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.

BACKGROUND: Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes. METHODS: The subjects were 22 patients (male/female, 5/17; age, 46.1±16.0 years; body mass index [BMI], 36.9±5.0 kg/m²) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy. Blood parameters, body composition, exercise tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and serum irisin were determined before and after intervention, and relationships among changes in these data were examined. RESULTS: There were significant decreases in body weight and BMI after the intervention. Irisin before the intervention was significantly positively correlated with HOMA-IR (r=0.434, P<0.05). The mean irisin level showed no significant change after the intervention in all participants. However, improvements in % body fat, subcutaneous fat area, triglycerides, and fasting glucose were significantly greater in patients with an increase in irisin compared to those with a decrease in irisin after the intervention. Patients with an increase in irisin also had significantly lower fasting insulin (9.7±4.8 vs. 16.4±8.2, P<0.05) and HOMA-IR (2.2±1.1 vs. 3.7±1.6, P<0.05) after the intervention, compared to patients with a decrease in irisin. CONCLUSION: Body weight reduction did not alter irisin levels. However, irisin may play important roles in fat and glucose metabolism and insulin resistance, and the effects of body weight reduction on irisin kinetics may be a key for obesity treatment.
Adipose Tissue ; Asian Continental Ancestry Group ; Body Composition ; Body Mass Index ; Body Weight* ; Cognitive Therapy ; Diet ; Exercise Therapy ; Exercise Tolerance ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Kinetics ; Metabolism ; Obesity ; Subcutaneous Fat ; Triglycerides

BACKGROUND: It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improvement of insulin resistance in female patients with obesity who reduce body weight. METHODS: We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m2) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardiopulmonary exercise was also performed by all patients. RESULTS: There were significant improvements in body weight (-10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (-20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (-19.3%±9.6%), total fat-free mass (-2.7%±4.3%), and % body fat (-10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=-0.280, R2=0.068, P<0.01). CONCLUSION: Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass.
Absorptiometry, Photon ; Adipose Tissue ; Body Composition ; Body Mass Index ; Body Weight* ; Cognitive Therapy ; Diet ; Exercise Therapy ; Exercise Tolerance ; Female* ; Homeostasis ; Humans ; Insulin Resistance* ; Insulin* ; Linear Models ; Muscle, Skeletal ; Obesity* ; Oxygen

Placenta previa presents a highest risk to pregnancy, and placenta accreta is the most serious. Placenta accreta requires cesarean delivery and often results in massive obstetric hemorrhage and higher maternal morbidity. Challenges associated with cesarean delivery techniques may contribute to increased maternal blood loss and morbidity rates. Several recent obstetric studies reported the usefulness of transverse uterine fundal incision for managing placenta accreta. We present a case of placenta percreta that was treated by a transverse fundal incision. We successfully avoided cutting through the placenta and helped decrease maternal blood loss. After delivery, the patient underwent a cesarean hysterectomy. Postoperative day 48, she experienced watery discharge and was diagnosed with vaginal fistula. We present our case and review the literature.
Hemorrhage ; Humans ; Hysterectomy* ; Placenta ; Placenta Accreta* ; Placenta Previa ; Pregnancy ; Vaginal Fistula*

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.

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 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.

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 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.