tbuckley/cabot-search huggingface dataset:
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure&lt;SUBTITLE&gt;The JNC 7 Report&lt;/SUBTITLE&gt;
Authors: Aram V Chobanian, George L Bakris, Henry R Black, William C Cushman, Lee A Green, Joseph L Izzo, Daniel W Jones, Barry J Materson, Suzanne Oparil, Jackson T Wright, Edward J Roccella
Journal: JAMA (2003)

"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.
The Effect of a Threshold Electrical Stimulus upon the Repolarization Process of the Left Ventricle of the Intact Dog Heart
Authors: L. H. NAHUM, H. LEVINE, H. GELLER, R. SIKAND
Journal: Circulation (1953)

A threshold stimulus applied either at apex or base of the intact dog ventricle at any depth of the myocardium produces a delay in repolarization during the following three to four normal beats, in an area equivalent to the size of the proximal zone of the precordial lead. This change in repolarization is not caused by postextrasystolic distension of the ventricle. The question is discussed whether a threshold stimulus initiates a propagated disturbance from the point of the electrodes or the larger area whose repolarization is altered.
Conditional ROCK Activation <b> <i>In vivo</i> </b> Induces Tumor Cell Dissemination and Angiogenesis
Authors: Daniel R. Croft, Erik Sahai, Georgia Mavria, Shuixing Li, Jeff Tsai, William M. F. Lee, Christopher J. Marshall, Michael F. Olson
Journal: Cancer Research (2004)

Abstract Progression of tumors to invasive and metastatic forms requires that tumor cells undergo dramatic morphologic changes, a process regulated by Rho GTPases. Elevated expression of RhoA and RhoC, as well as the Rho effector proteins ROCK I and ROCK II, are commonly observed in human cancers and are often associated with more invasive and metastatic phenotypes. To examine how ROCK contributes to the progression of solid tumors, we established a conditionally activated form of ROCK II by fusing the kinase domain to the estrogen receptor hormone-binding domain (ROCK:ER). ROCK:ER-expressing colon carcinoma cells grown as tumors in immunocompromised nude mice organized into discrete clusters surrounding blood vessels. However, ROCK:ER activation resulted in the aggressive dissemination of tumor cells into the surrounding stroma, indicating that increased ROCK signaling is sufficient to promote invasion from solid tumors. In addition, tumors in which ROCK:ER was activated were more highly vascularized, indicating that ROCK contributes to tumor angiogenesis. ROCK:ER activation resulted in changes to epithelial morphology and organization that facilitated motility in vitro, likely by inducing the redistribution of proteins such as ezrin, as well as adherens junction and extracellular matrix-binding proteins. These results suggest that ROCK inhibitors would be useful antimetastatic and antiangiogenic chemotherapeutic agents in tumors associated with elevated RhoA, RhoC, ROCK I, or ROCK II expression.
FoxM1B Transcriptionally Regulates Vascular Endothelial Growth Factor Expression and Promotes the Angiogenesis and Growth of Glioma Cells
Authors: Yujian Zhang, Nu Zhang, Bingbing Dai, Mingguang Liu, Raymond Sawaya, Keping Xie, Suyun Huang
Journal: Cancer Research (2008)

Abstract We previously found that FoxM1B is overexpressed in human glioblastomas and that forced FoxM1B expression in anaplastic astrocytoma cells leads to the formation of highly angiogenic glioblastoma in nude mice. However, the molecular mechanisms by which FoxM1B enhances glioma angiogenesis are currently unknown. In this study, we found that vascular endothelial growth factor (VEGF) is a direct transcriptional target of FoxM1B. FoxM1B overexpression increased VEGF expression, whereas blockade of FoxM1 expression suppressed VEGF expression in glioma cells. Transfection of FoxM1 into glioma cells directly activated the VEGF promoter, and inhibition of FoxM1 expression by FoxM1 siRNA suppressed VEGF promoter activation. We identified two FoxM1-binding sites in the VEGF promoter that specifically bound to the FoxM1 protein. Mutation of these FoxM1-binding sites significantly attenuated VEGF promoter activity. Furthermore, FoxM1 overexpression increased and inhibition of FoxM1 expression suppressed the angiogenic ability of glioma cells. Finally, an immunohistochemical analysis of 59 human glioblastoma specimens also showed a significant correlation between FoxM1 overexpression and elevated VEGF expression. Our findings provide both clinical and mechanistic evidence that FoxM1 contributes to glioma progression by enhancing VEGF gene transcription and thus tumor angiogenesis. [Cancer Res 2008;68(21):8733–42]
Cancer Cells in Transit: The Vascular Interactions of Tumor Cells
Authors: Konstantinos Konstantopoulos, Susan N. Thomas
Journal: Annual Review of Biomedical Engineering (2009)

Metastasis is a highly regulated, multistep process in which cancerous cells shed from the primary tumor and enter the circulatory system, where they interact extensively with host cells before they lodge and colonize the target organ. The adhesive interactions of circulating tumor cells with platelets, leukocytes, and endothelial cells facilitate their survival and extravasation from the vasculature, thus representing critical kick-off events for the colonization of distant organs. This review presents our current mechanistic knowledge on vascular interactions of tumor cells, and it discusses biochemical and cell and molecular biology techniques used for the identification of novel receptor-ligand pairs mediating these interactions. This review brings together diverse observations about the contributions of key molecular constituents, including selectins, fibrin(ogen), and CD44, in one mechanistic interpretation. Understanding the molecular underpinnings of adhesive interactions between tumor cells and host cells may provide guidelines for developing promising antimetastatic therapies when initiated early in the course of disease progression.
Increased prevalence of diastolic dysfunction in rheumatoid arthritis
Authors: K. P. Liang, E. Myasoedova, C. S. Crowson, J. M. Davis, V. L. Roger, B. L. Karon, D. D. Borgeson, T. M. Therneau, R. J. Rodeheffer, S. E. Gabriel
Journal: Annals of the Rheumatic Diseases (2010)

To compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA.A cross-sectional, community-based study comparing cohorts of adults with and without RA and without a history of HF was carried out. Standard two-dimensional/Doppler echocardiography was performed in all participants. Diastolic dysfunction was defined as impaired relaxation (with or without increased filling pressures) or advanced reduction in compliance or reversible or fixed restrictive filling.The study included 244 subjects with RA and 1448 non-RA subjects. Mean age was 60.5 years in the RA cohort (71% female) and 64.9 years (50% female) in the non-RA cohort. The vast majority (>98%) of both cohorts had preserved ejection fraction (EF> or =50%). Diastolic dysfunction was more common in subjects with RA at 31% compared with 26% (age and sex adjusted) in non-RA subjects (OR=1.6; 95% CI 1.2 to 2.4). Patients with RA had significantly lower LV mass, higher pulmonary arterial pressure and higher left atrial volume index than non-RA subjects. RA duration and interleukin 6 (IL-6) level were independently associated with diastolic dysfunction in RA even after adjustment for cardiovascular risk factors.Subjects with RA have a higher prevalence of diastolic dysfunction than those without RA. RA duration and IL-6 are independently associated with diastolic dysfunction, suggesting the impact of chronic autoimmune inflammation on myocardial function in RA. Clinical implications of these findings require further investigation.
New Horizons in Cardioprotection
Authors: Lisa Schwartz Longacre, Robert A. Kloner, Andrew E. Arai, Christopher P. Baines, Roberto Bolli, Eugene Braunwald, James Downey, Raymond J. Gibbons, Roberta A. Gottlieb, Gerd Heusch, Robert B. Jennings, David J. Lefer, Robert M. Mentzer, Elizabeth Murphy, Michel Ovize, Peipei Ping, Karin Przyklenk, Michael N. Sack, Richard S. Vander Heide, Jakob Vinten-Johansen, Derek M. Yellon
Journal: Circulation (2011)
Meta-Analysis of Regional Brain Volumes in Schizophrenia
Authors: I C Wright, S Rabe-Hesketh, P W Woodruff, A S David, R M Murray, E T Bullmore
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. METHOD: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. RESULTS: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. CONCLUSIONS: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.
The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study
Authors: T Hauser, A Mahr, C Metzler, J Coste, R Sommerstein, W L Gross, L Guillevin, B Hellmich
Journal: Thorax (2008)

There has been some concern that leucotriene receptor antagonists might precipitate the onset of Churg-Strauss syndrome (CSS). A study was undertaken to investigate the relationship between the leucotriene receptor antagonist montelukast and the onset of CSS.Medication histories of 78 patients with CSS from France and Germany were retraced by questioning the patients, treating physicians and dispensing pharmacists, and from medical records. Using a case-crossover research design, exposures to montelukast and other asthma medications during the 3-month "index" period immediately preceding the onset of CSS were compared with those of four previous 3-month "control" periods. Odds ratios (ORs) were computed by conditional logistic regression.The ORs for CSS onset were 4.5 (95% CI 1.5 to 13.9) for montelukast, 3.0 (95% CI 0.8 to 10.5) for inhaled long-acting beta(2) agonists, 1.7 (95% CI 0.5 to 5.4) for inhaled corticosteroids and 4.0 (95% CI 1.3 to 12.5) for oral corticosteroids. Montelukast exposure during control periods increased temporally over three consecutive calendar periods of CSS onset from 1999 to 2003 (p(trend) <0.0001).Montelukast use was associated with a 4.5-fold higher risk of CSS onset within 3 months. However, the positive estimates obtained for other long-term asthma control medications suggest that this link might be confounded by a general escalation of asthma therapy before CSS onset. The association between montelukast and CSS observed in this study is probably also explained by the increasing use of this medication over time.
NHS could save 500m a year on smarter purchasing of supplies
Authors: A. O'Dowd
Journal: BMJ (2011)

Savings of around £500m (€586m; $810m) a year are possible if NHS organisations improve their buying practices for basic supplies and equipment, it has been claimed.

Clinicians’ input in procurement is one way that acute trusts could tackle this costly problem, says a report from public spending watchdog the National Audit Office published this week.

But the report warns that the government’s plans to decentralise control of NHS organisations will make matters worse by giving ministers less influence on purchasing policies and reducing the lack of coordination between trusts on buying such items.

The report The procurement of consumables by NHS acute and Foundation trusts focuses on England’s NHS …
Prevalence, incidence and risk factors for overuse injuries of the wrist in young athletes: a systematic review
Authors: Laura S Kox, P Paul F M Kuijer, Gino M M J Kerkhoffs, Mario Maas, Monique H W Frings-Dresen
Journal: British Journal of Sports Medicine (2015)

Background Overuse wrist injuries can cause long-term symptoms in young athletes performing wrist-loading sports. Information on the prevalence, incidence and associated risk factors is required. Purpose We aimed to review the prevalence and incidence of overuse wrist injuries in young athletes and to identify associated risk factors. We focused on popular wrist-loading youth sports—gymnastics, tennis, field hockey, volleyball, judo and rowing. Study design Systematic review. Methods We conducted a literature search on athletes aged &lt;18 years performing wrist-loading focus sports. Prevalence, incidence and/or risk factor ORs for overuse wrist injuries were extracted directly or calculated from reported data. Results The search identified six studies on prevalence, five on incidence, and one on risk factors. Prevalence rates were 32–73% for wrist pain and 10–28% for overuse wrist injury . Incidence rates were 7–9% for wrist pain and 0.02–26% for overuse wrist injury. The three criteria associated with wrist pain were (with OR): age of 10–14 years (11.5), training intensity (1.2), and earlier onset of gymnastics training (1.97). Conclusions Prevalence and incidence of overuse wrist injuries was high in multiple studies of gymnasts, and largely unknown in other wrist-loading focus sports. Three key risk factors for wrist pain in gymnasts were age between 10 and 14 years, earlier training commencement, and training intensity. Using ‘wrist pain’ in defining overuse, and further investigating risk factors can aid in identifying overuse wrist injuries in young athletes.
Small intestinal length: a factor essential for gut adaptation.
Authors: L T Weaver, S Austin, T J Cole
Journal: Gut (1991)

Changes in small intestinal structure, cytokinetics, and function are dynamic ways in which the gut adapts to diet, disease, and damage. Adequate length provides a static 'reserve' permitting an immediate response to pathophysiological changes. The length of the small intestine from conception to adulthood using data taken from eight published reports of necropsy measurement of 1010 guts is described. Mean length at 20 weeks' gestation was 125 cm, at 30 weeks' 200 cm, at term 275 cm, at 1 year 380 cm, at 5 years 450 cm, at 10 years 500 cm, and at 20 years 575 cm. Prenatal small intestinal growth exceeded that of body length according to the law: small intestinal length alpha body length to the power 4/3. After birth there was a noticeable deceleration: small intestinal length alpha body length to the power 1/2. The coefficient of variation of small intestinal length postnatally was 24%, sixfold greater than for body length. The rapid prenatal small intestinal growth rate ensures that the mature newborn has adequate small intestine to meet postnatal nutritional demands, but handicaps the preterm infant who undergoes intestinal resection. The wide variation in lengths suggests a 'surplus' surface area that is immediately available to respond, independent of dynamic mucosal changes, to fluctuations in food availability, local intestinal disease, damage, rapid transit, and resection.
Molecular Classification of Patients With Unexplained Hamartomatous and Hyperplastic Polyposis
Authors: Kevin Sweet, Joseph Willis, Xiao-Ping Zhou, Carol Gallione, Takeshi Sawada, Pia Alhopuro, Sok Kean Khoo, Attila Patocs, Cossette Martin, Scott Bridgeman, John Heinz, Robert Pilarski, Rainer Lehtonen, Thomas W Prior, Thierry Frebourg, Bin Tean Teh, Douglas A Marchuk, Lauri A Aaltonen, Charis Eng
Journal: JAMA (2005)

Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides management, especially surveillance and prophylactic surgery.To systematically classify patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analysis in the context of central rereview of histopathology results.Prospective, referral-based study of 49 unrelated patients from outside institutions (n = 28) and at a comprehensive cancer center (n = 21), conducted from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A, STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of BRAF, MYH, and BHD, and rereview of polyp histology results were performed.Molecular, clinical, and histopathological findings in patients with unexplained polyposis.Of the 49 patients, 11 (22%) had germline mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had mutations in ENG, encoding endoglin, previously only associated with hereditary hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1). Of the 23 patients with hyperplastic/mixed polyposis, 2 had PTEN mutations. Substantial discrepancies in histopathology results were seen.Systematic molecular classification of 49 patients with unexplained hamartomatous or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG, for juvenile polyposis. Importantly, given the substantial proportion of patients found to have germline mutations, more extensive analysis of the known susceptibility genes is indicated. Rereview of histology results by a dedicated gastrointestinal pathologist should be considered routinely, as organ-specific surveillance rests on defining syndromic diagnosis.
Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study
Authors: Pierluigi Macchioni, Luigi Boiardi, Mariagrazia Catanoso, Giulia Pazzola, Carlo Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To compare the performance of published classification/diagnostic criteria for polymyalgia rheumatica (PMR), including the new 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, in a single-centre study. <h3>Methods</h3> We studied all consecutive patients with new-onset PMR seen in our centre over 6 years, whose diagnosis was confirmed during a prospective 12-month follow-up period. Subjects were classified by each of the seven different criteria. Sensitivity and specificity were compared. Control population consisted of all consecutive patients aged ≥50 years seen in a 4-year period in our early arthritis clinic who had a 12-month confirmation of a diagnosis of rheumatoid arthritis (RA) or other inflammatory articular diseases. <h3>Results</h3> Data were collected from 136 cases and 149 controls, including 94 patients with RA. The most sensitive criteria were the new 2012 EULAR/ACR classification criteria (92.6%). Adding ultrasound (US) specificity increased from 81.5% to 91.3% in total cases and from 79.7% to 89.9% in RA. Bird criteria had a sensitivity of 89.2% but the lowest specificity (40.2% in total cases and 72.5% in RA). Jones and Nobunaga criteria were the most specific criteria (96.7% and 97.8% in total cases and 98.6% and 99.5% in RA) but the less sensitive (63.1% and 58.2%) ones. Overall, discriminatory ability, as reflected by the area under the receiver operating characteristic curve, was better for the 2012 US EULAR/ACR criteria (0.920 in total cases and 0.910 in RA). <h3>Conclusions</h3> The new EULAR/ACR criteria in new-onset PMR patients perform best in discriminating PMR from RA and other inflammatory articular diseases. Ultrasound further increases the specificity of the criteria.