Objective The purpose of this study was to clarify the clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV.
Methods Among 1,489 pregnant women who visited our hospital in 2010, 26 were positive for hepatitis B surface antigens (HBsAg). Of these subjects, 21 from whom informed consent was obtained were included in this study. The clinical features and HBV markers, including genotypes, were investigated.
Results No adverse events were observed in the subjects or the neonates during pregnancy or the perinatal period. The HBV genotypes were C in 14 cases, D in six cases, and undetermined in one case. Hepatitis B e antigens and a high viral load (>7.0 log copies/mL) were found in four and six subjects with genotype C, respectively, and in none of subjects with genotype D. The alanine aminotransferase (ALT) levels and platelet counts were within the normal ranges during pregnancy in all subjects except two and three subjects with genotype C, respectively. Three subjects with genotype C showed transient elevations of ALT after delivery.
Conclusion The majority of subjects were anti-HBe-positive with normal ALT levels; however, some subjects with genotype C showed a high viral load, elevated ALT levels and/or low platelet counts. The pregnancies and deliveries were safe; however, transient elevations of ALT after delivery were observed in some subjects with genotype C.

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Objective Autoimmune hepatitis (AIH) is a chronic inflammatory disorder of unknown etiology that may proceed to cirrhosis, although some patients already have cirrhosis at the time of AIH diagnosis. The aim of this study was to clarify the clinical characteristics of AIH patients with cirrhosis in Japan.
Methods Questionnaires were sent to liver specialists at four research facilities. Data for 250 patients diagnosed with AIH using the scoring system of the International Autoimmune Hepatitis Group (IAIHG) between 1975 and 2010 were collected and analyzed.
Results The male-to-female ratio was 1:8.3 and the average patient age was 55.6 years. Liver cirrhosis was found in 51 AIH patients (20.4%). Of these, 43 patients (84.3%) had cirrhosis at presentation and eight patients (15.7%) developed cirrhosis during the follow-up period (average follow-up of 82.1 months). There were significant differences between the two groups with and without cirrhosis at presentation with regard to age and biochemical parameters at presentation. There were no significant differences in histology, with the exception of liver fibrosis. The overall 10-year probability of survival was 71.2% vs. 99.3% in the patients with and without cirrhosis (log-rank test, p<0.001). The relapse rate was significantly higher in the patients who developed cirrhosis during treatment than in those who did not develop cirrhosis during treatment (100% vs. 7.5%, p<0.001).
Conclusion Since liver cirrhosis has already developed at presentation in many AIH patients with cirrhosis, it is important to diagnose the disease in the early stage and administer treatment rapidly with corticosteroids or immunosuppressants. In addition, a history of relapse is a risk factor for the development of cirrhosis in Japanese patients with AIH.

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Objective The aim of this study was to investigate the relationship between the high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and homocysteine (Hcy) levels and cardiometabolic risk factors in subjects with and without metabolic syndrome (MetS) in a sample of the Tehranian population.
Methods In this cross-sectional study, 365 individuals aged ≥19 years were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). The serum levels of IL-6, hsCRP and Hcy were determined using the Enzyme Linked Immunosorbent Assay (ELISA) method.
Results Of the 365 subjects, aged a mean of 46.1±16.1 years, MetS was present in 160 (43.8%) individuals. The levels of hsCRP, Hcy and IL-6 were higher in the subjects with MetS. A gradual and significant increase in the levels of hsCRP was found in association with increasing numbers of MetS components after adjusting for sex and age. A strong linear augmentation in the hsCRP levels was observed as the numbers of MetS components increased. Additionally, an increase of 0.40 was observed in the hsCRP levels in association with increases in each component of MetS adjusted for age and sex. The best predictors for the levels of hsCRP, IL-6 and Hcy in the subjects with MetS were hip, waist to height ratio (WHtR) and height, respectively.
Conclusion Hip and WHtR are significant predictors of elevated levels of hsCRP and IL-6 associated with MetS, respectively.

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Objective We prospectively investigated the efficacy of the screening methods for asymptomatic coronary heart disease (CHD) in Japanese patients with type 2 diabetes using the treadmill tolerance test (TTT) as a first-line test or the American Diabetes Association (ADA) guidelines.
Methods The subjects included consecutive inpatients with type 2 diabetes (n=331) assessed with both electrocardiogram (ECG) at rest and TTT. Subjects with abnormal TTT findings were evaluated using stress myocardial perfusion scintigraphy (MPS).
Results A total of 60 out of 69 subjects with positive TTT findings underwent MPS, among whom a total of 22 subjects (6.6% of the total number of subjects) had positive MPS results. Among those with positive MPS results, a total of 14 subjects underwent coronary angiography, eight of whom were determined to have significant coronary artery stenosis. The prevalence rates of hypertension and micro/macroalbuminuria were significantly higher in the MPS-positive group (77.3% and 54.5%, respectively) than in the TTT-negative group (44.7% and 27.1%, respectively). Among the subjects with positive MPS results, 68.2% met the 1998 ADA criteria.
Conclusion Neither the TTT as a first-line test nor the ADA guidelines are sufficiently adequate screening methods to detect asymptomatic CHD in Japanese subjects with type 2 diabetes. Conducting routine screening for asymptomatic CHD in Japanese patients with type 2 diabetes may therefore not be very useful.

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Objective The main objective of our study was to describe the pulmonary distribution of consolidation and ground-glass opacity (GGO) in chest computed tomography (CT) scans of Streptococcus pneumoniae pneumonia. In addition, the percentage of other pulmonary abnormalities was also reported.
Methods We retrospectively evaluated chest CT examinations performed between November 2008 and January 2010 in 39 patients with S. pneumoniae pneumonia. Eight patients with Haemophilus influenzae pneumonia were also included for comparison.
Patients There were 19 women and 28 men with clinical symptoms of fever and productive cough and laboratory findings of leukocytosis with markedly high C-reactive protein levels. Chest X-ray scores before and after treatment were calculated. The average score before treatment was 4. The average score after treatment was 0. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusions. The distribution of parenchymal disease was also analyzed.
Results The chest CT findings in the patients with S. pneumoniae pneumonia consisted primarily of consolidation (56.4%), ground-glass opacity (71.7%), interlobular reticular opacity (69.2%), centrilobular nodules (53.8%), interlobular septal thickening (46.6%), bronchial wall thickening (46.6%), lymph node enlargement (10.2%) and pleural effusion (10.2%). Segmental distribution (65.7%) was seen more frequently than non-segmental distribution (35.9%). Abnormal findings were noticed bilaterally in 14 patients and unilaterally in 25 patients. On both the right and left sides, predominant zonal distributions were seen in the lower lobes. In contrast, among the eight patients with H. influenzae pneumonia, one patient had both segmental and non-segmental distributions and the remaining seven patients had only segmental distributions.
Conclusion In conclusion, segmental distributions of parenchymal abnormalities are more common than non-segmental distributions on chest CT scans of patients with S. pneumoniae pneumonia.

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Objective Post-transcriptional taurine modification at the first anticodon ("wobble") nucleotide is deficient in A3243G-mutant mitochondrial (mt) tRNA^Leu(UUR) of patients with myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Wobble nucleotide modifications in tRNAs have recently been identified to be important in the accurate and efficient deciphering of codons. We herein examined whether taurine can alleviate mitochondrial dysfunction in patient-derived pathogenic cells and prevent clinical symptoms in MELAS patients.
Methods and Results The addition of taurine to the culture media ameliorated the reduced oxygen consumption, decreased the mitochondrial membrane potential, and increased the oxidative stress in MELAS patient-derived cells. Moreover, high dose oral administration of taurine (0.25 g/kg/day) completely prevented stroke-like episodes in two MELAS patients for more than nine years.
Conclusion Taurine supplementation may be a novel potential treatment option for preventing the stroke-like episodes associated with MELAS.

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Objective Neurological manifestations of Behçet's disease (NB) are serious complications. However, their pathogenesis remains unclear. The current study examined the levels of proinflammatory cytokines, including IL-1β, IL-6, IL-8 and TNF-α, in cerebrospinal fluid (CSF).
Methods CSF cytokines were measured using an enzyme-linked immunosorbent assay. CSF was obtained from 17 patients with acute NB, 19 patients with chronic progressive NB and 20 patients with non-inflammatory neurological diseases, including cerebrovascular disease, cervical spondylosis and degenerative diseases.
Results CSF total cell counts and polymorph nuclear leukocyte counts were significantly lower in the patients with chronic progressive NB than in those with acute NB. The CSF levels of IL-6 and IL-8 were markedly elevated in the NB patients compared with those measured in the control patients. There were no significant differences in the CSF levels of IL-6 and IL-8 between the patients with acute NB and those with chronic progressive NB. In contrast, there were no significant differences in the CSF levels of IL-1β and TNF-α among the control, acute NB and chronic progressive NB patients. Consistently, the CSF levels of IL-6 and IL-8 were significantly decreased following successful treatment in both acute NB and chronic progressive NB patients, whereas the CSF levels of IL-1β and TNF-α were not changed significantly. Of note, the CSF levels of IL-6 were significantly correlated with the CSF levels of IL-8 in the patients with acute NB (r =0.7647, p =0.0003) but not in the patients with chronic progressive NB (r =0.1343, p =0.5835).
Conclusion These results indicate that CSF IL-6 and IL-8 play important roles in the pathogenesis of NB. However, the data also suggest that the mechanisms underlying the elevation of CSF IL-6 and IL-8 might be different in patients with acute NB and those with chronic progressive NB.

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Objective There are no rules to predict the time to infectivity negative conversion based on sputum smear conversion or culture conversion during chemotherapy in smear-positive tuberculosis patients. We aimed to develop and validate rules of sputum smear grades and cavitations in the lungs due to tuberculosis.
Methods This study was a retrospective cohort study that consisted of development (n=158, 64±19 years of age) and validation (n=214, 63±20 years of age) steps in different cohorts. We developed a rule with pretreatment smear grades and the existence of cavitations in the lungs due to tuberculosis as independent variables and the duration to infectivity negative conversion as the dependent variable in a Cox hazard model. The smear grade indicating the pretreatment bacterial load was classified into four grades according to the Japanese guidelines. The presence of cavitations was assessed on X-ray. Infectivity conversion was defined according to the criteria of the Japanese Ministry of Health, Labour and Welfare: a patient is currently receiving proper treatment and shows clinical improvement and sputum smears and cultures in any combination are consecutively negative three times.
Results <DEVELOPMENT> We developed an "Infectivity Conversion Score" classifying each patient with a smear grade of I though IV and assessing the existence of cavitations in the lungs due to tuberculosis. <VALIDATION> The median time to infectivity conversion in the validation cohort was 13, 22, 35 and 50 days for Infectivity Conversion Scores I through IV, respectively (p<0.001).
Conclusion We developed and validated Infectivity Conversion Scores.

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We herein report a case of pancreatic undifferentiated carcinoma involving intraductal pedunculated polypoid growth. Duodenoscopy disclosed a congested polypoid mass protruding from the orifice of the papilla of Vater. Endoscopic retrograde pancreatography (ERP) showed a polypoid lesion in Wirsung's duct and Santorini's duct. Pancreatic juice cytology using the cell block method revealed the presence of undifferentiated carcinoma. No extraductal invasion was detected on endoscopic ultrasonography and or intraductal ultrasonography. The patient therefore underwent pancreaticoduodenectomy. A histological examination revealed an intraductal polypoid tumor with a thin stalk without extraductal invasion. The tumor was composed of an abundant mixture of pleomorphic cells, spindle cells, giant cells, and a small amount of adenocarcinoma.

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A 65-year-old woman presenting with cardiac sarcoidosis underwent serial measurement of her serum high-sensitivity cardiac troponin I (Hs-cTnI) and N-terminal proB-type natriuretic peptide (NT-proBNP) concentrations. She was treated with 1,000 mg/day methylprednisolone for 2 days, which was subsequently replaced by 30 mg/day prednisolone, and decreased to 20 mg/day at the time of discharge, 2 months later. Her echocardiogram showed improvements in the left ventricular systolic and diastolic function, along with a decrease in the concentration of Hs-cTnI and NT-proBNP. This is the first report suggesting that Hs-cTnI might be a reliable means of assessing the effects of treatment of cardiac sarcoidosis.

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Thyroid lipomatosis is a rare condition characterized by the presence of abundant mature adipose tissue in the thyroid gland. We herein report the case of a 43-year-old man with chronic renal failure caused by amyloidosis presenting with an asymmetrically enlarging thyroid gland. The patient's thyroid hormone levels were normal, and test results for thyroid autoantibodies were negative. A thyroid scan showed diffuse uptake of the radioisotope with a cold area in the left lobe. The pathology of the thyroidectomy material indicated thyroid lipomatosis, and minimal amyloid staining was noted around the thyroid follicles. Thyroid lipomatosis should therefore be kept in mind when making a differential diagnosis of fatty infiltration of amyloid goiter.

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We herein report the first case of remarkable hypertriglyceridemia induced by aliskiren. A 42-year-old man with chronic kidney disease who had been taking antihypertensive medication for approximately 10 years was treated with aliskiren at a dose of 150 mg/day due to uncontrolled hypertension. Six weeks later, although the patient's blood pressure decreased, a laboratory examination revealed remarkable hypertriglyceridemia and an elevated creatinine level. We suspected the occurrence of an adverse event of aliskiren, and the medication was discontinued. Thereafter, the hypertriglyceridemia and elevated creatinine level spontaneously improved. Transient eosinophilia and a strong-positive response of drug lymphocyte stimulation test (DLST) to aliskiren occurred during the patient's clinical course, and we determined the remarkable hypertriglyceridemia to be an adverse event of aliskiren.

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Slowly Progressive Type 1 Diabetes (SPT1D) is characterized by the absence of insulin dependence at the onset of diabetes and persistent detection of islet cell autoantibodies. These patients with high titers of glutamic acid decarboxylase autoantibodies (GADA) are known to progress to insulin dependence within several years. Low-dose insulin injections have been reported to prevent or delay the decline of insulin secretion in SPT1D patients. We experienced the case of an SPT1D patient with preserved endogenous insulin secretion and good glycemic control achieved with α-glucosidase inhibitor (α-GI) treatment alone for 10 years despite having continuously elevated GADA titers. The details of this case suggest that α-GI treatment might have preventive effects on SPT1D progression.

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Rapidly progressive glomerulonephritis (RPGN) is characterized by the rapid deterioration of the renal function associated with crescent formation on renal biopsies. This report describes a case of RPGN caused by anti-glomerular basement membrane (GBM) glomerulonephritis in an elderly man with severe thrombocytopenia and a platelet count of 1.4×10⁴/μL. Thrombotic microangiopathy (TMA) and heparin-induced thrombocytopenia (HIT) were implicated in the severe decrease in platelets. This report also discusses the pathological background and clinical management of TMA and HIT among patients with anti-GBM glomerulonephritis.

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We herein report an unusual case of spontaneous parathyroid gland rupture. A man was admitted with respiratory distress in September 2010. He had been receiving hemodialysis since 1995. He was diagnosed secondary hyperparathyroidism in 2006 and began receiving cinacalcet therapy in 2009. His intact parathyroid hormone (iPTH) level decreased, and massive traumatic bleeding occurred, following which rupture of the parathyroid gland was detected during surgery. The ruptured gland showed nodular hyperplasia. Previous reports have indicated that parathyroid bleeding is associated with glandular hypertrophy. This is the first report of parathyroid apoplexy occurring after suppression of elevated parathyroid function caused by cinacalcet therapy.

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We herein report the clinical and laboratory characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis (PM/DM). We compared these characteristics with previously published findings. Previous reports and our present cases show that anti-OJ autoantibody-positive interstitial lung disease (ILD) patients with PM/DM lack the manifestations of Raynaud's phenomenon and sclerodactyly and show good prognoses and responses to glucocorticoid therapy. These results indicate that the presence of anti-OJ autoantibodies may be useful for predicting the prognosis of ILD and its clinical course in PM/DM patients.

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A 27-year-old man who had been a smoker since 14 years of age presented with exertional dyspnea. Approximately three years earlier, he had been occupationally been exposed to an organic solvent and felt dyspnea during its use. He later developed severe dyspnea and received treatment for asthma. He had no relevant family history. Chest auscultation revealed decreased breath sounds without rales. Spirometry and high-resolution computed tomography scans suggested a diagnosis of chronic obstructive pulmonary disease (COPD). Video-assisted thoracoscopic surgery performed to obtain a pathological diagnosis confirmed the presence of centrilobular emphysema. High susceptibility, smoking from an early age and organic solvent exposure may have caused early-onset COPD in this case.

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A 64-year-old woman presented with exertional dyspnea. The case was diagnosed as mixed connective tissue disease (MCTD) due to presence of swollen fingers, Raynaud's phenomenon, muscle weakness, positive anti-U1RNP antibody, pericarditis and interstitial pneumonia. Although the histology from a transbronchial lung biopsy (TBLB) indicated organizing pneumonia, corticosteroid therapy was postponed for two months at the patient's request. She died 8 weeks later from acute progressive interstitial pneumonia in spite of the administration of intravenous cyclophosphamide combined with prednisolone. The autopsy revealed exudative and organizing diffuse alveolar damage (DAD). Previous reports have shown that DAD is an extremely rare pulmonary complication in MCTD. This report presents a case of MCTD with acute respiratory failure. This case thus suggests that this therapy should be administered as soon as possible.

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An 81-year-old man was admitted to our hospital due to persistent fever and dyspnea with pulmonary infiltrates. He was treated successfully by discontinuing his current medications, including Sai-rei-to, and administering glucocorticoids. Drug lymphocyte stimulation tests showed a positive result for Sai-rei-to alone, and the resumption of other regular drugs did not re-induce the lung injury. Therefore, we diagnosed the patient with Sai-rei-to-induced lung injury. Sai-rei-to is a combination drug that consists of Sho-saiko-to and Gorei-san. This paper briefly reviews drug-induced lung injury caused by Sai-rei-to or its components with a case report.

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Fludarabine-based therapy is widely approved as a first-line treatment for chronic lymphocytic leukemia (CLL). This treatment is occasionally associated with prolonged myelosuppression. We herein describe the cases of CLL who underwent fludarabine, cyclophosphamide and rituximab (FCR) therapy. Bone marrow examinations performed during periods of prolonged myelosuppression revealed definite myelodysplastic changes in the myeloid and erythroid lineages. G-banded karyotyping analyses revealed cytogenetic abnormalities. The patients were diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Further administration of cytotoxic therapy was aborted, and no progression of t-MDS was recorded throughout the follow-up period in either case. In these cases, the t-MDS was characterized by a short latency interval and a benign clinical course. Because typical t-MDS with aggressive outcomes also occurs during prolonged myelosuppression, the transition of the clinical course in this setting should therefore be carefully watched.

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The early diagnosis and treatment of Takayasu arteritis (TA) is crucial to prevent the devastating complications of vascular insufficiency. This report describes a patient with a persistent fever in whom carotid artery tenderness led to a diagnosis of TA. This case suggests that carotid artery tenderness is a useful physical finding that warrants 2-deoxy-2-[Fluorine-18] fluoro-D-glucose positron emission tomography/computed tomography to confirm a diagnosis of early TA.

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We herein report two cases of multidrug-resistant tuberculosis (MDR-TB) in patients with a history of pulmonary nontuberculous mycobacteriosis (PNTM). A 50-year-old man was diagnosed with MDR-TB five years after receiving treatment for pulmonary Mycobacterium kansasii infection. In the second patient, a 72-year-old woman, the diagnosis of PNTM was confirmed twice with two bronchial washings; she was diagnosed with MDR-TB 29 months after presenting with PNTM. It is highly possible that these two patients were already infected with tuberculosis (TB) at the time of PNTM diagnosis and acquired resistance to anti-TB drugs as a result of undergoing treatment for PNTM.

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