tbuckley/cabot-search huggingface dataset:
Risk of Breast Cancer With Oral Contraceptive Use in Women With a Family History of Breast Cancer
Authors: Dawn M. Grabrick
Journal: JAMA (2000)

ContextOral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear.ObjectiveTo determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease.Design and SettingHistorical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996.ParticipantsA total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families.Main Outcome MeasureRelative risk (RR) of breast cancer associated with history of OC use by relationship to proband.ResultsAfter accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975.ConclusionsThese results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today.
Plasma Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-Binding Proteins, and Prostate Cancer Risk: a Prospective Study
Authors: P. Stattin
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer. Methods: We conducted a nested case–control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided. Results: Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218–240 ng/mL] versus 214 ng/mL [95% CI = 208–221 ng/mL]; P = .02) and IGFBP-3 (2611 ng/mL [95% CI = 2518–2704 ng/mL] versus 2498 ng/mL [95% CI = 2437–2560 ng/mL]; P = .04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (Pfor trend = .02) and IGFBP-3 (Pfor trend = .03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (Pfor trend = .01), whereas the risk associated with increased IGFBP-3 was lower (Pfor trend = .44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin. Conclusions: Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer.
Cyclosporin A Administration during Pregnancy Induces a Permanent Nephron Deficit in Young Rabbits
Authors: Anaïs Tendron, Stéphane Decramer, Eve Justrabo, Jean-Bernard Gouyon, Denis Salomon Semama, Thierry Gilbert
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Cyclosporin A (CsA) is an immunosuppressive agent used to prevent graft rejection and to treat autoimmune disorders. Successful pregnancies can be achieved among CsA-treated women, although it is known that CsA is nephrotoxic and crosses the human placenta. The aim of this study was to evaluate the harmlessness of CsA toward the embryonic kidney. Twenty-one pregnant rabbits were divided into four groups. Groups of six and four female animals were subjected to daily injections of 10 mg/kg per d CsA (administered subcutaneously) for 5 d, from day 14 to day 18 of gestation or from day 20 to day 24 of gestation, respectively. In the third group, five female animals received the CsA diluent (Cremophor) from day 14 to day 18 of gestation. The fourth group consisted of six untreated female animals. Pregnancy outcomes among CsA-treated does demonstrated a reduced number of living pups, which were also growth-retarded, with exposure to CsA from day 20 to day 24 of gestation. However, pups exposed to CsA from day 14 to day 18 of gestation exhibited normal fetal growth, and blood concentrations of CsA matched human data. Examinations of kidneys at birth demonstrated vacuolation of proximal and collecting tubules and ureteric bud ends. Increased glomerular volumes and decreased nephron densities suggested nephron mass reduction, which was quantitatively evaluated in 1-mo-old animals. The nephron numbers were reduced by 25 and 33% in day 14 to 18 CsA-treated and day 20 to 24 CsA-treated animals, respectively, which displayed compensatory adaptation of the existing nephrons. However, foci of segmental glomerular sclerosis were already present, which would possibly jeopardize renal function later in life.
After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?: Table 1
Authors: Richard J Wakefield, Maria Antonietta D'Agostino, Esperanza Naredo, Maya H Buch, Annamaria Iagnocco, Lene Terslev, Mikkel Ostergaard, Marina Backhaus, Walter Grassi, Maxime Dougados, Gerd R Burmester, Benazir Saleem, Eugenio de Miguel, Cristina Estrach, Kei Ikeda, Marwin Gutierrez, Robert Thompson, Peter Balint, Paul Emery
Journal: Annals of the Rheumatic Diseases (2012)

For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA.
Low Birth Weight Increases Risk for End-Stage Renal Disease
Authors: Bjørn Egil Vikse, Lorentz M. Irgens, Torbjørn Leivestad, Stein Hallan, Bjarne M. Iversen
Journal: Journal of the American Society of Nephrology (2007)

Case-control studies have shown an association between low birth weight and risk for renal failure. The Medical Birth Registry of Norway, which comprises data on all births in Norway since 1967, and the Norwegian Renal Registry, which comprises data on all patients who have developed ESRD in Norway since 1980, were used to examine whether birth-related variables were associated with risk for ESRD. Of the 2,183,317 children born between 1967 and 2004, 526 were found in the ESRD registry. Compared with birth weight in the 10th to 90th percentiles, births <10th percentile had a relative risk (RR) for ESRD of 1.7 (95% confidence interval 1.4 to 2.2; P < 0.001). Births with a weight for gestational age <10th percentile had an RR of 1.5 (95% confidence interval 1.2 to 1.9; P = 0.002). These associations were virtually identical after adjustment for birth-related confounders such as congenital malformations, multiple delivery, maternal age at birth, and maternal preeclampsia. Low birth weight was more strongly associated with development of ESRD during the first 14 years of life than after age 15. Low birth weight and low birth weight for gestational age were similarly associated with multiple causes of ESRD. In conclusion, in this cohort study with a maximum follow-up of 38 years, low birth weight and intrauterine growth restriction were associated with increased risk for ESRD.
Translational Impact of Nanoparticle–Drug Conjugate CRLX101 with or without Bevacizumab in Advanced Ovarian Cancer
Authors: Elizabeth Pham, Michael J. Birrer, Scott Eliasof, Edward G. Garmey, Douglas Lazarus, Christina R. Lee, Shan Man, Ursula A. Matulonis, Christian G. Peters, Ping Xu, Carolyn Krasner, Robert S. Kerbel
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Increased tumor hypoxia and hence elevated hypoxia-inducible factor-1α (HIF1α) is thought to limit the efficacy of vascular endothelial growth factor (VEGF) pathway–targeting drugs by upregulating adaptive resistance genes. One strategy to counteract this is to combine antiangiogenic drugs with agents able to suppress HIF1α. One such possibility is the investigational drug CRLX101, a nanoparticle–drug conjugate (NDC) containing the payload camptothecin, a known topoisomerase-I poison. Experimental Design: CRLX101 was evaluated both as a monotherapy and combination with bevacizumab in a preclinical mouse model of advanced metastatic ovarian cancer. These preclinical studies contributed to the rationale for undertaking a phase II clinical study to evaluate CRLX101 monotherapy in patients with advanced platinum-resistant ovarian cancer. Results: Preclinically, CRLX101 is highly efficacious as a monotherapy when administered at maximum-tolerated doses. Furthermore, chronic low-dose CRLX101 with bevacizumab reduced bevacizumab-induced HIF1α upregulation and resulted in synergistic efficacy, with minimal toxicity in mice. In parallel, initial data reported here from an ongoing phase II clinical study of CRLX101 monotherapy shows measurable tumor reductions in 74% of patients and a 16% RECIST response rate to date. Conclusions: Given these preclinical and initial clinical results, further clinical studies are currently evaluating CRLX101 in combination with bevacizumab in ovarian cancer and warrant the evaluation of this therapy combination in other cancer types where HIF1α is implicated in pathogenesis, as it may potentially be able to improve the efficacy of antiangiogenic drugs. Clin Cancer Res; 21(4); 808–18. ©2014 AACR.
Personal and Ambient Air Pollution is Associated with Increased Exhaled Nitric Oxide in Children with Asthma
Authors: Ralph J. Delfino, Norbert Staimer, Dan Gillen, Thomas Tjoa, Constantinos Sioutas, Kochy Fung, Steven C. George, Michael T. Kleinman
Journal: Environmental Health Perspectives (2006)

Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined.We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 microm in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period.The strongest positive associations were between FeNO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 microg/m3 personal PM2.5, 1.1 ppb FeNO [95% confidence interval (CI), 0.1-1.9]; for 0.6 microg/m3 personal EC, 0.7 ppb FeNO (95% CI, 0.3-1.1); for 17 ppb personal NO2, 1.6 ppb FeNO (95% CI, 0.4-2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with FeNO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5.PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.
Sensitisation Patterns To House Dust And Storage Mites In Two Different Climatic Areas Of Spain
Authors: V. Iraola, H. Pinto, F. Rodríguez, A. Huertas, J. Bartra, M. Boquete, M. Paniagua, S. Díaz Angulo, F. Carballada, J. Carnés
Journal: Journal of Allergy and Clinical Immunology (2010)
Time course of cigarette smoke-induced pulmonary inflammation in mice
Authors: A. I. D'hulst, K. Y. Vermaelen, G. G. Brusselle, G. F. Joos, R. A. Pauwels
Journal: European Respiratory Journal (2005)

Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations. Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells ( i.e. neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks. Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure. In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.
Assessing reproducibility: agreement vs correlation
Authors: A Diez Herranz
Journal: European Respiratory Journal (1994)

I have read with interest the paper by SENÉTERRE et al. [1].However, perhaps the method used to assess the reproducibility of the measurements is not the best one.The authors use Spearman's rank test, and they find an "excellent and highly significant" reproducibility, since r-value is 0.99 in all cases.Considering that correlation is different from agreement, BLAND and ALTMAN [2] have proposed a method for assessing observer agreement and variability in continuous measurements.It would be interesting to know if such high reproducibility would have been obtained had the proper statistical method been used, most of all because from their figure 4 [1] it seems that in several cases the difference between first and second slice, or between first and second observer, may be as high as about 500 pixels.Should a high reproducibility be obtained, this test must be correlated with physiological tests, but if reproducibility is low this technique cannot be recommended for clinical use in bronchoprovocation tests.
T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.
Authors: J Hara, S H Benedict, T W Mak, E W Gelfand
Journal: Journal of Clinical Investigation (1987)

We have analyzed T cell receptor alpha-chain gene configuration using three genomic joining (J) region probes in 64 children with acute lymphoblastic leukemia (ALL). 11 out of 18 T-ALLs were T3 positive; alpha-chain gene rearrangements were demonstrated in only two of 18, indicating that the majority of T-ALLs would have rearrangements involving J alpha segments located upstream of these probes. In contrast, 15 out of 46 B-precursor ALLs showed rearrangements of the alpha-chain gene and J alpha segments located approximately 20-30 kb upstream of the constant region were involved in 13 of these patients. Nine of 15 B-precursor ALLs with rearranged alpha-chain genes had rearrangements of both gamma- and beta-chain genes, whereas the remaining six had no rearrangements of gamma- and beta-chain genes. These findings indicated that alpha-chain gene rearrangement is not specific for T lineage cells and gamma- and/or beta-chain gene rearrangement does not appear essential for alpha-chain gene rearrangement, at least in B-precursor leukemic cells.
Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model Commentary: Helicobacter pylori eradication in primary care
Authors: A E Duggan, K Tolley, C J Hawkey, R F A Logan, B. C Delaney, F D R. Hobbs
Journal: BMJ (1998)

To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease.A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication.Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori.In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed. The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (62.63 pounds per patient). The cost of each additional effective eradication was 589.00 pounds (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years. Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone.Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori. Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing). Cost effectiveness should be an important part of choosing an eradication strategy for H pylori.
Intermittent weekly high-dose capecitabine in combination with oxaliplatin: a phase I/II study in first-line treatment of patients with advanced colorectal cancer
Authors: W. Scheithauer, G.V. Kornek, M. Raderer, B. Schüll, K. Schmid, F. Längle, H. Huber
Journal: Annals of Oncology (2002)
Changes in neural drive (EMGd) and neuromuscular coupling during histamine-induced bronchoconstriction in patients with asthma
Authors: M Gorini, A Spinelli, F Gigliotti, R Duranti, P Arcangeli, G Scano
Journal: European Respiratory Journal (1988)

This study was undertaken in order to assess the neural drive to the respiratory muscles and the inspiratory neuromuscular coupling in patients with bronchial asthma during histamine-induced bronchoconstriction. Bronchoconstriction was produced in a graded fashion, with histamine phosphate aerosol of increasing dose, in twelve asymptomatic asthmatic patients and was measured by FEV1. Inspiratory drive was measured by electromyographic activity of the diaphragm (EMGd) and the coupling of the neural drive to the respiratory muscles was assessed by the relationship of mouth occlusion pressure (P0.1) to EMGd. During the test we also measured electromyographic activity of the inspiratory intercostal (EMGint), sternomastoid (EMGsm) and expiratory abdominal (EMGab) muscles. Histamine caused a significant decrease in FEV1, a significant increase in P0.1, EMGd, EMGint, and a relevant increase in EMGsm, with no substantial increase in EMGab. An inverse significant relationship between the change in FEV1 and changes in P0.1, EMGd and EMGint and a significant correlation between the change in FEV1 and in the P0.1/EMGd ratio were observed. We conclude that a progressive increase in bronchospasm is accompanied by a progressive increase in respiratory neural drive and decrease in neuromuscular coupling. This could be caused both by an increase in lung volume and a lack of abdominal expiratory muscle recruitment.