tbuckley/cabot-search huggingface dataset:
Body Mass Index and Risk of Prostate Cancer in U.S. Health Professionals
Authors: Edward Giovannucci, Eric B Rimm, Yan Liu, Michael Leitzmann, Kana Wu, Meir J Stampfer, Walter C Willett
Journal: JNCI Journal of the National Cancer Institute (2003)

The relationship between body mass index (BMI) and prostate cancer risk may be complex because obesity is associated with various hormonal factors and because the influence of BMI may differ according to whether the cancers are hereditary or sporadic. We used data from the Health Professionals Follow-Up Study, in which 2896 incident cases of prostate cancer were reported from February 1, 1986, through January 31, 2000, to determine prospectively whether BMI was associated with the risk of hereditary (men <60 years of age or with a positive family history of prostate cancer) and sporadic (men ≥60 years of age and without such a family history) prostate cancer. The risk of prostate cancer in men with a higher BMI (≥30 kg/m2) was lower than that in men with a lower BMI (23–24.9 kg/m2) but only if they were younger (<60 years old) (relative risk = 0.52, 95% confidence interval = 0.33 to 0.83; Ptrend<.001) or had a family history of prostate cancer (relative risk = 0.74, 95% confidence interval = 0.45 to 1.19; Ptrend = .01). However, for groups with more sporadic cancers, BMI had a weak, non–statistically significant positive association with prostate cancer. We observed statistically significant interactions between BMI and age (Pinteraction<.001, two-sided Wald test) and between BMI and family history of prostate cancer (Pinteraction = .006, two-sided Wald test). Patterns for BMI and waist circumference were similar. Because obesity is associated with lower circulating concentrations of testosterone, our results suggest the hypothesis that androgens may play a more direct role for early-onset or hereditary prostate cancers than for sporadic prostate cancers.
PTH-092 Investigating The Role Of Physical Activity In Pancreatic Cancer – The Age At Which This Is Measured Is Important In Aetiological Studies And Is Independent Of Body Mass Index
Authors: N Noor, P Banim, R Luben, N Wareham, K-T Khaw, A Hart
Journal: Gut (2014)

<h3>Introduction</h3> There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although most studies do not report an inverse association. We investigated whether this may be related to the age at which PA is measured, using a validated questionnaire, and whether the effect of PA is independent of body mass index (BMI). <h3>Methods</h3> 23,639 participants, aged 40–74 years were recruited into the EPIC-Norfolk cohort study between 1993 and 1997. These participants completed validated questionnaires on both occupational and leisure time PA. From this, four levels of PA index were derived. The cohort was monitored for up to 17 years to identify those participants who developed pancreatic cancer. The hazard ratios (HRs) of developing cancer were estimated using Cox regression and adjusted for covariates (age, gender, cigarette smoking status and type 2 diabetes). Each analysis was first performed in those recruited of all ages and then in those younger and older than 60 years at recruitment. <h3>Results</h3> Within 17 years, 88 participants developed pancreatic cancer (55% female, median age of diagnosis 73 years, range 52–89 years). There was no association between PA and risk of pancreatic cancer in the whole cohort (trend HR=1.03, 95% CI: 0.84–1.27). However, in those recruited at younger than 60 years (n = 29 cases), higher levels of PA were associated with a decreased risk (highest vs. lowest category HR=0.27, 95% CI: 0.07–0.99, trend HR=0.75, 95% CI: 0.53–1.06, p = 0.11). When BMI was included, the associations were similar (highest vs. lowest category HR=0.25, 95% CI: 0.07–0.93, trend HR=0.73, 95% CI: 0.51–1.03, p = 0.08). In participants aged greater than 60 years (n = 59 cases), higher PA was associated with a non significant, increased risk both when BMI was unaccounted for (highest vs. lowest category HR=1.98, 95% CI: 0.94–4.16, p = 0.07, trend HR=1.23, 95% CI: 0.96–1.57, p = 0.10) and when BMI was included (trend HR=1.21, 95% CI: 0.94–1.55, p = 0.13). <h3>Conclusion</h3> The association between PA and cancer risk is dependent on the age at which PA is measured. This possibly reflects occupational activity and differences in general medical health with age or residual confounding. The associations were similar when adjusted for BMI, suggesting an independent mechanism of PA. If the inverse association of increased PA in younger participants is causal, one in six cases of pancreatic cancer might be prevented by encouraging more PA. Aetiological studies should measure PA at different ages when investigating pancreatic cancer. <h3>Disclosure of Interest</h3> None Declared.
Quality of Life and Pain in Advanced Stage Prostate Cancer: Results of a Southwest Oncology Group Randomized Trial Comparing Docetaxel and Estramustine to Mitoxantrone and Prednisone
Authors: Donna L. Berry, Carol M. Moinpour, Caroline S. Jiang, Donna Pauler Ankerst, Daniel P. Petrylak, Lynne V. Vinson, Primo N. Lara, Sharon Jones, Mary E. Taplin, Patrick A. Burch, Maha H.A. Hussain, E. David Crawford
Journal: Journal of Clinical Oncology (2006)

Palliation of bone pain can be achieved in men with androgen-independent prostate cancer treated with docetaxel and estramustine (DE) or mitoxantrone and prednisone (MP). While Southwest Oncology Group trial 99-16 demonstrated a survival improvement of DE over MP, the study also was designed to compare the palliation of disease-related symptoms.Pain palliation and global quality of life (QOL) were the two primary patient-reported outcomes. Pain was measured with the Present Pain Intensity scale of the McGill Pain Questionnaire-Short Form. The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (QLQ-C30) and its Prostate Cancer Module (PR25) measured QOL and symptom status. Pain and analgesic use were measured at random assignment, every cycle for eight cycles, and 1 year from random assignment; the QLQ-C30 and the PR25 were administered at random assignment, before cycle four (week 10) and cycle eight (month 6) and at 1 year. In addition to the primary intent-to-treat, missing at random analysis, sensitivity analyses were performed to assess robustness of global QOL conclusions under alternative informative missing data assumptions.Six hundred seventy four eligible patients received DE (n = 338) or MP (n = 336). In an intention-to-treat analysis, median overall survival was 17.5 months for the DE arm and 15.6 months for the MP arm (P = .02). There were no statistically significant differences in pain palliation between the treatment arms. The sensitivity analyses showed a consistent lack of statistically significant global QOL differences for the two arms.DE had superior clinical efficacy (overall survival, time-to-progression, and prostate-specific antigen declines) with similar global QOL and pain palliation in the MP arm.
Cardiff Crohn's disease jubilee: the incidence over 50 years.
Authors: J D Rose, G M Roberts, G Williams, J F Mayberry, J Rhodes
Journal: Gut (1988)

The incidence of Crohn9s disease in Cardiff between 1931 and 1985 has been examined using hospital diagnostic indices supplemented in recent years by records from clinicians, and the departments of pathology and radiology. Four hundred and seven new patients were confirmed after all notes had been reviewed. There has been a large increase from 0.18 cases/10(5) of the population per year in the 1930s to current values of 8.3/10(5)/year. The incidence continues to rise and shows an increasing proportion of patients with colorectal disease. Peak age specific incidences occur in the third and eighth decades of life.
Alfred Adler: A Historical Perspective
Authors: HEINZ L. ANSBACHER
Journal: American Journal of Psychiatry (1970)

The author presents some reasons for the current renaissance of interest in Adlerian psychology. He deals mainly with Adler's relationship to Freud, with Adlerian terms that have now achieved a new significance, with the consensual validation of Adler's theories by other psychologists, and with the relevance of Adler's psychology to current social movements.
Hymenoptera-Sting Hypersensitivity
Authors: Thomas B. Casale, A. Wesley Burks
Journal: New England Journal of Medicine (2014)

Anaphylactic reactions after a hymenoptera sting should be treated promptly with intramuscular epinephrine. Patients who have had such a reaction should carry injectable epinephrine and be referred to an allergist for insect-specific testing and subcutaneous immunotherapy if indicated.
Income distribution, socioeconomic status, and self rated health in the United States: multilevel analysis
Authors: B. P Kennedy, I. Kawachi, R. Glass, D. Prothrow-Stith
Journal: BMJ (1998)

To determine the effect of inequalities in income within a state on self rated health status while controlling for individual characteristics such as socioeconomic status.Cross sectional multilevel study. Data were collected on income distribution in each of the 50 states in the United States. The Gini coefficient was used to measure statewide inequalities in income. Random probability samples of individuals in each state were collected by the 1993 and 1994 behavioural risk factor surveillance system, a random digit telephone survey. The survey collects information on an individual's income, education, self rated health and other health risk factors.All 50 states.Civilian, non-institutionalised (that is, non-incarcerated and non-hospitalised) US residents aged 18 years or older.Self rated health status.When personal characteristics and household income were controlled for, individuals living in states with the greatest inequalities in income were 30% more likely to report their health as fair or poor than individuals living in states with the smallest inequalities in income.Inequality in the distribution of income was associated with an adverse impact on health independent of the effect of household income.
Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4
Authors: Jianchang Yang, Jerell R Aguila, Zaida Alipio, Raymond Lai, Louis M Fink, Yupo Ma
Journal: Journal of Hematology & Oncology (2011)

Sall4 is a key factor for the maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). Our previous studies have shown that Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell (HSC/HPC) expansion. The purpose of the current study is to further evaluate how Sall4 may affect HSC/HPC activities in a murine system. Lentiviral vectors expressing Sall4A or Sall4B isoform were used to transduce mouse bone marrow Lin-/Sca1+/c-Kit+ (LSK) cells and HSC/HPC self-renewal and differentiation were evaluated. Forced expression of Sall4 isoforms led to sustained ex vivo proliferation of LSK cells. In addition, Sall4 expanded HSC/HPCs exhibited increased in vivo repopulating abilities after bone marrow transplantation. These activities were associated with dramatic upregulation of multiple HSC/HPC regulatory genes including HoxB4, Notch1, Bmi1, Runx1, Meis1 and Nf-ya. Consistently, downregulation of endogenous Sall4 expression led to reduced LSK cell proliferation and accelerated cell differentiation. Moreover, in myeloid progenitor cells (32D), overexpression of Sall4 isoforms inhibited granulocytic differentiation and permitted expansion of undifferentiated cells with defined cytokines, consistent with the known functions of Sall4 in the ES cell system. Sall4 is a potent regulator for HSC/HPC self-renewal, likely by increasing self-renewal activity and inhibiting differentiation. Our work provides further support that Sall4 manipulation may be a new model for expanding clinically transplantable stem cells.
Control of Radiosensitivity of F9 Mouse Teratocarcinoma Cells by Regulation of Histone <b> <i>H2AX</i> </b> Gene Expression using a Tetracycline Turn-Off System
Authors: Kayo Yoshida, Takashi Morita
Journal: Cancer Research (2004)

Abstract The mouse histone H2AX has unique COOH-terminal serine residues that are phosphorylated in response to double-strand DNA breaks introduced by ionizing radiation. This suggests that H2AX acts to maintain genomic stability. We constructed a tetracycline (tet)-directed turn-off vector and integrated it into F9 mouse teratocarcinoma cells by homologous recombination. In homozygously recombined cells, expression of the histone H2AX gene was repressed to 0.02% of the expression observed in wild-type cells by the addition of doxycycline, an analog of tet. Sensitivity of cells with repressed H2AX expression to X-irradiation was increased 1.95×, indicating that DNA repair was impaired by repression of H2AX. When we s.c. injected tet-regulated F9 cells into the flanks of mice, tumor growth was slightly suppressed by X-irradiation in H2AX-repressed tumors, whereas without X-irradiation, tumor growth did not differ by H2AX status. Thus, H2AX might be a potential molecular target for sensitizing cancer cells to radiotherapy to minimize required irradiation doses.
Prevalence of Obesity, Diabetes, and Obesity-Related Health Risk Factors, 2001
Authors: Ali H. Mokdad, Earl S. Ford, Barbara A. Bowman, William H. Dietz, Frank Vinicor, Virginia S. Bales, James S. Marks
Journal: JAMA (2003)

Context Obesity and diabetes are increasing in the United States.Objective To estimate the prevalence of obesity and diabetes among US adults in 2001.Design, Setting, and Participants Random-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001.Main Outcome Measures Body mass index,based on self-reported weight and height and self-reported diabetes. ResultsIn 2001 the prevalence of obesity (BMI Ն30) was 20.9% vs 19.8% in 2000, an increase of 5.6%.The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an increase of 8.2%.The prevalence of BMI of 40 or higher in 2001 was 2.3%.Overweight and obesity were significantly associated with diabetes, high blood pressure, high cholesterol, asthma, arthritis, and poor health status.Compared with adults with normal weight, adults with a BMI of 40 or higher had an odds ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50)for diagnosed diabetes, 6.38 (95% CI, 5.67-7.17)for high blood pressure, 1.88 (95% CI,1.67-2.13)for high cholesterol levels, 2.72 (95% CI, 2.38-3.12)for asthma, 4.41 (95% CI, 3.91-4.97)for arthritis, and 4.19 (95% CI, 3.68-4.76)for fair or poor health. ConclusionsIncreases in obesity and diabetes among US adults continue in both sexes, all ages, all races, all educational levels, and all smoking levels.Obesity is strongly associated with several major health risk factors.
The Cellular Location of Self-antigen Determines the Positive and Negative Selection of Autoreactive B Cells
Authors: Helen Ferry, Margaret Jones, David J. Vaux, Ian S.D. Roberts, Richard J. Cornall
Journal: The Journal of Experimental Medicine (2003)

Systemic autoimmune disease is frequently characterized by the production of autoantibodies against widely expressed intracellular self-antigens, whereas B cell tolerance to ubiquitous and highly expressed extracellular antigens is strictly enforced. To test for differences in the B cell response to intracellular and extracellular self-antigens, we sequestered a tolerogenic cell surface antigen intracellularly by addition of a two amino acid endoplasmic reticulum (ER) retention signal. In contrast to cell surface antigen, which causes the deletion of autoreactive B cells, the intracellularly sequestered self-antigen failed to induce B cell tolerance and was instead autoimmunogenic. The intracellular antigen positively selected antigen-binding B cells to differentiate into B1 cells and induced large numbers of IgM autoantibody-secreting plasma cells in a T-independent manner. By analyzing the impact of differences in subcellular distribution independently from other variables, such as B cell receptor affinity, antigen type, or tissue distribution, we have established that intracellular localization of autoantigen predisposes for autoantibody production. These findings help explain why intracellular antigens are targeted in systemic autoimmune diseases.
Assessment of Survival in Patients With Primary Pulmonary Hypertension
Authors: Roland Wensel, Christian F. Opitz, Stefan D. Anker, Jörg Winkler, Gert Höffken, Franz X. Kleber, Rakesh Sharma, Manfred Hummel, Roland Hetzer, Ralf Ewert
Journal: Circulation (2002)

Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously.We studied 86 patients with PPH (58 female, age 46+/-2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60+/-2 mm Hg, average pulmonary vascular resistance was 1664+/-81 dyne x s x cm(-5), average serum uric acid level was 7.5+/-0.35 mg/dL, and average peak oxygen uptake during exercise (peak VO(2) was 11.2+/-0.5 mL x kg(-1) x min(-1). During follow-up (mean: 567+/-48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak VO(2) (P<0.0001) and low systolic blood pressure at peak exercise (peak SBP; P<0.0001). In a multivariable analysis, serum uric acid levels (all P<0.005) and diastolic blood pressure at peak exercise independently predicted survival (P<0.05). Patients with peak VO(2) < or =10.4 mL x kg(-1) x min(-1) and peak SBP < or =120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively).Peak VO(2) and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information.
2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk
Authors: David C. Goff, Donald M. Lloyd-Jones, Glen Bennett, Sean Coady, Ralph B. D’Agostino, Raymond Gibbons, Philip Greenland, Daniel T. Lackland, Daniel Levy, Christopher J. O’Donnell, Jennifer G. Robinson, J. Sanford Schwartz, Susan T. Shero, Sidney C. Smith, Paul Sorlie, Neil J. Stone, Peter W.F. Wilson
Journal: Journal of the American College of Cardiology (2013)
Maintenance of remission following 2 years of standard treatment then dose reduction with abatacept in patients with early rheumatoid arthritis and poor prognosis
Authors: Rene Westhovens, Manuel Robles, Antonio Carlos Ximenes, Jurgen Wollenhaupt, Patrick Durez, Juan Gomez-Reino, Walter Grassi, Boulos Haraoui, William Shergy, Sung-Hwan Park, Harry Genant, Charles Peterfy, Jean-Claude Becker, Bindu Murthy
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate maintenance of response while reducing intravenous abatacept dose from ∼10 mg/kg to ∼5 mg/kg in patients with early rheumatoid arthritis (RA) who achieved disease activity score (DAS)28 (erythrocyte sedimentation rate, ESR) &lt;2.6. <h3>Methods</h3> This 1-year, multinational, randomised, double-blind substudy evaluated the efficacy and safety of ∼10 mg/kg and ∼5 mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS28 (ESR) &lt;2.6 at year 2 of the AGREE study. The primary outcome was time to disease relapse (defined as additional disease-modifying antirheumatic drugs, ≥2 courses high-dose steroids, return to open-label abatacept ∼10 mg/kg, or DAS28 (C reactive protein) ≥3.2 at two consecutive visits). <h3>Results</h3> 108 patients were randomised (∼10 mg/kg, n=58; ∼5 mg/kg, n=50). Three and five patients, respectively, discontinued, and four per group returned to open-label abatacept. Relapse over time and the proportion of patients relapsing were similar in both groups (31% (∼10 mg/kg) vs 34% (∼5 mg/kg); HR: 0.87 (95% CI 0.45 to 1.69)). Mean steady-state trough serum concentration for the ∼10 mg/kg group was 20.3–24.1 µg/mL, compared with 8.8–12.0 µg/mL for the ∼5 mg/kg group. <h3>Conclusions</h3> This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS28 (ESR) &lt;2.6 after ≥1 year on abatacept (∼10 mg/kg). <h3>Trial registration number</h3> NCT00989235.
Phase I and Pharmacokinetic Study of Erlotinib for Solid Tumors in Patients With Hepatic or Renal Dysfunction: CALGB 60101
Authors: Antonius A. Miller, Daryl J. Murry, Kouros Owzar, Donna R. Hollis, Lionel D. Lewis, Hedy L. Kindler, John L. Marshall, Miguel A. Villalona-Calero, Martin J. Edelman, Raymond J. Hohl, Stuart M. Lichtman, Mark J. Ratain
Journal: Journal of Clinical Oncology (2007)

We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction.Patients were assigned to one of three cohorts: cohort 1, AST > or = 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients.Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean +/- standard deviation) was cohort dependent as follows: 1.9 +/- 0.2 L/h in cohort 1; 3.7 +/- 4.7 L/h in cohort 1a; 2.4 +/- 1.1 L/h in cohort 2; and 4.5 +/- 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017).Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.