tbuckley/cabot-search huggingface dataset:
Use of Spironolactone and Hydrochlorothiazide in Treatment of Oedema
Authors: R. O. Farrelly, R. N. Howie, J. D. K. North
Journal: BMJ (1960)

Over the last few years it has become increasingly apparent that excessive aldosterone secretion plays some part in the genesis and maintenance of oedema, whether this be due to congestive cardiac failure, the nephrotic syndrome, or hepatic cirrhosis (Luetscher and Johnson, 1954 ; Axelrad et al., 1955 ; Duncan et al., 1956 ; Dyrenfurth et al, 1957). Considerable interest therefore is attached to the diuretic action of the 17 spirolactone steroids developed by Kagawa et al. (1957). Most investigators are agreed that these compounds act as specific aldosterone antagonists (Wolff et al., 1957 ; Liddle, 1957, 1958 ; Salassa et al, 1958 ; Ross and Bethune, 1959). Two early spirolactone derivatives, SC.5233 and SC.8109, showed promise in the treatment of oedematous patients (Liddle, 1957, 1958 ; Boit? et al, 1958) and of cases of hepatic cirrhosis with ascites (Kerr et al, 1958). The former compound, however, was not active by mouth ; the second was, but only in large doses. A new derivative, spironolactone (SC.9420), which is more potent, has recently been developed (Gantt and Dyniewicz, 1959), and the purpose of this study was to investigate its clinical value.
Guided self management of asthma---how to do it
Authors: A. Lahdensuo
Journal: BMJ (1999)

Almost 75% of admissions for asthma are avoidable, and potentially preventable factors are common in deaths from asthma.1 2 At least 40% of people with asthma do not react appropriately when their symptoms worsen, and over 50% of patients admitted with acute asthma have had alarming symptoms for at least a week before admission.3 4 As many as 60% of asthmatic patients are poor at judging their dyspnoea.5 Self management of asthma involves the patient making therapeutic, behavioural, and environmental adjustments in accordance with advice from healthcare professionals.6 Guided self management of asthma is a treatment strategy in which patients are taught to act appropriately when the first signs of asthma exacerbations appear. In a recent Cochrane review, self management of asthma in adults was compared with usual care in 22 studies.7 Self management education reduced hospital admissions (odds ratio 0.57, 95% confidence interval 0.38 to 0.88), emergency room visits (0.71, 0.57 to 0.90), unscheduled visits to the doctor (0.57, 0.40 to 0.82), days off work or off school (0.55, 0.38 to 0.79), and nocturnal asthma (0.53, 0.39 to 0.72). Self management programmes that contained a written action plan showing patients how to act in early exacerbations showed a greater reduction in admissions to hospital than did programmes without a plan (0.35, 0.18 to 0.68). ### Box 1: Reasons for self management of asthma RETURN TO TEXT
Not all neighborhood effects are created equal
Authors: Rochelle S. Newman
Journal: Behavioral and Brain Sciences (2000)

Norris, McQueen &amp; Cutler provide two possible explanations for neighborhood effects. The first suggests that nonwords that are more similar to words tend to activate those words more than do less similar nonwords, and the second is based on sequential probabilities between phonemes. Unfortunately, neither explanation is sufficient to explain all reported neighborhood effects.
Abstract 3552: Mirk kinase mediates cisplatin resistance in ovarian cancers
Authors: Jing Hu, Eileen A. Friedman
Journal: Cancer Research (2010)

Abstract Epithelial carcinoma of the ovary is the fifth most frequent cause of cancer death in women, and the second most frequent gynecological malignancy. Cisplatin based regimens are the standard of care, but efficacy is limited by drug resistance. Cisplatin treatment increased intracellular levels of toxic reactive oxygen species (ROS) in each of four ovarian cancer cell lines in a dose-dependent manner, while concomitantly reducing cell numbers, which suggested that further increasing ROS levels might increase cisplatin toxicity. The serine/threonine kinase Mirk/dyrk1B is known to increase the expression of a cohort of antioxidant genes in various cells. Targeting Mirk expression by RNA interference also increased ROS levels in these ovarian cancer cell lines while decreasing levels of ferroxidase (ceruloplamin) which prevents the generation of hydroxyl radicals. A combination of Mirk depletion and cisplatin treatment enabled low levels of drug to increase ROS to toxic levels in both SKOV3 cells and TOV21G cells. Increased tumor cell death by the combination treatment was confirmed by loss of viable cells capable of dye exclusion, a decrease in cell number, and an increase in pro-apoptotic proteins. Mirk has a second function in ovarian cancer cells, to maintain cells in quiescent state where they are less vulnerable to chemotherapeutic drugs and radiation. The majority of ovarian cancer cells in human tumors are not cycling as shown by lack of Ki67 expression. Some of these cells may be in a reversible quiescent state where they can contribute to cancer spread under favorable growth conditions. Depletion of Mirk in SKOV3 cells enabled them to escape quiescence. Studies using cisplatin revealed a Mirk-dependent G0/G1 checkpoint in SKOV3 and other p53 mutant ovarian cancer cells. The Mirk gene is on the 19q13 amplicon which is found in about one-third of all ovarian cancers. The Mirk gene was amplified in the OVCAR3 cell line where it mediated both quiescence and increased expression of antioxidant genes which decreased cellular ROS levels. Mirk protein was expressed in 21 of 28 resected human ovarian cancers as shown by immunohistochemical analysis, and was detected in each of 7 ovarian cancer cell lines, where it was an active kinase. Mirk is not an essential gene for either murine embryogenesis or the viability of human diploid fibroblasts. Targeting Mirk in ovarian cancers may sensitize these tumors to lower levels of cisplatin, both by increasing ROS levels and by releasing tumor cells from quiescence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3552.
Attenuation of Interleukin 8-induced Nasal Inflammation by an Inhibitor Peptide
Authors: J. ALLEN D. COOPER, A. LYNN RIDGEWAY, JOHN PEARSON, RACHEL R. CULBRETH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Polymorphonuclear neutrophils (PMNs) infiltrate tissue in response to chemoattractants, including interleukin 8 (IL-8). Infiltrating PMNs clear microorganisms but also cause tissue damage. We previously reported the presence in human bronchial lavage of a peptide that inhibits PMN functions. The current project assessed (1) effects of a synthetic analog of this peptide (synthetic neutrophil inhibitor peptide, SNIP) on IL-8-induced nasal inflammation in humans, (2) effects of SNIP on PMN apoptosis and chemotaxis, (3) specific binding of SNIP to PMNs, and (4) evidence of larger molecules with the SNIP sequence. Results show that SNIP attenuates IL-8-induced nasal inflammation, inhibits in vitro PMN chemotaxis to IL-8, and accentuates PMNs apoptosis. PMNs contain specific SNIP-binding sites and the integrin CR3 (CD11b / CD18), or a CR3-associated molecule, is one SNIP-binding molecule. Chemotaxis to IL-8 is most potently inhibited by SNIP in the presence of fibrinogen, a CR3 ligand. Antiserum against the SNIP sequence recognizes a 70-kDa protein in bronchoalveolar lavage and an anti-SNIP immunoaffinity column binds a 70-kDa protein in U937 cell culture supernatant. U937 cell mRNA contains a 1.8-kb transcript detected with degenerate oligonucleotides designed from the SNIP sequence. These studies demonstrate that a synthetic inhibitor peptide can attenuate in vivo nasal inflammation through downregulatory effects on PMNs.
ECFMG Assessment of Clinical Competence of Graduates of Foreign Medical Schools
Authors: Alton I. Sutnick
Journal: JAMA (1993)

<h3>Objective.</h3> —To develop an assessment of clinical competence of graduates of foreign medical schools and to determine the reliability and validity of the assessment and the feasibility of large-scale administration. <h3>Design.</h3> —The Educational Commission for Foreign Medical Graduates (ECFMG) clinical competence study included (1) clinical encounters with standardized patients to assess history taking, physical examination, and communication skills; (2) laser videodisk pictorials to assess identification and interpretation of diagnostic procedures; (3) written clinical vignettes to assess diagnosis and management skills; and (4) assessment of spoken English. A uniform method of operating the test centers and of training the standardized patients was developed. <h3>Setting.</h3> —Medical schools and their primary teaching hospitals and affiliated hospitals. <h3>Participants.</h3> —Six hundred twenty-four first-year residents, of whom 525 are graduates of foreign medical schools. <h3>Main Outcome Measures.</h3> —Scores, reliability coefficients, validity measures, feasibility of multisite administration, trends of scores over time, and acceptability by examinees. <h3>Results.</h3> —The ECFMG clinical competence assessment was conducted at four geographically separate test centers. Reliability coefficients were high (.85) for the integrated clinical encounter and were in a reasonable range (.71 to.82) for all test components. The assessment adds to the predictability of the residents' performance in the hospital over that of current ECFMG certification examinations. Test security was addressed by demonstrating no consistent pattern of change in scores over testing dates. Virtually all examinees thought the assessment was appropriate. Standardized patients were able to assess spoken English accurately. <h3>Conclusion.</h3> —The feasibility of conducting a reliable and valid test of clinical competence for graduates of foreign medical schools was demonstrated for this test population. (<i>JAMA</i>. 1993;270:1041-1045)
Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease
Authors: Ramachandran S. Vasan, Martin G. Larson, Eric P. Leip, Jane C. Evans, Christopher J. O'Donnell, William B. Kannel, Daniel Levy
Journal: New England Journal of Medicine (2001)

Information is limited regarding the risk of cardiovascular disease in persons with high-normal blood pressure (systolic pressure of 130 to 139 mm Hg, diastolic pressure of 85 to 89 mm Hg, or both).
ACCIDENTAL INJURIES IN OFFICE PRACTICE
Authors: RICHARD KOVACS
Journal: JAMA (1933)

Primum non nocere—first of all do not cause any harm—is the classic Latin pronouncement as to the duties of the physician toward his patient. Legal authorities tell us that the average physician when taking charge of  patient must have the reasonable degree of learning and skill that is ordinarily possessed by physicians and surgeons in the locality where he practices. On the other hand, a physician who holds himself out as being specially versed in some phase of medicine is required to possess special knowledge and skill, not merely such knowledge and skill as the average physician has but such as is possessed by the average specialist.1  The modern development of medicine and surgery with the tendency to the extended use of apparatus for diagnostic and therapeutic purposes has made these demands much more complicated. The doctor is not only supposed to be  diagnostician and have
Abstract 219: Inhibition of CD133 expression induce the chemoresistance to 5-fluorouracil in the colon cancer cell line
Authors: Mi-Ra Lee, Sun-Young Ji, Khalilullah Mia-Jan, Mee-Yon Cho
Journal: Cancer Research (2014)

Abstract Background: The cancer stem cell (CSC) theory which postulates a small subset of tumor cells have the capacity in tumor initiation, progression and importantly resistance to chemotherapy. CD133 is a transmembrane glycoprotein that serves as a putative cancer stem cell (CSC) marker in colon cancer and its relationship with the chemoresistance has been on debate. In our previous clinical study, we found the patients with CD133+ colon cancer have better prognosis after 5 fluorouracil (5-FU) chemotherapy compared to CD133- tumors. Purpose: To understand the role of CSC marker expression in relation to chemoresistance in colon cancer, we evaluated the effect of CD133 inhibition in colorectal cancer (CRC) cell line on the genes expression which are related to chemoresistance or cell survival. Materials &amp; Methods: CD133 siRNA transfection was performed on CD133+ colon cancer cell line (Caco-2). The proliferation assay used to detect the cytotoxic effect of 5-FU chemotherapy. The change in expression of chemoresistance related genes (AKT1, ABCG2 and MDR1) and cell survival related genes (survivin and beta-catenin) were evaluated by qRT-PCR and western blotting at 48hrs and 72hrs after CD133 siRNA transfection. Results: The proliferation assay demonstrated the increased chemoresistance of colon cancer cells after inhibition of CD133 expression when 5µM 5-FU was treated (p=0.0014). The mRNA expression of chemoresistance related genes (AKT1, ABCG2, MDR1) and cell survival related genes (survivin and β-catenin) were all significantly increased after transfection (p&amp;lt;0.05) but there was no significant changes in expression at the protein level of all genes. Conclusions: The inhibition of CD133 expression in CD133+colon cancer cell line induce the chemoresistance to 5-FU chemotherapy through the increased expression of chemoresistance related genes. Therefore, CD133 expression seems to be related with the chemosensitivity to 5-FU in colon cancer despite the mechanism needs to be proven. Citation Format: Mi-Ra Lee, Sun-Young Ji, Khalilullah Mia-Jan, Mee-Yon Cho. Inhibition of CD133 expression induce the chemoresistance to 5-fluorouracil in the colon cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 219. doi:10.1158/1538-7445.AM2014-219
FATAL INJURIES OF THE HEAD IN CHILDREN
Authors: A. Prichard
Journal: BMJ (1855)

APRIL 6, esusctated from a state of suspended animation.*The acidents were, no doubt, chiefly due to the circumstance tat it had been the custom to use the diluted preparation more freely than pure chlorororm would have been used; still they illustrate equally well the compartive safety of diluted and undiluted chloroform, when used on a sponge or handkerchief.Dr. J. Mason Warren has informed me that, since these accidents, the governors of the hospital have prohibited the inhalation of any other agent than sulphuric ether, for pre- venting pain in surgical operations.
Hemin Upregulates Egr-1 Expression in Vascular Smooth Muscle Cells via Reactive Oxygen Species ERK-1/2–Elk-1 and NF-κB
Authors: Rukhsana N. Hasan, Andrew I. Schafer
Journal: Circulation Research (2007)

Reactive oxygen species (ROS) and oxidant stress are important mediators of cardiovascular pathologies including atherosclerosis. One source of ROS in the vasculature is free heme released from hemoglobin. Because Egr-1, the regulator of cell proliferation and apoptosis, is also induced by oxidant stress and is likewise implicated in atherosclerosis, we examined the regulation of Egr-1 by heme in vascular smooth muscle cells (SMCs). Hemin increased Egr-1 expression (mRNA, protein) within 30 minutes and ERK-1/2 phosphorylation and nuclear translocation within 5 minutes. Inhibiting hemin-induced ERK-1/2 activation by U0126 (MAPK-inhibitor), the antioxidant N -acetyl cysteine, the NADPH oxidase inhibitors apocynin and diphenyleneiodonium chloride, the superoxide scavenger tiron, or tricarbonyldichlororuthenium(II)-dimer (carbon-monoxide donor; CORM-2) blocked hemin-induced Egr-1 expression. Hemin activated Elk-1, SRF, and NF-κB and promoted their interaction with the Egr-1 promoter. Downregulating Elk-1 (via siRNA) or blocking NF-κB activation (via BAY-11-7082) abolished hemin induction of Egr-1. Finally, hemin-induced Egr-1 bound the promoters of tissue factor (TF), Plasminogen Activator Inhibitor (PAI)-1, and NGF-1A Binding (NAB)-2, upregulating their expression, and increased the biochemical activity of TF and PAI-1. Upregulation of Egr-1 and its target genes by heme-induced oxidant stress may be an important event in the initiation and progression of inflammatory vascular diseases such as atherosclerosis.
Composition of the domestic water supply and the incidence of fractures and encephalopathy in patients on home dialysis.
Authors: M M Platts, G C Goode, J S Hislop
Journal: BMJ (1977)

Of the 202 patients undergoing home dialysis in the Trent region, 11 developed dialysis encephalopathy, 21 suffered spontaneous fractures, and 36 who had undergone dialysis for over four years had neither of these complications. Because the incidence of complications seemed to be unevenly distributed the water supplies were analysed. Water supplied to the homes of the patients with fractures or encephalopathy contained significantly less calcium and fluorine and significantly more aluminium and manganese than that piped to patients without these complications. The high aluminium concentrations in the bone of patients with encephalopathy was confirmed, but aluminium concentrations in the brains from three patients with encephalopathy were not increased. Patients who undergo dialysis in areas where water contains high aluminium concentrations should be supplied with deionisers.
Electing WHO's next leader
Authors: G. Yamey
Journal: BMJ (2002)

See also Education and debate p 1294 and News p 1259 

Dr Gro Harlem Brundtland promised greater transparency when she took charge of the World Health Organization in 1998.1 The secretive bureaucracy that she inherited would be banished, along with the memory of her ill perceived predecessor, Hiroshi Nakajima. Despite her best efforts, successes have not arrived in legions.2 United Nations organisations change direction with reluctance. Little wonder that Brundtland has relinquished a second term as director general.

Nowhere will this inertia be more disturbing than in the selection of her successor from the 9 hopefuls who announced their candidacy last week (p 1259).3 WHO considers itself to be the world's ministry of health, and as such the world's six billion inhabitants, particularly those in low income countries, deserve better than seeing their “health minister” elected by a secret publicly unaccountable ballot of 32 faceless bureaucrats at next January's meeting of WHO's executive board. This powerful group is drawn from WHO's 192 member states, with national representatives serving their region on a rotational basis.

The board will elect a …
A Survey of Laboratory and Statistical Issues Related to Farmworker Exposure Studies
Authors: Dana B. Barr, Doug Landsittel, Marcia Nishioka, Kent Thomas, Brian Curwin, James Raymer, Kirby C. Donnelly, Linda McCauley, P. Barry Ryan
Journal: Environmental Health Perspectives (2006)

Developing internally valid, and perhaps generalizable, farmworker exposure studies is a complex process that involves many statistical and laboratory considerations. Statistics are an integral component of each study beginning with the design stage and continuing to the final data analysis and interpretation. Similarly, data quality plays a significant role in the overall value of the study. Data quality can be derived from several experimental parameters including statistical design of the study and quality of environmental and biological analytical measurements. We discuss statistical and analytic issues that should be addressed in every farmworker study. These issues include study design and sample size determination, analytical methods and quality control and assurance, treatment of missing data or data below the method's limits of detection, and post-hoc analyses of data from multiple studies. Key words: analytical methodology, biomarkers, laboratory, limit of detection, omics, quality control, sample size, statistics.
Where shall John go? New Zealand.
Authors: D P Edge
Journal: BMJ (1976)

Perhaps it was premembership depression which drove me away from the front articles into the realms of overseas fancy, or just the prospect of gloomy interviews and the possibility of buying another house we didn't really like (and could only just afford).Whatever the stimulus, fancy became fact and four months later we arrived with great relief in New Zealand.Five weeks in a wardrobe (hereinafter called a cabin) was not quite the sea cruise conjured up by the travel agent.But that is all water under the bridge and, being in the stern, we felt each ripple.This is an example of "whingeing" for which we British are infamous.One of the causes of this "English disease" is a preconception of "Britain in the South," which, in spite of the origins of a significant number of the three million population, New Zealand is not and has no desire to be.Of course there are similarities, but 12 000 miles and 100 years make this a very unreasonable expectation.New Zealand offers a wide range of opportunities to all those prepared to go and look for them, whether these be recreational or in the field of medicine.The emphasis is go and look, not wait and see. Hospital appointmentsNew Zealand still has a two-tier health system.General practice has a fee for service arrangement of which part is paid by the Government.In hospital practice, major hospitals are "public" hospitals employing both whole-time and part-time medical staff; private hospitals are usually structurally and financially separate.In addition to the two medical schools and two clinical schools in the four main centres, the country is served by base hospitals similar to the district general hospitals, providing a varied range of general and specialist experience.Junior staff appointments begin in early November and are usually made to the hospital rather than to specific firms.At house surgeon level (a general term here) the rotation occurs every three months and the programme of "runs" is hopefully designed to provide a comprehensive one-or two-year course and most include anaesthetics and at least one minor specialty.Two-year schemes may include paediatrics and obstetrics.Casualty duties are usually covered by house surgeons for definite periods.Registrar appointments are mainly six-monthly rotating posts, but may be for fixed periods as part of advanced training programmes in specialised units.Fifth and final year students from New Zealand and Australia are encouraged to undertake elective periods in peripheral hospitals as part of their training.
Growth of human B cell colonies from peripheral blood of patients with systemic lupus erythematosus.
Authors: A C Fay, S Price, A Trudgett, J D McCrea, M Haire, M W Boyd, T A McNeill
Journal: Annals of the Rheumatic Diseases (1986)

Human B cell colonies were grown from peripheral blood of 12 patients with systemic lupus erythematosus (SLE) and from 12 healthy control subjects. The SLE group showed a large increase (p less than 0.001) in the number of colony forming cells (CFC) present in peripheral blood as compared with controls. The CFC were of the pre-B cell type. There was also a loss of OKT8+ cell inhibition of B cell colony growth in the SLE group compared with control subjects.