Transdermal contraceptive patches

Many contraceptive methods have been developed for fertility regulation, either reversible or irreversible, in males and females. Oral contraceptives have been considered the most popular form of reversible contraception. However, they must be taken consistently, on a daily basis for 21 or 28 days of each menstrual cycle, in order to achieve the maximal outcomes of contraception. Moreover, their contraceptive efficacy has been reportedly affected by their interactions with many drug products taken concurrently for other conditions. To resolve the dilemma of daily compliance and the risk of potential interactions with drugs taken orally, several non-traditional delivery systems have been developed to permit contraceptive agents and their combinations to be administered via a non-oral route, and also at a lesser frequency of administration, so as to enhance treatment compliance, maximize therapeutic outcomes, and minimize adverse effects. One typical example is the successful development of the ethinylestradiol/norelgestromin patch for achieving contraception in females via transdermal delivery. With topical application on intact skin, each patch delivers a combination of norelgestromin and ethinylestradiol for a week. With a treatment schedule of 3 weeks with a patch on and 1 week without a patch for each menstrual cycle, the ethinylestradiol/norelgestromin patch has achieved a clinical efficacy that is considered bioequivalent to oral contraceptives (with an unintended pregnancy rate of 0.8% per woman-year for the patch versus 0.1% per woman-year for the combined oral contraceptive). Stimulated by the marketing success of the ethinylestradiol/norelgestromin transdermal contraceptive patch, and a growing recognition of the therapeutic benefits realized by delivering an orally inactive progestin via a transdermal route, other transdermal drug delivery systems (DDS), such as transdermal gels and a metered-dose transdermal spray system, have also been developed. Further transdermal contraceptive patches have also been developed. One of these is similar to the ethinylestradiol/norelgestromin patch, in that it is fabricated from an adhesive polymer matrix diffusion-controlled DDS; however, it has a two times smaller patch size (to minimize localized reactions at the application site). This was made possible by substituting norelgestromin with a more potent progestin called gestodene, that has a higher skin permeation rate. The other transdermal patch that has been developed employs a microreservoir partition-controlled delivery system, to provide dual-controlled delivery of estradiol (a natural estrogen) and levonorgestrel (another potent synthetic progestin) at constant rates (zero-order kinetics). Clinical studies have demonstrated that these two new patch systems may be attractive alternative forms of contraception, since ovulation inhibition has been achieved in all subjects who wear the transdermal patch for 3 weeks, replacing it on a weekly basis. A transdermal gel has been formulated to contain elcometrine, which has a progestational potency that is 100 times that of progesterone but is orally inactive, in an alcoholic solution. Preliminary clinical studies have indicated that suppression of ovulation was achieved in the majority of subjects receiving daily application of the transdermal gel. To address the problems associated with the dosing accuracy of the transdermal gel, due to difficulty controlling the area and size of the application site, the feasibility of delivering the transdermal gel from a metered-dose transdermal spray system is currently under evaluation by the Population Council.     

1例急性心梗并发心脏破裂的术后护理

目的：总结分析急性心梗并发心脏破裂的术后护理。方法：急行冠状动脉旁路移植（CABG）及心室穿孔修补术后的精心护理方法。结果：4天后，各项检测指标显示病人的生命体征趋向平稳，后康复出院。结论：AMI合并心脏破裂临床罕见，但在IABP及心肺辅助支持下紧急手术，护理工作中严密观察记录病情的微细变化，及时整护理方案，可有效控制和减少并发症的发生，患者有望获救。     

人天然白介素－2治疗恶性肿瘤的Ⅱ期临床观察

目的评价人天然白介素－２（ＩＬ－２）治疗恶性肿瘤的效果。方法采用ＩＬ－２加淋巴因子激活的杀伤细胞（ＬＡＫ细胞）全身输注治疗１４例实体瘤（恶性黑素瘤４例，肾癌２例，原发性肝癌和肠癌各３例，恶性淋巴瘤和恶性腮腺混合瘤各１例）和胸腹腔内注入治疗１０例癌性胸腹水（胃癌４例，卵巢癌２例，肠癌、乳腺癌、胰腺癌和肺癌各１例）。结果实体瘤缓解率为２１．４％（３／１４），胸腹水缓解率为７０％（７／１０）。不良反应有发热（＜３９℃）３例；恶心１例；肾功能障碍１例，停药后恢复正常。结论人天然ＩＬ－２具有一定的抗肿瘤作用。     

恶性胸水的综合诊断

对４２例恶性胸水患者进行胸水脱落细胞检查、胸膜活检、纤维支气管镜等多项检查方法诊断。结果：胸水脱落细胞检查阳性为３０／４２（７１．４％），胸膜活检阳性为２１／３２（６５．６％），两项检查其中一项或两项阳性３５例（８３．３％），并对各项检查意义进行讨论。     

虫草素的紫外与红外光谱特征

将北虫草剩余培养基中提取的结晶与3′-脱氧腺苷等7种物质比较,证明结晶与标准品的紫外特征一致,相关系数为0.9996。两者的红外光谱相同、液相色谱为单一峰,纯度大于98％。     

The effects of traumatic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression

Adult, male, Sprague-Dawley rats were anesthetized, intubated, and mechanically ventilated with 1.5-2.0% isoflurane in oxygen (30%) and air. Rats were prepared for fluid percussion traumatic brain injury (TBI), laser Doppler flowmetry, and measurement of brain tissue nitric oxide (NO) levels using an ISO-NO electrode system. After preparation, isoflurane was reduced to 1.5%, and the rats were randomly assigned to receive sham (n = 6), moderate (1.9 atm, n = 6), or severe (2.8 atm, n = 6) parasagittal fluid percussion TBI. CBF and brain tissue NO levels were measured for 4 h, and then isoflurane levels were increased to 4.0% and the rats were decapitated and the brains were removed. Total RNA was isolated from rat brains and cytokine expression was determined. Laser Doppler flow velocity remained constant in the sham-injured rats but decreased significantly in rats subjected to moderate (p < 0.05) or severe (p < 0.05) TBI. Brain tissue NO levels remained constant in the sham-injured rats but decreased significantly (p < 0.01) after moderate TBI. Severe TBI produced slight, insignificant reductions in NO levels. Cytokine expression was very low in the shaminjured rats. TBI-induced expression of mRNAs for interleukin-1 alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNFa). IL-1alpha and IL-1beta mRNA expression increased significantly (p < 0.05 vs. sham-injury) after severe TBI and IL-6 and TNFa mRNA expression increased significant (p < 0.05 vs. sham-injury) after both moderate and severe TBI. Other cytokine mRNA expression was unchanged after TBI.     

Bidirectional cavopulmonary shunt as a rescue procedure for right ventricular endomyocardial fibrosis

The surgical treatment for patients with endomyocardial fibrosis consists of resection of endocardial fibrotic tissue and replacement or repair of atrioventricular valve. Even after endocardiectomy and valvular remodeling, some patients exhibit very poor hemodynamic profile because of myocardial failure due to long-standing restriction of ventricle or ventricles. Here, we report a case of endomyocardial fibrosis in right ventricle who underwent endocardiectomy and valvular replacement followed by bi-directional cavopulmonary shunt to compensate weaning failure from cardiopulmonary bypass. The long-term outcome and the indication of bi-directional cavopulmonary shunt has not been confirmed, although it was effective for saving the life of patients with low cardiac output and acute right ventricular failure.     

不宜切除小肝癌射频与射频联合全身化疗的随机对照初步研究

目的 研究射频联合化疗治疗不宜切除小肝癌的临床安全性以及对肝癌原位复发率的影响。方法 ≤3cm不宜切除的原发性肝癌患者38例,其中27例1年随访资料完整。根据射频与射频联合全身化疗的随机分组方案入选标准,射频组12例,射频联合全身化疗组15例。在超声引导下行多电极射频治疗。化疗方案为：表阿霉素50mg,d1,3,静推;顺铂40mg,d1,3,静滴;氟脲嘧啶500mg,d1,2,3,静滴。观察患者术后1,4,7d的肝功能、血常规和并发症,术后1,6,12个月复查GT(增强),评价两组患者治疗的安全性及原位复发率。结果 两组射频术后1个月,均无原位复发。射频联合全身化疗组6,12个月的原位复发率较单射频组明显下降,差异有显著性。两组均无严重并发症,肝功能、血常规变化差异无显著性。结论 对≤3cm不宜切除的原发性肝癌患者,射频联合全身化疗是安全的,并能降低肝癌原位复发率。     

Inhibition of anchorage-independent growth and lung metastasis of A549 lung carcinoma cells by IkappaBbeta

To evaluate the role of the NF-kappaB signaling pathway in oncogenic transformation, we expressed IkappaBbeta, a specific inhibitor of NF-kappaB, in two human lung adenocarcinoma cell lines, A549 and H441. Expression of IkappaBbeta significantly reduced NF-kappaB activation induced by cotransfection with p65/RelA or TNF-alpha and abrogated the basal NF-kappaB activity in A549 cells. Transfection of IkappaBbeta into A549, H441 and K-ras-transformed NIH3T3 cells suppressed anchorage-independent growth as measured by colony formation in soft agar. Anchorage-independent growth of vector-transfected A549 cells in reduced serum could be enhanced by both EGF and IGF-I. In contrast, only EGF but not IGF-I could induce anchorage-independent growth of IkappaBbeta-expressing A549 cells, suggesting that the IGF-I signaling pathway regulating growth and survival may be blocked by IkappaBbeta. Interestingly, expression of IkappaBbeta suppressed growth of A549 cells in low serum in vitro without affecting in vivo growth subcutaneously in nude mice. However, metastatic growth of IkappaBbeta-expressing A549 cells in the lungs of nude mice was significantly inhibited. These results provide evidence that NFkappaB plays an important role in anchorage-independent growth and metastatic growth of lung carcinoma cells.