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We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA®), re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven®) and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven®, however, TEG again showed resistance to therapy. FEIBA® infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA® was recorded by TEG. NovoSeven® was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA® or NovoSeven®. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA® or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC. [ABSTRACT FROM AUTHOR]

The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of lupus nephritis during preactive phase (within seven months of age) in autoimmune lupus NZB × NZWF[sub 1] (B/WF[sub 1]) mice was examined. Treatment of CpG-ODN was started at the age of 2.75 months and continued until 6.25 months. Overt disease began at the age of six months and progressed linearly at the age of 6.75 months in CpG-ODN-treated, but not control ODN-treated (control) groups. Also compared to control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis (GN), with prominent deposits of IgG2a and C3, which paralleled increased titre of IgG2a type anti-nuclear antibody in the blood. Among several cytokines (interleukin, IL-6, IL-4, IL-1α, IL-10, interferon-γ and tumor necrosis factor-α) in blood, IL-6 production paralleled the development of lupus nephritis. The present study suggests that CpG-ODN may enhance IL-6 production. The role of IL-6 in the development of GN will be discussed. [ABSTRACT FROM AUTHOR]

We investigated the effects of estriol (E3) on endothelial function and bone mineral density (BMD) in very elderly women. Twenty-four very elderly women (80 +/- 3.5 years old) were administered CaCl2 with or without estriol treatment (2 mg/day) for 30 weeks (hormone replacement treatment [HRT] group vs control group). Endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation by nitroglycerin of the brachial artery, and BMD were assessed. Levels of plasma lipids and apoproteins were not changed; however, both plasma E3 and E2 were substantially increased (E2, 4.6 to 31.3 +/- 8.1; E3, <5 to 45.3 +/- 7.9 pg/mL) by HRT. The FMD value was also increased by HRT, as were the plasma nitrite/nitrate and cGMP values. The response to nitroglycerin was not changed. The BMD was increased by HRT, but decreased in the control group. There were significant differences between the HRT group and control group after 30 weeks' treatment in the levels of osteocalcin, P1CP, and urinary deoxypiridinoridine. E3 significantly improved BMD by inhibiting bone resorption. Endothelial function was improved in line with the antiatherosclerotic effects. E3 might be effective for use in HRT in elderly patients. [ABSTRACT FROM AUTHOR]

Objectives – Stress is involved in the development of symptoms of Meniere's disease (MD). Stress-related disease has been reported to be associated with disorders in the circadian rhythm of melatonin (MEL) which regulates that rhythm. We therefore investigated MEL circadian rhythm of patients with MD. Patients and methods – A comparison of 13 MD patients was made with age-matched controls. Saliva samples were collected every 3 h. A statistical analysis of the circadian rhythm of saliva MEL was performed for a circadian rhythm by the fit of a 24- and 12-h composite cosine model. In addition, we assessed the stress and depression status of the two groups. Results – The rhythmic amplitude of MEL in the MD group was significantly lower than that in the control group ( P < 0.05). The acrophase in the MD group was significantly earlier than that in the control group ( P < 0.05). MD patients had significantly higher stress score and depression score than control subjects ( P < 0.05). The amplitude in MD patients had no significant correlation with their otologic clinical data. Conclusions – These results suggest that MD patients have a MEL deficiency, which is related to their stress and depression status rather than the otologic pathological status of MD. [ABSTRACT FROM AUTHOR]

Background: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). Patients and methods: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m² or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). Results: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). Conclusion: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. [ABSTRACT FROM AUTHOR]

Background The Wisteria floribunda agglutinin-positive human Mac-2-binding protein ( WFA+-M2 BP) is a new liver fibrosis glycobiomarker with unique fibrosis-related glyco-alteration. WFA+-M2 BP is also a useful surrogate marker for the risk of developing hepatocellular carcinoma and for the liver functional reserve. Aim To evaluate the diagnostic ability of WFA+-M2 BP for liver fibrosis in the clinical setting and the clinical utility of WFA+-M2 BP for predicting the efficacy of direct-acting anti-viral ( DAA) treatment for chronic hepatitis C patients. Methods The study included 159 genotype 1 hepatitis C patients who received DAA-based treatment (telaprevir or simeprevir) combined with pegylated-interferon alpha plus ribavirin (108 telaprevir- and 51 simeprevir-based triple treatment). The relation between baseline serum WFA+-M2 BP and treatment efficacy was evaluated. Results The serum WFA+-M2 BP level significantly increased with the progress of liver fibrosis. Area under the receiver operating characteristic curve analysis identified 2.17 as the cut-off index ( COI) for WFA+-M2 BP for diagnosing advanced fibrosis. The sustained virological response ( SVR) rate was significantly, negatively correlated with the serum WFA+-M2 BP level. Multiple logistic regression analysis found a low serum WFA+-M2 BP level (<2.17 COI) to be independently associated with SVR (odds ratio, 4.35, P = 0.027). Even for prior nonresponders and patients with the interleukin-28B minor allele or histological advanced fibrosis, treatment outcome was favourable for patients with a low serum WFA+-M2 BP level. Conclusion Serum WFA+-M2 BP is a non-invasive liver fibrosis marker useful for predicting the efficacy of DAA-based triple therapy for chronic hepatitis C patients. [ABSTRACT FROM AUTHOR]

Background and study aims: Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled- off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. Patients and methods: A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011.The follow-up data were also reviewed to determine the long-term outcomes of the procedures. Results: Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory-Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. Conclusions: Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the clinical implications of leptin and its potential humoral regulators in long-term low-caloric diet therapy for obese humans. Background on obesity; Characteristics of the subjects; Data and methods used; Results and conclusions.

Lipoatrophic diabetes is caused by a deficiency of adipose tissue and is characterized by severe insulin resistance, hypoleptinemia, and hyperphagia. The A-ZIP/F-1 mouse (A-ZIPTg/+) is a model of severe lipoatrophic diabetes and is insulin resistant, hypoleptinemic, hyperphagic, and shows severe hepatic steatosis. We have also produced transgenic "skinny" mice that have hepatic overexpression of leptin (LepTg/+) and no adipocyte triglyceride stores, and are hypophagic and show increased insulin sensitivity. To explore the pathophysiological and therapeutic roles of leptin in lipoatrophic diabetes, we crossed LepTg/+ and A-ZIPTg/+ mice, producing doubly transgenic mice (LepTg/+:A-ZIPTg/+) virtually lacking adipose tissue but having greatly elevated leptin levels. The LepTg/+:A-ZIPTg/+ mice were hypophagic and showed improved hepatic steatosis. Glucose and insulin tolerance tests revealed increased insulin sensitivity, comparable to LepTg/+ mice. These effects were stable over at least 6 months of age. Pair-feeding the A-ZIPTg/+ mice to the amount of food consumed by LepTg/+:A-ZIPTg/+ mice did not improve their insulin resistance, diabetes, or hepatic steatosis, demonstrating that the beneficial effects of leptin were not due to the decreased food intake. Continuous leptin administration that elevates plasma leptin concentrations to those of LepTg/+:A-ZIPTg/+ mice also effectively improved hepatic steatosis and the disorder of glucose and lipid metabolism in A-ZIP/F-1 mice. These data demonstrate that leptin can improve the insulin resistance and diabetes of a mouse model of severe lipoatrophic diabetes, suggesting that leptin may be therapeutically useful in the long-term treatment of lipoatrophic diabetes. [ABSTRACT FROM AUTHOR]