小川 真規

BACKGROUND: New employees often exhibit stress reactions to changes in their environment and some of these may result in resignations. Employees in medical institutions are no exceptions. Considering the shortage of nurses in Japan, countermeasures are needed against the resignation of newly graduated nurses. Many studies have indicated that multifaced factors affect the resignation of newly graduated nurses. Even though individual characteristics are important factors in this regard, training and support for newly graduated nurses do not focus on the nurses' characteristics. The purpose of this study is to examine the characteristics influencing the early resignation of newly graduated nurses and suggest ways to support them and prevent their early resignation based on their characteristics. METHODS: With the approval of the Ethics Committee, various characteristics of 353 newly graduated nurses (personality, interpersonal relationships, trait anxiety, nurse orientation, desire to be a nurse, and self-proclaimed academic ability) were assessed using a transactional analysis, the State-Trait Anxiety Inventory, and self-reporting numerical rating scales. The characteristics of those who resigned within 1 year (case group) and those who did not (control group) were compared using chi-square test and logistic regression analysis. RESULTS: Our sample of 353 participants included 32 nurses from the case group and 304 nurses from the control group. Most participants showed similar personality traits. However, the control group had a significantly lower percentage with negative self, strong trait anxiety, negative self and strong trait anxiety, and low orientation compared to the case group. Our logistic regression analysis showed that strong trait anxiety and low nurse orientation are significantly related with the early resignation of nurses. CONCLUSIONS: The early resignation of newly graduated nurses may be prevented by understanding their characteristics at the time of gaining employment and implementing early intervention programs, such as education programs to reduce anxiety, and helping those with strong trait anxiety and low nurse orientation to find meaning in work.

BACKGROUND: Few studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health. AIMS: To test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs' mental health. METHODS: This cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs' mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms. RESULTS: Of the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54-1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10-2.63], P < 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10-2.52], P < 0.01) or colleagues/supervisors (3.19 [2.22-4.58], P < 0.001) were significantly more likely to have depressive symptoms. CONCLUSIONS: Being a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.

A high prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) may call for monitoring in geriatric long-term care facilities (g-LTCFs). We surveyed the distribution of ESBL-causative gene types and antimicrobial susceptibility in ESBL-PE strains from residents in g-LTCFs, and investigated the association between ESBL-causative gene types and antimicrobial susceptibility. First, we analyzed the types of ESBL-causative genes obtained from 141 ESBL-PE strains collected from the feces of residents in four Japanese g-LTCFs. Next, we determined the minimum inhibitory concentration values for alternative antimicrobial agents against ESBL-PE, including β-lactams and non-β-lactams. Escherichia coli accounted for 96% of the total ESBL-PE strains. Most strains (94%) contained blaCTX-M group genes. The genes most commonly underlying resistance were of the blaCTX-M-9 and blaCTX-M-1 groups. Little difference was found in the distribution of ESBL-causative genes among the facilities; however, antimicrobial susceptibility differed widely among the facilities. No specific difference was found between antimicrobial susceptibility and the number of ESBL-causative genes. Our data showed that ESBL-PEs were susceptible to some antimicrobial agents, but the susceptibility largely differed among facilities. These findings suggest that each g-LTCF may require specific treatment strategies based on their own antibiogram. Investigations into drug resistance should be performed in g-LTCFs as well as acute medical facilities.

Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with < 2 months residence at study onset or new admission during the study period. Three analyses were performed: (1) ESBL-E carriage statuses in Cohort 1 and Cohort 2; (2) changes in ESBL-E carriage statuses 3-12 months after the first testing and ≥ 12 months after the second testing; and (3) lengths of positive ESBL-E carriage statuses. Compared with the residents in Cohort 1, a significantly larger proportion of residents in Cohort 2 were positive for ESBL-E carriage (28.0% in Cohort 1 vs 40.0% in Cohort 2). In the subsequent testing results, 18.3% of residents who were negative in the first testing showed positive conversion to ESBL-E carriage in the second testing, while no patients who were negative in the second testing showed positive conversion in the third testing. The maximum length of ESBL-E carriage was 17 months. The findings indicated that some residents acquired ESBL-E through potential cross-transmission inside the LTCFs after short-term residence. However, no residents showed positive conversion after long-term residence, which indicates that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures could improve the ESBL-E prevalence in geriatric LTCFs.

目的:近年途上国へ派遣される労働者が増加している。途上国は衛生環境が悪いことが多く、健康管理(感染症対策)が重要となる。赴任前に健康指導を受ける労働者、指導を行う産業医の認識を調査し、海外派遣労働者のニーズに合った、効果的な健康管理を提案することを目的とした。方法:途上国へ派遣された経験を持つ労働者を対象にインターネット調査を行い、属性、業種、滞在期間、勤務企業概要、赴任前推奨ワクチン種、ワクチン費用負担、感染症事前教育の有無・役立ち度・理解度、持参薬の有無、自社の感染症対策への満足度を収集した。また、指導する側として、産業医資格取得講習参加者を対象に、アンケートにて属性、日常業務における途上国赴任予定労働者からの相談の有無、日常業務における途上国赴任予定者に対する感染症に関する指導の有無、途上国赴任に際し推奨するアドバイス項目を取得した。結果:労働者が事前に得ることで、自社の感染症対策満足度に寄与する要因として、会社規模に加え、事前教育、相談窓口の情報提供が挙げられた。これらを多くの産業医資格取得講習参加者は、提供すべきと回答したが、情報提供に自信がないと考えていることが明らかとなった。結論:海外派遣労働者には、海外派遣前に、企業と連携し、事前教育、相談窓口の情報を、積極的に提供すべきである。また、産業医など指導する側は、渡航医学についての知識や情報源についての理解を深める必要がある。(著者抄録)

目的:近年途上国へ派遣される労働者が増加している。途上国は衛生環境が悪いことが多く、健康管理(感染症対策)が重要となる。赴任前に健康指導を受ける労働者、指導を行う産業医の認識を調査し、海外派遣労働者のニーズに合った、効果的な健康管理を提案することを目的とした。方法:途上国へ派遣された経験を持つ労働者を対象にインターネット調査を行い、属性、業種、滞在期間、勤務企業概要、赴任前推奨ワクチン種、ワクチン費用負担、感染症事前教育の有無・役立ち度・理解度、持参薬の有無、自社の感染症対策への満足度を収集した。また、指導する側として、産業医資格取得講習参加者を対象に、アンケートにて属性、日常業務における途上国赴任予定労働者からの相談の有無、日常業務における途上国赴任予定者に対する感染症に関する指導の有無、途上国赴任に際し推奨するアドバイス項目を取得した。結果:労働者が事前に得ることで、自社の感染症対策満足度に寄与する要因として、会社規模に加え、事前教育、相談窓口の情報提供が挙げられた。これらを多くの産業医資格取得講習参加者は、提供すべきと回答したが、情報提供に自信がないと考えていることが明らかとなった。結論:海外派遣労働者には、海外派遣前に、企業と連携し、事前教育、相談窓口の情報を、積極的に提供すべきである。また、産業医など指導する側は、渡航医学についての知識や情報源についての理解を深める必要がある。(著者抄録)

OBJECTIVE: To survey occupational health-related activities conducted at hospitals certified by the Japan Council for Quality Health Care in the Kanto region of Japan. METHODS: The survey tool was sent to 470 hospitals and comprised the following items: hospital size, occupational health system, infection control practices, mental health services, promotion of work system reforms, and priorities in achieving occupational health. RESULTS: A total of 140 hospitals completed the survey. A monthly workplace inspection was conducted in approximately 60% of the hospitals. Testing of new employees for hepatitis and four other viruses was conducted in approximately 65% of the hospitals, and influenza vaccination was administered to the employees in all the hospitals. Most hospitals provided mental health services to their workers, which included consultation with an occupational physician. Work system reforms for changing conference time and task shifting or sharing were adopted in approximately 50% of the hospitals. Prevention of blood-borne pathogens, respiratory infections, and healthcare coverage for healthcare workers was identified as areas of improvement in several hospitals. CONCLUSIONS: Legally required infection control and occupational health-related practices were conducted in most hospitals. Additionally, several hospitals undertook work system reforms, including the management of changes in conference time and task shifting or sharing.

INTRODUCTION: Hand hygiene is crucial for infection control in long-term care facilities for elderly (LTCFEs), because it can be easily implemented in the low-resource settings of LTCFEs. This study investigated the actual status of hand hygiene adherence in LTCFEs, identified the factors inhibiting its appropriate implementation, and evaluated the effectiveness of a hand hygiene promotion program. METHODS: In this before-and-after study, participants were staff members (n = 142) at two LTCFEs in Gunma Prefecture, Japan. We modified the World Health Organization's "five moments for hand hygiene" and assessed participants' hand hygiene adherence rates in four situations: (1) Before touching around a resident's mucous membrane area; (2) Before medical practice or clean/aseptic procedures; (3) After body fluid exposure/risk or after touching around a resident's mucous membrane area; and (4) After touching a resident's contaminated environments. The study was divided into four phases. In Phase 1, participants self-assessed their hand hygiene adherence using a questionnaire. In Phase 2, we objectively assessed participants' pre-intervention adherence rates. In Phase 3, an intervention comprising various hand hygiene promotion measures, such as education and hands-on training on hand hygiene practices and timings, was implemented. In Phase 4, participants' post-intervention adherence rates were objectively measured. RESULTS: Although most participants reported high hand hygiene adherence rate in the self-assessment (93.1%), the pre-intervention evaluation revealed otherwise (16.8%). Participants' post-intervention adherence rates increased for all four situations (77.3%). CONCLUSION: The intervention program helped increase participants' hand hygiene adherence rates, indicating its effectiveness. Similar interventions in other LTCFEs may also improve adherence rates.

Influenza outbreaks at geriatric long-term care facilities (g-LTCFs) can be deadly and their prevention is important. However, the factors influencing disease transmission in g-LTCFs remain controversial. In this descriptive study, we tried to identify the potential risk factors influencing influenza outbreaks that occurred in different influenza seasons within a single g-LTCF with 100 residents in Gunma Prefecture. We reviewed the detailed facility records for all influenza cases in both residents and staff between January 2012 and June 2020. Facility preventive measures were also reviewed. We found that community meals may have been a potential source of transmission leading to the outbreaks. When influenza infection is noted, implementation of strict preventive measures and restriction of meal provision to resident rooms may help to prevent disease transmission and the development of an outbreak. Such measures may also be useful to prevent the transmission of other serious droplet-borne diseases within g-LTCFs.

OBJECTS: The number of workers dispatched to developing countries has increased recently. The sanitary conditions in these countries are different from those in developed countries and from what the workers are used to. Therefore, health control, especially infection control, is an important consideration for working there. In this study, we investigate workers' needs as well as the occupational physicians' skills concerning working in developing countries. We propose a more effective education system for health control. METHODS: Regarding workers who have lived in developing countries, we surveyed the company profiles, duration of stay, vaccination status, infectious education, medical assistance, and satisfaction with infection control strategies of their employer companies. Regarding occupational physicians, we surveyed their profiles, their experiences in consultation, and advice from/to the workers dispatched to developing countries as well as their suggestive advice for staying there. RESULTS: Factors that contributed to workers' satisfaction with their employment companies were prior education and health consulting services in addition to company size. Many occupational physicians believed that this kind of information should be supplied but they did not have the confidence to provide it. CONCLUSIONS: Workers who are dispatched overseas should receive prior education and access to health consulting services. It is necessary for information providers such as occupational physicians to be knowledgeable in travel medicine.

BACKGROUND: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization has been reported among residents in geriatric long-term care facilities (LTCFs). Some studies indicate that MRSA might be imported from hospitals into LTCFs via resident transfer; however, other studies report that high MRSA prevalence might be caused by cross-transmission inside LTCFs. We aimed to assess which factors have a large impact on the high MRSA prevalence among residents of geriatric LTCFs. METHODS: We conducted a cohort study among 260 residents of four geriatric LTCFs in Japan. Dividing participants into two cohorts, we separately analyzed (1) the association between prevalence of MRSA carriage and length of LTCF residence (Cohort 1: n = 204), and (2) proportion of residents identified as MRSA negative who were initially tested at admission but subsequently identified as positive in secondary testing performed at ≥2 months after their initial test (Cohort 2: n = 79). RESULTS: Among 204 residents in Cohort 1, 20 (9.8%) were identified as positive for MRSA. Compared with residents identified as MRSA negative, a larger proportion of MRSA-positive residents had shorter periods of residence from the initial admission (median length of residence: 5.5 vs. 2.8 months), although this difference was not statistically significant (p = 0.084). Among 79 residents in Cohort 2, 60 (75.9%) were identified as MRSA negative at the initial testing. Of these 60 residents, only one (1.7%) had subsequent positive conversion in secondary MRSA testing. In contrast, among 19 residents identified as MRSA positive in the initial testing, 10 (52.6%) were negative in secondary testing. CONCLUSIONS: The prevalence of MRSA was lower among residents with longer periods of LTCF residence than among those with shorter periods. Furthermore, few residents were found to become MRSA carrier after their initial admission. These findings highlight that MRSA in LTCFs might be associated with resident transfer rather than spread via cross-transmission inside LTCFs.

OBJECTIVES: The objectives of this study were to analyze current trends in occupational health activities by classifying reports from medical facilities in Japan. METHODS: Reports of current workplace-level occupational health activities from medical activities that were collected by the Japan Medical Association Occupational Health Committee were used for the study. Of 5,000 questionnaire forms sent to medical facilities, 1,920 responses were returned. The freely described reports on ongoing occupational health activities contained in these responses were classified according to each of the following aspects of reported activities: 1) details of occupational health activities including main actors in workplace-level actions; and 2) approaches taken for occupational safety and health. The classification of the reports was implemented by a working group comprising selected occupational health practitioners and researchers. RESULTS: Among 1,920 survey responses, 581 valid texts were analyzed. Altogether, 1,044 occupational health activities currently undertaken by the facilities were extracted. The reported activities that were classified according to details of occupational health activities mainly comprised "Measures for preventing overwork, labor management, and work-style reform" (35.7%), "Measures for improving mental health" (21.0%), and "Review of occupational safety and health management systems" (19.3%). Medical facilities implementing "Measures for mental health" alongside "Measures for preventing overwork, labor management, and work-style reform" were reported in 13.2% of the responding medical facilities. "Occupational health professionals or safety and health management staff" (71.7%) were the most frequent main actors of these activities, followed by "Members of the workplace" (18.4%) and "Outsourced experts" (2.4%). "Comprehensive safety and health management" (42.0%) was the most common approach taken for occupational safety and health, followed by "Management focusing on topics" (23.8%) and "Case management" (16.5%). Most of these activities focused on primary prevention aimed at labor management including prevention of overwork, work-style reform, and mental health promotion. Another key trend could be "Teamwork among occupational safety and health staff, workers, and employers at respective workplaces as well as outsourced experts." DISCUSSION: Several key trends were extracted from current occupational health activities at medical facilities. In most cases, these measures were implemented simultaneously. This suggests the importance of combining primary prevention measures for mental health with measures for labor management including prevention of overwork. These activities reflect emerging trends that incorporate teamwork between experts, workers, and employers, and provide new perspectives on workplace-level occupational safety and health activities.

目的:医療機関における産業保健活動について、現場での事例をもとに産業保健活動の傾向や実施主体別の分類を試み、現場レベルでの今後の産業保健活動を進めていくための方向性について検討した。対象と方法:日本医師会産業保健委員会が各医療機関を対象に実施した「医療機関における産業保健活動に関するアンケート調査」調査結果を活用した。自由記載欄に記載された現在取り組んでいる産業保健活動の記述内容を対象とし、複数名の専門家により各施設の産業保健活動の分類を試みた。特に、1.個別対策事例(具体的な取り組み事例・産業保健活動の主体)2.産業保健活動の取り組み方を反映した分類の2点に基づき分類を行い、各特徴について検討した。結果:有効回答数1,920件のうち、581件の自由記載があり、1,044件の個別の産業保健活動が整理された。1.個別対策事例のうち、具体的な取り組み事例については、個別対策毎の分類では「B労務管理・過重労働対策・働き方改革(35.7%)」、「Cメンタルヘルス対策関連(21.0%)」、「A労働安全衛生管理体制強化・見直し(19.3%)」等が上位となった。また、施設毎に実施した取り組みに着目した場合、「B労務管理・過重労働対策・働き方改革関連」と「Cメンタルヘルス対策関連等」を併せて実施している施設が施設全体の13.2%に認められた。産業保健活動の主体による分類では、「a:産業保健専門職・安全衛生管理担当者(71.7%)」が最も多く、「b:現場全体(18.4%)」、「c:外部委託(2.4%)の順となった。2.産業保健活動の取り組み方を反映した分類では(1)包括的管理(42.0%)が最も多く、(2)問題別管理(23.8%)、(3)事例管理(16.5%)の順となった。考察と結論:医療機関における産業保健活動として、過重労働対策を含む労務管理・働き方改革、メンタルヘルス対策への取り組みが多く実践されていた。特に、メンタルヘルスにおける一次予防対策と過重労働における一次予防対策を併せて実施している点、外部の産業保健機関、院内の各種委員会、産業保健専門職とが連携し産業保健活動が進められている点が認められた。厳しい労働環境にある医療機関においても、当面の課題に対処しつつ、医療従事者の健康と安全に関する課題を包括的に解決できる具体的な実践が進められつつある。また、各院内委員会や外部専門家との連携によりチームとして行う産業保健活動の進展が、益々期待される。(著者抄録)

Following publication of the original article [1], the authors spotted errors in their paper concerning the positive rate in the right side in Table 2. (Table Presented).

Following publication of the original article [1], the authors spotted errors in their paper concerning the positive rate in the right side in Table 2.

Tap water contamination is a growing concern in healthcare facilities, and despite chlorination, tap water in these facilities contains several pathogenic microorganisms causing healthcare-associated waterborne infections or nosocomial outbreaks. Shower units are particularly prone to contamination as they are conducive for bacterial growth and can even produce bioaerosols containing pathogenic bacteria. Shower units coupled with point-of-use (POU) water filters are a simple and safe option; however, their efficacy has been under-reported. Therefore, we determined the efficacy of showerheads attached with a POU filter capsule in preventing infections in our hospital. We investigated the presence of pathogenic bacteria in water sampled from three shower units. After replacing the original shower units with new ones incorporated with a sterile-grade water filter capsule (0.2 µm; QPoint™), the water samples were analyzed for up to 2 months. The POU filters removed several pathogenic bacteria (Mycobacterium, Pseudomonas, Stenotrophomonas, Aeromonas, and Klebsiella spp.). Filter effectiveness depends on regional water quality and we believe that effective tap water treatment combined with the use of POU filters (introduced at a reasonable cost in healthcare facilities) can considerably minimize waterborne diseases in hospitals and improve patient care.

In the current study, we report a case of a 46-year-old man who presented with sudden abdominal pain and was diagnosed with rupture of hepatic angiosarcoma (HAS). He underwent surgery, but died 13 days after the onset of the abdominal pain. Chronic exposure to carcinogens, such as thorium dioxide, arsenic, vinyl chloride, and radium, is associated with HAS. However, our patient had not been exposed to such carcinogens. He had submitted himself for annual medical checkups since he was employed. His liver was cirrhotic, and medical history data showed that he had had fatty liver for at least 10 years before HAS onset. Although liver cirrhosis may play a role in the occurrence of HAS, the connection of chronic fatty liver in the tumorigenesis remains unclear. Case reports regarding HAS with fatty liver are few. To the best of our knowledge, this is the first case of HAS occurring in a cirrhotic liver that advanced from persistent fatty stage. Given that HAS is a rare tumor, data collection is important for investigating its pathophysiology. Case presentations considering health conditions before HAS onset are limited therefore, we present a case of HAS with annual health checkup data before disease onset.

This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard beta of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging.

Aim: Exposure assessment of lead (Pb) and Arsenic (As) from food, water, and house dust intake were assessed among pregnant women, their children and fetuses in Pakistan and Japan, as well as their body burden of the metals in their blood. Method: Fifty families which included a pregnant woman, a fetus and the 1-3-year-old siblings were recruited in Karachi and Khairpur in Pakistan, and Shimotsuke and Asahikawa in Japan, respectively. Their dietary exposure to Pb and As was measured in 3-day food duplicates and drinking water by ICP-MP. Pb in house dust and respirable dust was evaluated with an energy dispersive X-ray fluorescence spectrometry. Nonradioactive isotope Pb profiles of blood specimens will be compared with those of the exposure origins, such as food duplicates, respirable house dust, the soils nearby, and gasoline. Results: Judging from the data collected and analyzed so far, contribution from dietary intake is highly correlated to higher body burden of Pb among Pakistani mothers. Additional data analyses will reveal the status of Pb and As body burden in Pakistani mothers, fetuses and their siblings, and causal sources of high body burden is delineated by Pb isotope profile analysis of different sources of Pb exposure.

Background: Aluminum is considered to be a relatively safe metal for humans. However, there are some reports that aluminum can be toxic to humans and animals. In order to estimate the toxicity of aluminum with respect to humans, we measured the aluminum concentration in urine of aluminum-handling and non-handling workers and investigated the relationships between their urinary aluminum concentrations and pre-clinical findings. Methods: Twenty-three healthy aluminum-handling workers and 10 healthy non-aluminum-handling workers participated in this study. Their medical examinations, which were otherwise unremarkable, included the collection of urine and blood. Urinary aluminum levels were analyzed using ICP analysis. As pre-clinical tests, we measured KL-6, SP-D, TRCP-5b, IL-6, and IL-8 in blood and delta-ALA and beta 2-microglobulin in urine. These were considered to be lung, bone, kidney and inflammation markers. Moreover, we measured 8-OHdG in urine as an oxidative DNA damage marker. Results: The aluminum concentration in urine ranged from 6.9 to 55.1 mu g/g cre (median: 20.1 mu g/g cre) in the aluminum-handling workers and from 5.6 to 15.6 mu g/g cre (median: 8.8 mu g/g cre) in the non-aluminum-handling workers, with a significant difference between them. In the pre-clinical findings, there were no significant differences between these two groups except in the case of delta-ALA. However, there were no significant relationships between aluminum concentration and the pre-clinical findings, work years, age or 8-OHdG in the aluminum-handling workers. Conclusions: While the excretion of aluminum in urine was elevated in aluminum-handling workers, our findings suggest that low-dose aluminum is not directly harmful to humans, at least when workers' urinary aluminum concentration is below 55 mu g/g cre.

To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden. Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry. Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 mu g/L, 0.34 mu g/L, and 0.96 mu g/dL, respectively. Urinary Cd level was 0.34 mu g/g creatinine (GM) and hair Hg was 1.31 mu g/g (GM). Approximately one-third (35 %) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 mu g/L). Hair Hg level exceeded U.S. EPA RfD (1.2 mu g/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg. Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.

Background: Biological monitoring is used to assess toluene exposure in medical examinations. The American Conference of Industrial Hygienists, Japanese Society for Occupational Health and Deutsche Forschungsgemeinschaft have proposed various biological exposure determinants, such as toluene in blood and urine, and o-cresol in urine. Toluene in blood is a common biomarker among them. Toluene is a volatile organic solvent; therefore, sample preservation under appropriate conditions before measurement is necessary. However, little study has been done on the stability of toluene in workers' blood samples under conditions simulating those of a medical examination. Finding: We carried out a pilot study on the stability of toluene in blood from humans, according to different methods of sample preservation. Toluene in blood was analyzed by head space-gas chromatography/mass spectrometry. The sealing performance of the vial was examined by using toluene-added blood and the stability of toluene in blood according to the preservation period was examined by using blood from toluene-handling workers, which was collected with vacuum blood tubes. The sealing performance of the headspace vial used in this study was good for three days and toluene in blood in tubes from workers was stable at least within 8 hours up to blood packing at 4 degrees C. Conclusion: We could propose that the collected blood need only be transferred into headspace vials on the collection day and analyzed within a few days, if the samples are preserved at 4 degrees C. Our data size is limited; however, it may be considered basic information for biological monitoring in medical examinations.

Intake of foods and drinks containing benzoic acid influences the urinary hippuric acid (HA) concentration, which is used to monitor toluene exposure in Japan. Therefore, it is necessary to control the intake of benzoic acid before urine collection. Recently, some reports have suggested that components of coffee, such as chlorogenic, caffeic, and quinic acids are metabolized to HA. In this study, we evaluated the influence of coffee intake on the urinary HA concentration in toluene-nonexposed workers who had controlled their benzoic acid intake, and investigated which components of coffee influenced the urinary HA concentration. We collected urine from IS healthy men who did not handle toluene during working hours, after they had consumed coffee, and we measured their urinary HA concentrations; the benzoic acid intake was controlled in these participants during the study period. The levels of chlorogenic, caffeic, and quinic acids in coffee were analyzed by LC-MS/MS. Urinary HA concentration increased significantly with increasing coffee consumption. Spectrophotometric LC-MS/MS analysis of coffee indicated that it contained chlorogenic and quinic acids at relatively high concentrations but did not contain benzoic acid. Our findings suggest that toluene exposure in coffee-consuming workers may be overestimated.

シックビル症候群患者の臨床所見並びに環境測定結果について：吉田辰夫ほか．関西労災病院環境医学研究センター―目的：シックハウス症候群の調査報告は数多くあるが，日本における職業性シックビルディング症候群（SBS）の症例報告は限られている．われわれは集団発生事例において臨床的な観察と環境濃度測定を実施した． 対象と方法：オフィス内に新設した耐火金庫室内部の塗装工事後に体調不良を訴え，当科を受診した事務職員11名（男性2名と女性9名）に問診，血液一般および生化学検査，免疫学的検査，肺機能検査，神経眼科的検査および精神心理検査を実施し，事務所内環境測定を塗装後27日後，55日後，132日後の3回実施した．非受診者（男性21名と女性1名）においては自記式質問紙調査を実施した． 結果：事務職員は工事終了9日後に仕事を始めたが，その直後に大半の従業員が異臭を感じ，頭痛，倦怠感，集中力の低下や眼の刺激を訴えた．塗装に使用された塗料はアクリル樹脂塗料で，金庫室内のトルエン，キシレン，総揮発性有機化合物（T-VOC）の27日後の濃度は2,972，2,610，7,100 μg/m³であったが，132日後には，78，113，261 μg/m³に低下していた．結論：自覚症状，アレルギー等の他の器質的疾患の検査は否定的なこと，環境測定結果から，受診者11名のうち女性7名をSBSと診断した．非受診者（男性22名と女性1名）における質問紙の回答でも，異臭や不快感などの訴えの出現と消滅の時期が金庫内のトルエンなどの濃度推移と一致していたことから，SBS診断の妥当性が確認された．<br> （産衛誌2011; 53: 25-32）<br>

N-Methyl-2-pyrrolidone (NMP) has been used in many industries and biological monitoring of NMP exposure is preferred to atmospheric monitoring in Occupational health. We developed an analytical method that did not include solid phase extraction (SPE) but utilized deuterium-labeled compounds as internal standard for high-performance liquid chromatography-electrospray ionization-mass spectrometry using a C30 column. Urinary concentrations of NMP and its known metabolites 5-hydoxy-N-methyl-2-pyrrolidone (5-HNMP), N-methyl-succinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were determined in a single run. The method provided baseline separation of these compounds. Their limits of detection in 10-fold diluted urine were 0.0001, 0.006, 0.008, and 0.03 mg/L, respectively. Linear calibration covered a biological exposure index (BEI) for urinary concentration. The within-run and total precisions (CV, %) were 5.6% and 9.2% for NMP, 3.4% and 4.2% for 5-HNMP, 3.7% and 6.0% for MSI, and 6.5% and 6.9% for 2-HMSI. The method was evaluated using international external quality assessment samples, and urine samples from workers exposed to NMP in an occupational area. (C) 2009 Elsevier B.V. All rights reserved.

Acetaldehyde is an intermediate of ethanol oxidation. It covalently binds to DNA, and is known as a carcinogen. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2* 2/*2 and ALDH2* 1/*2), and Aldh2 knockout mice appear to be a valid animal model for humans with inactive ALDH2. This review gives an over view of published studies on Aldh2 knockout mice, which were treated with ethanol or acetaldehyde. According to these studies, it was found that Aldh2 -/- mice (Aldh2 knockout mice) are more susceptible to ethanol and acetaldehyde-induced toxicity than Aldh2 +/+ mice (wild type mice). When mice were fed with ethanol, the mortality was increased. When they were exposed to atmospheres containing acetaldehyde, the Aldh2 -/- mice showed more severe toxic symptoms, like weight loss and higher blood acetaldehyde levels, as compared with the Aldh2 +/+ mice. Thus, ethanol and acetaldehyde treatment affects Aldh2 knockout mice more than wild type mice. Based on these findings, it is suggested that ethanol consumption and acetaldehyde inhalation are inferred to pose a higher risk to ALDH2-inactive humans. These results also support that ALDH2-deficient humans who habitually consume alcohol have a higher rate of cancer than humans with functional ALDH2.

In order to determine low levels of Cd in urine samples, we tried to remove Mo interference using ICP-MS with a dynamic reaction-cell technique, but failed due to the low sensitivity and the variance with the standards. We then performed solid-phase extraction (SPE) before the ICP-MS measurement. A commercially available chelating resin, NOBIAS PA-1, was used for SPE, and could effectively remove Mo from urine samples, permitting the accurate determination of Cd by ICP-MS. This SPE-ICP-MS method gave 0.012 mu g Cd L-1 as the method limit of quantification, and the mean recovery of Cd spiked with 0.0505 and 5.05 mu g L-1 was 93.1 and 97.6%, respectively.

Dimethyltin dichloride (DMTC) is widely used as a heat stabilizer in manufacturing the polyvinyl chloride. We previously reported a case of acute DMTC poisoning with neurological manifestations very similar to trimethylated tin JMT) encephalopathy, based on results of speciation analysis of methylated tins in the patient's urine with use of a combination of high performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS), which yielded peaks corresponding to DMT and TMT. In this study, we developed an analytical method to confirm TMT in urine using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and found TMT molecular ion in the patient's urine. (c) 2008 Elsevier B.V. All rights reserved.

Organotins are widely used as stabilizers of polyvinyl chloride and as catalysts or biocides. It is well known that dimethyltin (DMT) is less neurotoxic than trimethyltin (TMT). A Korean worker who was exposed to DMT compounds showed neurological symptoms similar to those of TMT encephalopathy, in association with high levels of both DMT and TMT in the urine and blood. The case suggested the possibility of the methylation of DMT in humans. Here, we investigated whether TMT is detected in the urine of mice and rats exposed only to DMT dichloride (DMTC). Three Slc:ICR mice and three Slc:Wistar rats were placed in individual metabolic cages, and one day later, they were injected intraperitoneally with DMTC (10 mg/kg body weight (wt); 5.4 mgSn/kg body wt; 45.5 micromol/kg body wt) over 4 consecutive days. Twenty-four hour urine samples were collected every evening for 11 consecutive days starting at baseline (before treatment). Speciation analyses of methyltin compounds in urine were performed using a combination of high performance liquid chromatograph-inductively coupled plasma mass spectrometry. High concentrations of DMT and time-dependent increase in TMT concentrations were found in both mice and rats during the 4-day treatment, and their concentrations decreased gradually after the cessation of treatment. The chemical compound of the detected peak was confirmed to be TMT by liquid chromatography-tandem mass spectrometry. Neither DMT nor TMT was detected in the samples collected at baseline. Our results indicate urinary excretion of TMT in mice and rats injected with DMTC, confirming the production of TMT in vivo, probably through methylation of DMT.

Aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde produced from ethanol into acetate and plays a major role in the oxidation of acetaldehyde in vivo. About half of all Japanese people have inactive ALDH2. We generated homozygous Aldh2 null (Aldh2-/-) mice by gene targeting knockout as a model of ALDH2-deficient humans. To investigate the mutagenicity of acetaldehyde, a micronucleus assay and a T-cell receptor (TCR) gene mutation assay were performed in Aldh2-/- mice and wild-type (Aldh2+/+) mice exposed to acetaldehyde. The mice were continuously exposed to 125 and 500 ppm of acetaldehyde vapor for 2 weeks. Another group was orally administered 100 mg/k once a day for 2 weeks continuously. The mice were killed after 2 weeks of exposure to acetaldehyde, and the frequency of micronucleated reticulocytes was measured by flow cytometry. We also observed the incidence of TCR gene mutations in T-lymphocytes by measuring the variant CD3(-)CD4(+) expression by flow cytometry. The frequency of micronucleated reticulocytes induced by acetaldehyde was significantly increased in Aldh2-/- mice, but not in Aldh2+/+ mice. TCR mutant frequency was also associated with acetaldehyde exposure in Aldh2-/- mice, especially after oral administration however, it was not associated with acetaldehyde exposure in Aldh2+/+ mice. In conclusion, Aldh2-/- mice showed high sensitivity in the micronuclei and TCR mutation assays compared with Aldh2+/+ mice after exposure to acetaldehyde.

Case Reports. We experienced two cases of acute lead poisoning due to occupational exposure to lead. The patients were engaged in stripping off antirust compounds including Pb from a bridge and re-painting it at the same work place. Both patients exhibited colic, arthralgia, and anemia. Blood lead levels were 73.1 mu g/dl and 96.3 mu g/dl. Intravenous CaEDTA chelation therapy was therefore performed. After chelation, blood lead levels decreased and symptoms gradually disappeared. Discussion. Although the patients were working with protective equipment, the workplace was in the mountains and there was no water for washing. The patients were thus unable to washing their hands and faces. We assume that they swallowed lead dust left on their hands and faces when they removed their clothing, and believe that this poisoning occurred due to lack of knowledge sufficient for protection.

Aldh (aldehyde dehydrogenase) 2 knockout (KO) mice have been generated in our laboratory. We evaluated the effects of subacute ethanol treatment on the survival rate, expression of Aldh1, Aldh2, Cytochrome P450 (Cyp) 1A1, Cyp2e1 and Cyp4b1 in wild (Aldh2 +/+) mice (C57BL/6) and Aldh2 knock out (Aldh2 ?/?) mice. Physiological saline (0.3 mL/day) was administered to 4 Aldh2 +/+ and 4 Aldh2 ?/? mice for 8 days as a control. Forty percent ethanol (0.3 mL/day ethanol 2 g/kg/day) was then administered to 5 Aldh2 +/+ and 9 Aldh2 ?/? mice for 8 days. Three mice of the ethanol administered Aldh2 +/+ group and eight mice of the ethanol administered Aldh2 ?/? group died during the 8 days. The weights of mice were decreased by ethanol exposure to 85% and 74% in Aldh2 +/+ and Aldh2 ?/? group, respectively. The survival rates of the ethanol administered Aldh2 +/+ and Aldh2 ?/? group were 40 and 11%. Liver and pancreas disorder was revealed in the ethanol administered Aldh2 +/+ and Aldh2 ?/? group in the results of serum chemical examination, immunohistochemical staining and western blot analysis. Cyp2e1 is more inducible to ethanol toxicity in Aldh2 ?/? mice compared with Aldh2 +/+ mice when ethanol is administered according to the results of quantitative PCR.

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/- control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.