Toxicological reviews最新文献

{"title":"The use of the osmole gap as a screening test for the presence of exogenous substances.","authors":"Roy A Purssell,&nbsp;Larry D Lynd,&nbsp;Yoshikata Koga","doi":"10.2165/00139709-200423030-00005","DOIUrl":"https://doi.org/10.2165/00139709-200423030-00005","url":null,"abstract":"<p><p>The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing serious adverse outcomes. The quantitative measurement of specific serum levels of these substances using gas chromatography is expensive, time consuming and generally only available at major tertiary-care facilities. Therefore, because these toxic substances are osmotically active and the measurement of serum osmolality is easily performed and more readily available, the presence of an osmole gap (OG) has been adopted as an alternative screening test. By definition, the OG is the difference between the measured serum osmolality determined using the freezing point depression (Osm(m)) and the calculated serum molarity (Mc), which is estimated from the known and readily measurable osmotically active substances in the serum, in particular sodium, urea, glucose, and potassium and ethanol (alcohol). Thus, the OG=Osm(m)-Mc, and an OG above a specific threshold (the threshold of positivity) suggests the presence of unmeasured osmotically active substances, which could be indicative of a toxic exposure. The objectives of this study were to review the principles of evaluating screening tests, the theory behind the OG as a screening test and the literature upon which the adoption of the OG as a screening test has been based. This review revealed that there have been numerous equations derived and proposed for the estimation of the Mc, with the objective of developing empirical evidence of the best equation for the determination of the OG and ultimately the utility of OG as a screening test. However, the methods and statistical analysis employed have generally been inconsistent with recommended guidelines for screening test evaluation and although many equations have been derived, they have not been appropriately validated. Specific evidence of the clinical utility of the OG requires that a threshold of positivity be definitively established, and the sensitivity and specificity of the OG in patients exposed to either EG or MeOH be measured. However, the majority of studies to date have only evaluated the relationship between the Osm(m) (mmol/kg H2O) and the Mc (mmol/L) in patients that have not been exposed to either MeOH or EG. While some studies have evaluated the relationship between the OG and serum ethanol concentration, these findings cannot be extrapolated to the use of the OG to screen for toxic alcohol exposure. This review shows that there has not been an appropriately designed empirical evaluation of the diagnostic utility of the OG and that its clinical utility remains hypothetical, having been theoretically extrapolated from the non-poisoned population.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 3","pages":"189-202"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423030-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25257473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices.","authors":"Yoshikata Koga,&nbsp;Roy A Purssell,&nbsp;Larry D Lynd","doi":"10.2165/00139709-200423030-00006","DOIUrl":"https://doi.org/10.2165/00139709-200423030-00006","url":null,"abstract":"<p><p>The present clinical use of serum osmometry is erroneous in two respects. The first, and the most important, is the incorrect assumption that serum behaves as a dilute 'ideal' solution and that the osmotic activity of a substance depends solely on the number of solute particles. The amount of variance from ideal behaviour of serum containing an exogenous substance is expressed by the osmotic coefficient (phi). We have calculated the osmotic coefficient for serum containing ethanol (alcohol) and recommend that the osmotic coefficient for serum containing other low molecular weight substances such as methanol (methyl alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is necessary for the accurate calculation of the contribution of these substances to the serum osmolality.Secondly, the practice of subtracting the calculated serum molarity from measured serum osmolality is not valid since it represents a mathematically improper expression. The units of these two terms are different. The 'osmole gap' (OG) is typically viewed as the difference between serum osmolality determined by an osmometer and the estimated total molarity of solute in serum by directly measuring the concentration of several substances and then substituting them into a published formula. Some authors call this sum the calculated or estimated osmolarity but, because the concentrations are measured directly and not with an osmometer, the calculated term represents molarity. The units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L. Therefore, the practice of subtracting calculated serum molarity from measured serum osmolality is not mathematically sound and is an oversimplification for ease of application. This mathematical transgression necessarily adds an error to the incorrectly calculated OG. Despite this, the OG is commonly used in clinical medicine. Serum osmolality can be converted to molarity provided the weight percentage and the density of the solution are known and thus, we recommend that this conversion be done prior to calculation of the gap. We recommend that the gap between measured serum osmolarity and calculated serum molarity be called the 'osmolar gap'. After having corrected for non-ideality for serum and for inconsistency of units, the standard value and reference range for this gap must be determined in an adequate number of patient populations and in a variety of clinical settings. An example of this determination, using data from a group of ethanol-poisoned patients is given. This correction should be applied before the evaluation of the osmolar gap as a screening test for other low molecular weight substances proceeds.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 3","pages":"203-11"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423030-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25257474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal interactions involving cytochrome p450 enzymes: a mini review.","authors":"Rupika Delgoda,&nbsp;Andrew C G Westlake","doi":"10.2165/00139709-200423040-00004","DOIUrl":"https://doi.org/10.2165/00139709-200423040-00004","url":null,"abstract":"<p><p>The metabolism of a drug can be altered by another drug or foreign chemical, and such interactions can often be clinically significant. Cytochrome P450 (CYP) enzymes, a superfamily of enzymes found mainly in the liver, are involved in the metabolism of a plethora of xenobiotics and have been shown to be involved in numerous interactions between drugs and food, herbs and other drugs. The observed induction and inhibition of CYP enzymes by natural products in the presence of a prescribed drug has (among other reasons) led to the general acceptance that natural therapies can have adverse effects, contrary to the popular beliefs in countries where there is an active practice of ethnomedicine. Herbal medicines such as St. John's wort, garlic, piperine, ginseng, and gingko, which are freely available over the counter, have given rise to serious clinical interactions when co-administered with prescription medicines. Such adversities have spurred various pre-clinical and in vitro investigations on a series of other herbal remedies, with their clinical relevance remaining to be established. Although the presence of numerous active ingredients in herbal medicines, foods and dietary supplements complicate experimentation, the observable interactions with CYP enzymes warrant systematic studies, so that metabolism-based interactions can be predicted and avoided more readily. This article highlights the involvement of CYP enzymes in metabolism-related drug-herb interactions and the importance of gaining a mechanism-based understanding to avoid potential adverse drug reactions, in addition to outlining other contributory factors, such as pharmacogenetics and recreational habits that may compound this important health issue.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 4","pages":"239-49"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423040-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25114527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digoxin-specific antibody fragments: how much and when?","authors":"D Nicholas Bateman","doi":"10.2165/00139709-200423030-00001","DOIUrl":"https://doi.org/10.2165/00139709-200423030-00001","url":null,"abstract":"<p><p>Digitalis glycoside poisoning is an important clinical problem and the development of digoxin-specific antibody fragments (Fab) 30 years ago has changed clinical practice. Nevertheless, doubts still exist as to the appropriate dose indications for therapy. This paper reviews relevant literature, describes the difficulties associated with current treatment protocols and proposes an approach to therapy, which is based on theoretical principles and evidence gleaned from currently available clinical data sets. In patients with 'acute' poisoning, serum digoxin concentrations do not equate to the total body burden, as tissue distribution will not have occurred, and the calculations for present protocols, which use serum concentrations, are therefore likely to result in too much antibody being administered. Since a therapeutic quantity of digoxin will have little effect in a normal individual, complete neutralisation of all digoxin is also unnecessary. The pharmacokinetic and dynamic logic of using a smaller initial loading dose than predicted from total body calculations is rational. It is recommended that half the calculated loading dose, either based on serum concentration or history, should be administered and the impact on clinical features observed. If a clinical response is not seen within 1-2 hours, a further similar dose should be given. In the event of a full response, patients should be monitored for 6-12 hours; a second dose should only be given in the event of recurrence of toxicity. In patients with 'chronic' digoxin poisoning, the serum digoxin concentration will reflect the total body load. However, since such patients are invariably receiving digoxin for therapeutic purposes, full neutralisation is again not indicated. In addition, tissue redistribution of digoxin from deeper stores will occur following the binding of biologically active digoxin in the circulation. This process will occur over a number of hours and if the total calculated dose of antibody is administered in a single bolus, significant quantities will be excreted prior to redistribution of digoxin. Pharmacokinetic logic, therefore, suggests that half the calculated loading dose, based on serum concentration, should be administered and the impact on clinical features observed; a second dose should be given in the event of recurrence of toxicity.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 3","pages":"135-43"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423030-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25257466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-hydroxybutyric acid: neurobiology and toxicology of a recreational drug.","authors":"C Guin Ting Wong,&nbsp;Katherine F Y Chan,&nbsp;K Michael Gibson,&nbsp;O Carter Snead","doi":"10.2165/00139709-200423010-00002","DOIUrl":"https://doi.org/10.2165/00139709-200423010-00002","url":null,"abstract":"<p><p>gamma-Hydroxybutyric acid (GHB) is a short-chain fatty acid that occurs naturally in mammalian brain where it is derived metabolically from gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. GHB was synthesised over 40 years ago and its presence in the brain and a number of aspects of its biological, pharmacological and toxicological properties have been elucidated over the last 20-30 years. However, widespread interest in this compound has arisen only in the past 5-10 years, primarily as a result of the emergence of GHB as a major recreational drug and public health problem in the US. There is considerable evidence that GHB may be a neuromodulator in the brain. GHB has multiple neuronal mechanisms including activation of both the gamma-aminobutyric acid type B (GABA(B)) receptor, and a separate GHB-specific receptor. This complex GHB-GABA(B) receptor interaction is probably responsible for the protean pharmacological, electroencephalographic, behavioural and toxicological effects of GHB, as well as the perturbations of learning and memory associated with supra-physiological concentrations of GHB in the brain that result from the exogenous administration of this drug in the clinical context of GHB abuse, addiction and withdrawal. Investigation of the inborn error of metabolism succinic semialdehyde deficiency (SSADH) and the murine model of this disorder (SSADH knockout mice), in which GHB plays a major role, may help dissect out GHB- and GABA(B) receptor-mediated mechanisms. In particular, the mechanisms that are operative in the molecular pathogenesis of GHB addiction and withdrawal as well as the absence seizures observed in the GHB-treated animals.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 1","pages":"3-20"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423010-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40895089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate.","authors":"Robert B Palmer","doi":"10.2165/00139709-200423010-00003","DOIUrl":"https://doi.org/10.2165/00139709-200423010-00003","url":null,"abstract":"<p><p>gamma-Hydroxybutyrate (GHB) is a GABA-active CNS depressant, commonly used as a drug of abuse. In the early 1990s, the US Drug Enforcement Administration (DEA) warned against the use of GHB and restricted its sale. This diminished availability of GHB caused a shift toward GHB analogues such as gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) as precursors and surrogates. Both GBL and 1,4-BD are metabolically converted to GHB. Furthermore, GBL is commonly used as a starting material for chemical conversion to GHB. As such, the clinical presentation and management of GBL and 1,4-BD intoxication shares a great deal of common ground with that for GHB. This similarity exists not only for acute intoxication but also for withdrawal in those patients with a history of extended high-dose abuse. This review examines the history of GHB analogue abuse as well as the clinical presentation and management of acute intoxication and withdrawal associated with abuse of these compounds.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 1","pages":"21-31"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423010-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40895090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity.","authors":"Christopher R DeWitt,&nbsp;Javier C Waksman","doi":"10.2165/00139709-200423040-00003","DOIUrl":"https://doi.org/10.2165/00139709-200423040-00003","url":null,"abstract":"<p><p>Calcium channel blockers (CCB) and beta-blockers (BB) account for approximately 40% of cardiovascular drug exposures reported to the American Association of Poison Centers. However, these drugs represent >65% of deaths from cardiovascular medications. Yet, caring for patients poisoned with these medications can be extremely difficult. Severely poisoned patients may have profound bradycardia and hypotension that is refractory to standard medications used for circulatory support.Calcium plays a pivotal role in cardiovascular function. The flow of calcium across cell membranes is necessary for cardiac automaticity, conduction and contraction, as well as maintenance of vascular tone. Through differing mechanisms, CCB and BB interfere with calcium fluxes across cell membranes. CCB directly block calcium flow through L-type calcium channels found in the heart, vasculature and pancreas, whereas BB decrease calcium flow by modifying the channels via second messenger systems. Interruption of calcium fluxes leads to decreased intracellular calcium producing cardiovascular dysfunction that, in the most severe situations, results in cardiovascular collapse.Although, CCB and BB have different mechanisms of action, their physiological and toxic effects are similar. However, differences exist between these drug classes and between drugs in each class. Diltiazem and especially verapamil tend to produce the most hypotension, bradycardia, conduction disturbances and deaths of the CCB. Nifedipine and other dihydropyridines are generally less lethal and tend to produce sinus tachycardia instead of bradycardia with fewer conduction disturbances.BB have a wider array of properties influencing their toxicity compared with CCB. BB possessing membrane stabilising activity are associated with the largest proportion of fatalities from BB overdose. Sotalol overdoses, in addition to bradycardia and hypotension, can cause torsade de pointes. Although BB and CCB poisoning can present in a similar fashion with hypotension and bradycardia, CCB toxicity is often associated with significant hyperglycaemia and acidosis because of complex metabolic derangements related to these medications. Despite differences, treatment of poisoning is nearly identical for BB and CCB, with some additional considerations given to specific BB. Initial management of critically ill patients consists of supporting airway, breathing and circulation. However, maintenance of adequate circulation in poisoned patients often requires a multitude of simultaneous therapies including intravenous fluids, vasopressors, calcium, glucagon, phosphodiesterase inhibitors, high-dose insulin, a relatively new therapy, and mechanical devices. This article provides a detailed review of the pharmacology, pathophysiology, clinical presentation and treatment strategies for CCB and BB overdoses.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 4","pages":"223-38"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423040-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25287119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical drug overdose case reports: from the world literature.","authors":"","doi":"10.2165/00139709-200423010-00007","DOIUrl":"https://doi.org/10.2165/00139709-200423010-00007","url":null,"abstract":"","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 1","pages":"59-63"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423010-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40895094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of bronchial responsiveness following exposure to inhaled occupational and environmental agents.","authors":"Graeme P Currie,&nbsp;Jon G Ayres","doi":"10.2165/00139709-200423020-00002","DOIUrl":"https://doi.org/10.2165/00139709-200423020-00002","url":null,"abstract":"<p><p>Inhalation of a range of agents can result in airway inflammation and/or irritation. This may result in occupational asthma or reactive airways dysfunction syndrome. Reactive airways dysfunction syndrome follows a single large exposure to a chemical agent but is now frequently embraced under the wider term of irritant-induced asthma, a term that also includes asthma due to persistent, lower dose irritant exposures. Bronchial hyperresponsiveness is a hallmark of both occupational asthma and reactive airways dysfunction syndrome, although some patients with occupational asthma may occasionally have typical clinical features without increased bronchial hyperresponsiveness. Following removal of the causal agent in occupational asthma, bronchial hyperresponsiveness generally returns towards normal over a 2-year period, although some individuals demonstrate increased bronchial hyperresponsiveness for longer. Measurement of specific bronchial hyperresponsiveness to the primary causal agent in occupational asthma is used diagnostically but not for assessing prognosis. Bronchial hyperresponsiveness to inhaled methacholine can be measured across individual workshifts to assess work-related change. It may also be measured at the end of a work period when exposure has occurred, and compared with values following a period away from work. There have been no direct, systematic comparisons of changes in methacholine responsiveness in the diagnosis of occupational asthma compared with the more frequently used serial peak flow measurements. Patients with reactive airways dysfunction syndrome classically exhibit non-specific bronchial hyperresponsiveness, which can be readily measured by evaluating responses to inhaled methacholine. Bronchial hyperresponsiveness in reactive airways dysfunction syndrome can persist for many years after initial exposure and serial changes can be used to assess recovery and subsequent disability over time.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 2","pages":"75-81"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423020-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing an analytical toxicology service: principles and guidance.","authors":"Robert J Flanagan","doi":"10.2165/00139709-200423040-00005","DOIUrl":"https://doi.org/10.2165/00139709-200423040-00005","url":null,"abstract":"<p><p>Many acutely poisoned patients are treated with no laboratory help other than general clinical chemistry and haematology. Emergency toxicological analyses (24-hour availability) that could influence immediate patient management such as iron, lithium and paracetamol (acetaminophen), are relatively few in number and are remarkably similar worldwide. These assays should be provided at hospitals with large accident and emergency departments. More complex, less frequently needed clinical toxicological assays that can often be offered on a less urgent basis are usually provided from regional or national centres because of the need to make best use of resources. Recommendations as to the assays that should be provided locally and at regional centres are available for the UK and US, and are generally applicable. Regional centres normally diversify into specialised therapeutic drug monitoring, urine screening for drugs of abuse, metals analysis and sometimes forensic work in order to widen the repertoire of tests available and to increase funding. Whatever the type and quantity of work undertaken and the instrumentation used, guidelines are now available delineating staff training, method validation, assay operation, quality control/quality assurance, and indeed virtually all other aspects of laboratory operation. These considerations notwithstanding, clinical interpretation of analytical results remains a difficult area and is the responsibility of the reporting laboratory, at least in the first instance.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 4","pages":"251-63"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423040-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25114528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}