免疫抑制剂在1型糖尿病发病初期的应用

1型糖尿病的主要病因为细胞免疫介导的自身免疫性破坏.对1型糖尿病自然病程的研究显示,在具有该病遗传易感性的遗传背景下,环境中的触发因素使得胰岛细胞中的某些成分成为淋巴细胞攻击的对象而发生了胰岛炎,并使胰岛β-细胞逐渐被破坏、胰岛β-细胞数目的逐渐减少,导致糖耐量异常发生,并进而发展为糖尿病[1].     

2型糖尿病胰岛β细胞凋亡机制

2型糖尿病（T2DM）是一种多基因遗传性疾病,其病因及发病机制目前尚不十分清楚。一般认为,T2DM的发生是多源性的,是环境因素和遗传因素共同作用的结果。近年研究证实,胰岛β细胞功能上的改变在发病初期起关键作用,由凋亡所致的β细胞数量减少及胰岛功能受损在整个病程中都起着重要的作用。本文就近年来2型糖尿病胰岛β细胞凋亡机制的研究进展作一综述。     

免疫调节疗法干预Ⅰ型糖尿病的研究进展

Ⅰ型糖尿病(IDDM)是一种由T细胞介导的胰岛β细胞特异性的自身免疫性疾病。其发病凶险。多出现严重代谢紊乱，并发症难以控制，一旦患病终生应用胰岛素治疗，严重影响患者的寿命和生活质量。近年来随着免疫学的飞速发展，使用免疫调节疗法防治Ⅰ型糖尿病的研究日趋成熟。本文就几种常用的免疫调节疗法做一综述。     

1型糖尿病听力损害及相关风险因素评估分析

<正>1型糖尿病(T1DM)好发于儿童及青少年,占糖尿病患者的10%~15%[1],是一种多因素自身免疫性疾病,特点是胰岛β细胞破坏,导致胰岛素绝对缺乏引起血糖升高。T1DM多数原因是由于自体免疫,极少数为先天特发性或胰岛β生成障碍所致。T1DM可引起机体多器官损害、功能障碍及器官衰竭。糖尿病与听力损害的相关讨论于1857年由Jord觔o最先提出,Bittar等[2]报     

自身免疫性糖尿病患者CD_4~+CD_(25)~+T细胞的变化

目的通过观察自身免疫性糖尿病患者外周血CD4+CD25+T细胞的变化,探讨其在发病中的可能作用。方法流式细胞仪检测20例LADA、20例T1DM、20例T2DM及21例正常对照外周血CD4+CD25+、CD3+CD8+T细胞。结果①LADA、T1DM组外周血CD4+CD25+T细胞低于T2DM、正常对照组(p均<0.05)。②LADA、T1DM患者外周血CD3+CD8+T细胞较T2DM、正常对照组增高(LADAvs正常对照p<0.01,其余p<0.05)。结论自身免疫性糖尿病患者免疫调节性CD4+CD25+T细胞减少,不能有效维持对胰岛自身抗原的耐受;外周细胞毒性CD3+CD8+T细胞增多进而破坏胰岛β细胞,导致自身免疫性糖尿病的发生和发展。     

高海拔缺氧对链脲佐菌素致大鼠胰岛损害程度的影响

[目的]通过观察西宁（低海拔）、木里（高海拔）地区链脲佐菌素（streptozotocin,STZ）糖尿病大鼠胰岛形态学特点,探讨高原缺氧环境对STZ糖尿病大鼠胰岛形态学影响。[方法]大鼠随机分成西宁、木里正常组;西宁、木里造模组。造模组大鼠空腹12h后腹腔注射STZ,以随机血糖≥16．7mmol/L为造模成功;采用免疫组织化学染色和原位末端转移酶标记技术（TdT-mediated dUTP nick end labeling,TUNEL）细胞凋亡检测分析胰岛面积、胰岛D细胞面积、平均光密度、平均累积光密度（integrated optical density,IOD）和胰岛细胞凋亡率。[结果]木里糖尿病组血糖水平低于西宁糖尿病组;糖尿病大鼠胰岛数量减少、萎缩、形状不规则,胰岛细胞变性,胰岛内β细胞分布稀少,胰岛染色颗粒较少,着色浅,凋亡细胞较正常组多;木里糖尿病组在β细胞面积、β细胞面积／胰岛面积和IOD上显著高于西宁糖尿病组。[结论]高海拔STZ糖尿病大鼠血糖较低;胰岛β细胞受损较轻;高原缺氧环境可能对STZ糖尿病大鼠胰岛β细胞有一定的保护作用。     

022儿童维生素D缺乏与1型糖尿病

维生素D不仅是钙磷代谢的调节剂,还具有免疫调节功能,在儿童及其生命后期自身免疫性糖尿病的发生中发挥重要作用,已有很多证据表明儿童期维生素D缺乏与1型糖尿病(T1DM)相关.维生素D活性产物1,25-(OH)2D3通过对各种细胞因子的影响,在局部胰腺损伤中调节Th1/Th2的平衡;并作用于树突状细胞(DC),抑制DC的分化、成熟和激活,引起不同致病性CD4+T细胞的功能受损,对T1DM的发生发展具有一定的保护作用.其作用在一定程度上受到胰岛自身抗原的影响.1,25-(OH)2D3类似物(Ro26-2198)在一定程度上也可阻止T1DM的发生发展.     

1型糖尿病相关单基因自身免疫性综合征临床进展

自身免疫反应破坏胰岛β细胞功能是1型糖尿病(T1DM)的重要病因,一些单基因自身免疫性综合征可伴有不同程度的T1DM发生,这是深入认识自身免疫和T1DM的重要疾病模型。本文对已知的8种与T1DM相关的单基因自身免疫性综合征的诊断、治疗、遗传检测等方面作综述,为T1DM的诊疗拓展思路。     

胰岛自身抗体检测在糖尿病诊治中的价值

<正>1型糖尿病又分为自身免疫性和特发性2个亚型。确认自身免疫性1型糖尿病有赖于在糖尿病患者中检测到针对胰岛β细胞各成分的自身抗体[1]。除了1型糖尿病,目前发现部分2型糖尿病患者经口服降糖药治疗几年后失效,出现胰岛素缺乏,考虑这类患者属于成人迟发型自身免疫性糖尿病(LADA)[2],体内也会出现针对胰岛β细胞各成分的自身抗体。     

CD8+T细胞在糖尿病发病中作用

目的探讨CD8＋T细胞在糖尿病发病中的作用。方法利用非肥胖糖尿病（NOD）背景的转基因小鼠,将CD4＋T细胞和CD8＋T细胞过继转移到有T细胞缺陷的NOD小鼠（即NOD.scid小鼠）,同时转移到特异性地在β细胞上表达共刺激分子CD80的有T细胞缺陷的NOD小鼠（即NOD.scid.Rip.B7小鼠）,观察两组受鼠胰岛炎和糖尿病的发病情况,并分析其差异。结果转移CD4＋T细胞时,糖尿病发病率在NOD.scid受鼠和NOD.scid.Rip.B7受鼠组的差异无统计学意义（P〉0.05）,转移CD8＋T细胞时,NOD.scid受鼠糖尿病发病率低于NOD.scid.Rip.B7组受鼠,差异有统计学意义（P〈0.001）。结论CD8＋T亚群启动了胰岛的淋巴细胞浸润,CD8＋T细胞是通过与胰岛β细胞直接作用启动糖尿病的发生。     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.     

Psychopathological features of a patient population of targets of workplace bullying

BACKGROUND: A strong association between workplace bullying and subsequent anxiety and depression, indicated by empirical research, suggests that bullying is an aetiological factor for mental health problems. AIMS: To evaluate levels of stress and anxiety-depression disorder developed by targets of workplace bullying together with outcome at 12 months and to characterize this population in terms of psychopathology and sociodemographic features. METHODS: Forty-eight patients (36 women and 12 men) meeting Leymann Inventory of Psychological Terror criteria for bullying were included in a prospective study. Evaluations were performed at first consultation and at 12 months using a standard clinical interview, a visual analogue scale of stress, the Hospital Anxiety and Depression (HAD) scale, the Beech scale of stress in the workplace and a projective test (Picture-Frustration Study). RESULTS: At first consultation, 81% of patients showed high levels of perceived stress at work and 83 and 52% presented with anxiety or depression, respectively. At 12 months, only 19% of working patients expressed a feeling of stress at work. There was a significant change in symptoms of anxiety while there was no change in symptoms of depression. Stress at work and depression influenced significatively capacity to go back to work. At 12-month assessments, workers showed a significantly better score on the HAD scale than non-workers. Over half the targets presented a neuroticism-related predominant personality trait. CONCLUSION: Workplace bullying can have severe mental health repercussions, triggering serious and persistent underlying disorders.     

The rise and fall in incidence of malignant mesothelioma from a British Naval Dockyard, 1979-1999

BACKGROUND: The incidence of malignant mesothelioma in Britain is predicted to rise over the next 15-25 years because of past failure to protect the workforce against inhalation of asbestos. In British Naval dockyards, alternative insulation materials and respiratory protection were introduced from the mid-1960s. Aims This study was carried out to investigate the effects of these control measures on mesothelioma deaths in dockyard workers. METHODS: Cases of mesothelioma of the pleura and peritoneum between 1979 and 1999 in workers from the Devonport Naval Dockyard, south-west England, were sought from coroners' and medico-legal records. RESULTS: Three hundred and one cases were identified, 7% peritoneal. The peak incidence occurred in 1991 with 25 cases per annum (quadratic model fit R(2) = 74.2%, P < 0.001) and we predict that by 2003 the incidence will fall to fewer than five cases per annum. The mean time between first exposure and presentation was 48.5 years [95% confidence interval (CI) = 47.3-49.8], but this was significantly shorter in the more heavily exposed trades, when compared with the less heavily exposed (42 years, 95% CI = 39.0-45.0, versus 49.5 years, 95% CI = 48.2-50.9). Those with higher exposure were also at significantly greater risk of peritoneal disease (P < 0.023, Fisher's exact test). CONCLUSION: The reduction in incidence of mesothelioma is greater than can be accounted for by reduction in numbers of dockyard workers over the last 50 years. Changes in insulation materials and improved industrial hygiene measures introduced into the Devonport Dockyard from the mid-1960s have resulted in an earlier decline in the incidence of malignant mesothelioma than that predicted for the British workforce as a whole.     

Organophosphate toxicity and occupational exposure

The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.     

Miliaria rubra of the lower limbs in underground miners

This report documents a case series of miliaria rubra of the lower limbs in miners at a deep underground metalliferous mine in tropical arid Australia. During the summer months of February and March 1999, all cases of miliaria rubra of the lower limbs in underground miners seen at the mine's medical centre were clinically examined and administered a questionnaire. Twenty-five patients were seen, an incidence of 56.4 cases per million man-hours. Miliaria rubra was most often located between the ankle and knee (88% of cases). Twenty-four percent had concurrent folliculitis and 20% had concurrent tinea. Thirty-two percent had a personal history of asthma. Walking through ground-water and splashing of the legs was common. Three to 4 weeks of sedentary duties in air conditioning was generally required to achieve resolution of miliaria rubra. The incidence of miliaria rubra of the lower limbs is 38% of the incidence of heat exhaustion at the same mine. The length of disablement is greater, however. Atopics may be at increased risk of miliaria rubra. Control measures are discussed.     

Planning research

The starting point for any research project should be a question.Once this has been defined and the relevant scientific literaturereviewed, a protocol should be drawn up. This will be used notonly as a guide to the conduct of the study and in the preparationof the final report, but also in seeking any financial supportand approvals that are required for the investigation. A protocolis normally arranged in sections covering the background tothe study, the question(s) that it will address, the methodsthat will be used for the collection and analysis of data, thestatistical power of the investigation (where relevant), anyethical considerations, and the financial input that will beneeded. A pilot study is often helpful where aspects of thestudy method are untried or of uncertainvalidity.     

Stress in the Norwegian police service

BACKGROUND: High levels of stress have been attributed to the conditions of police work, but there is little empirical evidence for this. AIMS: To develop a new instrument to measure job stress in the police; to assess the most severe and frequent police stressors; to compare levels of stress according to the demographic and organizational factors; and to study stress in relation to personality traits, work locus of control and coping strategies. METHODS: A comprehensive nationwide questionnaire survey of 3272 Norwegian police at all hierarchical levels, including the Norwegian Police Stress Survey (NPSS), the Job Stress Survey, the Basic Character Inventory, the Work Locus of Control Scale, and the Coping Strategies Scale. RESULTS: Work injuries were appraised as the most stressful but least frequent stressor and job pressure was reported the least severe but most frequent stressor. Females experienced job stressors less frequently, but appraised them as more severe than men did. Older police officers reported more job pressure severity and fewer work injuries. The police in districts where peer support was planned but not implemented, and who worked in districts with more than 50,000 inhabitants, perceived the lack of support more severely than others. The correlations between stress and personality traits, work locus of control, and coping were moderate. CONCLUSIONS: The NPSS captures police-specific stressors that are not adequately measured by global stress instruments. The study of stress in police work should preferably involve a nationwide use of police-specific stress instruments.