tbuckley/cabot-search huggingface dataset:
Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.
Authors: E M Deacon, G Pallesen, G Niedobitek, J Crocker, L Brooks, A B Rickinson, L S Young
Journal: The Journal of Experimental Medicine (1993)

Epstein-Barr virus (EBV) is associated with a number of different human tumors and appears to play different pathogenetic roles in each case. Thus, immunoblastic B cell lymphomas of the immunosuppressed display the full pattern of EBV latent gene expression (expressing Epstein-Barr nuclear antigen [EBNA]1, 2, 3A, 3B, 3C, and -LP, and latent membrane protein [LMP]1, 2A, and 2B), just as do B lymphoblastoid cell lines transformed by the virus in vitro. In contrast, those EBV-associated tumors with a more complex, multistep pathogenesis show more restricted patterns of viral gene expression, limited in Burkitt's lymphoma to EBNA1 only and in nasopharyngeal carcinoma (NPC) to EBNA1 and LMP1, 2A, and 2B. Recent evidence has implicated EBV in the pathogenesis of another lymphoid tumor, Hodgkin's disease (HD), where the malignant Hodgkin's and Reed-Sternberg (HRS) cells are EBV genome positive in up to 50% of cases. Here we extend preliminary results on viral gene expression in HRS cells by adopting polymerase chain reaction-based and in situ hybridization assays capable of detecting specific EBV latent transcripts diagnostic of the different possible forms of EBV latency. We show that the transcriptional program of the virus in HRS cells is similar to that seen in NPC in several respects: (a) selective expression of EBNA1 mRNA from the BamHI F promoter; (b) downregulation of the BamHI C and W promoters and their associated EBNA mRNAs; (c) expression of LMP1 and, in most cases, LMP2A and 2B transcripts; and (d) expression of the "rightward-running" BamHI A transcripts once thought to be unique to NPC. This form of latency, consistently detected in EBV-positive HD irrespective of histological subtype, implies an active role for the virus in the pathogenesis of HD and also suggests that the tumor may remain sensitive to at least certain facets of the EBV-induced cytotoxic T cell response.
Including older people in clinical research
Authors: Marion E T McMurdo, Miles D Witham, Neil D Gillespie
Journal: BMJ (2005)

Benefits shown in trials in younger people may not apply to older people 

T here are more old people alive today than at any time in history. Older people are, quite rightly, “the core business of the NHS.”1 The need to be able to draw on the results of good quality research to inform best practice in the specific management of older people is compelling. So we might expect that researchers would have eagerly embraced the participation of older people in clinical trials. Yet this is not the case. What do clinicians and researchers have to do to redress the serious bias against older people in clinical research?

The evidence that older people are being excluded from clinical research is widespread. Although the world is facing a global increase in the prevalence of diabetes mellitus, and by 2030 it is estimated that over 48 million older people in developed countries will have diabetes, the mean age of participants in the United Kingdom Progression of Diabetes Study was only 53 years. Guidelines on older people with diabetes have acknowledged …
Prehospital Cardiopulmonary Resuscitation
Authors: Richard O. Cummins
Journal: JAMA (1985)

TWO PARADOXES lie behind the question posed in the title of this article. First, rapid and widespread dissemination of the technique of cardiopulmonary resuscitation (CPR) occured before the underlying physiology was fully understood. Second, data that indicate discouragingly low coronary and carotid artery flow rates contrast sharply with the obvious lifesaving capacity of basic CPR. <h3>CPR</h3> In the early 1960s, Kouwenhoven et al<sup>1</sup>demonstrated the effectiveness of closed-chest compressions for cardiac arrest; rapid worldwide dissemination of the technique soon followed. By 1974, the endorsement of influential groups such as the American Heart Association secured broad acceptance for standard CPR.<sup>2</sup>Kouwenhoven and co-workers thought that during CPR blood was expelled by compression of the heart between the sternum and vertebral bodies. Later, however, various research laboratories conducted what were, in effect, post hoc investigations into the physiology of CPR; by the 1980s, few researchers subscribed to Kouwenhoven and co-workers'
The Child With Disabling Illness: Principles of Rehabilitation
Authors: Sheldon Berrol
Journal: JAMA (1982)

The first edition of this tome established itself as an essential text in the field of pediatric rehabilitation medicine. The editors of the second edition again present their material in four major sections. The first, on selected chronic medical illnesses, has significantly updated both its statistics and the medical management approach to the child with chronic asthma. The section on disorders of the neuromuscular system has added an important chapter on seizure disorders, producing a good, basic review. The chapter on cerebral palsy again concentrates primarily on motor effects and pays little attention to associated disorders such as sensory deficits. The section on disorders of the musculoskeletal system and injuries has added a brief but important discussion on "treatment of foot and ankle in cerebral palsy and myelomeningocele." This complements well the ensuing chapter on orthosis for children, which is well illustrated and conceptually well organized. The discussion of scoliosis
Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Heidi D. Nelson, M.E. Beth Smith, Jessica C. Griffin, Rongwei Fu
Journal: Annals of Internal Medicine (2013)

Background: Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. Purpose: To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer. Data Sources: MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists. Study Selection: English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. Data Extraction: Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria. Data Synthesis: Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer–specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer. Limitation: Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. Conclusion: Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. Primary Funding Source: Agency for Healthcare Research and Quality.
Black Lung Benefits
Authors: William R. Barclay
Journal: JAMA (1980)

The Black Lung Benefits Reform Act of 1977 awards compensation for pulmonary disability incurred as a consequence of employment as a coal miner. The intent of Congress as expressed in this act is simple and clear, but unfortunately administration of the act is difficult and often results in an unfair and inequitable distribution of public funds. Assessing disability by symptoms and measures of pulmonary function is not easy and often results in erroneous judgments. Disability, even when it exists, is rarely caused by coal particles alone but is usually the result of other factors such as cigarette smoking, which results in emphysema. A man in whom emphysema develops and who has a history of being a coal miner can receive compensation, while another victim of the same disease, who never worked in a coal mine, receives no compensation. As might be expected the prospect of being awarded a government pension
Hepatic activation of IKK/NFκB signaling induces liver fibrosis via macrophage-mediated chronic inflammation
Authors: Yoshiaki Sunami, Frank Leithäuser, Sarah Gul, Katja Fiedler, Nurdan Güldiken, Sigrid Espenlaub, Karl-Heinz Holzmann, Nora Hipp, Anca Sindrilaru, Tom Luedde, Bernd Baumann, Sebastian Wissel, Florian Kreppel, Marion Schneider, Karin Scharffetter-Kochanek, Stefan Kochanek, Pavel Strnad, Thomas Wirth
Journal: Hepatology (2012)

Liver damage in humans is induced by various insults including alcohol abuse, hepatitis B/C virus infection, autoimmune or metabolic disorders and, when persistent, leads to development of liver fibrosis. Because the nuclear factor-κB (NF-κB) system is activated in response to several of these stresses, we hypothesized that NF-κB activation in hepatocytes may contribute to fibrosis development. To activate the NF-κB signaling pathway in a time- and cell-type-specific manner in the liver, we crossed transgenic mice carrying the tetracycline-responsive transactivator under the control of the liver activator protein promotor with transgenic mice carrying a constitutively active form of the Ikbkb gene (IKK2 protein [CAIKK2]). Double-transgenic mice displayed doxycycline-regulated CAIKK2 expression in hepatocytes. Removal of doxycycline at birth led to activation of NF-κB signaling, moderate liver damage, recruitment of inflammatory cells, hepatocyte proliferation, and ultimately to spontaneous liver fibrosis development. Microarray analysis revealed prominent up-regulation of chemokines and chemokine receptors and this induction was rapidly reversed after switching off the CAIKK2 expression. Turning off the transgene expression for 3 weeks reversed stellate cell activation but did not diminish liver fibrosis. The elimination of macrophages by clodronate-liposomes attenuated NF-κB-induced liver fibrosis in a liver-injury-independent manner. Conclusion : Our results revealed that hepatic activation of IKK/NF-κB is sufficient to induce liver fibrosis by way of macrophage-mediated chronic inflammation. Therefore, agents controlling the hepatic NF-κB system represent attractive therapeutic tools to prevent fibrosis development in multiple chronic liver diseases.
Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites.
Authors: K H Park, L E Rubin, S S Gross, R Levi
Journal: Circulation Research (1992)

Hypoxia is a potent coronary-vasodilating signal; its mechanisms are still controversial. We have assessed the possible role of nitric oxide (NO) in hypoxic coronary vasodilatation (HCVD) in isolated guinea pig hearts perfused at constant pressure. HCVD was elicited by a 1-minute 100% N2 exposure; coronary flow doubled within 1 minute of hypoxia (early phase) and returned to baseline within 40 seconds after reoxygenation (late phase). The early phase of HCVD was associated with a rapid approximately eightfold increase in cGMP overflow, an indication of NO release. The specific NO synthase inhibitor N omega-methyl-L-arginine (NMA, 0.1-1 mM) antagonized HCVD and the associated increase in cGMP spillover (maximum inhibition, approximately 65%); excess arginine (1.2 mM) prevented both effects. The late phase of HCVD was associated with an increase in adenosine overflow and was attenuated by the adenosine receptor antagonist BW A1433 (1 microM; maximum inhibition, approximately 45%). Indomethacin (10 microM) inhibited HCVD in spontaneously beating hearts by approximately 35% but had no effect in hearts paced at faster rates. NMA and BW A1433 were more effective in combination than alone (maximum inhibition, approximately 72%). However, irrespective of the concentrations used, there was no synergism among the anti-HCVD effects of NMA, BW A1433, and indomethacin, nor was HCVD completely inhibited by the antagonists, whether alone or in combination. Our findings indicate that NO is an important mediator of the early phase of HCVD, whereas additional mechanisms and/or factors, including adenosine and vasodilatatory prostaglandins, contribute to the late phase.
Epilepsy in prisons: A diagnostic survey
Authors: J. Gunn, G. Fenton
Journal: BMJ (1969)

A previous study has suggested that epilepsy is commoner in prisons than in the general population. We devised a standard definition of "epilepsy" and then interviewed a representative sample of the "epileptics" in prisons. The results confirmed the initial conclusion, and showed the point prevalence of epilepsy in prison and Borstals to be at least 7.1/1,000 men.
Healthy eating in pregnancy
Authors: L. Poston
Journal: BMJ (2014)

Always a good idea, now with more supporting evidence

Most pregnant woman want to know the best foods to eat and what to avoid. The possible dangers of eating liver, the need to avoid unprocessed cheeses and too much tuna, and, above all, the importance of folate supplements are widely appreciated. Two linked papers from Australia (Dodd and colleagues; doi:10.1136/bmj.g1285) and Norway (Englund-Ogge and colleagues; doi:10.1136/bmj.g1446) have explored whether eating “healthily” can improve clinically important pregnancy outcomes.1 2

Dodd and colleagues looked at the global prevalence of overweight and obesity among women in antenatal care and the associated complications, including risks of gestational diabetes and delivery of overlarge infants. Women in their LIMIT trial were advised to maintain a balance of carbohydrates, fat, and protein in their diet; to reduce consumption of foods rich in refined carbohydrates and saturated fat; and to increase intake of fruit, fibre, and vegetables; a regimen that should reduce insulin resistance, central to the complications of obesity in pregnancy. They were also encouraged to take physical exercise. This randomised controlled trial of a lifestyle intervention in overweight and obese women was adequately powered to address clinical outcomes. Previously small and often poorly designed studies have been undertaken with a surrogate clinical endpoint, notably gestational weight gain. Meta-analysis of these has shown no evidence for …
Conversation Repair: Case Studies in Doctor-Patient Communication
Authors: C. R Whitehouse
Journal: BMJ (1995)

Frederic W Platt Little, Brown, $24.95, pp 194 ISBN 0 316 71082 2

“Problem-based learning in communication skills with the goal of enabling doctors to modify their attitudes to difficult patients and to manage consultations in a patient-centred way.” Put like that the main message of Conversation Repair sounds dull. It is not. That sentence probably contains more jargon than all seven chapters of this delightfully honest and fresh approach to teaching communication.

Frederic Platt has been teaching communication skills in Denver, Colorado, for 20 years. Here he brings together …
FAVORABLE EFFECTS OF FLAVONOIDS ON ENDOTHELIAL FUNCTION AND ARTERIAL STIFFNESS IN HEALTHY SMOKERS
Authors: Eleni Kokkou, Gerasimos Siasos, Dimitris Tousoulis, Evangelos Oikonomou, Marilena Kollia, Stamatios Kioufis, Marina Zaromitidou, Nikolaos Gouliopoulos, Aleksis Verveniotis, Dimitrios Athanasiou, Konstantinos Zisimos, Athanasios G. Papavassiliou, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
Intensive population-level screening and counseling did not reduce ischemic heart disease at 10 years
Authors: Dana J. Herrigel, Laura Rees Willett
Journal: Annals of Internal Medicine (2014)

Source Citation Jørgensen T, Jacobsen RK, Toft U, et al. Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial. BMJ. 2014;348:g3617. 24912589
The Birth of Quadruplets, with an Account of the Placentas and Fetal Membranes
Authors: Robert R. Ryan, George B. Wislocki
Journal: New England Journal of Medicine (1954)

THE placentas and membranes of the quadruplets in the case reported below were interesting because they were well preserved, thus affording an opportunity for the preparation of good illustrations and microscopical sections. There are few adequate illustrations of the placentas of quadruplets and quintuplets in the literature, owing partly to their rarity and partly to the fact that some were not preserved and studied whereas others were poorly preserved and still others delivered piecemeal or badly torn.The placentas and fetal membranes of twins have been the subject of extensive surveys by Guttmacher,1 and those of triplets by Saniter2 and . . .
Testosterone Medications Need New Label Information
Authors: Rita Rubin
Journal: JAMA (2015)

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Abstract S1-4: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of AMG 479 With Exemestane (E) or Fulvestrant (F) in Postmenopausal Women With Hormone-Receptor Positive (HR+) Metastatic (M) or Locally Advanced (LA) Breast Cancer (BC)
Authors: PA Kaufman, JM Ferrero, H Bourgeois, H Kennecke, R De Boer, W Jacot, J McGreivy, S Suzuki, E Loh, J. Robertson
Journal: Cancer Research (2010)

Abstract Background: AMG 479 is an investigational, fully human monoclonal antibody targeting the type 1 insulin-like growth factor receptor (IGF1R) that blocks binding of IGF-1 and IGF-2. Preclinical data suggest that inhibition of estrogen receptor (ER) and IGF1R signaling in ER+ BC can result in greater suppression of cell proliferation than achieved by blocking either pathway alone. Inhibition of the IGF1R-signaling pathway might enhance sensitivity of 2nd-line hormonal therapy in BC patients (pts). We conducted a 2-arm, double blind, placebo-controlled, randomized study evaluating the addition of AMG 479 to either E or F in M or LA BC pts who had progressed on prior endocrine therapy. Patients: Eligibility included: HR+ incurable M or LA BC; progression while receiving prior endocrine therapy for MBC or LA or within 12 months of completing adjuvant hormonal therapy; post menopausal; adequate glycemic control. HER2+ tumor status allowed. Study Design: Pts were randomly allocated 2:1 to either AMG 479 or placebo; E or F was per investigator. Pts received AMG 479 12 mg/kg IV or placebo Q2W + either E 25 mg QD PO or F 500 mg IM on day 1, 250 mg IM day 15 and 29, and Q4W thereafter. Eligible pts who progressed on the placebo arm could proceed on open-label AMG 479. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. MRI or CT scans were done every 8 weeks and bone scans every 12 weeks (for pts with bone involvement at screening). Endpoints: The primary endpoint was progression-free survival (PFS), as measured by modified RECIST v1.0 per investigator review. Results: 156 pts were randomized between March 2008 and July 2009. Median age, 61 (range 36-88) years; M vs LA BC, 154 (99%) vs 2 (1%). 127 pts (81%) had discontinued treatment as of May 2010. See table for efficacy. For pts receiving AMG 479 or placebo, the incidence of grade ≥3 AE was 42% and 24% and for serious AE, 25% and 18%. The most common grade ≥3 AEs (AMG 479/placebo) were: hyperglycemia (6%/0%), neutropenia (6%/2%), thrombocytopenia (4%/0%), asthenia (4%/2%), and increased AST (4%/0%). There were 5 grade 5 AEs; none were treatment related: 4 in the AMG 479 arm (2 PD, 1 sub occlusive syndrome [progression], and 1 pulmonary embolism [post-operative setting]) and 1 in the placebo arm (alteration of general status). 8% of pts in the AMG 479 arm vs 12% in the placebo arm had AEs that led to discontinuation of any study treatment. Conclusion: The combination of AMG 479 + E or F did not result in an improvement in PFS in this population of pts with HR+ M or LA BC. There were no unanticipated safety findings. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-4.