Possible cause of unnatural mass death of wild birds in a pond in Nishinomiya, Japan: sudden appearance of toxic cyanobacteria.

During the summer of 1995, about 20 spot-billed ducks died unnaturally in a pond (Shin-ike) in Nishinomiya, Hyogo Prefecture, Japan. The suspected cause was the sudden appearance of toxic freshwater bloom of cyanobacteria. However, no birds died in a nearby pond (Oo-ike) in which the cyanobacteria was also present. Morphological observation of these cyanobacteria by microscope revealed that they were almost unialgal and were both Microcystis aeruginosa. The lyophilized algal cell powder from Shin-ike contained large amounts of microcystins which showed acute toxicity for mouse, while that from Oo-ike had only a very small amount of microcystin-RR which did not show acute toxicity. Autopsy of one of the birds revealed that the liver was necrotic and severely jaundiced with a dark green color, suggesting the toxicity of the microcystins. These results point to the cause of the unnatural death of spot-billed ducks in Shin-ike as being the sudden appearance of toxic Microcystis aeruginosa. This was due to eutrophication of the pond, following the influx of untreated sewage related to damage from the Great Hanshinn Earthquake of January 1995. This is the first experimental report of toxic cyanobacteria being implicated in the mass death of wild birds in Japan.

Plasma insulin and blood pressure in normotensive Japanese men with normal glucose tolerance.

OBJECTIVE: To determine whether blood pressure within the normal range is associated with plasma insulin concentration in a Japanese population with normal glucose tolerance. METHODS: We studied 491 normotensive Japanese men with normal glucose tolerance, who had never been treated with antihypertensive medications. Plasma glucose and insulin response during a 75-g oral glucose-tolerance test, blood pressure, body mass index, serum lipids, alcohol consumption and smoking status were obtained. The subjects were divided into quartiles according to mean blood pressure level (< 79, 79-84, 85-91 and > or = 92 mmHg). To eliminate possible confounding factors, analysis of covariance was also performed. RESULTS: In univariate analyses the plasma insulin response after an oral glucose load, especially after 60 min, was significantly related to blood pressure level. Plasma glucose was related to blood pressure level only at fasting. When adjusted for age, body mass index, plasma glucose response and alcohol consumption, plasma insulin concentrations after 30 and 60 min in the highest quartile were significantly higher than those in the lowest quartile. CONCLUSIONS: Blood pressure was significantly and independently related to plasma insulin level after an oral glucose load in normotensive Japanese men with normal glucose tolerance. The results suggest that the relationship between blood pressure and insulin resistance already exists in a prehypertensive state even in a lean Asian population.

Mortality of inhabitants in an area polluted by cadmium: 15 year follow up.

OBJECTIVE: To assess the influence of environmental exposure to cadmium (Cd) on long term outcome of inhabitants living in an area polluted by Cd. METHODS: A follow up study for 15 years (from 1974-5 to 1991) was carried out on 2408 inhabitants (amounting to 95% of the target population, 1079 men and 1329 women) of the Kakehashi River basin in Ishikawa Prefecture, Japan. These inhabitants had been the subjects of the health impact survey in 1974-5 to evaluate (by measurement of urinary retinol binding protein (RBP)) renal dysfunction induced by Cd. Analysis of mortality was performed by dividing subjects into a urinary RBP positive (> or = 4 mg/l) group and RBP negative (< 4 mg/l) group. RESULTS: After adjustment for age with Cox's proportional hazard model, RBP > or = 4 mg/l showed a significant relation to mortality in both sexes. At this time, the mortality risk ratio of the RBP positive to negative group was 1.71 in the men and 1.42 in the women. When the SMRs according to causes of deaths in the RBP positive group were compared with those of the RBP negative group or the overall Japanese population increases of SMR for cardiovascular diseases, especially heart failure, and renal diseases were found in both sexes. CONCLUSION: These results suggest that the prognosis of the exposed inhabitants with renal tubular dysfunction is unfavourable, and these increases of mortality are due to heart failure and renal diseases.

[A study of thyroid hormone levels of inhabitants of the cadmium-polluted Kakehashi River basin].

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.

Prognostic factors of renal dysfunction induced by environmental cadmium pollution.

To assess the influence of environmental cadmium (Cd) exposure on long-term outcome, a follow-up study was conducted from 1981-1982 to March 1991 on 3178 inhabitants living in the Cd-polluted Kakehashi River basin. The standardized mortality ratios of the urinary beta 2-microglobulin (beta 2-MG)-, protein-, and amino acid-positive subjects of both sexes and the urinary glucose-positive female subjects were higher than those of the subjects with urinary-negative findings or the general Japanese population during the observation period. After adjusting for age using Cox's proportional hazards model, significant associations were found between mortality and urinary indices. In multiple comparisons using all of the indices, urinary protein and beta 2-MG in the women and urinary protein in the men were the factors most contributing to the mortality rates. In the urinary protein-negative female group as well, a significant association was found between urinary beta 2-MG and mortality. These results suggest that the prognosis of subjects with Cd-induced renal dysfunction is unfavorable, with the mortality rate increasing even in the early stage of proximal tubular dysfunction. Urinary protein and urinary beta 2-MG are important prognostic factors, with the latter, in particular, considered to be useful as an early index predictive of premature mortality.

Potassium/energy and phosphorus/calcium ratios reflect the quality of nutrition.

A nutritional survey and questionnaire regarding dietary habits were administered to 649 men ranging in age from 35 to 64 years receiving a one-day health screening examination. First, comparisons of nutrient intake based on the nutrient rate of the Recommended Dietary Allowances for Japanese (RDA), and the total score on the questionnaire regarding dietary habits according to the RDA rates of total energy and calcium (Ca) were investigated. Then, the comparisons of intake of food groups, intake of nutrients and the total score on the questionnaire regarding dietary habits according to potassium/energy (K/E) ratio and phosphorus/calcium (P/Ca) ratio were determined. Last, differences between comparisons with the nutrient rates of RDA and comparisons with K/E ratio and P/Ca ratio were investigated. The following results were obtained: 1. Even in the group with RDA rates of total energy or Ca of > or = 90% and < or = 110% the RDA rates of some other nutrients were out-side the appropriate range. 2. In the group with high K/E ratios, as compared to the group with low ratios, the intake of potatoes, pulses, fruits, green/yellow vegetables, other vegetables, soy sauce, other beverages, fish/shellfish, and milk products showed high values, while cereals and fats/oils showed low values. For this reason, in the former group as compared to the latter, the intake and RDA total energy rate showed low values whereas the intake and RDA rates of nutrients such as Ca, Fe, and vitamin A were low. 3. In the group with high P/Ca ratios, as compared to the group with low ratios, the intake of beer and meats showed high values while that of pulses, green/yellow vegetables, and milk products showed low values. For this reason, in the former group as compared to the other groups, despite the fact that the intake and RDA total energy rate tended to be higher, the intake of nutrients such as Ca, P, K, and vitamin A showed lower values. 4. The RDA rates of all of the nutrients of group with a high K/E ratio and the group with a low P/Ca ratio generally showed largely appropriate values. 5. These results suggest that indices reflecting the balance of minerals such as the K/E and P/Ca ratios more objectively reflect the quality of nutrition than comparisons based on the RDA rates of total energy and specific-nutrient.

Urinary beta 2-microglobulin concentration and mortality in a cadmium-polluted area.

A 9-y follow-up study of 3,178 persons who lived in a cadmium-polluted area was conducted to assess the influence of environmental cadmium exposure on long-term outcome. The standardized mortality ratios of the urinary beta 2-microglobulin-positive subjects (> 1,000 micrograms/g creatinine) of both sexes were higher than those of the general Japanese population, whereas the cumulative survival curves were lower than those of the urinary beta 2-microglobulin-negative group. A significant association was also found between urinary beta 2-microglobulin and mortality, using a Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary beta 2-microglobulin excreted. These results suggest that the prognosis for cadmium-exposed subjects with proximal tubular dysfunction is unfavorable. The mortality rate tended to become higher as the severity of renal dysfunction progressed.

[Study of an outbreak of itai-itai disease].

We studied an outbreak of itai-itai disease in the Jinzu River basin, in Toyama, Japan. One hundred and fifty females recognized as itai-itai disease patients till by 1990 were studied for the ages and years of onset and residence in the cadmium-polluted area. 1. Cases were recognized from as early as 1929, increased gradually to the peak of 1955-1959 and rapidly decreased up to the 1970s. 2. It was found that the later the patients was born, the younger the age of onset, though there was no difference of ages of onset between the cases born in the 1910s and the cases born from 1920. 3. The onset of itai-itai disease was most frequently seen at 50-59 years of residence in the cadmium-polluted area. It was found that the later a person started to inhabit the cadmium-polluted area, the shorter the period of residence in the cadmium-polluted area up to onset of itai-itai disease. 4. Comparing the patients who inhabited the cadmium-polluted area from birth and those who had moved there from non-polluted areas, the age of onset was higher in the latter, but there were no significant differences in the period of residence up to onset. From these findings, it appeared that itai-itai disease was not caused by aging, but by cadmium exposure starting from the 1910s.

[[Comparison of mortality rates of elderly people in China and Japan]].

"The mortality rates and causes of death among elderly people aged sixty five and over were compared between China and Japan. The data used for comparison was China's 1990 and Japan's 1990 vital statistics. It appears that the mortality rate in China was higher than Japan. Comparing the causes of death, it was found that the death rates involving cerebrovascular diseases, malignant neoplasms and heart diseases in urban districts of China [were] higher than those in Japan. Also the death rate of people with bronchitis in rural districts was significantly higher in China.... The differences in the medical systems and life styles in China and Japan were suspected as the reasons for the differences of death rates and causes of death...." (SUMMARY IN ENG)

High mortality and shortened life-span in patients with itai-itai disease and subjects with suspected disease.

A follow-up study was conducted from 1967 to 1987 for patients diagnosed as having itai-itai disease, subjects who were suspected of having the disease, and controls. Ninety-five subjects per category were selected after matching for age, sex, and residential area. The cumulative survival rate of the patients who had a definite diagnosis of itai-itai disease was significantly lower than that of the control group in every period after the first 3 y. The cumulative survival rate of the subjects who were suspected of having itai-itai disease and who had severe renal dysfunction due to cadmium pollution was significantly lower than that of the control group. These results demonstrate (1) the enduring negative influence of itai-itai disease on prognosis and (2) that the cadmium pollution-induced renal disorder adversely affects the health of the inhabitants of a cadmium-polluted area.

[A study on the survival rates for patients and suspected patients with Itai-itai disease].

A follow-up study was carried out from January 1967 to December 1986 on 148 patients with Itai-itai disease, 130 suspected patients (persons requiring observation), and 212 controls who were living in the same community as patients with Itai-itai disease. The relative survival rates for the three groups were calculated from a life expectancy table. Except for 1973 data, comparison of the annual data from 1968 to 1986 showed that the relative survival rates in the patient group were significantly lower than those in the control group. The relative survival rates in the suspected patient group were significantly lower than those in the control group between 1981 and 1986. Recently the differences of the relative survival rates between the patient group and the suspected patient group have become smaller and are not significant. These results show the long-lasting influence of Itai-itai disease on the prognoses of patients and suspected patients.

Studies on the cutaneous sensitization reaction of guinea pigs to purified aromatic chemicals.

The sensitization reactions to purified cinnamic aldehyde and its chemically related substances were investigated using the maximization test on guinea pigs. Mutual cross-sensitivities were also examined. Cinnamic aldehyde was found to be the most potent sensitizer in this series, and a strong cross-sensitizer. From the chemical structures of these substances, the following speculations were made. There was a tendency that as the number of hydrocarbons of alkyl groups replacing the alpha-hydrogen in the molecule increased, the rate of sensitization reaction declined. The conjugated system of double bonds was suspected to be a determinant factor in relation to the sensitization ability of the substances in this series.