tbuckley/cabot-search huggingface dataset:
Bahraini doctors are promised civilian trials after protests over harsh sentences
Authors: S. Arie
Journal: BMJ (2011)

Bahraini authorities seem to have ceded to international pressure and ordered a retrial of the 20 health workers convicted in late September to up to 15 years for alleged antigovernment activities while treating injured protesters earlier this year ( BMJ 2011;343:d6336, doi:10.1136/bmj.d6336).

Bahrain’s attorney general, Ali Alboainain, announced on Wednesday 5 October that the 20 should be “retried before the ordinary courts” after widespread complaints of an unfair trial by the special court whose military judge handed down the harsh sentences.

“The Department of Public Prosecutions seeks to establish the truth and to enforce the law, while protecting the rights of the accused,” he …
Statistical issues on the no-observed-adverse-effect level in categorical response.
Authors: T Yanagawa, Y Kikuchi, K G Brown
Journal: Environmental Health Perspectives (1994)

The determination of the value of the no-observed-adverse-effect level (NOAEL) when observed responses can be categorized by severity (categorical data) and sample sizes are small is discussed. The common situation of only two categories, where only the presence or absence of an effect is observed, is addressed first (dichotomous data). Three tests for dichotomous data are critically examined, including the Brown-La Vange test, a modified version of that test, and Dunnett's multiple comparison test. Although the modified test is an improvement, all three procedures have shortcomings in determining the value of the NOAEL, particularly when the sample size is small. An alternative method is suggested, based on the Akaike information criterion (AIC), which performs well. This method is extended to severity data with an arbitrary number of categories. Use of a dose-response curve for the NOAEL is discussed.
Review: Aspirin does not reduce CHD or cancer mortality but increases bleeding
Authors: Christopher M. Rembold
Journal: Annals of Internal Medicine (2012)

Source Citation Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:209-16. 22231610
The effect of etretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis
Authors: A. Lassus, J. Lauharanta, A. Eskelinen
Journal: British Journal of Dermatology (1985)

Eighty‐four patients with persistent palmoplantar pustulosis (PPP) of long duration were treated with either etretinate or one of three PUVA regimens. PUVA was given either with oral methoxsalen (thirteen cases), with a 1% methoxsalen cream (thirty‐three cases) or with trioxsalen baths (eighteen cases). Twenty patients were treated with etretinate. Patients were assessed every fourth week. A mean score for each group was calculated at each visit based on erythema, desquamation, induration and pustulation. In addition, the number of pustules was calculated at each visit. After 12 weeks four of twenty‐eight patients treated with local methoxsalen and fourteen of seventeen patients treated with etretinate had completely cleared. At this stage no patient treated with local trioxsalen or oral methoxsalen showed complete clearance.
DEATH FROM PULMONARY EMBOLISM FOLLOWING THE INJECTION OF VARICOSE VEINS
Authors: Leslie L. Nunn
Journal: JAMA (1941)

If one considers the many cases in which varicose veins are treated by the injection of sclerosing solutions, the dreaded complication of pulmonary embolism is relatively uncommon. Pennoyer<sup>1</sup>in 1930 stated that only 4 cases had been reported up to that time; he stated further that in all these cases injection may have been done in the presence of acute or subacute phlebitis. Since 1930 2 more cases have been reported in this country and several have appeared in the foreign literature. Since 400,000 cases had been reported in which injection had been done, the possibilities of such a complication seem to be almost nil. In 1928 McPheeters and Rice<sup>2</sup>reported 7 deaths in a series of 53,000 cases of injection therapy; Kettel<sup>3</sup>reported 20 deaths in a series of 60,000 cases, mortalities of 0.0025 per cent and 0.033 per cent respectively. These figures represent the combined
Plasma cells composing plasmacytoma have phenotypes different from those of myeloma cells
Authors: Akira Sakai, Teruhisa Fujii, Masaaki Noda, Hideo Hyodo, Kenji Oda, Akiro Kimura
Journal: American Journal of Hematology (1996)

We describe one relapsed case of plasmacytoma of mandibular bone. The organs of relapse were liver and bone marrow. At relapse, monoclonal gammopathy (IgG-κ) was observed without suppression of IgA and IgM. By immunostaining, the plasma cells of both the original mandibular bone and liver were positive for the same cytoplasmic immunoglobulin light chain κ. The proliferative plasma cells in the bone marrow had the phenotype of CD38+, CD19+, and CD56- by flow cytometry and showed the presence of the rearranged IgH gene by Southern blotting. In addition, the zone of the Ig class of the patient's serum was not so sharply defined by zone electrophoresis. These results suggest that the characteristics of plasma cells of plasmacytoma are different from those of multiple myeloma. © 1996 Wiley-Liss, Inc.
KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation
Authors: Benjamin L Kidder, Gangqing Hu, Keji Zhao
Journal: Genome biology (2014)

Abstract Background Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. Results Here, we show that KDM5B, which demethylates lysine 4 of histone H3, co-localizes with H3K4me3 near promoters and enhancers of active genes in ES cells; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, indicating that KDM5B functions to focus H3K4 methylation at promoters and enhancers. Spreading of H3K4 methylation to gene bodies and enhancer shores is linked to defects in gene expression programs and enhancer activity, respectively, during self-renewal and differentiation of KDM5B-depleted ES cells. KDM5B critically regulates H3K4 methylation at bivalent genes during differentiation in the absence of LIF or Oct4. We also show that KDM5B and LSD1, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes. Conclusions Our results provide global and functional insight into the role of KDM5B in regulating H3K4 methylation marks near promoters, gene bodies, and enhancers in ES cells and during differentiation.
Pleiotropic Biological Activities of Alternatively Spliced TMPRSS2/ERG Fusion Gene Transcripts
Authors: Jianghua Wang, Yi Cai, Wendong Yu, Chengxi Ren, David M. Spencer, Michael Ittmann
Journal: Cancer Research (2008)

TMPRSS2/ERG gene fusions are found in the majority of prostate cancers; however, there is significant heterogeneity in the 5' region of the alternatively spliced fusion gene transcripts. We have found that there is also significant heterogeneity within the coding exons as well. There is variable inclusion of a 72-bp exon and other novel alternatively spliced isoforms. To assess the biological significance of these alternatively spliced transcripts, we expressed various transcripts in primary prostatic epithelial cells (PrEC) and in an immortalized PrEC line, PNT1a. The fusion gene transcripts promoted proliferation, invasion, and motility with variable activities that depended on the structure of the 5' region encoding the TMPRSS2/ERG fusion and the presence of the 72-bp exon. Cotransfection of different isoforms further enhanced biological activity, mimicking the situation in vivo, in which multiple isoforms are expressed. Finally, knockdown of the fusion gene in VCaP cells resulted in inhibition of proliferation in vitro and tumor progression in an in vivo orthotopic mice model. Our results indicate that TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression and are consistent with our previous clinical observations indicating that certain TMPRSS2/ERG fusion isoforms are significantly correlated with more aggressive disease.
Sodium Diphenylhydantoin Reaction With Evidence of Circulating Antibodies
Authors: Donald S. Robinson
Journal: JAMA (1965)

SODIUM diphenylhydantoin (Dilantin Sodium) has produced many reactions with a variety of manifestations.<sup>1</sup>A large group of these reactions seem to be on a hypersensitivity basis and resemble well-known allergic reactions, ie, hives, serum sickness reactions, and thrombocytopenia. Others have been suggested as being in this category because of the typical temporal relationship between drug administration and onset of the reaction. In some patients readministration of sodium diphenylhydantoin has promptly brought on a recurrence of the reaction. Serious adverse reactions to this drug have included exfoliative dermatitis, polyarthritis, and lymphadenopathy simulating lymphoma. We have recently studied a patient with a sodium diphenylhydantoin reaction resembling a malignant lymphoma, in whom circulating antibodies against sodium diphenylhydantoin were demonstrated by the basophil degranulation test.<sup>2</sup> <h3>Report of a Case</h3> A 59-year-old white woman received severe injuries in an automobile accident in March 1963 and was comatose for three weeks. She recovered, but five
Brain rhythm that correlates with obesity.
Authors: K Adam
Journal: BMJ (1977)

inactive.The only reasonable correlation of the clubbing was with the growth of the glioma, which initially was too small to be detected but which grew to a large size.It may be concluded that the glioma was in some way the cause of the clubbing, an association that has not been made before.The coexistence of these two features may be important to avoid misdiagnosis in similar cases.This case also illustrates the difficulty in diagnosing the cause of transient neurological symptoms.4Although the clinical evidence pointed to a transient ischaemic attack, possibly from an endocardial thrombus, the correct diagnosis was a small cerebral tumour probably causing focal epilepsy.5
Book Review Fundamentals of the Stem Cell Debate: The Scientific, Religious, Ethical and Political Issues Edited by Kristen Renwick Monroe, Ronald B. Miller, and Jerome Tobis. 218 pp., illustrated. Berkeley, University of California Press, 2008. $50 (cloth); $19.95 (paper). 978-0-520-25210-3 (cloth); 978-0-520-25212-7 (paper).
Authors: John Hearn
Journal: New England Journal of Medicine (2008)
Evaluation of Monoclonal Humanized Anti-HER2 Antibody, Trastuzumab, in Patients With Recurrent or Refractory Ovarian or Primary Peritoneal Carcinoma With Overexpression of HER2: A Phase II Trial of the Gynecologic Oncology Group
Authors: Michael A. Bookman, Kathleen M. Darcy, Daniel Clarke-Pearson, Richard A. Boothby, Ira R. Horowitz
Journal: Journal of Clinical Oncology (2003)

Purpose: To evaluate the feasibility, toxicity, and efficacy of single-agent monoclonal antibody therapy targeting the human epidermal growth factor receptor 2 (HER2)/neu receptor in ovarian and primary peritoneal carcinoma. Patients and Methods: Eligible patients had measurable persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with 2+ or 3+ HER2 overexpression documented by immunohistochemistry. Intravenous trastuzumab was administered initially at a dose of 4 mg/kg, then weekly at 2 mg/kg. Patients without progressive disease or excessive toxicity could continue treatment indefinitely. Those with stable or responding disease at 8 weeks were offered treatment at a higher weekly dose (4 mg/kg) at time of progression. Patient sera were analyzed for the presence of the soluble extracellular domain of HER2, host antibodies against trastuzumab, and trastuzumab pharmacokinetics. Results: A total of 837 tumor samples were screened for HER2 expression, and 95 patients (11.4%) exhibited the requisite 2+/3+ expression level. Forty-five patients, all of whom received prior chemotherapy, were entered, and 41 were deemed eligible and assessable. There were only mild expected toxicities and no treatment-related deaths. Although an elevated level of the soluble extracellular domain of HER2 was detected in eight of 24 patients, serum HER2 was not associated with clinical outcome. There was no evidence of host antitrastuzumab antibody formation. Serum concentrations of trastuzumab gradually increased with continued therapy. An overall response rate of 7.3% included one complete and two partial responses. Median treatment duration was 8 weeks (range, 2 to 104 weeks), and median progression-free interval was 2.0 months. Conclusion: The clinical value of single-agent trastuzumab in recurrent ovarian cancer is limited by the low frequency of HER2 overexpression and low rate of objective response among patients with HER2 overexpression.
Drugs “refund” scheme proposed for England and Wales
Authors: Susan Mayor
Journal: BMJ (2007)

Officials in Nigeria have filed criminal and civil charges against Pfizer for its role in the deaths and disabilities of children who were treated with an experimental drug during a meningitis outbreak in Kano in 1996.The charges, filed by government prosecutors in Nigeria, follow three attempts by families of the children to sue in US courts.All three attempts were denied after Pfizer successfully argued that the US courts were not an appropriate forum.Four separate legal actions have been filed in Nigeria, including 31 criminal counts against 10 people, according to the Washington Post (www.washingtonpost.com, 2 Jun, "Pfizer faces new charges over Nigerian drug test").The plaintiffs also seek a total of $9bn (£4.5bn; €7bn) in civil suits.The charges stem from Pfizer's test of its unlicensed drug, trovafloxacin (Trovan) to treat 100 children with meningitis.A comparator group of 100 children were treated with a low dose of ceftriaxone.Suits on appeal in US courts charge Pfizer with causing harm to the children in both arms of the trial, alleging that a number of the children either died or were left deaf, mute, or brain damaged.The families allege that the company failed to tell them that their children were being enrolled in an experimental drug trial and that free, effective treatment was available from Médecins Sans Frontières at the same hospital.Five children in the trovafloxacin arm and six in the ceftriaxone arm died, according to Pfizer.Pfizer issued a statement in response to the charges, saying "Pfizer continues to emphasise-in the strongest terms-that the 1996 Trovan clinical study was conducted with the full knowledge of the Nigerian government and in a responsible and ethical way consistent with the company's abiding commitment to patient safety."Any allegations in these lawsuits to the contrary are simply untrue." Niger�ia files cr�iminal char�ges against Pfizer�
Reducing maternal mortality in the developing world: sector-wide approaches may be the key
Authors: E. Goodburn
Journal: BMJ (2001)

Reducing “the rate of maternal mortality by 75% by 2015” is one of the development targets that has been endorsed at numerous international meetings.1 This target was selected because maternal ill health is the largest contributor to the disease burden affecting women in developing countries; because the lifetime risk of maternal death is much greater in the poorest countries than in the richest (1 in 12 for women in east Africa compared with 1 in 4000 in northern Europe); and because interventions are cost effective (costing £2 ($3) per woman and £153 ($230) per death averted).2–5

#### Summary points

Reducing maternal mortality in developing countries is an international priority

Preventing maternal deaths requires a functioning health system

Sector-wide approaches allow donors to support improvements in health systems

Sector-wide approaches offer the opportunity to make a sustainable impact on maternal mortality

Improvements in maternal health can be used to measure the performance of sector-wide approaches

The technical interventions needed to prevent maternal deaths are well understood.6 Traditional maternal and child health interventions, such as providing antenatal care and training traditional birth attendants, have failed. 2 7 The availability, accessibility, use, and quality of essential obstetric care for life threatening conditions, including complications after abortion, need to be improved (box). 2 6 7 What is less clear is how an environment can be created to enable interventions to be made in settings with few resources.8

#### Causes of maternal deaths

Severe bleeding 25%

Indirect causes including anaemia, malaria, 20% heart disease

Infection 15%

Unsafe abortion 13%

Eclampsia 12%

Obstructed labour 8%

Other direct causes including ectopic pregnancy, 8% embolism, or complications of anaesthesia

Creating a functioning health system is the most obvious means of providing this type of environment. Most of the resources needed to improve essential obstetric care exist as integral parts of …
FRI0414 Tocilizumab in methotrexate-intolerant or contraindicated patients – a cost-utility model for scotland
Authors: C. Gibbons, A. Diamantopoulos, H. Pang, C. Huertas, F. Dejonckheere
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab (TCZ) is indicated for the treatment of adult rheumatoid arthritis (RA) that has responded inadequately to one or more disease-modifying antirheumatic drugs (“DMARD-IR patients”). Whilst typically given with methotrexate (MTX), TCZ may also be administered as monotherapy in patients who are intolerant of or contraindicated to MTX. The cost-effectiveness of this approach compared with current standard care in MTX-intolerant/contraindicated DMARD-IR patients has not previously been undertaken. <h3>Methods</h3> An economic model was developed to reflect the healthcare system and treatment pathway in Scotland. In the model, disease severity is represented by HAQ score; a surrogate health outcome which can be translated to utility scores and ultimately QALYs. The model captures the progression of HAQ score for each individual patient in an individual simulation process. ACR response rates are used as a measurement of response to treatment as these are readily available from TCZ trials as well as from RCTs of the other therapies included in this model. Benefits were expressed as quality adjusted life years (QALYs). Costs were calculated from a National Health Service Scotland and Personal Social Services perspective and included treatment costs as well as patient-condition-related costs. The analysis calculated incremental costs and benefits associated with the addition of TCZ in first line to the standard care pathway involving certolizumab pegol, etanercept and adalimumab. Treatment effects for TCZ monotherapy were based on efficacy data from the ACT-RAY trial (Dougados et al 2011). Data from comparator medicines were sourced from available monotherapy trials of adalimumab (van de Putte et al 2004), certolizumab pegol (Fleischmann et al 2009), and etanercept (Moreland et al 1999). <h3>Results</h3> Base case results estimated incremental costs of about £24,000 and incremental QALYs of 0.88. The incremental cost-effectiveness ratio (ICER) was £27,000 per QALY gained. The model was most sensitive to patient weight (which drives drug cost) and the parameters used in the HAQ-to-utility estimation equation. A probabilistic sensitivity analysis produced a very similar ICER of £27,500 per QALY gained. <h3>Conclusions</h3> The results of this analysis suggest that TCZ monotherapy represents an efficacious and cost-effective addition to the current standard of care in Scotland, for treating RA patients who are MTX intolerant. <h3>Disclosure of Interest</h3> C. Gibbons Employee of: Roche Products Limited, A. Diamantopoulos Consultant for: Roche Products Limited, H. Pang Employee of: Roche Products Limited, C. Huertas Employee of: Roche Products Limited, F. Dejonckheere Employee of: F.Hoffmann-La Roche
EFFECT OF LXR-623, ALONE OR IN COMBINATION WITH SIMVASTATIN, ON REGRESSION AND STABILIZATION OF ATHEROSCLEROTIC PLAQUES: AN MRI STUDY IN A MODEL OF ADVANCED ATHEROSCLEROSIS
Authors: Chiara Giannarelli, Giovanni Cimmino, Thomas M. Connolly, Borja Ibanez, Josè M. Garcia Ruiz, Giora Feuerstein, Matilde Alique, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2010)
Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease
Authors: Peter C. Rimensberger, Isabelle Spahr-Schopfer, Michel Berner, Edgar Jaeggi, Afksendiyos Kalangos, Beat Friedli, Maurice Beghetti
Journal: Circulation (2001)

Background —Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results —A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng · kg −1 · min −1 for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48±0.38 to 0.27±0.16 ( P &lt;0.001). Similarly, iloprost decreased the ratio from 0.49±0.38 to 0.26±0.11 ( P &lt;0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6±11.9 to 34.7±21.4 nmol/L during iNO ( P &lt;0.01), and plasma cAMP increased from 55.7±22.9 to 65.1±21.2 nmol/L during iloprost inhalation ( P &lt;0.05). Conclusions —In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.
Serum Cholesterol in Pentolinium -Treated Arterial Hypertension
Authors: HAROLD H. ORVIS, IRENE G. TAMAGNA, JOHN M. EVANS
Journal: Circulation (1958)

Serum lipids were serially determined in 11 patients receiving pentolinium therapy to evaluate changes secondary to blood pressure effects. Substantial reduction in total Cholesterol was observed, which in some cases was independent of the hypotensive effect of the drug. Fat absorption, studied in 6 patients, revealed diminished postprandial lipemia in each as compared to placebo determinations. However, few patients showed appreciable weight change during a year of therapy. The evidence suggests that the serum lipid changes secondary to pentolinium administration are due to a qualitative change in fat absorption.