tbuckley/cabot-search huggingface dataset:
β-Blockers for COPD inpatients
Authors: Samy Suissa, Pierre Ernst
Journal: Thorax (2012)

For clinicians who treat patients with respiratory diseases, the use of β-blockers has, for a long time, posed a dilemma because of the potential risk of bronchospasm and neutralisation of the effectiveness of β-2 agonists. This predicament is particularly challenging for patients with chronic obstructive pulmonary disease (COPD), many of whom have substantial cardiovascular comorbidity,1 and in whom the avoidance of β-blockers might deprive them of substantial cardiovascular benefit.

In the last few years, this restraint has been challenged, and rightfully so, in view of the general scarcity of data on this potential antagonism and, more importantly, its would-be effect on major outcomes. While caution is generally the sensible approach in drug safety, this is less the case here, as one would be withholding a treatment that has been demonstrated to be effective for cardiovascular disease. Several observational studies have examined the potential risks and benefits of β-blocker use in COPD. Most studies, to date, have looked at β-blocker use during the usual course of COPD without specifically examining their risk or benefit at the time of an acute exacerbation of COPD (AECOPD).2–5 

Stefan et al 6 address the question of the effects of β-blockers during a serious exacerbation requiring hospitalisation. The authors specifically evaluated whether β-blockers given early to patients hospitalised for AECOPD, and who also have ischaemic heart disease or heart failure, increase the risk of mortality. They used the US Premier hospitalisation database to identify a large cohort of over 35 000 patients hospitalised for COPD, and …
5-azacytidine and decitabine exert proapoptotic effects on neoplastic mast cells: role of FAS-demethylation and FAS re-expression, and synergism with FAS-ligand
Authors: Viviane Ghanim, Harald Herrmann, Gerwin Heller, Barbara Peter, Emir Hadzijusufovic, Katharina Blatt, Karina Schuch, Sabine Cerny-Reiterer, Irina Mirkina, Heidrun Karlic, Winfried F. Pickl, Sabine Zöchbauer-Müller, Peter Valent
Journal: Blood (2012)
Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris.
Authors: T Toyo-oka, T Aizawa, N Suzuki, Y Hirata, T Miyauchi, W S Shin, M Yanagisawa, T Masaki, T Sugimoto
Journal: Circulation (1991)

To elucidate the pathogenic contribution of a potent vasoconstrictor, endothelin-1, to coronary artery spasm, we provoked spasm with intracoronary administration of acetylcholine or ergonovine and performed sensitive immunoassays of plasma levels of endothelin-1 and atrial natriuretic factor (ANF) in the peripheral vein and coronary sinus of patients with a tentative diagnosis of vasospastic angina (VSA, n = 19). The validity of coronary sinus blood sampling was verified by simultaneous measurement of the ANF level. The plasma endothelin-1 levels in venous and coronary sinus blood of the spasm-provoked patients (n = 12) were 1.71-fold and 2.16-fold higher, respectively, than those of nonprovoked cases (n = 5, p less than 0.01). During left coronary spasm, the endothelin-1 level in coronary sinus transiently decreased from 2.27 +/- 0.14 to 1.76 +/- 0.14 pg/ml (p less than 0.01) and returned to the control level (1.98 +/- 0.20 pg/ml) after the spasm resolved, whereas the change was equivocal during right coronary spasm. In contrast, the patients in whom spasm was not provoked showed no changes and maintained low endothelin-1 levels both before and after the maximal provocation (0.90 +/- 0.13 versus 0.90 +/- 0.13 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of CC16 and CD14 polymorphisms in the german MAS cohort
Authors: Claudia Sengler, Assia Haider, Christine Sommerfeld, Susanne Lau, Bodo Niggemann, Mauro Baldini, Fernando D Martinez, Ingrid A Laing, Peter N Lesouef, Johannes Forster
Journal: Journal of Allergy and Clinical Immunology (2002)
Margaret E M O'Flynn (Foley)
Authors: F. F. Croft
Journal: BMJ (2014)

Margaret O’Flynn (nee Boulton, known professionally as Foley) devoted most of her career to the development and improvement of contraception, the sexual health of women, and management of the menopause, starting at a time when the level of such services was poor. She ultimately succeeded in delivering vastly improved facilities and services in Portsmouth and south east Hampshire. In 1970 she was awarded her FRCOG, becoming, with John Foley, the first husband and wife fellows of the Royal College of Obstetricians and Gynaecologists.

Margaret was born in January 1920 in Talke of the Hill, north Staffordshire, the first of two daughters of Ernest and Edith Boulton. She went to school at Orme Girls School and eventually became head girl. She was inspired by her headmistress, Miss Sprunt, to consider medicine and at 17 took her first MB in 1937. Having been advised by her mother to take off her gloves to show off her surgeon’s hands, and possibly displaying other more important attributes at her interview, she was offered a place at King’s College Hospital Medical School, where she started her second MB. At the declaration of war in 1939, her father, a former grenadier who saw active service in the first world war, encouraged her to contribute during the summer vacation to the war effort at North Staffordshire Royal Infirmary. In September 1939 King’s despatched their students to Glasgow to put them in a place of relative safety, and here she completed her 2nd MB. Returning to King’s in London, she and other students lived in converted wards on the top floor of the hospital. Each time a siren went off, she and other students reported for duty, fire watching on the roof, with long brooms to push …
Unsafe abortion: why restricting abortive drugs only makes a bad situation worse
Authors: Meera Kay
Journal: BMJ (2013)

This article studies the co-investment patterns of global sovereign wealth funds (SWFs) in the 1980–2014 period. Data show that collaborative investments are gaining momentum among SWFs. In terms of targets, large-capitalization stocks and companies operating in the infrastructure and public utilities industries appear to be the preferred targets. There is evidence of a home-bias effect and of a preference to invest in foreign countries in partnership with local funds. The co-investments within a social network framework show the existence of a “small world” of relationships among most SWFs. In particular, the network of co-investments is rather segmented, with some funds being “brokers” of relationships within their subgroup but with no one fund being able to dominate the strategies of the whole network. <b>TOPICS:</b>Private equity, global, legal/regulatory/public policy, statistical methods
905 ADHERENCE WITH TELAPREVIR BID vs. q8h DOSING IN TREATMENT-NAÏVE HCV-INFECTED PATIENTS: RESULTS FROM THE PHASE III OPTIMIZE STUDY
Authors: W. Sievert, M. Buti, K. Agarwal, Y. Horsmans, S. Zeuzem, E. Janczewska, L. Nyberg, R.S. Brown, C. Hezode, M. Rizzetto, R. Parana, S. De Meyer, R. De Masi, D. Luo, J. Witek
Journal: Journal of Hepatology (2013)
Studies on the Mechanism of Ventricular Activity
Authors: L. ALLEN SMITH, REXFORD KENNAMER, MYRON PRINZMETAL
Journal: Circulation Research (1954)

Controlled studies of ventricular excitation were performed in dogs exhibiting various Degreess of right and left bundle-branch block. Increases in the intraventricular conduction time during complete bundle-branch block are attributed to free wall as well as septal factors. Incomplete bundle-branch block may be either segmental or diffuse. In the segmental type, delayed excitation is present in only a portion of the involved ventricle. In the diffuse type, delayed excitation of the entire homolateral ventricle occurs, but some portions of the ventricle tend to be delayed to a greater extent than others. Certain segements of the ventricular myocardium appear to be supplied by fixed portions of the conducting system, without cross connections operating physiologically. The clinical implications of these observations are briefly discussed.
Effects of Chlorothiazide on Specific Renal Functions in Hypertension
Authors: A. C. CORCORAN, CATHEL MACLEOD, HARRIET P. DUSTAN, IRVINE H. PAGE
Journal: Circulation (1959)

Oral administration of chlorothiazide depresses glomerular filtration, increases blood urea, maintains sodium output in the face of decreased filtered sodium load, and paradoxically for a diuretic, in these and in tests done shortly after intravenous administration, increases the efficiency of water reabsorption.
Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome
Authors: Amir Zarrinpar, Amandine Chaix, Shibu Yooseph, Satchidananda Panda
Journal: Cell Metabolism (2014)

The gut microbiome and daily feeding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiome's contribution to host metabolism.
Demonstration and partial characterization of the interferon-gamma receptor on human mononuclear phagocytes.
Authors: A Celada, R Allen, I Esparza, P W Gray, R D Schreiber
Journal: Journal of Clinical Investigation (1985)

Radioiodinated recombinant human interferon-gamma (IFN gamma) bound to human monocytes, U937, and HL60 cells in a specific, saturable, and reversible manner. At 4 degrees C, the different cell types bound 3,000-7,000 molecules of IFN gamma, and binding was of comparable affinity (Ka = 4-12 X 10(8) M-1). No change in the receptor was observed after monocytes differentiated to macrophages or when the cell lines were pharmacologically induced to differentiate. The functional relevance of the receptor was validated by the demonstration that receptor occupancy correlated with induction of Fc receptors on U937. Binding studies using U937 permeabilized with digitonin showed that only 46% of the total receptor pool was expressed at the cell surface. The receptor appears to be a protein, since treatment of U937 with trypsin or pronase reduced 125I-IFN gamma binding by 87 and 95%, respectively. At 37 degrees C, ligand was internalized, since 32% of the cell-associated IFN gamma became resistant to trypsin stripping. Monocytes degraded 125I-IFN gamma into trichloroacetic acid-soluble counts at 37 degrees C but not at 4 degrees C, at an approximate rate of 5,000 molecules/cell per h. The receptor was partially characterized by SDS-polyacrylamide gel electrophoresis analysis of purified U937 membranes that had been incubated with 125I-IFN gamma. After cross-linking, the receptor-ligand complex migrated as a broad band that displayed an Mr of 104,000 +/- 18,000 at the top and 84,000 +/- 6,000 at the bottom. These results thereby define and partially characterize the IFN gamma receptor of human mononuclear phagocytes.
Hypoxic reperfusion to remove ischaemic catabolites prior to arterial reperfusion does not limit the size of myocardial infarcts in dogs
Authors: M. Tanaka, R. C Earnhardt, C. E Murry, V. J Richard, R. B Jennings, K. A Reimer
Journal: Cardiovascular Research (1991)

Although timely reperfusion limits myocardial infarct size, it has been postulated that reperfusion itself may kill some myocytes which were alive at the end of an episode of ischaemia (lethal reperfusion injury). The aim of this study was to test the hypothesis that ischaemic catabolites may "prime" myocardium for such injury and that preliminary hypoxic washout of such catabolites, prior to arterial reperfusion, would limit myocardial infarct size.Dogs underwent a 40 min occlusion of the left circumflex coronary artery, followed by 4 d reperfusion. In a treated group, a 5 min episode of coronary artery perfusion with hypoxic buffer was instituted at the end of this ischaemic episode, before blood reperfusion was restored. Control dogs received a similar volume of hypoxic buffer intravenously. Systemic fluid overload was attenuated by haemofiltration. The effect of this preliminary hypoxic washout on myocardial infarct size was assessed.18 anaesthetised, open chest dogs were used. After the acute study they recovered from surgery for 4 d and were then killed for further study.Infarct size, determined by microscopic evaluation, was not significantly different in the two groups, at (control) 31.3 (SEM 6.2)% v (hypoxic reperfusion) 25.8(3.9)% of the vascular area at risk. In control dogs, infarct size was inversely related to the amount of collateral blood flow (measured using microspheres); hypoxic reperfusion did not shift this relation (analysis of covariance, F = 0.236, NS).The washout of ischaemic catabolites by hypoxic perfusate prior to reoxygenation did not limit infarct size.
Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control
Authors: Peter J Barnes
Journal: BMJ (2007)

Asthma is one of the commonest chronic diseases worldwide and is effectively controlled in most patients with maintenance treatment. In those with moderate or severe persistent asthma, control may be achieved with an inhaled corticosteroid or a combination inhaler containing a corticosteroid and a long acting β2 agonist. The combination inhaler is more effective, but patients still require short acting β2 agonists such as salbutamol or terbutaline to relieve symptoms. I describe a new approach for acute exacerbation—SMART (single inhaler maintenance and reliever therapy). This uses the combination inhaler, rather than the short acting β2 agonist, as the reliever.

Using a formulation of budesonide plus formoterol (budesonide/formoterol) both as a reliever and as maintenance therapy once or twice daily is more effective in controlling asthma than conventional approaches using budesonide/formoterol, fluticasone/salmeterol, or high dose corticosteroids (budesonide or fluticasone) as the maintenance treatment with short acting β2 agonists as relievers (table⇓).1 2 3 4 5 The most striking benefits are fewer exacerbations (severe exacerbations, defined as needing a course of oral corticosteroids, are …
Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma
Authors: Henry J. Henk, April Teitelbaum, Jose Ricardo Perez, Satyin Kaura
Journal: American Journal of Hematology (2012)

Zoledronic acid (ZOL), an intravenous bisphosphonate, has been shown to reduce and delay the incidence of skeletal-related events (SREs) in multiple myeloma (MM) patients with bone disease. A retrospective claims-based analysis was conducted that used two distinct US managed care databases to examine the relationship between persistency with ZOL and clinical benefit. Patients >18 years, diagnosed with MM, and with at least one claim for ZOL (or a claim for malignant bone disease and ZOL initiation within 30 days) between 1/1/2001 and 12/31/2006 were included. Patients were evaluated for incidence of SREs and for mortality. Treatment persistency was defined as the absence of a >45 day gap between ZOL administrations. Of 1,655 patients in this analysis, 1,060 received ZOL and 595 received no intravenous bisphosphonate therapy. Compared with patients not receiving bisphosphonate therapy, ZOL-treated patients had lower incidences of SREs (P < 0.0001) and death (P = 0.0001). Longer persistency with ZOL was associated with lower risks of SREs (P = 0.001), fracture (P = 0.003), and death (P = 0.002) versus shorter persistency. Patients who were persistent with ZOL for ≥1.5 years had an incidence of 15.0 SREs and 6.2 fractures per 100 person-years. Patients who were persistent for 31-90 days had an incidence of 24.6 SREs and 14.0 fractures per 100 person-years, and patients not receiving intravenous bisphosphonates had an incidence of 32.2 SREs and 16.9 fractures per 100 person-years. These data from a real-world setting indicate that among MM patients, longer persistency with ZOL was associated with a lower risk of SREs and fracture.
Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage
Authors: S. I. Grivennikov, M. Karin
Journal: Annals of the Rheumatic Diseases (2011)

Up to 20% of all cancers arise in association with chronic inflammation and most, if not all, solid tumours contain inflammatory infiltrates. Immune cells have a broad impact on tumour initiation, growth and progression and many of these effects are mediated by proinflammatory cytokines. Among these cytokines, the pro-tumourogenic function of tumour necrosis factor (TNF) and interleukin 6 (IL-6) is well established. The role of TNF and IL-6 as master regulators of tumour-associated inflammation and tumourigenesis makes them attractive targets for adjuvant treatment in cancer.
Survival Patterns in Systemic Lupus Erythematosus
Authors: Stephen W. Zimmerman
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Daniel Wallace, MD, and co-workers.should be commended for their article on "Systemic Lupus Erythematosus—Survival Patterns" (1981;245:934). Their follow-up data will aid in projecting prognosis in individual patients with systemic lupus erythematosus (SLE) as well as organizing prospective controlled trials of therapy. I was interested in their finding that males with SLE have a significantly decreased survival compared with females. Several years ago I was impressed that there were relatively equal numbers of males and females with SLE entering our end-stage renal disease programs. This prompted me to examine prognosis with regard to sex in 75 patients with SLE and nephritis. Of the 17 males, seven experienced renal failure (defined as a serum creatinine level greater than 6 mg/dL, dialysis, or renal transplant), and four died. Four of 58 female patients with lupus nephritis experienced renal failure, and five died. Thus, 65% of the males experienced renal failure,
A National Survey of Public Health Officers' Interactions With the Media
Authors: George A. Gellert
Journal: JAMA (1994)

To assess the perceptions, practices, and needs of state and local health officers with respect to professional interactions with the media.A survey of 759 public health officers (56 state and 703 local) on jurisdiction demographics, frequency of media interactions, agency process for media contacts, provision and need for media training, and character of media relations.Fifty-two state health officers and 568 US local health officers responded, for a survey response rate of 82%.Media reporting was perceived as accurate 52% to 73% of the time, although reporters were seen as needing improved technical and scientific knowledge. Media were used frequently as a component of health education. State health jurisdictions were more likely than local jurisdictions to have a media protocol and designated media contact, to internally review media releases, to interact regularly with media, and to provide staff training on media relations. Media interaction time comprised print media (63%), television (19%), and ratio (17%). One third of the health officers found media relations adversarial, but most held a positive overall view of the media. Favorable evaluation of the media was associated with high frequency of media contact, high perceived accuracy of reporting, and presence of an institutional media protocol.While health officers evaluated media favorably, problem areas were identified where mutual education could improve the accuracy and value of media reporting on health issues. Training capacity for both professions should be developed to increase the effectiveness of public health in media relations.
GW25-e1534 SIRT1 protects against oxidative stress-induced endothelial progenitor cells apoptosis by inhibiting FOXO3a via FOXO3a ubiquitination and degradation
Authors: Yu-Qiang Wang, Qing Cao, Fei Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen
Journal: Journal of the American College of Cardiology (2014)
Ethacrynic Acid and Diabetes
Authors: Seymour Diamond
Journal: JAMA (1968)

<h3>To the Editor:—</h3> It now appears that we have a series of articles showing a suggested dose response related to the elevation of blood sugar in diabetic patients after being treated with ethacrynic acid. My colleague and I have shown that 100 mg of ethacrynic acid daily does not influence the carbohydrate metabolism of nondiabetic or diabetic individuals (<i>Dis Chest</i><b>51</b>:282-287, 1967). Dige-Peterson has shown that a daily dose of 150 mg of ethacrynic acid does not alter carbohydrate metabolism. In an excellent article, Russell et al (<i>JAMA</i><b>205</b>:81, 1968) have shown that the high maintenance dose of 200 mg daily alters the carbohydrate metabolism in diabetics when compared to a placebo medication but not to their control periods. The nondiabetogenic individuals did not show the above alteration. These studies certainly indicate that ethacrynic acid is a valuable and safe drug, even in the diabetic patient. They do