Relationship between cigarette smoking and one leg with eyes closed balance in Japanese men.

OBJECTIVE: To investigate the link between cigarette smoking and one leg with eyes closed balance in Japanese men. SUBJECTS AND METHODS: We used data from 4224 Japanese men, aged 43.3 ± 13.9 years, in this cross-sectional study. Balance, such as one leg with eyes closed balance was measured. In addition, cigarette smoking habits were obtained by well-trained medical staff. The effect of cigarette smoking on one leg with eye closed balance was evaluated. RESULTS: A total of 1613 men (38.2 %) had smoking habit and 1471 men (34.8 %) regularly exercised. Age-related changes in one leg with eyes closed balance were noted. One leg with eyes closed balance in subjects with cigarette smoking (30.9 ± 31.8 s) was significantly lower than those in subjects without cigarette smoking (32.4 ± 33.5 s) even after adjusting for confounding factors i.e. age, body weight and exercise habits. CONCLUSION: Cigarette smoking might be associated with one leg with eyes closed balance in Japanese men.

Relationship between cigarette smoking and muscle strength in Japanese men.

OBJECTIVES: To investigate the link between cigarette smoking and muscle strength in Japanese men. METHODS: We used data on 4249 Japanese men, aged 43.3±13.9 years, in this cross-sectional investigation study. Grip strength and leg strength were measured as indicators of overall muscle strength. Meanwhile, subjects' cigarette smoking habits were recorded by trained medical staff. The effect of cigarette smoking on muscle strength was evaluated. RESULTS: A total of 1618 men (38.1%) were smokers and 1481 men (34.9%) exercised regularly. Significant differences in muscle strength were noted between men with and without a Brinkman index of 400 or greater, after adjusting for age. After adjusting for age, height, body weight and exercise habits, associations between the Brinkman index and leg strength and the ratio of leg strength to body weight were attenuated. CONCLUSIONS: Cigarette smoking might be negatively associated with muscle strength, especially grip strength in Japanese men.

Relation between cigarette smoking and ventilatory threshold in the Japanese.

The link between cigarette smoking and ventilatory threshold (VT) was investigated. We used data for 407 men and 418 women not taking medication. Habits of cigarette smoking were obtained through interviews by well-trained staff. The influence of cigarette smoking on oxygen uptake, work rate, and heart rate at VT was evaluated. Oxygen uptake at VT in women and work rate at VT in men with cigarette smoking were significantly lower than in subjects without cigarette smoking after adjusting for age. The differences of parameters at VT did not reach significant levels after adjusting for age and exercise habits in both sexes. However, in women without exercise habits, there was significant difference of oxygen uptake at VT between women with and without cigarette smoking after adjusting for age [cigarette smoking (+): 11.5 ± 1.8 ml/kg/min, cigarette smoking (-): 12.4 ± 2.1 ml/kg/min, p = 0.0006]. The number of cigarettes smoked per day and the Brinkman Index were not clearly correlated with oxygen uptake at VT. A combination of promoting exercise habits and prohibiting cigarette smoking might be recommended for improving the aerobic exercise level, especially in women.

Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students.

BACKGROUND: The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT) has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST) in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6-kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10]) were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guérin (BCG), 207 (56%) were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046). The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon-gamma concentration than in the subgroup with the large increase in interferon-gamma concentration (0.3 vs. 0 pg/mL; p = 0.004). CONCLUSIONS/SIGNIFICANCE: As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin-10 level after exposure to specific antigens was inversely associated with that in the interferon-gamma level in a low-risk population.

Relationship between metabolic syndrome and cigarette smoking in the Japanese population.

OBJECTIVE: We investigated the link between metabolic syndrome and cigarette smoking in the Japanese population. METHODS: A total of 3,177 Japanese subjects aged 20-79 years were recruited in a cross-sectional clinical investigation study. Habits of cigarette smoking were obtained at interviews by well-trained staff. The diagnosis of metabolic syndrome was based on the new criterion in Japan. RESULTS: Four hundred and forty men (35.3%) and 142 women (7.4%) were current smokers. Three hundred thirty four men (26.8%) and 69 women (3.6%) were diagnosed as metabolic syndrome. The prevalence of current smoker in subjects with metabolic syndrome was significantly higher than in subjects with non-metabolic syndrome in men with and without adjustment for age. The prevalence of metabolic syndrome in men with Brinkman index > or = 600 was significantly higher than that in men with Brinkman index < 600. CONCLUSION: The present study indicated that cigarette smoking may be an important modifiable factor in Japanese men with metabolic syndrome.

Recent improvement in lung cancer screening: a comparison of the results carried out in two different time periods.

To evaluate recent improvements in lung cancer screening, we compared the results of recently conducted lung cancer screening with those of a previous screening. This study compared the survival of lung cancer patients detected by lung cancer screening conducted between 1976 and 1984 (early period) with that conducted between 1989 and 1997 (late period). Two hundred seventy-six patients with lung cancer were detected in the early period and 541 patients with lung cancer were detected in the late period. The median survival time (late : 49.8 vs. early : 27.8 months) and the 5-year survival rate (late : 47.8 vs. early : 34.8%) of the patients with lung cancer detected in the late period were significantly better than those in the early period (p = 0.0054). Among patients undergoing resection, the proportion of pathological stage I patients in the late period was significantly higher than that in the early period (late : 60.8 vs. early : 54.9%, p = 0.005). Multivariate analysis showed that the screening time period was a significant prognostic factor (hazard ratio = 0.685, 95% confidence interval : 0.563-0.832, p = 0.0002). These results were consistent with the findings of case-control studies of lung cancer screening programs in the late period recently conducted in Japan, which also showed a greater efficacy for screening than for previous case-control studies in the early period.

Systemic tumor embolism mimicking gefitinib ('IRESSA')-induced interstitial lung disease in a patient with lung cancer.

We describe a 55-year-old man with advanced adenocarcinoma of the lung who received gefitinib ('IRESSA'). After gefitinib administration for 7 months, computed tomography scan of the chest demonstrated diffuse ground glass opacity and he was suspected to have developed gefitinib-induced interstitial lung disease (ILD). However, transbronchial lung biopsy (TBLB) revealed tumor cells in the middle-size lung vessels. Afterwards, multiple infarctions of the brain, spleen and left kidney were detected. Then, he was considered to have developed systemic tumor emboli, a rare complication. The clinical presentation of this patient was difficult to discriminate from that of ILD, and TBLB was useful in the differential diagnosis.

Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer.

PURPOSE: The purpose of this study is to evaluate the usefulness of serum DNA methylation of five tumor suppressor genes for early detection of lung cancer. EXPERIMENTAL DESIGN: Methylation status in serum DNA from 200 patients undergoing bronchofiberscopic examination for abnormal findings on chest radiograph detected by lung cancer screening or surveillance was examined using methylation-specific PCR. RESULTS: Ninety-one patients were given a pathologic diagnosis of lung cancer, 9 other malignant diseases, and 100 nonmalignant pulmonary diseases. In patients with lung cancer, methylation was detected in 18.7% for MGMT, 15.4% for p16(INK4a), 12.1% for RASSF1A, 11.0% for DAPK, and 6.6% for RAR-beta, which was higher compared with that in patients with nonmalignant diseases. Age and smoking status seemed to associate with methylation status. Sensitivity, specificity, and predictive value of methylation in at least one gene for diagnosis of lung cancer were 49.5%, 85.0%, and 75.0%, respectively. Adjusted odds ratio (95% confidence interval) for having lung cancer was 5.28 (2.39-11.7) for patients with methylation in one gene and 5.89 (1.53-22.7) for those with methylation in two or more genes. It is of note that methylation was identified in 50.9% of stage I lung cancer patients, whereas serum protein tumor markers were positive in 11.3% of them. CONCLUSIONS: These results suggest that identification of promoter methylation of tumor suppressor genes in serum DNA could be useful for early detection of lung cancer.

[A case of a young woman with tuberculous peritonitis diagnosed owing to high value of ADA].

A 26-year-old woman visited the first hospital due to ascites in August 2003, She had continual abdominal pain diagnosed as Irritable bowel disease after a gastrointestinal and colon fiberscopy was performed. Chest-abdominal CT scan revealed normal chest, massive ascites and swollen ovary. To rule out malignancy, surgical biopsy was performed, which brought no significant findings. We focused on the high value of Adenosin deaminase (ADA) in ascites and strongly suspected tuberculotic peritonitis. Consequently, pathologist confirmed the existence of bacterial bodies stained by acid-fast stain after our consultation. Compared with the poor diagnostic accuracy of surgical biopsy, the value of ADA in ascites has a very high sensitivity and specificity. Considering the high risk of being infertile, to begin diagnostic medication of tuberculotic peritonitis is an acceptable choice for young women with a high value of ADA in the ascites.

Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione S-transferase-pi in patients with unresectable non-small cell lung cancer.

BACKGROUND: The prognostic significance of mutant p53 protein, p-glycoprotein (P-gp) and glutathione S-transferase-pi (GST-pi) in patients with unresectable non-small cell lung cancer (NSCLC) has not been established. MATERIALS AND METHODS: We performed immunohistochemical staining of p53, P-gp and GST-pi using transbronchial biopsy specimens obtained from previously untreated NSCLC patients. RESULTS: Of 45 patients examined, p53 immunostaining was positive in 18 (40%) patients. The objective response rate by cisplatin (CDDP)-based chemotherapy was significantly lower in patients with p53-positive tumors compared to those with p53-negative tumors (22% versus 59%, p = 0.0143). Survival of the patients with p53-positive tumors was significantly shorter than those with p53-negative tumors (median survival time: 4.6 months versus 12.2 months, p = 0.011), which was confirmed by the multivariate analysis (p = 0.0243). However, P-gp and GST-pi showed no significant relationship with either response rate or survival in patients with unresectable NSCLC receiving CDDP-based chemotherapy. CONCLUSION: p53 alteration is an independent and significant indicator to predict unfavorable prognosis in patients with unresectable NSCLC.

The efficacy of lung cancer screening conducted in 1990s: four case-control studies in Japan.

The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

[Preventive therapy in middle-aged and elderly persons selected from the population-based screening by mass miniature radiography--methodological aspect and adverse reactions].

The notification rate of tuberculosis in Japan was 31.0 per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.5 per 100,000 among those over 65 years of age. We conducted a study of preventive therapy in middle-aged and elderly persons selected from the population-based screening by the mass miniature radiography. The eligible criteria were 50-79 years of age, fibrous lesion which were compatible with healed tuberculosis and showed no change for at least one year, no previous treatment for tuberculosis, normal liver function tests, and no serious disease at the time of study. The eligible criteria for liver function tests in this study was less than 50 IU/L of AST and ALT value, and less than 1.5 mg/dl of T-bil level. A total of 13,219 people underwent TB screening in 4 cities in 1997 and 2 cities in 1998. Among them, 440 persons fulfilled the above criteria based on the screening records and chest X-ray films. The municipal offices sent letters to 418 people, except 22 whose addresses were unknown, to obtain permission to use their addresses and results of screening in our study. Permission was obtained from 137 persons and we sent them invitation letters for cost-free physical checkup service. Ninety-five persons visited us, and we offered them physical checkup and explained about our study. After obtaining the informed consent, we performed chest X-ray and sputum examination for 3 consecutive days. Finally 29 people were enrolled in the study. They were divided into 4 groups by sex and age, and were randomly assigned to one of two treatment groups. One group took 300 mg of INH per day for 6 months and the other group was only followed up by chest X-ray. Fourteen out of 29 persons began to take INH and received monthly liver function test. All the subjects were scheduled to follow by medical checkup every 6 months for 5 years. The proportion of taking INH tablets was estimated to range from 94% to 100%, based on the calendar for record of taking medication and the number of remaining tablets each month. Six (42.9%) of 14 persons reported adverse reactions. Two of 6 persons complained some of diarrhea, vomiting and gastrointestinal disturbance within 2 weeks, and discontinued taking INH, although none of them showed abnormal liver function tests. Two of 6 persons who reported some kinds of symptoms and 2 of 8 persons who did not complain of any symptoms showed abnormal liver function tests. The abnormal liver function tests had developed from 2 months after the beginning of INH taking in most of the persons and the abnormality improved after the completion of 6-month treatment. We have followed them for a maximum duration of 2.5 years, and 3 cases dropped out from the study. These defaulted cases had completed 6 months of INH. One person (69 y.o. male) was diagnosed as active TB by his chest X-ray film at the 6th month medical checkup, although it was not confirmed bacteriologically. One person (62 y.o. female) had the mastectomy for breast cancer 7 months before the entry to this study and relapsed at the 8th month after the entry. One person (73 y.o. female) was diagnosed as lung cancer at the medical checkup on 2.5 years. Besides them, 4 persons were suspected of worsening the abnormal shadows on chest X-ray films; one was from the INH group and three were from the follow-up group. However none of them was diagnosed clinically and bacteriologically as active tuberculosis.

[Discussing the current situation of tuberculosis case-finding by mass miniature radiography in Japan].

The system of tuberculosis (TB) case-finding by mass miniature radiography (MMR) was established and expanded for almost all Japanese citizens in the 1950s. And, as stipulated by the TB Prevention Law, periodic mass screenings for schools, inhabitants, employees and institutions have been carried out. Among those aged over 25 years, the proportion of people screened by MMR was estimated to be 60.3%. This means that about 54 million people aged over 25 years are receiving medical service with MMR every year. However, the detection rates of TB cases by MMR have declined markedly compared with those in 1950s. As of 1998, the detection rate was 0.03 per 1,000 for school children and students, 0.06 per 1,000 for employees, and 0.16 per 1,000 for inhabitants. The proportion of cases detected by MMR among newly notified TB cases was 12.8% in 1998, and this ratio has been almost constant for the last 10 years. This ratio was greater among young adult TB cases. Approximately 20% of notified TB cases aged 20-39 years were detected by MMR for employees. Although the purpose of MMR is to find the cases before discharging TB bacilli, 35.1% of the cases were bacteriologically confirmed, and this proportion was greater among elderly TB cases. The Japan Anti-Tuberculosis Association (JATA) has been carrying out MMR for a long time. Eight selected branches of JATA that has been doing high quality case-finding reported 228 TB cases out of 965,440 inhabitants aged over 40 years examined by MMR in 1996. Based on these results, the cost per TB case detected by MMR was calculated. The cost was 4.4 millions yen (yen) per case for all forms of TB, yen 2.3 millions for male, yen 8.4 millions for female, yen 7.3 millions for those aged 40-49 years and yen 1.8 millions for those aged over 80 years. TB detection rate by MMR for inhabitants was correlated with TB incidence rate in various areas, and based on this correlation, the cost was calculated for various incidence rates. For all forms of TB, the cost was yen 4.0 millions per case for an incidence rate of 30 per 100,000, and yen 6.7 millions for an incidence rate of 20 per 100,000. MMR is not economically cost-effective even among elderly people and in areas with incidence rate less than 50 per 100,000, because the medical expense for a TB patient treated under hospitalization for 2 months and outpatient's clinic for 4 months is approximately yen 0.9 millions in 1996. The decision making in continuation or abolition or limitation of MMR should be discussed from a wide range of cost-effectiveness analyses as well as from the view of public health service and willingness of people. For the purpose of decision making, this study provides the detection rates; the costs stratified by sex, age and incidence; and the proportion of cases detected by MMR among newly notified TB cases by age-group and bacteriological status.