Surgical resections in parous patients with distal ileal and colonic Crohn's disease.

The surgical resection rates among parous women with distal ileal and colonic Crohn's disease have been compared with resection rates among distal ileal (n = 197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had achieved their first pregnancy on average 8 years and 6.2 years respectively before the diagnosis of Crohn's disease was established. Resections for each patient were negatively correlated with parity in both groups. (Distal ileal disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)). Patients with distal ileal Crohn's disease and a history of pregnancy at diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57 (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer resections/patient when compared with the published resection group: mean (SD); 0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and colonic Crohn's disease, who had been pregnant in the past subsequently need fewer surgical resections. Pregnancy could influence the natural history of Crohn's disease either by decreasing immune responsiveness or by retarding fibrous stricture formation, which is the commonest indication for surgical intervention.     

Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.     

160例女性不孕症的四种病原体检测及意义

本文报告了对１６０例女性不孕症患者宫颈分泌物中解脲脲原体（Ｕｕ）、人型支原体（Ｍｈ）、沙眼衣原体（Ｃｔ）和淋病奈氏球菌（Ｎｇ）的测定，结果总体检出率７０％（１２０／１６０），明显高于对照组（同期早孕妇女），Ｐ＜０．０１。其中输卵管阻塞组阳性率８４．７８％（３９／４６），明显高于输卵管通畅组６３．４６％（３３／５２）及欠通畅组６４．５２％（４０／６２），Ｐ＜０．０５。且针对性治疗收到一定效果，提示妇女下生殖道Ｕｕ、Ｃｔ、Ｎｇ感染是输卵管阻塞性不孕的主要原因之一。对该类患者行三项检测，对不孕症的病因诊断及治疗有好处。     

鞍区肿瘤术后中枢性低钠血症的诊断和治疗

目的:探讨鞍区肿瘤术后中枢性低钠血症的诊断及处理方法。方法:对我科近四年鞍区肿瘤术后并发中枢性低钠血症的58例患者进行回顾性分析,术前、手术当日及术后每日定时检测血钠,观察尿量变化,测定中心静脉压,确定低钠血症的类型并给予相应的处理。结果:56例恢复正常,1例死于严重肺部感染,1例自动出院。结论:鞍区肿瘤易出现抗利尿激素分泌不当综合症和脑性耗盐综合症两种类型。前者需限水治疗,后者应予以充分补钠、补水,根据水、钠检测水平治疗。     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

脑卒中患者日常生活能力的评定

采用Ｂａｒｔｈｅｌ指数对１２０例脑卒中住院患者在发病后５￣６周进行日常生活活动（ＡＤＬ）能力的证实。因脑卒中遗留的功能不全，ＡＤＬ的受损率达６６．７％，肢体的Ｂｒｕｎｎｓｔｒｏｍ功能分级与ＡＤＬ积分高度相关，相关性下肢高于上肢；多元逐步回归分析显示，躯体（偏瘫）和心理（认知障碍和抑郁因素）影响ＡＤＬ的能力。认为ＡＤＬ能力的提高，不仅依赖于肢体功能障碍的改善，提高认知功能，改善情感状况，对于脑卒中患     

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)     

大鼠睾丸乳酸脱氢酶同工酶－C_4的分离纯化研究

采用加热、硫酸铵分段盐析和ＤＥＡＥ－ＳｅｐｈａｄｅｘＡ－５０柱层析，从大鼠睾丸中分离纯化了ＬＤＨ－Ｃ４。比活性提高７８４倍，活性回收率为１２．３％，纯化的ＬＤＨ－Ｃ４经聚丙烯酰胺凝胶电泳（ＰＡＧＥ）鉴定均为一条酶带，位于ＬＤＨ３和ＬＤＨ４之间。