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Yoshitaka Furuto, Mariko Kawamura, Jumpei Yamashita, Takahiro Yoshikawa, Akio Namikawa, Rei Isshiki, Hiroko Takahashi, Yuko Shibuya Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, JapanCorrespondence: Yoshitaka FurutoDepartment of Hypertension and Nephrology, NTT Medical Centre, 5-9-22, Higasi-Gotanda, Shinagawa-Ku, Tokyo, 141-8625, JapanTel +81 03-3448-6111Fax +81 03-3448-6058Email furuto19761006@yahoo.co.jpAbstract: It is reported that Helicobacter pylori (H. pylori) infection may be linked to non-digestive tract diseases, such as arteriosclerosis including dyslipidemia, diabetes, obesity, hypertension, and cardiovascular disease. Therefore, we reviewed recent studies available in PubMed dealing with the mechanisms of arteriosclerosis due to H. pylori infection and the effects of H. pylori eradication. Conventional studies suggested that H. pylori infection may increase the risk of arteriosclerosis. A large interventional study is required to clarify the causal relationships and the effects of bacterial eradication.Keywords: Helicobacter pylori infection, arteriosclerosis, hypertension

Yojiro Umezaki,1 Motoko Watanabe,2 Yukiko Shinohara,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Anna Miura,2 Miho Takenoshita,2 Yusuke Sato,3 Ichiro Minami,4 Jun Oyama,5 Akira Toriihara,5 Tatsuya Yoshikawa,2 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka 814-0193, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 3Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 4Department of Removable Partial Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 5Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, JapanCorrespondence: Akira ToyofukuDepartment of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8548, JapanTel/Fax +81- 3-5803-5909Email toyoompm@tmd.ac.jpBackground: Phantom bite syndrome (PBS) is characterized by an uncomfortable sensation during occlusion without any evident abnormality. A recent case–control study with single-photon emission computed tomography (SPECT) using 99mTc-ethyl cysteinate dimer could not find the specific features of regional cerebral blood flow (rCBF), which might be due to the heterogeneity of PBS. We analyzed the brain images of PBS corresponding to the clinical features by studying PBS subgroups.Methods: This study contributes to elucidating the pathophysiology of PBS by evaluating regional brain perfusion on SPECT and its clinical features. We performed SPECT using 99mTc-ethyl cysteinate dimer in 44 patients with PBS. The SPECT images were analyzed qualitatively and quantitatively.Results: Asymmetrical rCBF patterns were detected, corresponding to symptom laterality. Patients with PBS with right-side symptoms showed right-side-predominant rCBF asymmetry in the parietal region and left-side-predominant rCBF asymmetry in the thalamus, and vice versa. Moreover, the analysis of the association between rCBF and patient behaviors revealed that patients who blamed their dentists for their symptoms tended to have a symmetrical rCBF pattern.Conclusion: Patients with PBS showed blood flow imbalance in the thalamus and parietal region corresponding to symptom laterality. There are two types of symmetrical and asymmetrical rCBF patterns in the pathophysiology of PBS despite similar clinical manifestations.Keywords: phantom bite syndrome, cerebral blood flow, single-photon emission computed tomography

Takayuki Suga,1 Miho Takenoshita,1 Takeshi Watanabe,1 Trang TH Tu,1 Lou Mikuzuki,1 Chaoli Hong,1 Kazuhito Miura,2 Tatsuya Yoshikawa,1 Takahiko Nagamine,3 Akira Toyofuku1 1Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Gerodontology, Division of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, Hokkaido, Japan; 3Department of Psychiatric Internal Medicine, Sunlight Brain Research Center, Yamaguchi, JapanCorrespondence: Akira ToyofukuDepartment of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, JapanTel/Fax +81 3 5803 5898Email toyoompm@tmd.ac.jpObjective: To assess the therapeutic dose and safety of amitriptyline and the outcome following treatment with amitriptyline among older patients with burning mouth syndrome (BMS).Methods: 187 consecutive patients were prescribed amitriptyline as a first-line medication from April 2016 to September 2018 and followed-up for >1 month. Patients were divided into 3 groups: group 1, 113 patients aged

Yojiro Umezaki,1 Anna Miura,2 Yukiko Shinohara,2 Lou Mikuzuki,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Motoko Watanabe,3 Miho Takenoshita,2 Tatsuya Yoshikawa,2 Akihito Uezato,4 Toru Nishikawa,4 Ken Hoshiko,5 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 3Department of Oral and Maxillofacial Radiology, Tokyo Dental College, Tokyo, Japan; 4Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; 5Department of Pharmacy, Dental Hospital, Tokyo Medical and Dental University, Tokyo, Japan Objective: Oral cenesthopathy is characterized by foreign body sensations without medical and dental evidence for them. It is thought to be a rare disease in psychiatry, but many patients are visiting dental clinics seeking treatment to remove a foreign body. Even though the features of oral cenesthopathy might be different between a psychiatric clinic and a dental clinic, there has been no clinico-statistical study from dentists. In this study, we report a clinico-statistical study of patients with oral cenesthopathy in dentistry. Methods: This is a retrospective chart review of 606 outpatients with oral cenesthopathy in Tokyo Medical and Dental University from April 2010 through to March 2015. Results: A total of 159 male and 447 female patients were included in this study. The mean age was 62.08 years, and female patients were older than male patients. The trigger of the dental treatment and the acute phase of depression at the onset were significantly related (p=0.037). Only 128 patients (36%) had clinically significant improvement after 6 months of pharmacotherapy. No history of psychiatric disorders (odds ratio [OR] 0.479 [95% confidence interval {CI}: 0.262–0.875], p=0.017) and longer duration of illness (>18 months) (OR 2.626 [95% CI: 1.437–4.799], p=0.002) were significant factors for clinical outcomes. Conclusion: Patients with oral cenesthopathy in our clinic were predominantly elderly female patients. Dental treatment in the acute phase of depression might be a risk factor for oral cenesthopathy. Therefore, comprehending the situation of psychiatric disorder and obtaining adequate informed consent might be required to prevent the trouble concerning oral cenesthopathy. Keywords: oral cenesthopathy, delusional disorder somatic type, DDST, chart review, dentistry

Tadanobu Yoshikawa, Kanji Takahashi Department of Ophthalmology, Kansai Medical University, Osaka, Japan Purpose: To describe the outcomes of intravitreal injections of bevacizumab for choroidal neovascularization (CNV) associated with choroidal osteoma. Methods: Retrospective consecutive case series. Three eyes of three patients were studied. All patients were treated with intravitreal injections of bevacizumab for CNV associated with choroidal osteoma. Best-corrected visual acuity, central foveal thickness, tumor thickness on spectral domain optical coherence tomography, and subretinal pigmentation around the CNV were evaluated. Results: The mean number of intravitreal injections of bevacizumab was 2.0 (range 1–3). The mean follow-up time was 56.0 months (range 25–99 months). The mean LogMAR visual acuity worsened from 0.1 to 0.6. LogMAR visual acuity loss of 0.7 or worse occurred in two of three eyes. CNV was located in the subfoveal area in two eyes, and CNV was located in the juxtafoveal area in one eye. The mean central foveal thickness decreased from 407 µm to 251 µm. The mean tumor thickness decreased from 709 µm to 608 µm. All eyes had subretinal pigmentation around the CNV. Conclusion: Intravitreal injections of bevacizumab for subfoveal CNV associated with decalcified choroidal osteoma resulted in poor visual acuity. Keywords: choroidal osteoma, choroidal neovascularization, bevacizumab, Avastin, vascular endothelial growth factor

Naoki Ijiri,1 Hiroshi Kanazawa,1 Takahiro Yoshikawa,2 Kazuto Hirata1 1Department of Respiratory Medicine, 2Department of Sports Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan Background: New parameters in the 6-minute walk test (6MWT) are required for comprehensive analysis of exercise capacity in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to apply a novel index, the desaturation distance ratio (DDR), to clinical research on COPD as an estimate of exercise capacity and to examine whether DDR is a potential parameter for manifold analysis of exercise capacity in patients with COPD. Methods: A total of 41 patients with COPD (median age [interquartile range] =75 [68–79] years; and body mass index [BMI] =22.3 [19.4–23.8] kg/m2) participated in the study. The 6MWT was performed along with anthropometric measurements and a pulmonary function test. The “desaturation area” was measured as the total area above the curve created using peripheral oxygen saturation (SpO2) values observed at each minute during the 6MWT. Then the DDR was calculated as the ratio of the desaturation area to the 6-minute walk distance (6MWD). Results: The 6MWD was 370 (328–445) m, and the decline in SpO2 values (ΔSpO2) was -5.0% (-8.0% to -1.5%). The DDR correlated modestly with baseline pulmonary function in patients with COPD (forced expiratory volume in 1 second [% of predicted value]: r=-0.658, P

Kazuya Ofuji, Keigo Saito, Toshiaki Yoshikawa, Tetsuya NakatsuraDivision of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, JapanAbstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The treatment options for patients with advanced HCC are limited, and novel treatment strategies are required urgently. Glypican-3 (GPC3), a member of the glypican family of heparan sulfate proteoglycans, is overexpressed in 72%-81% of HCC cases, and is correlated with a poor prognosis. GPC3 regulates both stimulatory and inhibitory signals, and plays a key role in regulating cancer cell growth. GPC3 is released into the serum, and so might be a useful diagnostic marker for HCC. GPC3 is also used as an immunotherapeutic target in HCC. A Phase I study of a humanized anti-GPC3 monoclonal antibody, GC33, revealed a good safety profile and potential antitumor activity, and a Phase II trial is currently ongoing. In addition, the authors' investigator-initiated Phase I study of a GPC3-derived peptide vaccine showed good safety and tolerability, and demonstrated that the GPC3 peptide-specific cytotoxic T-lymphocyte frequency in peripheral blood correlated with overall survival in HCC patients. A sponsor-initiated Phase I clinical trial of a three-peptide cocktail vaccine, which includes a GPC3-derived peptide, is also underway. GPC3 is currently recognized as a promising therapeutic target and diagnostic marker for HCC. This review introduces the recent progress in GPC3 research, from biology to clinical impact.Keywords: GPC3, hepatocellular carcinoma, immunotherapy

Mariko Kawai,1 Tadanobu Yoshikawa,1 Ryuta Nishikomori,2 Toshio Heike,2 Kanji Takahashi11Department of Ophthalmology, Kansai Medical University, Osaka, 2Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, JapanAbstract: Cryopyrin-associated periodic syndrome (CAPS) is a group of rare hereditary autoinflammatory diseases caused by mutations of the NLRP3 gene, and leads to excessive production of the proinflammatory cytokine, interleukin-lß. A 35-year-old male presented with recurrent symptoms of urticarial-like rash, periodic fever, arthralgia, headache, and eye redness. His best-corrected visual acuity was 1.0 OD and 0.9 OS. Slit-lamp examination showed conjunctival and episcleral injection in both eyes. Ophthalmoscopy revealed obvious bilateral optic disc swelling and retinal vascular sheathing around the optic discs. Spectral domain optical coherence tomography also showed obvious optic disc swelling. Steroid and nonsteroidal anti-inflammatory drugs did not improve these symptoms. Genetic testing detected a heterozygous mutation of c.907G>A. Thus, the patient was genetically confirmed with CAPS. Visual acuity did not decrease for 3 years, although the optic discs became white in color. CAPS should therefore be distinguished from other disorders when examining optic disc swelling and/or uveitis patients with urticarial-like rash and periodic fever.Keywords: interleukin-lß, chronic infantile cutaneous and articular syndrome, cryopyrin-associated periodic syndrome, leucine-rich repeat-containing protein 3, optic disc swelling

Aiming to optimize rhodium recovery in the high temperature recycling process by minimizing rhodium loss into slags in an oxidizing atmosphere by controlling slag composition, the effects of representative slag components, such as Al2O3, MgO, and CuOx, on the dissolution behavior of rhodium into the Na2O-SiO2 slags was investigated. The solubility of rhodium was measured by equilibrating the sodium silicate based slags with pure solid rhodium at 1473 K in air. Considering that rhodium dissolved into slags as RhO1.5, the effect of the oxide addition on the activity coefficient of RhO1.5 in slags was determined. The dissolution of rhodium in slags was suppressed by the addition of Al2O3 and MgO, where Al2O3 behaved as an acidic oxide and MgO behaved as a diluent of slag basicity at a fixed Na2O/SiO2 ratio of 0.97. The content of copper in solid rhodium equilibrated with the CuOx bearing slags slightly increased with increasing content of CuOx, and CuOx was found to slightly enhance the dissolution of rhodium. Rhodate capacity of all slag systems increased with increasing optical basicity, suggesting that the correlation between rhodate capacity and the optical basicity enables the estimation of the content of rhodium in slags of which thermodynamic properties of rhodium are not clarified.

Takahiro Yoshikawa,1 Hiroshi Kanazawa21Department of Sports Medicine, Osaka City University Graduate School of Medicine, 2Department of Respiratory Medicine, Osaka City University Graduate School of Medicine, Osaka, JapanBackground: It is widely recognized that chronic obstructive pulmonary disease (COPD) includes a variety of extra pulmonary complications and comorbidities. Recently, adiponectin was shown to regulate cellular metabolism in humans. Cellular hydration state is affected by a variety of hormonal factors and regulates cellular metabolic state. Therefore, this study was designed to determine whether adiponectin is a possible factor involved in cellular hydration state in COPD.Methods: Thirty patients with COPD and 41 age-matched controls participated in the study. Plasma levels of total and high molecular weight (HMW) adiponectin were measured and anthropometry and pulmonary function tests were conducted. Intracellular water (ICW), extracellular water (ECW), and ECW/ICW ratio, which are parameters of cellular hydration state, were measured using bioelectrical impedance analysis.Results: Higher levels of total and HMW adiponectin in plasma were found in patients with COPD compared with levels in controls. A significant inverse correlation was observed between body mass index and plasma levels of total and HMW adiponectin in the control group. However, this significant correlation was not observed in patients with COPD. The plasma levels of total and HMW adiponectin were also not significantly correlated with any pulmonary function parameters in patients with COPD. Regarding the state of cellular hydration, the plasma levels of total adiponectin were inversely correlated with the ECW/ICW ratio and positively with ICW values in patients with COPD. Moreover, closer correlations were found between these parameters and plasma HMW adiponectin levels.Conclusion: The results of the present study suggest a novel association of the plasma adiponectin with cellular hydration state in patients with COPD. Accordingly, lower adiponectin levels may result in cellular shrinkage, leading to metabolic malfunction at a cellular level. Thus, our findings provide new insights regarding the preventive roles of adiponectin in the progression of comorbidities in COPD.Keywords: adiponectin, bioelectrical impedance analysis (BIA), cellular hydration, COPD, extra pulmonary phenotype

Masato Matsuoka,1 Nahoko Ogata,2 Kayako Matsuyama,1 Tadanobu Yoshikawa,1 Kanji Takahashi31Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, 2Department of Ophthalmology, Nara Medical University, Nara, 3Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, JapanBackground: To determine whether the intraocular pressure (IOP) in diabetic patients is significantly different from that in nondiabetic patients.Methods: The medical records of all patients who were initially examined in the Department of Ophthalmology, Kansai Medical University, Takii Hospital were reviewed. At the initial examination, patients had a detailed interview and underwent a comprehensive ophthalmic examinations. All patients were over 20 years of age and did not have glaucoma.Results: A total of 703 patients were evaluated. The mean (±standard error) IOP of the diabetic patients was 15.5 ± 0.2 mmHg (n = 206), and was significantly higher than the 14.0 ± 0.1 mmHg (n = 497) in the nondiabetic patients (P < 0.0001). The IOP was negatively correlated with age (r = –0.202; P = 0.024) in the diabetic patients and was weakly but significantly correlated with the glycosylated hemoglobin (HbA1c) level (r = 0.240; P = 0.015) in the group with diabetic retinopathy.Conclusion: The significantly higher IOP in diabetic patients and positive correlation of IOP with HbA1c levels in patients with diabetic retinopathy indicate that IOP in diabetic patients is higher, especially in those with poor control of diabetes.Keywords: diabetes mellitus, diabetic retinopathy, intraocular pressure, open-angle glaucoma

Tadanobu Yoshikawa, Kanji TakahashiDepartment of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, JapanAbstract: Choroidal osteoma is a benign tumor of the choroid. Herein, we report a rare case of decalcified choroidal osteoma found in the retina. A 27-year-old woman presented with visual loss. Her best-corrected visual acuity was 20/50 OS. Ophthalmoscopy of the left eye revealed a yellow-white calcified region accompanied by a decalcified region of four disc diameters in size. After 6 years, spectral-domain optical coherence tomography showed a tumor projected strongly upwards from the choroid and partially through the retina with serous retinal detachment, with both a lamellar appearance and mound-like area. The calcified region became more contractive than was observed on the first visit. Conversely, the decalcified region was wider than was observed on the first visit. Her best-corrected visual acuity was 20/400 OS. Choroidal osteoma was worsened by progression of decalcification. The decalcified choroidal osteoma resulted in poor visual acuity, and projected strongly upward from the choroid and into the retina.Keywords: osteoma, decalcification, choroidal osteoma