tbuckley/cabot-search huggingface dataset:
Management of variceal haemorrhage in cirrhosis: the relevance of the risk stratification
Authors: L. Amitrano, M. A. Guardascione, A. Menchise, F. Manguso, A. Balzano
Journal: Gut (2010)

We read with interest the recent article by Mehta et al updating the diagnosis and the primary and secondary prophylaxis of variceal haemorrhage (VH) in cirrhosis.1 We would like to comment on the relevance of the degree of liver failure on the current strategies of management of VH.2 3 Prognosis after the bleeding episode has improved greatly in the last two decades, with the implementation of patient intensive care management, the use of vasoactive drugs, routine prophylactic antibiotics and band ligation, and with efficacious schedules of rebleeding prophylaxis.4 5 Nevertheless, in a recent classification VH, either in compensated or decompensated patients, defines the stage IV of cirrhosis bearing a mortality rate of 57% at 1 year.6 These results come …
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Authors: Gregg L. Semenza
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis, which is disrupted in disorders affecting the circulatory system and in cancer. The role of HIFs in these diseases has been elucidated by clinical studies and by analyses of mouse models. HIFs play a protective role in the pathophysiology of myocardial ischemia due to coronary artery disease, limb ischemia due to peripheral arterial disease, pressure-overload heart failure, wound healing, and chronic rejection of organ transplants. In contrast, HIFs contribute to the pathogenesis of pulmonary arterial hypertension, systemic hypertension associated with sleep apnea, ocular neovascularization, hereditary erythrocytosis, and cancer.
Interrelationships among thyroxine, growth hormone, and the sympathetic nervous system in the regulation of 5'-iodothyronine deiodinase in rat brown adipose tissue.
Authors: J E Silva, P R Larsen
Journal: Journal of Clinical Investigation (1986)

Thyroxine (T4) and reverse triiodothyronine are potent inhibitors of brown adipose T4 5'-deiodinase (BAT 5'D). This effect does not require protein synthesis and is due to an acceleration of the rate of disappearance of the enzyme. Growth hormone (GH) also inhibits BAT 5'D but by a mechanism mediated through a long-lived messenger that correlates with growth rate. This explains the failure of BAT 5'D to increase abruptly after thyroidectomy as does the type II 5'-deiodinase in pituitary and central nervous system or the BAT 5'D itself after hypophysectomy. Although virtually inactive when given acutely, triiodothyronine replacement partially reduces BAT 5'D in hypophysectomized and thyroidectomized (Tx) animals probably as a result of improvement of systemic hypothyroidism and an increase in GH levels in the Tx rats. The fine balance between these inhibitory factors and the stimulatory effects of the sympathetic nervous system suggests an important physiologic role for the enzyme in this tissue.
Strategies for the control of voluntary movements with one mechanical degree of freedom
Authors: Gerald L. Gottlieb, Daniel M. Corcos, Gyan C. Agarwal
Journal: Behavioral and Brain Sciences (1989)

Abstract A theory is presented to explain how accurate, single-joint movements are controlled. The theory applies to movements across different distances, with different inertial loads, toward targets of different widths over a wide range of experimentally manipulated velocities. The theory is based on three propositions. (1) Movements are planned according to “strategies” of which there are at least two: a speed-insensitive (SI) and a speed-sensitive (SS) one. (2) These strategies can be equated with sets of rules for performing diverse movement tasks. The choice between SI and SS depends on whether movement speed and/or movement time (and hence appropriate muscle forces) must be constrained to meet task requirements. (3) The electromyogram can be interpreted as a low-pass filtered version of the controlling signal to the motoneuron pools. This controlling signal can be modelled as a rectangular excitation pulse in which modulation occurs in either pulse amplitude or pulse width. Movements to different distances and with loads are controlled by the SI strategy, which modulates pulse width. Movements in which speed must be explicitly regulated are controlled by the SS strategy, which modulates pulse amplitude. The distinction between the two movement strategies reconciles many apparent conflicts in the motor control literature.
Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs
Authors: Leo G. Frederick, Osman D. Suleymanov, James A. Szalony, Beatrice B. Taite, Anita K. Salyers, Lucy W. King, Larry P. Feigen, Nancy S. Nicholson
Journal: Circulation (1998)

Background —Inhibition of platelet aggregation by preventing the binding of fibrinogen to glycoprotein (GP) IIb/IIIa on activated platelets results in antithrombotic activity. We report on the antithrombotic effect of xemilofiban (SC-54684A), an oral GP IIb/IIIa antagonist, administered alone or with aspirin (ASA) in an acute thrombosis model. Methods and Results —Conscious dogs were treated with xemilofiban (1.25, 2.5, 5.0, or 6 mg/kg, n=6); low-dose (LD, 81 mg) ASA, n=7; high-dose (HD, 162 mg) ASA, n=6; xemilofibran 1.25 mg/kg plus LD ASA, n=6; xemilofibran 1.25 mg/kg plus HD ASA, n=6; or placebo, n=7. Dogs were anesthetized 60 minutes later, and the effects of the treatments were evaluated after electrolytic injury (250 μA for 180 minutes) in the left circumflex coronary artery. Bleeding time (BT) was assessed in a separate study. Incidence of thrombosis was reduced ( P &lt;0.05) by xemilofiban ≥2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA compared with placebo. Xemilofiban ≥2.5 mg/kg or xemilofiban 1.25 mg/kg plus HD ASA significantly increased time to occlusion, inhibited ex vivo platelet aggregation to collagen &gt;90%, and prevented or decreased ( P &lt;0.05) cyclic flow variations (CFVs) compared with placebo. BT was increased ( P &lt;0.05) with xemilofiban ≥2.5 mg/kg but not with xemilofiban 1.25 mg/kg plus HD ASA. Conclusions —Xemilofiban ≥2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA significantly reduced the incidence of thrombosis. These doses of xemilofiban or xemilofiban 1.25 mg/kg plus HD ASA increased time to occlusion, inhibited ex vivo platelet aggregation by &gt;90%, and prevented or reduced CFVs. Xemilofiban ≥2.5 mg/kg but not xemilofiban 1.25 mg/kg plus HD ASA significantly increased BT.
Homodimerization and Heterodimerization of the Glomerular Podocyte Proteins Nephrin and NEPH1
Authors: Peter Gerke, Tobias B. Huber, Lorenz Sellin, Thomas Benzing, Gerd Walz
Journal: Journal of the American Society of Nephrology (2003)

Nephrin and NEPH1, the gene products of NPHS1 and NEPH1, are podocyte membrane proteins of the Ig superfamily. Similar to the nephrin knockout, mice lacking NEPH1 show severe proteinuria leading to perinatal death. To identify the ligand of NEPH1, the extracellular domain of NEPH1 was fused to human IgG. This NEPH1-Ig fusion protein labeled the glomerular capillary wall of mouse kidneys in a staining pattern identical to NEPH1 and nephrin, prompting speculation that that NEPH1 might form homodimers and/or heterodimers with nephrin. In coimmunoprecipitation and pull-down assays, the NEPH1-Ig fusion protein precipitated wild-type NEPH1 from overexpressing HEK 293T cells. Truncational analysis revealed that the adhesive properties were not confined to a single Ig domain of NEPH1. Fusion proteins containing two Ig domains of NEPH1 were sufficient to immobilize NEPH1, but they failed to interact with control protein containing the phylogenetically related PKD repeats of polycystin-1. NEPH1 also precipitated nephrin, a protein with eight Ig domains and a fibronectin-like domain. Truncational analysis of nephrin revealed a very similar mode of interaction, i.e. , two nephrin Ig domains fused to human IgG precipitated either nephrin or NEPH1, but not the control protein. Both NEPH1 and nephrin interactions were strictly dependent upon posttranslational glycosylation, and bacterially expressed protein failed to bind NEPH1. These findings demonstrate that the Ig domains of NEPH1 and nephrin form promiscuous homodimeric and heterodimeric interactions that may facilitate cis- and trans- homodimerizations and heterodimerizations of these molecules at the glomerular slit diaphragm. E-mail: walz@med1.ukl.uni-freiburg.de
Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy
Authors: Charles J. Ryan, Matthew R. Smith, Johann S. de Bono, Arturo Molina, Christopher J. Logothetis, Paul de Souza, Karim Fizazi, Paul Mainwaring, Josep M. Piulats, Siobhan Ng, Joan Carles, Peter F.A. Mulders, Ethan Basch, Eric J. Small, Fred Saad, Dirk Schrijvers, Hendrik Van Poppel, Som D. Mukherjee, Henrik Suttmann, Winald R. Gerritsen, Thomas W. Flaig, Daniel J. George, Evan Y. Yu, Eleni Efstathiou, Allan Pantuck, Eric Winquist, Celestia S. Higano, Mary-Ellen Taplin, Youn Park, Thian Kheoh, Thomas Griffin, Howard I. Scher, Dana E. Rathkopf
Journal: New England Journal of Medicine (2012)

Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy.
Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity.
Authors: M Awwad, R J North
Journal: The Journal of Experimental Medicine (1988)

This study shows that intravenous injection of 1 mg of anti-L3T4 mAb (GK1.5) into thymectomized mice bearing the syngeneic L5178Y lymphoma results, after a delay of 2-3 d, in complete regression of this tumor and in long-term host survival. A flow cytofluorometric examination of the spleen cells of mAb-treated mice revealed that antibody treatment resulted in the elimination of greater than 98% of L3T4+ T cells, but had no effect on the Lyt-2+ T cells subset. Tumor regression was immunologically mediated, because L5178Y lymphoma cells were shown to be L3T4-, and regression of the tumor failed to occur in mice that had been lethally irradiated before anti-L3T4 mAb was given. Tumor regression was mediated by tumor-sensitized Lyt2+ T cells, as evidenced by the finding that treatment of tumor-bearing mice with anti-Lyt-2 mAb alone, or in combination with anti-L3T4 mAb, resulted in enhancement of tumor growth and a significant decrease in host survival time. Moreover, the spleens of mice whose tumors were undergoing regression in response to anti-L3T4 mAb treatment contained Lyt-2+ T cells capable, on passive transfer, of causing regression of a tumor in recipient mice. These results can be interpreted as showing that removal of tumor-induced L3T4+ suppressor T cells results in the release of Lyt-2+ effector T cells from suppression, and consequently in the generation of enough Lyt-2+ T cell-mediated immunity to cause tumor regression. This can only be achieved, however, if immunity to the tumor is mediated exclusively by Lyt-2+ T cells, as is the case for the L5178Y lymphoma. In the case of the P815 mastocytoma, treatment with anti-L3T4 mAb was without a therapeutic effect, and this was in keeping with the finding that immunity to this tumor is mediated by L3T4+, as well by Lyt-2+ T cells.
Determination of cytokines in synovial fluids: correlation with diagnosis and histomorphological characteristics of synovial tissue.
Authors: P Kahle, J G Saal, K Schaudt, J Zacher, P Fritz, G Pawelec
Journal: Annals of the Rheumatic Diseases (1992)

In a study aimed at correlating cytokine levels in synovial fluid with the pathology of rheumatoid arthritis (RA), tumour necrosis factor alpha, interleukin 1 beta and interferon gamma were immunoassayed in 27 patients with RA, 16 patients with other arthritides, 23 with osteoarthritis, 13 patients with trauma, and 18 patients at necropsy without inflammatory disease and not known to have had joint disease (median 27 hours after death). The results for interleukin 1 beta clearly show higher cytokine levels in patients with RA and other arthritides than in patients with osteoarthritis, trauma, or the patients at necropsy. Interferon gamma levels in patients with osteoarthritis and the patients at necropsy, however, were significantly greater than in patients with RA, and tumour necrosis factor alpha levels were also greater in the patients at necropsy compared with patients with RA. This study also correlated histomorphological patterns of synovitis and indicators of local inflammatory activity with synovial fluid cytokine levels, showing, for example, a positive association of interleukin 1 beta titre and a negative association of interferon gamma titre with ulcerogranulomatous synovitis (itself associated with RA). Taken together, these results extend and strengthen data suggesting a possible part played by increased synovial fluid levels of interleukin 1 beta in joint destruction in RA, but provide no evidence for increases in levels of tumour necrosis factor alpha or interferon gamma affecting the disease pathology.
Comparison of Sputum Induction with Fiberoptic Bronchoscopy in the Diagnosis of Tuberculosis
Authors: MARCUS B. CONDE, SERGIO L. M. SOARES, FERNANDA C. Q. MELLO, VALERIA M. REZENDE, LUCIANA L. ALMEIDA, ARTHUR L. REINGOLD, CHARLES L. DALEY, AFRANIO L. KRITSKI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Many patients with suspected pulmonary tuberculosis (PTB) do not produce sputum spontaneously or are smear-negative for acid-fast bacilli (AFB). We prospectively compared the yield of sputum induction (SI) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) for the diagnosis of PTB in a region with a high prevalence of tuberculosis and human immunodeficiency virus (HIV) infection. Fifty seven percent (143 of 251) of patients had diagnoses of PTB, of whom 17% (25 of 143) were HIV seropositive. There were no significant differences in the yields of AFB smears or cultures whether obtained via SI or BAL. Among 207 HIV-seronegative patients, the AFB smear and mycobacterial culture results from specimens obtained by SI and BAL were in agreement in 97% (202 of 207) (kappa test = 0.92) and 90% (186 of 207) (kappa test = 0.78), respectively. Among HIV-seropositive patients the agreements between AFB smear and culture results for SI and BAL specimens were 98% (43 of 44) (kappa test = 0.93) and 86% (38 of 44) (kappa test = 0.69), respectively. We conclude that SI is a safe procedure with a high diagnostic yield and high agreement with the results of fiberoptic bronchoscopy for the diagnosis of PTB in both HIV-seronegative and HIV-seropositive patients.
Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study
Authors: R. Noordam, D.A. Gunn, C.C. Tomlin, A.B. Maier, T. Griffiths, S.D. Catt, S. Ogden, P.E. Slagboom, R.G.J. Westendorp, C.E.M. Griffiths, D. van Heemst, A.J.M. de Craen
Journal: British Journal of Dermatology (2013)

Insulin-like growth factor (IGF)-1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of collagen expression.To assess whether serum IGF-1, IGF-binding protein (IGFBP)3 and the ratio between IGF-1 and IGFBP3, as a measure of IGF-1 bioavailability, are associated with facial ageing and skin wrinkling.From a random sample comprising 617 subjects from the Leiden Longevity Study, perceived age and skin wrinkling were assessed from facial photographs, and IGF-1 and IGFBP3 were measured in serum. The associations were assessed using linear regression models, adjusted for chronological age, sex, body mass index, smoking and sun exposure.Across tertiles of the ratio of IGF-1 to IGFBP3, and after adjusting for all potential confounding factors, the mean perceived age decreased from 60·6 years in the lowest tertile to 59·5 years in the highest (P = 0·045). Similarly, the mean skin wrinkling grade decreased from 4·8 in the lowest tertile to 4·5 in the highest (P = 0·011). Adding skin wrinkling as a covariate in the analysis between IGF-1 and perceived age diminished this association.This study demonstrates that a higher ratio of IGF-1 to IGFBP3 associates with a lower perceived age, via its association with reduced skin wrinkling. Whether high IGF-1 levels actually delay the accumulation of skin wrinkling now needs investigating.
Assessment of non-mydriatic photography in detection of diabetic retinopathy
Authors: R E J Ryder, S Young, T M Hayes
Journal: BMJ (1986)

advantage of Polaroid films is their relatively low resolution, which may fail to pick out fine vessels if the quality of the photograph is other than excellent.This finding coincides with our experience of working in a retinopathy clinic.Over the past eight months of using the non-mydriatic camera there were at least eight cases ofproliferative retinopathy which presented with lesions outside its photographic field.
Plasma Levels of Adiponectin Are Associated With Insulin Resistance and Serum Levels of Triglyceride in Japanese Metabolically Obese, Normal-Weight Men With Normal Glucose Tolerance
Authors: Akira Katsuki, Yasuhiro Sumida, Hideki Urakawa, Esteban C. Gabazza, Shuichi Murashima, Kazutaka Matsumoto, Kaname Nakatani, Yutaka Yano, Yukihiko Adachi
Journal: Diabetes Care (2003)

Adiponectin is expressed in and secreted from visceral fat, and its plasma level has been reported to correlate with insulin resistance and triglyceride metabolism in nondiabetic subjects (1,2). However, these relationships have not been evaluated in Japanese metabolically obese normal-weight (BMI <25 kg/m2 and visceral fat areas [evaluated by abdominal CT scanning] ≥100 cm2) men with normal glucose tolerance (NGT) (3–5).

The present study comprised 16 metabolically obese normal-weight men (aged 35.6 ± 1.8 [mean ± SE] years, BMI 23.8 ± 0.3 kg/m2, visceral fat areas 130.8 ± 5.2 cm2) and 15 age-matched normal men (BMI <25 and visceral fat …
Immune regulatory activity of CD34+ progenitor cells: evidence for a deletion-based mechanism mediated by TNF-α
Authors: Hilit Gur, Rita Krauthgamer, Esther Bachar-Lustig, Helena Katchman, Rinat Arbel-Goren, Alain Berrebi, Tirza Klein, Arnon Nagler, Antonio Tabilio, Massimo F. Martelli, Yair Reisner
Journal: Blood (2004)
Coronary Artery Disease in Young Women
Authors: H. Jurgen Engel
Journal: JAMA (1974)

Advanced coronary atherosclerosis was angiographically demonstrated in 21 women aged 40 years or younger. To facilitate the recognition of women susceptible to coronary atherosclerosis from those with chest pain of other cause, the patients' conditions were investigated with regard to various easily identifiable atherogenic risk factors. Eighty-six percent of the patients had at least three of five predisposing factors: family history (of coronary artery disease, hypertension, or diabetes mellitus), hypertension, hyperlipidemia, glucose intolerance, and cigarette smoking. Only three of the 21 patients were free of both hypertension and elevated serum cholesterol levels. Obesity and hyperuricemia were not found to improve the predictive yield. Data on pregnancies, menstruation, oophorectomies, and estrogen therapy did not afford clues regarding the cause of precocious coronary atherosclerosis in these young women.  (JAMA230:1531-1534, 1974)
The Influence of Health Systems on Hypertension Awareness, Treatment, and Control: A Systematic Literature Review
Authors: Will Maimaris, Jared Paty, Pablo Perel, Helena Legido-Quigley, Dina Balabanova, Robby Nieuwlaat, Martin Mckee
Journal: PLoS Medicine (2013)

Will Maimaris and colleagues systematically review the evidence that national or regional health systems, including place of care and medication co-pays, influence hypertension awareness, treatment, and control. Please see later in the article for the Editors' Summary
Effects of resistance training in children and adolescents: a meta-analysis: Table 1
Authors: Zoe A Michaleff, Steven J Kamper
Journal: British Journal of Sports Medicine (2011)

Behringer M, vom Heede A, Yue Z, et al. Pediatrics 2010;126:1199–210.[OpenUrl][1][CrossRef][2] There is emerging consensus that resistance training is safe and effective during all stages of childhood and adolescence. Little is known, however, about the influence of age and maturity on strength gains. In particular, it is not clear whether the onset of puberty, with its rapid increase in sex hormones corresponds to an increase in the response to strength training. The authors aimed to synthesise the best available evidence to determine whether resistance training programmes are effective in children and adolescents as well as to examine the influence of age, maturity and programme parameters on strength gains. Six biomedical databases were searched from … [1]: {openurl}?query=rft.jtitle%253DPediatrics%26rft.volume%253D126%26rft.spage%253D1199%26rft_id%253Dinfo%253Adoi%252F10.1542%252Fpeds.2010-0445%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1542/peds.2010-0445&link_type=DOI
Coverage of Nevirapine-Based Services to Prevent Mother-to-Child HIV Transmission in 4 African Countries
Authors: Elizabeth M. Stringer
Journal: JAMA (2010)

Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child.To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries.Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs.Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation).A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater.In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.