tbuckley/cabot-search huggingface dataset:
Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
Authors: Harold J. Burstein, Anthony D. Elias, Hope S. Rugo, Melody A. Cobleigh, Antonio C. Wolff, Peter D. Eisenberg, Mary Lehman, Bonne J. Adams, Carlo L. Bello, Samuel E. DePrimo, Charles M. Baum, Kathy D. Miller
Journal: Journal of Clinical Oncology (2008)

Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for >or= 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during >or= 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.
Changes in skin reactivity, specific IgE and IgG levels after one year of immunotherapy in olive pollinosis
Authors: L. MACCHIA, M. F. CAIAFFA, G. DI FELICE, C. PINI, G. BARILETTO, S. STRADA, A. TURSI
Journal: Allergy (1991)

Changes in specific skin reactivity, specific IgE and specific IgG after immunotherapy (IT) were investigated in olive pollinosis. Thirty patients, receiving IT with commercial extracts, were studied in comparison with a control group of seven patients, receiving only drug therapy. Skin reactivity, IgE and IgG were assessed before starting IT and 1 year later. Definite changes in the three considered parameters occurred in patients given IT with Olea europaea extracts; no variation was observed in the control group. The specific skin reactivity, evaluated by means of quantitative skin prick tests, significantly decreased (Skin Index geometrical mean from 2.73 to 0.88, P&lt;0.001); the specific IgE, measured by RAST, were surprisingly decreased (from 7.76 to 4.74 PRU/ml, P &lt; 0.001); the specific IgG, measured by ELISA, in basic conditions were detectable only in nine patients of 30, while, after IT, they were found in almost all patients with a remarkable increase (from 5.48 to 266.89 AU/ml, P &lt; 0.001). No correlation was found among the changes in the considered parameters, suggesting that, at least in olive pollinosis, specific skin reactivity, specific IgE and specific IgG are three variables depending on IT but reciprocally independent.
Islet Microenvironment, Modulated by Vascular Endothelial Growth Factor-A Signaling, Promotes β Cell Regeneration
Authors: Marcela Brissova, Kristie Aamodt, Priyanka Brahmachary, Nripesh Prasad, Ji-Young Hong, Chunhua Dai, Mahnaz Mellati, Alena Shostak, Greg Poffenberger, Radhika Aramandla, Shawn E. Levy, Alvin C. Powers
Journal: Cell Metabolism (2014)
Can early infection explain the sibling effect in adult atopy?
Authors: P. Cullinan, J.M. Harris, A.J. Newman Taylor, M. Jones, P. Taylor, J.R. Dave, P. Mills, S.A. Moffat, C.W. White, J.K. Figg, A.M. Moon, M.C. Barnes
Journal: European Respiratory Journal (2003)

Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection. The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK. The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors. In particular, a higher number of brothers appeared to offer protection. The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life “hygiene”. The sibling effect was unexplained by evidence of infection with either hepatitis A or Helicobacter pylori , or by counts of infections or antibiotic prescriptions in early life. There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy. Dog ownership and home moving in early life also displayed potentially protective associations. Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection. The findings support the suggestion that the “sibling effect” in atopy may not simply reflect protection by early infection.
The relation between dietary intake of individual fatty acids, FEV<sub>1</sub> and respiratory disease in Dutch adults
Authors: T M McKeever, S A Lewis, P A Cassano, M Ocké, P Burney, J Britton, H A Smit
Journal: Thorax (2007)

Background: A reduced dietary intake of n-3 fatty acids, in association with increased n-6 fatty acid intake, has been proposed as a potential aetiological factor for chronic obstructive pulmonary disease (COPD) and asthma. However, the relative importance of individual fatty acids within the n-3 and n-6 categories on this effect has not been widely investigated. We have studied the relation between individual fatty acid intakes, lung function and self-reported respiratory symptoms and diagnoses in a representative sample of more than 13 000 Dutch adults. Methods: Intake of individual fatty acids was estimated by a food frequency questionnaire and analysed in relation to measures of forced expiratory volume in 1 s (FEV 1 ) and to questionnaire reported wheeze, asthma and COPD symptoms. Results: After adjusting for confounding, we found no protective association between individual n-3 fatty acid intakes and FEV 1 . Higher intakes of some n-6 fatty acids were associated with lower FEV 1 , this effect being most marked for c22:4 n-6 docosatetraenoic acid (reduction in FEV 1 between the highest and lowest quintile of intake 54.5 ml (95% CI −81.6 to −27.4)). Most of the n-6 fatty acid effects interacted significantly with smoking, their effects being strongest in current smokers. Individual n-3 fatty acid intakes were generally associated with a higher risk of wheeze in the past year, but otherwise there was little or no association between fatty acid intake and wheeze, doctor diagnosed asthma or other respiratory symptoms. Conclusions: A high intake of n-3 fatty acids does not appear to protect against COPD or asthma, but a high intake of several n-6 fatty acids is associated with a significant reduction in FEV 1 , particularly in smokers. These findings indicate that high dietary intake of n-6 fatty acids, rather than reduced n-3 intake, may have an adverse effect on lung health.
Exercise-induced asthma. Pharmacological assessment of single drugs and drug combinations
Authors: C. W. Bierman
Journal: JAMA (1975)

The relative effectiveness of ephedrine, theophylline, and hydroxyzine hydrochloride and their combinations was studied in a two-part investigation of 16 youths who had asthma and exercise-induced asthma. The beneficial and adverse effects of the drugs in the control of asthma were studied in the first part of the investigation. Both theophylline and ephedrine were judged superior to placebo when given alone. When combined they were somewhat more effective than either agent alone, although adverse effects precluded their use in almost half of the subjects. The addition of hydroxyzine diminished the side effects sufficiently to make the combination acceptable to four subjects who refused to take ephedrine/theophylline. In the second part of the study, the relief of exercise-induced asthma was evaluated. Ephedrine had no effect, hydroxyzine had a weak effect on hastening recovery, but theophylline modified the postexercise response significantly. The three drugs together produced an additive effect superior to that of theophylline alone. (<i>JAMA</i>234:295-298, 1975)
Influence of dehydrocholate and taurocholate on bromsulphthalein uptake, storage, and excretion in the dog.
Authors: Y Delage, S Erlinger, M Duval, J P Bpenhamou
Journal: Gut (1975)

The influence of dehydrocholate on bromsulphtalein relative-storage capacity, bilary transport maximum (Tm), and fractional transfer rates between plasma, liver and bile have been studied in unanaesthetized dogs. In six dogs, storage capacity, Tm, and fractional transfer rates from plasma to liver, liver to bile, and liver to plasma were measured during 0-15 M NaCL infusion and the measurements were repeated under a dehydrocholate infusion of 95 mumol. min-1, ie, an infusion rate approaching the known biliary Tm of bile salts. It was found that: (a) storage capacity and fractional transfer rates from plasma to liver significantly lower during dehydrocholate infusions (respectively 18-0 plus or minus SD 9-0 mg-mg-1. 100 ml-1 and 0-120 plus or minus SD 0-035 min-1) than during NaCL infusions (respectively 47-0 plus or minus 21-0 mg. mg-1. 100 ml-1 and 0-280 plus or minus SD 0-055 min-1; P smaller than 0-001); (b) Tm and fractional transfer rates from liver to bile were also significantly lower during dehydrocholate infusion (respectively 3-2 plus or minus SD 1-1 mg. min-1 and 0-013 plus or minus SD 0-004 min-1) than during NaCl infusion (4-8 plus or minus SD 1-1 mg. min-1 and 0-033 plus or minus SD 0-017 min-1; P smaller than 0-02); (c) in three additional experiments, taurocholate had similar effects on storage capacity and Tm. These findings suggest that competition occurred between bile salts and bromsulphthalein for hepaticuptake and storage. They support the hypothesis that the decreased disappearance rate and relative storage capacity of bromsulphtalein observed during biliary obstruction may be due to competition between bile salts and bromsulphthalein for hepatic uptake and storage.
TCTAP A-084 Impact of Pre-dilatation Strategy on Vessel Response Following Stent Implantation in Patients with De Novo Coronary Artery Lesion
Authors: Kazuyuki Maeda, Katsuhisa Waseda, Hiroaki Takashima, Masanobu Fujimoto, Yasuo Kuroda, Takashi Kosaka, Akiyoshi Kurita, Hirohiko Ando, Soichiro Kumagai, Shinichiro Sakurai, Daiki Kato, Akihiro Suzuki, Shigeko Sato, Tomofumi Mizuno, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2014)
Salvage Chemotherapy for Patients With Germ Cell Tumors: Is There a Best Regimen?
Authors: Lawrence Henry Einhorn
Journal: Journal of Clinical Oncology (2012)

patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25:247-256, 2007 6. de Wit R, Skoneczna I, Daugaard G, et al: Randomized phase III study comparing paclitaxel–bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: Intergroup Study EORTC 30983. J Clin Oncol 30:792-799, 2012 7. Kollmannsberger C, Daneshmand S, So A, et al: Management of disseminated nonseminomatous germ cell tumors with risk-based chemotherapy followed by response-guided postchemotherapy surgery. J Clin Oncol 28:537-542, 2010 8. Olofsson SE, Tandstad T, Jerkeman M, et al: Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: A report from the Swedish-Norwegian Testicular Cancer Group. J Clin Oncol 29:2032-2039, 2011 9. Kris MG, Meropol NJ, Winer EP (eds): Accelerating progress against cancer: ASCO’s blueprint for transforming clinical and translational cancer research. http://www.asco.org/ASCOv2/Department%20Content/Cancer% 20Policy%20and%20Clinical%20Affairs/Downloads/Blueprint.pdf 10. Abernethy AP, Etheredge LM, Ganz PA, et al: Rapid-learning system for cancer care. J Clin Oncol 28:4268-4274, 2010 11. Frankovich J, Longhurst CA, Sutherland SM: Evidence-based medicine in the EMR era. N Engl J Med 365:1758-1759, 2011
Sildenafil and exercise capacity in hypoxic pulmonary hypertension
Authors: M M Mughal
Journal: Thorax (2004)

▴ Ghofrani HA, Reichenberger F, Kohstall MG, et al . Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp. Ann Intern Med2004;141:169–77

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This study examined the influence of oral sildenafil on pulmonary haemodynamics and exercise tolerance during hypoxia induced pulmonary hypertension in healthy mountaineers and trekkers who were not susceptible to high altitude pulmonary oedema. Fourteen healthy volunteers (12 men, …

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Symptomatic, frail, elderly patients: the urgent need for comprehensive assessment and management
Authors: Enrico Clini, Bianca Beghe, Leonardo M. Fabbri
Journal: European Respiratory Journal (2014)

The working hypotheses for screening and early diagnosis of chronic obstructive pulmonary disease (COPD) have been that: 1) long-term exposure to cigarette smoke or pollutants damages the airways and/or the lungs, and causes airflow obstruction [1, 2]; 2) airflow obstruction occurs primarily in the small airways, is asymptomatic in the early stages of the disease and is progressive in the majority of COPD patients [1–4]; and 3) forced expiratory volume in 1 s (FEV1) and its ratio with forced vital capacity are necessary in establishing the diagnosis of COPD, and in assessing the excessive decline in lung function [1], but are of little use, if any, in making the early, pre-symptomatic diagnosis of COPD [5].

These working hypotheses have been helpful in stimulating research in the field of structure–function relationships in the lung, and particularly in defining the role of airway and lung inflammation in the development of central and peripheral airway remodelling and emphysema [2, 3, 6]. Research focused on the respiratory system has also brought about the development of physiological and imaging methods to assess peripheral airways and lung parenchyma [7–9], and has furthered understanding of the natural history of COPD, particularly the progressive decline in lung function and its modulation by pharmacological intervention [10]. Thanks to the results of these studies, we now know much more about COPD, about the potential and limitations of screening [11] and early diagnosis based on spirometry, and about interventions in early asymptomatic and newly discovered COPD.

Screening subjects at risk, such as smokers, workers and populations exposed to environmental pollution, with serial measurements of FEV1 has been shown to identify COPD at an early stage, with …
APOBEC3B Upregulation and Genomic Mutation Patterns in Serous Ovarian Carcinoma
Authors: Brandon Leonard, Steven N. Hart, Michael B. Burns, Michael A. Carpenter, Nuri A. Temiz, Anurag Rathore, Rachel I. Vogel, Jason B. Nikas, Emily K. Law, William L. Brown, Ying Li, Yuji Zhang, Matthew J. Maurer, Ann L. Oberg, Julie M. Cunningham, Viji Shridhar, Debra A. Bell, Craig April, David Bentley, Marina Bibikova, R. Keira Cheetham, Jian-Bing Fan, Russell Grocock, Sean Humphray, Zoya Kingsbury, John Peden, Jeremy Chien, Elizabeth M. Swisher, Lynn C. Hartmann, Kimberly R. Kalli, Ellen L. Goode, Hugues Sicotte, Scott H. Kaufmann, Reuben S. Harris
Journal: Cancer Research (2013)

Abstract Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. Cancer Res; 73(24); 7222–31. ©2013 AACR.
Significant Effect of Polymorphisms in <i>CYP2D6</i> and <i>ABCC2</i> on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Breast Cancer Patients
Authors: Kazuma Kiyotani, Taisei Mushiroda, Chiyo K. Imamura, Naoya Hosono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Tanigawara, David A. Flockhart, Zeruesenay Desta, Todd C. Skaar, Fuminori Aki, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura, Hitoshi Zembutsu
Journal: Journal of Clinical Oncology (2010)

Purpose The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. Patients and Methods We studied 282 patients with hormone receptor–positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d. Results CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with ≤ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups. Conclusion Our results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen.
Admissions for depression have not increased among men in Republic of Ireland
Authors: D Walsh
Journal: BMJ (1998)

Editor—Shajahan and Cavanagh report a decline in the ratio of the rates of women to men first admitted to Scottish hospitals for depression from 1980 to 1995.1 The Health Research Board has data from Irish hospitals over 20 years, for which almost identical diagnostic categories were used (ICD-9, 296.1, 296.3, 298.0, 300.4, 309.0, 309.1, and 311). These data give little support to the Scottish experience (figure). Nor do they support an increasing rate of first admissions for men.
Health care and health status and outcomes for patients with type 2 diabetes.
Authors: M I Harris
Journal: Diabetes Care (2000)

OBJECTIVE: To evaluate access and utilization of medical care, and health status and outcomes that would be influenced by recent medical care, in a representative sample of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A national sample of 733 adults with type 2 diabetes was studied from 1991 to 1994 in the Third National Health and Nutrition Examination Survey. Structured questionnaires and clinical and laboratory assessments were used to determine the frequencies of physician visits, health insurance coverage, screening for diabetes complications, treatment for hyperglycemia, hypertension, and dyslipidemia; and the proportion of patients who met treatment goals and established criteria for health outcome measures including hyperglycemia, albuminuria, obesity, hypertension, and dyslipidemia. RESULTS: Almost all patients had 1 source of primary care (95%), 2 or more physician visits during the past year (88%), and health insurance coverage (91%). Most (76%) were treated with insulin or oral agents for their diabetes, and 45% of those patients taking insulin monitored their blood glucose at least once per day The patients were frequently screened for retinopathy (52%), hypertension (88%), and dyslipidemia (84%). Of those patients with hypertension, 83% were diagnosed and treated with antihypertensive agents and only 17% were undiagnosed or untreated; most of the patients known to have dyslipidemia were treated with medication or diet (89%). Health status and outcomes were less than optimal: 58% had HbA1c &amp;gt;7.0, 45% had BMI &amp;gt;30, 28% had microalbuminuria, and 8% had clinical proteinuria. Of those patients known to have hypertension and dyslipidemia, 60% were not controlled to accepted levels. In addition, 22% of patients smoked cigarettes, 26% had to be hospitalized during the previous year, and 42% assessed their health status as fair or poor. CONCLUSIONS: Rates of health care access and utilization, screening for diabetes complications, and treatment of hyperglycemia, hypertension, and dyslipidemia in type 2 diabetes are high; however, health status and outcomes are unsatisfactory. There are likely to be multiple reasons for this discordance, including intractability of diabetes to current therapies, patient self-care practices, physician medical care practices, and characteristics of U.S. health care systems.