Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity.

BACKGROUND: Cross-sensitivity of rash has been reported between various antiepileptic drugs (AEDs). However, few studies have determined the frequency and management of cross-sensitivity in patients with super-refractory status epilepticus (SRSE). AIMS OF THE STUDY: To examine the optimal AED for treating SRSE with cross-sensitivity. METHODS: We performed a retrospective review of adult patients with SRSE treated at Nagoya City University Hospital, in which we investigated the frequency of cross-sensitivity among patients with SRSE and their clinical and medical profiles. RESULTS: We identified 10 adult patients with SRSE, 5 of whom had cross-sensitivity. Stiripentol (STP) was administered when previously used AEDs had demonstrated cross-sensitivity and failed to control seizures. After initiation of STP, the dose of general anaesthetics was reduced, and status epilepticus (SE) eventually ceased with co-administered AEDs without additional adverse effects. The mean time to SE cessation after initiation of STP was 30.8 days (range, 18-46 days), mean duration of general anaesthesia was 101.2 days (range, 74-128 days), and mean number of AEDs was 9.0 (range, 6-11). CONCLUSIONS: This study suggests that cross-sensitivity between AEDs is common in adults with SRSE and that STP may be useful for treating SRSE with cross-sensitivity.

Time-Reversal Measurement of the p-Wave Cross Sections of the

The cross sections of the ^{7}Be(n,α)^{4}He reaction for p-wave neutrons were experimentally determined at E_{c.m.}=0.20-0.81 MeV slightly above the big bang nucleosynthesis (BBN) energy window for the first time on the basis of the detailed balance principle by measuring the time-reverse reaction. The obtained cross sections are much larger than the cross sections for s-wave neutrons inferred from the recent measurement at the n_TOF facility in CERN, but significantly smaller than the theoretical estimation widely used in the BBN calculations. The present results suggest the ^{7}Be(n,α)^{4}He reaction rate is not large enough to solve the cosmological lithium problem, and this conclusion agrees with the recent result from the direct measurement of the s-wave cross sections using a low-energy neutron beam and the evaluated nuclear data library ENDF/B-VII.1.

Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer.

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.

Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats.

OBJECTIVE: We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection. DESIGN: One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. RESULTS: Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. CONCLUSION: Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.

pH-Dependent membrane lysis by using melittin-inspired designed peptides.

We developed a membrane-lytic peptide (LP) having 26 amino acid residues composed of a helix-promoting hydrophobic segment (Leu-Ala repetitive sequence) and a cationic segment from melittin. In the presence of liposomes, LP interacts with liposomal surfaces to form a hydrophobic helix in the lipid bilayer in a wide pH range. In order to provide LP with a weakly acidic (endosomal) pH-controlled membrane-lytic activity, we have designed an LPE peptide series (a typical peptide, LPE3-1) with a hydrophobic segment in which Leu (L) residues are replaced by acidic Glu (E) residues. To analyze the pH-selective membrane-lytic activity of the designed peptides, both calcein leakage and membrane accessibility assays were performed. In the case of membrane disruption induced by the active pore formation, the incorporated calcein would leak from the liposomes and simultaneously the aqueous solution in the membrane surrounding would be accessible to the liposome interior at pH 5.0. The assays in the presence of LPE3-1 indicated no significant leakage or accessibility at pH 7.4, but a typical leakage and some accessibility to liposomes were positively observed at pH 5.0. In order to estimate whether the weakly acidic pH-controlled lytic activity is due to a secondary structural change of the hydrophobic segment of LPE3-1 in the liposome membrane, we have measured circular dichroism spectra. In the presence of liposomes, the minimum showing the characteristic helical structure was observed at 222 nm only under weakly acidic conditions. This pH dependence is in good agreement with the results from the leakage and accessibility assays. The pH-dependent membrane disruption properties of LPE3-1 may open a new avenue to gain insight into the interaction between peptides and lipids for the development of efficient drug/gene delivery systems.

Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.

BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs.

OBJECTIVE: The induction of synovial tissue to the meniscal lesion is crucial for meniscal healing. Synovial Mesenchymal stem cells (MSCs) are an attractive cell source because of their high proliferative and chondrogenic potentials. We examined whether transplantation of synovial MSCs promoted healing after meniscal repair of extended longitudinal tear of avascular area in a microminipig model. DESIGN: Longitudinal tear lesion was made in medial menisci and sutured in both knees, and then a synovial MSC suspension was administered for 10 min only in unilateral knee. The sutured meniscus was evaluated morphologically and biomechanically at 2, 4, and 12 weeks. The behavior of transplanted MSCs was also examined. RESULTS: The meniscal healing at 12 weeks was significantly better in the MSC group than in the control group; macroscopically, histologically and by T1rho mapping analysis. Transmission electron microscopic analysis demonstrated that the meniscus lesion was occupied by dense collagen fibrils only in the MSC group. Biomechanical analysis revealed that the tensile strength to failure of the meniscus higher in the MSC group than in the control group in each microminipig. Synovial tissue covered better along the superficial layer from the outer zone into the lesion of the meniscus in the MSC group at 2 and 4 weeks in each microminipig. Synovial MSCs labeled with ferucarbotran were detected in the meniscus lesion and adjacent synovium by MRI at 2 weeks. CONCLUSION: Transplantation of synovial MSCs promoted healing after meniscal repair with induction of synovium into the longitudinal tear in the avascular zone of meniscus in pigs.

Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

BACKGROUND: Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF. METHODS: The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination. RESULTS: On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema). CONCLUSIONS: Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.

Effects of transglucosidase on diabetes, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial.

In this 12-week, randomized, double-blind, placebo-controlled trial, the efficacy and safety of transglucosidase (TGD) were compared with placebo in patients with type 2 diabetes mellitus (T2DM). At 12 weeks, TGD 300 mg/day and TGD 900 mg/day significantly reduced HbA1c (0.18 and 0.21%) and insulin concentration (19.4 and 25.0 pmol/l), respectively, vs. placebo. TGD 300 mg/day and TGD 900 mg/day also significantly reduced low-density lipoprotein cholesterol (0.22 and 0.17 mmol/l, respectively). TGD 900 mg/day significantly reduced triglyceride by 0.24 mmol/l and diastolic blood pressure by 8 mmHg. Placebo was associated with a significant increase from baseline in body mass index, alanine aminotransferase and aspartate aminotransferase (0.17 kg/m(2) , 3 and 2 U/l, respectively), whereas TGD was not. TGD 300 mg/day significantly increased high-molecular-weight adiponectin by 0.6 µg/ml. Adverse events did not differ significantly between the groups. TGD resulted in lowering of HbA1c and blood insulin level and improvements in metabolic and cardiovascular risk factors in T2DM.

Relationship between sun-protection factor and application thickness in high-performance sunscreen: double application of sunscreen is recommended.

BACKGROUND: High-performance sunscreen protects both healthy consumers and photosensitive patients from strong ultraviolet (UV) exposure. The sun-protection factor (SPF), which indicates the efficacy of UV protection, is determined using a prescribed sunscreen application thickness of 2.0 mg/cm(2). Therefore, users should apply at least 2.0 mg/cm(2) of sunscreen to obtain the level of UV protection expected from a product. In most cases, however, users apply insufficient amounts of sunscreen. AIM: To determine the amount of sunscreen applied under specific conditions, and the relationship between application thickness and SPF value in high-performance sunscreen. METHODS: The amount of applied sunscreen was calculated under practical conditions and conditions that directed a double application. The SPF values of high-performance sunscreen applied at three thicknesses (2.0, 1.0 and 0.5 mg/cm(2)) were determined according to the international SPF testing method. RESULTS. The relationship between SPF value and application thickness correlated in a logarithmic curve. The mean application thickness under practical conditions was approximately 1 mg/cm(2), and directing subjects to use a double application increased the application thickness to nearly 2 mg/cm(2). CONCLUSION: Encouraging a double application of sunscreen will help users apply products at a thickness sufficient to achieve expected SPF efficacy. We recommend that guidance on double application of sunscreen should be posted in public locations where sunscreen is likely to be in use.

Renal impairment after laparoscopic radical nephrectomy affects hypoglycaemic therapy.

WHAT IS KNOWN AND OBJECTIVE: Renal impairment is unavoidable after laparoscopic radical nephrectomy (LRN) and is an important consideration for drug therapy. It is possible that the renal impairment after LRN causes adverse reactions following reduced elimination of some renally excreted drugs, such as hypoglycaemic drugs. However, there are few studies of renal function in patients with diabetes mellitus (DM) in the first week after LRN. The purpose of this study was to examine whether renal impairment after LRN affected glycaemic control. We assessed pre- and postoperative renal function of DM patients and examined whether re-administration of hypoglycaemic drugs in the first week after LRN causes episodes of hypoglycaemia. METHODS: Renal carcinoma patients undergoing LRN in Nagoya University Hospital from January 2007 to December 2009 were identified in a retrospective cohort study design. Patients were divided into non-DM (n = 60) and DM (n = 14) groups. RESULTS AND DISCUSSION: There were significant differences in postoperative estimated glomerular filtration rate values between the non-DM and DM groups. Four of nine patients (44%) experienced hypoglycaemia induced by re-administration of hypoglycaemic drugs, namely, sulfonylureas. WHAT IS NEW AND CONCLUSION: In the present study, we found the first evidence that renal impairment in the first week after LRN was a risk factor of hypoglycaemia. To prevent hypoglycaemia after LRN, assessment of renal function and the use of insulin therapy are important.

Long-term survival of young women receiving fertility-sparing surgery for ovarian cancer in comparison with those undergoing radical surgery.

OBJECTIVES: To compare the clinical outcome of patients with stage I epithelial ovarian cancer (EOC) who received with fertility-sparing surgery (FSS) with those who underwent radical surgery (RS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 572 patients were retrospectively evaluated. All patients were divided into three groups: group A {FSS (n=74); age, ≤ 40}; groups B and C [RS; age, 40 ≥{(B), n=52}; 40<{(C), n=446}]. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 90.8% (OS)/87.9% (DFS); group B, 88.3% (OS)/84.4% (DFS); group C, 90.6% (OS)/85.3% (DFS), respectively (OS, P=0.802; DFS, P=0.765). Additionally, there was no significant difference in OS and DFS among the three groups stratified to stage IA or IC (OS (IA), P=0.387; DFS (IA), P=0.314; OS (IC), P=0.993; DFS (IC), P=0.990, respectively). Furthermore, patients with a grade 1-2 or 3 tumours in the FSS group did not have a poorer prognosis than those in the RS group. CONCLUSIONS: Stage I EOC patients treated with FSS showed an acceptable prognosis compared with those who underwent RS.

B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes.

Immunization of mice with tumors genetically engineered to express the B7 costimulatory molecules amplifies the antitumor immune response mediated by CD8+ cytolytic T lymphocytes (CTL). In this report, we examined the effect of B7-CD28 costimulation on the hierarchy of tumor epitopes. Using a combination of affinity chromatography/reversed-phase high performance liquid chromatography and CTL cloning, we show that major histocompatibility complex (MHC) class I molecules from EL4 lymphoma cells can present at least six distinct CTL epitopes presented by MHC class I molecules. Nevertheless, mice immunized with wild-type B7-negative EL4 cells develop CTL only to one immunodominant epitope. In contrast, immunization with B7-transduced EL4 cells led to not only the amplification of the CTL response to this immunodominant epitope, but also to the recognition of five otherwise silent subdominant epitopes. The adoptive transfer of a CTL clone against such a subdominant epitope cured mice bearing EL4 lymphoma growing as an ascites tumor. The fact that CTL response can be spread to normally silent epitopes as a result of B7-CD28 costimulation suggests a novel approach to manipulate the hierarchy of CTL epitopes and offers an opportunity to explore novel targets for T cell-mediated cancer therapy.

Surgical correction for sinus venosus atrial septal defect with partial anomalous pulmonary venous connection in a dog.

A 5-year-old male toy poodle was referred for corrective surgery of an atrial septal defect. A sinus venosus-type atrial septal defect (ASD) with partial anomalous venous connection, suspected pulmonary hypertension, and pulmonary edema was confirmed by radiography, echocardiography, and cardiac computed tomography. Thoracic radiographs showed right heart enlargement. Echocardiography revealed right atrial and ventricular dilatation with mild flattening of the interventricular septum. Left-to-right shunt flow through the ASD was observed on color Doppler examination. Surgical correction of the sinus venosus ASD with a partial anomalous pulmonary venous connection was performed under cardiopulmonary bypass. A follow-up evaluation at 1 year after surgery showed resolution of the right-sided volume overload and no evidence of recurrence of ASD. Complications were not observed. Our findings indicate that surgical correction under cardiopulmonary bypass is a valid treatment option for an ASD with a partial anomalous pulmonary venous connection.

Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1.

Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, and lissencephaly. Mammalian O-mannosyl glycosylation is a rare type of protein modification that is observed in a limited number of glycoproteins of brain, nerve, and skeletal muscle. Here we isolated a human cDNA for protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1), which participates in O-mannosyl glycan synthesis. We also identified six independent mutations of the POMGnT1 gene in six patients with MEB. Expression of most frequent mutation revealed a great loss of the enzymatic activity. These findings suggest that interference in O-mannosyl glycosylation is a new pathomechanism for muscular dystrophy as well as neuronal migration disorder.

Transport and strong-correlation phenomena in carbon nanotube quantum dots in a magnetic field.

Transport through carbon nanotube (CNT) quantum dots (QDs) in a magnetic field is discussed. The evolution of the system from the ultraviolet to the infrared is analyzed; the strongly correlated (SC) states arising in the infrared are investigated. Experimental consequences of the physics are presented-the SC states arising at various fillings are shown to be drastically different, with distinct signatures in the conductance and, in particular, the noise. Besides CNT QDs, our results are also relevant to double-QD systems.

Calcium ion release from calcium hydroxide stimulated fibronectin gene expression in dental pulp cells and the differentiation of dental pulp cells to mineralized tissue forming cells by fibronectin.

AIM: The effect of calcium ions on dental pulp cells was examined and the mechanism of dentine bridge formation by calcium hydroxide was investigated. METHODOLOGY: Human dental pulp cells were treated with high concentration of calcium or magnesium ions for 24 h and fibronectin gene expression was measured by the quantitative PCR method. Human dental pulp cells were then cultured on fibronecin-coated dishes for 24 h, and osteocalcin and osteopontin gene expression, which are typical phenotypes of mineralized tissue forming cells, were measured by the quantitative PCR method. RESULTS: Fibronectin gene expression was stimulated by calcium ions dose-dependently. On the other hand, magnesium ions did not influence fibronectin gene expression. Furthermore, pulp cells cultured on fibronectin-coated dishes enhanced the expression of phenotypes of mineralized tissue forming cells. CONCLUSIONS: Calcium ions released from calcium hydroxide stimulates fibronectin synthesis in dental pulp cells. Fibronectin might induce the differentiation of dental pulp cells to mineralized tissue forming cells that are the main cells to form dentine bridges, via contact with cells.