tbuckley/cabot-search huggingface dataset:
Quantifying the Importance of Interleukin-6 for Coronary Heart Disease
Authors: Bruce Neal
Journal: PLoS Medicine (2008)

For many years it was widely believed that known vascular risk factors could explain only about half of all cardiovascular disease [1], leaving much to be discovered about other causes of stroke and heart attack. There has been considerable interest in the possible aetiological role of inflammation in vascular disease. Interleukin-6 (IL-6) is one of a number of inflammatory markers that have been studied [2]. There are, however, substantial and often unrecognised challenges to quantifying the full effects of risk factors such as IL-6.

A particular problem in establishing the true nature of the association between exposures and outcomes arises from the difficulty of achieving a good estimate of the true level of the risk factor of interest. It is very difficult to establish an individual's usual level of exposure to an inflammatory marker such as IL-6, because it has a short half life and is complex to assay. The same challenge also applies to well-established, and apparently easier to measure, determinants of risk such as blood pressure and cholesterol because they also fluctuate substantially over relatively short time periods [3]. Therefore a key strength of a new study by John Danesh and colleagues, reported in this issue of PLoS Medicine [4], is the substantial effort undertaken to overcome this problem and obtain reliable estimates of the association between IL-6 and coronary heart disease [5]. Whether the findings for IL-6 provide substantial new insight into the causation of cardiovascular disease is, however, rather less clear.
The Day's Mail
Authors: Preston J. Burnham
Journal: JAMA (1967)

To the Editor:—  The Figure shows one day's mail influx—besides the bills, the checks, and the purchased journals, which are not included. Nearly all of that illustrated hits the wastebasket without being opened.  It takes me only a minute or two to whip them one by one from my desk into the basket. But think of the cost to the drug companies, the post office, and, of course, to the patient and public at large, who ultimately pay for everything.  I do not know how to advise drug companies to advertise; I only believe that this direct mail is not the way to do it. Advertisers should give thought, too, to the possibility that this surplus literature may create prejudice against them.
THE CLASSIFICATION OF THE BODY CONSTITUENTS BY WATER CONTENT
Authors: H. G. Close
Journal: BMJ (1934)

98 JAN.,u,IMEDICAL 1OURNAL birth or later, and frequently associated with cerebral degeneration producing idiocy.It is a not infrequent cause of congenital blindness.I * ----o o o Female Male CHIARTS 27A and 27B.-Amaurosis sex-linked (Sedgwick).T_ I CHART 28.-Amaurotic family idiocy-" Tay Sach" (King, Rus, Stewart)
Effects of Cardiac Versus Circulatory Angiotensin-Converting Enzyme Inhibition on Left Ventricular Diastolic Function and Coronary Blood Flow in Hypertrophic Obstructive Cardiomyopathy
Authors: Michael Kyriakidis, Filippos Triposkiadis, John Dernellis, Aristides E. Androulakis, Panagiotis Mellas, Glafkos A. Kelepeshis, John E. Gialafos
Journal: Circulation (1998)

Background —Left ventricular (LV) diastolic function and coronary flow are impaired in hypertrophic obstructive cardiomyopathy (HOCM). This study was designed to evaluate the impact of cardiac and circulatory ACE inhibition on such derangements. Methods and Results —Twenty patients with HOCM underwent cardiac ACE inhibition with intracoronary (IC) enalaprilat (0.05 mg/min infused into the left anterior descending coronary artery for 15 minutes) followed by circulatory ACE inhibition with 25 mg sublingual (SL) captopril. Contrast ventriculography, pressure, and coronary flow measurements were performed at baseline, after IC enalaprilat infusion, and 45 minutes after SL captopril. Heart rate was not affected by the respective interventions (75±11 versus 76±13 versus 75±10 bpm; P =NS), whereas mean aortic pressure dropped slightly after IC enalaprilat and significantly after SL captopril (90±8 versus 85±10 versus 74±9 mm Hg; P &lt;.05). Compared with baseline, IC enalaprilat resulted in a decrease in LV end-diastolic pressure (17.6±5.9 versus 14.4±4.9 mm Hg; P &lt;.05), time constant of isovolumic LV pressure relaxation (τ G ) (69±9 versus 52±10 ms; P &lt;.05), and outflow gradient (45.2±6.9 versus 24.4±3.7 mm Hg; P &lt;.05) and in an increase in coronary blood flow (107±10 versus 127±12 mL/min; P &lt;.05) and coronary flow reserve (2.2±0.4 versus 2.6±0.3; P &lt;.05). After SL captopril, τ G was prolonged (60±13 ms; P &lt;.05 versus IC enalaprilat), and LV outflow gradient, coronary blood flow, and coronary flow reserve values returned to baseline (45.5±5.3 mm Hg, 107±12 mL/min, and 2.2±0.5, respectively; P =NS versus baseline). Conclusions —Activation of the cardiac renin-angiotensin system contributes to LV diastolic dysfunction as well as to the decreased coronary blood flow and coronary flow reserve in HOCM. Cardiac ACE inhibition restores and circulatory ACE inhibition aggravates the above derangements.
Abstract LB-2: Cullin-2 facilitates EGFR ubiquitination and degradation after trafficking of the receptor to the nucleus
Authors: Jayoung Kim, Michael R. Freeman
Journal: Cancer Research (2010)

Abstract Objectives of the study: The epidermal growth factor receptor (EGFR) can be overexpressed in bladder cancer and other malignancies and is a molecular risk factor associated with poor prognosis. Surface EGFR is able to traffic to the nucleus, where it can regulate gene expression as a component of transcription complexes. This non-canonical function for the EGFR correlates with tumor aggressiveness and unfavorable clinical outcome. We have identified cullin-2, a ubiquitin E3 ligase cofactor that associates with the Von Hippel-Lindau tumor suppressor protein (pVHL) and elongin B/C, by mass spectrometry as a putative component of an EGFR nuclear trafficking complex in human bladder cancer cells. The goal of the present study was to determine the potential role of cullin-2 in EGFR nuclear trafficking and function. Methodology: Various biochemical approaches, including co-IP/Western blotting and fluorescence imaging, were performed to analyze the association of EGFR and ubiquitin E3 ligase components, including cullin-2 and pVHL. Forced expression or silencing of cullin-2 was also performed. Results: Accumulation of EGFR in nuclei was shown within 30min after treatment of TCCSUP bladder cancer cells with the EGFR ligand HB-EGF. Ubiquitination and degradation of nuclear EGFR were observed 1h after stimulation. Cullin-2 binds to EGFR in the nucleus, leading to recruitment of pVHL upon HB-EGF treatment. The association of nuclear EGFR with the Rpt10/S5a and Rpt1 proteasome subunits implicates the proteasome in nuclear EGFR degradation, which is consistent with data indicating that nuclear EGFR degradation was suppressed by proteasomal inhibition. Silencing of endogenous cullin-2 or pVHL suppressed the degradation of nuclear EGFR. Collectively, these results suggest that cullin-2 is a mediating factor that connects nuclear EGFR to the ubiquitin E3 ligase and the proteasome, leading to proper feedback regulation after EGFR activation. Our findings provide new insight into the diverse intracellular mechanisms in which the EGFR participates and, in particular, its signaling roles in the nucleus in bladder cancer and possibly other cell types. 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 LB-2.
Changes in <scp>mRNA</scp> expression precede changes in micro <scp>RNA</scp> expression in lesional psoriatic skin during treatment with adalimumab
Authors: L. Raaby, A. Langkilde, R.B. Kjellerup, H. Vinter, S.H. Khatib, K.F. Hjuler, C. Johansen, L. Iversen
Journal: British Journal of Dermatology (2015)

Background Tumour necrosis factor (TNF)-α inhibition is an effective treatment for moderate to severe plaque-type psoriasis. A change in the cytokine expression profile occurs in the skin after 4 days of treatment, preceding any clinical or histological improvements. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, but miRNA expression has never been studied in psoriatic skin during treatment. Objective To investigate changes in miRNA expression in psoriatic skin during adalimumab treatment and to compare results with changes in miRNA expression in a mouse model of Aldara-induced psoriasis-like skin inflammation. Methods Punch biopsies were obtained from nonlesional and lesional psoriatic skin during adalimumab treatment. In the mouse model of Aldara-induced skin inflammation, biopsies were obtained from TNF-α knockout (KO), IL-17A KO and wild-type mice. miRNA expression levels were analysed with microarray, reverse transcriptase quantitative polymerase chain reaction and in situ hybridization. Results In psoriatic skin, no changes in miRNA expression were seen 4 days after treatment initiation. After 14 days of treatment, the expression of several miRNAs was normalized towards the level seen in nonlesional skin before treatment. miR-23b expression increased after 14 days of treatment and remained high for 84 days, despite unaltered levels at baseline. In the mouse model of Aldara-induced skin inflammation, the level of miR-146a increased, whereas no regulation was seen for miR-203, miR-214-3p, miR-125a, miR-23b or let-7d-5p. Conclusions This study demonstrates that the changes seen in the cytokine expression levels after 4 days of treatment with adalimumab are not facilitated by early changes in miRNA expression.
Bimodality in Blood Glucose Distribution
Authors: Teck-Onn Lim, Rugayah Bakri, Zaki Morad, Maimunah A. Hamid
Journal: Diabetes Care (2002)

OBJECTIVE—Bimodality in blood glucose (BG) distribution has been demonstrated in several populations with a high prevalence of diabetes and obesity. However, other population studies had not found bimodality, thus casting doubt on its universality. We address this question in four ethnic populations—namely Malay, Chinese, Indian, and the indigenous people of Borneo. RESEARCH DESIGN AND METHODS—A national health survey was conducted in Malaysia in 1996. A total of 18,397 subjects aged ≥30 years had post-challenge BG measurements taken. To test whether BG was consistent with a bimodal distribution, we fitted unimodal normal and skewed distribution as well a mixture of two normal distributions to the data by age and ethnic groups. RESULTS—Age-specific prevalence of diabetes varied from 1.3 to 26.3%. In all ethnic/age groups, the bimodal model fitted the log BG data better (likelihood ratio tests, all P values &amp;lt;0.001). CONCLUSIONS—Bimodality in BG distribution is demonstrable even in populations with a very low prevalence of diabetes and obesity. Previous studies that found unimodality had failed to detect the second mode because of inadequate sample size, bias due to treatment of subjects with known diabetes, and inclusion of subjects with type 1 diabetes in the sample. Bimodality implies that diabetes is a distinct entity rather than an arbitrarily defined extreme end of a continuously distributed measurement.
Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis
Authors: Antonio M. Vignola, Pascal Chanez, Giuseppina Chiappara, Liboria Siena, Anna Merendino, Clotilde Reina, Rosalia Gagliardo, Mirella Profita, Jean Bousquet, Giovanni Bonsignore
Journal: Journal of Allergy and Clinical Immunology (1999)
Impact of Congenital Narrowing of the Bulbar Urethra (Cobb&amp;rsquo;s Collar) andIts Transurethral Incision in Children
Authors: Katsuya Nonomura, Takayuki Kanno, Hidehiro Kakizaki, Toshiki Koyama, Tetsufumi Yamashita, Tomohiko Koyanagi
Journal: European Urology (1999)
An Invalid Transit
Authors: R. Davy
Journal: BMJ (1882)

THE "BRJ77SM.H MEDiL 7OWnLdAL fDqct g htn a&i be a&Wd so as io puiify the air of large buildings, witho4t csudng'dogbt, -by measns of a fn and tank.The figue (3) reprents a diagram of the application of tbe "che-miA lung* to a theatre or any other large building.A is a rotary fan, st in motion by an engine (not seen) which draws the vitiated atmo.pbere from the upper part of the building through the funnel-shaped otiic .ofB, placed in the ceiling where the air is hottest and mot ftll, aud forces It through the tank c, which contains the chemical solution.The air, entirely deprived of all its impurities, passes out through the tnmk D, at a temperature TegUlated at pleasure.By this angement, all draught Is avoided, the pure air being either distri- buted by the brnches opening out at the upper part of the several box or gallery floors of the building operated upon, or allowed to escape at once into the basement of the building, and-so flood it with pure air cooled or warmed at pleasure.
Remarks on the Causation of the Increased Intracranial Pressure Associated with Tumours within the Cranium
Authors: J. S. B. Stopford
Journal: BMJ (1926)

AIN-Y tlleories hiave fromii time to timle beeln suggested to ecxplaini the etiolooy of the iniereased initracranial pressure -w-biclh is so frequently associated With tuinsoulrs withlinl tho skrull.Nevertheless thle miiatter is still largely shlrouded in maystelr, altlhough careful observations made upon large ser ies of cases by a niumnber of inv-estigators offer solmie siognificant ilnformiation.Although clinical evidencee of raised initr acralnial pr essur e as mitaniifested .by. lheadaclle, 'vomitilln, and clholked dise is iiot an absolutely con]stanlt accollh)aninient of tuinours wl ithlinl tlhe cranillm, it is geiie'nally agreed that it occur-s at somie timile in the course of tlhe disease in upuwaids, of 80 per cent.Fromli researches which have been .madewith regard to tlhe , .presenice or absence of in- released intracrallial pres- sure it is clear that tlhe / -
Role of the Prostanoid EP4 Receptor in Iloprost-mediated Vasodilatation in Pulmonary Hypertension
Authors: Ying-Ju Lai, Soni Savai Pullamsetti, Eva Dony, Norbert Weissmann, Ghazwan Butrous, Gamal-Andre Banat, Hossein Ardeschir Ghofrani, Werner Seeger, Friedrich Grimminger, Ralph Theo Schermuly
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Iloprost is effective for the treatment of pulmonary hypertension. It acts through elevation of cAMP by binding to the prostacyclin receptor (IP receptor). However, there is evidence that patients with severe pulmonary hypertension have decreased expression of the IP receptor in the remodeled pulmonary arterial smooth muscle.We hypothesized that prostanoid receptors other than the IP receptor are involved in signal transduction by iloprost.Immunoblotting was used to detect the IP and prostanoid EP4 receptor in lung tissue from patients with idiopathic pulmonary arterial hypertension, and immunohistochemistry was used to detect these receptors in lung sections from rats treated with monocrotaline (MCT28d). Protein and mRNA were isolated from pulmonary arterial smooth muscle cells (PASMCs) from control and MCT28d rats treated with AH6809 (an EP2 receptor antagonist) and AH23848 (an EP4 receptor antagonist) in combination with iloprost. Intracellular cAMP was also assessed in these tissues.IP receptor expression was reduced in idiopathic pulmonary arterial hypertension patient lung samples and MCT28d rat lungs compared with the controls. Reverse transcriptase-polymerase chain reaction and immunoblotting of MCT28d rat PASMC extracts revealed scant expression of the IP receptor but stable expression of EP4 receptor, compared with controls. Iloprost-induced elevation in intracellular cAMP in PASMCs was dose-dependently reduced by AH23848, but not by AH6809.Iloprost mediates vasodilatory functions via the EP4 receptor in the case of low IP receptor expression associated with pulmonary arterial hypertension. This is a previously unrecognized mechanism for iloprost, and illustrates that the EP4 receptor may be a novel therapeutic approach for the treatment of pulmonary arterial hypertension.
Falling into the Doughnut Hole
Authors: Uptal D. Patel, Matthew M. Davis
Journal: Journal of the American Society of Nephrology (2006)

The Medicare Part D prescription drug benefit may facilitate provision of medications by subsidizing drug costs. However, beneficiaries with higher drug utilization may face higher out-of-pocket (OOP) costs under the benefit's "doughnut hole" provisions that substantially increase beneficiary cost-sharing. The Medicare Current Beneficiary Survey Cost and Use data for 1997 through 2001 were used to estimate the impact of the standard Part D benefit on drug expenditures. The sample consisted of adults who were not dually enrolled in Medicaid (41,617 without ESRD, 256 with ESRD). Outcomes were annual total and OOP drug spending projected to 2006, as well as estimates of individual spending changes under Part D. In 2006, ESRD beneficiaries will have mean annual total and OOP expenditures that are approximately twice that of their Medicare peers. The overall impact of Part D on OOP expenditures is similar among all beneficiaries; however, many individuals with employer-sponsored coverage and those with higher costs (especially those with ESRD) may face cost increases with significant monthly variability as a result of reaching the "doughnut hole," a no-coverage gap in the standard benefit. Therefore, ESRD beneficiaries face substantial total and OOP annual expenditures for medications, causing most to reach the Part D benefit gap. Higher OOP costs may lead to reductions in spending and medication use with subsequent treatment gaps that may lead to increased use of medical services. As the new legislation takes effect, policy makers who are considering modifications in the program may benefit from further research to monitor patterns and gaps in coverage, medication use and spending, and hospitalization and survival trends.
Properties and actions of bridged diphenyl acaricides.
Authors: R B March
Journal: Environmental Health Perspectives (1976)

The properties and actions of the bridged diphenyl acaricides are discussed. These pesticides, which are more or less structurally related to DDT, were the first of the specific acaricides to be developed. They exhibit remarkable properties of specificity, being primarily toxic to phytophagous mites but of very low toxicity to most nontarget species, including insects, fish, birds, and mammals. Although many important facets of their broad mode of action are understood, virtually nothing is known of their primary mode of action or the underlying bases of their specificities. In most ways they are model compounds for integrated control and pest management activities and thus merit greater attention than they have received to elucidate the fundamentals underlying their unusual properties and actions.
Intrathecal morphine as sole analgesic during labour
Authors: B W Perriss, A F Malins
Journal: BMJ (1980)

criticism of what is being undertaken.At a recent meeting the regional advisers thought that the development was a useful one and Dr van't Hoff, regional adviser for the West Midlands, is helping the editor over this.It seems to me-writing as a general physician, and remembering well the amount of work involved-that audit on the lines described in this letter is much more likely to be acceptable to the people who actually do the work than is the bureaucratic approach.
Health Implications of Childhood Obesity
Authors: FRANCIS E. JOHNSTON
Journal: Annals of Internal Medicine (1985)

Childhood obesity has immediate and long-term health risks. There is an increased risk of disease and emotional stress associated with obesity during the growing years, but there are greater risks if obesity continues into adolescence and adulthood. There are insufficient data to quantify the association of childhood and adult obesity. Although obese adults are more likely to have been heavy as children, most overweight children are of normal weight as adults. Childhood obesity is frequently associated with an accelerated growth pattern characterized by increased lean body mass, greater stature, and more rapid maturation.
Bone and joint changes in pneumatic drillers.
Authors: M J Burke, E C Fear, V Wright
Journal: Annals of the Rheumatic Diseases (1977)

A clinical and radiological survey of 34 men who were pneumatic drillers employed by the North East Gas Board, was carried out to determine the prevalence of osteoarthrosis. Mild osteoarthrosis of the elbows was found in 2 subjects only. Two drillers had radiological evidence of generalized osteoarthrosis elsewhere, and minor degenerative changes were present in the hands of 15 cases. Our findings do not support the view that pneumatic drillers are particularly prone to develop osteoarthrosis.
Low Termination of the Internal Saphenous Vein
Authors: P. G. Bevan, S. H. Green, F. A. R. Stammers
Journal: BMJ (1956)

MEDICAL JOUNLpredommantly "carbohydrate" defect, cortisone alone was used for maintenance therapy.As soon as the hypoglycaemia was recognized the patient was restored to consciousness with the intravenous adminis- tration of glucose.After this, oral glucose feeding sufficed to maintain adequate blood-sugar levels.It is suggested that the possibility should be borne in mind that hypoglycaemia may be contributing to loss of consciousness in-'thew Addisonian patient.I It would, therefore seem worth white to estinmiate the blood-sugar level as a routine in this type of -case. SummaryThe case of a woman with Addison's disease present- ing in hypoglycaemic coma is described.The coma, responded immediately to the administration of intra- venous glucose.The differential diagnosis is briefly discussed.
The biological impact of estrogens on gender differences in congestive heart failure
Authors: G SCHONFELDER
Journal: Cardiovascular Research (2005)

See also article by Pelzer et al.  [14]  (pages 604–612) in this issue. 

Heart failure seems to be a different entity in women than in men because of gender-related differences in the cardiovascular system. Myocardial hypertrophy is one independent risk factor for heart failure and represents a very important health issue because of morbidity and mortality. Men under the age 50 have a greater risk of contracting cardiovascular disease than age-matched women. Women with heart failure very often have different clinical features than men, such as age of onset and co-morbidities [1]. It is well documented that differences exist in remodeling and the response to injury when men are compared with women. The mechanisms underlying these gender-related differences, however, remain unresolved, and a large number of investigations have been initiated for the purpose of understanding the gender dependency in the pathogenesis of heart failure.

Pre-menopausal women have a reduced risk of contracting cardiovascular disease, and the incidence and severity of cardiovascular diseases strongly increase after menopause. Epidemiological, mostly observational studies showed less heart disease among women taking estrogens [2] (about a 50% reduction in cardiovascular disease). The pathophysiologic mechanisms provided enough biological plausibility for hormone replacement therapy (HRT) [3] because estrogens are believed to have indirect and direct cardioprotective properties. … 

*Tel.: +49 30 8445 1702; fax: +49 30 8445 1761. Email address: gilbert.schoenfelder{at}charite.de