Kazuyuki Omae

Effects of sarin on the nervous system of subway workers seven years after the Tokyo subway sarin attack.

Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack: Koichi Miyaki, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—This study was designed to assess the after effects of sarin exposure on the nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20 March, 1995. We performed a similar study 3 yr after the disaster. This time, we newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power. New subjects consisted of 23 male exposed subjects and 13 referent subjects matched for age and working types. Neurobehavioral tests for psychomotor function and memory, stabilometry, and Benton visual retention test were performed. As reported previously, the exposed group performed significantly less well in the psychomotor function test (tapping) than the referent group (117.8±1.2 vs. 105.6 ± 1.2 msec). Using merged data, this phenomenon was also observed in a dose‐dependent manner and the exposed group performed significantly less well in the backward digit span test (4.47 ± 1.17 vs. 5.11 ± 1.65 digits). These results indicate that chronic decline of psychomotor function and memory function still exist 7 yr after the sarin exposure.

Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage

Objectives: To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs. Methods: Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices. Results: Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S. Conclusions: The study outcomes with regard to the basis of serum immunochemistry biomarkers and HRCT indicate that exposure to hardly soluble indium compound dust may represent a risk for interstitial lung damage.

Interstitial pulmonary disorders in indium-processing workers

The production of indium-tin oxide has increased, owing to the increased manufacture of liquid-crystal panels. It has been reported that interstitial pneumonia occurred in two indium-processing workers; therefore, the present study aimed to evaluate whether interstitial pulmonary disorders were prevalent among indium workers. The study was carried out in 108 male workers in the indium plant where the two interstitial pneumonia patients mentioned above were employed, and included high-resolution computed tomography (HRCT) of the lungs, pulmonary function tests and analysis of serum sialylated carbohydrate antigen KL-6 and the serum indium concentration. Significant interstitial changes were observed in 23 indium workers on HRCT and serum KL-6 was abnormally high (>500 U·mL-1) in 40 workers. Workers with serum indium concentrations in the highest quartile had significantly longer exposure periods, greater HRCT changes, lower diffusing capacity of the lung for carbon monoxide and higher KL-6 levels compared with those in the lowest quartile. The serum indium concentration was positively correlated with the KL-6 level and with the degree of HRCT changes. In conclusion, the results of the present study indicated that serum KL-6 and high-resolution computed tomography abnormalities were prevalent among indium workers and that these abnormalities increased with the indium burden, suggesting that inhaled indium could be a potential cause of occupational lung disease.

Effects of SO2 on respiratory system of adult Miyakejima resident 2 years after returning to the island.

Effects of SO2 on Respiratory System of Adult Miyakejima Resident 2 Years after Returning to the Island: Satoko Iwasawa, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University

Causal Relationship between Indium Compound Inhalation and Effects on the Lungs

Causal Relationship between Indium Compound Inhalation and Effects on the Lungs: Makiko Nakano, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University

Indium Lung Disease

BACKGROUND Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. METHODS To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. RESULTS Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. CONCLUSIONS Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.

Surgical site infection risk factors identified by multivariate analysis for patient undergoing laparoscopic, open colon, and gastric surgery

BACKGROUND Surgical site infection (SSI) is an important clinical indicator of quality of patient care and infection control; therefore, we aimed to assess risk factors SSI in colon and gastric surgeries. METHODS SSI was assessed according to the National Nosocomial Infection Surveillance (NNIS) system (1999). Risk factors examined included operative approach, operative procedure, duration of operation, diabetes mellitus (DM), body mass index (BMI), age, and sex. RESULTS Among 3152 operated patients, 1675 patients were included in the study. The univariate analysis showed that male sex, high BMI, and long duration of operation were significant risk factors for colon surgery and that advanced age, presence of DM and long duration of operation were significant risk factors for gastric surgery. The multivariate analysis indicated that significant risk factors for SSI were BMI of 25 or above, open surgery, and long duration of operation for colon surgery and open surgery for gastric surgery. The SSI rate of laparoscopic colon surgery was 40%, less than that of open colon surgery, and that of laparoscopic gastric surgery was 75%, less than that of open gastric surgery. CONCLUSION The risk factors for SSI depend on whether the operation is laparoscopic or open and duration of operation. In addition, BMI (25 or above) and age (70 years or above) are risk factors for colon and gastric surgery, respectively.

Progression of human breast cancers to the metastatic state is linked to genotypes of catechol-O-methyltransferase

There is increasing evidence that catecholestrogens may contribute to the development of breast cancer. Specifically, inactivation of catecholestrogens may prevent the genesis and arrest the progression of the disease. Catechol-O-methyltransferase (COMT), Glutathione S-transferase (GST) M1 and GSTP1 are responsible for the detoxification of catecholestrogens, and are polymorphic in the human population. In this study, a PCR-based restriction fragment length polymorphism analysis was performed to determine genotypes of the COMT, GSTM1 and GSTP1 genes. We investigated the relationship between the germline polymorphism of these genes and clinico-pathological characteristics in 140 patients with breast cancer. Among 73 patients with the low activity COMT allele, 49 (67%) had regional lymph node metastasis. On the other hand, only 27 (40%) of 67 patients without the low activity allele had lymph node metastasis. The COMT genotype was significantly associated with clinical stage and the extent of regional lymph node metastasis of breast cancer (P<0.05). However, polymorphisms of the GSTM1 and GSTP1 gene were not associated with clinico-pathological factors. Our findings suggest that the allele encoding for low activity COMT may contribute to the progression of breast cancer.

Oral toxicity of bismuth in rat: Single and 28-day repeated administration studies

Oral Toxicity of Bismuth in Rat: Single and 28‐Day Repeated Administration Studies: Yuri Sano, et al. Department of Preventative Medicine and Public Health, School of Medicine, Keio University—The consumption and production of bismuth are increasing, however there is very little information about the direct toxic effect of bismuth. The present study aimed to characterize the potential toxic effects of bismuth through oral administration and observation for fourteen days following single dose of 0 and 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for twenty‐eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28‐d repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). We found no deaths and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute oral toxicity study and no changes attributable to bismuth in either males or females in the dose group up to 1,000 mg/kg of the 28‐d repeated‐dose toxicity study. Therefore, we determined that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg and the no‐observed‐adverse‐effect level (NOAEL) of bismuth is 1,000 mg/kg in both sexes. We conclude that the adverse toxic effects of bismuth as a simple metal substance are low compared to lead toxicity under the conditions tested in our studies.

Genotoxicity Studies of Heavy Metals: Lead, Bismuth, Indium, Silver and Antimony

Genotoxicity Studies of Heavy Metals: Lead, Bismuth, Indium, Silver and Antimony: Keiko Asakura, et al. Department of Preventive Medicine and Public Health, Keio University School of Medicine