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Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury
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作者 CAO Wei Hua JIANG Ting Ting +17 位作者 SHEN Ge DENG Wen WANG Shi Yu ZHANG Zi Yu LI Xin Xin LU Yao ZHANG Lu LIU Ru Yu CHANG Min WU Shu Ling GAO Yuan Jiao HAO Hong Xiao CHEN Xiao Xue HU Lei Ping XU Meng Jiao YI Wei XIE Yao LI Ming Hui 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第5期494-502,共9页
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was c... Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI. 展开更多
关键词 drug-induced liver injury CYTOKINES Non-steroidal anti-inflammatory drugs INFLAMMATION
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Ensemble Approach Combining Deep Residual Networks and BiGRU with Attention Mechanism for Classification of Heart Arrhythmias
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作者 Batyrkhan Omarov Meirzhan Baikuvekov +3 位作者 Daniyar Sultan Nurzhan Mukazhanov Madina Suleimenova Maigul Zhekambayeva 《Computers, Materials & Continua》 SCIE EI 2024年第7期341-359,共19页
This research introduces an innovative ensemble approach,combining Deep Residual Networks(ResNets)and Bidirectional Gated Recurrent Units(BiGRU),augmented with an Attention Mechanism,for the classification of heart ar... This research introduces an innovative ensemble approach,combining Deep Residual Networks(ResNets)and Bidirectional Gated Recurrent Units(BiGRU),augmented with an Attention Mechanism,for the classification of heart arrhythmias.The escalating prevalence of cardiovascular diseases necessitates advanced diagnostic tools to enhance accuracy and efficiency.The model leverages the deep hierarchical feature extraction capabilities of ResNets,which are adept at identifying intricate patterns within electrocardiogram(ECG)data,while BiGRU layers capture the temporal dynamics essential for understanding the sequential nature of ECG signals.The integration of an Attention Mechanism refines the model’s focus on critical segments of ECG data,ensuring a nuanced analysis that highlights the most informative features for arrhythmia classification.Evaluated on a comprehensive dataset of 12-lead ECG recordings,our ensemble model demonstrates superior performance in distinguishing between various types of arrhythmias,with an accuracy of 98.4%,a precision of 98.1%,a recall of 98%,and an F-score of 98%.This novel combination of convolutional and recurrent neural networks,supplemented by attention-driven mechanisms,advances automated ECG analysis,contributing significantly to healthcare’s machine learning applications and presenting a step forward in developing non-invasive,efficient,and reliable tools for early diagnosis and management of heart diseases. 展开更多
关键词 CNN BiGRU ensemble deep learning ECG arrhythmia heart disease
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AutoRhythmAI: A Hybrid Machine and Deep Learning Approach for Automated Diagnosis of Arrhythmias
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作者 S.Jayanthi S.Prasanna Devi 《Computers, Materials & Continua》 SCIE EI 2024年第2期2137-2158,共22页
In healthcare,the persistent challenge of arrhythmias,a leading cause of global mortality,has sparked extensive research into the automation of detection using machine learning(ML)algorithms.However,traditional ML and... In healthcare,the persistent challenge of arrhythmias,a leading cause of global mortality,has sparked extensive research into the automation of detection using machine learning(ML)algorithms.However,traditional ML and AutoML approaches have revealed their limitations,notably regarding feature generalization and automation efficiency.This glaring research gap has motivated the development of AutoRhythmAI,an innovative solution that integrates both machine and deep learning to revolutionize the diagnosis of arrhythmias.Our approach encompasses two distinct pipelines tailored for binary-class and multi-class arrhythmia detection,effectively bridging the gap between data preprocessing and model selection.To validate our system,we have rigorously tested AutoRhythmAI using a multimodal dataset,surpassing the accuracy achieved using a single dataset and underscoring the robustness of our methodology.In the first pipeline,we employ signal filtering and ML algorithms for preprocessing,followed by data balancing and split for training.The second pipeline is dedicated to feature extraction and classification,utilizing deep learning models.Notably,we introduce the‘RRI-convoluted trans-former model’as a novel addition for binary-class arrhythmias.An ensemble-based approach then amalgamates all models,considering their respective weights,resulting in an optimal model pipeline.In our study,the VGGRes Model achieved impressive results in multi-class arrhythmia detection,with an accuracy of 97.39%and firm performance in precision(82.13%),recall(31.91%),and F1-score(82.61%).In the binary-class task,the proposed model achieved an outstanding accuracy of 96.60%.These results highlight the effectiveness of our approach in improving arrhythmia detection,with notably high accuracy and well-balanced performance metrics. 展开更多
关键词 Automated machine learning neural networks deep learning arrhythmias
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Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors
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作者 Jiao-Jie Xue Su-Tian Hu +6 位作者 Chong-Chong Wang Zhi-Chong Chen Shi-Yao Cheng Shu-Qi Yu Hua-Jing Peng Yi-Tao Zhang Wei-Jie Zeng 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第5期1787-1795,共9页
BACKGROUND Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases.Among which,ventricular arrhythmia is a prevalent clinical concern.This suggests that ventri... BACKGROUND Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases.Among which,ventricular arrhythmia is a prevalent clinical concern.This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors.AIM To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery.METHODS We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection.These patients were evaluated by a 24-h ambulatory electrocardiogram(ECG)at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020.Additionally,41 general healthy age-matched and sexmatched controls were included.Patients were categorized into survival and non-survival groups.The primary endpoint was all-cause mortality,and secondary endpoints included major adverse cardiovascular events(MACEs).RESULTS Colorectal tumors comprised 90%of cases.Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors,100(76.92%)exhibited varying degrees of premature ventricular contractions(PVCs).Ten patients(7.69%)manifested non-sustained ventricular tachycardia(NSVT).The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG[27(21.3)vs 1(2.5),P=0.012]and 24-h ambulatory ECG[14(1.0,405)vs 1(0,6.5),P<0.001].Non-survivors had a higher PVC count than survivors[150.50(7.25,1690.50)vs 9(0,229.25),P=0.020].During the follow-up period,24 patients died and 11 patients experienced MACEs.Univariate analysis linked PVC>35/24 h to all-cause mortality,and NSVT was associated with MACE.However,neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis.CONCLUSION Patients with gastrointestinal tumors exhibited elevated PVCs.PVCs>35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors. 展开更多
关键词 Ventricular arrhythmia Gastrointestinal tumor Major adverse cardiovascular events PROGNOSTIC SURGERY
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Facing ethical concerns in the age of precise gene therapy:Outlook on inherited arrhythmias
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作者 Federico Carbone Fabrizio Montecucco 《World Journal of Cardiology》 2024年第2期64-66,共3页
This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of ... This editorial,comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology.We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias.As monogenic diseases with no or few therapeutic options available through standard care,inherited arrhythmias are ideal candidates to gene therapy in their treatment.Patients with inherited arrhythmias typically have a poor quality of life,especially young people engaged in agonistic sports.While genome editing for treatment of inherited arrhythmias still has theoretical application,advances in CRISPR/Cas9 technology now allows the generation of knock-in animal models of the disease.However,clinical translation is somehow expected soon and this make consistent discussing about ethical concerns related to gene editing in inherited arrhythmias.Genomic off-target activity is a known technical issue,but its relationship with ethnical and individual genetical diversity raises concerns about an equitable accessibility.Meanwhile,the costeffectiveness may further limit an equal distribution of gene therapies.The economic burden of gene therapies on healthcare systems is is increasingly recognized as a pressing concern.A growing body of studies are reporting uncertainty in payback periods with intuitive short-term effects for insurance-based healthcare systems,but potential concerns for universal healthcare systems in the long term as well.Altogether,those aspects strongly indicate a need of regulatory entities to manage those issues. 展开更多
关键词 ETHICS Inherited arrhythmias CRISPR/Cas9 Gene therapy Equitable accessibility
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Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury
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作者 TANG Ya LI Jun +4 位作者 QI Yazhi CAO Rui ZHAI Yan-ling HAN Yu-sheng XU Qiang 《Journal of Hainan Medical University》 CAS 2024年第4期8-14,共7页
Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced... Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI. 展开更多
关键词 Yigan capsule Anti-tuberculosis drug-induced liver INJURY HMGB1 RAGE NF-κB
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Clinical Efficacy of Metoprolol Succinate Extended-Release Tablets in the Treatment of Post-Myocardial Infarction Ventricular Arrhythmias
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作者 Hongrun Gao Xiaohua Zhu Lin Guo 《Journal of Clinical and Nursing Research》 2024年第8期169-174,共6页
Objective:To investigate the clinical efficacy of metoprolol succinate extended-release tablets in the treatment of post-myocardial infarction ventricular arrhythmias.Methods:The clinical data of 84 patients with post... Objective:To investigate the clinical efficacy of metoprolol succinate extended-release tablets in the treatment of post-myocardial infarction ventricular arrhythmias.Methods:The clinical data of 84 patients with post-myocardial infarction ventricular arrhythmia included in the study were collected and they were divided into Groups A and B with 42 cases each using the randomization method.Group A was treated with oral glucosamine hydrochloride,while Group B was administered oral metoprolol succinate extended-release tablets.Combined indicators were used to evaluate the improvement of clinical indicators,therapeutic effects,and the incidence of adverse reactions in the two groups.Results:The baseline data of the two groups of patients were not statistically significant(Pall>0.05);after treatment,the QT dispersion,corrected QT dispersion,and heart rate of Group B were lower than that of Group A(Pall=0.000<0.001);the 2 total clinical effectiveness of Group B was 95.24%,which was significantly higher than 80.95%in Group A(χ=4.087,P=0.043<0.05);the total incidence of adverse reactions in Group B was 4.76%,which was significantly lower than 219.04%in Group A(χ=4.087,P=0.043<0.05).Conclusion:In the treatment of post-myocardial infarction ventricular arrhythmia,the use of metoprolol succinate extended-release tablets can effectively correct the QT dispersion of patients,improve their heart rate,increase clinical effectiveness,and reduce the incidence of adverse reactions. 展开更多
关键词 Metoprolol succinate Myocardial infarction Ventricular arrhythmia Clinical efficacy
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Electrophysiologic Effects of Sophoridine on a Canine Model of Ischemic Ventricular Tachyarrhythmias
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作者 郭治彬 曹宏宇 +1 位作者 徐智 李青 《Journal of Chinese Pharmaceutical Sciences》 CAS 1996年第2期74-80,共7页
A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5 ̄8 days after acute myocardial infarction. The electrophysiologic e... A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5 ̄8 days after acute myocardial infarction. The electrophysiologic effects of sophoridine (Sop) and procainamide (PA) were observed in this canine model. With routine methods of PES, ventricular tachycardia (VT) and ventricular fibrilation (VF) could be reproducibly initiated in this model. Both drugs distinctly lengthened the QTc interval ( P <0.01) and the effective refractory period (ERP) in normal and ischemic ventricular myocardium ( P <0.01), decreased the dispersion of ERP in ischemic myocardium and the dispersion of ERP in left ventricle (P <0.05), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably ( P <0.01). Both drugs effectively prevented the PES-induced VT or VF and ischemia-induced VF ( P <0.05). The results indicated that this canine model is a good and reliable one, sophoridine and procainamide may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardial ischemic damage. 展开更多
关键词 SOPHORIDINE PROCAINAMIDE arrhythmia ISCHEMIC ELECTROPHYSIOLOGY Myocardial infarction
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drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease 被引量:16
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作者 Agustin Castiella Eva Zapata +1 位作者 M Isabel Lucena Raúl J Andrade 《World Journal of Hepatology》 CAS 2014年第4期160-168,共9页
The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-gr... The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of 展开更多
关键词 drug-induced LIVER injury AUTOIMMUNE HEPATITIS DRUGS drug-induced AUTOIMMUNE HEPATITIS drug-induced AUTOIMMUNE LIVER DISEASE
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Practical guidelines for diagnosis and early management of drug-induced liver injury 被引量:59
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作者 Kazuto Tajiri Yukihiro Shimizu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第44期6774-6785,共12页
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There a... The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication. 展开更多
关键词 DIAGNOSIS drug-induced liver injury GUIDELINES MANAGEMENT
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Cardiac arrhythmias and cardiac arrest related to mushroom poisoning: A case report 被引量:5
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作者 Shu Li Qing-Bian Ma +7 位作者 Ci Tian Hong-Xia Ge Yang Liang Zhi-Guo Guo Cheng-Duo Zhang Bei Yao Jia-Ning Geng Fran Riley 《World Journal of Clinical Cases》 SCIE 2019年第16期2330-2335,共6页
BACKGROUND Mushroom exposure is a global health issue.The manifestations of mushroom poisoning (MP) may vary.Some species have been reported as rhabdomyolytic,hallucinogenic,or gastrointestinal poisons.Critical or eve... BACKGROUND Mushroom exposure is a global health issue.The manifestations of mushroom poisoning (MP) may vary.Some species have been reported as rhabdomyolytic,hallucinogenic,or gastrointestinal poisons.Critical or even fatal MPs are mostly attributable to Amanita phalloides,with the development of severe liver or renal failure.Myocardial injury and even cases mimicking ST-segment elevation myocardial infarction (STEMI) have been previously reported,while cardiac arrhythmia or cardiac arrest is not commonly seen.CASE SUMMARY We report a 68-year-old woman with MP who suffered from delirium,seizure,long QT syndrome on electrocardiogram (ECG),severe cardiac arrhythmias of multiple origins,and cardiac arrest.She was intubated and put on blood perfusion.Her kidney and liver functions were intact;creatine kinase-MB was mildly elevated,and then fell within normal range during her hospital stay.We sent the mushrooms she left for translation elongation factor subunit 1α,ribosomal RNA gene sequence,and internal transcribed spacer sequence analyses.There were four kinds of mushrooms identified,two of which were found to be toxic.CONCLUSION This is the first time that we found cardiac toxicity caused by Panaeolus subbalteatus and Conocybe lactea,which were believed to be toxic to the liver,kidney,and brain.We suggest that intensive monitoring and ECG follow-up are essential to diagnose prolonged QT interval and different forms of tachycardia in MP patients,even without the development of severe liver or renal failure.The mechanisms need to be further investigated and clarified based on animal experiments and molecular signal pathways. 展开更多
关键词 MUSHROOM POISONING arrhythmia CARDIAC ARREST SEIZURE Case report
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C-reactive protein as a predictor of malignant ventricular arrhythmias in non-ST elevation myocardial infarction 被引量:4
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作者 Cheng-Gang WANG Xiu-Chuan QIN +3 位作者 Shao-Ping NIE Chun-Mei WANG Hui AI Bin QUE 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2019年第8期614-620,共7页
Objective To investigate whether C-reactive protein (CRP) is a biomarker of malignant ventricular arrhythmias (MVA) occurring in non-ST elevation myocardial infarction (NSTEMI) patients with Global Registry of Acute C... Objective To investigate whether C-reactive protein (CRP) is a biomarker of malignant ventricular arrhythmias (MVA) occurring in non-ST elevation myocardial infarction (NSTEMI) patients with Global Registry of Acute Coronary events (GRACE) scores < 140. Methods A total of 1450 NSTEMI patients were included in this study. Hs-CRP blood levels were measured via a turbidimetric immunoassay after confirming the diagnosis of NSTEMI with GRACE scores < 140. Results Consistent with prior studies, the MVA occurrence rate in our cohort was 6.7%, and patients with MVA exhibited a reduced left ventricular ejection fraction (46.1%± 6.9% vs. 61.5%± 8.7%, P = 0.032), a higher incidence of Killip classification > 1 (34.1% vs. 24.2%, P < 0.001), an increased surgical revascularization rate (34.1% vs. 9.7%, P < 0.001), and increased mortality (16.5% vs. 5.8%, P < 0.001). Serum hs-CRP levels were higher (P = 0.003) in NSTEMI patients with MVA, and this increase appeared unrelated to other clinical parameters. The C-statistic to discriminate MVA was 0.82 (95% CI: 0.74–0.89). Using receiver operating characteristics analysis, we optimized a cutoff point of 16 mL/L, and the sensitivity and specificity were 95% and 61%, respectively;the positive predictive value was 20% and the negative predictive value was 99%. Conclusions An hs-CRP assay is a potential MVA biomarker in low-risk NSTEMI patients with GRACE scores < 140. If validated in prospective studies, hs-CRP may offer a low-cost supplementary strategy for risk stratification for NSTEMI patients. 展开更多
关键词 BIOMARKER C-reactive protein MYOCARDIAL INFARCTION VENTRICULAR arrhythmias
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Drug-induced liver injury:Is it somehow foreseeable? 被引量:30
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作者 Giovanni Tarantino Matteo Nicola Dario Di Minno Domenico Capone 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第23期2817-2833,共17页
The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-4... The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider. 展开更多
关键词 drug-induced liver injury CytochromeP-450 Drug metabolism PHARMACOGENOMICS Herbalremedies
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NAT2*6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis 被引量:21
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作者 Norihide Higuchi Naoko Tahara +14 位作者 Katsunori Yanagihara Kiyoyasu Fukushima Naofumi Suyama Yuichi Inoue Yoshitsugu Miyazaki Tsutomu Kobayashi Koh-ichiro Yoshiura Norio Niikawa, Chun-Yang Wen, Hajime Isomoto,Saburou Shikuwa, Katsuhisa Omagari, Yohei Mizuta, Shigeru Kohno, Kazuhiro Tsukamoto Norio Niikawa Chun-Yang Wen Hajime Isomoto Saburou Shikuwa Katsuhisa Omagari Yohei Mizuta Shigeru Kohno Kazuhiro Tsukamoto 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第45期6003-6008,共6页
AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat... AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity. 展开更多
关键词 TUBERCULOSIS Anti-tuberculosis drugs drug-induced hepatotoxicity NAT2-haplotype DNA-baseddiagnosis
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Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists 被引量:19
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作者 Raúl J Andrade Mercedes Robles +3 位作者 Alejandra Fernández-Castaer Susana López-Ortega M Carmen López-Vega M Isabel Lucena 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第3期329-340,共12页
Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosi... Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected. 展开更多
关键词 drug-induced hepatotoxicity Causality assessment Diagnostic algorithms Clinical scales
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Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43(cx43) 被引量:15
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作者 Tao Wu Dan Wu +6 位作者 Qinghua Wu Bing Zou Xiao Huang Xiaoshu Cheng Yanqing Wu Kui Hong Ping Li 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第10期985-990,共6页
Objective: To explore the effect and mechanism of angiotensin II receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2... Objective: To explore the effect and mechanism of angiotensin II receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group. ischemia group. Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO). myocardial infarction group (MI). Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorpholouy of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level. Results: The intervention of lrbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P<0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (p<0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group (P<0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P<0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group (P<0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P<0.01(US) SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias. 展开更多
关键词 IRBESARTAN Myocardial lschemia CX43 CONNEXIN arrhythmias
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Dissecting the molecular pathophysiology of drug-induced liver injury 被引量:22
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作者 Hui Ye Leonard J Nelson +2 位作者 Manuel Gómez del Moral Eduardo Martínez-Naves Francisco Javier Cubero 《World Journal of Gastroenterology》 SCIE CAS 2018年第13期1373-1385,共13页
Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical... Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways. 展开更多
关键词 signaling PATHWAYS ACETAMINOPHEN drug-induced liver injury cell DEATH reactive oxygen species
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Evaluation of prognostic markers in severe drug-induced liver disease 被引量:13
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作者 Bo Li Zhi Wang +2 位作者 Jian-Jiang Fang Ci-Yi Xu Wei-Xing Chen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第4期628-632,共5页
AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule... AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy’s rule and the most important predictors for outcome. METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed. RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD,and 140 (52.8%) of them were female. hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminanthepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012). CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal medicine stands out as the most common drug for DILD. While antitubercular drugs are found to be the primary etiological factor for fetal DILD, hepatic encephalopathy, ascites, jaundice, alcohol abuse and direct bilirubin levels are associated with the death of DILD patients. 展开更多
关键词 drug-induced liver disease PROGNOSIS Prognostic marker MORTALITY
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Drug-induced autoimmune hepatitis:A minireview 被引量:7
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作者 Chin Kimg Tan Danielle Ho +1 位作者 Lai Mun Wang Rahul Kumar 《World Journal of Gastroenterology》 SCIE CAS 2022年第24期2654-2666,共13页
Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH inc... Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH. 展开更多
关键词 drug-induced liver injury drug-induced autoimmune hepatitis Autoimmune hepatitis REVIEW
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Contemporary review of drug-induced pancreatitis: A different perspective 被引量:12
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作者 Whitney Y Hung Odaliz Abreu Lanfranco 《World Journal of Gastrointestinal Pathophysiology》 CAS 2014年第4期405-415,共11页
Although gallstone and alcohol use have been consid-ered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are as-sociated with this disease state. The true incidence is unkno... Although gallstone and alcohol use have been consid-ered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are as-sociated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pan-creatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal rela-tionship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classifi-cation systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continu-ously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifacto-rial nature of acute pancreatitis call for a different ap-proach. In this article, we review the potential mecha-nisms of drug induced acute pancreatitis and providethe perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pan-creatitis with limited data. 展开更多
关键词 drug-induced PANCREATITIS MECHANISM
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