tbuckley/cabot-search huggingface dataset:
Bosutinib Versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results From the BELA Trial
Authors: Jorge E. Cortes, Dong-Wook Kim, Hagop M. Kantarjian, Tim H. Brümmendorf, Irina Dyagil, Laimonas Griskevicius, Hemant Malhotra, Christine Powell, Karïn Gogat, Athena M. Countouriotis, Carlo Gambacorti-Passerini
Journal: Journal of Clinical Oncology (2012)

Bosutinib is an oral Src/Abl tyrosine kinase inhibitor. The phase III Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA) trial compared bosutinib with imatinib in newly diagnosed, chronic-phase chronic myeloid leukemia (CML).A total of 502 patients were randomly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day.The complete cytogenetic response (CCyR) rate at 12 months was not different for bosutinib (70%; 95% CI, 64% to 76%) versus imatinib (68%; 95% CI, 62% to 74%; two-sided P = .601); therefore, the study did not achieve its primary end point. The major molecular response (MMR) rate at 12 months was higher with bosutinib (41%; 95% CI, 35% to 47%) compared with imatinib (27%; 95% CI, 22% to 33%; two-sided P < .001). Time to CCyR and MMR was faster with bosutinib compared with imatinib (two-sided P < .001 for both). On-treatment transformation to accelerated/blast phase occurred in four patients (2%) on bosutinib compared with 10 patients (4%) on imatinib. A total of three CML-related deaths occurred on the bosutinib arm compared with eight on the imatinib arm. The safety profiles of bosutinib and imatinib were distinct; GI and liver-related events were more frequent with bosutinib, whereas neutropenia, musculoskeletal disorders, and edema were more frequent with imatinib.This ongoing trial did not meet its primary end point of CCyR at 12 months, despite the observed higher MMR rate at 12 months, faster times to CCyR and MMR, fewer on-treatment transformations to accelerated/blast phase, and fewer CML-related deaths with bosutinib compared with imatinib. Each drug had a distinct safety profile.
Pemetrexed in Malignant Pleural Mesothelioma
Authors: Maitreyee Hazarika, Robert M. White, Brian P. Booth, Yong-Cheng Wang, Doo Y. Lee Ham, Cheng Yi Liang, Atiqur Rahman, Jogarao V.S. Gobburu, Ning Li, Rajeshwari Sridhara, David E. Morse, Richard Lostritto, Patricia Garvey, John R. Johnson, Richard Pazdur
Journal: Clinical Cancer Research (2005)

This report describes the data and analysis leading to the approval of pemetrexed (LY 231514, MTA, Alimta, Eli Lilly and Co., Indianapolis, IN) by the U.S. Food and Drug Administration (FDA) of a New Drug Application for the treatment of malignant pleural mesothelioma (MPM).The FDA review of the efficacy and safety of pemetrexed assessed in a randomized clinical trial of 448 patients with unresectable MPM comparing pemetrexed plus cisplatin with cisplatin alone, as well as preclinical pharmacology and chemistry data, are described. The basis for marketing approval is discussed.In one randomized, single-blind, multicenter international trial, 226 patients were randomized to the pemetrexed and cisplatin arm and 222 patients were randomized to cisplatin alone. Median survival times were 12.1 months for pemetrexed and cisplatin and 9.3 months for cisplatin (P = 0.021; hazard ratio, 0.766; 95% confidence interval, 0.61-0.96). Myelosuppression, predominantly neutropenia, was the most common toxicity of pemetrexed plus cisplatin. Other common adverse events were fatigue, leucopenia, nausea, dyspnea, vomiting, chest pain, anemia, thrombocytopenia, and anorexia.Pemetrexed in combination with cisplatin was approved by the FDA on February 4, 2004 for the treatment of patients with MPM whose disease is either unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) intra venous infusion over 10 minutes on day 1 of each 21-day cycle in combination with 75 mg/m(2) cisplatin infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections before the start and during therapy to reduce severe toxicities. Patients should also receive corticosteroids with the chemotherapy to decrease the incidence of skin rash. Approval was based on a demonstration of survival improvement in a single randomized trial. Response rates and time to tumor progression were not included in product labeling because of inconsistencies in assessments among the investigators, independent radiologic reviewers, and the FDA, reflecting the difficulty of radiographic assessments in malignant mesothelioma. Complete prescribing information is available on the FDA Web site at http://www.fda.gov/cder/approval/index.htm.
An empirical comparison of the St George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ) in a clinical trial setting
Authors: M. R.-v. Molken, B. Roos, J A Van Noord
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The Chronic Respiratory Questionnaire (CRQ) and the St George's Respiratory Questionnaire (SGRQ) are the two most widely used quality of life questionnaires in chronic obstructive pulmonary disease (COPD). A study was undertaken to compare directly the self-administered version of the CRQ and the SGRQ with respect to feasibility, internal consistency, validity, and sensitivity to changes resulting from bronchodilator therapy. <h3>METHODS</h3> One hundred and forty four patients with moderate or severe COPD were randomly assigned to receive three months of treatment with either salmeterol, salmeterol + ipratropium bromide, or placebo. Quality of life was measured at baseline and after 12 weeks of treatment. <h3>RESULTS</h3> The proportions of missing values per patient were low for both questionnaires (0.54% for the CRQ and 2% for the SGRQ). The internal consistency was good for both questionnaires (Cronbach's α coefficients ⩾0.84 for the CRQ and ⩾0.76 for the SGRQ). Factor analysis confirmed the original domain structure of the CRQ but not of the SGRQ. Correlations with forced expiratory volume in one second (FEV<sub>1</sub>) % predicted and peak expiratory flow rate (PEFR) were low for both questionnaires but better for the SGRQ than for the CRQ. The ability to discriminate between subjects with different levels of FEV<sub>1</sub> was somewhat better for the SGRQ. The correlations with symptom scores were comparable for both questionnaires. Cross sectionally, the scores of the two questionnaires were moderately to highly correlated (coefficients ranged from 0.35 to 0.72). Longitudinally, these correlations were lower (coefficients ranged from 0.17 to 0.54) but were still significant. The CRQ total and emotions score and the SGRQ symptoms score were the most responsive to change. The SGRQ symptoms domain was the only domain where the improvement in patients receiving combination treatment crossed the threshold for clinical relevance. <h3>CONCLUSIONS</h3> Since this analysis of reliability, validity, and responsiveness to change did not clearly favour one instrument above the other, the choice between the CRQ and the SGRQ can be based on other considerations such as the required sample size or the availability of reference values.
Tongue pain and giant cell arteritis
Authors: P. D. C. Kinmont, D. I. McCallum
Journal: BMJ (1967)

draws attention to the importance of pain in the tongue as a feature in giant cell arteritis.We have found glossitis in 12.6% of a series of 87 cases of temporal arteritis.''The glossitis varied from gangrene of the anterior two-thirds of the tongue to a sensa- tion of burning.Commonly the tongue was raw-beef red and sore.There were also examples of blistering and bruising, and this, together with the pathogenesis of other skin lesions in giant cell arteritis, has led us to suppose that in vascular areas such as the tongue, scalp, and face necrosis is due to haemorrhage rather than occlusion.'We agree with Dr. Henderson that the tongue should be examined in every case where giant cell arteritis is suspected, as it may present important confirmatory evidence.-We are, etc., P. D. C. KINMONT.Derby.
Abstract 20562: Metabolic Syndrome and Pulmonary Hypertension Due to Left Heart Disease
Authors: Rebecca R Vanderpool, Sebastian Shterental, Timothy N Bachman, Mark T Gladwin, Marc A Simon
Journal: Circulation (2014)

Heart failure (HF) and metabolic syndrome (MS) are two major healthcare burdens in the United States. A third of the adult population has 3 or more of the risk factors for MS which include obesity, hypertension, diabetes, hyperlipidemia and high HDL cholesterol. Abnormal LV diastolic function is prevalent in 29-35% of those with MS. HF patients with diastolic dysfunction (DD) who develop pulmonary hypertension (PH) have an increased rate of mortality that correlates with increased systolic right ventricular (RV) pressure. Post-capillary PH is most frequently due to elevated left atrial pressure (WHO group II PH) but some patients develop combined pre- and post-capillary PH due to an element of pulmonary vascular remodeling occurring in the setting of longstanding elevated left atrial pressure. We hypothesized that patients with DD and MS are pre-disposed to pulmonary vascular remodeling and the development of pre-capillary PH. DD patients with PH were identified from a right heart catheterization database based on mean pulmonary artery pressure > 25 mmHg and pulmonary capillary wedge pressure > 15 mmHg. Of 39 patients: 12 were classified as pre-metabolic syndrome (Pre-MS: Obesity and hypertension or Obesity and diabetes), 7 had MS (Obesity, hypertension and diabetes), and 21 had only DD. MS patients had significantly increased systolic RV pressure, pulmonary vascular resistance, transpulmonary gradient and pulse pressure compared to DD and Pre-MS patients (P   Figure 1. Pulmonary hemodynamics in non-obese (DD), pre-metabolic syndrome (Pre MS) and metabolic syndrome (MS) patients. * P
Reliability of core needle biopsy for determining ER and HER2 status in breast cancer
Authors: T.J.A. Dekker, V.T.H.B.M. Smit, G.K.J. Hooijer, M.J. Van de Vijver, W.E. Mesker, R.A.E.M. Tollenaar, J.W.R. Nortier, J.R. Kroep
Journal: Annals of Oncology (2012)
Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer
Authors: D. Cunningham, B. Sirohi, A. Pluzanska, B. Utracka-Hutka, J. Zaluski, R. Glynne-Jones, P. Koralewski, J. Bridgewater, P. Mainwaring, H. Wasan, J.-Y. Wang, C. Szczylik, P. Clingan, R.T.T. Chan, I. Tabah-Fisch, J. Cassidy
Journal: Annals of Oncology (2008)
Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis
Authors: Carlos J. Gallego, Brian H. Shirts, Caroline S. Bennette, Greg Guzauskas, Laura M. Amendola, Martha Horike-Pyne, Fuki M. Hisama, Colin C. Pritchard, William M. Grady, Wylie Burke, Gail P. Jarvik, David L. Veenstra
Journal: Journal of Clinical Oncology (2015)

To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics.We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY.The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.
Systematic Review: Strategies for Using Exercise Therapy To Improve Outcomes in Chronic Low Back Pain
Authors: Jill A. Hayden, Maurits W. van Tulder, George Tomlinson
Journal: Annals of Internal Medicine (2005)

Background: Exercise therapy encompasses a heterogeneous group of interventions. There continues to be uncertainty about the most effective exercise approach in chronic low back pain. Purpose: To identify particular exercise intervention characteristics that decrease pain and improve function in adults with nonspecific chronic low back pain. Data Sources: MEDLINE, EMBASE, PsychInfo, CINAHL, and Cochrane Library databases to October 2004 and citation searches and bibliographic reviews of previous systematic reviews. Study Selection: Randomized, controlled trials evaluating exercise therapy in populations with chronic (>12 weeks duration) low back pain. Data Extraction: Two reviewers independently extracted data on exercise intervention characteristics: program design (individually designed or standard program), delivery type (independent home exercises, group, or individual supervision), dose or intensity (hours of intervention time), and inclusion of additional conservative interventions. Data Synthesis: 43 trials of 72 exercise treatment and 31 comparison groups were included. Bayesian multivariable random-effects meta-regression found improved pain scores for individually designed programs (5.4 points [95% credible interval (CrI), 1.3 to 9.5 points]), supervised home exercise (6.1 points [CrI, −0.2 to 12.4 points]), group (4.8 points [CrI, 0.2 to 9.4 points]), and individually supervised programs (5.9 points [CrI, 2.1 to 9.8 points]) compared with home exercises only. High-dose exercise programs fared better than low-dose exercise programs (1.8 points [CrI, −2.1 to 5.5 points]). Interventions that included additional conservative care were better (5.1 points [CrI, 1.8 to 8.4 points]). A model including these most effective intervention characteristics would be expected to demonstrate important improvement in pain (18.1 points [CrI, 11.1 to 25.0 points] compared with no treatment and 13.0 points [CrI, 6.0 to 19.9 points] compared with other conservative treatment) and small improvement in function (5.5 points [CrI, 0.5 to 10.5 points] compared with no treatment and 2.7 points [CrI, −1.7 to 7.1 points] compared with other conservative treatment). Stretching and strengthening demonstrated the largest improvement over comparisons. Limitations: Limitations of the literature, including low-quality studies with heterogeneous outcome measures and inconsistent and poor reporting; publication bias. Conclusions: Exercise therapy that consists of individually designed programs, including stretching or strengthening, and is delivered with supervision may improve pain and function in chronic nonspecific low back pain. Strategies should be used to encourage adherence. Future studies should test this multivariable model and further assess specific patient-level characteristics and exercise types.
Patient perspectives in the management of psoriasis: Results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey
Authors: Mark G. Lebwohl, Hervé Bachelez, Jonathan Barker, Giampiero Girolomoni, Arthur Kavanaugh, Richard G. Langley, Carle F. Paul, Lluís Puig, Kristian Reich, Peter C.M. van de Kerkhof
Journal: Journal of the American Academy of Dermatology (2014)
Role of Nitric Oxide–Producing and–Degrading Pathways in Coronary Endothelial Dysfunction in Chronic Kidney Disease
Authors: Satoru Tatematsu, Shu Wakino, Takeshi Kanda, Koichiro Homma, Kyoko Yoshioka, Kazuhiro Hasegawa, Naoki Sugano, Masumi Kimoto, Takao Saruta, Koichi Hayashi
Journal: Journal of the American Society of Nephrology (2007)

Cardiovascular events are accelerated in chronic kidney disease (CKD). Although deranged nitric oxide (NO) pathways and asymmetric dimethylarginine (ADMA) cause endothelial dysfunction, no direct evidence for coronary artery endothelial dysfunction in CKD has been documented. CKD was induced in male dogs by heminephrectomy (1/2Nx) or five-sixths nephrectomy (5/6Nx). After 4 wk, renal ablation reduced GFR (control 76 [54 to 85]; 1/2Nx 38 [29 to 47]; 5/6Nx 15 [12 to 46] ml/min) and elevated plasma ADMA (control 1.88 [1.68 to 2.54]; 1/2Nx 2.51 [2.11 to 3.55]; 5/6Nx 3.84 [2.16 to 3.95] μmol/L). Coronary circulatory responses to acetylcholine revealed marked increases in coronary blood flow in control group (83 ± 17% increment) but blunted responses in 1/2Nx (34 ± 8% increment) and 5/6Nx (20 ± 4% increment). The acetylcholine-induced changes in epicardial arteriolar diameter, using needle-lens probe charge-coupled device videomicroscopy, showed similar results. The responsiveness to sodium nitroprusside did not differ among three groups. Plasma nitrite/nitrate levels decreased in 1/2Nx and 5/6Nx, and the mRNA expressions of dimethylarginine dimethylaminohydrolase-II (DDAH-II), ADMA-degrading enzyme, and endothelial NO synthase (eNOS) in coronary arteries were downregulated in 1/2Nx and 5/6Nx. Finally, 4-wk treatment with all-<i>trans</i> retinoic acid restored the impaired endothelium-dependent vasodilation and reversed the expression of eNOS but not DDAH-II. Coronary endothelial function is impaired in the early stage of CKD. The dysfunction is attributed to the downregulation of eNOS and/or DDAH-II in coronary arteries. Furthermore, the manipulation of NO pathways may constitute a therapeutic strategy for the prevention of coronary dysfunction in CKD.
Proteomics Identifies Thymidine Phosphorylase As a Key Regulator of the Angiogenic Potential of Colony-Forming Units and Endothelial Progenitor Cell Cultures
Authors: Giordano Pula, Ursula Mayr, Colin Evans, Marianna Prokopi, Dina S. Vara, Xiaoke Yin, Zoe Astroulakis, Qingzhong Xiao, Jonathan Hill, Qingbo Xu, Manuel Mayr
Journal: Circulation Research (2008)

Endothelial progenitor cell (EPC) cultures and colony-forming units (CFUs) have been extensively studied for their therapeutic and diagnostic potential. Recent data suggest a role for EPCs in the release of proangiogenic factors. To identify factors secreted by EPCs, conditioned medium from EPC cultures and CFUs was analyzed using a matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer combined with offline peptide separation by nanoflow liquid chromatography. Results were verified by RT-PCR and multiplex cytokine assays and complemented by a cellular proteomic analysis of cultured EPCs and CFUs using difference in-gel electrophoresis. This extensive proteomic analysis revealed the presence of the proangiogenic factor thymidine phosphorylase (TP). Functional experiments demonstrated that inhibition of TP by 5-bromo-6-amino-uracil or gene silencing resulted in a significant increase in basal and oxidative stress-induced apoptosis, whereas supplementation with 2-deoxy- d -ribose-1-phosphate (dRP), the enzymatic product of TP, abrogated this effect. Moreover, dRP produced in EPC cultures stimulated endothelial cell migration in a paracrine manner, as demonstrated by gene-silencing experiments in transmigration and wound repair assays. RGD peptides and inhibitory antibodies to integrin αvβ3 attenuated the effect of conditioned medium from EPC cultures on endothelial migration. Finally, the effect of TP on angiogenesis was investigated by implantation of Matrigel plugs in mice. In these in vivo experiments, dRP strongly promoted neovascularization. Our data support the concept that EPCs exert their proangiogenic activity in a paracrine manner and demonstrate a key role of TP activity in their survival and proangiogenic potential.
Medicine in the Far East.
Authors: W. S. Caldwell
Journal: JAMA (1900)

Bombay, India, Jan. 25, 1900. <h3>OBSTETRICS IN CHINA.</h3><h3>To the Editor:</h3> One of the most unfortunate consequences of the status of medicine in China is the helpless condition that the poor parturient woman finds herself in if any serious complication occurs during her labor. I saw a woman in Shanghai, who had been in labor for one week, brought into a hospital with an arm presentation. Version was performed and a dead child delivered, but the patient died three days later from sepsis. I saw another where the presentation was normal, but the disproportion between the diameters of the pelvis of the mother and the child's head were such that the latter could not pass, and where the poor woman had been in labor for six days. A craniotomy was done and the child delivered, but extensive sloughing of the bladder, rectum, and all the lower pelvic contents followed, and
Association of Genetic Variation in the <i><i>MET</i></i> Proto-Oncogene With Schizophrenia and General Cognitive Ability
Authors: Katherine E. Burdick, Pamela DeRosse, John M. Kane, Todd Lencz, Anil K. Malhotra
Journal: American Journal of Psychiatry (2010)

Objective Despite increased exposure to cancer risk factors, several studies have demonstrated a lower incidence of cancer in schizophrenia patients than in the general population. Lower cancer rates in first-degree relatives of schizophrenia patients suggest that the inverse relationship between cancer and schizophrenia may be related to genetic factors. Few studies of schizophrenia have focused on cancer-related genes. The MET proto-oncogene is primarily linked to tumor metastasis, but MET is also involved in neurodevelopment and influences risk for autism. Thus, MET may be of particular interest as a candidate gene for neuropsychiatric diseases with a developmental etiology, including schizophrenia. Method The authors examined the relationship between 21 single-nucleotide polymorphisms in MET and schizophrenia in 173 Caucasian patients and 137 comparison subjects. They then genotyped a second independent sample (107 patients and 112 comparison subjects) for replication. Finally, they tested for MET's effects on general cognitive ability (g). Results In the initial cohort, the authors identified four haplotype blocks and found one block to be globally associated with schizophrenia. In block 3, the most common haplotype was overrepresented in comparison subjects (frequency, 47%) relative to schizophrenia patients (frequency, 33%) (p=4.0×10–4; odds ratio=0.56). The authors replicated the block 3 finding in the second sample with similar frequencies: 46% in comparison subjects and 36% in schizophrenia patients (p=0.03; odds ratio=0.66). Moreover, the protective haplotype was associated with a higher g in the combined comparison sample. Conclusion These data suggest that MET variation influences schizophrenia risk and neurocognition, supporting a neurodevelopmental role across CNS-relevant phenotypes. These results add to the growing evidence suggesting an intriguing relationship between cancer-related genes and schizophrenia susceptibility.