Object  It was reported that the liver fibrosis is reduced in patients with chronic liver disease type C after eradication of HCV. Degree of fibrosis was expressed by the classical fibrosis scoring system (F0-F4) at present. However a change of subtle reduction of fibrosis cannot be expressed in its fibrosis score and thus we measured an area of fibrosis and compared detailed change of the fibrosis area in paired liver biopsy.
  Methods  For quantitative assessment of liver fibrosis, we measured an area of fibrosis using computed digital image analysis and pursued the rate of a fibrosis area for whole biopsied liver tissue of 25 patients with HCV infection (20 complete response patients to IFN therapy who showed viral eradication: CR and 5 non-treated ones with IFN but had conservative therapy: CT).
  Results  In CR group, fibrosis rate was 7.2±1.5% before therapy, 2.7±0.5% after the therapy and they were significantly regressed. In CT group, fibrosis rate was 8.4±4.3% at the first biopsy, 15.9±7.7% at the second biopsy.
  Conclusions  Regression of liver fibrosis could be confirmed in patients with virologic response to IFN even in patients with liver cirrhosis. Our quantitative evaluation provided information superior to that obtained by the classical fibrosis staging score system.

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  Objective  It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is not known. The profile in relation to age, gender and risk factors was evaluated to compare AMI and unstable angina pectoris (UAP).
  Methods  Findings from 984 patients including 580 patients with AMI (129 women, 451 men) and 404 patients with UAP (131 women, 273 men) were analyzed by the South Osaka Acute Coronary Syndrome Study Group (SACS). The primary endpoint of the study was in-hospital death. The primary endpoints of interest (cardiac death) were fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death.
  Results  Cardiac death during hospitalization within 30 days in AMI was higher in women than in men (12.4% vs 6.7%, p<0.05). On the other hand, in UAP there was no significant difference between women and men (1.5% vs 0.7%, NS). The incidence of cardiac death in AMI was significantly higher for patients 75 years old and older (19.0%) than for patients less than 55 years old (4.2%), 55-64 years old (3.5%) and 65-74 years old (4.7%) (p<0.001, respectively).
  Conclusions  Cardiac death was higher for women compared with men in patients with AMI. The worse prognosis for the AMI women patients was likely to be derived from less performance of percutaneous coronary intervention, and a high incidence of severe myocardial infarction. Further research should be focused on the analysis of various clinical backgrounds.

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  Objective  The presence of microalbuminuria is a renal marker of vascular endothelial damage, and is an independent and strong predictor of increased risk for cardiovascular mortality and morbidity. Elevated circulating C-reactive protein (CRP) levels have recently been reported to be a novel cardiovascular risk factor, and it has been suggested that this acute-phase protein impairs vascular endothelial function. The aim of the present study was to determine whether serum CRP level is a dependent or an independent risk factor of microalbuminuria in the general population.
  Methods  Subjects of this cross-sectional study were apparently healthy individuals drawn from the general Japanese population (mean age, 62; men, 2, 236; women, 4, 217). Serum CRP levels were determined using a highly sensitive kit and urine albumin-creatinine ratio (UACR) was calculated using a single urine sample. Multivariate logistic regression analysis was used to determine which risk factors (ie, age, hypertension, diabetes, obesity, hypercholesterolemia, smoking, and CRP) might predict the presence of microalbuminuria.
  Results  In addition to classical cardiovascular risk factors such as age, hypertension, diabetes and obesity, serum CRP levels are also significantly correlated with microalbuminuria in men (odds ratio=1.42, 95% CI=1.13-1.79; p<0.01) and women (odds ratio=1.25, 95% CI=1.05-1.49; p<0.01). When subjects with diabetes were excluded from the analysis, serum CRP levels continued to be a significant predictor for microalbuminuria (odds ratio=1.35, 95% CI=1.06-1.73; p<0.05 for men: odds ratio=1.23, 95% CI=1.03-1.47; p<0.05 for women).
  Conclusions  The present study has shown that low-grade inflammation as represented by high sensitivity CRP levels may be significantly related to the presence of microalbuminuria. This suggests that microalbuminuria may be a useful marker representing systemic low-grade inflammation as well as being an established cardiovascular risk factor in apparently healthy individuals.

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A 67-year-old man visited our hospital for the treatment of gastric carcinoma. Endoscopic mucosal resection was performed, however, histological examination of the resected specimen revealed tumor invasion to the submucosal layer with vessel invasion. Immunohistological studies were carried out on resected specimens and part of the cancerous lesion showed a positive reaction for alpha-fetoprotein (AFP), but the serum AFP level was normal. Additional distal gastrectomy with lymph node dissection revealed lymph node metastasis although there was no apparent finding of lymph node swelling by preoperative diagnostic imaging. This patient remains alive without disease for 3 years after surgery.

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A 44-year-old Japanese woman with a history of living-related renal transplantation was treated with interferon-β (IFN-β) for chronic infection with sero-group 2 hepatitis C virus (HCV). Serum HCV-RNA titer was 160 kilo-international units/ml. Treatment with intravenous IFN-β daily was given for 6 weeks. Serum HCV-RNA was undetectable at 3 weeks after initiating therapy. Renal graft rejection did not occur. Six months after completing therapy, she obtained sustained viral response. This case demonstrates that IFN-β therapy safely induced clearance of HCV in a renal transplant recipient with stable renal function, low viral load and/or HCV sero-group 2.

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A 67-year-old woman with rheumatic aortic stenosis for 20 years was admitted to our hospital. Although she had no overt symptoms, she had severe aortic valve stenosis with a transvalvular pressure gradient of more than 150 mmHg. She had also been suffering from anemia and mild chronic renal failure. A peripheral blood smear showed numerous fragmented erythrocytes. Hemoglobin was 8.4 g/dl, lactate dehydrogenase was 316 IU/l, haptoglobin was less than 7.3 mg/dl, and hemosiderinuria was evident. We diagnosed intravascular hemolysis related to aortic stenosis. After we performed an aortic valve replacement, fragmentation on the peripheral blood smear dramatically disappeared.

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We encountered a case of wide QRS tachycardia with chronic atrial fibrillation in Wolff-Parkinson-White syndrome. Unique features were late onset of syncope attacks associated with this tachycardia at an advanced age of 72 years old without previous documentation of Wolff-Parkinson-White syndrome on electrocardiogram. He had a high likelihood of sudden cardiac death. Catheter ablation using CARTO^TM system easily led to a successful ablation of the accessory pathway. The mechanism of late onset of the wide QRS tachycardia was attributed to possible changes of electrophysiologic properties including the atrio-ventricular node and/or the accessory pathway, and the unique location of the accessory pathway.

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We report a 48-year-old woman with right heart failure due to primary pulmonary hypertension. Continuous infusion of epoprostenol (prostaglandin I₂) for 1.5 years failed to control her condition, but she was later successfully treated with additional sildenafil for a few months. Her mean pulmonary artery pressure was originally 57 mmHg, increased to 62 mmHg with epoprostenol, and decreased to 45 mmHg with sildenafil. Additional sildenafil may be an effective and life-saving agent in patients with primary pulmonary hypertension who show a poor response to epoprostenol, which is considered to be very powerful medical treatment for the disease.

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A rare complication of possible secondary dilated cardiomyopathy to Kugelberg-Welander disease was described in a 53-year-old patient with this inherent motor neuron disease, whom we diagnosed after a genetic analysis of the defective survival motor neuron gene. An association of sleep disordered breathing of Cheyne-Stokes respiration was diagnosed, which was virtually eliminated with continuous positive airway pressure via nasal mask. Considering the paucity of therapeutic options in most degenerative neuromuscular disorders, ameliorations in not only sleep quality but also cardiac function with continuous positive airway pressure have clinical implications.

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We report 3 patients with alcoholic ketoacidosis (AKA). All had a history of excessive intake and abrupt termination of alcohol. They showed tachypnea, tachycardia, abdominal tenderness, and epigastralgia. Metabolic acidosis with an increased anion gap, decreased PaCO₂ and ketonemia were present. One patient whose ratio of 3-hydroxybutyric acid to acetoacetic acid was 4.0 was associated with diabetic ketoacidosis. All patients were successfully hydrated with electrolyte, glucose and thiamine. Complications such as liver dysfunction, lactic acidosis, acute pancreatitis, Wernicke's encephalopathy, rhabdomyolysis and heart failure were present. Attention should be paid to multiple complications in the treatment of AKA.

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Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium enhancement and attenuation in the intensity of the posterior lobe of the pituitary was detected without enhancement. Corticosteroid therapy resulted in the initial improvement of symptoms and gradual decrease in the tumor size but failed to cure polyuria due to DI. The use of desmopressin was necessary for a long period. None of these patients died from DI or central neurosarcoidosis.

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An 81-year-old woman presented with frequent episodes of hypoglycemia. Her serum level of insulin was normal, but her serum insulin-like growth factor (IGF)-II level was high. She was found to have a spindle cell sarcoma originated from the mesentery of the sigmoid colon, which was completely resected. Postoperatively, hypoglycemia ameliorated with concomitant reduction in serum IGF-II levels. Immunohistochemical study revealed positive immunostaining for IGF-II in tumor cells, and the abundant expression of IGF-II mRNA was demonstrated by RT-PCR. The presence of high molecular weight (HMW) form IGF-II in patient's serum was confirmed by immunoblotting. This is the first report of a patient with HMW form IGF-II-producing mesenteric sarcoma causing hypoglycemia.

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A 65-year-old man was admitted to our hospital because of dyspnea on exertion. He had oculocutaneous albinism innately and his parents were consanguineous. His chest roentgenogram on admission showed reticulonodular infiltrates and cystic changes throughout both lung fields, and 7 cm mass in the left middle field. Cytology of bronchoalveolar lavage fluid (BALF) revealed macrophages containing ceroid. The diagnosis of HPS was made clinically and the tumor was diagnosed as poorly differentiated adenocarcinoma of the lung. He died of respiratory failure. By autopsy, additional well-differentiated adenocarcinoma was detected. Cytology of BALF was useful to confirm ceroid accumulation in the lung.

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This article was retracted. See the Notification.

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A 57-year-old man consulted our hospital with a history of the gradual onset of dyspnea and a productive cough. Chest computed tomographic (CT) scans showed a nodular shadow in a cavity lesion, and reticulonodular, cystic, and ground-grass opacities in the bilateral lung fields with honeycombing. He was diagnosed as having pulmonary aspergilloma and idiopathic pulmonary fibrosis (IPF). As an outpatient, he suffered from dyspnea upon physical exertion with exacerbation of the high-resolution CT (HRCT) opacities. An inhalation provocation test for Aspergillosis fumigatus was positive and chronic hypersensitivity pneumonitis (CHP) caused by Aspergillus was finally diagnosed. Insidious CHP is sometimes misdiagnosed as IPF. The diagnosis of insidious CHP should be made on the basis of a detailed history, specific HRCT findings, and lymphocyte-dominant bronchoalveolar lavage fluid cell findings.

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We detected Epstein-Barr virus (EBV) reactivation in a patient with mantle cell lymphoma (MCL). The patient, a 53-year-old Japanese man, had been referred to our hospital because of generalized lymphadenopathy, hepatosplenomegaly and lymphocytosis and gave a history of intense skin reactions to mosquito bites. The biopsied lymph node contained a monotonous proliferation of medium-sized lymphocytes with scant cytoplasm and slightly irregular nuclei that were CD5⁺, CD20⁺ and CD23^-. Antibody titers of IgG against EBV viral capsid antigen and early antigen were increased, and EBV was detected in the lymphoma cells. This case may suggest a relationship between EBV and MCL.

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Multiple brain tumors of diffuse large B cell lymphoma (DLBL) were observed in a 75-year-old man with Waldenström's macroglobulinemia (WM). Paravertebral and multiple subcutaneous nodules occurred in succession and he died 4 months after onset. We investigated B cell monoclonality by means of polymerase chain reaction (PCR) analysis and sequencing of the immunoglobulin heavy chain of paraffin-embedded sections. The PCR product of the brain tumors showed a different rearrangement pattern from those of the other sections. The co-occurrence of DLBL with WM is rare, and some investigators have examined the clonality of the two malignancies. This case is important because DLBL brain tumors co-occurred with WM, enabling us to prove that DLBL and WM have different clonality.

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We report a 64-year-old woman with follicular thyroid cancer found by subacute bulbar palsy. Progressive bulbar palsy (PBP) was considered the most likely diagnosis, because no abnormal finding was detected on brain CT and blood test except for the decrease of free T₄. An echogram of the thyroid revealed a small nodule which was shown to be class IIb by fine needle biopsy. However, ²⁰¹Tl scintillation examination showed skull base metastasis. Follicular thyroid cancer sometimes seems to manifest as a distant metastasis with no clinically evident thyroid lesion. This case suggested the importance of a detailed survey for malignancy, when subacute bulbar palsy is seen.

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A 74-year-old woman with recurrent fever and multiple joint pain was admitted to Hokkaido University Hospital. Trans-esophageal echocardiogram revealed bacterial vegetation and destruction of the aortic valve. Although few bacteria grew in regular blood agar, Grampositive coccobacillus was specifically grown in chocolate blood agar and Brucella agar, and it was identified to be Abiotrophia defectiva. Infectious endocarditis caused by Abiotrophia defectiva was diagnosed, she was treated with diuretics, penicillin G and gentamicin, and she immediately improved. Infectious diseases caused by Abiotrophia defectiva are extremely rare, and identification of this pathogen is important, as its bacterial characteristics require proper attention.

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