Mikio Miyata

Symptom profile of multiple chemical sensitivity in actual life.

Objective: This study was conducted to confirm the definition of multiple chemical sensitivity (MCS) in actual life: that multiple symptoms are provoked in multiple organs by exposure to, and ameliorated by avoidance of, multiple chemicals at low levels. We used the Ecological Momentary Assessment to monitor everyday symptoms and the active sampling and passive sampling methods to measure environmental chemical exposure. Methods: Eighteen patients with MCS, diagnosed according to the 1999 consensus criteria, and 12 healthy controls participated in this study. Fourteen patients and 12 controls underwent 1-week measurement of physical and psychologic symptoms and of the levels of exposure to various chemicals. Linear mixed models were used to test the hypotheses regarding the symptom profile of MCS patients. Results: Some causative chemicals were detected in 11 of 14 MCS patients. Two other patients did not report any hypersensitivity episodes, whereas passive sampling showed far less exposure to chemicals than control subjects. Another subject reported episodic symptoms but was excluded from the following analyses because no possible chemical was detected. Eleven of the 17 physical symptoms and all four mood subscales examined were significantly aggravated in the interview based on “patient-initiated symptom prompts.” On the other hand, there were no differences in physical symptoms or mood subscales between MCS patients and control subjects in the interview based on “random prompts.” Conclusions: MCS patients do not have either somatic or psychologic symptoms under chemical-free conditions, and symptoms may be provoked only when exposed to chemicals. AS = active sampling; AS–PS method = active sampling and passive sampling methods; CAS = the concentration of exposure estimated by the AS method; CFS = chronic fatigue syndrome; CPS = the concentration of exposure estimated by the PS method; CS = chemical sensitivity; DAMS = Depression and Anxiety Mood Scale; DNPH = 2,4-dinitrophenyl-hydrazine; ED = electronic diary; EESI = Environmental Exposure and Sensitivity Inventory; EMA = Ecological Momentary Assessment; FM = fibromyalgia; M.I.N.I. = Mini International Neuropsychiatric Interview; MCS = multiple chemical sensitivity; PS = passive sampling; RSD = relative standard deviation; RSDAS = RSD of repeatability test in the AS method; RSDPS = RSD of repeatability test in the PS method; VOCs = volatile organic compounds.

Retinal degeneration in rats exposed to an organophosphate pesticide (fenthion)

Pigmented (Long-Evans) and albino (Wistar) rats were chronically exposed to an organophosphate pesticide (fenthion). Fenthion (50 mg/kg) was administered subcutaneously twice a week for 1 year; the total dosage for each animal ranged from 1.6 to 1.8 g. Concurrent with the fenthion administration, the amplitude of the scotopic electroetinogram (ERG) gradually declined, disappearing by the 12th month in all treated pigmented rats. For the albino experimental rats, however, the ERG amplitude disappeared as early as the 6th month in 7 out of 15 treated animals. Funduscopically, degeneration of the retina was observed in all rats when ERG responses had disappeared. Histopathological studies confirmed degeneration of the sensory retina and marked abnormalities in the pigment epithelium cells. Treated pigmented rats also had reduced a rhodopsin concentration in the retina by the 3rd month even though the photoreceptors were structurally normal. Interestingly, the plasma vitamin A levels remained normal and liver stores of vitamin A actually increased during the course of the study. Levels of butylcholinesterase in plasma and liver, on the other hand, were extremely reduced after 3 months of fenthion treatment. In general, the biochemical and functional (ERG) changes appeared before any structural damage could be detected in the retina.

Evaluation of subjective symptoms of Japanese patients with multiple chemical sensitivity using QEESI

ObjectivesThe Quick Environment Exposure Sensitivity Inventory (QEESI©) has been used as a questionnaire to evaluate subjective symptoms of patients with multiple chemical sensitivity (MCS), also known as idiopathic environmental intolerance, in Japan. However, no cutoff value for Japanese subjects has yet been established. We designed this study to establish a cutoff value for Japanese subjects using QEESI© for screening of MCS patients.MethodsA questionnaire using the QEESI© was administered to 103 MCS patients and 309 healthy control subjects matched for age and sex. QEESI© scores of the two groups were compared using logistic regression analysis, receiver operating characteristic analysis, and the Mann–Whitney test.ResultsCutoff values for Japanese subjects were determined for the Chemical Intolerance subscale (40), Symptom Severity subscale (20), and Life Impact subscale (10). The subjects whose scores exceeded the cutoff values in any two subscales accounted for 88.4% of the patients but only 14.5% of the controls.ConclusionsOur results suggest that subjects meeting two out of three subscale criteria can be screened as “patients suffering from a low level of environmental chemicals such as MCS” in Japan.

Experimental Behçet's disease and ultrastructural X-ray microanalysis of pathological tissues.

Environmental chemicals (benzene hexachloride(BHC) and dichlor diphenyl trichlor ethane(DDT) as organic chlorides, Sumithion as an organic phosphorated compound and copper powder) were mixed together and administered orally to pedigreed Pitman‐Moors strain miniature swine for a period of about one year. Oral aphthae, folliculitis, cutaneous and subcutaneous nodules, genital ulcers, hyperemia of conjunctiva and intestinal ulcers were observed in all treated animals.

Change in Human Electroretinography Associated with Thioridazine Administration

28 patients treated with thioridazine (TZ) were examined by electroretinography (ERG). The most characteristic feature was a decrease in amplitudes of the oscillatory potentials O2, O3

Use of QEESI© questionnaire for a screening study in Japan

QEESI© (Miller and Prihoda, 1999a: Toxicology and Industrial Health, 15, 370) was applied to 498 subjects, recruited from the general population of Miyagi prefecture, Japan, who had not been diagnosed previously as having multiple chemical sensitivity (MCS) or sick building syndrome. Seventeen (3.8%) of 440 subjects who returned valid completed questionnaires were classified as having symptoms ‘very suggestive’ of MCS using the four-classification system of Miller and Prihoda (1999a). We conducted detailed telephone interviews with these 17 individuals. All were visiting local hospitals on an outpatient basis with diagnoses other than MCS and had either current or previous presumed chemical exposure. Therefore, we recommended they undergo a medical check by MCS medical experts and indoor air quality assessment. Seven subjects participated in both the medical check and indoor air quality monitoring, six subjects participated in indoor air quality monitoring only and four subjects participated in neither. The seven subjects who participated in both the medical check and monitoring were diagnosed as having MCS by the above expert physicians. In nine houses of 13 subjects who participated in indoor environmental quality (IEQ) survey, acetaldehyde (9/9), formaldehyde (8/9), total volatile compounds (TVOCs) (6/9) and paradichlorobenzene (3/9) levels were above the respective guideline values for indoor air concentrations, outlined by the Ministry of Health, Labor and Welfare of Japan and were presumed to act as factors contributing to the subjects’ hypersensitivity and onset or development of symptoms. These results suggested that there might still be a population of patients not properly diagnosed as having MCS by clinicians in Japan. Therefore, we verified the efficacy of QEESI (Japanese version) for screening of MCS patients. The results of indoor air quality analysis suggested the manifestation and deterioration of MCS in Japan might be precipitated by indoor air pollutants, such as formaldehyde, acetaldehyde, volatile compounds (VOCs) and paradichlorobenzene.

Morphological study of the cataractous lens of the senescence accelerated mouse

A murine model of accelerated aging, the senescence accelerated mouse (SAM), has been developed. There are three accelerated senescence-resistant (SAM-R) strains and eight senescence-prone (SAM-P) strains. The SAM-P strains have an earlier onset and more rapid advancement of senescence resulting from a significantly shorter lifespan compared with the SAM-R strains. Spontaneous cataracts have been found in some individuals of the SAM-P/9 strain. The SAM -P/1 strain, which was used in the present study, has such systemic senescent characteristics as senile amyloidosis and alopecia, but it was previously thought that cataract does not occur in this strain. However, we found cataractous changes in the lens of these animals at early stages of their life. The earliest change was the appearance of a ripple-mark body at about 3 months of age. The number of rippled rings increased with age. These changes later induced refractive distortion of retinal vessels. Whole-mount flat preparations of the epithelium showed that the number of cells was markedly decreased at the advanced stages of cataract. At the late stages of life the lens cortex became liquefied and developed into a mature cataract. Cataract formation in this strain may be related to reduced viability of the lens epithelium.

Development and evaluation of an electromagnetic hypersensitivity questionnaire for Japanese people

The purpose of the present study was to evaluate the validity and reliability of a Japanese version of an electromagnetic hypersensitivity (EHS) questionnaire, originally developed by Eltiti et al. in the United Kingdom. Using this Japanese EHS questionnaire, surveys were conducted on 1306 controls and 127 self‐selected EHS subjects in Japan. Principal component analysis of controls revealed eight principal symptom groups, namely, nervous, skin‐related, head‐related, auditory and vestibular, musculoskeletal, allergy‐related, sensory, and heart/chest‐related. The reliability of the Japanese EHS questionnaire was confirmed by high to moderate intraclass correlation coefficients in a test–retest analysis, and high Cronbachs α coefficients (0.853–0.953) from each subscale. A comparison of scores of each subscale between self‐selected EHS subjects and age‐ and sex‐matched controls using bivariate logistic regression analysis, Mann–Whitney U‐ and χ 2 tests, verified the validity of the questionnaire. This study demonstrated that the Japanese EHS questionnaire is reliable and valid, and can be used for surveillance of EHS individuals in Japan. Furthermore, based on multiple logistic regression and receiver operating characteristic analyses, we propose specific preliminary criteria for screening EHS individuals in Japan. Bioelectromagnetics. 37:353–372, 2016.

Enhancing Effects of Fluorescein on β‐Lactam Rash I: High Incidence of Cefclidin Rashes in an Ophthalmological Volunteer Trial

Disseminated maculopapular eruptions were frequently observed in a volunteer trial of cefclidins use in ophthalmological and neurological examinations (8/12; 67%). It appeared at 8–12 days (mean ± SD, 9.6 ±1.1 days) from the initiation of the trial and subsided within 1–2 days (mean ± SD, 1.8 ± 0.4 days). Patch testing with cefclidin produced a ± reaction in 1 of 8 cases, and the drug‐induced lymphocyte stimulation test (DLST) elicited a positive response (SI: 2.8) in 1 of 8 and a weakly positive response (1.8≦SI<2) in 2 of 8. From these findings, it seems likely that the eruptions may be partially mediated by delayed type hypersensitivity (DTH) reactions to cefclidin. No such eruption was observed in the phase II trial of cefclidin where only 2.8% of 1.122 volunteers developed the eruption. The volunteers were given both fluorescein and oxybuprocain in their eyes to measure ocular tension on days –1, 0, 1, 3, 5, 7, 9, 11, 13 and weeks 3, 5, 7 after the initiation of cefclidin. Fluorescein and/or oxybuprocain may affect cefclidin to induce these abnormal reactions in the volunteers.

Survey on changes in subjective symptoms, onset/trigger factors, allergic diseases, and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity

BACKGROUND Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago. METHODS The new survey was conducted from 2012 to 2015 and the old survey was independently conducted from 1999 to 2003, meaning it was not a follow-up study. Patients were initially diagnosed by physicians at five medical institutions with MCS specialty outpatient services, with 111 and 103 patients participating in the new and old surveys, respectively. The controls were a general population living in Japan, with 1313 and 2382 participants in the new and old surveys, respectively. Subjective symptoms and ongoing chemical exposure were evaluated using a quick environmental exposure sensitivity inventory. Additionally, from clinical findings recorded by an attending physician, the prevalence of allergic diseases and presumed onset/trigger factors were evaluated. Differences between new and old surveys were analyzed using logistic regression analyses and significance tests. RESULTS Compared with ten years ago: (1) Regarding factors affecting patients with ongoing chemical exposures, the proportion of patients affected decreased significantly for two items only (insecticides and second-hand smoke). The proportion of controls showing ongoing exposure to 8 out of 10 items changed significantly. (2) In patients, scores for chemical intolerances, other intolerances, and life impacts increased significantly. (3) In terms of the prevalence of allergic diseases among patients with MCS, bronchial asthma (adjusted odds ratio [AOR]: 5.19), atopic dermatitis (AOR: 3.77), allergic rhinitis (AOR: 5.34), and food allergies (AOR: 2.63) increased significantly, while hay fever (AOR: 0.38) and drug allergies (AOR: 0.40) decreased significantly. (4) With regard to construction and renovation, which was the presumed predominant onset/trigger factor for MCS 10 years ago, this decreased from 68.9% to 35.1%; in contrast, electromagnetic fields (0.0%-26.1%), perfume (0.0%-20.7%), and medical treatment (1.9%-7.2%) increased significantly, confirming the diversification of onset/trigger factors. CONCLUSION Compared to ten years ago, for patients with MCS, an increase in avoidance behavior toward chemical substance exposures, which were presumed to be aggravating factors for symptoms, was confirmed. It has been suggested that the ongoing chemical exposure of the general population in Japan has largely changed. In addition, for patients with MCS, chemical intolerances and life impacts have become severe, the prevalence of the main allergic diseases has increased, and onset/trigger factors have become diversified.