tbuckley/cabot-search huggingface dataset:
Effects of rapid stimulation on the transmembrane action potentials of rabbit sinus node pacemaker cells.
Authors: I Kodama, J Goto, S Ando, J Toyama, K Yamada
Journal: Circulation Research (1980)

We studied the mechanism of post-overdrive suppression in superfused rabbit sinus node pacemaker cells. Small specimens of sinus node tissue isolated from rabbit hearts were driven at a fast rate (overdrive) for 10-120 seconds using single sucrose gap methods. During the control perfusion (35 degrees C Tyrode's solution), overdrive caused a progressive decrease in maximum diastolic potential (MDP), overshoot (OS), and maximum rate of depolarization at phase 0 [dV/dt)max]. After cessation of the overdrive, the rate of diastolic depolarization decreased, and the spontaneous activity was suppressed temporarily (post-overdrive suppression). MDP, OS, (dV/dt)max, and the spontaneous activity returned within a few seconds to the level observed before overdrive. Atropine (2 x 10(-6) g/ml) did not influence the effects of overdrive. After ouabain administration (3 x 10(-7) g/ml) or in low temperature perfusate (25 degrees C), the effects of overdrive were accentuated, and a marked suppression of spontaneous activity with a long pause of over several seconds was seen following the overdrive. These results suggest that the post-overdrive suppression of sinus node is attributable, at least in part, to ionic shifts following overdrive, and may be potentiated by metabolic dysfunction of pacemaker cells.
Atopic Sensitization and the International Variation of Asthma Symptom Prevalence in Children
Authors: Gudrun Weinmayr, Stephan K Weiland, Bengt Björkstén, Bert Brunekreef, Gisela Büchele, William O C Cookson, Luis Garcia-Marcos, Maia Gotua, Christina Gratziou, Marianne van Hage, Erika von Mutius, Mall-Anne Riikjärv, Peter Rzehak, Renato T Stein, David P Strachan, John Tsanakas, Kristin Wickens, Gary W Wong, Non Renseigné, Isabella Annesi-Maesano
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further.To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma.Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI).The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01).The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.
Reply to M.M.J. Zanders et al
Authors: David Margel, David Urbach, Neil Fleshner, Peter C. Austin
Journal: Journal of Clinical Oncology (2014)

The term "confounding by indication" is typically used to denote a particular form of confounding in studies of medications whereby the apparent effect of a medication is actually a result of the condition for which it is prescribed.In this instance (ie, in the study by Margel et al 1 ), all of the comparisons were within patients with diabetes, so the underlying indication for the medication was the same.One might argue that metformin users differ from users of other antidiabetic
The effects of blood pressure reduction on cyclosporine nephrotoxicity in the rat.
Authors: R A Lafayette, G Mayer, T W Meyer
Journal: Journal of the American Society of Nephrology (1993)

The effects of blood pressure reduction on cyclosporine nephrotoxicity were studied over 12 months in four groups of rats. Group 1 received no drugs and served as controls. Groups 2, 3, and 4 received cyclosporine (CyA), approximately 9 mg/kg.day, in their food. In addition, Group 3 received enalapril and Group 4 received minoxidil, hydrochlorothiazide, and reserpine. Time-averaged monthly systolic blood pressure was equal in Groups 1 and 2 (136 +/- 1 and 135 +/- 1 mm Hg, respectively). Antihypertensive agents reduced average systolic blood pressure in Groups 3 and 4 (116 +/- 1 and 117 +/- 1 mm Hg, respectively). Morphometric studies showed that 12 months of CyA treatment caused interstitial fibrosis with an increase in the fractional volume of cortical interstitium (VvInt: Group 2, 20 +/- 1%; Group 1, 11 +/- 1%) and a reduction in mean glomerular volume (VG. Group 2, (2.00 +/- 0.06) x 10(6) mu 3; Group 1, (2.48 +/- 0.06) x 10(6) mu 3). These structural changes were accompanied by a significant reduction in GFR (Group 2, 2.27 +/- 0.10 mL/min; Group 1, 2.76 +/- 0.10 mL/min). Cotreatment with enalapril reduced interstitial fibrosis (VvInt, 14 +/- 1%) and maintained VG (2.23 +/- 0.08 x 10(6) mu 3) and GFR (2.56 +/- 0.08 mL/min) at near-normal values in Group 3. In contrast, the combination antihypertensive regimen increased the extent of interstitial fibrosis (VvInt, 24 +/- 1%) and further lowered VG (1.72 +/- 0.05 x 10(6) mu 3) and GFR (1.72 +/- 0.05 mL/min) in Group 4. These results show that sustained treatment with a moderate dose of CyA causes interstitial fibrosis and impairs renal function in rats. The administration of enalapril, but not minoxidil, reserpine, and hydrochlorothiazide, limits renal injury in this model.
Lung disease after exposure to polyvinyl chloride dust.
Authors: M Antti-Poika, H Nordman, J Nickels, H Keskinen, A Viljanen
Journal: Thorax (1986)

Cases of lung disease after exposure to polyvinyl chloride (PVC) dust have been described.' 2 The association between pneumoconiosis and PVC dust is also supported by animal experiments3 -and epidemiological studies.6-8Case report I 1.-\ 0
Report of Colombian Registry for Hereditary Angioedema
Authors: Maria Margarita Olivares, Rosa Farfan, Carlos E. Olmos, Catalina Gomez, Jorge Sanchez, Maria C. Ortega-Lopez, Jairo A. Rodriguez, Jorge Rabal, Mauricio Sarrazola, Susana Diez-Zuloaga, Alejandro Carreno, Alejandro Echenique, Eduardo Jr De Zubiria, Gerardo Ramirez
Journal: Journal of Allergy and Clinical Immunology (2016)
A Clinical Prediction Rule for Delirium After Elective Noncardiac Surgery
Authors: E R Marcantonio, L Goldman, C M Mangione, L E Ludwig, B Muraca, C M Haslauer, M C Donaldson, A D Whittemore, D J Sugarbaker, R Poss
Journal: JAMA (1994)

<h3>Objective.</h3> —To develop and validate a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively. <h3>Design.</h3> —Prospective cohort study. <h3>Setting.</h3> —General surgery, orthopedic surgery, and gynecology services at Brigham and Women's Hospital, Boston, Mass. <h3>Patients.</h3> —Consenting patients older than 50 years admitted for major elective noncardiac surgery between November 1, 1990, and March 15, 1992 (N=1341). <h3>Measurements.</h3> —All patients underwent preoperative evaluations, including a medical history, physical examination, laboratory tests, and assessments of physical and cognitive function using the Specific Activity Scale and the Telephone Interview for Cognitive Status. Postoperative delirium was diagnosed using the Confusion Assessment Method or using data from the medical record and the hospital's nursing intensity index. Patients were followed up for the duration of hospitalization to determine major complication rates, length of stay, and discharge disposition. <h3>Results.</h3> —Postoperative delirium occurred in 117 (9%) of the 1341 patients studied. Independent correlates included age 70 years or older; self-reported alcohol abuse; poor cognitive status; poor functional status; markedly abnormal preoperative serum sodium, potassium, or glucose level; noncardiac thoracic surgery; and aortic aneurysm surgery. Using these seven preoperative factors, a simple predictive rule was developed. In an independent population, the rule stratified patients into groups with low (2%), medium (8%, 13%), and high (50%) rates of postoperative delirium. Patients who developed delirium had higher rates of major complications, longer lengths of stay, and higher rates of discharge to long-term care or rehabilitative facilities. <h3>Conclusions.</h3> — Using data available preoperatively, clinicians can stratify patients into risk groups for the development of delirium. Since delirium is associated with a variety of adverse outcomes, patients with substantial risk for this complication could be candidates for interventions to reduce the incidence of postoperative delirium and potentially improve overall surgical outcomes. (<i>JAMA</i>. 1994;271:134-139)
Working memory as a mental workspace: Why activated long-term memory is not enough
Authors: Robert H. Logie, Sergio Della Sala
Journal: Behavioral and Brain Sciences (2003)

Working-memory retention as activated long-term memory fails to capture orchestrated processing and storage, the hallmark of the concept of working memory. The event-related potential (ERP) data are compatible with working memory as a mental workspace that holds and manipulates information on line, which is distinct from long-term memory, and deals with the products of activated traces from stored knowledge.
Prebiotic carbohydrates: not sweet yet for Crohn's disease?
Authors: P. Marteau
Journal: Gut (2011)

The double-blind placebo controlled study performed by Benjamin et al 1 published in Gut ( in press ) shows that the daily consumption of 15 g fructo-oligosaccharides (FOS) worsens the clinical signs of active Crohn's disease. The message for the clinician and the patient is clear: despite a strong rationale and hopes from open studies,2 there is presently no evidence of efficacy of prebiotics in Crohn's disease. The same conclusion applies for probiotics and synbiotics.3 However, one should avoid throwing the baby out with the bath water.

Descriptive studies of the microbiota and microenvironment in Crohn's disease have repeatedly shown dysbiosis, which is probably partly a consequence of the ecological modifications induced …
Patterns of Use and Risks Associated With Erythropoiesis-Stimulating Agents Among Medicare Patients With Cancer
Authors: Dawn L. Hershman, Donna L. Buono, Jennifer Malin, Russell McBride, Wei Yann Tsai, Alfred I. Neugut
Journal: JNCI Journal of the National Cancer Institute (2009)

Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist. We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results–Medicare database; who were diagnosed with colon, non–small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided. Among 56 210 patients treated with chemotherapy from 1991 through 2002, 15 346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 ( P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991–2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12 522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34 820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups. Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.
Hormonal appetite control is altered by shift work: a preliminary study
Authors: Cibele Aparecida Crispim, Jim Waterhouse, Ana Raimunda Dâmaso, Ioná Zalcman Zimberg, Heloisa Guarita Padilha, Lila Missae Oyama, Sérgio Tufik, Marco Túlio de Mello
Journal: Metabolism (2011)
Letter to the editor: Successful treatment of methimazole‐induced agranulocytosis by granulocyte colony‐stimulating factor
Authors: Kenji Yokoyama, Toru Sato, Sadao Nakajima, Masao Chino, Satoru Komatsumoto, Masaharu Nara, Shinichiro Okamoto
Journal: American Journal of Hematology (1992)
Fine Structural Localization of Acetylcholinesterase at a Cholinergic Vasodilator Nerve-Arterial Smooth Muscle Synapse
Authors: CHRISTOPHER BELL
Journal: Circulation Research (1969)

An electron-microscope study of the localization of acetylcholinesterase (AChE) has been made in the main uterine artery of the guinea pig, which is supplied by cholinergic dilator and adrenergic constrictor nerves. Large bundles of nonterminal axons were present in the outer adventitia, and terminal axons, containing numerous vesicles, were scattered through the inner adventitia up to 1µ away from the outer layer of smooth muscle cells. About 50% of these axons were within 0.2µ of a muscle cell; the minimum neuromuscular gap found was 0.05µ. No axons were within the media. The outer membranes of axons stained either heavily or lightly for AChE. These two distinct classes appear to represent cholinergic and noncholinergic axons, respectively. In late pregnancy, all cholinergic terminal axons which contained vesicles and were not separated from the muscle by Schwann or elastic tissue were associated with heavy postsynaptic staining which was restricted to that region of the muscle membrane adjacent to the axon. In tissue from virgin animals, most cholinergic terminal axons were associated with only scanty postsynaptic staining. The increase in postsynaptic AChE during pregnancy can be correlated with the increase in sensitivity of the arterial muscle to acetylcholine over this period. Assuming that the association of heavy AChE staining both pre- and postsynaptically is indicative of a functional cholinergic synapse, acetylcholine released up to 1µ away from the muscle may participate in transmission from vasodilator axons in this vessel. Since postsynaptic AChE staining is restricted to discrete areas on the outer muscle cells, probably only these cells are directly affected by transmitter released from nerves.
Control of belching by the lower oesophageal sphincter.
Authors: J B Wyman, J Dent, R Heddle, W J Dodds, J Toouli, J Downton
Journal: Gut (1990)

The mechanism that controls venting of gas from the stomach into the oesophagus was studied manometrically in 14 healthy subjects. The stomach was distended abruptly with one litre of carbon dioxide. Gas reflux was characterised by an abrupt increase in basal oesophageal body pressure to intragastric pressure. Reflux of gas from the stomach into the oesophagus occurred during transient lower oesophageal sphincter relaxations that generally had a pattern distinctly different from swallow-induced lower oesophageal sphincter relaxation. Thus, at the onset of an episode of gas reflux lower oesophageal sphincter pressure had relaxed to 3 mmHg, or less, in 96% of instances. After gas loading of the stomach the prevalence of gas reflux was significantly less when the subjects were supine (1.2/10 min) than when they were sitting (6.8/10 min) (p less than 0.001). The lower oesophageal sphincter relaxations associated with most episodes of gas reflux had a distinctive pattern that resembled those of the lower oesophageal sphincter relaxations associated with acid gastro-oesophageal reflux.
Assessment of peripheral artery tonometry in the detection of treadmill exercise-induced myocardial ischemia
Authors: Pierre Chouraqui, Robert P Schnall, Itsik Dvir, Alan Rozanski, Ehtasham Qureshi, Alexander Arditti, Jerold Saef, Paul D Feigin, Jacob Sheffy
Journal: Journal of the American College of Cardiology (2002)
Effect of Helicobacter pylori colonisation on gastric mucosal eicosanoid synthesis in patients taking non-steroidal anti-inflammatory drugs.
Authors: N Hudson, M Balsitis, F Filipowicz, C J Hawkey
Journal: Gut (1993)

Colonisation with Helicobacter pylori may influence susceptibility to gastroduodenal injury and ulceration in patients taking non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to determine if Helicobacter pylori colonisation altered eicosanoid synthesis by gastric mucosa in these patients. Sixty five patients with long-standing NSAID intake and 23 control subjects underwent endoscopy. In vitro gastric antral biopsies were stimulated by vortex mixing and eicosanoid measurements determined by radioimmunoassay. Helicobacter pylori colonisation was determined by a CLO test (a gel based rapid urease test) and histological assessment. Median prostaglandin E2 synthesis by gastric mucosa was 61.0 (interquartile range: 19.2-73.1) pg/mg in control subjects colonised with Helicobacter pylori compared with 46.5 (23.3-65.5) pg/mg in Helicobacter pylori negative subjects. This was not significantly different. Treatment with NSAIDs was associated with a significant difference (p < 0.001) in prostaglandin E2 (PGE2) synthesis between those colonised with Helicobacter pylori (37.5(22.0-77.3) pg/mg) compared with patients not infected (12.6(7.0-19.3) pg/mg). Values in patients taking NSAIDs who were colonised were not different from control subjects. Synthesis of PGE2 was strongly associated with type B (chronic active), but not type C (chemical) gastritis. Dyspeptic symptoms were more common in subject colonised with Helicobacter pylori (p < 0.002) and were associated with higher PGE2 synthesis. In patients taking NSAIDs Helicobacter pylori colonisation removes rather then enhances depression of PGE2 synthesis associated with NSAIDs and may promote dyspepsia associated with ulcers and prevent superficial mucosal injury.
Capsule Endoscopy versus Colonoscopy for the Detection of Polyps and Cancer
Authors: André Van Gossum, Miguel Munoz-Navas, Iñaqui Fernandez-Urien, Cristina Carretero, Gérard Gay, Michel Delvaux, Marie Georges Lapalus, Thierry Ponchon, Horst Neuhaus, Michael Philipper, Guido Costamagna, Maria Elena Riccioni, Cristiano Spada, Lucio Petruzziello, Chris Fraser, Aymer Postgate, Aine Fitzpatrick, Friedrich Hagenmuller, Martin Keuchel, Nathalie Schoofs, Jacques Devière
Journal: New England Journal of Medicine (2009)

An ingestible capsule consisting of an endoscope equipped with a video camera at both ends was designed to explore the colon. This study compared capsule endoscopy with optical colonoscopy for the detection of colorectal polyps and cancer.We performed a prospective, multicenter study comparing capsule endoscopy with optical colonoscopy (the standard for comparison) in a cohort of patients with known or suspected colonic disease for the detection of colorectal polyps or cancer. Patients underwent an adapted colon preparation, and colon cleanliness was graded from poor to excellent. We computed the sensitivity and specificity of capsule endoscopy for polyps, advanced adenoma, and cancer.A total of 328 patients (mean age, 58.6 years) were included in the study. The capsule was excreted within 10 hours after ingestion and before the end of the lifetime of the battery in 92.8% of the patients. The sensitivity and specificity of capsule endoscopy for detecting polyps that were 6 mm in size or bigger were 64% (95% confidence interval [CI], 59 to 72) and 84% (95% CI, 81 to 87), respectively, and for detecting advanced adenoma, the sensitivity and specificity were 73% (95% CI, 61 to 83) and 79% (95% CI, 77 to 81), respectively. Of 19 cancers detected by colonoscopy, 14 were detected by capsule endoscopy (sensitivity, 74%; 95% CI, 52 to 88). For all lesions, the sensitivity of capsule endoscopy was higher in patients with good or excellent colon cleanliness than in those with fair or poor colon cleanliness. Mild-to-moderate adverse events were reported in 26 patients (7.9%) and were mostly related to the colon preparation.The use of capsule endoscopy of the colon allows visualization of the colonic mucosa in most patients, but its sensitivity for detecting colonic lesions is low as compared with the use of optical colonoscopy. (ClinicalTrials.gov number, NCT00604162.)
Functionally Compensating Coevolving Positions Are Neither Homoplasic Nor Conserved in Clades
Authors: Gregory B Gloor, Gaurav Tyagi, Dana M Abrassart, Andrew J Kingston, Andrew D Fernandes, Stanley D Dunn, Christopher J Brandl
Journal: Molecular Biology and Evolution (2010)

We demonstrated that a pair of positions in phosphoglycerate kinase that score highly by three nonparametric covariation measures are important for function even though the positions can be occupied by aliphatic, aromatic, or charged residues. Examination of these pairs suggested that the majority of the covariation scores could be explained by within-clade conservation. However, an analysis of diversity showed that the conservation within clades of covarying pairs was indistinguishable from pairs of positions that do not covary, thus ruling out both clade conservation and extensive homoplasy as means to identify covarying positions. Mutagenesis showed that the residues in the covarying pair were epistatic, with the type of epistasis being dependent on the initial pair. The results show that nonconserved covarying positions that affect protein function can be identified with high precision.
Transfection of antisense core 2 β1,6-N-acetylglucosaminyltransferase-1 cDNA suppresses selectin ligand expression and tissue infiltration of B-cell precursor leukemia cells
Authors: J Kikuchi, H Ozaki, C Nonomura, H Shinohara, S Iguchi, H Nojiri, H Hamada, A Kiuchi, M Nakamura
Journal: Leukemia (2005)