tbuckley/cabot-search huggingface dataset:
HDL and ABC Transporters Reduce the Proliferation of Hematopoietic Stem and Progenitor Cells, with Anti-atherogenic Consequences
Authors: Alan R. Tall
Journal: Circulation (2011)

Leukocytosis is a risk factor for athero-thrombotic disease in humans, and develops in animal models of atherosclerosis in response to feeding high fat, high cholesterol diets. The ATP binding cassette transporters ABCA1 and ABCG1 promote cholesterol efflux to apoA-1 and HDL, respectively and are targets of LXR transcription factors. Mice lacking ABCA1/G1 develop a dramatic myeloproliferative phenotype with monocytosis and neutrophilia, associated with expansion and proliferation of hematopoietic stem and myeloid progenitor populations (HSPCs). The transporters are highly expressed in HSPCs where they act to control proliferative responses to growth factors (IL-3, GM-CSF) by regulating plasma membrane lipid rafts and cell surface expression of the common beta subunit of the IL-3/GM-CSF receptor. In Western type diet fed Apoe-/- mice, monocytosis and neutrophilia also develop in association with proliferation and expansion of hematopoietic stem, multipotential progenitor and myeloid progenitor cell populations in the bone marrow and spleen. Apoe is highly expressed in long term hematopoietic stem cells and to a lesser extent in progenitor populations, and acts in a cell autonomous fashion to control myeloid proliferation, monocytosis and accumulation of monocytes in atherosclerotic lesions. Treatment of Apoe-/- mice with infusions of reconstituted HDL and/or LXR activator resulted in normalization of HSPC proliferation, monocytosis and neutrophilia. Together, the findings suggest that ApoE acts in concert with the ATP binding cassette transporters ABCA1 and ABCG1 to control HSPC and myeloid proliferation, monocytosis and atherogenesis. LXR activators and rHDL infusions exert anti-atherogenic effects by controlling HSPC and myeloid proliferation.
Abstract 3524: Implementation of the American Heart Association Get With the Guidelines Heart Failure Program (GWTG-HF) Reduces Length of Stay and Decreases Cost for Hospitalized Heart Failure Patients at St. Joseph’s Regional Medical Center (SJRMC)
Authors: Robert T Faillace, Richard B Siegrist, Steven Duchensky, Lorraine Marut, Ilene Matza, Lucena Sarimento, Kathleen Cahill, Eileen Bogdanowitz, Michele Sabatino
Journal: Circulation (2007)

Hospitalized heart failure patients (HF) may not consistently receive standards of care and hospitals frequently realize a financial loss in the care of HF patients. GWTG-HF makes it more likely to ensure optimal care, decrease direct cost and increase hospital profit in the management of HF patients. HYPOTHESIS: Utilization of GWTG-HF with a multi-disciplinary team would be associated with a consistent application of standards of care, shorter duration of hospitalization and less direct cost for hospitalized HF patients. METHODS: GWTG-HF was fully operational in 2006 with a multi-disciplinary team consisting of a Physician Champion, Advanced Practice Nurses (APNs), Case Managers and RNs. APNs utilized GWTG-HF at the point of service and worked collaboratively with attending physicians. We compared the average length of stay, total number of hospitalized days, patient revenue, total direct cost, contribution margin, and the profit/loss for hospitalized HF patients in 2005 to those in 2006. RESULTS: There were 773 cases of HF admissions in 2005 as compared to 781 in 2006. Overall compliance with GWTG-HF Core Measures in 2006 was 98% (HF-1 D/C Instructions 99%; HF-2 Left ventricular systolic (LVS) function evaluation 96%; HF-3 ACEI/ARB for LVS dysfunction 98%; HF-4 Smoking cessation advice 100%; Beta Blocker Use 95%). The average length of stay (LOS) in 2005 was 6.7 days as compared to 6.3 days in 2006 (p &lt;0.02). The total number of hospital days in 2005 was 5,145 as compared to 4,880 in 2006 (p&lt;0.02). Between 2005 and 2006 patient revenue increased by $279,847 (p&lt;0.01), direct cost decreased by $348,014 (p&lt;0.05), contribution margin increased by $627,861 (p=0.06) and the full cost profit margin increased by $309,460 (NS). CONCLUSION: Utilization of GWTG-HF at SJRMC is associated with a high compliance with standards of hospitalized HF care, decrease in average LOS, decrease in total number of hospital days and decrease in direct cost. Although not statistically significant, hospital contribution margin and profit increased for acutely decompensated HF patients.
Characterization of Gonococcal Antigens Responsible for Induction of Bactericidal Antibody in Disseminated Infection
Authors: Peter A. Rice, Dennis L. Kasper
Journal: Journal of Clinical Investigation (1977)

The role of gonococcal antigens in serum bactericidal activity was determined for an isolate of Neisseria gonorrhoeae from a patient with disseminated gonococcal infection (DGI). Gonococcal outer membranes were purified by differential ultracentrifugation of sheared organisms treated with EDTA. The membranes were solubilized in an endotoxin-disaggregating buffer, and the proteins were separated from the endotoxin by molecular sieve chromatography. Chemical characterization of the endotoxin from the DGI strain revealed the presence of heptose (7.8% of carbohydrate composition) and 2-keto-3-deoxyoctonate (6.1%, wt/wt) in concentrations similar to rough endotoxins of gram-negative enteric bacteria. Dermal Schwartzman reactions were positive for this endotoxin (4 mug) and the corresponding outer membrane (139 mug), but negative for the protein fraction (>500 mug). The patient's whole serum or the IgG fraction, each with complement, reduced the number of the infecting organisms by greater than 1 log(10) in a bactericidal assay. Outer membrane and its protein and endotoxin fractions (0.8-500 mug) from the DGI strain were separately preincubated with the patient's convalescent serum and specific inhibition of bactericidal activity occurred with the endotoxin fraction (25 mug) and the outer membrane (100 mug); the protein (500 mug) exhibited no inhibition. Similar results were obtained by inhibiting the bactericidal activity of rabbit antiserum, prepared by intravenous inoculation of an isolate from a patient with pelvic inflammatory disease, with antigen purified from that strain. That this was specific immune inhibition and not anticomplementary activity was shown by the failure of these antigens to inhibit other complement-dependent bactericidal systems.
Information on Cost-Effectiveness: An Essential Product of a National Comparative Effectiveness Program
Journal: Annals of Internal Medicine (2008)

The American College of Physicians recently highlighted the need to provide increased information comparing the effectiveness of health care interventions to ensure the rational and effective practice of medicine. Comparative effectiveness refers to the evaluation of the relative clinical effectiveness, safety, and cost of 2 or more medical services, drugs, devices, therapies, or procedures used to treat the same condition. The College further recommended the establishment of an adequately funded, trusted national entity that should prioritize, sponsor, or produce both comparative clinical and cost-effectiveness data. This article addresses the need for the proposed entity to develop cost-effectiveness information. It examines the current reluctance to develop and use cost-effectiveness in the United States; it argues for the importance of this information for all health care stakeholders; and it makes specific recommendations regarding how this information can best be made available and used for the good of the public and our patients.
Abstract 10120: Endothelial Cell-specific Lkb1 Deletion Causes Endothelial Dysfunction and Hypertension in Mice In Vivo
Authors: Wencheng Zhang
Journal: Circulation (2013)

Background:  Liver kinase B1 (LKB1), a tumor suppressor, is a central regulator of cell polarity and energy homeostasis. The roles of LKB1 in endothelial function  in vivo  have not been explored.   Methods and Results:  The endothelium-specific LKB1 knockout ( LKB1 endo   -/- ) mice were generated by crossbreeding LKB1 flox/flox  mice with VE-cadherin Cre approach.  LKB1 endo   -/-  mice exhibited hypertension, cardiac hypertrophy and impaired endothelium-dependent relaxation. In addition, in parallel with reduced levels of both endothelial nitric oxidase (eNOS) activity and phosphorylated (Thr172) AMP-activated protein kinase (AMPK), a downstream enzyme of LKB1,  LKB1 endo   -/-  mice expressed high levels of caveolin-1. Further, siRNA silencing of caveolin-1 normalized the eNOS activity in LKB1-deficient endothelial cells. Furthermore, human antigen R (HuR) bound with AU-rich elements of caveolin-1 mRNA 3’ UTR resulting in increased stability of caveolin-1 and genetic knockdown of HuR decreased caveolin-1 level in LKB1-deficient endothelial cells. Finally, we found that inhibition of LKB1 or AMPK induced the translocation of HuR from nuclei to cytosol and overexpression of constitutively active AMPK (CA-AMPK) led to decreased caveolin-1 level. Consistently, administration of CA-AMPK in  LKB1 endo   -/-  mice lowered blood pressure with improved endothelial function  in vivo .   Conclusions:  Our findings indicate that endothelial cell LKB1 plays an essential role in regulating eNOS activity, endothelial function, and blood pressure through modulating AMPK-mediated caveolin-1expression.
Abstract 104: The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi -Organ Dysfunction Trial (TOPHR HIT)
Authors: Laurie J Morrison, Sandro Rizoli, Brian Schwartz, Shawn Rhind, Sandra Black, Donald T Stuss, Andrew Baker
Journal: Circulation (2006)

Study Goal: To evaluate the feasibility of a prehospital randomized controlled trial comparing 250 ml of Hypertonic Saline and Dextran (HSD ) to Normal Saline (NS) for head injured adult trauma pat...
Cluster randomised trials
Authors: N. Freemantle, J. Wood, M. K Campbell, J. M Grimshaw
Journal: BMJ (1999)

Editor—In their editorial on cluster randomised trials Campbell and Grimshaw correctly identify the importance of the appropriate choice of the unit of analysis.1 Unfortunately, they display a disappointingly poor grasp of the basis of estimation, and the specific recommendations that they make are inappropriate.

The authors’ plea for a standardised approach to the analysis and reporting of cluster randomised trials is misguided. The framework that they describe has the patient as the principal unit of the experiment, with the correlation between patients in the same cluster having to be taken into account in the analysis. Following the recommendations in the editorial may, however, make investigators prey to the same errors that the authors are counselling them to guard against.

Although some trials fall naturally into the framework that the authors describe, others do not. It is not helpful in their own example of an educational intervention to implement a clinical guideline. There, the clinician (whose behaviour is the target of the intervention) is clearly the principal unit of the experiment. We are interested in the change in his or her behaviour as a result of the intervention, the average size of the change, and how the size varied between clinicians. Focusing on the estimation of these quantities of direct interest should lead to a sensible and interpretable analysis. Recognising that such estimates should be fit for purpose should lead to a sensible design.2

Adjusting the analysis on the basis of the intracluster correlation coefficient assumes the observed covariance structure to be the true structure, without taking into account measurement error. It is robust only where a reasonable estimate of variability at the clinician level is available. Thus to suggest that such methods are more efficient than aggregated analyses at the level at which the intervention is targeted is incorrect. The authors’ quest for information on intracluster correlation coefficients is a search for an answer to the wrong problem. Thoughtless focus on correlation coefficients could lead to the use of values estimated in one study for calculations of sample size in quite a different area, which is probably worse than doing no such calculation at all.

The authors also suggest incorrectly that covariates at the patient level may not be examined in aggregated analyses. Generalised linear modelling provides the opportunity of specifying covariates at the patient level while analysing at the level at which the intervention is targeted.3
下肢周围动脉疾病的诊断 对多数病例，多普勒超声安全、低廉，准确性足以指导治疗
Authors: Andrew, Bradbury, Donald, Adam, 施德兵（译）, 符伟国（校）
Journal: BMJ (2007)

在近期的BMJ中，Collins和其同事撰写的一篇系统性综述比较了多普勒超声扫描、磁共振血管造影和CT血管造影在评估下肢动脉疾病诊断中的准确性。（见本期第344页），这篇综述还评价了这些检查方法对患者治疗结果的影响。该综述发现造影剂增强磁共振血管造影较CT血管造影特异度更高（能更好的排除下肢动脉50％及以上的狭窄），较多普勒超声扫描敏感度更强（能更好的发现下肢动脉50％及以上的狭窄）。与传统血管造影相比，磁共振血管造影一般更易被患者接受。然而，这些结果对实践中的临床医生有何意义？
Abstract 2895: Steep Activation-Recovery Interval Restitution Predicts the Vulnerability of Ventricular Arrhythmia in Patients with Structural Heart Disease
Authors: Tetsu Watanabe, Michiyasu Yamaki, Naoki Nozaki, Joji Nitobe, Yuichi Tsunoda, Isao Kubota
Journal: Circulation (2006)

Electrophysiological abnormalities play a role in occurrence of life-threatening ventricular arrhythmia in patients with structural heart disease. However, risk stratification of patients with impl...
Candidate molecular markers for oral precancer and cancer
Authors: R. Ralhan, N. Chakravarti, J. Kaur, S. Soni, A. Kumar, S. D. Gupta, S. Bahadur, N. K. Shukla, S. V. S. Deo
Journal: Journal of Clinical Oncology (2005)

9598 Background: Alterations in expression of cell cycle regulators and retinoid receptors are implicated in human cancers. The development of oral cancer is a multistep process. We hypothesized that altered expression of retinoic acid receptors (RARα, β, γ) and retinoid X receptor RXRα and their relationship with cell cycle regulators (p53, cyclinD1, pRb, p16, p21) is associated with development, progression and prognosis of oral cancer. Methods: Immunohistochemical analysis of RARα, β, γ and RXRα proteins was carried out on serial sections from 220 oral squamous cell carcinomas (OSCCs), 98 potentially malignant lesions (61 hyperplasias, 37 dysplasias) and 81 matched histologically normal oral tissues and correlated with expression of cell cycle regulators p53, CyclinD1, pRb, p16 and p21 in these tissues as well as in tumor free margins and with clinicopathological parameters. The prognostic relevance of these factors was assessed in 100 of these SCC patients who were followed-up for a maximum period of 94 months. Results: Expression of retinoid receptors RARβ, RARγ, RXRα and cell cycle regulators p16, pRb and p21 was decreased in majority of oral SCCs as well as in potentially malignant lesions. Accumulation of p53 in tumor free margins was associated with adverse prognosis. Multivariate stepwise logistic regression analysis indicated that the significant predictors of transition from: normal to potentially malignant stage were p16, RARβ and RARα +/p21-; hyperplasia to dysplasia was RARα +/ p53+ and potentially malignant to malignant phenotype were cyclinD1 and RARα +. Multivariate analysis using Cox’s proportional Hazard’s model showed that RARα +/p21- phenotype was associated with reduced disease free survival. Conclusions: Analysis of alterations in expression of retinoid receptors at the protein level at different stages in development and progression of oral SCC and their interactions with cell cycle regulators in multistep oral tumorigenesis underscored, for the first time, their diagnostic and prognostic significance for this disease. No significant financial relationships to disclose.
Expression of the Lung Resistance Protein Predicts Poor Outcome in De Novo Acute Myeloid Leukemia
Authors: Martin Filipits, Gudrun Pohl, Thomas Stranzl, Ralf W. Suchomel, Rik J. Scheper, Ulrich Jäger, Klaus Geissler, Klaus Lechner, Robert Pirker
Journal: Blood (1998)
Same information, different decisions: format counts
Authors: J. Wyatt
Journal: BMJ (1999)

Information in Practice p 1527 

The function of information is to help us make better decisions.1 The amount of clinical information, measured by journal articles, has doubled over two decades,2 but thanks to evidence based approaches the content now seems more reliable. For example, the review article has changed from a vehicle to advance the author's reputation3 to a balanced synthesis of evidence we can safely use to inform clinical and policy decisions.4 To justify this special position, much effort is expended on assembling reliable content—from comprehensive literature searches4 to peer review and the editorial process.5 However, just assembling the right words and …
May occur secondary to misuse of diuretics and potassium supplements
Authors: E. Strivens, A. Siddiqi, R. Fluck, A. Hutton, D. Bell
Journal: BMJ (1996)

arrhythmias and hyperkalaemia unrelated to exposure to suxamethonium.Secondly, both hyperkalaemic periodic paralysis and Andersen's syndrome are dominantly inherited, and other family members may be at risk of sudden death.Thirdly, both conditions are amenable to treatment.
Interleukin-10–Treated Human Dendritic Cells Induce a Melanoma-Antigen–Specific Anergy in CD8+ T Cells Resulting in a Failure to Lyse Tumor Cells
Authors: Kerstin Steinbrink, Helmut Jonuleit, Gabriele Müller, Gerold Schuler, Jürgen Knop, Alexander H. Enk
Journal: Blood (1999)
Human Papillomavirus Testing for Triage of Women With Cytologic Evidence of Low-Grade Squamous Intraepithelial Lesions: Baseline Data From a Randomized Trial
Authors: T. A. S. C. o. U. S./L.-G. S. I. L. T. S. (ALTS) Group
Journal: JNCI Journal of the National Cancer Institute (2000)

Human papillomavirus (HPV) infections appear to be central to the development of cervical cancer. This study addresses the question of whether testing women who have low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix for HPV DNA is useful as a triage strategy.Four clinical centers in different areas of the United States participated in a randomized clinical trial of the use of HPV DNA testing in women with cytologic evidence of atypical squamous cells of undetermined significance (ASCUS) or LSIL. The study sample in this article consists only of women who had LSIL at enrollment. Within 6 months of an LSIL diagnosis (based on a Pap smear read by a community-based cytopathologist), women who were 18 years of age or older completed a standardized questionnaire and underwent a pelvic examination that included collection of cervical specimens for HPV DNA testing by Hybrid Capture II (HCII)(R) assay.Among the 642 women referred with LSIL who had analyzable test results, the mean chronologic age and age at first coitus were similar among the four clinical centers, despite the centers' ethnic and geographic diversity. Overall, HPV DNA was detected in cervical samples from 532 (82.9%) of the 642 women (95% confidence interval = 79.7%-85.7%). This high frequency of HPV positivity was confirmed by polymerase chain reaction (PCR) assays in a subset of 210 paired specimens tested by HCII and PCR (81.4% were positive by both methods).Because a very high percentage of women with an LSIL diagnosis from Pap smears are positive for HPV DNA by HCII testing, there is limited potential for this assay to direct decisions about the clinical management of women with LSIL. The role of HPV testing in the management of women with ASCUS is still under study.
Abstract 5943: Electrical Dysynchrony Acutely Increases Interstitial Matrix Metalloproteinase Activity
Authors: Rupak Mukherjee, Juozas A Zavadzkas, William T Rivers, Julie E McLean, Eileen I Chang, Christine N Koval, Robert E Stroud, Francis G Spinale
Journal: Circulation (2008)

Increased matrix metalloproteinase (MMP) abundance occurs with adverse LV remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained dyssynchronous electrical activation of the LV, with consequent dyskinesia, alter interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n=10, 30–35 kg) was achieved by pacing (120 bpm) at left atrial ( A ) and LV sites ( V) such that normal A-V electrical activation (60 min) was followed by regional early V activation for 60 min within 1.5 cm of the V site , and restoration of normal A-V pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the V pacing site and a remote LV site were monitored at 30 min intervals. With early V activation, segmental shortening was reduced (8.4±0.6% vs 1.2±0.9%, p&lt;0.05) at the V site, but not at the remote site (8.5±0.3%). Interstitial MMP activity was similar at remote and V sites during initial A-V pacing (1172±187 vs. 1332±87 fluoro units, resp). Dyssynchrony increased interstitial MMP activity at the V site compared to the remote region (Figure ). Restoration of A-V pacing normalized segmental shortening (8.5±0.4%), but MMP activity remained elevated. This study, for the first time, demonstrates that despite restoration of mechanical function, disturbances in electrical conduction - in and of itself - can directly cause regional MMP activation, and therefore, contribute to myocardial remodeling.
PTH-081 The use of dry blood spot testing for hepatitis C within needle exchange services
Authors: B P Stephens, S O Keeffe, J M Tait, P McIntyre, J F Dillon
Journal: Gut (2010)

<h3>Introduction</h3> Diagnosing hepatitis C virus (HCV) in current injecting drug users has often proved challenging. This is due to the individuals reluctance to have medical staff obtain venous blood from their preferred injecting sites in addition to generally poor venous access. Dry blood spot testing (DBST) has proven to be a robust method of determining HCV status. The aim of this study was to evaluate the ease of use of DBST in clinical practice. <h3>Methods</h3> This was a 3-month pilot study. Staff within a needle exchange service were given appropriate training in the use of DBST. Testing for HCV was offered to all individuals who accessed needle exchange services during this period. A follow-up appointment was given for 2 weeks after testing and a referral to specialist services was offered to those individuals who tested positive. <h3>Results</h3> A total of 140 individuals were tested during the study period, 100% of samples obtained were processed successfully. 63.6% (89/140) of the individuals tested were male, the age range was between 18 and 51 years. 92.9% (130/140) attended a follow-up appointment for their results. Of the 7.1% who did not receive results, 2.9% (4/140) were HCV positive and 4.3% (6/140) were negative. 30.7% (43/140) were positive for HCV antibodies. Of the 39 individuals who received their positive results, all were offered referral to specialist services and only 10% (4/39) did not wish further input at this time. Of the 35 referred into specialist service 88% (31/35) have attended an appointment to be reviewed by the specialist team to provide further information and/or check HCV PCR. <h3>Conclusion</h3> The study has shown DBST is easy to use and can be carried out without difficulty by staff within drug services. The offer of HCV testing was well received by the particular client group and over 90% of individuals returned for their results. Knowing HCV status also allowed staff to reiterate the appropriate harm reduction measures. 90% accepted referral to specialist services and 88% attended a follow-up appointment therefore suggesting that providing BBV testing is valuable in a group who are often envisaged as being too chaotic to engage with health services.