tbuckley/cabot-search huggingface dataset:
US panel calls for research into effects of Ritalin
Authors: F. Charatan
Journal: BMJ (1998)

A National Institutes of Health consensus panel of experts from North America which met earlier this month has called for urgent clarification of the diagnosis of attention deficit hyperactivity disorder (ADHD) and research into the long term effects of treatment with methylphenidate hydrochloride (Ritalin).

Attention deficit hyperactivity disorder is estimated to affect 3-5% of school age children in the United States, and is the most commonly diagnosed behaviour disorder in childhood. The panel found that there is no consistency in treatment, diagnosis, or follow up for children with the disorder.

Dr David Kupfer, Thomas Detre professor and chairman of the department of psychiatry at the University …
Blood Pressure Reactivity to Psychological Stress Predicts Hypertension in the CARDIA Study
Authors: Karen A. Matthews, Charles R. Katholi, Heather McCreath, Mary A. Whooley, David R. Williams, Sha Zhu, Jerry H. Markovitz
Journal: Circulation (2004)

A longstanding but controversial hypothesis is that individuals who exhibit frequent, large increases in blood pressure (BP) during psychological stress are at risk for developing essential hypertension. We tested whether BP changes during psychological stress predict incident hypertension in young adults.We used survival analysis to predict hypertensive status during 13 years of follow-up in a sample of >4100 normotensive black and white men and women (age at entry, 18 to 30 years) enrolled in the CARDIA study. BP responses to 3 psychological challenges--cold pressor, star tracing, and video game tasks--were measured. Hypertensive status was defined as use of antihypertensive medication or measured BP > or =140/90 mm Hg. After adjustment for race, gender, covariates (education, body mass index, age, and resting pressure), and their significant interactions, the larger the BP responses were to each of the 3 tasks, the earlier hypertension occurred (P<0.0001 to <0.01). The systolic BP effect for the cold pressor task was apparent for women and for whites in race- and gender-specific models, whereas the diastolic BP effect for the video game was apparent for men.Young adults who show a large BP response to psychological stress may be at risk for hypertension as they approach midlife.
An update on contraindications for lung function testing
Authors: B. G. Cooper
Journal: Thorax (2010)

Guidelines on contraindications for lung function tests have been based on expert opinion from >30 years ago. High-risk contraindications to lung function testing are associated with cardiovascular complications such as myocardial infarct, pulmonary embolism or ascending aortic aneurysm. Slightly less risky but still serious contraindications are predominantly centred on recovery from major thoracic, abdominal or head surgery. Less serious surgical procedures will present a possible risk, but the RR depends upon whether the lung function is essential or can wait until the patient's condition improves. In recent decades there have been moves towards less invasive surgical techniques, keyhole surgery and new technology such as laser surgery which minimise the amount of collateral damage to surrounding tissues. In thoracic surgery there is a shift in emphasis to quicker postsurgical mobility. Furthermore there has been little analysis of the scientific facts behind the current recommendations and contraindications. The principle absolute and relative contraindications are in need of revision, and recommended times of abstaining from lung function tests needs to be reviewed. This review aims to outline the key issues and suggests newer recommendations for contraindications for performing lung function using a risk matrix, as well as offering alternative approaches to testing patients who may be at risk of complication from testing. In general, the previous recommendation of waiting for 6 weeks after surgical procedures or medical complications before performing lung function can often now be reduced to <3 weeks with modern less invasive surgical techniques.
Evaluation of blood perfusion by laser speckle contrast analysis in different areas of hands and face in patients with systemic sclerosis
Authors: A Sulli, B Ruaro, M Cutolo
Journal: Annals of the Rheumatic Diseases (2014)

Laser speckle contrast analysis (LASCA) is a new safe technique to quantify blood perfusion (BP) at different body areas. While several techniques have been used in systemic sclerosis (SSc) to evaluate BP at the level of hands with quite reproducible and similar results, limited information is available about BP at other specific body sites that may be affected by Raynaud's phenomenon, like nose.1–5

We assessed by LASCA (Pericam PSI, Perimed) BP in different skin areas of hands and face in patients with SSc in comparison with healthy subjects.3 ,6 ,7 After scan acquisition, regions of interest (ROIs) were created at central area of fingertips and periungual areas from II to V finger bilaterally, palm and dorsum of both hands, as well as at the level of the face (forehead, tip of nose, zygomas and perioral region) (see figure 1). BP was recorded as perfusion units (PU).



Figure 1 
Regions of interest (see white open circles) for evaluation of blood perfusion (BP) by Laser Speckle Contrast …
Augmented receptor-mediated Ca2+ mobilization causes supersensitivity of contractile response to serotonin in atherosclerotic arteries.
Authors: Y Miwa, K Hirata, Y Matsuda, M Suematsu, S Kawashima, M Yokoyama
Journal: Circulation Research (1994)

We have previously reported that atherosclerotic arteries obtained from Watanabe heritable hyperlipidemic (WHHL) rabbits exhibit a marked increase of contractile response to serotonin (5-hydroxytryptamine [5-HT]) and ergonovine and that these augmented contractile responses to specific agonists may play an important role in the pathogenesis of vasospasm. In the present study, we investigated whether supersensitivity to 5-HT in atherlosclerotic arteries was due to an increase in 5-HT receptor-mediated Ca2+ mobilization or to an increase in Ca2+ sensitivity of the contractile elements. We measured simultaneously both isometric tension and [Ca2+]i in fura 2-loaded aortic smooth muscle strips from control and WHHL rabbits. Muscle tension in the high K+ (72.7 mmol/L)-stimulated states and [Ca2+]i in both resting and high K(+)-stimulated states did not differ between control and WHHL rabbits. In atherosclerotic aortas from WHHL rabbits, the dose-response curves of both tension and [Ca2+]i for 5-HT were shifted to the left at lower threshold concentrations and one-half maximally effective dose. The maximum response of contraction produced by 5-HT in WHHL rabbits was augmented compared with that in control rabbits (123 +/- 17% versus 33 +/- 7% of the 72.7 mmol/L K(+)-induced contraction, P &lt; .001). The maximum response of [Ca2+]i produced by 5-HT was also augmented in WHHL rabbits compared with control rabbits (29 +/- 4% versus 10 +/- 0.9% of the 72.7 mmol/L K(+)-induced [Ca2+]i, P &lt; .001). In contrast, the responses of contraction and [Ca2+]i to phenylephrine were similar between control and WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhancement and suppression of signaling by the conserved tail of IgG memory–type B cell antigen receptors
Authors: Keisuke Horikawa, Stephen W. Martin, Sarah L. Pogue, Karlee Silver, Kaiman Peng, Kiyoshi Takatsu, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (2007)

Immunological memory is characterized by heightened immunoglobulin (Ig) G antibody production caused in part by enhanced plasma cell formation conferred by conserved transmembrane and cytoplasmic segments in isotype-switched IgG B cell receptors. We tested the hypothesis that the IgG tail enhances intracellular B cell antigen receptor (BCR) signaling responses to antigen by analyzing B cells from Ig transgenic mice with IgM receptors or chimeric IgMG receptors containing the IgG tail segment. The IgG tail segment enhanced intracellular calcium responses but not tyrosine or extracellular signal–related kinase (ERK) phosphorylation. Biochemical analysis and crosses to CD22-deficient mice established that IgG tail enhancement of calcium and antibody responses, as well as marginal zone B cell formation, was not due to diminished CD22 phosphorylation or inhibitory function. Microarray profiling showed no evidence for enhanced signaling by the IgG tail for calcium/calcineurin, ERK, or nuclear factor κB response genes and little evidence for any enhanced gene induction. Instead, almost half of the antigen-induced gene response in IgM B cells was diminished 50–90% by the IgG tail segment. These findings suggest a novel “less-is-more” hypothesis to explain how switching to IgG enhances B cell memory responses, whereby decreased BCR signaling to genes that oppose marginal zone and plasma cell differentiation enhances the formation of these key cell types.
The regulatory BCL2 promoter polymorphism (-938C&gt;A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma
Authors: G.F. Lehnerdt, P. Franz, A. Bankfalvi, S. Grehl, A. Kelava, H. Nückel, S. Lang, K.W. Schmid, W. Siffert, H.S. Bachmann
Journal: Annals of Oncology (2009)
Trends in Breast Cancer by Race and Ethnicity
Authors: A. Ghafoor, A. Jemal, E. Ward, V. Cokkinides, R. Smith, M. Thun
Journal: CA A Cancer Journal for Clinicians (2003)

In this article, the American Cancer Society (ACS) describes trends in incidence, mortality, and survival rates of female breast cancer in the United States by race and ethnicity. It also provides estimates of new cases and deaths and shows trends in screening mammography. The incidence and survival data derive from the National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality data are from the National Center for Health Statistics. Approximately 211,300 new cases of invasive breast cancer, 55,700 in situ cases, and 39,800 deaths are expected to occur among women in the United States in 2003. Breast cancer incidence rates have increased among women of all races combined and white women since the early 1980s. The increasing rate in white women predominantly involves small (< or = 2 cm) and localized-stage tumors, although a small increase in the incidence of regional-stage tumors and those larger than five cm occurred since the early 1990s. The incidence rate among African American women stabilized during the 1990s for all breast cancers and for localized tumors. African American women are more likely than white women to be diagnosed with large tumors and distant-stage disease. Other racial and ethnic groups have lower incidence rates than do either white or African American women. However, the proportion of disease diagnosed at advanced stage and with larger tumor size in all minorities is greater than in white persons. Death rates decreased by 2.5% per year among white women since 1990 and by 1% per year among African American women since 1991. The disparity in mortality rates between white and African American women increased progressively between 1980 and 2000, so that by 2000 the age-standardized death rate was 32% higher in African Americans. Clinicians should be aware that 63% and 29% of breast cancers are diagnosed at local- and regional-stage disease, for which the five-year relative survival rates are 97% and 79%, respectively. This information, coupled with decreasing mortality rates and improvements in treatment, may motivate women to have regular mammographic and clinical breast examinations. Continued efforts are needed to increase the availability of high-quality mammography and treatment to all segments of the population.
Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia
Authors: Ulf Thunberg, Gerard Tobin, Anna Johnson, Ola Söderberg, Leonid Padyukov, Magnus Hultdin, Lars Klareskog, Gunilla Enblad, Christer Sundström, Göran Roos, Richard Rosenquist
Journal: The Lancet (2002)
An interlaboratory quality control programme for the measurement of tuberculosis drugs
Authors: Rob E. Aarnoutse, Marieke G.G. Sturkenboom, Karen Robijns, Anneke R. Harteveld, Ben Greijdanus, Donald R.A. Uges, Daniel J. Touw, Jan-Willem Alffenaar
Journal: European Respiratory Journal (2015)

Tuberculosis (TB) remains a major global health problem. Inadequate exposure to TB drugs constitutes one of the main factors underlying suboptimal treatment response and development of resistance, as evidenced by results from: the in vitro hollow fibre model [1]; clinical studies on relationships between drug concentrations and response [2–5]; a pharmacogenetic trial [6]; and a recent meta-analysis [7]. Quality control in TB drug measurement is essential for the development of new drugs and for patient care <http://ow.ly/KxWNc>
Evolution and Resolution of Long-term Cardiac Memory
Authors: Alexei Shvilkin, Peter Danilo, Jie Wang, Daniel Burkhoff, Evgeny P. Anyukhovsky, Eugene A. Sosunov, Motoki Hara, Michael R. Rosen
Journal: Circulation (1998)

Background —Cardiac memory (CM) refers to T-wave changes induced by ventricular pacing or arrhythmia that accumulate in magnitude and duration with repeated episodes of abnormal activation. We report herein the kinetics of long-term CM and its association with the ventricular action potential. Methods and Results —Dogs were paced from the ventricles at rates of 110 to 120 bpm for ≈3 weeks. CM characterized by gradual sinus rhythm T vector rotation toward the paced QRS vector evolved in all dogs regardless of pacing site (left ventricular [LV] anterior apex or base, posterior LV, or right ventricular free wall). Cardiac hemodynamics and myocardial flow (microsphere studies) were unaltered by the pacing. Recovery time for the memory T wave to return to control increased with duration of the previous pacing. The protein synthesis inhibitor cycloheximide markedly ( P &lt;.05) and reproducibly attenuated evolution of CM. When pacing was performed from the atrium, CM did not occur. Standard microelectrode techniques were used to study action potential from the LV free wall of control and CM dogs. CM was associated with increased action potential duration in epicardial and endocardial but not midmyocardial cells, significantly altering the transmyocardial gradient for repolarization. Conclusions —CM is a dynamic process for which the final T vector is predicted by the paced QRS vector and which is associated with significant changes in epicardial and endocardial but not midmyocardial cell action potential duration, such that the transmural gradient of repolarization is altered. It is unaccompanied by evidence of altered hemodynamics or flow, requires a change in pathway of activation, and appears to require new protein synthesis.
Effect of Ingested Interferon-α on β-Cell Function in Children With New-Onset Type 1 Diabetes
Authors: Kristina I. Rother, Rebecca J. Brown, Miriam M. Morales, Elizabeth Wright, Zhigang Duan, Carol Campbell, Dana S. Hardin, Jadranka Popovic, Robert C. McEvoy, David M. Harlan, Philip R. Orlander, Staley A. Brod
Journal: Diabetes Care (2009)

To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes.Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal.Individuals in the placebo group (n = 30) lost 56 +/- 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-alpha lost 29 +/- 54 and 48 +/- 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups.Ingested hrIFN-alpha was safe at the doses used. Patients in the 5,000-unit hrIFN-alpha treatment group maintained more beta-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-alpha. Further studies of low-dose ingested hrIFN-alpha in new-onset type 1 diabetes are needed to confirm this effect.
Analysis of tidal expiratory flow pattern in the assessment of histamine-induced bronchoconstriction.
Authors: M J Morris, R G Madgwick, D J Lane
Journal: Thorax (1995)

BACKGROUND--There are times in clinical practice when it would be useful to be able to assess the severity of airways obstruction from tidal breathing. Three indices of airways obstruction derived from analysis of resting tidal expiratory flow have previously been described: (1) Tme/TE = time to reach maximum expiratory flow/expiratory time; (2) Krs = decay constant of exponential fitted to tidal expiratory flow versus time curve; and (3) EV = extrapolated volume--that is, area under the curve when the fitted exponential is extrapolated to zero flow. In this paper a further index--dtr/TE, time from the beginning of expiration till the rapid decay of flow begins/expiratory time--is evaluated. The aim of this study was to assess the ability of these indices to detect mild airways obstruction. METHODS--A histamine bronchial provocation test was performed in 20 adult patients with a diagnosis of asthma or symptoms of cough and/or shortness of breath. Baseline forced expiratory volume in one second (FEV1), functional residual capacity (FRC), and specific inspiratory conductance (sGaw) were measured and the measurements repeated after the final inhalation of histamine. Expiratory flow patterns during quiet breathing over five consecutive representative breaths were analysed before and after histamine. The test was concluded in 12 subjects when FEV1 had decreased by 20% of the post saline value, and in the remaining eight after inhalation of 16 or 32 mg/ml histamine. RESULTS--FEV1, sGaw, FRC, Krs, EV, and dtr/TE were all different after histamine (paired t test). For Tme/TE no difference was shown. Change in EV detected change in end tidal volume but underestimated it compared with the change measured by body plethysmography. Percentage fall in Krs after histamine correlated with percentage fall in FEV1 (r = 0.527, Pearson correlation coefficient). This was of a similar order to the correlation between the percentage fall in sGaw and in FEV1 (r = 0.543). CONCLUSIONS--Analysis of expiratory tidal flow-time patterns predicted a decrease in FEV1 following histamine challenge as did measurement of sGaw. This analysis of tidal breathing would be useful in circumstances where forced expiratory manoeuvres are unreliable or inapplicable.
Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein
Authors: Serena Marchiò, Massimo Alfano, Luca Primo, Daniela Gramaglia, Luca Butini, Luisa Gennero, Enrico De Vivo, Wadih Arap, Mauro Giacca, Renata Pasqualini, Federico Bussolino
Journal: Blood (2005)
Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. II. Demonstration of idiotypic determinants on suppressor T cells.
Authors: J Z Weinberger, R N Germain, S T Ju, M I Greene, B Benacerraf, M E Dorf
Journal: The Journal of Experimental Medicine (1979)

The ability of NP-coupled syngeneic spleen cells to induce antigen-specific T-suppressor cells capable of binding to NP-BSA-coated Petri dishes and mediating transfer of specific suppressive activity to NP was demonstrated. Furthermore, in strains of mice bearing the Ig-1b allotype, including SJL, and in (non-Ig-1b x Ig-1b)F1 hybrids, the NP-specific suppressor cells also interferes with expression of immunity after priming with NIP-BGG. Anti-NPb anti-idiotype antiserum plus complement treatment effectively abrogated the ability to transfer suppression. Formal genetic mapping of the fine specificity of cross-reactivity with Ig-1 allotypic congenic mice implies that expression of this trait is linked to the Ig-1b heavy chain linkage group. The sensitivity of NP-suppressor cells of appropriate strains to anti-idiotype treatment was also consistent with the formal mapping data. These experiments suggest that there are shared V-region structures on antibody and T cells that are crucial in the suppression pathway for the same antigen.
Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease
Authors: S. McPherson, S. F. Stewart, E. Henderson, A. D. Burt, C. P. Day
Journal: Gut (2010)

Accurate evaluation of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) is important to identify patients who may develop complications. The aim of this study was to compare the diagnostic performance of simple non-invasive tests in identifying advanced fibrosis among patients with biopsy-proven NAFLD.Consecutive patients with biopsy proven NAFLD were recruited from the Newcastle Hospitals Fatty Liver Clinic from 2003 to 2009. The AST/ALT ratio, AST to platelet ratio index, BARD (weighted sum of BMI>28=1 point, AST/ALT ratio>0.8=2 points, diabetes=1 point), FIB-4 (agexAST (IU/l)/platelet count (x10(9)/litre)x radicalALT (IU/l)) and NAFLD fibrosis scores were calculated from blood tests taken at time of biopsy.145 patients (82 male (61%), mean age 51+ or -12 years) were included. The mean body mass index was 35+ or -5 kg/m(2). 73 subjects (50%) had diabetes. 93 patients (64%) had non-alcoholic steatohepatitis. 27 (19%) had advanced fibrosis (Kleiner stage 3-4). The FIB-4 score had the best diagnostic accuracy for advanced fibrosis (area under receiver operator characteristic curve (AUROC) 0.86), followed by AST/ALT ratio (AUROC 0.83), NAFLD fibrosis score (AUROC 0.81), BARD (AUROC 0.77) and AST to platelet ratio index (AUROC 0.67). The AST/ALT ratio, BARD score, FIB-4 and NAFLD fibrosis scores had negative predictive values greater than 90% (93%, 95%, 95% and 92% respectively). Positive predictive values were modest. In order to exclude advanced fibrosis liver biopsy could potentially be avoided in 69% with AST/ALT ratio, 62% with FIB-4, 52% with NAFLD fibrosis score and 38% with BARD.The ALT/AST ratio, FIB-4 and NAFLD fibrosis scores can reliably exclude advanced fibrosis in a high proportion of patients with NAFLD, allowing liver biopsy to be used in a more directed manner.