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A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between KCNJ5- and CACNA1D-mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs.

Aldosterone-producing adenoma (APA) is a form of primary aldosteronism (PA). Recent studies suggested that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are involved in the pathogenesis of APA. We report a case of a 62-year-old man diagnosed as PA with left adrenal mass. He underwent adrenalectomy for treatment. We identified a novel somatic deletion mutation in ATP2B3 in the adrenal tumor: c.1269_1274delTGTGCT which spans three codons (423-425) resulting in p.Val424_Leu425del. Immunohistochemical analysis revealed strong expression of aldosterone synthase (CYP11B2) in the tumor tissue, which is consistent with APA. Here, we identified a novel somatic deletion mutation in ATP2B3, which results in the amino acid sequences increasing intracellular calcium concentrations as reported previously, leading to increased aldosterone synthase (CYP11B2) expression and following excess aldosterone production in the APA cells. The novel ATP2B3 mutation detected in our case supports the pathogenic significance of the locus spanning the codon 424-426 of ATP2B3.

We present a case of a 62‐year‐old diabetic woman with acute pyelonephritis and spondylitis caused by Salmonella typhi. She was admitted to Tokyo Medical Dental University Hospital, Tokyo, Japan, because of unconsciousness and was diagnosed with sepsis by retrograde pyelonephritis as a result of Salmonella typhi. Antibiotics treatment was immediately started; however, she subsequently developed lumbar spondylitis, and long‐term conservative treatment with antibiotics and a fixing device were required. This is the first report of a diabetic patient who developed retrograde urinary tract infection with Salmonella typhi, followed by sepsis and spondylitis. The infection could be a result of diabetic neuropathy, presenting neurogenic bladder and hydronephrosis. The patient was successfully treated with antibiotics and became asymptomatic with normal inflammatory marker levels, and no clinical sign of recurrence was observed in the kidney and spine at 4 months.

We compared skin and subcutaneous tissue strains in legs with lymphedema (LE) of varying severity and legs with lipodermatosclerosis (LDS) using real-time tissue elastography. Strain was assessed at the inner thigh and calf in 62 legs with LE (International Society of Lymphology [ISL] stage 0: 16, stage I: 5, stage II: 28, late stage II: 7, stage III: 6) and 15 legs with LDS. In thighs and calves with LE, skin strain and subcutaneous tissue strain did not significantly differ between ISL stage 0, that is, asymptomatic legs, and other stages. However, strain values in calves with LDS were lower than values in calves with stage 0, II and late II LE. These results indicate that skin and subcutaneous tissue strains were not lower in legs with symptomatic LE than in asymptomatic legs until an advanced stage.

Objectives To study the differences in impact on venous hemodynamics between larger size strong graduated elastic compression stockings (GECS) and appropriate size strong/moderate GECS. Method In healthy legs fitted for a small (Group S; n = 8) and large (Group L; n = 8) GECS, air plethysmography was performed without GECS, with an appropriate size strong GECS (GECS1), with a three-size too large strong GECS (GECS2), and with an appropriate size moderate GECS (GECS3) in this order. Results In Group S, interface pressure with GECS2 was equal to or higher than that with GECS3. Decreased venous volume, unchanged ejection volume, and decreased residual volume were achieved by GECS, but differences in these parameters among GECS were not observed. Although insignificant, a similar tendency was found in Group L. Conclusions A larger size strong GECS seemed to have equivalent interface pressure and impact on venous hemodynamics compared to an appropriate size moderate or strong GECS.

Background Increased visceral adiposity is strongly associated with non-alcoholic fatty liver disease (NAFLD). However, little attention has been paid to the association between the change in subcutaneous adipose mass and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether increased subcutaneous adipose tissue (gynoid fat mass) could be protective against the progression of NAFLD in Japanese patients with type 2 diabetes. Methods This is a retrospective observational study of 294 Japanese patients with type 2 diabetes (65 ± 10 years old, 40% female). Liver attenuation index (LAI) measured by abdominal computed tomography was used for the assessment of hepatic steatosis. Both gynoid (kg) and android (kg) fat masses were measured by the whole body dual-energy X-ray absorptiometry. One-year changes in LAI, gynoid, and android fat masses were evaluated in both male and female patients. Linear regression analysis with a stepwise procedure was used for the statistical analyses to investigate the association of the changes in gynoid and android fat masses with the change in LAI. Results LAI levels at baseline were 1.15 ± 0.31 and 1.10 ± 0.34 in female and male patients (p = 0.455). The change in gynoid fat mass was significantly and positively associated with the change in LAI in both univariate (standardized β 0.331, p = 0.049) and multivariate (standardized β 0.360, p = 0.016) models in the female patients. However, no significant association was observed in males. In contrast, the increase in android fat mass was significantly associated with the reduced LAI in both genders in the multivariate models (standardized β −0.651, p

Cu(0.5 at.%Mg) alloy films were deposited on glass substrates, and annealed at 200–400 °C in vacuum. The resistivity of the Cu(Mg) films was reduced to about 3.0 μΩcm after annealing at 200 °C for 30 min, and the tensile strength of adhesion of the Cu(Mg) films to the glass substrates was increased to 30–40 and 35–55 MPa after annealing at 250 and 300 °C, respectively. The reduction in resistivity can be explained as reduced impurity scattering and grain-boundary scattering, since Mg segregation to the film surface and Cu(Mg)/glass interface, and consequent Cu grain growth, were observed. Increased adhesion of the Cu(Mg) films to glass substrates after annealing was also explained by the strong segregation of Mg atoms, and the formation of a reaction layer at the interface. Mg atoms were observed to have reacted with the glass substrates and formed a thin crystalline MgO layer at the interface in the samples annealed at 300 °C, while Mg atoms were highly concentrated above the Cu(Mg)/glass interface without oxide formation at the interface in the samples annealed at 250 °C. Thus, the process temperature and time to obtain low-resistivity and high-adhesion Cu alloy films on glass substrates could be reduced to 250 °C and 30 min using Cu(Mg) films.

Background: The efficacy of lubiprostone for chronic constipation has been established through phase III clinical trials. Nevertheless, the continuation of lubiprostone therapy is reportedly difficult due to the development of nausea. The objective of this study is to determine whether the administration of itopride hydrochloride can reduce lubiprostone-related nausea. Methods: Two hundred and thirty-five patients who were receiving lubiprostone (24 μg capsule twice daily) were enrolled. Seventy-one patients took a prophylactic dose of itopride (50 mg tablet twice daily) together with lubiprostone to prevent nausea. Thus, the patients were divided into 2 groups: lubiprostone alone (164; control group) and combination therapy with lubiprostone and itopride (71; itopride group). Efficacy measures included changes in constipation scoring system scores, the incidence of treatment-related adverse events including nausea, and the percentage of patients who discontinued treatment within two weeks after administration. Results: Of the 235 patients who were enrolled, 196 were available for analysis. Both treatment groups experienced statistically significant improvements in constipation scoring system scores. The percentage of patients who reported ≥1 adverse event was significantly higher in the control group (40.9%) than in the itopride group (21.9%). The percentage of patients experiencing nausea was statistically and significantly lower in the itopride group than in the control group (9.4% versus 22.7%). The itopride regimen was also statistically superior compared to the control regimen in terms of treatment discontinuation. Conclusion: The prophylactic administration of itopride can decrease the risk of nausea in patients receiving lubiprostone and consequently reduce the risk of treatment discontinuation.

Objective: To investigate the safety and efficacy of a novel arm sleeve composed of a conventional arm sleeve extending to a wider area of the body. Materials and Methods: Five subjects with post-mastectomy upper extremity lymphedema, who had already been using their own arm sleeve, used a brand-new conventional arm sleeve for 2 weeks, followed by a novel arm sleeve for 2 weeks. The adverse events, arm-related symptoms, interface pressures, and subcutaneous fluid distributions observed by magnetic resonance imaging (MRI) were assessed. Results: The use of the novel arm sleeve resulted in a graduated compression extending to the shoulder (forearm, 21.8 ± 3.7 mmHg; upper arm, 15.2 ± 3.3 mmHg; shoulder, 8.8 ± 3.1 mmHg). By eliminating the wring seen in the conventional arm sleeve, the disturbed proximal diffusion of the subcutaneous fluid and venous occlusion were successfully avoided, as confirmed by MRI. No adverse event or worsening of arm-related symptoms was reported. Conclusion: The novel arm sleeve seemed to provide graduated compression to a wider area, allowing improved subcutaneous fluid and venous drainage without any adverse events. Therefore, the novel arm sleeve may be recommended as a compression therapy option for upper extremity lymphedema.

Objectives: To elucidate the differences in subcutaneous ultrasound findings between dependent edema (DE) and secondary lower extremity lymphedema (LE). Materials and Methods: Twenty legs in 10 patients with DE and 54 legs in 35 patients with LE, who first visited our clinic between April 2009 and December 2012, were studied retrospectively. Subcutaneous echogenicity and echo-free space (EFS) were assessed at 8 points on the thigh and leg using an 8–12 MHz ultrasound transducer. Results: In DE, echogenicity was increased most in the lower leg, without a difference between the medial and lateral side. The EFS was most remarkable in the lower leg, and the lateral side was more severe. In the early stages of LE, echogenicity was similarly increased in the medial thigh and in the leg, while remarkable EFS was observed only in the lower leg. As clinical severity progressed, echogenicity increased in all parts of the lower extremity. EFS also increased in all parts of the leg, but the lower leg was still the most severe. Conclusion: Echogenicity seemed to progress differently in DE and LE, but EFS progressed similarly and according to gravity. The current ultrasound findings may have added some diagnostic value in differentiating these conditions.

Background Our objectives were to elucidate the pathophysiology of leg edema in immobile patients and to discuss reasonable management of this condition. Methods and results The 30 patients with leg edema had visited our clinic between April 2009 and March 2013; they suffered from severe gait disturbance, had no significant venous abnormalities detected using duplex ultrasound, and did not have any systemic diseases that could cause leg edema. Here, we review their symptoms, examinations, and treatments. Among 59 edematous legs of the 30 patients, 30 legs (51%) had symptoms that indicated advanced chronic venous insufficiency. The ankle range of motion and calf : ankle circumference ratio were abnormal in only 3 (5%) and 10 (17%) of the legs, respectively. The severity of edema and subcutaneous inflammation, which was confirmed using ultrasonography, was significantly influenced by gravity. Air plethysmography and lymphangioscintigraphy were completed in 15 and 10 patients, respectively, neither of which revealed any significant abnormalities. Reasonable success for all patients was achieved by compression therapy and physical therapy without medications. Conclusions It was assumed that leg edema in these immobile patients was mainly caused by venous stasis because of the immobility itself, not because of anatomical problems. The patients were successfully managed by compression and physical therapy alone.