Chronic kidney disease (CKD) is defined as either kidney damage with urine, imaging, and histologic abnormalities, or a low estimated glomerular filtration rate (GFR) for more than 3 months. The GFR is calculated using either the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. CKD is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease. In Japan, the prevalence of ESRD is increasing and is currently more than 2,000 per million population. More than 40% of incident ESRD is due to diabetes mellitus (DM). The prevalence of a low GFR (<60 ml/min/1.73 m²) is estimated to be 20% of the adult population. Studies based on several community-based screening programs suggest that Japan has a higher prevalence of CKD than any other country. Early detection and treatment of CKD are necessary to decrease the incidence of ESRD and cardiovascular disease.

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Aim To clarify changes in the prevalence of reflux symptoms and reflux esophagitis over a period of 5 years.
Subjects and Methods Five hundred thirty-nine study subjects (male: 408, mean age 47.3 years) were assessed using a reflux symptom questionnaire and endoscopic examinations conducted twice, 5 years apart.
Results At enrollment, 88 patients had reflux symptoms and 44 had reflux esophagitis (RE). After 5 years, 58 and 53 patients were diagnosed as having reflux symptoms and RE, respectively. Only 26% of the patients with reflux symptoms at enrolment had the symptoms after 5 years. The presence of reflux symptoms and an increase of BMI were significant risk factors for the presence of reflux symptoms after 5 years.
Conclusion Reflux symptoms frequently disappear after 5 years. It is difficult to identify individuals who will still have symptoms after 5 years on the basis of clinical characteristics.

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Background The prevalence of excess weight, including overweight and obesity, is increasing with a high cost on health in society.
Methods Consecutive cases with excess weight, aged between 50 and 70 years and desiring weight loss, were divided into two subgroups according to wishes of patients about whether they prefer medication or just a diet. Metformin at a daily dose of 2,550 mg was given to the medication group.
Results As for the very high prevalences, 84.8% (313/369) of cases at or above the age of 50 years were overweight or obese, 67.2% (248/369) of them had white coat hypertension (WCH) or hypertension (HT), 52.5% (194/369) of them had impaired glucose tolerance (IGT) or diabetes mellitus (DM), and 68.8% (254/369) of them had dyslipidemia. Initially 143 cases with excess weight preferred the diet and 162 of them preferred the metformin therapy. But 42 cases (25.9%) stopped the drug because of excessive anorexia. At the end of the six-month period, there were highly significant differences between the two groups according to prevalences of resolved WCH, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, overweight, and obesity and a decreased fasting plasma glucose below 110 mg/dL (p<0.001 for all).
Conclusion Due to the very high prevalences of excess weight and probably many associated disorders with the excess weight, including IGT or DM, WCH or HT, and dyslipidemia, above the age of 50 years, and the detected significant benefits of metformin on all of the above parameters, metformin treatment should be initiated in patients with excess weight in their fifties.

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Objective To evaluate the association between γ-glutamyl transferase (GGT) and homocysteine in plasma.
Methods Combined results of GGT, total homocysteine, vitamin B12, folate and creatinine levels were analyzed in outpatients referred for laboratory testing over the past 5 years.
Results Cumulative results for homocysteine, GGT, B12, creatinine, folate could be retrieved for 449 outpatients >35 years old over the study period. The concentration of homocysteine significantly increased among tertiles of GGT activity. In multivariable linear regression analysis, GGT activity was independently associated with homocysteine concentration, independent of age, gender, folate, vitamin B12 and serum creatinine levels.
Discussion Plasma GGT activity might be a useful means to predict homocysteine concentration in the general population.

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Objective Metabolic syndrome (MetS) is one of the coronary risk factors for cardiovascular disease and is closely related with sleep-disordered breathing (SDB). Our aim in this study was to estimate the relationship between sleep-related breathing events and coronary risk factors, including MetS.
Methods We determined the prevalence of MetS in 195 patients with cardiovascular disease. Based on Japanese MetS criteria, 56 patients had MetS (Group A), whereas 139 patients did not (Group B). We assessed SDB and sleep-related breathing events, including nocturnal desaturation, in both groups using a type 3 apparatus (Morpheus^®; Teijin Pharma Limited, Tokyo, Japan).
Results Seventy-seven percent of the patients with MetS (43/56) met the criteria for SDB based on apnea hypopnea index (AHI). The AHI value was significantly greater in Group A than in Group B (30.1±19.0/hr vs. 17.7±14.7/hr; p <0.001). Nocturnal oximetry showed that Group A spent a greater percentage of time at pulse-oximetric oxygen saturation below 90% (CT 90) than did Group B (10.6±13.2% vs. 5.0±12.5%; p <0.01). On multivariate logistic regression analysis for CT 90, MetS showed that the odds ratio was 2.629 (95% confidence interval: 1.259-5.592; p=0.011).
Conclusion These results suggest that SDB is common in cardiovascular patients with MetS. Patients with MetS frequently experience a sleep-related breathing event. Compared with the incidence of apnea hypopnea, MetS is an equivalently strong factor of nocturnal desaturation in patients with cardiovascular disease.

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Objective Although osteoporosis in men previously was relatively neglected, bisphosphonates have been strongly suggested as potent therapeutic agents. However, there are few studies on the effects of risedronate in male osteoporosis, especially in Japanese with primary osteoporosis. The aim of our study was to prospectively evaluate the effects of risedronate on bone mineral density (BMD) and bone turnover in Japanese male patients.
Methods According to the therapeutic regimen, the subjects were divided into two groups (group A, 22 with risedronate; group B, 10 without risedronate). During a one-year study duration, we measured bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) every 3 months, and BMD at 7 sites by dual-energy X-ray absorptiometry every 6 months.
Patients The subjects were 32 Japanese male patients with untreated primary osteoporosis.
Results In group A, but not in group B, BMD was significantly increased at the lumbar spine both at 6 months and 12 months, and at the femoral neck at 12 months, compared with baseline. Likewise, in group A, but not in group B, both BAP and NTx were significantly decreased at all time points measured (3 months, 6 months, and 12 months), compared with baseline.
Conclusion These results confirmed the beneficial effects of risedronate upon increasing BMD and reducing bone turnover markers in Japanese male patients with primary osteoporosis, comparable to those previously reported in postmenopausal patients with osteoporosis.

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Objective Subacute thyroiditis (SAT) is a transient inflammatory disease of the thyroid. We evaluated the clinical characteristics based on laboratory and imaging studies in patients with SAT before treatment.
Patients We reviewed the medical records of 852 patients (107 men and 745 women) with SAT who visited our thyroid clinic at Kuma Hospital from 1996 through 2004.
Results SAT developed most often in female patients aged 40 to 50 years, with significant seasonal clusters during summer to early autumn. While the rates of any virus infections and diseases did not differ from those in the general population, recurrent episodes of SAT at intervals of 13.6±5.6 years accounted for 1.6% of all cases. At the onset of SAT, 28.2% of patients had temperatures greater than 38°C and typical symptoms associated with thyrotoxicosis developed in more than 60% of patients. Before treatment, most of the abnormal laboratory findings associated with thyrotoxicosis, inflammation, and liver dysfunction reached peak levels within 1 week after onset. Ultrasound examination showed that half of the patients with unilateral thyroid pain presented with bilateral hypoechogenic area in the thyroid and the rate of bilateral hypoechogenic area tended to increase 2 months after onset.
Conclusion Laboratory studies of thyroid dysfunction and inflammation related to SAT presented peak levels within 1 week after onset.

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Objective To examine the long-term effects of tacrolimus in steroid-dependent myasthenia gravis (MG) patients.
Patients and Methods We administered tacrolimus at 3 mg/day to 10 generalized MG patients presented with clinical worsening by a reduction in dose of prednisolone. The effects of tacrolimus were assessed by using the MG activities of daily living (MG-ADL) profile and the post-intervention status criteria provided by the Myasthenia Gravis Foundation of America (PSC-MGFA).
Results Seven patients were able to use tacrolimus without serious adverse effects for 1.0-5.1 years (mean 3.1 years). Further, its administration improved myasthenic symptoms to the level of pharmacologic remission or minimal manifestations of PSC-MGFA in 5 patients and made it possible to discontinue prednisolone administration in 4 of those 5. However, despite improvements caused by tacrolimus, the reduction in dose of prednisolone caused worsening of symptoms in another 2 patients. In addition, blood trough levels of tacrolimus lower than the recommended range were effective to maintain long-term improvements in 2 patients.
Conclusions Administration of tacrolimus induced long-term improvements and enabled replacement of prednisolone in patients with intractable steroid-dependent MG.

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Objective Several reports of bone marrow dysplasia in patients with systemic lupus erythematosus (SLE) have been published. However, the reports are restricted primarily to descriptions of the erythroid lineage; no follow-up studies have been reported, and the clinical significance of the dysplasias is unknown. Therefore, in the present study, the dysplasias noted in bone marrow aspirates obtained from SLE patients were characterized.
Patients and Methods The smears of bone marrow aspirates obtained from 17 SLE patients who had bone marrow aspiration due to cytopenia (WBC<1,500/μl, or Hb<10.5 g/dl, or platelet count <10×10⁴/μl) were examined retrospectively. Of the 17 patients, 4 had a repeat bone marrow aspiration during follow-up. Clinical and laboratory data were obtained from the medical records.
Results Of the 17 SLE patients, 12 had dysplasias, including: erythroid cell multinuclearity (trinuclear or more) (5 patients), megaloblastoid changes (4), pseudo-Pelger abnormalities (6), annular nuclear myeloid cells (2), separated nuclear megakaryocytes (4), and micromegakaryocytes (5). In the 4 patients who had follow-up bone marrow aspiration, these dysplasias were correlated with disease activity; some abnormalities disappeared with remission of SLE. Diffuse proliferative glomerulonephritis (3 patients) and cerebral lupus/neuropsychiatric lupus (4 patients) were seen only in patients with dysplasia.
Conclusion This study found that bone marrow dysplasia can be observed in all lineage cells of SLE patients, and that the dysplasia is reversible during the course of the disease. The presence of dysplasias appears to be associated with disease severity.

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An intrahepatic mass was incidentally found in a 41-year-old man with a history of a traffic accident injury which resulted in removal of a ruptured spleen. Hepatic splenosis was considered in the differential diagnosis but magnetic resonance imaging showed hypointensity on T2-weighted images, atypical for normal spleen. Histologically, the mass showed sinusoidal structures and lymphoid follicular aggregates. Immunohistochemical study showed that the phenotype of the vascular lining cells was CD8-positive, CD31-positive, and CD34 negative, the pattern diagnostic for ectopic spleen. In addition, severe iron deposition was histologically demonstrated, which was considered as the cause of the hypointense T2-weighted images.

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A 51-year-old man developed type 1 diabetes mellitus following 24 weeks of treatment with recombinant α-2b peginterferon plus ribavirin for chronic hepatitis C. Pancreatic autoantibody tests were negative before the start of therapy, but a significant increase in glutamic acid decarboxylase (GAD) antibody titer was seen after 24 weeks of treatment. Six months after the onset of type 1 diabetes mellitus, the patient continues to receive 40 units of insulin daily. The clinical course suggested that recombinant α-2b peginterferon plus ribavirin provoked type 1 diabetes mellitus, therefore, in patients who are candidates for interferon therapy the presence of pancreatic autoantibodies and the fasting plasma glucose level should be investigated before and during treatment.

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We report a 53-year-old woman with Cushing's syndrome due to an adrenocortical adenoma, who underwent unilateral adrenalectomy and developed symptomatic hypercalcemia during the thyrotoxic period of painless thyroiditis, while tapering off a daily supplemented dose of cortisol. A study of patients with thyrotoxicosis and hypoadrenalism at our institute revealed that mild hypercalcemia was present in 9.9% of those with thyrotoxicosis and 5.0% of those with hypoadrenalism. The present case suggests that the simultaneous occurrence of thyrotoxicosis and hypoadrenalism may lead to overt hypercalcemia due to a synergistic increase in bone resorption and impaired urinary excretion of calcium.

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We report the treatment of four thyrotoxic patients. Two were cases of type I amiodarone-induced thyrotoxicosis (AIT) treated with methimazole. The third Graves' disease patient, who became hypothyroid 25 years after subtotal thyroidectomy, developed type II AIT. Furthermore, one case with heart failure and ventricular tachycardia, who developed an adverse reaction to antithyroid agents and was prescribed amiodarone, underwent total thyroidectomy. The clinical course was uneventful, and the patient is doing well. Since amiodarone contains a large amount of iodine, it is frequently difficult to make a differential diagnosis. Surgical treatment of Graves' disease patients is recommended when immediate control of hyperthyroidism and heart failure is required.

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The patient was a 30-year-old woman with a disease of common variable immunodeficiency. She was admitted to our hospital because of abnormal findings on her chest radiographs in an annual health screening. Chest computed tomography showed multiple reticulonodular infiltrates in both lower lung fields. The surgical lung biopsy specimen demonstrated involvement of mature small lymphocytes with a mixture of other mononuclear cells in the lung parenchyma and bronchiolar walls. The patient was diagnosed to have lymphoid interstitial pneumonia. The patient was treated with prednisolone and intravenous supplement of immunoglobulin, resulting in radiographically and clinically stable disease.

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A 69-year-old woman who had been diagnosed with chronic pulmonary thromboembolism (CPTE) developed ground glass opacities in the right lung where perfusion scintigraphy showed defects of the bloodstream. Bronchoalveolar lavage fluid (BALF) showed that some macrophages had phagocytosed hemosiderin. Video-assisted thoracoscopic surgical biopsy revealed lung fibrosis, narrowing of the pulmonary artery and organization of many cholesterol granulomas. We hypothesized that hyperperfusion of the bronchial artery, which occurred to compensate for hypoperfusion of the pulmonary artery, induced alveolar hemorrhage following thrombolytic and anticoagulation treatments, and that the degraded products from blood cells induced the formation of lung fibrosis and cholesterol granulomas.

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The patient was a 67-year-old man with diabetes mellitus who had been to a hot spring spa a few days before his admission. The diagnosis of Legionella pneumonia was made using a urinary antigen assay. Intravenous pazufloxacin and oral clarithromycin were started. However, despite these treatments, he developed acute respiratory distress syndrome (ARDS). He was administered the combination of intravenous pazufloxacin and erythromycin, corticosteroid, and sivelestat for two weeks. Then he was successfully recovered. The outcome suggests that treatment with corticosteroid and sivelestat, in addition to a combination of appropriate anti-Legionella antibiotics, should be considered for patients with severe Legionella pneumonia with ARDS.

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A 57-year old man with desquamative interstitial pneumonia (DIP) showed a marked increase in eosinophils in the bronchoalveolar lavage (BAL) fluid. The patient was referred to our hospital for abnormal shadows on his chest X-ray with no symptoms in May 2007. Computed tomography (CT) showed patchy, peripheral predominate ground-glass opacity. The BAL fluid revealed an increase of the total number of cells, including markedly elevated levels of eosinophils (62.1%), in contrast with only a slight increase of peripheral blood eosinophils, or minimal eosinophils in the alveolar spaces and interstitium of the thoracoscopic lung biopsy specimen. Since the specimens showed findings compatible with a DIP pattern, we diagnosed the patient with DIP. Although it is a rare entity, we should therefore consider DIP in the differential diagnosis when we encounter patients with a marked increase in the number of BAL eosinophils.

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Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, characterized by the absence of motor weakness and the presence of normal muscle enzyme levels. ADM is sometimes accompanied by interstitial pneumonia that shows a rapid progressive course associated with a poor prognosis. We describe a 70-year-old man who presented rapidly progressive interstitial pneumonia associated with clinically ADM (C-ADM); he was successfully treated with polymyxin B-immobilized fiber column (PMX) hemoperfusion.

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We report a chronic myeloproliferative disease-unclassifiable (CMPD-U) patient who achieved hematological remission following imatinib mesylate (imatinib). Chromosomal and molecular analyses demonstrated no genetic abnormalities of c-abl, bcr-abl, c-kit or platelet-derived growth factor receptor (PDGFR) genes from hematopoietic cells. Although there has been one report of CMPD-U patient with chromosomal abnormalities of the PDGFR gene having complete hematologic responses upon treatment with imatinib, there have not been similar reports of patients without chromosomal abnormalities. This is the first case report of a CMPD-U patient with no chromosomal abnormalities who completely responded to treatment with imatinib.

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A 50-year-old man presented with a sudden onset of right-sided hearing disturbance. His hearing disturbance improved gradually, however, dysarthria, right-sided facial weakness and dysesthesia, and gait disturbance was developed 11 days after the onset of hearing disturbance. MR imaging revealed fresh infarctions of the right dorsolateral pons and middle cerebellar peduncle localized in the territory of anterior inferior cerebellar artery. Unilateral hearing disturbance could be an isolated manifestation prior to ipsilateral anterior inferior cerebellar artery infarction.

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Intradural extramedullary tuberculoma of the spinal cord (IETSC) is a rare complication of tuberculosis, which can occur as a paradoxical response to antituberculous therapy. A 46-year-old woman with tuberculosis meningitis developed an acute sensory disturbance and paraplegia eight weeks after the antituberculous treatment was started. MRI revealed a cystic lesion at the Th 2 and 3 vertebrae levels, and continuous dural thickening. Laminectomy was performed; soft granulomas were unexpectedly observed inside the dura matter. After the operation, the patient experienced progressive improvement in motor strength. IETSC should be known as rare but possible complication of tuberculous meningitis.

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We report a rare case of prosthetic valve endocarditis caused by Acinetobacter genomic species 13 TU. This patient had rheumatic heart disease and received prosthetic mitral valve replacement eleven years previously. He was admitted due to tarry stool. Endoscopic procedure showed two gastric ulcers and some mucous breaks at the distal esophagus. He had a fever on the eleventh hospital day. Persistent Acinetobacter bacteremia was noted with conjunctiva hemorrhage. The pathogen was identified as Acinetobacter genomic species 13 TU by PCR-based method. According to his whole course of disease, the most possible portal of entry was via the endoscopic procedure.

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A hepatic central bisegmentectomy was performed on a 36-year-old Iranian man with suspected cystic echinococcosis. Hepatic computed tomography (CT) scan findings showed a large cystic lesion, which included many small round shaped cystic lesions. The diagnosis of hepatic cystic echinococcosis was confirmed during surgery. The aforementioned CT scan findings may be specific findings for cystic echinococcosis, in spite of a low appearance rate.

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