SELEGILINE IN THE TREATMENT OF BEHAVIOURAL DISTURBANCE IN ALZHEIMER'S DISEASE

Objective. The purpose of this study was to examine the behavioural and cognitive effects of selegiline in a group of moderately behaviourally disturbed AD patients. Design. This was a 14-week randomized double-blind placebo-controlled study of selegiline (10 mg) and placebo. Setting. An outpatient clinic in an urban-based tertiary referral centre in the USA. Patients. Twenty-five outpatients meeting NINCDS criteria for probable Alzheimer's disease with associated behavioural disturbance. Measures. The Brief Psychiatric Rating Scale (BPRS), the Dementia Mood Assessment Scale (DMAS) and the Alzheimer Disease Assessment Scale (Cognitive) (ADAS-COG). Results. In the primary analysis, improvement on the BPRS and DMAS scores with selegeline treatment did not reach statistical significance. A secondary analysis using a parallel design showed a significant benefit of drug treatment on BPRS scores with a trend towards improvement on the DMAS. Among the 10 subjects who could be tested, there was a significant improvement in cognitive function on the ADAS-COG with selegiline compared to placebo. Conclusions. Short-term selegiline treatment produced an improvement in behaviour and had a significant effect on cognition in a subset of testable patients. © 1997 by John Wiley & Sons, Ltd.     

THE PATHOLOGICAL AND BIOLOGICAL NATURE OF SCREEN-DETECTED BREAST CARCINOMAS: A MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from ‘clinical’ cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history. © 1997 John Wiley & Sons, Ltd.     

Comparative biological activities of potent analogues of α-melanotropin

Several α-melanotropin (α-MSH) analogues with para substituted aromatic and nonaromatic amino acids in the 7-position of the hormone were prepared and their melanotropic activities determined in the frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. D and L-Phe(p-NO₂), D- and L-Tyr, D- and L-Ala, and Gly were substituted in the 7-position. The use of substituted D or L-aromatic amino acids in the 7th position of the central Ac-[Nle⁴] -α-MSH_4–11 - NH₂ fragment resulted in a loss in potency relative to the corresponding phenylalanine-containing analogue. The loss in potency cannot be due entirely to steric hindrance at the melanophore receptor, since nonaromatic amino acids substituted in the 7th position of this octapeptide fragment also generally led to a loss in biological activity. We reported previously that replacement of phenylalanine-7 by its D enantiomer led to a marked increase in potency in each fragment analogue tested. Analogues containing other D amino acids in the 7th position also were more potent than their L amino acid-containing analogues with one exception: Ac-[Nle⁴, Ala⁷]-α-MSH_4–11-NH₂ was more potent than Ac-[Nle⁴, D-Ala⁷]-α-MSH_4–11-NH₂ in the frog skin bioassay. Replacement of phenylalanine-7 by glycine resulted in a large decrease in potency in both bioassays, illustrating the importance of the side chain group, in this position of α-MSH, to biological potency of the hormone.     

长沙市甲基苯丙胺使用情况“应答者驱动抽样”流行病学调查

目的：了解长沙市甲基苯丙胺使用的流行情况。方法：采用同伴驱动抽样（respondent—driven sampling,RDS）,通过自拟问卷对长沙市最近3个月内使用过甲基苯丙胺的成年人进行抽样调查。结果：接受调查的129人以男性、汉族、有伴侣（包括配偶、男女朋友及同居者）、初高中学历、处于就业状态、年收入较高者为主;平均年龄为29．0a±s7．8a（最小18a,最大48a）;102人进行过HIV抗体检测,皆为阴性;有94（72．9％）人曾使用过其他非法成瘾性物质包括k粉、摇头丸、海洛因、大麻、丁丙诺啡、曲马多、美沙酮及安定;尚未发现使用可卡因及快克者。长沙市甲基苯丙胺以冰和麻古两种形式存在并被使用。使用方式全为冰壶抽吸,使用场所均为私人场所（家里、宾馆及出租房）。最近三个月内甲基苯丙胺的平均使用天数为21．4d±s31．3d（中位数10d）,冰毒的平均用量为每次0．3g,麻古3．8片。甲基苯丙胺的可及性很强,大多数人（87／126,69．0％）都能“比较容易或非常容易”地获取。使用甲基苯丙胺常见的原因有：吸毒同伴的存在、追求刺激、以及为了摆脱不良情绪状态等,很少有人用来减肥。使用甲基苯丙胺产生的不良后果主要包括对使用者的饮食、体重、健康、经济、情绪的影响以及家庭关系的伤害。结论：甲基苯丙胺在长沙易于获得、在同伴间广为传播,其使用对使用者本人及其家庭带来了严重的危害;因此相关部门有必要采取截断毒品来源、开展相关的禁毒宣传措施。     

Pharmaceutics: The Effect of Dose on the Characterization of Aerodynamic Particle-size Distributions of Beclomethasone Dipropionate Metered-dose Inhalers

The aerodynamic particle-size distribution for two doses of a Becloforte metered-dose inhaler (MDI) was measured by use of a twin-stage impinger (TSI), the new multi-stage (five-stage) liquid impinger (MSLI) and the Andersen cascade impactor (ACI) (n = 5 for each apparatus). The mean (s.d.) fine-particle doses measured by the three techniques for the Becloforte MDI were 40.3 (1.2), 45.7 (0.5) and 41.8 (0–4)% w/w, respectively; the median mass aerodynamic diameters (MMAD) measured using the MSLI and the ACI were 3.50 and 3.73 μm, respectively. The MSLI fine particle (< 6.8 μm) doses for 2, 5, 10, 20, 30 and 40 doses from Becloforte MDIs (n = 5 for each dose) were 49.7 (0.7), 52.9 (1.2), 45.3 (0.6), 45.5 (0.71), 45.9 (0.7) and 46.4 (0.7)% w/w, respectively. Values obtained using the ACI (< 5.8 μm) were 40.8 (1.0), 41.0 (0.8), 44.4 (0.5), 43.1 (0.4), 42.8 (0.5) and 40.4 (0.4)% w/w (n = 4). MMAD values measured with the MSLI were 3.39, 3.46, 3.75, 3.91, 4.15 and 4.45 μm, respectively; using the ACI they were 3.46, 3.54, 3.61, 3.66, 3.73 and 3.85 μm. The results indicate that the measured aerodynamic particle-size distributions of beclomethasone dipropionate MDIs are affected by the dose dispensed and by the apparatus used for measurement.     

Preparation and properties of Nα-Bpoc-amino acid pentafluorophenyl esters

The preparation and properties are reported of several N^x-Bpoc -amino acid pentafluorophenyl esters, including those bearing tert-butyl-, allyl- and trityl-based protecting groups. These derivatives have been used in the solid-phase peptide synthesis of sevral short peptides.     

Subchronic and Chronic Inhalation Toxicity of Antimony Trioxide in the Rat

Fischer 344 rats were exposed by inhalation to Sb₂O₃ (antimonytrioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and23.46 mg/m³ for 6 hr/day, 5 days/week for 13 weeks followedby a 27-week observation period. Subsequently, an inhalationon-cogenicity study was conducted at exposure levels of 0, 0.06,0.51, and 4.50 mg/m³ for 12 months followed by a 12-month observationperiod. The Sb₂O₃ in the subchronic study had a mass medianaerodynamic diameter (MMAD) of 3.05 ± 0.21 microns (mean± SD) with a geometric standard deviation (GSD) of 1.57± 0.06. In the chronic study, the MMAD was 3.76 ±0.84 and the GSD was 1.79 ± 0.32. Except for the eyes,no adverse clinical observations were attributed to Sb₂O₃ ineither study. In the subchronic study, corneal irregularitieswere seen after about 2 weeks of exposure and did not abateduring the observation period. In the chronic study, ophthalmoscopicevaluation at 24 months revealed a dose-related increase incataracts of 11, 24, 28, and 32% (both sexes combined) for eachgroup, respectively. Body weights were significantly lower (6%)than the control group's weights in the 23.46 mg/m³ males inthe subchronic study. These rats did not recover this weightduring the 27-week observation period. Body weights of the femalesin both studies and males in the chronic study were unaffected.There were no Sb₂O₃ effects on clinical chemistry or he-matologyin either study. Mean absolute and relative lung weights weresignificantly increased in the 4.92 and 23.46 mg/m³ groups inthe subchronic study. The 23.46 mg/m³ group's lung weights didnot recover to control levels during the 27-week observationperiod. Lung weights for rats in the chronic study were unaffected.Microscopic changes in the lungs in the subchronic and chronicstudy were limited to subacute-chronic interstitial inflammation,increased numbers of alveolar-in-traalveolar macrophages, foreignmaterial in the alveolar-in-traalveolar macrophages in the peribronchialand perivascular (chronic study only) lymphoid aggregates andin the peribronchial lymph nodes, granulomatous inflammation/granulomas,and fibrosis. In the chronic study, any observed neoplasms occurredwith comparable incidence among all groups and were within thehistorical range for controls. Clearance of Sb₂O₃ from the lungwas burden dependent and was reduced by 80/ in the 4.50 mg/m³group in the chronic study. The previously reported studies,which found Sb₂O₃ to be a carcinogen, were run at higher lungburdens. Under the exposure conditions of the current study,Sb₂O₃ was not a carcinogen.