tbuckley/cabot-search huggingface dataset:
Obstruction of the pulmonary artery by granulomatous vasculitis: a clinical, morphological, and immunological analysis
Authors: G Schett
Journal: Annals of the Rheumatic Diseases (2002)

he case of a 45 year old woman presenting with fever of unknown origin,headache,polyarthralgia,and chest pain is described. Computed tomography scans and angiography disclosed a mediastinal tumour with a complete obstruction of the right pulmonary artery, positron emission tomography scans showed a tracer accumulation in the walls of the pulmonary artery and the aorta. Thoracotomy was performed and subsequent histological analysis of multiple biopsy specimens led to the diagnosis of a form of giant cell arteritis of the pulmonary artery. Immunological analysis of the cytokine profile of peripheral blood mononuclear cells (PBMC) showed a markedly increased production of tumour necrosis factor α (TNFα) and interleukin 2 (IL2) and a normalisation of TNFα production after successful treatment. In contrast, the production of interferon γ, IL4, IL6, IL10, and IL13 was normal. Furthermore, an expanded subset of double positive CD4+/CD8+ T cells was remarkable, as well as an increased expression of the IL2 receptor on PBMC. Immunomodulatory treatment with steroids and methotrexate was started and led to a rapid resolution of symptoms and morphological changes. The right pulmonary artery, however, remained occluded. The particular features of this case are reviewed with consideration of its clinical, diagnostic, histopathological, and immunological characteristics and are compared with other reported findings.
Researching the Cost of Research
Authors: James R. Wright, Mark N. Levine
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.08.972 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14559890 Researching the Cost of Research James R. WrightxJames R. WrightSearch for articles by this author , Mark N. LevinexMark N. LevineSearch for articles by this author Show More Hamilton Regional Cancer Center, Cancer Care Ontario, Department of Medicine, McMaster University, Henderson Research Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada https://doi.org/10.1200/JCO.2003.08.972 Full Text PDF Figures and Tables "Researching the Cost of Research." Journal of Clinical Oncology, 21(22), pp. 4081–4082© 2003 by American Society of Clinical Oncology
Increased Na+/H+-exchange activity is the cause of increased [Na+]i and underlies disturbed calcium handling in the rabbit pressure and volume overload heart failure model
Authors: A Baartscheer
Journal: Cardiovascular Research (2003)

Objective: Cytosolic sodium ([Na+]i) is increased in heart failure (HF). We hypothesize that up-regulation of Na+/H+-exchanger (NHE) in heart failure is causal to the increase of [Na+]i and underlies disturbance of cytosolic calcium ([Ca2+]i) handling. Methods: Heart failure was induced in rabbits by combined volume and pressure overload. Age-matched animals served as control. [Na+]i, cytosolic calcium [Ca2+]i and cytosolic pH (pHi) were measured in isolated left ventricular midmural myocytes with SBFI, indo-1 and SNARF. SR calcium content was measured as the response of [Ca2+]i to rapid cooling (RC). Calcium after-transients were elicited by cessation of rapid stimulation (3 Hz) in the presence of 100 nmol/l noradrenalin. NHE and Na+/K+-ATPase activity were inhibited with 10 μmol/l cariporide and 100 μmol/l ouabain, respectively. Results: At all stimulation rates (0–3 Hz) [Na+]i and diastolic [Ca2+]i were significantly higher in HF than in control. With increasing frequency [Na+]i and diastolic [Ca2+]i progressively increased in HF and control, and the calcium transient amplitude (measured as total calcium released from SR) decreased in HF and increased in control. In HF (at 2 Hz), SR calcium content was reduced by 40% and the calcium gradient across the SR membrane by 60%. Fractional systolic SR calcium release was 90% in HF and 60% in control. In HF the rate of pHi recovery following acid loading was much faster at all pHi and NHE dependent sodium influx was almost twice as high as in control. In HF cariporide (10 μmol/l, 5 min) reduced [Na+]i and end diastolic [Ca2+]i to almost control values, and reversed the relation between calcium transient amplitude and stimulation rate from negative to positive. It increased SR calcium content and SR membrane gradient and decreased fractional systolic SR depletion to 60%. Cariporide greatly reduced the susceptibility to develop calcium after-transients. In control animals, cariporide had only minor effects on all these parameters. Increase of [Na+]i with ouabain in control myocytes induced abnormal calcium handling as found in HF. Conclusions: In HF up-regulation of NHE activity is causal to increased [Na+]i and secondarily to disturbed diastolic, systolic and SR calcium handling. Specific inhibition of NHE partly normalized [Na+]i, end diastolic [Ca2+]i, and SR calcium handling and reduced the incidence of calcium after-transients. Chronic treatment with specific NHE inhibitors may provide a useful future therapeutic option in treatment of developing hypertrophy and heart failure.
There will be blood... a complete audit cycle
Authors: M. Pericleous, C. Murray, M. Hamilton, O. Epstein, R. Negus, J. O'Beirne
Journal: Gut (2011)

<h3>Introduction</h3> Acute upper GI bleeding (AUGIB) has 7% new-admission mortality.1 The authors studied the management of patients with AUGIB at the Royal Free Hospital (RFH), London. The aim was to compare our performance to the standard practice as set by SIGN guidelines,2 and determine ways of improving delivery of care. <h3>Methods</h3> The authors randomly selected 15% of patients3 who presented with haematemesis, melaena, or both, and had an oesophagogastroduodenoscopy (OGD) in April to October 2009. Acute assessment and management were matched to the SIGN guidelines (audit standard). The authors developed local guidelines, and presented their findings in various forums including the Grand Round and clinical governance meetings. The authors collaborated with the <i>British Medical Journal</i> (BMJ) and Cerner Millennium electronic patient record system to create an electronic Action Set for the assessment and emergency management of adult patients presenting with AUGIB. The Action Set went live in April 2010 and the authors reaudited using the same standard and target. <h3>Results</h3> Prior to the introduction of the Action Set 0% of doctors calculated the pre-OGD Rockall score. This increased to 33% following implementation (figure 1). The authors also noticed an increase from 25% to 100% of those patients who were admitted with a pre-OGD Rockall score of ‘zero’ and were correctly discharged with follow-up plans (figure 2). 34% of patients were correctly identified as not appropriate to receive a proton pump inhibitor (PPI) prior to OGD as compared to 15% previously. Inappropriate use of PPIs after OGD was reduced from 96% to 75%. Incorrect administration of intravenous PPI infusions dropped from 100% to 33%. <h3>Conclusion</h3> Several areas of deviation from the guidelines were identified. The authors emphasised the usefulness of pre/full-Rockall scores as a risk-stratifying tool in order to determine potential discharges, create more beds and improve health economics for the Trust. Appropriate use of PPIs can reduce rebleeding rates,4 improve mortality5 and reduce costs. The Action Set consists of a set of orders based on clinical evidence that can be used for the assessment and management of AUGIB. Local and SIGN guidelines and useful contacts/bleep numbers are incorporated in the workflow. The tool ‘captures’ patients with suspected AUGIB and records/time-stamps every event in the patient9s journey. Tests and procedures are automatically ordered and auditable data is streamed, collected and analysed weekly. The Action Set includes e-prescribing and nurse ordering functionality. Even with minimal use the authors noticed improvements in several areas including guideline adherence, clinical outcomes and cost-cutting.
HERC2 Is an E3 Ligase That Targets BRCA1 for Degradation
Authors: Wenwen Wu, Ko Sato, Ayaka Koike, Hiroyuki Nishikawa, Hirotaka Koizumi, Ashok R. Venkitaraman, Tomohiko Ohta
Journal: Cancer Research (2010)

Abstract The breast cancer suppressor BRCA1 forms a stable heterodimeric E3 ubiquitin ligase with BARD1. Each protein controls the abundance and stability of the other, and loss of the interaction leads to BRCA1 degradation. Here, we show that HERC2, a protein recently implicated in DNA damage repair, targets BARD1-uncoupled BRCA1 for degradation. HERC2 shuttles between the nucleus and the cytoplasm. Its COOH-terminal HECT-containing domain interacts with an NH2-terminal degron domain in BRCA1. HERC2 ubiquitinates BRCA1; this reaction depends on Cys4762 of HERC2, the catalytic ubiquitin binding site, and the degron of BRCA1. The HERC2-BRCA1 interaction is maximal during the S phase of the cell cycle and rapidly diminishes as cells enter G2-M, inversely correlated with the steady-state level of BRCA1. Significantly, HERC2 depletion antagonizes the effects of BARD1 depletion by restoring BRCA1 expression and G2-M checkpoint activity. Conversely, BARD1 protects BRCA1 from HERC2-mediated ubiquitination. Collectively, our findings identify a function for HERC2 in regulating BRCA1 stability in opposition to BARD1. The HERC2 expression in breast epithelial cells and breast carcinomas suggests that this mechanism may play a role in breast carcinogenesis. Cancer Res; 70(15); 6384–92. ©2010 AACR.
Precision and accuracy of Morgan ventilometers at continuous and sinusoidal flows
Authors: JD Hart, RT Withers, RC Tucker
Journal: European Respiratory Journal (1994)

The P.K. Morgan Mark II Ventilometer comprises a turbine transducer and a control/readout unit, which contains either a VENTX5A or VENTX6A programme. This equipment is used to measure minute ventilation during oxygen consumption tests. The precision and accuracy of six of these devices (a VENTX5A with two turbines, and two VENTX6As each with two different turbines) were examined during continuous and pulsatile flows; accuracy was affected by the syringe rate during the calibration procedure. The reference standard was a 350 l Collins chain-compensated gasometer. At continuous flows, the two VENTX5A devices showed accuracies of 99.5-100.5% over the range 60-160 l.min-1 whereas those for the four VENTX6As were 99.3-102.1% over the range 60-200 l.min-1. The mean accuracies of sinusoidal flows for the VENTX5A ranged between 96.1-101.3% for minute volumes spanning 15-200 l.min-1; comparable data for the VENTX6As were 95.9-98.9%. These mean accuracies improved to 98.1-101.3% for the VENTX5A at measured minute volumes &gt; 80 l.min-1. Omission of the two lowest tidal volumes (1 and 1.5 l) for the VENTX6As narrowed the range of accuracy to 96.9-98.5%. The coefficients of variation for five trials at each minute ventilation were 0-0.2%. We conclude that, while the P.K. Morgan Mark II Ventilometer has excellent precision, its accuracy is dependent on the calibration syringe rate, minute ventilation and program.
The Birmingham Epidermolysis Bullosa Severity score: development and validation
Authors: C. Moss, A. Wong, P. Davies
Journal: British Journal of Dermatology (2009)

Objective severity scores facilitate clinical care and research. However, the rarity and heterogeneity of epidermolysis bullosa (EB) make scoring difficult.To develop a severity score covering all subtypes of EB at all ages that is simple, valid, sensitive and reliable.Score items and weightings were generated by expert consensus, and refined for content and face validity. The Birmingham EB Severity (BEBS) score was tested on 97 patients aged 0-64 years.Eleven items were scored: area of damaged skin, involvement of nails, mouth, eyes, larynx and oesophagus, scarring of hands, skin cancer, chronic wounds, alopecia and nutritional compromise. Area was allocated 50 points, and the 10 other items 5 points each, giving a maximum score of 100. Lowest BEBS scores occurred in Weber-Cockayne EB simplex (median 1.0; range 0.1-3.0; n = 12), highest scores in generalized non-Herlitz junctional EB (28.5; 5.0-62.0; n = 7), Hallopeau-Siemens recessive dystrophic EB (HS-RDEB) (22.9; 4.3-69.0; n = 23) and Herlitz junctional EB (H-JEB) (14.4; 2.5-49.3; n = 9), and intermediate scores in dominant dystrophic EB (5.3; 0.5-15.9; n = 19), Dowling-Meara EB simplex (DM-EBS) (6.3; 2.8-22.5; n = 16) and non-Hallopeau-Siemens recessive dystrophic EB (7.8, 2.8-27.8; n = 11). Intra- and interobserver correlations were high. With age, scores increased for H-JEB (r = 0.9, P = 0.001) and HS-RDEB (r = 0.73, P = 0.001) and decreased for DM-EBS (r = -0.62, P = 0.01), with positive but nonsignificant correlations for the other types.The BEBS score appears valid and reproducible, gives appropriate scores for different subtypes, and reflects changes with age.
Relationship Between Release of Platelet/Endothelial Biomarkers and Plasma Levels of Sertraline and<i>N</i>-Desmethylsertraline in Acute Coronary Syndrome Patients Receiving SSRI Treatment for Depression
Authors: Victor L Serebruany, Raymond F Suckow, Thomas B Cooper, Christopher M O'Connor, Alex I Malinin, K Ranga R Krishnan, Louis T van Zyl, Vladimir Lekht, Alexander H Glassman
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: In a platelet/endothelial biomarker substudy of the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. METHOD: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N=23) or placebo (N=32). Twenty-six serial plasma samples collected at week 6 (N=12) and week 16 (N=14) were analyzed. Platelet factor 4 (PF4), β-thromboglobulin (β-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B2 (TxB2), prostacyclin (6-keto-PGF1α), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. RESULTS: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-desmethylsertraline with PF4 (week 6: r=–0.69 and –0.33, respectively; week 16: r=–0.63 for both), β-TG (week 6: r=–0.43 and –0.29; week 16: r=–0.66 and –0.57), PECAM-1 (week 6: r=–0.82 and –0.49; week 16: r=–0.60 for both), P-selectin (week 6: r=–0.82 and –0.49; week 16: r=–0.73 and –0.43), and TxB2 (week 6: r=–0.66 and –0.59; and week 16: r=–0.64 and –0.41). Regression analysis revealed some borderline correlations for endothelial markers such as 6-keto- PGF1α and E-selectin and a positive correlation for VCAM-1. CONCLUSIONS: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial.
Hospital-Initiated Transitional Care Interventions as a Patient Safety Strategy
Authors: Stephanie Rennke, Oanh K. Nguyen, Marwa H. Shoeb, Yimdriuska Magan, Robert M. Wachter, Sumant R. Ranji
Journal: Annals of Internal Medicine (2013)

Hospitals now have the responsibility to implement strategies to prevent adverse outcomes after discharge. This systematic review addressed the effectiveness of hospital-initiated care transition strategies aimed at preventing clinical adverse events (AEs), emergency department (ED) visits, and readmissions after discharge in general medical patients. MEDLINE, CINAHL, EMBASE, and Cochrane Database of Clinical Trials (January 1990 to September 2012) were searched, and 47 controlled studies of fair methodological quality were identified. Forty-six studies reported readmission rates, 26 reported ED visit rates, and 9 reported AE rates. A "bridging" strategy (incorporating both predischarge and postdischarge interventions) with a dedicated transition provider reduced readmission or ED visit rates in 10 studies, but the overall strength of evidence for this strategy was low. Because of scant evidence, no conclusions could be reached on methods to prevent postdischarge AEs. Most studies did not report intervention context, implementation, or cost. The strategies hospitals should implement to improve patient safety at hospital discharge remain unclear.
Mechanisms of Inflammatory Responses in Obese Adipose Tissue
Authors: Shengyi Sun, Yewei Ji, Sander Kersten, Ling Qi
Journal: Annual Review of Nutrition (2012)

The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient metabolic pathways and to obesity-associated complications such as insulin resistance and type 2 diabetes. Despite these advances, however, many open questions remain including how inflammatory responses are initiated and maintained, how nutrients impact the function of various immune populations, and how inflammatory responses affect systemic insulin sensitivity. Here we review recent studies on the roles of various immune cells at different phases of obesity and discuss molecular mechanisms underlying obesity-associated inflammation. Better understanding of the events occurring in adipose tissue will provide insights into the pathophysiological role of inflammation in obesity and shed light on the pathogenesis of obesity-associated metabolic syndrome.
Cardiomyopathy in Children With Down Syndrome Treated for Acute Myeloid Leukemia: A Report From the Children's Oncology Group Study POG 9421
Authors: Maureen M. O'Brien, Jeffrey W. Taub, Myron N. Chang, Gita V. Massey, Kimo C. Stine, Susana C. Raimondi, David Becton, Yaddanapudi Ravindranath, Gary V. Dahl
Journal: Journal of Clinical Oncology (2008)

To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421.Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m(2) and mitoxantrone 80 mg/m(2). Outcomes and toxicity were evaluated prospectively and were compared with the non-DS-AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events.In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS-French-American-British (FAB) M7 (91.7%) and non-DS-non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS-M7 (36.3%) or the non-DS-non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure.The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.
Auditory Filters, Features, and Redundant Representations
Authors: Jan Schnupp
Journal: Neuron (2006)

Responses in auditory cortex tend to be weaker, more phasic, and noisier than those of auditory brainstem and midbrain nuclei. Is the activity in cortex therefore merely a "degraded echo" of lower-level neural representations? In this issue of <i>Neuron</i>, Chechik and colleagues show that, while cortical responses indeed convey less sensory information than auditory midbrain neurons, their responses are also much less redundant.
SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker
Authors: Mark N Wu, William J Joiner, Terry Dean, Zhifeng Yue, Corinne J Smith, Dechun Chen, Toshinori Hoshi, Amita Sehgal, Kyunghee Koh
Journal: Nature Neuroscience (2009)
Defense Mechanisms Reported by Patients With Borderline Personality Disorder and Axis II Comparison Subjects Over 16 Years of Prospective Follow-Up: Description and Prediction of Recovery
Authors: Mary C. Zanarini, Frances R. Frankenburg, Garrett Fitzmaurice
Journal: American Journal of Psychiatry (2012)

Objective The authors assessed the defensive functioning of 290 patients with borderline personality disorder and compared it with that of 72 patients with other forms of axis II psychopathology over 16 years of prospective follow-up. They also assessed the relationship between time-varying defenses and recovery from borderline personality disorder. Method The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was initially administered at study entry. It was readministered at eight contiguous 2-year follow-up periods. Results Borderline patients had significantly lower scores than axis II comparison subjects on one mature defense mechanism (suppression) and significantly higher scores on seven of the other 18 defenses studied: one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image-distorting/borderline defenses (projective identification and splitting). Over the follow-up period, borderline patients showed significant improvement on 13 of the 19 defenses studied, with significantly higher scores over time on one mature defense (anticipation) and significantly lower scores on two neurotic defenses (isolation and undoing), all immature defenses, and all image-distorting/borderline defenses except primitive idealization. In addition, four time-varying defense mechanisms were found to predict time to recovery: humor, acting out, emotional hypochondriasis, and projection. Conclusions Taken together, these results suggest that the longitudinal defensive functioning of borderline patients is distinct and improves substantially over time. They also suggest that immature defenses are the best predictor of time to recovery.
The Physician's Role in the Cost-Containment Problem
Authors: Stephen J. Dresnick
Journal: JAMA (1979)

The seemingly uncontrolled increase in the cost of medical care is one of the major problems facing the American physician. Although the reasons for escalated costs are multifactorial, the physician does play an important role in the problem. Several studies have suggested that physicians, the cost generators, are unaware of the economic impact of the care they provide. In the preparation of this report, 70 medical students, 316 interns and residents, and 41 faculty members at the University of Miami School of Medicine were surveyed on their knowledge of frequently ordered hospital billing items. A common lack of knowledge was noted in all three groups of respondents, with the faculty scoring as poorly as the medical students. Major efforts must be directed toward the cost education of physicians. (<i>JAMA</i>241:1606-1609, 1979)