tbuckley/cabot-search huggingface dataset:
Practical management of sudden cardiac arrest on the football field
Authors: Efraim Benjamin Kramer, Martin Botha, Jonathan Drezner, Yasser Abdelrahman, Jiri Dvorak
Journal: British Journal of Sports Medicine (2012)

Sudden cardiac arrest (SCA) remains a tragic occurrence on the football field. The limits of preparticipation cardiovascular screening make it compulsory that prearranged emergency medical services be available at all football matches to immediately respond to any collapsed player. Management of SCA involves prompt recognition, immediate cardiopulmonary resuscitation (CPR) and early defibrillation. Any football player who collapses without contact with another player or obstacle should be regarded as being in SCA until proven otherwise. An automated external defibrillator (AED), or manual defibrillator if an AED is not available, should be immediately accessible on the field during competitions. This study presents guidelines for a practical and systematic approach to the management of SCA on the football field.
Respiratory diseases in pregnancy bullet 3: Tuberculosis in pregnancy and the puerperium
Authors: P Ormerod
Journal: Thorax (2001)

3 The cases of tuberculo- sis in all these ethnic minority groups have a very diVerent age distribution from those of UK origin, with a median age usually under 30 years compared with over 50 years in the white population. The increase in the number of patients with tuberculosis who become preg- nant is therefore due to the increasing pro- portion of women of child bearing age. Similar trends have been reported in the USA 45 and in most developed countries in Europe. In devel- oping countries the rise in tuberculosis is also predominantly aVecting the young, mainly the 15-44 age group, fuelled in sub-Saharan Africa by HIV co-infection. 6 This review considers aspects of tuberculosis in pregnancy and does not cover reduced fertility from genital tuber- culosis, although this is an important cause of infertility, especially in developing countries. 7
Signal requirements for the generation of CD4+ and CD8+ T-cell responses to human allogeneic microvascular endothelium.
Authors: R Pardi, J R Bender
Journal: Circulation Research (1991)

Microvascular endothelium has been implicated as a major target in the rejection of vascularized allografts. In an attempt to dissect the stepwise generation of the T-cell-mediated immune response to microvascular endothelial cells (ECs), we analyzed the requirements for the two major T-cell subsets, CD4+ and CD8+, in the triggering of proliferative and cytotoxic responses to allogeneic ECs in vitro. Results demonstrate that resting ECs are unable to stimulate a functional response by purified T, CD4+, and CD8+ cells in the absence of costimulatory signals. T cells and CD8+ cells develop both proliferative and cytotoxic anti-EC responses by the addition of as little as 2 units/ml interleukin-2, 10 units/ml interleukin-1, or irradiated monocytes autologous to the responder lymphocytes, whereas only autologous monocytes are capable of triggering CD4+ T-cell precursors to proliferate and become anti-EC-specific effector cytotoxic T lymphocytes. CD8+ cell-mediated anti-EC cytotoxicity is directed toward allogeneic major histocompatibility complex (MHC) class I determinants on ECs and involves recognition by the CD3/T-cell receptor complex and the CD8 molecule on the effector T cells. CD4+ cells can be driven to proliferate, produce interleukin-2, and become anti-EC-specific cytotoxic T lymphocytes despite the lack of detectable membrane MHC class II determinants on the target cells. Chloroquine inhibition experiments demonstrate that autologous monocytes/macrophages are required by CD4+ T-cell precursors for the processing of EC-derived alloantigens and their subsequent presentation in the context of self-MHC molecules. These results are in agreement with the adoptive transfer experiments in experimental allograft models and suggest that the coordinate engagement of cells of the CD4, CD8, and monocyte/macrophage series is more effective than the individual cell subsets in the
γ-Aminobutyric Acid Inhibits Cholangiocarcinoma Growth by Cyclic AMP–Dependent Regulation of the Protein Kinase A/Extracellular Signal-Regulated Kinase 1/2 Pathway
Authors: Giammarco Fava, Luca Marucci, Shannon Glaser, Heather Francis, Sharon De Morrow, Antonio Benedetti, Domenico Alvaro, Julie Venter, Cynthia Meininger, Tushar Patel, Silvia Taffetani, Marco Marzioni, Ryun Summers, Ramona Reichenbach, Gianfranco Alpini
Journal: Cancer Research (2005)

Abstract We studied the effect of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in the regulation of cholangiocarcinoma growth. We determined the in vitro effect of GABA on the proliferation of the cholangiocarcinoma cell lines (Mz-ChA-1, HuH-28, and TFK-1) and evaluated the intracellular pathways involved. The effect of GABA on migration of Mz-ChA-1 cells was also evaluated. In vivo, Mz-ChA-1 cells were s.c. injected in athymic mice, and the effects of GABA on tumor size, tumor cell proliferation, apoptosis, collagen quantity, and the expression of vascular endothelial growth factor-A (VEGF-A) and VEGF-C (cancer growth regulators) were measured after 82 days. GABA decreased in vitro cholangiocarcinoma growth in a time-dependent and dose-dependent manner, by both cyclic AMP/protein kinase A– and d-myo-inositol-1,4,5-thriphosphate/Ca2+-dependent pathways, leading to down-regulation of extracellular signal-regulated kinase 1/2 phosphorylation. Blocking of GABAA, GABAB, and GABAC receptors prevented GABA inhibition of cholangiocarcinoma proliferation. GABA inhibited Mz-ChA-1 cell migration and, in vivo, significantly decreased tumor volume, tumor cell proliferation, and VEGF-A/C expression whereas increasing apoptosis compared with controls. An increase in collagen was evident in GABA-treated tumors. GABA decreases biliary cancer proliferation and reduces the metastatic potential of cholangiocarcinoma. GABA may represent a therapeutic agent for patients affected by malignancies of the biliary tract. (Cancer Res 2005; 65(24): 11437-46)
Repeated sprint training in normobaric hypoxia
Authors: Harvey M Galvin, Karl Cooke, David P Sumners, Katya N Mileva, Joanna L Bowtell
Journal: British Journal of Sports Medicine (2013)

Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4±1.5 years, 1.83±0.07 m, 88.1±8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10×6 s, 30 s recovery) over 4 weeks in either hypoxia (13% F i O 2 ) or normoxia (21% F i O 2 ). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10×6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33±12%) than the normoxic group (14±10%, p&lt;0.05). During the 10×6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9±9%, normoxic (−0.3±8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.
Bronchoalveolar lavage findings in a patient with the organic dust toxic syndrome.
Authors: E Raymenants, M Demedts, B Nemery
Journal: Thorax (1990)

A previously healthy student developed the organic dust toxic syndrome after unloading a grain silo for one day. Bronchoalveolar lavage seven days later showed a total cell count six times normal with 70% lymphocytes. This suggests that the previously described acute neutrophil influx into the alveolar spaces in this syndrome is rapidly replaced by a lymphocyte dominated infiltration.
Cancer-Specific Mortality of Asian Americans Diagnosed With Cancer: A Nationwide Population-Based Assessment
Authors: Q.-D. Trinh, P. L. Nguyen, J. J. Leow, D. Dalela, G. F. Chao, B. A. Mahal, M. Nayak, M. Schmid, T. K. Choueiri, A. A. Aizer
Journal: JNCI Journal of the National Cancer Institute (2015)

Racial disparities in cancer survival outcomes have been primarily attributed to underlying biologic mechanisms and the quality of cancer care received. Because prior literature shows little difference exists in the socioeconomic status of non-Hispanic whites and Asian Americans, any difference in cancer survival is less likely to be attributable to inequalities of care. We sought to examine differences in cancer-specific survival between whites and Asian Americans. The Surveillance, Epidemiology, and End Results Program was used to identify patients with lung (n = 130 852 [16.9%]), breast (n = 313 977 [40.4%]), prostate (n = 166 529 [21.4%]), or colorectal (n = 165 140 [21.3%]) cancer (the three leading causes of cancer-related mortality within each sex) diagnosed between 1991 and 2007. Fine and Gray's competing risks regression compared the cancer-specific mortality (CSM) of eight Asian American groups (Chinese, Filipino, Hawaiian/Pacific Islander, Japanese, Korean, other Asian, South Asian [Indian/Pakistani], and Vietnamese) to non-Hispanic white patients. All P values were two-sided. In competing risks regression, the receipt of definitive treatment was an independent predictor of CSM (hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.35 to 0.40; HR = 0.55, 95% CI = 0.53 to 0.58; HR = 0.61, 95% CI = 0.60 to 0.62; and HR = 0.27, 95% CI = 0.25 to 0.29) for prostate, breast, lung, and colorectal cancers respectively, all P < .001). In adjusted analyses, most Asian subgroups (except Hawaiians and Koreans) had lower CSM relative to white patients, with hazard ratios ranging from 0.54 (95% CI = 0.38 to 0.78) to 0.88 (95% CI = 0.84 to 0.93) for Japanese patients with prostate and Chinese patients with lung cancer, respectively. Despite adjustment for potential confounders, including the receipt of definitive treatment and tumor characteristics, most Asian subgroups had better CSM than non-Hispanic white patients. These findings suggest that underlying genetic/biological differences, along with potential cultural variations, may impact survival in Asian American cancer patients.
Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival
Authors: C. M. Ohri, A. Shikotra, R. H. Green, D. A. Waller, P. Bradding
Journal: European Respiratory Journal (2008)

There is a marked survival advantage for patients with nonsmall cell lung cancer (NSCLC) expressing high numbers of macrophages in their tumour islets. The primary aim of the present study was to determine the immunological phenotype of NSCLC-associated macrophages. CD68 + macrophages expressing markers of a cytotoxic M1 phenotype or a noncytotoxic M2 phenotype were identified in the islets and stroma of surgically resected tumours from 20 patients with extended survival (median 92.7 months) and 20 with poor survival (median 7.7 months), using immunohistochemistry. The islet density of both M1 and M2 macrophages was markedly increased in extended compared with poor survival patients. In the extended survival group, M1 islet density was significantly increased compared with M2 density, 70% of islet macrophages were positive for M1 markers versus 38% for M2, and the islet:stromal ratio of M1 macrophages was markedly increased compared with M2. The 5-yr survival for patients with above and below median expression of M1 macrophages in the islets was &gt;75 and &lt;5%, respectively. Macrophages infiltrating the tumour islets in nonsmall cell lung cancer were predominantly of the M1 phenotype in patients with extended survival. The survival advantage conferred by islet macrophage infiltration may be related to their cytotoxic antitumour activity.
Common Carotid Artery Intima-Media Thickness and Brain Infarction
Authors: Pierre-Jean Touboul, Alexis Elbaz, Cornelia Koller, Christian Lucas, Valérie Adraï, François Chédru, Pierre Amarenco, for the GÉNIC Investigators
Journal: Circulation (2000)

Background —The use of intima-media thickness (IMT) as an outcome measure in observational studies and intervention trials relies on the view that it reflects early stages of atherosclerosis and cardiovascular risk. There is little knowledge concerning the relation between IMT and brain infarction (BI). Methods and Results —We investigated the relation of IMT with BI and its subtypes in 470 cases and 463 controls. Cases with BI proven by MRI were consecutively recruited and classified into subtypes by cause of BI. Controls were recruited among individuals hospitalized at the same institutions and matched for age, sex, and center. IMT was measured at the far wall of both common carotid arteries (CCA) using an automatic detection system. Adventitia-to-adventitia diameters and CCA-IMT were measured on transverse views; lumen diameter was computed using these measures. Mean (±SEM) CCA-IMT was higher in cases (0.797±0.006 mm) than in controls (0.735±0.006 mm; P &lt;0.0001). This difference remained after adjustment for lumen diameter and when analyses were restricted to subjects free of previous cardiovascular or cerebrovascular history. The difference in CCA-IMT between cases and controls was significant in the main subtypes. The risk of BI increased continuously with increasing CCA-IMT. The odds ratio per SD increase (0.150 mm) was 1.82 (95% confidence interval, 1.54 to 2.15); adjustment for cardiovascular risk factors slightly attenuated this relation (odds ratio, 1.73; 95% confidence interval, 1.45 to 2.07). Conclusions —An increased CCA-IMT was associated with BI, both overall and in the main subtypes. An increased IMT may help select patients at high risk for BI.
A fibrin based model for rheumatoid synovitis
Authors: O Sanchez-Pernaute
Journal: Annals of the Rheumatic Diseases (2003)

Intracavitary fibrin clots may initiate pannus formation and the immunopathology of RA. Two critical steps, probably host dependent, may determine the development of RA: an altered regulation of extravascular haemostasis or an aberrant reactivity of synovial fibroblasts to the adhered fibrin clots. Current treatments for RA target events downstream of fibrin deposition, perhaps agents acting at an earlier stage should be tried.
Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice.
Authors: M G von Herrath, T Dyrberg, M B Oldstone
Journal: Journal of Clinical Investigation (1996)

Oral administration of self-antigens has been proposed as a therapy to prevent and treat autoimmune diseases. Here we report that oral treatment with insulin prevents virus-induced insulin-dependent diabetes mellitus (IDDM) in a transgenic (tg) mouse model. Such mice express the viral nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter in their pancreatic beta cells and < 2% spontaneously develop diabetes. However, 2 mo after challenge with LCMV, IDDM occurs in > 95% of tg mice but not in controls. Oral treatment with 1 mg of insulin twice per week for 2 mo starting either 1 wk before or 10 d after initiating LCMV infection prevents IDDM in > 50% of the tg mice (observation time 8 mo). Thus, insulin therapy is effective in preventing progression to overt IDDM in prediabetic tg mice with ongoing islet infiltration. Oral administration of insulin does not affect the generation of LCMV-NP-specific anti-self cytotoxic T lymphocytes nor the infiltration of lymphocytes into the pancreas. However, less beta cells are destroyed in insulin-treated mice, upregulation of MHC class I and II molecules does not occur, and antiviral (self) cytotoxic T lymphocytes are not found in the islets, events present in tg mice developing IDDM. The majority of lymphocytes in the islets of insulin-treated tg mice without IDDM produces IL-4, IL-10, and TGF-beta. In contrast, lymphocytes from islets of tg mice developing IDDM mainly make gamma-IFN.
Cancer statistics, 2013
Authors: Rebecca Siegel, Deepa Naishadham, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2013)

Abstract Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,660,290 new cancer cases and 580,350 cancer deaths are projected to occur in the United States in 2013. During the most recent 5 years for which there are data (2005‐2009), delay‐adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.5% per year in women. Overall, cancer death rates have declined 20% from their peak in 1991 (215.1 per 100,000 population) to 2009 (173.1 per 100,000 population). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate). Over the past 10 years of data (2000‐2009), the largest annual declines in death rates were for chronic myeloid leukemia (8.4%), cancers of the stomach (3.1%) and colorectum (3.0%), and non‐Hodgkin lymphoma (3.0%). The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of approximately 1.18 million deaths from cancer, with 152,900 of these deaths averted in 2009 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket and other underserved populations. CA Cancer J Clin 2013;. © 2013 American Cancer Society.
Neutrophil depletion protects against murine acetaminophen hepatotoxicity
Authors: Zhang‐Xu Liu, Derick Han, Basuki Gunawan, Neil Kaplowitz
Journal: Hepatology (2006)

We previously reported that liver natural killer (NK) and NKT cells play a critical role in mouse model of acetaminophen (APAP)-induced liver injury by producing interferon gamma (IFN-γ) and modulating chemokine production and subsequent recruitment of neutrophils into the liver. In this report, we examined the role of neutrophils in the progression of APAP hepatotoxicity. C57BL/6 mice were given an intraperitoneal toxic dose of APAP (500 mg/kg), which caused severe acute liver injury characterized by significant elevation of serum ALT, centrilobular hepatic necrosis, and increased hepatic inflammatory cell accumulation. Flow cytometric analysis of isolated hepatic leukocytes demonstrated that the major fraction of increased hepatic leukocytes at 6 and 24 hours after APAP was neutrophils (Mac-1+Gr-1+). Depletion of neutrophils by in vivo treatment with anti-Gr-1 antibody (RB6-8C5) significantly protected mice against APAP-induced liver injury, as evidenced by markedly reduced serum ALT levels, centrilobular hepatic necrosis, and improved mouse survival. The protection was associated with decreased FasL-expressing cells, cytotoxicity against hepatocytes, and respiratory burst in hepatic leukocytes. In intracellular adhesion molecule (ICAM)-1–deficient mice, APAP caused markedly reduced liver injury when compared with wild-type mice. The marked protection in ICAM-1–deficient mice was associated with decreased accumulation of neutrophils in the liver. Hepatic GSH depletion and APAP-adducts showed no differences among the antibody-treated, ICAM-1–deficient, and normal mice. In conclusion, accumulated neutrophils in the liver contribute to the progression and severity of APAP-induced liver injury. (HEPATOLOGY 2006;43:1220–1230.)
Cardioprotective Role of the Mitochondrial ATP-Binding Cassette Protein 1
Authors: Hossein Ardehali, Brian O’Rourke, Eduardo Marbán
Journal: Circulation Research (2005)

The mechanism by which mitochondria exert protection against oxidant stress is not clear. We recently showed that a purified mitochondrial fraction containing 5 coimmunoprecipitating proteins (succinate dehydrogenase, adenine nucleotide translocator, ATP synthase, inorganic phosphate carrier, and mitochondrial ATP-binding cassette protein 1 or mABC1) displayed mitochondrial ATP-sensitive K+-channel activity. mABC1, a member of the ABC family of proteins, is the only protein in this complex whose function is not known. A yeast homologue of mABC1 protein, Mdl1p, was recently identified to have a novel role for induction of cellular resistance to oxidant stress. Based on these observations, we hypothesized that mABC1 plays a key role in protection of myocardial cells against oxidant stress. We studied the function of mABC1 by modulating the levels of this protein in neonatal rat cardiomyocytes using various molecular techniques, followed by assessment of cell viability and measurement of mitochondrial membrane potential. RNA interference resulted in reduced mABC1 mRNA and protein levels and was associated with significantly attenuated loss of tetramethylrhodamine ethyl ester fluorescence under basal conditions and an increase in trypan blue stained cells. In contrast, adenovirally mediated expression of mABC1 resulted in protection against oxidant stress loss of mitochondrial membrane potential. These results support the notion that mABC1 protein plays a major role in cellular protection against oxidant stress, identifying mABC1 as a novel target for cardioprotective therapeutics.
Outcomes of the Childhood Asthma Prevention Study at 11.5 years
Authors: Brett G. Toelle, Frances L. Garden, Kitty K.W. Ng, Elena G. Belousova, Catarina Almqvist, Chris T. Cowell, Euan R. Tovey, Karen L. Webb, Stephen R. Leeder, Guy B. Marks
Journal: Journal of Allergy and Clinical Immunology (2013)
An innately dangerous balancing act: intestinal homeostasis, inflammation, and colitis-associated cancer
Authors: Mark Asquith, Fiona Powrie
Journal: The Journal of Experimental Medicine (2010)

Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses to the intestinal microbiota, and by chronic intestinal inflammation. Several recent studies demonstrate the importance of innate microbial recognition by immune and nonimmune cells in the gut. Paradoxically, either diminished or exacerbated innate immune signaling may trigger the breakdown of intestinal homeostasis, leading to IBD and colitis-associated cancer (CAC). This dichotomy may reflect divergent functional roles for immune sensing in intestinal epithelial cells and leukocytes, which may vary with distinct disease mechanisms.
The Antiviral Effector IFITM3 Disrupts Intracellular Cholesterol Homeostasis to Block Viral Entry
Authors: Samad Amini-Bavil-Olyaee, Youn Jung Choi, Jun Han Lee, Mude Shi, I-Chueh Huang, Michael Farzan, Jae U. Jung
Journal: Cell Host & Microbe (2013)
The Basis for Progress in Chemotherapy
Authors: C. G. Zubrod
Journal: CA A Cancer Journal for Clinicians (1973)

In the not too distant past, a paper on cancer chemotherapy would have been read only by a few of the author's most loyal friends.Obviously, a new day is here.Chemotherapy has effected pro found changes in the outlook for patients with disseminated cancer and physicians everywhere are eager to make chemo therapeutictreatments available to their patients.This paper will attempt to out line the basis for progress in cancer chemotherapyâ€"its present status, past history and future directions.