tbuckley/cabot-search huggingface dataset:
Neurosurgeons told to watch for signs of “twiddler's syndrome”
Authors: Roger Dobson
Journal: BMJ (2007)

the chief medical officer for England, has named, in his latest annual report, "unacceptably poor" hand hygiene in hospitals and the chronic lack of organs for transplantation as the two most pressing public health issues.Despite improvements in some hand hygiene practices, he said, such as more widespread use of alcohol based handrubs, the percentage of healthcare staff complying with hand cleaning protocols seldom exceeded 60%-and was often even lower."Patients find it astonishing and alarming that often nurses and doctors do not routinely wash their hands," said Professor Donaldson."However, they often don't feel able to ask doctors or nurses if they've washed their hands."He said it might be possible to empower patients by providing them with their own alcohol based handrubs, which they would be able to offer to clinical staff.A pilot study to test this was already being organised in an NHS hospital, overseen by the hospital hygiene expert Didier Pittet of the World Health Organization.Professor Donaldson also renewed calls for the introduction of an opt-out system for organ donation, in which it would be assumed that people were willing to donate their organs unless they specified otherwise.This was, he said, vital to save lives "among a group of people who are currently dying at a rate of one a day."He said: "There is a shortage of organs in this country, as there is in other countries, and the situation is getting worse."He acknowledged that parliament had already rejected such an opt-out system, but he added: "Confronted with the worsening situation, people who opposed it in the past may now wish to change their minds.
A molecular switch controls interspecies prion disease transmission in mice
Authors: Christina J. Sigurdson, K. Peter R. Nilsson, Simone Hornemann, Giuseppe Manco, Natalia Fernández-Borges, Petra Schwarz, Joaquín Castilla, Kurt Wüthrich, Adriano Aguzzi
Journal: Journal of Clinical Investigation (2010)

Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The β2-α2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar β2-α2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β2-α2 loop structure for prion transmissibility between different species.
Advocacy: yes we can
Authors: Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2012)

It is an honor and privilege to address you as president of the American Society for Clinical Investigation. For more than 100 years, this organization has represented the best of physician-scientists. Since it is now 2012, there is the possibility that this could be the last ASCI presidential address. But we will assume the Mayans miscalculated and that we should look to the future. With the ASCI moving into its second century, this year we decided it was time to solicit the opinion of its membership and essentially ask ASCI members, “How are we doing? What do we want from ASCI?” We surveyed ASCI members about key areas: membership, council service, fiscal policy, The Journal of Clinical Investigation, this meeting, and what membership expected from this organization.
Long-term Quality of Life and Risk Factors for Recurrence After Laparoscopic Repair of Paraesophageal Hernia
Authors: Anne O. Lidor, Kimberley E. Steele, Miloslawa Stem, Richard M. Fleming, Michael A. Schweitzer, Michael R. Marohn
Journal: JAMA Surgery (2015)

Laparoscopic repair of paraesophageal hernia (PEH) has been shown to result in excellent relief of symptoms and improved quality of life (QOL) despite a relatively high radiographically identified recurrence rate.To assess potential risk factors for recurrence and long-term change in QOL after laparoscopic repair of PEH.This was a prospective study of 111 patients who underwent elective laparoscopic repair of type III PEH with biological mesh buttressed over a primary cruroplasty from April 3, 2009, through July 31, 2014, at the Department of Surgery, Johns Hopkins University of Medicine. We administered a modified version of a validated gastroesophageal reflux disease-specific QOL tool to patients before and at 2, 12, and 36 months after the procedure. Higher QOL scores represent greater severity of symptoms. An upper gastrointestinal tract barium-contrast radiographic examination was performed at 1 year to assess for recurrence. Demographic factors, comorbidities, and preoperative radiographic findings were analyzed as possible indicators for recurrence using logistic regression.Quality of life, measured by the gastroesophageal reflux disease-specific QOL tool, and recurrence, defined as a PEH of greater than 2 cm.Median patient age was 61 years, 63.1% of patients were women, and 81.1% of patients were white. Four patients required reoperation, of which only 1 was for symptomatic recurrent PEH. The mean follow-up time for the 36-month QOL assessment was 43.5 months. The overall preoperative and 2-, 12-, and 36-month QOL scores were 28.50, 10.18, 9.74, and 10.58, respectively (P < .001). Recurrences were found in 19 of the 70 patients (27%) who completed the 1-year radiographic examination. Compared with baseline, all individual symptoms improved significantly except for early satiety (mean [SD] score, 3.18 [1.88] at baseline vs 2.07 [1.70] at the 36-month follow-up; P = .07), nausea (1.69 [1.63] vs 0.77 [1.25]; P = .08), pain with swallowing (1.06 [1.50] vs 0.53 [0.90]; P = .73), and bloating/gas (3.28 [1.71] vs 2.23 [1.72]; P = .05) at the 36-month QOL assessment. Although not statistically significant, preoperative hernias containing most of the stomach were more likely to recur after repair when compared with those involving gastric cardia and fundus (odds ratio, 3.74 [95% CI, 0.93-15.14]; P = .06).Overall, laparoscopic repair of PEH with biological mesh results in excellent long-term QOL. The cause of recurrence is likely multifactorial and individualized to each patient. Further evaluation of novel techniques and unidentified patient factors is needed.
Risk-Taking Behavior
Authors: T. Tourlentes
Journal: JAMA (1993)

This is a thoughtfully selected and well-arranged presentation of interrelated psychosocial research efforts by 16 recognized authorities with broad knowledge and expertise in the study of human risk-taking behaviors. Editor J. Frank Yates has managed to pull this diverse theoretical and methodological information together into a readable and useful whole. However, for the most part, these studies are not medically or psychiatrically focused and probably will prove of limited interest or direct utility to the average practicing physician. From a research-oriented viewpoint, there is significantly more to be gained, of course. Chapter 8, "Risk Taking and Health," by Adler, Kegeles, and Genevro, is notable in this regard, especially the discussion of models for studying health behaviors and two examples of health problems studied. One deals with identifying and changing risky behaviors related to the acquired immunodeficiency syndrome, the other with behaviors connected with unwanted pregnancies. Other obvious aspects of health
Knob-positive and knob-negative Plasmodium falciparum differ in expression of a strain-specific malarial antigen on the surface of infected erythrocytes.
Authors: S B Aley, J A Sherwood, R J Howard
Journal: The Journal of Experimental Medicine (1984)

We have investigated the expression of a strain-specific malarial antigen on the surface of erythrocytes infected with knobless (K-) variants of knob-positive (K+) strains of Plasmodium falciparum. Aotus blood infected with K+ or K- parasites derived from two independent geographical isolates (Malayan camp and Santa Lucia) was surface iodinated by the lactoperoxidase method. Infected and uninfected erythrocytes were then separated by a new procedure involving equilibrium density sedimentation on a Percoll gradient containing sorbitol. Strain-specific antigens were readily identified on the surface of erythrocytes infected with either of the K+ strains by their characteristic size and detergent solubility. These proteins were not detected on the surface of erythrocytes infected with either of the K- variants nor on uninfected erythrocytes isolated from K+- or K- -infected blood. These results are consistent with a role for the strain-specific surface antigen in cytoadherence of P. falciparum-infected erythrocytes. Our findings represent the second biochemical difference (with the knob-associated histidine-rich protein) between K+ and K- P. falciparum.
Systemic Effect Comparisons of Six Inhaled Corticosteroid Preparations
Authors: Richard J. Martin, Stanley J. Szefler, Vernon M. Chinchilli, Monica Kraft, Myrna Dolovich, Homer A. Boushey, Reuben M. Cherniack, Timothy J. Craig, Jeffrey M. Drazen, Joanne K. Fagan, John V. Fahy, James E. Fish, Jean G. Ford, Elliott Israel, Susan J. Kunselman, Stephen C. Lazarus, Robert F. Lemanske, Stephen P. Peters, Christine A. Sorkness
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Section:ChooseTop of pageAbstract <<METHODSSTATISTICAL DESIGN AND ME...RESULTSDISCUSSIONReferencesCITING ARTICLES
Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3
Authors: Larissa Fabritz, Dierk Damke, Markus Emmerich, Susann G. Kaufmann, Kathrin Theis, Andreas Blana, Lisa Fortmüller, Sandra Laakmann, Sven Hermann, Elena Aleynichenko, Johannes Steinfurt, Daniela Volkery, Burkhard Riemann, Uwe Kirchhefer, Michael R. Franz, Günter Breithardt, Edward Carmeliet, Michael Schäfers, Sebastian K.G. Maier, Peter Carmeliet, Paulus Kirchhof
Journal: Cardiovascular Research (2010)

AimsClinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). β-Adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease.
Cytokine-Stimulated GTP Cyclohydrolase I Expression in Endothelial Cells Requires Coordinated Activation of Nuclear Factor-κB and Stat1/Stat3
Authors: Annong Huang, Ying-Yi Zhang, Kai Chen, Kazuyuki Hatakeyama, John F. Keaney
Journal: Circulation Research (2004)

Endothelial production of nitric oxide (NO) is dependent on adequate cellular levels of tetrahydrobiopterin (BH4), an important cofactor for the nitric oxide synthases. Vascular diseases are often characterized by vessel wall inflammation and cytokine treatment of endothelial cells increases BH4 levels, in part through the induction of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for BH4 biosynthesis. However, the molecular mechanisms of cytokine-mediated GTPCH I induction in the endothelium are not entirely clear. We sought to investigate the signaling pathways whereby cytokines induce GTPCH I expression in human umbilical vein endothelial cells (HUVECs). Interferon-gamma (IFN-gamma) induced endothelial cell GTPCH I protein and BH4 modestly, whereas high-level induction required combinations of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha). In the presence of IFN-gamma, TNF-alpha increased GTPCH I mRNA in a manner dependent on nuclear factor-kappaB (NF-kappaB), as this effect was abrogated by overexpression of a dominant-negative IkappaB construct. HUVEC IFN-gamma treatment resulted in signal transducer and activator of transcription 1 (Stat1) activation and DNA binding in a Jak2-dependent manner, as this was inhibited by AG490. Conversely, overexpression of Jak2 effectively substituted for IFN-gamma in supporting TNF-alpha-mediated GTPCH I induction. The role of IFN-gamma was also Stat1-dependent as Stat1-null cells exhibited no GTPCH I induction in response to cytokines. However, Stat1 activation with oncostatin M failed to support TNF-alpha-mediated GTPCH I induction because of concomitant Stat3 activation. Consistent with this notion, siRNA-mediated Stat3 gene silencing allowed oncostatin M to substitute for IFN-gamma in this system. These data implicate both NF-kappaB and Stat1 in endothelial cell cytokine-stimulated GTPCH I induction and highlight the role of Stat3 in modulating Stat1-supported gene transcription. Thus, IFN-gamma and TNF-alpha exert distinct but cooperative roles for BH4 biosynthesis in endothelium that may have important implications for vascular function during vascular inflammation.
Metabolic Syndrome and Diabetes, Alone and in Combination, as Predictors of Cardiovascular Disease Mortality Among Men
Authors: Timothy S. Church, Angela M. Thompson, Peter T. Katzmarzyk, Xuemei Sui, Neil Johannsen, Conrad P. Earnest, Steven N. Blair
Journal: Diabetes Care (2009)

OBJECTIVE To examine cardiovascular disease (CVD) mortality risk in men with diabetes only, metabolic syndrome only, and concurrent metabolic syndrome and diabetes. RESEARCH DESIGN AND METHODS We examined CVD mortality risk by metabolic syndrome and diabetes status in men from the Aerobics Center Longitudinal Study (ACLS) (mean ± SD age 45.1 ± 10.2 years). Participants were categorized as having neither diabetes nor metabolic syndrome (n = 23,770), metabolic syndrome only (n = 8,780), diabetes only (n = 532), or both (n = 1,097). The duration of follow-up was 14.6 ± 7.0 years with a total of 483,079 person-years of exposure and 1,085 CVD deaths. RESULTS Age-, examination year–, and smoking-adjusted CVD death rates (per 1,000 man-years) in men with neither metabolic syndrome nor diabetes, metabolic syndrome only, diabetes only, and both were 1.9, 3.3, 5.5, and 6.5, respectively. CVD mortality was higher in men with metabolic syndrome only (hazard ratio 1.8 [95% CI 1.5–2.0]), diabetes only (2.9 [2.1–4.0]), and both (3.4 [2.8–4.2]) compared with men with neither. The presence of metabolic syndrome was not associated (1.2 [0.8–1.7]) with higher CVD mortality risk in individuals with diabetes. In contrast, the presence of diabetes substantially increased (2.1 [1.7–2.6]) CVD mortality risk in individuals with metabolic syndrome. CONCLUSIONS The presence of diabetes was associated with a threefold higher CVD mortality risk, and metabolic syndrome status did not modify this risk. Our findings support the fact that physicians should be aggressive in using CVD risk–reducing therapies in all diabetic patients regardless of metabolic syndrome status.
HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events
Authors: Anand Rohatgi, Amit Khera, Jarett D. Berry, Edward G. Givens, Colby R. Ayers, Kyle E. Wedin, Ian J. Neeland, Ivan S. Yuhanna, Daniel R. Rader, James A. de Lemos, Philip W. Shaul
Journal: New England Journal of Medicine (2014)

It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).
Mechanisms of Hypertension
Authors: E. Marie Freel, John M.C. Connell
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Hypertension is a common disorder that affects a large heterogeneous patient population. Subgroups can be identified on the basis of their responses to hormonal and biologic stimuli. These subgroups include low-renin hypertensives and nonmodulators. Aldosterone, the principal human mineralocorticoid, is increasingly recognized as playing a significant role in cardiovascular morbidity, and its role in hypertension has recently been reevaluated with studies that suggest that increased aldosterone biosynthesis (as defined by an elevated aldosterone to renin ratio) is a key phenotype in up to 15% of individuals with hypertension. It was reported previously that a polymorphism of the gene (C to T conversion at position −344) encoding aldosterone synthase is associated with hypertension, particularly in individuals with a high ratio. However, the most consistent association with this variant is a relative impairment of adrenal 11β-hydroxylation. This review explores the evidence for this and provides a hypothesis linking impaired 11β-hydroxylation and hypertension with a raised aldosterone to renin ratio. It is also speculated that there is substantial overlap between this group of patients and previously identified low-renin hypertensives and nonmodulators. Thus, these groups may form a neurohormonal spectrum reflecting different stages of hypertension or indeed form sequential steps in the natural history of hypertension in genetically susceptible individuals.
GPs are invited to lead new public health approach to end of life care
Authors: A. O'Dowd
Journal: BMJ (2014)

GPs in clinical commissioning groups have been invited to lead a new public health approach to end of life care in England.

On 10 September, Public Health England and the National Council for Palliative Care—an umbrella charity for workers involved in palliative, end of life, and hospice care—opened applications to be one of six “pathfinder communities” to pioneer this new approach. Implementing the newly launched Dying Well …
Functional polymorphisms of the <i>FAS</i> /<i>FASLG</i> genes are associated with risk of alopecia areata in a Chinese population: a case-control analysis
Authors: X. Fan, L. Shangguan, M. Li, C.Y. Li, B. Liu
Journal: British Journal of Dermatology (2010)

Background The Fas/Fas ligand system plays a key role in regulating cell growth and apoptosis. Previous findings have suggested that FAS and FASLG polymorphisms are associated with systemic lupus erythematosus, autoimmune hepatitis, vitiligo and other autoimmune‐related disorders. However, to the best of our knowledge, there is no reported study on the associations between FAS and FASLG polymorphisms and the risk of alopecia areata. Objectives To investigate the associations between FAS and FASLG polymorphisms and the risk of alopecia areata in a Chinese Han population. Methods In a hospital‐based case–control study of 84 patients with alopecia areata and 84 controls, we genotyped FAS 1377G>A, FAS 670A>G and FASLG 844T>C polymorphisms and assessed their association with alopecia areata risk. Results We found that a reduced risk of alopecia areata appeared to be associated with the FAS 670AG genotype [adjusted odds ratio (OR) 0·43; 95% confidence interval (CI) 0·22–0·86] when compared with the FAS 670AA genotype, but no risk was associated with any of the FAS 1377G>A and FASLG 844T>C genotypes. In the combined analysis, we found that the presence in individuals of two at‐risk alleles of the three FAS/FASLG polymorphisms was associated with a lower risk of alopecia areata (adjusted OR 0·21; 95% CI 0·05–0·89) when compared with the presence of six at‐risk alleles. Conclusions These results suggest that genetic variants in the FAS and FASLG genes may contribute to the aetiology of alopecia areata.
P163 Factors influencing histological confirmation of diagnosis in lung cancer patients
Authors: S. Chandramouli, M. Cheema
Journal: Thorax (2011)

<h3>Background</h3> The National Lung Cancer Audit routinely reports to each unit the percentage of their patients who have received histological confirmation of a diagnosis of lung cancer. This could therefore be interpreted as a key performance indicator for a cancer unit. We studied the factors that influenced the rate of histological confirmation of diagnosis in our population. <h3>Methods</h3> Data were extracted from our existing lung cancer database from January 2009 to May 2011. Demographics and clinical data were analysed to assess the factors that led to failure of confirmation of histological diagnosis. <h3>Results</h3> Out of 907 patients with lung cancer, 183 (20%) did not have a histological diagnosis. Based on TNM staging, 10% had stage I, 5% stage II, 19% stage III and 50% stage IV disease. Co-morbidities were significant in this group—57% had severe COPD, 12% had IHD and 11% had had a previous CVA. Of the 183 patients identified, 49 (27%) had at least one attempt at obtaining histology that proved to be non-diagnostic, either bronchoscopy (46 pts) or other procedure (3 pts). 41 (22%) were actively treated—6 (15%) had radical treatment, 5 (12%) had palliative chemotherapy and 29 (70%) had palliative radiotherapy. Performance status (PS) and co-morbidities were the main factors affecting decision to obtain histology. As the Abstract P163 table 1 suggests, patients without histology tended to be older (p&lt;0.0008) and a greater proportion had a PS of three or more. <h3>Conclusion</h3> These data suggest that patients who do not ultimately receive histological confirmation of a diagnosis of lung cancer are a heterogenous population. In most cases the factors that influenced the failure to obtain histology were poor performance status and co-morbidities. We conclude that the percentage of lung patients without histological confirmation of diagnosis may ultimately reflect the overall health of the local population rather than the specific quality of a lung cancer unit9s clinical practice. As such we would advocate caution when interpreting differences in this parameter between units.
Leukotriene C4 generation from human eosinophils stimulated with IgG-Aspergillus fumigatus antigen immune complexes
Authors: O. Cromwell, R. Moqbel, Penny Fitzharris, Lesia Kurlak, Christine Harvey, G.M. Walsh, R.J. Shaw, A.B. Kay
Journal: Journal of Allergy and Clinical Immunology (1988)