Insertion polymorphism of CYP2E1 and urinary N-methylformamide after N,N- dimethylformamide exposure in Japanese workers.

OBJECTIVES: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. METHODS: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. RESULTS AND CONCLUSIONS: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF.

Causal relationship between a case of severe hepatic dysfunction and low exposure concentrations of N,N-dimethylformamide in the synthetics industry.

A 19-year-old man suffered hepatic dysfunction after 5 months of exposure to N,N-dimethylformamide (DMF) at his job in the synthetic resins industry. Laboratory data revealed elevated levels of AST (578 IU/l), ALT (1193 IU/l), and gamma-GTP (107 IU/l), no viral infection with HAV, HBV, or HCV, and no history or evidence of hepatic injury, although he did have a slight abdominal abnormality and swelling which was detected by palpation. His urinary N-methylformamide level, as a biological exposure index of DMF, was 42.8 mg/l, indicating 10-30 ppm of DMF exposure. After 2 months he was reinstated in two workplaces, the former where he worked in the morning and the other in the afternoon where environmental DMF concentrations were less than those in the former workplace. On the 18th day after his reinstatement, his liver function became exasperated again. After the second period of medication and one month of rest from work, he had fully recovered and was reinstated, but to a workshop without DMF exposure.

Hyperthermia combined with re-irradiation for neck node metastasis from head and neck cancer.

UNLABELLED: The effects of hyperthermia combined with re-irradiation were compared with those of reirradiation alone using retrospectively matched-pair analysis. Between 1984 and 1997, 12 patients were treated with hyperthermia combined with re-irradiation for neck node metastasis from squamous cell carcinoma of the head and neck. During the same period, 12 patients treated with re-irradiation alone were selected retrospectively using the same anatomical diagnosis, nodal site, and nodal size. Recurrent nodes were heated by a 2450MHz microwave or 13MHz radio frequency 4 times on average for 30 to 50 min immediately before radiotherapy. The maximum temperatures were >41degrees C in 83% and >42 degrees C in 58% of patients. RESULTS: The median survival and median recurrence periods were 12 months and 6 months, respectively in both groups. The response rate was 83% in both groups. Nodal size and radiation dose, but not heating temperature, were prognostic factors. Five patients in the hyperthermia group experienced skin ulcers or burns as acute complications. Late complications were observed in one patient in the hyperthermia group and 3 patients in the re-irradiation-alone group. CONCLUSION: Heating induced acute complications and had no significant effect on the tumors. Further advances in hyperthermic technique are required.

Vaginal applicators (ovoids) for local control and alleviation of rectal complications of cervical cancers treated by brachytherapy.

PURPOSE: To assess the effects of vaginal applicators (ovoids) on dose distribution, local control and rectal complications in cervical cancers treated by brachytherapy. METHODS: From 1984 to 1992, 41 patients (15 stages I+II; 26 stages III+IV) were treated by high-dose-rate brachytherapy (20 Gy in 4 fractions) after external beam irradiation (36-56 Gy). Twenty-three patients were treated by standard application of both intrauterine tandem and ovoids, and 18 patients were treated by non-standard application. RESULTS: The five-year, local-relapse-free rates by standard application and tandem alone were 69 and 65% overall; 83 and 100% for stages I+II; and 62 and 49% for stages III+IV. Local control was related to tumor response following the external beam irradiation and initial tumor size by multivariate analysis. Rectal complications seen in patients followed for more than 1 year were 33% after standard application and 22% for tandem use alone. The rectal doses given for standard application (24 Gy) and tandem use (16 Gy) were significantly different. CONCLUSIONS: The ovoid sources did not always contribute to local control, and occasionally led to rectal complications. The optimization of brachytherapy was dependent on patients' anatomy, tumor size, and tumor response.

A cross-sectional observation of the health effects of hydrazine hydrate and differences of its metabolism by NAT2 polymorphism.

OBJECTIVES: To summarize the results of two studies that attempted to clarify: (1) the health effects of hydrazine hydrate (HH) (N2H4 x H2O: CAS No. 7803-57-8); and (2) the influence of allelic polymorphism of N-acetyltransferase (NAT2) on the metabolism of HH. METHODS: A cross-sectional survey was carried out on 172 male HH-exposed workers and 125 male referent workers at five factories in Japan. The biological half-lives of HH after 1 h of exposure were determined in 12 workers, four workers in each of three NAT2 phenotypes. Clinical examinations were performed and acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. NAT2 phenotypes were assessed. RESULTS: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine and acetylhydrazine in urine, and the cumulative exposure level were 0.0109 ppm, 0.8660 micromol/g x Cr, and 2.80 ppm-years, respectively. There was no difference and no dose-dependent change in the health examination items between HH-exposed and referent workers after adjusting confounding factors, nor in terms of the differences of NAT2 phenotypes. Of 90 subjective symptoms, complaints of nightmares were significantly related to HH exposure. The half-life of urinary hydrazine and acetylhydrazine on rapid, intermediate, and slow phenotypes was 1.68, 3.01, and 4.46 h, respectively. CONCLUSION: This study suggested that current and cumulative exposure to HH did not affect the workers' health, and the half-life of the slow phenotype was longer than those of the rapid and intermediate phenotypes.

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Synergistic effects of hyperthermia and intratumorous injection of anti-cancer drugs.

In an attempt to improve the combined effects of hyperthermia and anti-cancer drugs, an intratumorous (i.t.) injection of the drugs was performed and its effect compared with that obtained by intraperitoneal (i.p.) injection. Using Lewis lung carcinoma growing in the legs of BDF1 mice, weakly toxic drug derivatives, Aclarubicin (ACR), a new platinum complex (DWA2114R), or Peplomycin (PEP) were injected either into the center of the tumors, or intraperitoneally, before or after usual hyperthemia in a 43.5-43.7 degrees C water bath for 45 min. The effects on tumor growth delay and the number of lung metastases were assessed, and the enhancement ratios (ERs) due to the combination were calculated. Tumor growth inhibition by i.t. injection was enhanced additively with ACR (ER; 1.2) and synergistically with DWA2114R (ER; 3.49) and PEP (ER; 2.4) plus hyperthermia. Hyperthermia after i.t. injections of DWA2114R (ER; 3.4) was more effective than either i.t. or i.p. injections after hyperthermia (ER; 2.4). Lung metastases were also inhibited significantly by the combination of hyperthermia and drugs, except when emulsified PEP was injected three times. It was concluded that the i.t. injection of DWA2114R was of value when used in combination with hyperthermia.

[Industrial hygienic study on nursing activities. II. Investigation on heart rate and energy expenditure of ward nurses on shift].

By using a Holter electrocardiograph (ECG), we calculated the heart rates of ward nurses on day shift which included different activities. Energy expenditure was calculated from the heart rate data and nurse work load was evaluated. The following results were obtained. 1) Average heart rates during working hours were 86 (beats/min) in children ward nurses, 77 in ophthalmology ward nurses, 85 in surgery ward nurses, 85 in mixed ward nurses, 85 in neurosurgery ward nurses, 81 in circulatory organs ward nurses and 83 in ICU ward nurses. 2) The energy expenditures were calculated to be 1,891 kcal in children ward nurse on day shift, 1,866 kcal in ophthalmology ward nurses, 1,969 kcal in surgery ward nurses, 1,899 kcal in mixed ward nurses, 1,976 kcal in neurosurgery ward nurses, 1,873 kcal in circulatory organs ward nurses and 1,744 kcal in ICU ward nurses. 3) The highest energy expenditures in direct nursing care were 918 kcal (48.3%) in mixed ward nurses; in assisting medical examination and treatment, 770 kcal (39.1%) in surgery ward nurses and in indirect nursing care, 679 kcal (35.9%) in children ward nurses. 4) The longest working hours in direct nursing care were 217 min (42.5%) in neurosurgery ward nurses; in assisting medical examination and treatment, 193 min (37.8%) in surgical ward nurses and in indirect nursing care, 207 min (40.5%) in children word nurses. The results indicated that the energy expenditure calculated from the average heart rate of ward nurses on day shift was very high in all wards. The attributable causes are discussed in this report.

Possible role of metallothionein on the gastrointestinal absorption and distribution of cadmium.

Although the role of metallothionein (MT) has been suggested by many researchers, the exact biological or physiological roles of MT are still unclear. Up to the present, the role of this ubiquitous low molecular weight protein has variously been reported as 1) the regulation of the normal absorption and homeostasis of essential metals such as zinc (Zn), copper (Cu), 2) the chelation and detoxification of toxic metals such as cadmium (Cd) or mercury (Hg). The mechanisms of Cd uptake from gastrointestinal lumen and its consecutive transport from the intestinal mucosa into blood circulation and tissue are not well known. The chemical form of Cd is an important factor on its gastrointestinal absorption. It has been reported that Cd in foods such as meat, seafoods, and vegetable is existing mainly as Cd-MT or MT-like Cd binding proteins. Also it is well known that MT is induced in the intestinal tissue by oral Cd administration. Until today, the mechanism of gastrointestinal absorption has been mainly discussed about Cd ion. However, it needs the consideration including the chemical form of Cd such as Cd-MT in foods or Cd bound by MT induced in the intestinal tissue. Namely, it is important to assess the possible role of MT on gastrointestinal absorption and its consecutive tissue distribution of Cd.

Industrial hygienic study on nursing activities investigation on heart rate and energy expenditure of cranial nerves and ICU ward nurses.

Using a Holter electrocardiograph (ECG), we calculated the heart rates of ward nurses during day shifts, a time in which various activities are undertaken. Energy expenditures were calculated from the heart rate data and nursing workloads were evaluated. The following results were obtained. 1) The energy expenditures per day were 3302 kcal in the cranial neurology ward, 3064 kcal in the ICU. 2) The energy expenditures during working hours were 1976 kcal for the day shift (510 minutes) in the cranial neurology ward, 1744 kcal in the ICU, 1867 kcal for the evening shift (495 min) in the cranial neurology ward, 1645 kcal for the evening shift in the ICU and 1947 kcal for the night shift (570 min) in the cranial neurology ward, 1839 kcal for the night shift in the ICU. 3) The highest energy expenditures for different activities were 949 kcal (78.0%) for day shift in direct nursing care in the cranial neurology ward, 722 kcal (43.8%) for the evening shift in assisting with medical examination and treatment in the ICU, 754 kcal (41.0%) for the night shift in assisting with medical examination and treatment in the ICU ward. 4) The longest working hours were 217 min (48.0%) for the day shift in direct nursing care in the cranial neurology ward, 252 min (50.9%) for the evening shift, 234 min (41.0%) for the night shift in assisting with medical examination and treatment in the ICU. The results indicate that the energy expenditures of ward nurses are higher than those of other workers. The reasons for this difference are discussed in this report.

Industrial hygienic study on nursing activities comparison of energy expenditure between pedometer and Holter electrocardiograph.

Few objective and quantitative studies have been made on energy expenditure during hospital nursing activities. The pedometer is a light handy instrument, which gives highly accurate results, and is a minimal burden for subjects. To ascertain daily energy expenditures, we used a pedometer. Twelve day-shift nurses served as subjects, in whom the number of steps token in 16 hours, from getting up until going to bed, was measured. We used the data obtained to calculate energy expenditures for 24 hours. In addition, eight nurses were chosen from among these subjects to undergo simultaneous pedometry and Holter electrocardiography. These data were also used to calculate energy expenditures. The following results were obtained. 1) The maximum total number of steps was 13897, the minimum 9899 and the mean +/- standard deviation was 11478.4 +/- 1285.8. 2) As to the energy expenditure of the eight nurses who were both pedometer and Holter electrocardiograph, the highest energy expenditure calculated from pedometry results was 2648 kcal. the lowest 2455 kcal, and the mean +/- standard deviation was 2514.1 +/- 55.5. The highest energy calculated from Holter electrocardiographic data was 3040 kcal, the lowest 2683 kcal, and the mean +/- standard deviation was 2868.1 +/- 108.0. The correlation coefficient was r = 0.59, (P < 0.05).

[Industrial hygienic study on nursing activities. I. Investigation on heart rate and energy expenditure of ward nurses by nursing activity].

Using a Holter electrocardiograph (ECG), we recorded the heart rates of ward nurses by working hours and nursing activity. Energy expenditure was calculated from the heart rate data and nurse work lord was evaluated. The following results were obtained. 1) Average heart rates were 77 (beats/min) for day-shift nurse in surgical ward, 76 for evening-shift nurse in mixed, ward, and 74 for night-shift nurse in mixed ward. 2) The energy expenditures per day were calculated to be 3,474 kcal for day-shift nurse in surgical ward, 3,060 kcal for evening-shift nurse in mixed ward, and 3,238 kcal for night-shift nurse in mixed ward. 3) The energy expenditures during working hours were 2,110 kcal/510 min for day-shift nurse in surgical ward, 1,805 kcal/495 min for evening shift nurse, and 2,014 kcal/570 min for night-shift nurse in mixed ward. 4) The highest energy expenditures of nurse engaged in direct nursing care were 834 kcal (39.5%) for day-shift nurse in surgical ward, 632 kcal (34.9%) for evening-shift nurse in mixed ward, and 790 kcal (39.2%) for night-shift nurse in mixed ward. 5) The longest working hours were 174 min (34.1%) in assisting with medical examinations and treatment by day-shift nurse, 155 min (31.3%) in direct care by evening-shift nurse, and 222 min (39.0%) by night-shift nurse. The results indicate that the energy expenditure calculated from the average heart rate of ward nurses in higher than that of other types of workers. The reason for this difference is discussed in this report. Also, this study showed that the energy expenditure determined by this method does not necessarily increase in proportion to working hours.

Evaluation of methyl bromide exposure on the plant quarantine fumigators by environmental and biological monitoring.

The study was undertaken to assess the potential risk of exposure to methyl bromide (MB) gas of plant quarantine fumigators who wore full facepiece gas masks with respirator canisters. The mean ambient concentrations of MB determined by a personal sampling device exceeded the TLV-ACGIH level of 5 ppm in the degassing processes at three fumigation sites except at the silos. The mean urinary bromine concentration of 379 non-MB workers was 6.3 +/- 2.5 mg/l with 95% confidence limits of 10 mg/l. There were 44.6% of 251 MB workers whose urinary bromine levels exceeded the 10 mg/l. There was a significantly positive correlation between the urinary bromine concentrations of the MB workers and the ambient MB concentrations in the degassing process. The MB levels in the workers' exhalation were positive in the degassing process, while those were below the detection limit in the dispersion process. Three possible routes through which the workers are exposed to MB gas are considered to exist: leakage through the interstice between the facepiece of a gas mask and the wearer's face, breakthrough of MB gas in the respirator canister, and percutaneous absorption of MB gas. Biological monitoring of urinary bromine and exhalatory MB as well as environmental monitoring of the ambient MB provided useful information for evaluating exposure of workers to MB.

Studies on the use of monoclonal antibodies in the investigation of blood stains contaminated by bacteria.

On the basis of some models (bacteria and animal blood groups), it was demonstrated that monoclonal antibody-preparations obviously possess a much higher specificity against the ABO-properties of human than the usual human antisera or lectins. The behaviour of polyclonal and monoclonal reagents for ABO-determination should now be tested in comparative studies using contaminated blood stain material. The results presented in this paper suggest advantages in using monoclonal antibodies.

A mechanism of cadmium poisoning: the cross effect of calcium and cadmium in the calmodulin-dependent system.

The effects of the intraventricular (IVT) administration of cadmium on the amount of dopamine (DA) in various regions of the mice brain were analyzed immunohistochemically using a microphotometry system. DA levels in the neostriatum and nucleus accumbens were increased by approximately 30% (p less than 0.01) by the IVT administration of CdCl2 (1 mumol/kg). This effect was abolished by the calmodulin antagonist, W-7 (4.2 micrograms/mouse, IVT). The effects of cadmium on DA levels in the brain were very similar to those seen with calcium. Combining these results with our previous finding that calmodulin does not have the ability to distinguish between calcium and cadmium, a mechanism of cadmium poisoning is suggested in which cadmium activates catecholamine synthesizing enzyme and numerous other enzymes through calmodulin-dependent systems, thereby disturbing many functions in the organism.

[Determination of bromide ions in total blood, plasma and urine by ion chromatography with amperometric detection].

A direct injection method is described for the determination of bromide ions in plasma and urine by ion chromatography. After being diluted 10-20 times with eluent, the sample was directly injected into an ion chromatograph equipped with amperometric detection. Calibration curves were obtained in the range of 0.05 to 5 micrograms/ml of bromide ions. The coefficient of variation was calculated to be in the range of 1.3-9.4% for 10 repeated measurements and recovery was over 93%. The correlation between analytical results by the proposed method (Y) and those by a spectrophotometric method (X) of 169 urine samples in fumigators was expressed by the equation Y = 0.952 + 1.012X (correlation coefficient (r): 0.952). On the other hand, the correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 47 total-blood samples in fumigators was expressed by the equation Y = 1.070 + 0.841 X (correlation coefficient (r): 0.931). The correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 40 plasma samples in healthy workers was expressed by the equation Y = 0.633 + 0.871 X (correlation coefficient (r): 0.955). The proposed method is much more practical than other methods such as the spectrophotometric method and neutron activation analysis in epidemiological studies, because the proposed method is highly accurate and reproducible over longer periods. The proposed method is useful in biological fluid monitoring of bromide ions.

Efficiency of respirator canisters with methyl bromide.

Two kinds of respirator canisters, an organic vapor (OV) canister containing activated carbon and a methyl bromide (MB) canister containing activated carbon impregnated with triethylenediamine were investigated for their filtration efficiency of MB gas under various conditions of MB concentration, humidity and temperature. At lower MB concentrations, the breakthrough time of the OV canister was shorter than that of the MB canister. It also decreased with an increase in temperature, whereas the breakthrough time of the MB canister did not change with temperature. Humidity affected the breakthrough times of the OV canister as much as those of the MB canister. The desorption and the remaining filtration efficiency of MB gas were examined in both canisters which had been used for fumigation in plant quarantine. More than 5 ppm of MB gas leaked from 11 out of 18 used OV canisters, whereas less than 0.1 ppm MB leaked out from each of the used MB canisters. The mean remaining breakthrough time of the used OV canisters was 9.3 min, whereas that of the used MB canisters was 74.4 min. From the present study, it was shown that the gas masks with the OV canisters were not suitable for fumigating with MB gas.

[The protective effect of simultaneous selenium administration on acute cadmium toxicity and metallothionein].

The present study was conducted to elucidate the protective action of simultaneous selenium administration against acute cadmium toxicity. The remarkable testicular damages caused by cadmium, that is, hemorrhagic inflammation, atrophy and necrosis, were lessened by simultaneous selenium administration. Cadmium concentration in blood, especially in plasma, increased significantly during the early period after cadmium administration with selenium. Cadmium and selenium in plasma were found in the same fractions of high molecular weight reported by previous workers as the high molecular weight complex containing cadmium and selenium. Cadmium in testis was also noted in the high molecular weight fraction during the early period. However, cadmium in the high molecular weight fraction of plasma and testis were unstable and decreased rapidly by lapse in time. Cadmium concentration in liver was lower than that in the group administered cadmium alone during the increasing phase of plasma cadmium. However, in contrast with the decreased cadmium level in plasma, cadmium in liver and testis increased gradually. Cadmium increased in liver and testis were also found in the metallothionein fraction. In the testis protected from acute cadmium toxicity, the inhibitory effect of glutathione S-transferase activity by cadmium was not detectable and the activity was maintained at the level of the control (saline administered group). Moreover, the increased cadmium in the metallothionein fraction was related to the decrease of cadmium in the high molecular weight fraction of the testis homogenate. In addition, a positive correlation was observed between metallothionein concentration and glutathione S-transferase activity.(ABSTRACT TRUNCATED AT 250 WORDS)