Mortality and survival for Minamata disease.

Analysis of mortality of 439 deaths that occurred among 1483 patients with Minamata disease (MD) in Kumamoto Prefecture, Japan was performed from the end of 1981. Causes of death and survival rates were studied by means of the standardized mortality ratio (SMR) and life-table technique. Of the 439 deaths (29.6%) in MD cases, the first death occurred in 1954. There was a first peak incidence in 1956 when MD was initially reported, however, the majority of deaths occurred after 1972 when a second and much larger peak was evident. In 1970 an important milestone occurred when the Public Nuisance Relief Law (an anti-pollution law) was enacted. Among its provisions, this law required and enabled verification of MD among people suspected of having been exposed. In contrast to the early cases, later cases of MD were older and their mean age-at-death was not different from that of the general population. The mortality rate for all causes of death was significantly higher in both sexes compared to the general population. Significantly lower survival rates were noted for older patients. The cause-specific mortality rates also showed significantly increased SMRs for liver diseases and nephritis-nephrosis-nephrotic syndrome in male patients, and for nephritis-nephrosis-nephrotic syndrome and other diseases in females. On the other hand, the SMR for senility without mention of psychosis was significantly lower than expected in both sexes.

Methylmercury exposure and mortality in southern Japan: a close look at causes of death.

This study examines mortality patterns by cause of death to investigate the effect of exposure to methylmercury in a small area of Minamata City (Kumamoto Prefecture, Japan), which has the highest concentration of patients with Minamata disease. Standardised mortality ratios (SMRs) are computed by cause of death for the study area, using the age specific rates of the entire city as a standard. The SMRs for liver cancer and chronic liver disease in the study area are significantly higher than unity and are consistent with the mortality patterns of registered Minamata disease patients. While an excess mortality is observed for cerebral haemorrhage, mortality from cerebral infarction and other cerebrovascular diseases is considerably lower in the study area. The multiple risk factors of liver related diseases and a possible explanation for the cerebrovascular mortality patterns are discussed to suggest further investigation.

An epidemiological study with risk analysis of liver diseases in the general population living in a methyl mercury polluted area.

STUDY OBJECTIVE: The aim was to determine the actual prevalence of liver disease and to investigate the contribution of various risk factors to liver disease among the population in a methyl mercury polluted area. DESIGN: The study was a population based cross sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors for liver diseases. SETTING: The study was confined to a small rural town 10 km north of Minamata City. SUBJECTS: 1406 persons aged 50 to 69 years were examined (78.3% of the total population of this age in the locality). MEASUREMENTS AND MAIN RESULTS: Measurements of liver disease were made on the basis of haematological, physical, and ultrasonographic examinations. Data on liver risk factors were collected by questionnaire, and by measurement of body height, weight (obesity), and hepatitis B surface antigen (HBsAg). The prevalence rate of liver tumour was 0.5% in males, liver cirrhosis was found in 0.5% of males and 0.1% of females, and hepatitis was seen in 5.4% of males and 1.0% of females. Frequency rates of risk factors for liver disease among subjects with obesity were significantly higher in the female patient group, and the frequency rate among subjects with alcoholic drinking habits was significantly higher in the male patient group. The odds ratio of past history of blood transfusion showed the highest value among other related factors (7.73) and the attributable risk for this was very high (87.1%); HBsAg was next in rank (odds ratio 3.04; attributable risk 67.1%). CONCLUSIONS: The prevalence of liver disease in this methyl mercury polluted area was not increased, contrary to what was expected based on the standard mortality ratios. The main risk factors for liver disease in this area appear to be alcoholic drinking habits and a history of blood transfusion.

Follow-up studies on the distribution of haemoglobin levels in female farm workers.

Haemoglobin concentrations in about 1000 women agricultural workers in Japan were measured every year, except in 1972, during the period 1967-77. Improvements were noted in the course of this investigation, and these were predominantly associated with the fact that those in the study community began to pay attention to the problem of low haemoglobin levels and to improve their diet, with an increase in daily food intake, particularly of animal protein and iron. In addition, a marked decrease in anaemia caused by hookworm also played an important role. In this paper, the change in haemoglobin concentration during the period of study are described and the aetiology is discussed.

Noise-induced hearing loss in relation to vibration-induced white finger in chain-saw workers.

From the viewpoint of the etiologies of noise-induced permanent threshold shift (NIPTS) and vibration-induced white finger (VWF), the association between VWF and hearing loss was examined among 499 chain-saw workers who underwent a compulsory health examination for vibration syndrome. They were classified by age, duration of noise and vibration exposure, and the severity of VWF. The severity of VWF was evaluated according to the following criteria: no prior history; VWF history, but symptoms had disappeared; VWF present but appearing rarely; frequent appearance of VWF (more than 20 times per winter season). In three age groups (ie, 40-49, 50-59, 60-69 years) with 5-9 years of exposure, the chainsaw workers with VWF had a significantly greater hearing loss at higher frequencies than those without VWF. However, in the 10- to 14-year exposure groups, a significant difference was not found between the VWF and non-VWF groups, except that the 50- to 59-year age groups showed a significant difference in mean age. It was suggested that interindividual differences in susceptibility to noise and vibration may be the reason for the synergistic effects of noise and vibration.

Pathological changes observed in the finger biopsy of patients with vibration-induced white finger.

Lesion biopsies of 60 fingers from 30 patients with vibration-induced white finger (VWF) and control observations from seven fingers of five referents demonstrated three main characteristic pathological changes. First, in each case, the muscular layers of the arteries revealed intense thickening with strong hypertrophy of individual muscle cells without intimal fibrosis. Periarterial fibrosis was also noted. Arteriosclerosis with foamy cells, lipid deposition, and fibrous sclerosis was occasionally observed. The second main change was demyelinating neuropathy in the peripheral nerves in which a marked loss of nerve fibers had occurred. There was also an increase in the number of Schwann cells and fibroblasts with strong collagen formation. Severe loss of myelin sheath frequently occurred, and relatively smaller axons without myelin which appeared to have regenerated were observed. Perineural fibrosis was also noted. In the third main pathological change connective tissues with collagen were increased not only in the perivascular and perineural lesions, but also abundantly in the corium of the skin. The elastic fibers there had been destroyed. These three principal pathological changes are very useful for the histopathological diagnosis of VWF.

Vibration exposure and prevention in Japan.

Working conditions of vibration exposure have generally improved, but many difficult problems must be solved such as (1) hygienic improvements in a variety of vibrating tools; (2) improving working conditions, for example, by limiting the time of operation in spite of economic difficulties such as those faced by those who work on a piece rate basis; (3) gathering more complete information about the risk population because of the large number of self-employed in informal employment sectors; and (4) finding work places after rehabilitation for patients, particularly in mountainous rural areas or in small scale industries. Historical observation of vibration and preventive measures in Japanese national forests was presented on the basis of the results of a retrospective cohort study in Kyushu, Japan. Prevalence rate of VWF remarkably changed from 58.4% in the groups that began to operate chain saws in 1960 to only a few cases in the groups who started the operation after 1971. When we compare the relationships between the results of long term cohort study and the consequences of preventive measures of vibration syndrome, the most important factor is the decrease of vibration exposure (improvement in chain saws plus the time restriction system). The comprehensive prevention system used in Japanese national forests consists of the following: (1) Health care system; (2) Work regulation system; (3) System for improving mechanized tools; (4) Warming system to protect against cold conditions; and (5) Education and training system.

Vibration dose, disturbance stage, and examination results and subjective symptoms in vibration syndrome.

The 1973 national survey of 461 chainsaw operators in private forests was reexamined with respect to vibration exposure dose and the Stockholm Workshop Scale (CIRP and SN stages). Vibration dose (VD) was calculated by the formula "ahw(eq.4h) x D (days) x Y (years)". Vibration dose index (VDI) was calculated according to the level of VD. Subjects were divided into five VDI, for CIRP stage, and four SN stage groups. Examination results and prevalence of subjective symptoms were compared between VDI-1 and other VDI groups, CIRP-0 and other CIRP groups, and SN-0 and other SN groups. VD had higher values in CIRP-2 and 3, and SN-2 and 3 than CIRP-0 and SN-0, respectively. The most severe CIRP-3 and SN-3 appeared at higher rate in VDI-4 and 5 groups than in VDI-1 group. VDI had a correlation with mean value of prevalence of CIRP, vibrotactile perception, mean SN stage and fingertip pinch strength. A correlation was observed between skin temperature and CIRP stage, and between vibrotactile perception and SN stage. Decrease of muscle strength and difficulty in fine finger movement were associated with severe sensorineural disturbance.

Correlations among examination findings, subjective symptoms and classification of stages in vibration syndrome.

From data collected in 1966, 1973, 1986 and 1989, we analyzed the correlations among examination findings, subjective symptoms, stages in the disorder of vibration syndrome and vibration exposure. As vibration syndrome progressed and vibration exposure accumulated, abnormality of examination findings, the prevalence of vibration induced white finger (VWF), numbness (N) and other subjective symptoms increased. Abnormality of examination findings and prevalence of subjective symptoms in the VWF(+) N(+) group were greatly different from those in the VWF(-) N(-) group. Both findings and symptoms showed closer correlations with VWF(+) than with N(+). Stages in the disorder traced the progression from VWF(-)N(-) to VWF(-)N(+), then to VWF(+)N(+/-), and finally to VWF(+/++)N(+/++). Pathophysiologically, it seems that VWF(+) and N(+) relayed many more cold and pain signals from the hand to the central nervous system. Such signals may activate autonomic nervous activity. In the recovery, subjective symptoms correlated more closely with N(+) than with VWF(+). This is because VWF involves the autonomic nervous system's hyperactivity and hypersensitivity to cold, both of which subside gradually in the recovery; N, however, involves pathological changes in nerve tissue which are irreversible.

Evaluation of body composition using dual-energy X-ray absorptiometry, skinfold thickness and bioelectrical impedance analysis in Japanese female college students.

We compared three methods for evaluating body composition: dual-energy X-ray absorptiometry (DXA), skinfold thickness (Skinfolds), and bioelectrical impedance analysis (BIA). Subjects were 155 healthy young college-aged Japanese females whose mean+/-SD (range) age, body height, body weight and body mass index (BMI) were 20.1+/-0.3 (19.6-21.1) y, 158.9+/-4.7 (145.4-172.6) cm, 52.0+/-6.8 (39.4-84.6) kg and 20.6+/-2.3 (16.5-32.5), respectively. Their mean skinfold thickness at the triceps and subscapular were 16.9+/-4.7 (8.0-31.0) and 16.0+/-5.7 (7.0-40.0) mm, respectively. Mean body fat mass percentages evaluated by DXA, Skinfolds and BIA were 29.6+/-5.1, 22.8+/- 5.3 and 25.8+/-4.7%, respectively. Body fat mass was 15.4+/-4.4, 12.1+/-4.5 and 13.6+/-4.5 kg, respectively. Simple correlation coefficients between the three methods for body fat mass percentages provided the following coefficients: r=0.741 for DXA vs. Skinfolds, r=0.792 for DXA vs. BIA and r=0.781 for Skinfolds vs. BIA. Simple correlation coefficients for body fat mass were as follows: r=0.898 for DXA vs. Skinfolds, r=0.927 for DXA vs. BIA and r=0.910 for Skinfolds vs. BIA (all p<0.001). There were significant differences in the values among the three methods with the Skinfolds providing the lowest body fat mass and percentage, and DXA the highest (p<0.001). They all appear to be strongly correlated for evaluating body composition: however, different cut-off values for defining obese and lean need to be defined for each method.

Effect of dietary magnesium level on nephrocalcinosis and growth in rats.

We studied the extent of kidney calcification by varying dietary levels of Mg, based on pathological examinations and calcium (Ca) and magnesium (Mg) balance tests. AIN-76 diets containing varying levels of Mg--0.3 (-M), 1.3 (1/20M), 2.4 (1/10M), 9.2 (1/5M), 19 (control), 38 (2M), 102 (5M), and 187 (10M) mmol/kg diet--were fed to 3-week-old male Fischer-344 rats for 14d. Although the magnitude of abnormality was highest in kidney of rats fed the -M diet, the damage was normalized as the dietary level of Mg increased, with increasing serum Mg concentration and urinary excretion of Mg. We found almost no deposition of Ca in rats fed the 10M diet. The mechanism by which the high dietary Mg induces these effects most likely involves a competition between Mg and Ca for reabsorption in proximal and/or distal tubules, since these diets increased the urinary excretion of Ca. However, these high Mg diets decreased food intake and body weight gain compared with the control diet, although these indices were not decreased in rats fed the 2M diet. The results suggest that a dietary magnesium level approximately twice the normal level effectively reduces kidney calcification while maintaining normal growth in rats.

A multiple regression analysis of hemoglobin values and iron status in Japanese farmers.

The authors performed multiple regression analysis of hemoglobin values and the parameters related to iron dynamics. The subjects consisted of 37 farmers whose Hb, Ht, GB, SI, %-St, SFR and FEP was examined once a month for one year. 19.2% of the female farmers had anemia of which 73.8% was iron-deficiency anemia, 13.7% being latent iron deficiency. Hb, GB and FEP in males and SI, %-St, SFR, FEP in females revealed clear seasonal variations. Multiple correlation coefficient between Hb and SI, %-St, SFR, FEP as independent variables was significant in females but not in males, and the ratio of contribution (38.7%) was not very high, however, the multiple correlation coefficient was significantly high (0.622). Standard regression coefficients between Hb and SFR, FEP were significantly high (p less than 0.01). When Ht and GB were added to these 4 variables, multiple correlation coefficients (male, 0.906; female, 0.957) were remarkably high, which means serum-related variables such as Ht and GB have an undeniably important role as explanatory variables of hemoglobin levels. These standard regression coefficients showed seasonal changes.

An experimental study on changes in finger blood pressure during chain-saw operation.

In this study finger blood pressure was observed by using a new method to determine if vasoconstriction activated by sympathetic nervous system takes part in changes in peripheral circulation with exposure to vibration, noise and tool weight. Finger blood pressure was measured every one minute by ambulatory monitoring system. The time profile of a single experiment consisted of 5 minutes pre-exposure period followed by one exposure period lasting 2 minutes and a post exposure period of 5 minutes. Measurement was carried out as a factorial experiment of combination of vibration (17.8 m/s2 in X-axis, 20.0 m/s2 in Y-axis and 50 m/s2 in Z-axis), noise (105 dBA) and tool weight (7.9 kg). Finger blood pressure increased significantly under the following conditions: vibration + noise + tool weight > vibration + noise .=. vibration .=. tool weight > noise .=. control. During exposure period the combination with vibration, noise and finger grip exercise induced 29.7 mmHg of increases on average in finger blood pressure. On the other hand, finger blood pressure was increased 9.5 mmHg by vibration alone. These results agreed with our previous studies which observed the decreases of finger skin temperature and finger blood flow during the same conditions. The present study suggests that possible activation of the sympathetic nervous system may be involved in the physiological mechanisms of the changes in blood flow during chain-saw operation.

Validity of function tests on the upper extremities in establishing a prognosis in vibration syndrome.

The validity of function tests on the upper extremities as prognostic tools in vibration syndrome was evaluated over a sequence of observation periods. The subjects examined were 672 forest workers using chain saws who had had some complaints and who had shown abnormal findings in the function tests. The function tests consisted of peripheral circulatory and sensory tests, including cold provocation and motor tests of functional capacity in the upper extremities. From the results of testing, 23 variables were selected and examined by multivariate analysis. The four principal components were extracted by principal component analysis, and the factor score of the peripheral circulatory disturbances component was found to be highly correlated with the severity of VWF (Vibration-induced White Finger). The course of VWF and the nail compression test had high standard regression coefficients with the severity of vibration syndrome. The course of finger numbness, pinching power, pain threshold, skin temperature and X-ray findings in the elbow joints had high discriminant function values for the evaluation of the severity of vibration syndrome.

Whole-body vibration and health effects in the agricultural machinery drivers.

Recently farm mechanization has been widespread and developing rapidly, in particular riding farm machines are increasingly used in paddy fields in Japan. We have no information available on the actual situation regarding whole-body vibration on the seats of these farm machines from the standpoint of labour protection. Measurement and evaluation of whole-body vibration was performed on the seats of popular riding agricultural machineries. Whole-body vibration on the seats of combine harvesters and wheel tractors exceeded exposure limits and the fatigue-decreased proficiency boundary limit of 8 hr and also shortened the reduced comfort boundary limits of ISO 2631 (1985). Some combines, tractors and carieers had only less than one hour exposure duration as compared with the ISO 2631-1 standard (1997). On the other hand a questionnaire was also performed on the subject of agricultural machine operators. Any specific injury or other effects, i.e. low back injuries were not found among the group of operators as compared with those in non-operator farmers. It seems to be difficult to find out the health effects of whole-body vibration itself, because there may be a lot of causes, i.e. working posture, operating heavy materials, in farm working conditions.

Effect of cigarette smoking on prevalence of summer-type hypersensitivity pneumonitis caused by Trichosporon cutaneum.

We investigated the effect of cigarette smoking on the prevalence of summer-type hypersensitivity pneumonitis (SHP) caused by Trichosporon cutaneum. In the adult family members of SHP patients, we found that 27 of 41 (65.9%) nonsmokers were SHP patients, compared with 3 of 11 (27.3%) smokers (p less than .05). Also, the prevalence of anti-T. cutaneum antibody was significantly lower in the smokers (p less than .05). A questionnaire provided to 209 SHP patients revealed that the smoking rates of male and female SHP patients were significantly lower (p less than .01) than rates in the normal Japanese population. However, no difference was found in serum anti-T. cutaneum antibody activities or the bronchoalveolar lavage lymphocyte phenotypes for smoking and nonsmoking SHP patients. It was concluded that cigarette smoking had a suppressive effect on the outbreak of SHP, but smoking caused no further suppression after the disease was established.

Hand-arm vibration, noise, temperature and static load--an experimental study of peripheral circulation while operating chain-saws.

From the viewpoint of elucidating the etiological mechanism of vibration-induced white finger (VWF), a model experiment was designed using a chain-saw under laboratory conditions. Finger skin temperature and finger blood flow were measured simultaneously as indicators of peripheral circulatory movement, using a thermister and an apparatus for measuring tissue blood flow based on the thermal diffusion method. In the first project (Experiment A), five healthy subjects operated a chain-saw at a high working speed with-out actually cutting anything. In the second project (Experiment B), seven healthy subjects were exposed to three different kinds of experiments with combinations of hand-arm vibration, noise and tool weight at about 15 degrees C room temperature. In the third project (Experiment C), the effects of tool weight and grip force were examined. In the fourth project (Experiment D), patients suffering from vibration disease were exposed to hand-arm vibration and the noise of a chain-saw for 2 minutes. In experiment A, the mean value of the normalized finger skin temperature decreased gradually with cyclic changes corresponding to each exposure and break period. Changes in finger blood flow had almost the same pattern as the changes of skin temperature, but the recovery of blood flow during a 30 sec break period was notable and a slight elevation of the base line was observed. In experiment B, the mean value for the normalized finger skin temperature decreased much more when the subjects operated a chain-saw at a high working speed than when they operated the chain-saw with the noise isolated by double hearing protection. On the other hand, the results obtained in experiment C indicated that the effect of tool weight should be considered as an important factor for investigating the acute changes in peripheral circulation. In experiment D, some patients showed an unusual pattern in the change of blood flow during a post exposure period which was not seen in healthy subjects.

Vibration exposure dose dependency of clinical stage, examination results and symptoms in vibration syndrome.

The vibration exposure dose dependency of clinical stage, examination results and symptoms are valuable for evaluation of exposure effect in vibration syndrome. The 1973 national survey of 461 chain saw operators in private forests was reexamined with respect to vibration exposure dose (VD) and clinical stage (Stockholm Workshop scales: CIRP-0 to 3 and SN-0 to 3 stages). VD was calculated by the formula "ahw(eq.4h) x D (days) x Y (years)". Vibration exposure dose index (VDI) was calculated according to the VD level. Subjects were divided into five VDI, four CIRP stage and four SN stage groups, respectively. Ratio of four CIRP and SN in VDI, examination results and prevalences of symptoms were compared between VDI-1 and the other VDI groups. Vibration dose dependency was observed in Stockholm Workshop scales (CIRP and SN stage) and examination results (prevalence of CIRP, vibrotactile perception threshold, prevalence of numbness in hands, and fingertip pinch strength). Higher VDI (VDI-5) was associated with higher prevalence of hypersensitivity to cold, muscle weakness and deterioration of finger function. Which formula is more useful to evaluate cumulative vibration effects is still controversial.

Hand-arm vibration in tropical rain forestry workers.

Working conditions and health hazards including vibration syndrome related to forestry work using chain-saws were studied in Papua New Guinea and Indonesia. The subjects comprised 291 workers including 97 chain-saw operators. The health examination consisted of peripheral circulatory and sensory tests in the upper extremities. The vibration spectrum measured at the handle of the chain-saw indicated that these acceleration levels would lead to a moderately high risk of hand-arm vibration syndrome (HAVS). The peripheral circulatory function tests revealed dysfunction after more than five years vibration exposure. However, in general, the results of the function tests and subjective complaints showed fewer health problems compared to those of Japanese forestry workers. The reason of such differences of vibration effects seem to be the following: (1) warmer climate (more than 25 degrees C throughout the year), (2) young workers and short work experience. (3) short time vibration exposures on working days in the natural forests, (4) seasonal changes in logging work (5) healthy workers effects. Thus, we found no clear evidence that the workers of our study suffered from HAVS. A principal component analysis was applied. The factor score of the components of the reactive dynamics of peripheral circulation differed significantly after more than five years' exposure. On the other hand, we cannot deny the possibility that subclinical dysfunction of peripheral circulation may be caused by chain-saw operation in the tropics in future. Further investigations on the HAVS among forestry workers in the tropic environment are needed.

[Difference by sex and age of mercury concentration in red blood cells].

The mercury concentration in red blood cells (RBCs) is one of the most useful indicators for people exposed to methylmercury. Sex- and age-related differences in mercury concentrations in red blood cells were studied by considering fish consumption in 1,253 adults (511 males and 742 females) participating in a mass health examination conducted in a town of Kumamoto Prefecture in 1989. The results were as follows: 1. The mercury concentrations in RBCs showed lognormal distributions for both sexes with a higher mode in males than in females. The geometric mean of the mercury concentrations in the RBCs was 28.5 ng/g (ranging from 5.6 to 71.0 ng/g) for males and 20.4 ng/g (ranging from 3.7 to 70.4 ng/g) for females and was significantly higher in males than in females. The mercury concentration in RBCs decreased with aging for both sexes. 2. The mercury concentrations in RBCs significantly increased with the amount of fish consumption for both sexes. The mercury concentrations in RBCs were significantly higher in drinkers than in non-drinkers for males and the concentrations increased significantly with body weight for females. 3. The mercury concentrations in RBCs were higher in males than in females and decreased with aging for both sexes under conditions of a constant level of fish consumption. 4. In couples who consumed same amount of fish, the mercury concentrations in RBCs were significantly higher in husbands than in wives. These results suggest that the mercury concentrations in RBCs are higher in males than in females and decreases with aging under a constant level of fish consumption.