tbuckley/cabot-search huggingface dataset:
Pretreatment Quality of Life As a Predictor of Distant Metastasis and Survival for Patients With Nasopharyngeal Carcinoma
Authors: Fu-Min Fang, Wen-Ling Tsai, Chih-Yen Chien, Hui-Chun Chen, Hsuan-Chih Hsu, Tai-Lin Huang, Tsair-Fwu Lee, Hsuan-Ying Huang, Chien-Hung Lee
Journal: Journal of Clinical Oncology (2010)

The purpose of this study was to examine the prognostic value of pretreatment quality of life (QoL) data on locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with nasopharyngeal carcinoma (NPC).A total of 347 new patients with NPC, who were curatively treated by conformal radiotherapy from March 2003 to December 2007, were recruited. The Taiwan Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 was completed before treatment. Multivariate Cox's proportional hazards models were used to analyze the impact of clinical and QoL variables on the treatment results.The 5-year LRC, DMFS, and OS rates were 72.9%, 79.1%, and 68.4%, respectively. After adjusting the clinical variables, 10 QoL variables were observed to be significantly (P < .05) related to OS, and four QoL variables were related to DMFS. No QoL variable was predictive of LRC. Among the QoL variables that significantly predicted OS and DMFS, physical functioning was the most powerful predictor. A 10-point increase in the physical functioning score was associated with a 23% (95% CI, 12% to 34%) reduction in the likelihood of death and a 22% (95% CI, 9% to 36%) reduction in the likelihood of distant metastasis.Our findings indicate that pretreatment QoL variables, especially physical functioning, provide easily available prognostic value for distant metastasis and survival in patients with NPC.
An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population.
Authors: T E Arbuckle, Z Lin, L S Mery
Journal: Environmental Health Perspectives (2001)

The toxicity of pesticides on human reproduction is largely unknown--particularly how mixtures of pesticide products might affect fetal toxicity. The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, we examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (&lt; 12 weeks) and late (12-19 weeks) spontaneous abortions. We observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.1-2.1], triazines (OR = 1.4; 95% CI, 1.0-2.0), and any herbicide (OR = 1.4; 95% CI, 1.1-1.9). For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), thiocarbamates (OR = 1.8; 95% CI, 1.1-3.0), and the miscellaneous class of pesticides (OR = 1.5; 95% CI, 1.0-2.4) was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions. Older maternal age (&gt; 34 years of age) was the strongest risk factor for spontaneous abortions, and we observed several interactions between pesticides in the older age group using Classification and Regression Tree analysis. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.
The Impact of a Physician Awareness Group and the First Year of Training on Hematology-Oncology Fellows
Authors: Mikkael A. Sekeres, Miriam Chernoff, Thomas J. Lynch, Eydie I. Kasendorf, Daniel H. Lasser, Donna B. Greenberg
Journal: Journal of Clinical Oncology (2003)

To assess the impact of a Balint-like physician awareness group on hematology-oncology fellows' attitudes and measure changes in attitudes during the first fellowship year.We used a modified crossover design in which one half of a fellowship class at a time was exposed to the group intervention over a 2-year period (2000 to 2002). Two 14-fellow classes were followed for 1 year each and were given three "attitudes" questionnaires, at the beginning, middle, and end of the academic year.Forty Balint group sessions were held during the 2-year study period; 82 questionnaires of the 84 administered (98%) were recovered. Instrument content and criterion validity were demonstrated, as was topic domain reliability. Overall, mean attitude scores increased following the group intervention, from 3.6 (95% CI, 3.5 to 3.7) to 3.7 (95% CI, 3.6 to 3.8; P =.09). Within domains, scores increased in a "fellow's views of him/herself as a physician," from 3.8 (95% CI, 3.6 to 3.9) to 4.1 (95% CI, 3.9 to 4.2; P =.008) and "comfort dealing with emotional patient/clinical situations," from 3.5 (95% CI, 3.3 to 3.7) to 3.7 (95% CI, 3.6 to 3.9; P =.11). Changes in responses to individual questions included: an increase in fellows' comfort with the technical aspects of being an oncologist (P <.03); an increase in fellows' comfort with discussing the stress of home at work (P <.023); and an increase among fellows in feeling pressed for time to discuss psychosocial issues with patients (P =.035).A physician awareness group was feasible and enhanced fellows' development as physicians. Further research is needed to determine how to incorporate such groups into oncology fellowships.
Effect of anaemia and cardiovascular disease on surgical mortality and morbidity
Authors: Jeffrey L Carson, Amy Duff, Roy M Poses, Jesse A Berlin, Richard K Spence, Richard Trout, Helaine Noveck, Brian L Strom
Journal: The Lancet (1996)

Guidelines have been offered on haemoglobin thresholds for blood transfusion in surgical patients. However, good evidence is lacking on the haemoglobin concentrations at which the risk of death or serious morbidity begins to rise and at which transfusion is indicated.A retrospective cohort study was performed in 1958 patients, 18 years and older, who underwent surgery and declined blood transfusion for religious reasons. The primary outcome was 30-day mortality and the secondary outcome was 30-day mortality or in-hospital 30-day morbidity. Cardiovascular disease was defined as a history of angina, myocardial infarction, congestive heart failure, or peripheral vascular disease.The 30-day mortality was 3.2% (95% CI 2.4-4.0). The mortality was 1.3% (0.8-2.0) in patients with preoperative haemoglobin 12 g/dL or greater and 33.3% (18.6-51.0) in patients with preoperative haemoglobin less than 6 g/dL. The increase in risk of death associated with low preoperative haemoglobin was more pronounced in patients with cardiovascular disease than in patients without (interaction p < 0.03). The effect of blood loss on mortality was larger in patients with low preoperative haemoglobin than in those with a higher preoperative haemoglobin (interaction p < 0.001). The results were similar in analyses of postoperative haemoglobin and 30-day mortality or in-hospital morbidity.A low preoperative haemoglobin or a substantial operative blood loss increases the risk of death or serious morbidity more in patients with cardiovascular disease than in those without. Decisions about transfusion should take account of cardiovascular status and operative blood loss as well as the haemoglobin concentration.
Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care
Authors: S. Goodacre
Journal: BMJ (2004)

Objectives To measure the effectiveness and cost effectiveness of providing care in a chest pain observation unit compared with routine care for patients with acute, undifferentiated chest pain. Design Cluster randomised controlled trial, with 442 days randomised to the chest pain observation unit or routine care, and cost effectiveness analysis from a health service costing perspective. Setting The emergency department at the Northern General Hospital, Sheffield, United Kingdom. Participants 972 patients with acute, undifferentiated chest pain (479 attending on days when care was delivered in the chest pain observation unit, 493 on days of routine care) followed up until six months after initial attendance. Main outcome measures The proportion of participants admitted to hospital, the proportion with acute coronary syndrome sent home inappropriately, major adverse cardiac events over six months, health utility, hospital reattendance and readmission, and costs per patient to the health service. Results Use of a chest pain observation unit reduced the proportion of patients admitted from 54% to 37% (difference 17%, odds ratio 0.50, 95% confidence interval 0.39 to 0.65, P < 0.001) and the proportion discharged with acute coronary syndrome from 14% to 6% (8%, −7% to 23%, P = 0.264). Rates of cardiac event were unchanged. Care in the chest pain observation unit was associated with improved health utility during follow up (0.0137 quality adjusted life years gained, 95% confidence interval 0.0030 to 0.0254, P = 0.022) and a saving of £78 per patient (−£56 to £210, P = 0.252). Conclusions Care in a chest pain observation unit can improve outcomes and may reduce costs to the health service. It seems to be more effective and more cost effective than routine care.
Therapeutic Potential of Spleen Tyrosine Kinase Inhibition for Treating High-Risk Precursor B Cell Acute Lymphoblastic Leukemia
Authors: Tatiana Perova, Ildiko Grandal, Lauryl M. J. Nutter, Eniko Papp, Irina R. Matei, Joseph Beyene, Paul E. Kowalski, Johann K. Hitzler, Mark D. Minden, Cynthia J. Guidos, Jayne S. Danska
Journal: Science Translational Medicine (2014)

Intensified and central nervous system (CNS)-directed chemotherapy has improved outcomes for pediatric B cell acute lymphoblastic leukemia (B-ALL) but confers treatment-related morbidities. Moreover, many patients suffer relapses, underscoring the need to develop new molecular targeted B-ALL therapies. Using a mouse model, we show that leukemic B cells require pre-B cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) signaling in vivo for survival and proliferation. In diagnostic samples from human pediatric and adult B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small-molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated the growth of 69 B-ALL samples in vitro, including high-risk (HR) subtypes. Orally administered fostamatinib reduced heavy disease burden after xenotransplantation of HR B-ALL samples into immunodeficient mice and decreased leukemia dissemination into spleen, liver, kidneys, and the CNS of recipient mice. Thus, SYK activation sustains the growth of multiple HR B-ALL subtypes, suggesting that SYK inhibitors may improve outcomes for HR and relapsed B-ALL.
GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial
Authors: Stephanie Krause, Ulrike Landherr, Carl-David Agardh, Simone Hausmann, Katarina Link, Jesse M. Hansen, Kristian F. Lynch, Michael Powell, Jadwiga Furmaniak, Bernard Rees-Smith, Ezio Bonifacio, Anette G. Ziegler, Åke Lernmark, Peter Achenbach
Journal: Diabetes Care (2014)

Patients with latent autoimmune diabetes in adults (LADA) express autoantibodies against the 65-kDa isoform of GAD (GADA). Intervention with recombinant human GAD65 formulated with aluminium hydroxide (GAD-alum) given twice subcutaneously to LADA patients at intervals of 4 weeks was safe and did not compromise β-cell function in a Phase II clinical trial. GADA affinity has been shown to predict progression to type 1 diabetes. Here, we asked whether GADA affinity was affected by the GAD65 antigen-specific vaccination and/or associated with β-cell function in participants of this trial.GADA affinity was measured in sera of 46 LADA patients obtained prior to the first week and 20 weeks after the second injection with GAD-alum or placebo using competitive binding experiments with [125I]-labeled and unlabeled human GAD65.At baseline, GADA affinities ranged from 1.9 × 10(7) to 5.0 × 10(12) L/mol (median 2.8 × 10(10) L/mol) and were correlated with GADA titers (r = 0.47; P = 0.0009), fasting (r = -0.37; P = 0.01) and stimulated (r = -0.40; P = 0.006) C-peptide concentrations, and HbA1c (r = 0.39; P = 0.007). No significant changes in affinity were observed from baseline to week 24. Patients with GADA affinities in the lower first quartile (<4 × 10(9) L/mol) had better preserved fasting C-peptide concentrations at baseline than those with higher affinities (mean 1.02 vs. 0.66 nmol/L; P = 0.004) and retained higher concentrations over 30 months of follow-up (mean 1.26 vs. 0.62 nmol/L; P = 0.01).Intervention with GAD-alum in LADA patients had no effect on GADA affinity. Our data suggest that patients with low GADA affinity have a prolonged preservation of residual β-cell function.
Effect of Hypoxia on Myocardial Relaxation in Isometric Cat Papillary Muscle
Authors: William H. Frist, Igor Palacios, Wm. John Powell
Journal: Journal of Clinical Investigation (1978)

Myocardial relaxation is an important energy-dependent process. Hypoxia, unlike ischemia, has not been shown to impair myocardial relaxation. This difference may be because (a) the traditional index to assess isometric muscle relaxation (half time to relaxation or RT½) reflects both changes in developed tension as well as relaxation and (b) the relaxation process is highly sensitive to temperature and previous papillary muscle studies have been conducted under hypothermic conditions. The present study examines the effect of hypoxia on the relaxation process of 31 isometrically contracting kitten papillary muscles at hypothermic (29°C) and euthermic (38°C) conditions using RT½, the peak rate of tension fall (−dT/dt) and −dT/dt normalized for tension ([peak −dT/dt]/T and max [−dT/dt per T]). Hypoxia at 29°C resulted in a fall in RT½ from 278±11 (SEM) to 230±17 ms (P < 0.01) and no change in (peak −dT/dt)/T and max (−dT/dt per T). However, at 38°C, hypoxia impaired relaxation as reflected in a prolongation of RT½ from 101±6 to 126±8 ms (P < 0.01) in spite of a substantial fall in peak tension. Moreover, (peak −dT/dt)/T decreased from −15.4±0.7 to −11.0±0.8/s (P < 0.01) and max (−dT/dt per T) decreased from −25.1±1.8 to −13.8±0.9/s (P < 0.01). In conclusion, the present study demonstrates that hypoxia impairs the relaxation process of cardiac muscle.
TFAP2C Controls Hormone Response in Breast Cancer Cells through Multiple Pathways of Estrogen Signaling
Authors: George W. Woodfield, Annamarie D. Horan, Yizhen Chen, Ronald J. Weigel
Journal: Cancer Research (2007)

Abstract Breast cancers expressing estrogen receptor-α (ERα) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERα, other pathways of estrogen response have been identified including ERβ and GPR30, a membrane receptor for estrogen, and the key mechanisms regulating expression of ERs and hormone response remain controversial. Herein, we show that TFAP2C is the key regulator of hormone responsiveness in breast carcinoma cells through the control of multiple pathways of estrogen signaling. TFAP2C regulates the expression of ERα directly by binding to the ERα promoter and indirectly via regulation of FoxM1. In so doing, TFAP2C controls the expression of ERα target genes, including pS2, MYB, and RERG. Furthermore, TFAP2C controlled the expression of GPR30. In distinct contrast, TFAP2A, a related factor expressed in breast cancer, was not involved in estrogen-mediated pathways but regulated expression of genes controlling cell cycle arrest and apoptosis including p21CIP1 and IGFBP-3. Knockdown of TFAP2C abrogated the mitogenic response to estrogen exposure and decreased hormone-responsive tumor growth of breast cancer xenografts. We conclude that TFAP2C is a central control gene of hormone response and is a novel therapeutic target in the design of new drug treatments for breast cancer. [Cancer Res 2007;67(18):8439–43]
Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer
Authors: Richard R. Love, Adriano V. Laudico, Nguyen Van Dinh, D. Craig Allred, Gemma B. Uy, Le Hong Quang, Jonathan Disraeli S. Salvador, Stephen Sixto S. Siguan, Maria Rica Mirasol-Lumague, Nguyen Dinh Tung, Noureddine Benjaafar, Narciso S. Navarro, Tran Tu Quy, Arturo S. De La Peña, Rodney B. Dofitas, Orlino C. Bisquera, Nguyen Dieu Linh, Ta Van To, Gregory S. Young, Erinn M. Hade, David Jarjoura
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes.
Effect of ethanol on the synthesis and secretion of hepatic secretory glycoproteins and albumin
Authors: Dean J. Tuma, Richard B. Jennett, Michael F. Sorrell
Journal: Hepatology (1981)

The effects of ethanol on the synthesis and secretion of serum glycoproteins and albumin, a nonglycosylated protein, were studied in rat liver slices. Serum glycoproteins and albumin were determined by immunoprecipitation from either the incubation medium or from the washed slices. When ethanol (10 mM) was present in the incubation medium, [14C]glucosamine incorporation in secretory glycoproteins was decreased. This inhibitory effect was, however, much greater in the secretory proteins released into the medium than in those retained in the liver slices. Similar inhibitions by ethanol were also observed when leucine or valine were used as a label for either total export proteins or albumin. Since ethanol impaired protein synthesis, and inhibitor of protein synthesis, cycloheximide, was used so that both the control and ethanol-treated slices had identical pools of protein acceptors available for glycosylation. When cycloheximide alone was added to the slices, glucosamine radioactivity of secretory glycoproteins was equally reduced in both the medium and the liver. When cycloheximide and ethanol were both present, decreased appearance of glucosamine-labeled proteins in the medium was observed when compared to the slices containing cycloheximide alone; however, radioactivity of secretory glycoproteins retained in the liver was elevated. Ethanol also decreased the appearance of fucose-labeled glycoproteins in the medium without altering fucose incorporation into the total pool of secretory glycoproteins. The effects of ethanol on hepatic protein secretion independent of its effect on synthesis were further determined by prelabeling proteins with either [14C]leucine or [14C]fucose. Ethanol impaired the secretion of these prelabeled proteins into the medium. The results of this study show that ethanol impairs both the synthesis and secretion of secretory glycoproteins and albumin.
Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.
Authors: D E Goldberg, A F Slater, R Beavis, B Chait, A Cerami, G B Henderson
Journal: The Journal of Experimental Medicine (1991)

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.
Severe polyneuropathy complicating active Crohn's disease: rapid response to Infliximab
Authors: S Rodino
Journal: Gut (2003)

Caution with the use of cyclosporin in pregnancyWe read the article by Alstead and Nelson-Piercy with great interest. 1 We report a case (submitted for publication) of a woman with fulminant ulcerative colitis in the 29th week of pregnancy.Her disease was refractory to steroids, but she refused to have cyclosporin whilst pregnant.She therefore underwent an emergency Caesarean section and was given intravenous cyclosporin post-operatively.After 48 hours of treatment she developed severe hypertension with hypertensive encephalopathy and seizures.Although cyclosporin has been considered to be safe for both mother and foetus, we would like to highlight concerns that it is associated with potentially life threatening side effects.As a result, patients must be counselled thoroughly about the potential morbidity associated with this treatment and monitored closely.We agree with Dr Alstead in that cyclosporin should be used with extreme caution in pregnancy and the postnatal period.
Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia
Authors: J.Y. Petit, U. Veronesi, R. Orecchia, G. Curigliano, P.C. Rey, E. Botteri, N. Rotmensz, V. Lohsiriwat, M. Cassilha Kneubil, M. Rietjens
Journal: Annals of Oncology (2012)
Tubular Expression of KIM-1 Does not Predict Delayed Function After Transplantation
Authors: Bernd Schröppel, Bernd Krüger, Liron Walsh, Melissa Yeung, Shay Harris, Krista Garrison, Jonathan Himmelfarb, Susan M. Lerner, Jonathan S. Bromberg, Ping L. Zhang, Joseph V. Bonventre, Zhu Wang, Alton B. Farris, Robert B. Colvin, Barbara T. Murphy, John P. Vella
Journal: Journal of the American Society of Nephrology (2009)

Injured epithelial cells of the proximal tubule upregulate the glycoprotein kidney injury molecule 1 (KIM-1), suggesting its potential as a biomarker of incipient kidney allograft injury. It is unknown whether KIM-1 expression changes in kidney allografts with delayed graft function (DGF), which often follows ischemia-reperfusion injury. Here, we prospectively measured KIM-1 RNA and protein expression in preperfusion biopsies of 30 living- and 85 deceased-donor kidneys and correlated the results with histologic and clinical outcomes after transplantation. We detected KIM-1 expression in 62% of deceased-donor kidneys and only 13% of living-donor kidneys (P < 0.0001). The level of KIM-1 expression before reperfusion correlated inversely with renal function at the time of procurement and correlated directly with the degree of interstitial fibrosis. Surprising, however, we did not detect a significant correlation between KIM-1 staining intensity and the occurrence of DGF. Our findings are consistent with a role for KIM-1 as an early indicator of tubular injury but do not support tissue KIM-1 measurement before transplantation to identify kidneys at risk for DGF.