Afatinib is an oral tyrosine kinase inhibitor (TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring (TDM) in clinical settings. This study sought to develop a simple and sensitive com-petitive enzyme-linked immunosorbent assay (ELISA) to quantify afatinib in plasma for routine phar-macokinetic applications. An anti-afatinib antibody was obtained using (S)-N-4-(3-chloro-4-fluor-ophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine (CTQD), which has the same sub-structure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods (Y = 0.976X – 0.207, r = 0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.

Recently, the number of athletes who receive acupuncture therapy is increasing. However, most of these athletes receive acupuncture therapy with single-acupuncture and/or electro-acupuncture to a local point, or a trigger point. We experienced two water polo athletes who were improved using acupuncture and moxibustion therapy with “zuisho” therapy. Case 1 was 16 year old man. He became aware of pain in his right thumb after training, which continued with extended training time, a numbness in his left hand appeared more, and he received acupuncture and moxibustion therapy. These symptoms disappeared immediately with acupuncture and moxibustion therapy using the standard traditional methods, such as contact needling to a yuan point, and in situ acupuncture to a back shu point, etc. Case 2 was 17 year old man. He received acupuncture and moxibustion therapy for lumbago and stiffness of the neck. These symptoms disappeared immediately after acupuncture and moxibustion therapy using the standard traditional methods such as contact needling to a yuan point, and inserting needles into a back shu point, an extra meridian, etc. In these two cases, symptoms were improved with “zuisho” therapy, and both could continue with longer and more strenuous training. This suggests that acupuncture and moxibustion therapy using the standard traditional methods are useful for athletes.
Acupuncture ; Therapeutic procedure ; symptoms <1> ; Training ; Water

The long-term results of a “tighter” tricuspid annuloplasty (TAP) by De Vega's technique for secondary tricuspid regurgitation (TR) were studied. From June 1985 to July 1993, 122 patients underwent TAP following mitral valve surgery in our clinic. The analysis was performed on 50 patients who were followed up for more than 5 years (a mean of 75.1 months ranging from 60 to 96 months). The patients consisted of 13 males and 37 females with a mean age of 53.7 years (range from 28 to 71 years). The echocardiogram taken after long-term follow-up showed that the right ventricular inflow peak velocity at rest was a mean of 0.72m/s ranging from 0.53 to 1.04m/s, while the mean pressure half time was 76.7±14.9msec. Significant residual TR was observed in 16% at 1 month, 6% at 1 year, 10% at 3 years, and 12% at 5 years or more after operations. We conclude that a “tighter” TAP by De Vega's technique for secondary TR seems to be effective for the long-term reduction of residual TR and is not a causative factor for tricuspid stenosis.

We report a case of an anorectic 71-year-old male post-gastrectomy patient who was successfully treated with Koso-san and Rikkunshi-to. The patient underwent resection for early gastric cancer (0-IIa+IIc). After partial gastrectomy, he suffered from nausea and vomiting. He was treated with endoscopic balloon dilatation at the anastomotic site, and was simultaneously treated with some western drugs. However, he was completely unable to eat because of nausea and vomiting. Oriental medicine was then recommended. We treated him with Kampo medicines in combination with parenteral nutrition. After the administration of Koso-san, his nausea and vomiting disappeared immediately and he could ingest a fluid diet. Further, after the administration of Koso-san and Rikkunshi-to, his food intake increased. Finally, he could eat ordinary meals and his food intake reached an adequate level. This suggests that Koso-san and Rikkunshi-to are useful in the treatment of anorectic patients after gastrectomy.

A study was conducted to establish a method for quantitative evaluation of both the rate and degree of muscle oxygenation during ramp exercise using Near Infrared Spectroscopy (NIRS), and to determine the relationship of the indices to body composition and physical fitness. The subjects were 13 healthy men. After a warm-up period of 3 min at 20-W, the ramp exercise test was conducted. The exercise consisted of an increasing work rate at a slope of 20 W/min on a cycle ergometer performed until volitional fatigue. The NIRS probe used in the cycling exercise was placed on the vastus lateralis muscle. After 30 min of exercise, calibration was performed by cuff occlusion for 10 min with a pressure of 260 mmHg for quantitative determination of the NIRS curve. The oxygenation curve measured by NIRS during the exercise initially exhibited a linear decrease as the work rate increased. This rate of decrease in oxygenation was indicated by the NIRS slope (%/W) obtained from the calibration curve. In later stages of the exercise, the NIRS curve became flattened with increased work rate. The breaking point between the sloping phase and the flat phase was named the “NIRS Threshold 2, NT 2”. In addition, the rate of decrease in oxygenation at the end of exercise per maximal NIRS decrease obtained from the calibration curve was indicated as the %NIRS fall. The mean NIRS slope and %NIRS fall were 0.3±0.1%/W (range, 0.13 to 0.50%/W) and 29.9±11.8% (range, 12.0 to 50.0%), respectively. NT 2 was observed in 8 of the 13 subjects. The subjects were divided into two groups (NT 2 (+) and NT 2 (-) ) based on the appearance of NT 2. Both the NIRS slope and %NIRS fall in the NT 2 (+) group were significantly higher than those in the NT 2 (-) group. The NIRS slope was significantly correlated with VO₂/wt at VT (r=0.73, p<0.05) and wattage at VT (r=0.86, p<0.0001) . The %NIRS fall was significantly correlated with VO₂/wt at peak (r=0.80, P<0.001) . The NIRS slope and %NIRS fall were not significantly correlated with body mass index, %fat or thigh circumference.
These findings suggest that the NIRS slope indicates the efficiency of oxygen exchange in muscles activated during incremental exercise, and that the %NIRS fall indicates the ability to utilize Oxy-Hb+Mb against maximal oxygenation capacity in muscles. The NIRS slope and %NIRS fall can therefore be used as indices of muscular limitation during exercise, and as indices of muscular adaptation during exercise.

BACKGROUND : Norm-referenced equations to predict the 6-minute walk distance (6MWD) in healthy Japanese subjects have not been established. The current study aimed to determine the reference values for 6MWD in healthy Japanese adults.
METHODS : Ninety-seven healthy Japanese men and women aged 40-79 years were recruited from Kyoto city using posters and flyers. Measurements of 6MWD were performed twice on an indoor 30 m track with 20 minutes rest between the two tests. Before performing the tests, age, gender, height, body weight, waist circumference, a questionnaire for health status, spirometry, and a 12-lead electrocardiogram were recorded. The 6MWD was measured following guidelines published in 2002 by the American Thoracic Society.
RESULTS : The mean age of the study subjects was 57.0±9.4, and 63 of the 97 subjects were female. The mean 6MWD for all subjects was 672±83 m, with a range of 483-903 m. The 6MWD is significantly correlated with age, height, waist circumference, forced vital capacity (FVC), and forced expiratory volume in one second (FEV₁). A multiple linear model showed age, waist circumference, and FVC were significantly associated with 6MWD and the model explained 35% of the variability in 6MWD. When FVC was replaced by height, the regression model also explained 32% of the variation. The measured 6MWD of Japanese subjects was similar to the predicted 6MWD using the equations derived from Caucasian subjects.
CONCLUSIONS : The 6MWD was affected to a substantial degree by age, waist circumference, height, and FVC in healthy Japanese adults.

A 45-year-old man was admitted with several histories of cerebral infarction. Transesophageal echocardiography showed a small tumor on the anterior mitral leaflet. Open heart surgery was performed. The tumor was removed including a part of the anterior mitral leaflet and mitral valve plasty was done. The post-operative course was uneventful. Papillary fibroelastoma was diagnosed pathologically. To avoid embolic complication, an early surgical procedure is recommended.

The purpose of this study was to examine the association between the pedometer-determined steps per day and physical fitness in order to evaluate the usefulness of the pedometer-determined physical activity to help individuals meet the recommended exercise target level of the Ministry of Health, Labour and Welfare (MHLW). The subjects consisted of 222 men and 172 women aged 71 years in community-dwelling elderly. The subjects wore a pedometer for 7 consecutive days to measure daily steps. The functional capacity was assessed based on the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) and self-reported performance of tasks (stair-climbing and chair-rising). Physical fitness tests included handgrip strength, knee extensor strength, leg extensor power, stepping, one-leg standing time with eyes open and maximal walking speed at 10 m. The men and women took on average 6,561±2,907 and 6,329±2,451 steps/day, respectively. Our subjects seemed to be highly functioning elderly, because the total scores of TMIG-IC (maximum : 13 scores) were on average 12 for men and women. The average of steps/day was significantly correlated with stair-climbing, chair-rising and knee extensor strength in men and women, and with body weight, body mass index (BMI), percent body fat (%Fat) and leg extensor power in women. The BMI and %Fat levels were significantly lower while the handgrip strength and knee extensor strength were significantly higher in women who attained to the level of the pedometer-determined physical activity as recommended by the MHLW.The present study suggests that both men and women who take a lot of steps on a daily basis tend to demonstrate excellent leg strength and thus have a good ability to perform the tasks of daily living. In addition, the degree of obesity tends to be lower in women who regularly take a lot of steps. In addition, the number of daily steps taken has been recognized to be linked to gender, and such a link has also been suggested to be stronger in women than in men.

This prospective study was designed to clarify the association between the incidence of falls and physical fitness in healthy community-dwelling elderly people without history of fall-related injuries within 1-5 years before the baseline assessment. Six hundred and one elderly subjects aged 60-79 years who lived independently participated in baseline assessments from March 2002 to March 2004, and were followed up for one year to detect falling. Demographic items (age and sex), chronic disease, self-rated health, difficulty in performing any activity, tendency to stay at home, body mass index (BMI), %vital capacity, handgrip and knee extension strength, stepping rate, one-leg standing with eyes opened, trunk flexion at sitting position, maximum walking speed, instrumental activity of daily living (IADL), and General Health Questionnaire (GHQ30) were assessed at baseline. Four hundred and eighty-one participants (80.0%) completed the 1-year follow-up.The fall incidence was 13.1%. In men, fallers had lower BMI and decreased maximum walking speed, however, neither showed significant odds ratio (OR) for fall. In women, fallers had lower knee extension strength and the ratio of weak side to strong side (WS/SS ratio) in knee extension strength compared to non-fallers. The age-adjusted OR for fallers in the lowest quartile (knee extension strength＜0.681kg/BW) was 3.07 (95%CI : 1.02-9.22) compared to highest quartile (＞0.980 kg/BW), while the multiple-adjusted OR was not significant (OR＝2.88, 95%CI : 0.94-8.79). However, the multiple-adjusted OR for fallers in the lowest quartile of the WS/SS ratio in knee extension strength (＜0.771) was 4.49 (95%CI : 1.40-14.37) compared to highest quartile (＞0.947).As for conclusion, without history of fall-related injuries, only a weak association between falls and physical fitness was observed in men. In women, the unbalanced knee extension strength was associated with falls. The WS/SS ratio in knee extension strength might be a key factor in predicting falls in women.

The effects of exercise and dietary therapy on the prevention of diabetic nephropathy (DN) were compared. Thirty-two male OLETF rats were divided into four groups (Ex, Diet, Sed, Pre) . Fourteen LETO rats served as the normal controls. Therapy was conducted for 10 weeks from age 22 to 31 weeks. The Ex group was trained by voluntary exercise, and the Diet group had a restricted food intake resulting in the same BW as that of the Ex group. The Ex developed a significant increase in urinary albumin excretion compared to the Diet group, although significantly less than the Sed group. Blood pressure in the Ex group showed a tendency to be higher during therapy. BW and serum lipids were significantly reduced, and glucose intolerance was improved in both the Ex and Diet groups. There were no differences in the metabolic indices between the Ex and Diet groups. The Ex group showed a significantly heavier kidney weight and a tendency for enlargement of the glomerular area and volume. The protective effect of DN through improvement of the metabolic dis-order by exercise might be offset by exercise-induced renal loads. Control of exercise intensity and blood pressure appear to be important as well as the improvement of glucose intolerance and lipid metabolisms in exercise therapy to prevent an occurrence and development of DN.