Objective: Endothelial dysfunction is thought to represent the initial stage in the development of atherosclerosis. Recently, noninvasive examination of endothelial function has become possible using flow-mediated endothelium-dependent dilation of the brachial artery (FMD) during reactive hyperemia. We examined whether FMD has prognostic value for the prediction of subsequent cardiovascular events.
Methods: Patients were followed prospectively every month until the occurrence of the cardiovascular events.
Patients: The study subjects comprised 221 consecutive patients (men 108, mean age 61.4±10.6, ischemic heart disease 152, cardiomyopathy 28, arrhythmia 12, valvular disease 5, congenital heart disease 3, and cardioneurosis 21). The mean FMD was 4.77±2.85% and this value was used to divide the patients into the 2 groups (Group 1: FMD ≥4.7%; Group 2: FMD <4.7%).
Results: There were 110 patients in Group 1 (men 36, mean age 60.5±10.9), and 111 patients in Group 2 (men 72, mean age 62.2±10.3). Patients were followed until the occurrence of at least 1 of the major clinical cardiovascular events. Seven cardiovascular events occurred in Group 1 (6.4%, 1.14 events per 100 patient-years), while 16 occurred in Group 2 (2.88 events per 100 patient-years). Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiovascular events in Group 2 than in Group 1.
Conclusion: The present results demonstrated that the magnitude of FMD in the brachial artery was a good predictor of subsequent cardiovascular events.

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Objective: Restenosis after stent implantation is caused by endothelial cell damage and subsequent neointimal formation. The objective of this study is to elucidate the relevance of endothelial progenitor cells (EPCs) in the development of in-stent restenosis in patients undergoing stent implantation.
Patients or Materials: The subjects were 46 patients who underwent coronary stenting. Blood samples were collected at the time of follow-up coronary angiography after coronary stenting. EPCs were isolated from blood samples and cultured. Their phenotypes were confirmed by uptake of acetylated low-density lipoprotein and binding of fluorescein isothiocyanate-labeled Ulex europaeus agglutinin 1 lectin. The number of colony-forming units (CFUs) and the senescent cells, determined by acidic β-galactosidase staining, was counted. Angiogenic growth factors secreted by EPCs, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), and macrophage chemoattractant protein (MCP-1) from the culture medium were also measured by enzyme-linked immunosorbent assay.
Results: Patients with in-stent restenosis (defined as >40% stenosis, n=16) had a decreased number of CFUs (p<0.05), and increased senescent cells (p<0.05), compared to patients without restenosis (n=30). There was no significant difference of angiogenic growth factors (VEGF, HGF, b-FGF, and MCP-1) secreted by EPCs between the two groups. On multivariate analysis, an increased number of senescent EPCs was the indepen-dent factor associated with in-stent restenosis (OR 1.10, 95% CI 1.01 to 1.20).
Conclusion: These data suggested that EPCs might be involved in the development of in-stent restenosis.

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OBJECTIVE: Specialist care is reportedly associated with favorable therapeutic results, although detailed outcomes of recent large-scale prospective surveys of specialist care have yet to be published. The goal of this study was to elucidate the effects of one year's specialist care on the management of type 2 diabetes.
PATIENTS AND METHODS: A multi-centered, prospective observational study was undertaken. 754 type 2 diabetes patients, who made their first visit to one of eleven participating outpatient clinics specializing in diabetes care, were enrolled. Routine structured diabetes care according to established guideline, including diabetes self-management education, was provided to all patients at each clinic visit. Parameters relating to glycemic control, serum lipids, blood pressure, patient follow-up status and others were followed for twelve months.
RESULTS: The HbA_1C level had improved significantly from 8.4±2.2% at baseline to 6.8±1.2% after six months and was 7.0±1.3% after twelve months (mean±SD). The higher the baseline HbA_1C level, the greater the subsequent improvement. Moreover, the most dramatic improvements in HbA_1C levels were seen within the first three months. The proportion of patients satisfying all of the therapeutic goals was extremely low at baseline and remained at less than 10% after twelve months of specialist care.
CONCLUSIONS: Diabetic patients under specialist care experienced substantial improvement, especially in glycemic control, as early as a few months after the first visit. However, 35 percent of patients dropped out during the 12-month study period and this is one area that needs to be improved.

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Objective: We investigated the link between metabolic syndrome and proteinuria in Japanese.
Methods: A total of 12,023 Japanese subjects, aged 20-79 years, were recruited in a cross-sectional clinical investigation study. From this group, we used data of 2,121 subjects for further investigation. Proteinuria was measured by using urine strip devices. The diagnosis of metabolic syndrome was based on the new criterion in Japan.
Results: In the first analysis, 224 men (6.0%) and 359 women (4.3%) were diagnosed as trace positive (±) and 155 men (4.1%) and 147 women (1.8%) were diagnosed as positive (+≤) with proteinuria. In the second analysis, 264 men (29.7%) and 45 women (3.7%) were diagnosed as metabolic syndrome. Prevalence of proteinuria in subjects with metabolic syndrome was significantly higher than that in subjects with non metabolic syndrome in both sexes. In addition, the atherogenic index was significantly higher in subjects with metabolic syndrome than in subjects with non-metabolic syndrome.
Conclusion: The present study indicated that metabolic syndrome might be an important factor in the etiology of proteinuria in Japanese.

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Objective: Carotid intima-media thickness (IMT) is a useful surrogate marker of cardiovascular disease. Associations between hyperuricemia, metabolic syndrome and carotid IMT have been reported, but few of the studies have been conducted in a Japanese population.
Methods: A total of 1,128 subjects (498 men aged, 68±14 years and 630 women aged 72±12 years) were divided into 4 groups according to serum uric acid (SUA) quartiles. We first investigated the association between SUA concentrations and metabolic syndrome; then, we assessed whether there is an independent association of SUA with carotid IMT in a population subdivided according to gender and metabolic syndrome status.
Results: In women, the prevalence of visceral obesity and metabolic syndrome were significantly increased with increased SUA quartiles, but not in men. After adjusting for age, smoking status, LDL-cholesterol, creatinine and history of diabetes mellitus, the odds ratios (95% CI) of sex-specific quartiles of SUA for metabolic syndrome were 1.0, 1.37 (0.79-2.37), 1.37 (0.79-2.38), and 1.80 (1.03-3.15) in men, and 1.0, 1.04 (0.56-1.94), 2.35 (1.30-4.22), and 2.20 (1.16-4.20) in women. After adjusting for various known risk factors, the prevalence of carotid atherosclerosis (IMT≥1.0 mm) was higher in subjects in the second, third and fourth quartiles of SUA concentration with odds ratios (95% CI) of 2.41 (1.08-5.37), 3.33 (1.49-7.42), and 2.73 (1.17-6.35), respectively in men without metabolic syndrome but not in men with metabolic syndrome or in women with or without metabolic syndrome.
Conclusion: The prevalence of metabolic syndrome was significantly increased according to SUA values only in women. In men without metabolic syndrome, SUA was found to be an independent risk factor for incidence of carotid atherosclerosis.

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Objective: It is well known that the serum level of KL-6 can be an indicator of disease activity in patients with interstitial pneumonia (IP). However, surgical lung biopsy is often required for the diagnosis of IP, although this can result in IP exacerbation.
Methods: The effect of surgical lung biopsy on the serum level of KL-6 in patients with IP was analyzed. Thirty-two cases of IP were examined in this study. There were no cases showing exacerbation of IP.
Results: The serum level of KL-6 demonstrated 1067±550 U/ml (mean±SD) before lung biopsy, 991±471 U/ml a day, 824±377 U/ml 4 days and 826±384 U/ml 7 days after lung biopsy. The serum KL-6 levels on the 1st, 4th, 7th day after the lung biopsy were significantly lower than that before the lung biopsy (P<0.05, P<0.01 and P<0.01, respectively). The percent decrease of the serum KL-6 levels on the 4th day (the lowest level) was dependent on the urine volume, and the analysis of the urinary levels of KL-6 showed a transient increase in urinary KL-6 excretion, suggesting that the decrease in serum KL-6 levels associated with surgical lung biopsy may be caused by this increase in urinary KL-6 excretion.
Conclusion: Surgical lung biopsy of patients with IP has little effect on the increase in serum KL-6 levels. An elevation of serum KL-6 after surgical lung biopsy may indicate exacerbation of IP.

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A 77-year-old man hospitalized for epigastric pain showed jaundice of the skin and conjunctivae. Laboratory tests revealed elevated hepatobiliary enzymes and inflammatory markers, and imaging studies demonstrated a 12 cm hepatic cyst compressing the common bile duct. The diagnosis was a giant hepatic cyst causing obstructive jaundice. Cyst drainage and sclerotherapy with 5% monoethanolamine oleate was performed twice, resulting in almost complete disappearance of the cyst. Obstructive jaundice due to a hepatic cyst, as seen in this case, is relatively rare and this report includes a review of other similar cases in Japan.

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Bifid intrathoracic rib is a very rare anomaly of the ribs that is characterized by an osseous prominence of a rib into the thoracic cavity. We report a 21-year-old woman with bifid intrathoracic rib arising from the anterior-lateral portion of a depressed 4th rib, based on findings from chest radiography and computed tomography (CT). This is only the second reported case of this type of intrathoracic rib worldwide. We discuss differential diagnoses for this case and suggest a classification of intrathoracic rib from the perspective of morphology and developmental biology.

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A 51-year-old man developed anemia, and was diagnosed with pure red cell aplasia through the absence of erythroid progenitors. Initially, he was treated with cyclosporine and prednisolone for 6 months but they were ineffective. Large granular lymphocyte (LGL) leukemia with the T-cell γ δ phenotype evolved after 6 months showing CD2+, CD3+, CD8- and CD56- with the T-cell receptor β gene rearrangement, clonalities of γ and δ genes and complex chromosome abnormality simultaneously with hemophagocytic syndrome (HPS). Epstein-Barr virus (EBV) genomic DNA was detected in the bone marrow cells. Administration of bolus methylprednisolone was ineffective, and the patient died one month later. In the present patient, it seemed that lymphoproliferative disease of large granular lymphocytes (LDGL) manifested initially as PRCA, γδ LGL leukemia evolved, and finally fatal HPS become complicated, presumably caused by the EBV reactivation in the immunodeficiency state with the administration of immunosuppressants.

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Involvement of cranial nerves is rare in plasma cell leukemia (PCL). Here, we report a case of PCL presenting with unilateral abducens paralysis. Cranial magnetic resonance imaging (MRI) disclosed a mass in the sphenoid sinus. Although the patient showed an initial response to chemotherapy, he died of disease progression 5 months later. Cytogenetic analysis showed translocation of chromosomes 11 and 14, t(11;14) (q13;q32), with additional complex abnormalities. This case implies an association between clinical manifestations and chromosomal abnormalities.

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A 78-year-old man with a history of mycosis fungoides was referred for evaluation of a right adrenal mass. A physical examination showed the left cervical lymph node to be palpable, which was later shown to be caused by a diffuse large B-cell lymphoma. The patient was diagnosed with concurrent mycosis fungoides and a diffuse large B-cell lymphoma. Three courses of chemotherapy were performed, however, the patient died of advanced disease. Autopsy findings showed that the right adrenal and soft tissue masses had an identical B-cell origin. Although the exact mechanism remains unclear, the pathogenesis of this rare association is discussed.

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Moyamoya disease is a cerebrovascular disorder characterized by bilateral stenosis or occlusion of the terminal portions of the internal carotid arteries accompanied by typical net-like collateral vessels in the basal ganglia. Although the etiology of moyamoya disease remains unknown, hereditary and immunogenic as well as hemodynamic factors have been implicated in the underlying mechanism of moyamoya disease. We report two patients with confirmed moyamoya disease and a patient with probable moyamoya disease complicated with Graves' disease. We reviewed the literature and summarized 23 cases of moyamoya disease or probable moyamoya, coexisting with Graves' disease.

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We report a 65-year-old man with classic polyarteritis nodosa (PAN) who developed subarachnoid hemorrhage. Polyarteritis nodosa was strongly suspected, however, the biopsy specimens of kidney and sural nerve showed no findings of vasculitis and the serum titer of antimyeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA) was negative. Cranial magnetic resonance angiography showed no findings of aneurysms. He developed subarachnoid hemorrhage (SAH) during the course and died. Autopsy confirmed fibrinoid necrosis in the medium-sized artery of multiple organs. To our knowledge, this is the first report of a case of classic PAN accompanied by SAH in which MPO-ANCA proved negative.

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Löfgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among white people, but is considered rare among Japanese people. We present the case of a 26-year-old Japanese woman with Löfgren's syndrome. The patient complained of polyarthritis and EN of the lower extremities that lasted for 3 months. A chest radiograph revealed BHL and nodular shadows. The angiotensin-converting enzyme (ACE) level was within the normal range. Transbronchial lung biopsy revealed a noncaseating granuloma with giant cells. Six Japanese cases of Löfgren's syndrome have been reported previously. Five of the seven Japanese patients with Löfgren's syndrome had normal ACE levels; all of them exhibited BHL. Löfgren's syndrome should be considered as a possibility when examining a patient with EN and articular symptoms, even if the patient is Japanese.

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