Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.     

Magnetic resonance imaging in occipital lobe epilepsy with frequent seizures

Magnetic resonance imaging and single-photon emission computed tomography provide useful information in the evaluation of the pathophysiology of epileptic foci. Ictal magnetic resonance imaging in a 7-year-old male with occipital lobe epilepsy revealed mild swelling of the left temporo-occipital region, with hyperintensity on T(2)-weighted and fluid attenuated inversion recovery images. This lesion, however, was not detected on diffusion-weighted imaging. An ictal single-photon emission computed tomography study using 99mTc-ECD demonstrated left temporo-occipital hyperperfusion. T(2)-weighted and fluid attenuated inversion recovery images revealed hyperintensity without atrophy 4 months after control of his seizures. The focus in nonconvulsive status epilepticus has been reported as showing hyperintensity on T(2)-weighted, fluid attenuated inversion recovery and diffusion-weighted images. Since hyperintensity on diffusion-weighted imaging reflects cytotoxic intracellular edema due to excitotoxicity, and his ictal diffusion-weighted image exhibited no remarkable change, the lesions in the left temporo-occipital region resulted from vasogenic edema. Cytotoxic edema resulting from excitotoxicity leads to neuronal death, causing cortical atrophy. Thus, diffusion-weighted imaging is a useful tool to predict the prognosis of frequent seizures.     

Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma

AIM: To investigate the effect of HER-2/neu protein overexpression on chemoresistance and prognosis in patients with epithelial ovarian carcinoma. METHODS: A total of 141 ovarian carcinoma tissues surgically resected between 1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of the patients and immunohistochemical results were compared by chi2-test. Survival analysis was performed by the Kaplan-Meier method and the log-rank test. RESULTS: HER-2/neu overexpression was detected in 18 cases (12.8%). There were no significant differences in histopathological subtypes (P = 0.3550), FIGO stages (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the cases with HER-2/neu overexpression and the cases without HER-2/neu overexpression. Among the 58 cases which responded to chemotherapy, only five cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu overexpression. Overexpression of HER-2/neu had a tendency to relate with chemoresistance of epithelial ovarian carcinoma, but there were no statistically significant differences (P = 0.0817). No association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.4970). CONCLUSIONS: The results of the current study show that although HER-2/neu overexpression has a tendency to be associated with chemoresistance, it can not be a prognostic factor for the patients with epithelial ovarian carcinoma.     

Humoral immune responses against norovirus infections of children

In 2 infants with gastroenteritis associated with Norovirus (NoV), serum immunoglobulin (Ig) G, IgM, IgA, and fecal IgA antibody responses against NoV were examined by enzyme-linked immunosorbent assay using 11 different antigenic and genetic types of NoV virus-like particles expressed in insect cells. These two cases were putative primary single NoV infections, because antibodies against NoVs were not detected in acute-phase serums. In one of two cases, long-term excretion of virus RNA for 33 days was observed. Serum IgG responses demonstrated strong seroresponse to the homologous type, and weak seroresponse to the heterologous types within the genogroup. After more than 2 years, the IgG antibody titer remained high to the homologous type and low to the heterologous type within the genogroup. IgM and IgA were specific to the homologous type. IgM was short lived and the serum IgA antibody titer remained low to the homologous type for a long period. These results improve our understanding of the humoral immune response to NoV infection.     

Hippocampal BDNF and TrkB expression in young rats after status epilepticus

BACKGROUND: The immature brain is more susceptible to seizures than mature brains but less vulnerable to seizure-induced neuronal loss. We studied age-related susceptibility and vulnerability to kainic acid-induced status epilepticus (KASE) in rats in terms of hippocampal expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B receptor (TrkB). METHODS: Immunohistochemical and Western analysis were performed after kainic acid (KA)-induced status epilepticus (SE). RESULTS: KA doses required to induce SE increased from 1.5 mg/kg in 1-week-old rats to 10 mg/kg at 4 weeks of older. After SE the older rats showed spontaneous seizures and hippocampal pyramidal neuronal loss-unlike rats under 4 weeks old. Hippocampal BDNF protein expression had increased fivefold in 1-week-old rats and threefold in 8-week-old rats 1 day after SE, returning to baseline 2 days after SE. TrkB expression showed little effect from KASE at either age. CONCLUSIONS: These results indicated that the critical period as for vulnerability to SE was the age of 4-week-old and older in the rat. Since the response patterns of BDNF and TrkB to SE were similar between neonatal and the adult rats, our study revealed that the observed transient upregulation of BDNF did not contribute to cause epilepsy in neonatal rats.     

Extraosseous Benign Notochordal Cell Tumor Originating in the Lung: A Case Report

Benign notochordal cell tumors (BNCTs) are tumors originating in the axial skeleton, where chordomas occur. Although very rare, some cases of extraosseous chordoma, such as in the soft tissue and lungs, have been reported. We report a case of a primary tumor showing the notochordal characteristics of BNCTs within the axial skeleton.An asymptomatic 57-year-old woman presented with an abnormal shadow on her chest radiograph; chest computed tomography revealed a well-defined round nodule. The resected sample tissue contained a jelly-like small nodule. Histologically, it was identified as a BNCT, based on minimal nuclear atypia, extremely low mitotic activity within the tumor cells lying in a sheet-like arrangement, and focal immunopositivity for brachyury.This is the third case report of BNCT originating in the lungs; BNCTs are considered asymptomatic tumors that are identified by using highly developed chest imaging technology; however, our findings also suggest that these notochordal tumors may potentially originate from extraosseous sites that lack ideal precursor cells. Our case suggests that notochordal tumors can arise from organs that are unrelated to known notochordal development.     

Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients

A single-nucleotide polymorphism (SNP) G276T in the adiponectin gene has been associated with lower plasma adiponectin levels and insulin resistance, which are related to the prevalence of type 2 diabetes or diabetic complications of macroangiopathy. We performed a case-control study to examine whether the SNP276 of the adiponectin gene was also related to early diabetic nephropathy. SNP276 was examined with genomic DNA obtained from 108 type 2 diabetic patients with microalbuminuria (urinary albumin creatinine ratio [ACR] between 30 mg/g x Cr and 300 mg/g x Cr; case subjects), and 208 patients with normoalbuminuria (ACR < 30 mg/g x Cr; control subjects). The genotype distribution and G allele frequency of SNP276 in the case subjects (0.71) did not significantly differ from the control subjects (0.69). There were no differences among the genotypes of the adiponectin gene regarding age, duration of diabetes, body mass index (BMI), hemoglobin A(1c) (HbA(1c)), serum lipids, serum creatinine, and plasma adiponectin levels. These data suggest that SNP276 of the adiponectin gene is not an independent risk factor for incipient diabetic nephropathy in Japanese type 2 diabetic patients.     

Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer

Purpose

The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation.

Methods

Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9?±?3.8 years, range 28–46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012–2014. Early (PNf, t2–t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB₁, and texpB₂) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms.

Results

Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0–7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB₁, and texpB₂. The proportion of female embryos was 69–71 and 25–26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74–78 % of them, increasing their proportion by 57 % compared to the average.

Conclusions

Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.

     

Intrahepatic expression of the co-stimulatory molecules programmed death-1, and its ligands in autoimmune liver disease

Liver-infiltrating T cells play an essential role in the immunopathogenesis of autoimmune liver disease. Programmed death-1 (PD-1) and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that are involved in the regulation of immune responses. The ligation of PD-1 inhibits T-cell receptor-mediated T cell proliferation and cytokine production, and PD-1-deficient mice develop various organ-specific autoimmune diseases. To investigate the expressions of PD-1 and its ligands in autoimmune liver disease, in particular autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), immunohistochemical analysis was performed. Liver biopsy specimens obtained from 17 patients with AIH and PBC were studied. PD-1 was expressed on more than half of the liver-infiltrating T cells within the portal tract. Some of the intrahepatic T cells expressed B7-H1 in patients with AIH and PBC. B7-H1 and B7-DC were mainly expressed on some Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC) within the sinusoids and their expression was upregulated in autoimmune liver disease. These results suggest that the interaction of PD-1 on T cells with increased expression of B7-H1 and B7-DC on KC and LSEC might be involved in the downregulation of autoreactive lymphocytes and result in the regulation of pathogenesis in autoimmune liver disease.