A pilot trial of an online guided self-help cognitive behavioral therapy program for bulimia nervosa and binge eating disorder in Japanese patients.

BACKGROUND: The purpose of this study was to develop an internet-based Guided Self-Help CBT (iGSH-CBT) for Bulimia Nervosa (BN) / Binge Eating Disorder (BED) for Japanese patients and to test its feasibility. METHODS: A single-arm feasibility study. After baseline assessment, patients underwent a 16-week iGSH-CBT program, our Japanese adaption of the European-based Salut BN program. During the treatment period, weekly email support from trained counselors was provided. Evaluations were performed at baseline, after 8 weeks, at the end of the 16-week intervention, and at 2 months after treatment had ended. The primary outcome measure was the change in the weekly frequency of objective binging. Secondary outcomes were the change in the weekly frequency of objective purge episodes, responses on self-report questionnaires of the frequencies of binging and purging, psychopathological characteristics of eating disorders found on BITE, EDE-Q, EDI-2, HADS and EQ-5D, measurements of motivation, and completion of intervention (vs. dropout). RESULTS: Participants were 9 female outpatients with BN (n = 5) or BED (n = 4), of whom 8 (88.9%) attended the assessment at the end of the 16-week intervention. Mean age was 28 years (SD = 7.9). Percent change of the weekly frequency of objective binging was -4.40%, and at the end of the 16-week intervention 25% of the participants had achieved symptom abstinence. CONCLUSIONS: No adverse events were observed during the treatment period and follow-up, and the implementation and operation of the program could be performed without any major problems, confirming the feasibility of iGSH-CBT for BN and BED for Japanese patients. Although no significant change was observed in the weekly frequency of objective binging, the abstinence rate from bulimic behaviors of those who completed the assessments was 25.0% at the end of treatment, and the drop-out rate was 11.1%. iGSH-CBT may be an acceptable and possibly even a preferred method of CBT delivery for Japanese patients with BN or BED, and our Japanese adaptation of Salut BN seems feasible. TRIAL REGISTRATION: UMIN, UMIN000031962. Registered 1 April 2018 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000036334.

Ifenprodil tartrate treatment of adolescents with post-traumatic stress disorder: A double-blind, placebo-controlled trial.

BACKGROUND: Several lines of evidence suggest that glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptor plays a role in certain behavioral manifestations common to Post-Traumatic Stress Disorder (PTSD). Ifenprodil tartrate is a neuroprotective agent that binds to the GluN2B subunit of the NMDA receptor. The aim of this study is to confirm whether ifenprodil tartrate is effective in the adolescent PTSD patients. METHODS: This is a randomized, double-blind, placebo-controlled trial. Ten adolescent (13 to 18 years old) PTSD patients were randomized into two arms: placebo (n = 4), 40 mg/day ifenprodil tartrate (n = 6) for 4 weeks. All of the patients were assessed by IES-R-J (Primary outcome measure), TSCC-J, CDRS-R, DSRS-C-J and CGI-I. RESULTS: A comparison of baseline IES-R-J total scores and 4-week end-point scores showed a mild trend of improvement (p = 0.0895) and the difference score was -9.314. A comparison of baseline scores and 2-week intermediate-point scores showed that IES-R-J hyperarousal subscores and TSCC-J subscores (dissociation subscores, sexual concerns subscores) improved significantly. A comparison of baseline TSCC-J sexual concerns subscores and 4-week end-point scores improved significantly. CONCLUSIONS: Our study may prove to be an short-term effective alternative safe treatment for adolescent patients with PTSD.

Establishment of a Japanese version of the Sick, Control, One Stone, Fat, and Food (SCOFF) questionnaire for screening eating disorders in university students.

OBJECTIVE: This study aimed to validate the Sick, Control, One stone, Fat, and Food (SCOFF) questionnaire in relation to the Eating Disorders Examination Questionnaire (EDE-Q) and to examine the appropriateness of a question concerning weight loss among Japanese university students. The psychometric properties of the two Japanese versions were determined among 649 Japanese college students. The original version (SCOFF-O) employed the original item 3, whereas the revised version (SCOFF-2.5) modified the item to "Have you recently lost more than 2.5 kg within three months?" Validity was tested relative to EDE-Q. RESULTS: The test-retest reliabilities of SCOFF-O and SCOFF-2.5 were 0.52 and 0.57, while the correlations of SCOFF-O and SCOFF-2.5 with EDE-Q were r = 0.53 and r = 0.56. The sensitivity and specificity of SCOFF-O were 65.2 and 89.7, and those of SCOFF-2.5 were 69.5 and 86.5, respectively. There were significant correlations between the question concerning losing 2.5 kg and the EDE-Q subscales. The Japanese version of SCOFF-2.5 is an appropriate tool for the early screening of eating disorders among Japanese university students.

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

Clozapine-induced myocarditis: Follow-up for 3.5 years after successful retrial.

Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine-induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myocarditis over 3.5 years of observation. It may be possible to take clozapine for a long time even after clozapine-induced myocarditis, and thus improve the life expectancy of schizophrenia patients.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

AIM: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. METHODS: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. RESULTS: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. CONCLUSION: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Negative regulation of Ca(2+) influx during P2Y(2) purinergic receptor activation is mediated by Gbetagamma-subunits.

We have previously reported that P2Y(2) purinoceptors and muscarinic M(3) receptors trigger Ca(2+) responses in HT-29 cells that differ in their timecourse, the Ca(2+) response to P2Y(2) receptor activation being marked by a more rapid decline of intracellular Ca(2+) concentration ([Ca(2+)](i)) after the peak response and that this rapid decline of [Ca(2+)](i) was slowed in cells expressing heterologous beta-adrenergic receptor kinase (betaARK). In the present study, we demonstrate that, during P2Y(2) receptor activation, betaARK expression increases the rate of Gd(3+)-sensitive Mn(2+) influx, a measure of the rate of store-operated Ca(2+) entry from the extracellular space, during P2Y(2) activation and that this effect of betaARK is mimicked by exogenous alpha-subunits of G(q), G(11) and G(i2). The effect of betaARK on the rate of Mn(2+) influx is thus attributable to its ability to scavenge G protein betagamma-subunits released during activation of P2Y(2) receptor. We further find that the effect of betaARK on the rate of Mn(2+) influx during P2Y(2) receptor activation can be overcome by arachidonic acid. In addition, the UTP-induced Mn(2+) influx rate was significantly increased by inhibitors of phospholipase A(2) (PLA(2)) and an siRNA directed against PLA(2)beta, but not by an siRNA directed against PLA(2)alpha or by inhibitors of arachidonic acid metabolism. These findings provide evidence for the existence of a P2Y(2) receptor-activated signalling system that acts in parallel with depletion of intracellular Ca(2+) stores to inhibit Ca(2+) influx across the cell membrane. This signalling process is mediated via Gbetagamma and involves PLA(2)beta and arachidonic acid.

Reliability of the proposed international classification of high-resolution computed tomography for occupational and environmental respiratory diseases.

PURPOSE: We have developed a classification of high-resolution computed tomography (HRCT) images for screening, surveillance and epidemiological studies of respiratory diseases caused by occupational and environmental factors. The proposed classification consists of three parts: a guideline explaining the elements of the classification scheme, a reading sheet, and reference films to aid in assessing thin-section CT films. We assessed the reliability of the proposed classification system by blinded, independent trial reading. MATERIALS AND METHODS: Seven independent radiologists and pulmonologists performed a trial reading to measure the reliability of the classification system using HRCT films from 27 pneumoconiosis patients and 7 normal controls. RESULTS: The agreement was moderate to good for rounded opacities (weighted kappa=0.68 and 0.64), irregular opacities (0.59, 0.48), honeycombing (0.65, 0.47), emphysema (0.76, 0.62) and large opacities (0.48, 0.52). Ground glass opacities (0.16, 0.20) showed poor to fair agreement. Intra-reader agreement of each of the seven readers was moderate to good (mean: weighted kappa=0.52-0.80) for parenchymal findings, but the agreement was relatively low (mean weighted kappa=0.52) for ground glass opacities. CONCLUSION: The proposed classification is able to describe early dust-related fibrotic changes and provide a semi-quantitative description of the HRCT features of major fibrotic changes in the parenchyma and pleura. Reliability, as measured by inter-reader agreement, was satisfactory.

Railways and asbestos in Japan (1928-1987)--epidemiology of pleural plaques, malignancies and pneumoconioses-.

Asbestos has been an indispensable insulating material for railway industries, especially steam locomotives (SLs). This review (1928-1987) consists of three parts. 1) Pleural plaques: Since the 1970s, pleural plaques have been regarded as evidence of past asbestos inhalation, and more recently recognized as a risk factor of asbestos-related malignancies. For diagnostic criteria on plain radiographs, the modified ILO 1980 International Classification of Radiographs of Pneumoconioses was used. Most cases had pleural plaques with normal lungs. Large plant workers showed a significantly higher rate of plaques than workers in smaller plants. Bilateral plaques were dominant followed by the left, then the right lung, and chest wall plaques were dominant over the diaphragm. The manifestation of pleural plaques was more correlated to years since the onset of the asbestos exposure than the sum of asbestos work years, although the result was not significant. The boilermen of railway ferry steamers had a significantly higher plaque rate than other seamen. CT studies on plaques started in 1978. 2) Asbestos-related malignancies: Five retrospective cohort studies 1960-1970 were made on primary lung cancer incidence and mortality among 350,000 active railway men with smoking information. The follow-up period was 20 yr at the longest. Almost all plant workers showed a tendency of higher incidence or mortality than the controls. Two cases of mesothelioma were reported in 1980. 3) Pneumoconioses: Most studies (1928-1975) had relatively low prevalence rates among SL-related workers.

[Application of a jaw motion tracking device that measures six degrees of freedom using optoelectronic].

PURPOSE: A jaw motion tracking device that measures six degrees of freedom has recently been developed. Understanding jaw motion is useful, but previous measurement methods were impractical for use in dental clinics. The overall aim of this study was to demonstrate the simple operation, low cost, and high precision of a recently developed jaw tracking device. In addition, this study explored its potential clinical applications. METHODS: In this study, we compared two jaw motion tracking devices: a digital system type of device and an optical type of device. First we established a baseline occlusal plane from which to measure jaw motion in the same subject with both devices. The jaw motion signals were sampled at a frequency of 100 Hz. The subjects were three healthy women (mean age +/- SD = 26.3 +/- 1.2 years) who were recruited from among the crown-and-bridge faculty of Tsurumi University of Dentistry. The jaw motions measured were open-close movement, sagittal border movement, and frontal border movement. In addition, the kinematic axis point was calculated from the sagittal border movement. Data from the digital system type of device and data from the optical device were compared. The data were selected to measure rotation and translocation, i.e. jaw position about protrusion, both laterotrusion and maximal opening of the mouth. RESULTS: The root mean square (RMS) error of position measurement was 0.163 mm with MM-JI-E and 0.178 mm with the optical type of device. The RMS error of jaw motion measurement with the optical type of device was maximum at 0.8mm and minimum at 0.1mm. This was similar to that with digital system type of jaw motion tracking device. CONCLUSION: This study showed the possibility of developing clinical applications for this jaw motion device.

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation.

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers' pneumoconiosis, silicosis, hematite miners' pneumoconiosis, welders' pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.

Sarcoidosis and tuberculosis: epidemiological similarities and dissimilarities. A review of a series of studies in a Japanese work population (1941-1996) and the general population (1959-1984).

AIM: The aim of this review is to discuss the epidemiological relationship between sarcoidosis and tuberculosis. METHODS: We have used a series of health surveillance data in a Japanese work population of 460,000 employees including 70,000 working in Tokyo (1941-1996) and the data from a nation-wide sarcoidosis survey in the general population (1959-1991). The work population was annually x-rayed and tuberculin tested. The data of primary tuberculosis were obtained from a 17 year cohort study of tuberculin positive converters and primary pulmonary sarcoidosis data from the registry of the disease (1952-1996) in the same work population. Hilar lymphadenopathy (HL) was observed as a common marker of the two diseases. RESULTS: 1) Sarcoidosis HL was not detected in the work population until tuberculosis HL decreased. 2) BHL was rare in primary tuberculosis, but occurred in 95.5% of sarcoidosis subjects. 3) In both diseases, HL resolved in a few years, though accompanying extra-pulmonary involvements delayed the resolution of sarcoidosis BHL. 4) The grade of tuberculin sensitivity prior to sarcoidosis was not a risk factor for developing sarcoidosis. 5) Several well-documented sarcoidosis cases remained tuberculin-negative before and at the time of diagnosis of the disease and after resolution of pulmonary involvement. 6) Age-specific incidence curves showed a mono-modal curve in tuberculosis and a bimodal curve in sarcoidosis. 7) Tuberculosis prevalence was higher in the South of Japan, while sarcoidosis was higher in the North. CONCLUSIONS: These epidemiological dissimilarities do not support a tuberculosis etiology of sarcoidosis.

Epidemiology of sarcoidosis: new frontiers to explore.

Epidemiologic studies have been playing frontier roles to explore determinants of sarcoidosis by observing affected persons with the related population. Since 1990, more than 100 epidemiologic papers have been added to the Medline and PubMed databases. Of them, just a few were dated after March 2001. This article is focused on the papers after that time, referring to a number of previous important epidemiologic studies. The review is arranged according to two major epidemiologic categories: (1) host-related findings such as age, sex, race, familial clustering, and lifestyle; and also (2) time- and space-related findings such as exposures, geographical variation, local clustering, climate and seasonal variation, migration, and time-space clustering (transmission).

Substance P-evoked Cl(-) secretion in guinea pig distal colonic epithelia: interaction with PGE(2).

Interaction between substance P (SP) and PGE(2) on Cl(-) secretion in the guinea pig distal colonic epithelia was investigated. A short-circuit current (I(sc)) was measured as an index of ion transport. Mucosa preparations deprived of muscle and submucosa of distal colon were mounted in the Ussing flux chamber and treated with TTX and piroxicam to remove the influences of neuronal activity and endogenous PG synthesis, respectively. Although SP (10(-7) M) itself evoked little increase in I(sc), exogenous PGE(2) concentration dependently enhanced the response of SP. The effect of PGE(2) on the SP-evoked response was mimicked by forskolin and 8-bromoadenosine cAMP. Depletion of Ca2+ from the bathing solution reduced the PGE(2)-dependent response of SP. Effects of PGE(2), SP, and SP in the presence of PGE(2) on intracellular Ca2+ concentration ([Ca2+](i)) in isolated crypt cells were measured by the confocal microscope fluorescence imaging system. SP, but not PGE(2), temporally evoked an increase in [Ca2+](i) but declined to the baseline within 3 min. A return of the SP-evoked increase in [Ca2+](i) was slower in the presence of PGE(2) than SP alone. These results suggest that PGE(2) synergistically enhances SP-evoked Cl(-) secretion via an interaction between the intracellular cAMP and [Ca2+](i) in the epithelial cells. In conclusion, SP and PGE(2) could cooperatively induce massive Cl(-) secretion in guinea pig distal colon at epithelial levels.