tbuckley/cabot-search huggingface dataset:
Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis
Authors: Maite Martínez-Uña, Marta Varela-Rey, Ainara Cano, Larraitz Fernández-Ares, Naiara Beraza, Igor Aurrekoetxea, Ibon Martínez-Arranz, Juan L. García-Rodríguez, Xabier Buqué, Daniela Mestre, Zigmund Luka, Conrad Wagner, Cristina Alonso, Richard H. Finnell, Shelly C. Lu, Luz M. Martínez-Chantar, Patricia Aspichueta, José M. Mato
Journal: Hepatology (2013)

Methionine adenosyltransferase 1A ( MAT1A ) and glycine N -methyltransferase ( GNMT ) are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis and degradation, respectively. Mat1a ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis. Gnmt -deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis by way of the phosphatidylethanolamine (PE) N -methyltransferase (PEMT) pathway is stimulated in Gnmt−/− mice. We also propose that the excess PC thus generated is catabolized, leading to TG synthesis and steatosis by way of diglyceride (DG) generation. We observed that Gnmt−/− mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of Gnmt−/− mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine-deficient diet reverted the flux from PE to PC of Gnmt−/− mice to that of wildtype animals and normalized DG and TG content preventing the development of steatosis. Gnmt−/− mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis. Conclusion : These findings indicate that excess SAMe reroutes PE towards PC and TG synthesis and lipid sequestration. (Hepatology 2013;58:1296–1305)
Subclavian Steal Syndrome
Authors: Brian J. Potter, Duane S. Pinto
Journal: Circulation (2014)

“Subclavian steal” refers to a syndrome of symptoms relating to arterial insufficiency in a branch of the subclavian artery stemming from flow reversal,attributable to occlusive disease in the subclavian artery proximal to that branch that is usually atheroscleroticin cause. Most patients are asymptomatic,but patients with IMA bypass grafts may manifest angina elicited by exercise of the upper extremity ipsilateral to the graft and stenosis (so called“coronary-subclavian steal”).Subclavian steal may also manifest as vertebrobasilar insufficiency or,most commonly, arm claudication.Subclavian steal should be considered among patients exhibiting suggestive symptoms. A meticulous examination of segmental pulses and pressures,as well as judicious use of duplex ultrasonography, magnetic resonance angiography, computed tomography angiography, or conventional angiography can confirm the presence of subclavian stenosis. Symptomatic patients benefit from either percutaneousor surgical revascularization,depending on both anatomic and patient factors. Subclavian stenosis,regardless of symptoms, is a marker of atherosclerotic disease and increased risk for cardiovascular and cerebrovascular events.
Group-Based Trajectory Modeling in Clinical Research
Authors: Daniel S. Nagin, Candice L. Odgers
Journal: Annual Review of Clinical Psychology (2010)

Group-based trajectory models are increasingly being applied in clinical research to map the developmental course of symptoms and assess heterogeneity in response to clinical interventions. In this review, we provide a nontechnical overview of group-based trajectory and growth mixture modeling alongside a sampling of how these models have been applied in clinical research. We discuss the challenges associated with the application of both types of group-based models and propose a set of preliminary guidelines for applied researchers to follow when reporting model results. Future directions in group-based modeling applications are discussed, including the use of trajectory models to facilitate causal inference when random assignment to treatment condition is not possible.
Gadolinium-Associated Plaques
Authors: Robert M. Gathings, Raveena Reddy, Daniel Santa Cruz, Robert T. Brodell
Journal: JAMA Dermatology (2014)

A new condition, gadolinium-associated plaques (GAP), is reported in 2 patients. It is related to a particular type of gadolinium (gadodiamide) used for contrast-enhanced radiologic studies.Erythematous plaques, 0.5 to 2.5 cm in diameter, were pruritic in one case and asymptomatic in a second case. Findings from the histopathologic examination revealed eosinophilic, collagenous, round or ovoid bodies (sclerotic bodies) in various stages of calcification. Previously, these sclerotic bodies were thought to be pathognomonic for nephrogenic systemic fibrosis (NSF) in the setting of chronic renal disease with associated gadolinium exposure. Neither patient had NSF, while only 1 of these patients had renal disease. The patient who did not have renal disease received high doses of gadolinium.Physicians should be aware that GAP can occur without NSF or renal disease and is associated with the use of radiologic dyes. Sclerotic bodies have been reported only in association with gadolinium exposure (eg, gadodiamide) either in the sclerotic skin in NSF or in GAP.
Peter John Lennox Holt
Authors: R. Holt, T. Warnes, R. Bernstein
Journal: BMJ (2008)

Peter John Lennox Holt (“Lennox”) was born in Chorley, Lancashire, in 1932. Raised by his mother, his father having died before he was born, he was to be greatly influenced by his uncle Dr John Rigby, a local general practitioner. Under his uncle’s guidance, he developed a passion for medicine and became a third generation doctor.

By the age of 15 Lennox had developed chronic mastoiditis, which was to leave him partially deaf in one ear. The suggested cure …
Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients
Authors: DH Yates, SA Kharitonov, PJ Barnes
Journal: European Respiratory Journal (1997)

Increased concentrations of exhaled nitric oxide (NO) occur in patients with asthma, and exhaled NO may be useful for assessing the effect of drug therapy on airway inflammation. Beta2-agonists have been proposed to have both proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo-controlled studies were conducted. Firstly, exhaled NO was measured in 18 asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and forced expiratory volume in one second (FEV1) were measured at 15 min intervals for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long-acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for on-line recording. In Study 1, exhaled NO showed no significant change at any time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS, exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach statistical significance. In Study 2, treatment with salmeterol increased FEV1, but exhaled NO levels were not significantly changed, either after budesonide treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65 ppb). Our results confirm that single high dose salbutamol does not increase exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids. Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled glucocorticosteroids. However, regular use of salmeterol resulted in no change in exhaled nitric oxide, either used alone or in combination with inhaled glucocorticosteroids.
Health Policy Basics: Medicaid Expansion
Authors: Ryan A. Crowley, William Golden
Journal: Annals of Internal Medicine (2013)

Medicaid is the largest single source of health insurance coverage in the United States, providing insurance for more than 62 million persons and families in 2013. The Patient Protection and Affordable Care Act sought to expand Medicaid eligibility to nearly all low-income persons with incomes up to 138% of the federal poverty level. However, the U.S. Supreme Court ruled that states’ expansion would be optional. Although more than half of the states and the District of Columbia have opted to expand Medicaid starting in 2014, many states continue to oppose increasing access to the program. This article will discuss the basic provisions of the expansion and the benefits and challenges patients and physicians may face as Medicaid grows.
Physical Activity Advice Only or Structured Exercise Training and Association With HbA<sub>1c</sub>Levels in Type 2 Diabetes
Authors: Daniel Umpierre
Journal: JAMA (2011)

OFdiabetes management, along with dietary and pharmacological interventions. 1,2Current guidelines recommend that patients with type 2 diabetes should perform at least 150 minutes per week of moderate-intensity aerobic exercise and should perform resistance exercise 3 times per week. 1,2Previous meta-analyses 3-6 demonstrated that structured exercise training including aerobic and resistance exercises reduces hemoglobin A 1c (HbA 1c ) levels by approximately 0.6%.However, only 1 previous review separately analyzed associations of aerobic exercise, resistance training, and the combination of aerobic exercise and resistance training on change in HbA 1c levels. 5Since publication of this metaanalysis, 2 large randomized trials 7,8 were published that reported contradictory findings regarding the types of For editorial comment see p 1808.CME available online at www.jamaarchivescme.comand questions on p 1817.Context Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear.Objective To conduct a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) assessing associations of structured exercise training regimens (aerobic, resistance, or both) and physical activity advice with or without dietary cointervention on change in hemoglobin A 1c (HbA 1c ) in type 2 diabetes patients.
Complete and incomplete intestinal metaplasia at the oesophagogastric junction: prevalences and associations with endoscopic erosive oesophagitis and gastritis
Authors: M Voutilainen, M Farkkila, M Juhola, J-P Mecklin, P Sipponen
Journal: Gut (1999)

Intestinal metaplasia (IM) is a common finding at the oesophagogastric junction, but the aetiopathogenesis of the different IM subtypes-that is, incomplete IM (specialised columnar epithelium, SCE) and complete IM- and their associations with gastro-oesophageal reflux disease and Helicobacter pylori gastritis are unclear.1058 consecutive dyspeptic patients undergoing gastroscopy were enrolled. The gastric, oesophagogastric junctional, and oesophageal biopsy specimens obtained were stained with haematoxylin and eosin, alcian blue (pH 2.5)-periodic acid Schiff, and modified Giemsa.Complete junctional IM was detected in 196 (19%) of the 1058 subjects, and in 134 (13%) was the sole IM subtype. Incomplete junctional IM (SCE) was detected in 101 (10%) subjects, of whom 62 (61%) also had the complete IM subtype. Of patients with normal gastric histology (n = 426), 6% had complete IM and 7% junctional SCE. The prevalence of both types of IM increased with age in patients with either normal gastric histology or chronic gastritis (n = 611). Epithelial dysplasia was not detected in any patients with junctional IM. In multivariate analysis, independent risk factors for incomplete junctional IM were age (odds ratio (OR) 1.3 per decade, 95% confidence interval (CI) 1.2 to 1.6), endoscopic erosive oesophagitis (OR 1.9, 95% CI 1.1 to 3.2), and chronic cardia inflammation (OR 2.9, 95% CI 1.3 to 6.2), but not gastric H pylori infection (OR 1.0, 95% CI 0.6 to 1.7). In univariate analysis, junctional incomplete IM was not associated with cardia H pylori infection. Independent risk factors for "pure" complete junctional IM (n = 134) were age (OR 1.2 per decade, 95% CI 1.0 to 1.4), antral predominant non-atrophic gastritis (OR 2.6, 95% CI 1.3 to 5.2), antral predominant atrophic gastritis (OR 2.1, 95% CI 1.1 to 5.2), and multifocal atrophic gastritis (OR 7.1, 95% CI 2.5 to 19.8). In univariate analysis, junctional complete IM was strongly associated with chronic cardia inflammation and cardia H pylori infection (p<0. 001).Both complete and incomplete junctional IM are independent acquired lesions that increase in prevalence with age. Although IM subtypes often occur simultaneously, they show remarkable differences in their associations with gastritis and erosive oesophagitis: junctional complete IM is a manifestation of multifocal atrophic gastritis, while the incomplete form (SCE) may result from carditis and gastro-oesophageal reflux disease. The frequency of dysplasia in intestinal metaplasia at the oesophagogastric junction appears to be low.
Efficacy of the CCR5 Antagonist Maraviroc in Reducing Early, Ritonavir-Induced Atherogenesis and Advanced Plaque Progression in Mice
Authors: Sabrina Cipriani, Daniela Francisci, Andrea Mencarelli, Barbara Renga, Elisabetta Schiaroli, Claudio D’Amore, Franco Baldelli, Stefano Fiorucci
Journal: Circulation (2013)

CCR5 plays an important role in atherosclerosis and ischemic cardiovascular diseases, as well as in HIV replication and diffusion. HIV infection is characterized by a high burden of cardiovascular diseases, particularly in subjects exposed to ritonavir-boosted protease inhibitors. Maraviroc, a CCR5 antagonist antiretroviral drug, might provide benefit for patients with M-tropic HIV infections at high risk for cardiovascular diseases.Exposure to maraviroc limits the evolution and associated systemic inflammation of ritonavir-induced atherosclerotic in ApoE(-/-) mice and inhibits plaques development in a late model of atherosclerosis in which dyslipidemia plays the main pathogenic role. In ritonavir-treated mice, maraviroc reduced plaque areas and macrophage infiltration; downregulated the local expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and interleukin-17A; and reduced tumor necrosis factor-α and RANTES (regulated on activation, normal T cell expressed, and secreted). Moreover, maraviroc counterregulated ritonavir-induced lipoatrophy and interlelukin-6 gene expression in epididymal fat, along with the splenic proinflammatory profile and expression of CD36 on blood monocytes. In the late model, maraviroc inhibited atherosclerotic progression by reducing macrophage infiltration and lowering the expression of adhesion molecules and RANTES inside the plaques. However, limited systemic inflammation was observed.In a mouse model of genetic dyslipidemia, maraviroc reduced the atherosclerotic progression by interfering with inflammatory cell recruitment into plaques. Moreover, in mice characterized by a general ritonavir-induced inflammation, maraviroc reversed the proinflammatory profile. Therefore, maraviroc could benefit HIV-positive patients with residual chronic inflammation who are at a high risk of acute coronary disease despite a suppressive antiretroviral therapy. To determine these benefits, large clinical studies are needed.
Job sharing in general practice.
Authors: E F Nicol
Journal: BMJ (1987)

A questionnaire survey of 500 consecutive patients consulting their general practitioners was undertaken to compare job sharing part time partners and full time partners in respect of patients9 perception of and satisfaction with the availability of the doctor they wished to consult. Comparison of linear analogue scales of patients9 satisfaction with the availability of their chosen doctor showed no significant difference between job sharing partners and full time partners. Nevertheless, significantly fewer patients were able to see the full time partner of their choice within two days than were able to see the job sharing partner of their choice within the same period. In this study patients were as satisfied with the availability of job sharing partners as they were with that of full time partners; the findings highlight important considerations for practices wishing to appoint partners with a limited commitment.
Use of glucocorticoids and risk of venous thromboembolism
Authors: Eva Wikström Jonsson
Journal: Thorax (2013)

Use of glucocorticoids and risk of venous thromboembolismIn this Danish population-based case-control study, the association between use of glucocorticoids and risk of venous thromboembolism was studied.The study included 38 765 cases of venous thromboembolism and 387 650 age-matched and sex-matched controls.Conditional logistic regression, adjusted for risk factors for venous thromboembolism, was used to estimate incidence rate ratios (IRR) and 95% CI for glucocorticoid users versus non-users.Diagnoses were retrieved from the Danish national Registry of Patients, and controls were identified from the Danish Civil Registration System.Glucocorticoid use was estimated from the Danish national Database of Reimbursed Prescriptions.Systemic glucocorticoid use was associated with an increased risk of venous thromboembolism.The risk seemed to increase with increasing cumulative dose.The highest adjusted IRR (3.06; 95% CI 2.77 to 3.38) was seen in new users of systemic glucocorticoids.New use of inhaled glucocorticoids and current use of glucocorticoids also increased the risk of venous thromboembolism.However, glucocorticoids given during hospitalisation and outpatient clinic visits were not recorded and may have contributed.Since many illnesses and inflammatory conditions treated with glucocorticoids also may increase the risk of venous thromboembolism, the associations have to be interpreted with care.The authors state that the temporality of the association, the effect being strongest at initiation of therapy, is in line with an effect on coagulation.However, the possibility of residual confounding by disease activity must be kept in mind.Although the association may not be causal, we should be aware that patients treated with glucocorticoids may be at increased risk of venous thromboembolism.
Mammostrat As an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in the Tamoxifen Versus Exemestane Adjuvant Multicenter Trial Pathology Study
Authors: John M.S. Bartlett, Kenneth J. Bloom, Tammy Piper, Thomas J. Lawton, Cornelis J.H. van de Velde, Douglas T. Ross, Brian Z. Ring, Robert S. Seitz, Rodney A. Beck, Annette Hasenburg, Dirk Kieback, Hein Putter, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, Daniel Rea
Journal: Journal of Clinical Oncology (2012)

Some postmenopausal patients with hormone-sensitive early breast cancer remain at high risk of relapse despite endocrine therapy and, in addition, might benefit from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk and may inform treatment decisions. We tested the efficacy of this panel in the Tamoxifen versus Exemestane Adjuvant Multicenter (TEAM) trial.Pathology blocks from 4,598 TEAM patients were collected, and tissue microarrays (TMAs) were constructed. The cohort was 47% node-positive, and 36% of patients in the cohort were treated with adjuvant chemotherapy. Triplicate 0.6-mm(2) TMA cores were stained, and positivity for p53, HTF9C, CEACAM5, NDRG1, and SLC7A5 was assessed. Cases were assigned a Mammostrat risk score, and distant relapse-free survival (DRFS) and disease-free survival (DFS) were analyzed.In multivariate regression analyses, which were corrected for conventional clinicopathologic markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in estrogen receptor (ER) -positive node-negative patients (n = 1,226) who did not receive chemotherapy (P = .004). Additional analyses in all patients not exposed to chemotherapy, irrespective of nodal status (n = 2,559) and in the entire cohort (n = 3,837) showed Mammostrat scores provided additional information on DRFS in these groups (P = .001 and P < .001, respectively; multivariate analyses). No differences were seen between the two endocrine treatment regimens.The Mammostrat score predicts DRFS for patients treated with exemestane and patients treated with tamoxifen followed by exemestane irrespective of nodal status and chemotherapy. The ability of this test to provide additional outcome data after treatment provides additional evidence of its use in risk stratification of ER-positive postmenopausal patients with breast cancer.
Long-Term Arrhythmia-Free Survival in Patients With Severe Left Ventricular Dysfunction and No Inducible Ventricular Tachycardia After Myocardial Infarction
Authors: Sarah Zaman, Arun Narayan, Aravinda Thiagalingam, Gopal Sivagangabalan, Stuart Thomas, David L. Ross, Pramesh Kovoor
Journal: Circulation (2014)

A negative electrophysiology study (EPS) may delineate a subgroup of patients with severely impaired left ventricular ejection fraction (LVEF) whose care can be safely managed long-term without an implantable cardioverter-defibrillator.Consecutive patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction underwent early (median 4 days) LVEF assessment. Patients with LVEF ≤40% underwent EPS. A prophylactic implantable cardioverter-defibrillator was implanted for a positive (inducible monomorphic ventricular tachycardia) but not a negative (no inducible ventricular tachycardia or inducible ventricular fibrillation/flutter) EPS result. Patients who would have become eligible for a late primary prevention implantable cardioverter-defibrillator with LVEF ≤30% or ≤35% with New York Heart Association class II/III heart failure were included and analyzed according to EPS result. Patients with LVEF >40%, ineligible for EPS, were followed up as control subjects (n=1286). The primary end point was survival free of death or arrhythmia (resuscitated cardiac arrest or sustained ventricular tachycardia/ventricular fibrillation). EPS performed in 128 patients with LVEF ≤30% or with LVEF ≤35% and heart failure was negative in 63% (n=80) and positive in 37% (n=48). Implantable-cardioverter defibrillators were implanted in <0.1%, 4%, and 90% of control, EPS-negative, and EPS-positive patients, respectively. The distribution of time to death or arrhythmia was comparable in control patients and EPS-negative patients with LVEF ≤30% or with LVEF ≤35% and heart failure (P=0.738), who both differed significantly from EPS-positive patients (P<0.001). At 3 years, 91.8 ± 3.2%, 93.4 ± 1.0%, and 62.7 ± 7.5% of control, EPS-negative, and EPS-positive patients were free of death or arrhythmia, respectively.Revascularized patients with ST-segment-elevation myocardial infarction with severely impaired left ventricular function but no inducible ventricular tachycardia have a favorable long-term prognosis without the protection of an implantable cardioverter-defibrillator.