tbuckley/cabot-search huggingface dataset:
Accidental breaches of the doping regulations in sport: is there a need to improve the education of sportspeople? * Commentary
Authors: S J Somerville, M Lewis
Journal: British Journal of Sports Medicine (2005)

To identify educational needs of elite sportspeople with respect to the doping laws.A questionnaire survey of 196 Olympic level sportspeople from the fields of athletics, cycling, rowing, and sailing. The questionnaire addressed the date and source of the last doping educational update, the usefulness of current resources, sources of help, and possible ways of improving the system. The questionnaire also sought to estimate the use of nutritional supplements in these sports.Seventy four (38%) athletes responded to the questionnaire. Over 90% of responders had received a doping educational update in the last six months, and most agreed with the statement "I have received the information I need to avoid getting into trouble with the doping laws". Despite this, more than half of responders agreed with the statements "I should receive reminders more often" and "The authorities should do more to educate sportspeople". In addition, there were four people who admitted taking a banned substance by accident. Forty one (55%) reported taking supplements. The team doctor was the most popular source if information on a substance or product was required, with 62% and 66% of subjects stating that they would contact their team doctor when based in the United Kingdom and abroad respectively. The UK Sports website was often suggested in relation to ways of improving knowledge.There is a need to alter the educational process, particularly with respect to contingency planning for minor illness. The use of internet based resources for up to date information about banned substances needs to be promoted, and access to the internet improved. The educational needs of team doctors with respect to the doping laws need to be assessed.
Can Serum β-Hydroxybutyrate Be Used to Diagnose Diabetic Ketoacidosis?
Authors: Mae Sheikh-Ali, Brad S. Karon, Ananda Basu, Yogish C. Kudva, Lisa A. Muller, Jia Xu, W. Frederick Schwenk, John M. Miles
Journal: Diabetes Care (2008)

OBJECTIVE—Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO3] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA. RESEARCH DESIGN AND METHODS—A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum β-hydroxybutyrate (βOHB) that corresponds to a HCO3 level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission βOHB and HCO3 values were recorded from 466 encounters, 129 in children and 337 in adults. RESULTS—A HCO3 level of 18 mEq/l corresponded with βOHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold βOHB values to define DKA, there was substantial discordance (∼≥20%) between βOHB and conventional diagnostic criteria using HCO3, pH, and glucose. In patients with DKA, there was no correlation between HCO3 and glucose levels on admission and a significant but weak correlation between βOHB and glucose levels (P &amp;lt; 0.001). CONCLUSIONS—Where available, serum βOHB levels ≥3.0 and ≥3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO3 level for that purpose. The marked variability in the relationship between βOHB and HCO3 is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis.
HIV-1 Directly Kills CD4+ T Cells by a Fas-independent Mechanism
Authors: Rajesh T. Gandhi, Benjamin K. Chen, Stephen E. Straus, Janet K. Dale, Michael J. Lenardo, David Baltimore
Journal: The Journal of Experimental Medicine (1998)

The mechanism by which HIV-1 induces CD4+ T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected bystander cells. This question was studied using a reporter virus system in which infected cells are marked with the cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4+ T cells and induction of apoptosis. The great majority of HIV-induced T cell death in vitro involves direct loss of infected cells rather than indirect effects on uninfected bystander cells. Because of its proposed role in HIV-induced cell death, we also examined the Fas (CD95/Apo1) pathway in killing of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells in the presence of a caspase inhibitor that completely blocks Fas-mediated apoptosis. HIV-1 also depletes CD4+ T cells in PBMCs from patients who have a genetically defective Fas pathway. These results suggest that HIV-1 induces direct apoptosis of infected cells and kills T cells by a Fas-independent mechanism.
Incidence of Dementia and Alzheimer Disease in 2 Communities
Authors: Hugh C. Hendrie, Adesola Ogunniyi, Kathleen S. Hall, Olusegun Baiyewu, Frederick W. Unverzagt, Oye Gureje, Sujuan Gao, Rebecca M. Evans, A. O. Ogunseyinde, A. O. Adeyinka, Beverly Musick, Siu L. Hui
Journal: JAMA (2001)

ContextAlzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced.ObjectiveTo compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations.DesignThe Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance.Setting and ParticipantsA total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively.Main Outcome MeasuresIncident cases of dementia and AD in each of the 2 populations.ResultsThe age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval {CI}, 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]).ConclusionThis is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD.
Complement-mediated killing of schistosomula of Schistosoma mansoni by rat eosinophils in vitro.
Authors: F J Ramalho-Pinto, D J McLaren, S R Smithers
Journal: The Journal of Experimental Medicine (1978)

Eosinophils from the peritoneal cavity of normal rats, in the presence of fresh normal rat serum (NRS), adhered to schistosomula of Schistosoma mansoni in vitro and killed the majority of parasites within 18 h. The reaction differed from the previously described antibody-mediated eosinophil adherence to schistosomula which occurs in heat-inactivated immune rat serum (IRS) and where adherence is mediated through Fc receptors. Adherence of eosinophils in fresh NRS was shown to be due to the activation of complement at the schistosomular surface by the alternative pathway, and it was effected through C3 receptors. The ability of eosinophils to kill in Fc-mediated adherence. This enhancement of killer activity may be due to the generation by complement activation of eosinophil chemotactic factors which increase the concentration of cells at the target surface. It is suggested that eosinophil adherence mediated through complement activation could be the principla mechanism of destroying schistosomula in the host.
Full Coverage for Preventive Medications after Myocardial Infarction
Authors: Niteesh K. Choudhry, Jerry Avorn, Robert J. Glynn, Elliott M. Antman, Sebastian Schneeweiss, Michele Toscano, Lonny Reisman, Joaquim Fernandes, Claire Spettell, Joy L. Lee, Raisa Levin, Troyen Brennan, William H. Shrank
Journal: New England Journal of Medicine (2011)

Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes.
TISSUE FACTOR PATHWAY INHIBITOR AND THE REVISED THEORY OF COAGULATION
Authors: George J. Broze
Journal: Annual Review of Medicine (1995)

▪ Abstract Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma proteinase inhibitor that regulates tissue factor-induced coagulation. TFPI directly inhibits activated factor X and, in a factor Xa-dependent fashion, produces feedback inhibition of the factor VIIa/tissue factor catalytic complex. The properties of this rediscovered inhibitor appear, at least in part, to explain the clinical requirement for both the extrinsic and intrinsic pathways of the cascade and waterfall theories of blood clotting and have led to a reformulation of the coagulation mechanism. In the revised hypothesis, factor VIIa/tissue factor is responsible for the initiation of coagulation, but owing to TFPI-mediated inhibition, sustained hemostasis requires the persistent and amplified procoagulant action of intrinsic factors VIII, IX, and XI.
Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation
Authors: RV Blanden, IFC McKenzie, U Kees, RW Melvold, HI Kohn
Journal: The Journal of Experimental Medicine (1977)

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D') bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D') was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.
Chemotherapy for Breast Cancer During Pregnancy: An 18-Year Experience From Five London Teaching Hospitals
Authors: Alistair E. Ring, Ian E. Smith, Alison Jones, Catherine Shannon, Eleni Galani, Paul A. Ellis
Journal: Journal of Clinical Oncology (2005)

Purpose The rare association between breast cancer and pregnancy means that few oncologists gain an expertise in this area. In particular, there are few published data concerning the use of chemotherapy for breast cancer during pregnancy. In this retrospective case series, we describe the experiences of five hospitals in London, United Kingdom, and how they manage this condition. Patients and Methods Retrospective searches were performed at five London hospitals in order to identify women who received chemotherapy for breast cancer while pregnant. Results Twenty-eight women were identified who had received chemotherapy for breast cancer during pregnancy. Twenty-four women received adjuvant or neoadjuvant chemotherapy for early breast cancer, and four women received palliative chemotherapy for metastatic disease. A total of 116 cycles of chemotherapy were administered during pregnancy. Sixteen women were treated with anthracycline-based chemotherapy and 12 received cyclophosphamide, methotrexate, and fluorouracil. All but one of the women were treated after the first trimester. One spontaneous abortion occurred in the woman treated during her first trimester; otherwise, there were no serious adverse consequences for the mothers or neonates. Conclusion These data provide evidence that in terms of peripartum complications and immediate fetal outcome, chemotherapy can be safely administered to women during the second and third trimesters of pregnancy.
Effect of Timing of Vagal Stimulation on Heart Rate in the Dog
Authors: EUGENE DONG, BRUCE A. REITZ
Journal: Circulation Research (1970)

The effects of right vagus nerve stimulation on heart rate were examined in 16 dogs anesthetized with chloralose (60 mg/kg, iv) and urethane (600 mg/kg, iv) after a bilateral cervical vagotomy. Two protocols were followed. In the first, trains of 1, 3, or 5 stimuli, 2 msec each in duration, 10 to 15 v in magnitude, and separated by 10 msec were delivered at predetermined times after "P" wave onset as a single stimulation. In the second, the stimulation was carried out repetitively for 2 minutes at a predetermined frequency. Typically, in the first, the later in the cycle the stimulation occurred, the greater was the prolongation of the included cycle. With one stimulus in the stimulation, a typical P-P interval was 574 msec with a "P" to stimulation delay of 4 msec, and 620 msec when the "P" to stimulation delay was 200 msec. With five stimuli moving the stimulation through a range of 200 msec, the change in P-P interval was 150 msec. There was a functional dependence of the P-P cycle length on the time of arrival of the inhibitory pulse. The slope of this relationship is a function of the number of stimuli in the stimulation. With repetitive stimulation in the second protocol, there were zones wherein the heart rate synchronized to the vagal stimulation rate not only at the fundamental frequency but also at harmonics and subharmonics. This range of entrainment was also dependent upon the number of stimuli in the stimulation. The data suggest the possibility of phase shift as a mechanism for vagal regulation of heart rate.
Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis
Authors: L Padyukov
Journal: Annals of the Rheumatic Diseases (2003)

Rheumatoid arthritis (RA) is a genetically complex disease where the response to different treatments varies greatly between different patients. This is the case with the tumour necrosis factor (TNF) blocking agents, where 20-40% of patients have been described as non-responders. No predictive markers exist as yet for the prognosis of response.To analyse whether polymorphisms of several cytokine genes are associated with the responsiveness to TNF blockade with etanercept.123 patients with active RA were treated with etanercept and response rates were determined after three months using American College of Rheumatology (ACR)20 and disease activity score (DAS)28 response criteria. Genotyping was done for TNF (-308 TNFA), interleukin (IL)10 (-1087 IL10), transforming growth factor (TGF)beta1 (codon 25 TGFB1), and IL1 receptor antagonist (intron 2 IL1RN).24 patients (20%) were defined as non-responders owing to their failure to fulfil any of the ACR20 or DAS28 response criteria. None of the recorded alleles was alone significantly associated with responsiveness to treatment. However, a certain combination of alleles (-308 TNF1/TNF1 and -1087 G/G) was associated with good responsiveness to etanercept (p<0.05). In addition, a combination of alleles influencing interleukin 1 receptor antagonist (IL1Ra) and TGFbeta1 production (A2 allele for IL1RN and rare C allele in codon 25 of TGFB1 gene) was associated with non-responsiveness (p<0.05).Genetic polymorphisms, which may influence the balance of pro- and anti-inflammatory cytokines of relevance for the course of RA, are associated with clinical responsiveness to etanercept treatment.
PERK–Dependent Regulation of Ceramide Synthase 6 and Thioredoxin Play a Key Role in<i>mda</i>-7/IL-24–Induced Killing of Primary Human Glioblastoma Multiforme Cells
Authors: Adly Yacoub, Hossein A. Hamed, Jeremy Allegood, Clint Mitchell, Sarah Spiegel, Maciej S. Lesniak, Besim Ogretmen, Rupesh Dash, Devanand Sarkar, William C. Broaddus, Steven Grant, David T. Curiel, Paul B. Fisher, Paul Dent
Journal: Cancer Research (2010)

Abstract Melanoma differentiation associated gene-7(mda-7) encodes IL-24, a cytokine that can selectively trigger apoptosis in transformed cells. Recombinant mda-7 adenovirus (Ad.mda-7) effectively kills glioma cells, offering a novel gene therapy strategy to address deadly brain tumors. In this study, we defined the proximal mechanisms by which Ad-mda-7 kills glioma cells. Key factors implicated included activation of the endoplasmic reticulum stress kinase protein kinase R–like endoplasmic reticulum kinase (PERK), Ca++ elevation, ceramide generation and reactive oxygen species (ROS) production. PERK inhibition blocked ceramide or dihydroceramide generation, which were critical for Ca++ induction and subsequent ROS formation. Activation of autophagy and cell death relied upon ROS formation, the inhibition of which ablated Ad.mda-7–killing activity. In contrast, inhibiting TRX induced by Ad.MDA-7 enhanced tumor cytotoxicity and improved animal survival in an orthotopic tumor model. Our findings indicate that mda-7/IL-24 induces an endoplasmic reticulum stress response that triggers production of ceramide, Ca2+, and ROS, which in turn promote glioma cell autophagy and cell death. Cancer Res; 70(3); 1120–9
Transposition of a pericardial-derived vascular adipose flap for myocardial salvage after infarct
Authors: C. Galvez-Monton, C. Prat-Vidal, S. Roura, J. Farre, C. Soler-Botija, A. Llucia-Valldeperas, I. Diaz-Guemes, F. M. Sanchez-Margallo, A. Aris, A. Bayes-Genis
Journal: Cardiovascular Research (2011)

Coronary artery occlusion is associated with the risk of ventricular remodelling, heart failure, and cardiogenic shock. Novel strategies are sought to treat these ominous complications. We examined the effect of a pericardial-derived fat flap secured over an acute infarct caused by coronary occlusion. A novel intervention consisting of the pericardial isolation of a vascularized adipose flap and its transposition fully covering acute infarcted myocardium was developed in the swine model of coronary artery ligation (n= 52). Left ventricular (LV) ejection fraction and LV end-diastolic and end-systolic volumes were assessed using magnetic resonance imaging (MRI). Infarct size and gene expression analysis were performed on Day 6 and 1 month. Histological changes, collagen volume fraction (CVF), and vascular density were also evaluated on postmortem sections. One month after the intervention, a 18.8% increase in LV ejection fraction (P= 0.007), and significant reductions in LV end-systolic (P= 0.009) and LV end-diastolic volumes (P= 0.03) were found in treated animals compared with the control-MI group. At Day 6, histopathology confirmed a significant infarct size reduction (P= 0.018), the presence of vascular connections at the flap-myocardium interface, and less apoptosis in the infarct border zone compared with control animals (P< 0.001). Up-regulation of genes involved in cell cycle progression, cellular growth and proliferation, and angiogenesis were identified within the flap. Our results indicate that a vascular fat flap exerts beneficial effects on LV function and limits myocardial remodelling. Future studies must confirm whether these findings provide an alternative therapeutic approach for myocardial salvage after infarction.
High prevalence of vertebral deformities in COPD patients: relationship to disease severity
Authors: A Kjensli, J A Falch, M Ryg, T Blenk, G Armbrecht, L M Diep, I Ellingsen
Journal: European Respiratory Journal (2009)

Bone mineral density decreases with advancing chronic obstructive pulmonary disease (COPD) severity, but it is not known whether this is reflected in higher fracture rates. The present authors wanted to compare the prevalence of vertebral deformities in COPD patients with those in a population-based reference group to determine whether the number of deformities was related to the severity of COPD and how far the use of oral corticosteroids (OCS) influenced the prevalence of deformities. In the present cross-sectional study of 465 COPD patients and 462 controls, vertebral deformities were found in 31% of the COPD patients and 18% of the controls. In subjects who had never or sporadically used OCS, deformities were found in 29% of the COPD patients and 17% of the controls. In females, the average number of vertebral deformities was almost two-fold when COPD severity increased from Global Initiative of Chronic Obstructive Lung Disease stage II to III. In males, the use of OCS had a small but significant influence. Prevalence of vertebral deformities was significantly higher in chronic obstructive pulmonary disease patients than in the controls. In females, the average number of deformities was related to chronic obstructive pulmonary disease severity even after adjustment for other known risk factors. The difference between patients and controls remained significant even in those who never or sporadically used oral corticosteroids.