Liver fibrosis attributed to lipid lowering medications: two cases

We identified two cases of chronic active hepatitis with liver fibrosis induced by lipid lowering drugs of the statin and fibrate classes despite regular monitoring of transaminases. There are few reports of clinically significant hepatitis induced by these drugs and even fewer cases of fibrosis. Given the growing use of these drugs, there are implications for monitoring patients on long-term therapy for liver damage.     

Ototoxicity of common topical antimycotic preparations

OBJECTIVE: To determine the ototoxic effects of five commonly used topical antimycotic agents-clotrimazole, miconazole, nystatin, tolnaftate, and gentian violet-in the guinea pig. DESIGN: A controlled animal study in which the ototoxicity of commonly used topical antifungal agents was investigated by measurement of hair cell loss. METHODS: Several readily available topical antimycotic preparations were instilled into the middle ears of female Hartley guinea pigs over a 1-week period. Two weeks after the last instillation, the animals were euthanized. An active control group was treated with neomycin to confirm the adequacy of the treatment in delivering a known ototoxin; an untreated control group defined the normal distribution of hair cells. The temporal bones were removed, and the cochleas were fixed and dissected. The basilar membranes were examined under the scanning electron microscope. A map of hair cell survival was made for each row in segments of each turn. RESULTS: The untreated control animals had no discernible hair cell loss in the two lower turns. In the apical turn and sometimes the third turn, loss of hair cells was a common finding, this is a known effect of aging in this species. The animals treated with neomycin had damage consistently in the basal turn, sometimes extending into the second turn, as well as the expected hair cell loss in the apical turn. Clotrimazole, miconazole, or tolnaftate did not cause any hair cell loss in the first two turns. Hair cell loss in the third and fourth turns was similar to that of the untreated control group. Likewise, nystatin exhibited no evidence of ototoxicity. Of note, however, the preparation used in this study left a persistent residue in the round window niche. Of the first four animals treated with gentian violet, three developed pronounced behavioral signs of vestibular damage, and three demonstrated extensive middle ear inflammation and extensive new bone growth. Hair cell counts were not attempted because the extreme bone growth interfered with successful perfusion and dissection. CONCLUSIONS: Extrapolating from guinea pigs to humans requires caution. However, it is likely that guinea pigs are, if anything, more susceptible to topical ototoxins than are humans. The specific antimycotics clotrimazole, miconazole, and tolnaftate appear to be safe. Gentian violet has the potential for severe damage. The persistent residue left by the nystatin preparation is cause for concern and is a reminder that both the active ingredient and vehicle must be considered in evaluation of safety.     

An animal model for external ear canal inflammation

OBJECTIVE: To develop an animal model for testing efficacy of anti-inflammatory drugs designed to treat external ear canal (EAC) disease. METHODS: Histological and morphometric methods were used to characterize EAC inflammation produced by topical application of tetradecanoylphorbol acetate (TPA) in mice. The effects of both single and repeated TPA applications were studied. A treatment trial was performed to evaluate the effects of a ciprofloxacin/hydrocortisone suspension on TPA-induced EAC inflammation. In 10 animals, two bilateral applications of TPA were made, spaced 24 hours apart. Immediately after the second TPA application, otic suspension was applied unilaterally four times over a 48-hour period. The contralateral EACs were left untreated to provide TPA-only controls. RESULTS: Twenty-four hours after a single TPA application, EAC skin showed polymorphonuclear (PMN) leukocyte infiltration, vascular dilation, and thickening of the dermis and epidermis. Dermal and epidermal thickening were more pronounced after two TPA applications and PMN leukocyte infiltration remained high 48 hours after a second TPA placement. After treatment with the otic suspension, PMN leukocyte counts were reduced by an average of 76% relative to EACs that received TPA only. There was also statistically significant reduction of dermal swelling and a trend toward reduced epidermal thickness. Vascular dilation was clearly reduced as well EACs that received four applications of the suspension alone showed no adverse effects compared with those that received saline. CONCLUSION: TPA-induced inflammation of the mouse EAC provides a suitable model for testing the therapeutic efficacy of anti-inflammatory agents being considered for clinical use.     

用MTT法检测抗真菌药物对白念珠菌的敏感性

目的:了解白念珠菌对氟康唑和伊曲康唑的敏感性。方法:采用MTT微量稀释法,检测58株白念珠菌对两种抗真菌药物的敏感性。结果:绝大部分菌株对两种抗真菌药物敏感,部分菌株为剂量依赖性敏感,氟康唑对白念珠菌的敏感率高于伊曲康唑,两者比较有统计学差异,并且对氟康唑耐药的菌株往往对伊曲康唑也耐药。结论:MTT微量稀释法具有结果客观、易于分析、灵敏度高的特点。本研究结果提示,临床上存在交叉耐药菌株感染现象,应引起重视。     

糖尿病足的病原体分布及其耐药性分析

目的探讨本地区糖尿病足感染病原体分布及其耐药性,为临床合理应用抗菌药物提供依据。方法对糖尿病足感染患者的创面分泌物进行细菌和真菌培养,用K-B法或稀释法行药敏试验。结果95例糖尿病足感染分泌物标本中69例(72.6%)培养出病原体,分离出病原体106株,其中革兰阳性菌51株(占48.1%),革兰阴性菌50株(占47.2%),真菌5株(占4.7%);产超广谱β-内酰胺酶(ESBLs)的细菌15株,占肠杆菌科细菌的34.1%。糖尿病足感染以凝固酶阴性葡萄球菌、金黄色葡萄球菌、变形杆菌和大肠埃希菌为主,也可见真菌感染。药敏试验结果提示多重交叉耐药,革兰阴性菌对亚胺培南及加β-内酰胺酶抑制剂的抗菌药物较为敏感,革兰阳性菌对万古霉素、氯霉素及头孢菌素较敏感;大肠埃希菌对常用抗菌药物均有耐药;凝固酶阴性葡萄球菌和肠球菌除万古霉素外,对其他临床常用抗菌药物也均有耐药性。结论糖尿病足感染的病原体分布广泛,对抗菌药物耐药率高,应选择广谱抗菌药物联合用药。     

国产番泻叶的泻下及抗骨质疏松作用研究

目的：探讨国产番泻叶的泻下及雌性激素样抗骨质疏松作用。方法：比较国产与进口商品番泻叶提取物对小鼠排便和肠蠕动作用的影响,观察其泻下通便的效果。并通过观察对去势雌性小鼠动情周期、子宫重、股骨重的变化和血钙、血磷、降钙素含量的影响,研究由国产番泻叶制备而得的番泻总苷提取物的雌性激素样抗骨质疏松作用。结果：两种商品番泻叶提取物与生理盐水对照组相比均能显著增加墨汁推进率、缩短首次排便时间,增加6h排便量,两种商品之间无显著性差异。由国产番泻叶制备而得的番泻总苷提取物能缩短去势小鼠动情周期,有雌性激素样促进子宫增生和骨质钙化的作用。结论：国产番泻叶具有较好的泻下通便作用,并初步发现其具有雌性激素样抗骨质疏松作用。     

抗菌肽Alloferon-1串联式重组表达及其表达产物体外抗肿瘤活性的研究

目的:构建串联式表达Alloferon-1的原核重组表达系统,检测合成及重组表达的Alloferon-1体外抗肿瘤细胞活性。方法:采用连接引物PCR法,构建含6×His-EK-8×Alloferon-1-EK-6×His序列的人工融合基因;采用常规分子生物学方法克隆并构建该人工融合基因及其原核表达系统;采用SDS-PAGE和BioRad凝胶图象分析系统了解目的重组产物8×rAlloferon-1-EK表达情况和产量;采用Ni-NTA亲和层析及EK酶切和Sephadex G-50层析法提纯8×rAlloferon-1-EK及rAlloferon-1-EK;采用MTT法检测rAlloferon-1-EK体外抑制KB、SGC和HL-60肿瘤细胞增殖的作用,并与直接合成的Alloferon-1(sAlloferon-1)和Alloferon-1-EK(sAlloferon-1-EK)的抗肿瘤作用比较。结果:获得了序列正确的目的人工融合基因克隆及其原核表达系统pET42a-8×rAlloferon-1-EK-E.coliBLDE3。在IPTG诱导下,该原核重组表达系统可表达串联式目的重组蛋白8×rAlloferon-1-EK,其产量约为细菌总蛋白的30%。Ni-NTA和Sephadex G-50层析后,可分别获得8×rAlloferon-1-EK和rAlloferon-1-EK。在25~100μg/ml剂量范围内,sAlloferon-1、sAlloferon-1-EK和rAlloferon-1、rAlloferon-1-EK均有明显抑制KB、SGC和HL-60肿瘤细胞生长及增殖的效果(P<0.01),且四者抑制作用无明显差异(P>0.05)。结论:本研究成功构建了串联表达rAlloferon-1的原核表达系统,其表达产物具有与合成的Alloferon-1和Alloferon-1-EK相似的体外抗肿瘤细胞活性。     

新型农村合作医疗农民协议委托筹资方式研究

为探索适宜的个人筹资方式,对安徽省东至县新型农村合作医疗试点的协议委托筹资方式通过现场关键人物访谈和相关利益者小组座谈,探讨了协议委托筹资方式产生的背景、操作过程及运作效果,并进行了分析与评价,对存在的风险提出了可行的规避措施。     

基层医院清洁手术抗菌药物应用与费用分析

目的了解基层医院清洁手术预防应用抗菌药物情况,规范抗菌药物的预防应用,降低医疗成本。方法设计统一调查表,调查某市13家县级医院2004年9月份清洁手术应用抗菌药物情况。结果共调查639例清洁手术患者,抗菌药物预防使用率为98.28%(628/639);抗菌药物平均使用时间为(7.60±2.57)d;单一用药占55.25%(347/628),联合用药占44.75%(281/628);用第三代头孢菌素以上及广谱抗菌药物者占50.64%(318/628);人均抗菌药物费用为人民币(1 064.64±286.51)元,占药品费用的43.38%,心胸外科、神经外科患者平均抗菌药物费用较高,分别为(2 783.10±653.39)元、(1 991.56±623.32)元。结论基层医院清洁手术抗菌药物预防使用率高,用药时间长、起点高等是不合理用药的主要表现,也是造成抗菌药物费用高的主要原因。     

156例新生儿化脓性脑膜炎病原菌分布及其耐药性分析

目的分析某院2000年1月-2005年12月收治的156例化脓性脑膜炎新生儿病原菌分布及其耐药性，为临床合理用药治疗提供依据。方法无菌抽取脑脊液进行普通培养和高渗培养，采用法国生物梅里埃API系统鉴定细菌；药敏试验采用K—B法，超广谱β-内酰胺酶（ESBLs）检测采用双纸片扩散法。结果共获需氧菌156株，其中革兰阴性（G^-）杆菌42株（26．92％），以大肠埃希菌（11株，26．19％）、不动杆菌属（5株，11．91％）、肺炎克雷伯菌（4株，9．52％）、变形杆菌（4株，9．52％）为主，检出产ESBLs菌12株（28．57％）；革兰阳性（G^＋）球菌103株（66．03％），以表皮葡萄球菌（56株，54．37％）、溶血葡萄球菌（7株，6．80％）为主；其他菌种11株（7．05％）。2003-2005年G^-杆菌占全部检出菌的比率为35．14%，高于2000-2002年的检出率19．51％（X^2=4．83，P〈0．05）。G^-杆菌对亚胺培南、头孢曲松、头孢哌酮等较敏感；G^＋球菌对头孢噻肟、头孢哌酮、头孢曲松等较敏感。结论新生儿化脓性脑膜炎病原菌以表皮葡萄球菌、大肠埃希菌、溶血葡萄球菌为主，G^-杆菌检出率有逐年上升趋势，临床应根据药敏结果合理选择抗菌药物。