tbuckley/cabot-search huggingface dataset:
Biomarkers of environmental benzene exposure.
Authors: C Weisel, R Yu, A Roy, P Georgopoulos
Journal: Environmental Health Perspectives (1996)

Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is greater at environmental exposures than that at higher occupational exposures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different metabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses to a population exposed to lower, environmental levels of benzene is uncertain. Time-series measurements of the biomarker, exhaled breath, were used to evaluate a physiologically based pharmacokinetic (PBPK) model. Biases were identified between the PBPK model predictions and experimental data that were adequately described using an empirical compartmental model. It is suggested that a mapping of the PBPK model to a compartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physiologically based pharmacokinetic model.
Exercise and Health: The Evidence and the Implications
Authors: R. Sanders Williams
Journal: JAMA (1982)

Books about exercise have appeared in recent years at a rate that has exceeded the availability of new data or fresh ideas on the subject. Indeed, the authors of this book begin with the question, "Why another book on exercise?" Happily for the reader, they have provided us with a useful and generally well-written work. Though most of the material is available from other recent books or reviews, the first four chapters present an admirably concise and lucid review of epidemiologic evidence linking exercise habits to health and disease. Physiological data on the effects of habitual exercise and animal studies are reviewed, but more superficially. The middle chapters offer standard fare on exercise prescription and risks similar to that available from numerous sources, and they are palatable enough. The final chapters present a commendable effort to develop strategies at the community, state, and national levels to emphasize exercise as a
Procedural Volume and Outcomes With Radial or Femoral Access for Coronary Angiography and Intervention
Authors: Sanjit S. Jolly, John Cairns, Salim Yusuf, Kari Niemela, Philippe Gabriel Steg, Matthew Worthley, Emile Ferrari, Warren J. Cantor, Anthony Fung, Nicholas Valettas, Michael Rokoss, Goran K. Olivecrona, Petr Widimsky, Asim N. Cheema, Peggy Gao, Shamir R. Mehta
Journal: Journal of the American College of Cardiology (2013)
Macrophages: Central regulators of hepatic fibrogenesis and fibrosis resolution
Authors: Prakash Ramachandran, John P. Iredale
Journal: Journal of Hepatology (2012)

Hepatic fibrosis is the common end point to chronic injury of varied aetiology. There is now excellent evidence in both human studies and animal models that liver fibrosis is a bidirectional process with a significant reversible component. The hepatic stellate cell (HSC), following activation to a myofibroblast phenotype, is the principal cell producing extracellular matrix (ECM) during fibrogenesis and is the main source of TIMP-1, which inhibits the endogenous matrix-degrading activity of matrix metalloproteinases (MMPs), thus promoting scar deposition. Furthermore, apoptosis of activated HSCs is a critical feature of scar resolution. However, emerging evidence indicates that it is the hepatic macrophage that is the master regulator of this dynamic fibrogenesis–fibrosis resolution paradigm.
Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect.
Authors: H Ding, X L Gao, R Hirschberg, J V Vadgama, J D Kopple
Journal: Journal of Clinical Investigation (1996)

The actions of insulin-like growth factor 1 (IGF-1) on protein turnover and of the IGF-1 receptor (IGF-1R) were examined in skeletal muscle of rats with chronic renal failure (CRF) and sham operated (SO), pair-fed controls. Acidemia was prevented in CRF rats with NaHCO3. Serum IGF-1 and skeletal muscle IGF-1 and IGF-1 mRNA were reduced in CRF rats. Dose-response studies revealed impaired stimulation of protein synthesis and suppressed inhibition of protein degradation by IGF-1 in epitrochlearis muscle of CRF rats. Neither IGF-1 analogues with low affinity to IGF binding proteins nor proteinase inhibitors obliterated the IGF-1 resistance. In CRF rats, skeletal muscle IGF-1R mRNA was increased; displacement ligand binding studies and affinity labeling of the IGF-1R alpha subunit indicated increased total skeletal muscle IGF-1R number with normal affinity. However, both autophosphorylation of the IGF-1R beta subunit (i.e., IGF-1R tyrosine kinase) and the IGF-1R tyrosine kinase activity towards exogenous insulin receptor substrate-1, a natural substrate for IGF-1R tyrosine kinase, were reduced in CRF fats. These data indicate that in skeletal muscle of CRF rats there is resistance to the IGF-1 effects on protein synthesis and degradation and decreased IGF-1 and IGF-1 mRNA levels; IGF-1R mRNA and number are increased; but activity of IGF-1R tyrosine kinase is impaired. This postreceptor defect may be a cause of the skeletal muscle resistance to IGF-1 in CRF.
Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus
Authors: John G. McHutchison, Bruce R. Bacon, Stuart C. Gordon, Eric Lawitz, Mitchell Shiffman, Nezam H. Afdhal, Ira M. Jacobson, Andrew Muir, Mohammed Al-Adhami, Mary L. Morris, Julie A. Lekstrom-Himes, Susan M. Efler, Heather L. Davis
Journal: Hepatology (2007)

CPG 10101, a synthetic oligodeoxynucleotide (ODN), is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. In this multicenter Phase 1b trial, 60 HCV-positive patients (50 genotype 1 HCV) were randomized and received either placebo or CPG 10101 at 0.25, 1, 4, 10, or 20 mg subcutaneously (SC) twice weekly for 4 weeks or at 0.5 or 0.75 mg/kg SC once weekly for 4 weeks. Dose-dependent cytokine induction was observed after administration of CPG 10101. At 24 hours after administering the highest dose of 0.75 mg/kg CPG 10101, interferon (IFN)-γ-inducible protein 10 (IP-10) had a mean increase over baseline levels (±SD) of 15,057 (±9769) pg/ml ( P &lt; 0.01, compared to placebo); IFN-α had a 106 (±63.3) pg/ml increase ( P &lt; 0.01); and 2′5′-oligoadenylate synthetase (OAS) had a 163 (±120.6) pmol/dl increase ( P &lt; 0.01). Decreases in HCV RNA also were dose-dependent, with the greatest group geometric mean maximum reduction of 1.69 ± 0.618 log10 ( P &lt; 0.05) observed in the 0.75 mg/kg dose group. Decreases ≥1 log10 were seen in 22 of 40 patients who received ≥1 mg CPG 10101, with 3 patients exceeding a 2.5-log10 reduction. CPG 10101 was well tolerated, and adverse events were consistent with CPG 10101's mechanism of action. Conclusion: In this Phase 1 study, CPG 10101 was associated with dose-dependent increases in markers of immune activation and decreases in HCV RNA levels. The data support further clinical studies of CPG 10101 for treating chronic HCV infection.
Errors of judgment and the logic of conversation
Authors: Norbert Schwarz
Journal: Behavioral and Brain Sciences (2004)

Experimental procedures routinely violate the cooperative principle of conversational conduct by presenting irrelevant information in a way that implies its relevance to the task at hand. This contributes to an overestimation of the prevalence of judgment errors relative to natural contexts. When research participants are aware that the usual norms of conversational conduct do not apply, the emerging errors are attenuated or eliminated.
Electronic cigarettes as a method of tobacco control
Authors: R. Borland
Journal: BMJ (2011)

ABSTRACT  Gammaherpesvirus pathogenesis is dependent on the ability of these viruses to establish a lifelong latent infection and the ability to reactivate from latency. Immediate-early genes of theses viruses are thought to be critical regulators of lytic replication and reactivation from latency. The gene 50-encoded Rta is the only immediate-early gene product that appears to be conserved among all characterized gammaherpesviruses. Previous studies have demonstrated that, in Epstein-Barr virus (EBV), Kaposi9s sarcoma-associated virus, and gammaherpesvirus 68 (γHV68, also referred to as murine gammaherpesvirus 68), ectopic expression of Rta in latently infected cell lines can lead to induction of the viral cycle. Recently, studies employing null mutants of EBV have provided a formal demonstration that both Rta and the BZLF1 gene product, Zta, the two EBV immediate-early gene products, are essential for EBV replication. Here we generate and characterize a gene 50-null mutant γHV68 and demonstrate that the gene 50 product Rta is essential for virus replication. Providing γHV68 Rta in trans was sufficient to restore replication of the gene 50-null virus. Notably, Rta expressed from the spliced form of the gene 50 transcript was sufficient to complement growth of the gene 50-null virus. In addition, we provide evidence that loss of Rta expression leads to a complete defect in viral DNA replication and a significant defect in late antigen expression. This work lays the foundation for characterizing the role of Rta in γHV68 chronic infection of mice.
Thiazide-Induced Immune Hemolytic Anemia
Authors: Jose M. Vila
Journal: JAMA (1976)

SINCE the first report of drug-induced hemolytic anemia produced by stibophen,<sup>1</sup>the list has been expanded to include 16 other drugs and chemical compounds.<sup>2</sup> This group of hemolytic anemias has been classified as "immune" because to become antigenic the drug must combine with a macromolecule in the serum, thus forming a drug-antidrug complex.<sup>3</sup>This complex attaches to the red blood cell (RBC) membrane by an unknown mechanism and leads to RBC destruction either by activation of complement or by binding of active C3 to the RBC surface, with subsequent recognition by the macrophages and destruction in the reticuloendothelial system.<sup>4</sup> Several drugs have been reported to produce hemolysis without binding complement.<sup>5-7</sup>In these cases, RBC destruction is probably due to coating of RBCs by immunoglobulins. In the present case, an oral antihypertensive drug that is a combination of methyldopa and hydrochlorothiazide (Aldoril) produced immune hemolytic anemia
Sex Differences in Neurological Outcomes and Mortality After Cardiac Surgery
Authors: Charles W. Hogue, Benico Barzilai, Karen S. Pieper, Laura P. Coombs, Elizabeth R. DeLong, Nicholas T. Kouchoukos, Victor G. Dávila-Román
Journal: Circulation (2001)

Background —The purpose of this study was to evaluate whether women undergoing cardiac surgery are more likely to suffer neurological complications than men and whether these complications could explain, at least in part, their higher perioperative mortality. Methods and Results —The Society of Thoracic Surgery National Cardiac Surgery Database was examined for the years 1996 and 1997 to determine the frequency of new neurological events (stroke, transient ischemic attack, or coma) occurring after cardiac surgery. We reviewed clinical information on 416 347 patients (32% women) for whom complete neurological outcome data were available. New neurological events after surgery were higher for women than for men (3.8% versus 2.4%, P =0.001). For the whole group, the 30-day mortality was higher for women than for men (5.7% versus 3.5%, P =0.001), and among those patients who suffered a perioperative neurological event, mortality was also significantly higher for women than men (32% versus 28%, P =0.001). After adjustment for other risk factors (eg, age, history of hypertension and/or diabetes, duration of cardiopulmonary bypass, and other comorbid conditions) by multivariable logistic regression, female sex was independently associated with significantly higher risk of suffering new neurological events after cardiac surgery (OR 1.21, 95% CI 1.14 to 1.28, P =0.001). Conclusions —Women undergoing cardiac surgery are more likely than men to suffer new perioperative neurological events, and they have higher 30-day mortality when these complications occur. The higher incidence of perioperative neurological complications in women cannot be explained by currently known risk factors.
Teenagers, smoking, and vaping
Authors: D. Kamerow
Journal: BMJ (2015)

Does it matter what young people smoke?



Front page headlines across the United States on 17 April screamed the news that electronic cigarettes were becoming the smoke of choice among teenagers. In 2014, for the first time, more young people “vaped” e-cigarettes than smoked conventional tobacco cigarettes.1

Is this true? Is it news? If so, is it bad news or good?

The data come from a reliable source, the annual US National Youth Tobacco Survey, which is administered in schools to around 20 000 middle and high school students every year and has a very respectable response rate of 70% to 75%. Cluster sampling and weighting are used to obtain a nationally representative sample of students who attend public and private schools in grades 6-12. The only hitch is that they changed the way they asked about e-cigarettes in the 2014 survey (more about this below).

As reported by analysts from the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA), the data look dramatic indeed.2 The key survey question asked about use of …
Peripheral Neuropathy of the Alcoholic: I, Aetiological Role of Aneurin and Other B-complex Vitamins
Authors: J. Fennelly, O. Frank, H. Baker, C. M. Leevy
Journal: BMJ (1964)

Peripheral neuropathy in alcoholics is usually attributed to a lack of aneurin (Victor and Adams, 1961) ; however, it is often not possible to document this relation by diagnostic or thera- peutic tests.Demonstration that pantothenic acid (Hodges et al., 1958) or pyridoxine (Biehl and Vilter, 1954) deficiency may cause peripheral nerve dysfunction suggests that lack of these or other B-complex vitamins may also contribute to neuropathy in the malnourished alcoholic.The present investi- gation was therefore undertaken to evaluate further the role of aneurin and other B-complex vitamins in the development of this condition.The study consisted of (a) determining circu- lating levels of aneurin, riboflavin, nicotinic acid, pantothenic acid, biotin, pyridoxine, vitamin BI2, and folic acid in alcoholic patients with and without neuropathy; and (b) an evaluation of the responsiveness of patients with neuropathy to various members of the B-complex group.
Stress-Induced Right Ventricular Ischemia in Recurrent Pulmonary Outflow Stenosis in Repaired Tetralogy of Fallot
Authors: Rajiv Gupta, Atiar M. Rahman, Vani Vijayakumar
Journal: Clinical Nuclear Medicine (2005)

Radionuclide uptake by the right ventricle during myocardial perfusion imaging is minimal compared with the left ventricular myocardium and is not given much importance. However, right ventricular hypertrophy from pressure or volume overload may increase right ventricular radiotracer uptake and demonstrate reversible stress-induced perfusion abnormalities in the presence of normal coronary arteries. We report a case of right ventricular ischemia secondary to right ventricular hypertrophy from recurrent right ventricular outflow tract stenosis in a patient with repaired tetralogy of Fallot. Advances in the management of congenital heart disease have led to more patients surviving to adulthood. These patients subsequently present to cardiologists in adulthood with sequelae or complications arising from previous surgery undertaken during childhood.
Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia
Authors: Florencia McAllister, Jennifer M. Bailey, Janivette Alsina, Christopher J. Nirschl, Rajni Sharma, Hongni Fan, Yanique Rattigan, Jeffrey C. Roeser, Rachana H. Lankapalli, Hao Zhang, Elizabeth M. Jaffee, Charles G. Drake, Franck Housseau, Anirban Maitra, Jay K. Kolls, Cynthia L. Sears, Drew M. Pardoll, Steven D. Leach
Journal: Cancer Cell (2014)
An Error-Correcting Map for Quartets Can Improve the Signals for Phylogenetic Trees
Authors: Stephen J. Willson
Journal: Molecular Biology and Evolution (2001)

From the DNA sequences for N taxa, the (generally unknown) phylogenetic tree T that gave rise to them is to be reconstructed. Various methods give rise, for each quartet J consisting of exactly four taxa, to a predicted tree L(J) based only on the sequences in J, and these are then used to reconstruct T. The author defines an "error-correcting map" (Ec), which replaces each L(J) with a new tree, Ec(L)(J), which has been corrected using other trees, L(K), in the list L. The "quartet distance" between two trees is defined as the number of quartets J on which the two trees differ, and two distinct trees are shown to always have quartet distance of at least N - 3. If L has quartet distance at most (N - 4)/2 from T, then Ec(L) will coincide with the correct list for T; and this result cannot be improved. In general, Ec can correct many more errors in L. Iteration of the map Ec may produce still more accurate lists. Simulations are reported which often show improvement even when the quartet distance considerably exceeds (N - 4)/2. Moreover, the Buneman tree for Ec(L) is shown to refine the Buneman tree for L, so that strongly supported edges for L remain strongly supported for Ec(L). Simulations show that if methods such as the C-tree or hypercleaning are applied to Ec(L), the resulting trees often have more resolution than when the methods are applied only to L.
Topical Timolol for Recalcitrant Wounds
Authors: Liza R. Braun, Sonia A. Lamel, Nicholas A. Richmond, Robert S. Kirsner
Journal: JAMA Dermatology (2013)

Patient 1 A woman in her 80s with a history of venous insufficiency based on clinical presentation and vascular studies presentedwithmultiplepainfululcerationsonthebilateral ankles. She developed wounds in 1972 with subsequent trauma that led to repetitive skin breakdown.Her currentwounds began 1 year ago. The patient was initially treated with multilayered elastic compression bandages (Profore; Smith & Nephew), which were changed weekly, and various foam dressings (Allevyn; Smith & Nephew; Mepilex Ag; Molnlycke Health Care).When herwound failed to heal, adjuvant therapies, including serial applications of porcine small intestine submucosa (Oasis;HealthpointBiotherapeutics), bilayered living skin equivalent (Apligraf; Organogenesis) and an autologous splitthickness graft from the thighwere used but did not result in complete closure. After 6months, thewoundwas 3.2 cm2 and a β2-adrenergic receptor (B2AR) antagonist, topical timolol, 0.5% (Timoptic;AtonPharma),was instilled, 1dropevery2 cm of wound edge weekly, then covered with silicone foam and 3-layer compression. All wounds, including her target ulcer, were fully epithelialized after 8 weeks of treatment, and the patient was prescribed a compression apparatus (JuxtaCure; CircAid Medical Products) to prevent recurrence.
The Clinical Response of Rheumatic Fever and Acute Carditis to ACTH
Authors: Benedict F. Massell, Joseph E. Warren, George P. Sturgis, Buford Hall, Ernest Craige
Journal: New England Journal of Medicine (1950)

A NEW era in the study and treatment of rheumatic diseases began on April 13, 1949, when Hench and his co-workers1 announced their observations on the remarkably beneficial effects of the adrenocortical hormone, Cortisone (originally called Compound E), and of the pituitary adrenocorticotrophic hormone (ACTH) on rheumatoid arthritis. Six weeks later Hench and his associates2 reported that Cortisone also had a favorable influence on 3 patients suffering from acute rheumatic fever and rheumatic carditis. The opinion was expressed that ACTH would probably have similar effects to that of Cortisone in rheumatic fever.Since May 17, 1949, we have had the . . .
Clinical and cost effectiveness of booklet based vestibular rehabilitation for chronic dizziness in primary care: single blind, parallel group, pragmatic, randomised controlled trial
Authors: L. Yardley, F. Barker, I. Muller, D. Turner, S. Kirby, M. Mullee, A. Morris, P. Little
Journal: BMJ (2012)

<b>Objective</b> To determine the clinical and cost effectiveness of booklet based vestibular rehabilitation with and without telephone support for chronic dizziness, compared with routine care. <b>Design</b> Single blind, parallel group, pragmatic, randomised controlled trial. <b>Setting</b> 35 general practices across southern England between October 2008 and January 2011. <b>Participants</b> Patients aged 18 years or over with chronic dizziness (mean duration &gt;five years) not attributable to non-vestibular causes (confirmed by general practitioner) and that could be aggravated by head movement (confirmed by patient). <b>Interventions</b> Participants randomly allocated to receive routine medical care, booklet based vestibular rehabilitation only, or booklet based vestibular rehabilitation with telephone support. For the booklet approach, participants received self management booklets providing comprehensive advice on undertaking vestibular rehabilitation exercises at home daily for up to 12 weeks and using cognitive behavioural techniques to promote positive beliefs and treatment adherence. Participants receiving telephone support were offered up to three brief sessions of structured support from a vestibular therapist. <b>Main outcome measures</b> Vertigo symptom scale-short form and total healthcare costs related to dizziness per quality adjusted life year (QALY). <b>Results</b> Of 337 randomised participants, 276 (82%) completed all clinical measures at the primary endpoint, 12 weeks, and 263 (78%) at one year follow-up. We analysed clinical effectiveness by intention to treat, using analysis of covariance to compare groups after intervention, controlling for baseline symptom scores. At 12 weeks, scores on the vertigo symptom scale in the telephone support group did not differ significantly from those in the routine care group (adjusted mean difference −1.79 (95% confidence interval −3.69 tο 0.11), P=0.064). At one year, both intervention groups improved significantly relative to routine care (telephone support −2.52 (−4.52 to −0.51), P=0.014; booklet only −2.43 (−4.27 to −0.60), P=0.010). Analysis of cost effectiveness acceptability curves showed that both interventions were highly cost effective; at very low QALY values, the booklet only approach was most likely to be cost effective, but the approach with additional telephone support was most likely to be cost effective at QALY values more than £1200 (€1488; $1932). Using the booklet approach with telephone support, five (three to 12) patients would need to be treated for one patient to report subjective improvement at one year. <b>Conclusions</b> Booklet based vestibular rehabilitation for chronic dizziness is a simple and cost effective means of improving patient reported outcomes in primary care. <b>Trial registration</b> ClinicalTrials.gov NCT00732797.