Octreotide LAR was useful for avoiding hypoglycemia in an elderly patient with insulinoma.

An 80-year-old woman was admitted to our hospital with a hypoglycemia attack. She was diagnosed with insulinoma based on her high insulin level at the time of the hypoglycemia attack and the presence of a hypervascular tumor in her pancreas. The patient refused surgical treatment and octreotide was used to prevent hypoglycemia.It is known that octreotide suppresses the secretion of insulin from the pancreas; however, insulin secretion is not always suppressed in patients with insulinoma. Moreover, there is no particular protocol for the use of octreotide in the treatment of insulinoma.We examined the effect of octreotide in preventing hypoglycemia using CGM. The injection of octreotide (50 µg) at 21: 00 prevented hypoglycemia during the night.However the patient could not perform self-injection due to the sequelae of a cerebral infarction. We therefore chose to have her eat an extra meal at 11 pm.After a while the patient became exhausted by eating meals at night. We examined the effects of octreotide LAR using CGM, and it was found to prevent hypoglycemia for 4 weeks. The patient's QOL was improved by being released from a restriction that affected her daily life.

Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study).

INTRODUCTION: In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required. Therefore, we aim to determine the effects of treatment with SGLT-2 inhibitors or metformin for reducing visceral fat in 106 Asian patients with type 2 diabetes who were undergoing treatment with the DPP-4 inhibitor sitagliptin (50 mg daily) for poor glycaemic control. METHODS AND ANALYSIS: A prospective, multicentre, blinded-endpoint phase IV randomised controlled study will be conducted to evaluate the safety and efficacy of a 24-week treatment with either an SGLT-2 inhibitor (ipragliflozin) or metformin for reducing visceral fat and plasma glucose levels in patients with type 2 diabetes. Patients who satisfy the eligibility criteria will be randomised (1:1) to receive ipragliflozin (50 mg daily) or metformin (1000 mg daily). The primary outcome is the rate of change in the total area of visceral fat for patients in both treatment groups, measured using CT, after 24 weeks of therapy. Two radiologists, blinded to the clinical information, will perform centralised analysis of the images in a unified measurement condition. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of each hospital. This study is ongoing and due to finish in April 2017. The findings of this study will be disseminated via peer-reviewed publications and conference presentations, and will also be disseminated to participants. TRIAL REGISTRATION NUMBER: UMIN000015170, R000016861 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000016861); Pre-results.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.

AIMS/INTRODUCTION: To assess the efficacy and safety of sitagliptin compared with α-glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone. MATERIALS AND METHODS: In the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20-79 years with type 2 diabetes who had glycated hemoglobin 6.9-8.8% on stable metformin (500-1,500 mg/day) or pioglitazone (15-30 mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50 mg/day) or an α-glucosidase inhibitor (0.6 mg/day voglibose or 150 mg/day miglitol) for 24 weeks. The primary end-point was change in glycated hemoglobin from baseline to week 12. All data were analyzed according to the intention-to-treat principle. RESULTS: After 12 weeks, reductions in adjusted mean glycated hemoglobin from baseline were -0.70% in sitagliptin and -0.21% in the α-glucosidase inhibitor groups respectively; between-group difference was -0.49% (95% confidence interval -0.66 to -0.32, P < 0.0001), meeting the predefined non-inferiority criterion (0.25%) and showing statistical significance. This statistical significance also continued after 24 weeks. Although sitagliptin did not affect bodyweight, α-glucosidase inhibitors decreased bodyweight significantly from baseline (-0.39 kg; P = 0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an α-glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P = 0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group. CONCLUSIONS: Sitagliptin showed greater efficacy and better tolerability than an α-glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type 2 diabetes inadequately controlled by insulin-sensitizing agents. This trial was registered with UMIN (no. 000004675).

A patient with POEMS syndrome: the pathology of glomerular microangiopathy.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is potentially fatal multisystem disorder but its renal complication has often been overlooked because renal involvement is not necessarily included in the diagnostic criteria of POEMS. This report documents the patient with POEMS syndrome with long-term renal histopathological changes evaluated by renal biopsy. A 32-year-old Japanese woman presented with symptoms consistent with POEMS syndrome associated with proteinuria and IgA-λ type monoclonal gammopathy. Initial renal biopsy for confirmation of diagnosis revealed the proliferation of glomerular capillary loops located in the expanded mesangial matrices associated with glomerular enlargement. Electron microscopy examination of the renal biopsy revealed the presence of double contoured glomerular basement membrane containing peculiar fibrillary structure. The patient was therefore initially diagnosed as membranoproliferative glomerulonephritis (MPGN)-like lesion without any significant immunoglobulins and complements deposition. The patient was subsequently admitted to hospital on five occasions due to renal dysfunction and anasarca for the next four years of her clinical course. The severity of anasarca was correlated mainly with serum titer of vascular endothelial growth factor (VEGF) during this period. Acute renal failure occurred at the last admission and the second biopsy was performed. An increased mesangial matrix and frequent global sclerosis of the glomeruli with arteriolosclerosis was noted in this second biopsy compared to the first one. These findings of renal biopsies suggest that the glomerular microangiopathy of POEMS syndrome may occur in the context of systemic capillary leak syndrome superimposed on chronic endothelial injury.

Acute myelogenous leukemia with Leptotrichia trevisanii bacteremia.

A 74-year-old woman visited an otolaryngology clinic with pharyngeal pain, and was diagnosed with a peritonsillar abscess. She received antibiotics and underwent incisional drainage, but displayed high white blood cell and blast cell counts, and was referred to our hospital. Gram-negative rods (Leptotrichia trevisanii) were detected in blood cultures performed on admission. She was diagnosed with bacteremia and acute myelogenous leukemia (FAB classification: M1). After antibiotic therapy, she temporarily recovered from the bacteremia, but subsequently died on day 34. Although Leptotrichia trevisanii bacteremia is extremely rare, clinicians should consider it in cases involving immunocompromised patients with oral lesions.

Lifestyle and osteoporosis in middle-aged and elderly women: Chiba bone survey.

Osteoporosis causes an enormous health and economic impact in Japan. We investigated the relation between lifestyle and bone fracture in middle-aged and elderly women. This was a population-based, multicenter, cross-sectional survey for postmenopausal osteoporosis in Chiba City, Japan (Chiba bone survey). This survey included 64,809 Japanese women aged > 40 years. All participants underwent anthropometric measurements including bone mineral density (BMD) and completed a structured, nurse-assisted, self-administered questionnaire also including patient lifestyle. Bone fracture during the recent 5 years was observed in 5.3%, and the fracture group had significantly higher age, BMI, and prevalence of delivery, family histories of kyphosis and hip fracture, diabetes mellitus (DM), dyslipidemia, kidney disease, exercise, fall, and osteoporosis, and had significantly lower BMD and proportion of menstruating participants. Logistic regression analysis revealed that bone fracture was closely associated with not only low bone mass but also age, fall, family histories of kyphosis and hip fracture, DM, kidney disease, menopause, and lifestyle factors of dieting, exercise, and alcohol. Women's health care focusing on lifestyle-related fracture risks such as dieting, exercise, and alcohol appears necessary to prevent bone fracture in postmenopausal osteoporosis.

Cerebellar haemorrhage associated with persistent primitive trigeminal artery.

A 55-year-old woman was admitted to our hospital because of sudden onset of dizziness and gait ataxia. A brain CT scan revealed a small cerebellar haemorrhage located in the right vermis. Brain MR angiography revealed left persistent primitive trigeminal artery (PPTA) and basilar artery (BA) dysplasia proximal to the shunting PPTA without arteriovenous malformation (AVM) or aneurysm. We speculate that BA dysplasia due to the PPTA, along with poorly controlled hypertension resulted in overload of the superior cerebellar artery blood vessels through the PPTA, leading to a haemorrhage in the right vermis. BA dysplasia and a PPTA without an obvious AVM or aneurysm possibly leading to cerebellar haemorrhage is rare. PPTA is a relatively common vascular anomaly; hence, we must consider it in the differential diagnosis for brain haemorrhages that may be caused by the specific haemodynamic consequences of PPTA.

[Refractory acquired hemophilia A in which factor VIII inhibitor was not detected at onset and thereafter deteriorated after total hip replacement arthroplasty].

A 58-year-old man was admitted to a general hospital to undergo total hip replacement arthroplasty for idiopathic osteonecrosis of the right femoral head. Pre-operative screening examination demonstrated isolated prolonged aPTT. Factor VIII (FVIII) activity was mildly decreased but there was no detectable FVIII inhibitor, so he was diagnosed as having congenital hemophilia. Surgery was performed safely with administration of FVIII preparation but 33 days postoperatively bleeding from the right hip joint appeared. It was not controllable with FVIII preparation and he was therefore admitted to our hospital.Laboratory examination at admission demonstrated prolonged aPTT (111.1 sec), reduced FVIII activity (3.0%), and the presence of FVIII inhibitor (17.0 B.U./ml). He was diagnosed with acquired hemophilia and administered Factor IX complex concentrates, prednisolone and cyclophosphamide. However, these treatments had only a temporary effect. Rituximab was administered every week and his condition soon improved. This case suggests that acquired hemophilia, in which there was no detectable FVIII inhibitor, may change to refractory disease after surgery. As a result, surgeons should pay careful attention to the preoperative presence of any mild coagulation abnormalities.

Successful autologous peripheral blood stem cell transplantation for a patient with primary adrenal lymphoma with hemophagocytic syndrome.

The adrenal glands are often an affected extranodal site in advanced non-Hodgkin lymphoma, but primary adrenal lymphoma (PAL) is extremely rare. Histologic examination of adrenal glands from patients with PAL reveals predominantly diffuse large B-cell lymphoma. Adrenal insufficiency is observed in about two thirds of patients. The prognosis of patients with PAL is poor: > 90% of patients die within 1 year of diagnosis, and long-term survivors are few. Effective therapeutic management of the condition has not been established. Herein, we report a 57-year-old man with PAL of diffuse large B-cell type that was later accompanied by hemophagocytic syndrome. He was initially treated with combination chemotherapy (1 cycle of CHOP [cyclophosphamide/doxorubicin/vincristine/prednisone] and 4 cycles of rituximab plus CHOP) and subsequently underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) in his first complete remission. He has been well and disease free for 39 months since undergoing auto-PBSCT. The successful outcome of using auto-PBSCT in the treatment of a patient with PAL suggests that this therapeutic approach has value in treating this poor-prognostic disease.

The importance of bacterial superantigens produced by Staphylococcus aureus in the treatment of atopic dermatitis using povidone-iodine.

Atopic dermatitis (AD) is frequently associated with intestinal and cervical lesions. Staphylococcus aureus produces many kinds of toxins, the bacterial superantigens. The detection rate of toxins was 80.1% from 196 S. aureus strains. Neurological examinations revealed abnormalities in 59 out of 81 AD patients. Cervical magnetic resonance imaging (MRI) was performed in 46 patients randomly and showed abnormal findings in 38 of these patients. In 23 patients who underwent MRI and duodenal biopsy, 3 were found to be normal neurologically and 2 patients showed normal duodenal tissue. However, 18 patients had abnormal findings both on neurological examination and in duodenal tissue. Serial duodenal biopsy tests were performed in 10 AD patients. In 5 patients, the findings of chronic duodenitis disappeared after the therapy with povidone-iodine. These data indicate that the therapy was effective not only for the skin lesions, but improved gastrointestinal tract lesions and cervical myelopathy, by eradicating bacterial superantigens.

Assessment of myocardial perfusion and fatty acid metabolism in a patient with Churg-Strauss syndrome associated with eosinophilic heart disease.

Churg-Strauss syndrome is characterized by asthma, eosinophilia and systemic necrotizing vasculitis; cardiac involvement (ie, eosinophilic heart disease) is the major cause of morbidity and mortality, although there are no reports of an association between left ventricular dysfunction because of eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. A patient presented with Churg-Strauss syndrome associated with eosinophilic heart disease that had progressed to dilated cardiomyopathy. Coronary angiography, thallium-201 ((201)Tl) and iodine-123 beta-methyl-iodophenyl pentadecanoic acid ((123)I BMIPP) myocardial single photon emission computed tomography (SPECT) were performed to evaluate left ventricular dysfunction. Although coronary angiography was normal and (201)Tl SPECT showed no apparent image defect, (123)I BMIPP SPECT showed diffuse decreased accumulation, excepting the apex. The left ventricular dysfunction in patients with eosinophilic heart disease is associated with impaired myocardial fatty acid metabolism rather than with impaired myocardial blood flow.

Lung abscess caused by Actinomyces odontolyticus.

A 64-year-old woman with periodontal disease was admitted because of fever, right chest pain, and bloody sputum. Her chest radiograph revealed a nodular shadow in the right middle lung fields. From the results of a needle aspiration biopsy, she was diagnosed with a lung abscess due to Actinomyces odontolyticus (A. odontolyticus) and Streptococcus spp. The patient improved quickly with antibiotics. To our knowledge, only nine cases of pulmonary infection due to A. odontolyticus have been reported, and we report the first case in Japan. Although respiratory disease caused by A. odontolyticus is rare, the association of this organism should be considered even in healthy individuals.

n-3 long-chain FA decrease serum levels of TG and remnant-like particle-cholesterol in humans.

A large number of papers have reported that administration of n-3 FA reduced serum TG concentrations in hypertriglyceridemic patients. However, few studies have examined the effect of n-3 FA on serum concentrations of remnant-like particle (RLP) cholesterol. Volunteers (n = 41) whose serum TG concentrations were 100-300 mg/dL were recruited and randomly assigned to either an n-3 FA group or a control group with stratification by sex, age, and serum TG level in a double-blind manner. The subjects in the n-3 FA group were administered 125 mL of fermented soybean milk with fish oil containing 600 mg of EPA and 260 mg of DHA/d for 12 wk. The controls consumed control soybean milk with olive oil. Fasting blood samples were obtained before the start of administration and at 4, 8, and 12 wk. EPA concentrations in red blood cells increased significantly in all but one subject in the n-3 FA group, with no significant changes in the control group. TG levels decreased more in the n-3 FA group than in the control group at weeks 4 (P < 0.05), 8 (P < 0.01), and 12 (P < 0.05) with their baseline as covariate. RLP cholesterol levels decreased more in the n-3 FA group than in the control at weeks 8 (P < 0.01) and 12 (P < 0.05) with their baseline as covariate. The groups did not differ in the other lipid levels. It is likely that n-3 long-chain FA may exert anti-atherosclerotic effects by lowering serum TG and RLP-cholesterol levels even at the dose of 860 mg/d.

Localized necrotizing angiitis of the ileum.

A 20-year-old woman was hospitalized repeatedly because of intermittent bouts of intestinal obstruction and the symptoms usually improved with conservative treatments. One year after the first admission the patient was hospitalized in emergency and a laparotomy revealed a circular stricture with a pinhole perforation in the ileum. Histological sections of the stricture showed the characteristic features of microscopic polyangiitis varying from active to resolving stages, which were localized in the ileum. Fibrinoid necrosis, fibroblastic and fibrous proliferation of the intima and fibrous replacement of the media with a variable pan- and perivascular inflammatory cell infiltrate were characteristic in the muscular arteries and arterioles. Vascular occlusion by pale eosinophilic, fibrillar-like materials resembling livedo racemosa of the skin, was noticed in the small arterioles and capillaries. Under no prophylaxis, the postoperative course was uneventful with no recurrence of the illness at an 18-month follow up. The pathological alterations were distributed focally, occasionally segmentally, and haphazardly, and required detailed examination by stepwise sections for the histological diagnosis.

[Role of public hospitals regarding the support of patients at home].

Eight sickbeds for the support of patients at home were established in Chiba Municipal Hospital in response to a request from the Chiba City Medical Association in 1997. These sickbeds were run by physicians and nurses in the hospital and nurses from Chiba City Public Health Center to promote a tight relation among the medical care, the health care and the public welfare systems. The role of the public health nurses is to receive and manage the documents of the patients from regional medical practitioners and to communicate with the related organizations. These sickbeds were set up to offer medical care, educational teaching to the family, and the social environment to support the patients at home. The patients, who were consulted by regional medical practitioners, were pre-registered by them. The length of stay at the hospital was limited to 2 weeks. The number of patients who were registered and hospitalized increased every year: thus 374 patients receiving treatment from 44 medical practitioners have already been registered. The average age of the patients was 81.1 and almost all of the patients were sick in bed for the whole day at home. Sixty-three patients were hospitalized making use of those sickbeds this year. Further promotion of the relation among the organizations involved in medical care, health care, and welfare is very important to support the patients to be able to stay at home.