tbuckley/cabot-search huggingface dataset:
Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer
Authors: Joseph A. Sparano, Fengmin Zhao, Silvana Martino, Jennifer A. Ligibel, Edith A. Perez, Tom Saphner, Antonio C. Wolff, George W. Sledge, William C. Wood, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2015)

To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome.A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided.When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor-positive, human epidermal growth factor receptor 2-nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death.Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor-positive disease.
IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells
Authors: Simone Magagnin Wajner, Iuri Martin Goemann, Ana Laura Bueno, P. Reed Larsen, Ana Luiza Maia
Journal: Journal of Clinical Investigation (2011)

Nonthyroidal illness syndrome (NTIS) is a state of low serum 3,5,3′ triiodothyronine (T3) that occurs in chronically ill patients; the degree of reduction in T3 is associated with overall prognosis and survival. Iodothyronine deiodinases are enzymes that catalyze iodine removal from thyroid hormones; type I and II deiodinase (D1 and D2, respectively) convert the prohormone thyroxine T4 to active T3, whereas the type III enzyme (D3) inactivates T4 and T3. Increased production of cytokines, including IL-6, is a hallmark of the acute phase of NTIS, but the role of cytokines in altered thyroid hormone metabolism is poorly understood. Here, we measured the effect of IL-6 on both endogenous cofactor–mediated and dithiothreitol-stimulated (DTT-stimulated) cell sonicate deiodinase activities in human cell lines. Active T3 generation by D1 and D2 in intact cells was suppressed by IL-6, despite an increase in sonicate deiodinases (and mRNAs). N-acetyl-cysteine (NAC), an antioxidant that restores intracellular glutathione (GSH) concentrations, prevented the IL-6–induced inhibitory effect on D1- and D2-mediated T3 production, which suggests that IL-6 might function by depleting an intracellular thiol cofactor, perhaps GSH. In contrast, IL-6 stimulated endogenous D3–mediated inactivation of T3. Taken together, these results identify a single pathway by which IL-6–induced oxidative stress can reduce D1- and D2-mediated T4-to-T3 conversion as well as increasing D3-mediated T3 (and T4) inactivation, thus mimicking events during illness.
Obstruction in the Rectum Caused by a Carcinomatous Tumour; Successfully Relieved by Lumbar Colotomy
Authors: T. B. Curling
Journal: BMJ (1863)

cepting his sight, since the variola.He had never been vaccinated.He had brown hair, and grey irides.It was twenty years since the small-pox.He was a thin, pale man.The irides were of good lustre.The pupils dilated widely with atropine.The lens, humours, etc., were quite clear.The ftindus oscillated in such constant motion, shaking like the head in par- alysis aaitans, that it was difficult to focus any part.Voluntary effort increased rather than diminished this; ,and when he was told to fix his eye on any object the fundus only shook the more.The optic discs in both
Catatonia: A window into the cerebral underpinnings of will
Authors: Ricardo de Oliveira-Souza, Jorge Moll, Fátima Azevedo Ignácio, Paul J. Eslingerc
Journal: Behavioral and Brain Sciences (2002)

The will is one of the three pillars of the trilogy of mind that has pervaded Western thought for millennia, the other two being affectivity and cognition (Hilgard 1980). In the past century, the concept of will was imperceptibly replaced by the cognitive-oriented behavioral qualifiers “voluntary,” “goal-directed,” “purposive,” and “executive” (Tranel et al. 1994), and has lost much of its heuristic merits, which are related to the notion of “human autonomy” (Lhermitte 1986). We view catatonia as the clinical expression of impairment of the brain mechanisms that promote human will. Catatonia is to the brain systems engaged in will, as coma is to the reticular ascending systems that promote sleep and wakefulness (Plum 1991).
Differential myocardial abundance of collagen type I and type III mRNA in dilated cardiomyopathy: effects of myocardial inflammation
Authors: Matthias Pauschinger, Andrea Doerner, Andrew Remppis, Roman Tannhäuser, Uwe Kühl, Heinz-Peter Schultheiss
Journal: Cardiovascular Research (1998)

Objective: The collagen subtypes I (Col I) and III (Col III) are essential components of the cardiac extracellular matrix (ECM) maintaining the functional integrity of the heart. Histological, immunohistological, and biochemical studies, however, demonstrate characteristical changes of the ECM in dilated cardiomyopathy, myocarditis, ischemic cardiomyopathy, and hypertensive heart disease. Methods: In order to investigate possible effects of inflammatory processes on mRNA abundance of Col I and Col III, we examined 24 patients with the presumptive clinical diagnosis of dilated cardiomyopathy (EF=30±11%). 12 Patients were classified as idiopathic dilated cardiomyopathy without any evidence of myocardial inflammation; the remaining 12 patients were classified as inflammatory cardiomyopathy due to the immunohistologically documented inflammatory myocardial process. Results: Quantification of reverse transcription polymerase chain reaction (RT–PCR) products revealed significant differences as to the mRNA abundance ratio Col III/Col I between subgroups of patients with inflammatory cardiomyopathy (1.16±0.18) and idiopathic dilated cardiomyopathy (2.77±0.65) regardless of left ventricular dysfunction (p≤0.05). Conclusion: It is not yet known, whether different Col III/Col I ratios differentially influence diastolic compliance. Our data suggest that inflammatory mechanisms seen in inflammatory cardiomyopathy influence the mRNA abundance of collagen subtypes I and III.
Adenosine deaminase inhibition augments interstitial adenosine but does not attenuate myocardial infarction
Authors: P. H Silva, D. Dillon, D. G. Van Wylen
Journal: Cardiovascular Research (1995)

The objectives were to determine the effects of the adenosine deaminase inhibitor pentostatin (deoxycoformycin) on interstitial fluid (ISF) adenosine before, during, and after myocardial ischaemia and to ascertain whether augmented endogenous ISF adenosine reduces myocardial infarction.Untreated anaesthetised dogs (n = 11) were compared to dogs treated with intravenous pentostatin 30 min before ischaemia (0.2 mg.kg-1; n = 11). The changes in ISF adenosine, adenosine metabolites, and lactate were assessed by cardiac microdialysis, using dialysate concentrations as indices of ISF levels. Both groups were exposed to 60 min of regional myocardial ischaemia followed by 3 h of reperfusion.Although ISF adenosine increased during ischaemia in untreated animals, inosine and hypoxanthine were the predominant purine metabolites which accumulated in the ISF. Pentostatin increased dialysate adenosine 3.5-fold before ischaemia, resulted in a sustained and pronounced augmentation of adenosine during ischaemia, and maintained the raised ISF adenosine during early reperfusion. However, the augmentation of ISF adenosine was not associated with a reduction in infarct size [untreated = 33.3(SEM 4.8)% of the area at risk; pentostatin treated = 35.6(4.6)% of the area at risk], nor did pentostatin alter the ischaemia induced increase in ISF lactate. Plasma adenosine, as measured by a microdialysis probe in the femoral artery, increased in pentostatin treated animals upon reperfusion, leading to systemic hypotension, increased blood flow in the non-ischaemic region, and an attenuated reactive hyperaemia in the ischaemic region.Although inhibition of adenosine deaminase effectively enhances ISF adenosine before and during ischaemia, the increase before ischaemia does not "precondition" the myocardium, nor does the augmentation of adenosine during and after ischaemia attenuate necrosis in this model of ischaemia. Therefore, the enhancement of ISF adenosine to the extent provided by adenosine deaminase inhibition alone is not sufficient to protect the heart in the way seen with ischaemic preconditioning.
Discontinuation of<i>Mycobacterium avium</i>Complex Prophylaxis in Patients with Antiretroviral Therapy–Induced Increases in CD4<sup>+</sup>Cell Count
Authors: J. S. Currier, P. L. Williams, S. L. Koletar, S. E. Cohn, R. L. Murphy, A. E. Heald, R. Hafner, E. L. Bassily, H. M. Lederman, C. Knirsch, C. A. Benson, H. Valdez, J. A. Aberg, J. A. McCutchan
Journal: Annals of Internal Medicine (2000)

Background: Patients infected with HIV who experience increases in CD4+ cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain. Objective: To compare the rate of M. avium complex infection in patients with increased CD4+ cell counts who receive azithromycin and those receiving placebo. Design: Randomized, double-blind, placebo-controlled trial. Setting: 29 university-based clinical centers in the United States. Participants: 643 HIV-1–infected patients with a previous CD4+ cell count less than 0.05 × 109 cells/L and a sustained increase to greater than 0.10 × 109 cells/L during antiretroviral therapy. Intervention: Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322). Measurements: Mycobacterium avium complex cultures, CD4+ cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals. Results: During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, −0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). Conclusions: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4+ cell count while receiving antiretroviral therapy.
Lung infections bullet 4: Pathogenesis of lower respiratory tract infections due to Chlamydia, Mycoplasma, Legionella and viruses
Authors: P. Andersen
Journal: Thorax (1998)

Acute infection of the lower respiratory tract comprises bronchitis, bronchiolitis, and pneumonia. From a clinical point of view it may be difficult to distinguish these disease entities and one infection may progress into another. The most common pathogens causing these infections are the primary respiratory viruses (respiratory syncytial virus (RSV), influenza virus, adenoviruses, parainfluenza virus, and rhinovirus1 2), Mycoplasma pneumoniae ,3 and Chlamydia species.4-6 Legionella may cause pneumonia and non-pneumonic upper respiratory tract infection and approximately 85% of c ases are caused by L pneumophila . Long lasting sequelae such as bronchiectasis, lung fibrosis, and decreased lung function are seen after lower respiratory tract infections7-10 and it has been debated whether respiratory tract infection can cause chronic bronchial asthma.6 11-13 

Acute bronchitis is an inflammatory condition of the bronchi often caused by infectious agents, although in many cases no aetiology can be established.14 15 It shares many pathological and clinical features with bronchiolitis, and the same agents may induce both conditions. Most cases of acute bronchitis of known aetiology are due to respiratory viruses such as influenza virus, adenovirus, RSV, rhinovirus, and coronavirus,1 2 16 and a few are caused by M pneumoniae , Bordetella pertussis and C pneumoniae .4 5 15 17 Legionella infections limited to the bronchial tree are not described.

### ADHERENCE OF PATHOGENS

The pathogenesis has not been studied for all agents, but the transmission of disease is thought to occur through droplet spread from an infected person. After inhalation the infectious agent may adhere to different receptors such as acid containing glycoproteins or the adhesion molecule ICAM-1 on respiratory epithelial cells.18 19 The infectious chlamydial particle is the elementary body that attaches itself to and enters a susceptible cell where it changes to the larger metabolically active reticulate body.20 …
A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study
Authors: P. Vici, M. Brandi, F. Giotta, P. Foggi, F. Schittulli, L. Di Lauro, N. Gebbia, B. Massidda, G. Filippelli, D. Giannarelli, A. Di Benedetto, M. Mottolese, G. Colucci, M. Lopez
Journal: Annals of Oncology (2011)
Psychological adjustment in parents of young children with atopic dermatitis: which factors predict parental quality of life?
Authors: P. Warschburger, H.TH. Buchholz, F. Petermann
Journal: British Journal of Dermatology (2004)

Background Bringing up children with atopic dermatitis (AD) is widely perceived as being stressful because parenting demands considerable time and energy. There have been only a few studies to assess the extent of problems experienced by the parents. Objective To assess the psychosocial well‐being of parents caring for a young child with AD and to examine the relationship between parental quality of life and disease‐related and sociodemographic variables. Methods One hundred and eighty‐seven parents of young children with AD attending an inpatient rehabilitation clinic participated in the study. At admission, parents completed a set of questionnaires (assessing health‐related quality of life, coping with the disease, family functioning). Dermatologists assessed disease severity using the severity scoring of AD index (SCORAD). Results In general, parents cope well with their situation. Compared with normal values, high rates of psychological distress were observed in a subsample of parents of children with AD. Parents of children with a higher severity of disease reported a significantly higher impact on family functioning, a greater financial burden and a higher level of disease management. Parental disease management could be predicted by the familial situation, their personal well‐being and the severity of disease of their child. Differences attributed to their child's gender or age were not observed. Conclusions Childhood AD has a profound impact on the emotional and social well‐being of many of the parents. The results underline the importance of psychological treatment approaches designed to increase parental well‐being and ability to cope with stress and social strain.
Respiratory findings of acromegalic patients
Authors: Muhammed Emin Akkoyunlu, Fatmanur Karaköse, Mahmut Muzaffer Ilhan, Levent Kart, Hatice Ozcelik, Mehmet Bayram, Murat Sezer, Ertugrul Tasan
Journal: European Respiratory Journal (2012)

Acromegaly results from the long-term hypersecretion of growth hormone (GH) and elevation of levels of its peripheral mediator insulin-like growth factor-1.Acromegaly is known to signicantly increase mortality rate. Cardiovascular diseases are the most common causes of death in acromegalic patients. Moreover acromegalic patients with cardiac hypertrophy have a decreased cardiopulmonary performance during exercise as compared to normal subjects. The aim of our study was to assess pulmonary functions and the cardiopulmonary response to exercise in acromegaly. Ten patients who were followed by endocrinology department outpatients clinic were enrolled to study. Disease activity was evaluated by growth hormone levels. All the patients were evaluated by the body measurements, pulmonary function tests, body plethismography results. CPETs of the patients were performed. Ten patients(2 Male, 8 Female) were enrolled to study. Two of them were new diagnosed active acromegaly and 8 of them were under treatment. Mean age was 37.8± 10,5. Two patients were evaluated for pulmonary function for the study before treatment while they were active disease duration. All the patient9s FEV/FVC ratio were greater than %70 (Mean: 80.7±8,8). All the TLC values of the patients were nearly upper limit of normal.When the CPETs were performed, 2 patients whose active disease test were ended because of the early arrhythmia and hipertension. None of the patients could reach maximal exercise capacity because of the muscular fatique and all the patients VO2 max were reduced.Non invasive CPET results were compatible with poor effort.
Introduction of a Quality Management System and Outcome After Hematopoietic Stem-Cell Transplantation
Authors: Alois Gratwohl, Ronald Brand, Dietger Niederwieser, Helen Baldomero, Christian Chabannon, Jan Cornelissen, Theo de Witte, Per Ljungman, Fiona McDonald, Eoin McGrath, Jakob Passweg, Christina Peters, Vanderson Rocha, Ineke Slaper-Cortenbach, Anna Sureda, Andre Tichelli, Jane Apperley
Journal: Journal of Clinical Oncology (2011)

A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We therefore tested the hypothesis that the introduction of JACIE improved patient survival.Data on 41,623 allogeneic (39%) and 66,281 autologous (61%) HSCTs for an acquired hematologic disorder performed between 1999 and 2007 by 421 teams in Europe were used to assess the outcomes of patients who received a transplantation at baseline (> 3 years before application or no application), during preparation (3 years before application), during application (time from application to accreditation), and after JACIE accreditation. The analysis was clustered by team and stratified for year of HSCT, donor type, disease, conditioning, and gross national income per capita of the respective country. Patient's risks were adjusted for by their European Group for Blood and Marrow Transplantation score.Patient outcome was systematically better when the transplantation center was at a more advanced phase of JACIE accreditation, independent of year of transplantation and other risk factors. Improvement was robust as quantified for relapse-free survival after allogeneic HSCT compared with baseline by a hazard ratio (HR) of 0.96 (95% CI, 0.90 to 1.03; P = .22) for preparation, 0.95 (95% CI, 0.88 to 1.03; P = .20) for application, and 0.86 (95% CI, 0.78 to 0.95; P = .01) for the accreditation (test for trend P = .01). Improvement from baseline was similar after autologous HSCT (HR for accreditation, 0.83; 95% CI, 0.74 to 0.93; P < .01).Even with all the limitations of an observational study, these findings support the hypothesis that introduction of a comprehensive clinical quality management system is associated with improved outcome of patients after HSCT.
Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect
Authors: Michael Milyavsky, Igor Shats, Alina Cholostoy, Ran Brosh, Yosef Buganim, Lilach Weisz, Ira Kogan, Merav Cohen, Maria Shatz, Shalom Madar, Eyal Kalo, Naomi Goldfinger, Jun Yuan, Shulamit Ron, Karen MacKenzie, Amir Eden, Varda Rotter
Journal: Cancer Cell (2007)
Sphingosine-1-Phosphate Protects Proliferating Endothelial Cells from Ceramide-Induced Apoptosis but not from DNA Damage–Induced Mitotic Death
Authors: Stéphanie Bonnaud, Colin Niaudet, Géraldine Pottier, Marie-Hélène Gaugler, Julie Millour, Jacques Barbet, Laure Sabatier, François Paris
Journal: Cancer Research (2007)

Abstract Because of the central role of the endothelium in tissue homeostasis, protecting the vasculature from radiation-induced death is a major concern in tissue radioprotection. Premitotic apoptosis and mitotic death are two prevalent cell death pathways induced by ionizing radiation. Endothelial cells undergo apoptosis after radiation through generation of the sphingolipid ceramide. However, if mitotic death is known as the established radiation-induced death pathway for cycling eukaryotic cells, direct involvement of mitotic death in proliferating endothelial radiosensitivity has not been clearly shown. In this study, we proved that proliferating human microvascular endothelial cells (HMEC-1) undergo two waves of death after exposure to 15 Gy radiation: an early premitotic apoptosis dependent on ceramide generation and a delayed DNA damage–induced mitotic death. The fact that sphingosine-1-phosphate (S1P), a ceramide antagonist, protects HMEC-1 only from membrane-dependent apoptosis but not from DNA damage–induced mitotic death proves the independence of the two pathways. Furthermore, adding nocodazole, a mitotic inhibitor, to S1P affected both cell death mechanisms and fully prevented radiation-induced death. If our results fit with the standard model in which S1P signaling inhibits ceramide-mediated apoptosis induced by antitumor treatments, such as radiotherapy, they exclude, for the first time, a significant role of S1P-induced molecular survival pathway against mitotic death. Discrimination between ceramide-mediated apoptosis and DNA damage–induced mitotic death may give the opportunity to define a new class of radioprotectors for normal tissues in which quiescent endothelium represents the most sensitive target, while excluding malignant tumor containing proproliferating angiogenic endothelial cells that are sensitive to mitotic death. [Cancer Res 2007;67(4):1803–11]
The Binding of Cations by Chondroitin Sulfate
Authors: Saul J. Farber, Maxwell Schubert
Journal: Journal of Clinical Investigation (1957)

Chondroitin sulfate, isolated from beef nasal cartilage, was prepared as the crystalline calcium salt by methods previously described (10).This calcium salt was con- verted to the sodium or potassium salt by the use of the sodium or potassium form of Dowex-50.Chondromucoprotein as the potassium salt and desulfated chondroitin sulfate as the methyl ester were prepared by methods described elsewhere (11, 12).For convenience these substances will be referred to as Na2ChS, KChS, or