Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells.

INTRODUCTION: Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. MATERIALS AND METHODS: We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005-50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. RESULTS: In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. CONCLUSION: This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.

A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation.

BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months. He showed progressive decrement of compound muscle action potential in the deltoid muscle evoked by 3-Hz repetitive nerve stimulation, a positive edrophonium test, and elevated levels of serum anti-acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG. No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes). Administration of prednisolone and tacrolimus was insufficient to alleviate his symptoms; however, the use of rituximab successfully improved his condition. CONCLUSIONS: Myasthenic symptoms appeared in the process of tapering prednisolone for the treatment of chronic GVHD, supporting the diagnosis of MG associated with chronic GVHD. The present case proposes a possibility that reduction of Tregs might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy with rituximab is beneficial for treatment of refractory MG and GVHD.

The impact of evacuation on the incidence of chronic kidney disease after the Great East Japan Earthquake: The Fukushima Health Management Survey.

BACKGROUND: About 146,000 people were forced into long-term evacuation due to the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. Disaster is known to induce hypertension in survivors for a certain period, but it is unclear whether prolonged disaster stress influences chronic kidney disease (CKD). We conducted an observational cohort study to elucidate the effects of evacuation stress on CKD incidence. METHODS: Participants were individuals living in communities near the Fukushima nuclear power plant, aged 40-74 years without CKD as of their 2011 general health checkup (non-evacuees: n = 9780, evacuees: n = 4712). We followed new-onset CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria] using general annual health checkup data from 2012 to 2014. Association between evacuation and CKD incidence was analyzed using the Cox proportional hazard model. RESULTS: Mean age of the participants at baseline was 65 years, 46.7% were men, and baseline eGFR was 75.7 ml/min/1.73 m2. During the mean follow-up period of 2.46 years, CKD incidence rate was 80.8/1000 and 100.2/1000 person-years in non-evacuees and evacuees, respectively. Evacuation was a significant risk factor of CKD incidence after adjusting for age, gender, obesity, hypertension, diabetes, dyslipidemia, smoking, and baseline eGFR [hazard ratio (HR): 1.45; 95% confidence interval (CI) 1.35-1.56]. Evacuation was significantly associated with the incidence of eGFR <60 ml/min/1.73 m2 (HR: 1.48; 95% CI 1.37-1.60), but not with the incidence of proteinuria (HR: 1.21; 95% CI 0.93-1.56). CONCLUSION: Evacuation was a risk factor associated with CKD incidence after the disaster.

A case of lymphomatosis cerebri mimicking inflammatory diseases.

BACKGROUND: Lymphomatosis cerebri (LC) is a rare subtype of primary central nervous system malignant lymphoma. The typical features of this disease exhibited on magnetic resonance imaging (MRI) without contrast enhancement are similar to those observed with diffuse leukoencephalopathy, mimicking white matter disorders such as encephalitis. Clinical features and examination findings that are suggestive of inflammatory diseases may indeed confound the diagnosis of LC. CASE PRESENTATION: A 66-year-old woman with continuous fever over a two-month period developed left hemiparesis despite presenting in an alert state with normal cognitive function. Sampling tests showed autoantibodies in the serum and inflammatory changes in the cerebrospinal fluid. The results from an MRI demonstrated multiple non-enhanced brain lesions in the splenium of the corpus callosum and deep white matter. Single photon emission computed tomography revealed increases in blood flow in the basal ganglia, thalamus and brainstem. No systemic malignancies were found. The patient was suspected of having a diagnosis of nonvasculitic autoimmune inflammatory meningoencephalitis and treated with intravenous methylprednisolone pulse therapy. Her fever transiently dropped to within the normal range. However, she had a sudden seizure and a second MRI exhibited infiltrative lesions gradually extending throughout the whole brain. We performed a brain biopsy, and LC was histologically diagnosed. The patient received whole-brain radiation therapy, which diminished the fever and seizures. The patient died one year after the initial onset of fever. CONCLUSIONS: The present case yields an important consideration that brain neoplasms, especially LC, cannot be ruled out, even in cases with clinical characteristics and examinations consistent with inflammatory diseases. Careful follow-up and histological study are vital for the correct diagnosis of LC.

Mitogen-activated protein kinases-dependent induction of hepatocyte growth factor production in human dermal fibroblasts by the antibiotic polymyxin B.

Hepatocyte growth factor (HGF) stimulates migration and proliferation of keratinocytes and has been suggested to be involved in wound healing. The cationic antibiotic polymyxin B (PMB) is commonly used as a topical antibiotic for wound care. If PMB possesses an HGF-inducing activity, the antibiotic is potentially beneficial for wound healing in addition to minimizing chances of infection. In this study, we found that PMB markedly induced HGF production from various types of cells including human dermal fibroblasts. Its effect was stronger than the effects of epidermal growth factor and cholera toxin and was comparable to the effect of 8-bromo-cAMP. Among the polymyxin family and polymyxin derivatives, colistin was also effective, whereas colistin methanesulfonate had only a marginal effect and PMB nonapeptide was ineffective. The stimulatory effect of PMB was accompanied by upregulation of HGF gene expression. Increase in phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) was observed from 0.25 h to 6h after the addition of PMB, while increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) was detected from 24h to 60 h after PMB addition. The MAPK/ERK kinase inhibitor PD98059, the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 all potently inhibited PMB-induced HGF production. Lastly, proliferation of human dermal fibroblasts was significantly stimulated by PMB. These results indicate that PMB-induced HGF production and proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the induction of HGF production.

Different degrees of loss of function between GEFS+ and SMEI Nav 1.1 missense mutants at the same residue induced by rescuable folding defects.

Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) differ in their clinical severity and prognosis even though mutations of the Na(v) 1.1 sodium channel are responsible for both disorders. We compared the electrophysiologic properties of two mutant Na(v) 1.1 channels characterized by distinct amino acid substitutions at the same residue position: GEFS+ (A1685V) and SMEI (A1685D). Both the mutants showed complete loss of function when expressed alone. However, the function of A1685V can be partly rescued by the ß(1) subunit, consistently with a folding defect, whereas that of A1685D was not rescued. These electrophysiologic differences are consistent with the divergence in clinical severity between GEFS+ and SMEI.

Nephrotic Syndrome and Atypical Posterior Reversible Encephalopathy Syndrome in a Patient with Parkinson's Disease.

A 59-year-old man with advanced Parkinson's disease treated using levodopa-carbidopa intestinal gel (LCIG) presented with leg edema, hypoalbuminemia, and proteinuria at 1 year after the treatment. He subsequently developed a generalized tonic-clonic seizure, and brain magnetic resonance imaging indicated vasogenic edema in the white matter of the left frontal subcortex. He was diagnosed with nephrotic syndrome (NS) and atypical posterior reversible encephalopathy syndrome (PRES). LCIG cessation and corticosteroid treatment improved the NS. To our knowledge, this is the first case report of NS and atypical PRES in patients with Parkinson's disease. Patients being treated with LCIG should be closely monitored for NS.

[Wernicke encephalopathy in a non-alcoholic patient with diabetic nephropathy under hemodialysis].

A 75-year-old man with diabetic nephropathy treated with hemodialysis visited to a medical office because of slight fever, and received intravenous glucose infusion without any vitamins. Thereafter, he noticed gait disturbance and began to tell inconsistent stories. He was admitted to our hospital due to aggravation of these symptoms. On admission, he was disoriented and not able to sit by himself because of severe truncal ataxia without weakness. He had also gaze direction nystagmus. Based on clinical features, we considered him as having Wernicke's encephalopathy (WE) and treated him with 100 mg thiamine per day. The thiamine supply diminished these symptoms soon. Plasma thiamine level prior to the administration was 7 ng/ml, which confirmed the diagnosis. MRI did not disclose any abnormalities frequently seen in WE. WE is a life-threatening disease, and 'early detection, early cure' is important for recovering without sequelae. The thiamine deficiency is often seen in dialysis patients because of dietary restrictions as well as its loss during dialysis. This case gives us the caution; when hemodialysis patients present acute/subacute gait disturbance and/ or abnormal mental state, we should consider WE. Furthermore, high-risk patients, such as elderly patients under hemodialysis may need some supplement including thiamine even at preclinical stage.

Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp.

Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation. Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14,000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon.

Induction of hepatocyte growth factor expression by maleic acid in human fibroblasts through MAPK activation.

Carboxylic acids have various biological activities and play critical roles in cellular metabolic pathways such as the tricarboxylic acid (TCA) cycle. It has been shown that some carboxylic acids induce cell proliferation and production of cytokines or growth factors. However, there have been no reports on effects of carboxylic acids on hepatocyte growth factor (HGF) expression. In this study, we found that only maleic acid among various carboxylic acids examined markedly induced HGF production from human dermal fibroblasts. Maleic acid also induced HGF production from human lung fibroblasts and neuroblastoma cells. The stimulatory effect was accompanied by upregulation of HGF gene expression. Increase in phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) but not in phosphorylation of p38 was observed from 6 h and up to 24 h after maleic acid addition. The ERK kinase inhibitor PD98059 and the JNK inhibitor SP600125 potently inhibited maleic acid-induced HGF production, while the p38 inhibitor SB203580 did not significantly inhibit the production. The protein synthesis inhibitor cycloheximide completely inhibited upregulation of HGF mRNA induced by maleic acid but superinduced HGF mRNA expression upregulated by 12-O-tetradecanoylphorbol 13-acetate (TPA). These results suggest that maleic acid indirectly induced HGF expression from human dermal fibroblasts through activation of ERK and JNK and that de novo protein synthesis is required for maleic acid-induced upregulation of HGF mRNA.

Effects of lifestyle on hepatobiliary enzyme abnormalities following the Fukushima Daiichi nuclear power plant accident: The Fukushima health management survey.

Dramatic lifestyle changes due to the Fukushima Daiichi Nuclear Power Plant accident increased the prevalence of hepatobiliary enzyme abnormalities (HEA). We aimed to evaluate associations of HEA with specific lifestyle- and disaster-related factors in residents who lived near the Fukushima Daiichi Nuclear Power Plant.This cross-sectional study included 22,246 residents who underwent a Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Residents were divided into 2 groups based on residential area and housing status after the accident. Associations between HEA and lifestyle- and disaster-related factors, including psychological distress, were estimated using logistic regression analysis adjusted for demographic and lifestyle factors.HEA was present in 27.3% of subjects. The prevalence of HEA was significantly higher in evacuees than controls (29.5% vs 25.7%, P < .001). There were significant differences in various lifestyle characteristics and the prevalence of post-traumatic stress disorder between evacuees and controls. Multivariable logistic regression analysis showed that age, sex, moderate to heavy drinking, and low/no physical activity were significantly associated with HEA regardless of evacuation status. Changes in jobs and unemployment were significantly associated with HEA in controls and evacuees, respectively.Lifestyle and disaster-related factors, but not psychological distress, were associated with HEA among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.

Epilepsy and ion channels.

Many mutations of genes for ion channels result in some epilepsies. Their electrophysiological studies reveal pathophysiological mechanisms underlining epilepsy and also mechanism of action of several antiepileptic drugs. In this review, We briefly summarize pathophysiology of epilepsy and the mechanisms of antiepileptic drugs.

Cryptogenic NORSE: Its distinctive clinical features and response to immunotherapy.

OBJECTIVE: To report the distinctive clinical features of cryptogenic new-onset refractory status epilepticus (C-NORSE) and the C-NORSE score based on initial clinical assessments. METHODS: A retrospective study was conducted for 136 patients with clinically suspected autoimmune encephalitis who underwent testing for autoantibodies to neuronal surface antigens between January 1, 2007, and August 31, 2016. Eleven patients with C-NORSE were identified. Their clinical features were compared with those of 32 patients with anti-NMDA receptor encephalitis (NMDARE). RESULTS: The clinical outcome of 11 patients (median age, 27 years; 7 [64%] women) with C-NORSE was evaluated after a median follow-up of 11 months (range, 6-111 months). Status epilepticus was frequently preceded by fever (10/11 [91%]). Brain MRIs showed symmetric T2/fluid-attenuated inversion recovery hyperintensities (8/11 [73%]) and brain atrophy (9/11 [82%]). Only 2 of the 10 treated patients responded to the first-line immunotherapy, and 4 of the 5 patients treated with IV cyclophosphamide responded to the therapy. The long-term outcome was poor in 8 patients (73%). Compared with 32 patients with NMDARE (median age, 27 years; 24 [75%] women), those with C-NORSE had more frequent prodromal fever, status epilepticus, ventilatory support, and symmetric brain MRI abnormalities, had less frequent involuntary movements, absent psychobehavioral symptoms, CSF oligoclonal bands, or tumor association, and had a worse outcome. The C-NORSE score was higher in patients with C-NORSE than those with NMDARE. CONCLUSIONS: Patients with C-NORSE have a spectrum of clinical-immunological features different from those with NMDARE. The C-NORSE score may be useful for discrimination between them. Some patients could respond to immunotherapy.

Discovery of a Slow Tight Binding LPA1 Antagonist (ONO-0300302) for the Treatment of Benign Prostatic Hyperplasia.

Scaffold hopping from the amide group of lead compound ONO-7300243 (1) to a secondary alcohol successfully gave a novel chemotype lysophosphatidic acid receptor 1 (LPA1) antagonist 4. Wash-out experiments using rat isolated urethra showed that compound 4 possesses a tight binding feature to the LPA1 receptor. Further modification of two phenyl groups of 1 to pyrrole and an indane moiety afforded an optimized compound ONO-0300302 (19). Despite its high i.v. clearance, 19 inhibited significantly an LPA-induced increase of intraurethral pressure (IUP) in rat (3 mg/kg, p.o.) and dog (1 mg/kg, p.o.) over 12 h. Binding experiments with [3H]-ONO-0300302 suggest that the observed long duration action is because of the slow tight binding character of 19.

Persistent prevalence of polycythemia among evacuees 4 years after the Great East Japan Earthquake: A follow-up study.

We previously reported that the lifestyle of evacuees significantly increased the prevalence of polycythemia compared with non-evacuees at an average of 1.6 years (2011-2012) from the previous annual health checkup before the Great East Japan Earthquake (GEJE). Here we analyzed how the prolonged evacuation affected the prevalence of polycythemia an average of 2.5 years (2013-2014) after the previous data. Subjects were individuals aged 40-90 years living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture who had attended the annual health checkups since 2008. The prevalence of polycythemia and changes in its defining factors of red blood cell count (RBC), hemoglobin (Hb) level, hematocrit (Ht) level were compared between before and after the GEJE in 7713 individuals (3349 men and 4364 women) receiving follow-up examinations both 2011-2012 and 2013-2014. RBC, Hb levels and Ht levels in 2011-2012 were higher among evacuees than non-evacuees in both men and women. However, all levels in 2013-2014 were on the decline from those in 2011-2012. On the other hand, among evacuees, Hb and Ht levels continued to be higher than before the GEJE in both men and women evacuees. The prevalence of polycythemia, which was diagnosed if one of the defining factors was beyond the standard value, was significantly higher among evacuees than non-evacuees regardless of the presence or the absence of overweight/obesity, smoking, and hypertension. Therefore, prolonged evacuation is a cause of polycythemia even 3 to 4 years after the GEJE and regular health management of evacuees is important.

Changes in Hepatobiliary Enzyme Abnormality After the Great East Japan Earthquake: The Fukushima Health Management Survey.

Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3-4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3-4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.

Lifecorder: a new device for the long-term monitoring of motor activities for Parkinson's disease.

OBJECTIVE: To quantitatively evaluate motor activity, its fluctuations, and drug effects in patients with Parkinson's disease (PD), the Lifecorder, a new monitoring device, was attached to a group of patients for several weeks. This enabled the continuous recording of motor activity in ten scaled magnitudes at two-minute intervals for 6 weeks. PATIENTS AND METHODS: Thirteen patients with PD who required dopamine receptor agonist therapy were monitored with Lifecorder, and seven healthy subjects served as the control group. The data obtained with this device correlated well with the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr grading. The dose of cabergoline, a D2-receptor agonist, was increased every 2 weeks, until optimum improvement was achieved. RESULTS: By adding cabergoline, the mean UPDRS improved from 40.5 to 28.4, which was significant. In parallel, the mean daily walking count (WC) also increased from 2,459 to 3,315 steps (p < 0.01) and movement-related calorie consumption (MCC) increased from 56 to 74 kcal (p < 0.05). UPDRS thus correlated well with WC and MCC (p < 0.05) obtained with this device. The improvement ratio of WC and MCC of each individual patient was compared with that of UPDRS. WC, and MCC shifted in parallel with UPDRS with one exception. The daily time-dependent fluctuation of motor activity was clearly shown by the Excel-generated graphs to improve with D-agonist therapy. In contrast to enhanced daytime activities, nocturnal restfulness was also clearly documented with this device. CONCLUSION: The unique properties of Lifecorder make this device a useful adjunct to the UPDRS for the objective evaluation of Parkinsonian motor activity. The device has a significant advantage over conventional clinical scales, as daytime as well as nocturnal motor activity can be objectively evaluated over long time periods ranging from one hour to one month, and the magnitude of motor activity is quantifiable in relation to the time-course.

[Marked thickening of the peripheral nerves in chronic inflammatory polyradiculoneuropathy associated with HCV infection].

We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a middle-aged patient with hepatitis C virus (HCV) infection. A 49-year-old man presented chronic progressive distal motor weakness and sensory disturbances. Laboratory findings indicated chronic liver dysfunction due to HCV infection, transient positive serum cryoglobulinemia and marked decreased motor and sensory conduction velocities in electrodiagnosis. Lumbar MRI showed marked hypertrophy of the bilateral lumbar radicular nerve roots. Steroid treatment, not IVIg, improved neurological manifestation of this patient, but the serum HCV-RNA level was extremely increased after this treatment. Choice of treatment for patients suffered from CIDP associated with HCV infection is still controversial. Newly discovered patients with HCV infection are increased in Japan in number according to the routine check their anti-HCV antibodies. It is important to monitor carefully the serum HCV-RNA level in CIDP patients associated with HCV infection when steroid treatment is initiated.

[Remarkable rightward shift of the mediastinum during a urological operation in the left kidney position--a case report].

Mediastinal rightward shift without involving cardiovascular collapse and dyspnea occurred after a left nephroureterectomy. An 86-year-old female (height, 142 cm; weight, 53 kg) with ureteral cancer was scheduled for an elective nephroureterectomy. Preanesthetic electrocardiogram revealed supraventricular premature contractions and sinus tachycardia (116 beats.min-1) and preanesthetic chest X-ray film revealed cardio-thoracic ratio of 60% and pleural adhesion of the right apex of the lung. Anesthesia was maintained with a combination of inhalation anesthetics (oxygen, nitrous oxide and sevoflurane) and thoracic epidural lidocaine. Artificial ventilation was used during the anesthesia. The operation was uneventful. A chest radiograph taken at the end of the operation demonstrated a large mass-like shadow in the right field of the lung. However, dyspnea or cardiovascular collapse was not observed. The vesicular sounds were auscultated in the left lung field. Results of arterial blood gas analysis during spontaneous respiration were within normal ranges. A CT scanning of the chest showed that the great vessel and the heart had been in the right thoracic cavity. Therefore, we considered that a rightward mediastinal shift had occured during the operation.