Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Antibacterial activity of lysozyme-chitosan oligosaccharide conjugates (LYZOX) against Pseudomonas aeruginosa, Acinetobacter baumannii and Methicillin-resistant Staphylococcus aureus.

The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. This study evaluated the antibacterial activity of lysozyme-chitosan oligosaccharide conjugates (LYZOX) against Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA), which should resolve the problem of antibiotic-resistant bacteria. Bactericidal tests showed that LYZOX killed 50% more P. aeruginosa (NBRC 13275), A. baumannii and MRSA than the control treatment after 60 min. In addition, LYZOX was shown to inhibit the growth of P. aeruginosa (NBRC 13275 and PAO1), A. baumannii and MRSA better than its components. To elucidate the antibacterial mechanism of LYZOX, we performed cell membrane integrity assays, N-phenyl-1-naphthylamine assays, 2-nitrophenyl ß-D-galactopyranoside assays and confocal laser scanning microscopy. These results showed that LYZOX affected bacterial cell walls and increased the permeability of the outer membrane and the plasma membrane. Furthermore, each type of bacteria treated with LYZOX was observed by electron microscopy. Electron micrographs revealed that these bacteria had the morphological features of both lysozyme-treated and chitosan oligosaccharide-treated bacteria and that LYZOX destroyed bacterial cell walls, which caused the release of intracellular contents from cells. An acquired drug resistance test revealed that these bacteria were not able to acquire resistance to LYZOX. The hemolytic toxicity test demonstrated the low hemolytic activity of LYZOX. In conclusion, LYZOX exhibited antibacterial activity and low drug resistance in the presence of P. aeruginosa, A. baumannii and MRSA and showed low hemolytic toxicity. LYZOX affected bacterial membranes, leading to membrane disruption and the release of intracellular contents and consequent bacterial cell death. LYZOX may serve as a novel candidate drug that could be used for the control of refractory infections.

Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease.

BACKGROUND: There is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease. METHODS: We conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model. RESULTS: Mean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups. CONCLUSIONS: Mild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.

Propionibacterium acnes-derived insoluble immune complexes in sinus macrophages of lymph nodes affected by sarcoidosis.

BACKGROUND: Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions. METHODS: We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes. RESULTS: Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 µm diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance. CONCLUSIONS: P. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.

Radiopathological Features and Identification of Mycobacterial Infections in Granulomatous Nodules Resected from the Lung.

BACKGROUND: Pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG). Mycobacterial infection is a common cause of granulomas. OBJECTIVE: The purpose of this study was to evaluate the radiopathological features and the methods for identifying mycobacterial infections in granulomatous nodules resected from the lung. METHODS: Thirty-five solitary lesions resected because of suspected lung cancer were enrolled, including 22 nonfungal granulomatous lesions and 13 benign lesions as controls. The radiological, microbiological, and histological findings were reviewed. To identify mycobacterial infection, immunohistochemical (IHC) staining, IS6110 polymerase chain reaction (PCR), and real-time PCR for the detection of Mycobacterium tuberculosis (TB) were performed using formalin-fixed and paraffin-embedded tissue specimens. The correlations between the radiopathological features and the median maximum standardized uptake value (SUVmax) of 18F-FDG PET were also evaluated. RESULTS: Mycobacteria were isolated from the cultures of 10 of the granulomatous lesions, including TB from 2 and Mycobacterium avium complex from 8. The mean size of the nodules in the culture-positive group was significantly larger than that of those in the culture-negative group (30.5 ± 13.1 vs. 15.1 ± 6.3 mm, p = 0.003). IHC stainings were positive in 15 granulomas. Eight granulomas were positive in IS6110 PCR, and 7 of them were also positive in real-time PCR. SUVmax was ≥2.5 in all of the PCR-positive granulomas. CONCLUSION: The most frequent cause of granulomatous lesions was mycobacterial infection. It seemed that the culture result was associated with nodule size and that the results of IS6110 were associated with 18F-FDG-uptake.

Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan.

Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels. Methods The data were collected from the medical records. Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement. Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time. Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required.

[Fatal nontuberculous mycobacterial lung disease caused by Mycobacterium kyorinense: a case report with five years of follow-up].

An 85-year-old man with dementia first visited our hospital 5 years ago, complaining of hemoptysis. He was hospitalized 2 years later owing to fever, cough, and dyspnea. A chest computed tomography scan showed infiltration with a cavity in the left upper lobe. He was diagnosed with nontuberculous mycobacterial lung infection on the basis of the presence of acid-fast bacilli in the sputum and repeated bronchoalveolar lavage specimens; however, we were unable to identify the isolate by DNA-DNA hybridization. Although his general condition had slightly improved after treatment initiation, intermittent chemotherapy owing to the adverse effects of the drugs and dementia led to rapid disease progression and death. After his death, the isolated mycobacterium was identified as Mycobacterium kyorinense by sequence analysis of the hsp 65 and rpoB genes.

Immunological responses and epitope mapping by tuberculosis-associated antigens within the RD1 region in Japanese patients.

Tuberculosis remains a major global health problem worldwide, and hence there is a need for novel vaccines that better induce cellular-mediated immunity (CMI). In search of a better vaccine target, the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and the interferon-γ ELISPOT assay (ELISPOT) were used to compare the magnitude of CMI in patients. Results of the ELISPOT assay led to the discovery of specific epitopes within the early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10) proteins. Both peptides showed a strong association with several HLA class II DRB1 molecules in the Japanese population. Using ESAT-6-specific HLA class II tetramers, we determined that the expression of ESAT-6-specific CD4+ lymphocytes was significantly decreased in treated patients compared with active patients. In addition, programmed death-1 (PD-1)/killer cell lectin-like receptor G1 (KLRG-1) double positive cells were found only in treated patients and not in those with active TB. These data could provide clues for the development of novel tuberculosis vaccines.

Discrimination of Mycobacterium abscessus subsp. massiliense from Mycobacterium abscessus subsp. abscessus in clinical isolates by multiplex PCR.

The rapidly growing mycobacterium M. abscessus sensu lato is the causative agent of emerging pulmonary and skin diseases and of infections following cosmetic surgery and postsurgical procedures. M. abscessus sensu lato can be divided into at least three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Clinical isolates of rapidly growing mycobacteria were previously identified as M. abscessus by DNA-DNA hybridization. More than 30% of these 117 clinical isolates were differentiated as M. abscessus subsp. massiliense using combinations of multilocus genotyping analyses. A much more cost-effective technique to distinguish M. abscessus subsp. massiliense from M. abscessus subsp. abscessus, a multiplex PCR assay, was developed using the whole-genome sequence of M. abscessus subsp. massiliense JCM15300 as a reference. Several primer sets were designed for single PCR to discriminate between the strains based on amplicons of different sizes. Two of these single-PCR target sites were chosen for development of the multiplex PCR assay. Multiplex PCR was successful in distinguishing clinical isolates of M. abscessus subsp. massiliense from samples previously identified as M. abscessus. This approach, which spans whole-genome sequencing and clinical diagnosis, will facilitate the acquisition of more-precise information about bacterial genomes, aid in the choice of more relevant therapies, and promote the advancement of novel discrimination and differential diagnostic assays.

[Pulmonary thromboembolism with pulmonary tuberculosis].

Out of 77 patients who were admitted to our hospital because of pulmonary tuberculosis from January 2007 to October 2009, 3 patients (3.9%) suffered from pulmonary thrombotic embolism (PTE) and/or deep venous thrombosis (DVT). Case 1: An 80-year-old male with elevated D-dimer was diagnosed with PTE on the basis of an enhanced chest CT showing filling defects in the bilateral pulmonary arteries. Case 2: A 39-year-old male presented with prolonged high-grade fever even after administration of anti-tuberculosis drugs and complained of weakness. His D-dimer was high on admission and became still higher; then, edema was found on his left lower limb, and he was diagnosed with DVT on the basis of lower limb ultrasonography showing isoechoic thrombosis from the IVC to the left popliteal vein. An IVC filter was needed to treat his lesion. Case 3: A 69-year-old female with elevated D-dimer and edema on the right lower limb was diagnosed with PTE and DVT on the basis of chest CT findings. Since anti-coagulation therapy could not be continued due to intestinal bleeding, an IVC filter was placed. All 3 cases presented with no dyspnea and two of the three cases showed no hypoxemia. Even in cases of pulmonary tuberculosis without dyspnea, D-dimer seems to be useful for the early diagnosis of thromboembolism.

Pulmonary Artery Leiomyosarcoma Diagnosed without Delay.

A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT) revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma). Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score) for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.

Successful diagnosis of a combined thymic epithelial tumor by endobronchial ultrasound-guided transbronchial needle aspiration.

INTRODUCTION: Endobronchial ultrasound-guided tranbronchial needle aspiration (EBUS-TBNA) can be applied to not only the determination of the clinical stages of lung cancer, but also the diagnosis of lymphadenopathies such as lymphoma and sarcoidosis. CASE REPORT: We report the successful diagnosis of a combined thymic epithelial tumor in a 68-year-old female by EBUS-TBNA. The patient presented with a 6-month history of dysesthesia in bilateral legs. Chest computed tomography revealed a 5.5 cm-tumor with heterogeneous enhancement in the superior and anterior mediastinum. The serum levels of ProGRP and NSE were elevated and anti-Hu antibody was positive at the time of diagnosis. A biopsy by EBUS-TBNA revealed histological evidence of a combined thymic epithelial tumor consisting of small cell neuroendocrine carcinoma and thymic carcinoma. Chemo-radiotherapy reduced the tumor remarkably in size, but the patient's neurologic symptoms remained. CONCLUSION: This case suggests that EBUS-TBNA is a safe and useful technique for the diagnosis of paratracheal mediastinal tumors.

Quality of life of lung cancer patients receiving outpatient chemotherapy.

An increasing number of cancer patients receive outpatient chemotherapy as an alternative to inpatient chemotherapy. The aim of this study was to investigate whether quality of life (QOL) during outpatient chemotherapy was better than QOL prior to hospital discharge, and to explore possible related factors prior to hospital discharge that affected the QOL of lung cancer patients who received outpatient chemotherapy. Lung cancer inpatients who were scheduled for outpatient chemotherapy were assessed two times (prior to hospital discharge and during outpatient chemotherapy) using the Functional Assessment of Cancer Therapy-Lung and Hospital Anxiety and Depression Scale. A total of 40 patients completed all assessments, both prior to hospital discharge and during outpatient chemotherapy. In the present study, QOL during outpatient chemotherapy was not significantly different when compared with the QOL prior to hospital discharge, and predictors prior to hospital discharge for a better QOL of patients during outpatient chemotherapy included better social, emotional and physical well-being. These results suggest that medical staff, in particular those involved in outpatient chemotherapy, need to recognize social and emotional as well as physical well-being prior to hospital discharge, regardless of cancer-related factors and the personal characteristics of the patients.

Gastric myoelectrical differences between Parkinson's disease and multiple system atrophy.

The electrogastrogram (EGG) was recorded for 24 hours in 17 Parkinson's disease (PD) patients, 17 multiple system atrophy (MSA) patients, and 8 healthy control subjects to elucidate the differences in the EGG findings between the two diseases. Eight EGG segments (3 preprandial, 3 postprandial, and 2 sleep segments) were selected from the total recording for spectral analysis, from which we obtained the dominant frequency (DF), instability coefficient of DF (ICDF), and low (LFR%), normal (NFR%), and high (HFR%) range power percentages of the total power. PD patients showed irregular slow waves, high HFR%, and high ICDF, whereas MSA patients showed regular slow waves and low ICDF. Although DF and NFR% increased after meal in controls, postprandial increases in DF and NFR% were less significant in both patient groups compared to the controls. The PD patients presented gastric dysrhythmias indicating gastric pacemaker disturbances. The MSA patients showed regular slow waves with low variability of the slow wave rhythm (low ICDF), which might have resulted from the involvement of gastric autonomic nerve function.

Astrocytic tau pathology positively correlates with neurofibrillary tangle density in progressive supranuclear palsy.

Tufted astrocytes (TAs) are considered reliable, specific markers for the neuropathologic diagnosis of progressive supranuclear palsy (PSP). It is known that neurofibrillary tangles (NFTs) may relate directly to neurodegeneration, but the role of glial tau pathology is not well determined. To examine the hypothesis that TAs are as pathogenic as NFTs and that both might have a common accumulation, we evaluated the topographic relationship between TAs and NFTs in 12 cases of PSP. The sections of 13 different parts of the brain were stained using the Gallyas-Braak method, and TAs and NFTs were counted and compared statistically. The number of TAs significantly correlated with that of NFTs in the central gray matter, pontine nuclei, and tegmentum, which are responsible for the main symptoms in PSP. In the examined allocortex, however, NFTs were abundant without accompanying TAs. Staining with the specific antibody for 4-repeat tau (RD4) and 3-repeat tau (RD3) was performed to clarify this discrepancy from the standpoint of tau isoforms. NFTs in the entorhinal cortex were stained with both RD3 and RD4, but NFTs in the premotor cortex were stained with only RD4. The nature of NFTs in the allocortical area was different from that of the isocortex in PSP. TAs in the isocortex may share the same pathologic cascade with NFTs stained only by RD4. These results suggest that TAs are part of the same pathologic process as NFTs in PSP.

[Thyroid crisis and protein C deficiency in a case of superior sagittal sinus thrombosis].

We report the case of a 28-year-old woman who presented simultaneously with superior sagittal sinus thrombosis and thyroid crisis, and was subsequently found to have protein C deficiency. February 3, 2003, she admitted complaining of abdominal pain. The diagnosis of appendicitis was made, and she was operated on under lumbar anaesthesia. Day 7, she developed acute headache and distal weakness of the left lower limb. On examination she was alert, with a temperature of 38 degrees C, a sinus tachycardia of 124/min and blood pressure 164/84 mmHg. Neurological examination revealed neck stiffness and left hemiparesis, predominantly in her lower limb. Gadlinium-enhanced brain MRI revealed extensive superior sagittal sinus thrombosis. CT scan demonstrated infarction in the right frontal cortex, and subarachnoid hemorrhage adjacent to the right cerebellar tentorium. The patient was treated with a free radical scavenger edarabon, and glycerin. No anticoagulant therapy was instituted. Over the next 24 hours, her condition worsened. She became comatose, as well as developing a generalized tonic-clonic seizure. Day 12, laboratory examinations revealed an undetectable TSH-level CTSH (thyroid stimulating hormone) <0.005 mcIU/ml), with a level of free thyroxin 7.77 ng/dl (0.9-1.7), free triiodothyronin 29.6 pg/ml (2.3-4.3), and positive anti-TSH receptor antibodies determined subsequently. Coagulation factor VIII activity was 155% (normal range 60-150). Protein C deficiency (antigen 59%, activity 49%) was also present, suggesting a congenital type I heterozygous deficiency. A diagnosis of thyroid crisis on the basis of Graves' disease was made. The patient remained comatose and died on Day 16, with renal failure. The patient had protein C deficiency, a well-established risk factor for cerebral venous thrombosis (CVT). However, additional risk factors are required in most cases to precipitate CVT. In our case, this trigger was most likely thyroid crisis, suggesting that thyrotoxicosis, probably through hypercoagulability, may be a predisposing factor for the development of CVT.

Chronic inflammatory demyelinating polyneuropathy associated with idiopathic hemochromatosis.

We describe a 50-year-old woman who developed chronic inflammatory demyelinating polyneuropathy (CIDP) one year after onset of hemochromatosis. Electrodiagnostic studies showed evidence of multifocal demyelination. Marked hypergammaglobulinemia with positive anti-nuclear and anti-DNA antibodies was found. Corticosteroid treatment resulted in a significant lessening of neurological symptoms. This is the first case of CIDP with hemochromatosis. The association may be coincidental, but the altered immune system by hemochromatosis was possibly related to the development of CIDP in this patient.

[A patient with Guillain-Barré syndrome and recurrent episodes of ST elevation and left ventricular hypokinesis in the anterior wall].

A-65-year old woman who developed total ophthalmoplegia, areflexia in all her limbs and ataxia after upper respiratory tract infection was admitted to our hospital on the second day of illness. On day 3, she developed severe tetraparesis and respiratory failure which required mechanical ventilation, and Guillain-Barré syndrome (GBS) was diagnosed. On day 4, bilateral ptosis, facial diplegia, and neck muscle weakness appeared, and her all limbs were flaccid and immobile. An electrophysiological study suggested axonal damage. Marked blood pressure fluctuation also appeared on day 4. On day 5, an electrocardiogram showed a ST-segment elevation in leads V1 through V4 and the echocardiography showed anterior hypokinesia of the left ventricle. Her serum creatine kinase was normal. Left ventricular dysfunction and ST-segment elevation were normalized within hours, but a transient ST-segment elevation re-occurred on day 6. An electrocardiogram on day 13, showed inverted T waves in diffuse leads, which inversion continued. ST-segment elevation and hypokinesia in this patient were restricted to the left anterior descending branch, therefore, coronary spasm of that branch was considered the possible mechanism. In contrast, inverted T wave was due to either catecholamine cardiotoxicity or diffuse cardiac ischemia. Abnormalities of electrocardiogram were presumably due to cardiovascular autonomic dysfunction of GBS.