Objective Uric acid (UA) is a cardiovascular risk marker associated with oxidative stress and inflammation. Recently, atrial fibrillation (AF) has been associated with inflammation and oxidative stress. The objective of this observational study was to investigate the association between UA levels and AF in hypertensive patients.
Methods Consecutive patients with hypertension were screened. We excluded subjects with coronary artery disease, congestive heart failure, diabetes, valvular heart disease, congenital heart disease, cardiomyopathy, renal failure, inflammatory conditions, thyroid dysfunction, respiratory diseases, and those who were taking drugs that affect UA metabolism (apart from diuretics). The final study population consisted of 451 patients. Fifty of them (11%) had AF (paroxysmal: 38; persistent: 8; permanent: 4). Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded.
Results After univariate analysis, age, duration of hypertension, serum creatinine, serum UA, left atrial diameter (LAD), interventricular septum thickness, and left ventricular posterior wall thickness were significantly increased in patients with AF compared with non-AF patients, while the estimated glomerular filtration (eGFR) level was much lower in patients with AF than in those without AF. After multivariate logistic regression analysis, the independent predictors of AF were UA (OR: 1.008; 95% CI: 1.003-1.013, p=0.002) and LAD (OR: 1.160; 95% CI: 1.068-1.260; p<0.001).
Conclusion We demonstrated an independent association between increased serum UA levels and AF in hypertensive patients. Undoubtedly, larger studies in different populations should further examine this potential association as well as the underlying pathophysiological mechanisms.

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Objective Metabolic syndrome (MS) is associated with an increased risk of coronary artery disease (CAD) and type 2 diabetes mellitus (DM). In MS, adipose tissue has been shown to function as a paracrine and an endocrine organ secreting various adipocytokines. In the current study, adiponectin, tumor necrosis factor-α (TNF-α) and leptin gene expressions in the epicardial adipose tissue (EAT), paracardial adipose tissue (PAT) and subcutaneous adipose tissue (SAT) were investigated in MS patients with CAD and in non-MS patients without CAD.
Methods and Results Thirty-seven patients with MS undergoing coronary artery bypass grafting due to CAD (MS group) and twenty-three non-MS patients without CAD undergoing heart valve surgery (control group) were recruited prospectively to the study. Relative gene expressions of adiponectin, TNF-α and leptin in EAT, PAT and SAT were compared between two groups of patients. Adiponectin gene expression in EAT and PAT were significantly lower in MS group compared to the control group (p<0.0001, p=0.04, respectively) while SAT adiponectin gene expression did not differ significantly (p=0.64). TNF-α and leptin gene expressions were found to be statistically significantly higher in EAT, PAT and SAT of the MS group (p<0.0001, for all).
Conclusion Our results demonstrate that TNF-α and leptin gene expressions increase prominently in the EAT, PAT and SAT while adiponectin gene expression decreases significantly in EAT and PAT in MS patients with CAD. These findings suggest that disturbances in expression of adiponectin, TNF-α and leptin in EAT, PAT and SAT might play an important role in MS patients with CAD.

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Objective To explore the correlation between anti-thyroid autoantibodies and hepatitis C virus (HCV) infection.
Methods We collected 462 samples with positive thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb). Matched for age and gender, 380 subjects with negative TPOAb and TgAb were selected as controls. A third-generation enzymelinked immunosorbent assay (ELISA) was used to examine the presence of anti-HCV antibody. We also examined RNA HCV expression of subjects with positive anti-HCV antibody. Separate groups of 195 subjects with hepatitis C, 150 healthy subjects, and 150 subjects with hepatitis B were tested for thyroid-related markers.
Results The HCV infection rate was 1.30% in 462 subjects with positive thyroid autoantibodies, and 0.53% in 380 subjects who were negative for thyroid autoantibodies. There was no significant difference in the HCV infection rate between the two groups (χ²=1.322, p>0.05). In subjects with hepatitis C, 30.77% were TPOAb positive and 30.77% were TgAb positive; subjects with hepatitis C appeared to show significantly higher positivity of antithyroid autiantibodies when compared with healthy subjects and those with hepatitis B (χ²=21.496, χ²=30.454, p<0.01).
Conclusion The HCV infection rate did not seem to be higher in subjects with abnormal thyroid autoimmunity. However, the positivity of thyroid autoantibodies appeared to be increased in subjects with hepatitis C, suggesting that thyroid-related markers should be examined in hepatitis C patients.

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Objective The incidence and risk factors for symptomatic vertebral fracture were analyzed in glucocorticoid-treated male patients.
Methods This was an observational cohort study at Shimoshizu National Hospital in Japan. Analyzed were 161 male patients newly treated with high-dose glucocorticoid (≥20 mg/day prednisolone equivalent) (initial age: 53.5±16.9, initial glucocorticoid dose: 38.9±12.9 mg/day (0.66±0.23 mg/kg/day), follow-up time: 70.4±52.5 months) and 33 male patients with no glucocorticoid (initial age: 52.7±13.0, follow-up time: 76.4±62.7 months). The vertebral fracture was determined by x-rays.
Results Symptomatic vertebral fractures occurred more frequently in the high-dose glucocorticoid group (21.1%) than in the no glucocorticoid group (3.0%). Using Cox model, the adjusted hazard ratio (HR) for the high-dose glucocorticoid group was 8.16 (95% confidence interval: 1.09-60.86) relative to the no glucocorticoid control group. In the high-dose glucocorticoid group, Kaplan-Meier analyses demonstrated that the incidence of fractures in the patients with glucocorticoid dose increase was significantly higher in comparison with those with no glucocorticoid dose increase. Cox model demonstrated that the risk was independently higher in every 10-year increment of initial age with HR 1.58 (1.18-2.13), in every 10 mg increment of initial dose of prednisolone with HR 2.03 (1.43-2.88), in every dose increase of glucocorticoid increase with HR 3.63 (2.04-6.46), and with each 1-gram decrease of cumulative dose of glucocorticoid with HR 0.88 (0.84-0.93).
Conclusion In male patients, high-dose glucocorticoid causes a significantly high prevalence of symptomatic vertebral fractures, and the independent risk factors are age, initial glucocorticoid dose, glucocorticoid dose increase, and decrease of cumulative glucocorticoid dose.

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Objective The effect of pioglitazone on high-density lipoprotein cholesterol (HDL-C) has been attracting attention. However, there are limited data on the characteristics of patients who are likely to respond to pioglitazone in terms of the improvement in HDL-C levels (lipid responders). In the present study, the characteristics of lipid responders were investigated.
Methods Five hundred and sixty-three patients with type 2 diabetes who started pioglitazone treatment were followed for six months. They were divided into two groups according to the response to pioglitazone. Subjects whose HDL-C levels increased by 10% or more from the baseline were defined as lipid responders. The odds ratios (OR) for becoming lipid responders were calculated using logistic regression.
Results Significant patients' characteristics of lipid responders were age, HbA1c, HDL-C and low-density lipoprotein cholesterol (LDL-C), yielding adjusted ORs of 0.76 [95% confidence interval (CI)=0.61-0.93] for an increment of 10 years, 0.79 (95% CI=0.66-0.95) for an increment of 1%, 0.83 (95% CI=0.72-0.96) for an increment of 10 mg/dL and 0.93 (95% CI=0.87-1.00) for an increment of 10 mg/dL, respectively. Patients with sulfonylurea treatment and those with both sulfonylurea and metformin treatment were less likely to become lipid responders than diet-treated patients with ORs of 0.32 (95% CI=0.15-0.69) and 0.41 (95% CI=0.19-0.87), respectively.
Conclusion Pioglitazone could be beneficial especially for patients with young age, low HbA1c, low HDL-C or low LDL-C levels at baseline in terms of the improvement in HDL-C levels. Use of sulfonylureas at baseline could attenuate the effect of pioglitazone on HDL-C.

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Objective Obstructive Sleep Apnea Syndrome (OSAS) is a common sleep-related breathing disorder. Associations among Apnea-Hypopnea Index (AHI), Resting Metabolic Rate (RMR), body habitus differences, and otorhinolaryngologic abnormality may clarify the characteristics of patients with OSAS. In order to test this hypothesis, we aimed to compare the RMR, Modified Mallampati Scores (MMS), anthropometric measurements and body composition of male OSAS patients with simple snorers and to investigate the association among these parameters.
Methods MMS were calculated, overnight polysomnography was performed, body mass index, neck, shoulder, chest, waist, hip and abdomen circumferences, body fat amount and ratio, lean body weight, body water amount and RMR were measured for all of the patients.
Patients Ninety-eight male patients with suspected OSAS were included in the study.
Results Fifty-one patients were diagnosed as OSAS and 47 patients were diagnosed as simple snorers. RMR, total body water, neck, shoulder and chest circumferences were significantly higher in OSAS patients than the simple snorers. The majority of the simple snorers was seen to have a MMS of stage 2 whereas OSAS patients had MMS of stages 3 and 4. AHI was significantly correlated with neck, shoulder, chest circumferences, total body water amount, MMS and RMR. Chest girth was found as the most important single predictor of sleep apnea in multivariate analysis.
Conclusion We suggest that the increased RMR and chest circumference might have occured due to the condition resulting from the elevated AHI in patients with OSAS. Mallampati score should be routinely evaluated in OSAS patients.

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Background and Objective Mucosal irregularity and hypervascularity associated with primary lung cancer in large airways are observed by bronchoscopy. The aim of this study was to evaluate microcirculation at subepithelial invasion sites of lung cancer.
Methods and Patients Between July 2001 and June 2007, 12 patients who had subepithelial invasion sites of lung cancer in the large airways (aged 52 to 74 years, 12 males) were enrolled into this study. They were 6 patients with adenocarcinoma, 4 patients with squamous cell carcinoma, and 2 patients with small cell carcinoma. We compared 12 control subjects without endobronchial abnormality (aged 51 to 83 years, 9 males and 3 females). The patients underwent conventional bronchoscopy and subsequent high magnification bronchovideoscopy with the conventional imaging and the narrow band imaging (NBI). For evaluating microcirculation of subepithelial invasion, hemoglobin index was calculated.
Results In high magnification view, aberrant microvessels and/or irregular mucosal thickening were observed at subepithelial invasion sites of lung cancer. Irregularly enlarged microvessels were increased and formed an aberrant microvessel network on the surface of irregular mucosa. The diameter of aberrant microvessels was significantly increased compared to normal microvessels. By switching to NBI, the aberrant microvessels were more clearly visualized. The levels of hemoglobin index were significantly higher in subepithelial invasion sites of lung cancer compared to normal mucosa.
Conclusion In subepithelial invasion of lung cancer, aberrant microvessels are thought to be characteristic and subepithelial microcirculation may be increased.

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Objective To describe the characteristics of cases with drug-associated rhabdomyolysis reported to the U.S. Food and Drug Administration (FDA).
Methods A retrospective analysis of all drug-associated rhabdomyolysis cases reported to FDA between January 2004 and December 2009 was conducted. The analyses included the number of unique cases, age, gender, body weight and proportion of fatal outcome. Time to onset from beginning of the suspected drugs and frequently reported suspected drugs were also tabulated.
Results There were 8,610 cases of drug-associated rhabdomyolysis in the database. Both case numbers and proportion of the fatal outcome appeared stable over the study period. Average age was 43.3 years old. The reported ratio of male to female was approximately 5 to 3. More than half of reported cases developed rhabdomyolysis within a month after beginning the suspected drug. Potential high risk groups for fatal outcome, such as age group younger than 10 years old and body weight group less than 50 kg were suggested. Suspected drugs for younger cases and their probable indication appear to be different from adult cases. There has been long standing controversial concern regarding an increased risk when a fibric acid derivative is added to an HMG-CoA reductase inhibitor. This study suggested that concomitant use of these two kinds of agents may be associated with a lower risk for fatal outcome, whereas renal dysfunction appeared to be associated with a higher risk for fatal outcome among the HMG-CoA reductase inhibitor-associated rhabdomyolysis cases.
Conclusion The characteristics of cases of drug-associated rhabdomyolysis were described. Because of the various limitations of a spontaneous reporting-system database, the reported number should be interpreted with caution.

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Background and Aim The treatment of choice for allergic bronchopulmonary aspergillosis (ABPA) is oral corticosteroids (OCS). However, they are associated with numerous adverse effects. Inhaled corticosteroids (ICS) are associated with fewer side-effects; however, their role in the management of ABPA remains controversial. In this retrospective study, we evaluate the role of high doses of ICS in serological ABPA (ABPA-S).
Methods Patients with ABPA-S were treated with a combination of formoterol/budesonide (24-1600 micrograms per day), and followed up with history, physical examination, chest radiograph and total IgE levels at 6, 12, 18 and 24 weeks. Asthma control was evaluated using the Global Initiative for Asthma (GINA) criteria. OCS were initiated if the IgE levels continued to rise after six months of therapy with ICS.
Results There were 8 men and 13 women with a mean (SD) age of 39.3 (12.9) years. There was subjective improvement in all patients treated with ICS but none had complete control of asthma. After six months of therapy with ICS, the median IgE levels increased by 99.3%. After the initiation of OCS, there was complete resolution of asthma symptoms in 19 patients, and IgE levels fell by a median of 52.6% at six weeks. The median duration of follow-up was 15 months after OCS therapy. Eighteen patients achieved complete remission and three patients had a relapse in the first three months after stopping OCS. One patient required long-term OCS and was classified as glucocorticoid-dependent ABPA.
Conclusion High doses of ICS alone have no role in the management of ABPA-S and should not be used as first-line therapy. In patients receiving OCS or alternate therapy, ICS can be used as an add-on therapy for the control of symptoms of asthma.

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Objective and Design To investigate the association between the severity of sepsis and changes in sialylation of serum proteins we have conducted a single center pilot study.
Subjects and Methods Sialylation of transferrin (with enzyme-linked lectin assay-ELLA) and total serum proteins (with colorimetric assay) as well as serum iron and transferrin levels were measured in 27 patients with sepsis through the first eight days of the disease.
Results Total serum sialylation increased in the first two days, transferrin sialylation decreased, while serum iron and transferrin fell. Patients who developed severe sepsis had either a small or marked change in transferrin sialylation while in patients with mild sepsis sialylation decreased moderately.
Conclusion We hypothesize that the change in transferrin sialylation could be a reflection of the intensity of inflammatory response which is insufficient if under-expressed and detrimental if over-expressed. This new feature is a potential marker of sepsis severity early in the disease.

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Objective Acinetobacter baumannii is an important nosocomial pathogen associated with a high mortality rate. However, no objective and quantitative severity scores are available for the severity stratification. We aimed to assess the effectiveness of SOFA and APACHE II scores calculated at the onset of bacteremia in predicting the mortality of patients with A. baumannii bacteraemia.
Patients and Methods A total of 110 patients with A. baumannii bacteremia were included in this retrospective study during the 40-month study period. Information including clinical and laboratory data was collected.
Results Multivariate analysis showed that both SOFA and APACHE II scores were independent outcome predictors after adjustment for other parameters. Goodness-of-fit was good for SOFA and APACHE II, and both models displayed excellent AUROCs (SOFA: 0.83 ± 0.06, APACHE II: 0.82 ± 0.08 in predicting 14-day mortality; SOFA: 0.85 ± 0.04, APACHE II: 0.81 ± 0.04 in predicting in-hospital mortality). There was no significant difference in the predictions of the two scoring systems, and the scores were highly correlated (r²=0.724, p <0.001). We found that SOFA >8, APACHE II >29 and SOFA >7, APACHE II >23 are associated with significantly higher 14-day and in-hospital mortality rates, respectively.
Conclusion SOFA and APACHE II scores assessed at the onset of bacteremia are reliable risk stratifying tools in predicting 14-day and in-hospital mortality in A. baumannii bacteremia. For ease of calculation, the use of SOFA rather than APACHE II score to predict mortality of A. baumannii bacteremia might have clinical application.

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Objective Analysis of an outbreak of Bordetella pertussis infection in a university laboratory. To prevent and control the outbreak, we conducted a survey of the laboratory staff and their family members, and we investigated the clinical features of adult pertussis.
Patients and Methods During the outbreak, four out of the 10 laboratory staff and five out of 16 family members had a primary complaint of cough. Seven of nine patients were diagnosed as definitive B. pertussis infection using serology and PCR.
Results Clinical findings and laboratory data in adult patients with B. pertussis infection demonstrated non-specific cough and normal WBC and lymphocyte count. The patients who received clarithromycin prior to 14 days after clinical onset demonstrated a shorter duration of cough symptoms than patients who received clarithromycin at 14 days or more after clinical onset (duration of cough after administration of clarithromycin: 17.8 ± 6.48 days versus 35.3 ± 5.38 days; duration of total cough after clinical onset: 24.8 ± 6.65 days versus 56.8 ± 6.50 days).
Conclusion The clinical findings of adult pertussis are different from pertussis in children. The efficacy of macrolide therapy clearly differed between the catarrhal phase and paroxysmal phase. Physicians should consider B. pertussis in the differential diagnosis of an outbreak of non-specific respiratory infection even in adult populations.

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An autoimmune pancreatitis (AIP) patient with metachronous and multiple extrapancreatic lesions is reported. Initial symptoms were proptosis, oculomotor deficits, and a visual field deficit of the left eye, and swelling of bilateral lacrimal glands. Swelling of the right salivary gland and elevated serum levels of hepatobiliary enzymes were detected. AIP associated with IgG4-related orbital pseudotumor, IgG4-related sclerosing dacryoadenitis and sialadenitis, and IgG4-related sclerosing cholangitis was diagnosed. All symptoms and lesions improved with steroid therapy. Although an orbital pseudotumor is a rare extrapancreatic lesion of AIP, we should know that AIP patients may describe unusual symptoms such as abnormal visual field.

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A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.

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A 59-year-old man exhibited an enlarged right inguinal lymph node in February 2009. A pathological diagnosis of follicular lymphoma (FL), grade 3A, was made based on a biopsy specimen from the right inguinal lymph node. The immunophenotypes of the lymphoma cells were CD3-, CD5+, CD7-, CD10+, CD19+, CD20+, CD23+, IgM+, Igκ-, and Igλ+. Fluorescence-activated cell sorting (FACS) dual staining indicated that the cells were double-positive for both CD5 and CD20. Mantle cell lymphoma (MCL), small lymphocytic lymphoma (SLL) and CD5-positive diffuse large B-cell lymphoma (DLBCL) were ruled out by the presence of cyclin D1-, CD10+, and the pathological findings. Based on these findings, the patient was diagnosed as having CD5-positive FL. Eight cycles of rituximab plus six cycles of CHOP were performed, and complete remission was achieved. To our knowledge, this is a rare case of CD5-positive FL. A literature review suggested a relatively higher incidence in younger and male patients. Remarkably, patients with grade 3 tend to undergo a transformation from CD5-positive FL to DLBCL.

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We report a 60-year-old man with diffuse large B-cell lymphoma harboring both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32). Although he received six courses of conventional combination chemotherapy plus rituximab, early relapse occurred. Four courses of an intensive salvage regimen and high-dose chemotherapy with autologous peripheral blood stem cell transplantation were performed. The patient has remained in complete remission for over 24 months. This case is noteworthy because both genetic abnormalities are implicated in lymphomagenesis.

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Adult onset Langerhans cell histiocytosis (LCH) is a rare disorder. Its clinical features have been well described in children, however remain poorly defined in adults. Optimal treatment strategy is still under debate. We have encountered two cases of adult onset LCH, which obtained a durable disease control by combination chemotherapy using prednisone, vinblastine and 6-mercaptopurine. Herein, we report their clinical features together with a review of the current literature.

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A 26-year-old man was admitted to our hospital because of high fever, drowsiness, memory disturbance, and disorientation due to H1N1 influenza virus-associated encephalitis/encephalopathy. All of his symptoms rapidly improved following methylprednisolone pulse therapy. The diffusion-weighted image of brain magnetic resonance imaging (MRI) revealed a large transient hyperintense signal lesion on the central splenium of the corpus callosum. This MRI finding in conjunction with a complete clinical recovery has been previously observed in cases of clinically mild seasonal influenza-associated encephalitis/encephalopathy, and can be also a useful clue for the diagnosis of new type of influenza, H1N1 influenza virus infection complicated by encephalitis/encephalopathy.

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We report a patient with human T-cell lymphotropic virus type I (HTLV-I) infection, who presented with proximal extremity neurogenic muscular weakness followed by fulminant myelopathy, but with no upper motor symptoms. The symptoms were inconsistent with the World Health Organization or El Escorial criteria for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or amyotrophic lateral sclerosis (ALS). This case indicates that fulminant myelopathy without upper motor neuronal symptoms may occur long after the onset of HTLV-I-associated neurogenic proximal muscular weakness. Additionally, we report that treatment with high-dose steroid pulse therapy partially improves symptoms of lightning pain and sensory disturbance.

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We report a case of Churg-Strauss syndrome (CSS) complicated by severe cardiac failure and peripheral neuropathy. Two courses of methylprednisolone pulse therapy were unable to control the disease activity. Repeated intravenous administration of high-dose human immunoglobulin (IVIg) was added together with intravenous cyclophosphamide pulse therapy (IVCY), and the patient's cardiac function and neurological symptoms were gradually ameliorated without any adverse event. Although glucocorticoid and cyclophosphamide comprise the standard therapy for patients with CSS, a number of patients with severe complications appear to be resistant to such conventional treatment. IVIg is thought to be an effective therapeutic option for such patients.

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IgG4-related systemic disease is a recently described entity that can elude even the most astute diagnostician. Patients with the disease, characterized by the infiltration of polyclonal IgG4-positive plasmacytes, can present with single or multi-organ involvement. Manifestations include dacryoadenitis, sialadenitis, thyroiditis, pneumonitis, retroperitoneal fibrosis, pancreatitis, sclerosing cholangitis, tubulointerstitial nephritis, prostatitis, and hypophysitis. We describe a biopsy-confirmed case with extensive multi-organ involvement, including hypophysitis, dacryoadenitis, retroperitoneal fibrosis and tubulointerstitial nephritis. By reporting this case, we hope to bring IgG4-related systemic disease to the attention of the broader medical community as it is an elusive disease that commonly responds to systemic corticosteroids.

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