tbuckley/cabot-search huggingface dataset:
Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea
Authors: Camila Bononi Almeida, Lucas Eduardo Botelho Souza, Flavia Costa Leonardo, Fabio Trindade Maranhão Costa, Claudio C. Werneck, Dimas Tadeu Covas, Fernando Ferreira Costa, Nicola Conran
Journal: Blood (2015)
Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial Events
Authors: Dominic P.J. Howard, Amitava Banerjee, Jack F. Fairhead, Linda Hands, Louise E. Silver, Peter M. Rothwell
Journal: Circulation (2015)

Background— There are few published data on the incidence and long-term outcomes of critical limb ischemia, acute limb ischemia, or acute visceral ischemia with which to inform health service planning, to monitor prevention, and to enable risk prediction. Methods and Results— In a prospective population-based study (Oxfordshire, UK; 2002–2012), we determined the incidence and outcome of all acute peripheral arterial events in a population of 92 728. Risk factors were assessed by comparison with the underlying population. A total of 510 acute events occurred in 386 patients requiring 803 interventions. Two hundred twenty-one patients (59.3%) were ≥75 years of age, and 98 (26.3%) were ≥85 years old. Two hundred thirty patients (62.3%) were independent before the event, but 270 (73.4%) were dead or dependent at the 6-month follow-up, and 328 (88.9%) were dead or dependent at 5 years. The 30-day survival was lowest for patients with acute visceral ischemia (28.2%) compared with acute limb ischemia (75.3%) and critical limb ischemia (92.6%; P &lt;0.001). Risk factors (all P &lt;0.001) were hypertension (age- and sex-adjusted risk ratio, 2.75; 95% confidence interval, 1.95–3.90), smoking (adjusted risk ratio, 2.14; 95% confidence interval, 1.37–3.34), and diabetes mellitus (adjusted risk ratio, 3.01; 95% confidence interval, 1.69–5.35), particularly for critical limb ischemia (adjusted risk ratio, 5.96; 95% confidence interval, 3.15–11.26). Two hundred eighty-eight patients (77.2%) had known previous cardiovascular disease, and 361 (96.8%) had vascular risk factors, but only 203 (54.4%) were on an antiplatelet and only 166 (44.5%) were on a statin. Although 260 patients (69.7%) were taking antihypertensives, 42.9% of all blood pressures recorded during the 5 years before the event were &gt;140/90 mm Hg. Of 88 patients (23.6%) with incident cardioembolic events, 62 had known atrial fibrillation (diagnosed before the event), of whom only 14.5% were anticoagulated despite 82.3% having a CHA 2 DS 2 VASC score ≥2 without contraindications. Conclusions— The clinical burden of peripheral arterial events is substantial. Although the vast majority of patients have known vascular disease in other territories and multiple treatable risk factors, premorbid control is poor.
Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study
Authors: Ian McKeith, John O'Brien, Zuzana Walker, Klaus Tatsch, Jan Booij, Jacques Darcourt, Alessandro Padovani, Raffaele Giubbini, Ubaldo Bonuccelli, Duccio Volterrani, Clive Holmes, Paul Kemp, Naji Tabet, Ines Meyer, Cornelia Reininger
Journal: The Lancet Neurology (2007)
Nutritional risk screening 2002 - Application in pneumology
Authors: Christina Priegnitz, Ilona Kietzmann, Kerstin Richter, Wolfgang Galetke, Winfried Randerath
Journal: European Respiratory Journal (2012)

Background   Malnutrition has a prevalence of ca. 20-50% of all inpatients and is recognized as a relevant risk factor concerning morbidity and mortality. In a German multicenter study (Pirlich et al., 2006) malnutrition was detected in 27% of patients, affecting significantly more women. Malnutrition according to the WHO (BMI    Methods:   705 consecutive patients in our clinic specialized in pneumology were analyzed in respect of age, sex, BMI, disease, malnutrition risk (NRS) and length of stay.   Results   Risk of malnutrition (MN risk) according to NRS was found in 14.3% of patients, while according to WHO only 2.5% were malnourished. In those older than 65 years, these values were 19.6% and 1.5% respectively. There was no relevant difference between sexes. Age significantly contributed to MN risk (OR 1.054, p   Conclusion   The application of a validated screening tool significantly contributes to detected patients at risk for malnutrition. Especially patients older than 65 as well as those with specific diseases need increased attention regarding MN risk. An early intervention could help to reduce length of stay.
Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19
Authors: Mei Zhou, Xueyan Wang, Van Phung, Darrin A. Lindhout, Kalyani Mondal, Jer-Yuan Hsu, Hong Yang, Mark Humphrey, Xunshan Ding, Taruna Arora, R. Marc Learned, Alex M. DePaoli, Hui Tian, Lei Ling
Journal: Cancer Research (2014)

Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic overexpression of FGF19 drives HCC development in a process that requires FGFR4. In this study, we describe an engineered FGF19 (M70) that fully retains bile acid regulatory activity but does not promote HCC formation, demonstrating that regulating bile acid metabolism is distinct and separable from tumor-promoting activity. Mechanistically, we show that FGF19 stimulates tumor progression by activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70 inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to improve the treatment of chronic liver disease and cancer.
Parietaria judaica–specific T-cell clones from atopic patients: Heterogeneity in restriction, Vβ usage, and cytokine profile☆, ☆☆, ★
Authors: F SALLUSTOA, S CORINTIA, C PINIA, M BIOCCAB, G BRUNOB, G DIFELICEA
Journal: Journal of Allergy and Clinical Immunology (1996)
Air Pollution–Associated Changes in Lung Function among Asthmatic Children in Detroit
Authors: Toby C. Lewis, Thomas G. Robins, J. Timothy Dvonch, Gerald J. Keeler, Fuyuen Y. Yip, Graciela B. Mentz, Xihong Lin, Edith A. Parker, Barbara A. Israel, Linda Gonzalez, Yolanda Hill
Journal: Environmental Health Perspectives (2005)

In a longitudinal cohort study of primary-school-age children with asthma in Detroit, Michigan, we examined relationships between lung function and ambient levels of particulate matter < or = 10 microm and < or = 2.5 microm in diameter (PM10 and PM2.5) and ozone at varying lag intervals using generalized estimating equations. Models considered effect modification by maintenance corticosteroid (CS) use and by the presence of an upper respiratory infection (URI) as recorded in a daily diary among 86 children who participated in six 2-week seasonal assessments from winter 2001 through spring 2002. Participants were predominantly African American from families with low income, and > 75% were categorized as having persistent asthma. In both single-pollutant and two-pollutant models, many regressions demonstrated associations between higher exposure to ambient pollutants and poorer lung function (increased diurnal variability and decreased lowest daily values for forced expiratory volume in 1 sec) among children using CSs but not among those not using CSs, and among children reporting URI symptoms but not among those who did not report URIs. Our findings suggest that levels of air pollutants in Detroit, which are above the current National Ambient Air Quality Standards, adversely affect lung function of susceptible asthmatic children.
US groups set standards of outpatient care
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Americans make more than a billion visits to doctors' surgeries and hospital outpatient and emergency departments for medical care every year, but until now there have been few standards for gauging the quality of care that doctors provide in the outpatient setting.

This month a set of voluntary national standards was agreed on by more than 260 healthcare providers such as healthcare plans, consumers' groups, professionals' organisations, purchasers of health care (such as employers), federal agencies, and research and quality improvement organisations.

The groups were brought together by the National Quality Forum, a private, non-profit organisation that aims to standardise the measurement and reporting of the quality of health care. The standards are based …
The effect of menstruation on the pulmonary carbon monoxide diffusing capacity.
Authors: R H Sansores, R T Abboud, C Kennell, N Haynes
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We studied variations in DLCO during the menstrual cycle in 14 healthy women with a mean age of 29 (SD, 7) yr. Eight were using oral contraceptives, and six were not. DLCO was determined 1 to 7 d before the onset of menses, daily during each of the first 4 d of menses, and 5 to 10 d after onset of menses. In both groups of subjects, the highest values for DLCO were obtained before menses, the lowest were on the third day of menses, whereas after completion of menses the values increased but were not as high as prior to menses. The mean DLCO for all subjects was 23.1 (SD, 3.2) ml/min/mm Hg before menses, 20.9 (SD, 3.0) on the third day of menstruation, and 21.6 (SD, 3.3) 5 to 10 d after onset of menses. The mean percent difference between DLCO before and on the third day of menses in all 14 subjects was 9.2 (SD, 4.4) %. There were no significant changes in hemoglobin on these days to account for the changes in DLCO. Pulmonary capillary blood volume determined in 10 of the subjects did not show a significant change. It is concluded that DLCO can vary significantly during the menstrual cycle, with the highest values occurring prior to menses and the lowest values occurring on the third day of menses, with a mean difference between them of 9%. These variations need to be considered when evaluating DLCO in female patients in the menstrual age group.
Leukotriene E4–induced pulmonary inflammation is mediated by the P2Y12 receptor
Authors: Sailaja Paruchuri, Hiroyuki Tashimo, Chunli Feng, Akiko Maekawa, Wei Xing, Yongfeng Jiang, Yoshihide Kanaoka, Pamela Conley, Joshua A. Boyce
Journal: The Journal of Experimental Medicine (2009)

Of the potent lipid inflammatory mediators comprising the cysteinyl leukotrienes (LTs; LTC4, LTD4, and LTE4), only LTE4 is stable and abundant in vivo. Although LTE4 shows negligible activity at the type 1 and 2 receptors for cys-LTs (CysLT1R and CysLT2R), it is a powerful inducer of mucosal eosinophilia and airway hyperresponsiveness in humans with asthma. We show that the adenosine diphosphate (ADP)–reactive purinergic (P2Y12) receptor is required for LTE4-mediated pulmonary inflammation. P2Y12 receptor expression permits LTE4 -induced activation of extracellular signal-regulated kinase in Chinese hamster ovary cells and permits chemokine and prostaglandin D2 production by LAD2 cells, a human mast cell line. P2Y12 receptor expression by LAD2 cells is required for competition between radiolabeled ADP and unlabeled LTE4 but not for direct binding of LTE4, suggesting that P2Y12 complexes with another receptor to recognize LTE4. Administration of LTE4 to the airways of sensitized mice potentiates eosinophilia, goblet cell metaplasia, and expression of interleukin-13 in response to low-dose aerosolized allergen. These responses persist in mice lacking both CysLT1R and CysLT2R but not in mice lacking P2Y12 receptors. The effects of LTE4 on P2Y12 in the airway were abrogated by platelet depletion. Thus, the P2Y12 receptor is required for proinflammatory actions of the stable abundant mediator LTE4 and is a novel potential therapeutic target for asthma.
Can children with autism integrate first and third person representations?
Authors: Simon Baron-Cohen
Journal: Behavioral and Brain Sciences (1996)

Abstract Barresi &amp; Moore contrast two theories of autism: (1) in autism there is a general inability to integrate first and third person information (of any kind), and (2) in autism there is a specific inability to represent an agent's perceptual or volitional mental state being about another agents mental state. Two lines of experimental evidence suggest that the first of these is too broad, favoring instead the more specific “theory of mind” account.
Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma.
Authors: J W Fleming, A M Watanabe
Journal: Circulation Research (1988)

One component of muscarinic receptor inhibition of the function of cardiac ventricles is mediated by the inhibition of activated adenylate cyclase activity in sarcolemma. We have shown previously that muscarinic agonists inhibit GTP- but not Gpp(NH)p-activated adenylate cyclase activity, and various studies in other tissues indicate that nonhydrolyzable GTP analogues prevent inactivation of the enzyme. These data have suggested a role for GTP hydrolysis in the mechanism of inhibition of adenylate cyclase. The present study demonstrates that purified canine cardiac sarcolemma displays high-affinity GTPase activity that is reciprocally related to adenylate cyclase activity. The high-affinity GTPase activity was stimulated by muscarinic agonists and blocked by atropine. Furthermore, the one-half maximal effects of oxotremorine for binding to muscarinic receptors, stimulation of high-affinity GTPase activity, and inhibition of adenylate cyclase activity were similar. Muscarinic stimulation of GTPase activity and inhibition of adenylate cyclase activity required functional activity of the pertussis toxin (IAP) substrate(s). Treatment of sarcolemmal membranes with IAP attenuated the ability of oxotremorine to both stimulate high-affinity GTPase activity and inhibit adenylate cyclase activity. These studies indicate that muscarinic receptor stimulation of high-affinity GTPase activity dependent on functional IAP substrate(s) is closely linked to the mechanism of muscarinic inhibition of adenylate cyclase activity.
Contractile deactivation and uncoupling of crossbridges. Effects of 2,3-butanedione monoxime on mammalian myocardium.
Authors: J K Gwathmey, R J Hajjar, R J Solaro
Journal: Circulation Research (1991)

We investigated the effects of 1 and 3 mM 2,3-butanedione monoxime (BDM, diacetyl monoxime) on excitation and contraction of cardiac muscle in several types of preparations at various levels of organization. We selected a concentration of BDM that was not expected to affect sarcolemmal calcium flux and action potential duration in cardiac tissue. Two indicators were used to record intracellular calcium. Aequorin, a bioluminescent calcium indicator, was used in studies with ferret papillary muscle preparations, and fura-2, a fluorescent calcium indicator, was used in studies with guinea pig cardiac myocytes. In both cases, addition of BDM resulted in a reduction of peak intracellular calcium released from the sarcoplasmic reticulum and a reduction of peak twitch force. The duration of the action potential of isolated myocytes was slightly abbreviated in the presence of BDM. In studies on the calcium current in the myocytes, addition of BDM was associated with reduced calcium current at any potential. Peak calcium current was reduced by 7.9 +/- 1% in the presence of BDM. In tetanized ferret papillary muscles, BDM reduced maximal calcium-activated force by 30 +/- 5% and increased the calcium ion concentration required for half-maximal force by 0.1 +/- 0.01 microM. The Hill coefficient was reduced from 5.00 +/- 0.11 to 3.40 +/- 0.20. Maximal shortening velocity of ferret papillary muscles was increased in the presence of BDM from 1.55 +/- 0.24 to 2.04 +/- 0.33 mm/sec. Ca2+ binding to troponin C in skinned fiber preparations from guinea pig, bovine, and canine hearts was unaffected by addition of up to 10 mM BDM. Our results indicate that BDM affects both calcium availability and responsiveness of the myofilaments to Ca2+. Uncoupling of contractile activation from excitation may also result from altered crossbridge kinetics.
Clinical significance of inflammatory back pain for diagnosis and screening of patients with axial spondyloarthritis
Authors: J. Braun, R. Inman
Journal: Annals of the Rheumatic Diseases (2010)

Inflammatory back pain (IBP) is the leading symptom of patients with spondyloarthritis (SpA), but its value for diagnosis, classification and screening in primary care is not well defined. Although often used since 1977, its clinical significance has not been extensively studied. As shown recently, most but clearly not all patients with axial SpA have IBP. Therefore IBP has not been included in current criteria for axial SpA as a first-line criterion. The value of IBP for diagnosis of SpA increases in the presence of other more or less sensitive and specific features of SpA such as response to exercise and physical therapy and/or treatment with non-steroidal anti-inflammatory agents.
Development and evaluation of a community based, multiagency course for medical students: descriptive survey
Authors: A. Lennox, S. Petersen
Journal: BMJ (1998)

Objective: To develop and evaluate an effective, community based, multiagency course (involving doctors, nurses, non-health statutory workers, and voluntary organisations) for all Leicester medical students, in response to the General Medical Council's recommendation of preparing the doctors of tomorrow to handle society's medical problems. Design: Survey evaluating a task oriented, problem solving course, designed by medical students in partnership with the University of Leicester and the local community. The students, staff, and participating agencies and patients all helped in the evaluation of the first course. The students' performance on the course was also individually assessed. Setting: Inner city housing estate with Jarman index 64.1 in Leicester. Subjects: All third year medical students at Leicester University. Main outcome measures: Results of the student assignments and students' responses to a questionnaire. Results of feedback questionnaires distributed to the patients and agency representatives. Results: In a two month period, 168 students completed the first course. 163 students passed the criterion referenced assignment, 50 of whom achieved an "excellent" grade. 166 completed the questionnaire, with 159 wishing to see the course continue in the present format and 149 saying that the course linked theoretical teaching with the practical experiences gained in the community. Conclusions: The University of Leicester has a viable mechanism for providing a community based, multiagency course for all its medical students. Many of the principles applied in the development and implementation of the course could be transferred to other medical schools. #### Key messages
Disorders of Bone Remodeling
Authors: Xu Feng, Jay M. McDonald
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

The skeleton provides mechanical support for stature and locomotion, protects vital organs, and controls mineral homeostasis. A healthy skeleton must be maintained by constant bone modeling to carry out these crucial functions throughout life. Bone remodeling involves the removal of old or damaged bone by osteoclasts (bone resorption) and the subsequent replacement of new bone formed by osteoblasts (bone formation). Normal bone remodeling requires a tight coupling of bone resorption to bone formation to guarantee no alteration in bone mass or quality after each remodeling cycle. However, this important physiological process can be derailed by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and secondary diseases, which lead to the development of various bone disorders in both women and men. We review the major diseases of bone remodeling, emphasizing our current understanding of the underlying pathophysiological mechanisms.
Idiopathic Interstitial Pneumonia
Authors: Kevin R. Flaherty, Talmadge E. King, Ganesh Raghu, Joseph P. Lynch, Thomas V. Colby, William D. Travis, Barry H. Gross, Ella A. Kazerooni, Galen B. Toews, Qi Long, Susan Murray, Vibha N. Lama, Steven E. Gay, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Current guidelines recommend that the clinician, radiologist, and pathologist work together to establish a diagnosis of idiopathic interstitial pneumonia. Three clinicians, two radiologists, and two pathologists reviewed 58 consecutive cases of suspected idiopathic interstitial pneumonia. Each participant was provided information in a sequential manner and was asked to record their diagnostic impression and level of confidence at each step. Interobserver agreement improved from the beginning to the end of the review. After the presentation of histopathologic information, radiologists changed their diagnostic impression more often than did clinicians. In general, as more information was provided the confidence level for a given diagnosis improved, and the diagnoses rendered with a high level of confidence were more likely congruent with the final pathologic consensus diagnosis. The final consensus pathologist diagnosis was idiopathic pulmonary fibrosis in 30 cases. Clinicians identified 75% and radiologists identified 48% of these cases before presentation of the histopathologic information. Histopathologic information has the greatest impact on the final diagnosis, especially when the initial clinical/radiographic diagnosis is not idiopathic pulmonary fibrosis. We conclude that dynamic interactions between clinicians, radiologists, and pathologists improve interobserver agreement and diagnostic confidence.