In earlier papers we advanced the hypothesis that “psychotic manifestations in the elderly occur under circumstances when they fail to cope with environmental stress. Major factors causing such maladaptation are intellectual impairment and environmental stressors”. The environment of a bedridden patient is limited to his or her immediate surroundings, and the quality of the relationship with the caretaker represents the primary stress in the environment. In order to test the foregoing hypothesis, we studied 125 bedridden patients living at home in Saku City, Nagano Prefecture regarding the frequency of psychotic manifestations (delusions, hallucinations, nocturnal delirium) and the caretaker-patient relationship. In evaluating the relationship we employed a revised edition of the caretaker-patient relationship score (CPR score) which added questions regarding “esteem” to the original version.
When matched for ADL and the degree of intellectual impairment, those without psychotic manifestations had better relationships as measured by the CPR score than those with psychotic manifestations. This tendency was most prominent when the elderly had moderate intellectual impairment (p<0.01). These findings support our hypothesis regarding the occurrence of psychotic manifestations in the bedridden elderly. Scores obtained using this scale are concordant with the impressions of three public health nurses, suggesting the validity of the scale. Factor analysis of the questionnaire revealed that “esteem” for the elderly constituted an independent factor, suggesting that a good relationship between the caretaker and the patient entails the factor of esteem.

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Hyperbaric Oxygen Therapy (HBO) is a remarkably effective therapy against hypoxic disorders; however, problems concerning the safety of this therapy still remain. One method of counteracting the toxicity of HBO is to limit the magnitude of compressed pressure and the exposure time to avoid the onset of acute conditions such as convulsions. A reliable indicator of the toxicity is also needed.
The hydroxyl radical (sdot;OH) is the fastest reacting and most injurious radical, so it was selected as the target for the evaluation of HBO in this study.
Rabbits were exposed to HBO conditions for between one and four ATA (atmospheres absolute) for 60min., and the hydroxyl radical was studied with the lapse of time by electron spin resonance (ESR).
As a result, it was determined that, in conditions above 3 ATA, breathing pure oxygen for 60min. creates problems even if acute oxygen toxicity is not recognized.
It is, thus, necessary to establish standards for safety and adaptability of HBO.
The advantages of HBO have been discussed; however, the responses of oxygen free radicals should be studied more carefully. It is also essential to determine the oxygen toxicity. Such studies may be expected to give us data which can be of great use in HBO.

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¹⁴C-Labeled diethylene glycol was synthesized from radioactive ethylene glycol with a good yield and specific radioactivity.
As a result of animal experiments using this labeled compound, the following findings were made:
1) After single oral administration, the peak of radioactivity in blood was found at 1h, and, thereafter, the radioactivity decreased slowly. The radioactivity in tissues and organs persisted for a long period. A high radioactive concentration was detected in stomach and just relatively high concentrations were observed in liver, pancreas and kidney. About 55% of the dose was excreted in urine by 24h after administration.
2) The radioactivity in tissues distributed evenly after repeated oral administration, as in the case of single administration, and accumulation in any particular tissue or organ was not observed. In every tissue and organ of 24h after final repeated administration, each radioactive concentration was found to be higher than the corresponding value at 24h after a single oral administration.
3) Transference of radioactivity to milk occurred, and the peak of concentration in milk was observed at 6h after oral administration; however, its ratio to the concentration in dam blood increased with time until 24h.
4) Transference of radioactivity in bile began just after oral administration, but the amount was small.
5) About 21% of the dose was excreted in expiration by 24h after single oral administration.
6) Percutaneous absorption took place in animals with abraded skin much more than in animals with normal skin.
7) In the dialysis experiment, ¹⁴C-diethylene glycol did not combine with normal plasma, but binding of radioactivity to plasma was noted in plasma 1h and 24h after oral administration.
8) About 93% of radioactive urinary metabolites were identified as intact dethylene glycol, and the remaining 7% as oxalic acid. All radioactive expiration was the form of carbon dioxide.

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Four hundred and forty-one primary school children in Kashima district in Ibaraki prefecture were examined in 1980 and reexamined in 1982 in terms of flow-volume curve parameters, respiratory symptoms, past history of illnesses and other familial factors, including parental smoking habits, method of home heating, etc. Analyzable data were collected from 351 of the subjects. Subjects were classified into three groups according to their past history of respiratory illnesses.
In pulmonary function parameters sensitive to changes in relatively peripheral airways (Vmax50, Vmax25), children with a history of bronchial asthma or wheezing bronchitis (8 boys and 11 girls) showed a slightly, but significantly lower mean value than a control group, but this was not the case for FVC or FEV₁. These results may indicate the important role of respiratory illness accompanied by wheezing on the growth of the respiratory system. The relevance of the above findings to the natural history of chronic respiratory illnesses is also discussed.

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The luminol-dependent chemiluminescence method (LC method) measures the light emitted by luminol through oxidation with reactive oxygen species produced during phagocytosis. Using the LC method technique, we previously succeeded in making a simultaneous multiple measurement system and reported it in this journal.
In this paper, we examine the reproducibility of intermeasurement with this system and also report on the serum opsonic activities of inhabitants of a rural area in Oita prefecture.
1. For the purpose of producing 4 standard serums graded by the activity of the thermolabile opsonic activator, inactivated serum (56°C, 30min.) and normal serum are mixed in specified proportions. The reproducibility of the standard serums was examined 17 times in 4 months and for each measurement the concentration of the neutrophile suspension and the number of simultaneously measured samples were different.
2. Peak time and peak height of chemiluminescence of each standard serum were represented by the ratio calculated from the values of the corresponding standard serum consisting of only pooled normal serum. Good reproducibility was observed in the case of the standard serums which had a large proportion of pooled normal serum.
3. In the case of the representation of the pooled normal serum ratio using the least squares method calculated from the measurement values of 4 standard serums, the coefficient of variation of the peak height ranged from 2.0 to 3.1%.
4. Serum opsonic activities of 88 inhabitants in a rural area of Oita prefecture were measured 5 times in 2 days by this system and the reproducibility in regard to peak height of standard serums used for these measurements was good.
5. In the serums of inhabitants in the rural area, there were some which showed a larger peak height or a shorter peak time than the standard serum consisting of only pooled normal serum, but the mean values were slightly smaller than those of the pooled normal serum.
6. The serums were simultaneously measured using the same neutrophil suspension and changes were recognized not only in peak time but also in peak height in each serum. Thus, we concluded that serum opsonic activity is not indicated by peak time alone; it is also necessary to consider peak height as an indicator together with peak time.

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Eight group of rats, with 4 animals in each group, were subcutaneously injected with a single dose of methylmercury (MMC) of 0 (control), 5, 10, 15, 20, 25, 30 or 35mg/kg body weight, respectively. Two days after the injection, two out of four animals in each group were sacrificed by cardiac puncture. Another two in each group of rats were sacrificed on day 7 after the injection. Gas-chromatographic analyses of fatty acids were carried out on the samples of liver, kidney, brain, blood cells and plasma taken from the rats to investigate the effects of MMC on lipid metabolism. The effect of quantitative changes of food consumption on the lipid components is also discussed in this paper. Results obtained are as follows:
1) Following the injection of MMC, the amount of food consumption of rats decreased with increases in the dose of MMC. Weight gain ratios during the experimental period of 7 days after the injection of MMC were dependent on the amount of food consumption.
2) Two days after the injection, the concentrations of polyenic acid of the ω-6 series (ω-6) in the liver and those of the ω-3 series (ω-3) in the kidney and plasma increased with increases in the dose of MMC, while the concentrations of saturated and monoenic acids (Sat+Mono), ω-6, ω-3 and hydroxy fatty acid (OH-FA) in the brain decreased with increases in the dose of MMC. Taking the dose of MMC into account, however, the concentrations of ω-3 in plasma increased with decreases in the amount of food consumption.
3) Seven days after the injection, the concentrations of Sat+Mono, ω-6 and ω-3 in the liver and blood cells, and ω-3 in plasma decreased with increases in the dose of MMC, while those of Sat+Mono, ω-6, ω-3 and OH-FA in the brain increased with increases in the dose of MMC.
4) From the above-mentioned, the changes in lipid components induced by MMC are analyzed for the probable underlying mechanism of the development of neurological disturbances in MMC poisoning.

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The demand for institutional care in hospitals is greatly increasing. In 1984/85 in S. City, Osaka, the number of bed-days in hospitals of inpatients covered by the National Health Insurance Scheme, their number and the number of their insurance receipts were 32.6%, 28.3%, and 31.4% higher, respectively, than in 1981/82. The demand from inpatients aged 70-or-more was the largest factor in these increases. Of the total increase in bed-days, 68.0% was accounted for by this group. Bed-days of inpatients aged 70-and-over per 100 insured persons increased 32.6% between 1981/82 and 1984/85, and those of inpatients aged under 70 increased 10.4%. The main factor in the increase in bed-days was a significant increase in the average bed-days per year of inpatients aged 70-and-over. There was also a significant increase in the rate of admission of inpatients aged under 70.
When patients aged 70-and-over were divided into those who stayed for 180 days or more in the year and those who stayed for less than 180 days, the first group contributed 92.8% of the increase in bed-days per 100 insured persons. The number of inpatients aged 70-and-over who stayed for 180 days or more accounted for 2.6% of the total number of inpatients in 1981/82. This figure rose to 4.0% in 1984/85. The percentages were not large, but the difference between rates of admission was significant. The main factor in the increase in bed-days of inpatients aged 70-and-over who stayed for 180 days or more was this increase in the rate of admission.
Patients with diseases of the circulatory system had the largest number of bed-days. Of the total increase in bed-days of inpatients aged 70-and-over who stayed 180 days or more, 89.4% was occupied by an increase in bed-days of inpatients with these diseases.
The most striking characteristic of the demand for hospital care in Japan is the increase in the number of elderly inpatients who stay for long periods. This increase has greatly contributed to an increase in the total bed-days for insured persons. We also found a positive relationship between the length of hospitalization and the number of beds in the hospital.

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Pregnant and nursing rats were given water containing 1, 000ppm manganese (MnCl₂ was used) ad libitum and the transfer of Mn to fetuses and sucklings was investigated. Administration of Mn during the first half of the gestation period before placentation produced no difference in Mn concentration in embryos, including chorions, from the control group. However, when Mn was administered during the second half of the gestation period, the fetal and placental concentrations of Mn were 2.7 and 1.9 times, respectively, as high as those in the control group, and the dams showed significantly higher Mn concentrations in the liver and kidney than the control group (p<0.01). It is, therefore, considered that Mn is more likely to transfer to fetuses when given after placentation than when given during the first half of the gestation period. During the period of lactation, a significant difference was found only between the Mn concentrations in the livers of dams of the control group and the treated group (p<0.01). Sucklings began to show increased concentrations of Mn in the stomach and intestinal tract on the 8th day after birth, and the total Mn content in the liver, kidneys, and whole body, excluding the stomach and intestinal tract, was four to seven times as high as that of the control group on the 20th day after birth. These results suggest that the transfer of Mn into sucklings via milk during lactation is much greater than that into fetuses during pregnancy.

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To investigate the microwave dose-death relationship, animal experiments concerned with ambient temperature and body size were performed. Microwaves with a frequency of 2, 450MHz were radiated on the rat's entire body under various power densities. Each exposure group consisted of five rats.
The results obtained were as follows.
1) For rats weighing 185-215g, mean time to death was related to microwave power density. The highest power level (100mW/cm²) resulted in the shortest time to death (8.0min) at the ambient temperature of 22°C. There was no significant relationship between the power density and the rectal or brain temperature at death. However, brain temperature was slightly lower than rectal temperature.
2) For rats weighing 185-215g, mean time to death was related to ambient temperature. The highest ambient temperature (22°C) resulted in the shortest time to death (12.7min) at the power density of 50mW/cm². Rectal temperature at death was also related to ambient temperature. The highest ambient temperature (22°C) resulted in the lowest rectal temperature (45°C).
3) Mean time to death of rats was related to body weight. The heaviest body weight (590-610g) resulted in the longest time to death (25.2min), at the power density of 50mW/cm² under the ambient temperature of 22°C. However, no relationship was observed between rectal temperature and body weight when the rats died.
4) Concerning rats weighing less than 315g, the LD₅₀ value was less than 10mW/cm² at the ambient temperature of 22°C.
From these results, it is concluded that ambient temperature and body weight must be taken into consideration in the evaluation of the permissible level of microwave.

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Using the system which I developed for the monitoring of body surface circulation, the peripheral circulatory function of workers who used vibrating tools was studied at rest, and then the peripheral circulatory movements during handgrip and local vibration exposure were examined. Workers using vibrating tools were divided into three groups; group A without any symptoms, group B with numbness and/or pain but without Raynaud's phenomenon, and group C with Raynaud's phenomenon.
The results obtained were as follow;
1) In fifty-six workers using vibrating tools, the skin temperature showed no significant differences among the three groups but the finger blood flow of group C was significantly less than that of group A (p<0.01).
2) In a short-term handgrip test using a hand dynamometer with a constant strength, the skin temperature showed no significant change. The finger blood flow of group A and group B significantly decreased as compared with the value at rest but that of group C showed no significant change.
3) In a five-minute handgrip test using a hand dynamometer with a constant strength, the finger blood flow of six workers with no symptoms significantly decreased from one minute after the start of the test as compared with the value at rest and maintained its significantly low level. Thereafter, the skin temperature significantly fell from two minutes after the start of the handgrip test and continued to fall during handgrip. After the end of handgrip, the finger blood flow returned to the level at rest and the skin temperature significantly rose as compared with the value at rest.
4) In the exposure to local vibration (60Hz, 50m/sec²) of eighteen workers using vibrating tools, the finger blood flow of group A significantly increased after the start of exposure but group C did not show any increase. The finger blood flow of group B showed a slight increase but it was not significant.
It was concluded that the newly developed system for monitoring the body surface circulation was useful not only for diagnosis of peripheral circulatory disorders but also in the elucidation of its pathogenesis.

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In vitro and in vivo short term mutagenicity tests are widely used for screening environmental and industrial chemicals for carcinogenic potential. It is necessary to evaluate chemical carcinogens with the in vivo mutagenicity test system because of the difficulty of extrapolating the results of in vitro mutagenicity tests to human beings. But the in vivo mutagenicity test system has a low sensitivity for screening carcinogenic potential compared with the in vitro test.
The in vivo micronucleus test developed by Schmid is commonly used because of its simplicity, reproducibility, and economic return. We have tried to modify this test to elevate its sensitivity.
Verapamil is a calcium antagonist administered to patients with heart disease. It is known that verapamil has the ability to increase the permeability of the cell membrane. It is important that mutagens reach the DNA strands through the cell membrane in order to induce mutagenic changes of cells.
The aim of this study is to investigate the effects of a calcium antagonist on the sensitivity of in vivo and in vitro micronucleus tests using vincristine as a mutagen.
In the in vivo micronucleus test, both single and consecutive administration of verapamil showed a dose-response relationship between the dose of verapamil or vincristine and the incidence of micronucleated polychromatic erythrocytes (MPCE). However, there were no significant differences in MPCE incidence between single and consecutive administration of verapamil.
On the other hand, in in vitro micronucleus test, the longer the incubation time of vincristine and verapamil with cultured bone marrow cells, the higher the MPCE induction rates. The dose-response relationship between the incidence of MPCE and the concentration of verapamil or vincristine was also observed in the in vitro micronucleus test.
This present study suggests that the sensitivity of the micronucleus test can be increased by verapamil, a calcium antagonist.

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