White and Gray Matter Abnormality in Burning Mouth Syndrome Evaluated with Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging.

PURPOSE: Burning mouth syndrome (BMS) is defined by a burning sensation or pain in the tongue or other oral sites despite the presence of normal mucosa on inspection. Both psychiatric and neuroimaging investigations have examined BMS; however, there have been no analyses using the neurite orientation dispersion and density imaging (NODDI) model, which provides detailed information of intra- and extracellular microstructures. Therefore, we performed voxel-wise analyses using both NODDI and diffusion tensor imaging (DTI) models and compared the results to better comprehend the pathology of BMS. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy control subjects were prospectively scanned using a 3T-MRI machine using 2-shell diffusion imaging. Diffusion tensor metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) and neurite orientation and dispersion index metrics (intracellular volume fraction [ICVF], isotropic volume fraction [ISO], and orientation dispersion index [ODI]) were retrieved from diffusion MRI data. These data were analyzed using tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS). RESULTS: TBSS analysis showed that patients with BMS had significantly higher FA and ICVF and lower MD and RD than the healthy control subjects (family-wise error [FWE] corrected P < 0.05). Changes in ICVF, MD, and RD were observed in widespread white matter areas. Fairly small areas with different FA were included. GBSS analysis showed that patients with BMS had significantly higher ISO and lower MD and RD than the healthy control subjects (FWE-corrected P < 0.05), mainly limited to the amygdala. CONCLUSION: The increased ICVF in the BMS group may represent myelination and/or astrocytic hypertrophy, and microstructural changes in the amygdala in GBSS analysis indicate the emotional-affective profile of BMS.

Effect of antipsychotic use by patients with schizophrenia on deceleration capacity and its relation to the corrected QT interval.

OBJECTIVE: Schizophrenia patients treated with antipsychotics are at higher risk of sudden cardiac death. Decreased deceleration capacity (DC) of the heart rate is an accurate predictor of cardiac mortality. We evaluated the risk of sudden cardiac death due to antipsychotic use by assessing DC and examining the association between DC and the corrected QT interval (QTc) in schizophrenia patients. METHODS: We measured the DC and QTc of 138 schizophrenia patients. We then compared the DC of 86 age- and sex-matched healthy controls with that of 86 schizophrenia patients. We investigated the correlation of DC of approximately 138 schizophrenia patients with prescribed doses of antipsychotics using linear regression analysis. We compared the DC of schizophrenia patients with and without prolonged QT intervals. RESULTS: We found DC significantly differed between schizophrenia patients on antipsychotic medication and healthy controls. Additionally, DC was negatively correlated with antipsychotic use, especially chlorpromazine, zotepine, olanzapine and clozapine, in a dose-dependent manner. There was no significant association between DC and the QTc. CONCLUSION: Assessing DC could facilitate monitoring and identification of increased risk of cardiac mortality in patients with schizophrenia that take antipsychotics. Assessing both DC and the QTc may enhance the accuracy of predicting sudden cardiac death.

Non-native acoustic modeling for mispronunciation verification based on language adversarial representation learning.

Non-native mispronunciation verification is designed to provide feedback to guide language learners to correct their pronunciation errors in their further learning and it plays an important role in the computer-aided pronunciation training (CAPT) system. Most existing approaches focus on establishing the acoustic model directly using non-native corpus thus they are suffering the data sparsity problem due to time-consuming non-native speech data collection and annotation tasks. In this work, to address this problem, we propose a pre-trained approach to utilize the speech data of two native languages (the learner's native and target languages) for non-native mispronunciation verification. We set up an unsupervised model to extract knowledge from a large scale of unlabeled raw speech of the target language by making predictions about future observations in the speech signal, then the model is trained with language adversarial training using the learner's native language to align the feature distribution of two languages by confusing a language discriminator. In addition, sinc filter is incorporated at the first convolutional layer to capture the formant-like feature. Formant is relevant to the place and manner of articulation. Therefore, it is useful not only for pronunciation error detection but also for providing instructive feedback. Then the pre-trained model serves as the feature extractor in the downstream mispronunciation verification task. Through the experiments on the Japanese part of the BLCU inter-Chinese speech corpus, the experimental results demonstrate that for the non-native phone recognition and mispronunciation verification tasks (1) the knowledge learned from two native languages speech with the proposed unsupervised approach is useful for these two tasks (2) our proposed language adversarial representation learning is effective to improve the performance (3) formant-like feature can be incorporated by introducing sinc filter to further improve the performance of mispronunciation verification.

Structural connectivity changes in the cerebral pain matrix in burning mouth syndrome: a multi-shell, multi-tissue-constrained spherical deconvolution model analysis.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome. Previous studies have attempted to determine the brain connectivity features in BMS using functional and structural magnetic resonance imaging. However, no study has investigated the structural connectivity using multi-shell, multi-tissue-constrained spherical deconvolution (MSMT-CSD), anatomically constrained tractography (ACT), and spherical deconvolution informed filtering of tractograms (SIFT). Therefore, this study aimed to assess the differences in brain structural connectivity of patients with BMS and healthy controls using probabilistic tractography with these methods, and graph analysis. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy volunteers underwent 3-T magnetic resonance imaging. MSMT-CSD-based probabilistic structural connectivity was computed using the second-order integration over fiber orientation distributions algorithm based on nodes set in 84 anatomical cortical regions with ACT and SIFT. A t-test was performed for comparisons between the BMS and healthy control brain networks. RESULTS: The betweenness centrality was significantly higher in the left insula, right amygdala, and right lateral orbitofrontal cortex and significantly lower in the right inferotemporal cortex in the BMS group than that in healthy controls. However, no significant difference was found in the clustering coefficient, node degree, and small-worldness between the two groups. CONCLUSION: Graph analysis of brain probabilistic structural connectivity, based on diffusion imaging using an MSMT-CSD model with ACT and SIFT, revealed alterations in the regions comprising the pain matrix and medial pain ascending pathway. These results highlight the emotional-affective profile of BMS, which is a type of chronic pain syndrome.

Effects of Antipsychotics on Arrhythmogenic Parameters in Schizophrenia Patients: Beyond Corrected QT Interval.

PURPOSE: Antipsychotic drugs have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect marker for proarrhythmic risk. Recently, improved methods, namely, QT dispersion (QTD), QTD ratio (QTDR), T wave peak-to-end interval (Tp-e), Tp-e/QT ratio and Tp-e/QTc ratio, have been regarded as proarrhythmic risk markers. We attempted to reevaluate the risk of sudden cardiac death due to antipsychotics use by measuring these improved evaluation methods. PATIENTS AND METHODS: We retrospectively evaluated QTc, QTD, QTDR, Tp-e, Tp-e/QT ratio and Tp-e/QTc ratio from the medical records of 410 patients with schizophrenia diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, or 5th Edition. Information on drugs administered was obtained from medical records. We investigated the correlation between each index on ECG and medication, such as antipsychotics, prescribed to participants with linear regression analysis. We also compared each index between 235 healthy controls and 235 patients matched for age and sex. RESULTS: Positive correlations between QTc and levomepromazine and brexpiprazole were identified. Levomepromazine and lithium were positively correlated with QTD. Levomepromazine, quetiapine, asenapine, clozapine and carbamazepine were positively correlated with QTDR. Levomepromazine, olanzapine, brexpiprazole and lithium were positively correlated with Tp-e. Olanzapine, brexpiprazole and lithium were positively correlated with the Tp-e/QT ratio. Olanzapine, brexpiprazole and lithium were positively correlated with Tp-e/QTc ratio. Significant differences in all indexes were noted between the patients and healthy controls. CONCLUSION: According to our results, the prediction of the risk of sudden cardiac death by each index was inconsistent. We should evaluate the predictive factor of ventricular arrhythmia according to various electrocardiogram indexes because QTc alone could not identify the risk of sudden cardiac death.

Time-dependent responses in brain activity to ongoing hot stimulation in burning mouth syndrome.

Burning mouth syndrome (BMS) is classified into idiopathic orofacial pain conditions. Although central and peripheral neuropathic mechanisms are believed to be involved, the etiology remains to be fully elucidated. The present study examined temporal brain responses to an ongoing hot stimulus to investigate the pain modulating system in patients with BMS. The thermal stimulation sequence comprised baseline (32°C, 40 s) to warm (40°C, 32 s) to baseline (32°C, 40 s) to hot (49°C, 32 s), which was repeated four times using a Peltier thermode. These warm and hot stimuli were applied on the right palm and right lower lip in two separate sessions. Functional magnetic resonance imaging data were acquired by recording echo-planar images with a block design. Brain activity induced by purely hot stimulation (49°C vs. 40°C) applied to the palm was more pronounced than that induced by lip stimulation and in patients with BMS compared with controls. Comparison of brain activity between the first 16 s and second 16 s of the stimulus revealed pronounced time-dependent facilitation in patients with BMS during lip stimulation. These findings indicate that the pain modulating system in patients with BMS is dysregulated and that the brain in BMS is highly sensitized to pain information originating from the trigeminal system.

A perspective from experimental studies of burning mouth syndrome.

Burning mouth syndrome (BMS) is one of the most frequently seen idiopathic pain conditions in a dental setting. Peri- and postmenopausal women are most frequently affected, and patients who experience BMS complain of persistent burning pain mainly at the tip and the bilateral border of the tongue. Recent studies have assessed whether BMS is a neuropathic pain condition, based on morphologic changes in biopsied tongue specimens, and whether there are abnormal pain responses in patients with this disease. Somatosensory studies have reported some abnormal findings in sensory and pain detection thresholds with inconsistency; however, the most distinct finding was exaggerated responses to painful stimuli. Imaging and electrophysiologic studies have suggested the possibility of dysregulation of the pain-modulating system in the central nervous system, which may explain the enhanced pain responses despite the lack of typical responses toward quantitative sensory tests. Basic studies have suggested the possible involvement of neuroprotective steroids, although the underlying mechanisms of this condition have not been elucidated. Experimental studies are looking for preferable supportive therapies for BMS patients despite the obscure pathogenesis.

An updated review on pathophysiology and management of burning mouth syndrome with endocrinological, psychological and neuropathic perspectives.

Burning mouth syndrome (BMS) is a chronic oro-facial pain disorder of unknown cause. It is more common in peri- and post-menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line-derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network-related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first-line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well-designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands.

Investigation of the Proarrhythmic Effects of Antidepressants according to QT Interval, QT Dispersion and T Wave Peak-to-End Interval in the Clinical Setting.

OBJECTIVE: Some antidepressants have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death. However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Therefore, we reevaluated the risk of sudden cardiac death due to antidepressants using improved. METHODS: , namely, QT dispersion (QTD), T wave peak-to-end interval (Tp-e), and Tp-e/QT ratio. METHODS: We compared the effects of antidepressants on QTc (QT/RR1/3), QTD, Tp-e, and Tp-e/QT ratio in 378 patients with mood disorder. We also compared each index between 165 healthy controls and 215 randomly selected age-matched patients. RESULTS: Age (p<0.01), sex (p<0.05), tricyclic antidepressant (TCA) use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly associated with a prolonged QTc. We also found that age (p<0.01), TCA use (p<0.05), and clomipramine (p<0.01) and mianserin (p<0.05) use in particular, significantly prolonged QTD. However, there was no correlation between each variable and Tp-e or Tp-e/QT ratio. Significant differences in QTc and QTD were found between the patients and healthy controls. CONCLUSION: From our results, prediction of risk of sudden cardiac death by QTD, Tp-e, or Tp-e/QT ratio was inconsistent. Increased QTD may be more suitable for predicting sudden cardiac death due to antidepressants.

Electrooculography-based continuous eye-writing recognition system for efficient assistive communication systems.

Human-computer interface systems whose input is based on eye movements can serve as a means of communication for patients with locked-in syndrome. Eye-writing is one such system; users can input characters by moving their eyes to follow the lines of the strokes corresponding to characters. Although this input method makes it easy for patients to get started because of their familiarity with handwriting, existing eye-writing systems suffer from slow input rates because they require a pause between input characters to simplify the automatic recognition process. In this paper, we propose a continuous eye-writing recognition system that achieves a rapid input rate because it accepts characters eye-written continuously, with no pauses. For recognition purposes, the proposed system first detects eye movements using electrooculography (EOG), and then a hidden Markov model (HMM) is applied to model the EOG signals and recognize the eye-written characters. Additionally, this paper investigates an EOG adaptation that uses a deep neural network (DNN)-based HMM. Experiments with six participants showed an average input speed of 27.9 character/min using Japanese Katakana as the input target characters. A Katakana character-recognition error rate of only 5.0% was achieved using 13.8 minutes of adaptation data.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. METHODS: Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. RESULTS: In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. CONCLUSION: Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Improving Eye Motion Sequence Recognition Using Electrooculography Based on Context-Dependent HMM.

Eye motion-based human-machine interfaces are used to provide a means of communication for those who can move nothing but their eyes because of injury or disease. To detect eye motions, electrooculography (EOG) is used. For efficient communication, the input speed is critical. However, it is difficult for conventional EOG recognition methods to accurately recognize fast, sequentially input eye motions because adjacent eye motions influence each other. In this paper, we propose a context-dependent hidden Markov model- (HMM-) based EOG modeling approach that uses separate models for identical eye motions with different contexts. Because the influence of adjacent eye motions is explicitly modeled, higher recognition accuracy is achieved. Additionally, we propose a method of user adaptation based on a user-independent EOG model to investigate the trade-off between recognition accuracy and the amount of user-dependent data required for HMM training. Experimental results show that when the proposed context-dependent HMMs are used, the character error rate (CER) is significantly reduced compared with the conventional baseline under user-dependent conditions, from 36.0 to 1.3%. Although the CER increases again to 17.3% when the context-dependent but user-independent HMMs are used, it can be reduced to 7.3% by applying the proposed user adaptation method.

Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia.

BACKGROUND: Alterations in one-carbon metabolism (OCM) have been observed in patients with schizophrenia (SZ), but a comprehensive study of OCM has not yet been conducted. A carbon atom is transferred from l-serine to methionine during OCM, but the relationship between l-serine and methionine in SZ is not yet known. We investigated the relationship between l-serine and methionine to obtain a comprehensive understanding of OCM in SZ. METHODS: We recruited forty-five patients with SZ and thirty normal controls (NC). Whole blood, plasma, and DNA specimens were obtained from all participants. Plasma l-serine, d-serine, glycine, methionine, and total homocysteine levels were measured using high-performance liquid chromatography. Plasma vitamin B12 and total folate were measured using a chemiluminescent protein-binding immunoassay. Clinical symptoms were estimated using the positive and negative syndrome scale (PANSS). The methylenetetrahydrofolate reductase (MTHFR) C667T genotype and A298C genotype, which are involved in MTHFR activity, were determined using the TaqMan genotyping assay system. RESULTS: Analysis of variance was used to confirm that the SZ cohort has higher plasma homocysteine levels and lower plasma folate levels than the NC group. Multi-regression analysis revealed a relationship between l-serine and methionine in the NC group but not in the SZ group. The MTHFR genotype did not affect the relationship between l-serine and methionine in each group. The total PANSS score was significantly related to d-serine and folate levels and to age. Positive PANSS scores were significantly related to both glycine and sex. In addition, both glycine and d-serine were significantly correlated with negative PANSS scores. CONCLUSIONS: We found impairment of the relationship between l-serine and methionine in SZ. Clinical symptoms of SZ were partially correlated with the OCM components. These findings contributed to our understanding of OCM alteration in SZ and may explain why the alteration occurs.

Headache attributed to temporomandibular disorders and masticatory myofascial pain.

We investigated the temporal association between temporomandibular disorders (TMD)-related symptoms and headache during TMD treatment for patients who fulfilled the diagnostic criteria for headache attributed to TMD (HATMD) specified in the Diagnostic criteria for TMD (DC/TMD) and International classification of headache disorders (ICHD)-3 beta. The study enrolled 34 patients with HATMD induced by masticatory myofascial pain but not by temporomandibular arthralgia. Facial pain intensity, the pressure pain threshold of pericranial muscles, and maximum unassisted opening of the jaw were assessed at an initial examination and before and after physical therapy. The intensity and frequency of headache episodes and tooth contact ratio were also recorded before and after the intervention. Headache intensity and frequency significantly decreased, and these reductions were temporally related to improvements in facial pain intensity, maximum unassisted opening, and pressure pain threshold during TMD treatment. Linear regression analysis showed significant correlations between facial pain intensity and headache intensity and between tooth contact ratio and pressure pain threshold. Among patients who fulfilled the DC/TMD and ICHD-3 beta diagnostic criteria for HATMD, headache improved during TMD treatment, and the improvement was temporally related to amelioration of TMD symptoms. These findings suggest that sensitization in the central and peripheral nervous systems is responsible for HATMD. (J Oral Sci 58, 195-204, 2016).

Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia.

The pathophysiology of schizophrenia may involve N-methyl-D-aspartate receptor (NMDAR) hypofunction. D-3serine and glycine are endogenous l-serine-derived NMDAR co-agonists. We hypothesized that the l-serine synthesis pathway could be involved in schizophrenia. We measured the activity of phosphoserine phosphatase (PSP), a rate-limiting enzyme in l-serine synthesis, in peripheral blood mononuclear cells of 54 patients with schizophrenia and 49 normal control subjects. Plasma amino acid (l-serine, d-serine, glycine, glutamine, and glutamate) levels were measured by high performance liquid chromatography. Peripheral blood mRNA expression levels of PHGDH, PSAT1, PSP, and SR, determined by quantitative real-time PCR were compared between patients and controls. PSP activity was higher in patients than in controls, especially in male patients. In male patients, the plasma l-serine concentration was higher than that in controls. In patients, PSP activity was negatively correlated with plasma d-serine and glycine levels. Furthermore, PSP activity was positively correlated with plasma l-serine concentration. These results were statistically significant only in male patients. PSP, PSAT1, and PHGDH mRNA levels were lower in patients than in controls, except when the PHGDH expression level was compared with ACTB expression. In summary, we found the l-serine synthesis system to be altered in patients with schizophrenia, especially in male patients.

Efficacy of distortion correction on diffusion imaging: comparison of FSL eddy and eddy_correct using 30 and 60 directions diffusion encoding.

Diffusion imaging is a unique noninvasive tool to detect brain white matter trajectory and integrity in vivo. However, this technique suffers from spatial distortion and signal pileup or dropout originating from local susceptibility gradients and eddy currents. Although there are several methods to mitigate these problems, most techniques can be applicable either to susceptibility or eddy-current induced distortion alone with a few exceptions. The present study compared the correction efficiency of FSL tools, "eddy_correct" and the combination of "eddy" and "topup" in terms of diffusion-derived fractional anisotropy (FA). The brain diffusion images were acquired from 10 healthy subjects using 30 and 60 directions encoding schemes based on the electrostatic repulsive forces. For the 30 directions encoding, 2 sets of diffusion images were acquired with the same parameters, except for the phase-encode blips which had opposing polarities along the anteroposterior direction. For the 60 directions encoding, non-diffusion-weighted and diffusion-weighted images were obtained with forward phase-encoding blips and non-diffusion-weighted images with the same parameter, except for the phase-encode blips, which had opposing polarities. FA images without and with distortion correction were compared in a voxel-wise manner with tract-based spatial statistics. We showed that images corrected with eddy and topup possessed higher FA values than images uncorrected and corrected with eddy_correct with trilinear (FSL default setting) or spline interpolation in most white matter skeletons, using both encoding schemes. Furthermore, the 60 directions encoding scheme was superior as measured by increased FA values to the 30 directions encoding scheme, despite comparable acquisition time. This study supports the combination of eddy and topup as a superior correction tool in diffusion imaging rather than the eddy_correct tool, especially with trilinear interpolation, using 60 directions encoding scheme.

QT is longer in drug-free patients with schizophrenia compared with age-matched healthy subjects.

The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n = 85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia.

Development of acute pancreatitis caused by sodium valproate in a patient with bipolar disorder on hemodialysis for chronic renal failure: a case report.

BACKGROUND: Cases of acute pancreatitis caused by sodium valproate (VPA) have been reported by many authors thus far. However, most of these were cases with epilepsy. Chronic renal failure is also regarded as a risk factor for acute pancreatitis. Here, we report a case of acute pancreatitis development due to VPA in a patient with bipolar disorder on hemodialysis for chronic renal failure. CASE PRESENTATION: The patient was a 52-year-old Japanese male who was diagnosed as bipolar disorder on hemodialysis for renal failure. He was treated with VPA and manic symptoms gradually stabilized. However, the patient complained of severe abdominal pain. Blood amylase was found to be markedly high, and computed tomography revealed pancreatomegaly and an increased amount of peripancreatic fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We discontinued oral medication, and he was started on a pancreatic enzyme inhibitor, antibiotics, and transfusion, and he showed improvement. CONCLUSION: It has been reported that acute pancreatitis induced by VPA is caused by intermediate metabolites of VPA. We consider that patients with renal failure are prone to pancreatitis caused by VPA because of the accumulation of these intermediate metabolites. We need close monitoring for serious adverse effects such as pancreatitis when we prescribe VPA to patients with bipolar disorder on hemodialysis for chronic renal failure, although VPA is safer than other mood stabilizers.

Immune and endocrine function in patients with burning mouth syndrome.

OBJECTIVES: Research suggests that varied etiologic factors are responsible for burning mouth syndrome (BMS). We examined the role of immune and endocrine function in the pathology of BMS. METHODS: We conducted a case-control study to evaluate immune (lymphocyte subpopulations) and endocrine (hypothalamus-pituitary-adrenal axis and sympathetic-adrenomedullary system) function in 47 female BMS patients and 47 age-matched female controls presenting at an university clinic. Psychological state was assessed with the Zung Self-Rating Depression Scale and Taylor Manifest Anxiety Scale. RESULTS: BMS patients were significantly more anxious than controls (P=0.011). Plasma adrenaline level was significantly lower (P=0.020) in BMS patients than in controls, and linear regression analysis of all patients combined revealed that depression level was significantly positively associated with plasma noradrenaline and cortisol levels (P=0.002 and 0.001, respectively). However, as compared with controls, BMS patients had a significantly lower CD8(+) cell count (P<0.001) and a significantly higher CD4/CD8 ratio (P=0.002). Discriminant analysis revealed that CD8(+) cell count and CD4/CD8 ratio were independent variables that distinguished BMS patients from controls. DISCUSSION: The immunoendocrine system is substantially involved, and may have a key role, in the mechanism of chronic pain in BMS patients. Immune function was significantly and specifically suppressed in BMS, although the hypothalamic-pituitary-adrenal axis and sympathetic nervous system were predominantly activated by psychological stress that was not specific to BMS.