甲苯二异氰酸酯吸入致小鼠肺损伤的病理学观察

为观察甲苯二异氰酸酯 (TDI)吸入引起的肺损伤 ,将 30只小鼠均分为 5组 ,分别吸入 4.30± 0 .6 0mg·m 3 TDI 0～ 4周 ,常规留取病理及电镜标本。实验结果显示 :TDI吸入早期肺间质局灶性增生、水肿 ,小气道及血管周围大量淋巴细胞及嗜酸性粒细胞浸润。TDI吸入后 3周 ,肺间质弥漫性增生 ,部分肺组织有炎性肉芽肿形成及肺实变 ,间质增生以弹力纤维及网状纤维增生为主。扫描电镜示气道上皮细胞纤毛脱落 ,气管腔内炎性细胞渗出 ,TDI吸入早期分泌细胞功能亢进 ,晚期功能低下。透射电镜示Ⅱ型肺泡上皮及肺毛细血管基底膜增生 ,血管内皮电子密度增加 ,线粒体肿胀。以上结果提示 :吸入TDI可引起小鼠肺内多方面损伤。     

长期吸入TDI对鼠肺损伤的病理实验研究

为观察长期吸入甲苯二异氰酸酯（TDI）引起的小鼠肺损伤，将30只小鼠均分为5组，即对照组未吸入TDI，实验组吸入1周、2周、3周、4周TDI（4．30±0．60）mg／m3，对照组4周后行常规病理检查，实验组于吸入结束后行常规病理及电镜检查，常规病理切片示肺间质增生、水肿，且以弹力纤维及网状纤维增生为主，小气道及血管周围炎性细胞浸润；扫描电镜示气道上皮细胞纤毛脱落，吸入TDI早期分泌细胞功能亢进，晚期功能低下，透射镜示Ⅱ型肺泡上皮及肺毛细血管损伤，以上结果提示，长期吸入TDI可引起小鼠肺内多方面损伤。     

甲苯二异氰酸酯对小鼠肺内CD11b及ICAM-1表达的影响

目的研究甲苯二异氰酸酯(TDI)引起的小鼠肺损伤及与粘附分子CD11b和ICAM-1的关系.方法将12只小鼠分为2组,实验组吸入(4.30±0.60)mg/m3 TDI 2周,实验结束后常规留取肺标本并行快速冰冻切片,免疫组织化学方法检测肺内炎症细胞CD11b及肺内血管内皮ICAM-1的表达.结果实验组肺内炎症细胞增多,以巨噬细胞和淋巴细胞为主.实验组肺内炎症细胞CD11b及血管内皮细胞ICAM-1表达明显高于对照组.结论 TDI可引起小鼠肺内炎症细胞出游,炎症细胞表面CD11b及毛细血管内皮ICAM-1的过度表达是炎症细胞出游的原因之一.     

博莱霉素致大鼠肺纤维化及与肺血管内皮细胞损伤的关系

目的 探讨血管内皮损伤与博莱霉素(BLM)致大鼠肺纤维化发生间的关系。方法 实验组大鼠经气管灌注BLM制作肺纤维化模型,采用免疫组化及图像分析系统对其肺组织中血管内皮细胞生长因子(VEGF)进行定性、定量分析。结果 (1)组织学观察:染BLM后3、7 d,大鼠肺泡腔及间隔水肿,炎细胞渗出,肺泡Ⅰ型及Ⅱ型上皮细胞变性、坏死,肺泡上皮细胞基底膜断裂,血管内皮细胞肿胀,核浓缩;7、14 d,大鼠肺泡Ⅱ型上皮细胞增生,肺泡间隔有较多成纤维细胞及新生毛细血管形成;28 d,大鼠肺泡间隔增厚,肺泡结构破坏,肺组织明显纤维化样改变。(2)VEGF免疫组化染色:对照组大鼠肺组织呈弱表达,主要分布于肺泡Ⅱ型上皮细胞、支气管黏膜上皮细胞、肺泡巨噬细胞及肺间质细胞。染BLM组大鼠VEGF呈明显高表达,其中,3 d至28 d,大鼠肺泡Ⅱ型上皮细胞VEGF持续高表达,表达量明显高于对照组,差异有统计学意义(P<0.05,P<0.01);7、14、28 d,大鼠肺间质细胞VEGF呈高表达;3 d至28 d,大鼠肺泡巨噬细胞VEGF表达均升高,与对照组的差异均有统计学意义(P<0.05,P<0.01)。结论 VEGF持续高表达与大鼠血管内皮细胞损伤有关,而血管内皮细胞的损伤可能是BLM诱发大鼠肺纤维化的重要启动因素之一。     

高氧对新生大鼠肺组织超微结构的影响

目的 探讨高氧对新生大鼠肺组织超微结构的影响.方法 SD(Sprague-Dawley)大鼠48只随机分为高氧试验组和空气对照组,高氧试验组吸入95%以上高氧建立高氧肺损伤模型.采用透射电镜观察新生大鼠3、7、14 d肺组织超微结构变化,14d后比较空气对照组和高氧试验组肺泡Ⅱ型上皮细胞及血管内皮细胞变性坏死发生率的差异.结果 吸入高氧3d新生大鼠肺泡Ⅱ型上皮细胞出现板层小体结构松散,部分血管内皮细胞肿胀,随着高氧吸入时间的延长,14d时肺泡Ⅱ型上皮细胞、血管内皮细胞产生了致死性损害作用,出现了类似早产儿支气管肺发育不良的肺组织形态学特征.两组肺泡Ⅱ型上皮细胞(空气对照组和高氧试验组分别为24.0%和68.0%,χ2=39.32,P＜0.005)及血管内皮细胞变性坏死发生率(空气对照组和高氧试验组分别为15.0%和39.0%,χ2=14.99,P＜0.005)存在显著的统计学差异.结论 持续高氧吸入可造成新生大鼠肺泡Ⅱ型上皮细胞和血管内皮细胞损害.     

新生大鼠高氧肺损伤肺组织超微结构及VEGF蛋白表达变化

【目的】探讨高氧对新生大鼠肺组织超微结构的影响及其血管内皮生长因子(vascular endothelial growthfactor VEGF)蛋白表达的变化。【方法】新生SD大鼠48只随机分为高氧试验组和空气对照组,高氧试验组吸入95%以上高氧建立高氧肺损伤模型。采用透射电镜和免疫组化观察新生大鼠3、71、4 d肺组织超微结构和VEGF蛋白表达变化。【结果】吸入高氧3 d新生大鼠肺泡Ⅱ型上皮细胞(AEC-II)出现板层小体结构松散,部分血管内皮细胞肿胀,随着高氧吸入时间的延长,14 d时AEC-II、血管内皮细胞产生了致死性损害作用,出现了类似早产儿支气管肺发育不良的肺组织形态学特征。VEGF蛋白在高氧吸入3 d时出现降低,7 d明显降低,到14 d时进一步降低。【结论】持续高氧吸入可造成新生大鼠肺肺泡Ⅱ型上皮细胞和血管内皮细胞损害。高氧可抑制VEGF蛋白在新生大鼠肺内的表达,VEGF可能在新生鼠肺发育和高氧肺损伤发病机理中起重要作用。     

细胞外组蛋白在氯气所致小鼠急性呼吸窘迫综合征中的变化

目的研究细胞外组蛋白在急性呼吸窘迫综合征(ARDS)发病过程中的变化,探索其具体作用及临床价值。方法通过氯气染毒复制小鼠ARDS模型,在不同浓度氯气染毒条件下,检测血浆中细胞外组蛋白H4、血管内皮细胞损伤标志物sTM、肺组织病理的改变;分析组蛋白H4与sTM的关系。结果正常小鼠血浆中组蛋白H4的平均浓度为(076±017)μg/ml;氯气染毒后,小鼠血浆中组蛋白H4水平升高;当200 ppm氯气染毒(30min)后12 h,血浆中组蛋白H4的平均浓度为(768±247)μg/ml。氯气浓度越高,血浆中组蛋白升高越明显,二者具有明显的正相关性。在氯气吸入损伤中,血浆中内皮损伤标志物sTM也明显升高,且与血浆中组蛋白H4具有明显的相关性(r=0830 2)。HE染色镜下可见,染毒小鼠肺组织炎症细胞浸润,肺泡间隔增宽,肺泡上皮细胞和血管内皮细胞肿胀,且随氯气浓度增高损伤加重。结论细胞外组蛋白在氯气所致ARDS小鼠血浆中明显升高,且与肺损伤程度密切相关,提示其可能在ARDS发病机制中起重要作用。     

改良型甲苯二异氰酸酯哮喘小鼠模型的建立

目的采用气管滴注方式进行甲苯二异氰酸酯(toluene-diisocyanate,TDI)激发给药,改进TDI哮喘小鼠模型建立方法,并对模型的建立进行评价。方法将20只SPF级健康雌性BALB/c小鼠随机分为TDI组和溶剂对照组,每组10只。TDI组小鼠第1、8天于耳背分别涂抹20μl 0.3%TDI致敏,第15天采用气管滴注法给予20μl 0.01%TDI进行激发,溶剂对照组给予等量溶剂(丙酮与橄榄油混合物)。激发结束后,观察各组小鼠的行为学改变。致敏实验后每组取6只小鼠收集支气管肺泡灌洗液(BALF)并进行炎细胞计数分类,以ELISA法检测BALF上清中白细胞介素-4(IL-4)、γ-干扰素(IFN-γ)含量;以HE染色观察小鼠肺组织病理变化。结果激发结束后,TDI组小鼠均出现呼吸急促、点头呼吸、弓背、前肢缩抬等行为学改变,溶剂对照组未出现上述症状。TDI组小鼠BALF中白细胞总数、嗜中性粒细胞、淋巴细胞、单核细胞、嗜酸性粒细胞、嗜碱性粒细胞数目均高于溶剂对照组,且嗜中性粒细胞、嗜酸性粒细胞百分比高于溶剂对照组,BALF中细胞因子IL-4、IFN-γ含量高于溶剂对照组,差异均有统计学意义(P0.05)。HE染色可见TDI组小鼠肺组织内支气管管壁破坏明显,管腔增厚,支气管管腔内及肺泡腔内有大量的炎细胞浸润,而溶剂对照组未见明显病理变化。结论采用气管滴注方式进行TDI激发给药,可成功建立TDI哮喘小鼠模型。     

吸烟相关性间质性肺疾病

纸烟的烟雾中包含尼古丁、煤焦油、一氧化碳等多种有害物质,吸入肺内后易于沉积在范围广阔、纤毛上皮细胞少、气流流速慢的小气道(＜2mm),故细支气管远端尤其在呼吸细支气管、肺泡区域受害早、损伤大.继续吸烟使病变的部位和程度不断扩大而形成各种类型的吸烟相关性间质性肺疾病(SR-ILD),致病原因为烟雾中有害物质激活和聚集了肺泡内的巨噬细胞、T淋巴细胞(尤其CD8+)和中性粒细胞,这些炎性细胞释放多种介质引起气道、肺实质、肺血管的病变,并随吸烟逐渐加重.     

急性肺损伤新生大鼠肺组织细胞凋亡及其相关基因的表达和意义

【目的】　探讨细胞凋亡与其相关基因Fas/FasL系统表达在缺氧、缺氧后吸入纯氧致肺损伤发病机理中的意义。　【方法】　通过复制缺氧、缺氧后吸入纯氧大鼠肺损伤模型,采用TUNEL法、原位杂交检测、SqRT-PCR技术观察肺组织细胞凋亡情况、FasmRNA、FasLmRNA表达强度探讨其相关基因的表达。　【结果】　缺氧组或缺氧后吸入纯氧组在缺氧4 h后即可见大鼠肺泡上皮细胞和肺血管内皮细胞出现凋亡现象,并随着时间延长,细胞凋亡指数增高(P均<0.01),同时FasmRNA、FasLmRNA表达均上调,且缺氧后吸入纯氧组大鼠FasmRNA、FasLmRNA表达均较单纯缺氧组明显增强(P<0.05)。　【结论】　细胞凋亡与FasmRNA、FasLmRNA表达的上调可能参与缺氧和缺氧后吸入纯氧时导致的肺损伤。     

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.