tbuckley/cabot-search huggingface dataset:
Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice
Authors: Zengxuan Nong, Herminia González-Navarro, Marcelo Amar, Lita Freeman, Catherine Knapper, Edward B. Neufeld, Beverly J. Paigen, Robert F. Hoyt, Jamila Fruchart-Najib, Silvia Santamarina-Fojo
Journal: Journal of Clinical Investigation (2003)

Hepatic lipase (HL) has a well-established role in lipoprotein metabolism. However, its role in atherosclerosis is poorly understood. Here we demonstrate that HL deficiency raises the proatherogenic apoB-containing lipoprotein levels in plasma but reduces atherosclerosis in lecithin cholesterol acyltransferase (LCAT) transgenic (Tg) mice, similar to results previously observed with HL-deficient apoE-KO mice. These findings suggest that HL has functions that modify atherogenic risk that are separate from its role in lipoprotein metabolism. We used bone marrow transplantation (BMT) to generate apoE-KO and apoE-KO x HL-KO mice, as well as LCAT-Tg and LCAT-Tg x HL-KO mice, chimeric for macrophage HL gene expression. Using in situ RNA hybridization, we demonstrated localized production of HL by donor macrophages in the artery wall. We found that expression of HL by macrophages enhances early aortic lesion formation in both apoE-KO and LCAT-Tg mice, without changing the plasma lipid profile, lipoprotein lipid composition, or HL and lipoprotein lipase activities. HL does, however, enhance oxidized LDL uptake by peritoneal macrophages. These combined data demonstrate that macrophage-derived HL significantly contributes to early aortic lesion formation in two independent mouse models and identify a novel mechanism, separable from the role of HL in plasma lipoprotein metabolism, by which HL modulates atherogenic risk in vivo.
Misleading false positives
Authors: J. Stuart
Journal: BMJ (1985)

haematological findings confirmed a current infection with Epstein-Barr virus producing acute infectious mononucleosis.The diagnosis of infectious mononucleosis was established by clinical, haematological, and sero- logical features, which included the presence of specific antibody to Epstein-Barr virus.2Advances in virology and immunology now permit us to recognise increasing numbers of diseases caused by Epstein-Barr virus.2Infectious mononucleosis and appendicitis are two common acute illnesses which affect the same age group.Many primary Epstein-Barr virus infections are probably missed because the full spectrum of illness is not yet known.Although isolation of the virus adds weight to any causal relation based on serological reactions, recovery of Epstein-Barr virus from throat swabs or blood has not yet been attempted on any large group of sick children with ill defined diseases.I suggest that the time has come to look at the relationship of Epstein-Barr virus to appendicitis.B THALAYASINGAM
Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: A double-blind, randomized, placebo-controlled evaluation of two doses
Authors: Jeffrey L. Anderson, Jack C. Askins, Edward M. Gilbert, Ronald H. Miller, Deborah L. Keefe, John C. Somberg, Roger A. Freedman, Lawrence R. Haft, Jay W. Mason, Jan N. Lessem
Journal: Journal of the American College of Cardiology (1986)
Evaluation of Computational Docking to Identify Pregnane X Receptor Agonists in the ToxCast Database
Authors: Sandhya Kortagere, Matthew D. Krasowski, Erica J. Reschly, Madhukumar Venkatesh, Sridhar Mani, Sean Ekins
Journal: Environmental Health Perspectives (2010)

BackgroundThe pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion.ObjectivesAs part of an evaluation of different approaches to predict compound affinity for nuclear hormone receptors, we used the molecular docking program GOLD and a hybrid scoring scheme based on similarity weighted GoldScores to predict potential PXR agonists in the ToxCast database of pesticides and other industrial chemicals. We present some of the limitations of different in vitro systems, as well as docking and ligand-based computational models.MethodsEach ToxCast compound was docked into the five published crystallographic structures of human PXR (hPXR), and 15 compounds were selected based on their consensus docking scores for testing. In addition, we used a Bayesian model to classify the ToxCast compounds into PXR agonists and nonagonists. hPXR activation was determined by luciferase-based reporter assays in the HepG2 and DPX-2 human liver cell lines.ResultsWe tested 11 compounds, of which 6 were strong agonists and 2 had weak agonist activity. Docking results of additional compounds were compared with data reported in the literature. The prediction sensitivity of PXR agonists in our sample ToxCast data set (n = 28) using docking and the GoldScore was higher than with the hybrid score at 66.7%. The prediction sensitivity for PXR agonists using GoldScore for the entire ToxCast data set (n = 308) compared with data from the NIH (National Institutes of Health) Chemical Genomics Center data was 73.8%.ConclusionsDocking and the GoldScore may be useful for prioritizing large data sets prior to in vitro testing with good sensitivity across the sample and entire ToxCast data set for hPXR agonists.
The management of established postherpetic neuralgia: a comparison of the quality and content of traditional vs. systematic reviews
Authors: None Ladhani, None Williams
Journal: British Journal of Dermatology (1998)

In the face of an exponential increase in published biomedical studies, dermatologists frequently turn to review articles in order to keep abreast of important developments in the treatment of skin diseases. Traditional review articles have recently been criticized on the basis of their incompleteness and susceptibility to bias. Such biases can be minimized by employing a systematic approach to gathering, combining and interpreting the evidence of treatment efficacy. Using eight predetermined quality criteria, we compared the quality of 10 traditional reviews with one systematic review of treatments for postherpetic neuralgia, which were identified from the Medline database for 1992–96. None of the 10 traditional review articles satisfied all eight criteria: one satisfied five, two satisfied four and the rest satisfied two or fewer criteria. There was a wide variation in the recommendations of the authors for the treatment of postherpetic neuralgia, often based on anecdotal evidence and clinical experience. On the other hand, the systematic review fulfilled seven of the eight quality criteria, failing only to discuss future directives. Furthermore, treatment recommendations were made solely on the basis of randomized controlled trials, which are considered to be the gold standard for measuring the benefits of any intervention. The variation in quality and treatment recommendations of traditional reviews is worrying. Systematic reviews should be encouraged in dermatology because they provide a summary of evidence of the effects of dermatological treatments, which has been derived using explicit methods widely accepted within science.
RELATION OF RELAPSES IN TYPHOID TO DURATION OF CHLORAMPHENICOL THERAPY
Authors: JOSEPH E. SMADEL
Journal: JAMA (1949)

During the past year much information has accumulated on the use of chloramphenicol (chloromycetin®) in the treatment of typhoid. This confirms the original report of Woodward and others,<sup>1</sup>covering the observations on 10 patients, which clearly indicated that the new antibiotic was of great value in this disease. Continued experience reveals that fever disappears by lysis during the first three or four days of treatment. Our early observations,<sup>1</sup>as well as those of McDermott and his associates,<sup>2</sup>brought out that relapses of typhoid were common in treated patients. In order to eliminate such occurrences, we have prolonged the course of treatment in persons infected with Salmonella typhosa. Analysis of the results obtained in 44 patients with typhoid who received chloramphenicol therapeutically under our observation has indicated a striking relation between the duration of chemotherapy and the incidence of relapses. Although our observations are being reported in detail
METHADONE-INDUCED QTC PROLONGATION IS ASSOCIATED WITH CYP2C19 GENOTYPE AND WITH PLASMA ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDENE (EDDP) CONCENTRATION: A POSSIBLE MECHANISTIC LINK
Authors: John Carlquist, David Moody, Eric Johnson, Marian Jacobsen, John Huntinghouse, Jeffrey Rollo, Stacey Knight, Wenfang B. Fang, Dawn Niemann, Mark Morgan, J. Muhlestein, Jeffrey Anderson
Journal: Journal of the American College of Cardiology (2014)
Hepatitis C and G co-infection: Response to interferon therapy and quantitative changes in serum HGV-RNA
Authors: J G McHutchison, O V Nainan, M J Alter, A Sedghi-Vaziri, J Detmer, M Collins, J Kolberg
Journal: Hepatology (1997)

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities raise two theoretical questions. First, could HGV coinfection play any role in the response of HCV to antiviral therapy and second, would this coinfected population have changes in serum HGV-RNA induced by interferon. To address these questions, 98 patients with documented chronic HCV underwent interferon therapy (3 million units three times a week) for 6 months. Response to therapy was categorized using standard biochemical criteria. Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%) patients with HCV infection had detectable serum HGV-RNA. There was no difference between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT) values, HCV-RNA levels, HCV genotype, histological severity, or other demographic features were analyzed. Interferon response was similar in both groups and HGV was not associated with outcome following therapy. Antiviral therapy appeared to induce a reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In two patients, the fall in serum HGV-RNA correlated with biochemical response, independent of changes in HCV-RNA. These observations indicate that a larger study of an HGV population is required to more clearly define the relationship between HCV and HGV coinfection and their response to antiviral therapy.
Misoprostol in the prevention of gastroduodenal damage in rheumatology.
Authors: A B Ballinger, P J Kumar, D L Scott
Journal: Annals of the Rheumatic Diseases (1992)

Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) are at an increased risk of gastroduodenal erosions, ulcers, and the associated complications of haemorrhage, perforation, and death. Many NSAID associated ulcers that bleed or perforate have been asymptomatic until the time of presentation and conversely many patients with dyspepsia do not have ulcers. Symptoms are a poor guide to the presence of an ulcer. During continued treatment with NSAIDs misoprostol is the best choice for NSAID induced gastroduodenal damage; it achieves higher rates of healing than other drugs in these circumstances. Misoprostol is superior to other drugs in the prevention of gastric damage but misoprostol and H2 antagonists are of similar benefit in the duodenum. Prophylactic studies have all used endoscopic damage as an endpoint, and much larger studies will be needed to show an effect of misoprostol on the incidence of ulcer complications. There are no clear guidelines as to which patients should receive prophylactic treatment with misoprostol but those particularly at risk of ulcer complications--that is, those with previous peptic ulceration, the elderly, medically unfit, patients receiving large doses of NSAIDs, and those patients receiving steroids in addition to NSAIDs--should be considered.
Preventable Drug Reactions — Causes and Cures
Authors: Louis M. Sherwood, Edith E. Parris, Kenneth L. Melmon
Journal: New England Journal of Medicine (1971)

MODERN therapeutic agents have contributed favorably to the physician's ability to influence the course of many diseases. Their use has also created a formidable health problem: 18 to 30 per cent of all hospitalized patients have a drug reaction,1 , 2 and the duration of their hospitalization is about doubled as a consequence.1 2 3 4 In addition, 3 to 5 per cent of all admissions to hospitals are primarily for a drug reaction,1 , 5 and 30 per cent of these patients have a second reaction during their hospital stay. The economic consequences are staggering: one seventh of all hospital days is devoted to the care . . .
Localized erythema multiforme due to lymphatic obstruction
Authors: MADALENE C.Y. HENG, MILTON FEINBERG
Journal: British Journal of Dermatology (1982)

Two cases of localized erythema multiforme are described with lesions limited to areas of lymphatic obstruction. It is thought that the blockade of the reticulo-endothelial system predisposed to the deposition of immune complexes in the lymphoedematous skin.
Egg protein sensitization in patients with bird feather allergy
Authors: B. Añibarro Bausela, M. Marjín Estekban, F. Martínez Alzamora, C. Pascual Marcos, J. A. Ojeda Casas
Journal: Allergy (1991)

We have studied the hypersensitivity lo hens egg protein and chicken meal in 25 adults with a previous diagnosis of bronchial asthma and rhinoconjunctivitis due to bird feather sensitization. Seventeen of the 25 reported good tolerance to the ingestion of egg and chicken meat. The skin tests were negative to both antigens in 15 of them, and positive for egg in two. All 17 patients had negative RAST to chicken meat and egg protein. The remaining eight patients had intolerance to egg, and three of them also to chicken meat ingestion; in seven of the eight eases allergic to egg, the alimentary intolerance began after the clinical symptoms of bird feather sensitization. In all eight cases the skin tests were positive to egg yolk, and in live of them also to egg white and chicken meal. These patients evidenced specific serum IgE antibodies to egg yolk, four of them to egg while, and seven to chicken meat. These results demonstrate (he high frequency (32%) of the association of sensitization lo egg proteins, particularly egg yolk, in a selected population of patients with known allergy to bird feathers, thus suggesting that in some patients feather sensitization could trigger or somehow facilitate the later sensitization to egg yolk proteins.
Putting Health Care on the National Agenda
Authors: William J. Bicknell
Journal: JAMA (1994)

<i>Putting Health Care on the National Agenda</i>is a timely and readable volume written for an audience that might be defined as most of us: everyone who is not a student of health policy but interested in becoming more informed in order to better participate in our nation's great health care debate. Birenbaum's goal is to be comprehensive and provocative and to provide criteria for assessing reform with a focus on financing and coverage. He notes that he has never written with such intensity or urgency. This makes for an easy and engaging read. Though not lengthy, this is a book of sweeping breadth. The first section, in six chapters, addresses "A System in Need of Direction." Here Birenbaum moves from the widespread dissatisfaction with health care through changes in the doctor-patient relationship, to hospitals, business, and the uninsured. The reader leaves this section with a good appreciation of the
A fundamental role of mAbp1 in neutrophils: impact on β2 integrin–mediated phagocytosis and adhesion in vivo
Authors: Jürgen Schymeinsky, Ronald Gerstl, Ingrid Mannigel, Katy Niedung, David Frommhold, Klaus Panthel, Jürgen Heesemann, Michael Sixt, Thomas Quast, Waldemar Kolanus, Attila Mocsai, Jürgen Wienands, Markus Sperandio, Barbara Walzog
Journal: Blood (2009)
NHS Gloucestershire keeps 80m community services in public hands
Authors: C. Dyer
Journal: BMJ (2012)

<h3>Introduction</h3> Plethysmographic lung volumes are the gold standard for identifying restrictive lung defects (reduced TLC), and are useful for delineating obstructive defects (increased RV/TLC).1 Interpretation of these measurements may, however, be limited without appropriate reference equations. The BTS recommend equations by Rosenthal2 (based on white subjects) for children. However, to our knowledge, no ethnic-specific plethysmographic equations have been published for black children, in whom lower spirometric values are known to exist. <h3>Aim</h3> To evaluate the appropriateness of plethysmographic reference equations in healthy young children according to ethnic origin. <h3>Methods</h3> Healthy children (68 black and 115 white) aged 6–12 yrs underwent plethysmography measurements according to standardised guidelines.1 Results were adjusted for sex and height and expressed as %predicted and z-scores using recommended equations.2 Unpaired t-tests were used to establish ethnic differences. <h3>Results</h3> Ethnic differences in lung volumes were dependent on the outcome: Black children had significantly lower FRC (∼6% or 0.3z) and TLC (∼8% or 0.6z), but no significant differences in RV such that their RV/TLC ratio was significantly higher (Abstract P137 table 1). In addition, relatively poor agreement between observed vs predicted FRC was seen in healthy white children. To avoid misdiagnosis, the limits of normality (mean±2 SD) need to be adjusted to cater for these discrepancies. These preliminary data suggest that, based on the Rosenthal equations, the lower limit of normal for TLC, (to detect restriction), would be ∼75% predicted (−2.1z) for black children and ∼80% predicted (−1.7z) for white children. For detecting hyperinflation using RV/TLC the upper limit of normal would be ∼148% predicted (2.3z) for black children and ∼135% predicted (1.7z) in white children, whereas for FRC they would be ∼111%predicted (0.4z) and 122% predicted(1.2z) in black and white children respectively. <h3>Conclusion</h3> Ethnic differences in lung volumes exist and cannot be accounted for by a simple correction factor. Current paediatric plethysmographic reference equations are not appropriate, and may lead to misdiagnosis unless limits of normality are adjusted. Caution in interpretation is recommended until more appropriate reference equations can be developed. This requires prospective plethysmographic lung volume data collection using standardised protocols in children from different ethnic backgrounds.
Monitoring may need to be prolonged in patients given warfarin and amiodarone
Authors: B. Tomlinson, R. P Young, T. Y K Chan, J. A J H Critchley, J. C N Chan
Journal: BMJ (1996)

practice, we do not suppose that automated reporting represents an acceptable alternative gold standard.Furthermore, we made a specific distinction between major abnormalities, which are generally easily distinguished,3 and minor abnormalities, which are generally harder to distinguish.We also pointed out that patients with a murmur will require echocardiography because patients with valvar heart disease may have a normal echocardiogram; this may explain part of the difference between Khandekar and colleagues' and our findings (in our service, referrals for assessment of murmurs were not encouraged and few such referrals were received).We accept Simon Sanderson's comments about predictive values and prevalence, although we think that his qualifications strengthen our case.One of our chieffindings was the exceptional negative predictive value of the electrocardiogram (that is, a normal electrocardiogram virtually excludes chronic heart failure secondary to left ventricular systolic dysfunction).This was subsequently confirmed by data from the coronary artery surgery study's registry.4Sanderson's recalculation of our results on the basis of a lower prevalence yields an even more exceptional negative predictive value of 99.9%.We are pleased to see that Gregory Y H lip and colleagues are so far in agreement with our findings that they have extended them to acute heart failure in hospital practice.One of our reasons for publishing our findings in a general medical journal was the fact that, while they may do little more than "confirm a longstanding clinical impression," they do confirm it and provide evidence for it.They are therefore of interest to a wider audience than general practitioners alone.
Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism.
Authors: L J Mandarino, K S Wright, L S Verity, J Nichols, J M Bell, O G Kolterman, H Beck-Nielsen
Journal: Journal of Clinical Investigation (1987)

To determine whether activation by insulin of glycogen synthase (GS), phosphofructokinase (PFK), or pyruvate dehydrogenase (PDH) in skeletal muscle regulates intracellular glucose metabolism, subjects were studied basally and during euglycemic insulin infusions of 12, 30, and 240 mU/m2 X min. Glucose disposal, oxidative and nonoxidative glucose metabolism were determined. GS, PFK, and PDH were assayed in skeletal muscle under each condition. Glucose disposal rates were 2.37 +/- 0.11, 3.15 +/- 0.19, 6.71 +/- 0.44, and 11.7 +/- 1.73 mg/kg X min; glucose oxidation rates were 1.96 +/- 0.18, 2.81 +/- 0.28, 4.43 +/- 0.32, and 5.22 +/- 0.52. Nonoxidative glucose metabolism was 0.39 +/- 0.13, 0.34 +/- 0.26, 2.28 +/- 0.40, and 6.52 +/- 1.21 mg/kg X min. Both the proportion of active GS and the proportion of active PDH were increased by hyperinsulinemia. PFK activity was unaffected. Activation of GS was correlated with nonoxidative glucose metabolism, while activation of PDH was correlated with glucose oxidation. Sensitivity to insulin of GS was similar to that of nonoxidative glucose metabolism, while the sensitivity to insulin of PDH was similar to that of glucose oxidation. Therefore, the activation of these enzymes in muscle may regulate nonoxidative and oxidative glucose metabolism.
Darzi review: Right of patients to drugs recommended by NICE is strengthened
Authors: R. Coombes
Journal: BMJ (2008)

Patients in England will have a new legal right to drugs approved by the National Institute for Health and Clinical Excellence (NICE) if a doctor says they are clinically appropriate.

The right, outlined in health minister Ara Darzi’s review of the NHS, applies to drugs and treatments recommended by NICE technology appraisals. The findings of technology appraisals, which advise on whether to use a single drug or treatment and in what circumstances, are already mandatory for primary care trusts within three months of being issued.

But the new right doesn’t extend to treatments recommended by NICE guidelines, a separate tier of advice from technology appraisals. In 2004, for example, NICE issued guidelines recommending that primary care trusts should offer women three attempts at in vitro fertilisation treatment; last month, however, a survey showed that only nine of England’s 151 trusts …