tbuckley/cabot-search huggingface dataset:
Platelet Response to Clopidogrel Is Attenuated in Diabetic Patients Undergoing Coronary Stent Implantation
Authors: Tobias Geisler, Nicole Anders, Maria Paterok, Harald Langer, Konstantinos Stellos, Stephan Lindemann, Christian Herdeg, Andreas E. May, Meinrad Gawaz
Journal: Diabetes Care (2007)

Type 2 diabetes is accompanied by platelet function disorders leading to an accelerated process of atherosclerosis and increased risk for atherothrombotic complications (1–4). Previous data (5,6) suggest a worse outcome for diabetic patients after acute coronary events. Recently, a high variability of response to clopidogrel measured by platelet function tests has been reported (7) among patients with percutaneous coronary intervention (PCI), and hyporesponsiveness to clopidogrel has been considered to influence cardiac outcome in these patients (8–10). Impaired response to antiplatelet therapy in diabetic patients has been reported (11,12) in small patient collectives. However, little is known about the effects of type 2 diabetes on response after a 600-mg clopidogrel loading dose in large unselected cohorts of patients with symptomatic coronary artery disease (CAD).

Type 2 diabetic and nondiabetic patients treated by coronary stenting for symptomatic CAD were consecutively enrolled in this study. The protocol was approved by the local ethics committee, and signed informed consent was obtained from all patients. Patients with known platelet function disorders, thrombocytopenia (<105 cells/mm3), or any contraindications against clopidogrel were excluded. A loading dose of 600 mg clopidogrel was given to all patients before PCI, followed by 75 mg every day. All patients received a daily dose of 100 mg aspirin before PCI. A standard dose of heparin was given to all patients immediately before PCI unless there were no contraindications. Type 2 diabetes was defined according to the recommendations of the American Diabetes Association (13).

Patient blood was collected ≥6 h (46.6 ± 99.3 h) after administration of 600 mg clopidogrel, when maximum platelet inhibition was expected (14). Among the subgroups of diabetic …
Back Pain. The Facts
Authors: A. Kim Burton
Journal: British Journal of Sports Medicine (1987)

Furthermore, the probes exhibited 100% response times of approximately 60 s to square wave stimuli of 10'C.While the leads used in our laboratory are only 4 m in length, Nicholls (1983) stresses that the AD 590 transducer is particularly useful for remote sensing applications since it is insensitive to voltage drops over long lines because of its high impedance current output. SAFETY PRECAUTIONSAfter use the rectal probe was scrubbed in a warm Savlon solution to remove all traces of faeces.It was then disinfected by immersion for at least 60 min in undiluted, glutaraldehyde based 'Wavicide-Aid(T.M.)" in accordance with the recommendations of the Australian AIDS Task Force (1985).The electronic equipment satisfied the requirements of the Standards Association of Australia (1980).
Impact of Diabetes Mellitus on Complications and Outcomes of Adjuvant Chemotherapy in Older Patients With Breast Cancer
Authors: Tomasz P. Srokowski, Shenying Fang, Gabriel N. Hortobagyi, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2009)

To evaluate whether diabetes affects patterns of adjuvant chemotherapy use, toxic effects of chemotherapy, and breast cancer outcomes.By using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged 66 years or older who had stages I through III breast cancer that was diagnosed between 1992 and 2002. Multivariable regression analyses were performed to determine the effect of diabetes on use of chemotherapy, toxicities, and outcomes. The risks of all-cause mortality and breast cancer-specific (BCS) mortality were estimated with the Kaplan-Meier method.Our cohort had 70,781 men and women, of whom 14,414 (20.36%) had diabetes. Among people who received chemotherapy (n = 11,826), 21.0% were diabetics. In this group, diabetics had lower odds of receiving anthracyclines (odds ratio [OR], 0.78; 95% CI, 0.71 to 0.87) and taxanes (OR, 0.86; 95% CI, 0.75 to 0.99). Diabetes was associated with increased odds of being hospitalized for any chemotherapy toxicity (OR, 1.38; 95% CI, 1.23 to 1.56), for infection or fever (OR, 1.43; 95% CI, 1.2 to 1.7), for neutropenia (OR, 1.22; 95% CI, 1.03 to 1.45), for anemia (OR, 1.24; 95% CI, 1.05 to 1.47), and for any cause (OR, 1.32; 95% CI, 1.19 to 1.46). Patients with diabetes had higher all-cause mortality (hazard ratio [HR], 1.35; 95% CI, 1.31 to 1.39). There was a significant interaction between diabetes and chemotherapy use for BCS mortality. Diabetic and nondiabetic patients who did not receive chemotherapy had similar BCS mortality, but diabetic patients who did receive chemotherapy had higher BCS mortality than nondiabetic patients (OR, 1.20; 95% CI, 1.07 to 1.35).In this observational, hypothesis-generating study, patients who have breast cancer and diabetes are at increased risk of chemotherapy-related toxicities compared with nondiabetic patients who are receiving chemotherapy and have higher all-cause mortality.
Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study
Authors: P Cullinan
Journal: Thorax (2004)

It is frequently asserted that antibiotic prescriptions in childhood are associated with the development of allergic disease, especially asthma. A study was undertaken to establish the direction of this relationship.A retrospective cohort study of 746 adults was performed in three general practices. Antibiotic prescriptions in the first 5 years of life, collected from contemporary medical records, were related to self-reports of asthma and hay fever and the results of skin prick testing with common aeroallergens.There was no relationship between early antibiotic prescription and atopy, either for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages. The significant associations between prescriptions at ages 4 and 5 and hay fever (OR 1.23 and 1.16, respectively) were explained by coexisting asthma. Relationships between antibiotic use and asthma (allergic or otherwise) were statistically significant and strengthened with increasing age of prescription, but were largely confined to antibiotics prescribed for lower respiratory symptoms.The reported associations between childhood antibiotic use and asthma are most plausibly explained by "reverse causation"--the tendency for prescriptions to be written for the early manifestations of pre-existing asthma.
Primary non-Hodgkin's lymphoma of the CNS treated with BVAM or CHOD/BVAM chemotherapy before radiotherapy.
Authors: E M Bessell, F Graus, J A Punt, J L Firth, D T Hope, A J Moloney, A Lopez-Guillermo, S Villa
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess whether chemotherapy that includes drugs that cross the blood-brain barrier improves survival in primary CNS non-Hodgkin's lymphoma (PCNSL) when combined with radiotherapy. PATIENTS AND METHODS Thirty-four patients, with no evidence of human immunodeficiency virus type 1 (HIV-1) infection, were treated with the related chemotherapy regimens of carmustine (BCNU), vincristine, cytarabine, and methotrexate (BVAM; 12 patients), cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/BVAM (17 patients) and intensified CHOD/BVAM (five patients) between 1986 and 1994. The median age was 60 years (range, 16 to 73) and 47% had a performance status of 3 or 4 (Eastern Cooperative Oncology Group [ECOG]/World Health Organization [WHO]). Ten patients were treated with BVAM chemotherapy between 1986 and 1989, and subsequently 17 patients were treated with CHOD/BVAM (cytarabine 3 g/m2). Twenty of these 27 patients received whole-brain radiotherapy (craniospinal in four). RESULTS The complete response (CR) rate at the completion of chemotherapy was 63% for BVAM and 67% for CHOD/BVAM; more neutropenia occurred with CHOD/BVAM. The 5-year actuarial probability of survival of all 34 patients was 33% (95% confidence interval [CI], 14% to 52%), with so far only one recurrence after 2 years. Using multivariate analysis, age (P = .0005) and number of tumors at diagnosis (P = .0358) were prognostic factors. All five patients aged &gt; or = 70 years died during or shortly after chemotherapy. Performance status was not an independent variable. CONCLUSION The BVAM or CHOD/BVAM regimens can be delivered despite neutropenia without significant treatment delay or dose reduction in patients less than 70 years of age. Further intensification of this type of chemotherapy is probably not possible with patients of this age, many of whom have a poor performance status.
The RNA Helicase p68 Is a Novel Androgen Receptor Coactivator Involved in Splicing and Is Overexpressed in Prostate Cancer
Authors: Emma L. Clark, Anne Coulson, Caroline Dalgliesh, Prabhakar Rajan, Samantha M. Nicol, Stewart Fleming, Rakesh Heer, Luke Gaughan, Hing Y. Leung, David J. Elliott, Frances V. Fuller-Pace, Craig N. Robson
Journal: Cancer Research (2008)

Abstract The androgen receptor (AR) is a member of the nuclear steroid hormone receptor family and is thought to play an important role in the development of both androgen-dependent and androgen-independent prostatic malignancy. Elucidating roles by which cofactors regulate AR transcriptional activity may provide therapeutic advancement for prostate cancer (PCa). The DEAD box RNA helicase p68 (Ddx5) was identified as a novel AR-interacting protein by yeast two-hybrid screening, and we sought to examine the involvement of p68 in AR signaling and PCa. The p68-AR interaction was verified by colocalization of overexpressed protein by immunofluorescence and confirmed in vivo by coimmunoprecipitation in the PCa LNCaP cell line. Chromatin immunoprecipitation in the same cell line showed AR and p68 recruitment to the promoter region of the androgen-responsive prostate-specific antigen (PSA) gene. Luciferase reporter, minigene splicing assays, and RNA interference (RNAi) were used to examine a functional role of p68 in AR-regulated gene expression, whereby p68 targeted RNAi reduced AR-regulated PSA expression, and p68 enhanced AR-regulated repression of CD44 splicing (P = 0.008). Tyrosine phosphorylation of p68 was found to enhance coactivation of ligand-dependent transcription of AR-regulated luciferase reporters independent of ATP-binding. Finally, we observe increased frequency and expression of p68 in PCa compared with benign tissue using a comprehensive prostate tissue microarray (P = 0.003; P = 0.008). These findings implicate p68 as a novel AR transcriptional coactivator that is significantly overexpressed in PCa with a possible role in progression to hormone-refractory disease. [Cancer Res 2008;68(19):7938–46]
Resolution of pericardial effusion after removal of ovarian fibroma-- a Meigs'-like syndrome
Authors: Sohail Qaisar, Faizel Osman, Michael Pitt
Journal: Journal of the Royal Society of Medicine (2005)

Meigs' syndrome consists of benign ovarian tumour with ascites and pleural effusion that resolve after resection of the tumour. 1 A variant with pericardial effusion has not to our knowledge been reported. CASE HISTORYA woman of 58 was admitted after two weeks of increasing breathlessness and pleuritic chest pain.On examination she was tachycardic and tachypnoeic, with raised venous pressure and signs of bilateral pleural effusions.She was in sinus rhythm.Breast and abdominal examinations were unremarkable and she had no lymphadenopathy.On the electrocardiogram there was non-specific T-wave inversion in the inferior leads, and arterial blood gas analysis (on air) pointed to type 1 respiratory failure.Cardiomegaly and bilateral pleural effusions were seen on chest radiography, and an echocardiogram showed pericardial thickening with a 2 cm global pericardial effusion but no evidence of cardiac tamponade.CT of the thorax and abdomen confirmed the pericardial and pleural effusions (Figure 1) and also revealed ascites and a 9 cm right ovarian mass (Figure 2); the chest, abdomen and pelvis were otherwise disease-free.CT pulmonary angiography excluded significant pulmonary embolism, and on cardiac catheterization pulmonary artery and capillary wedge pressures were normal.There was no evidence of a constrictive process.The coronary arteries were normal as was left ventricular function; a pericardial biopsy, obtained by thoracoscopy, showed no histological abnormality.The patient underwent total abdominal hysterectomy and bilateral salphingo-oophorectomy and the pelvic mass proved to be an ovarian fibroma.Thereafter the pleural and pericardial effusions as well as the ascites resolved completely-as confirmed by repeat echocardiography and CT of chest and abdomen.
Controlled randomised trial of visual biofeedback versus muscle training without a visual display for intractable constipation.
Authors: D Koutsomanis, J E Lennard-Jones, A J Roy, M A Kamm
Journal: Gut (1995)

Training to contract the abdominal muscles effectively and to relax the pelvic floor during defecation straining helps some patients with severe constipation. Hitherto all such training has used a visible or audible signal of sphincter muscle activity as a biofeedback method to assist in relaxation. A randomised controlled trial comparing the outcome of muscular training without any biofeedback device with the same training supplemented by an electromyographic (EMG) record visible to the patient is reported. Significant symptomatic improvement was noted and electromyographic measurements confirmed a decrease in pelvic floor muscle activity during defecation straining after treatment in both groups. The outcome was similar in the two treatment groups. Muscular coordination training using personal instruction and encouragement without a visual display is thus a potentially successful treatment suitable for outpatient use by paramedical personnel.
Cell-Autonomous and Non–Cell-Autonomous Mechanisms of HGF/MET–Driven Resistance to Targeted Therapies: From Basic Research to a Clinical Perspective
Authors: Simona Corso, Silvia Giordano
Journal: Cancer Discovery (2013)

Abstract Targeted therapies have opened new perspectives in clinical oncology. However, clinicians have observed a lack of response in a relevant percentage of patients and frequent relapse in patients who initially respond. Therefore, a compelling challenge is to identify mechanisms underlying resistance and strategies to circumvent these hurdles. A growing body of evidence indicates that MET, the tyrosine kinase receptor for hepatocyte growth factor (HGF), is frequently implicated in resistance to targeted therapies. In this review, we highlight cell-autonomous and non–cell-autonomous mechanisms through which MET drives resistance, and we discuss some unsolved issues related to the selection of patients who could benefit from combined therapies. Significance: Resistance is, at present, the major limitation to the efficacy of targeted therapies. Inappropriate MET activation is very frequently implicated in the onset of primary and secondary resistance to these therapies. Deciphering the role of the HGF/MET axis in resistance to different drugs could guide the design of new clinical trials based on combinatorial therapies, and it might help to overcome, or possibly prevent, the onset of resistance. Cancer Discov; 3(9); 978–92. ©2013 AACR.
Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses
Authors: Maciej Lazarczyk, Christian Pons, José-Andrès Mendoza, Patricia Cassonnet, Yves Jacob, Michel Favre
Journal: The Journal of Experimental Medicine (2007)

Epidermodysplasia verruciformis (EV) is a genodermatosis associated with skin cancers that results from a selective susceptibility to related human papillomaviruses (EV HPV). Invalidating mutations in either of two genes (EVER1 and EVER2) with unknown functions cause most EV cases. We report that EVER1 and EVER2 proteins form a complex and interact with the zinc transporter 1 (ZnT-1), as shown by yeast two-hybrid screening, GST pull-down, and immunoprecipitation experiments. In keratinocytes, EVER and ZnT-1 proteins do not influence intracellular zinc concentration, but do affect intracellular zinc distribution. EVER2 was found to inhibit free zinc influx to nucleoli. Keratinocytes with a mutated EVER2 grew faster than wild-type keratinocytes. In transiently and stably transfected HaCaT cells, EVER and ZnT-1 down-regulated transcription factors stimulated by zinc (MTF-1) or cytokines (c-Jun and Elk), as detected with luciferase assays. To get some insight into the control of EV HPV infection, we searched for interaction between EVER and ZnT-1 and oncoproteins of cutaneous (HPV5) and genital (HPV16) genotypes. HPV16 E5 protein binds to EVER and ZnT-1 and blocks their negative regulation. The lack of a functional E5 protein encoded by EV HPV genome may account for host restriction of these viruses.
Inhibition of the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Pathway but not the MEK/ERK Pathway Attenuates Laminin-Mediated Small Cell Lung Cancer Cellular Survival and Resistance to Imatinib Mesylate or Chemotherapy
Authors: Junji Tsurutani, Kip A. West, Jacqueline Sayyah, Joell J. Gills, Phillip A. Dennis
Journal: Cancer Research (2005)

The fact that small cell lung cancer (SCLC) is commonly incurable despite being initially responsive to chemotherapy, combined with disappointing results from a recent SCLC clinical trial with imatinib, has intensified efforts to identify mechanisms of SCLC resistance. Adhesion to extracellular matrix (ECM) is one mechanism that can increase therapeutic resistance in SCLC cells. To address whether adhesion to ECM increases resistance through modulation of signaling pathways, a series of SCLC cell lines were plated on various ECM components, and activation of two signaling pathways that promote cellular survival, the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathway, was assessed. Although differential activation was observed, adhesion to laminin increased Akt activation, increased cellular survival after serum starvation, and caused the cells to assume a flattened, epithelial morphology. Inhibitors of the PI3K/Akt/mTOR pathway (LY294002, rapamycin) but not the MEK/ERK pathway (U0126) abrogated laminin-mediated survival. SCLC cells plated on laminin were not only resistant to serum starvation-induced apoptosis but were also resistant to apoptosis caused by imatinib. Combining imatinib with LY294002 or rapamycin but not U0126 caused greater than additive increases in apoptosis compared with apoptosis caused by the inhibitor or imatinib alone. Similar results were observed when adenoviruses expressing mutant Akt were combined with imatinib, or when LY294002 was combined with cisplatin or etoposide. These studies identify laminin-mediated activation of the PI3K/Akt/mTOR pathway as a mechanism of cellular survival and therapeutic resistance in SCLC cells and suggest that inhibition of the PI3K/Akt/mTOR pathway is one strategy to overcome SCLC resistance mediated by ECM.
The Use of Computed Tomography in Pediatrics and the Associated Radiation Exposure and Estimated Cancer Risk
Authors: Diana L. Miglioretti, Eric Johnson, Andrew Williams, Robert T. Greenlee, Sheila Weinmann, Leif I. Solberg, Heather Spencer Feigelson, Douglas Roblin, Michael J. Flynn, Nicholas Vanneman, Rebecca Smith-Bindman
Journal: JAMA Pediatrics (2013)

IMPORTANCE Increased use of computed tomography (CT) in pediatrics raises concerns about cancer risk from exposure to ionizing radiation.OBJECTIVES To quantify trends in the use of CT in pediatrics and the associated radiation exposure and cancer risk.DESIGN Retrospective observational study.SETTING Seven US health care systems.PARTICIPANTS The use of CT was evaluated for children younger than 15 years of age from 1996 to 2010, including 4 857 736 child-years of observation.Radiation doses were calculated for 744 CT scans performed between 2001 and 2011.MAIN OUTCOMES AND MEASURES Rates of CT use, organ and effective doses, and projected lifetime attributable risks of cancer. RESULTSThe use of CT doubled for children younger than 5 years of age and tripled for children 5 to 14 years of age between 1996 and 2005, remained stable between 2006 and 2007, and then began to decline.Effective doses varied from 0.03 to 69.2 mSv per scan.An effective dose of 20 mSv or higher was delivered by 14% to 25% of abdomen/pelvis scans, 6% to 14% of spine scans, and 3% to 8% of chest scans.Projected lifetime attributable risks of solid cancer were higher for younger patients and girls than for older patients and boys, and they were also higher for patients who underwent CT scans of the abdomen/pelvis or spine than for patients who underwent other types of CT scans.For girls, a radiation-induced solid cancer is projected to result from every 300 to 390 abdomen/pelvis scans, 330 to 480 chest scans, and 270 to 800 spine scans, depending on age.The risk of leukemia was highest from head scans for children younger than 5 years of age at a rate of 1.9 cases per 10 000 CT scans.Nationally, 4 million pediatric CT scans of the head, abdomen/pelvis, chest, or spine performed each year are projected to cause 4870 future cancers.Reducing the highest 25% of doses to the median might prevent 43% of these cancers. CONCLUSIONS AND RELEVANCEThe increased use of CT in pediatrics, combined with the wide variability in radiation doses, has resulted in many children receiving a high-dose examination.Dose-reduction strategies targeted to the highest quartile of doses could dramatically reduce the number of radiation-induced cancers.
Unusual human lymphoma phenotype defined by monoclonal antibody.
Authors: A C Aisenberg, B M Wilkes
Journal: The Journal of Experimental Medicine (1980)

The phenotype of three large cell (histiocytic) lymphomas of man has been defined with convential lymphocyte surface marker techniques, a panel of monoclonal antisera of hybridoma derivation (Ortho Pharmaceutical Corp.), and the fluorescence microscope. Two tumors exhibited surface IgG of lambda light-chain type, whereas the third was negative for surface Ig but contained the same Ig in the cytoplasm. With the monoclonal antisera, all three were found to bear two surface antigens (OKT9 and OKT10) previously described on early thymocytes, and were devoid of the Ia antigen. The available knowledge suggests that these neoplasms represent the expansion of a clone of B lymphocytes along the pathway that leads to plasma cell differentiation rather than a clone with both B and T surface membrane markers.
Topology-Bayes versus Clade-Bayes in Phylogenetic Analysis
Authors: W. C. Wheeler, K. M. Pickett
Journal: Molecular Biology and Evolution (2007)

Several features of currently used Bayesian methods in phylogenetic analysis are discussed. The distinction between Clade-Bayes and Topology-Bayes is presented and illustrated with an empirical example. Three problems with Bayesian phylogenetic methods--exaggerated clade support, inconsistently biased priors, and the impossibility of hypothesis testing of cladograms--are shown to be the result of using a Clade-based Bayesian approach. Topology-based Bayesian methods do not share these shortcomings.