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美国退伍军人中海湾战争疾病与抗胆碱酯酶暴露之间的流行病学关联。

Epidemiological association in US veterans between Gulf War illness and exposures to anticholinesterases.

作者信息

Kurt T L

机构信息

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas 75235, USA.

出版信息

Toxicol Lett. 1998 Dec 28;102-103:523-6. doi: 10.1016/s0378-4274(98)00259-8.

DOI:10.1016/s0378-4274(98)00259-8
PMID:10022306
Abstract

To investigate complaints of Gulf War veterans, epidemiologic, case-control and animal modeling studies were performed. Looking for OPIDP variants, our epidemiologic project studied 249 Naval Reserve construction battalion (CB24) men. Extensive surveys were drawn for symptoms and exposures. An existing test (PAI) was used for neuropsychologic. Using FACTOR, LOGISTIC and FREQ in 6.07 SAS, symptom clusters were sought with high eigenvalues from orthogonally rotated two-stage factor analysis. After factor loadings and Kaiser measure for sampling adequacy (0.82), three major and three minor symptom clusters were identified. Internally consistent by Cronbach's coefficient, these were labeled syndromes: (1) impaired cognition; (2) confusion-ataxia; (3) arthro-myo-neuropathy; (4) phobia-apraxia; (5) fever-adenopathy; and (6) weakness-incontinence. Syndrome variants identified 63 patients (63/249, 25%) with 91 syndromes. With pyridostigmine bromide as the drug in these drug-chemical exposures, syndrome chemicals were: (1) pesticide-containing flea and tick collars (P < 0.001); (2) alarms from chemical weapons attacks (P < 0.001), being in a sector later found to have nerve agent exposure (P < 0.04); and (3) insect repellent (DEET) (P < 0.001). From CB24, 23 cases, 10 deployed and 10 non-deployed controls were studied. Auditory evoked potentials showed dysfunction (P < 0.02), nystagmic velocity on rotation testing, asymmetry on saccadic velocity (P < 0.04), somatosensory evoked potentials both sides (right P < 0.03, left P < 0.005) and synstagmic velocity after caloric stimulation bilaterally (P-range, 0.02-0.04). Brain dysfunction was shown on the Halstead Impairment Index (P < 0.01), General Neuropsychological Deficit Scale (P < 0.03) and Trail Making part B (P < 0.03). Butylcholinesterase phenotypes did not trend for inherent abnormalities. Parallel hen studies at Duke University established similar drug-chemical delayed neurotoxicity. These investigations lend credibility that sublethal exposures to drug-chemical combinations caused delayed-onset neurotoxic variants.

摘要

为了调查海湾战争退伍军人的投诉,开展了流行病学、病例对照和动物模型研究。在寻找有机磷中毒迟发性神经病变(OPIDP)变体时,我们的流行病学项目研究了249名海军后备役建筑营(CB24)的人员。针对症状和接触情况进行了广泛调查。使用现有的一项测试(PAI)进行神经心理学评估。在SAS 6.07中使用FACTOR、LOGISTIC和FREQ程序,通过正交旋转两阶段因子分析,寻找具有高特征值的症状群。在进行因子载荷分析以及Kaiser抽样适当性测度(0.82)后,确定了三个主要症状群和三个次要症状群。这些症状群经Cronbach系数检验具有内部一致性,被标记为综合征:(1)认知受损;(2)意识模糊 - 共济失调;(3)关节 - 肌肉 - 神经病变;(4)恐惧症 - 失用症;(5)发热 - 腺病;(6)虚弱 - 失禁。综合征变体确定了63名患者(63/249,25%)存在91种综合征。在这些药物 - 化学物接触中,以溴化吡啶斯的明为药物,与综合征相关的化学物有:(1)含杀虫剂的跳蚤和蜱虫项圈(P < 0.001);(2)化学武器袭击警报(P < 0.001),所在区域后来被发现存在神经毒剂暴露(P < 0.04);(3)驱虫剂(避蚊胺)(P < 0.001)。从CB24中选取了23例病例,以及10名已部署和10名未部署的对照进行研究。听觉诱发电位显示功能障碍(P < 0.02),旋转测试时的眼球震颤速度、扫视速度不对称(P < 0.04),双侧躯体感觉诱发电位(右侧P < 0.03,左侧P < 0.005)以及双侧冷热刺激后的眼球震颤速度(P范围为0.02 - 0.04)。在霍尔斯特德损伤指数(P < 0.01)、综合神经心理缺陷量表(P < 0.03)和连线测验B部分(P < 0.03)中均显示出脑功能障碍。丁酰胆碱酯酶表型未显示出内在异常的趋势。杜克大学对母鸡进行的平行研究证实了类似的药物 - 化学物延迟神经毒性。这些调查为亚致死剂量的药物 - 化学物组合导致迟发性神经毒性变体提供了可信度。

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