The influence of gonadal function and the effect of gonadal suppression treatment on final height in growth hormone (GH)-treated GH-deficient children.

One hundred and sixty-one children with idiopathic GH deficiency who received GH treatment were followed until they reached their final height. Final height was found to be influenced by gonadal function. In 108 patients who had spontaneous puberty (91 boys and 17 girls; group A), the mean final height was 151.8 +/- 6.6 (+/- SD) cm in boys and 141.7 +/- 7.4 cm in girls. In 29 patients with combined GH and gonadotropin deficiency (23 boys and 6 girls; group C), whose pubertal development was induced artificially at age 19.5 +/- 2.1 yr in the boys and 18.6 +/- 1.8 yr in the girls, the mean final height was 163.7 +/- 3.9 cm in boys and 151.0 +/- 5.1 cm in girls. The differences in final height between groups A and C were significant in both boys and girls. The shorter final height in group A was caused by the shorter pubertal duration and smaller pubertal height gain than those in normal children. In 24 patients (17 boys and 7 girls; group B) who developed early signs of puberty, gonadal suppression therapy with cyproterone acetate and/or medroxyprogesterone acetate was given. The mean SD score of the final height in these 24 patients was -2.1 +/- 0.6, significantly higher than that in group A. This beneficial effect of gonadal suppression treatment on final height was caused by increases in the duration of puberty and the pubertal height gain.

A preliminary evaluation of intra- and interindividual variations of hOGG1 messenger RNA levels in peripheral blood cells as determined by a real-time polymerase chain reaction technique.

The hOGG1 (8-oxoguanine-DNA glycosylase) gene may contribute to further understanding of the relation between oxidative DNA damage and carcinogenesis. A real-time PCR technique was used to determine mRNA levels in peripheral blood cells to assess the possibility of using hOGG1 mRNA as a biomarker in epidemiological studies. To evaluate the intra- and interindividual variation of hOGG1 mRNA levels in peripheral blood cells, we measured them in five healthy nonsmokers three times over a 1-year period. The beta-actin mRNA level in each subject was set equal to 100, and the levels of hOGG1 mRNA were found to range from 1.6-17.6. The intraindividual variation range was 1.8-6.4. Although the difference in the mRNA levels between the sampling dates was not significant (P = 0.73), a significant difference in mRNA levels was found between the subjects (P < 0.01). The subjects seemed to fall into groups according to their individual levels. This preliminary study may provide initial information on the hOGG1 mRNA level of peripheral blood cells as a biomarker in epidemiological studies on oxygen radicals, oxygen radical-related agents, and cancer.

Atmospheric pollution due to mobile sources and effects on human health in Japan.

Following the rapid economic growth after World War II, diseases associated with environmental pollution frequently occurred due to delayed implementation of countermeasures against environmental pollution. These diseases are exemplified by Minamata disease, Itai-itai disease, chronic arsenic poisoning, and Yokkaichi asthma. After multiple episodes of these pollution-related diseases were experienced, the government and the private sector made joint efforts to reduce environmental pollution. As a result of these efforts and because of changes in the industrial structure, pollution-related diseases have declined. Instead, however, air pollution from automobile exhaust and the health effects of automobile exhaust on people living along roads with heavy traffic began to attract the public's attention after an increase in the use of automobiles. The epidemiological surveys carried out by the Environmental Agency and the Tokyo Metropolitan Government also have suggested unfavorable effects of automobile-caused air pollution on people living in large cities or along major roads. To solve this problem, it seems imperative to promote the reasonable use of automobiles and to work toward more efficient transportation of goods based on analyses of city structure, the life-styles of city dwellers, and the socioeconomic composition of cities. In addition, the discharge of pollutants from automobiles could be controlled.

Efficacy of triple therapy comprising rabeprazole, amoxicillin and metronidazole for second-line Helicobacter pylori eradication in Japan, and the influence of metronidazole resistance.

BACKGROUND: The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic-resistant strains and the problem of re-treatment in cases of eradication failure. AIM: To perform drug sensitivity testing for metronidazole in 92 H. pylori-positive patients who had failed eradication treatment with first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, and were administered metronidazole-containing second-line therapy. METHODS: Second-line eradication therapy, consisting of rabeprazole (20 mg b.d.), amoxicillin (750 mg b.d.) and metronidazole (250 mg b.d.), was administered for 1 week and the eradication rates and influence of metronidazole resistance were determined. RESULTS: The eradication rates for rabeprazole-amoxicillin-metronidazole were 88% (81/92) using intention-to-treat analysis and 91% (81/89) using per protocol analysis. The eradication rates were 97% (61/63) for metronidazole-sensitive strains and 82% (18/22) for metronidazole-resistant strains. CONCLUSIONS: As second-line H. pylori eradication treatment in Japan, rabeprazole-amoxicillin-metronidazole triple therapy is effective, even with metronidazole-resistant strains.

Eradication rates of clarithromycin-resistant Helicobacter pylori using either rabeprazole or lansoprazole plus amoxicillin and clarithromycin.

BACKGROUND: The resistance of Helicobacter pylori to clarithromycin has become one of the primary reasons for eradication failure. AIM: To compare the eradication rates of triple therapy using amoxicillin (A), clarithromycin (C) and rabeprazole (R) or lansoprazole (L) against clarithromycin-sensitive and clarithromycin-resistant strains. METHODS: Two hundred and ninety-five patients were randomly divided into four groups and treated for 1 week: 147 cases were treated with RAC, i.e. 49 cases with R20C400 (10 mg R + 750 mg A + 200 mg C, twice daily), 48 cases with R40C400 (20 mg R + 750 mg A + 200 mg C, twice daily) and 50 cases with R40C800 (20 mg R + 750 mg A + 400 mg C, twice daily); 148 cases with treated with LAC (30 mg L + 750 mg A + 200 mg C, twice daily). RESULTS: According to intention-to-treat and per protocol analyses, the eradication rates were 88% and 91% with RAC and 78% and 81% with LAC; the eradication rates with R20C400, R40C400 and R40C800 were 94%, 81% and 86%, respectively, in the intention-to-treat analysis. In addition, the eradication rates for clarithromycin-sensitive strains with RAC and LAC were 98% and 89%, respectively, and for clarithromycin-resistant strains with RAC and LAC were 8.1% and 0%, respectively. CONCLUSIONS: The eradication rate was significantly higher with RAC than LAC. The eradication rate for clarithromycin-resistant strains was low in both groups, and an improved eradication rate could not be achieved by changing the dose of clarithromycin or proton pump inhibitor.

Time-dependent effects of stressor application on metastasis of tumor cells in the lung and its regulation by an immunomodulator in mice.

The effects of the timing of stressor application on transplanted tumor cells and its possible regulation by an immunomodulator was investigated. Male C57 BL/6N mice were subjected to rotational stressor for 7 days relative to tumor cell inoculation: stressor after inoculation of Lewis lung cancer cells, stressor during inoculation and stressor before inoculation. Stressor application and tumor cell inoculation induced transient decreases in body weight, particularly in mice stressed after inoculation. The mice exposed to the stressor during inoculation or before inoculation showed significant increases in the number of metastatic foci relative to control mice. Early administration of an immunomodulator, PSK, significantly attenuated the increase of metastatic foci in stressed mice. The weights of thymus gland and spleen at 14 days after inoculation were similar in the three stressor groups and the control group. Application of the stressor reduced NK cell activity of the normal mice as well as tumor bearing mice. The lowest pre-inoculation NK cell activity was observed in mice stressed for 7 days beginning on the day of inoculation. The NK cell activity decreased in the tumor bearing mice which were stressed at the time of tumor inoculation. Decreased NK cell activity was reversed at day 14 after tumor inoculation. The mice exposed to the stressor after inoculation showed lowest level of NK cell activity relative to mice exposed to the stressor before or during inoculation. The treatment of mice with PSK reduced these changes significantly. The present results suggest that the rotational stress reduces splenic NK cell activity, which may influence the magnitude of tumor metastasis, depending on the time of tumor cell injection. Further, administration of an immunomodulator may counteract the reduction of the NK cell activity.

Pulmonary function development in children with past history of asthma.

STUDY OBJECTIVE: The aim was to examine whether or not the children with a past history of asthma but free from asthmatic attacks for several years show a different growth pattern in pulmonary function from control children. DESIGN: A community based cohort was surveyed three times during a four year follow up period. SETTING: Kashima district in Ibaraki prefecture, Japan. PARTICIPANTS: In 1980, 441 primary school children between 113 and 124 months of age were enrolled as an initial cohort; 325 of these provided reliable results in each of the three surveys. MAIN RESULTS: A level and a slope of FVC, FEV1, Vmax50, and Vmax25 were calculated for each child, based on a general linear model analysis. Past histories of each child were determined from a standardised questionnaire. The children with a history of doctor diagnosed asthma showed a lower Vmax50 level (p < 0.005) and a lower level and slope of Vmax25 (p < 0.005, p < 0.01) than control children, even when only those who did not suffer from wheezing attacks during the follow up period were considered. CONCLUSIONS: Indices of peripheral airways function in children with an asthmatic history were reduced even if they had been in remission for several years. The difference in pulmonary function in comparison to control children might become greater at the time of the adolescent growth spurt.

Elevated serum levels of pantropic p53 proteins in chromium workers.

OBJECTIVES: This study investigated the possibility of applying serum pantropic p53 proteins in molecular epidemiologic studies, as a biomarker of environmental carcinogenesis. The serum levels of pantropic p53 proteins were determined in workers with past exposure to hexavalent chromium compounds. METHODS: Thirty-one male workers occupationally exposed to hexavalent chromium compounds in the production of chromium compounds for 0 to 23 years served as the exposed group. The referents were 10 volunteers without work-related exposure to chemicals. In the determination of pantropic p53 proteins, commercially available kits for enzyme-linked immunosorbent assay were used which quantitatively detected both mutant and wild-type human p53 proteins. RESULTS: The serum level of pantropic p53 proteins was in the range of 116.4 to 1122.6 pg/ml for the exposed workers and of 117.4 to 305.8 pg/ml for the referents. Nineteen percent of the exposed workers had a high p53 protein level (6 out of 31) when compared with the referents. All but 1 of the 6 workers had been occupationally exposed to chromium compounds for more than 11 years. Two of the 3 workers with a past history of lung cancer also showed high levels. CONCLUSIONS: Our findings confirm that the application of p53 proteins as a biomarker of environmental carcinogenesis merits further exploration.

Comparison of longitudinally and cross-sectionally determined age-related decline in spirometric measurements.

In order to compare the longitudinally and cross-sectionally determined annual decline of spirometric measurements, we measured spirograms from 326 male adults four times over five years. Acceptable results were obtained three times or more in 269 subjects aged 30 to 55 at the initial survey. Longitudinal annual changes in the height-squared proportional values of forced vital capacity (CFVC), forced expiratory volume in one second (CFEV1), and maximal expiratory flow at 50% and 25% of FVC (CVmax 50 and CVmax 25), was estimated by the model in which the effect of each individual's level was included as an explanatory variable. The cross-sectional annual change in those indices was determined by including the effect of each survey's level in the model. The longitudinal estimate of annual decline was significantly smaller than the cross-sectional estimate for all indices except CVmax 25. No evidence suggested that systemic error of measurement or a learning effect caused significant bias in the data. The discrepancy in the estimated annual changes seemed to be caused by the cohort effect in our subjects, since the cross-sectional analysis is primarily sensitive to harmful factors operating in the past. We concluded that the longitudinal data for individuals or groups should not be compared with any reference value based on a cross-sectional analysis.

Effect of lifetime cigarette consumption on time domain spirogram indices.

A cross-sectional analysis on the dose-related change in time domain spirogram indices induced by lifetime cigarette consumption was conducted to examine the ability of those indices to detect early changes in the lung periphery in comparison with conventional spirometric indices. The subjects were asymptomatic healthy male workers from three occupational cohorts including asbestos workers and welders. They were asked to perform the forced expiration maneuver at least three times to obtain reliable results. A total of 893 subjects were enrolled in the study, and 484 of them who were aged 30 years or more and were free from chronic respiratory symptoms and abnormalities in chest radiography and spirometry, were analyzed. Although conventional indices, such as forced expiratory volume in one second and maximal midexpiratory flow, were not significantly different between smokers and nonsmokers, the standard deviation of transit times and of time constant distribution in smokers were significantly elevated compared with nonsmokers. Furthermore a dose-related change according to lifetime cigarette consumption was observed in those indices. We conclude that time domain spirogram indices, especially the standard deviation of time constant distribution, would be more useful than conventional indices in detecting early changes in the lung periphery.