International Cooperative Study Research Articles

生態圏核種移行モデルの妥当性検証 ＢＩＯＭＯＶＳ計画の成果と展望

An international cooperative study named BIOMOVS has been carried out from 1986 under the auspices of the Swedish National Institute of Radiation Protection. The objective of this study is to validate models for estimating the transfer and bioaccumulation of radionuclides and stable trace substances in the biosphere. The Japan Atomic Energy Research Institute has participated in the study from the beginning. This report describes test scenarios and results for Phase I which was performed until 1990. The report also introduces suggested themes and prospects for Phase II started in 1992.

Use of calibrants in food colour measurement: An international cooperative study

AbstractThe agreement between a number of laboratories and instrument types (tristimulus colorimeters, spectrophotometers) in the measurement of colours distributed around a central point in colour space was studied. The improvement gained by calibration against the central colour as opposed to calibration against a white standard is quantified and its variation with distance from the centroid is shown. In this way the limits of applicability of the so‐called hitching post procedure are defined.

The value of indirect immunofluorescence and solid phase techniques for ANCA detection: A report on the first phase of an international cooperative study on the standardization of ANCA assays

This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies.

Nutrition and cancer: general considerations.

With the International Cooperative Study on the Epidemiology of Coronary Heart Disease (more commonly known as the Seven Countries Study) we examined sixteen “chunk” samples of men aged 40 to 59, resident for more than five years in each area.

The Concept of Regime `Effectiveness'

Two major questions in the study of international cooperation are: (i) Under which conditions is some kind of cooperative arrangement likely to be established? (ii) Under which conditions will the arrangement established be effective? Arguing that good reasons can be given for shifting some of our research efforts from the former to the latter question, and that a fair amount of conceptual groundwork remains to be done in order that regime `effectiveness' can be systematically studied, the author briefly examines three questions: (i) What precisely is the object to be evaluated? (ii) Against which standard is this object to be evaluated? And, (iii) what kinds of measurement operations do we have to perform in order to attribute a certain score of `effectiveness' to a certain arrangement?

International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group.

1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.

The International Cooperative Study on the Timing of Aneurysm Surgery. The North American experience.

The timing of aneurysm surgery after subarachnoid hemorrhage is a major neurosurgical controversy addressed by the International Cooperative Study on the Timing of Aneurysm Surgery (1980-1983). The present report examines the results of this trial in the subgroup of patients admitted to North American centers. The method of study was a large, multicenter, prospective, epidemiological survey. Neurosurgeons were required to indicate prospectively the interval to planned aneurysm surgery at the time of patient admission. Outcome at 6 months was determined by a blinded evaluator, and overall management results were analyzed by the planned surgical interval. Seven hundred seventy-two (21.9% of the total study population) patients admitted from days 0 to 3 after subarachnoid hemorrhage were accrued in North American centers. Overall outcome in patients planned for surgery in days 0-3 was equivalent in terms of mortality (after adjustment for prognostic variables) to patients planned for days 11-32, but the early patients had significantly improved rates of good recovery (70.9% versus 61.7%, p less than 0.01). Patients planned for surgery during the days 7-10 interval had nearly twice the mortality of patients in the other intervals. In contrast to the results from the overall trial, which found no difference between early and delayed surgery, results were best in North American centers when surgery was planned between days 0 and 3 after subarachnoid hemorrhage. These findings argue strongly for early diagnosis and referral for surgical intervention of North American patients suspected of having a ruptured cerebral aneurysm.

Findings of the International Cooperative INTERSALT Study.

INTERSALT, an international cooperative study on electrolytes and other factors related to blood pressure, found, in within-population analyses involving 10,079 persons, a significant positive association between 24-hour urinary sodium excretion and systolic blood pressure and between the sodium/potassium ratio and systolic blood pressure. These significant findings were derived from analyses for individuals from all 52 centers and from the 48 centers remaining when persons from four low sodium centers were excluded. Potassium excretion of individuals was significantly and independently related inversely to their systolic blood pressure. For men and women, both separate and combined, the relation between sodium and systolic blood pressure was stronger for older than younger adults, perhaps reflecting the result of longer exposure with age or diminished capacity to handle a sodium load. Relations between electrolyte excretion and diastolic blood pressure in individuals were weaker than for systolic blood pressure. Body mass index and heavy alcohol consumption of individuals were strongly and independently related to blood pressure. In cross-population analyses with n = 52 or n = 48, sample median sodium excretion was significantly and independently related to the slope of systolic blood pressure and diastolic blood pressure with age. Other ecological analyses yielded inconsistent results. Four isolated populations showed low sodium excretion, low sodium/potassium excretion, low body mass index, and low alcohol consumption; sample median blood pressures were low, there was little or no upward slope of blood pressure with age, and high blood pressure was rare or nonexistent.

Performance of Assessment Models for Estimating the Transfer of Mercury in a Lake Ecosystem.

The performances of assessment models for estimating the transfer and bioaccumulation of mercury in a lake ecosystem were tested by being applied to a test scenario proposed in an international cooperative study named BIOMOVS. Two kinds of models have been developed to estimate mercury concentration in fish. One uses a bioaccumulation factor approach which is applied to an ecosystem in equilibrium, whereas the other is a dynamic model in which both the change of the concentration in water and the metabolism in fish are taken into account. For this scenario, the former was not adequate but the latter could predict more accurately because the concentrations were not in equilibrium. The limitations of applications were suggested for the two models employed here. It would be important in the present case to take into account that equilibrium was not attained in the ecosystem and the metabolism of mercury in the fish was very slow.

Phototoxic properties of perfumes containing bergamot oil on human skin: Photoprotective effect of UVA and UVB sunscreens

As part of an international cooperative study of the photophysical, photomutagenic and photocarcinogenic properties of bergamot oil and the effect of UVA and UVB sunscreens, the phototoxic properties of model perfumes containing 5, 15 and 50 ppm 5-methoxypsoralen (5-MOP) in bergamot oil with and without a suncreen have been investigated on human skin. It has been confirmed that the photosensitivity of human skin is maximal 2 h after perfume application. Interestingly the addition of a UVA sunscreen is more efficient for decreasing the phototoxic properties of bergamot oil than is a UVB suncreen. The addition of sunscreens in a model perfume containing 50 ppm 5-MOP in bergamot oil can reduce the phototoxic properties of this perfume to a toxicity equivalent to that produced by the application of a model perfume containing 15 ppm 5-MOP without sunscreens. However, despite their promising protective effect in vitro, UVB and UVA sunscreens at low concentration (0.5%–1%) in perfumes cannot suppress the phototoxicity of bergamot oil on human skin

Effect of multiple dosing of phenacetin on micronucleus induction: A supplement to the International and Japanese cooperative studies

Effect of multiple dosing of phenacetin on micronucleus induction: A supplement to the International and Japanese cooperative studies

The International Cooperative Study on the Timing of Aneurysm Surgery

A prospective, observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms. Sixty-eight centers contributed 3521 patients in a 2 1/2-year period beginning in December, 1980. Analysis by a prespecified "planned" surgery interval demonstrated that there was no difference in early (0 to 3 days after the bleed) or late surgery (11 to 14 days). Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval. Surgical results were better for patients operated on after 10 days. Patients alert on admission fared best; however, alert patients had a mortality rate of 10% to 12% when undergoing surgery prior to Day 11 compared with 3% to 5% when surgery was performed after Day 10. Patients drowsy on admission had a 21% to 25% mortality rate when operated on up to Day 11 and 7% to 10% with surgery thereafter. Overall, early surgery was neither more hazardous nor beneficial than delayed surgery. The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery.

The International Cooperative Studyon the Timing of Aneurysm Surgery

✓ The International Cooperative Study on the Timing of Aneurysm Surgery evaluated the results of surgical and medical management in 3521 patients between December, 1980, and July, 1983. At admission, 75% of patients were in good neurological condition and surgery was performed in 83%. At the 6-month evaluation, 26% of the patients had died and 58% exhibited a complete recovery. Vasospasm and rebleeding were the leading causes of morbidity and mortality in addition to the initial bleed. Predictors for mortality included the patient's decreased level of consciousness and increased age, thickness of the subarachnoid hemorrhage clot on computerized tomography, elevated blood pressure, preexisting medical illnesses, and basilar aneurysms. The results presented here document the status of management in the 1980's.

Effects of multiple dosing of phenacetin in the micronucleus test

As a part of the international cooperative study to identify the most sensitive regimen in the micronucleus test, phenacetin was given i.p. to male CD-1 mice at doses of 37.5, 75, 150, 300, 400, and 600 mg/kg once, twice, thrice or four times and the bone marrow cells were harvested 24 h after the final dosing. Positive responses were seen at 600 mg/kg after single and triple dosing and at 400 and 600 mg/kg after double dosing. No dose level gave a positive response after quadruple dosing. A repeated-dosing effect was detected at double and triple dosing. Although triple dosing gave the highest magnitude of micronuclei at 600 mg/kg, double dosing showed a sufficient sensitivity and was more convenient from the viewpoint of selecting a suitable test dose and carrying out the micronucleus test.

Antifíbrsnolytic Therapy and Cerebral Vasospasm

The role of antifibrinolytic drugs in the management of patients with aneurysmal subarachnoid hemorrhage continues to remain uncertain. Recent controlled studies suggest that although these agents may alter the course of the illness, they confer no benefit in terms of overall outcome. Confronted with these data, clinicians in North America have radically altered their management of patients with ruptured aneurysms in the last decade. In the Timing of Surgery Study (1980-1983), 54% of patients were treated with antifibrinolytic drugs and only 32% underwent surgical clipping of the aneurysm on days 0-3 from the subarachnoid hemorrhage. In contrast, only 13% of the patients in the Randomized Trial of Nicardipine in Subarachnoid Hemorrhage (1987-1989) received antifibrinolytics, whereas 53% had early surgery (unpublished observations). Further study will be required to determine if this strategy has resulted in an improvement in overall outcome. Some observers have suggested that as effective therapy for symptomatic vasospasm evolves (e.g., with hypertensive or hypervolemic therapy or calcium antagonists), the adverse effects of antifibrinolytic drugs on brain ischemia may be ameliorated. This idea must be confirmed by further evaluation of the combined use of these treatments. In the interim, antifibrinolytic drugs, if used at all, should be used with caution, and their use should be restricted to those patients judged not to be candidates for early surgery. If therapy cannot be started before day 7 after subarachnoid hemorrhage, it should not be started at all, as the reduced rate of rebleeding after the first 7 days does not justify the increased risk of brain ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug use in pregnancy: a preliminary report of the international co-operative drug utilization study

In a field, such as drug use in pregnancy, where knowledge is often based on scanty information, and systematic permanent surveillance is needed, so as to avoid reliance on data obtained in widely differing contexts, an international co-operative network was set up, using a cheap and standardized interview technique. The study, originally European, can now be considered 'intercontinental', as the twenty-five countries where data is already being collected represent four of the five continents. Thirteen participating countries have already returned about ten thousand completed forms. Fifteen per cent of the 9714 enrolled women took no drugs at any state of pregnancy, while each taker received an average of 2.6 (range 1-13) prescriptions. Intracountry and intercountry differences were found in prescribing habits and in other characteristics of the population. Although the large amount of data collected is still being processed, preliminary findings indicate that this study seems to have been warranted.

International Cooperative Study on the Relationship Between Dietary Factors and Blood Pressure

To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the International Cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 45 centers in 20 countries. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, and blood test. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. In within-center multiple regression analyses, body mass index (BMI) was strongly positively and independently associated with BP. Urine magnesium (Mg) excretion was negatively and independently associated with BP. In cross-center simple regression analyses, systolic and diastolic BP showed significant correlations with BMI (p less than 0.01) and 24-h urinary sodium (Na) excretion (p less than 0.005) in men and significant inverse correlations with urinary 3-methylhistidine (3-MH) divided by creatinine (p less than 0.01 and p less than 0.005, respectively) in men, and were inversely correlated with urinary Mg in women (p less than 0.05). Therefore, Na and BMI adversely affect BP, whereas animal protein and Mg intakes may have beneficial influence on BP.

International Cooperative Study on the Relationship Between Dietary Factors and Blood Pressure

International Cooperative Study on the Relationship Between Dietary Factors and Blood Pressure

Predictive and Preventive Pathology of Cardiovascular Diseases

The development of genetic models for research on hypertension and stroke, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), have contributed not only to the elucidation of the pathogenesis of hypertension-related cardiovascular diseases (CVD) but also to their prediction and prevention. Since both genetic and environmental factors are involved in the pathogenesis of hypertension and stroke in SHR and SHRSP, the detection of the genetic factors and the control of environmental factors have been proven to be useful as predictive and preventive measures against hypertension and related CVD. Early rise in blood pressure, sympathetic overresponsiveness, early development of cardiovascular hypertrophy, increased salt-sensitivity and membrane abnormalities detected in vascular smooth muscle cells (VSMC) from SHR and SHRSP, which are related to the pathogenesis of hypertension, have been examined for their applicability to the prediction of hypertension in man. Pathogenic mechanisms of stroke in SHRSP have been studied by electron microscopy, and VSMC degeneration and necrosis were noted to start at the outer media of intracerebral arteries which were exposed to local hypoxia and hyponutrition due to limited diffusion through the blood-brain barrier. Macrophages are involved in the process of arterionecrosis with fibrin deposition in SHRSP, and their involvement has also been proven immunohistochemically in human autopsy cases. Moreover, reduction of regional cerebral blood flow, hypoxic vulnerability of the brain detected by the NMR technique and additional cellular abnormalities such as membrane fragility and accelerated lipid incorporation may possibly be applied to the prediction of stroke and atherosclerotic diseases in man. On the other hand, experimental control of cellular, neural and vascular mechanisms of hypertension and stroke in these animal models have been proven to be effective for the prevention of CVD not only pharmacologically but also non-pharmacologically by dietary sodium reduction, and increased intake of potassium, calcium, protein and dietary fiber. The applicability of dietary control of hypertension and stroke to humans has been supported by our epidemiological studies in Japan as well as by the WHO-coordinated international cooperative study on cardiovascular diseases and alimentary comparison (WHO CARDIAC study). These new experimental and epidemiological findings are extending new horizons in medicine, where the main medical activity should be focused on the prediction of diseases by detecting genetic disposition as well as on prevention by the control of environmental factors.

Cerebral Revascularization: A Review

A review of the development and current methods of surgical revascularization of the cerebral circulation is presented. In addition to the conventional superficial temporal artery to middle cerebral artery (STA-MCA) bypass, the techniques of interposition vein grafting and vertebrobasilar revascularization are discussed. The results and implications of the International Cooperative Study are reviewed. Extracranial-intracranial (EC-IC) bypass grafting remains an essential procedure in the treatment of many cerebrovascular conditions, including Moya Moya disease and giant intracranial aneurysms. The efficacy of interposition vein grafts, as well as the EC-IC bypass in the treatment of vertebrobasilar insufficiency, acute cerebral ischemia, cerebral vasospasm, and multi-infarct dementia, remains to be determined. Several alternative revascularization procedures, including proximal MCA anastomosis and omental transposition, are in development.