A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.

Cost-Effectiveness Analysis of the Diagnosis and Treatment of Primary Aldosteronism in Japan.

Approximately 10% of cases of hypertension in Japan are caused by primary aldosteronism (PA), amounting to about 4 million patients in total. Primary aldosteronism due to unilateral aldosterone hypersecretion is potentially curable by adrenalectomy. The clinical benefits of identifying and treating PA have been reported internationally, but its cost-effectiveness is unclear. We examined whether diagnosing and treating hidden PA in hypertensive population was cost-effective compared with suboptimal treatment. Our hypothetical patient was a 50-year-old man diagnosed with stage I-III hypertension. We established a Markov decision model based on plausible clinical pathways and prognoses of PA. We applied cost-effectiveness analysis comparing a comprehensive diagnostic strategy for PA (measurement of plasma aldosterone/renin ratio, 2 loading tests, imaging, and selective adrenal venous sampling) with a suboptimal strategy to manage hypertension by medication unless the typical signs of PA or other complication were manifest. Outcome measures were expected costs, expected effectiveness, and incremental cost-effectiveness ratio. The robustness of the findings was established by one-way and scenario sensitivity analyses. The comprehensive PA diagnostic strategy increased the expected costs by 64 004 JPY and expected life-years by 0.013 compared with standard treatment. The incremental cost-effectiveness ratio for the diagnosis of PA was 4 923 385 JPY per year. Our findings were sensitive to the outcomes of screening and treatment, and the costs of continuous or periodic medication for hypertension and the treatment of stroke and its complications.

Upper-extremity Musculoskeletal Disorders in Keyboard Operators in Brazil: A Cross-sectional Study.

This study sought to determine the prevalence of upper-extremity musculoskeletal disorders (UEMSDs) among keyboard operators in Sao Paulo, Brazil, and to compare this prevalence with that among other office workers. One hundred and thirty keyboard operators (mean age 33 years, 60 male/70 female) and 138 office workers (mean age 35 years, 82 male/56 female) from two computing centers were interviewed by a research assistant using a standardized questionnaire. Symptomatic subjects, defined as those who reported upper extremity pain or lost work time due to pain in the preceding 12 months, were examined by a rheumatologist. Mean (SD) lengths of employment were 9 (6) years for keyboard operators and 8 (6) years for office workers. Upper-extremity pain during the preceding seven days was reported by 66 keyboard operators (51%) and by 18 office workers (13%) (p < 0.0001); during the preceding 12 months, by 90 keyboard operators (69%) and by 26 office workers (19%) (p < 0.0001). UEMSDs were diagnosed following physical examination in 50 keyboard operators and in 12 office workers (9%) (p < 0.0001). Tenosynovitis was the most common disorder diagnosed among the keyboard operators (n = 23). Among the keyboard operators the prevalence of UEMSDs was significantly lower for males (p = 0.017, OR = 0.38, 95%CI = 0.17-0.86). The presence of a diagnosed UEMSD was significantly associated with duration of employment (p = 0.005) and lack of or insufficient rest breaks (p = 0.012). Keyboard operators had significantly more UEMSDs than did office workers. Strategies aimed at the reduction of repetitive strain injuries among keyboard operators, such as the provision of adequate work breaks, should be evaluated.

Urinary Phenylglyoxylic Acid Excretion after Exposure to Ethylbenzene among Solvent-exposed Chinese Workers.

Factory surveys were conducted in the second half of work weeks on 360 solvent workers (202 men and 158 women) and 281 controls in China. Monitoring personal exposures showed that ethylbenzene exposure was low (geometric mean 1.8 ppm) and was accompanied by coexposure to toluene (1.5 ppm) and three xylene isomers (6.7 ppm). Urine samples collected at the end of the eight-hour shift were analyzed for phenylglyoxylic and mandelic acids by high-pressure liquid chromatography at 257 nm. Despite the low level of the exposures, a significant correlation was observed between ethylbenzene exposure and urinary phenylglyoxylic acid, with high (0.6-0.7) correlation coefficients, suggesting that urinary phenylglyoxylic acid is a good marker of occupational exposure to ethylbenzene. Mandelic acid also correlated with ethylbenzene exposure, but with much smaller coefficients (0.2), possibly because the method employed was more sensitive to phenylglyoxylic acid than to mandelic acid.

Subtle increase in leukocyte counts in association with drinking and smoking habits.

Peripheral leukocyte counts were examined in venous blood of more than 800 male workers exposed to toluene, xylenes, a combination of the two, or neither. Information on the social habits of smoking and drinking was obtained in an occupational health interview. The analysis showed that smoking (15 cigarettes/day on average) induced a significant increase (by 7%) in leukocyte counts, and that an additional increase was induced when the drinking habit was coupled with smoking. Drinking alone tended to increase the leukocyte counts but the effect was statistically nonsignificant, possibly because the number of nondrinking smokers was limited. The study stresses the importance of paying attention to smoking and drinking habits when evaluating hematological parameters such as peripheral leukocyte counts in solvent-exposed workers.

Effects of smoking and drinking habits on urinary o-cresol excretion after occupational exposure to toluene vapor among Chinese workers.

The relationship between the time-weighted average intensity of exposure to toluene and o-cresol concentration in shift-end urine was investigated in nearly 500 factory workers of both sexes in China, together with a similar number of nonexposed control subjects. Toluene concentration (25 ppm as geometric mean and 550 ppm as the maximum) was monitored by diffusive sampling using carbon cloth as adsorbent followed by gas chromatographic (GC) analysis. o-Cresol (up to 7 mg/l) was measured by GC after acid hydrolysis of samples. Urinary o-cresol levels correlated significantly (r = 0.69-0.77; p < 0.01) with toluene exposure in men, women and the two sexes in combination, regardless of correction for urine density. When compared with hippuric acid, however, o-cresol was less sensitive as an indicator of exposure to toluene and is not a suitable biological marker for detecting low level toluene exposure. Since urinary o-cresol level was significantly reduced by smoking, drinking, and the two habits combined, it cannot be considered reliable as an indicator of exposure to toluene.

Absence of mutagenicity in peripheral lymphocytes of workers occupationally exposed to methyl methacrylate.

Chromosome aberration rates and sister chromatid exchange frequency were examined in the peripheral lymphocytes of 38 male workers who were engaged in organic glass production and exposed to methyl methacrylate (MMA) vapors at the concentrations of 0.9 ppm to 71.9 ppm. The results were compared with the findings in the concurrent nonexposed male subjects. Comparison of the exposed group with the nonexposed controls showed that there were no exposure-related changes in chromosome aberration rate. SCE frequency was higher in the exposed group than in the controls, but this was considered to be due to higher ages of the former group than that of the latter. In fact, selection of nonsmokers and further classification of the exposed nonsmokers into two groups of those with exposure below and above a median MMA concentration (ca. 4 ppm) failed to show any difference among the three nonsmoking groups in cytogenetic parameters, or any dose-dependency. The present results, although in a limited number of subjects, indicate that occupational methyl methacrylate exposure under the conditions studied is not associated with mutagenicity. This conclusion confirms the absence of mutagenicity of methyl methacrylate in humans, and is in general agreement with a majority of the results of studies on mutagenicity in vitro, animal carcinogenicity and occupational cancer epidemiology of methyl methacrylate.

Exposure monitoring and health effect studies of workers occupationally exposed to cyclohexane vapor.

A survey was conducted in the second half of a working week on 33 women who either applied glue (with cyclohexane as an almost exclusive solvent component) or worked in the vicinity of glue application. Carbon cloth-equipped diffusive samplers were used for personal measurement of time-weighted average intensity of exposure to the solvent. The geometric mean and the highest cyclohexane concentration observed in air were 27 ppm and 274 ppm, respectively. Concentrations of cyclohexanol in urine samples and cyclohexane in whole blood and serum collected at the end of a shift showed significant correlations with the solvent exposure levels. Urinary cyclohexanone also correlated, but with a smaller correlation coefficient. The observation suggests that cyclohexanol in urine and cyclohexane in blood or serum collected at the end of a shift are useful indicators of occupational exposure to cyclohexane vapor. Quantitative estimation of balance at the end of the shift suggested that only a minute portion (< 1%) of cyclohexane absorbed is excreted in the urine as cyclohexanol, almost exclusively as a glucuronide. A survey of subjective symptoms revealed an increase in the prevalence of "dimmed vision " and "unusual smell", but hematology and serum biochemistry testing did not indicate any specific signs.

Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers.

In order to investigate possible effects of smoking and drinking on the metabolism of toluene in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift-end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to toluene. There was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits.

Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene.

The correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers.

Increase in sister chromatid exchange rates in association with occupational exposure to N,N-dimethylformamide.

The effects of occupational exposure to N,N-dimethylformamide (DMF) on sister chromatid exchange (SCE) rates were studied in peripheral lymphocytes from 22 DMF-exposed women (aged 22-52 years) in comparison with 22 sex-, age-, and residence-matched controls. All subjects were nonsmokers and nondrinkers as confirmed by medical interview. The 22 pairs were divided by the intensity of exposure to DMF into 3 subgroups of high-exposed (8 pairs with mean DMF exposure at 5.8 ppm), middle-exposed (5 pairs with DMF at 0.7 ppm in combination with toluene at 0.9 ppm), and low-exposed (9 pairs with DMF at 0.3 ppm). The SCE rates were significantly higher in the high (P less than 0.005) and middle (P less than 0.01) exposed than in their matched pairs, and the increase was related to the intensity of DMF exposure.

Subjective symptom increase among dry-cleaning workers exposed to tetrachloroethylene vapor.

Subjective symptoms, hematology, serum biochemistry and other clinical signs were investigated in 56 dry-cleaning workers exposed to tetrachloroethylene at 20 ppm (as a geometric mean of 8-hr time-weighted average), and the results were compared with the findings in 69 non-exposed controls from the same factories. There were exposure-related increases in the prevalence of subjective symptoms during the work as well as in the past 3 month period, whereas there was no significant changes in hematology. Effects of the exposure on liver and kidney functions were also negative as judged by emission enzyme activities, BUN and creatinine in the serum.

Hepatitis B virus prevalence in industrialized cities in China.

The prevalence of HBV infection was investigated by radioimmunoassay for HBsAg, anti-HBs and anti-HBc in over 1000 workers in large scale factories located in four industrial cities (Jinxi, Shanghai, Wuxi and Xian) in 1987 to 1990. The age dependency of the prevalence was not evident. The overall prevalence rate of those positive for any of the three markers was 62.6%. The rate was significantly (p < 0.01) higher than the rates found in Beijing in a previous study but lower than the values observed in earlier studies.

Prevalence of hepatitis B virus infection markers among factory workers in Beijing, China.

Nearly 1,000 serum samples were obtained from apparently healthy workers of both sexes in various factories in Beijing during 1988-1989 and were examined for hepatitis B virus infection markers by radioimmunoassay. The overall prevalence (all ages and both sexes combined) of cases positive for HBsAg, anti-HBs and anti-HBc were 3.7%, 36.6% and 37.7%, respectively and the rate of those negative to any of the three markers studied was 56.1%. The infection rate was lower than the values reported early in the 1980s for Beijing populations or the values for populations in other parts of China.

Sister chromatid exchanges in peripheral lymphocytes of workers exposed to benzene, trichloroethylene, or tetrachloroethylene, with reference to smoking habits.

The frequencies of sister chromatid exchanges (SCE) were studied in peripheral lymphocytes from four groups of solvent workers, i.e. 36 nonsmoking women exposed to benzene at about 50 ppm on the average, 38 men and women (male smokers and nonsmokers, and female nonsmokers) exposed to trichloroethylene (TRI) at 7 ppm, 27 men and women (both smokers and non-smokers) with tetrachloroethylene (TETRA) exposure, and 19 workers (both smokers and nonsmokers in men, and nonsmokers in women) exposed to a mixture of TRI (at 8 ppm) and TETRA (at 17 ppm) (TRI + TETRA). The results were compared with the findings in control subjects matched by age, sex, smoking habits and place of residence. No significant increase in SCE frequencies was observed in association with exposure to benzene, TRI, TETRA or TRI + TETRA. The SCE frequency was, however, significantly higher in the TRI-, TETRA- or TRI + TETRA-exposed smoking men than in the concurrent nonsmoking controls of the same sex. Possible synergism between solvent exposure and smoking is discussed.

Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene.

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.

Blood cadmium levels in the populations of 3 Chinese cities.

Blood samples were collected from male and female factory workers aged greater than or equal to 16 years (with no occupational exposure to metals including cadmium) in the 3 cities of Hefei (323 subjects), Shenyang (78 subjects), and Jinxi (137 subjects) in China from 1985 to 1987. The samples were analyzed for cadmium in a single laboratory by automated flameless atomic absorption spectrophotometry under strict quality control. The effect of smoking was evident in Hefei, Shenyang and Jinxi, while the effect of aging was not apparent. There were no sex or regional differences in blood cadmium levels in non-smokers in the 3 cities (e.g., 1.2, 1.3 and 1.4 micrograms/l as geometric means in non-smoking women in Hefei, Shenyang and Jinxi, respectively). There was general agreement in blood cadmium levels between the present results and the values reported in the literature, although the latter values were generally based on small study populations.