tbuckley/cabot-search huggingface dataset:
MPs insist that NHS whistleblowers are protected
Authors: A. O'Dowd
Journal: BMJ (2012)

Clinicians who raise concerns about professional standards at their place of work must be protected from any resulting disciplinary action, according to MPs.

MPs on the influential parliamentary health select committee have called for guarantees that doctors who blow the whistle about poor practice should not be subjected to punitive action as a consequence.

The committee published a report on 7 March as a follow-up to the responses given by government and four healthcare regulatory bodies to accountability reports published by the committee in 2011.

The new report says that “doctors and other practitioners who have raised concerns about …
Bacteremic necrotizing pneumococcal pneumonia in children.
Authors: E Kerem, Y Bar Ziv, B Rudenski, S Katz, D Kleid, D Branski
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Necrotizing pneumonia, massive necrosis of lung tissue, is a serious, often fatal, complication of lobar pneumonia. Four children 1.3 to 7.5 yr of age were hospitalized with bacteremic pneumococcal pneumonia. All of them were acutely ill on presentation with arterial desaturation, and they developed anemia and thrombocytosis. Two patients had pleural effusion requiring drainage. A chest CT scan revealed segmental or lobar pulmonary liquification, which led to the diagnosis of necrotizing pneumonia. This finding could be demonstrated early in the course of the disease. Subsequently, all of the patients developed cavitating lesions. With adequate antipneumococcal therapy and/or chest tube drainage, all of the patients recovered completely; however, clinical improvement was prolonged: fever lasted 9 to 20 days, and length of hospitalization was 12 to 26 days. Contrary to that in adults, complete recovery is anticipated in children with bacteremic necrotizing pneumococcal pneumonia, and no invasive investigations are required.
Targeting the Loss of the <i>von Hippel-Lindau</i> Tumor Suppressor Gene in Renal Cell Carcinoma Cells
Authors: Patrick D. Sutphin, Denise A. Chan, James M. Li, Sandra Turcotte, Adam J. Krieg, Amato J. Giaccia
Journal: Cancer Research (2007)

Abstract Late-stage clear cell renal carcinoma poses a formidable clinical challenge due to the high mortality rate associated with this disease. Molecular and genetic studies have identified functional loss of the von Hippel-Lindau (VHL) gene as a frequent and crucial event in the development of the malignant phenotype of clear cell renal carcinomas. Loss of VHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. The objective of this study was to evaluate the possibility of targeting VHL loss through pharmacologic means. Chromomycin A3 (ChA3) was identified through in silico analysis of existing publicly available drug profiles from the National Cancer Institute as an agent that seemed to selectively target VHL-deficient clear cell renal carcinoma cells. Genotype-selective toxicity was first determined through short-term viability assays and then confirmed with clonogenic studies. Coculture of fluorescently labeled VHL-deficient and VHL-positive cells showed discriminate killing of the VHL-deficient cells with ChA3. Mechanistically, overexpression of hypoxia-inducible factor (HIF)-2α in VHL-positive clear cell renal carcinoma cells phenocopied loss of VHL with respect to ChA3 toxicity, establishing ChA3 as a HIF-dependent cytotoxin. This study shows the feasibility of selectively targeting the loss of the VHL tumor suppressor gene in clear cell renal carcinoma for potential clinical benefit and may have greater ramifications in the development of new targeted therapies for the treatment of cancer and other genetic diseases. [Cancer Res 2007;67(12):5896–905]
Deforming arthropathy in systemic lupus erthematosus.
Authors: A S Russell, J S Percy, W M Rigal, G L Wilson
Journal: Annals of the Rheumatic Diseases (1974)

Arthritis is a well-recognized feature of systemic lupus erythematosus (SLE), which may be confused with the joint manifestations ofrheumatoid arthritis (Tumulty, 1954).Two recent reviews of the articular disorders of SLE have emphasized that, apart from aseptic necrosis, destructive and deforming arthritis is rare in this disease (Pekin and Zwaifler, 1970; Labowitz and Schumacher, 1971).Arthritis without deformity has indeed been suggested as one of the preliminary American Rheumatism Association criteria for the diagnosis of SLE (Cohen, Reynolds, Franklin, Kulka, Ropes, Shulman, and Wallace, 1971).
An Inverse Relationship Between Perceived Harm and Participation Willingness in Schizophrenia Research Protocols
Authors: Laura Weiss Roberts, Katherine Green Hammond, Jinger Hoop
Journal: American Journal of Psychiatry (2006)

Objective: This study attempted to clarify how people with schizophrenia evaluate the potential harm associated with various research-related procedures and how these assessments relate to participation willingness. Method: The authors conducted a semistructured interview among participants with schizophrenia. Results: Sixty participants with schizophrenia rated four procedures as harmful (e.g., symptom induction), five procedures as moderately harmful (e.g., being given a placebo), and six procedures as not harmful (e.g., undergoing a physical examination). Rated willingness to participate was inversely related to the participants' perceptions of harmfulness for all procedures. Conclusions: In this study, people living with schizophrenia perceived different research procedures as posing different levels of possible harm. Potential harm appears to be an important consideration in protocol enrollment decisions. This work reaffirms the value of clarifying the strengths of seriously ill people who may choose to participate in research.
Regulation of T cell receptor delta gene rearrangement by c-Myb.
Authors: C Hernández-Munain, P Lauzurica, M S Krangel
Journal: The Journal of Experimental Medicine (1996)

Developmental activation of VDJ recombination at the T cell receptor (TCR) delta locus is controlled by an intronic transcriptional enhancer (E delta). Transcriptional activation by E delta is dependent on c-Myb. To determine whether c-Myb plays a role in the activation of TCR-delta gene rearrangement, we compared VDJ recombination in transgenic mice carrying two versions of a human TCR-delta gene minilocus recombination substrate. One includes a wild-type E delta, whereas the other carries an E delta with a mutation that abrogates c-Myb binding. We demonstrate that an intact Myb binding site is necessary for efficient rearrangement of the minilocus substrate, suggesting that c-Myb plays a crucial role in activating VDJ recombination at the endogenous TCR-delta locus.
Rapid virological response in hepatitis C virus genotype 1 and early ribavirin exposure
Authors: Chia‐Yen Dai, Wan‐Long Chuang, Jee‐Fu Huang, Ming‐Yen Hsieh, Ming‐Lung Yu
Journal: Hepatology (2008)

We read with great interest the article by Loustaud-Ratti et al., published in a recent issue of HEPATOLOGY.1 The authors concluded that ribavirin exposure at day 0 (D0), an early pharmacokinetic predictor, is significantly related to sustained virological response (SVR) to 48-week combination therapy with peginterferon alfa 2a and ribavirin, and amantadine which was added at week 12 and for 36 weeks. The authors also proposed a minimum area under the curve at hour 0-4 (AUC0-4h) threshold of 1755 μg.hour/L at D0 as a target for ribavirin dose adjustment. In their study, the authors defined rapid virological response (RVR) by either a nondetectable viral load or a viral load drop >2 log10 international units (IU)/mL at week 4, and defined early virological response (EVR) by a nondetectable viral load at week 12. These definitions are not in accordance with the general consensuses that at least a 2-log10 decline from baseline hepatitis C virus (HCV) RNA level is applied to EVR but not RVR.2-4 Although the authors used the quantitative real-time polymerase chain reaction assay HCV Ampliprep TaqMan to determine RVR at week 4, which was more sensitive (cut-off 15 IU/mL) than the Cobas Roche Amplicor polymerase chain reaction assay (cut-off 50 IU/mL), the reason why the authors chose special definitions of RVR and EVR and the impact on the interpretations of RVR and EVR should be elucidated. Meanwhile, the percentages of RVR were markedly different by the definition of the authors [50.0% (12/24)] and as defined by the general consensus [8.3% (2/24)]. With peginterferon alfa and ribavirin therapy, Ferenci et al. previously reported that about 10% of patients infected with HCV genotype 1 achieved RVR.5 Other studies have demonstrated that the percentage of RVR in patients with hepatitis C genotype 1 was 16%-26.7%.4, 6-8 We have recently reported a RVR rate of 43.5% (87/200) among Taiwanese patients infected with HCV genotype 1 in our randomized trial.9 The rates of RVR in patients with hepatitis C genotype 1 differ greatly from different areas. Although we applaud the study conducted by Loustaud-Ratti et al.,1 the predictive value of ribavirin exposure at D0 for SVR and the proposed target for ribavirin dose adjustment of minimum AUC0-4h threshold of 1755 μg.h/L need further confirmatory studies in different countries. Chia-Yen Dai* , Wan-Long Chuang* , Jee-Fu Huang ?, Ming-Yen Hsieh , Ming-Lung Yu* ?, * Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ? Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.
Sex Hormone–Binding Globulin Levels Predict Insulin Sensitivity, Disposition Index, and Cardiovascular Risk During Puberty
Authors: Kaspar Sørensen, Lise Aksglaede, Thor Munch-Andersen, Niels Jacob Aachmann-Andersen, Joergen Holm Petersen, Linda Hilsted, Jørn Wulff Helge, Anders Juul
Journal: Diabetes Care (2009)

Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of glucose metabolism and metabolic risk during puberty.This was a cross-sectional study on 132 healthy Caucasian children and adolescents evaluated by an oral glucose tolerance test, a dual-energy X-ray absorptiometry scan, direct oxygen uptake measurement during cycle ergometry, and fasting blood samples.SHBG levels declined with advancement of puberty in both boys (P < 0.001) and girls (P = 0.019). SHBG was significantly positively associated with insulin sensitivity in boys (P < 0.001) and girls (P < 0.001). In addition, SHBG was a strong predictor of insulin sensitivity (P = 0.001) and the only predictor of the disposition index (P = 0.031) after adjustment for puberty, fat mass, and aerobic fitness. SHBG was significantly negatively associated with metabolic risk (P = 0.032) and with hypersensitive C-reactive protein levels (P = 0.030) after adjustment for relevant confounders.SHBG was a strong predictor of insulin sensitivity and metabolic risk during puberty. Thus, we hypothesize that SHBG integrates the marked changes in glucose metabolism and body composition that occur during the pubertal transition.
Helpless without SAP
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

Wild-type CD4+ T cells (black circles), but not SAP-deficient CD4+ T cells (closed squares), restore antibody production in SAP-deficient mice. CD4

+ T cells that lack the adaptor protein SAP are little help to B cells, according to Cannons and colleagues on page [1551
Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients with diabetes and chronic kidney disease
Authors: Natalie A. Bello, Eldrin F. Lewis, Akshay S. Desai, Inder S. Anand, Henry Krum, John J.V. McMurray, Kurt Olson, Scott D. Solomon, Karl Swedberg, Dirk J. van Veldhuisen, James B. Young, Marc A. Pfeffer
Journal: European Journal of Heart Failure (2015)
Comparison of the accuracy of steroid placement with clinical outcome in patients with shoulder symptoms
Authors: J A Eustace, D P Brophy, R P Gibney, B Bresnihan, O FitzGerald
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To study the effect of accuracy on the clinical outcome of local steroid injections to the shoulder. <h3>METHODS</h3> 37 patients with shoulder symptoms of at least two months’ duration received local injections of a mixture of triamcinolone and radiographic contrast material using a standardised technique. Radiographs of the joint were taken immediately afterwards. Details of the patients’ symptoms (assessed by visual analogue scales) and range of movement at the joint were obtained before and two weeks after the injection. At follow up the patients were also assessed by means of a five point global rating scale of maximum and current benefit. <h3>RESULTS</h3> 14 of the 38 procedures (37%) were judged to be accurately placed: four of the 14 attempted subacromial injections (29%) and 10 of the 24 attempted glenohumeral injections (42%). There were significant differences in relation to outcome between the accurately placed and the inaccurately placed groups. <h3>CONCLUSIONS</h3> Accuracy of steroid placement by injection in patients with shoulder symptoms may significantly affect the clinical outcome.
An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma
Authors: Wei Xiong, Xiaosong Wu, Sarah Starnes, Sarah K. Johnson, Jeff Haessler, Siqing Wang, Lijuan Chen, Bart Barlogie, John D. Shaughnessy, Fenghuang Zhan
Journal: Blood (2008)
Clinical evaluation of the efficacy of the P2X<sub>7</sub>purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine
Authors: Edward C Keystone, Millie M Wang, Mark Layton, Sally Hollis, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The P2X<sub>7</sub> purinergic receptor antagonist AZD9056 was evaluated in a phase IIa study and subsequently in a phase IIb study to assess the effects of orally administered AZD9056 on the signs/symptoms of rheumatoid arthritis (RA), with American College of Rheumatology 20% response criteria (ACR20) as the primary outcome. <h3>Methods</h3> Both studies were randomised, double-blind, placebo-controlled, parallel-group studies in patients with RA receiving methotrexate or sulphasalazine. Phase IIa was an ascending-dose trial in two cohorts (n=75) using AZD9056 administered daily over 4 weeks. Phase IIb included an open-label etanercept treatment group. Patients were randomised to receive treatment for 6 months with 50, 100, 200 or 400 mg AZD9056 (oral, once a day) or matching placebo (oral, once a day), or subcutaneous etanercept (50 mg once a week). <h3>Results</h3> In phase IIa, 65% of AZD9056 recipients at 400 mg/day responded at the ACR20 level compared with 27% of placebo-treated patients. A significant reduction in swollen and tender joint count was observed in the actively treated group compared with placebo, whereas no effect on acute-phase response was observed. Of 385 randomised patients in the phase IIb study, 383 received treatment. AZD9056 (all doses) had no clinically or statistically significant effect on RA relative to placebo as measured by the proportion of patients meeting the ACR20 criteria at 6 months and further supported by secondary end points. In both studies AZD9056 was well tolerated up to 400 mg/day. <h3>Conclusions</h3> AZD9056 does not have significant efficacy in the treatment of RA, and the P2X<sub>7</sub> receptor does not appear to be a therapeutically useful target in RA. <h3>Trial registration number</h3> ClinicalTrials.gov NCT00520572.
New Anticoagulants for Treatment of Venous Thromboembolism
Authors: Jeffrey I. Weitz
Journal: Circulation (2004)

Treatment of venous thromboembolism (VTE) usually starts with concomitant administration of heparin or low-molecular-weight heparin (LMWH) and a vitamin K antagonist. The parenteral anticoagulant, which is given for at least 5 days, is stopped once the vitamin K antagonist produces a therapeutic level of anticoagulation. Although the introduction of LMWH has simplified the initial treatment of VTE, problems remain. LMWH must be given by daily subcutaneous (SC) injection and vitamin K antagonists require routine coagulation monitoring, which is inconvenient for patients and physicians. Recently, 3 new anticoagulants have been introduced in an attempt to overcome these limitations. These include fondaparinux and idraparinux, synthetic analogs of the pentasaccharide sequence that mediates the interaction of heparin and LMWH with antithrombin, and ximelagatran, an orally active inhibitor of thrombin. These agents produce a predictable anticoagulant response; thus, routine coagulation monitoring is unnecessary. Because they do not bind to platelets or platelet factor 4, fondaparinux and idraparinux do not cause heparin-induced thrombocytopenia (HIT). Unlike vitamin K antagonists, ximelagatran has a rapid onset of action, thereby obviating the need for concomitant administration of a parenteral anticoagulant when starting treatment. The lack of an antidote for these new agents is a drawback, particularly for idraparinux, which has a long half-life.
High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial
Authors: Ulrich F. H. Leuschner, Birgit Lindenthal, Günter Herrmann, Joachim C. Arnold, Martin Rössle, Hans‐Jörg Cordes, Stefan Zeuzem, Jasper Hein, Thomas Berg
Journal: Hepatology (2010)

In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13-15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo-controlled study was initiated with a high dose of UDCA (23-28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the modified Brunt score, 185 patients with histologically proven NASH were randomized [intention to treat (ITT)], and 147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time was 18 months. At entry, the treatment groups were comparable. A second biopsy sample was obtained from 139 of 185 patients (NAS: 107/137). The primary criterion for evaluation was a change in the liver histology; the secondary criteria were single histological variables and liver biochemistry. Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355). Only lobular inflammation improved significantly (P for the modified Brunt score = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in lobular inflammation were also observed in males, younger patients up to 50 years of age, slightly overweight patients, and patients with hypertension and an increased histology score. The fibrosis score did not change (P for ITT = 0.133, P for PP = 0.140). With the exception of γ-glutamyl transferase, UDCA did not improve laboratory data. Conclusion: High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo. Hepatology 2010
American Medical Association sues biggest US health plan over claims of underpayment of doctors
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

<b>Background:</b> Coeliac disease (CD) is an autoimmune disease often characterised by malnutrition and linked to a number of complications such as an increased risk of lymphoma, adverse pregnancy outcome, and other autoimmune diseases. Tuberculosis (TB) affects a large proportion of the world population and is more common in individuals with malnutrition. We investigated the risk of TB in 14 335 individuals with CD and 69 888 matched reference individuals in a general population based cohort study. <b>Methods:</b> Cox proportional hazards method was used to calculate the risk of subsequent TB in individuals with CD. In a separate analysis, the risk of CD in individuals with prior TB was calculated using conditional logistic regression. <b>Results:</b> CD was associated with an increased risk of subsequent TB (hazard ratio (HR) 3.74, 95% CI 2.14 to 6.53; p&lt;0.001). Similar risk estimates were seen when the population was stratified for sex and age at CD diagnosis. Individuals with CD were also at increased risk of TB diagnosed in departments of pulmonary medicine, infectious diseases, paediatrics, or thoracic medicine (HR 4.76, 95% CI 2.23 to 10.16; p&lt;0.001). The odds ratio for CD in individuals with prior TB was 2.50 (95% CI 1.75 to 3.55; p&lt;0.001). <b>Conclusions:</b> CD is associated with TB. This may be due to malabsorption and lack of vitamin D in persons with CD. Individuals with TB and gastrointestinal symptoms should be investigated for CD.
Enhanced mismatch mutation analysis: a new high throughput screening method for simultaneous detection of point mutation and gross gene rearrangement designed for BRCA1 and BRCA2 genes.
Authors: B Gastaldello, J Champ, D Lafon, A Fraud, M Longy, J Viovy, J Weber, F Bonnet, N Sevenet
Journal: Cancer Research (2009)

Abstract Abstract #1102 Background : Recent studies showed that large genetic rearrangements (duplication or deletion of one or several exons) are of great importance in genetic diseases. Only few methods such as QMPSF and MLPA fit a routine use for these large deletions and duplications. They have to be performed additionally to a point mutation detection method (usually sequencing or dHPLC), which is labor intensive, time consuming and expensive. We present here a method called Enhanced Mismatch Mutation Analysis (EMMA) based on heteroduplex analysis that offers great sensitivity for point mutation detection and simultaneously detection of gross gene rearrangement by capillary electrophoresis.&amp;#x2028; Material and Methods : EMMA is able to detect point mutations in PCR fragment ranging from 200 bp to 550 bp. It is thus possible to perform size multiplexing and analyze up to 6 fragments in the same run. PCR multiplex fragments of different sizes are prepared by semi-quantitative PCR. Separations are performed in multi-capillary electrophoresis. Poly(acrylamide-g-poly(dimethylacrylamide)) is used as a self coating sieving matrix; this separation matrix contains also additives like free nucleotides for a better sensitivity. One of the fragment is chosen as a reference for peak area normalization.&amp;#x2028; Results : A series of 30 patients has been screened for BRCA1 and BRCA2 genes simultaneously by EMMA and the classical package dHPLC-QMPSF. All mutations and polymorphism detected by dHPLC have been detected by EMMA and new polymorphisms have been characterized for those genes. Furthermore, we will present the whole results of the positive mutation controls of BRCA1 and BRCA2 of the Institut Bergonie molecular genetic lab database screened by EMMA.&amp;#x2028; Discussion : Using a unique condition of capillary electrophoresis separation for a lower number of PCR reaction for each gene (9 for BRCA1 and 15 for BRCA2), EMMA demonstrates a 5 times saving of lab time for technician, and displays a large easiness to use it in a routine way for molecular diagnosis. Finally this technology will benefit of a grant of French Ministry of Industry to be spread in molecular lab of Comprehensive Cancer Centers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1102.