tbuckley/cabot-search huggingface dataset:
Tuberculosis in prisons: anatomy of global neglect
Authors: J. O'Grady, M. Maeurer, R. Atun, I. Abubakar, P. Mwaba, M. Bates, N. Kapata, G. Ferrara, M. Hoelscher, A. Zumla
Journal: European Respiratory Journal (2011)

Infectious diseases can be transmitted readily within prisons due to close contact between prisoners. Tuberculosis (TB) and HIV/AIDS are two important causes of morbidity and mortality from infectious diseases worldwide [1, 2]; prisons have become reservoirs for these diseases in many settings. TB prevalence among prisoners worldwide can be up to 50 times higher than national averages [3, 4]. Prisons account for a substantial proportion of the TB burden in the USA [5] and TB in prisons poses a major problem in the rest of the world, especially in countries of the former Soviet Union [6, 7] and sub-Saharan Africa (SSA) [8, 9]. Co-infection with HIV in prisoners with active or latent TB is well documented [4, 10, 11] and this presents difficult diagnostic and management challenges to prison health systems.

Apart from immunosuppression due to HIV, the high concentration of TB in prisons is often related to prisoner-associated risk factors such as poor nutrition, stress, drug and alcohol abuse, malnutrition, and associated chronic illnesses [3, 4, 9]. In addition, poor prison living conditions and mass incarceration [12] with inadequate ventilation, in such congregate settings, promote the transmission of Mycobacterium tuberculosis between prisoners. Such host and environmental risk factors facilitate new M. tuberculosis infections to progress to active disease, or may cause re-activation of latent TB in prisoners, the risk of which is at least an order of magnitude higher in prisons than in the general community [3]. Prisons serve as reservoirs of drug-resistant TB [10–12] which is increasingly being reported from Eastern European [6, 7, 10, 11, 13] and SSA prisons [8 …
A Phase II Study of Lapatinib in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Jonas A. de Souza, Darren W. Davis, Yujian Zhang, Arun Khattri, Tanguy Y. Seiwert, Serdal Aktolga, Stuart J. Wong, Mark F. Kozloff, Sreenivasa Nattam, Mark W. Lingen, Rangesh Kunnavakkam, Kerstin M. Stenson, Elizabeth A. Blair, Jeffrey Bozeman, Janet E. Dancey, Everett E. Vokes, Ezra E.W. Cohen
Journal: Clinical Cancer Research (2012)

This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy.Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue.Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects.
Nuclear Overexpression of p53 Protein in Transitional Cell Bladder Carcinoma: A Marker for Disease Progression
Authors: A. S. Sarkis, G. Dalbagni, C. Cordon-Cardo, Z.-F. Zhang, J. Sheinfeld, W. R. Fair, H. W. Herr, V. E. Reuter
Journal: JNCI Journal of the National Cancer Institute (1993)

Approximately one third of the patients with superficially infiltrative transitional cell (T1-TNM pathological staging system) bladder carcinoma who are treated with transurethral resection alone have disease progression. Despite precise pathologic staging and grading, clinical outcome in these patients is not predictable. Recent reports reveal that mutations of the p53 tumor suppressor gene (also known as TP53) occur commonly in bladder cancers.The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer.We examined deparaffinized tumor tissue specimens from transurethral resection in 43 patients with T1 bladder cancer who had not received adjuvant therapy. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody PAb1801, which stains both wild-type and mutant p53 proteins. The data were then correlated with the following conventional prognostic variables: age, sex, histologic presence of associated carcinoma in situ, and vascular invasion of tumor. Disease progression rates per 100 person-years were calculated.Median follow-up was 119 months. None of the urothelial and stromal cells from normal bladder specimens showed nuclear overexpression of p53 protein, but patients with T1 bladder tumors could be stratified into two groups with different patterns of staining for p53 protein. Eighteen patients (42%) had no more than 20% tumor cells with positive nuclear staining (group A), while the remaining 25 patients (58%) had 20% or more tumor cells with nuclear immunoreactivity (group B). Patients in group B had a significantly lower progression-free interval (P < .001). Disease progression rates were 20.5% per year for group B and 2.5% for group A.These results suggest that T1 bladder cancers exhibiting nuclear overexpression of p53 protein have a higher probability of disease progression. This study also suggests that p53 overexpression is an important prognostic factor in these patients and may be useful in selecting appropriate therapy.Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.
Relationship Between Activated Clotting Time and Ischemic or Hemorrhagic Complications
Authors: Sorin J. Brener, David J. Moliterno, A. Michael Lincoff, Steven R. Steinhubl, Kathy E. Wolski, Eric J. Topol
Journal: Circulation (2004)

Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal activated clotting time (ACT) for prevention of ischemic or hemorrhagic complications.We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with higher rates of events. The incidence of major or minor bleeding at 48 hours, by ACT quartile, was 2.9%, 3.5%, 3.8%, and 4.0%, respectively (P=0.04 for trend). In a multivariable logistic model with a spline transformation for ACT, there was a linear increase in risk of bleeding as the ACT approached 365 seconds (P=0.01), which leveled off beyond that value. Increasing UFH weight-indexed dose was independently associated with higher bleeding rates (OR 1.04 [1.02 to 1.07] for each 10 U/kg, P=0.001).In patients undergoing PCI with frequent stent and potent platelet inhibition use, ACT does not correlate with ischemic complications and has a modest association with bleeding complications, driven mainly by minor bleeding. Lower values do not appear to compromise efficacy while increasing safety.
Sleep and Its Disorders
Authors: A. N. Vgontzas, MD, A. Kales, MD
Journal: Annual Review of Medicine (1999)

Sleep disorders are very prevalent in the general population and are associated with significant medical, psychological, and social disturbances. Insomnia is the most common. When chronic, it usually reflects psychological/behavioral disturbances. Most insomniacs can be evaluated in an office setting, and a multidimensional approach is recommended, including sleep hygiene measures, psychotherapy, and medication. The parasomnias, including sleepwalking, night terrors, and nightmares, have benign implications in childhood but often reflect psychopathology or significant stress in adolescents and adults and organicity in the elderly. Excessive daytime sleepiness is typically the most frequent complaint and often reflects organic dysfunction. Narcolepsy and idiopathic hypersomnia are chronic brain disorders with an onset at a young age, whereas sleep apnea is more common in middle age and is associated with obesity and cardiovascular problems. Therapeutic naps, medications, and supportive therapy are recommended for narcolepsy and hypersomnia; continuous positive airway pressure, weight loss, surgery, and oral devices are the common treatments for sleep apnea.
Respiratory Muscles Performance Is Related to Oxygen Kinetics During Maximal Exercise and Early Recovery in Patients With Congestive Heart Failure
Authors: Serafim Nanas, John Nanas, Christos Kassiotis, George Alexopoulos, Anastasia Samakovli, John Kanakakis, Elias Tsolakis, Charis Roussos
Journal: Circulation (1999)

Dyspnea and fatigue are the main causes of exercise limitation in chronic heart failure (CHF) patients, whose peak inspiratory (Pi(max)) and expiratory pressures (Pe(max)) are often reduced. The aim of this study was to examine the relationship between respiratory muscle performance and oxygen kinetics.A total of 55 patients (NYHA class I to III) and 11 healthy subjects underwent cardiopulmonary exercise tests (CPET) on a treadmill. In 45 of the 55 patients (group I) and in healthy subjects (group II), pulmonary function tests, Pi(max), and Pe(max) were measured before and 10 minutes after exercise, and oxygen kinetics were monitored throughout and during early recovery from CPET. The first degree slope of oxygen consumption (VO(2)) decline during early recovery (VO(2)/t-slope) and VO(2) half-time (T(1/2)) were calculated. In 10 of the 55 CHF patients (group III), the measurements of Pi(max) were repeated 2, 5, and 10 minutes after CPET. A >10% reduction in Pi(max) after CPET (subgroup IA) was measured in 11 of 45 patients. In contrast, 34 of 45 CHF patients (subgroup IB) and all control subjects (group II) had Pi(max)>90% of baseline value after CPET. Subgroup IA patients had significantly lower peak VO(2) (13.5+/-2.1 versus 17.8+/-5.6 mL. kg(-1). min(-1); P<0.001), lower anaerobic thresholds (10.1+/-2.4 versus 13.6+/-4.6 mL. kg(-1). min(-1); P=0.003) and lower VO(2)/t-slopes (0.365+/-0.126 versus 0.519+/-0.227 L. min(-1). min(-1); P=0.008) than subgroup IB patients.The reduction of Pi(max) after exercise is associated with prolonged early recovery of oxygen kinetics, which may explain, in part, the role played by respiratory muscles in exercise intolerance in CHF patients.
Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents
Authors: A. Haegens, J. H. J. Vernooy, P. Heeringa, B. T. Mossman, E. F. M. Wouters
Journal: European Respiratory Journal (2007)

During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to characterise MPO internalisation by lung epithelial cells and to investigate the effect of MPO on oxidative stress, DNA damage and cytokine production by lung epithelial cells. Human alveolar and bronchial epithelial cells were stimulated with MPO, with or without priming the cells with pro-inflammatory stimuli. MPO protein was detected in the cell cytoplasm. Expression of haemoxygenase (HO)-1 and DNA strand breakage were determined. The production of interleukin (IL)-8 and -6 were measured. Analyses of MPO-stimulated cells demonstrated MPO presence in the cells. HO-1 expression was increased after MPO stimulation and increased further when cells were primed before MPO stimulation. MPO exposure also induced DNA strand breakage. Interestingly, MPO inhibited IL-8 production in bronchial, but not alveolar epithelium. In conclusion, alveolar and bronchial epithelial cells can internalise myeloperoxidase. Stimulation with myeloperoxidase increases haemoxygenase-1 expression and DNA strand breakage, suggesting cell damaging capacity of myeloperoxidase. In addition, myeloperoxidase inhibited interleukin-8 production by bronchial epithelial cells, indicating a negative feedback loop for neutrophil recruitment.
Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study
Authors: Farhad Ravandi, Ellen K Ritchie, Hamid Sayar, Jeffrey E Lancet, Michael D Craig, Norbert Vey, Stephen A Strickland, Gary J Schiller, Elias Jabbour, Harry P Erba, Arnaud Pigneux, Heinz-August Horst, Christian Recher, Virginia M Klimek, Jorge Cortes, Gail J Roboz, Olatoyosi Odenike, Xavier Thomas, Violaine Havelange, Johan Maertens, Hans-Günter Derigs, Michael Heuser, Lloyd Damon, Bayard L Powell, Gianluca Gaidano, Angelo-Michele Carella, Andrew Wei, Donna Hogge, Adam R Craig, Judith A Fox, Renee Ward, Jennifer A Smith, Gary Acton, Cyrus Mehta, Robert K Stuart, Hagop M Kantarjian
Journal: The Lancet Oncology (2015)
The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses TH2 differentiation
Authors: Makoto Kuwahara, Masakatsu Yamashita, Kenta Shinoda, Soichi Tofukuji, Atsushi Onodera, Ryo Shinnakasu, Shinichiro Motohashi, Hiroyuki Hosokawa, Damon Tumes, Chiaki Iwamura, Veronique Lefebvre, Toshinori Nakayama
Journal: Nature Immunology (2012)
A Prospective Study of Cigarette Smoking and Risk of Colorectal Adenoma and Colorectal Cancer in U.S. Women
Authors: E. Giovannucci, G. A. Colditz, M. J. Stampfer, D. Hunter, B. A. Rosner, W. C. Willett, F. E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article A Prospective Study of Cigarette Smoking and Risk of Colorectal Adenoma and Colorectal Cancer in U.S. Women Get access Edward Giovannucci, Edward Giovannucci Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Graham A. Colditz, Graham A. Colditz Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital; Department of Epidemiology, Harvard School of Public Health, Boston Search for other works by this author on: Oxford Academic PubMed Google Scholar Meir J. Stampfer, Meir J. Stampfer Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital; Department of Epidemiology, Harvard School of Public Health, Boston Search for other works by this author on: Oxford Academic PubMed Google Scholar David Hunter, David Hunter Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital; Department of Epidemiology, Harvard School of Public Health, Boston Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernard A. Rosner, Bernard A. Rosner Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter C. Willett, Walter C. Willett Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital; and Department of Epidemiology and Department of Nutrition, Harvard School of Public Health Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank E. Speizer Frank E. Speizer * Channing Laboratory, Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, Mass * Correspondence to: Edward Giovannucci, M.D., Channing Laboratory, 180 Longwood Ave., Boston, MA 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 3, 2 February 1994, Pages 192–199, https://doi.org/10.1093/jnci/86.3.192 Published: 02 February 1994 Article history Received: 12 July 1993 Revision received: 05 November 1993 Accepted: 15 November 1993 Published: 02 February 1994
Remarks on a Case of Epileptiform. Neuralgia Treated by Nerve-Stretching
Authors: T. G. Stewart
Journal: BMJ (1879)

0N returning from my autumn holiday, last year, I found among the patients under treatment, in my department in the Royal Infirmary, one who had been sent up from the surgical wards, suffering from epilepti- form neuralgia.He was a man of seventy years, and was employed as a station-master on one of the railways of Cumberland.There was no e';idence of hereditary predisposition to nervous disease; he was a temperate man, and his surroundings had been for the most part favour- able.In his railway work, he had naturally been somewhat exposed to the weather and a good deal to draughts, but never in any extraordinary degree.He had been perfectly healthy till the year I862, when he was seized with facial neuralgia.At first, the pain was of a burning cha- racter, and it gradually increased in severity, the paroxysms becoming, as time went on, more frequent and intense, until at last his life was almost intolerable to hinm; indeed, had it not been for the remissions during which the pain was easier, and the periods of immunity during which he was entirely well, it would have been so.These periods of
Prophylactic Urokinase in the Management of Long-Term Venous Access Devices in Children: A Children's Oncology Group Study
Authors: Peter W. Dillon, Gary R. Jones, Holly A. Bagnall-Reeb, Jonathon D. Buckley, Eugene S. Wiener, Gerald M. Haase
Journal: Journal of Clinical Oncology (2004)

Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions.This study was a prospective, randomized phase III multicenter trial conducted by the Children's Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection.Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P =.02), a longer time to first occlusive event (log-rank analysis, P =.006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P =.003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P =.05) and longer time to first infection (log-rank, P =.07), but the difference was significant only in tunneled catheters.Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration.
CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO
Authors: Marc Feldmann, Antony Basten
Journal: The Journal of Experimental Medicine (1972)

Tissue cultures with two compartments, separated by a cell impermeable nuclepore membrane (1 micro pore size), were used to investigate the mechanism of T-B lymphocyte cooperation. It was found that collaboration was as effective when the T and B lymphocyte populations were separated by the membrane as when they were mixed together. Critical tests were performed to verify that the membranes used were in fact cell impermeable. The specificity of the augmentation of the B cell response by various T cell populations was investigated. Only the response of B cells reactive to determinants on the same molecule as recognized by the T cells was augmented markedly. Specific activation of thymocytes by antigen was necessary for efficient collaboration across the membrane. The response of both unprimed and hapten-primed spleen cells was augmented by the T cell "factor" although, as expected, hapten-primed cells yielded greater responses. The T cell factor acted as efficiently if T cells were present or absent in the lower chamber. Thus the site of action of the T cell factor was not on other T cells, but was either on macrophages or the B cells themselves. The T cell-specific immunizing factor did not pass through dialysis membranes. The experiments reported here help rule out some of the possible theories of T-B cell collaboration. Clearly T-B cell contact was not necessary for successful cooperation to occur in this system. Possible theoretical interpretations of the results and their bearing on the detailed mechanism of T-B lymphocyte cooperation are discussed.
Time for a preventative strategy for TB in the UK: further evidence for new entrant screening in primary care
Authors: Onn Min Kon
Journal: Thorax (2014)

In 2012, a total of 8751 cases of TB in the UK were reported at a rate of 13.9 cases per 100 000—this figure is on the background of an increase over two decades in notifications and rates with no evidence of any reduction since peaking in 2005.1 This rise has been largely attributed to TB in the foreign-born, with 73% of all cases of TB being born in high-incidence countries. By contrast, the cases of TB in the UK born have been static over the last decade. Given that these cases are largely due to reactivation disease,2 a strategy of TB control purely based on detection and treatment of active pulmonary disease is unlikely to cause a significant change in these statistics. Hence, despite the change in TB screening to the port of exit, this is also unlikely to be effective given that the major burden of latent disease will not be detected by plain radiology.

A strategy of screening in the USA has been credited with the decreasing rates of TB there which is in stark contrast …