小剂量米非司酮和左炔诺孕酮用于紧急避孕的临床研究

目的：以左炔诺孕酮为参比制剂,探讨10mg米非司酮用于紧急避孕的临床效果。副反应及可接受性。方法：采用随机对照性的试验方法,征集100例单次无保护性交72小时内来院就诊的要求紧急避孕的妇女,随机分配到观察组（n=50）和对照组（n=50）,观察组单次口服10mg米非司酮,对照组口服左炔诺孕酮0．75mg,12小时后再服左炔诺孕酮0．75mg,服药后嘱两组对象按时随访直至月经复潮。并观察其避孕效果,副反应,对月经的影响及药物的可接受性。结果：采用Dixon方法计算。两组对象各有1例妊娠,观察组避孕效果达81．19％,对照组为81．06％,统计学上无明显差并,两组副反应轻,无任何不良反应发生。结论：小剂量米非司酮用于紧急避孕与左炔诺孕酮是同样有效的。     

不同剂量伊曲康唑口服联合外用抗真菌药物治疗足癣的疗效观察

目的比较伊曲康唑200mg／d与400ne／d口服联合外用复方酮康唑乳膏治疗足癣的疗效。方法36例非角化型足癣患者随机分为2组,分别采用不同剂量伊曲康唑口服联合外用复方酮康唑乳膏治疗1周,比较停药2周时两组患者的治疗有效率和真菌清除率。结果200mg组治疗有效率为83．3％（15／18）,痊愈率为55．6％（10／18）,真菌清除率为66．7％（12／18）;400mg组治疗有效率为88．9％（16／18）,痊愈率为55．6％（10／18）,真菌清除率为77．8％（14／18）;统计学分析两组之间差异无显著性。结论伊曲康唑200mg／d口服即可有效治疗非角化型足癣,增加伊曲康唑口服剂量至400mg/d并不能提高治疗效果。     

米非司酮治疗围绝经期功能失调性子宫出血的临床观察

目的：观察诊断性刮宫术后加用米非司酮治疗围绝经期功能失调性子宫出血（功血）的临床效果。方法：将32例确诊为围绝经期功血的患者。口服米非司酮10mg,1次／天,连服3个月。观察月经情况、子宫大小、内膜厚度,激素水平。结果：所有患者用药期间均出现闭经,其中10例直接进入绝经期．余22例停药32-72天恢复月经,其中8例月经稀发、量少;5例于停药3,15个月绝经,恢复月经者中有1例于停药15个月复发,改行宫腔镜子宫内膜切割术。结论：米非司酮治疗围绝经期功血有效,复发率低．副反应小。是目前比较理想的药物治疗方案。     

伊曲康唑治疗复发性外阴阴道念珠菌病38例临床观察

目的了解国产伊曲康唑（商品名“美扶”）治疗复发性外阴阴道念珠菌病的疗效。方法收集38例复发性外阴阴道念珠菌病为治疗组,口服伊曲康唑200mg,1次／d,连续7d,以后每次月经第1天口服伊曲康唑200mg,1次／d,连续6个月经周期停药,而对照组20例则单子硝酸咪康唑栓200mg阴道外用,方法同前。两组完成冲击治疗后1周、3个月、6个月评价疗效。结果1周后治疗组总有效率为92．1％,对照组为90％,两组相比无统计学差异。3个月、6个月后治疗组的复发率分别为3．2％、6．7％,对照组为28．6％、38．5％,两组相比有统计学意义。结论伊曲康唑短程冲击治疗加长期间断给药对复发性外阴阴道念珠菌病的治疗和预防复发效果满意。     

米非司酮治疗子宫内膜异位症疗效的临床研究

目的:研究米非司酮治疗子宫内膜异位症的疗效及副反应。方法:选择94例卵巢子宫内膜异位症患者,采用随机抽样的方法分为米非司酮组(简称米组)和内美通治疗组(简称内组),米组46例,内组48例。利用t检验和x~2检验。结果:米组有效率为91．42%,内组有效率为43．75%,二者比较,P＞0．05,差别无统计学差异;而副反应米组明显低于内组,体重增加米组为15．00%,内组为43．75%,二者比较,P＜0．01,说明存在统计学差异;谷丙转氨酶(ALT)异常米组为4．40%,内组为25．00%,二者比较,P＜0．05,存在统计学差异。结论:米非司酮治疗卵巢子宫内膜异位症与内美通具有相同的疗效,副反应明显低于内美通。     

奎硫平与阿立哌唑治疗老年期首发精神分裂症临床分析

目的:观察奎硫平与阿立哌唑治疗老年期首发精神分裂症的临床疗效和安全性.方法:将我院收治的老年期首发精神分裂症患者108例随机分为A组和B组,每组54例,A组患者口服奎硫平,起始剂量50 mg/d,最大剂量450 mg/d,平均(327.8±75.8)mg/d;B组患者口服阿立哌唑,起始剂量5 mg/d,最大剂量30 mg/d,平均(21.5± 3.6) mg/d;疗程12周.于治疗前及治疗后2、4、8、12周末应用阳性症状和阴性症状量表(PANNS)评价临床疗效,应用副反应量表(TESS)评价药物不良反应.结果:①治疗12周后,A组痊愈19例(35.2％),显效15例(27.8％),好转15例(27.8％),无效5例(9.3％),显效率为63.0％,有效率为90.7％;B组痊愈20例(37.0％),显效14例(25.9％),好转15例(27.8％),无效5例(9.3％),显效率为70.0％,有效率为90.7％,两组比较无统计学差异(P＞0.05).②治疗2周末开始两组PANNS量表各项得分及总分均有所降低,与治疗前比较有统计学意义(P＜0.05);两组组间比较PANNS量表各项得分及总分无统计学差异(P＞0.05).③A组头晕、口干、食欲减退多于B组,B组失眠、恶心、呕吐、心动过速多于A组(P＜0.05).结论:奎硫平与阿立哌唑治疗老年首发精神分裂症不良反应虽有异同,但两种药物临床疗效相当,适合老年首发精神分裂症的治疗.     

米菲司酮不同剂量治疗子宫肌瘤的临床疗效观察

目的观察米菲司酮不同给药剂量治疗子宫肌瘤的临床疗效。方法将子宫肌瘤患者分成两组,A组25例,每天服用米菲司酮25mg,B组21例,每天服用米菲司酮10mg,均从月经第一天开始服用,连续三个月。治疗期间每月复查肝、肾功能,治疗开始和结束分别测量子宫和子宫肌瘤的体积和内膜厚度。结果A组肌瘤体积缩小了42.58%(P<0.01),B组肌瘤缩小了41.55%(P<0.01),两者之间无显著性差异(P>0.05)。而两组的药物副作用也无显著差别。结论每日口服米菲司酮10mg可以有效的缩小子宫肌瘤,副作用小。     

新生儿接种流感嗜血杆菌乙型肝炎偶联疫苗（COMVAX^TM）的安全性和免疫效果研究

将出生时接种过重组酵母乙肝疫苗的131名HBsAg阴性母亲的新生儿,随机分为两组,一组接种COMVAX^TM,另一组接种单价乙肝疫苗和单价流感嗜血杆菌偶联疫苗,出生时第一针乙肝疫苗接种后,应用2,4,13月程序免疫,在2,4月免疫后,接种COMVAX^TM组和对照组新生儿中无一例发生重度副反应,接种COMVAX^TM组新生第一针免疫前（2月）和二针免后一个月（5月）的抗－HBs阳转率分别为53．73％和95．00％,抗全GMT分别为104．10和56．29,均与接种单价组无显著差异,第二针免疫后一个月接种COMVAX^TM组96．00％新生儿抗－PRP抗体达到长期保护临界值（1.0ug/ml)水平,而接种单价流感嗜血杆菌疫苗组新生儿为95．20％,结果表明,对于健康母亲所生的新生儿,接种COMVAX^TM疫苗,抗－HBs和抗－PRP抗体阳转率及滴度均不低于接种单价疫苗组。     

大豆多糖联合环磷酰胺对S180荷瘤小鼠抗肿瘤增效作用研究

目的 从免疫学角度研究大豆多糖对环磷酰胺的减毒增效作用及其机制.方法 选用昆明种小鼠80只,随机分为阴性对照;大豆多糖(SSPS)组:50、100、200 mg/(kg· d);阳性对照:环磷酰胺(CP) 25 mg/(kg·d);大豆多糖联合环磷酰胺组:(1)CP 25 mg/(kg·d)+SSPS mg/(kg·d)、(2)CP 25 mg/(kg·d)+SSPS 100 mg/(kg·d)、(3)CP25 mg/(kg·d)+SSPS200 mg/(kg·d);0.2 mL/只,腋下接种S180,腹腔给药,连续给药10d.测定大豆多糖联合环磷酰胺对S180荷瘤小鼠瘤重、胸腺指数、脾指数的影响,ELISA法检测S180荷瘤小鼠外周血血清中细胞因子IL-2含量的影响.结果 大豆多糖能够抑制S180荷瘤小鼠的肿瘤生长,其抑瘤率分别为24.10％、35.39％和39.75％,与环磷酰胺合用后其抑瘤率为89.87％、91.91％和92.63％(P＜0.05,P＜0.01),q值0.99 ～1.00,具有协同作用;且合用后提高了环磷酰胺所致免疫低下小鼠的胸腺指数和脾指数;并促进S180荷瘤小鼠分泌IL-2.结论 大豆多糖通过增加荷瘤小鼠免疫功能而减轻环磷酰胺对机体的毒副反应,增强其抗肿瘤作用.     

氟康唑联合克霉唑阴道片治疗复发性外阴阴道念珠菌病临床观察

目的 探讨和分析氟康唑联合克霉唑栓阴道片治疗复发性外阴阴道念珠菌病的临床疗效.方法 选择复发性外阴阴道念珠菌病患者94例,随机分为实验组和对照组各47例.实验组分别于d1、d4口服氟康唑150 mg,同时克霉唑阴道片500 mg阴道用药;对照组于d1、d4仅用克霉唑阴道片500 mg阴道用药.两组均于月经期后重复用克霉唑阴道片500 mg单次,实验组同时口服氟康唑150 mg单次,连续使用6个月,治疗结束后1周、1个月、3个月各复查1次.结果 两组治疗后1周的总有效率无显著差异,实验组为93.62％,对照组为85.11％;但治疗后1个月实验组的复发率为0,而对照组的复发率为12.5％;治疗后3个月实验组复发率为2.27％,对照组为14.29％,两组在1个月及3个月复发率的比较均有显著差异.结论 氟康唑联合克霉唑阴道片对复发性外阴阴道念珠菌病的治疗和预防复发效果满意.     

The use of progesterone antagonists and progesterone receptor modulators in contraception

Progesterone antagonists (PAs) and progesterone receptor modulators (PRMs) have contraceptive potential by suppressing follicular development, delaying the surge of luteinizing hormone (LH), retarding endometrial maturation, and promoting endometrial bleeding. Mifepristone, in daily doses of 2-10 mg, blocks the LH surge and ovulation. Many of the studies were conducted in women not at risk of pregnancy, and thus the contraceptive efficacy is not yet known. Nevertheless, there is evidence that daily doses of 2 or 5 mg of mifepristone have contraceptive potential. Because of anovulation, there may be an unopposed estrogen effect on the endometrium, although this risk may be mitigated by the noncompetitive anti-estrogenic activity exhibited by both PAs and PRMs. Low doses of PAs and PRMs, which do not affect ovulation, retard endometrial maturation, indicating that the endometrium is exquisitely sensitive to these compounds. This raises the prospect of endometrial contraception, i.e. prevention of endometrial maturation without disturbing ovulation or producing alterations in bleeding patterns. This approach works well in monkeys but was not found to be very promising when given to women not using contraception. On the other hand, 200 mg mifepristone administered 48 h after the LH surge, which has minimal or no effect on ovulation and bleeding patterns, is an effective contraceptive; yet, it is not a practical approach to contraception. Late luteal phase administration of mifepristone produces menstrual bleeding. However, when mifepristone was administered every month at the end of the cycle either alone or together with prostaglandins, it was not very effective in preventing pregnancy. In contrast, a mifepristone-prostaglandin combination has been shown to be a very effective treatment for occasional menstrual regulation, with vaginal bleeding induced in 98% of pregnant women, with menses delay of 11 days or less. Mifepristone is an excellent agent for emergency contraception when used within 120 h of unprotected intercourse. It is also possible that PAs and PRMs may be used to reduce the occurrence of bleeding irregularities induced by progestin-only contraceptive methods. Both classes of progesterone receptor ligands may also have contraceptive efficacy by having a pharmacological effect on the embryo or altering tubal transport or other aspects of tubal physiology.     

Levonorgestrel and mifepristone in emergency contraception

Research on new technologies by the Special Programme of Research, Development and Research Training in Human Reproduction at WHO has led to the development of two new methods for emergency contraception, the levonorgestrel regimen and a low-dose mifepristone regimen. In 4 years, the levonorgestrel regimen has already been approved in some 95 countries. We review this research and present combined data from our multinational trials and combined estimates of efficacy for mifepristone and for levonorgestrel separately. Data were available for 6283 women in 10 mg mifepristone groups and 4098 women in levonorgestrel groups. One of these studies compared the two methods, namely a randomized, double-blind trial in which we also investigated a single dose of 1.5 mg of levonorgestrel. Both levonorgestrel and mifepristone are effective for emergency contraception and prevent a high percentage of pregnancies when used within a few days after coitus. Mifepristone is associated with later return of menses compared to levonorgestrel.     

Comparison of Yuzpe regimen,danazol, and mifepristone (RU486) in oral postcoital contraception.

OBJECTIVE--To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN--Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING--Community family planning clinic. SUBJECTS--616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES--Number of pregnancies, incidence of side effects, and timing of next period. RESULTS--The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS--Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.     

Mifepristone: a novel estrogen-free daily contraceptive pill

When the first synthetic progesterone antagonist (mifepristone) was synthesized over 20 years ago, it was clear that it had a potential as an antifertility agent. Research into the use of antiprogestogens for contraception have concentrated on three general approaches: (1) inhibition of ovulation, (2) inhibition of implantation and (3) disruption of implantation or "menstrual induction". The effect of mifepristone on the ovarian and endometrial cycle depends on dose, timing and frequency of administration. Doses of 10 mg per day or more suppress follicular development and estradiol levels. Ovulatory cycles are maintained in the dose of less than 2 mg although there is increased variability in cycle length. The endometrium shows some minor asynchronous changes, although these are not sufficient to prevent pregnancy. We have chosen to investigate daily doses between 2 and 5 mg which inhibit ovulation and menstruation in over 90% of cycles while still maintaining follicular development and levels of estradiol within the range found during the follicular phase. The endometrium shows proliferative or cystic changes lined by a layer of inactive glandular epithelium set in densely packed stroma. There is, however, an absence of proliferative activity as reflected by a reduced mitotic index and Ki67 staining. These unusual histological appearances are associated with downregulation of PR but a massive upregulation of AR in particularly glandular epithelium. The antiproliferative effect of mifepristone is reassuring suggesting that the risk of atypical hyperplasia due to the effect of prolonged exposure to estrogen unopposed by progesterone is low. In a pilot study, there were no pregnancies in 200 months of exposure in 50 women who used this method as their sole method of contraception. Daily mifepristone could provide a novel contraceptive method which should be devoid of the risks associated with estrogen containing combined oral contraceptive (COC), e.g. venous thromboembolism. The health benefits of avoiding the morbidity associated with menstruation are considerable. Recent surveys suggest that amenorrhoea would be popular with many women.     

Termination of pregnancy with reduced doses of mifepristone. World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation.

OBJECTIVES--To compare the abortifacient efficacy and side effects of three doses of the antiprogestin mifepristone plus prostaglandin for termination of early pregnancy. DESIGN--Randomised, double blind multicentre trial. SETTING--11 departments of obstetrics and gynaecology and of family planning, mostly in university hospitals, in seven countries. SUBJECTS--1182 women with an early pregnancy (menstrual delay of 7-28 days) requesting abortion. INTERVENTIONS--Single doses of 200 mg, 400 mg, or 600 mg mifepristone followed, 48 hours later, by vaginal pessary of 1 mg of the prostaglandin E1 analogue gemeprost. MAIN OUTCOME MEASURES--Outcome of treatment; duration and subjective amount of menstrual bleeding; side effects and complications; and concentrations of haemoglobin. RESULTS--Outcome was similar with the three doses of mifepristone. Of the 1151 women with known outcome, 95.5% had a complete abortion (364 (93.8%) of those given 200 mg mifepristone, 368 (94.1%) of those given 400 mg, and 367 (94.3%) of those given 600 mg), 3.7% had an incomplete abortion (14 (3.6%), 15 (3.8%), and 14 (3.6%)), 0.3% had a missed abortion (three (0.8%), one (0.3%), and none), and 0.4% had a continuing live pregnancy (two (0.5%), two (0.5%), and one (0.3%)). Of the 43 women who had incomplete abortion, 23 underwent emergency uterine curettage (usually for haemostatic purposes) and three of these women were given a blood transfusion. The numbers of reported complaints, bleeding patterns, and changes in blood pressure and haemoglobin concentrations were similar with the three treatments. CONCLUSIONS--For termination of early pregnancy a single dose of 200 mg mifepristone is as effective as the currently recommended dose of 600 mg when used in combination with a vaginal pessary of 1 mg gemeprost.     

Lessons from an audit of unplanned pregnancies.

To determine the effectiveness of contraceptive use a two year audit of pregnant women registered in one group practice was carried out. The methods of contraception used by women with unplanned pregnancies were studied and the rates of failure assessed. Of the 518 pregnancies during the study, 187 (36%) were unplanned. Unplanned pregnancies were most common in the 15-19 age group (54 out of 187), and women aged under 25 used contraceptives less reliably than women aged 25 and over. The combined pill was the most effective method of contraception in all age groups. The methods that resulted in most unplanned pregnancies were the sheath in women aged 25 and over and incorrect use of oral contraceptive or no contraception in those aged under 25. The fear of side effects was an important reason why women did not use the combined pill, being cited by 22 out of 134 women, and inappropriate medical advice was cited by a further 20 women. More discussion between doctors and patients and readily available information on the use of oral contraceptives might help to reduce the number of unplanned pregnancies.     

Endocervical prostaglandin E2 gel for preinduction cervical softening

A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.     

Endocervical prostaglandin E2 gel for preinduction cervical softening

A single, endocervical application of a new commercial preparation of prostaglandin E₂ (PGE₂) gel, 0.5 mg of PGE₂ in 2.5 ml (3g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE₂ vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55 %) of the gel group, 15/41 (37 %) in the tablet treated women, and 8/40 (20 %) in those receiving placebo. Od interest was the observation that of women with very unfavorable induction features (Bishop score 0–2), the cervical gel treatment resulted in a 6/8 (75 %) success rate compared with 2/13 (15 %) success for the vaginal tablet and 0/7 (0 %) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.