Niemann-Pick C1-like 1 (NPC1L1) has recently been identified and has been shown to have features of a plasma membrane transporter, including a secretion signal, 13 predicted transmembrane domains, extensive N-linked glycosylation sites and a sterol-sensing domain. It is highly expressed on the surface of absorptive jejunal enterocytes. NPC1L1 has been shown to be a direct target of ezetimibe, and an ezetimibe-sensitive pathway plays a role in intestinal cholesterol absorption. Ezetimibe-based therapy represents an exciting new area in the treatment of dyslipidemia.

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Objective It is widely acknowledged that identification and treatment of gestational diabetes mellitus (GDM) results in better maternal and neonatal outcomes. However, the utility of the glucose challenge test (GCT) remains controversial regarding the diagnostic approach and decision making.
Methods We performed a retrospective analysis on the database of our Laboratory Information System to retrieve results of GCT and oral glucose tolerance test (OGTT), which were performed on consecutive female outpatients referred by the gynecologists over the last 3 years.
Results Cumulative results for GCT and OGTT were retrieved for 724 female outpatients and screening test was abnormal in 114 of them. This group was classified in terms of normal glucose tolerance (NGT), one abnormal value for the 100-g-3h OGTT (OAV) and GDM. GDM was diagnosed only in 34 subjects (4.7%). No statistically significant differences were observed in the basal plasma glucose and 1-h GCT values among groups. Multivariable logistic regression analysis demonstrated that age, OGTT values ≥180 mg/dL at 1 hour and OGTT values ≥155 mg/dL at 2 hours, but not GCT values, were independent predictors for GDM (p=0.048, p=0.012 and p<0.001, respectively).
Conclusions Results of our retrospective analysis on an unselected population are consistent with the hypothesis that GCT is not predictive of GDM and its diagnostic significance remains questionable.

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Objective Visceral fat accumulation is an underlying component of the metabolic syndrome (MetS). Hypoadiponectinemia is one of the key molecules of the MetS. In the present study, we investigated the relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men.
Patients and Methods The study group comprised 1,520 Japanese employed men (mean age: 45.6±10.4 years, ± SD), who had undergone an annual health check-up both in 2004 and 2005. In addition to parameters measured in the annual health check-up, visceral fat area (VFA) and serum adiponectin concentration were measured by the bioelectrical impedance analysis method and a sandwich enzyme-linked immunosorbent assay (ELISA) system, respectively.
Results Visceral fat accumulation was identified in 56.1% of the subjects with hyperuricemia. There was significant positive correlation between visceral fat area and serum uric acid levels (r=0.223, p<0.0001), and negative correlation between serum adiponectin concentration and serum uric acid levels (r=-0.198, p<0.0001). The one-year change in VFA was associated with the one-year change in serum uric acid levels. Stepwise multiple regression analysis showed that VFA and the serum adiponectin concentration were significant explanatory variables for serum uric acid levels.
Conclusion Hyperuricemia is significantly associated with visceral fat accumulation and hypoadiponectinemia in Japanese men.

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Objective We investigated whether or not "low dose" metformin could prevent weight gain induced by pioglitazone.
Research Design and Methods Sixty-nine patients with type 2 diabetes received 500-750 mg metformin a day for 12 weeks as an observation period before the start of the intervention. After an observation period, inadequately controlled patients (hemoglobin A1c ≥7.5%, n=34) received additional treatment with 15 mg pioglitazone (+P, M+P group). The other patients (n= 35) continued metformin monotherapy (Met group). In addition, another group consisting of 28 patients treated with 15 mg pioglitazone alone (Pio group) was observed. Body mass index (BMI), as well as several clinical parameters of glycemic control and lipid metabolism, was compared before and after 24 weeks of intervention.
Results BMI increased significantly in the Pio group [24.0±3.8 vs. 24.8±4.3 kg/m², (mean ± SD), p<0.001], but not in the M+P group (25.1±3.5 vs. 25.3±3.4 kg/m², NS) and Met group (24.0±3.3 vs. 24.0±3.5 kg/m², NS). In addition to improvement in glycemic control, a significant reduction in the atherogenic index of plasma (AIP), defined as log [TG ×0.0112/HDL-C ×0.02586], was observed in the Pio group (0.06±0.23 vs. -0.04±0.27, p<0.05) and M+P group (0.08±0.24 vs. -0.001±0.252, p<0.01), but not in the Met group.
Conclusion This study indicates potential benefits of the addition of pioglitazone to "low dose" metformin in terms of improvement of glucose and lipid metabolism without weight gain.

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Background An increased incidence of pneumococcal infection triggered by influenza infection has been reported.
Objective To examine the effectiveness of the additive inoculation of influenza vaccine (I-V) and 23-valent pneumococcal vaccine (P-V) to prevent lower respiratory tract infections.
Methods 105 Japanese patients with chronic respiratory disease underwent the additive inoculation of I-V and P-V between October 2002 and January 2003, and their medical records were used to retrospectively examine the number of bacterial respiratory infections, number of hospitalizations, and length of hospital stay in the 2 years prior to and after P-V inoculation. Among them [chronic obstructive pulmonary disease (COPD): 45; bronchial asthma: 24; bronchiectasis: 20 (including diffuse panbronchiolitis); and other diseases: 16], 98 patients were evaluated, except for seven patients who died of diseases other than respiratory infections within the 2 years after P-V inoculation. Subjects were 51 to 91 years of age (median: 74 yrs), the male-female ratio was 63:42, and 32 patients were on home oxygen therapy.
Results After P-V inoculation, decreases in the number of respiratory infections (3.16 vs. 1.95 infections; p=0.0004) and in the number of hospitalizations (0.79 vs. 0.43 hospitalizations; p=0.001) were observed. Furthermore, an analysis including other factors, i.e., number of patients on home oxygen therapy and influenza season, also revealed a decreased number of hospitalizations.
Conclusions The additive inoculation of I-V and P-V in Japanese patients with chronic respiratory disease prevented the development of bacterial respiratory infections and warrants further study in patients with respiratory disease.

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Objective To review diagnostic procedures, therapeutic modalities, and follow-up methods in patients with suspected lung tumors.
Methods We retrospectively examined 70 patients who underwent a complete medical checkup because they had been positive for sputum cytology and had presented no chest X-ray findings for the 10-year period between 1994 and 2004. To make a diagnosis, we conducted the first complete medical checkup that included chest X-ray, sputum cytology, chest computed tomography (CT), and bronchoscopy. In the case that no diagnosis could be made, we repeated the chest X-ray and sputum cytology every 3 to 6 months and additionally conducted chest CT and bronchoscopy according to abnormal findings.
Results Among 70 patients, there were 36 and 13 who were diagnosed during the first complete medical checkup and follow-up, respectively, 13 who remained undiagnosed, and eight for whom follow-up was discontinued. Among the 49 diagnosed patients, 40, 8, and 1 patient had lung cancer, upper respiratory tract carcinoma (URTC), and esophageal carcinoma (EC), respectively. Among the 40 patients with lung cancer, 34 had a stage 0 or I tumor and 15 were radically treatable by photodynamic therapy and endobronchial irradiation. Nine among 11 patients whose lung cancer was detected during follow-up had a stage 0 or IA tumor.
Conclusion Not only lung cancer but also URTC and EC were successfully detected in patients who were positive for sputum cytology and presented negative chest X-ray. Radical treatment was possible in 38 (76%) of 50 diagnosed patients, thus indicating the importance of follow-up through these procedures.

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Objective This study investigated the relationship between mental retardation and lifetime events in patients with Duchenne muscular dystrophy (DMD).
Methods The data on mental retardation and ages of lifetime events (first walking, loss of ambulation, introductions of ventilator support and tube nutrition and death) were collected retrospectively, and the relationships between the factors were analyzed.
Patients Among 194 DMD patients admitted to our hospital between 1995 and 2007, 74 patients underwent evaluation of their intelligence quotient (IQ).
Results Twenty-eight patients (38%) demonstrated mental retardation (IQ<70). DMD patients with mental retardation started walking later, required ventilator and tube nutrition support earlier, and died earlier than those without mental retardation.
Conclusions Since the prognosis of DMD patients with mental retardation was worse than that of those without mental retardation, more careful treatment is necessary for DMD patients with mental retardation.

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After a 17-year-old woman with ulcerative colitis was treated with granulocyte apheresis, chest imaging showed multiple nodular infiltrates, including one which seemed to have a cavity. Wegener's granulomatosis was suspected because proteinase-3 anti-neutrophil cytoplasmic antibody levels were increased. Transbronchial lung biopsy specimen showed nonspecific findings. Chest imaging showed clearing of pulmonary infiltrates without any therapy or discontinuation of mesalazine, which is known to cause lung toxicity. To the best of our knowledge, this is the first report of extra-intestinal pulmonary complications of ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody resembling Wegener's granulomatosis and spontaneous improvement.

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We present a case of hepatocellular carcinoma (HCC), showing an atypical "nodule-in-nodule" appearance on ultrasonogram (US). In general, a "nodule-in-nodule" appearance is found as a hyperechoic tumor containing a hypoechoic nodule. In the present case, however, there was a hyperechoic subnodule in the center of the tumor, which was surrounded by a hypoechoic tumor area. Histologically, the subnodule consisted of moderately differentiated HCC with a markedly dilated pseudoglandular structure, and the outer tumor consisted of well-differentiated HCC with a thin-trabecular pattern. It should be noted that there is a rare HCC with dilated pseudoglandular structure showing the inversed "nodule-in-nodule" appearance.

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A 53-year-old man was admitted to our hospital for dyspnea, associated with atrial tachycardia. He underwent mitral valve replacement and Maze operation for mitral regurgitation and atrial fibrillation and since then he suffered from drug refractory atrial tachycardia followed by cardiogenic shock with systolic heart failure. Atrial tachycardia with rapid ventricular response was medically refractory, and radical catheter ablation was thought to be very difficult due to post Maze operation, mitral mechanical valve replacement and unstable hemodynamics. Thus, atrioventricular nodal ablation, which was s safe procedure compared to the radical ablation for this patient, and biventricular pacemaker implantation, which required coronary venoplasty, were performed. Combination therapy may be one of the treatments for heart failure patients with drug refractory tachyarrhythmias.

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A 77-year-old Japanese man was admitted due to hypoglycemia induced by small amount of insulin. He was diagnosed type 2 diabetes in 1978 and the pancreatic cancer in 1993. Resection of the pancreas head and duodenum was performed. Subsequently, anastomotic stenosis appeared to induce appetite loss. His flavor for carbohydrate-rich food accelerated protein malnutrition. Fatty liver and pancreas atrophy were diagnosed in 1999. After he was diagnosed as secondary kwashiorkor, nasal feeding of protein-rich food improved his fatty liver as well as his general condition rapidly. Anastomotic stenosis and pancreas atrophy contributed to a combination of type 2 diabetes and kwashiorkor.

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A 54-year-old man experienced weight gain. He was diagnosed as having hyperglycemia, hypertension and liver damage. Liver biopsy showed steatohepatitis. We initially suspected him as having hyperadrenocorticism. However, both adrenocorticotropic hormone and cortisol levels were low. Later, it was revealed that he took medicine to relieve his gonalgia. His hyperglycemia, hypertension and liver damage improved after he discontinued taking the medicine. An analysis of this medicine showed that it contained desoximetasone, a glucocorticoid compound that had not been approved for medical use in Japan. To adequately diagnose clinical conditions, it is necessary to survey the patient's medicinal history in detail.

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A 54-year-old man with Graves' disease had been treated with thiamazole (5 mg/day). His thyroid hormone level was increased after exodontia in February 2006. Although his prescribed dose of thiamazole was increased after exodontia on the fourth day, he developed thyroid crisis on exodontia 52nd day. Laboratory findings also showed renal dysfunction (from Cr 1.0 mg/dL in July 2005 to Cr 1.8 mg/dL on exodontia 37th day). His thyroid hormone level was normalized after subtotal thyroidectomy; however, serum Cr level was still high. He was diagnosed with interstitial nephritis as a result of renal biopsy, and he was treated with prednisolone 30 mg/day. This present case developed thyroid crisis even though the quantity of thiamazole was increased after exodontia. It seems that interstitial nephritis, as well as exodontia, is an aggravation factor of thyroid function. After a poor response to anti-thyroid drugs, it is necessary to prevent thyroid crisis by determining the aggravating factor and to then provide appropriate treatment.

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A 30-year-old woman was diagnosed as having Vogt-Koyanagi-Harada (VKH) syndrome. Her past history was Graves' disease. She was administered 1 g of methylprednisolone for three days, which was followed by oral prednisolone. Four weeks later, she developed hyperglycemic hyperosmolar coma. She was treated with intravenous normal saline and insulin, and glycemic control was improved. She was diagnosed as having type 1 diabetes mellitus (DM) because of positive test results for glutamic acid decarboxylase (GAD) antibodies and islet cell antibodies. Her human leukocyte antigen (HLA) genotypes were DQB1^*0401 and DRB1^*0405, which were susceptible genes for VKH syndrome, type 1 DM and Graves' disease. Therefore, we should consider that VKH syndrome might be associated with type 1 DM or Graves' disease.

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We describe a rare and interesting progressive case of lymphocytic hypophysitis accompanied later by paresis of the left abducens nerve. A 42-year-old woman was diagnosed as having lymphocytic hypophysitis accompanied by diabetes insipidus and hypopituitarism. She had no symptoms of visual disturbance at that time. She was not treated with steroids because she is a carrier of the hepatitis B virus. Later, in 2006, she complained of progression of symptoms and double vision for a few months. Her pituitary gland showed further enlargement. The patient was diagnosed as having progressive lymphocytic hypophysitis accompanied by paresis of the left abducens nerve, which was subsequently confirmed by biopsy. The progression of lymphocytic hypophysitis in patients not receiving steroid therapy should be carefully monitored.

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An unusual case of refractory pneumothorax secondary to lung cancer in a 69-year-old man patient with idiopathic pulmonary fibrosis (IPF) is described. High-pressure suction applied through chest tube did not resolve the large right pneumothorax. Acute exacerbation of IPF has also appeared. Respiratory state worsened acutely, and the patient died on the fifth hospital day. In the present case, the large right pneumothorax was initially thought to be associated with IPF because pneumothorax is common in patients with IPF. However, postmortem microscopic examination revealed that the refractory pneumothorax was secondary to perforation of the pleura due to a necrotic peripheral lung cancer.

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Thrombocytosis or a high platelet count (a count greater than 400×10⁹/L) is a common observation especially with the increased ordering of routine complete blood counts. When found, it may create a diagnostic challenge as transient elevations in platelet counts can occur for a number of reasons such as inflammation or infection, and these usually resolve spontaneously; but an elevated platelet count may be the only indication of an underlying serious disease to which no other clinical findings pertain. The report details a case of extreme thrombocytosis which masked an underlying diagnosis of inflammatory bowel disease.

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We report a case of liver sarcoidosis with dysphagia. Although akinesia of the soft palate, disappearance of the palatal reflex, and pyramidal signs indicated brainstem lesions, brain magnetic resonance imaging showed no lesion and the focus was obscure. Iritis, parotiditis, and hilar lymphadenopathy supported the diagnosis of sarcoidosis. However, lung biopsy was normal. Finally, sarcoidosis was diagnosed by liver biopsy. We speculated that microgranulomas in the brainstem that did not exhibit imaging abnormalities causing the neurological symptoms and that liver biopsy can be an effective diagnostic tool even for cases that presented with neurological signs, but no gastrointestinal symptom.

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A 59-year-old man was admitted for further investigation of headache. Neurological examination revealed memory loss, disorientation, and bilateral intention tremor. Legionella pneumophila antigen was detected in the urine. Brain magnetic resonance diffusion-weighted images showed marked hyperintensity in the splenium of the corpus callosum without other abnormalities. Single photon emission CT with Tc-99m hexamethyl-propyleneamine oxime showed multi-focal hypoperfusion in the brain, involving mainly the cerebellum and frontal lobe. This is the first report demonstrating cerebellar and frontal lobe hypoperfusion without corresponding MRI abnormalities in a patient with central nervous system Legionnaires' disease.

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We describe a case of systemic lupus erythematosus (SLE) with enteritis and peritonitis who later developed pneumatosis cystoides intestinalis (PCI). A 35-year-old woman with SLE relapsed with enteritis and peritonitis. Prednisolone (PSL) effectively improved her symptoms. However, 6 weeks later, she developed PCI. Tapering of PSL, administration of intravenous cyclophosphamide, prokinetic agents and antibiotics, bowel rest with intravenous hypernutrition therapy and hyperbaric oxygen therapy successfully improved PCI. Although PCI is a rare complication of SLE, the present case suggests that lupus enteritis could be a risk factor for PCI, and that high-dose PSL could cause additional insult to PCI.

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We present the case of a 70-year-old man diagnosed with Mycobacterium abscessus pulmonary infection complicated with rheumatoid arthritis who was treated with corticosteroids. He died despite treatment according to the recommended regimen of imipenem, clarithromycin, and amikacin. Autopsy revealed granulomatous lesions throughout the bilateral lungs. We conclude that M. abscessus infection may have a fatal outcome because of the drug resistance of the pathogen. This case suggests that rheumatoid arthritis might be a risk factor for M. abscessus pulmonary infection, but further studies are necessary for clarification.

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