Salvage radiotherapy for locoregional recurrence of esophageal cancer after surgery.

OBJECTIVE: There is no consensus on the optimal treatment for patients with locoregional recurrence of esophageal cancer after surgery. The objective of this study was to investigate the outcomes and prognostic factors associated with salvage radiotherapy in patients with locoregional recurrence of esophageal cancer after surgery. METHODS: We reviewed 80 patients with locoregional recurrence of esophageal cancer after surgery who were treated with radiotherapy. The median dose was 60 Gy, and 29 patients (36%) received elective nodal irradiation. Fifty-three patients (66%) received concurrent chemotherapy (mostly 5-fluorouracil and cisplatin) during radiotherapy. Overall survival, progression-free survival and in-field recurrence rate were assessed. RESULTS: The median follow-up period was 17 months. Two-year overall survival, progression-free survival and in-field recurrence rate were 50.3%, 23.5% and 41.3%, respectively. On multivariate analysis, a maximum diameter of locoregional recurrence lesions <30 mm was associated with higher overall survival (P = 0.044). Disease-free interval between surgery and locoregional recurrence >14 months was associated with higher PFS (P = 0.003). Late grade 3 toxicities occurred in three patients (3.8%). No grade 4 or higher toxicity was observed. CONCLUSIONS: Salvage radiotherapy demonstrated efficacy in achieving in-field control with acceptable toxicity. However, the high rate of out-of-field metastases led to poor progression-free survival and overall survival, particularly in cases involving large lesions and a short disease-free interval. A prospective study is warranted to establish a treatment strategy, particularly considering the combined use of effective anti-cancer drugs.

Biological effects of hydrogen peroxide administered intratumorally with or without irradiation in murine tumors.

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H2 O2 were investigated using computed tomography. The effects of H2 O2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H2 O2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H2 O2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H2 O2 was injected before irradiation. The group irradiated immediately after H2 O2 injection showed the longest tumor growth delay. Dose-modifying factors were 1.7-2.0 when combined with single irradiation and 1.3-1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H2 O2 . H2 O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2 O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.

Simultaneous boost radiotherapy versus conventional dose radiotherapy for patients with newly diagnosed glioblastoma: a multi-institutional analysis.

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB.

Late genitourinary toxicity in salvage radiotherapy for prostate cancer after radical prostatectomy: impact of daily fraction doses.

OBJECTIVE: To evaluate the impact of daily fraction doses on late genitourinary (GU) toxicity after salvage radiotherapy (SRT) for prostate cancer. METHODS: This multi-institutional retrospective study included 212 patients who underwent SRT between 2008 and 2018. All patients received image-guided intensity-modulated SRT at a median dose of 67.2 Gy in 1.8-2.3 Gy/fraction. The cumulative rates of late grade ≥2 GU and gastrointestinal (GI) toxicities were compared using Gray test, stratified by the ≤2.0 Gy/fraction (n = 137) and ≥2.1 Gy/fraction groups (n = 75), followed by multivariate analyses. The total dose was represented as an equivalent dose in 2-Gy fractions (EQD2) with α/ß = 3 Gy. RESULTS: After a median follow-up of 63 months, the cumulative rates of 5-year late grade ≥2 GU and GI toxicities were 14% and 2.5%, respectively. The cumulative rates of 5-year late grade ≥2 GU toxicity in the ≥2.1 Gy/fraction and ≤2.0 Gy/fraction groups were 22% and 10%, respectively (P = .020). In the multivariate analysis, ≥2.1 Gy/fraction was still associated with an increased risk of late grade ≥2 GU toxicity (hazard ratio, 2.37; 95% confidence interval, 1.12-4.99; P = .023), while the total dose was not significant. CONCLUSION: The present results showed that ≥2.1 Gy/fraction resulted in a higher incidence of late grade ≥2 GU toxicity in SRT. ADVANCES IN KNOWLEDGE: The impact of fraction doses on late GU toxicity after SRT remains unknown. The results suggest that higher fraction doses may increase the risk of late GU toxicity in SRT.

Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy.

The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and < 66 Gy groups (n = 66) were compared using the Log-rank test, followed by univariate and multivariate analyses and a subgroup analysis. After a median follow-up of 73 months, 6-year biochemical relapse-free survival, cRFS, cancer-specific survival, and overall survival rates were 58, 92, 98, and 94%, respectively. Six-year cRFS rates in the ≥ 66 Gy and < 66 Gy groups were 94 and 87%, respectively (p = 0.022). The multivariate analysis revealed that Gleason score ≥ 8, seminal vesicle involvement, PSA at BCR after RP ≥ 0.5 ng/ml, and a dose < 66 Gy correlated with clinical relapse (p = 0.015, 0.012, 0.024, and 0.0018, respectively). The subgroup analysis showed the consistent benefit of a dose ≥ 66 Gy in patients across most subgroups. Doses ≥ 66 Gy were found to significantly, albeit borderline, increase the risk of late grade ≥ 2 GU toxicity compared to doses < 66 Gy (14% vs. 3.2%, p = 0.055). This large multi-institutional retrospective study demonstrated that a higher SRT dose (≥ 66 Gy) resulted in superior cRFS.

Intensity-modulated radiation therapy with the central shielding technique for patients with uterine cervical cancer†.

We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8-41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18-24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3-18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients.

Relationship between radiation doses to heart substructures and radiation pneumonitis in patients with thymic epithelial tumors.

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (RP) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. This retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of RP in thoracic radiotherapy.

Evolutionary Analysis of the VP1 and RNA-Dependent RNA Polymerase Regions of Human Norovirus GII.P17-GII.17 in 2013-2017.

Human norovirus (HuNoV) GII.P17-GII.17 (Kawasaki2014 variant) reportedly emerged in 2014 and caused gastroenteritis outbreaks worldwide. To clarify the evolution of both VP1 and RNA-dependent RNA polymerase (RdRp) regions of GII.P17-GII.17, we analyzed both global and novel Japanese strains detected during 2013-2017. Time-scaled phylogenetic trees revealed that the ancestral GII.17 VP1 region diverged around 1949, while the ancestral GII.P17 RdRp region diverged around 2010. The evolutionary rates of the VP1 and RdRp regions were estimated at ~2.7 × 10-3 and ~2.3 × 10-3 substitutions/site/year, respectively. The phylogenetic distances of the VP1 region exhibited no overlaps between intra-cluster and inter-cluster peaks in the GII.17 strains, whereas those of the RdRp region exhibited a unimodal distribution in the GII.P17 strains. Conformational epitope positions in the VP1 protein of the GII.P17-GII.17 strains were similar, although some substitutions, insertions and deletions had occurred. Strains belonging to the same cluster also harbored substitutions around the binding sites for the histo-blood group antigens of the VP1 protein. Moreover, some amino acid substitutions were estimated to be near the interface between monomers and the active site of the RdRp protein. These results suggest that the GII.P17-GII.17 virus has produced variants with the potential to alter viral antigenicity, host-binding capability, and replication property over the past 10 years.

Examination of validity of a conditioned odor aversion (COA) procedure using low-dose of organic solvent as an applied procedure of the conditioned taste aversion.

Smell of very low dose of chemical might evoke subjective physical symptoms in human by some process of learning named the aversion conditioning. But few scientific evidences of the hypothesis have been reported so far. Validity of conditioned odor aversion (COA) using low-doses of organic solvent as odor conditioned stimulus (CS) was examined. In conditioning phase, water-deprived male Sprague-Dawley rats were presented low, medium or high dose solution for 30 min followed by 0.3 M Lithium Chloride (LiCl) solution or saline injection. The xylene solution and drink water were simultaneously provided on the next day as two-bottle test. Consumption of medium dose of xylene solution was significantly decreased in LiCl injection group as compared with saline group. There was no difference between LiCl and saline injected animals in low group. Animals in high dose did not access to xylene even on the conditioning. These results indicate that animals showed high sensitivity for discrimination against concentration of xylene and that the medium dose of xylene functioned as the CS. We concluded that the COA used in the present study may be one of useful procedures to investigate olfaction of animal.

Repeat stereotactic body radiotherapy (SBRT) for local recurrence of non-small cell lung cancer and lung metastasis after first SBRT.

BACKGROUND: This study evaluated the safety and efficacy of repeat SBRT for local recurrence of stage I non-small-cell lung cancer (NSCLC) and solitary lung metastasis. METHODS: Thirty-one patients with in-field local relapse of NSCLC (n = 23) or lung metastasis (n = 8) underwent repeat SBRT. All patients had grade 2 or lower radiation pneumonitis after the first SBRT. Local recurrence was diagnosed with CT and FDG-PET in 17 patients and by biopsy in 14. The median interval between the first and second SBRT was 18 months (range, 4-80). The first SBRT dose was mainly 48-52 Gy in 4 fractions (n = 25) according to the institutional protocols. Second SBRT doses were determined based on the tumor size and distance to organs at risk, and were mostly 48-52 Gy in 4 fractions (n = 13) or 60 Gy in 8 fractions (n = 13). RESULTS: At 3 years, overall survival and local control rates were 36 and 53%, respectively, for all 31 patients. Four patients showed no further recurrence for > 5 years (63-111 months) after the second SBRT. Radiation pneumonitis after the second SBRT was grade 2 in 4 patients, and no grade 3 pneumonitis was observed. CONCLUSION: Repeat SBRT was safe. Local control and survival rates were higher than expected. SBRT should be an important treatment option for local recurrence of NSCLC or lung metastasis after previous local SBRT. TRIAL REGISTRATION: This retrospective study was approved by the ethics committee of our institution (September, 2017; approval number: 27-10).

Analysis of urinary metabolites of polycyclic aromatic hydrocarbons in incineration workers.

Incineration workers are exposed to various pyrolysis products of organic materials, heavy metals and polycyclic aromatic hydrocarbons (PAHs). In this study, the exposure of incineration workers to PAHs was evaluated by measuring urinary metabolites of pyrene and naphthalene. The concentrations of urinary 1-hydroxypyrene (1OHP), a metabolite of pyrene, and 2-naphthol (2NP), a metabolite of naphthalene, were measured among 100 workers in 4 different types of incinerators, both before and after their work shifts. These incinerators were two old types, one modern type and one outdoors. The medians of urinary 1OHP of before and after the work shifts obtained from all workers were 0.067 and 0.044 mug/gCr, respectively; and the medians of urinary 2NP were 7.5 and 10.0 mug/gCr, respectively. A significant increase of 2NP after the work shift was found at one old incinerator. A significant decrease of metabolites was found at the other old incinerator. Significant correlations were found between urinary metabolites and cigarettes smoked per day. The effect of smoking on urinary metabolite levels was also important. Significant correlations were found between urinary 1OHP and 2NP levels in all workers. In multiple regression analysis smoking habit and incinerator type were found as significant factors. The improvement of the work environment, through decreasing exposure to both tobacco smoke and hazardous work shift-related substances, should be an occupational health aim.

Relationship between blood lead level and work related factors using the NIIH questionnaire system.

Over an 11-yr period (1990-2000), a questionnaire survey on work environmental management and environmental improvement was conducted on 259 lead-handling factories and 7,623 subjects. Labour Inspection Offices identified these factories as requiring environmental improvement, or possessing a desire to improve their working environment. We analyzed factors affecting blood lead levels (PbBs). These factors were gender, age, employment duration, factory size, work environment control (WEC) class, and job categories. The PbB of men was found to be higher than that of women, and may be due to the differences in job distribution. PbB increased along with increasing age and employment duration. PbB declined as the factory size increased. The odds ratio (OR) of PbB higher than 20 microg/dl according to factory size was significantly high even after adjusting for WEC class. This demonstrates that not only the working environment but also safety management was poorer among small-scale factories that large-scale factories. The rise of PbB along with the increase of WEC class confirmed that the results of work environment measurement are correlated with individual exposure levels. The risk of having a 20 microg/dl or higher PbB was different for various lead handling jobs. Smelting or refining lead had the highest risk for lead exposure while painting or baking had the lowest risk. As our study population was not a randomly selected sample, we are unable to generalize our results for workers across Japan. However, we were able to indicate which jobs pose a high-risk and the effectiveness of using the work environment control class as an index of worksite environment levels.

[Relationship between length of sleep and oxidative stress marker, urinary 8-hydroxy-2'-deoxyguanosine].

OBJECTIVES: In this study, we aim to examine whether the length of sleep modifies the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OH-dG). METHODS: Subjects were 146 workers who were engaged in management, clerical work, laboratory work, or business at a certain company. We obtained information on the subjects concerning gender, body mass index, drinking and smoking habits, and the lengths of habitual and previous night sleep among others using self-reported questionnaires, which were then confirmed by interview. Urine specimens were collected in the morning and those from the second or later void were used to measure 8-OH-dG and creatinine levels. The amount of 8-OH-dG normalized by creatinine content was used as the indicator of 8-OH-dG excretion (Spot Urine 8-OH-dG: SU8-OH-dG). We excluded subjects who took sleeping pills the previous night or habitually, and those whose levels were beyond the three-standard-deviation range. The subjects were then classified into three equal-sized groups according to the length of sleep, either habitual or the previous night. RESULTS AND CONCLUSION: (1) A long or a short previous night's sleep, drinking alcohol more than once a week, and habitual use of medicine increased SU8-OH-dG level among female subjects. (2) A short previous night's sleep and habitual smoking, and a short previous night's sleep and habitual use of medicine had interactions which increased SU8-OH-dG level among male subjects but the length of a previous night's sleep itself did not have an effect on SU8-OH-dG level. (3) The length of habitual sleep had no effect on SU8-OH-dG level.

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

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.

Isomer pattern and elimination of dioxins in workers exposed at a municipal waste incineration plant.

The aim of this study was to clarify patterns of serum concentrations of dioxins in the employees of a waste incineration plant and to estimate elimination rates and half-lives of serum dioxin isomers, and the maximum serum concentrations of dioxin isomers at the time of plant shutdown. Sixteen subjects participating 3 times or more in annual health examinations during an 8-yr period from 2000 to 2007 were recruited for this study. Serum concentrations of dioxins expressed as TEQ/g lipid decreased gradually after plant shutdown with the highest decrease observed in polychlorinated dibenzofurans (PCDFs) followed by polychlorinated deibenzo-p-dioxins (PCDDs) and then coplanar PCBs. The serum toxic equivalency (TEQ) concentrations of PCDF and PCDD congeners in the employees were higher than those in the general population survey by the Ministry of the Environment, Japan, whereas the serum concentrations of coplanar PCBs were similar to those in the general population. The estimated half-lives and elimination rates of PCDDs and PCDFs in the highly exposed workers increased compared with the moderately exposed workers. The estimated geometric mean serum concentrations of PCDDs, PCDFs and total dioxins at the time of plant shutdown were 35, 53 and 107 pg TEQ/g lipid, respectively.

A cross-sectional analysis of dioxins and health effects in municipal and private waste incinerator workers in Japan.

This cross-sectional study was intended to examine health effects of 678 male workers employed during an 8-yr period from 2000 to 2007 at 36 municipal and private waste incineration plants in Japan. Blood samples were obtained for analysis of concentrations of dioxins including coplanar polychlorinated biphenyls (coplanar PCBs) and evaluation of health effects. Health effects including diabetes were surveyed via a physician's interview or clinical data from blood samples. There was a certain difference in serum concentrations of polychlorinated dibenzofurans (PCDFs) between the incinerator workers and Japanese general population, although no differences in the concentrations of total dioxins or polychlorinated dibenzo-p-dioxins (PCDDs) were found between the two groups. A few positive correlations between serum levels of PCDDs and PCDFs and the results of laboratory and physiological tests were found, but coplanar PCBs showed significant relations with 14 parameters of the tests. The background serum levels of PCDDs, PCDFs and total dioxins were significantly associated with the prevalence of diabetes. No essential differences in serum concentrations of total dioxins and in prevalence of diabetes between our subjects and the general population suggested that the incinerator workers were marginally exposed to dioxins in the workplace without any recognizable adverse health effects.

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine values measured by an ELISA correlated well with measurements by high-performance liquid chromatography with electrochemical detection.

Measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) has recently become more popular as a means of assessing oxidative stress in the human body. Although using high-performance liquid chromatography with electrochemical detection (HPLC-ECD) is a reliable method of measuring 8-oxo-dG, easier and simpler alternative methods may be preferred, if they are quantitatively accurate. The ELISA method is the likeliest candidate for a useful alternative. Anti-8-oxo-dG monoclonal antibody N45.1 has been shown to have better specificity for 8-oxo-dG than other anti-8-oxo-dG antibodies, but the urinary 8-oxo-dG values measured by ELISA using N45.1 have been claimed to only weakly correlate with the values obtained by HPLC-ECD. Because the commercial ELISA kit has been improved, we compared the urinary 8-oxo-dG values measured by the ELISA with the values obtained by HPLC-ECD. We sampled the urine of 72 healthy Japanese individuals and measured their urinary 8-oxo-dG levels by the ELISA with appropriate controls and by HPLC-ECD. When X was defined as the values of 8-oxo-dG measured by HPLC-ECD, and Y was defined as the values of 8-oxo-dG measured by the ELISA, simple regression analysis showed the most likely relationship to be Y = 1.83X + 0.8. The correlation coefficient was 0.88, which indicated a good correlation between X and Y. These results show that the ELISA can be applied to studies comparing relative urinary 8-oxo-dG values among several groups, if the studies do not require determination of the exact concentration of 8-oxo-dG in urine.

[Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene or tetrachloroethylene].

Since the late 1980s, there has been an increasing tendency in the number of case reports on Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene from Asian countries. Recently, mass outbreaks of it have been disclosed in the Philippines and China. Besides trichloroethylene, although the number is small, a similar health disorder has also occurred in workers using tetrachloroethylene. Since the above-mentioned facts are not yet well recognized in the occupational health community, this review is aimed at making clear (1) the clinical features of the health disorder, (2) details of patients' jobs, working environments, and exposure to hazardous chemicals, and (3) the relationship between exposure to trichloroethylene or tetrachloroethylene and the health disorder. Based on a critical review of articles, the following were pointed out. First, it is important to carefully observe the health status of workers exposed to trichloroethylene or tetrachloroethylene and to take countermeasures to reduce exposure. Secondly, circumstantial evidence suggests a cause-effect relationship between the two chemicals and the health disorder; but at the present time it is impossible to rule out the participation of unelucidated factors promoting the occurrence of the health disorder or the existence of a hidden genuine causative substance. Therefore further investigation to trace such a case is needed. Thirdly, the mechanism of the health disorder and the reason why there seems to be a large inter-individual difference in sensitivity to the causative agent should be clarified.

Seasonal and inter-day variation in serum high-sensitivity C-reactive protein in Japanese male workers: a longitudinal study.

Although seasonal variation in high-sensitivity C-reactive protein (hsCRP) has been studied cross-sectionally and longitudinally, the results to date have been mixed. Here, to test seasonal variation in this compound with regard to within-subject, inter-day variation, we conducted a longitudinal follow-up study with repeated measurements in Japanese workers with low hsCRP. Blood samples were obtained from four male indoor daytime workers, who were aged 32-57 and commuted to offices in Kawasaki City, on six days within 2-wk windows in February and October, 2008. Serum hsCRP was measured using ultrasensitive latex-enhanced immunonephelometry. Among the subjects with detectable levels of hsCRP, individual median serum hsCRP levels were 38-74% higher in October than in February (p=0.03). This study identified the presence of a seasonal variation in the serum hsCRP level of Japanese workers with low hsCRP levels.