[Tuberculosis prevention measure in medical and correlated facilities].

Tuberculosis (TB) infection of healthcare workers in medical and correlated facilities is serious issue. For the prevention of TB transmission in the facilities, there are five important matters which are management of work environment, self protection manner, TB infection screening, a system for infection control, and TB education. The air containing TB nuclei must be exhausted from the work space mechanically, the workers should wear N95 mask at high risk places, regular chest X-ray examination and periodically QuantiFERON test for healthcare workers should undergo, the infection control committee must be active and TB education course for healthcare workers must be held annually.

Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer.

The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2) administered twice daily on days 1-14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level 2) was administered starting from level 1. Because only one patient among the 6-patient cohort at level 1 and no patient among the 3-patient cohort at level 2 experienced defined dose-limiting toxicity (DLT), level 2 was determined as the recommended dose. In phase II, 60 patients were treated at the recommended dose for median 3 cycles, and the overall response rate was 30% (95% confidence interval [CI], 18.9-43.2%), and the median overall and progression-free survival times were 15.2 (95% CI: 10.5-17.7) and 4.9 (95% CI: 3.5-5.6) months, respectively. The most frequent toxicities experienced were neutropenia, febrile neutropenia and appetite loss; all toxicities were however well manageable. The present regimen showed a potent activity with mild toxicity in untreated NSCLC.

Risks of chest X-ray examination for students.

Chest X-ray (CXR) examination is considered essential for health checkups of students;thus, it is important to objectively assess the CXR for a better understanding of the appropriate X-ray exposure dose, and the risks such an examination entails. Accordingly, we performed a multi-institutional study regarding students' CXR exposure, during a 6year-period from 2002 (partially including 2001) to 2007, with the collaboration of national, municipal, and private universities and colleges in Japan. A glass badge was worn by the students at the time of CXR screening examination. These glass badges were collected, and their X-ray exposure doses were measured. The results indicated a tendency of decreasing exposure dose over the 6 years, though the difference was not significant. In a comparison of the chest X-ray systems within institutions (own X-ray equipmentinside systems) with those outside the institution (mobile X-ray equipmentoutside systems), the average exposure dose with the outside systems exceeded that of the inside systems. Both inside and outside systems included a few X-ray machines with which the exposure was more than 1mSv. Based on these facts, individuals in charge of student health checkups should be aware of the exposure dose of each chest fluorographic system at their institution.

Lung cancer screening--comparison of computed tomography and X-ray.

Recent studies on lung cancer screening with CT disclosed a discrepancy between its efficiency in detecting early lung cancer and a lack of proof for decreasing mortality from lung cancer. The present study, in a city in Japan where an X-ray screening program is provided, bi-annual CT screening was performed for X-ray screening negative subjects for 4 years. Ten patients with lung cancer were detected among 22,720 person-year subjects (0.044%) through the X-ray screening. Among the X-ray screening-negative subjects, 3305 subjects participated in a CT screening program resulting in the detection of 15 patients with lung cancer (0.454%). All 15 cases detected by CT screening and 5 of the 10 cases detected by X-ray screening were at stage IA. In respect of gender, histological type and CT findings, patients detected by CT screening had a better prognostic profile than those detected by X-ray screening. Survival was significantly better in the former than the latter, both in its entirety comparison and in a comparison limited to patients who underwent surgery. In conclusion, CT screening might have the potential to detect lung cancer with good prognostic factors not limited to early detection. Sufficiently long follow-up time, therefore, would be required to evaluate the efficacy for decreasing lung cancer mortality with CT screening.

Phase II study of weekly irinotecan and cisplatin for refractory or recurrent non-small cell lung cancer.

Even with the standard first-line chemotherapy, advanced non-small cell lung cancer (NSCLC) recurs in most cases. The purpose of this study is to develop a new chemotherapeutic regimen for patients with NSCLC that has relapsed or was refractory to previous chemotherapy. Patients with proven NSCLC refractory or recurrent after previous single-regimen chemotherapy, PS of 0-2, age of 15 years or older, adequate organ functions and measurable lesions were treated with irinotecan at 60 mg/m(2) and cisplatin at 25 mg/m(2) with 1000 ml hydration on day 1. This administration, considered as one cycle, was repeated every week without rest unless encountering defined skip and dose-reduction criteria. The treatment was administered for six cycles over a 49-day period, both median values, to 48 patients, with a response rate of 26%, progression free and median survival times of 3 and 11 months, respectively, and a 1-year survival rate of 46%. The most frequent grade 3 or 4 toxicities were neutropenia, anaemia and nausea, which were manageable. Subset analyses suggested that the response rate was independent of response to the first-line chemotherapy. In conclusion, second-line chemotherapy of weekly irinotecan and cisplatin with minimum hydration seemed effective, with tolerable toxicity, and is potentially useful irrespective of the outcome of previous chemotherapy.

Assessment of the homogeneous efficacy of carbon ions in the spread-out Bragg peak for human lung cancer cell lines.

PURPOSE: The aim of this study was to assess the radiosensitivities and homogeneous efficacy in the spread-out Bragg peak (SOBP) for lung cancer cell lines exposed to carbon ions. MATERIALS AND METHODS: The dose-dependent survival rates of seven cell lines exposed to carbon ions, fast neutrons, and photons were obtained using colony-forming assays in vitro. The relative biological effectiveness (RBE) of carbon ions and fast neutrons to photons was determined by comparing the doses at the 10% and 1% survival levels. RESULTS: The RBEs at 13, 40, 50, and 80 keV/microm were 1.20-1.29, 1.55-1.80, 1.57-2.00, and 1.69-2.58, respectively, at the 10% survival level. The RBE of 290 MeV carbon ions increased with increasing linear energy transfer. The biological dose (relative physical dose x RBE) distributions in the SOBP did not statistically differ at the proximal, mid, or distal points at the 10% (p = 0.945) and 1% (p = 0.211) survival levels, respectively; however, deviation of the biological dose at 10% and 1% survival were 3%-16% and 6%-24%, respectively. Furthermore, 290 MeV carbon ions at 80 keV/microm in the SOBP were nearly equivalent to 30 MeV fast neutrons. CONCLUSION: Our results demonstrate nearly homogeneous effectiveness in the SOBP, although we are aware of the deviation in some cell lines.

State of hepatitis C viral replication enhances activation of NF-kB- and AP-1-signaling induced by hepatitis B virus X.

We examined the effect of hepatitis B virus X (HBx) on NF-kB- and AP-1- mediated transcription in human hepatocellular carcinoma cell lines, Huh-7 with or without subgenomic hepatitis C virus (HCV) RNA. Expression of HBx in Huh-7 cells with HCV resulted in 4.9 times increased NF-kB-activation and 3.8 times AP-1-activation whereas that without HCV resulted in 2.4 times increased NF-kB-activation and 2.3 times AP-1-activation. Interestingly, the expression of the matured form of HCV core protein, Core173, did not activate NF-kB- or AP-1-transcription in either Huh7 with or without HCV replicon. HBx protein might play an important role in HCV-related hepatocarcinogenesis.

5-aza-2'-deoxycytidine sensitizes hepatoma and pancreatic cancer cell lines.

Hepatocellular carcinoma (HCC) and pancreatic cancer are at the forefront of chemotherapy-resistant tumors with poor prognosis. Even with innovative treatment regimens, response rates remain low and the duration of response is short. We examined whether the suppression of DNA methylation was capable of enhancing the sensitivity of hepatoma and pancreatic cancer cell lines to 5-fluorouracil (5-FU). 5-aza-2'-deoxycytidine (5-aza-dC) at 2 microM, a specific DNA methylation inhibitor, did not induce cell death in Huh-7 with or without HCV, HLE, HepG2 and MIA PaCa-2 cells. However, a combination of 5-aza-dC with 5-FU showed a reduction in cell viability and induction of apoptosis in these cell lines to a greater degree than with 5-FU only. These findings underline the fact that DNA methylation plays a key role in conferring chemoresistance to hepatoma and pancreatic cancer, and the combination of DNA methylation inhibitor with chemotherapy could be a novel and highly effective tool for future targeted therapy of chemoresistant tumors.

Acute-onset autoimmune hepatitis resembling acute hepatitis: a case report and review of reported cases.

We report a 54-year-old Japanese man, whose ALT level was 1689 IU/L, without increased gamma-globulin level or autoantibodies. He could not be diagnosed as autoimmune hepatitis (AIH) using scoring systems, and his liver function became normalized after steroid treatment. Recently, AIH with acute presentation of disease and acute-onset AIH without bridging fibrosis have been increasingly reported but cases without the character of increasing gamma-globulin level or autoantibodies before immunosuppressive treatment are extremely rare. This is the third such case report in the literature.

Amantadine inhibits hepatitis A virus internal ribosomal entry site-mediated translation in human hepatoma cells.

The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal entry site (IRES) was investigated using a bicistronic reporter construct containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives were transfected with in vitro transcripts, and the reporter gene activity was determined. IFN suppressed both cap-dependent and HAV IRES-dependent translation, while amantadine specifically inhibited HAV IRES-dependent translation. In contrast to IFN, by reporter assay, amantadine did not activate the interferon-stimulated response element (ISRE) or interferon gamma-activated sequence (GAS)-associated pathways. Immunoblot analysis revealed that amantadine had no effect on PKR and on IFN-regulatory factor-1 (IRF-1) expression. These findings demonstrated a novel antiviral effect of amantadine against HAV with or without HCV infection.

Prevalence of obesity in patients with acute hepatitis; is severe obesity a risk factor for fulminant hepatitis in Japan?

BACKGROUND/AIMS: The prevalence of obesity in acute convalescent hepatitis and fulminant hepatitis has not been reported. The aim of this study was to investigate whether obesity affected the disease severity in Japanese patients with acute hepatitis. METHODOLOGY: 31 non-severe acute hepatitis (NS-AH) and 24 severe acute hepatitis and 14 fulminant hepatitis patients (S-AH) between January 1995 and December 2001 were analyzed retrospectively. Height and weight were used to calculate the body mass index (BMI) in these 69 patients. RESULTS: Mean height, weight and BMI were not significantly different between S-AH and NS-AH patients. Two severely obese (BMI greater than 35kg/m2) patients had developed S-AH. CONCLUSIONS: Severe obesity may be one of the prognostic factors in acute hepatitis. Further studies are needed.

Individually different "weights" of quality of life assessment in patients with advanced nonsmall-cell lung cancer.

BACKGROUND AND OBJECTIVE: The structure of quality of life (QOL) assessment was investigated by estimating subject-specific as well as population-averaged "weights" for four domains (functional, physical, mental, and psychosocial) relative to global QOL. METHODS: Among 583 eligible patients with advanced nonsmall-cell lung cancer in two phase III trials, 377 completed QOL questionnaires at baseline, and during treatment. A random coefficients model was applied, using the global QOL score and scores for the four domains as response and explanatory variables, respectively. RESULTS: A large diversity in subject-specific weights was found for the physical and psychosocial domains during treatment and for the psychosocial and functional domains after treatment. The population-averaged weights of all domains were significant during treatment (especially the physical domain), as well as after treatment (except the functional domain). CONCLUSION: Thus, all four domains were associated with global QOL, and the associations varied among individual patients as well as among the domains.

[Pulmonary toxisity].

Pulmonary toxicities, with special reference to interstitial pneumonia, due to cancer chemotherapy and/or chest irradiation were reviewed. Two sorts of mechanism of development of the interstitial pneumonia are considered; one is directly cytotoxic action to pneumocytes and/or pulmonary capillary endothelium and the other is an allergic mechanism against anticancer drug or its derivatives. The risk factors of cancer therapy induced interstitial pneumonia are an aged, poor performance status, and underlying interstitial pulmonary diseases. Recently some new serum markers involving KL-6 for interstitial pneumonia have been reported and further studies are needed to clarify whether these markers are predictive of subsequent pulmonary damage by anti-cancer treatments.

[Problems about tuberculin skin test raised from consultations and countermeasures--influence to the interpretation of tuberculin skin test in case of the stoppage of BCG revaccination abolition and the introduction of induration measurement].

Since people have very limited access to informations on TB, Chiba Anti-TB Association started "Chiba Kekkaku Dial 110", free TB consultation service through telephone, fax and e-mail, since October 1997. We received 1453 consultations during three years by September 2000. The most frequent consultations was about tuberculin skin test (TST) that amounted to 383, 26.4% of the all consultations. We reviewed the consultations on TST to know why consultations on TST are so frequent and what are problems clients want to know. We categorized the consultations according to the professions of clients and three periods of TST, that is, before testing, during testing and reading, and post reading. There were 178 (46.5%) consultations from health professionals, 134 (35.0%) from general citizens and the rest of them were from those unknown job. The health professionals were 94 physicians, 34 public health nurses, 23 school nurses, 19 nurses, 2 medical technicians, 2 radiographers and 4 others. Consultation after tuberculin reading was the most frequent: 93 out of 178 consultations from health professionals and 97 out of 134 from general citizens. Especially, difficulty in the interpretation of the reading result was common reason of the consultations in both health professionals (69/93) and general citizens (89/97). They feel difficulties in TST result because of widely practiced BCG revaccination and booster phenomenon due to the repetition of TST. Furthermore, TST reading results vary very much between readers especially in double redness (erythema), and it sometimes affects the diagnosis of tuberculosis infection. Therefore, if repeated TST and BCG revaccination practices in children are abolished, most of those consultations might be solved. When induration measurement is used in TST according to the international standard, the complexity of the classifications of the result seems to be dissolved. Considering the current practices in Japan, we recommend that the size of TST induration should be measured and recorded as we measure and record erythema. And induration should be referred in interpretation when they diagnose TB infection with TST.