Synthesis and cholinergic properties of bis[[(dimethylamino)methyl]furanyl] analogues of ranitidine.

The histaminergic H2 antagonist, ranitidine, has also been found to significantly inhibit acetylcholinesterase (AChE) in vitro. In an effort to develop novel, nonquaternary AChE inhibitors capable of penetrating into the CNS and alleviating the cholinergic deficit characteristic of Alzheimer's disease, a series of bis[[(dimethylamino)methyl]furanyl] analogues of ranitidine has been synthesized. All compounds were evaluated for human erythrocyte AChE inhibitory activity and compared to ranitidine, physostigmine, and tetrahydro-9-aminoacridine (THA). The most active AChE inhibitors were N,N'-disubstituted derivatives of 2-nitro-1,1-ethenediamine and 4,6-dinitro-1,3-benzenediamine, with compound 8 demonstrating activity greater than physostigmine. Deletion of the diaminonitroethene group in a series of alkyl and aryl bis-thioethers, yielded a number of slightly less active compounds, comparable in potency to THA. The 13 most active AChE inhibitors all demonstrated a more selective inhibition of AChE, as opposed to butyrylcholinesterase inhibition, than did THA. Compounds 3 and 22 were equally active to THA in potentiating rat ileal contractions. Binding studies demonstrated M1 and M2 cholinergic receptor affinities slightly greater than or equal to THA. Differential receptor binding studies showed compound 12 resembled THA in agonist/antagonist activity. Compounds 11-13 significantly elevated mouse brain acetylcholine levels, when administered at 80% of their approximate lethal doses, but were less active than THA or physostigmine.     

医械时代

曾几何时,一个小药箱,一个听诊器,就是一个医生的全部家当。但今天这也许意味着医疗事故官司和失去患者信任度的双重危险。在科学日益昌明的现在,医者和患者都越来越仰仗更昂贵、更先进的仪器,而在这现象之后,是各种医疗仪器设备的迅速普及,是诊疗过程的快速、高效和缜密,是更多科技新发明对人体的近距离关照,当然随之衍生出来的,还有过度医疗服务的不当取利,和种种难见阳光的幕后交易。     

人血浆三尖杉酯碱高效液相色谱测定法

本文建立了在常温常速离心条件下进行样品预处理的人血浆三尖杉酯碱高效液相色谱荧光测定法。本法批内CV%为3.08～3.47%,批间CV%为4.36～5.28%,回收率范围为93.6～95%,标准曲线在12.5～500ng/ml范围内线性良好(r=0.998)。方法简单、快速、准确,适于临床应用。     

青少年型帕金森病的临床特征

目的　探讨青少年型帕金森病 (PD)的临床特征。方法　对 2 8例青少年型PD患者的临床资料进行回顾性分析。结果　 2 8例中 5例有家族史 ,呈常染色体隐性遗传 (AR JP) ;症状轻、病程长 ,症状常左右不对称 ,腱反射活跃和症状波动较常见 ;头部CT或MRI检查一般正常 ;对多巴制剂反应良好 ,但其所诱发的症状波动出现早。与散发性PD患者相比 ,AR JP患者发病年龄更早 ,为 (2 0 6± 5 6 8)岁 ,病程更长 ,为 (9 5±5 77)年 ,而病情较轻、症状波动和腱反射活跃更多见 ,多巴制剂不良反应更常见。结论　青少年型PD具有独特的临床特征 ,可能是一个独立的疾病实体。AR JP与散发性青少年型PD临床特征不同 ,提示二者可能具有不同的发病机制。     

注射吸毒致破伤风的临床特点及分析

目的探讨注射吸毒致破伤风的诊断与治疗。方法回顾性分析了9例注射吸毒者破伤风的临床资料。结果9例注射吸毒致破伤风的病人中,5例治愈,4例死亡,死亡原因:3例因呼吸肌痉挛和分泌物过多阻塞呼吸道窒息死亡,1例因呼吸衰竭死亡。结论注射后皮肤和软组织感染可认为是引起破伤风外伤伤口。注射吸毒破伤风应按重症破伤风处理。及时气管切开或气管插管机械辅助呼吸可降低死亡率。     

隆突性皮纤维肉瘤23例临床分析

本文报告了我科1978～1990年间收治的降突性皮纤维肉瘤23例,均经组织学证实.治疗以手术切除为主,术后局部复发率为65.2%.无一例发生转移.切除不彻底是复发的主要原因.作者指出广泛切除是防止复发的主要措施,手术前后的放疗有可能减少复发.     

Doctor – How do I use my EpiPen?

Parents and children who have been prescribed an Epipen are often unable to demonstrate its correct administration. One contributory factor may be that doctors are unfamiliar with the EpiPen and are unable to demonstrate the correct administration of the pen to the family. The aim of this study was to determine the rate of correct EpiPen demonstration by junior and Senior Medical Staff at a major tertiary paediatric Hospital. Junior and Senior medical staff were scored on their ability to correctly use the EpiPen trainer. A 6 step scoring system was used. One-hundred doctors were recruited (Residents n = 31, Senior Residents n = 39, Fellow/Consultants n = 30). Junior and Senior Medical staff had similar scores for EpiPen demonstration, the number that needed to read the EpiPen instructions prior to use and the frequancy of accidental self-injection into the thumb. Only two doctors (2%) demonstrated all 6 administration steps correctly. The most frequent errors made were not holding the pen in place for >5 seconds (57%), failure to apply pressure to activate (21%), and self-injection into the thumb (16%). Ninety five doctors needed to read the instructions, and of these, only 39 (41%) then proceeded to correctly demonstrate the remaining 5 steps. Forty-five doctors had previously dispensed an EpiPen, but only three demonstrated its use to parents/children with a trainer. The majority of doctors do not know how to use an Epipen and are unable to provide appropriate education to parents/children. In 37% of cases, the demonstration would not have delivered adrenaline to a patient.     

Weight of edged spherical lenses in simulated eyewire shapes

Eyewire shapes of some currently available spectacle frames were constructed mathematically and weights of spherical lenses cut to these shapes were computed for different decentrations in three commonly used lens materials. The results confirm a previous observation that the edged shape of a negative lens has only a minor effect on its weight, although this is often not the case for positive lenses. The appropriate diameters of circular centred lenses to be used in comparing lens weight for different materials were also examined Relative to those adopted in previous studies, it was found that the weight of a larger lens, 58 mm diameter for negative lenses and 65 mm diameter for positive lenses, would more adequately represent the average weight of edged lenses in modern spectacle frames.