PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

T‐cell migration across the blood‐brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P‐selectin glycoprotein ligand‐1 (PSGL‐1) and its endothelial ligands E‐ and P‐selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL‐1 or E/P‐selectins does not result in ameliorated EAE, we speculated that T‐cell entry into the spinal cord is independent of PSGL‐1 and E/P‐selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL‐1^?/? proteolipid protein‐specific T cells in inflamed spinal cord microvessels of WT or E/P‐selectin^?/? SJL/J mice during EAE. T‐cell rolling but not T‐cell capture was completely abrogated in the absence of either PSGL‐1 or E‐ and P‐selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T‐cell invasion into the CNS parenchyma. Thus, PSGL‐1 interaction with E/P‐selectin is essential for T‐cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T‐cell rolling is not required for successful T‐cell entry into the CNS and initiation of EAE.     

Outcome Prediction in Moderate and Severe Traumatic Brain Injury: A Focus on Computed Tomography Variables

Background

With this study we aimed to design validated outcome prediction models in moderate and severe traumatic brain injury (TBI) using demographic, clinical, and radiological parameters.

Methods

Seven hundred consecutive moderate or severe TBI patients were included in this observational prospective cohort study. After inclusion, clinical data were collected, initial head computed tomography (CT) scans were rated, and at 6 months outcome was determined using the extended Glasgow Outcome Scale. Multivariate binary logistic regression analysis was applied to evaluate the association between potential predictors and three different outcome endpoints. The prognostic models that resulted were externally validated in a national Dutch TBI cohort.

Results

In line with previous literature we identified age, pupil responses, Glasgow Coma Scale score and the occurrence of a hypotensive episode post-injury as predictors. Furthermore, several CT characteristics were associated with outcome; the aspect of the ambient cisterns being the most powerful. After external validation using Receiver Operating Characteristic (ROC) analysis our prediction models demonstrated adequate discriminative values, quantified by the area under the ROC curve, of 0.86 for death versus survival and 0.83 for unfavorable versus favorable outcome. Discriminative power was less for unfavorable outcome in survivors: 0.69.

Conclusions

Outcome prediction in moderate and severe TBI might be improved using the models that were designed in this study. However, conventional demographic, clinical and CT variables proved insufficient to predict disability in surviving patients. The information that can be derived from our prediction rules is important for the selection and stratification of patients recruited into clinical TBI trials.     

Retroperitoneal hemorrhage after percutaneous coronary intervention in the current practice era: Clinical outcomes and prognostic value of abdominal/pelvic computed tomography

Background : Retroperitoneal hemorrhage (RPH) is a serious but infrequent complication of percutaneous coronary intervention (PCI). This study aimed to describe the clinical outcomes of patients who developed RPH following PCI in the current practice era, with particular focus on treatment strategies and the related prognostic value of abdominal/pelvic computed tomography (CT). Methods : Among 20,904 patients undergoing PCI, we identified 93 RPH (0.45%) confirmed by CT or by unequivocal surgical findings. We identified three groups with RPH for comparison: patients who developed refractory shock (systolic blood pressure <80 mm Hg for ≥30 min despite fluids and vasopressors, n = 16 [17.2%]); patients with transient hypotension (<30 min, n = 34 [36.6%]); and patients without hypotension (n = 43 [46.2%]). The primary endpoint was a composite of in‐hospital mortality, myocardial infarction, and cerebral vascular accident (CVA). Results : Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Patients who developed refractory shock had significantly more bleeding quantified by abdominal/pelvic CT (P < 0.001), had a higher rate and amount of red blood cell transfusion (P < 0.001), and were managed invasively more frequently (68.7%) than the rest of the population. The primary endpoint trended higher in patients presenting with refractory shock; however, this difference was not statistically significant. The volume of bleeding quantified by CT and the timing of imaging diagnosis did not correlate with the primary endpoint. Red blood cell transfusion, but not clopidogrel discontinuation, was associated with the primary endpoint. Conclusions : RPH remains as a serious complication of PCI and is associated with high rates of mortality and morbidity independently of the therapeutic strategy. In patients who were hemodynamically stable, RPH volume as quantified by non‐contrast abdominal/pelvic CT did not contribute to prognosis. © 2011 Wiley Periodicals, Inc.     

Changes in interpersonal conflicts among adolescents during psychodynamic therapy

Abstract

The core conflictual relationship theme (CCRT) method was used in psychodynamic therapy with 10 adolescents to study change in interpersonal conflicts in the course of treatment. Relationship anecdote paradigm interviews were conducted at the beginning of therapy and before termination 8 to 9 months later. Adolescents were asked to describe 4 relationship episodes for each of the following significant others: parents, peers, and therapist. The CCRTs for the 3 relationships were different: The main wishes toward the parents were to be close and to be given independence; toward friends, to be close and to be open; and toward the therapist, to be helped and to be understood. The responses of other and self toward parents were significantly more negative than responses in other relationships. Responses of self and other in the therapeutic relationship were significantly more positive. At the end of therapy the interactions with parents were more positive, whereas those with the therapist grew more ambivalent.     

Cellular diversity of human placental stem villi: an ultrastructural and immunohistochemical study

The aim of the study was to investigate the distribution and differentiation of cell types in the stroma of human placental stem villi (SV). A total of 14 human term placental tissues were studied. Double immunolabeling was performed for desmin-vimentin, desmin--smooth actin and vimentin--smooth actin. Cytokeratin 7, proliferating cell nuclear antigen immunolabeling was also performed. Parallel tissue samples were examined by transmission electron microscopy. HSCORE was performed for the semi-quantitative analysis of distribution of cells in the stroma of SV. Vimentin-labeled cells were mostly distributed in the subtrophoblastic area. Desmin-vimentin double immunolabeling was mainly localized in the triangular area and to a lesser degree in the perivascular area and vessel walls (p=<0.001). However, desmin- smooth actin labeling was observed predominantly in the vessel wall and perivascular area. Vimentin- smooth actin immunoreactivity was significantly stronger in the triangular and perivascular areas compared to the vessel walls (p=0.003).

Ultrastructurally, cells in the stroma of SV were mesenchyme cells, reticulum cells, fibroblasts, myofibroblasts, smooth muscle cells, and Hofbauer cells, filamented and vacuolated cells. The differentiation of myofibroblasts in the triangular and perivascular areas may play a role in maturation of SV and villous contractility, modulation of the intervillous space and this may have effects on maternofetal placental circulation.     

Structural brain changes in prenatal methamphetamine-exposed children

The global use of methamphetamine (MA) has increased substantially in recent years, but the effect of MA on brain structure in prenatally exposed children is understudied. Here we aimed to investigate potential changes in brain volumes and cortical thickness of children with prenatal MA-exposure compared to unexposed controls. Eighteen 6-year old children with MA-exposure during pregnancy and 18 healthy controls matched for age, gender and socio-economic background underwent structural imaging. Brain volumes and cortical thickness were assessed using Freesurfer and compared using ANOVA. Left putamen volume was significantly increased, and reduced cortical thickness was observed in the left hemisphere of the inferior parietal, parsopercularis and precuneus areas of MA-exposed children compared to controls. Compared to control males, prenatal MA-exposed males had greater volumes in striatal and associated areas, whereas MA-exposed females predominantly had greater cortical thickness compared to control females. In utero exposure to MA results in changes in the striatum of the developing child. In addition, changes within the striatal, frontal, and parietal areas are in part gender dependent.