Objective To examine the effects of fenofibrate, an antilipotropic drug, on uric acid metabolism in healthy male subjects and on urate transporter 1 (URAT1).
Methods Fenofibrate was administered to nine male volunteers at a dose of 300 mg (corresponding to 200 mg of micronized fenofibrate), and the metabolic parameters of uric acid were investigated for more than 12 hours. In addition, the effect of fenofibrate on URAT1-expressing cells was examined.
Results After the administration of fenofibrate, the concentration of serum uric acid had significantly decreased from 5.8±0.4 mg/dL to 4.3±0.3 mg/dL at 10 h. Uric acid clearance and the fractional excretion of uric acid increased. Fenofibric acid, a fenofibrate metabolite, inhibited URAT1 to an extent similar to that observed with benzbromarone and losartan.
Conclusion Fenofibrate decreased serum uric acid levels by increasing its urinary excretion, most likely through the inhibition of URAT1 by fenofibric acid, its major metabolite.

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Objective This study assessed the diagnostic rate of pulmonary tuberculosis (PTB) using fiberoptic bronchoscopy (FBS) in patients with suspected PTB, and negative pre-bronchoscopy smear and polymerase-chain reaction (PCR) in sputum.
Patients and Methods We retrospectively reviewed 201 culture-positive PTB patients that underwent FBS because both smear and PCR results in sputum were negative. The positive rates of smear for acid fast bacilli, PCR for Mycobacterium tuberculosis, the presence of granuloma in transbronchial biopsy (TBB), and culture of M. tuberculosis were analyzed. In addition, the radiographic features, contribution of FBS to rapid and/or definitive diagnosis of PTB, and drug susceptibility results of M. tuberculosis were also reviewed.
Results There were 136 males and 102 patients under the age of 40 years; non-cavitary (156 cases) and minimal disease (119 cases) on radiographs predominated. The positive rates of FBS were: 44% (smear), 62% (PCR), 61% (TBB), and 87% (culture). These rates increased in smear and PCR examinations when taken from wider spread shadows on radiographs. The combination of the various bronchoscopy samples increased the diagnostic rate to 92% when all examinations were combined. Positive culture results depended on FBS procedures in 80 cases. Twenty-one cases showed resistance to at least one of the major anti-tuberculous agents.
Conclusion This analysis revealed high positive rates of PTB from bronchoscopy samples, providing rapid and definitive ability for PTB diagnosis, and details of drug susceptibility. Therefore, FBS is an important diagnostic procedure in patients with suspected PTB whose sputum specimens were negative both for smear and PCR analyses.

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Objective To retrospectively evaluate the efficacy and safety of gefitinib in elderly patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor mutations.
Methods and Patients Nine patients aged 70 years or older who had advanced NSCLC with mutations of the epidermal growth factor receptor gene were treated with gefitinib, 250 mg daily. Clinical data, types of epidermal growth factor receptor mutations, efficacy and toxicity of gefitinib were evaluated in these patients. Tumor responses were assessed by computed tomography scan using the Response Evaluation Criteria in Solid Tumors.
Results Six patients showed a partial response, and the other three exhibited stable disease. The overall response rate was 66.7%. The median progression-free survival was 396 days, whereas the median over all survival was 523 days. No serious toxicities were observed.
Conclusion Gefitinib is very efficacious and safe for elderly patients with adenocarcinoma of the lung harboring an EGFR tyrosine kinase mutation. The present data support the use of gefitinib in this particular subgroup.

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Background Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is considered to be a nearly fatal condition during the clinical course of IPF, as it is unresponsive to most conventional therapies.
Subjects and Methods To evaluate the efficacy of cyclosporin A (CsA) for AE of IPF, we conducted a retrospective study on autopsied IPF cases who developed AE and were treated with corticosteroids (CS) combined with CsA. The subjects comprised 11 males with a mean age of 69.9 years. The clinical features and prognosis of the CsA-treated group was compared to a group of 11 autopsied IPF cases with a mean age of 68.7 years who developed AE and were treated with CS alone (non-CsA-treated group).
Results CS pulse therapy followed by CS maintenance treatment were conducted in all cases of AE. Patients in the CsA-treated group received in addition a low dosage of CsA (100-150 mg). Although 7 out of 11 patients in the CsA-treated group died of AE per se, 4 patients survived the AE. Only 2 patients died during the first episode of AE. In comparison, 7 out of 11 patients in the non-CsA-treated group died during the first episode of AE. The mean survival period after the first onset of AE was 285 days in the CsA-treated group and 60 days in the non-CsA-treated group. The prognosis of the CsA-treated group therefore was significantly better than that of non-CsA-treated group after AE of IPF.
Conclusion Administration of CsA combined with CS may be efficacious in the treatment of AE of IPF.

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Objective To compare two systemic inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC), as a component of metabolic syndrome (MetS).
Methods Data of hs-CRP and WBC from 2,185 Japanese men and 1,383 Japanese women were examined using receiver operating characteristic (ROC) curve for diagnosing MetS and Spearman's correlation coefficients.
Results The area under ROC curve (AUC) of hs-CRP was 0.71 in men and 0.74 in women. The AUC of WBC was 0.65 in men and 0.69 in women. The optimal cutoff point (sensitivity; specificity) of hs-CRP was 0.40 mg/L (0.69; 0.65) in men and 0.35 mg/L (0.67; 0.72) in women. The optimal cutoff point (sensitivity; specificity) of WBC was 5,600/L^-6 (0.61; 0.61) in men and 5,000/L^-6 (0.65; 0.63) in women. Correlations between obesity parameters, blood pressure, and liver function tests were stronger with hs-CRP than with WBC. But, no correlation between MetS-related risk factors was stronger with WBC than with hs-CRP.
Conclusion Hs-CRP is superior to WBC as an inflammatory component of MetS in Japanese. However, WBC may be useful when hs-CRP is not available because WBC is routinely measured in clinical practice.

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Objective Primary care has potential to play a role for improving the patient care in Japanese health care system; however, little information is available about how patients perceive the roles of primary care physicians (PCPs) within the Japanese health care system. We aimed to assess population-level preferences for PCPs and investigated the extent to which preferences vary in relation to different population groups in Japan.
Methods Data were extracted from a cross-sectional questionnaire survey in October 2003. An 18-item questionnaire was used to measure the preferences for PCPs. Exploratory factor analysis was performed to identify latent factors, while confirmatory factor analysis was used to evaluate the fit of the structure using structural equation modeling (SEM).
Patients Nationally representative sample of the adult Japanese general population was chosen by controlling for age, sex, and the size of cities.
Results A total of 2,453 adults ≥18-years-old were analyzed. SEM provided a 4-factor structural model of the population-level preference for PCPs, such as clinical competence (path coefficient (pc)=0.72), gate-keeping (pc=0.64), communication with patients or specialists (pc=0.49) and high education (pc=0.25) and demonstrated the best goodness-of-fit. Those who were middle aged, have a high family income, and a high level of education, placed more importance on gate-keeping characteristics, and the rural residents emphasized communication rather than clinical competence.
Conclusion Our results indicate that the preferences for PCPs are divided into four main factors and underscore the variation among preferences according to different population groups, such as age, socioeconomic and educational status, and places of living. These variations should be considered to improve the primary care system in Japan.

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Acute viral infections can lead to heart inflammation, including acute myocarditis. We report a rare case of myopericarditis in a young immunocompetent adult, in a context of recent Cytomegalovirus (CMV) infection.
The clinical presentation was an influenzae-like syndrome, classical for a CMV infection, without any chest pain or dyspnea, but a systematic exploration showed multiple inflammation-compatible myopericardial images on MNR-scan. The diagnosis of asymptomatic myopericarditis was established. We present the MNR-scan findings and discuss the CMV cardiac effects and systematic cardiac MRI interest in viral infection.

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We report the case of a 50-year-old man admitted for cardiac tamponade. He was diagnosed with acute pneumonia. He had no previous medical history, but exhibited a body mass index of 41. Two days before admission, he complained of chest pain irradiating to the neck lateral side. Massive cardiac tamponade developed over 48 hours. There was no obvious cause for immunodepression. Pericardial puncture was ineffective, due to obesity and fluid high viscosity. Surgery was undertaken (Marfan intervention). Pericardial fluid was found to be purulent; direct examination revealed nocardia as bacteria with typical filamentous, branching rods. Despite adapted antibiotic treatment the patient died within a few hours. Acute pericarditis due to Nocardia is discussed.

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Understanding the clinical characteristics of transthyretin familial amyloid polyneuropathy (TTR-FAP) is critical for early diagnosis and timely referral for liver transplantation. Here, we describe a 52-year-old man who had slight paresthesia for four years and whose final diagnosis of TTR-cardiac amyloidosis caused by sporadic FAP was delayed despite annual electrocardiography. Curative liver transplantation was postponed because of progressive cardiac involvement. This experience highlights the difficulties associated with diagnosing TTR-FAP, especially when it is sporadic, and underscores the importance of slight changes in ECG that could indicate FAP.

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Emergency coronary angiography of a 53-year-old man with acute coronary syndrome revealed stenosis in right coronary artery. During angioplasty, the ECG change showed three kind of ST deviation, namely inferior ST elevation with precordial ST depression, inferior ST elevation with precordial ST elevation, and inferior ST depression with precordial ST elevation. The present case shows that the ST deviation of the inferior ischemia with right ventricular ischemia takes various patterns. This phenomenon is decided by degree of right main coronary and right side branch blood flow.

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Acute myocardial infarction (MI) complicated with acute pancreatitis has been rarely reported. A 68-year-old man presented to our department 15 hours after development of epigastric pain. In addition to his symptoms, the elevated serum pancreatic enzymes and the image study on abdominal computerized tomography all led to the diagnosis of acute pancreatitis. Elevated cardiac biomarkers and a standard 12-lead electrocardiogram (ECG) demonstrating ST-segment elevation in 5 of the 6 precordial leads suggested an attack of MI. Oral intake was resumed after medical management for his acute pancreatitis and acute MI. Coronary angiogram on day 11 revealed total occlusion of the middle segment of the left anterior-descending coronary artery. Subsequently, angioplasty with stenting was done. The patient was discharged without significant complications. It is critical to make a rapid but detailed differential diagnosis of abdominal pain. Even though acute pancreatitis-associated ECG abnormalities have been reported previously, any ECG abnormalities in a patient presenting abdominal pain should be evaluated and treated cautiously. Thorough clinical evidence, including history, physical findings, ECG, image studies and serum biomarkers, are informative in seeking and analyzing possible etiologies.

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A 59-year-old man was found to have diabetes mellitus five months after the diagnosis of pernicious anemia. Although the urinary C-peptide level corresponded to a non-insulin-dependent stage (39.9 μg/day), the markedly extremely elevated titers of GAD antibody suggested that this case very likely represented a non-insulin-dependent stage of slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Because thyroid and adrenal functions were normal, this our case was not considered to be polyglandular autoimmune syndrome (PGAS). We report this case because patients with pernicious anemia and SPIDDM in the absence of PGAS are rare in Japan.

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Central diabetes insipidus (CDI) could occurs in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), because of infiltration of leukemic cells into the neurohypophysis or some other reason and it is closely associated with abnormalities of chromosome 7. We report a case of MDS with abnormalities of chromosome 7, presenting as CDI followed by deterioration of polyuria and hyponatremia with a decreased extracellular fluid volume. Magnetic resonance imaging (MRI) revealed symmetrically enhanced lesions in the hypothalamus. Fludrocortisone treatment normalized his serum sodium level and cerebral salt wasting syndrome (CSWS) was suspected.

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The serum thyroid stimulating hormone (TSH) level is decreased in acromegalic patients. Although this phenomenon is thought to be caused by the enhanced secretion of somatostatin which suppresses TSH production, it has not yet been proven. We describe a 60-year-old woman with acromegaly who showed a low concentration of TSH. We diagnosed her as painless thyroiditis based on an increased level of thyroglobulin, depressed radioactive iodine uptake (RAIU), normal vascularity and mild swelling of the thyroid, and normal T3, T4, free T3 and free T4 levels. To our knowledge, this is the second reported case of acromegaly complicated by painless thyroiditis. The differential diagnosis between central hypothyroidism and painless thyroiditis is so important. Since it is difficult to diagnose precisely based on only the data of a low level of TSH and normal levels of thyroid hormones, we consider that measurement of thyroglobulin and RAIU is necessary when the complication of painless thyroiditis is suspected.

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Hypothermia is a life-threatening medical condition defined as an unintentional fall in body temperature below 35°C. Exposure to cold environment stimulates the thermoregulatory system to maintain the body temperature within the physiological range. Patients with malnutrition and/or diabetes mellitus are at high risk for accidental hypothermia, and acute kidney injury, which is mainly caused by pre-renal factors, occurs in relation to hypothermia. However, acute exacerbation of pre-existing chronic kidney disease has been rarely reported. Here, we present a patient with diabetes mellitus and malnutrition who developed two separate episodes of hypothermia followed by acute exacerbation of chronic kidney disease.

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We report a case of pulmonary capillary hemangiomatosis-like foci (PCH-like foci), presenting as multiple ground-glass opacities (GGOs) on high resolution computed tomography (HRCT). The patient underwent a left lingual segmentectomy to make a definite diagnosis of these GGOs on chest CT. Histological findings were similar to PCH; however, there were no clinical symptoms or findings of pulmonary hypertension. Accordingly, PCH-like foci was diagnosed.

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We report a 20-year-old woman with Crohn's disease (CD) who developed anterior neck pain while being treated with the anti-tumor necrosis factor (TNF)-α monoclonal antibody, infliximab. She showed no symptoms suggestive of active CD except for tenderness along the left common carotid artery with marked increases in serum TNF-α and inflammatory reactions. Based on thickened walls of large vessels with enhancement effects on computed tomography, she was diagnosed as having associated Takayasu's arteritis (TA), which was successfully treated with corticosteroid. Even if CD is controlled by infliximab, other autoimmune disorders, such as TA, may develop as a complication.

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Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by upper and lower motor neuron damage. Mutations of Cu/Zn superoxide dismutase gene (SOD1) account for 20% of familial ALS (FALS). We report a unique clinicogenotype of a Japanese family with a novel SOD 1 mutation. A 37-year-old woman (the proband) noticed muscle weakness in the left lower limb. Her mother had developed progressive lower motor neuron signs in four extremities at 38 years of age. Subsequently she was diagnosed as ALS and died of respiratory failure at 15 months after clinical onset. Neurological examination of the proband showed absent muscle stretch reflexes in the let knee and the left ankle without Babinski signs. Mild to moderate degree of muscle weakness existed in the left lower extremity. Muscle atrophy was presented in the left thigh. Initial pulmonary function revealed forced vital capacity of 91.1%. Electromyography disclosed ongoing denervation muscle potentials in the left lower extremity. SOD1 analysis demonstrated amino acid substitution of glycine by serine at codon 85 (G85S) in exon 4. Six months later, marked muscle weakness and atrophy expanded to four extremities. All muscle stretch reflexes were absent. Three months later, ventilator support with a tracheostomy was needed. The patient died at 18 months after clinical onset. Clinical hallmarks of this FALS family indicate that G85S mutation of SOD1 may cause rapidly progressive form of pure lower motor neuron signs.

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In recent years, biologics have been widely administered for treating rheumatoid arthritis (RA): however, the safety of these drugs has not been adequately established in embryos and fetuses. We report the case of a pregnant RA patient treated with etanercept, an anti-tumor necrosis factor (TNF) agent. She continued to receive etanercept treatment after becoming pregnant without any complications, finally giving successful birth to a baby girl at 39 weeks. This suggests that etanercept may be selected to treat RA patients with active arthritis who desire pregnancy with lower risks.

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A 64-year-old woman with hypertension and hyperlipidemia was admitted to our hospital for the investigation and management of general fatigue, anorexia, a 5-kg weight loss, and a 4-week history of high-grade fever. She had no symptoms of headache, myalgia, or arthralgia, and the physical examination was unremarkable. The laboratory tests revealed renal dysfunction with urine abnormalities that had not been observed 1 year earlier. A renal biopsy showed granulomatous small arteritis without necrotic lesions or glomerular pathology. An immunohistochemical study of the infiltrating leukocytes showed a predominance of CD4⁺ T cells followed by CD8⁺ T cells, and only a few macrophages. The condition drastically improved after treatment with 30 mg/day of oral prednisolone. The granulomatous renal arteritis was considered a variant of giant cell arteritis, because it showed the peculiar finding of a few macrophages in the granulomatous lesions.

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