Sub-100 W picosecond output from a phase-conjugate Nd:YVO4 bounce amplifier.

We demonstrated >80 W picosecond output at a pulse repetition frequency of 100 MHz from a dual Nd:YVO(4) amplifier laser system consisting of a phase-conjugate Nd:YVO(4) bounce amplifier combined with a second diode-side-pumped Nd:YVO(4) bounce amplifier. The output exhibited high quality spatial form with M(2) < 1.8 and a pulse duration (FWHM) of 9.2 ps. A peak power of >7.4 MW with an average power of 78.5 W was also achieved at a pulse repetition frequency of 1.0 MHz.

Serum level of advanced glycation end-products (AGEs) is an independent determinant of plasminogen activator inhibitor-1 (PAI-1) in nondiabetic general population.

Glucose can react nonenzymatically with amino groups of proteins to form senescent macroprotein derivatives termed advanced glycation end-products (AGEs). Recently, AGEs have been shown to play an important role in atherosclerosis even in nondiabetic subjects. However, the molecular mechanism underlying this is not fully understood. We have now investigated whether serum AGE level was an independent determinant of plasminogen activator inhibitor-1 (PAI-1), a major physiological inhibitor of fibrinolysis, in nondiabetic general population. One-hundred and eighty-six nondiabetic Japanese subjects underwent a complete history and physical examination, determination of blood chemistries, PAI-1, and AGEs. Uni- and multivariate analyses were applied for the determinants of PAI-1 levels. The average PAI-1 levels were 29.7+/-23.8 ng/ml in males and 21.8+/-17.1 ng/ml in females, respectively. Univariate regression analysis showed that PAI-1 levels were associated with age (inversely, p=0.003), male (p=0.003), body mass index (BMI) (p<0.001), HDL-cholesterol (inversely, p<0.001), triglycerides (p<0.001), fasting plasma glucose (p<0.001), insulin (p<0.001), uric acids (p<0.001), AGEs (p=0.037), and alcohol intake (p<0.001). By the use of multiple regression analyses, BMI (p<0.001), male (p=0.003), fasting plasma glucose (p=0.005), age (inversely, p=0.017), and AGEs (p=0.034) remained significant. The present study is the first demonstration that serum AGE level was one of the independent determinants of PAI-1 in nondiabetic general population. The AGE-associated thrombogenic abnormality may be involved in atherogenesis in nondiabetic subjects.

Reproducibility of urinary cadmium, alpha1-microglobulin, and beta2-microglobulin levels in health screening of the general population.

The present study examined whether levels of cadmium, and alphal- and beta2-microglobulin in urine (Cd-U, ac-MG-U, and beta2-MG-U, respectively) were reproducible in urine samples collected from the same subjects on multiple occasions. For this purpose, two databases on background exposure to cadmium in Japan-one from study I between 2000 and 2001 and the other from study II in 2002-were revisited to find 231 apparently healthy, nonpregnant, nonlactating adult women who participated in both studies and thus had provided two urine samples. The databases contained information on Cd-U, alphal,-MG-U, and beta2-MG-U, creatinine (CR), and specific gravity (SG) as well as smoking and other lifestyle factors. Of the 231 women, 195 who had never smoked were selected for the present analysis. Cd-U as well as alpha1-MG-U were reproducible (e.g., with correlation coefficients [r] between study I and II results of 0.4 to 0.6) when measured on two occasions 9 to 10 months apart. The r values were lower for beta2-MG-U (r0.3). Exclusion of urine samples with inadequate urine density(i.e., CR <0.5 or >3.0 g/L or SG <1.010 or >1.030) resulted in substantial improvement of the agreements between the two measures (e.g., r = 0.6 to 0.7 for Cd-U and alpha1-MG-U). CR and SG correlated closely with each other, especially in low-density urine samples (r >0.9), and therefore the effects of CR and SG could not be evaluated separately. In the overall evaluation,single determination (i.e., without repeated urine sampling) of Cd-U and alpha1-MG-U should be acceptable, and it may also be acceptable for beta2-MG-U. Use of samples with adequate urine density rather than application of density correction to low-density urine samples in recommended.

No effects of hematuria and proteinuria in school days, and probably current pregnancy and current lactation also, as risk factors of cadmium-induced renal tubular dysfunction among adult women in general populations in Japan.

This study was initiated to examine if hematuria and proteinuria in school days, current pregnancy, or current lactation are risk factors of cadmium-induced tubular dysfunction for adult women among general populations in Japan. For this purpose, a database of 9,967 never-smoking adult women were reviewed for urinary levels of cadmium (Cd) and three other elements, calcium (Ca), magnesium (Mg), and zinc (Zn), and two tubular dysfunction markers of alpha1-microglobulin (alpha1-MG) and beta2-microglobulin (beta2-MG); the analyte concentrations were corrected for creatinine (cr) and expressed as, e.g., Cd-Ucr. From the total, 160 cases were selected as those who were informed of urinary abnormality (i.e., proteinuria, hematuria, or both) in their school days (the abnormality being found to be transient, later), and each case was matched by age and prefecture of residence. Separately, seven women with persistent urinary abnormality, seven pregnant women, and six lactating women were identified, and the case was matched with three cases each of the same age and living in the same prefecture. Statistical analyses showed that Cd-Ucr and other markers were not elevated in the transient urinary abnormality group as compared with the matched controls. This was also observed in the subjects with persistent abnormality. In the pregnant women, alpha1-MG-Ucr and possibly beta2-MG-Ucr were elevated, but Cd-Ucr did not increase, suggesting that the observed elevation in alpha1-MG and beta2-MG was not due to the effects of Cd but a part of the physiology of pregnancy itself. There was no change in marker levels in lactating women except for an increase in alpha1-MG. In overall evaluation, it was considered prudent to conclude that urinary abnormality in school days does not increase the risk of Cd-induced nephrotoxicity in adult women, whereas the negative findings with pregnancy and lactation should be taken as preliminary because the numbers of cases studied were limited.

alpha1-Microglobulin as a promising marker of cadmium-induced tubular dysfunction, possibly better than beta2-microglobulin.

The purpose of the present study was to evaluate the validity of alpha1-microglobulin (alpha1-MG) in comparison with popularly used beta2-microglobulin (beta2-MG). A database on 8975 cases of never-smoking adult women was revisited; the data were based on spot urine samples from the women in 10 prefectures all over Japan. The validity of alpha1-MG was examined following essentially the same protocol as beta2-MG was examined in a previous study. Comparisons were made for alpha1-MG as observed (e.g. alpha1-MG(ob)), as corrected for creatinine (CR or cr) (e.g. alpha1-MGcr) and as corrected for a specific gravity (SG or sg) of 1.016 (e.g. alpha1-MGsg). A cut-off value of 5.0 mg alpha1-MG/g cr or l was deduced from 400 microg beta2-MG/g cr taking advantage of the regression equation between alpha1-MG and beta2-MG. The prevalence of alph1-microglobulinuria as corrected for a specific gravity of 1.016 (or alpha1-MGsg-uria in short) was essentially unchanged irrespective of SG, except for in very dense or very thin urine samples. alpha1-MGcr-uria prevalence decreased at higher CR. Comparison of the present observation with previous findings on beta2-MG-uria prevalence showed that the variation in prevalence of MG-uria as a function of urine density was smaller for alpha1-MGsg whereas it was substantially larger for beta2-MGcr, and thus it appeared prudent to consider alpha1-MGsg rather than beta2-MGcr as a marker of tubular dysfunction.

Critical evaluation of alpha1- and beta2-microglobulins in urine as markers of cadmium-induced tubular dysfunction.

The purpose of the study was to examine the validity of alpha1-microglobulin (alpha1-MG) in comparison with popularly used beta2-microglobulin (beta2-MG). A database was revisited to select ca. 7,500 spot urine samples (of adequate urine density) from non-pregnant, non-lactating and never-smoking adult women. The validity of the MGs was examined in terms of stability of the MG-uria prevalence in urine samples of various creatinine (CR or cr) concentration or specific gravity (SG or sg). Comparisons were made for MGs as observed (e.g., alpha1-MGob), as corrected for CR (e.g., alpha1-MGcr) and as corrected for SG of 1.016 (e.g., alpha1-MGsg). A cut-off value of 5.7 mg/g cr (or mg/l) for alpha1-MG was deduced from a cut-off value of 400 microg/g cr (or mcirog/l) for beta2-MG, because the correlation between alpha1-MGcr and beta2-MGcr was statistically significant. The prevalence of a 1-MGsg-uria was essentially unchanged (i.e., from a low of 13.6% to a high of 17.0%, or 1.2 times) except for in very dense or very thin urine samples, in contrast, beta2-MGcr-uria showed a substantial increase (from 0.0% to 2.8% with an infinite rate) as a reverse function of a decrease in CR in urine. The prevalence of uncorrected markers, i.e., alpha1-MGob-uria and beta2-MGob-uria, showed even greater CR- or SG-dependent changes. Thus, it appeared prudent to consider a alpha-MGsg rather than beta2-MGcr as a marker of tubular dysfunction among a general population with various urine density.

Bias induced by the use of creatinine-corrected values in evaluation of beta2-microgloblin levels.

The present study was initiated to examine if the correction for creatinine (CR or cr) is the best approach among the three methods of correction for CR, correction for a specific gravity (SG or sg) and the use of observed values in managing difference in urine density. For this purpose, a database previously developed on 10,753 adult women in 10 non-polluted areas in Japan was re-visited for information on age, urinary levels of Cd, Mg, Ca, Zn, beta(2)-MG, and creatinine, and urine specific gravity as well as smoking habits. Never-smoking women with various urine density counted 8975 cases (the various urine density group). From these cases, 7081 cases with adequate urine density (i.e. 0.5 g/l < or = CR < or = 3.0 g/l and 1.010 < or = SG < or = 1.030) were selected (the adequate urine density group). When a beta(2)-MG level of 400 microg/g CR or 400 microg/l was taken as a cut-off value for beta(2)-MG-uria, both the prevalence of beta(2)-MG(cr)-uria [i.e. cases with beta(2)-MG (as corrected for CR) in excess of 400 microg/g cr] and that of beta(2)-MG(sg)-uria increased as a function of the decrease in Cd(cr) or Cd(sg). The prevalence of beta(2)-MG(ob)-uria also varied as a function of CR and SG, especially of CR, but its range of variation was smaller than the corresponding changes in beta(2)-MG(cr)-uria prevalence. A noteworthy advantage for the use of observed values over that of SG-corrected values was the minimum effect of age. In over-all evaluation, therefore, the recommended approach appeared to be the use of non-corrected observed values (after selection of urine samples for adequate urine density if desired) or correction for SG, rather than correction for CR.

Comparative evaluation of four urinary tubular dysfunction markers, with special references to the effects of aging and correction for creatinine concentration.

Comparative evaluation was made on alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG), as a marker of renal tubular dysfunction after environmental exposure to cadmium (Cd), with special references to the effects of aging and correction for creatinine concentration. For this purpose, a previously established database of 817 never-smoking Japanese women (at the ages of 20 to 74 years) on hematological [hemoglobin, serum ferritin (FE), etc.] and urinary parameters [alpha(1)-MG, beta(2)-MG, creatinine (cr), and a specific gravity] was revisited. For the present analysis, the database was supplemented by the data on RBP and NAG in urine. The exposure of the women to Cd was such that the geometric mean Cd in urine was 1.3 microg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by alpha(1)-MG and then beta(2)-MG, and RBP was least so although the correlations were all statistically significant. The observed values of the markers gave the best results, whereas correction for a urine specific gravity gave poorer correlation, and it was the worst when correction for creatinine concentration was applied. Age was the most influential confounding factor. The effect of age appeared to be attributable at least in part to the fact that both creatinine and, to a lesser extent, the specific gravity decreased as a function of age. Iron deficiency anemia of sub-clinical degree as observed among the women did not affect any of the four tubular dysfunction markers. In conclusion, NAG and alpha(1)-MG, rather beta(2)-MG or RBP, are more sensitive to detect Cd-induced tubular dysfunction in mass screening. The use of uncorrected observed values of the markers rather than traditional creatinine-corrected values is recommended when comparison covers people of a wide range of ages.

Analysis for threshold levels of cadmium in urine that induce tubular dysfunction among women in non-polluted areas in Japan.

OBJECTIVE: To examine if there is a threshold in urinary cadmium concentration that induces elevation in urinary microglobulins. METHODS: The database developed in a previous field survey (Ezaki et al. 2002) was employed. In the survey conducted in 2000 and 2001, more than 10,000 middle-aged women (with no occupational exposure to Cd) in ten prefectures all over Japan gave morning spot urine samples, which were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U), and creatinine (cr). The urinary analyte concentrations were corrected for cr concentration (to be expressed as, e.g., Cd-Ucr), and the data thus obtained were subjected to statistical evaluation. The largest geometric mean (GM) for Cd-Ucr among the ten prefecture was 3.2 microg Cd/g cr, and the maximum Cd-Ucr observed among the women studied was 20.9 microg Cd/g cr. RESULTS: Both alpha(1)-MG-Ucr and beta(2)-MG-Ucr increased as a function of the increase in Cd-Ucr among all the women and also in sub-populations of narrow age ranges (i.e., 41-50 and 51-60 years), with no apparent threshold Cd-Ucr. Comparison of the cases exceeding cut-off alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels also indicated a Cd dose-dependent increase in the prevalence, similarly without a threshold Cd-Ucr. In addition, such findings were essentially reproducible when elevation in alpha(1)-MG-Ucr and beta(2)-MG-Ucr levels was examined with the three essential elements, especially with Ca-Ucr and Mg-Ucr, although less clearly with Zn-Ucr. The observations as a whole suggest a possibility that the dose-dependent increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr with no apparent threshold for element concentration is not specific to Cd-Ucr but common to other elements. CONCLUSIONS: No threshold Cd-Ucr was detected in relation to the increases in alpha(1)-MG-Ucr and beta(2)-MG-Ucr. The element dose-dependent increases in the two MGs with no threshold in the element concentration might be not limited to Cd, but common to other elements. Further studies are apparently necessary.

No clear-cut evidence for cadmium-induced renal tubular dysfunction among over 10,000 women in the Japanese general population: a nationwide large-scale survey.

OBJECTIVE: To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan. METHODS: This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, alpha(1)-MG-Ucr and beta(2)-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr. RESULTS: Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 microg/g cr, the highest (3.2 microg/g cr) and lowest GM values(0.8 microg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41-50 and 51-60 years), however, failed to show close correlation of alpha(1)-MG-Ucr and log beta(2)-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log alpha(1)-MG-Ucr (but not on log beta(2)-MG-Ucr) in LRA when a cut-off value of 5.00 mg for alpha(1)-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both alpha(1)-MG-Ucr and beta(2)-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with alpha(1)-MG-Ucr and beta(2)-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for alpha(1)-MG-U. CONCLUSIONS: In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in alpha(1)-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd.

No significant effect of iron deficiency on cadmium body burden or kidney dysfunction among women in the general population in Japan.

OBJECTIVE: To examine if iron-deficient conditions modify body burden or health effects of cadmium among women in the general population in Japan. METHODS: In 2002, 1,482 women aged 20 to 74 years in six prefectures in Japan provided informed consent to participate in this study. They offered peripheral blood and spot urine samples, and answered questionnaires on their social habits and health conditions. Never-smoking, non-pregnant and non-lactating healthy women (1,190 subjects) were selected from the volunteers. Blood samples were analyzed for serum iron, ferritin and total iron-binding capacity (TIBC) in addition to red blood cell (RBC) counts and hemoglobin (Hb) concentration as markers of anemia and iron deficiency. Urine samples were analyzed for cadmium (Cd), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG) as markers of Cd burden and Cd-induced tubular dysfunction; the measures were expressed after being corrected for creatinine (cr) as, e.g., Cd-Ucr. RESULTS: The subjects were classified into anemic (37 women) and iron-deficient (388 women) groups separately from healthy controls (765 women), taking ferritin (<20 ng/ml) and Hb (<10 g/100 ml) as classification indicators. Strictly matched pairs (with regard to age and prefecture) were established for 36 anemic and 280 iron-deficient cases. Comparison between the cases and the matched controls showed that serum iron was lower and TIBC was higher in accordance with lower levels of ferritin and Hb in the anemic and iron-deficient groups, although the RBC count was only slightly reduced (the anemic group) or stayed essentially unchanged (the iron-deficient group). In contrast, no significant increase in Cd-Ucr, alpha(1)-MG, or beta(2)-MG was observed in either the anemic group or the iron-deficient group compared with the matched controls. Cd-Ucr in one case of clinical anemia, however, tended to be higher than the levels among women of the same age range and from the same prefecture. Her alpha(1)-MG-Ucr and beta(2)-MG-Ucr, however, remained un-elevated. CONCLUSIONS: The current level of iron deficiency among women in the general population in Japan may not induce significant increase in Cd body burden or Cd-induced tubular dysfunction.

Threshold levels of urinary cadmium in relation to increases in urinary beta2-microglobulin among general Japanese populations.

Through literature survey, paired data on cadmium (Cd) and beta(2)-microglobulin (beta(2)-MG) levels (as corrected for creatinine concentration) in urine (i.e., Cd-Ucr and beta(2)-MG-Ucr) among Japanese populations were available for 32 groups of men and 58 groups of women in 12 publications. Plotting of the Cd-Ucr and beta(2)-MG-Ucr data for the groups of women showed that beta(2)-MG-Ucr stayed unchanged when Cd-Ucr was at lower levels, whereas beta(2)-MG-Ucr increased sharply when Cd-Ucr was in excess of 10-20 microg/g cr. Regression analysis was made for groups of women with no elevation in beta(2)-MG-Ucr, and those with >400 or >1000 microg beta(2)-MG-U/g cr. A threshold Cd-Ucr level in relation to an increase in beta(2)-MG-Ucr was estimated as Cd-Ucr at the point of intercept of the two regression lines, one with no beta(2)-MG-Ucr elevation, and the other with >400 or >1000 microg beta(2)-MG-U/g cr. Cd-Ucr at the point of flexion thus calculated was 11-12 microg/g cr. Such observation was quantitatively reproduced by the analysis of data for men, giving 10-11 microg Cd-U/g cr at the point of flexion. This study suggests that the relationship of beta(2)-MG-Ucr with Cd-Ucr is not linear but in the shape of letter 'J', i.e., beta(2)-MG-Ucr increases sharply when Cd-Ucr is in excess of 10-12 microg/g cr.

Monitoring of occupational exposure to tetrachloroethene by analysis for unmetabolized tetrachloroethene in blood and urine in comparison with urinalysis for trichloroacetic acid.

OBJECTIVE: The present study was initiated to examine a quantitative relationship between tetrachloroethene (TETRA) in blood and urine with TETRA in air, and to compare TETRA in blood or urine with trichloroacetic acid (TCA) in urine as exposure markers. METHODS: In total, 44 workers (exposed to TETRA during automated, continuous cloth-degreasing operations), and ten non-exposed subjects volunteered to participate in the study. The exposure to vapor was monitored by diffusive sampling. The amounts of TETRA and TCA in end-of-shift blood and urine samples were measured by either head-space gas chromatography (HS-GC) or automated methylation followed by HS-GC. The correlation was examined by regression analysis. RESULTS: The maximum time-weighted average (TWA) concentration for TETRA-exposure was 46 ppm. Regression analysis for correlation of TETRA in blood, TETRA in urine and TCA in urine, with TETRA in air, showed that the coefficient was largest for the correlation between TETRA in air and TETRA in blood. The TETRA in blood, in urine and in air correlated mutually, whereas TCA in urine correlated more closely with TETRA in blood than with TETRA in urine. The TCA values determined by colorimetry and by the GC method were very similar. The biological marker levels at a hypothetical exposure of 25 ppm TETRA were substantially higher in the present study than were the levels reported in the literature. Possible reasons are discussed. CONCLUSIONS: Blood TETRA is the best marker of occupational exposure to TETRA, being superior to the traditional marker, urinary TCA.

Blood lead level to induce significant increase in urinary delta-aminolevulinic acid level among lead-exposed workers: a statistical approach.

The present study was initiated to examine the quantitative relationship between blood lead (Pb-B) and urinary delta-aminolevulinic acid (ALA-U) among Pb-exposed workers, and to find a threshold Pb-B level to induce an increase in ALA-U. For this purpose, pairs of venous blood and spot urine samples were collected from 8,274 men and 5,856 women (14,130 workers in total) who were occupationally exposed to inorganic lead. The blood and urine samples were analyzed for Pb-B and ALA-U by atomic absorption spectrometry and colorimetry, respectively, and the correlation between pairs of measures were subjected to statistical analysis. The assumption of the 3rd degree regression for correlation gave a substantially greater correlation coefficient (0.645 for men and 0.619 for women) than 1st or 2nd degree regression, whereas only very small improvement in the coefficient was achieved with 4th to 6th degree ones. Logarithmic conversion of the parameters was not effective in improving the correlation. The assumption of the 3rd degree regression followed by calculation of the local minimum gave 22, 29 and 23 micrograms/100 ml Pb-B for men, women, and men + women, respectively, as the threshold Pb-B to induce ALA-U increase. Pb-B to elevate ALA-U to the 95% upper normal limit (8 mg/l, common to men and women) was 62, 50 and 58 micrograms/100 ml for men, women and men + women, respectively. The validity of the 3rd degree regression assumption as a tool to calculate a threshold from experimental or epidemiological data is discussed.

Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis.

OBJECTIVES: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. METHODS: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. RESULTS: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35-40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. CONCLUSIONS: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm.

[The practical theory of occupational health planning: Part One--The theoretical background of the target population setting and needs assessment procedures (OPST research report 2)].

The OPSS is an 8 stage program which was developed as a practical tool for occupational health services planning. This paper examines the theoretical aspects of the first two stages. The OPSS is a planning tool with a theoretical grounding in OHP (The practical theory of Occupational Health Planning). The target population setting has two functions. The first is to establish the physician's first-hypothesis to design a program. The other is deciding the group which has an occupational health problem in a company. The Needs Assessment helps to clarify the physician's hypothesis, which may be weak due to the limited knowledge of various demands of the employees and senior management. On the other hand, the risks and needs vary according to what kind of expert looks at a situation. To date, occupational physicians have been limited to their medical background in determining only risks and needs. However, understanding the various stakeholders in a particular environment means that any project will be more relevant to all concerned. Another limitation of the occupational physicians hypothesis can be the lack of objective data to support it. This makes it difficult to persuade senior management to sign on to a program. The Needs Assessment procedure with OHQ steps is useful in a number of ways. The Observation step allows for finding risks and needs from various situations in the company from the occupational physician's viewpoint (prehypothesis setting). Hearing is for understanding the subject's demands and finding common themes in the company (final hypothesis setting). Finally, the questionnaire step is for providing objectivity of these common themes and quantitative data for the next Priority Setting procedure. The BITOP (Budget, Information, Time, Order, key Person) has been proposed as a way to diagnose the structural and functional aspects of an organization's procedures. Budget tracks the financial flow through the organization, while Information identifies key information sources. Time helps to understand the reaction speeds of a company against environmental changes in the business community. Order looks at the flow of information from senior management through strategic gatekeepers. Understanding this flow helps the occupational physician to identify specific issues at various levels of the organization. Finally, key Person looks at the flow of information up through the organization, and identifies which key executives the occupational physician needs cooperation from in order for the project to be approved and successful. The above two procedures are essential tasks for insuring that an occupational physician can effectively implement a project that identifies what is necessary for the company and what the company wants to do, and works effectively within the organizational structure.

[The practical theory of occupational health planning: Part Two--The theoretical background from the priority setting procedure to the post project appraisal making procedure (OPST research report 3)].

This report focuses on the final six procedures of the 8-stage OPSS. The first two procedures were covered in an earlier report. This paper examines the theoretical underpinnings of these six procedures. In the Priority Setting procedure, three factors are compared (TCP; Time/timing, cost, and population) for the OPSS in the general community, and also those in industry. These sometimes differ, especially with respect to responsibility and implementation. TCP allows the appropriate factors to be considered for a more objective prioritization of the various factors. As discussed earlier, the first TCP is used for prioritizing occupational health problems through the Needs assessment procedure. The second TCP prioritizes the countermeasures of those problems selected in the first TCP. In the Program Design procedure, we discuss the MIO (Merit, Impact, Outcome). Merit is defined as the effectiveness of a program as viewed by the company, taking into account the managerial and social merits. Impact refers to the behavioral effectiveness and behavioral change from the viewpoint of the program designer. Outcome refers to the effectiveness of the program from the traditional medical and epidemiological view-point. The study goes on to discuss the relationship amongst participation level, program development, and the subject's compliance, as a means to ensure that subjects participate indirectly through both steps of OHQ. In the Presentation procedure, we summarize the flow of effective presentations in the company setting. This covers initial understanding of the target audience wants, together with what the planner wants to focus on. In this way common issues and themes can be developed. Further assistance is given with strategy formation, presentation aids, time category presentations, evaluation and feedback. In the Process and Final Evaluation procedures, we discuss the objectives, and their significance to the overall process. In the Post Project Appraisal Making procedures, the previous three procedures are strongly affected by each proceeding procedure. In OPSS, we did not include the program development step in the Program Design procedure because the development skills can be referred from behavioral sciences methodologies. In the final part of this paper, we discuss the merits of the underlying theories of behavioral sciences, which have potential to apply to the occupational health settings.

[Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis].

A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of HTLV-I sequence in cord blood mononuclear cells of neonates born to HTLV-I antigen/antibody-positive mothers by polymerase chain reaction.

We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV-I) provirus in cord blood mononuclear cells of neonates born to HTLV-I carrier mothers. Out of 40, three subjects were found to contain the HTLV-I provirus genome. These three subjects remained HTLV-I sequence-positive in follow-up study. On the other hand, when examined by a conventional technique for detection of HTLV-I-associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV-I-associated antigen-negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV-I infection in neonates born to HTLV-I carriers.

[Detection of HTLV-I genome in infants born to HTLV-I seropositive mothers by polymerase chain reaction].

We developed a new method to detect human T cell leukemia virus type I (HTLV-I) provirus by amplifying the pX region of the HTLV-I genome by means of the polymerase chain reaction (PCR) method. This new method was used to examine babies delivered by HTLV-I carrier women for HTLV-I vertical transmission. It was found that intra-uterine infection with HTLV-I can occur, though rarely, and some babies carry HTLV-I provirus despite their negative response to HTLV-I antibody, and, noticeably, some of the babies found negative by the conventional antigen detection method may be positive when tested by the PCR method. It was also confirmed with the PCR method that the incidence of vertical transmission of HTLV-I can be reduced to about 1/5 by replacing breast feeding with bottle feeding and frozen mother's milk feeding. It was also found that vertical transmission of HTLV-I can occur at high incidence rates even when the duration of breast feeding is 3 months or less.