Vero细胞口服狂犬病疫苗的研究

本试验采用ＣＴＮ－１株经Ｖｅｒｏ细胞传１５代，病毒滴度均在７．０～８．０ｌｏｇＬＤ５０／ｍｌ之间。给８只犬分别口服８．１ｌｏｇＬＤ５０的疫苗３０天的中和抗体几何平均效价为１：１１０，中和抗体的平均国际单位为２．５９ＩＵ／ｍｌ，阳转率为１００％；给４只犬分别口服７．４３ｌｏｇＬＤ５０的疫苗，阳转率为５０％，中和抗体的平均国际单位为２．４８ＩＵ／ｍｌ。选用３５－６０日龄的乳犬１６只口服１０个剂量的疫苗，并在口服后５、１０、２０天、３个月各杀３只犬取脑及唾液腺分别在ＢＨＫ２１细胞上盲传２代，同时在昆明种小白鼠乳鼠脑内盲传２代，进行病毒分离，均为阴性，余下犬观察１２个月均正常。总之该口服狂犬病疫苗对犬具有较好的安全性及口服免疫原性。     

狂犬病疫联合干扰素的应用研究

目的 研究ＩＦＮ＋２－２－１程序和２－２－１程序应用的可行性,探讨ＩＦＮ的免疫调节作用。方法 ＩＦＮ＋２－２－１程序;于０、７、１４天分别注射５．０、５．０、２．５ＩＵ ＰＨＫＣＶ,于０天同时加注２０万ＩＵα－ＩＦＮ;２－２－１程序;于０、７、１４天分别注射５．０、５．０、２．５ＩＵＰＨＫＣＶ;对照：应用ＷＨＯ推荐的常规程序。结果 ①３种程序免疫后的ＧＭＴ;７天时分别为１．７１、１．５７、１．２１     

G—CSF配合大剂量CTX和VCR动员自体外周血干细胞的研究

本研究对１２例拟行ＡＰＢＳＣＴ的患者予ＶＣＲ１－２ｍｇ／ｍ２，体表面静注及ＣＴＸ７ｇ／＾２体表面积静滴，５－７天后予Ｇ－ＣＳＦ１００μｇ／ｍ＾２体表面积静注５－７天，白细胞升至３．０×１０＾９／Ｌ以上时，用ＣＳ３０００血细胞分离机单次收集单个核细胞ＭＮＣ〉２．８×１０＾８／ｋｇ，ＣＤ＾＋３４〉．６×１０＾６／ｋｇ，ＣＦＵ－ＧＭ〉３．９×１－０＾４／ｋｇ，ＡＰＢＳＣＴ后，全部患者于＋５天－＋１０天白     

阿柯萨B3m病毒致低硒鼠心肌病变检出率与病毒中和抗体？…

５周龄ＢＡＬＢ／Ｃ雄性鼠经低硒,常合成饲料喂养５周后,腹腔注射ＣｏｓａｃｋｉｅＢ３ｍ病毒（ＣＶＢ３ｍ）１０００ＴＣＤ５００．１ｍｌ,对照组注射１６４０营养液０．１ｍｌ,７天后处列主脏常规切片,ＨＥ染色光镜下检查心肌病变。取血清测定ＣＶＢ３ｍ病毒中和抗体效价。     

心尖肥厚型心肌病心电图1例

患者男性 ,４０岁。因胸闷１年 ,加重３天入院。曾诊断为冠心病。体检 :ＢＰ１１０／７０ｍｍＨｇ,心界不大 ,心尖搏动强有力 ,心率６８次／ｍｉｎ ,心律齐 ,心尖区可闻及Ⅱ级收缩期杂音及第３心音。肝脾无肿大。Ｘ线胸片及血清心肌酶检查正常。心电图 (图１)示 :窦性心律 ,心率６０次／ｍｉｎ ,Ｐ＿Ｒ间期０．１４ｓ ,ＱＲＳ时间０．０８ｓ ,ＱＲＳ波群在Ⅱ导联呈Ｒ型 ,Ｖ５ 导联呈ＲＳ型 ,Ｖ６ 导联呈Ｒｓ型 ,没有Ｑ波 ,而Ｖ１、２ 导联呈ＱＳ型 ,没有ｒ波 ,Ｖ４～６ＳＴ段压低＞０．０５ｍＶ ,Ｔ波Ｉ、ａＶＬ浅倒 ,Ｖ３～６ 深尖倒置 ,Ｖ…     

乙肝疫苗第三针接种剂量对疫苗效果的影响

为了观察乙肝疫苗第三针减量接种后的效果,对１２６名接种乙肝疫苗于第三针减量接种（接种剂量分别为２μｇ,５μｇ,１０μｇ,２０μｇ或未接种）的儿童进行了长达９年的追踪观察。结果显示９年中各组抗体水平（ＧＭＴ）均无显性差异（Ｐ〉０．０５）,第９年（Ｔ１０６）时各组ＧＭＴ分别为７．０,６．４,９．９,６．１,９．７,５．４和７．４,ＨＢＶ人年感染率各组亦无显性差异（Ｐ〉０．０５）,疫苗保护率各组均大     

应用ELISA法监测改进剂量后狂犬病疫苗（PHKC－RV）免后抗体水平

应用ＥＬＩＳＡ法监测改进剂量后狂犬病疫苗（ＰＨＫＣ－ＲＶ）免后抗体水平山西省大同市卫生防疫站王升,苑富莲,芦全香,石振坤,张秀芳狂犬病疫苗接种是降低狂犬病发病率根本的措施,疫苗质量直接影响其预防效果。我国自１９９２年５月开始将疫苗剂量由１．３ＩＵ提高...     

尿激酶和前列腺素E1联合溶解深静脉血栓的临床研究

目的：观察静脉内联用尿激酶（ＵＫ）和前列腺素Ｅ１（ＰＧＥ１）对下肢深静脉血栓（ＤＶＴ）患者的溶栓效果。方法：将８９例经静脉造影确诊为ＤＶＴ患者分为联合溶栓组［ＵＫ＋ＰＧＥ１ｎ＝５１，第１组（病程＜２周）：先静脉注射ＵＫ１０万ＩＵ，接着静脉滴注ＵＫ（３万ＩＵ／ｈ）及ＰＧＥ１（１００μｇ／ｄ）持续２～３天，之后持续静脉滴注肝素钠５～７天，再服用华法林（使凝血酶原时间为基础对照的１．５～２．０倍）３～６个月；第２组（病程＞２周）：静脉注射ＵＫ１０万ＩＵ后，静脉滴注ＵＫ２０万ＩＵ及ＰＧＥ１１００μｇ，每日１次，连用７～１０天，再服华法林３～６个月］和常规治疗组（肝素，ｎ＝３８，剂量同上）。以血管造影为标准判断溶栓效果。结果：联合溶栓组的疗效明显优于常规治疗组（Ｐ＜０．０１）；其疗效与病程长短关系密切，病程小于２个月者疗效显著（显效率７５％，总有效率９６．５％）；无严重并发症发生。结论：静脉内联用ＵＫ和ＰＧＥ１治疗ＤＶＴ是一种安全、有效的治疗方法。     

滤纸片法TRH兴奋试验在碘缺乏病中的应用

本文将血清法ＴＲＨ兴奋试验改为血滤纸片法，在新疆严重碘缺乏病区测定地方性克汀病２６例，其中粘肿型１０例、混合型１０例、神经型６例。滤纸片法ＴＲＨ兴奋试验结果：基础ＴＳＨ值（ＴＳＨ０）、ＴＳＨ峰值（注射ＴＲＨ３０，钟后的最高值ＴＳＨ３０，）、△ＴＳＨ绝对增值（ＴＳＨ３０，峰值减ＴＳＨ０）对不同类型的克汀病人分别为：粘肿型ＴＳＨ０１２０．２９±９３．７４μＩＵ／ｍｌ、ＴＳＨ３０，２２５．３０±１１２．０７μＩＵ／ｍｌ、△ＴＳＨ１０５．０１μＩＵ／ｍｌ；混合型ＴＳＨ０１０．５８±９．３６μＩＵ／ｍｌ、ＴＳＨ３０，６４．７８±３３．９８μＩＵ／ｍｌ；△ＴＳＨ５４．２０μＩＵ／ｍｌ；神经型ＴＳＨ０１．９８±０．６３μＩＵ／ｍｌ、ＴＳＨ３０，２６．７６±４９．９２μＩＵ／ｍｌ、△ＴＳＨ２４．７６μＩＵ／ｍｌ。三型克汀病间差异显著（Ｐ＜０．０１）．粘肿型克汀病ＴＳＨ对ＴＲＨ兴奋试验的应答反应呈超常强反应型，峰值呈持续状态，混合型次之，神经型呈弱或延迟反应型。另外还测定了８～１０岁不同组别的儿童８９例，ＴＲＨ兴奋试验结果分别为：２８例正常对照组的ＴＳＨ０、ＴＳＨ３０，各为３．５５±０．９８μＩＵ／ｍｌ、３０．４８±１１．４     

胸腺肽α1单用及联合干扰素—α1b治疗慢性乙型肝炎疗效观察

目的研究单用胸腺肽α１（Ｔα１）及联合应用干扰素（ＩＦＮ）对慢性乙型肝炎（ＣＨＢ）的治疗作用。方法３６例ＣＨＢ患者随机分为Ａ、Ｂ两组,Ａ组采用Ｔα１和ＩＦＮ联合治疗;Ｂ组单用Ｔα１,疗程均为６个月。结果治疗后６月时ＡＬＴ水平在Ａ、Ｂ两组分别下降至（７２．１±４．７７）Ｕ／Ｌ和（７３．７±３７．９）Ｕ／Ｌ,较治疗前（２２６．７±２１９．４）Ｕ／Ｌ和（１７０．１±１６５．６）Ｕ／Ｌ明显下降（Ｐ＝０．００２７和０．０００３）。ＨＢＶＤＮＡ水平在Ａ、Ｂ两组分别下降到（１３０±２８３）ｍＥｑ／ｍｌ和（３７３±８２５）ｍＥｑ／ｍｌ,较治疗前（８０７±１２２２）ｍＥｑ／ｍｌ和（８８３±１４３８）ｍＥｑ／ｍｌ明显下降（Ｐ＝０．００１９和０．０１９）。治疗后６月时,具有ＡＬＴ完全反应者,Ａ组和Ｂ组分别为８例（４４％）和９例（５０％）,具有ＨＢＶ清除反应者Ａ组为８例（４４．４％）,Ｂ组为７例（３８．８％）。结论采用Ｔα１或Ｔα１联合ＩＦＮα１ｂ治疗ＣＨＢ均能取得较好的效果     

Immunogenicity and safety of purified Vero-cell rabies vaccine in severely rabies-exposed patients in China

The immunogenicity and safety of a purified Vero-cell rabies vaccine (PVRV, VERORAB; Aventis Pasteur, France) were evaluated in 171 patients treated for severe exposure to rabies (WHO category III contacts) at the Shandong Provincial Antiepidemic Station in Jinan and an EPI center in Ping Yin, China. Post-exposure treatment consisted of a single dose of equine rabies immunoglobulin (ERIG, 40 IU/kg body weight) on Day (D) 0, and intra-muscular administration of PVRV on D 0, 3, 7, 14 and 28. Antirabies antibody levels were evaluated on D 0, 7, 14, 28, 90 and 180 using the rapid fluorescent focus inhibition test. By D 14 all subjects had seroconverted (> or = 0.5 IU/ml), with a geometric mean titer of 50.3 IU/ml. Antibody titers remained above the seroprotection threshold in all patients for 3 months, and in 98.2% of subjects for 6 months. All patients were still alive 6 months after the start of treatment. PVRV and ERIG were shown to be well tolerated and no serious adverse events were observed. Following PVRV administration, 12 patients (7.0%) had at least one local reaction (mostly pruritus, erythematous rash and pain). Fourteen patients (8.2%) developed local reactions at the site of ERIG administration. Twelve patients (7.0%) developed systemic reactions following post-exposure treatment, the most frequent of which were pruritus, rash and vertigo. This study demonstrates that PVRV is immunogenic and safe in Chinese patients treated according to WHO recommendations for severe rabies exposure.     

Evaluation of the safety, immunogenicity, and pharmacokinetic profile of a new, highly purified, heat-treated equine rabies immunoglobulin, administered either alone or in association with a purified, Vero-cell rabies vaccine

A clinical evaluation of a new, purified, heat-treated equine rabies immunoglobulin (PHT-Erig), F(ab′)₂ preparation, was carried out in Thailand and in the Philippines—two countries where rabies is endemic. An initial prospective, randomised, controlled trial (Study 1), compared the safety and pharmacokinetics (serum concentrations of rabies antibodies) after administration either of PHT-Erig or of a commercially-available, equine rabies immune globulin (Erig PMC). A second trial (Study 2) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine, the purified Vero-cell rabies vaccine (PVRV), administered in association with either Erig PMC or PHT-Erig. In Study 1, 27 healthy, Thai adults received a 40 IU kg⁻¹ dose of either Erig PMC (n=12) or PHT-Erig (n=15) via the intramuscular (IM) route; half of the dose was injected into the deltoid area and the other half into the buttocks. Serum for rabies antibody determination and F(ab′)₂ concentration was collected at hours (H) 0, 6 and 12, and on day (D) 2, 3, 4, 6, 8, 10, 12 and 15. Both products were safe, with no serious adverse events, and in particular, no anaphylactic reactions or serum sickness was reported. A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products. Nonetheless, the relative bioavaibility of 93% and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar. The antibody level in either group were low throughout the 15-day study period. The geometric mean titer (GMT) values ranged from group 0.027–0.117 IU ml⁻¹ in the Erig group and from 0.029 to 0.072 IU ml⁻¹ in the PHT-Erig. There was no significant difference between the evolution of GMT values for the two groups. In Study 2, 71 healthy volunteers received 40 IU kg⁻¹ via the intramuscular route of either Erig PMC (n=36) or PHT-Erig (n=35) on D0, in association with five doses of PVRV on D0, D3, D7, D14 and D28. The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 (before injection) D3, D7, D14 and D28. No serious reactions were reported in either group. In particular, no immediate (anaphylactic type) or delayed (serum sickness) allergic reactions were observed. Over the 28-day follow-up period, GMT profiles of the two groups were statistically equivalent. On D14, 100% of the subjects had protective antibody titers (anti-rabies antibodies ≥0.5 IU ml⁻¹, which is the WHO-recommended level of seroconversion), and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen. On D28, the GMT values were 33.2 IU ml⁻¹ (95% CI, 23.8–46.1 IU ml⁻¹) in the Erig PMC/PVRV group and 31.4 IU ml⁻¹ (95% confidence interval, CI, 23.4–42.2 IU ml⁻¹) in the PHT-Erig/PVRV group, showing evidence of adequate vaccine-induced antibody responses in both groups. The increased purity, the heat-treatment step introduced in the manufacturing process of PHT-Erig, and the good clinical results substantiate the use of this new generation, purified equine F(ab′)₂ preparation in the post-exposure prophylaxis of rabies.     

Post-exposure prophylaxis with purified vero cell rabies vaccine during pregnancy--safety and immunogenicity

This study was conducted with the main objective of determining the safety and immunogenicity of purified vero cell rabies vaccine (PVRV) during pregnancy. Twenty nine pregnant women exposed to rabies were vaccinated with PVRV as per the Essen regimen advocated by World Health Organization. None of the women experienced any adverse side effects to the vaccine. The intrauterine growth and development monitored by ultrasound examination was found to be normal and the outcome of pregnancy was satisfactory. There were no congenital anomalies in any of the infants born and they were healthy and had normal growth and development during the one year follow-up period. The rabies neutralizing antibody titers from day 14 to day 365 following vaccination in these women was adequate and well above the minimum protective level of 0.5 iu/ml of serum. Protective levels of antibodies were also present in serum of some of the babies tested, for up to 3 months of age. The mothers and infants followed for one year period were doing well at the end of the study period. Consequently, PVRV was found safe and immunogenically efficacious during pregnancy.     

Immunogenicity and effectiveness of post-exposure rabies prophylaxis with a new chromatographically purified Vero-cell rabies vaccine (CPRV): a two-stage randomised clinical trial in the Philippines

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (PVRV) (Verorab; Pasteur Merieux Connaught). The immunogenicity and effectiveness of post-exposure rabies prophylaxis with this new vaccine were evaluated in a two-stage clinical trial conducted in the Philippines. In both study stages. post-exposure treatment consisted of five injections of vaccine [(D)ays 0, 3, 7, 14, 28], together with a dose of rabies immunoglobulin (RIG) of equine or human origin on D0. In stage 1, 231 subjects with low-risk rabies exposure (WHO category I or II), and who had a negative ERIG skin test, were treated with either CPRV (n = 114) or PVRV (n = 117). By D14, all subjects in each group had achieved rabies antibody titres over ten times that recommended by the WHO as indicating seroconversion (> or = 0.5 IU/ml). The kinetics of the immune response to vaccination were very similar in the two groups, and at D28, the immunogenicity of CPRV was equivalent to that of PVRV (one-sided equivalence test). Following these positive results, 132 subjects with severe rabies exposure were included in the second stage of this trial. All were scheduled to receive four vaccine doses with CPRV. After D14, only those 57 patients with confirmed rabies exposure (animal with positive FA test) and seven patients for whom rabies exposure could not be excluded (animal lost or not tested) completed the treatment and were followed for one year to assess survival. After 1 year, 62 patients treated for confirmed or possible severe rabies exposure had been examined and were still alive. Two patients contacted by letter and telephone confirmed good health 7 and 16 months after exposure. No severe local or systemic reactions were reported in either stage of the study, and no treatment-related serious adverse event occurred. This two-stage clinical trial attests to the safety and satisfactory immunogenicity of CPRV in post-exposure rabies treatment, and confirms the effectiveness of a new rabies vaccine in patients with severe confirmed exposure.     

Simulated post-exposure rabies vaccination with purified chick embryo cell vaccine using a modified Thai Red Cross regimen.

OBJECTIVES: Currently, two intradermal regimens for the administration of cell culture rabies vaccines are approved by the WHO for rabies post-exposure prophylaxis: the two site Thai Red Cross regimen (TRC) and the eight site regimen. For the TRC regimen the volume of vaccine recommended per dose is 0.1 ml of purified Vero cell rabies vaccine (PVRV) and 0.2 ml of purified chick embryo cell vaccine (PCEC). The objective of the present study was to evaluate comparatively the immune response to PCEC and PVRV vaccines administered by the TRC regimen using a uniform dose of 0.1 ml of vaccine. METHODS: Forty-two subjects received TRC regimen (2-2-2-0-1-1) with 0.1 ml of PCEC vaccine and 38 subjects received the same regimen with PVRV. The rabies neutralizing antibody response in these subjects on days 10, 28, 90 and 180 was determined by the standard mouse neutralization test (MNT). RESULTS: There was adequate antibody response with both the vaccines and 100% seroconversion was observed by day 10. Furthermore, the antibody titers obtained with PCEC did not differ significantly from those obtained with PVRV on all days tested (p > 0.05). CONCLUSIONS: It can be concluded from the results that an adequate antibody response can be obtained with PCEC vaccine when administered by the TRC regimen even after reducing the quantity of vaccine from 0.2 ml to 0.1 ml per intradermal dose. The feasibility of using this regimen in true post-exposure cases needs to be further evaluated.     

Naturally acquired antibodies to tetanus toxin in humans and animals from the galápagos islands

A serologic survey using a highly sensitive enzyme-linked immunosorbent assay confirmed the anticipated finding of naturally acquired antibodies to tetanus toxin both in humans and animals on the Galápagos Islands. In 57 inhabitants (mean age, 31.3 years) who had not been vaccinated against tetanus, antibody to tetanus toxin was detected in the blood in varying titers (geometric mean [reciprocal] titer [GMT], 0.015 international units [IU]/ml). In one individual the titer of antibody was greater than 12.5 IU/ml. Two individuals who had never been vaccinated against tetanus but who had reported having had clinical tetanus had titers of antibody to tetanus toxin of 0.02 IU/ml and 0.3 IU/ml, respectively. All nine of the animals studied showed antibody to tetanus toxin (GMT, 0.028 IU/ml).     

A new Vero cell rabies vaccine: results of a comparative trial with human diploid cell rabies vaccine in children.

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.     

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

AIM: The study was initiated to evaluate the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine inage group >40 years and to study the response of a single booster dose in primary non-responders to the hepatitis B vaccination.METHODS: A total of 102 volunteers without markers of hepatitis B infection (negative for HBsAg, anti-HBc antibody,HBeAg and anti-HBs antibody) received 20μg of recombinant HB vaccine intramuscularly at 0, 1, and 6 months. Anti HBs titers were evaluated by a quantitative Elisa kit at 90 and 210 days. A booster dose of 20μg HB vaccine was given after 6 months of the 3^rd vaccine dose to the 15 nonresponders and anti-HBs titers were measured after 1 month.RESULTS: Seroprotection (anti-HBs GMT^3 10 IU/L) was achieved in 85.3 % (87/102) volunteers. The mean GMT titers of the vaccine responders was 136.1 IU/L. Of the seroprotected individuals, there were 32.4% (33/102) hyporesponders (anti-HBs titers <10-99 mIU/ml) and 52.9% (54/102) were responders (anti-HBs titers > 100IU/L). All the non-responders(15/15) responded to a single dose of the booster dose of recombinant HB vaccine and their mean anti-HBs antibody titers were more than 100.5mIU/ml after the booster dose.CONCLUSION: Recombinant hepatitis B vaccine offers good seroprotection in the age group >40 years and has a good safety profile. A single booster dose after 6 months in primary non-responders leads to good seroprotective anti-HBs antibody titers. However, larger population based studies are needed to evaluate the role of a booster dose in selected group of non-responders and whether such an approach will be cost effective.     

人用狂犬病纯化疫苗(Vero细胞)临床观察及免疫学效果研究

目的　研究人用狂犬病纯化疫苗的安全性和保护性。方法　采用狂犬病疫苗暴露后免疫程序接种受试人群 ,I期临床接种 2 0人 ,II、III期临床接种 30 4人 ,观察注射后反应 ,采用小鼠脑内中和试验法测定其中 6 2人中和抗体水平。结果　全部受试者有 13.2 7%出现轻度副反应 ,无中强度副反应 ,中和抗体阳转率为 10 0 % ,中和抗体GMT为 11.89IU/ml。结论　该疫苗对人体安全且具有较好的免疫原性