Objective The aim of this study was to evaluate the efficacy of combination therapy of peginterferon and ribavirin in patients infected with hepatitis C virus (HCV) genotype 1b and low virus load.
Methods Inclusion criteria were HCV-genotype 1b, serum HCV RNA level of <100 KIU/mL at the initiation time of treatment. A total of 60 were enrolled in this retrospective cohort study. The treatment period of combination therapy was 39.8±16.1 weeks.
Results Of the 60 study patients, 47 had sustained virological response (SVR) by the intention to treat analysis. SVR occurred when serum HCV RNA was negative 8 weeks after the initiation of the treatment (p=0.004) and continuance of negative HCV RNA during treatment was ≥30 week (p=0.016). In rapid virological response, all of seven patients with continuance of negative HCV RNA 20 to 29 weeks during treatment had SVR. In early virological response nine of 10 patients with continuance of negative HCV RNA of 30 to 39 week during treatment had SVR.
Conclusion The duration of combination therapy for chronic hepatitis C should be determined based on the time of attainment of negative HCV RNA in patients with genotype 1b and low-virus load.

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Background Plasma brain natriuretic peptide (BNP) is used as a marker of congestive heart failure. Moreover, plasma BNP levels are increased in patients with acute ischemic stroke, in particular, cardioembolic stroke. We investigated whether the plasma BNP level can also be used as a biological marker to differentiate specific stroke subtype, in particular cardioembolic stroke from the other ischemic stroke subtypes.
Methods Consecutive patients (total 200; 124 males, 76 females; mean age, 71.4 years) with acute ischemic stroke within 24 hours of onset were prospectively enrolled. We measured plasma BNP on admission. Patients were divided into four groups according to the TOAST classification: large-vessel disease (LVD), cardioembolism (CE), small-vessel disease (SVD), and other stroke. Correlation between plasma BNP level and stroke subtype was then examined.
Results Cardioembolism (41%) was the most frequent stroke subtype, followed by other stroke (34%), SVD (16%), and LVD (9%). Age, female, atrial fibrillation, NIHSS score ≥7 on admission and mRS score ≥3 at discharge were significantly higher in CE than in the other stroke subtypes. The mean plasma BNP level of the CE group was significantly higher than that of the other 3 subtypes (409.6 pg/mL for CE, 94.0 pg/mL for LVD, 37.4 pg/mL for SVD, and 156.9 pg/mL for others, p<0.001). The optimal cut-off concentration, sensitivity, and specificity of plasma BNP levels to distinguish CE from other stroke subtypes were 140.0 pg/mL, 80.5% and 80.5%, respectively.
Conclusion Plasma BNP level is significantly higher in CE patients than in other stroke subtypes, and thus physicians should strongly consider CE when the plasma BNP level is over 140.0 pg/mL in patients with acute ischemic stroke.

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Objective Metformin is the drug of choice to treat obese type 2 diabetes patients because it reduces either insulin-resistance and body weight. We aimed to comparatively test the efficacy and tolerability of pioglitazone and sibutramine in metformin-intolerant obese type 2 diabetic patients treated with sibutramine.
Materials and Methods Five hundred and seventy-six consecutive Caucasian obese type 2 diabetic patients were evaluated during a 12-months period and fifty-two patients were resulted intolerant to metformin at maximum dosage (3,000 mg/day). All intolerant patients to metformin received a treatment with pioglitazone (45 mg/day) and sibutramine (10 mg/day) and they were compared with fifty-three patients treated with metformin (3,000 mg/day) and sibutramine (10 mg/day) for 6 months in a single-blind controlled trial. We assessed body mass index, waist circumference, glycated hemoglobin, Fasting Plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, lipid profile, systolic blood pressure, diastolic blood pressure and heart rate at baseline and after 3, and 6 months.
Results No body mass index change was observed at 3, and 6 months in pioglitazone + sibutramine group, while a significant reduction of body mass index and waist circumference was observed after 6 months in metformin + sibutramine group (p<0.05). A significant decrease of glycated hemoglobin, Fasting Plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin and HOMA index was observed after 3, and 6 months in both groups (p<0.05, and p<0.01, respectively). A significant Tg reduction was present after 6 months (p<0.05) in both groups respect to the baseline values. No systolic blood pressure, diastolic blood pressure and heart rate change was obtained after 3, and 6 months in both groups.
Conclusion Pioglitazone and sibutramine combination appears to be a short-term equally efficacious and well-tolerated therapeutic alternative respect to metformin-intolerant obese type 2 diabetic patients treated with sibutramine.

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Objective To verify the relationships between the values of plasma glucose (PG) and hemoglobin A_1c(HbA_1c) in type 2 diabetic outpatients.
Methods The pre- and postbreakfast PG and HbA_1c values were monitored every month for 44-90 months. The single regression lines between the values of PG and HbA_1c were compared for the slopes and intercepts on the designated ordinates of the regression lines.
Patients or Materials Nine patients of type 2 diabetes not treated with insulin: three males and six females, aged 43-79 years participated.
Results The HbA_1c level was combined with the pre- and postbreakfast PG values obtained at one month prior to its determination, because the combinations were correlated most strongly. The slopes of the regression line ranged from 0.33-0.50% /mmol/L and the intercepts at PG level equal to 9.6 mmol/L ranged from 6.95-9.77% in the relationship between the values of 1-month earlier prebreakfast PG and HbA_1c. Twenty-eight pairs had significantly different intercepts. Meanwhile, there was no pair that had significantly different slopes. Similar results were obtained in the relationship between the values of 1-month earlier postbreakfast PG and HbA_1c.
Conclusion There was interindividual divergence of the regression lines which was due to the difference in the intercepts but not the slopes.

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Background Hypothyroid patients have increased risk of cardiovascular diseases, and several mechanisms have been considered responsible in these patients. Although, a few studies demonstrated fibrinolytic system changes in hypothyroid patients, there is no study demonstrating TAFI activity in hypothyroid Hashimoto's thyroiditis patients. The aim of this study was to evaluate TAFI activity status and the effect of L thyroxin hormone replacement treatment on fibrinolytic system in this patient group.
Methods Thirty patients with hypothyroid Hashimoto thyroiditis (all were female and the mean age was 44.3±14.6 years, ranging between 17-68 years) were enrolled to study. Their TSH levels were high (27.2±5.2 mU/L) and Free T3 and Free T4 hormone levels were below than normal. In this study, euthyroid 20 healthy volunteers (mean age 32.5±4.9 years, range 26-42 years) were adopted. L-thyroxin treatment before and after TAFI activity levels were measured in patients.
Results In the control group, TAFI activity levels were 9.6±0.4 μg/mL. In patients with L-thyroxin before and after treatment there were high levels of TAFI activity value of 14.2±0.9 and 12.9±0.8 μg/mL, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels were decreased but they were not statistically significant (p=0.187). When compared to the control group, high levels of TAFI activity were observed in the patient group (p<0.0001).
Conclusion Our data demonstrated that in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement.

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This article has been retracted due to a violation of the journal's "Information for Authors".

Editor in Chief
Internal Medicine

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Background Prognostic factors related to community-acquired bacterial meningitis (BM) in adult patients have been evaluated using multivariate analysis in the Netherlands, where the rate of antibiotic resistance was low. However, an evaluation of these factors in countries with a high rate of antibiotic resistance has not yet been done. Thus, we studied the prognostic factors in adults with community-acquired BM in our hospitals, which are located in Tokyo, Japan, where the rate of antibiotic resistance is high.
Methods We selected 71 consecutive adult patients with community-acquired BM in which the pathogens were identified and then classified the patients into two groups based on the Glasgow Outcome Scale: a favorable outcome group (n=48), and an unfavorable outcome group (n=23). Their clinical and laboratory variables were analyzed using single logistic regression analysis followed by multiple logistic regression analysis.
Results The overall mortality rate was 23%. The rate of antibiotic resistance was 54.9%. The most common resistant bacteria were penicillin-resistant Streptococcus pneumoniae, followed by methicillin-resistant Staphylococcus aureus. The Glasgow Coma Scale score (GCS) at the initiation of antibiotic therapy and a low thrombocyte count were identified as significant unfavorable prognostic factors (GCS: p=0.020, odds ratio=0.528, 95%CI=0.309-0.902; thrombocyte count: p=0.037, odds ratio=0.802, 95%CI=0.652-0.987). The presence of antibiotic-resistant bacteria was not identified as a prognostic factor.
Conclusion Patients with a low GCS at the initiation of antibiotic therapy and low thrombocyte counts had unfavorable outcomes. With appropriate antibiotic administration, the antibiotic-resistant bacteria were not identified as an unfavorable prognostic factor, even in an area with a high rate of antibiotic resistance.

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Objective Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type is the most frequent type of non-Hodgkin's lymphoma to primarily involve the lung. Pulmonary MALT lymphoma, also known as bronchial-associated lymphoid tissue (BALT) lymphoma, is a rare disease and the clinicopathological features have yet to be clearly elucidated.
Patients and Methods The present study retrospectively reviewed 13 patients (8 men, 5 women) with BALT lymphoma from 3 institutions between 1989 and 2007 to assess clinicopathological features.
Results At diagnosis, the median age was 61.6 years (range, 37-80 years), and 11 patients were asymptomatic while 2 had non-specific pulmonary symptoms. Two patients had a history of Sjögren's syndrome. Computed tomography of the chest revealed bilateral disease in 7 patients, lung nodules in 8 patients and air space consolidation with or without air bronchogram in 5 patients. In all cases, disease was localized within the lung at the initial diagnosis. Of the 13 patients, 5 remain untreated, while 8 received various combinations of treatment (surgery alone in 6 patients, surgery plus chemotherapy in 1 patient, and radiotherapy alone in 1 patient). Twelve patients remained alive during the median follow-up of 31.3 months (range, 2-147 months), while 1 patient died from unknown causes.
Conclusion The present study indicates that BALT lymphoma tends to be limited to the lung on the initial diagnosis and responds well to local therapy such as surgery. Prognosis for this lymphoma tends to be indolent.

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Objective The Consolidated Standards for Reporting of Trials (CONSORT) statement was developed to improve the quality of randomized controlled trial (RCT) reports. We assessed the quality of current Japanese RCT reports by conducting a cross-sectional study to examine the extent to which they adhere to the CONSORT statement.
Methods Reports of RCTs conducted in Japan that were published in medical journals between January and March 2004 were sampled from MEDLINE. The proportion of adherence to each item in the CONSORT checklist was evaluated for each report. Additionally, information on ethics reporting and funding sources was collected.
Results A total of 98 RCT reports from Japan were evaluated, and adherence to the CONSORT statement was found to be suboptimal. Only 6 of 29 items in the checklist were described in more than 80% of reports. Adherence to key methodological items of the CONSORT statement was as follows: 23% for sample size determination, 39% for random sequence generation, 17% for allocation concealment, 29% for blinding, 53% for numbers analyzed, and 6% for inclusion of a flow diagram. Adherence to additional items was 82% for ethics committee approval, 92% for receiving informed consent, and 20% for disclosing funding sources.
Conclusion Our study on adherence of recent RCT reports from Japan to the CONSORT statement reveals that there is a significant need for improvement. Further investigation on the quality of RCT reports and ways to improve reporting quality is required.

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Autoimmune hepatitis is a chronic liver disease, and both genetic background and environmental factors are related to its pathogenesis. Here, we report that out of five members of a family with similar human leukocyte antigen haplotypes, two developed autoimmune hepatitis, one was positive for antinuclear antibody, and the remaining two had no features of autoimmunity. The two patients with autoimmune hepatitis had a history of medication use, whereas the other family members did not. Our familial study suggests that in addition to genetic background, medication use and other environmental factors may be related to the onset of autoimmune hepatitis.

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Congenital portal systemic encephalopathy without liver cirrhosis and/or portal hypertension is rare. An 86-year-old man with senile dementia was admitted due to disturbance of consciousness. His serum ammonia level was high, but there was no evidence of liver cirrhosis or portal hypertension on laboratory tests and upper abdominal enhanced computed tomography (CT). However, on lower abdominal enhanced CT, a meso-caval shunt was found in the right lower abdomen. Superior mesenteric arteriography revealed a shunt flowing into the inferior vena cava via the right gonadal vein. The shunt was closed by balloon occluded retrograde transvenous obliteration, and dementia-like symptoms improved.

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We describe an 83-year-old woman who developed a pyogenic liver abscess complicated with early bile duct carcinoma. After percutaneous abscess drainage, endoscopic retrograde cholangiography revealed a filling defect in the extrahepatic bile duct suggestive of a bile duct tumor. Resection of the extrahepatic bile duct with regional lymph node dissection was carried out. The resected specimen showed a polypoid tumor in the middle bile duct and histologic examination revealed well-differentiated tubular adenocarcinoma limited to the mucosal layer. These findings suggest that careful investigation of the biliary tract is necessary in patients with pyogenic liver abscess, because of the possible association of bile duct cancer.

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The primitive neuroectodermal tumor (PNET) of the pancreas, a member of Ewing's sarcoma family of tumors, is extremely rare. We treated a 37-year-old Japanese man who had a solitary pancreatic tumor 40 mm in diameter and multiple hepatic tumors with surgical resection. The PNET was positive for CD99 on immunohistochemical staining. Fluorescence in situ hybridization (FISH) was also performed, which revealed a Ewing sarcoma breakpoint region 1 (EWSR1) 22q12 rearrangement. According to the Japan-Ewing protocol, chemotherapy with Ifomide (ifosfamide), etoposide, vincristine, and cyclophosphamide was given after surgery. To the best of our knowledge, to date 13 PNET cases have been reported with a mean age for all patients of 19.3 years old. Surgical resection was performed in most cases and some patients received postoperative chemotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.

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A male patient with chronic bloody stool was diagnosed as juvenile polyposis at the age of 28. He had thirty to forty colonic polyps and some were removed endoscopically, while gastric polyps were too numerous to intervene. As the polyposis advanced gradually, the patient developed intractable anemia and serious hypoproteinemia. Albumin scintigram revealed protein losing gastropathy due to progressive gastric polyposis. Total gastrectomy was carried out at the age of 34 and the patient has achieved remarkable and sustainable improvement.

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This is a case report of a 60-year-old woman with acute myocardial infarction (AMI) who had coronary aneurysms and thrombus in the right coronary artery detected by multi-detector row computed tomography (MDCT). In this case, MDCT was useful for clarifying the thrombus complicated with coronary aneurysms, which was considered to be the cause of AMI. Thus, warfarin was started as an anticoagulant therapy for thrombus.

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Cytomegalovirus-associated colitis (CMV colitis) typically occurs in patients in the immunosuppressed state. A diabetic ketoacidosis state further deteriorates immunological functions. However, diabetic patients in a hyperglycemic state developing CMV colitis have been rarely observed. During the course of this study, we came across a case of diabetic ketoacidosis (DKA) with CMV colitis, which is reported herein.

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We report a 69-year-old woman who had isolated adrenocorticotropic hormone (ACTH) deficiency. Subsequently, she had Takotsubo cardiomyopathy during acute adrenal crisis. Replacement therapy with hydrocortisone sufficiently improved her cardiomyopathy. We conclude that her myocardial dysfunction was closely related to adrenal insufficiency and suggest that in certain circumstances, adrenal crisis may cause Takotsubo cardiomyopathy.

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A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D₃ with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

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A 30-year-old man patient was admitted to our clinic with complaints including cough, dyspnea, and chest pain. He had been diagnosed with pulmonary Langerhans' cell histiocytosis (LCH) 9 years previously. HRCT of the thorax demonstrated the presence of diffuse emphysematous areas in both lungs with a honeycomb appearance, an increase in reticular density at the lower lobes, a mass lesion in the left hilus, and a mass lesion at the lower lobe of the left lung. Histological diagnosis of TBNA from the right lower paratracheal and subcarinal lymph nodes was adenocarcinoma. Chemotherapy was begun, but the patient died due to respiratory failure after two courses of chemotherapy. We present this case as an example of the rare development of bronchogenic carcinoma during the long-term course of LCH.

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Home-related chronic hypersensitivity pneumonitis (HP) is sometimes difficult to discriminate because patients do not have an obvious history of antigen exposure. We report two HP cases which developed in an office area and in a home: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP followed up as idiopathic pulmonary fibrosis following isolation of Cladosporium cladosporioides and Cladosporium herbarum, respectively. Lymphocyte stimulating activity and antibody titer to these fungi were increased in these patients. Since Cladosporium spp. and several other fungi are present ubiquitously in our living environment, it is difficult to eliminate the antigen from the patients' environment to control the disease. Cladosporium spp. can be key antigens in inducing chronic HP in the home environment.

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A 24-year-old woman with chronic myeloid leukemia (CML) chronic phase was started on imatinib in August 2004 and complete hematologic response (CHR) was achieved. In May 2006, controlled ovarian hyperstimulation was started after stopping imatinib. Her pregnancy test was positive in October 2006. At 32 weeks, she had 29% metaphases positive for the Ph chromosome; CHR was sustained. She had a normal delivery at 38 weeks without any complications. Five weeks after delivery, imatinib was resumed. Complete molecular response was sustained 5 months after re-administration of imatinib. A CML patient may give a birth after intentionally stopping imatinib before conception.

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Interferon-α (IFN-α), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-α therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-α had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-α.

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A 28-year-old woman presented with classic signs of measles and subsequently developed bilateral retro-bulbar optic neuritis and Guillain-Barré syndrome. Her radiographic and CSF findings were consistent with acute measles encephalitis. However, encephalopathy, such as behavioral changes and alteration in consciousness, was not presented. Improvements in the clinical, radiographic, and electrophysiological studies were observed during the steroid therapy. The overlap of CNS and PNS involvement as neurological complications of measles infection is very rare.

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We report a case of a 49-year-old woman with headache who was diagnosed with cerebral venous thrombosis (CVT) of the superior sagittal and right transverse sinuses. Serial gradient recalled-echo T2*-weighted imaging (T2*WI) studies demonstrated dynamic changes of thrombosed segments. T2*WI is useful not only as a diagnostic tool for CVT, but also in evaluating changes to thrombus.

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