Background Even high-normal albuminuria is reportedly associated with cardiovascular events.
Objective We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels.
Patients and Methods The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and <300 μg/mg·creatinine and a UCAR ≥300 μg/mg·creatinine, respectively.
Results The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 μg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to <30 μg/mg·creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR.
Conclusion The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

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Objective Involvement of different NADPH oxidase (NOX) homologues in late endothelial progenitor cell (EPC) senescence induced by angiotensin II (Ang II) remains rarely studied systemically. The goal of our study was to determine NOX homologues which are correlated with late EPCs senescence induced by Ang II. The inhibitory effect of telmisartan was also studied.
Methods and Materials Late EPCs were obtained from mononuclear cells isolated from peripheral venous blood. Stimulated by Ang II with telmisartan (Tel) or VAS2870 pretreatment or siRNA prior silencing, NOX was detected by RT-PCR and Western blot. Cell senescence was measured by the acidic β-galactosidase activity assay and cell cycle analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometer based on DCFH-DA.
Results A bi-phasic change existed in NOX level after Ang II stimulation. Translocated NOX5 was correlated with early and rapid ROS production, but it contributed little to EPCs senescence. NOX2 and NOX4 were correlated with the late and slow phase and contributed greatly to EPCs senescence. There were no significant changes in NOX1 or NOX3. Telmisartan effectively depressed NOX change and delayed late EPCs senescence.
Conclusion Ang II accelerates late EPCs senescence mainly via increased ROS originating from NOX2 and NOX4 up-regulation or translocated NOX5. Telmisartan effectively inhibited that cascade reaction and delayed EPCs senescence.

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Objective The aim of this study was to evaluate the effects of health checkup and the health education "Hokenshido" program based on the concept that visceral fat accumulation causes metabolic syndrome (MetS), leading to cardiovascular disease (CVD).
Methods and Subjects Based on the Japanese definition of metabolic syndrome, in the annual health checkup for general subjects, the measurement of waist circumference and use of "Where am I?" chart on the way to develop atherosclerosis were introduced. The study group comprised 3,174 Japanese employees [2,440 males (46±11 years, mean ± SD), 734 females (43±10 years)], who underwent annual health checkup in 2003, 2004, and 2005. The medical staff provided "Hokenshido" for subjects assessed as having MetS and/or at high risk for CVD.
Results The prevalence of the MetS in 2003, 2004 and 2005 decreased in males (20.8%, 17.2%, 14.4%, p<0.001) and females (3.0%, 2.2%, 1.9%, p=0.359), respectively. Among subjects with MetS at baseline, the number of subjects with MetS significantly decreased in males (508, 287, 247, p<0.0001) and females (22, 8, 6, p<0.0001), respectively. Mean waist loss was 1.6 cm in males (<0.0001) and 1.5 cm in females (<0.001). Among subjects with metabolic syndrome at baseline, the mean waist loss was 2.5 cm in males (<0.0001) and 3.9 cm in females (<0.05). Fatal atherosclerotic vascular events were not recorded in this study period.
Conclusion Health check-up and the "Hokenshido" program reduced the prevalence of the MetS, which might lead to prevention of CVD.

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Background The aim of this study was to compare the long-term procedural outcomes, the stability of atrioventricular conduction, and the new onset of atrial fibrillation (AF), after ablation of atrioventricular nodal reentrant tachycardia (AVNRT).
Methods and Results Consecutive patients with AVNRT (n=109), who underwent slow-pathway ablation, were divided into two groups based on the median age of the studied patients: the younger group aged <55 years and the older group aged ≥55 years. During a mean follow-up period of 60.6 months, the rate of change in the PR interval from before ablation to follow-up was significantly greater in older patients compared with younger patients. However, there was no delayed-onset high-degree AV block during follow-up in either group. No patients in the younger group suffered from persistent AF, whereas persistent AF occurred in 5/54 (9.3%) older patients. Multivariate Cox analysis revealed that atrial vulnerability, with induction of AF during the electrophysiological study, was the only predictor of the development of AF (Hazard ratio: 13.9, 95% confidence interval: 1.62-119.2, p<0.01).
Conclusion Slow-pathway ablation of AVNRT is a reliable strategy even in older patients. However, physicians should consider regular long-term follow-up of older patients with atrial vulnerability, in order to assess the subsequent development of AF.

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Backgound Dehydroepiandrosterone (DHEA) is an adrenal hormone reported to prevent body weight gain, diabetes mellitus and atherosclerosis. We hypothesized that DHEA is involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD) often associated with obesity and insulin resistance. In this study, we aimed to examine the clinical significance of serum DHEA sulfate (DHEAS) in patients with NAFLD.
Methods We determined serum DHEAS, serum alanine aminotransferase (ALT), serum lipids, plasma fasting glucose and insulin levels in 158 Japanese men who had neither viral hepatic diseases nor alcohol intake exceeding 20 g/day. NAFLD was diagnosed by the presence of fatty change of the liver by echotomographic examination.
Results Among the study subjects, 69 were diagnosed as having NAFLD. Their serum DHEAS levels were significantly higher than in 89 subjects without NAFLD. Serum DHEAS levels in 19 NAFLD patients with elevated ALT levels (>40 U/L) were significantly higher than in the other 50 NAFLD patients with normal ALT levels (≤40 U/L). Multivariate regression analysis demonstrated that serum ALT was positively correlated with serum DHEAS, serum triglyceride and body mass index.
Conclusion Serum DHEAS levels are increased in patients with NAFLD with elevated ALT levels. Increased serum DHEAS may be a component of the pathophysiology of NAFLD.

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Background Patients with diffuse panbronchiolitis (DPB) are routinely treated with erythromycin, clarithromycin, and roxithromycin. The clinical effect of azithromycin on DPB has not been confirmed in a large cohort.
Objective The present study was undertaken to investigate the clinical effects of azithromycin on patients with DPB.
Methods Fifty-one patients with DPB treated with azithromycin in Shanghai Pulmonary Hospital, China, from July 2001 to April 2007 were analyzed retrospectively. Azithromycin (500 mg a day) was administrated intravenously in the first 1-2 weeks, taken orally (500 mg, once a day) for 3 months, and tapered to 3 times a week for 6-12 months. The patients were followed up until September 1, 2009. The therapeutic effect, according to their clinical and radiological findings, arterial gas analysis, lung function, and sputum bacterium before and after the therapy, was categorized into the following five grades: 1) cured; 2) improved; 3) no response; 4) aggravation, and 5) relapse.
Results With azithromycin therapy, 14 (27.5%) patients with DPB were completely cured. The symptoms were eliminated to certain degrees for the other 36 cases (70.6%) of DPB. Five-year survival in this cohort was 94.1%.
Conclusion Azithromycin is effective and well tolerated for patients with diffuse panbronchiolitis.

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Objective Age is known to influence the risk of both cerebral ischemic lesions and impaired cognitive function. Diabetes mellitus (DM) can also be associated with cognitive impairment. However, there has been no study of neuropsychological performance in association with glucose metabolism status and cerebral ischemic lesions in same-aged, community-dwelling elderly persons. The present study was performed to clarify which cognitive domains are associated with impaired glucose metabolism/DM and whether the association is independent of cerebral ischemic lesions.
Subjects and Methods A total of 172 residents in Takahata, Japan, all of whom were 78 years old, were evaluated in multiple domains through neuropsychological tests and brain MR images, as well as a medical check-up including tests for glucose metabolism status and conventional vascular risk factors. Glucose metabolism status was determined by analysis of HbA1c level.
Results In multiple regression analyses, performance on a verbal fluency (VF) test and the Trail Making Test-Part B, both of which represent executive function, was associated with HbA1c level, even after adjustment for sex, education, cerebral ischemic lesions, and conventional vascular risk factors. The subjects with DM also showed lower VF scores than did those without DM.
Conclusion The results of the present study demonstrate that impaired glucose metabolism, independent of the conventional vascular risk factors and cerebral ischemic lesions, may be associated with a decline in executive function in community-dwelling elderly.

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Objective The first symptom of giant cell arteritis (GCA) is usually a headache. Japan has a low prevalence of GCA, and clinical features of this disorder have not been fully investigated. We conducted a retrospective evaluation of clinical features in patients with giant cell arteritis who visited a headache clinic in Japan.
Methods Clinical and demographic data were obtained from clinical examinations, face-to-face interviews, and hospital records.
Patients Subjects comprised 19 patients (9 men, 10 women).
Results Mean age at disease onset was 78.1 ± 4.8 years (range, 71-86 years). Seventeen of 19 patients (89.5%) had consulted other medical institutions before consulting our hospital, but only 2 of those patients had been diagnosed with GCA at these medical institutions. Manifestations at disease onset included headache (89.5%), ear pain (5.3%), and jaw pain (5.3%). Ocular manifestations were reported in 2 patients (10.5%). No loss of vision occurred. One patient showed trigeminal nerve palsy involving the third division of the nerve. Jaw claudication was observed in 3 patients (15.8%). Concomitant polymyalgia rheumatica was seen in 3 patients (15.8%). No patient showed upper respiratory tract symptoms, arm claudication, or aortic aneurysms.
Conclusion Although most patients had consulted other medical institutions before consulting our hospital, they were not diagnosed with GCA at these institutions. Infrequent clinical findings of GCA and lack of symptoms other than headache may contribute to the high rate of unrecognized and misdiagnosed cases of GCA.

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Objective Diseases presenting extrapyramidal symptoms are accompanied by nigral cell loss. In the previous study, we demonstrated the reduction of the neuromelanin-positive volume of substantia nigra (SN) pars compacta (SNc) in patients with Parkinson's disease (PD) using 3-Tesla MRI. In the present study we investigated the neuromelanin-positive SNc volume in patients with the other parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and compared the results with those with PD, spinocerebellar ataxia (SCA) and controls.
Patients and Methods Axial T1-weighted (T1W) images were obtained with a 3-Tesla MRI scanner. The border of the neuromelanin-positive region of the SNc was traced manually on these images with a pentablet pointing device and the SNc volume was calculated. The SNc volumes of 28 patients with MSA, 11 patients with PSP and 10 patients with CBD were compared with those of 80 patients with PD, 9 patients with SCA and 54 patients who had suffered mild acute ischemic stroke as controls. The mean volumes for the left and right SN were used for statistical analyses.
Results The volumes of the neuromelanin-positive SNc region in patients with MSA, PSP and CBD, but not SCA were reduced to the same extent as PD patients compared with controls.
Conclusion Reduced volume of the neuromelanin-positive SNc region of patients with MSA, PSP and CBD was detected by neuromelanin MR imaging. Volumetric evaluation of neuromelanin MR imaging may provide a biomarker of nigral degeneration in patients with MSA, PSP and CBD as in patients with PD.

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A 53-year-old woman was admitted because of a giant pancreatic tumor. Hypercalcemia and a high serum parathyroid hormone-related peptide (PTHrP) level were observed. A hypoglycemic attack occurred during pancreatectomy, and the surgical specimen revealed a PTHrP-secreting glucagonoma. Liver metastases developed 1 and 5.5 years later, and bone metastases appeared 6 years after surgery. Her serum PTHrP concentrations remained normal after surgery, despite re-elevation of the serum glucagon concentration after recurrence. The clinical course of this case illustrates the process of development of neuroendocrine tumors secreting two or more hormones.

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We injected acetylcholine (Ach) into the coronary artery to ascertain whether coronary vasospasm contributed to the syncopal events or chest oppression suffered by 3 patients with long QT syndrome (LQTS). During the test, a quadripolar electrode catheter was placed in the right ventricle and the activation-recovery interval was reanalyzed from the stored data. Intracoronary Ach transiently prolonged the QT intervals in all 3 patients without inducing coronary vasospasm. The Ach-induced QT prolongation was associated with enhanced spatial and temporal dispersion of intra-ventricular repolarization. The electrophysiological abnormalities were consistent with the putative arrhythmogenic mechanisms identified in experimental studies of LQTS.

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A 62-year-old woman presented with a markedly increased serum ALP level of skeletal origin during a regular follow-up of chronic hepatitis C. Serum calcium, phosphorus, and intact-PTH levels were normal and bone turnover markers were increased. Her generalized bone density was diffusely increased. These findings were consistent with hepatitis C-associated osteosclerosis (HCAO). She underwent cholecystectomy, as gallbladder cancer was suspected; however, histopathological findings demonstrated xanthogranulomatous cholecystitis. After cholecystectomy, serum ALP level and bone turnover markers were gradually decreased. This may indicate the existence of a novel osteogenic factor in the gallbladder in HCAO.

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A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on ^99mTc scintigraphy, ¹²³I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.

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Elective abortion complicated by bilateral renal cortical necrosis (BRCN) is not common in a developed country. We reported a patient having anuric acute renal failure after elective abortion. Initial laboratory studies implied thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome, but plasma exchange was not prescribed since magnetic resonance imaging study suggested BRCN soon after. The patient was treated as septic abortion and reached partial renal recovery after antibiotic treatment and short-term hemodialysis. Early diagnosis of BRCN is essential not only for prognosis prediction but also for treatment decision. We suggest that any anuric patient in suspicion of BRCN should receive MRI study as soon as possible.

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A 68-year-old man was admitted with acute renal failure caused by cholesterol embolization after undergoing carotid artery stenting. Hemodialysis therapy (HD) was immediately required because of uremia, using nafamostat mesilate as an anticoagulant for HD. However, blue toes and gangrene of the feet worsened. To prevent use of anticoagulants and stabilize BP, HD was changed to peritoneal dialysis (PD). After starting PD, blue toes and gangrene improved markedly. Residual renal function also partially recovered. Although BP was unstable during HD, stability of BP and avoidance of anticoagulants during PD therapy might have contributed to the good results.

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A 70-year-old woman was admitted to our hospital because of sudden hearing loss. She was treated with intratympanic dexamethasone, but her hearing impairment progressed. After admission, she developed scleritis of her left eye. Laboratory findings included elevated white blood cell count and C-reactive protein level, microhematuria, and proteinuria. Serology was positive for myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA), but negative for proteinase 3 (PR3)-ANCA. Renal biopsy revealed a single glomerulus with extensive glomerular tuft necrosis, indicating necrotizing vasculitis. She was diagnosed with MPO-ANCA-associated polyangiitis. ANCA-related polyangiitis should be considered in the differential diagnosis of sudden deafness or scleritis.

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Williams-Campbell syndrome is a rare disease, characterized by a congenital deficiency of cartilage in the fourth to sixth order bronchi, leading to chronic respiratory failure with recurrent pulmonary infections. An effective and practical treatment has not yet been established. A 31-year-old man who was diagnosed as Williams-Campbell syndrome by inspiratory and expiratory computed tomography findings developed recurrent pulmonary infections and showed progressive deterioration of dyspnea. Domiciliary NPPV was administered, followed by a dramatic improvement of respiratory failure and a decrease in the episodes of pulmonary infections. NPPV may have an advantage in adults with Williams-Campbell syndrome who have severe respiratory failure and recurrent pulmonary infections.

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We report on a 73-year-old man with systemic lymphadenopathy and chest computed tomography (CT) findings of bilateral diffuse ground-glass opacities and interlobular septal thickening. He also had pulmonary arterial hypertension (PAH). Several lymph node biopsies were attempted, without a definitive diagnosis. A thoracoscopic lung biopsy was performed, and the specimen was diagnosed as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Lymphoma cells had invaded lung vessels, resulting in PAH. We should include pulmonary lymphoma in the differential diagnosis of patients with PAH and chest CT findings of diffuse ground-glass opacities and interlobular septal thickening.

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We report a rare case of chronic myelomonocytic leukemia (CMML) with pericardial effusion. After receving the diagnosis of CMML, she had been successfully treated with hydroxycarbamide (HU). However, she was admitted to our hospital due to pericardial effusion. The majority of the cells in the pericardial fluid were monocytes. We made the diagnosis of pericardial involvement with CMML cells and intravenously administered etoposide (100 mg/body daily for 5 days). Although CMML cells disappeared from the peripheral blood, the pericardial effusion still persisted. This case indicates that pericardial effusion is a possible and life-threatening complication in CMML patients despite stably controlled leukocytes.

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A 23-year-old female was diagnosed as having simultaneous ulcerative colitis (UC) relapse and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL) without FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene. Pathological findings of colon specimens were compatible with UC, however, focal severe infiltration of eosinophils was observed in the rectum, which is unusual in UC, suggesting eosinophil-mediated organ damage. Although imatinib mesylate (IM) is usually ineffective for the treatment of HES/CEL with negative-F/P fusion gene, in the present case it led to the remission of HES/CEL and UC at a higher drug dosage level (400 mg/day). That suggested the presence of unknown tyrosine kinase abnormalities not yet categorized.

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Echocardiography and magnetic resonance imaging revealed biventricular non-compaction cardiomyopathy with ventricular (VSD) and atrial (ASD) septal defects in an unconscious, 23-year-old hypoxemic man. Doppler echocardiography showed a left-to-right shunt across the VSD and a right-to-left shunt across the ASD. Cardiac catheterization revealed elevated right atrial pressure, although pulmonary pressure was normal. We considered that the atrial right-to-left shunt had induced the hypoxemia, which was related mainly to right ventricular dysfunction in this biventricular non-compaction cardiomyopathy, but it was not related to pulmonary hypertension.

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We report the case of a 38-year-old woman, affected by a cutaneous form of mycosis fungoides (MF) who presented with a history of loud snoring associated with sleep apnea. A polysomnographic study confirmed the presence of severe obstructive sleep apnea syndrome (OSAS). Cranial and neck MRI revealed a neoplastic infiltration of the tongue base and the posterior pharynx wall. Upper airway neoplastic infiltration is rarely reported as a cause of OSAS and extra-cutaneous localizations of MF are uncommon. This is the first case in the literature of a patient with nocturnal polysomnogram documented OSAS caused by a mucosal involvement of MF.

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A patient with adult-onset Still's disease (AOSD) resistant to multiple drugs was treated in our hospital. Even biologics that block tumor necrosis factor (TNF) were ineffective. However, this patient responded quite well to tocilizumab, an interleukin (IL)-6 receptor blocker, suggesting that it is among the promising candidate drugs for multiple-drug resistant AOSD. Although the serum levels of most inflammatory markers such as C-reactive protein (CRP) and ferritin were reduced promptly by tocilizumab, that of IL-18 remained high. Thus, IL-18 is considered to have a further upstream position than IL-6 or to be at the same level as IL-6 in the inflammatory cascade of AOSD. This finding casts light on the pathogenesis of AOSD, and drugs that target IL-18 may prove beneficial in the treatment of this inflammatory disease.

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A 26-year-old woman was referred to our department due to fever and skin rash after having taken medication for a common cold. Physical examination revealed erythematous skin changes on her body associated with mucosal involvement in her eyes and oral cavity. Peripheral blood examination revealed leukopenia and thrombocytopenia. Liver function test showed hyperbilirubinemia. She was managed with high dose intravenous immunoglobulin (IVIG) at 1.0 gm/kg of body weight infused for 5 consecutive days. Although the patient's skin lesion improved dramatically with IVIG therapy, her hyperbilirubinemia aggravated progressively. Eighteen months after her presentation, liver cirrhosis was diagnosed by ultrasonography, laboratory and liver biopsy findings.

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We report a case of renal tubular acidosis (RTA) in a patient with HIV infection and AIDS. A 33-year-old HIV-positive man with Hepatitis C and tuberculous lymphadenitis was admitted due to deep venous thrombosis and generalized muscle weakness. He had never received anti-retroviral medication. The blood gases and serum electrolytes showed hyperchloremic normal anion gap metabolic acidosis with severe hypokalemia and alkaline urine. Diagnosis of distal RTA was made. His renal function and serum globulin level remained within normal range throughout his illness. Clinicians should be alert to renal tubular disorders in HIV/AIDS patients even in the absence of anti-retroviral therapy or hypergammaglobulinemic state.

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Management of ischemic heart disease in pregnant women is still difficult, as there is little experience with many of the newer treatments such as clopidogrel. The safety of clopidogrel in pregnancy is unknown, especially in combination with aspirin. Its use during gestation has been described in a few case reports. We describe the case of a 36-year-old woman in her 9th week of pregnancy with a history of chronic hypertension, dyslipidemia and CAD, who required antiplatelet treatment. Clopidogrel and aspirin were administrated until one week before delivery and a healthy child was born at 36 weeks of pregnancy by caesarean section, without any complication.

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