib arm and 3.5 months in the chemotherapy arm (hazard ratio [HR] = 1.45; 95% CI, 0.98 to 2.15; P = .06). Median survival times were 6.5 and 9.7 months, respectively (HR = 1.73; 95% CI, 1.09 to 2.73; P = .018). Patients who crossed over to erlotinib had a median survival of 14.9 months. Sex, histology, skin rash, and smoking history predicted outcome with erlotinib. Rash and diarrhea were more common with erlotinib; emesis, alopecia, peripheral neuropathy, and fatigue were more common with chemotherapy. QOL was similar between the two arms. Molecular correlation was limited by available samples.Unselected patients with advanced NSCLC and PS 2 are best treated with combination chemotherapy as first-line therapy. Erlotinib may be considered in patients selected by clinical or molecular markers.
A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking
Authors: Prescott G. Woodruff, Laura L. Koth, Yee Hwa Yang, Madeleine W. Rodriguez, Silvio Favoreto, Gregory M. Dolganov, Agnes C. Paquet, David J. Erle
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Macrophages are believed to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain.
Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial
Authors: F. Ciardiello, N. Normanno, E. Maiello, E. Martinelli, T. Troiani, S. Pisconti, F. Giuliani, C. Barone, G. Cartenì, A.M. Rachiglio, V. Montesarchio, G. Tonini, D. Rizzi, S. Cinieri, R. Bordonaro, A. Febbraro, F. De Vita, M. Orditura, F. Fenizia, M. Lambiase, A. Rinaldi, F. Tatangelo, G. Botti, G. Colucci
Journal: Annals of Oncology (2014)
Support for young people with diabetes
Authors: Carine de Beaufort, Peter Swift
Journal: BMJ (2006)

Reducing psychological distress may improve metabolic control 

T he prevalence in Europe of insulin dependent (type 1) diabetes in children by age 15 is about 3 per 1000 and rising at roughly 2-5 % yearly.1 This complex and chronic illness interferes with almost every aspect of day to day life and can be a considerable burden for the child and the family. Therapeutic goals include “promotion of optimal health, social wellbeing and quality of life for all diabetic children around the world.”2

Living with diabetes entails continuous daily attention to a complex array of management options, including insulin administration and dose adjustments around variable meals and exercise, blood glucose monitoring and its interpretation, maintaining a healthy diet, and understanding the need for early detection of both acute and long term complications. This is daunting for many young people. In this week's BMJ Winkley …