Objective Obesity is related to an increased prevalence of reflux esophagitis and gastroesophageal reflux disease symptoms. This study was performed to clarify the influence of gender on time-course changes in the rate of a high BMI and incidence of reflux esophagitis in Japanese subjects.
Methods The subjects included individuals who visited a medical center for medical checkups between April 2000 and March 2001, April 2005 and March 2006 and April 2010 and March 2011. At each examination, the subjects underwent upper gastrointestinal endoscopy to determine the presence of reflux esophagitis, size of the diaphragmatic hiatus and degree of gastric mucosal atrophy. A body mass index (BMI) of ≥25 kg/m² was defined as a high BMI.
Results A multiple logistic regression analysis showed that a high BMI, milder degree of gastric mucosal atrophy and larger size of diaphragmatic hiatus were significant predictive factors for the presence of reflux esophagitis in both men and women. The number of male subjects with reflux esophagitis and a high BMI increased during the 10-year examination period. In contrast, the number of individuals with reflux esophagitis and a high BMI was not increased among women. For both men and women, the proportions of patients with a large diaphragmatic hiatus and mild gastric mucosal atrophy increased during the 10-year period.
Conclusion The prevalence of reflux esophagitis in the female subjects remained constant over 10 years, different from that observed in the men. A lack of change in BMI may be an important factor accounting for the constant prevalence of reflux esophagitis in women.

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Objective The aim of this study was to clarify the indications for oral glucose tolerance tests (OGTT) in non-alcoholic fatty liver disease (NAFLD) subjects with a HbA1c level of ≤6.4%, fasting plasma glucose (FPG) level of <126 mg/dL and no history of diabetes.
Patients A total of 569 NAFLD subjects underwent 75-g OGTT. The plasma glucose and insulin levels were analyzed periodically for three hours during the OGTT examinations. Impaired fasting glucose (IFG) was defined as a plasma glucose level of ≥100 mg/dL to <126 mg/dL. Diabetes was defined as a two-hour post-load plasma glucose level of ≥200 mg/dL. Elevated insulin resistance was defined as a homeostasis model assessment-insulin resistance (HOMA-IR) of ≥2.5. Insulin secretory insufficiency was defined as an insulinogenic index of <0.4.
Results The prevalence of diabetes on the OGTT was 7.7% (44/569) among the NAFLD patients with an HbA1c level of ≤6.4%, FPG level of <126 mg/dL and no history of diabetes. A multivariate analysis showed that diabetes occurred more frequently when the subjects had IFG [odds ratio (OR) 5.13; 95% confidential interval (CI) 3.01-8.76; p<0.001] and an HbA1c level of 5.7-6.4% (OR 5.45; 95% CI 3.33-8.93; p<0.001). Of the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 22.8% (28/123) exhibited a pattern of diabetes on OGTT. Regarding insulin dynamics, among the NAFLD subjects with both IFG and an HbA1c level of 5.7-6.4%, 25.2% (31/123) had elevated IR alone, 25.2% (31/123) had insulin secretory deficiency alone and 27.6% (34/123) had both elevated insulin resistance and insulin secretory deficiency.
Conclusion NAFLD subjects with IFG and an HbA1c level of 5.7-6.4% should undergo OGTT in order to determine whether they have diabetes and/or abnormal insulin dynamics.

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Objective The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudinal Study (JALS) score, which is calculated from the traditional atherosclerotic coronary risk, is associated with the incidence of coronary vasospasms.
Methods We performed vasospasm provocation tests with acetylcholine in 109 patients referred to our hospital due to suspected vasospastic angina and subsequently calculated the atherosclerotic risk score according to the JALS score. Consequently, coronary vasospasms were evoked in 51 patients. The patients were divided into three groups according to the tertile of the JALS score: 1st, <28, n=36; 2nd, 28-41, n=36, 3rd, >42, n=37. The third tertile exhibited the greatest risk for vasospasms. A multivariate logistic regression analysis revealed that the JALS score (odds ratio: 1.686, p<0.05) was independently associated with the incidence of vasospasms.
Conclusion The JALS score can serve as a useful tool for evaluating patients with suspected coronary vasospasms.

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Objective Although lipid disorders are a well-known risk factor for cardiovascular disease (CVD) in the general population, the optimal management with lipid-lowering therapy to reduce CVD risks and mortality in hemodialysis (HD) patients remains controversial. In the clinical setting, dyslipidemia can be diagnosed based on the detection of elevated lipid concentrations at the beginning of HD. This study investigated changes in the levels of serum lipids during a single HD session.
Methods The serum total cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol levels were measured in 31 HD patients at zero, two and four hours after the beginning of a single HD session. The data were analyzed using the Wilcoxon signed-rank test, a linear mixed model and Spearman's rank correlation analysis.
Results The serum total cholesterol, HDL cholesterol and non-HDL cholesterol levels increased significantly during the HD session. Even after the lipid parameters were corrected for changes in the total protein level, the total cholesterol and HDL cholesterol levels increased, whereas the non-HDL cholesterol levels did not change significantly. The percentage change in the serum levels of these lipid fractions correlated strongly with the percentage change in the ultrafiltration volume per body weight. In contrast, the serum triglyceride levels were decreased significantly at two hours compared with the levels noted at the beginning of HD and gradually increased at four hours.
Conclusion The serum lipid levels are influenced significantly by HD treatment and ultrafiltration. Evaluating the degree of dyslipidemia at the beginning of a HD session may therefore underestimate the levels of serum lipids in HD patients with a large amount of weight gain, thus resulting in the use of insufficient lipid-lowering therapy.

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Objective The increasing population of elderly people in Japan has accelerated the demand for a simple screening test to detect cognitive and affective declines in mild cognitive impairment (MCI) and the early stage of dementia.
Methods We compared the cognitive and affective functions, activities of daily living (ADLs) and the results of four computerized touch-panel screening tests in 41 MCI subjects, 124 patients with Alzheimer's disease (AD) and 75 age- and gender-matched normal controls.
Results All computerized touch-panel games were successfully used to discriminate the AD patients from the normal controls (** p<0.01). Although there were no differences in the findings of the conventional cognitive assessments, the results of the flipping cards game were significantly different (** p<0.01) between the normal controls (19.3±9.5 sec) and MCI subjects (30.9±18.4 sec). Three conventional affective assessments, the ADL score, Abe's behavioral and psychological symptoms of dementia (ABS) (** p<0.01) and the apathy scale (AS) (* p<0.05), could be used to discriminate the MCI subjects (ABS, 0.9±1.5; AS, 12.8±5.9) from the normal controls (ABS, 0.1±0.4; AS, 8.9±5.3).
Conclusion In the present study, all four touch-panel screening tests could be employed to discriminate AD patients from normal controls, whereas only the flipping cards game was effective for distinguishing MCI subjects from normal controls. Therefore, this novel touch-panel screening test may be a more sensitive tool for detecting MCI subjects among elderly patients.

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Objective In Japan, reducing the consumption of miso soup and Japanese pickles, both traditional Japanese dishes, is recommended in order to decrease dietary salt intake. With the Westernization of dietary habits, however, these dishes are now consumed less frequently, and thus a reduction in their effect on sodium intake is suspected. This study examined cross-sectional associations between the frequency of intake of miso soup and Japanese pickles and the estimated 24-hour urine sodium excretion using data obtained from health examination surveys conducted in 2013 in Sado City, Japan.
Methods The level of daily salt intake was estimated based on spot urine sodium and creatinine measurements. The frequency of intake of miso soup and Japanese pickles was determined using a self-reported questionnaire. Multiple linear regression models were used to assess associations.
Results Among a total of 8,821 participants (3,956 men; age range, 19-97 years), the mean daily salt intake was 9.4 g/day. The frequency of intake of miso soup and Japanese pickles increased with age and was associated with the level of daily salt intake (p for trend <0.0001). A linear regression model analysis adjusted for age, sex, body mass index, hypertension, diabetes, hypercholesterolemia and chronic kidney disease revealed that daily salt intake was associated with the frequency of intake of miso soup (p<0.0001) and Japanese pickles (p<0.0001) in all age groups, except those ≥80 years of age.
Conclusion These findings suggest that reducing the consumption of miso soup and Japanese pickles may be an effective approach for decreasing the level of dietary salt intake in the general Japanese population, although not in octogenarians or nonagenarians.

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A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.

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Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis.

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A 73-year-old man with a history of intermittent claudication for the previous six years visited our hospital. His ankle-brachial index (ABI) was very low on both sides, and computed tomography (CT) indicated bilateral aorto-iliac occlusive disease (AIOD). As he refused to undergo open surgery, endovascular treatment (EVT) was administered. After the first and second EVT sessions, the intermittent claudication improved completely. In addition, the ABI normalized (right: 1.01, left: 0.99), and CT demonstrated full expansion of the stents. His post-EVT course was uneventful for 18 months. The use of EVT to treat AIOD is technically feasible and may serve as a potential treatment option for patients with an inoperable condition.

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We herein report the case of a preeclampsia patient with comorbid peripartum cardiomyopathy (PPCMP). A 22-year-old woman in the 26th week of gestation was admitted with acute pulmonary edema. Hypertension and proteinuria were detected, and echocardiography showed an ejection fraction of 33%. It is remarkable that PPCMP particularly that associated with preeclampsia was observed in the early gestational period. In conclusion, while dyspnea and pretibial edema are often noted during normal pregnancies, the potential for PPCMP should be considered if these symptoms are excessive and/or comorbid paroxysmal nocturnal dyspnea and orthopnea are present, even in patients with preeclampsia.

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The recent trends in avoiding sunbathing and eating fewer fish products have resulted in a high prevalence of vitamin D deficiency in the general Japanese population. We herein report the case of a young woman with enduring anorexia nervosa (AN) who suffered from osteomalacia, thoracic deformities and respiratory failure. Her vitamin D deficiency had been overlooked for years. Although the serum 25-hyroxyvitamin D [25(OH)D] level is a marker of vitamin D stores, it is not routinely examined because the cost is not covered by the national health insurance program. However, measuring the serum 25(OH)D levels in AN patients with hypocalcemia is recommended to prevent osteomalacia and osteoporosis.

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A 73-year-old woman was admitted due to weight loss and generalized malaise. The basal levels of all the anterior pituitary hormones, except for prolactin, were reduced. However, they were all elevated in response to exogenous hypothalamic hormones. After starting hydrocortisone replacement, the patient had polyuria of >5,000 mL/day. T1-weighted MRI depicted a low signal of an oval mass in the sella turcica and an iso-intense signal of another mass at the pituitary stalk. These findings indicate a hypothalamic type of hypopituitarism and masked central diabetes insipidus which possibly derived from the atypical occupation of Rathke's cleft cyst at the pituitary stalk.

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A 32-year-old man on peritoneal dialysis (PD) was hospitalized for seven days due to fever. A diagnosis of yeast-like fungal peritonitis was made by Gram staining. The patient was started on intravenous micafungin and oral fluconazole therapy following removal of the PD catheter. A fungal pathogen was isolated from the peritoneal fluid and identified as Cryptococcus species. Based on antifungal susceptibility testing, the treatment was changed to voriconazole and continued for 3 months. A genetic analysis identified the isolate as Cryptococcus laurentii (C. laurentii). This patient was diagnosed with C. laurentii PD-related peritonitis and was successfully treated with voriconazole and removal of the PD catheter.

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We herein report our experience with patients who had nontuberculous mycobacterial lung disease (NTM disease) accompanied by organizing pneumonia (OP). Out of 98 NTM disease patients who had undergone a biopsy or surgical resection, 11 patients had OP that was revealed histologically. After excluding six patients who had OP-related diseases (idiopathic interstitial pneumonia, rheumatoid arthritis, etc.), the remaining five patients were studied. Two of them (a 73-year-old man and a 66-year-old woman) showed common clinical feature: acute-onset symptoms of cough and fever, infiltrating shadows and dramatic improvement following treatment with a corticosteroid and anti-mycobacterial therapy. Our cases demonstrate that NTM disease is sometimes accompanied by OP histologically, and some such cases show common clinical features.

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We herein describe a case in which a massive hemorrhage unexpectedly occurred after the removal of a pleural drainage tube which had been in place for five days. One possible explanation for that event was the damage of the intercostal artery during tube insertion into the thoracic cavity. This is an extremely rare but severe complication. Therefore, the present report provides useful information for physicians who treat patients with respiratory diseases.

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A 76-year-old man complaining of exertional dyspnea was admitted to our hospital. Chest computed tomography revealed bilateral diffuse ground-glass opacities and small nodules. A transbronchial lung biopsy revealed tumor cell emboli in the pulmonary arteries. The patient was diagnosed with gastric adenocarcinoma using an endoscopic stomach biopsy; however, the interstitial opacities progressively worsened and he died of acute respiratory failure. An autopsy revealed extensive pulmonary tumor embolisms (PTE) with associated ischemic damages, e.g., infarctions, alveolar wall thickening with cuboidal metaplasia, hemorrhage, and diffuse alveolar damage. The ground-glass opacities in the chest computed tomography findings appear to correlate with the pathological ischemic changes associated with PTE.

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We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

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A 66-year-old man with non-Hodgkin lymphoma (NHL) developed progressive multifocal leukoencephalopathy (PML) after undergoing chemotherapy including rituximab. Although the administration of mefloquine at a dose of 500 mg weekly temporarily led to a dramatic decrease in the copy number of JC Virus DNA in the cerebrospinal fluid, the patient's symptoms gradually worsened. The CD4⁺ T count remained continuously low, at least until approximately five months after the last cycle of chemotherapy. A postmortem examination performed 10 months after the onset of PML disclosed a severe condition associated with rituximab-treated PML originating from NHL and a high mefloquine concentration in the brain. The accumulation of further data regarding mefloquine treatment in PML cases may help to elucidate the optimal dosage and time window for effectively treating PML.

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We herein report a case of ischemic stroke in a 69-year-old man with unilateral moyamoya vessels originating from the proximal portion of the left middle cerebral artery. In addition, digital-subtraction angiography demonstrated a string-of-beads-like appearance in the cavernous portion of the left internal carotid artery. A genetic analysis revealed a heterozygous c.14576G>A variant in ring finger protein 213. The patient's younger brother had a history of hemorrhagic stroke and had been diagnosed with moyamoya disease. We finally considered that the unilateral moyamoya vessel and string-of-beads appearance observed in the current case were not simply caused by atherosclerosis, but rather represented symptoms within the moyamoya spectrum.

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Bee venom acupuncture has been widely used in Oriental medicine with limited evidence of effectiveness. Most of the complications due to bee venom acupuncture are local or systemic allergic reactions. However, serious medical and neurological complications have also been reported. We herein describe the treatment of a 68-year-old woman who developed progressive quadriplegia 10 days after receiving multiple honeybee venom sting acupuncture treatments. The electrophysiological findings were consistent with Guillain-Barré syndrome (GBS). The temporal relationship between the development of GBS and honeybee venom sting acupuncture is suggestive of a cause-and-effect relationship, although the precise pathophysiology and causative components in honeybee venom need to be verified.

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Venous stasis is generally accepted to be a predisposing factor for venous thrombosis. However, benign causes of inferior vena cava (IVC) obstruction with associated thrombus formation have not been well described. We herein present a case of IVC compression caused by a distended ileal neobladder measuring 2,000 mL in capacity that led to IVC thrombosis. Following transurethral drainage for six weeks and anticoagulation therapy with warfarin for six months, the thrombus completely disappeared. The patient was considered to have a hypercoagulable state resulting from an acute urinary tract infection, a condition that may be associated with an increased risk of thrombosis.

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