Associations between hazard indices of di-n-butylphthalate and di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men.

The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.

A cross sectional study of the respiratory health of workers handling printing toner dust.

BACKGROUND: Although recent case reports have suggested possible respiratory effects of solid toner dust inhalation, this hypothesis has not been verified by epidemiological studies. OBJECTIVES: To conduct a cross sectional study to evaluate the association between the biological indices of lung fibrosis and toner dust exposure in an occupational cohort handling solid toner dust in their work life. METHODS: A total of 600 male toner workers and 212 control subjects were surveyed in terms of their subjective respiratory symptoms, pulmonary functions, and chest radiographic findings. In addition to the exposure history, the current working conditions and personal exposure levels to toner dust were also examined. RESULTS: Although subjects handling toner for more than 20 years tended to show a higher prevalence of respiratory symptoms and minimal chest x ray abnormalities, there was no consistent relation between the exposure to toner dust and the biological responses of the respiratory system. CONCLUSION: Deterioration of respiratory health related to toner dust exposure is less likely to occur in current well controlled work environments, especially if the powdered toner is handled carefully. Nonetheless, it is important to collect further epidemiological evidence on the biological effects of toner dust inhalation, preferably using a longitudinal study design.

Development of a portable pneumomagnetic measurement device.

For some time, we have been using a large device, in our laboratory, to measure the remanent field from magnetic contaminants in the human lung (magnetopneumography, or MPG). But this device is too large and cumbersome to transport to worksites to assess the magnetic contaminants in the lungs of workers. Further, it is inconvenient and expensive for workers of small or medium-sized companies to come to our campus to be magnetically examined. To solve this problem, we have developed a succession of portable devices which can easily be transported to worksites to perform MPG measurements. We here describe our most recent portable MPG device, and present a typical result of the MPG measurements. The lungs of many workers have so far been measured, and we find that the device can produce accurate measurements at the worksites, beyond our expectation. One reason, we find, is that the background magnetic noise at worksites usually is much less than that at our Kanda campus, located in the center of Tokyo, where the level of magnetic noise caused by subways is high. Therefore, some measurements, which are unable to be done at our campus,can be successfully completed at worksites by using this portable device. We note that the level of the magnetic noise during the recordings greatly depends on the exact location of the workplace measuring site.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

Inhibition of binding of E- and P-selectin to sialyl-Lewis X molecule suppresses the inflammatory response in hypersensitivity pneumonitis in mice.

The carbohydrate structure of sialyl-Lewis X (SLe(x)) can function as a ligand for E- and P-selectin, which play important roles in mediating the initial interactions of leukocytes with the endothelium in inflammatory responses. In this study we evaluated the effects of inhibiting E- and P-selectin function with the SLe(x) molecule on the inflammatory response in an experimental murine model of hypersensitivity pneumonitis (HP). Antigen exposure induced marked interstitial and especially perivascular and peribronchiolar infiltration with lymphocytes and granuloma formation, in murine lung sensitized with Saccaropolyspora rectivirgula. These pathologic changes were significantly suppressed with SLe(x) ganglioside analogues through a reduction in the numbers of lymphocytes in bronchoalveolar lavage fluid, as evidenced by the lung index and histologic scores indicating the severity of the inflammatory response. Using specific antibodies, we also evaluated the immunohistochemical localization of SLe(x) in mononuclear cells in granulomas, and of E- and P-selectin in vascular endothelium. Our findings suggest that the molecular interaction between SLe(x), and E- and P-selectin mediates lymphocyte recruitment into the lung parenchyma, which is critical for the inflammatory response in experimental murine models of HP.

[An outbreak of Legionnaire's disease associated with a Japanese spa].

From June 24 to July 5, 1996, 3 patients were admitted to the same hospital with atypical pneumonia. One of the patients, a 52-year-old man, demonstrated progressive pulmonary infiltrates and severe hypoxemia, and finally required mechanical ventilation. All 3 patients had elevated antibody titers for Legionella pneumophila serogroup 1, and had visited the same spa prior to the onset of their symptoms. On September 25, 1996 the district health department inspected the spa, and isolated Legionella pneumophila serogroup 1 from the facility's hot water tanks and outlets. Although it has been reported that many spas in Japan are contaminated with Legionellaceae, the outbreak we encountered suggests that Japanese spas, like whirlpool spas in Europe and North America, can be a source of Legionnaire's disease.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1997)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 17 institutions around the entire Japan, 512 strains of presumably etiological bacteria were isolated mainly from the sputa of 440 patients with lower respiratory tract infections during the period from October in 1997 to September in 1998. MICs of various antibacterial agents and antibiotics were determined against 100 strains of Staphylococcus aureus, 81 strains of Streptococcus pneumoniae, 85 strains of Haemophilus influenzae. 71 strains of Pseudomonas aeruginosa (non-mucoid strains), 27 strains of Pseudomonas aeruginosa (mucoid strains), 33 strains of Moraxella subgenus Branhamella catarrhalis, 17 strains of Klebsiella pneumoniae etc., and the susceptibilities of these strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 55.0%. The frequency of the drug resistant bacteria decreased comparing to the previous year's 67.3%. Arbekacin (ABK) and vancomycin (VCM) showed the most potent activities against MRSA. Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80S of 0.063 microgram/ml against S. pneumoniae. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP)+PC-resistant S. pneumoniae (PRSP) had decreased gradually, that is, in 1995 the frequency of it was 40.3%, but that was 30.9% in 1997. Against H. influenzae and M.(B.) catarrhalis, all the drugs showed good activities. But the sensitive strains of them against ceftazidime (CAZ) had decreased in 1997, compared those in 1995 and 1996. Meropenem (MEPM), IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains). And TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains). All drugs except ampicillin (ABPC) were more active against K. pneumoniae in 1997 than that in 1996. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 45.5% of all the patients showing a slight increase year by year. About the proportion of diagnosed diseases, not so particular changes were recognized as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 33.6% and 29.1%, respectively. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these had reversed in bacterial pneumonia. The tendency in bacterial pneumonia had been acknowledged since 1995. The increase of S. aureus and P. aeruginosa (both mucoid and non-mucoid strains) isolated after administration of antibiotics, has suggested the decrease of the susceptibility of these strains against antibiotics. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 24.5%, H. influenzae 21.4%, S. aureus 18.4% and P. aeruginosa 12.2%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa was not affected. The frequencies of P. aeruginosa was 47.8% after administration over 15 days. From patients administered antibiotics of penicillins and cephems. S. aureus was mainly detected with 31.7-58.3%, and from patients administere

Longitudinal observation of pulmonary function decline in male Japanese workers: design, baseline results, and methodological considerations of handling pulmonary function data.

To investigate the possible work-relatedness of obstructive lung disorders, 402 male Japanese employees who had continued to work in two natural mineral fiber processing factories (97% of the total number of employees) were first surveyed in 1985 and 1986. Follow-up surveys were repeated essentially annually until 1995. The surveys included forced spirometry and questionnaires concerning respiratory status. Pulmonary function in 328 workers could be examined acceptably for three years or more with at least three acceptable survey results. Correlation analyses clearly indicated that second-order height proportional values should be used to standardize conventional spirometric indices for subjects' body size difference. No consistent association was observed between pulmonary function values and room temperature at the time of measurement. Within-subject coefficient of variations of forced expiratory volume in one second and forced vital capacity were as low as 2% to 3% for data one year apart. Those coefficients of variations were almost constant throughout the entire study period. It seems critically important to minimize the measurement error of forced expiration maneuvers and keep it constant throughout all of the surveys, by striving to control the quality of pulmonary function data.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.

Three cases of primary pulmonary amyloidosis.

In three cases of primary pulmonary amyloidosis the chief complaint was hemosputum. The diagnosis of amyloidosis was made using histochemical analysis of bronchial wall biopsy in all cases; multiple nodular lesions were observed in trachea and bronchi on flexible fiberoptic bronchoscopy. The surface of the tracheobronchial mucosa was smooth but bled easily. In one patient, chest X-ray film showed a solitary nodular shadow in the left lower lung field. These three cases were tracheobronchial amyloidosis, and one case was combined with nodular parenchymal type amyloidosis.

Change in obstructive pulmonary function as a result of cumulative exposure to welding fumes as determined by magnetopneumography in Japanese arc welders.

OBJECTIVES: To examine the effect of chronic exposure to welding fumes on pulmonary function by a direct estimate of fumes accumulated in the lungs. METHODS: The strength of the residual magnetic field of externally magnetised lungs (LMF) was used as an estimate of fumes accumulated in the lungs. The results of forced spirometry manoeuvres obtained in 143 of 153 male welders in the original sample were cross sectionally evaluated according to LMF. Seven conventional forced spirogram indices and two time domain spirogram indices were used as pulmonary function indices, and height squared proportional correction was performed when necessary. RESULTS: The distribution of LMF values was considerably skewed towards positive. There was a weak but significant positive relation between age and log transformed LMF. Obstructive pulmonary function indices correlated well with LMF. After adjustment for age and smoking, however, a significant association with LMF was only found with percentage rate of forced expiratory volume in one second (FEV1%) divided by forced vital capacity (FVC) and mu, and average component of assumed time constant distribution of lung peripheral units. Neither FVC nor vital capacity (VC), as indices of restrictive disorders, showed a significant association with LMF. Based on the results of multiple regression analyses, a 0.6% decrease in FEV1% and 0.039 unit increase in mu were expected for each doubling of LMF. CONCLUSION: Obstructive changes in pulmonary function were found to be related to level of cumulative exposure to welding fume in male Japanese arc welders after controlling for age and smoking, assuming that LMF adequately reflects accumulation of welding fumes in the lungs.

[Age-related decline in forced expiratory volume in one second and forced vital capacity based on a longitudinal observation of Japanese males].

Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of 243 healthy male Japanese workers were measured on as annual basis over seven years, and their longitudinal decline was compared with the age coefficient of cross-sectional prediction equations reported previously for Japanese adults. In this study, a man, assumed to be 1.65 meter tall, was expected to have a respective 22 ml and 11 ml decline annually in FEV1 and FVC. Age-related differences of those indices obtained from cross-sectional prediction equations, however, ranged from 22 ml to 31 ml a year in FEV1 and from 16 ml to 25 ml in FVC for men of the same height. Furthermore, in those equations, age was simply employed as a first-order explanatory variable for ages ranging from the later teens to over sixties, although age-related acceleration of FVC decline is suggested in this study. These results indicate that evaluations of measurements relating to time-series pulmonary functions on cross-sectional prediction equations might be biased. This is probably due to the influence of age-cohort. It seems necessary to build up the reference standards for longitudinal pulmonary function change for an appropriate evaluation of time-series data of FVC and EFV1.

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1995)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 567 strains of presumably etiological bacteria were isolated mainly from the sputa of 459 patients with lower respiratory tract infections during the period from October 1995 to September 1996. MICs of various antibacterial agents and antibiotics were determined against 74 strains of Staphylococcus aureus, 82 strains of Streptococcus pneumoniae, 104 strains of Haemophilus influenzae, 85 strains of Pseudomonas aeruginosa (non-mucoid strains), 18 strains of Pseudomonas aeruginosa (mucoid strains), 52 strains of Moraxella subgenus Branhamella catarrhalis, 25 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 52.7%. Arbekacin (ABK) showed the most highest activity against S. aureus with MIC80 of 0.5 micrograms/ml. Vancomycin (VCM) showed the next highest activity with MIC80 of 1 microgram/ml. These drugs showed the high activities against MRSA with MIC80S of 1 microgram/ml. 2) S. pneumoniae. Most of drugs tested showed potent activities against S. pneumoniae. Imipenem (IPM) and panipenem (PAPM), carbapenems, showed the most potent activity with MIC80S of 0.063 microgram/ml. Cefotaxime (CTX), cefmenoxime (CMX) and cefpirome (CPR) of cephems showed the next most potent activities with MIC80S of 0.25 microgram/ml. Erythromycin (EM) and clindamycin (CLDM) showed low activities with MIC80S 128 micrograms/ml or high. Among these strains, however, 48.8% and 65.9% of respective strains were quite toward sensitive these agents with MICs of 0.063 microgram/ml. 3) H. influenzae. The activities of all drugs were potent against H. influenzae test with all MICs at 4 micrograms/ml or below. Cefotiam (CTM), CMX, cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activity with MIC90S to 0.063 microgram/ml. 4) P. aeruginosa. (mucoid strains) IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80S of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS) and carumonam (CRMN) showed next potent activity, with MIC80S of 2 micrograms/ml. The MIC80S of the other drugs ranged from 4 micrograms/ml to 32 micrograms/ml. 5) P. aeruginosa (non-mucoid strains). TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80S of 1 microgram/ml. The MIC80 of ampicillin (ABPC) was 128 micrograms/ml in 1994, it was 16 micrograms/ml in 1995. 6) K. pneumoniae. All drugs except ABPC were active against K. pneumoniae. CPR and CRMN showed the most potent activities against K. pneumoniae with MIC80S of 0.063 microgram/ml. The MIC80S of the other drugs ranged from 0.125 microgram/ml to 2 micrograms/ml. 7) M. (B.) catarrhalis. Against M. (B.) catarrhalis, all the drugs showed good activities with MIC80S at 4 micrograms/ml or below. And MICs of all strains were 8 micrograms/ml or below. IPM, OFLX and minocycline (MINO) showed the most potent activity with MIC80S of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examine for 567 isolates from 459 cases. The examination of age distribution found that the proportion of patients with ages over 60 years was 66.3% of all the patients showing a slight increase over that in 1994. Proportion of differe

Inhibition by beraprost sodium of thrombin-induced increase in endothelial macromolecular permeability.

Effect of beraprost sodium (BPS), a long-acting and orally active stable analogue of PGI2, on the macromolecular permeability of cultured vascular endothelial cells (HUVEC) was detected by the transport of FITC-albumin. Thrombin treatment resulted in induction of FITC-albumin transport across the endothelial cell monolayer. The albumin transport induced by thrombin was not accompanied by any damage to the cells. BPS had no effect on the permeability of resting endothelial monolayers, while BPS inhibited the thrombin-induced increase in the albumin permeability in a dose-dependent manner (30-1000 nM). Treatment of the cells with PGI2 or dibutyryl cAMP caused a significant inhibition of the thrombin-induced increase in the albumin permeability. These results strongly suggested that BPS suppressed the thrombin-induced macromolecular permeability in HUVEC through the elevation of its intracellular cAMP, and that BPS was a suppressor against inflammatory vascular changes such as exudation.

[Chemiluminescence assays for cytokines in serum: influence of age, smoking, and race in healthy subjects].

Evidence is accumulating that cytokines are important intermediates in the pathogenesis of many diseases such as asthma and pulmonary fibrosis. However, a major limitation to clinical studies of cytokines has been the inability to measure these important biomarkers in serum from normal, healthy controls. Without this capability, interpretation of apparently elevated levels in problematic, and evaluation of diseased level is impossible. We have recently developed chemiluminescence ELISA (CL-ELISA), resulting in a 100-fold increase in sensitivity. To assess the influence of age, smoking, and race on serum cytokine levels in healthy population, we measured IL-4, 5, 6, 10, IFN-gamma, and GM-CSF in serum of healthy Japanese (n = 38), and Americans (n = 10) using CL-ELISA. In this small population with narrow age range, no difference between smokers and nonsmokers was found for any cytokine. No correlations between age and cytokines was demonstrated. However, Japanese samples had lower levels of IL-4, 5, and 10 than American samples. Further evaluation using more controlled study design and larger populations will be necessary to determine whether this difference is due to inherent racial differences in Th2 cell function.

Decline in annual lung function in workers exposed to asbestos with and without pre-existing fibrotic changes on chest radiography.

OBJECTIVES: To examine whether or not workers with pre-existing mild pulmonary fibrosis have accelerated decline in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC), under low level exposure to chrysotile asbestos. METHODS: All male workers in two asbestos manufacturing factories were followed up annually for six years to compare their declines in FEV1 and FVC. The values of FEV1 and FVC were divided by the square of the person's height to adjust for body size differences (FEV1/Ht2 and FVC/Ht2, respectively). Annual change was calculated for each subject as a slope of the simple linear regression with FEV1/Ht2 or FVC/Ht2 regressed according to age. Analysis was conducted on 242 middle aged workers who had normal routine spirometry values, normal chest radiographs or mild pneumoconiosis up to 1/2 grade, without changes either in smoking habit or severity of pneumoconiosis during the study period, and with acceptable spirograms in three or more surveys. The occupational environment, in terms of chrysotile asbestos, had been well controlled below the threshold limit value of Japan at that time--namely, 2 fibres/micromilligrams. RESULTS-There was no significant effect from the interaction between pre-existing mild pulmonary fibrosis and low level of exposure to chrysotile asbestos on the accelerated annual decline of FEV1/Ht2, or FVC/Ht2. Fibrosis significantly contributed to annual changes in FEV1/Ht2, even after adjustment for mean FEV1 and smoking. The point estimate of the contribution was - 4.9 ml/m2/y. No significant independent contribution of exposure was found in decline of either FEV1/Ht2 or FVC/Ht2. CONCLUSIONS: Pre-existing pulmonary fibrosis is an independent risk factor for accelerated annual decline of FEV1, even when mild and stable. Additional decline due to exposure to chrysotile asbestos is less probable if it is well controlled under the current threshold limit value.

Longitudinal changes in time domain spirogram indices and their variability.

The purpose of this study was to describe longitudinal changes in time domain spirogram indices and their variability. We therefore measured forced expiratory spirograms of 326 middle-aged male employees in two asbestos-using factories four times over 5 yrs. From the original sample of 326, 225 healthy subjects, who provided reliable results for three or more surveys, were selected for analysis. The mean and standard deviation of transit time and their log-transformed values (MTT, STT, ln(MTT), and ln(STT), respectively), as well as two indices of the estimated time constant distribution (Mu and Sigma, respectively) were analysed using a longitudinal model. The longitudinally estimated annual increase of MTT, STT, ln(MTT), and ln(STT) was about three times larger than the cross-sectional estimate, whilst they were comparable in Mu and Sigma. A highly significant contribution of between-subject variability was found in all indices. This was particularly remarkable in the mean components. The between-subject variability was about eight times larger than the error variance in Mu, and three times in MTT and ln(MTT). We conclude that the longitudinal data of transit time indices should not be compared with cross-sectional reference values, and that the magnitude of error variance of these indices in longitudinal repeated measurements will be rather less than the cross-sectional counterpart reported previously.

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.