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Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population., Koda et al. present the results of a randomized phase 3 trial comparing granulocyte colony-stimulating factor versus placebo in patients with acute spinal cord injury. While the primary endpoint was not met, a sub-analysis revealed a trend towards superior efficacy of G-CSF versus placebo in an elderly population.

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752.

Objective Changes in metabolic syndrome and its components with lifestyle modification were evaluated in Japanese men. Methods We used data for 160 Japanese men (45.6±8.8 years) with a 1-year follow up. Anthropometric, blood examination and blood pressure measurements were evaluated. Metabolic syndrome was defined by using a criterion in Japan. All subjects were given instructions by well-trained medical staff on how to change their lifestyle. Results With a 1-year follow-up, anthropometric parameters, blood pressure (BP), triglyceride and HDL cholesterol were significantly improved and the prevalence of metabolic syndrome was significantly reduced. The number of subjects with abdominal obesity at baseline and at follow-up was higher (81 men) than that of subjects with other components at baseline and at follow-up. Parameters at baseline were significantly correlated with changes in parameters for one year. With lifestyle modification, the level of 163 mmHg in systolic BP (SBP), 115 mmHg in diastolic BP (DBP), 226 mg/dL in triglyceride and 33 mg/dL in HDL cholesterol at baseline was estimated to improve to the level without medications with a 1-year follow up. Conclusion Lifestyle modification is useful for improving metabolic syndrome and its components. However, items of metabolic syndrome were improved, even when the abdominal circumference was greater than the normal value for Japanese men.

Medical waste poses health hazards, increases the environmental load and is costly to dispose of. To solve the above problems, we applied the hazard analysis and critical control point system (HACCP) to the management of wastes generated from endoscopy. First, the wastes in three hospitals were quantified. The number and weight of waste per case differed significantly among the three hospitals. Second, HACCP was applied to the endoscopy unit of Hospital X for a year. Wastes were segregated into five types and weighed. We found that 25.8% of ‘infectious waste’ was in fact ‘non‐infectious waste’ and ‘non‐infectious plastic waste’. The numbers of needles and needle caps did not correspond in two occasions (needle‐loss rate: 0.42%). Bacterial counts of the waste container were determined to investigate infection hazard. The counts were 0 cfu/cm2 in all examinations except one occasion. The waste control manifests were reviewed, and all entries were consistent with the waste sent for disposal. In Hospital X wh...

Objective We investigated the link between a reduction in waist circumference and metabolic syndrome. Methods 105 obese Japanese men were enrolled in this study with a 1-year follow-up. Anthropometric and body composition parameters, i.e. height, body weight, body fat percentage, waist circumference and hip circumference, blood pressure, triglyceride, HDL cholesterol and blood sugar, were evaluated. Metabolic syndrome was diagnosed using criteria developed in Japan. Results After a 1-year follow-up, the parameters of metabolic syndrome were significantly improved. The prevalence of metabolic syndrome was significantly reduced in subjects with at least 3 cm of waist circumference reduction (Group R). However, in subjects without such reduction (Group C), the prevalence of metabolic syndrome was similar to baseline levels. The prevalence of abdominal obesity, hypertension and dyslipidemia was also significantly reduced in Group R. In addition, there were remarkable differences of delta triglyceride (delta represents positive changes in parameters) and delta HDL cholesterol between Group R and Group C. Conclusion At least 3 cm of waist circumference reduction may be beneficial for improving metabolic syndrome in obese Japanese men.

Objectives: We investigated the correlation between changes in body weight and body composition parameters. Methods: We used the data of 2635 Japanese (40.2±12.2 years) at baseline and at 1-year follow-up from a database of 13522 subjects, which is available at the Okayama Southern Institute of Health in Okayama prefecture, Japan. Body weight, waist circumference at the umbilical level, hip circumference, and body fat percentage were used in the analyses. Results: Body composition parameters were significantly reduced after 1 year. Changes in body weight significantly correlated with changes in waist circumference, changes in hip circumference, and changes in body fat percentage. A decrease in body weight of 3 kg corresponded to a 3.45 cm decrease in waist circumference in men and a 2.83 cm decrease in that in women. Conclusion: A decrease in body weight of 3 kg corresponded to an almost 3 cm decrease in waist circumference at the umbilical level in Japanese men and women.

Aim: To re-evaluate exercise intensity for overweight Japanese men by ventilatory threshold (VT). Methods: Cross sectional clinical intervention study. Subjects and materials: One hundred and ten overweight Japanese men aged 32–59 years were recruited. The average body mass index was 28.5 ± 2.5 kg/m2. Aerobic exercise level was evaluated by measuring VT. Fifty per cent heart rate (HR) reserve by Karvonen's formula was calculated and compared with HR at VT. Fat distribution was evaluated by visceral fat and subcutaneous fat areas measured with computed tomography scanning at umbilical levels. Anthropometric parameters such as height, body weight and body fat percentage were also measured. Results: There was significant correlation between HR at VT and 50% HR reserve by Karvonen's formula (r = 0.642, p

Objective: To investigate the difference between air displacement plethysmograph (ADP) and bioelectrical impedance (BI) for assessing body composition changes during weight loss in Japanese women. Design: Cross-sectional and longitudinal investigation study. Subjects: In a first cross-sectional study, we used data of 7380 Japanese women aged 14–83 years [body mass index (BMI): 22.6 ± 3.7 kg/m2] at baseline. Among the participants, we used data of 54 women (BMI: 25.9 ± 3.9 kg/m2) for a 5-month follow-up study. Measurements: Body fat percentage was evaluated by ADP and BI, and body fat (kg) and lean body mass (kg) were calculated. Anthropometric parameters, such as height, weight, BMI, waist circumference, hip circumference and waist hip ratio, were also measured. In a second longitudinal study, they were also investigated before and after the study. Results: In a first cross-sectional study, body fat percentage was 31.2 ± 7.0% in ADP and 25.7 ± 6.8% in BI. A significant relationship was observed between ADP and BI (r = 0.761, p

Aim: To investigate the link between serum leptin concentrations and exercise. Design: Cross-sectional and longitudinal studies of an exercise intervention. Subjects: 110 Japanese overweight men aged 32–59 years were recruited. At baseline, the average body mass index (BMI) was 28.5 ± 2.5 kg/m2. From this group, we used data of 36 overweight men (BMI, 28.9 ± 2.3) for a 1-year exercise programme. Measurements: Leptin was measured at baseline and after 1 year. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters, aerobic exercise level, muscle strength and flexibility were also investigated at baseline and after 1 year. Results: In the first analysis, using cross-sectional data, leptin was significantly correlated with total body fat (r = 0.760, p

Objective: To investigate the link between a reduction in blood pressure (BP) and daily exercise. Design: Cross-sectional and longitudinal clinical intervention study with exercise education. Subjects: 43 overweight Japanese men aged 32–59 years (BMI, 29.0±2.3 kg/m 2 ) at baseline. Among the participants, a randomly selected 23 overweight men (BMI, 28.5±1.7) were further enrolled into the 10 months exercise program. Measurements: BP was measured every week and steps per day were also recorded every day throughout the observation period. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical level, at before, 5 months and after intervention. Anthropometric parameters were also measured at same point. Aerobic exercise level, muscle strength, flexibility and calorie intake and insulin resistance (HOMA index) were investigated at before and after the study. Results: In a cross sectional analysis, systolic BP (SBP) and diastolic BP (DBP) were significantly correlated with body composition. In a second longitudinal analysis, SBP was significantly reduced at 2 months and DBP was also reduced at 3 months, and almost maintained until the end of the observation period. Increasing daily walking was observed in 3 months and maintained until 10 months. Body composition, aerobic exercise level, muscle strength, flexibility and insulin resistance were significantly improved. There was positive correlation between ΔDBP and Δvisceral fat area (1–5, 5–10, 1–10 months). By stepwise multiple regression analysis, only Δvisceral fat area was independently related to ΔDBP at a significant level (1–10 months: ΔDBP=−0.608+0.105Δvisceral fat area, r 2 =0.227, P =0.0334). Conclusion: The present study indicated daily exercise lowers BP and visceral fat area is the critical factor for BP change.

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index ≧26.4) subjects, aged 20–79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist–hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist–hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist–hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle.

Twenty-four previously treated patients with refractory or relapsed small cell lung cancer (SCLC) were entered into a prospective, multicenter phase II study. All 24 patients had been pretreated with some form of cisplatin-based chemotherapy. The median time of chemotherapy was 4.2 months (range 1.4-9.4 months). Patients were treated with a dose of 25 mg/m2 of vinorelbine weekly. Twenty-four patients were eligible for response and for toxicity. Partial response was observed in 3 out of 24 eligible patients (12.5%; 95% confidence interval, 2.7-32.4%). All 3 patients who responded had previous chemotherapy including vincristine. The most common toxicity was leukopenia (91.7%, 66.7% in WHO 3-4 grade) and anemia (70.8%, 20.8% in WHO 3 grade). Nonhematological toxicities were moderate and mild. These results support a two-state sequential study design of previously untreated patients for further phase II study in SCLC.

Oral BOF-A2 (Emitefur), a new derivative of 5-fluorouracil (5-FU) containing both 1-ethoxymethyl-5-FU (EMFU), a masked form of 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP), an inhibitor of 5-FU degradation, was administered to 71 non-small cell lung cancer (NSCLC) patients in a multi-center phase II study. The patients were scheduled to receive at least 2 courses of treatment, each consisting of 200 mg twice daily for 2 weeks followed by a 2-week rest period. Out of 62 evaluable patients, 11 (18%) responded (8 of 44 adeno- and 3 of 15 squamous cell carcinomas). Thirty-four patients showed no change and 17 progressive disease. The incidences of gradeor = 2 hematologic toxicity were 5-8% for leukopenia, thrombocytopenia, and anemia. The incidences of non-hematologic toxicity of gradeor = 2, such as anorexia, nausea/vomiting, and diarrhea, were close to 20% or lower.

Between April 1981 and December 1987, 148 patients with newly diagnosed small cell lung cancer (SCLC) were treated using combination chemotherapy with or without thoracic irradiation and prophylactic cranial irradiation (PCI) in a series of cooperative therapeutic trials. With a minimum follow-up of 4.7 years, 13 (9%) patients survived and were free of SCLC. These included 11 (15%) of 76 patients with limited disease and two (3%) of 72 patients with extensive disease. Three died without any evidence of SCLC (one each from second leukemia, non-small cell lung cancer, and unrelated disease). The remaining 10 (7%) patients are currently alive and free of SCLC beyond 4.7 years. Since late relapse beyond 5 years is a very rare event, these patients may have been cured. However, late toxicity of PCI must be kept in mind. Three among the 10 patients have suffered from neuropsychologic symptoms of varying degrees in severity. Although the long-term survival rate is a benchmark in the treatment of SCLC, modifications of therapy that may potentially avoid such toxicities should be considered hereafter.

反回神経麻痺を契機に発見された肺癌患者19例について, 反回神経麻痺の原因となった病変の胸部単純写真と胸部断層写真, CTによる検出能を比較検討した. 胸部単純写真では, 反回神経麻痺の原因となった肺癌病変をまったく読影困難なものが1例, 見落とし易いと思われたものが2例あった. CT像では全例で反回神経麻痺の原因となった病変が明瞭に描出されていた. 反回神経麻痺を訴える患者で, 耳鼻科領域に原因となる病変を指摘できない時, 胸部単純写真では異常を指摘し得なくても肺癌が原因となっている場合があり, CT検査は不可欠と考えられた.

Objective : To investigate the link between visceral fat (V) accumulation and physical fitness. Design : Cross-sectional clinical investigation study. Subjects : Twenty-eight overweight Japanese women with abdominal obesity (abdominal obesity) (body mass index, BMI≧25, visceral fat area≧100cm 2 ) aged 38–65 years (BMI 29.5±3.3kg/m 2 ) were enrolled in this study. They were compared with age and sex matched 28 normal weight subjects (BMI 2 ) and 28 overweight subjects without abdominal obesity (overweight) (BMI≧25, visceral fat area 2 ). Measurements : Fat distribution was evaluated by visceral fat and subcutaneous fat (S) areas measured by computed tomography (CT) scanning at umbilical level. Anthropometric parameters, aerobic exercise level, muscle strength, flexibility and blood examination were also investigated. Results : Anthropometric and body composition parameters were significantly higher in abdominal obesity subjects than those in normal weight subjects. BMI, waist circumference, waist hip ratio and visceral fat (V) area were also significantly higher than those in overweight subjects. Reduced oxygen uptake at ventilatory threshold (VT), lowering weight bearing index (WBI), and elevation of blood enzymes were noted in abdominal obesity subjects. There were significant relationships between oxygen uptake at VT and visceral fat area, and also between oxygen uptake at VT and WBI. Conclusion : Reduced aerobic exercise level and WBI are characteristic and visceral fat may play an important role for the etiology in Japanese women with abdominal obesity.

Objective: It is known that the accumulation of abdominal fat is one of the risk factors for atherosclerosis. Although exercise is commonly prescribed to reduce body weight, the efficacy of low intensity exercise for the reduction of abdominal visceral adipose tissue remains to be investigated. Research design and methods: Thirty one obese Japanese males (body mass index (BMI) ≥25) ranging in age from 32 to 59, participated in a 1-year follow up study and they were instructed to have a modest increase in daily activity and record their daily walking. Before and after exercise prescription, body composition, blood pressure, physical fitness i.e. aerobic exercise level, muscle strength and flexibility were recorded. Insulin resistance was evaluated using a homeostasis model assessment, the HOMA index. Results: HOMA index, parameters of body composition, blood pressure, triglyceride and HDL cholesterol were significantly improved. The aerobic exercise level, leg strength, weight-bearing index (leg strength/body weight) and the steps taken per day were significantly increased. By stepwise multiple regression analysis, Δvisceral adipose tissue area was the major determinant for ΔHOMA index. (ΔHOMA index=−0.386+0.016 Δvisceral adipose tissue area, r2=0.267, P

In an attempt to determine the prognostic significance of pretreatment factors for patients with advanced non-small cell lung cancer (NSCLC), 24 pretreatment clinical variables were analyzed for 185 patients with NSCLC who underwent chemotherapy and/or radiotherapy between 1985 and 1994. Following univariate analysis, we applied two multivariate statistical techniques. In a Cox regression mode, independently significant factors influencing patient survival included performance status (PS), disease stage, hemoglobin level, and serum calcium level. Recursive partitioning and amalgamation (RPA) resulted in three distinct prognostic subgroups based on PS, stage, weight loss, and hemoglobin level. The best survival was observed for patients with a good PS and Stage III disease who had a hemoglobin level > 11 g/dl. The worst survival was observed for patients with a poor PS and presence of weight loss irrespective of stage. All other patients had an intermediate prognosis. Median survival times were 95.1 weeks, 17.1 weeks and 39.3 weeks, respectively (P < 0.00005). The results of our analyses show that three important prognostic subgroups could readily be discerned using RPA.

both the muscle driver and RNAi transgene were tested. Larvae expressing RNAi against Gγ1 expressed in the visceral muscle cleared in an average of 176.3 min versus 135.7 min for larvae lacking the muscle driver (p

both the muscle driver and RNAi transgene were tested. Larvae expressing RNAi against Gγ1 expressed in the visceral muscle cleared in an average of 176.3 min versus 135.7 min for larvae lacking the muscle driver (p

1968年以降10年間にわれわれの施設で取扱かった小細胞癌症例について, 化学療法の成績を中心に検討を加えた. その結果, 多剤併用療法は単独療法に比べ有効率が高く, 多剤併用療法の中では, cyclophosphamide, vincristine, methotrexate, procarbazine 4剤併用療法の効果がもっとも優れていた. 治療効果別の生存期間をみると, 腫瘤完全退縮例のmedian survivalは12ヶ月以上 (平均18.4ヶ月以上), 部分退縮例では8.4ケ月 (7.8ヶ月), 無効例では4.3ヶ月 (4.2ヶ月) であり, 有効例と無効例の生存期間には明らかな差が示された.

肺癌患者の細胞性免疫能把握のパラメーターとしてPHAによるリンパ球幼若化反応, ツベルクリン反応, 末梢リンパ球数, Leucocyte migration inhibition testについて検討した. その結果これらのパラメーターと肺癌の進展度あるいは癌化学療法による臨床経過との亀間に関連性がうかがわれた. 同時に溶連菌剤OK-432投与における検討から本剤の免疫化学療法における有用性が示唆された.

Streptococcal agent OK-432 was administered at maintenance levels with conventional inductive chemotherapeutic agents to stage III and IV lung cancer patients. Survival rates were longer in patients treated with OK-432 than in patients treated without OK-432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found in patients treated by OK-432. A low grade fever was present as a side effect of this agent in some patients. The results suggest that OTK-432 may be useful immunotherapeutic agent in combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer.

A 54-year-old man with small cell carcinoma of the esophagus and extensive metastases to the liver and bone is presented herein. Ectopic hormone production and a high level of serum NSE (neuron specific enolase), as revealed by biochemical and radioimmunoassay, suggested that this tumor was derived from the cells of the APUD (amine precursor and dehydroxylation) series. He was treated with a combination chemotherapy, resulting in a prompt remission with significant palliation lasting five months. Small cell carcinoma of the esophagus is as responsive to chemotherapy as small cell carcinoma of the lung. Although this is an uncommon tumor, recognition is important because of its responsiveness to chemotherapy and the potential for significant palliation of symptoms without surgical intervention.