The General Measure of the Functional Assessment of Cancer Therapy scale (FACT-G) was developed in an English-speaking culture (USA). To determine if FACT-G could be used in Japan, a cross-cultural ...validation was performed. The Japanese version was created through an iterative forward-backward translation sequence used throughout the FACT multi-lingual translation project. In evaluating psychometric testing, its construct validity was investigated by factor analysis and multi-trait scaling analysis. Clinical validity was estimated by known-groups comparison using stage, performance score (PS) and patient location, and validated longitudinally by PS. The FACT-G (version 3) was given to 180 patients with lung cancer. Analyses showed that the scales of Physical, Functional, Emotional Well-Being, and Relationship with Doctors were constructively valid in Japan. Japanese patients felt that familial relationships were different than those with friends and neighbors, indicating that the Social/Family Well-Being scale needed cultural adaptation. Two items concerning coping with illness and acceptance of illness did not load predictably onto their respective scales and were considered to be cross-culturally problematic. However, clinical validity demonstrated its sensitivity. Japanese version 4 has been improved to address the weakness in an attempt to become an instrument that is applicable across cultures.
The Biomass Burning and Lightning Experiment phase C (BIBLE‐C) aircraft mission was carried out near Darwin, Australia (12°S, 131°E) in December 2000. This was the first aircraft experiment designed ...to estimate lightning NO production rates in the tropics, where production is considered to be most intense. During the two flights (flights 10 and 13 made on December 9 and 11–12, respectively) enhancements of NOx (NO + NO2) up to 1000 and 1600 parts per trillion by volume (pptv, 10‐s data) were observed at altitudes between 11.5 and 14 km. The Geostationary Meteorological Satellite (GMS) cloud (brightness temperature) data and ground‐based lightning measurements by the Global Positioning and Tracking System (GPATS) indicate that there were intensive lightning events over the coast of the Gulf of Carpentaria, which took place upstream from our measurement area 10 to 14 h prior to the measurements. For these two flights, air in which NOx exceeded 100 pptv extended over 620 × 140 and 400 × 170 km2 (wind direction × perpendicular direction), respectively, suggesting a significant impact of lightning NO production on NOx levels in the tropics. We estimate the amount of NOx observed between 11.5 and 14 km produced by the thunderstorms to be 3.3 and 1.8 × 1029 NO molecules for flights 10 and 13, respectively. By using the GPATS lightning flash count data, column NO production rates are estimated to be 1.9–4.4 and 21–49 × 1025 NO molecules per single flash for these two flight data sets. In these estimations, it is assumed that the column NO production between 0 and 16 km is greater than the observed values between 11.5 and 14 km by a factor of 3.2, which is derived using results reported by Pickering et al. (1998). There are however large uncertainties in the GPATS lightning data in this study and care must be made when the production rates are referred. Uncertainties in these estimates are discussed. The impact on the ozone production rate is also described.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR ...mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone.
We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life.
The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84%
67%
< .001; PFS, 20.9
11.9 months; hazard ratio for death or disease progression, 0.490
< .001), although PFS2 was not significantly different (20.9
18.0 months;
= .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9
38.8 months; hazard ratio for death, 0.722;
= .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3%
31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group.
Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.
Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the ...effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.
Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, ...it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and-control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*IF homozygotes was 2.2 (95%, confidence interval 1.1-4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozvgotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*IF gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found.
Japanese pulmonologists, experienced in treating patients with diffuse panbronchiolitis (DPB) prior to the 1980s, have uniformly observed that new incidences of DPB are now a rare event in Japan. ...However, there is no epidemiological data to support this observation. We examined epidemiological trends of the number of patients with DPB in a large company.
The computerized health records of JR East Company employees were used to identify patients with DPB and then these were followed up using the assessments of these patients in JR Tokyo General Hospital and two other JR hospitals. The whole study period was 27 years (1976-2003), although detailed analyses were carried out for three specific periods; the first was 1976-1980, the second was 1989-1993, and the third was 1999-2003.
In the first period, 11 DPB cases (four incidence, and seven prevalence) were detected among a total of 355,572 workers. In the second period, three DPB cases (one incidence, and two prevalence) were identified from a total of 180,359 workers. In the third period, no case was found in a total of 144,485 workers.
This epidemiological trend suggests that both the incidence and prevalence of DPB may have decreased.
To evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC).
Sixteen patients with refractory or relapsed SCLC were ...entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival.
Seven patients (47%; 95% confidence limits for an overall response rate, 21.4% to 71.9%) responded to CPT-11 with a median duration of response of 58 days. The major toxicities were myelosuppression (predominantly leukopenia), diarrhea, and pulmonary toxicity.
CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC.
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