Effect of therapeutic plasma exchange on phenytoin plasma concentration in patients receiving intravenous fosphenytoin therapy.

We report for patients with encephalitis treated with plasma exchange (PE) and fosphenytoin. In patient 1, phenytoin levels decreased on the maintenance dose, and the phenytoin concentration was <10 µg/mL on day 12 of administration. In patient 2, the phenytoin levels was <10 µg/mL on day 4. Increasing the fosphenytoin dose pushed the phenytoin level into therapeutic range. There were no differences between the areas under the concentration-time curve of phenytoin with and without PE. We previously reported a decline in phenytoin levels after prolonged use of fosphenytoin. Therefore, dose adjustment of fosphenytoin in patients undergoing PE may be unnecessary.

Color change in Perlodel® tablets induced by LED lighting - photolysis of bromocriptine mesylate.

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.

Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children's Study.

This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

Built environment and cardio-metabolic health: systematic review and meta-analysis of longitudinal studies.

Built environment attributes may be related to cardio-metabolic diseases (e.g. type 2 diabetes, heart disease and stroke) and their risk factors, potentially by influencing residents' physical activity. However, existing literature reviews on the built environment and health for the most part focus on obesity as the outcome and rely on cross-sectional studies. This systematic review synthesized current evidence on longitudinal relationships between built environment attributes and cardio-metabolic health outcomes among adults and on the potential mediating role of physical inactivity. By searching eight databases for peer-reviewed journal articles published in the English language between January 2000 and July 2016, the review identified 36 articles. A meta-analysis method, weighted Z-test, was used to quantify the strength of evidence by incorporating the methodological quality of the studies. We found strong evidence for longitudinal relationships of walkability with obesity, type 2 diabetes and hypertension outcomes in the expected direction. There was strong evidence for the impact of urban sprawl on obesity outcomes. The evidence on potential mediation by physical activity was inconclusive. Further longitudinal studies are warranted to examine which specific built environment attributes influence residents' cardio-metabolic health outcomes and how physical inactivity may be involved in these relationships.

Effects of water viscosity and tongue ingestion site on tongue pressure during food bolus propulsion.

The purpose of this study was to help provide data to help to implement effective rehabilitation following surgery for oral cancer by comparing tongue pressure production for water and thickened water from the anterior and posterior parts of the tongue during swallowing. Ten healthy volunteers (7 men, 3 women; age 27.6 ± 1.5 years) participated in the experiments. Tongue pressure during 3 mL water and 3 mL thickened water at the anterior and posterior tongue during swallowing was measured using a sensor sheet system with five measuring points on the hard palate. The sequential order of the points, maximal magnitude and duration of tongue pressure at each point were compared based on water viscosity and tongue ingestion site. There was a common pattern in the sequential order of tongue pressure generation among the two swallowing conditions. The maximal magnitude of tongue pressure was significantly higher when swallowing thickened water than when swallowing water at all points except for the anterior-median and mid-median part. Moreover, the pressure at all sites during posterior ingestions was significantly lower than that during anterior ingestion. The present results provide mean values of tongue pressure during voluntarily triggered swallowing in anterior ingestion and posterior ingestion in young, healthy dentate individuals; these values can be clinically referenced for tongue pressure measurement in the evaluation of patients with dysphagia. The use of reference values may help streamline the diagnosis, treatment and rehabilitation of dysphagia.

Visuomotor adaptation in head-mounted virtual reality versus conventional training.

Immersive, head-mounted virtual reality (HMD-VR) provides a unique opportunity to understand how changes in sensory environments affect motor learning. However, potential differences in mechanisms of motor learning and adaptation in HMD-VR versus a conventional training (CT) environment have not been extensively explored. Here, we investigated whether adaptation on a visuomotor rotation task in HMD-VR yields similar adaptation effects in CT and whether these effects are achieved through similar mechanisms. Specifically, recent work has shown that visuomotor adaptation may occur via both an implicit, error-based internal model and a more cognitive, explicit strategic component. We sought to measure both overall adaptation and balance between implicit and explicit mechanisms in HMD-VR versus CT. Twenty-four healthy individuals were placed in either HMD-VR or CT and trained on an identical visuomotor adaptation task that measured both implicit and explicit components. Our results showed that the overall timecourse of adaption was similar in both HMD-VR and CT. However, HMD-VR participants utilized a greater cognitive strategy than CT, while CT participants engaged in greater implicit learning. These results suggest that while both conditions produce similar results in overall adaptation, the mechanisms by which visuomotor adaption occurs in HMD-VR appear to be more reliant on cognitive strategies.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours.

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.

Application of a barometer for assessment of oral functions: Donders space.

We developed a barometer applicable to a small space, to assess oral and pharyngeal functions. Negative oral pressure during rest and pressure changes during swallowing were measured in a space between the palate and tongue (STP). Twenty volunteers were asked to sit in a chair in a relaxed upright position. A sensor was placed on the posterior midline of hard palate. Recording commenced just before subjects closed their lips and continued. Subjects were asked to swallow saliva and keep the apposition. Finally, subjects were asked to open their mouth. Recordings were performed five times, and 5 s of continuous data in each phase was averaged. To verify the reliability of the system, the same procedure was accomplished with twin sensors. When the jaw and lips were closed, the pressure slightly decreased from atmospheric pressure (-0·17 ± 0·24-kPa). After swallowing, the pressure in STP showed more negative value (-0·50 ± 0·59-kPa). There is a significant difference between the values in open condition and after swallowing (P < 0·001) and between values after swallowing and final open condition (P < 0·05). Twin sensor showed almost the same trajectories of pressure changes for all the recordings. Obtained negative pressure might generate about 0·71-N of force and would be enough to keep the tongue in the palatal fossa at rest. The system detected large negative/positive pressure changes during swallowing. We conclude this system may be a tool to evaluate oral functions.

Efficacy of sucroferric oxyhydroxide treatment in Japanese hemodialysis patients and its effect on gastrointestinal symptoms.

Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in adult dialysis patients. Studies in Japan about the side effects of SFOH treatment indicate that the incidence of diarrhea (25%) is greater while that of constipation (2.9%) is lesser in comparison to that observed upon treatment with an existing phosphate binder. In the present study, the effect of treatment with a combination of the existing phosphate binders and SFOH on the serum phosphorus level and digestive symptoms was observed in hemodialysis patients with hyperphosphatemia, which is untreatable using only the existing phosphate binders. We evaluated the serum phosphorus levels and gastrointestinal symptoms (using the gastrointestinal symptom rating scale) of 6 patients (2 men, 4 women) before and 2, 4, 6, and 8 weeks after continuous administration. The serum phosphorus levels before and 2, 4, 6, and 8 weeks after combination treatment were 7.4±1.0 mg/dL, 5.9±1.3 mg/dL, 5.8±1.5 mg/dL, 5.8±1.4 mg/dL, and 5.8±1.3 mg/dL, respectively, with significant reduction in the levels being observed 2 weeks after administration (p<0.05) and persisting even 8 weeks after continuous administration. The constipation scores before and 2, 4, and 8 weeks after drug administration were 2.39±0.85, 2.34±1.93, 2.56±1.44, and 3.28±2.19, respectively, with no changes observed during the investigation period. The diarrhea scores before and 2, 4, and 8 weeks after drug administration were 2.22±0.91, 2.06±1.16, 1.28±0.39, and 1.06±0.13 respectively. The scores improved significantly, 4 weeks after drug administration (p<0.05), and the improvement persisted, even 8 weeks after continuous administration. Thus, by using a combination of the existing phosphate binders and SFOH, we were able to reduce the serum phosphorus level in patients with hyperphosphatemia, which is untreatable using the existing phosphate binder alone, with no sign of exacerbation of the gastrointestinal symptoms despite a few contradictory case reports.