tbuckley/cabot-search huggingface dataset:
Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy
Authors: Roman Rouzier, Charles M. Perou, W. Fraser Symmans, Nuhad Ibrahim, Massimo Cristofanilli, Keith Anderson, Kenneth R. Hess, James Stec, Mark Ayers, Peter Wagner, Paolo Morandi, Chang Fan, Islam Rabiul, Jeffrey S. Ross, Gabriel N. Hortobagyi, Lajos Pusztai
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported “breast intrinsic” gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor–negative subtypes. Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.
Liver Histology and Surgical Outcomes After Preoperative Chemotherapy With Fluorouracil Plus Oxaliplatin in Colorectal Cancer Liver Metastases
Authors: Thomas Aloia, Mylène Sebagh, Marylène Plasse, Vincent Karam, Francis Lévi, Sylvie Giacchetti, Daniel Azoulay, Henri Bismuth, Denis Castaing, René Adam
Journal: Journal of Clinical Oncology (2006)

Purpose Preoperative chemotherapy for colorectal liver metastases (CLM) can produce histologic changes in the nontumor-bearing liver (NTBL) that may impact on surgical outcomes. Patients and Methods From a cohort of 303 patients treated for CLM with liver resection, 92 patients (75 received preoperative chemotherapy: group C+; and 17 were chemotherapy naïve: group C−) were randomly selected for detailed pathologic analysis. Preoperative chemotherapy consisted of fluorouracil (FU)/leucovorin alone (23 patients, the majority chronomodulated) or in combination with oxaliplatin (52 patients, all chronomodulated). To determine associations between study factors, clinical and operative variables were compared with pathology data and surgical outcomes. Results Although clinical and operative factors were similarly distributed, C+ patients, compared with C− patients, were more likely to receive intraoperative RBC transfusions (mean units: 1.9 v 0.5, respectively; P = .03) and to have vascular abnormalities in the NTBL (52% v 18%, respectively; P = .01). Presence of the most severe forms of vascular alterations was closely associated with RBC transfusion requirements (P = .04). In contrast, moderate to severe steatosis was similarly distributed (C− group, 12%; C+ group, 13%). Although perioperative mortality and morbidity rates were similar in all groups, more than 12 courses of chemotherapy, compared with ≤ 12 courses, predisposed patients to reoperation (11% v 0%, respectively; P = .04) and to longer hospitalization (15 v 11 days, respectively; P = .02). Conclusion The main hepatic lesion induced by preoperative FU/oxaliplatin chemotherapy in patients with CLM is vascular and not steatosis. Detailed pathologic analysis determined that the most severe vascular lesions are associated with increased intraoperative transfusions. The risk for other postoperative complications is related to the duration of preoperative chemotherapy administration.
Immunoglobulin Heavy Chain Locus Events and Expression of Activation-Induced Cytidine Deaminase in Epithelial Breast Cancer Cell Lines
Authors: Gavin Babbage, Christian H. Ottensmeier, Jeremy Blaydes, Freda K. Stevenson, Surinder S. Sahota
Journal: Cancer Research (2006)

When cells transform, phenotypic and genetic profiles can be dramatically altered. Nevertheless, a recent report identifying IgG in breast cancer cells was unexpected, revealing differentiation features normally associated with B lymphocytes. To extend these findings, we focused on immunoglobulin variable (V) region gene analysis using well-defined breast cancer cell lines expressing the epithelial marker, epithelial cell adhesion molecule (EpCAM). V(H) gene transcripts were identifiable by nested reverse transcription-PCR either as single or dual V, diversity (D), and joining (J) rearrangements in four of six lines, most being potentially functional. V(D)J transcripts were observed in sequential cultures, indicating stable expression. To exclude coexisting lymphocytes, each cell line was shown to be EBV negative, with CD19/CD20 and cytoplasmic/surface immunoglobulin also absent by flow cytometry. Identified V(H) transcripts were then sought in individual tumor cells, isolated as EpCAM+ single cells by flow cytometry. Importantly, in three of three selected cell lines, V(H) genes were identifiable in a significant fraction (approximately 32%) of single cells. In five of six identified V(H) genes, somatic mutations were apparent with no intraclonal variation, indicating cessation of mutational activity. V(H) transcripts were pre- and post-isotype switch, with activation of switch events evident from expressed germ-line switch transcripts in two of six lines. Strikingly, six of six cell lines expressed activation-induced cytidine deaminase (AID) essential for mutational and switch activity. These data suggest either a de novo rearrangement and modification of V(H) genes in epithelial tumor cells or assimilation of lymphocyte-derived chromatin. Constitutive AID activation in malignant epithelial cells further raises a potential for inducing aberrant mutational activity.
A CASE OF BLASTOMYCOSIS
Authors: JAMES H. SEQUEIRA
Journal: British Journal of Dermatology (1903)

Journal Article A CASE OF BLASTOMYCOSIS Get access JAMES H. SEQUEIRA, M.D.Lond., M.R.C.P. Lond., F.R.C.S.Eng. JAMES H. SEQUEIRA, M.D.Lond., M.R.C.P. Lond., F.R.C.S.Eng. Assistant Physician to the Skin Department of the London Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 15, Issue 4, 1 April 1903, Pages 121–125, https://doi.org/10.1111/j.1365-2133.1903.tb16488.x Published: 01 April 1903
Cardiorespiratory Fitness and Vigorous Leisure-Time Physical Activity Modify the Association of Small Size at Birth With the Metabolic Syndrome
Authors: David E. Laaksonen, Hanna-Maaria Lakka, John Lynch, Timo A. Lakka, Leo Niskanen, Rainer Rauramaa, Jukka T. Salonen, Jussi Kauhanen
Journal: Diabetes Care (2003)

OBJECTIVE—Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome. RESEARCH DESIGN AND METHODS—Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and Vo2max were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study. RESULTS—Men with a ponderal index (kg/m3) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in &amp;lt;25 min/wk of vigorous LTPA and in men with a Vo2max &amp;lt;28.6 ml · kg−1 · min−1 or &amp;lt;2.44 l/min. In active and fit men, however, the association was absent. CONCLUSIONS—Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.
Immediate Postoperative Renal Function Deterioration in Cardiac Surgical Patients Predicts In-Hospital Mortality and Long-Term Survival
Authors: Berthus G. Loef, Anne H. Epema, Ton D. Smilde, Robert H. Henning, Tjark Ebels, Gerjan Navis, Coen A. Stegeman
Journal: Journal of the American Society of Nephrology (2004)

Postoperative renal function deterioration is a serious complication after cardiac surgery with cardiopulmonary bypass and is associated with increased in-hospital mortality. However, the long-term prognosis of patients with postoperative renal deterioration is not fully determined yet. Therefore, both in-hospital mortality and long-term survival were studied in patients with postoperative renal function deterioration. Included were 843 patients who underwent cardiac surgery with cardiopulmonary bypass in 1991. Postoperative renal function deterioration (increase in serum creatinine in the first postoperative week of at least 25%) occurred in 145 (17.2%) patients. In these patients, in-hospital mortality was 14.5%, versus 1.1% in patients without renal function deterioration (P < 0.001). Multivariate analysis significantly associated in-hospital mortality with postoperative renal function deterioration, re-exploration, postoperative cerebral stroke, duration of operation, age, and diabetes. In patients who were discharged alive, during long-term follow-up (100 mo), mortality was significantly increased in the patients with renal function deterioration (n = 124) as compared with those without renal function deterioration (hazard ratio 1.83; 95% confidence interval 1.38 to 3.20). Also after adjustment for other independently associated factors, the risk for mortality in patients with postoperative renal function deterioration remained elevated (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32). The elevated risk for long-term mortality was independent of whether renal function had recovered at discharge from hospital. It is concluded that postoperative renal function deterioration in cardiac surgical patients not only results in increased in-hospital mortality but also adversely affects long-term survival.
Economic Analysis of Influenza Vaccination and Antiviral Treatment for Healthy Working Adults
Authors: Patrick Y. Lee, David B. Matchar, Dennis A. Clements, Joel Huber, John D. Hamilton, Eric D. Peterson
Journal: Annals of Internal Medicine (2002)

Background: Physicians have several treatment options for influenza, including vaccination and various antiviral therapies. However, the optimal influenza prevention and treatment strategy is unknown. Objective: To compare the relative health values of contemporary treatment strategies for influenza in a healthy sample of working adults. Design: Cost-benefit analysis using a decision model. Data Sources: Previously published data. Target Population: Healthy employed adults 18 to 50 years of age. Time Horizon: A complete influenza season. Perspective: Societal. Interventions: Eight treatment options (yes or no) based on the possible combinations of vaccination and antiviral therapy (rimantadine, oseltamivir, or zanamivir or no treatment) should infection develop. Outcome Measures: Cost in U.S. dollars, including the value of symptom relief and medication side effects, which was assigned a monetary value through a conjoint analysis that used a "willingness-to-pay" approach. Results: In the base-case analysis, all strategies for influenza vaccination had a higher net benefit than the nonvaccination strategies. Vaccination and use of rimantadine, the most cost-beneficial strategy, was $30.97 more cost-beneficial than nonvaccination and no use of antiviral medication. The health benefits of most antiviral treatments equaled or exceeded their costs for most scenarios. The choice of the most cost-beneficial antiviral strategy was sensitive to the prevalence of influenza B and to the comparative workdays gained by each antiviral therapy. Conclusions: Vaccination is cost-beneficial in most influenza seasons in healthy working adults. Although the benefits of antiviral therapy for persons with influenza infection appear to justify its cost, head-to-head trials of the various antiviral therapies are needed to determine the optimal treatment strategy.
Overexpression of h-prune in Breast Cancer is Correlated with Advanced Disease Status
Authors: Massimo Zollo, Alessandra Andrè, Antonio Cossu, Maria C. Sini, Anna D'Angelo, Natascia Marino, Mario Budroni, Francesco Tanda, Gianluigi Arrigoni, Giuseppe Palmieri
Journal: Clinical Cancer Research (2005)

The h-prune gene is involved in cellular motility and metastasis formation in breast cancer through interacting with the nm23-H1 protein. The aim of this study was to better define the clinical and pathologic role of h-prune in breast cancer patients.Using immunohistochemistry, we assessed h-prune and nm23-H1 protein expression in two series of breast cancer patients: (i) in 2,109 cases with pathologic reports on primary tumors and (ii) in 412 cases with detailed clinical information. To assess the role of DNA amplification in gene activation, the h-prune copy number was evaluated by fluorescence in situ hybridization analysis in 1,016 breast cancer cases.In the patients tested (n = 2,463), 1,340 (54%) had an increased level of h-prune expression; a positive immunostaining for nm23-H1 was observed in 615 of 2,061 (30%) cases. Overexpression of h-prune was associated with multiple gene copy number at chromosome 1q21.3 in a very limited fraction of cases (68 of 1,016; 6.7%), strongly indicating that alternative pathways induce h-prune activation in breast cancer. Multivariate Cox regression analysis showed that neither h-prune overexpression nor decreased nm23-H1 immunostaining is independent prognostic factors. However, a significant association of h-prune overexpression with either advanced lymph node status (P = 0.017) or presence of distant metastases (P = 0.029) was observed.Although not significantly correlated with overall survival, positive h-prune immunostaining identifies subsets of breast cancer patients with higher tumor aggressiveness. Further investigations using larger collections of advanced breast cancer patients are required for assessing the predictive role of h-prune in breast cancer.
Polymorphism in Glutamate-Cysteine Ligase Modifier Subunit Gene Is Associated With Impairment of Nitric Oxide–Mediated Coronary Vasomotor Function
Authors: Shin-ichi Nakamura, Seigo Sugiyama, Daisuke Fujioka, Ken-ichi Kawabata, Hisao Ogawa, Kiyotaka Kugiyama
Journal: Circulation (2003)

Background— The minor −588T allele of polymorphism −588C/T of a modifier subunit gene in glutamate-cysteine ligase (GCLM), a rate-limiting enzyme for glutathione (GSH) synthesis, was associated with lower plasma GSH levels and was a risk factor for myocardial infarction. Methods and Results— We examined effects of the −588C/T polymorphism on coronary arterial diameter and blood flow responses to intracoronary infusion of acetylcholine in 157 consecutive subjects who had normal coronary angiograms. In multivariate linear regression analysis with covariates including traditional risk factors, the minor −588T allele had an independent association with impaired dilation or enhanced constriction of epicardial coronary arteries in response to acetylcholine, and it was independently associated with blunted increase in coronary flow response to acetylcholine. In a subgroup of 59 consecutive subjects, constrictor responses of epicardial coronary diameter to intracoronary infusion of N G -monomethyl- l -arginine, reflecting the presence of coronary nitric oxide (NO) bioactivity, had an inverse and independent association with the −588T allele in multivariate analysis. Conclusions— The −588T polymorphism of the GCLM gene causes a decrease in endothelial NO bioactivity, leading to impairment of endothelium-dependent vasomotor function in large and resistance coronary arteries. The GCL–GSH–NO axis may play a role in the defense system against coronary artery disease.
Bilateral maxillary fused second and third molars: a rare occurrence
Authors: Rui-Zhen Liang, Jin-Tao Wu, You-Nong Wu, Roger J Smales, Ming Hu, Jin-Hua Yu, Guang-Dong Zhang
Journal: International Journal of Oral Science (2012)

This case report describes the diagnosis and endodontic therapy of maxillary fused second and third molars, using cone-beam computed tomography (CBCT). A 31-year-old Chinese male, with no contributory medical or family/social history, presented with throbbing pain in the maxillary right molar area following an unsuccessful attempted tooth extraction. Clinical examination revealed what appeared initially to be a damaged large extra cusp on the buccal aspect of the distobuccal cusp of the second molar. However, CBCT revealed that a third molar was fused to the second molar. Unexpectedly, the maxillary left third molar also was fused to the second molar, and the crown of an unerupted supernumerary fourth molar was possibly also fused to the apical root region of the second molar. Operative procedures should not be attempted without adequate radiographic investigation. CBCT allowed the precise location of the root canals of the right maxillary fused molar teeth to permit successful endodontic therapy, confirmed after 6 months.
Thinking Outside the Box: Recent Advances in the Analysis and Presentation of Uncertainty in Cost-Effectiveness Studies
Authors: Andrew H. Briggs, Bernie J. O'Brien, Gordon Blackhouse
Journal: Annual Review of Public Health (2002)

▪ Abstract As many more clinical trials collect economic information within their study design, so health economics analysts are increasingly working with patient-level data on both costs and effects. In this paper, we review recent advances in the use of statistical methods for economic analysis of information collected alongside clinical trials. In particular, we focus on the handling and presentation of uncertainty, including the importance of estimation rather than hypothesis testing, the use of the net-benefit statistic, and the presentation of cost-effectiveness acceptability curves. We also discuss the appropriate sample size calculations for cost-effectiveness analysis at the design stage of a study. Finally, we outline some of the challenges for future research in this area—particularly in relation to the appropriate use of Bayesian methods and methods for analyzing costs that are typically skewed and often incomplete.
New Gastrostomy Catheter
Authors: W. G. Hendry
Journal: BMJ (1964)

after pyloroplasty.This is one of several reasons why gastro-enterostomy should be avoided.In cases of severe dumping the gastro-enterostomy is probably best taken down and replaced by pyloroplasty.May I, too, comment on gastrostomy after vagotomy and pyloroplasty-referred to by Professor A. W. Kay (28 March, p. 822) ?Hendry taught me to use neither naso-gastric intubation nor gastrostomy after this opera- tion, nor to use a naso-gastric tube before operation.In over 200 cases I can confirm his teaching.There is no need whatever for any form of gastric suction after vagotomy and pyloroplasty.Fluids by mouth in the immediate post-operative period need not be severely restricted.With "tubeless " vag- otomy fluids and electrolytes are not with- drawn and do not, therefore, need to be replaced.Post-operative intravenous fluids, or even rectal fluids, are not routinely neces- sary, though in hot weather we give saline in the theatre to combat fluid loss there and to allay post-operative thirst.-Iam, etc.,
Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study
Authors: Mary E Tinetti, Gail McAvay, Mark Trentalange, Andrew B Cohen, Heather G Allore
Journal: BMJ (2015)

<b>Objective</b> To estimate the association between guideline recommended drugs and death in older adults with multiple chronic conditions. <b>Design</b> Population based cohort study. <b>Setting</b> Medicare Current Beneficiary Survey cohort, a nationally representative sample of Americans aged 65 years or more. <b>Participants</b> 8578 older adults with two or more study chronic conditions (atrial fibrillation, coronary artery disease, chronic kidney disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, and thromboembolic disease), followed through 2011. <b>Exposures</b> Drugs included β blockers, calcium channel blockers, clopidogrel, metformin, renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazides; and warfarin. <b>Main outcome measure</b> Adjusted hazard ratios for death among participants with a condition and taking a guideline recommended drug relative to participants with the condition not taking the drug and among participants with the most common combinations of four conditions. <b>Results</b> Over 50% of participants with each condition received the recommended drugs regardless of coexisting conditions; 1287/8578 (15%) participants died during the three years of follow-up. Among cardiovascular drugs, β blockers, calcium channel blockers, RAS blockers, and statins were associated with reduced mortality for indicated conditions. For example, the adjusted hazard ratio for β blockers was 0.59 (95% confidence interval 0.48 to 0.72) for people with atrial fibrillation and 0.68 (0.57 to 0.81) for those with heart failure. The adjusted hazard ratios for cardiovascular drugs were similar to those with common combinations of four coexisting conditions, with trends toward variable effects for β blockers. None of clopidogrel, metformin, or SSRIs/SNRIs was associated with reduced mortality. Warfarin was associated with a reduced risk of death among those with atrial fibrillation (adjusted hazard ratio 0.69, 95% confidence interval 0.56 to 0.85) and thromboembolic disease (0.44, 0.30 to 0.62). Attenuation in the association with reduced risk of death was found with warfarin in participants with some combinations of coexisting conditions. <b>Conclusions</b> Average effects on survival, particularly for cardiovascular study drugs, were comparable to those reported in randomized controlled trials but varied for some drugs according to coexisting conditions. Determining treatment effects in combinations of conditions may guide prescribing in people with multiple chronic conditions.