Objective: Pharmacogenomics (PGx) is the study of the relationship between the efficacy and/or safety of drugs and the genetic polymorphism.  Since PGx information can be used to personalize medical treatments, there has been a recent increase in the development of drug and companion diagnostic devices based on genome-wide analyses.  Therefore, we surveyed the contents of PGx information in package inserts and interview forms (IF) of Japanese pharmaceuticals, and investigated potential problems with the PGx information supplied by Japanese pharmaceuticals.
Methods: PGx information content in package inserts and the IF used by Japanese pharmaceuticals was compared with that listed in the U.S. pharmaceuticals “Table of Pharmacogenomic Biomarkers in Drug Labeling.”
Results: There were 166 PGx information content listings for 137 drugs described in the “Table of Pharmacogenomic Biomarkers in Drug Labeling.”  However, there were 31 PGx information content listings for 20 biomarkers of 24 drugs that were described in the U.S. but not the Japanese package inserts.  In addition, there was no PGx information for 17 biomarkers of 20 drugs in both the Japanese package inserts and the IF.  We additionally found that 57.7% of the biomarkers with PGx information listed in the package inserts were for drugs that are normally covered by in vitro diagnostic medical insurance.  These biomarkers were mainly the gene mutations and expression of the target molecules.
Conclusions: The Japanese PGx information associated with gene mutations and expression of the target molecules was similar to the U.S. PGx information.  However, the contents of the PGx information for drug-metabolizing enzymes differed widely among each of the drugs.  In order to more effectively use PGx information, a more careful inspection of the information regarding efficacies and side effects will need to be undertaken to ensure better evaluations of patient therapies.

Male mice of dd-strain, at 3 weeks of age were used at the start of the exercise training. The exercise training continued successively throughout the 3 to 7 weeks of age. The trained group was divided groups ; namely, light-, middle- and heavy-trained groups, which were exercised on a treadmill. The treadmill exercise program for light-, middle- and heavy-trained groups consisted of running at speeds of 6 m/min, 10 m/min and running up a 10% grade at a speed of 12 m/min for 10 min 5 times a week, respectively. The untrained group was used as control under normal laboratory condition. The skin and Achilles tendon of the four groups were sampled and their collagen content were examined by means of concentration of hydroxyproline. The collagen content in the skin of growing mice did not recognize significant difference among the four groups. On the other hand, the collagen content in the Achilles tendon of growing mice clearly recognized significant difference between the middle-trained and untrained groups and/or between the middle-trained and light-trained groups. However, middle-exercise training reduced the accumulation of collagen in the Achilles tendon of grow. ing mice.

OBJECTIVESIt is crucial to consider covariates relevant for outcome variables in developing dose-effect relations of environmental hazardous toxins. The aim of this study was to clarify the covariates affecting hand tremor and postural sway in children.

METHODSHand tremor and postural sway, as well as hair mercury concentrations, were measured in 155 boys and 148 girls at age 7 years.

RESULTSCurrent mercury concentrations in child hair ranged from 0.35 to 6.32 μg/g (geometric mean, 1.71 μg/g for boys and 1.58 μg/g for girls), and were not significantly correlated with the neuromotor parameters. All hand tremor and postural sway parameters, except for tremor intensity at 1-6 Hz with non-dominant hand, were significantly larger in the boys than in the girls. Using multiple regression analysis, some postural sway parameters were related negatively to age in the boys and girls (p<0.05), and positively to height (p<0.05). Similarly, hand tremor parameters were positively related to age, height and heart rate either in the boys or in the girls (p<0.05). Also, there were positive relationships between tremor intensity at 1-6 Hz and transversal and sagittal sways at 1-2 Hz and 2-4 Hz (p<0.05).

CONCLUSIONSHeart rate and postural sway, together with age, sex, and height, should be considered in interpreting hand tremor in children. Hand tremor or postural sway may not be so sensitive or specific to methylmercury exposures at levels of less than 7 μg/g in hair.

Objective: To investigate the role of postgraduate clinical training at the emergency department of Tenri Hospital in teaching the diagnostic process in the general outpatient department.
Method: Patients seen by 11 first-year residents at the emergency department were consecutively registered with summary sheets. Further information was added, and an analysis was performed of: 1) the distribution of chief complaints in the emergency and general outpatient departments and 2) initial diagnoses and the diagnostic process in the emergency department and the final diagnoses.
Results: The distributions of chief complaints in 89 cases in the emergency department and in 183 cases in the general outpatient department were closely correlated (p=0.0016). Diagnoses in the emergency department were correct in 58% of cases. Treatment was incorrect in 3% of cases.
Conclusion: The distributions of chief complaints in the emergency and general outpatient departments were similar. In our hospital the emergency department plays a major role in postgraduate clinical training by teaching the diagnostic process for the general outpatient department. Clinical management, including decision making for further tests and consultation, in the emergency department by first year residents did lead to any major adverse events.

BACKGROUND/AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) has emerged as a palliative treatment for malignant gastric outlet obstruction (GOO). Although covered SEMSs can prevent tumor ingrowth, frequent migration of covered SEMSs may offset their advantages in preventing tumor ingrowth. METHODS: We conducted this multicenter, single-arm, retrospective study at six tertiary referral centers to evaluate the safety and efficacy of a partially covered SEMS with an uncovered large-bore flare at the proximal end as an antimigration system in 41 patients with symptomatic malignant GOO. The primary outcome was clinical success, and the secondary outcomes were technical success, stent dysfunction, adverse events, and survival after stent placement. RESULTS: The technical and clinical success rates were 100% and 95%, respectively. Stent dysfunctions occurred in 17 patients (41%), including stent migration in nine (23%), tumor ingrowth in one (2%), and tumor overgrowth in four (10%). Two patients (5%) developed adverse events: one pancreatitis and one perforation. No procedure-related death was observed. CONCLUSIONS: A novel partially covered SEMS with a large-bore flare proximal end was safe and effective for malignant GOO but failed to prevent stent migration. Further research is warranted to develop a covered SEMS with an optimal antimigration system.
Gastric Outlet Obstruction* ; Humans ; Palliative Care ; Pancreatitis ; Retrospective Studies ; Self Expandable Metallic Stents ; Stents* ; Tertiary Care Centers

The infrapatellar fat pad is functionally deformed with joint movement and is involved in adjusting the internal pressure of the knee joint. On the other hand, it can also become a source of anterior knee pain due to inflammation and degeneration. A young female handball player experienced anterior knee pain. No obvious abnormality was observed on basic X-ray and magnetic resonance images. Dynamic observation using ultrasonic diagnostic imaging showed poor kinetics with infiltration of the infrapatellar fat pad into the patellar ligament and the tibial condyle, with the knee joint in extension on the affected side compared with the normal side. Knee joint range of movement (affected side vs. normal side) was restricted to 140° p / 150° flexion and extension - 10° p / 5°, and there was infrapatellar tenderness in the affected region. Patella baja was confirmed compared with the normal side. In addition, the flexibility of the infrapatellar fat pad was reduced. From these findings, it was inferred that the cause of pain was restriction of knee joint extension due to reduced flexibility of the infrapatellar fat pad. Treatment of the infrapatellar fat pad, joint range training exercises, and muscle strengthening training exercises were carried out. Pain and restricted range of joint movements improved and the patient could returned to competitive sports.

OBJECTIVESExposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women.

METHODSA cross-sectional study was carried out among 327 women at age 24-49 years to determine hair mercury levels and estimate daily mercury intakes from seafood by using a food frequency questionnaire.

RESULTSHair mercury levels in the women and daily mercury intake ranged from 0.11 to 6.86 (median 1.63) μg/g and from 0.77 to 144.9 (median 15.0) μg/day, respectively. The hair mercury was positively correlated with the daily mercury intake (p<0.001). When the women were divided into two subgroups based on artificial hair-waving, hair coloring/dyeing, residence (non-fishing and fishing areas), and working status, a significant difference in the hair mercury level was observed between the women with and without artificial hair-waving only (p<0.001). The multiple regression analysis showed that the log-transformed hair mercury level was significantly related to the log-transformed daily mercury intake (standardized regression coefficient βs=0.307) and artificial hair-waving (βs=-0.276); but not to hair coloring/dyeing, residence, working status or age. Permanent hair treatment was estimated to reduce total mercury in hair by approximately 30%, after adjusting for daily mercury intake and other possible factors.

CONCLUSIONSThese findings suggest that hair mercury is not the best biomarker of methylmercury exposure when a study population includes women with artificial hair-waving.

BACKGROUND/AIMS: In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. METHODS: Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. RESULTS: In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced non-occlusion cholangitis. CONCLUSIONS: The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted.
Arm ; Asian Continental Ancestry Group ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis ; Cholecystitis ; Drainage ; Humans ; Liver Abscess ; Pancreatic Neoplasms ; Pancreatitis ; Pilot Projects* ; Retrospective Studies ; Sewage ; Stents*

A 51-year-old man was referred to our hospital with pain and coldness of the upper left extremity. Contrasted computed tomography revealed a silhouette protruding into the aortic arch. Peripheral embolism in upper left extremity by tumor or thrombosis was suspected. Magnetic resonance imaging revealed a mobile mass in the aortic arch. To prevent recurrent embolization, the mass and the aortic arch to which the mass was attached were excised and partial arch replacement was performed under cardiopulmonary bypass. Histologically, the mass was a fibrin thrombus with no malignancy. The aortic wall showed only mild atherosclerosis of the intima. No thrombotic predisposition such as protein S or C deficiency or antiphospholipid antibody syndrome was observed. Anticoagulant therapy was started and the patient was discharged on postoperative day 10 without recurrent thromboembolism. Three years have passed since the operation and there is no recurrence of thromboembolism.

An 87-year-old man underwent a transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. Approximately 8 months later, he was readmitted to our institution because of a cerebral infarction. Viridans Streptococcus was identified from the blood culture, and transesophageal echocardiography revealed a mobile mass on the leaflet. Prosthetic valve endocarditis (PVE) was diagnosed and we initially administered intravenous antibiotic therapy for 4 weeks, after which the patient underwent surgical aortic valve replacement. Herein, we report on the surgical AVR in the patient using a pericardial valve after successful removal of the infected prosthetic valve, and discuss some issues related to this rare complication after TAVI.