Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

A systematic review of resident‐as‐teacher programmes

Context Residents in all disciplines serve as clinical teachers for medical students. Since the 1970s, there has been increasing evidence to demonstrate that residents wish to teach and that they respond positively to formal teacher training. Effective resident‐as‐teacher (RaT) programmes have resulted in improved resident teaching skills. Current evidence, however, is not clear about the specific features of an effective RaT programme. Objectives This study was performed in order to investigate the effectiveness of RaT programmes on resident teaching abilities and to identify the features that ensure success. Methods of assessment used to ascertain the effectiveness of RaT programmes are also explored. Methods The literature search covered the period between 1971 and 2008. Articles focusing on improving resident teaching skills were included. Each study was reviewed by two reviewers and data were collected using a standard abstraction summary sheet. Study outcomes were graded according to a modified Kirkpatrick's model of educational outcomes. Results Twenty‐nine studies met review inclusion criteria. Interventions included workshops, seminars, lectures and teaching retreats. Twenty‐six studies used a pre‐ and post‐intervention outcome comparison method. Subjective outcome measures included resident self‐evaluation of teaching skills or evaluation by medical students, peers and faculty members. Objective outcome measures included written tests, evaluation of teaching performance by independent raters and utilisation of objective structured teaching examinations. One study objectively measured learning outcomes at the level of medical students, utilising the results of an objective structured clinical examination. Overall resident satisfaction with RaT programmes was high. Participants reported positive changes in attitudes towards teaching. Participant knowledge of educational principles improved. Study methodologies allowed for significant risks of bias. Conclusions More rigorous study designs and the use of objective outcome measures are needed to ascertain the true effectiveness of RaT programmes. Future research should focus on determining the impact of RaT programmes on learning achievement at the level of medical students.     

尿流改道及膀胱重建术的现状与展望

膀胱全切术后尿液的贮存与排出一直是未能满意解决的问题。自从1852年Simon报道输尿管乙状结肠吻合以来，经过一个多世纪的不断改进与创新，特别是1982年Kock用去管重建法制作贮尿囊的可控膀胱以来，尿流改道与膀胱重建术有了跨时代的进步和发展，显地提高了患术后生活质量。     

手法治疗肘关节错缝86例

2000年1月-2005年10月共治疗肘关节错缝86例,临床效果满意,现报告如下。1临床资料86例中男61例,女25例;年龄13~46岁。受伤机制:均为跌倒时手掌着地,肘关节过伸导致。摄X线片未见骨折及关节异常。肘关节伸屈活动障碍,伸20°~40°,屈90°~110°,屈伸平均(70·57°±3·01°)的活动范围。肘关节轻度肿胀,以内后方为甚,压痛点为尺骨半月切迹的内侧,强作旋后活动时会引起剧烈疼痛,肘三角正常。受伤至就诊时间1~3 d,平均1·5 d。2治疗方法2·1复位左肘错缝者坐于靠背椅上,助手立于患者侧背后方,紧握患者上臂,术者于患者前侧,左手握患者腕部,右手…     

The correlation between TNF-α, IL-6 in cervical mucous during follicular development and ovulation stimulation in different protocols

Objective To investigate the correlation between TNF-α and IL-6 levels in cervical mucous during follicular development and ovulation stimulation in different protocols.Methods 36 infertile women were set up as experimental groups,divided into CC, HMG, IVF-ET group,each group consisted of 12 infertile women and 15 women with normal menstrual cycles were choiced as control group.Cervical mucous during follicular phase, luteal phase and ovulation phase were collected.TNF-α, IL-6 levels in cervical mucous were measured by radioimmunology assay (RIA).Follicular development were monitored by transvaginal ultrasonagraphy.Results (1) TNF-α levels in cervical mucous of experimental groups and control group were periodically various among the reproductive cycle.It increased during follicular phase, reached to peak during ovulation phase, and decreased during luteal phase (P＜0.05).IL-6 levels had no obvious periodical changes.(2) Compared with CC and control group, levels of TNF-α,IL-6 in HMG and IVF-ET group were significantly higher (P＜0.05).(3) Levels of TNF-α and IL-6 in cervical mucous were positively correlated with the dominant follicle diameter (r=0.261, r=0.192 respectively,P＜0.05).(4) TNF-α and IL-6 showed positive correlation in the reproductive cycle (r=0.782,P＜0.05).Conclusions (1) TNF-α level shows a cyclic change in the reproductive cycle and peaks during ovulation,whereas IL-6 level does not.(2) TNF-α and IL-6 may play a certain role in the process of follicular development and ovulation.(3)The levels of TNF-α and IL-6 are up-regulated by gonadotrophic hormone.(4) TNF-α and IL-6 may have coordination properties and participate in the same biological effects.     

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion

Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged‐matched cohorts of children with and without otitis media with effusion The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA₂ is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG₂ acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non‐parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti‐PCP and the IgG₂ anti‐PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG₂ anti‐PCP against IgA total anti‐PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age‐related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.