Objective Both brain natriuretic peptide (BNP) and cardiac sympathetic activity are useful surrogate markers of congestive heart failure. BNP is known to be secreted in response to sympathetic tone. This study examined the relationship between the cardiac sympathetic system and BNP.
Patients and Methods Sixty patients with chronic ischemic heart failure (mean age,72 years-old; 46 males and 14 females) who had undergone cardiac catheterization and were classified as NYHA II underwent resting ^99mTc-sestamibi quantitative gated imaging (MIBI) and ¹²³I-metaiodobenzylguanidine imaging (MIBG). MIBI was used to obtain left ventricular (LV) dimension. MIBG was used to obtain the washout rate and the H/M ratios as well as the extent of LV washout rate abnormality (RSNA), which was defined as the number of regions with a regional washout rate of more than mean+2SD of 15 normal subjects on a two-dimensional polar map divided into 20 regions. Blood samples were obtained to measure neurohormones such as BNP, renin activity, noradrenaline, and angiotensin II.
Results Simple linear regression analysis showed that BNP had significant correlations to age, LVEF, LV end diastolic volume, LV end systolic volume, RSNA, global washout rate, myocardial ischemia, and LV end diastolic pressure. Among them, multiple linear regression analysis showed that only RSNA (partial regression coefficient =0.618, p<0.002) had a significant positive correlation with BNP.
Conclusion This study suggested that the extent of cardiac sympathetic overactivity in the LV could enhance BNP release.

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Objective To find useful indices to identify subjects at high risk for developing diabetes.
Methods We retrospectively reviewed 75-g oral glucose tolerance test (OGTT) surveys conducted during 1980 to 2001 in a Japanese community. Using personal charts of the surveys, 230 non-diabetics were followed for progression to type 2 diabetes. The usefulness of HbA_1C, fasting (Glucose₀) and 1-hour (Glucose₆₀) glucose levels during OGTT, and indices for insulin resistance and/or secretion to identify high risk subjects for diabetes were then analyzed.
Materials Data described in personal charts of the OGTT program for residents of Nishikawa Town, Niigata Prefecture, Japan.
Results During the 4.3±2.7 years of follow-up, 52 subjects progressed to type 2 diabetes. Assessing glucose and insulin levels during OGTT, Glucose₀, Glucose₆₀, "Insulin Response Ratio" (IRR₃₀, Insulin at 30 minutes / Fasting insulin; IRR₆₀, insulin at 60 minutes / fasting insulin), and insulin secretion / insulin resistance index (ISIRI₃₀) were significantly associated with progression to type 2 diabetes even after the result for OGTT, body mass index, and familial history of diabetes were adjusted. These were also able to identify still higher risk subjects for type 2 diabetes from those with impaired glucose tolerance (IGT) although other indices for insulin resistance or secretion and hemoglobin A_1C were less contributable for this purpose.
Conclusion A combination of Glucose₀ and Glucose₆₀ can most cost effectively identify high risk subjects for type 2 diabetes from IGT. IRR₃₀, IRR₆₀ and ISIRI₃₀ can also be used for such identification. However, further studies are needed to clarify whether these indices are superior to Glucose₀ and Glucose₆₀.

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Objective Management of chronic kidney disease (CKD) is a critical issue in public health in attempt to prevent kidney failure and dialysis dependency. Since 1998, diabetes mellitus has been the leading cause of dialysis dependency in Japan. Previous reports demonstrated that the prevalence of CKD in diabetic patients was high; however albuminuria was not always present. This cross-sectional survey was performed 1) to indicate the prevalence of CKD and co-morbid illness in diabetic patients seen at diabetic clinics, and 2) to demonstrate the relationship between estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR).
Patients and Methods A total of 288 consecutive adult type 2 diabetic patients seen at four diabetic clinics in the Tokyo Metropolitan Area were enrolled in November 2007. We excluded patients with kidney failure. Estimated GFR was calculated by the MDRD Study equation with the Japanese coefficient.
Results Patients had a mean age (+/- SD), 61 (+/- 12); male, 58%; mean BMI, 25.2 kg/m² (+/- 5.2); and mean HbA_1c, 7.1% (+/- 1.3). The prevalence of CKD stage 3 was 38% (109/288) with 64% (70/109) of them being normoalbuminuric. Co-morbid illnesses, including hypertension (p<0.001) and old stroke (p=0.02), were significantly higher in CKD stage 3 patients.
Conclusion Our patients were relatively young and obese, reflecting urban clinical settings. The prevalence of CKD stage 3 patients was high. Clinicians need to check both eGFR and ACR to avoid underdiagnosis of CKD and diabetic kidney disease.

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Background Sevelamer, a nonabsorbed hydrogel that binds phosphate, is reported to reduce the serum urate concentration in maintenance hemodialysis patients, however the urate-lowering mechanism remains obscure. In this study we verify the urate-lowering effect of sevelamer in Japan in which the hemodialysis environment is different from that of western countries, and we also clarify the urate-lowering mechanism of sevelamer.
Methods A total of 127 Japanese patients undergoing maintenance hemodialysis were investigated. These patients consisted of 93 males and 34 females, and their mean age was 58.4±12.4 years (range, 25-88 years). The mean duration of hemodialysis was 8.7±6.1 years (range, 0.5-27.5 years). Sevelamer was added to each patient's former prescription for the treatment of hyperphosphatemia, and the changes in laboratory data before and after administration of sevelamer were compared. In order to clarify the mechanism of urate-lowering effect by sevelamer, a urate adsorption experiment was carried out in vitro.
Results Sevelamer significantly decreased serum phosphate value three and six months after administration. Sevelamer showed a significant reduction in serum urate values in maintenance hemodialysis patients with hyperuricemia, but not in patients with normouricemia. The change rate of serum urate correlated with the change rate of serum phosphate and the change rate of serum calcium × phosphate product, but did not correlate with that of serum calcium. Sevelamer hydrochloride adsorbed urate in vitro.
Conclusion Sevelamer decreases serum urate possibly by adsorbing urate in hemodialysis patients.

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Objective To investigate the role of circulating hepcidin, which is a homeostatic regulator of iron metabolism and a mediator of inflammation, in anemia associated with rheumatoid arthritis.
Methods Forty patients with rheumatoid arthritis (19 with anemia and 21 without anemia), 12 patients with iron deficiency anemia and 14 healthy adults were studied. Serum hepcidin levels were analyzed with hepcidin prohormone solid phase enzyme-linked immunosorbent assay.
Results The mean serum hepcidin levels were significantly higher in patients with rheumatoid arthritis with anemia compared to healthy adults and those with iron deficiency anemia. The active rheumatoid arthritis group had significantly higher mean serum hepcidin levels than the inactive rheumatoid arthritis group. In the rheumatoid arthritis group, serum hepcidin levels were positively correlated with disease activity, but inversely correlated with hemoglobin levels. The serum hepcidin level was found to be a significant predictor for hemoglobin level.
Conclusion Serum hepcidin levels are closely associated with disease activity in rheumatoid arthritis patients and might play a role in the pathobiology of chronic disease anemia associated with rheumatoid arthritis.

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Objective The prevalence of complex sleep apnea syndrome (CompSAS) among Asian patients with obstructive sleep apnea syndrome (OSAS) has not yet been reported. Distinguishing CompSAS from pure OSAS is difficult using only diagnostic polysomnography (PSG). We examined the prevalence of CompSAS in Japanese patients with OSAS and the possibility to distinguish CompSAS from pure OSAS by analyzing the severity of respiratory events based on either sleep body position or sleep stage using a diagnostic PSG.
Patients and Methods A retrospective chart review of 297 consecutive Japanese patients who were 15 years of age or older with a primary diagnosis of OSAS who were referred for CPAP titration (AHI≥20 events/hr).
Results Seventeen patients (5.7%) out of the 297 patients who had an obstructive apnea hypopnea index (AHI) of 20 or higher showed adverse increases in central apnea index (CAI) by the treatment with CPAP whereas obstructive apnea index (OAI) and mixed apnea index (MAI) were significantly decreased. In the results, the AHI on the PSG for CPAP titration reached only approximately half of the values on the diagnostic PSG. In these CompSAS patients, both the total CAI and the CAI in the supine position during NREM sleep on the diagnostic PSG were significantly higher than those in the OSAS group. The sleep body position did not so strongly affect the AHI, OAI and MAI in the CompSAS group. Multiple, stepwise, and logistic regression analyses revealed that the CAI in the supine position during NREM (p=0.026) was a significant variable to distinguish CompSAS from OSAS statistically although the variables were within the normal range.
Conclusion The prevalence of CompSAS in Japanese OSAS patients may be lower when compared with Caucasian patients. The increase of CAI in the supine position during NREM sleep on diagnostic PSG may be a characteristic feature in CompSAS.

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A 65-year-old man who had undergone retropubic prostatectomy for prostate adenocarcinoma presented with sudden dyspnea and chest pain. Contrast-enhanced multi-slice computed tomography (MSCT) revealed thrombi in the left internal jugular vein (IJV) and in branches of the right pulmonary artery. Ultrasonography showed that the thrombus which occluded the left IJV was hypoechoic and mobile. After beginning anticoagulant therapy, he again presented with dyspnea and transient hypotension. MSCT and ultrasonography showed that the IJV thrombus had moved and caused a new embolism of the left pulmonary artery branch. This is a rare case of a patient who experienced non-catheter-related thrombosis of the IJV.

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We performed mutational analyses of a woman patient with congenital nephrogenic diabetes insipidus referred to us during pregnancy. The diagnosis was made during the neonatal period, after which she was treated with spironolactone and hydrochlorothiazide. Our examination showed the patient to be apparently in good health without definite evidence of dehydration. Serum and urine osmolality were 220 mOsm/L and 50 mOsm/L, respectively, and the serum concentration of AVP was 2.7 pg/mL. Results of a water-deprivation test performed after delivery were compatible with nephrogenic diabetes insipidus. Mutational analyses showed that the patient was a compound heterozygote with point mutations at nucleotide position 298 (G to A; G100R) in exon 1 and nucleotide position 374 (C to T; T125M) in exon 2 of the aquaporin 2 gene, which have been previously described.

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A 53-year-old man was hospitalized with general fatigue, headache, dizziness and polyuria. The laboratory findings revealed anterior hypopituitarism and central diabetes insipidus. He also showed eye movement disorder and facial sensory impairment. These symptoms were treated successfully with conservative medical treatment. Concurrently, abnormal pituitary MR imaging findings were revealed. Pituitary abscess was primarily suspected on MR imaging findings, although it was difficult to differentiate pituitary apoplexy by MR imaging findings, alone. In this report, we propose a new diagnostic approach of pituitary abscess, using a combination of CT, MR imaging and clinical manifestations, without either pituitary surgery or pituitary biopsy.

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A 33-year-old woman was hospitalized for examination of edematous laryngopharynx. She was acromegalic. A pituitary adenoma with elevated serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) was detected, indicating acromegaly caused by GH-secreting pituitary adenoma. Multiple pigmented nevi were also noted without overt short stature and cubitus valgus. Chromosome analysis revealed that she had contracted Turner syndrome with 47,XXX/45,X/46,XX mosaicism. Transsphenoidal resection of the tumor decreased serum GH and IGF-I levels, but the edema was not improved. Both premature ovarian failure and hypertension appeared after surgery. This case may indicate the important relationships between GH/IGF-I and Turner syndrome.

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Agrobacterium radiobacter, a Gram-negative bacillus, is recognized as an emerging opportunistic human pathogen that has a propensity to cause infections in patients with indwelling foreign devices. Here, we describe the first reported case of catheter-related bacteremia caused by A. radiobacter in a hemodialysis patient with a long-term tunneled-cuffed hemodialysis catheter. This case shows that A. radiobacter should be included in the list of pathogens that can cause catheter-related bacteremia in hemodialysis patients.

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We report a case of pulmonary Mycobacterium abscessus (M. abscessus) infection with destructive growth in the entire right lung. The patient was 56-year-old woman who had had pulmonary tuberculosis at the age of 40 and had been diagnosed as having pulmonary Mycobacterium abscessus infection 4 years prior to admission at our hospital. Although various antibiotics were administered, persistent fever, hemoptysis and weight loss developed. After undergoing a right pneumonectomy, her clinical symptoms improved dramatically and sputum excretions of M. abscessus ceased. No relapse of the disease has been observed in the 2 years since surgery. Pneumonectomy was very effective for refractory M. abscessus infection that destroyed the right lung.

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A 66-year-old woman complained of fever, sore throat, and neck pain due to pharyngitis and painful lymph node swelling. CBC revealed severe pancytopenia and markedly hypocellular marrow. The administration of antibiotics and granulocyte-colony stimulating factor (G-CSF) successfully ameliorated the inflammatory lesions, and hematopoiesis recovered. Causes for pancytopnenia was unlikely to be virus infection or drugs, and aplastic anemia was also unlikely since only the plasma levels of tumor necrosis factor-α (TNF-α) was markedly elevated, erythropoietin (EPO) was slightly elevated, interferon-γ (IFN-γ) was normal, and flow cytometric analysis for paroxysmal nocturnal hemoglobinuria (PNH)-type cells was negative. These results suggested that the cause of impaired hematopoiesis in the present patient might have been due to elevated TNF-α in overwhelming infection, although the pathogen was not identified.

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Chronic active Epstein-Barr virus (EBV) infection, which is considered to be a childhood disease, often develops into natural killer (NK) or T-cell lymphoma after recurrent infectious mononucleosis (IM)-like symptoms. We describe a 56-year-old woman who developed NK-cell lymphoma after 9 months of recurrent IM-like symptoms. The patient had an unusual anti-EBV antibody profile. Increased levels of EBV genome were detected in the liver and peripheral blood. Several chemotherapy regimens were ineffective, and the patient died of progression of lymphoma. Certain subtypes of NK-cell lymphoma showing a long-lasting prodrome related to chronic EBV infection may exist.

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We report a rare case of primary cutaneous diffuse large B-cell lymphoma (DLBCL) with Burkitt-like morphology. A 54-year-old man presented with multiple subcutaneous tumors. Pathological examination showed morphological features resembling Burkitt or Burkitt-like lymphoma (BL/BLL) with high MIB-1 positivity. Cytogenetic studies revealed no 8q24/c-myc translocation. After the diagnosis of Burkitt-like DLBCL, the patient was treated with CODOX-M chemotherapy (cyclophosphamide, doxorubicin, vincristine, cytarabine and methotrexate), which led to durable remission. The present case suggests that short-term, high-intensity chemotherapy used for BL/BLL may be appropriate for primary cutaneous Burkitt-like DLBCL, as well as systemic lymphoma with Burkitt-like morphology.

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A 26-year-old man developed acute disseminated encephalomyelitis (ADEM) after Mycoplasma pneumoniae infection, and was admitted after developing disturbed consciousness. Magnetic resonance images revealed lesions in the midbrain, bilateral internal capsules, left corona radiata, white matter of the left occipital lobe, and thoracic spinal cord. He was diagnosed with subclinical measles infection since no anthema was observed despite the fact that his serum and cerebrospinal fluid samples were positive for measles IgM antibodies. ADEM following mixed infection with measles and M. pneumoniae is rare, and it is not clear whether an additional infection with measles influenced the onset of ADEM after M. pneumoniae infection. Symptoms did not improve with steroid or immunoglobulin treatment, but improvement in symptoms was observed after plasmapheresis.

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A 52-year-old man was admitted with a brain abscess in the left basal ganglia. He had a paradoxical brain embolic mechanism owing to a pulmonary arteriovenous fistula (PAVF) and was diagnosed as having a right-to-left shunt by transesophageal echocardiography (TEE) and transcranial color Doppler (TCD) with saline contrast medium. We determined that the brain abscess was caused by the PAVFs without Rendu-Osler-Weber disease. TEE and TCD with saline contrast medium were very useful for identifying the presence of the right-to-left shunt that caused the brain abscess.

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