tbuckley/cabot-search huggingface dataset:
Interaction of polymorphonuclear leucocytes with patellar cartilage of immobilised arthritic joints: a scanning electron microscopic study.
Authors: P L van Lent, F H Wilms, W B van den Berg
Journal: Annals of the Rheumatic Diseases (1989)

Short term immobilisation (seven days) of an antigen induced arthritic knee joint of the mouse led to attachment of polymorphonuclear leucocytes to the cartilage surface and severe cartilage damage. The events at the patellar cartilage surface were studied by scanning electron microscopy and compared with the changes found in non-immobilised arthritic joints. At day 7 the immobilised arthritic joint showed an articular cartilage which was covered by a mat of fibrinous material and cell remnants. Moreover, inflammatory cells, clearly attached to the cartilage, showed large protrusions of their membranes. The cartilage surface, furthermore, showed numerous fissures of varying size and depth. These cartilage changes were much more pronounced in immobilised arthritic joints than in non-immobilised arthritic joints, and clear cell adhesion was exclusively found in the former. These findings show that immobilisation of inflamed mouse knee joints leads to increased damage and thus although clinical immobilisation is used to relieve pain, this may also risk damage to the articular cartilage.
Role of Inducible Nitric Oxide Synthase in the Pulmonary Vascular Response to Birth-Related Stimuli in the Ovine Fetus
Authors: Robyn L. Rairigh, Thomas A. Parker, D. Dunbar Ivy, John P. Kinsella, I-Da Fan, Steven H. Abman
Journal: Circulation Research (2001)

To determine whether type II nitric oxide synthase (NOS II) contributes to the NO-mediated fall in pulmonary vascular resistance (PVR) at birth, we studied the effects of selective NOS II antagonists N-(3-aminomethyl) benzylacetamidine dihydrochloride (1400W) and aminoguanidine (AG) and a nonselective NOS antagonist, nitro-L-arginine (L-NA), during mechanical ventilation with low FIO(2) (<10%), high FIO(2) (100%), and inhaled NO (20 ppm) in 23 near-term fetal lambs. Intrapulmonary infusions of AG, 1400W, and L-NA increased basal PVR before delivery (P<0.05). In control animals, ventilation with low and high FIO(2) decreased PVR by 62% and 85%, respectively. Treatment with AG and 1400W attenuated the fall in PVR by 50% during ventilation with low and high FIO(2) (control versus treatment, P<0.05 for each intervention). L-NA treatment attenuated the fall in PVR during ventilation with low and high FIO(2) to a similar degree as the NOS II antagonists. To test the selectivity of the NOS II antagonists, we studied the effects of acetylcholine and inhaled NO in each study group. Acetylcholine-induced pulmonary vasodilation remained intact after treatment with selective NOS II antagonists but not after treatment with nonselective NOS blockade with L-NA. In contrast, the response to inhaled NO was similar between treatment groups. We conclude that selective NOS II inhibition is as effective as nonselective NOS blockade in attenuating pulmonary vasodilation at birth and speculate that NOS II activity contributes to NO-mediated pulmonary vasodilation at birth. We additionally speculate that stimulation of the airway epithelium by rhythmic distension and increased FIO(2) may activate NOS II release at birth.
Endoscopic Retrograde Cholangiopancreatography after a Liquid Fatty Meal: Effect on Deep Common Bile Duct Cannulation Time
Authors: M. Barrie, S. Klein, C. Brown, M. Edge, J. Affronti, Q. Cai
Journal: Endoscopy (2006)

Background and Study Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is an important gastrointestinal endoscopic procedure in the study and treatment of pancreaticobiliary diseases. The critical step of the procedure is cannulation of the common bile duct (CBD) and/or the pancreatic duct. Cannulation can be a technical challenge at times. Fat is a natural stimulator for bile secretion and relaxation of the sphincter of Oddi. The objective of this study was to determine the effect of a liquid fatty meal on deep CBD cannulation during ERCP. Patients and Methods: We performed a randomized double-blind study in 84 patients to examine the effect of a liquid fatty meal on deep CBD cannulation during ERCP, in a teaching medical center. In the study group, each patient had a liquid fatty meal orally about 1 hour before the procedure. In the control group, each patient had the same volume of a non-fat meal. The appearance of the major papilla, the cannulation rate, the cannulation time, and the fluoroscopy time during cannulation were compared for the two groups. Results: The orifice of the CBD/pancreatic duct was much more easily identified in the group who ingested the fatty meal. Compared with the non-fat meal group, in the fatty meal group the mean and the median deep CBD cannulation times were shorter, at 8.0 minutes vs. 14.7 minutes (P = 0.005) and 8.0 minutes vs. 11.5 minutes (P = 0.008), respectively. Additionally, in the fatty meal group, the mean and the median fluoroscopy times during deep CBD cannulation were lower, at 3.3 minutes vs. 6.1 minutes (P = 0.040) and 2.5 minutes vs. 3.9 minutes (P = 0.013), respectively. There were no complications, such as aspiration, associated with the liquid meals given shortly before the ERCP procedure. Conclusions: To avoid prolonged cannulation and unnecessary radiation exposure, patients should have a liquid fatty meal before ERCP procedures.
The Associations of Optic Disc Hemorrhage with Retinal Nerve Fiber Layer Defect and Peripapillary Atrophy in Normal-tension Glaucoma
Authors: Kazuhisa Sugiyama, Goji Tomita, Yoshiaki Kitazawa, Eiji Onda, Hisashi Shinohara, Ki Ho Park
Journal: Ophthalmology (1997)
Government cleared of favouring Labour party donor for smallpox vaccine supply
Authors: C. White
Journal: BMJ (2003)

Allegations that the government deliberately awarded the contract for the supply of emergency smallpox vaccine to one of its donors have been refuted by a report from the spending watchdog, the National Audit Office.

The report, published last week, was prompted by the secrecy surrounding the government's procurement of the vaccine, which fuelled suspicion among other suppliers and some MPs that the government had something to hide.

The report found no link between two personal donations of £50 000 ($79 000; €73 000) to the Labour party made by …
Endoscopic Retrograde Cholangiopancreatography: Toward a Better Understanding of Competence
Authors: P. S. Jowell
Journal: Endoscopy (1999)

Most physicians, and probably all our patients, would like to know that when a medical procedure is performed, the individual who is carrying it out has been credentialed as competent. However, development of a meaningful definition of competence has become the Holy Grail of credentialing. The Oxford Dictionary definition of competence, “sufficiency of qualification; capacity to deal adequately with a subject”, provides little guidance to those in the profession who seek to quantify competence more precisely.
Trial of New Bronchodilator, Terbutaline, in Asthma
Authors: B. J. Freedman
Journal: BMJ (1971)

Terbutaline, a new bronchodilator acting on beta-adrenergic receptors, was given to 10 asthmatic patients, who received on separate days 5 mg orally, 10 mg orally, and 0.25 mg subcutaneously. The ventilatory response was assessed by measurement of the FEV(1) before and at intervals after administration. The cardiovascular response was assessed by measurement of the heart rate and blood pressure and by electrocardiography at the same times as spirometry was performed.The ventilatory response to all three doses and by both routes was satisfactory. The maximal increase in FEV(1) after 5 mg orally was only slightly less than that after 10 mg. The maximal increase in heart rate after 5 mg orally was about half that which occurred after 10 mg. It is concluded that 5 mg orally and 0.25 mg subcutaneously are suitable doses.In general a modest fall in blood pressure affected the diastolic more than the systolic. On E.C.G. the T wave was often depressed, and in one patient, it was inverted. A trough-like depression of the QRS baseline occurred several times. The significance of the E.C.G. changes is uncertain.
Health ministers from around the world make H1N1 top priority
Authors: N. Siva
Journal: BMJ (2009)

Health ministers from around the world agreed last week that H1N1 remains the top global health threat.

Gillian Merron, UK Public Health Minister, said, “Diseases don’t respect borders so we need an international response to them. The global effort to tackle the [H1N1] pandemic has been impressive and would not have been possible without such cooperation.” She was speaking at the 10th ministerial meeting of the Global Health Security Initiative hosted by the Department of Health in London.

The initiative was set up in 2001 as a response to the terrorist events of 11 September and the subsequent threats …
Public knowledge of AIDS and the DHSS advertisement campaign.
Authors: S Mills, M J Campbell, W E Waters
Journal: BMJ (1986)

score.Our virtual abandonument of preoperative arteriography has brought savings in time, money, and patiet discomfort, while our limb salvage rate has remained steady at over 90%.Though non-invasive scoring cannot provide an anatomical picture,, in conjunction with insonation -of the pedal arch it does seem to indicate the correct site for distal anastomosis of the graft, and in practice this is all that is required.Provided that the surgical team is prepared to undertake bypass to all levels in the leg, non-invasive scoring can be the sole preoperative strategic investigation in most patients needing femorodistal bypass.We consider that the method merits wider assessment.
Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery
Authors: Heng Zhang, Xin Yuan, Haibo Zhang, Sipeng Chen, Yan Zhao, Kun Hua, Chenfei Rao, Wei Wang, Hansong Sun, Shengshou Hu, Zhe Zheng
Journal: Circulation (2015)

Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain.The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50-2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01-2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10-1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17-2.48) in inconsistent users and 1.23 (95% CI, 0.76-1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43-3.20) and for never users (HR, 1.59; 95% CI, 1.07-2.63). Consistent results were obtained in equivalent sensitivity analyses.In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence.
Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons
Authors: Anne P. Beigneux, Brandon S.J. Davies, Peter Gin, Michael M. Weinstein, Emily Farber, Xin Qiao, Franklin Peale, Stuart Bunting, Rosemary L. Walzem, Jinny S. Wong, William S. Blaner, Zhi-Ming Ding, Kristan Melford, Nuttaporn Wongsiriroj, Xiao Shu, Fred de Sauvage, Robert O. Ryan, Loren G. Fong, André Bensadoun, Stephen G. Young
Journal: Cell Metabolism (2007)
The assessment of serum hepatitis C virus RNA 12 weeks after the end of treatment using TaqMan polymerase chain reaction is less relevant than after 24 weeks for predicting sustained virological response
Authors: Tatsuo Kanda, Fumio Imazeki, Shuang Wu, Shingo Nakamoto, Osamu Yokosuka
Journal: Hepatology (2011)

We read with great interest the article by Martinot-Peignoux et al.1 In this report from France, undetectable serum hepatitis C virus (HCV) RNA at 12 weeks (W+12) (409 patients) post-treatment follow-up was as relevant as undetectable serum HCV RNA at 24 weeks (W+24) (sustained virological response [SVR]; 408 patients) after the end of treatment. Current standard therapy is based on a combination of pegylated interferon (PEG-IFN) and ribavirin, but it leads to only ∼50% SVR in patients with HCV genotype 1 and high viral loads.2 IFN reduced the risk for HCC, especially among patients with SVR.3, 4 Then, we need to accurately judge whether the patient is SVR or non-SVR, applying the present standard for the judgment of SVR with the undetectability of serum HCV RNA at post-treatment W+24. We investigated 102 patients with chronic hepatitis C genotype 1 treated with PEG-IFN-alfa 2a plus ribavirin for 48 weeks. Some of these patients had already been included in previous reports.5, 6 Serum HCV RNA was measured using the COBAS TaqMan HCV test with a detection limit of 1.2 logIU/mL. At the W+24 post-treatment follow-up, 40 (39.2%) patients had SVR, and 31 (48.4%) and 9 (23.6%) were treatment naïve and previously treated patients, respectively. At W+12, serum HCV RNA was undetectable in 42 patients, and 40 patients were SVR (PPV, 95.2%). We found two relapsers at W+24 (undetectable at W+12). In the case of using direct-acting antivirals, earlier knowledge of treatment outcome would be useful for retreatment for the same patient. Taken together, our findings show that W+12 undetectable serum HCV RNA is not suitable for predicting persistent virological response. Further understanding of the mechanism of relapse could be useful in reducing the post-treatment follow-up period from the current standard of 24 weeks. Tatsuo Kanda M.D., Ph.D.*, Fumio Imazeki M.D., Ph.D.*, Shuang Wu M.D., Ph.D.*, Shingo Nakamoto M.D., Ph.D.*, Osamu Yokosuka M.D., Ph.D.*, * Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, Chiba, Japan.
Immunization with T cell receptor V beta chain peptides deletes pathogenic T cells and prevents the induction of collagen-induced arthritis in mice.
Authors: T M Haqqi, X M Qu, D Anthony, J Ma, M S Sy
Journal: Journal of Clinical Investigation (1996)

Collagen-induced arthritis (CIA) in susceptible strains of mice is an animal model of T cell-mediated inflammatory polyarthritis. Analysis of T cell receptor (TCR) V beta gene usage in cells isolated from arthritic joints of BUB/BnJ (BUB) mice (H-2q, TCR V beta a) showed that TCR V beta chain gene usage was limited to TCR V beta 3 and V beta 10 gene families. All of the BUB mice immunized with a mixture of TCR V beta 3 and TCR V beta 10 peptides, but not with control TCR V beta 14 peptide, were refractory to the induction of CIA. Immunization with TCR V beta 3 and V beta 10 peptides completely blocked the development of clinical and subclinical inflammation, formation of pannus and synovial hyperplasia, and the erosion of cartilage and bone. Further studies revealed that preimmunization of BUB mice with V beta 10 peptide alone was sufficient to render the mice resistant to CIA. Analysis of TCR V beta chain gene expression in lymph node cells from arthritic and arthritis-protected mice showed the expression of TCR V beta 10 subfamily in all of the arthritic mice, but not in arthritis-protected mice. Immunization with TCR V beta peptides did not diminish the humoral responses to chicken type-II collagen and also elicited significant levels of anti-V beta 3 and anti-V beta 10 peptide antibodies. Antibodies cross-reactive with mouse chicken type-II collagen were detected in both the arthritic and arthritis-protected mice. Adoptive transfer of serum from arthritis-protected BUB mice significantly delayed the onset (P < 0.005) of arthritis in recipient BUB mice. In contrast, mice injected with serum from arthritic mice had early onset of arthritis. These results demonstrate that immunization of BUB mice with TCR V beta chain peptides elicited antibodies reactive with the self-TCR and prevented the induction of collagen-induced arthritis by eliminating or downregulating pathogenic T cells and consequently blocking the development of humoral immune response. These findings may have clinical applications in treating human autoimmune diseases characterized by common TCR gene usage.
The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: Effectiveness of early intervention with budesonide in mild persistent asthma
Authors: William W. Busse, Søren Pedersen, Romain A. Pauwels, Wan C. Tan, Yu-Zhi Chen, Carl Johan Lamm, Paul M. O'Byrne
Journal: Journal of Allergy and Clinical Immunology (2008)
Protein Kinase G Phosphorylates Ca <sub>v</sub> 1.2 α <sub>1c</sub> and β <sub>2</sub> Subunits
Authors: Lin Yang, Guoxia Liu, Sergey I. Zakharov, Andrew M. Bellinger, Marco Mongillo, Steven O. Marx
Journal: Circulation Research (2007)

Voltage-dependent Ca 2+ channel function (Ca v 1.2, L-type Ca 2+ channel) is required for cardiac excitation-contraction (E-C) coupling. Ca v 1.2 plays a key role in modulating cardiac function in response to classic signaling pathways, such as the renin-angiotensin system and sympathetic nervous system. Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with Ca v 1.2 current through the actions of cAMP and cGMP. Cardiac cGMP, which activates protein kinase G (PKG), is regulated by nitric oxide (NO), and natriuretic peptides. Although PKG has been reported to activate or inhibit Ca v 1.2 function, it is still unclear whether Ca v 1.2 subunits are PKG substrates. We have identified phosphorylation sites within the α 1c and β 2a subunits that are phosphorylated by PKGIα in vitro. We demonstrate that a subset of these phosphorylation sites is modulated, in a cGMP-PKG–specific manner, in intact HEK cells heterologously expressing α 1c and β 2a subunits. Using phospho-epitope–specific antibodies, we show that the phosphorylation of these residues is enhanced by PKG in intact cardiac myocytes. Activation of PKG in HEK cells transfected with α 1c and β 2a subunits caused an inhibition of Ca v 1.2 whole-cell current. PKG-mediated inhibition of Ca v 1.2 current was significantly reduced by coexpression of an alanine-substituted Ca v 1.2 β 2a subunit (Ser 496 ). Our results identify a molecular mechanism by which cGMP-PKG regulates Ca v 1.2 phosphorylation and function.
Communicable and non-communicable disease
Authors: F. Godlee
Journal: BMJ (2011)

A clinical image would seem an obvious choice for the BMJ ’s front cover. But each time we decide to use one we have to think an extra thought—will it upset the postal workers or readers’ children? Anything remotely gory tends to cause complaints. In the past we have covered potentially alarming or offensive images with an opaque wrapper. But we felt this was unnecessary for this week’s cover. I’m sure you (and the Royal Mail) will tell us if we were wrong.

Either way we hope you’ll appreciate the image and read the two linked articles. They highlight the dangers of what A Fogo and colleagues call “rapidly …
Loss of p73 promotes dissemination of Myc-induced B cell lymphomas in mice
Authors: Alice Nemajerova, Oleksi Petrenko, Lorenz Trümper, Gustavo Palacios, Ute M. Moll
Journal: Journal of Clinical Investigation (2010)

Mice engineered to express c-Myc in B cells (Emu-myc mice) develop lethal lymphomas in which the gene encoding the p53 tumor suppressor is frequently mutated. Whether the p53 homolog p73 also functions as a tumor suppressor in vivo remains controversial. Here we have shown that p73 loss does not substantially affect disease onset and mortality in Emu-myc mice. However, it does alter the phenotype of the disease. Specifically, p73 loss decreased nodal disease and increased widespread extranodal dissemination. We further found that p53 acted as the dominant tumor suppressor during the onset of Emu-myc-driven B cell lymphomagenesis, while p73 modulated tumor dissemination and extranodal growth. Immunophenotyping and expression profiling suggested that p73 loss allowed increased maturation of malignant B cells and deregulated genes involved in lymphocyte homing and dissemination of human lymphomas. Consistent with this, p73 expression was frequently downregulated in a large cohort of human mature aggressive B cell lymphomas, and both the incidence and degree of p73 downregulation in these tumors correlated with their extranodal dissemination status. These data indicate that p73 is a modifier of Myc-driven lymphomas in mice, favoring tumor dissemination, and suggest that p73 could be a biomarker for human B cell lymphoma dissemination, a notion that can now be tested in clinicopathologic correlation studies.
HIV drugs halve infection rate in men who have sex with men, study finds
Authors: B. Roehr
Journal: BMJ (2010)

Once a day dosing of a pill containing two standard antiretrovirals offers significant protection against infection with the virus, a large trial has found.

The international pre-exposure prophylaxis initiative trial, published on 23 November in the New England Journal of Medicine (doi:10.1056/NEJMoa1011205), took place in six countries on four continents.

The trial enrolled 2499 high risk men or transgender women who have sex with men, randomising them to receive once a day dosing of either the combination treatment of tenofovir with emtricitabine (marketed as Truvada) or placebo. The analysis was based on a median use of the drug of 1.2 years.

HIV disproportionately affects men who have sex with men, who constitute about half of all infected people in developed countries. In sub-Saharan Africa men who have …
The Prevention of Hospitalization; Treatment Without Admission for Psychiatric Patients.
Authors: Daniel Blain
Journal: JAMA (1963)

This book poses the most important question in American psychiatry today: whether it is better to hospitalize psychotic patients or treat them through extra-hospital resources. As the authors state, "If we believe it is better to hospitalize, our present hospitals will always be full, new facilities for inpatients will have to be built, and our states will continue to labor under the financial burden of trying to provide adequate staffs and services. But if... it is better not to hospitalize, then the way is open for the development of extra-hospital facilities... and eventually the 'liquidation' of the state hospital as we know it. The state hospital will then function primarily to provide leadership for community-based care of the mentally ill." The subject of this book is a project subsidized by an NIH grant and entitled, "Prevention of Hospitalization of Psychotic Patients Referred to the Massachusetts Mental Health Center." Succinctly described