Proper genomic profiling of (BRCA1-mutated) basal-like breast carcinomas requires prior removal of tumor infiltrating lymphocytes

BRCA1-mutated breast carcinomas may have distinct biological features, suggesting the involvement of specific oncogenic pathways in tumor development. The identification of genomic aberrations characteristic for BRCA1-mutated breast carcinomas could lead to a better understanding of BRCA1-associated oncogenic events and could prove valuable in clinical testing for BRCA1-involvement in patients. Methods: For this purpose, genomic and gene expression profiles of basal-like BRCA1-mutated breast tumors (n=27) were compared with basal-like familial BRCAX (non-. BRCA1/. 2/. CHEK2*1100delC) tumors (n=14) in a familial cohort of 120 breast carcinomas. Results: Genome wide copy number profiles of the BRCA1-mutated breast carcinomas in our data appeared heterogeneous. Gene expression analyses identifi

Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration

Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local protective antibodies, i.e. S-IgA. Most commercially available vaccines however are inactivated non-replicating vaccines and have a low immunogenicity when administered intranasally. Local administration of these vaccines would therefore need an adjuvant to boost systemic and local antibody responses. Here we explored the use of a safe adjuvant system, i.e. bacterium-like particles (BLPs) derived from the food-grade bacterium in Lactococcus lactis, in the induction of protective antibody responses after intranasal immunization of mice. Supplementation of HI NI split vaccine with BLPs significantly increased levels of serum influenza-specific IgG and hemagglutination-inhibiting antibodies: this was dependent on the dose of admixed BLPs and number of immunizations. Admixing BLPs further boosted local influenza-specific S-IgA antibody levels at lung and nasal mucosal sites, but also at distant mucosal sites such as the vaginal mucosal tissue. Mice immunized IN with BLP-adjuvanted vaccine and IM with non-adjuvanted vaccine were protected against weight loss upon homologous infection with H1N1 A/PR/8/34. Full protection against weight loss upon heterologous challenge with Hi NI A/PR/8/34 was seen in mice immunized IN with BLP-adjuvanted H1N1 A/New Caledonia-derived split virus vaccine, but not in those receiving the split virus vaccine IM. Mice immunized IN with BLP-adjuvanted vaccine had significantly lower lung viral titers upon homologous and heterologous challenge when compared to titers detected in mice immunized by IM injection of non-adjuvanted vaccine. Thus, adjuvantation of IN-administered influenza vaccines with BLPs effectively enhances systemic and local antibody responses leading to a superior protection against homologous and heterologous influenza infection compared to conventional IM immunization. (C) 2012 Elsevier Ltd. All rights reserved

Association between infection and fever in terminations of pregnancy using misoprostol : A retrospective cohort study

Background: Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. Methods: A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. Results: The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Conclusion: Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP

Association between infection and fever in terminations of pregnancy using misoprostol : A retrospective cohort study

Background: Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. Methods: A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. Results: The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Conclusion: Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP

Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders

BACKGROUND AND PURPOSE: Radially oriented hypointense stripes in hyperintense cerebral white matter are recognized on T2-weighted images of certain lysosomal storage disorders. We compared in vivo and postmortem MR imaging with histopathologic findings in three patients with metachromatic leukodystrophy (MLD), globoid cell leukodystrophy (GLD), and infantile GM1 gangliosidosis (GM1) to understand this characteristic MR imaging pattern. METHODS: The in vivo MR imaging protocol comprised T1- and T2-weighted spin-echo and fluid-attenuated inversion recovery imaging. Postmortem MR imaging, including coronal 1-cm-thick brain sections, was performed after at least 5 weeks of formalin fixation and included T2-weighted spin-echo images and 3D fluid-attenuated inversion recovery images with high spatial resolution. Afterward, the sections were embedded in paraffin, whole-mount sections were made, and neuropathologic stains were applied. RESULTS: Similar imaging features were found in the three patients on in vivo and postmortem images, with more prominent stripes in GLD and MLD than in GM1. Neuropathologic examination revealed that the stripes were related to relative sparing of myelin in the perivenular regions in GM1 and MLD, but lipid-containing glial cells were also present in these areas in MLD. Perivenular clusters of globoid cells containing lipid material in absence of any myelin corresponded to the stripes in GLD. CONCLUSION: Results of our postmortem study showed that radial stripes of white matter on MR images represented relative myelin sparing in some lysosomal storage disorders, but they may also represent lipid storage

Association between infection and fever in terminations of pregnancy using misoprostol:a retrospective cohort study

Background: Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. Methods: A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. Results: The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Conclusion: Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP

Leucoencephalopathy with brainstem and spinal cord involvement and high lactate: quantitative magnetic resonance imaging

Leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is a white matter disorder caused by DARS2 mutations. The pathology is unknown. We observed striking discrepancies between improvement on longitudinal conventional magnetic resonance images and clinical deterioration and between large areas of high signal on diffusion-weighted imaging and small areas with low apparent diffusion coefficient values. These observations prompted a longitudinal and quantitative magnetic resonance imaging study. We investigated eight patients (two males, mean age 27 years). Maps of T<inf>2</inf> relaxation times, fractional anisotropy, apparent diffusion coefficients, signal on diffusion-weighted imaging, and axial and radial diffusivities were generated. Brain metabolites, obtained by chemical shift imaging, were quantified. Data analysis focused on: (i) white matter with low apparent diffusion coefficient; (ii) white matter with high T<inf>2</inf> values; (iii) white matter with intermediate T<inf>2</inf> values; and (iv) normal-appearing white matter. The areas were compared with similarly located areas in eight matched controls. In five patients, T<inf>2</inf>-weighted images, spectroscopy, apparent diffusion coefficient maps and diffusion-weighted imaging maps were compared with those obtained 5-7 years ago. In white matter with low apparent diffusion coefficient, axial and radial diffusivities were decreased and fractional anisotropy was high. T2 values were intermediate. These areas with truly restricted diffusion were small and often observed at the periphery of areas with high T<inf>2</inf> values. In the white matter with high and intermediate T<inf>2</inf> values, apparent diffusion coefficients and axial and radial diffusivities were increased and fractional anisotropy decreased. The signal on diffusion-weighted imaging was highest in white matter with high T<inf>2</inf> values, an effect of T<inf>2</inf> shinethrough. Chemical shift imaging in both white matter types showed increased lactate, increased myo-inositol and decreased N-acetylaspartate, most pronounced in white matter with high T<inf>2</inf> values. Normal-appearing white matter was comparable with white matter of control subjects. Over time, mild decreases in T2 signal intensities, signal on diffusion-weighted imaging and in extent of the low apparent diffusion coefficient areas were seen. In conclusion, the disease process in leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is extremely slow. We hypothesize that diffusion restriction is the first stage of the disease caused by intramyelinic water accumulation, followed by slow shift and then loss of the surplus of water. On conventional T <inf>2</inf> images this leads to improvement. We hypothesize that it is loss of water rather than structural restoration that causes the change in T <inf>2</inf> signal intensity, which would be in better agreement with the slow clinical deterioration. © 2011 The Author

Proper genomic profiling of (BRCA1-mutated) basal-like breast carcinomas requires prior removal of tumor infiltrating lymphocytes

BRCA1-mutated breast carcinomas may have distinct biological features, suggesting the involvement of specific oncogenic pathways in tumor development. The identification of genomic aberrations characteristic for BRCA1-mutated breast carcinomas could lead to a better understanding of BRCA1-associated oncogenic events and could prove valuable in clinical testing for BRCA1-involvement in patients. Methods: For this purpose, genomic and gene expression profiles of basal-like BRCA1-mutated breast tumors (n=27) were compared with basal-like familial BRCAX (non-. BRCA1/. 2/. CHEK2*1100delC) tumors (n=14) in a familial cohort of 120 breast carcinomas. Results: Genome wide copy number profiles of the BRCA1-mutated breast carcinomas in our data appeared heterogeneous. Gene expression analyses identifi