TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II–infused mice

Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II–dependent TGF-β activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-β in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-β activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II–induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-γ, IL-4, IL-6, or TNF-α signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-β activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-β neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-β in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.     

The higher the educational level of the first-time mother,the lower the fetal and post-neonatal but not the neonatal mortality in Belgium (Flanders)

Objective

To assess, in a homogenous population of primiparous women, how fetal and infant (=first year of life) mortality varied by the mothers’ level of education.

Study design

We conducted an observational study in Flanders (Northern Belgium) involving 170,948 primiparous women who delivered in Flanders during the period 1999–2006, and their 174,495 babies. We linked the maternal education (3 levels) with a series of obstetrical and perinatal events, with special emphasis on fetal and infant death. A logistic regression analysis was performed to adjust for confounders.

Results

The incidence of fetal (0.21% – high level of education; 0.35% – medium level; 0.84% – low level) and infant mortality (0.32%; 0.41%; 0.70%, respectively), followed an inverse maternal educational gradient: higher with a lower level of education. However, neonatal death (0–27 days) was independent of the educational level of the mother. The age of the woman at delivery, the use of assisted reproductive technology and the incidence of twin birth increased while the rates of preterm birth (7.7% – high level; 8.9% – medium level; 10% – low level) and low birth weight (7.2%; 9.5%; 11.8%, respectively) decreased with the mother's educational level.

Conclusion

Perinatal and obstetrical outcome differ according to the level of the education of the mother, which is a determinant of the incidence of fetal and post-neonatal death but not of early and late neonatal death (0–27 days).     

Treatment of vocal fold scar by carbon dioxide laser and collagen injection: retrospective study on 12 patients

Vocal fold scars are the result of injury to the vocal fold lamina propria. This condition leads to an impaired vibration and usually to poor voice quality. The purpose of our study was to compare the pre- and posttreatment voice assessment scores in patients treated by CO₂ laser-assisted freeing of the scar followed by collagen injection. A group of 12 patients (10 women and 2 men) with vocal fold scars was studied retrospectively. Voice assessment was based on stroboscopy and on perceptual scores using the Grade (G) of the GRABS scale, subjective evaluation by the use of the Voice Handicap Index (VHI), aerodynamic measurements [maximum phonation time (MPT) and phonation quotient (PQ)], and acoustical measurements (frequency range and low intensity). Stroboscopy showed an improvement on the mucosal vocal fold wave and on the glottic competence. The mean VHI was improved from 63.16 to 45.5; G from 2 to 1.41; MPT from 7.05 to 8.62 s; and PQ from 463.02 to 358.54 ml/s. CO₂ laser freeing of vocal fold scars followed by collagen injection, combined with speech therapy, improved significantly the aerodynamic parameters (efficiency of voice), but not the acoustical scores.     

CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation.

A retrospective analysis of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (G-PBMC) products harvested from healthy donors indicates significant variability in both the absolute number and relative proportion of CD34, CD3, and CD14 cells obtained. This report examined whether variations in the cellular composition of G-PBMC products correlated with clinical outcomes after myeloablative allogeneic transplantation. The numbers of CD34, CD3, and CD14 cells infused into 181 human leukocyte antigen (HLA)-identical sibling recipients were analyzed with respect to tempo of engraftment, acute graft-versus-host-disease (GVHD), clinical extensive chronic GVHD, overall survival, and disease relapse. Neither acute GVHD, overall survival, nor disease relapse was statistically significantly associated with CD34, CD3, or CD14 cell doses or the CD14 to CD3 ratio. CD3 and CD14 cell doses and CD14 to CD3 ratios did not correlate with the tempo of neutrophil and platelet engraftment. However, increasing CD34 cell numbers were significantly associated with accelerated neutrophil (P =.03) and platelet (P =.01) engraftment. Higher doses of CD34 cells (> 8.0 x 10(6)/kg) were also associated with a significantly increased hazard of clinical extensive chronic GVHD (HR = 2.3, 95% confidence interval [CI] 1.4-3.7, P =.001), but neither CD3 nor CD14 doses were statistically significantly associated with chronic GVHD. It was concluded that CD34 cell dose in G-PBMC grafts appears to affect both the engraftment kinetics and the development of clinical extensive chronic GVHD in HLA-identical sibling recipients but without a demonstrable impact on survival, relapse, and acute GVHD. Given the morbidity associated with extensive chronic GVHD, efforts to further accelerate engraftment in HLA-matched sibling transplants by increasing CD34 cell number in G-PBMC products may be counterproductive.     

Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians

Various studies have shown that, in mammals, neurons and glial cells are capable of synthesizing bioactive steroids, or neurosteroids, which regulate the activity of the central nervous system (CNS). However, although steroid hormones are involved in the regulation of behavioral and neuroendocrine processes in amphibians, neurosteroid biosynthesis has never been studied in the CNS of non-mammalian vertebrates. Reviewed here are several data sets concerning the production of unconjugated and sulfated neurosteroids in amphibians. These data were obtained by investigating the immunohistochemical localization and activity of 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) and hydroxysteroid sulfotransferase (HST), in the frog brain. Numerous 3β-HSD-immunoreactive neurons were detected in the anterior preoptic area, nucleus of the periventricular organ, posterior tuberculum, ventral and dorsal hypothalamic nuclei. 17β-HSD-like immunoreactivity was found in ependymal gliocytes bordering the lateral ventricles of the telencephalon. Two populations of HST-immunoreactive neurons were localized in the anterior preoptic area and the dorsal magnocellular nucleus of the hypothalamus. High amounts of progesterone (PROG), 17-hydroxyprogesterone (17OH-PROG), testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) were measured in the frog brain by combining HPLC analysis of tissue extracts with radioimmunoassay detection. Incubation of telencephalic or hypothalamic explants with tritiated pregnenolone ([³H]PREG) yielded the synthesis of various metabolites including PROG, 17OH-PROG, DHEA and T. Incorporation of [³⁵S]3′-phosphoadenosine 5′-phosphosulfate ([³⁵S]PAPS) and [³H]PREG or [³H]DHEA into frog brain homogenates led to the formation of [³H,³⁵S]pregnenolone sulfate ([³H,³⁵S]PREGS) or [³H,³⁵S]DHEAS, respectively. Altogether, these results demonstrate that the process of neurosteroid biosynthesis occurs in amphibians as previously seen in mammals.     

Acute paraplegia revealing an intraspinal neurenteric cyst in a child

The authors report a case of intraspinal neurenteric cyst in a 22-month-old child, who presented with acute paraplegia following a vesicourethrogram. Despite 8 days' delay in surgical decompression, he made a complete neurological recovery. Neurenteric cysts are rare congenital lesions of the spinal canal lined with an epithelium of endodermal origin. They are usually located at the cervicothoracic junction and present with progressive mild to moderate signs of myelopathy. This is a unique case in regard both to its clinical presentation and to the excellent outcome after 8 days of complete paraplegia.     

Trans-Sinusal Frontal Approach for Olfactory Groove Meningiomas

The authors report on their experience with the trans-sinusal frontal approach in removing olfactory groove meningiomas. Six tumors were operated on by the trans-sinusal frontal approach, using a bicoronal incision; two tumors developed on one side, and there were four bilateral olfactosellar tumors. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked through a real subfrontal route along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stages of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, were removed along with the tumor. Tumor extensions toward the sella and the optic canals were removed without brain retraction, opening of the Sylvian fissure, or dissection of the carotid arteries. All patients made a good neurologic recovery; intellectual impairment disappeared within 1 month, and visual acuity normalized within 2 weeks. Olfactory nets were preserved on the contralateral side in unilateral tumors. The trans-sinusal frontal approach is technically easy and safe to achieve. Osteotomy and replacement of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, imageguided surgery allows precise deliniation of its limits and the free bone flap, including the calvarial outer layer, tangentially cut from one supraorbital canal to the other. The cosmetic result is perfect, as the normal contour of the forehead is maintained without any scar or visible burr hole. The trans-sinusal frontal approach gives access to the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoid processes. The trans-sinusal frontal approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas, whatever their size.     

Development and Validation of an ELISA for the Detection of Bluetongue Virus Serotype 4-Specific Antibodies

In this article, we describe the development and evaluation of a double antigen sandwich enzyme-linked immunosorbent assay (ELISA) able to detect serotype 4-specific antibodies from BTV-4 infected or vaccinated animals using a recombinant BTV-4 VP2 protein. The coding sequence of VP2 was inserted into a pVote plasmid by recombination in the Gateway^® cloning system. Vaccinia virus (VacV) was used as a vector for the expression of the recombinant VP2. After production in BSR cells, recombinant VP2 was purified by immunoprecipitation using a FLAG tag and then used both as the coated ELISA antigen and as the HRP-tagged conjugate. The performance of the ELISA was evaluated with 1186 samples collected from BTV negative, infected or vaccinated animals. The specificity and sensitivity of the BTV-4 ELISA were above the expected standards for the detection of anti-BTV-4 VP2 antibodies in animals reared in Europe or in the Mediterranean basin. Cross-reactions were observed with reference sera for serotypes 10 and 20, and to a lesser extent with serotypes 12, 17 and 24, due to their genetic proximity to serotype 4. Nevertheless, these serotypes have never been detected in Europe and the Mediterranean area. This ELISA, which requires only the production of a recombinant protein, can be used to detect BTV serotype 4-specific antibodies and is therefore an attractive alternative diagnostic method to serum neutralization.