Prevention of Hemophilus influenzae type b disease

To determine the efficacy of rifampin prophylaxis in eradication of oropharyngeal carriage of Hemophilus influenzae type b and prevention of secondary H influenzae type b disease, we conducted a multicenter placebo-controlled trial among selected persons with invasive H influenzae type b disease. Households and day-care classrooms were randomized so that their members received either rifampin (initially at a dose of 10 mg/kg/dose for two to four days [rifampin-10], but subsequently at 20 mg/kg/dose for four days [rifampin-20]) or placebo. Pretherapy H influenzae type b colonization rates were similar in the treatment groups. Therapy with either rifampin regimen significantly reduced carriage (rifampin-20, 97%; rifampin-10, 63%; placebo, 28%). New acquisition of carriage was also significantly reduced by either rifampin regimen (rifampin-20 or rifampin-10, 2% v placebo, 6%). No rifampin-resistant H influenzae type b isolates emerged after treatment. Four of 765 placebo-treated contacts experienced secondary disease in contrast to zero of 1,112 rifampin-treated contacts. Because chemoprophylaxis of close contacts with rifampin seems to reduce significantly the risk of secondary H influenzae type b disease, we recommend the administration of prophylaxis in households or day-care classrooms where children younger than 4 years have been exposed to the disease.     

不同剂量野百合碱联合异丙肾上腺素对大鼠血流动力学变化及心指数、右心肥厚指数研究

目的研究不同剂量野百合碱联合异丙肾上腺素对大鼠血流动力学变化及心指数、右心肥厚指数。方法采用SD大鼠64只,雌雄各半,体重200~250 g,随机分为空白对照组(n=16);模型组(n=48)。模型组分为高剂量组(n=16):80 mg/kg野百合碱采取腹腔一次性注射;10 mg/kg异丙肾上腺素采取腹腔连续注射1周;中剂量组(n=16):55 mg/kg野百合碱采取腹腔一次性注射;8 mg/kg异丙肾上腺素采取腹腔连续注射1周;低剂量组(n=16):30 mg/kg野百合碱采取腹腔一次性注射,3 mg/kg异丙肾上腺素采取腹腔连续注射1周。动物饲养到第6周后,行肺动脉压和右心室内压检测,心系数和右心室肥厚指数测定。结果与对照组比较,低剂量平均肺动脉压和右室收缩压均无差异变化;中剂量组平均肺动脉压、右室收缩压均有差异变化(P0.05),低剂量组心系数和右心室肥厚指数均无差异显著。中剂量组心系数差异极显著(P0.01),右心室肥厚指数差异显著(P0.05)。结论说明采用一次性注射野百合碱55 mg/kg,联合连续注射8 mg/kg异丙肾上腺素1周。既保证了大鼠的存活率,又保证了肺动脉高压的成功形成,野百合碱和异丙肾上腺素能对大鼠产生肺动脉高压,导致心气虚弱。     

慢性肾功能衰竭及接受替代治疗者并发结核感染的治疗

慢性肾衰及接受替代治疗者并发结核感染时，其治疗与一般抗结核治疗有所不同。应用常规剂量异烟肼时，神经毒性明显增多，且可出现精神与行为异常，加大维生素Ｂ６的剂量后可以防止。乙胺丁醇的剂量为１５ｍｇ／（ｋｇ·ｄ）时，视力障碍的发生率仍高达１７．６％。同时服用环胞素Ａ与利福平时，环胞素Ａ的剂量需增加１～４倍。异烟肼与硫唑嘌呤同时服用时，血白细胞减少的发生率增加。     

医用纳米级Fe3O4磁流体的急性毒理学实验研究

目的　检测医用纳米级Fe3 O4磁流体的急性毒性 ,为进一步研究其长期毒性以及载附药物的临床试验打下基础。方法　按不同浓度不同容积分别通过口服法、静脉注射法及腹腔注射法给予小鼠医用纳米级Fe3 O4磁流体 ,观察小鼠的急性毒性反应和主要脏器的病理学改变。结果　小鼠口服半数致死剂量LD50 >2 10 4 8mg/kg ,最大无毒性剂量ED0 为 32 0 10mg/kg ;静脉注射LD50 >4 38 5 0mg/kg ,ED0 为 16 0 0 5mg/kg ;腹腔注射LD50 >15 78 6mg/kg ,ED0 为 32 0 10mg/kg。主要脏器未见明显病理改变。 结论　医用纳米级Fe3 O4磁流体在动物体内的急性毒性很低 ,可以考虑作为药物载体。     

DBP对雄性小鼠睾丸标志酶活性的影响

目的观察邻苯二甲酸二丁酯（DBP）对雄性小鼠睾丸标志酶活性的影响。方法选择健康成年雄性昆明种小鼠130只,随机分为13组,每组10只。分别对小鼠进行相同作用时间、不同剂量及相同剂量、不同作用时间的DBP腹腔注射染毒。相同作用时间、不同剂量染毒组5组,即0（对照组）、250、500、1000和2000mg/（kg.bw）,1次/d,连续染毒3d。相同剂量[4000mg/（kg.bw）]、不同作用时间染毒组共8组,即0（对照组）、0.5、4、12、24、36、48和72h。测量小鼠脏器湿重、睾丸细胞乳酸脱氢酶（LDH）、葡萄糖-6-磷酸脱氢酶（G-6-PD）。结果DBP可引起小鼠睾丸组织匀浆中LDH、G-6-PD活性升高;DBP一次进入体内所引起的睾丸标志酶活性变化可在72h恢复正常水平。结论DBP对雄性小鼠具有一定的生殖毒性。     

小剂量尿激酶溶栓治疗不稳定性心绞痛的临床疗效--多中心随机对照研究

目的探讨小剂量尿激酶(UK)与低分子肝素(enoxaparin,商品名克赛)和阿司匹林(商品名巴米尔)联合治疗不稳定性心绞痛(UA)的临床疗效.方法采用单盲、对照的完全随机化方法.UK剂量为0.5万IU/kg于60min内静脉滴入,连续治疗3天.在第1天静滴UK前1h静脉推注低分子肝素30mg,口服阿司匹林0.3g,然后低分子肝素1mg/kg皮下注射,12h 1次,共6天,阿司匹林0.3g,每日1次,6天后改为0.1g,每日1次.主要终点为30天内病死率和心肌梗死发生率.结果共入选UA患者791例(包括69例非Q波性急性心肌梗死患者),小剂量UK组389例,对照组402例.30天的心脏死亡率两组间无显著性差异(2.0%与4.0%,P＞0.05).急性心肌梗死发生率小剂量UK组明显低于对照组(0.5%与2.5%,P＜0.05),减少频发心绞痛发生率小剂量UK组亦优于对照组(第1周29.3%与41.0%,P＜0.01;第4周5.9%与11.2%,P＜0.05).结论小剂量UK与低分子肝素和阿司匹林联合应用治疗发病急骤的UA可明显降低急性心肌梗死和频发心绞痛的发生率.     

藤茶和荷叶提取物对高脂血症大鼠降血脂作用的实验研究

目的建立高血脂动物模型,观察藤茶和荷叶提取物对高血脂模型大鼠血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、Lee＇s指数的影响.方法用高脂饲料喂养造模后,随机分为模型组、高剂量组20mg/kg、中剂量组10 mg/kg、低剂量组5 mg/kg及降脂药物组180 mg/kg,连续给药25 d.观察：①TC、TG、HDL-C;②体重变化;③肝重/体重比;④体脂湿重测定;⑤Lee＇s指数.结果各剂量实验组TC、TG和HDL值与模型组及降脂药物组比较差别无显著性（P＞0.05）;但中剂量和高剂量实验组与实验前比较TC值有显著降低（P＜0.05）,高剂量组与模型组比较,Lee＇s指数下降,差别有显著性（P＜0.05）.结论藤茶和荷叶提取物有降低血清胆固醇和减肥作用.     

曲妥珠单抗联合长春瑞滨对Her-2/neu高表达的转移性乳腺癌的治疗作用

目的 观察曲妥珠单抗联合长春瑞滨治疗Her-2/neu高表达的转移性乳腺癌的疗效与毒副作用.方法 21例Her-2/neu高表达转移性乳腺癌患者,接受曲妥珠单抗联合长春瑞滨方案治疗,曲妥珠单抗2mg/kg静脉滴注d1,d8,d15或者6 mg/kg静脉滴注d1,(首次加2 mg/kg),长春瑞滨25 mg/m2静脉推注d1、d8,每21 d重复一次.结果 全组21例共完成56个周期(中位数2周期,范围1～6周期),均可评价疗效.完全缓解1例,部分缓解6例,病情稳定4例.病情进展10例,客观有效率(完全缓解加部分缓解)33.33%,中位疾病进展时间3.5个月,1年生存率33%.主要不良反应是骨髓抑制及周围神经炎,部分患者有发热和轻度的心肌劳损.结论 曲妥珠单抗联合长春瑞滨方案治疗Her-2/neu高表达的重度复治的转移性乳腺癌患者,仍有一定疗效,且毒副作用轻.     

单用表阿霉素缓释剂及联合表阿霉素游离剂腹腔化疗治疗肝癌的疗效

目的 观察单用表阿霉素(EPI)聚乳酸(PLA)缓释微球(MS)及联合游离表阿霉素(FEPI)腹腔化疗治疗肝癌的疗效.方法 将35只H_(22)腹水型肝癌荷瘤小鼠分为7组,每组5只,分别予空白微球,生理盐水,低、中、高剂量载药微球(分别含EP19、18、36mg/ks),FEPI(9mg/kg)和EPI-PLA-MS+FEPI(各含EPI4.5mg/kg),经腹腔注射给药,计算动物生命延长率.结果 EPI-PLA-MS能有效延长荷瘤鼠的生存时间,并呈量效关系,小鼠最大耐受量约为18～36 mg/kg.联合用药组的平均生存时间、中位生存时间和生命延长率均达到最高值,分别为(40.0 ± 16.9)d、33.5d和222.58%.结论 EPI-PLA-MS缓释剂与游离剂型联合腹腔化疗是一种新型、高效的给药方式,可有效治疗肝癌.     

Treatment of chronic drug-resistant pulmonary tuberculosis with rifampin and ethambutol

Twenty patients with chronic pulmonary tuberculosis completed eight months of rifampin-ethambutol treatment. Half the patients received daily 600 mg. rifampin and 25 mg./kg. ethambutol for the first two months and subsequently 15 mg./kg. The others received the same dosage of ethambutol and 450 mg. rifampin daily. The average time of sputum conversion was seven weeks and 11 weeks in the two groups respectively. The patients tolerated these drug regimens well.

Rifampin blood levels and urinary excretion were studied monthly during the therapy. They indicated that after a short period of treatment the elimination of this drug became faster owing to increased excretion of rifampin, and particularly of its desacetyl metabolite, in the bile. Liver damage resulted in a slower excretion rate. Rifampin should be taken on an empty stomach because simultaneous food intake reduces the peak blood concentration.

     

大剂量氨溴索对ARDS患者氧合指数和病死率的影响

目的观察大剂量氨溴索对急性呼吸窘迫综合征（ARDS）患者氧合指数和病死率的影响。方法将86例入住ICU的ARDS患者随机分成大剂量氨溴索治疗组（观察组）和对照组。对照组采用常规综合治疗和机械通气治疗,观察组在对照组治疗的基础上加用大剂量氨溴索[15mg∕（kg.d）]分3次静脉滴注治疗,共7d。观察两组患者治疗前后呼吸频率、氧合指数（PaO2/FiO2）和PaCO2的变化,记录两组患者28d病死率。结果两组患者入ICU时年龄、呼吸频率（次/min）、PaO2/FiO2以及PaCO2（mmHg）比较差异均无统计学意义（P〉0.05）。治疗7d后观察组呼吸频率明显比对照组慢（[19.5±5.6）VS（28.0±4.9）],差异有统计学意义（P〈0.01）;观察组PaO2/FiO2明显比对照组高（[356.0±36.7）VS（290.6±32.3）],差异有统计学意义（P〈0.01）;观察组PaCO2与对照组比较差异有统计学意义（P〈0.01）,但两组患者PaCO2值均在正常范围内;观察组28d病死率虽比对照组低（23.3%VS 30.23%）,但差异无统计学意义（P〉0.05）。结论大剂量氨溴索能提高ARDS患者的氧合指数,改善呼吸功能。     

Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.     

不同剂量地佐辛预注对全麻诱导期血流动力学及脑电双频指数的影响

目的观察不同剂量地佐辛静脉预注对全麻诱导期间血流动力学和脑电双频指数（BIS）的影响。方法80例拟行气管插管全麻择期手术患者,美国麻醉医师协会（ASA）Ⅰ-Ⅱ级,随机分为4组,每组各20例。各组麻醉诱导前用药分别为：D1组：地佐辛0．05mg／kg;D2组：地佐辛0．1mg／kg;D3组：地佐辛0．2mg／kg;C组：生理盐水5mL。4组患者均给予芬太尼3tLg／kg,异丙酚2mg／kg,罗库溴铵0．6mg／kg,快速诱导后气管插管。观察给药前（T0）、麻醉诱导后气管插管前（T1）、气管插管即刻（T2）、气管插管后1min（T3）、3min（T4）、5min（T5）时脑电双频指数（BIS）、平均动脉压（MAP）、心率（HR）的变化。结果MAP、HR值比较,C组、D1组在T2-4时点明显高于T1时点（P〈O．05）,D2组仅在T2、T3时升高（P〈0．05）,D3组变化不明显;但相同时点比较,MAP、HR值D2、D,组低于C组（P〈0．05）。BIS值比较,与T1时比较,C组、D1组在T2、T3时明显升高（P〈0．05）,D2组仅在T2时升高（P〈0．05）,D3组在T4、T5时显著低于T1时（P〈0．05）,D3组在T2-5时明显低于C组（P〈0．05）。结论地佐辛0．1—0．2mg／kg预注可有效抑制气管插管时的心血管应激反应,维持全麻诱导期血流动力学稳定。     

CYP4F2基因多态性对心脏机械瓣膜置换术后患者华法林初始剂量的影响

  目的  研究细胞色素P-450 4F2（CYP4F2）基因多态性对心脏机械瓣膜置换术后患者华法林初始剂量的影响。  方法  收集2013年1月?2015年12月期间于我院心脏外科接受心脏机械瓣膜置换术后需服用华法林的患者350例,华法林剂量术后初始阶段国际标准化比值（INR）≥2的患者称为达标组,INR<2的患者称为非达标组。留取血样标本检测每位患者的CYP4F2基因型,分析CYP4F2基因多态性对心脏机械瓣膜置换患者术后华法林初始剂量（心脏机械瓣膜术后5～10 d患者住院期间的平均每日剂量）的影响。  结果  本研究发现在所有患者人群中,不同CYP4F2基因型患者间华法林的初始剂量差异无统计学意义;但在INR达标组的患者中,CYP4F2 TT基因型患者的华法林初始剂量高于CYP4F2 CC基因型患者〔（3.37±0.68） mg vs.（2.94±0.74） mg,P<0.05〕;同基因型患者,INR未达标组CYP4F2 CC〔（4.02±0.58） mg vs.（2.94±0.74） mg〕和CYP4F2 CT基因型〔（4.15±0.88） mg vs.（3.18±0.82） mg〕患者华法林的初始剂量大于INR达标组患者（P<0.05）。纳入性别,年龄,体质量指数（BMI）,合并疾病（高血压,糖尿病,冠心病,房颤）,细胞色素P-450 2C9（CYP2C9）、CYP4F2和维生素K过氧化物还原酶复合体1（VKORC1）基因多态性以及INR达标与否等因素进行多元线性回归分析,回归方程为:华法林初始剂量（mg）=?8.634+0.352×BMI（kg/m2）+1.102×CYP4F2基因型（CC或CT取值1,TT取值2）+2.147×VKORC1（AA或AG取值1,GG取值2）+1.325×INR（达标取值0,不达标取值1）,回归方程的决定系数 R2=0.431（P<0.05）。  结论  CYP4F2基因多态性对心脏机械瓣膜置换术后患者的华法林初始剂量有影响,同时该作用也受机体特征和其他因素的影响。     

无环鸟苷脂质体口服液对动物模型的抗病毒效果观察

将无环鸟苷以熔融法制成无环鸟苷多相脂质体口服液，然后观察其对鸭乙肝病毒感染的动物模型的抗病毒效果，将２８只被鸭乙肝病毒感染后的雏鸭分为４组，即无环鸟苷组（５ｍｇ／ｋｇ），无环鸟苷脂质体Ｉ组（４ｍｇ／ｋｇ）无环鸟苷脂质体ＩＩ组（２ｍｇ／ｋｇ）和生理盐水对照组，结果显示３组治疗组的血清和肝组织中的病毒ＤＮＡ均受到明明的抑制说明无环鸟苷经用脂质体包裹以后，仅用原剂量的１／３就可达到同样满意的抗病毒效果。     

奥卡西平治疗癫痫的临床观察

目的 观察奥卡西平（OCBZ）治疗癫痫的疗效、耐受性和安全性。方法 68例癫痫患者采用开放性自身对照研究,其中36例进入单药治疗组,32例进入添加治疗组。剂量为0.15～0.3g,分早晚两次,维持剂量每天600～1200mg,最大未超过1.8g;儿童按10mg/kg/d,分两次服用,增加剂量每周不超过10mg/kg/d。分两次服用,最大不超过35mg/kg/d。分析两组24周以上的疗效、不良反应、耐受性和安全性。结果 本组总有效率为85.3%,完全控制为36.8%;其中单药治疗组控制率44.4%,总有效率为91.7%,添加治疗组控制率为28.1%,总有效率为78.1%。最常见的副及应为头昏、头痛、嗜睡、皮疹、纳差等,单治组副反应总发生率为30.6%,添加组副反应发生率为53.1%,两组比较,添加治疗组出现的反应相对多于单药治疗组。两组耐受性好,安全性高。结论 奥卡西平治疗癫痫安全、稳定、有效。     

羟基喜树碱联合氟尿嘧啶/亚叶酸钙治疗晚期大肠癌的临床观察

目的观察HFL方案（羟基喜树碱＋氟尿嘧啶／亚叶酸钙）治疗晚期大肠癌中羟基喜树碱（喜素）的最大耐受剂量、剂量限制性毒性,确定喜素最佳应用剂量,同时观察该方案的疗效。方法共人选晚期大肠癌患者18例,喜素剂量分为6级,从4mg/／m^2开始向上爬坡,各组分别静脉滴注喜素4,6,8,10,12,14mg／m^2,第1—5天。5氟尿嘧啶（5-FU）／亚叶酸钙（LV）（5-FU425mg／m^2第1—5天,LV20mg／m^2第1—5天）于喜素静脉点滴完毕后,静脉注射。每4周为1个周期。观察药物的毒性反应和疗效。结果10,12,14mg／m^2组各有两例出现Ⅳ度骨髓抑制,HFL方案的主要毒性反应是骨髓抑制、消化道反应,毒性与剂量相关。剂量限制性毒性为骨髓抑制。该方案中喜素的最大耐受剂量（MTD）为10mg／m^2第1—5天。结论HFL方案治疗晚期大肠癌患者的耐受性良好,推荐剂量8mg／m^2。     

Secondary Haemophilus influenzae type b in day-care facilities. Risk factors and prevention

The risk factors for acquisition of secondary day-care-associated Haemophilus influenzae type b disease were evaluated in a cohort of children in Seattle-King County, Washington; Atlanta; and the state of Oklahoma. During the study period, 129 primary cases were identified in children less than 5 years old who attended day-care facilities. In ten instances (8%), a secondary case occurred between one and 60 days after a primary case in the same classroom. Risk of secondary disease in classroom contacts was strongly age related: 2.4% in children 0 to 11 months old, 1.2% in children 12 to 23 months old, and 0.0% in children 24 to 59 months old. Controlling for age, children attending day-care more hours per week were more likely to transmit or acquire secondary disease. Risk of secondary disease for children in other classrooms at a center where a case had occurred was not significantly greater than risk of primary disease. Administration of rifampin to classroom contacts of a child with invasive H influenzae was effective in preventing secondary cases (95% confidence interval for rifampin efficacy, 47% to 100%). For children 0 to 23 months old not treated with rifampin, risk of secondary disease was 2.7% (95% confidence interval, 1.1% to 4.3%), a risk approaching that reported in household contacts.     

依达拉奉合并东灵迪芙治疗急性脑梗死32例临床观察

目的:比较依达拉奉单药及合并东灵迪芙对急性脑梗死(ACI)的治疗效果。方法:随机选取发病48h以内的ACI患者101例,分依达拉奉与东灵迪芙合并治疗组(即治疗组32例)及东灵迪芙单药治疗组(即对照1组52例),依达拉奉单药治疗组(即对照2组17例)。治疗组:依达拉奉注射液30mg+(NS)250mL静脉滴注,2次/d,共7d;合并以东灵迪芙注射液按隔天10IU,5IU,5IU方案治疗;对照1组:以东灵迪芙注射液按隔天10IU,5IU,5IU方案治疗;对照2组:依达拉奉注射液30mg+(NS)250mL静脉滴注,2次/d,共7d。治疗前后定期对患者进行欧洲卒中评分(ESS)、日常生活能力评分(ADL)和常规检查,以治疗第21d ESS增分率和ADL增分率作为主要疗效判断标准。结果:21d后治疗组、对照1组和对照2组的ESS增分率分别为(58.9±27.8、36.8±23.4、34.1±24.1),治疗组与两对照组相比差异有极显著性(P<0.001),两对照组疗效相当(P>0.05),ADL增分率分别为(63.4±33.6、30.4±31.8、31.2±31.7),治疗组与两对照组相比差异有极显著性(P<0.001),两对照组疗效相当(P>0.05)。结论:依达拉奉与东灵迪芙合并治疗效果明显优于依达拉奉与东灵迪芙单药治疗组。依达拉奉与东灵迪芙单药治疗组疗效相当。     

维生素B_6抗血小板聚集作用研究

在12例可疑高凝状态的病人中,以维生素B6体外处理血小板后测定ADP及胶原诱导的血小板聚集;在7例同类病人中测定口服维生素B6前后ADP及胶原诱导的血小板聚集,维生素B6用量每日4mg／kg×10天。结果显示.在体内、外试验中。维生素B6对ADP及胶原诱导的血小板聚集均有显著抑制作用。值得深入研究维生素B6作为一种新的抗血小板药物的临床应用前景。