Impaired fear extinction in mice lacking protease nexin‐1

The serine protease inhibitor protease‐nexin‐1 (PN‐1) has been shown to modulate N‐methyl‐d ‐aspartate receptor (NMDAR)‐mediated synaptic currents and NMDAR‐dependent long‐term potentiation of synaptic transmission. Here, we analysed the role of PN‐1 in the acquisition and extinction of classical auditory fear conditioning, two distinct forms of learning that both depend on NMDAR activity in the amygdala. Immunostaining revealed that PN‐1 is expressed throughout the amygdala, primarily in γ‐aminobutyric acid containing neurons of the central amygdala and intercalated cell masses (ITCs) and in glia. Fear extinction was severely impaired in mice lacking PN‐1 (PN‐1 KO). Consistent with a role for the basal nucleus of the amygdala in fear extinction, we found that, compared with wild‐type (WT) littermate controls, PN‐1 KO mice exhibited decreased numbers of Fos‐positive neurons in the basal nucleus after extinction. Moreover, immunoblot analysis of laser‐microdissected amygdala sub‐nuclei revealed specific extinction‐induced increases in the level of phosphorylated alpha‐calcium/calmodulin protein kinase II in the medial ITCs and in the lateral subdivision of the central amygdala in WT mice. These responses were altered in PN‐1 KO mice. Together, these data indicate that lack of extinction in PN‐1 KO mice is associated with distinct changes in neuronal activity across the circuitry of the basal and central nuclei and the ITCs, supporting a differential impact on fear extinction of these amygdala substructures. They also suggest a new role for serine protease inhibitors such as PN‐1 in modulating fear conditioning and extinction.     

Brain motor excitability and visuomotor coordination in 8-year-old children born very preterm

ObjectiveOur study aimed to test in 8 years old children born very prematurely whether a faulty primary motor cortex (M1) functioning could parallel visuomotor coordination difficulties.MethodsTen very preterm children (PT; gestational age ?32 weeks; 6 boys; 8 years 6 months, SD 4 months) were compared to seven healthy term peers (4 boys; 8 years 4 months, SD 4 months). Clinical assessment comprised two standardized tests for motor skills and visuomotor coordination. Transcranial magnetic stimulation (TMS) was applied over M1 area of the preactivated first dorsal interosseous muscle to measure the corticomotor excitability and the short intracortical inhibition (SICI).ResultsPT scores were significantly lower on the Developmental Test of Visual-Motor Integration (p = 0.0018) and on the Movement Assessment Battery for Children (p = 0.038). In parallel, the dominant hemisphere worked differently with no SICI in PT (p = 0.009) and more variability of corticomotor excitability (p = 0.001).ConclusionsThese intertwined neurophysiological findings suggest that a faulty motor programming in the dominant M1 of PT could explain visuomotor coordination deficits.SignificanceOur study contributes to the understanding of possible mechanisms that underlie motor difficulties commonly observed in children who were born premature. In addition, the effectiveness of rehabilitation interventions may be better understood by applying TMS as an outcome measure in the future.     

Tumor-like enlargement of the optic chiasm in an infant with Alexander disease

We report a patient with infantile Alexander disease (AXD) due to the recurrent p.Arg79Cys GFAP mutation. In addition to typical AXD abnormalities, magnetic resonance imaging demonstrated a tumor-like lesion of the optic chiasm suggestive of a glioma. A transient papilloedema appeared during the follow-up and the lesion partially regressed despite a worsening of white matter involvement. Rare radiological and pathological tumor-like lesions have already been reported in AXD patients. This patient confirms that enlargement of the optic chiasm is a rare feature of AXD, possibly linked to abnormal astrocytic proliferation.     

Partial Colpectomy is a Risk Factor for Urologic Complications of Colorectal Resection for Endometriosis

Study ObjectiveTo evaluate urologic complications after colorectal resection for endometriosis.DesignCohort study (Canadian Task Force classification II-2).SettingTertiary referral university hospital and expert center in endometriosis.PatientsOne hundred sixty-six women with colorectal endometriosis proven by transvaginal sonography and magnetic resonance imaging.InterventionOpen or laparoscopic colorectal resection for endometriosis.Measurements and Main ResultsForty-four patients (26.5%) experienced at least 1 urologic complication, including infection. Eight patients (4.8%) experienced postoperative symptomatic hydronephrosis requiring ureteral stent in 3 cases, a percutaneous nephrostomy in 1 case, and expectant management for the last 4. Urologic fistulas occurred in 5 patients (3%). Postoperative voiding dysfunction requiring self-catheterization was observed in 48 patients (28.9%). With univariate analysis, a relationship was found between voiding dysfunction and partial colpectomy (p = .001) and American Society of Reproductive Medicine total score (p = .02), and between the occurrence of urinary fistula and the use of prophylactic ureteral catheterization (p = .015) and parametrectomy (p = .02). A relationship was found between postoperative symptomatic hydronephrosis and the use of prophylactic ureteral catheterization (p = .003).ConclusionColorectal resection for endometriosis can lead to urologic complications, particularly for patients requiring partial colpectomy, of which patients need to be informed.     

Preliminary evaluation of a fuzzy logic-based automatic quantitative analysis in myocardial SPECT.

This study validates a new quantitative myocardial perfusion SPECT software. METHODS: The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a <5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography. RESULTS: The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively. CONCLUSION: The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.     

Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma

Osteosarcoma is the most common primary malignant bone tumour. Currently osteosarcoma classification is based on histological appearance. It was the aim of this study to use a more systematic approach to osteosarcoma classification based on gene expression analysis and to identify subtype specific differentially expressed genes. We analysed the global gene expression profiles of ten osteosarcoma samples using Affymetrix U133A arrays (five osteoblastic and five non-osteoblastic osteosarcoma patients). Differential gene expression analysis yielded 75 genes up-regulated and 97 genes down-regulated in osteoblastic versus non-osteoblastic osteosarcoma samples, respectively. These included genes involved in cell growth, chemotherapy resistance, angiogenesis, steroid- and neuropeptide hormone receptor activity, acute-phase response and serotonin receptor activity and members of the Wnt/ß-catenin pathway and many others. Furthermore, we validated the highly differential expression of six genes including angiopoietin 1, IGFBP3, ferredoxin 1, BMP, decorin, and fibulin 1 in osteoblastic osteosarcoma relative to non-osteoblastic osteosarcoma. Our results show the utility of gene expression analysis to study osteosarcoma subtypes, and we identified several genes that may play a role as potential therapeutic targets in the future.     

Chondrosarcoma of the hand: is a wide surgical resection necessary?

Chondrosarcomas of the hand are rare and generally treated with surgical resection. Thirteen patients with Grade 1 chondrosarcoma of the small bones of the hand were followed up for a mean of 99.8 months (range, 26-293 months). In eight patients (Group 1) curettage and reconstruction with cancellous bone was done and in five patients (Group 2) a wide resection was done. No patient experienced relapse in Group 2. In Group 1 one patient had a local relapse 18 months after intralesional resection. Using the Musculoskeletal Tumor Society score for evaluation, the clinical results showed an average of 98% and 95% of the normal function in Groups 1 and 2, respectively. None of the patients had evidence of systemic spread of the disease. With a relapse rate of 12.5% and no distant metastases after curettage, intralesional resection is the preferred method of treatment in Grade 1 chondrosarcoma of the hand, allowing the patient to avoid amputation and major loss of function.     

Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a unique case

Tumours of perivascular epithelioid cells (PEComas) are being increasingly reported at visceral and somatic sites. Both benign and malignant variants have been identified, although clinical follow-up is often limited, which prevents meaningful predictions of behavior. We report the case of a malignant soft tissue PEComa with histologically confirmed regional lymph node metastases and radiologically confirmed pulmonary metastases. The light microscopic appearance and immunohistochemical profile (HMB-45, smooth muscle actin positive) and electron microscopic appearance support perivascular epithelioid cell differentiation.     

Patency of the supraclinoid internal carotid artery branches after flow diversion treatment. A meta-analysis

Background and purpose

Placement of flow-diverters across the ostia of major ICA branches carries a risk of arterial occlusion. We determined the rate of occlusion of the supraclinoid ICA branches and the related symptoms, following coverage with flow-diverters.