tbuckley/cabot-search huggingface dataset:
Meeting Report: Methylmercury in Marine Ecosystems—From Sources to Seafood Consumers
Authors: Celia Y. Chen, Nancy Serrell, David C. Evers, Bethany J. Fleishman, Kathleen F. Lambert, Jeri Weiss, Robert P. Mason, Michael S. Bank
Journal: Environmental Health Perspectives (2008)

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences-Superfund Basic Research Program workshop titled "Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure," convened by the Dartmouth Toxic Metals Research Program on 15-16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and to articulate research and monitoring priorities to better understand how marine food webs have become contaminated with MeHg. Although human health effects of Hg contamination were a major theme, the workshop also explored effects on marine biota. The workgroup focused on three major topics: a) the biogeochemical cycling of Hg in marine ecosystems, b) the trophic transfer and bioaccumulation of MeHg in marine food webs, and c) human exposure to Hg from marine fish and shellfish consumption. The group concluded that current understanding of Hg in marine ecosystems across a range of habitats, chemical conditions, and ocean basins is severely data limited. An integrated research and monitoring program is needed to link the processes and mechanisms of MeHg production, bioaccumulation, and transfer with MeHg exposure in humans.
Pharmacogenetics in Breast Cancer Therapy
Authors: Sing-Huang Tan, Soo-Chin Lee, Boon-Cher Goh, John Wong
Journal: Clinical Cancer Research (2008)

Abstract Interindividual and interethnic variability of drug pharmacokinetics and pharmacodynamics may be contributed by commonly occurring genetic polymorphisms of drug-metabolizing enzymes and transporters. Polymorphisms of CYP2D6 in particular have been associated with effects on tamoxifen disposition and clinical efficacy, with interethnic differences in distribution of functional alleles that affect metabolizer phenotype. Other tamoxifen-related genetic variants of CYP3A4, CYP3A5, and sulfotransferase1A1 (SULT1A1) are also briefly reviewed here. Polymorphisms of CYP19A1 (aromatase gene) have been reported to correlate with clinical outcomes from aromatase inhibitors in small studies but require further confirmation. Many studies on chemotherapy are based on hypothesis-generating association studies and need to be validated through larger-scale cooperative group studies. For anthracyclines, polymorphisms in genes such as carbonyl reductase 3 (CBR3), ATP-binding cassette subfamily B, member 1 (ABCB1), glutathione-related transporter genes, and oxidative stress–related genes have been reported to correlate with clinical outcomes. The pharmacogenetics of taxanes has been extensively investigated, but associations of genetic polymorphisms in drug-metabolizing enzymes and transporters reported in earlier small studies have not been validated in a recent large clinical trial. Allelic variants associated with gemcitabine, capecitabine/5-fluorouracil, vinorelbine, and platinum disposition are reviewed. No pharmacogenetic studies have been published for targeted agents thus far, although several potential candidate genes warrant investigation. Future pharmacogenetic studies will need to focus on integration of multiple drug pathways to allow a more comprehensive analysis of genetic factors influencing drug efficacy and toxicity.
Pharmacokinetic-hemodynamic interactions between vasopressin and nitroglycerin: Comparison between intravenous and cutaneous routes of nitrate delivery
Authors: Andres T. Blei, Steve Friedman, Jeanne Gottstein, Gary Robertson, Ho-Leung Fung
Journal: Hepatology (1985)

Addition of nitroglycerin (NTG) improves the hemodynamic response to vasopressin and may thus be useful in the treatment of gastrointestinal hemorrhage. We studied in the rat the influence of vasopressin on the disposition of a constant intravenous infusion of NTG and the cutaneous absorption of NTG ointment. The effect of NTG on the pharmacokinetics of vasopressin was also defermined. Animals were divided into four groups: control, NTG, vasopressin and vasopressin + NTG. Infusions (or ointments) were maintained for 70 min; cardiac output and regional blood flows were determined with the microsphere technique. Both intravenous and cutaneous NTG resulted in similar hemodynamic responses. Vasopressin caused generalized vasoconstriction, while the addition of NTG reversed the deleterious systemic hemodynamic effects of vasopressin. Addition of vasopressin to NTG did not alter NTG systemic clearance nor did NTG affect vasopressin clearance. Of note, the systemic clearance of NTG was directly correlated with the cardiac output (r = 0.804), supporting a model of NTG distribution where blood vessels and/or extrahepatic tissues are the site of elimination of the drug. The marked reduction in skin blood flow by vasopressin did not decrease the steady–state plasma concentration of NTG nor the estimated cutaneous absorption rate of NTG ointment, indicating that cutaneous blood flow is not an important determinant in the absorption of NTG ointment. The skin is an appropriate route of delivery for NTG when combined with vasopressin.
P27 Personal allergen exposures are increased by changes in sleep position and improved by temperature-controlled laminar airflow
Authors: R. Gore, R. Boyle, H. Hanna, A. Custovic, C. Gore, P. Svensson, J. Warner
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Aeroallergens are released directly from bedding into the breathing zone, and contribute importantly to asthma symptoms. Adults change their sleep position between 3 and 45 times per night. The effect of these turns on inhaled particulate exposures is unknown. We aimed to investigate the effects of changing position on breathing zone particulate exposures and the effect of a novel Temperature-controlled Laminar Airflow (TLA) device on reducing such exposures. <h3>Methods</h3> A simulated bedroom was constructed containing bedding from a cat owner. Five healthy volunteers lay recumbent under an active and an inactive TLA device for 175 min. Volunteers made scheduled turns in bed to simulate normal sleep. Real-time total particle levels (≥0·5 μm diametre) within the breathing zone were measured by laser particle counting. Inhaled cat allergen exposure was measured by nasal air sampling. Time series analysis was used to evaluate changes in particulate exposures with turning. <h3>Results</h3> A greater proportion of larger particles than smaller ones were disturbed by turning over (F=20.6, df=5, p&lt;0.001). With the TLA switched off, 9% (95% CI 4 to 18) of total overhead particles &gt;10 μm diametre were accounted for by turning over, compared with 0.2% (95% CI 0.07 to 0.5) of particles &gt;0.5 μm diameter. TLA treatment reduced total particle numbers (size &gt;0.5 μm) by 3010-fold (p&lt;0.001) and significantly reduced the turn-associated increase for all particle sizes (Abstract P27 Figure 1, p&lt;0.015). Similar turn-associated increases in nasal air sampler cat particle counts were seen. TLA treatment reduced nasal cat allergen exposures by sevenfold (p=0.043). <h3>Conclusions</h3> Turning over in bed causes a significant increase in breathing zone exposures to particulates which are within the respirable size range. TLA treatment dramatically reduces overhead breathing zone total particulate exposures and also reduces nasal cat allergen exposure. TLA treatment attenuates the increase in particulate exposures caused by turning over. Treatments which result in better sleep quality and a reduced number of bodily turns may result in a reduction in personal breathing zone particulate exposures in bed.
The structural basis of MRI bone erosions: an assessment by microCT
Authors: Andreas Albrecht, Stephanie Finzel, Matthias Englbrecht, Jürgen Rech, Axel Hueber, Philipp Schlechtweg, Michael Uder, Georg Schett
Journal: Annals of the Rheumatic Diseases (2012)

To determine whether erosions appearing in MRI in patients with rheumatoid arthritis (RA) represent true erosions.50 RA patients received 1.5 T MRI and microCT (μCT) of the dominant hand. Erosion counts were assessed in coronal T1 weighted MRI sections and in coronal as well as axial μCT sections of the metacarpophalangeal (MCP) joints II-IV. Extent of erosions was assessed by RA MRI Score (RAMRIS) erosion score (MRI) and by three-dimensional assessment of erosion volume (μCT).111 of the 600 evaluated joint regions showed erosions in the MRI and 137 in the μCT. In only 28 regions false negative lesions (μCT positive, MRI negative) were found, all of which were very small lesions with a volume of less than 10 mm(3). Only two results were false-positive (μCT negative, MRI positive). RAMRIS erosion scores were strongly correlated to erosion volumes in the μCT (Pearson's r=0.514, p<0.001). Mean RAMRIS erosion scores were below 1 with erosion volumes up to 1.5 mm(3), below 2 with erosion volumes up to 20 mm(3) and over 2 with volumes of more than 20 mm(3).MRI erosions are generally based on true cortical breaks as shown by μCT. MRI is sensitive to detect bone erosions and only very small lesions escape detection. Moreover, RAMRIS erosion scores are closely linked to the absolute size of bone erosions in the μCT.
VISUALIZATION OF MYOCARDIAL SCARRING/FIBROSIS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: CARDIAC MAGNETIC RESONANCE VS DUAL SOURCE COMPUTED TOMOGRAPHIC IMAGING
Authors: Aya Kino, Jennifer Berliner, James C. Carr, Robert O. Bonow, Lubna Choudhury
Journal: Journal of the American College of Cardiology (2010)
THE VALUE OF ANTISEPTICS IN THE CONTROL OF BACTERIAL INFECTIONS
Authors: C. H. Browning
Journal: BMJ (1934)

The question, How far can infections by pathogenic organisms be influenced for the benefit of the host by means of antiseptics?incidentally involves inquiry into the properties of antiseptics which suit them for such purposes, and also into the methods of their application.By " antiseptic " is understood a substance of ascertained chemical constitution harmful 'to the activities of micro- organisms.The problem, then, is one of chemotherapy in the sense defined by Ehrlich.Restricting consideration to the ordinary bacteria, we shall see that success has been chiefly obtained where the drug can be brought into close contact with the site of a localized infection in a wound or natural cavity.Therefore the chemotherapy of bacterial infections is at present most intimately associated with surgery.-Generalized bacterial infections are still practically beyond the reach of antiseptics.This admis- sion must not be interpreted as the confession of failure: the antiseptics now available have very great therapeutic potentialities, and the advances already made open up still wider prospects.It must be remembered, too, that until recently little has been done to correlate biological and chemical work on the problems.In order to clarify the present position the scientific origin of antiseptic treatment will be traced, and the limitations of the older antiseptics w7ill be noted. Lister and Antiseptic TherapyLister was without doubt the first to employ antiseptics on a scientific basis.Fortunately, his guiding principles are authoritatively summarized by the late Sir Hector Cameron in the Dr. James VVatson Memorial Lectures (1907), which had been submitted for revision to Lister himself." It was hard, perhaps, to appreciate the fact that carbolic acid was not used by Lister (as it undoubtedly had been previously used by others) as ' a local dressing of wounds ' with the view of acting directly, and with a specific healing influence, on the wounded 'tissues, but rather that it was employed to destroy germs which, if they reached the wound in the living state, had the power of preventing the natural processes of repair.. His constant aim was to place wounds, as far as possible, in conditions resembling those of subcutaneous injuries, free from the access of external morbid agencies, as well as from direct irritation by foreign substances."Lister, it is true, applied carbolic acid to the soiled tissues exposed in a compound fracture for the express purpose of destroying pathogenic bacteria which had
Reproductive Disruption in Wild Longear Sunfish ( <i>Lepomis megalotis</i> ) Exposed to Kraft Mill Effluent
Authors: Jennifer A. Fentress, Stacy L. Steele, Henry L. Bart, Ann Oliver Cheek
Journal: Environmental Health Perspectives (2005)

Worldwide, wild fish living in rivers receiving municipal and industrial discharges may experience endocrine disruption as a result of exposure to anthropogenic pollutants. The purpose of this study was to evaluate the hormonal status of wild fish in a U.S. river receiving unbleached kraft and recycled pulp mill effluent (Pearl River at Bogalusa, LA). We evaluated two alternative hypotheses: the effluent contained constituents that suppressed male and female reproduction, or it contained an androgenic substance that masculinized females. To evaluate the likelihood of fish exposure to effluent, we marked 697 longear sunfish (Lepomis megalotis) over a 2-year period; 83% of recaptured fish were found at the site of initial capture, and only one fish migrated from an effluent-receiving site to a reference site. We can reasonably assume that fish captured from an effluent-receiving site are residents, not transitory migrants. To diagnose endocrine disruption, we measured sex steroid hormone [17beta-estradiol (E2), testosterone (T), and 11-ketotestosterone (11KT)] and vitellogenin (VTG) concentrations in male and female longear sunfish captured at two sites upstream and two sites downstream of the effluent outfall. Kraft pulp mill effluent did not affect male reproductive physiology but did suppress female T and VTG levels when effluent constituted>or=1% of river flow. Masculinization was not observed. Longear sunfish in the Pearl River experience moderate reproductive suppression in response to unbleached kraft and recycled pulp mill effluent.
The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad
Authors: Anna Melin, Åsa B Tornberg, Sven Skouby, Jens Faber, Christian Ritz, Anders Sjödin, Jorunn Sundgot-Borgen
Journal: British Journal of Sports Medicine (2014)

Low energy availability (EA) in female athletes with or without an eating disorder (ED) increases the risk of oligomenorrhoea/functional hypothalamic amenorrhoea and impaired bone health, a syndrome called the female athlete triad (Triad). There are validated psychometric instruments developed to detect disordered eating behaviour (DE), but no validated screening tool to detect persistent low EA and Triad conditions, with or without DE/ED, is available.The aim of this observational study was to develop and test a screening tool designed to identify female athletes at risk for the Triad.Female athletes (n=84) with 18-39 years of age and training ≥5 times/week filled out the Low Energy Availability in Females Questionnaire (LEAF-Q), which comprised questions regarding injuries and gastrointestinal and reproductive function. Reliability and internal consistency were evaluated in a subsample of female dancers and endurance athletes (n=37). Discriminant as well as concurrent validity was evaluated by testing self-reported data against measured current EA, menstrual function and bone health in endurance athletes from sports such as long distance running and triathlon (n=45).The 25-item LEAF-Q produced an acceptable sensitivity (78%) and specificity (90%) in order to correctly classify current EA and/or reproductive function and/or bone health.The LEAF-Q is brief and easy to administer, and relevant as a complement to existing validated DE screening instruments, when screening female athletes at risk for the Triad, in order to enable early detection and intervention.
The Effects of Poverty on Child Health and Development
Authors: J. Lawrence Aber, Neil G. Bennett, Dalton C. Conley, Jiali Li
Journal: Annual Review of Public Health (1997)

Poverty has been shown to negatively influence child health and development along a number of dimensions. For example, poverty–net of a variety of potentially confounding factors—is associated with increased neonatal and post-neonatal mortality rates, greater risk of injuries resulting from accidents or physical abuse/neglect, higher risk for asthma, and lower developmental scores in a range of tests at multiple ages. Despite the extensive literature available that addresses the relationship between poverty and child health and development, as yet there is no consensus on how poverty should be operationalized to reflect its dynamic nature. Perhaps more important is the lack of agreement on the set of controls that should be included in the modeling of this relationship in order to determine the “true” or net effect of poverty, independent of its cofactors. In this paper, we suggest a general model that should be adhered to when investigating the effects of poverty on children. We propose a standard set of controls and various measures of poverty that should be incorporated in any study, when possible.
Lysosomal iron in pulmonary alveolar proteinosis: a case report
Authors: H. L. Persson, L. K. Vainikka
Journal: European Respiratory Journal (2009)

Pulmonary alveolar proteinosis is characterised by accumulation of surfactant-like material in the distal air spaces. Since lysosomes play a crucial role for degradation of large biomolecules taken up from the cell's environment, it was hypothesised that oxidant-induced lysosomal disruption and ensuing cell death might play a role in disease development. In the present study, alveolar macrophages, harvested by whole-lung lavage from a patient diagnosed with pulmonary alveolar proteinosis, are shown to contain large amounts of undigested material within lysosomes, and the same organelle exhibits increased amounts of haemosiderin-bound iron. Compared with murine macrophage-like J774 cells (iron exposed or not), the status of human macrophages was pro-oxidative, i.e. macrophages exhibited a low level of the antioxidant glutathione and large amounts of iron available for Fenton-type chemistry. As a consequence, macrophageal lysosomes were particularly fragile when exposed to physiological concentrations of hydrogen peroxide (generated by glucose oxidase in culture medium). Such lysosomal disruption resulted in extensive cell death by both necrosis and apoptosis independent of caspase-3 activation. Considering the potential role of iron-catalysed oxidant-induced lysosomal rupture and ensuing cell killing for pulmonary alveolar proteinosis pathology and disease progression, whole-lung lavage might be considered early in those cases in which cytochemical staining reveals great numbers of haemosiderin-laden alveolar macrophages.
Complement-Mediated Loss of Endothelium-Dependent Relaxation of Porcine Coronary Arteries
Authors: Gregory L. Stahl, Wende R. Reenstra, Gyorgy Frendl
Journal: Circulation Research (1995)

Abstract Reperfusion of the ischemic myocardium results in the loss of endothelium-dependent relaxation. We have shown recently that the alternate complement pathway is activated immediately on reperfusion of the ischemic porcine myocardium. We hypothesized that complement activation directly attenuates endothelium-dependent relaxation of porcine coronary arteries. Bradykinin (BK) or substance P concentration-dependently relaxed precontracted (U46619, 50 nmol/L) left anterior descending coronary artery (LAD) rings in vitro. Addition of zymosan to human (10%) or porcine (10%) serum for 30 minutes significantly ( P &lt;0.05) increased the EC 50 of BK-induced LAD relaxation from 4±1 to 418±159 nmol/L (n=8) and from 9±3 to 281±132 nmol/L (n=7), respectively. Similarly, addition of zymosan to 10% human serum (HS) for 30 minutes increased the EC 50 of substance P–induced LAD relaxation from 0.4±0.1 to 30±14 nmol/L (n=9, P &lt;.05). Basal release of nitric oxide was reduced significantly in LAD rings exposed to zymosan-activated HS compared with HS alone. Addition of soluble CR1 (sCR1, 10 nmol/L) to zymosan-activated HS preserved BK-induced relaxation (EC 50 ) of the LAD rings (control, 4±1 nmol/L; sCR1+zymosan+serum, 2±1 nmol/L; n=6). Zymosan-activated C8-depleted HS (10%) did not attenuate the EC 50 of BK-induced coronary artery relaxation (3±1 to 3±1 nmol/L, n=7, P =NS). Zymosan-activated C8-depleted HS plus C8 (6 μg/mL) increased the EC 50 of BK-induced coronary artery relaxation from 4±1 to 423±141 nmol/L (n=12, P &lt;.05). We have further demonstrated that C5b-9 complexes can be found on the luminal surface of LAD endothelial cells after 5 minutes of exposure to zymosan-activated HS by using C5b-9 reactive monoclonal antibody fluorescent immunohistochemistry and confocal microscopy. We conclude that complement activation directly attenuates endothelium-dependent relaxation through the formation of the terminal membrane attack complex (C5b-9).
Sneezing induced by sexual ideation or orgasm: an under-reported phenomenon
Authors: Mahmood F Bhutta, Harold Maxwell
Journal: Journal of the Royal Society of Medicine (2008)

We describe a hitherto under-recognized curious response in some individuals: of sneezing in response either to sexual ideation or in response to orgasm. Our review suggests that it may be much more common than expected. We surmise that an indiscrete stimulation of the parasympathetic nervous system may be an underlying mechanism to explain this and other reported unusual triggers of sneezing.