2014 Volume 16 Issue 3 Published: 28 June 2014

  

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  Pay attention to safety of nucleotides in longterm treatment of chronic hepatitis B

  Ren Hong

  2014, 16(3): 129-3.

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  Emphasis on drug-induced liver injury in the elderly

  Ding Huiguo

  2014, 16(3): 132-2.

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论著

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  Bibliometric analysis on hepatotoxicity due to antifungal drugs

  Bai Yan;Li Yue;Liu Bin;Wang Kun;Mei Hekun;Zhang Ying;Wang Jin;Wang Rui

  2014, 16(3): 134-5.

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  To investigate the research progress of hepatotoxicity due to antifungal drugs, in order to provide a reference for clinical safety use of antifungal drugs.Methods"Antifungal drugs" and "hepatotoxicity" were selected as the keywords, and PubMed, Embase, Web of Science, Chinese Academic Periodical Full-text Database China HowNet Chinese Academic Journal (CNKI) and Chinese Biomedical Literature database (CBMdisc) were searched. All literature on hepatotoxicity due to antifungal drugs were selected. A database of literature accepted for final bibliometric study was established by using Microsoft Excel. The parameters of bibliometrics such as published time (years), the top 5 countries and institutes in publishing, literature′s type, published time (years), top 5 journals in publishing number, top 10 articles in terms of cited frequency were studied. The main content and hotspot of literature were analyzed. The clinical manifestations, mechanism, incidence and prophylactico-therapeutic measures of hepatotoxicity due to antifungal drugs were summarized.ResultsA total of 221 articals (193 in English, 28 in Chinese) were enrolled in the study, of which 116 were original articles, 49 reviews and 56 case reports. The published time of first original publication of hepatotoxicity due to antifungal drugs were 1976. The journal which published largest number of articles was Mycoses. The highest citation number of individual article was 531. The main clinical manifestations were weak, right upper quadrant pain, diarrhea, jaundice, cholestasis and fever. The severe cases could cause liver failure. Laboratory examination showed elevated serum transaminases, bilirubin, and alkaline phosphatase. The incidence of liver toxicity due to azole antifungals was higher, the incidence of liver toxicity due to amphotericin B was lower. The antifungal drugs should be used with caution in patients with hypohepatia. For the patients who used antifungal drugs for long time, the liver function should be monitored regularly. If liver injury occurs, the antifungal drugs should be stopped immediately. Some patients′ liver function test results could return to the normal levels before administration of the symptomatic treatment and the supportive liver protection therapy. The mechanism of hepatotoxicity due to antifungal drugs was unknown, it may be related to the damage of cytoplasmic membrane structure and inhibition of metabolism in cytochrome P450 2D6 enzyme. ConclusionsThe research abroad on hepatotoxicity due to antifungal drugs are ahead of China. Hepatotoxicity due to antifungal drugs is partially reversible.
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  Efficacy and safety of endoscopic embolization with Glubran-2 glue for gastric varices in liver cirrhosis

  hang Shibin;Song Yanming;Feng Li;Zhao Yuan;Ding Huiguo

  2014, 16(3): 139-4.

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  ObjectiveTo preliminarily evaluate efficacy and safety of endoscopic embolization with Glubran-2 glue for gastric varices in liver cirrhosis.MethodsForty-nine patients with cirrhosis gastric varices, admitted to Beijing You′an Hospital from January 2011 to December 2012, underwent endoscopic embolization with Glubran-2 glue under gastroscopy. Of the 49 cases, 40 were males and 9 females with age of 34-82 (55±11) years. Of these patients, 19 were at Child-Pugh class A, 23 class B, and 7 class C. Of the 49 patients, 22(44.9%) had isolated gastric varices (IGV) and 27 patients (55.1%) had gastro-esophaged varices (GOV). The methods were as follows: 50% glucose was prefilled in injection syringe and, after injecting Glubran-2 glue at the location of gastric varices, the left Glubran-2 glue in injection syringe was injected into the varicose vein via the 50% glucose. The Glubran-2 glue was given by way of one spot or multiple spot and each spot needed Glubran-2 glue 1.0-3.0 ml. The endoscopic embolization completed at one time as possible. The situation of varicose veins disappearing was observed under gastroscopy at months 1, 3, 6 after treatment. Safety evaluation index included postoperative burning sensation below the xiphoid, ectopic embolism, fever, blood routine test before operation and at 3 days after operation, and liver and renal functions before operation and at months 1, 3, 6 after operation.ResultsThe total dose of Glubran-2 glue for IGV patients was 2.0-12.0 ml every patient with an average dose of (4.7±2.6) ml and for GOV patients was 1.0-9.0 ml with an average dose of (4.2±2.1) ml. Of the 49 patient, varicose veins of 45 patients (91.8%) disappeared and varicose veins of 4 patients(8.2%) improved; extrusions of glue was seen in 18 patients (36.7%) at one month, 30 patients (61.3%) at 3 month, and 1 patient (2.0%) at 6 months after treatment. All the patients experienced burning sensation below the xiphoid after glue injection. Three patients presented with fever after operation but their temperature did not exceed 38 ℃. No patient developed ectopic embolism. Nine patients (18.4%) deve-loped errhysis due to local ulcer because of extrusions of glue and massive haemorrhage did not occur. There were no obvious differences in blood routine test and liver and renal functions before and after treatment.ConclusionEndoscopic embolization with Glubran-2 glue is effective and safe for treatment of gastric varices in liver cirrhosis patients.
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  Analysis of risk signals of liver injuries related to nonsteroidal anti-inflammatory drugs using reporting odds ratio

  Lan Xi;Wang Shengfeng;Zhai Suodi;Ren Jingtian;Jiao Ligong

  2014, 16(3): 143-4.

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  ObjectiveTo analyze risk signals of liver injuries related to nonsteroidal anti-inflammatory drugs (NSAID) and application of reporting odds ratio (ROR) in data mining.MethodsA search of adverse drug reaction(ADR) reports in Beijing of national monitoring system of adverse drug reaction from January 1st 2013 to December 31st 2013 was conducted using keywords "liver" and "gallbladder" . Of these filtered reports, the cases whose causal relationship of drugs and liver injuries was judged as "positive", "likely", or "possible" were enrolled into liver injury group and the rest cases were all enrolled into non-liver injury group. Using NSAID as the target drugs and the other drugs as non-target, ROR and its 95% confidence interval (CI) of liver injuries related to NSAID were calculated according to formula of ROR. The lower limit of 95% CI >1 was regarded as suggestive of ADR signal.ResultsAfter removing duplication, 14 657 patients were enrolled in the study, which comprised liver injury group 626 patients including 35 cases of liver injuries due to NSAID and non-liver injury group 14 031 patients. Of the 35 patients with liver injuries related to NSAID, 30 patients were associated with single-preparation NSAID and 6 patients were associated with compound-preparation. The ROR levels and their 95% CI of single-preparation NSAID, compound-preparation NSAID, and general NSAID were respectively 1.78 (1.22-2.61), 1.80(0.78-4.15), and 1.76 (1.24-2.51). Both of the lower limits of 95% CI of live injuries related to single-preparation NSAID and general NSAID were higher than 1 and there were ADR signals. Thirty-seven kinds of drugs were involved by 35 cases of liver injuries. Of them, the ROR levels and their 95% CI of single-preparation parecoxib, single-preparation aspirin, compound-preparation ibuprofen and pseudoephedrine, and compound-preparation parace-tamol and amantadine hydrochloride were respectively 8.00(2.03-27.78), 2.45(1.43-4.21), 22.00(1.40-359.32), and 11.22(1.02-123.94) and there were ADR signals.ConclusionsAttention should be paid to liver injuries related to NSAID. The method of ROR can help analyze ADR signals and provide useful early-warning of drug safety.
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  Comparison and analysis of antimicrobial susceptibility of pathogens from infected patients in Departments of Internal Medicine and Surgery

  Kang Jianbang;Tian Zhihong;LI Xiaoxia;Zhang Runmei;Duan Jinju;Zhang Ruiqin

  2014, 16(3): 147-6.

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  ObjectiveTo understand the species and susceptibility of pathogens isolated from patients hospitalized in Departments of Internal Medicine and Surgery, and provide scientific basis for reasonable application of antibacterials and prevention and control of drug-resistant bacteria.MethodsThe pathogen isolation and drug sensitive test reports were collected from inpatients in Departments of Internal Medicine and Surgery in Second Hospital of Shanxi Medical University in 2012. The specimens included urine, blood, secretions, sputum, feces, throat swabs, cerebrospinal fluid, and so on. The original data were analyzed by WHONET 5.5 and SPSS 16.0 software and the distribution and susceptibility of pathogens isolated from patients hospitalized in Departments of Internal Medicine and Surgery were compared.ResultsA total of 4 268 strains of bacteria were isolated from 4 092 patients. Of them, 2 257 strains were isolated from 2 182 patients in the Department of Internal Medicine and 2 011 were isolated from 1 910 patients in the Department of Surgery. The top 5 bacteria in Department of Internal Medicine were Escherichia coli, Klebsiellapneumonia, Pseudomonas aeruginosa, Coagulase-positive Staphylococcus aureus, and Aerobacter cloacae. The top 5 bacteria in Department of Surgery were Escherichia coli, Pseudomonas aeruginosa, Klebsiellapneumonia, Acinetobacter baumannii，and Aerobacter cloacae. The antimicrobial susceptibility of some pathogens isolated from patients in Department of Internal Medicine were higher than that in Department of Surgery, they were as follows: Escherichia coli vs. cefoperazone/sulbactam, cefepime, ceftazidime, ceftriaxone, amd cefuroxime nitrofurantoin［62.7%(271/432) vs. 580%(202/348), 65.5%(283/432) vs. 55.5%(193/348), 63.8%(275/431) vs. 53.3%(185/347), 41.8%(180/431) vs. 34.4%(120/349), 34.0%(146/430) vs. 26.6%(93/349)］; Enterobacter cloacae vs. cefepime［94.4%(151/160) vs. 83.3%(140/168)］; Pseudomonas aeruginosa vs. amikacin ［92.2%(190/206) vs. 86.1%(230/267)］; Acinetobacter baumannii vs. imipenem, meropenem, cefoperazone/sulbactam, ciprofloxacin, and minocycline ［30.1%(31/103) vs. 19.0%(41/216), 29.7(30/101) vs. 17.5%(38/217), 19.4%(20/103) vs. 10.8%(23/213), 19.2%(19/99) vs. 9.8%(20/204), 23.2%(22/95) vs. 11.1%(22/198)］. The antimicrobial susceptibility of some pathogens isolated from patients in Department of Internal Medicine were lower than that in Department of Surgery, they were as follows: Staphylococcus aureus vs. trimethoprim/sulfamethoxazole, gentamicin, clindamycin ［54.8% (40/73) vs. 78.9%(71/90), 50.0%(37/74) vs. 71.3%(62/87), 28.8%(21/73) vs. 46.6%(41/88)］; Klebsiella pneumoniae vs. levofloxacin ［77.3%(269/348) vs. 90.5%(239/264)］, Pseudomonas aeruginosa vs. tobramycin ［81.8%(148/181) vs. 88.7%(235/265)］. The differences above mentioned were statistically significant (all P< 0.05). ConclusionsThe species of bacteria isolated from patients in Department of Internal Medicine and Surgery are different and the susceptibility of the same kind of bacteria to the same kind of antibacterial agent is also different. Clinician should use antibacterials rationally according to the results of drug sensitivity tests.
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  Correlation analysis on polymorphisms of multidrug resistance 1 gene and nephrotoxicity induced by cyclosporine in heart transplant recipients

  Shi Xiujin;Wei Guoyi;Lin Yang;Zhang Haibo;Zhong Yu;Bai Yuguo;Zhou Yang;Jia Yixin

  2014, 16(3): 153-6.

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  ObjectiveTo explore the correlation between polymorphisms of multidrug resistance 1(MDR1) gene and nephrotoxicity induced by cyclosporine (CsA) in heart transplant recipients. Methods
  The patients who received cardiac transplantation in Beijing Anzhen Hospital from January 2004 to December 2012, postoperative immunosuppression treatment with CsA, and follow-up for at least 12 months, were selected as subjects. All patients were divided into the kidney injury group and the no kidney injury group according as whether kidney injury occurred after CsA treatment. Leukocyte genomic DNA was extracted from the blood which was taken for CsA concentration monitoring after heart transplant. According to information sites in HapMap database, genotype and allele frequencies of 16 tags of MDR1 SNP were analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). SNP allele frequencies were compared with frequencies obtained from dbSNP database and non-conditional binary logistic regression analysis was used to analyze the correlation between the SNP genetic polymorphisms and kidney injury induced by CsA.ResultsA total of 65 patients were entered into this study. Of them, 19 patients were in the kidney injury group (17 males and 2 females) with age of 18-59 (44±13) years and 46 patients were in the no kidney injury group (39 males and 7 females) with age of 14-71 (42±15) years. There was no statistically significant difference in age and gender between the 2 groups (P>0.05 for all comparisons). According to MALDI-TOF MS detection results, the differences of allele frequencies in 16 tag SNP and corresponding data in dbSNP database, and the differences of allele frequencies in 16 tag SNP between the 2 groups were not statistically significant (all P>0.05). Based on the non-conditional Logistic regression analysis, there was no significant correlation between genetic frequency of MDR 1 in these 16 Tag SNP and the CsA nephrotoxicity in patients with kidney injury.ConclusionNo statistically significant correlation between MDR1 gene polymorphism and nephrotoxicity induced by cyclosporine in heart transplant recipients is found.
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  Effects of sarcoplasmic reticulum Ca2+ -ATP enzyme in myocardial damage due to daunorubicin in rats

  Luo Lingjuan;Xie Xinmei;He Wenting;Zeng Fanye;Zhang Hongliang

  2014, 16(3): 159-4.

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  ObjectiveTo explore the mechanism of in myocardial damage due to daunorubicin (DNR) in rats.MethodsSD rats were divided into the control group and the DNR group using a random-digital table, each group comprised 15 rats. The rats in the DNR group received intraperitoneal injection of daunorubicin 3.5 mg/kg once a week for 4 weeks. The rats in the control group received intraperitoneal injection of same volume of 0.9% sodium chloride solution once a week for 4 weeks. The rats′behavior changes in the 2 groups were observed. The electrocardiographic examination, expression of sarcoplasmic reticulum Ca2+-ATP enzyme (SERCA2a) and histopathological test were performed at the end of 1, 3 and 4 weeks of the experiment on 5 rats in the 2 groups, respectively. ResultsThe subacute myocardial injury rat model could be reproduced by DNR intraperitoneal injection. The rats in the DNR group developed lassitude, drumble and drowsiness from the second week. The control group rats′activity, body weight and feeding were normal. The electrocardiographic examination in DNR group showed the following results: voltage of QRS wave decreased by more than 30% compared with the normal, ST segment elevation, and P wave peaked. Myocardial tissue histopathological examination revealed turbid cytoplasm, vacuolation, disordered arrangement of muscle fiber, and broadened fiber gaps. The expression of SERCA2a were moderately positive in both groups at the end of the first week. The expression of SERCA2a were weakly positive in the DNR group at the end of the third and fourth weeks. The number of SERCA2a positive cells in the DNR group at the end of the third and fourth weeks was significantly less than that in the control group at the same time points ［(42.2±1.2) vs (65.30±1.6), (35.2±6.0) vs (66.7±1.5), all P＜0.05］.ConclusionDNR may inhibit the expression of SERCA2a in myocardial tissue and it may be one of the mechanisms of DNR′s myocardial toxicity.

综述

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  Tenofovir-induced kidney-bone damage: prevention and management

  Jiang Yuyong;Cai Haodong

  2014, 16(3): 163-5.

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  Tenofovir is a new class of nucleotide reverse transcriptase inhibitor with effective for treating HIV-infection and chronic hepatitis B. The potential renal toxicity of tenofovir is related to renal excretion. Renal histopathology revealed tubular injury. The main clinical manifestations of renal damage are decreased phosphorus and increased serum creatinine, and Fanconi syndrome, interstitial nephritis and acute renal failure may also develop. The bone toxicity of tenofovir is secondary to renal toxicity. The clinical manifestations include muscle weakness, bone pain and bone fracture. Tenofovir caused kidney-bone damage are associated with underlying diseases, gene polymorphism, plasma drug concentration and drug interactions. Patients taking tenofovir should be regularly monitored for renal function and electrolyte. The hypophosphatemia were treated with phosphate supplementation. The drug dosage should be adjusted when creatinine clearance rate is <50 ml/min. Renal function was improved markedly after tenofovir withdrawal in some patients, but part of patients progressed to chronic kidney disease.
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  Clinical application and adverse reactions of febuxostat

  Yang Xue;Xue Yu;Zou Hejian

  2014, 16(3): 168-3.

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  Febuxostat is a new type of selective xanthine oxidase inhibitor, which mainly be used for the treatment of hyperuricemia patients with gout symptoms. The recommended initial dose of febuxostat is 40 mg once daily. In the present, there is no sufficient evidence to demonstrate that the clinical effects of febuxostat in reducing the uric acid are better than that of allopurinol. However, it is reported that febuxostat in 80 mg has better treatment effects in gout patients with diabetes or ≥ 65 years old. The common adverse reactions of febuxostat are liver dysfunction, diarrhea, headache, nausea, rash, and so on. The differences of adverse reactions in cardiovascular system between febuxostat and allopurinol are not statistically significant.
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  Drug-induced delirium

  Zheng Shanshan;Mei Dan

  2014, 16(3): 171-4.

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  Drug-induced delirium is a common drug-induced diseases, which is especially common in patients who are at advanced ages, with nervous system disease, experienced surgical operations or in critically ill patients. Drug-induced delirium is mainly associated with neurological dysfunction, which is caused by drugs affecting neurotransmitter synthesis, release and metabolism. Anticholinergic medicines and antidepressant medicines have a relatively high pathogenic rate. Rational use of drugs can avoid drug induced delirium. Besides, early diagnosis and treatment is quite important.

病例报告

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  病例报告

  Third degree atrioventricular block caused by levofloxacin

  Lyu Xiaofei;Nian Min;Li Haiqin;Qiu Su

  2014, 16(3): 175-2.

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  A 21-year-old female with acute gastroenteritis received an intravenous infusion of levofloxacin 0.4 g, once daily. She developed palpitation, sense of suppression in the chest and dizzy suddenly during the intravenous infusion on day 3. Electrocardiographic examination showed the following results: heart rate 39 times/min, third degree atrioventricular block, junctional escape beat and ventricular escape. Levofloxacin was withdrawn immediately. Twenty-six minutes later, third degree atrioventricular block converted to first-degree atrioventricular block and the heart rate was 58-66 times/min spontaneously.
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  病例报告

  Atrioventricular block related to azithromycin

  Li Ying;Xu Zheng;Zhang Haiying;Feng Wanyu;Gong Pihua

  2014, 16(3): 176-2.

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  An 86-year-old female patient with pulmonary infection was treated with IV infusions of ceftriaxone sodium 2.0 g once daily, azithromycin 0.5 g once daily, and ambroxol hydrochloride 30 mg twice daily. About 30 minutes after the fourth infusion of azithromycin, the patient abruptly developed chest tightness and suffocation. Electrocardiography showed Ⅲ degree atrioventricular block. Azithromycin was stopped immediately and she was treated with oxygen inhalation. One hour later, the symptoms of chest tightness and suffocation disappeared. Five hours later, a repeat electrocardiography showed sinus rhythm. Azithromycin was not given again and the similar symptoms did not recur any more.
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  Tripterygium glycosides-induced amenorrhea

  Lu Min;Zhou Ying;Cui Yimin;Bai Wenpei

  2014, 16(3): 177-2.

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  A 41-year-old female patient received tripterygium glycosides 20 mg thrice daily, prednisone 20 mg once daily, valsartan 80 mg once daily, amlodipine besylate 5 mg once daily, calcium carbonate 750 mg thrice daily and calcitriol 0.25 μg once daily for glomerulonephritis and renal hypertension. Tripterygium glycosides and prednisone had to discontinue because the patients developed amenorrhea about one month after the therapy, and amenorrhea has lasted for five months. The sex hormone levels were measured as follows: luteinizing hormone 29 U/L, follicle-stimulating hormone 7 U/L, estradiol 1 168 pmol/L, prolactin 0.02 nmol/L, testosterone 0.12 nmol/L; progesterone 1.5 nmol/L. Hormone replacement therapy with dydrogesterone 10 mg twice daily for 10 days was given. Her menstruation started on day 4 after dydrogesterone discontinuation and lasted for 5 days. The regular menstrual cycle has been restored.
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  病例报告

  Somnambulism and delirium caused by midazolam maleate

  Wei Ming;Niu Xiangping

  2014, 16(3): 179-1.

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  A 67-year-old female patient received midazolam maleate 7.5 mg at bedtime for insomnia. She experienced falling asleep fast and better sleep quality during the initial treatment period. Three months later, she self-medicated double dosage due to poor sleep. Two months later, she developed auditory hallucination occasionally during the daytime and suffered somnambulism frequently at night, and complicated by delirium and agitation. Midazolam maleate was discontinued and switched to doxepin 25 mg every night. At a follow-up 2 weeks later, the symptoms of somnambulism and delirium disappeared.
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  病例报告

  Anaphylactic shock due to somatostatin for injection

  Qin Li;Liu Miao;Wu Rongrong;Cao Mingxue;Zhu Hong;Xia Hui;Liu Fengqun

  2014, 16(3): 180-2.

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  A 51-year-old male hepatitis B patient with decompensated liver cirrhosis received IV infusions of somatostatin 3 mg for continuous 12 hours, lansoprazole 30 mg every 12 hours, vitamin K1 10 mg once daily due to upper gastrointestinal hemorrhage. The IV infusions of vitamin K1 and lansoprazole were completed within 2 hours and the patient did not present discomfort symptoms. About 2.5 hours after the IV infusion of somatostatin, the patient developed chills and dyspnea. Somatostatin was withdrawn immediately. About 10 minutes later, he lost consciousness and had no response to voice stimuli. His heart rate was 160 times/min, respiratory rate was 32 breaths/min, and blood pressure undetectable. He was treated with oxygen mask. Intravenous dexamethasone 10 mg, subcutaneous injection of epinephrine 1 mg and intramuscular injection of promethazine 25 mg were given. About 20 minutes later, the patient slowly began to regain consciousness, but still had listlessness and apathy. His symptoms such as chills and dyspnea disappeared 1.5 hours later, and then his heart rate was 110 times/min, respiratory rate was 23 breaths/min, and blood pressure was 109/50 mmHg. His therapy was changed to octreotide acetate 0.5 mg in 0.9% sodium chloride injection 60 ml every 12 hours via IV pump, lansoprazole and vitamin K1 were continued, the similar symptoms did not recur.
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  病例报告

  Enoxaparin sodium-induced thrombocytopenia

  Liu Jun;Wei Jun

  2014, 16(3): 181-2.

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  A 63-year-old male patient received anticoagulation therapy with a SC injection of enoxaparin sodium 4 000 U twice daily on the first day after mitral valve and aortic valve replacement. His platelet counts were within normal range before surgery and on the first day after surgery. On day 2 after surgery，his platelet count decreased to 41×109/L and a SC injection of recombinant human　interleukin-11 15 mg once daily was given. On day 3 after surgery，his platelet count was 22×109/L. Enoxaparin sodium was withdrawn. On days 4 and 5，the platelet counts increased to 45×109/L and 59×109/L，respectively. On day 6, his platelet count was 128×109/L.
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  Severe delayed diarrhea and myelosuppression due to irinotecan

  Zhao Xia;Li Yan;Xu Wei;Han Yi

  2014, 16(3): 183-2.

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  A 63-year-old woman with colon cancer was treated with a chemotherapy consisting of irinotecan and oxaliplatin. She was given irinotecan 200 mg plus oxaliplatin 200 mg by subclavian vein intubation on the first day, and irinotecan 160 mg on the 8th day. On day 7, the patient developed yellow stools. The chemotherapy discontinued. Drugs for protection of intestinal mucosa and antidiarrheal agent were given. On day 8 night, she had a fever. The temperature was 38.0 ℃. Laboratory tests showed the following values: WBC count 0.27×109/L，platelet count 117×109/L. Anti-infection therapy was given. On day 14, the severe watery stool appeared again, laboratory tests showed following values: serum potassium 2.26 mmol/L, sodium 126 mmol/L. She received the therapies for infection control and correcting electrolyte imbalance. On day 16, the patient presented persistent fever, severe abdominal distension with intestinal paralysis. Laboratory tests showed following values: WBC count 0.25×109/L，platelet count 25×109/L. She was given imipenem and cilastatin sodium and octreotide. On day 18, her blood pressure decreased to 70/40 mmHg, blood oxygen saturation was not monitored. She was in a coma. On day 19, the patient died despite all rescue measures.