N－（1－乙氧羰基－3－苯氨甲酰基丙基）甘氨酰甘氨酸衍生物的合成

报道４个Ｎ－（１－［１－乙氧羰基－３－（对甲）苯氨甲酰基］丙基甘氨酰｝－Ｎ－取代甘氨酸（ＸＩ１～４）和５个１－［１－乙（或甲）氧羰基－３－（对甲）苯氨甲酰基］丙基－４－取代－１，４－哌嗪－２，５－二酮（ＸＩＩ１～５）共９个估计有血管紧张素转化酶抑制活性化合物的合成和鉴定。所有这些化合物及９个相应的酯（Ｘ１～９）均未见文献报道。药理初试结果，化合物ＸＩＩ２，ＸＩＩ５，ＸＩ４和ＸＩＩ１均有较强降压活性。     

Multicentre randomised controlled trials in obstetrics and gynaecology: an analysis of trends over three decades

To assess the trend in multicentre randomised controlled trials (RCTs), a database of 670 RCTs was assembled from four generic obstetric and gynaecological journals ( Acta Obstetricia et Gynecologica Scandinavica , British Journal of Obstetrics & Gynaecology , Obstetrics & Gynecology and American Journal of Obstetrics & Gynecology ) for 1975, 1980, 1985, 1990, 1995, 2000 and 2005. During this period, there was an inflationary trend with the proportion of published multicentre RCTs (from 12.9% in 1975 of all RCTs to 23.8% in 2005; P  = 0.008). Multicentre RCTs had multiauthored publications (OR = 2.90; 95% CI 1.99–4.22) and more often received external funding (OR = 2.41; 95% CI 1.70–3.48) than single centre RCTs. The inflationary trend in multicentre RCTs requiring funding and collaboration represents the increasing complexity of medical research necessary to underpin evidence-based practice.     

Liposomal Bupivacaine: Extended Duration Nerve Blockade Using Large Unilamellar Vesicles that Exhibit a Proton Gradient

Background: There is a clinical requirement for longer-acting local anesthetics, particularly for the management of postoperative and chronic pain. In this regard, liposomes have been suggested to represent a potentially useful vehicle for sustained drug release after local administration. In the current study, the authors used a transmembrane pH gradient to efficiently encapsulate bupivacaine within large unilamellar vesicles. They report on the kinetics of drug uptake and release and the duration of nerve blockade.

Methods: The rate and extent of bupivacaine uptake into large unilamellar vesicles that exhibit a pH gradient (interior acidic) were determined and compared to drug association with control liposomes that did not exhibit a proton gradient. In subsequent studies, researchers examined the kinetics of bupivacaine release from these liposome systems in vitro. Using the guinea pig cutaneous wheal model, the rate of clearance of the liposome carrier was monitored after intradermal administration, using a radiolabelled lipid marker, and the duration of nerve blockade produced by free and liposomal bupivacaine was compared.

Results: Bupivacaine was rapidly and efficiently accumulated within liposomes that exhibited a pH gradient (interior acidic) with trapping efficiencies of 64-82% of total drug, depending on the initial bupivacaine:phospholipid ratio. Little uptake was seen, however, for control vesicles that did not exhibit a transmembrane proton gradient. Using an in vitro model of drug clearance, liposomally encapsulated bupivacaine was found to be slowly released for a longer period of time compared with either the free drug or bupivacaine associated with control (no pH gradient liposomes). In the guinea pig cutaneous wheal model, more than 85% of the liposomal carrier was found to remain at the site of administration for 2 days. The sustained drug release afforded by liposomes that exhibited a pH gradient resulted in an increase in the duration of nerve blockade of as much as threefold compared with either the free drug or bupivacaine in the presence of control (no pH gradient) liposomes. Recovery of half maximal response (R2.5) after administration of 0.75% free bupivacaine, for example, was approximately 2 h, whereas the same dose of bupivacaine in pH gradient liposomes exhibited a R2.5 of approximately 6.5 h.     

A multimodal neurophysiological assessment in terminal renal failure

A prospective multimodal neurophysiological study was conducted on 36 patients with end-stage renal failure, 16 of whom subsequently underwent renal transplantation (TR). Nerve conduction study and somatosensory evoked potentials revealed that peripheral conduction deficit, often sub-clinical, was the commonest abnormality, and TR resulted in substantial improvement. Visual evoked potentials demonstrated subclinical impairment, which did not improve after TR. The brainstem auditory evoked potentials were essentially normal and unaffected by TR.     

Evidence that 5α-pregnan-3α-ol-20-one is the metabolite responsible for progesterone anesthesia

Tadpoles (Rana catesbeiana) were anesthetized with [³H]-progesterone (PG) in order to identify the steroid responsible for anesthesia. PG and its metabolites in brain were resolved (HPLC) and quantitated following sacrifice at different behavioral endpoints. The results support the hypothesis that 5α-pregnan-3α-ol-20-one mediates the loss and the return of the righting response. The observed levels for PG were not consistent with such a role. Neither PG nor 5α-pregnan-3α-ol-20 produced analgesia.     

Rotation of Listing's plane during vergence.

When visually fixating targets on an isovergence surface, the position of each eye was constrained to a plane. Thus, Listing's law holds during vergence. The planes were, however, rotated temporally with respect to those when viewing distant targets. The effect of this rotation was to produce a torsion which depended on eye elevation; extorsion of the two eyes for downward gaze and intorsion for upward gaze. The saccadic velocity command was relatively unaffected during vergence. Computer simulations suggest that the saccadic tonic command and the vergence command interact multiplicatively in three dimensions.     

The pursuit of excellence in nursing care: what does it mean?

This study explores the meaning of excellence in nursing care held by nurses Qualitative data were collected from 156 undergraduate and postgraduate nurses by means of an open-ended questionnaire Respondents were asked to reflect on practice which enabled a clear understanding of the meanings given to excellence in nursing care In addition, details of their nursing background, level of nursing experience, and demographics were sought Responses were content-analysed for themes by three coders Four major themes emerged (1) professionalism, (2) holistic care, (3) practice, (4) humanism The fourth theme comprised three sub-themes (a) enabling personal qualities, (b) nurse-patient relationships, and (c) nurse-health team relationships Responses revealed that professionalism constituted an all-encompassing theme subsuming all others Findings suggested that the client is the central focus of excellent nursing care at all times According to these respondents, nurses who deliver excellent nursing care implement nursing in a professional and competent manner, demonstrate a holistic approach to caring, possess certain personal qualities which enhance practice, and relate to patients, families, peers, hospital administrators and community members in a competent, cooperative manner An important aspect of this study is the differential quality of responses provided by respondents, who were students enrolled in a nursing degree programme compared to respondents who were state-registered nurses and concurrently undertaking higher degree studies The final result is suggestive of the stages of transition through which nurses pass in their quest for excellence     

Babies of HIV infected women in Edinburgh

Acquired Immune Deficiency Syndrome (AIDS) was first recognised in children in 1982. This paper describes a paediatric counselling and screening clinic in Edinburgh for babies born to women who are Human Immunodeficiency Virus Positive.