Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

山莨菪碱治疗麻醉剂依赖性

阿片成瘾者２５０例（男性２２２例，女性２８例，年龄３０±ｓ５ａ）应用山莨菪碱０．５－２ｍｇ／（ｋｇ·ｄ），分２－３次加入１０％葡萄糖２５０ｍＬ或５％葡萄糖生理盐水５００ｍＬ静脉滴注；东莨菪碱０．０２－０．０３ｍｇ／ｋｇ加入１０％葡萄糖２５０ｍＬ静脉滴注１次，必要时对重患者追加１次，疗程５－７ｄ。结果戒断症状均有改善（Ｐ＜０．０１），２７例需加用羟丁酸钠。不良反应轻，可作为阿片瘾者的脱瘾药物。＊Ｐ＜０．０１。碱确能解除阿片药物戒断症状。其对阿片戒断症状缓解时间在治疗４－５ｄ后，强烈觅药渴求也随之逐渐消失。１５０例（６０％）要求进食，１７５例（７０％）仍需借助安眠药睡眠。另６５例（２６％）戒断症状阵发性发作，每次持续０．５－１ｈ，症状轻重不一，轻者流泪、全身弥漫性疼痛，重者焦躁不安、心中猫抓虫咬样难受，甚至想自残，可配合艾司唑仑３－４ｍｇ／ｄ，ｐｏ或氯硝西泮６－１０ｍｇ／ｄ，ｐｏ；也可用氯硝西泮１－２ｍｇ／次，ｉｍ，每日２－３次；针刺胃俞、脾俞、中脘、足三里、印堂、太阳、百会、内关、合谷、命门、夹脊和肾俞穴位，根据临床症状任选其中３－５个穴位进行治疗或心理治疗能快速减轻患者戒断症状。治程中２７例（１０．８％）重?     

应用小鼠在Y形迷宫中的自主选择能力测定急性及慢性东莨菪碱与吗啡对记忆的影响

应用Ｙ型迷宫研究了急性与慢性东莨菪碱和吗啡对小鼠记忆能力的影响。单剂量东莨菪碱（１ｍｇ／ｋｇｉｐ）和吗啡（１０ｍｇ／ｋｇｉｐ）均能显著损害小鼠的短时记忆（ｗｏｒｋｉｎｇｍｅｍｏｒｙ）。重复给药后东莨菪碱的这种作用很快消失。但吗啡每天一次，连续３次给药这种作用加强，连续５次给药这种作用反而减弱。东莨菪碱不能损害小鼠长时记忆（ｒｅｆｅｒｅｎｃｅｍｅｍｏｒｙ），而吗啡对长时记忆有损害作用。结果还提示小鼠短时记忆不受自发活动能力的影响。     

Tolerance and dependence to opiates

In the 19th century, investigators recognized that addiction to opiates involves tolerance and dependence. In the United States, the National Academy of Sciences and the Public Health Service initiated systematic investigations into opiate addiction in 1929. Tolerance and dependence to morphine, the prototype for opiate drugs, were the emphasis of human studies for the next fifty years. This presentation highlights salient features of tolerance and dependence learned in these studies and relates these findings to clinical use in treating pain.     

Prothrombin times and activated partial thromboplastin times in toxicology: a comparison of different blood withdrawal sites for wistar rats

The prothrombin time (PT) and the activated partial thromboplastin time (APTT) for untreated male Wistar rats were determined on the Sysmex CA-5000 Instrument for blood taken from the orbital sinus, tail vein, vena cava and aorta. Boxplot and statistical analysis was performed. Only orbital sinus puncture yields unpredictable and unacceptable variation/prolongation of clotting times.     

高浓度吗啡对体外培养的小鼠淋巴细胞增殖的抑制效应

高浓度吗啡对体外培养的小鼠淋巴细胞增殖的抑制效应北京医科大学药理学教研室陆正武，林志彬利用不同刺激原诱导的淋巴细胞增殖反应，研究吗啡的体外作用机制。结果表明：（１）高浓度吗啡（≥０．１ｍｍｏｌ·Ｌ－１）以剂量依赖方式，抑制ＣｏｎＡ／ＬＰＳ所致淋巴细胞...     

地塞米松预防术后硬膜外吗啡镇痛的部分并发症

目的：观察静脉注射地塞米松（Dex)对减少手术后与硬膜外吗啡镇痛有关的部分并发症的发生率的作用。方法：随机双盲选择48例在硬膜外麻醉下行妇科肿瘤手术病人进行观察。所有病人在手术后均接受硬膜外吗啡镇痛。Dex组病人（n=24)在手术毕静注Dex8mg，对照组病人（n=24)则给予等量生理盐水。结果：在手术后24h内，Dex组病人手术后总的恶性呕吐发生率为16．7％，明显低于对照组病人的50％（P＜0．01）。两组病人手术后皮肤瘙痒的发生率无明显差异，镇痛效果也无明显差异。结论：预防性静脉注射Dex可减少术后硬膜外吗啡镇痛引起的恶心呕吐的发生率。     

氯胺酮复合不同药物用于硬膜外术后镇痛的观察

目的 :探讨氯胺酮复合不同药物用于硬膜外术后镇痛的效果 ,为硬膜外应用氯胺酮合剂镇痛提供依据。方法 :择期行下腹部或下肢手术病人 75例 ,随机分成 5组 :Ⅰ组氯胺酮 30mg ;Ⅱ组氯胺酮 30mg加罗哌卡因 15mg ;Ⅲ组氯胺酮 30mg加咪唑安定 3mg ;Ⅳ组氯胺酮 30mg加吗啡 2mg ;Ⅴ组吗啡 2mg ,镇痛剂均用生理盐水稀释至 5ml。观察镇痛效果 ,镇痛持续时间和不良反应。结果 :Ⅰ组术后完全无痛者占 5 3 33% ,明显少于Ⅳ、Ⅴ组的 86 6 7% (P <0 0 5 ) ;镇痛持续时间 7 13h ,明显短于其他 4组 (P <0 0 5 )。Ⅳ、Ⅴ组恶心、呕吐、皮肤瘙痒发生率明显高于其他 3组 ,Ⅰ组有 1例出现谵妄。结论 :硬膜外腔注入氯胺酮有镇痛作用 ,加用罗哌卡因、咪唑安定等可增强其镇痛效果 ,延长镇痛时间     

Effects of opiates on the growth of neuron-enriched cultures from chick embryonic brain

Neuron-enriched cultures derived from 6-day-old chick embryo cerebral hemispheres were treated with morphine or methadone, 10(-5) M or 10(-6) M, on days 4-6 or 6-8 in culture and were evaluated morphologically and biochemically at day 9 using phase contrast microscopy and choline acetyltransferase activity (ChAT) as a cholinergic marker. The treatment of the cultures with morphine markedly affected their growth pattern; specifically, we observed an increased number of flat cells presumptively glia, and aggregates sided by flat cells and devoid of thick bundles of neuritic processes that normally characterize neuron-enriched cultures. These morphologic changes were reflected in a drastic decrease of ChAT activity in cultures treated from day 4 to day 6 but not from 6 to 8. In contrast to morphine, exposure to 10(-6) M methadone from day 4 to day 6 resulted in reduced ChAT activity but the growth pattern of the cultures remained morphologically intact. We suggest that morphine exerts a general neurotoxic effect whereas methadone may affect some specific cholinergic function.     

Evaluation of the effects of opioid agonists and antagonists under a delayed matching-to-sample procedure in pigeons

The effects of several opioid agonists and antagonists were examined in pigeons performing under a delayed matching-to-sample procedure. The mu agonists morphine and l-methadone, the kappa agonists U 50,488 and ethylketocyclazocine, and the opioid antagonist naloxone had no effect on the accuracy of responding. These drugs were, however, behaviorally active as evidenced by the dose-dependent decreases in rates of responding associated with their administration. In contrast, the sigma agonists (+) N-allylnormetazocine and phencyclidine decreased the accuracy of responding in a dose-dependent fashion. The relative magnitude of these drug-induced decreases in accuracy were similar across the no delay (0-s), short (2-s), and long (8-s) delay intervals. For these drugs, accuracy-decreasing effects were obtained only at doses that reduced rates of responding. The results of the present investigation parallel those reported in pigeons responding under drug discrimination tasks, in which the discriminative stimulus properties produced by the mu and kappa agonists are similar to each other but distinguishable from those produced by the sigma agonists.Recipient of Research Scientist Development Award DA 00033 from the National Institute on Drug Abuse