tbuckley/cabot-search huggingface dataset:
Explaining variations in survival in breast cancer in the Eastern Region of England
Authors: A.C. Voogd, J.W.W. Coebergh
Journal: Annals of Oncology (2009)

In their study on treatment and survival of patients with breast cancer treated in 10 hospitals in the Eastern Region of England from 1999 to 2003, Wishart et al. [1.Wishart G.C. Greenberg D.C. Chou P. et al.Treatment and survival in breast cancer in the Eastern Region of England.Ann Oncol. 2010; 21: 291-296Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar] found significant interhospital survival differences for patients with 1–3 positive axillary lymph nodes but not for patients with negative lymph nodes. Differences in the selection of appropriate adjuvant systemic treatment between hospitals are mentioned as a possible explanation for this finding. The authors provide no data to support their assertion, although data on the use of adjuvant systemic treatment for each hospital were available to them. But the explanation given seems unlikely because treatment guidelines for the use of adjuvant systemic treatment have always been much more straightforward for patients with positive lymph nodes than with negative nodes. Therefore, one would expect the variation in adjuvant systemic treatment to have been much larger for patients with negative axillary lymph nodes than with 1–3 positive nodes. Already since the 1980s, or at least since the early 1990s, all node-positive patients are recommended to receive hormonal treatment or chemotherapy, depending on their menopausal status and the hormone receptor status of their tumour. It has taken much more effort to reach consensus about the use of systemic treatment in node-negative patients and guidelines have changed rapidly since the first publications by the Early Breast Cancer Trialists’ Collaborative Group [2.Goldhirsch A. Wood W.C. Gelber R.D. et al.Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer.J Clin Oncol. 2003; 21: 3357-3365Crossref PubMed Scopus (644) Google Scholar]. Age, estrogen receptor or progesterone receptor status, tumour size and tumour grade all play a role in the decision to use chemotherapy, hormonal therapy or a combination of both when nodes are negative [3.Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group.Lancet. 1998; 352: 930-942Abstract Full Text Full Text PDF PubMed Scopus (2046) Google Scholar]. In our view, only if variation in the use of systemic treatment appears to be larger for patients with 1–3 positive lymph nodes than for patients with negative lymph nodes, this could be a plausible explanation for the observed survival differences between the hospitals in this subgroup. Perhaps, the authors could provide such data.
MASS SCREENING FOR NEUROBLASTOMA IN INFANTS IN JAPAN
Authors: Tadashi Sawada, Toshikazu Nakata, Nobuo Takasugi, Kazuichi Maeda, Yoshiyuki Hanawa, Kuniki Shimizu, Munehiro Hirayama, Takeo Takeda, Takeshi Mori, Ryo Koide, Akio Tsunoda, Noboru Nagahara, Keiko Yamamoto
Journal: The Lancet (1984)
Changes in smoking habits and risk of asthma: a longitudinal population based study
Authors: N.S. Godtfredsen, P. Lange, E. Prescott, M. Osler, J. Vestbo
Journal: European Respiratory Journal (2001)

A common statement from exsmokers is that symptoms of asthma develop shortly after smoking cessation. This study, therefore, investigated the relationship between smoking cessation and development of asthma in a large cohort from the Copenhagen City Heart Study (CCHS). The CCHS is a longitudinal, epidemiological study of the general population from the capital of Denmark, conducted between 1976 and 1994. The study population involved the 10,200 subjects who provided information on self-reported asthma and smoking habits from the first two examinations (baseline and 5-yr follow-up), and the 6,814 subjects who also attended the third and last examination (10-yr follow-up). The point-prevalence of smoking cessation as well as the asthma incidence between examinations was estimated, and a multivariate logistic regression model was used to examine the relationship between changes in smoking habits and development of asthma. During the study period, asthma incidence increased from 1.2–4.2%. Between examinations 1,316 subjects quit smoking. Smoking cessation between examinations was significantly related to reported asthma at follow-up. With never-smokers as the reference group and following adjustment for sex, age, chronic bronchitis, level of forced expiratory volume in one second and pack-yrs of smoking, the odds ratio (OR) for developing asthma when quitting smoking between examinations was 3.9 (95% confidence interval (CI) 1.8–8.2) from baseline to first follow-up and 3.1 (95% CI 1.9–5.1) from first to second follow-up. Continuing smoking also increased the risk of asthma significantly (OR 2.6 and 2.0, respectively). The results indicate that exsmokers have a higher incidence of self-reported asthma than never-smokers. It is likely that subjects perceive chronic obstructive pulmonary disease as asthma, hence the relationship between smoking cessation and asthma might be due to misclassification rather than causality.
Chemotherapeutic Effects on Mammalian Tumor Cells. I. Modification of Leukemia L1210 Growth Kinetics and Karyotype With an Alkylating Agent
Authors: Ralph E. Johnson, Marvin Zelen, Nigel H. Kemp
Journal: JNCI Journal of the National Cancer Institute (1965)

A biologically and cytogenetically stable ascites line of Leukemia L1210 has been exposed to cyclophosphamide under certain defined conditions. Several sublines, developed from tumors recurrent after drug therapy, have been found to be substantially modified from the parent tumor with respect to virulence and karyotype. The findings suggest the tumor cells surviving treatment with cyclophosphamide exhibit a prolonged lag phase with gradual recovery of proliferative rate. Possible interpretations of these changes are discussed, and a mathematical model for the prediction of alteration of tumor growth by chemotherapy is presented.
Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits
Authors: Joshua W Buckholtz, Michael T Treadway, Ronald L Cowan, Neil D Woodward, Stephen D Benning, Rui Li, M Sib Ansari, Ronald M Baldwin, Ashley N Schwartzman, Evan S Shelby, Clarence E Smith, David Cole, Robert M Kessler, David H Zald
Journal: Nature Neuroscience (2010)
Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time
Authors: Dar‐In Tai, Shi‐Ming Lin, I‐Shyan Sheen, Chia‐Ming Chu, Deng‐Yn Lin, Yun‐Fan Liaw
Journal: Hepatology (2009)

The baseline alanine aminotransferase (ALT) level was reported to have prognostic value in chronic hepatitis B virus (HBV) infection, during which ALT may change over time. Instead of baseline ALT, this study aimed to study the prognostic value of the height of ALT during the course of chronic HBV infection. A total of 4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg) carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3 years. Maximal ALT levels during follow-up were correlated with long-term outcomes using morbidity and mortality data from hospital records, cancer registration, and national mortality database. Baseline ALT level was normal in 3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean follow-up period of 13.4 ± 5.2 (3.0-28.7) years. The incidence of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with increasing maximal ALT level during follow-up, especially in those with maximal ALT of at least 2 times ULN, as compared with those who maintained normal ALT. Cox regression analysis indicated that age at entry, sex, and maximal ALT level during follow-up were significant independent factors associated with the development of cirrhosis, HCC, and mortality whereas cirrhosis was also an independent factor for HCC development and mortality. Conclusion: Persistently normal ALT was associated with excellent long-term prognosis, whereas increasing ALT levels of at least 2 times ULN during follow-up was associated with increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an appropriate threshold for anti-HBV therapy, whereas those with ALT 1 to 2 times ULN require liver biopsy for decision. (HEPATOLOGY 2009.)
Joint effects of coffee consumption and serum gamma‐glutamyltransferase on the risk of liver cancer
Authors: Gang Hu, Jaakko Tuomilehto, Eero Pukkala, Timo Hakulinen, Riitta Antikainen, Erkki Vartiainen, Pekka Jousilahti
Journal: Hepatology (2008)

Only three Japanese prospective studies have suggested an inverse association between coffee drinking and liver cancer risk. No prospective studies on the association between serum gamma-glutamyltransferase (GGT) and liver cancer risk have been reported. We aimed to determine the single and joint associations of coffee consumption and serum GGT with the risk of primary liver cancer. Study cohorts included 60,323 Finnish participants who were 25-74 years of age and free of any cancer at baseline. During a median follow-up period of 19.3 years (interquartile range: 9.3-29.2 years), 128 participants were diagnosed with an incident liver cancer. The multivariable-adjusted (age, sex, alcohol consumption, education, smoking, diabetes and chronic liver disease at baseline and during follow-up, and body mass index) hazards ratios of liver cancer in participants who drank 0-1, 2-3, 4-5, 6-7, and ≥8 cups of coffee daily were 1.00, 0.66, 0.44, 0.38, and 0.32 (P for trend = 0.003), respectively. Further adjustment for serum GGT in subgroup analysis affected the results only slightly. The multivariable-adjusted and coffee-adjusted hazard ratio of liver cancer for the highest versus the lowest quartile of serum GGT was 3.13 (95% confidence interval = 1.22-8.07). The multivariable-adjusted inverse association between coffee consumption and liver cancer risk persisted when stratified by baseline factors: age more/less than 50 years, current smoker/never smoked/ever smoked, alcohol drinker/never drinker, obese/nonobese, and the highest/lowest three quartiles of serum GGT. A combination of very low coffee consumption and high level of serum GGT was associated with nearly nine-fold increased risk. Conclusion: Coffee drinking has an inverse and graded association with the risk of liver cancer. High serum GGT is associated with an increased risk of liver cancer. (HEPATOLOGY 2008.)
Mycobacterium malmoense infection of the knee
Authors: R Callaghan
Journal: Annals of the Rheumatic Diseases (2003)

A 53 year old woman presented to the rheumatology department in November 1988 with polyarthralgia, Raynaud’s phenomenon, proximal weakness, and high creatine kinase. Muscle biopsy confirmed an inflammatory myopathy. Treatment was started with high dose corticosteroids and azathioprine. During the next 10 years her myositis was persistently active and her disease modifying treatment was changed to oral methotrexate, and then a combination of oral cyclosporin and intramuscular methotrexate. She continued receiving doses of prednisolone above 10 mg.

In May 1998 she developed a tense effusion of her right knee. Several synovial aspirates were negative for culture and crystals (mycobacterium was not tested for at this stage). Synovial microscopy showed ++ polymorphs (range 0 to +++, quantitative leucocyte counts were not performed) and no red blood cells. Her C reactive protein became raised at 39 mg/l and her blood neutrophil count was 18×109/l. Plain radiography showed mild degenerative changes only. Ultrasound confirmed a knee effusion, which communicated with her prepatella bursa. At this time her muscle disease was in remission. For the next two years her knee remained intermittently swollen with fluctuating high C reactive protein and neutrophil counts. …
The role of paf in embryo physiology
Authors: Chris O'Neill
Journal: Human Reproduction Update (2005)

Embryo-derived paf (1-o-alkyl-2-acetyl-sn-gylcero-3-phosphocholine) is produced by de novo synthesis. This synthesis commences soon after fertilization and persists throughout the preimplantation phase. Paf is produced and released by the embryos of all mammalian species studied to date. Its release from the embryo involves binding to extracellular albumin in a manner that protects paf from enzymatic degradation. Released paf causes a range of alterations in maternal physiology, including platelet activation, changes in oviductal, endometrial and maternal immune function. Paf also acts in an autocrine fashion as a trophic/survival factor for the early embryo. In vitro, supplementation of culture media with paf improves embryo development. Embryo-derived paf's autocrine actions are transduced by 1-o-phosphatidylinositol-3-kinase, which induces characteristic calcium transients within the early embryo. The calcium transients require both the influx of external calcium and release of inositol trisphosphate-dependent internal calcium stores. Buffering these transients compromised embryo development in a manner that was reversed by exogenous paf. Assisted reproductive technologies compromise the production of paf by some embryos and retard the expression of the paf receptor. This deprivation of paf's action is one of the factors limiting the survivability of embryos produced by assisted reproductive technologies. Paf is one of several autocrine and paracrine trophic/survival factors that act on the early embryo. These factors probably act cooperatively and may, to some degree, be mutually redundant. As the earliest-released and the best-described embryotrophin, paf provides an important exemplar for understanding the role of ligand-mediated trophic support of the early embryo.
Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies
Authors: Ranjana H. Advani, Joseph J. Buggy, Jeff P. Sharman, Sonali M. Smith, Thomas E. Boyd, Barbara Grant, Kathryn S. Kolibaba, Richard R. Furman, Sara Rodriguez, Betty Y. Chang, Juthamas Sukbuntherng, Raquel Izumi, Ahmed Hamdy, Eric Hedrick, Nathan H. Fowler
Journal: Journal of Clinical Oncology (2012)

Purpose Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients and Methods Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Results Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Conclusion Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.
Assessment of Response to Induction Therapy and Its Influence on 5-Year Failure-Free Survival in Group III Rhabdomyosarcoma: The Intergroup Rhabdomyosarcoma Study-IV Experience—A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Megan Burke, James R. Anderson, Simon C. Kao, David Rodeberg, Stephen J. Qualman, Suzanne L. Wolden, William H. Meyer, Philip P. Breitfeld
Journal: Journal of Clinical Oncology (2007)

Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS.We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response.Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS.In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.
Effect of prostaglandin E2 on chloride transport across the rabbit thick ascending limb of Henle. Selective inhibitions of the medullary portion.
Authors: J B Stokes
Journal: Journal of Clinical Investigation (1979)

Prostaglandins are present in large quantities in the kidney and have been shown to directly affect transepithelial transport. The present studies were designed to examine whether prostaglandin E2 could affect chloride transport across the thick ascending limb of Henle. Isolated segments of the cortical and medullary thick ascending limb of Henle were perfused in vitro and the transepithelial voltage and net chloride flux were measured. Exposure of the medullary thick ascending limb to 2 microM prostaglandin E2 resulted in a fall in net chloride transport of 40--50% with a concomitant fall in voltage. In contrast, net chloride transport in the cortical thick ascending limb was not affected by prostaglandin E2. Under similar conditions, the medullary thick ascending limb possessed twice the capacity to transport chloride than did the cortical thick ascending limb. The results suggest that endogenous renal prostaglandins may play a modulating role in the addition of salt to the renal medullary interstitium and may, under some circumstances, by chloruretic.
Corticosteroids for Bacterial Meningitis in Adults in Sub-Saharan Africa
Authors: Matthew Scarborough, Stephen B. Gordon, Christopher J.M. Whitty, Neil French, Yasin Njalale, Alex Chitani, Timothy E.A. Peto, David G. Lalloo, Eduard E. Zijlstra
Journal: New England Journal of Medicine (2007)

In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection.
Unsuspected Pulmonary Emboli in Cancer Patients: Clinical Correlates and Relevance
Authors: Casey L. O'Connell, William D. Boswell, Vinay Duddalwar, Amy Caton, Lisa S. Mark, Cheryl Vigen, Howard A. Liebman
Journal: Journal of Clinical Oncology (2006)

Advances in computed tomography (CT) scanning have led to the detection of unsuspected pulmonary emboli (PE) on routine cancer staging scans. We hypothesized that these patients had signs or symptoms suggestive of PE that may have been overlooked by their health care providers.A retrospective chart review was performed on 59 patients found on routine cancer staging CT scans to have unsuspected PE. Information on patient demographics, malignancy characteristics, risk factors for venous thromboembolism (VTE), and symptoms was recorded. A retrospective case-control analysis was then performed using two age- and stage-matched control patients for each patient who had similar staging CT scans performed during the same period.Fifty-two patients with unsuspected PE were identified. Forty-four percent had signs or symptoms commonly associated with PE; when fatigue was included, 75% were symptomatic. Ninety-two control patients were identified for 46 of the case patients. Patients with unsuspected PE were significantly more likely to have had a prior history of VTE (20% v 3%; P = .007). The patients with PE were significantly more likely than control patients to complain of fatigue (54% v 20%; P = .0002) and shortness of breath (22% v 8%; P = .02). There was no difference between the groups in administration of chemotherapy within 30 days, central venous catheter use, or erythropoietin therapy.Seventy-five percent of patients found to have unsuspected PE on cancer staging CT scans were symptomatic. Fatigue and shortness of breath were significantly more common in patients with unsuspected PE than in control patients.
Major Depression, Adjustment Disorders, and Post-Traumatic Stress Disorder in Terminally Ill Cancer Patients: Associated and Predictive Factors
Authors: Tatsuo Akechi, Toru Okuyama, Yuriko Sugawara, Tomohito Nakano, Yasuo Shima, Yosuke Uchitomi
Journal: Journal of Clinical Oncology (2004)

Purpose Few studies have been conducted to elucidate the psychological distress of terminally ill cancer patients. This study attempted to determine the prevalence of adjustment disorders (AD), major depression (MD), and post-traumatic stress disorder (PTSD) among terminally ill cancer patients, to identify factors that contribute to them, and to determine how they change longitudinally. Patients and Methods Consecutive terminally ill cancer patients were recruited. Patients were assessed for psychiatric disorders by structured clinical interview twice: once at the time of their registration with a palliative care unit (baseline), and again at the time of their palliative care unit admission (follow-up). Possible contributed biomedical and psychosocial factors were evaluated. Results The proportions of patients diagnosed with AD, MD, and PTSD at baseline (n = 209) were 16.3%, 6.7%, and 0% respectively, whereas at follow-up (n = 85), 10.6% were diagnosed with AD and 11.8% with MD. Lower performance status, concern about being a burden to others, and lower satisfaction with social support were significantly associated with AD/MD at baseline. There were changes in the diagnosis of AD and MD in 30.6% of the patients. Only the Hospital Anxiety and Depression Scale at the baseline was significantly predictive of AD/MD at follow-up. Conclusion The factors underlying psychological distress are multifactorial. Early intervention to treat subclinical anxiety and depression may prevent subsequent psychological distress.