629 research outputs found

    Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

    Get PDF
    The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed

    Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1

    Get PDF
    Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis

    The development of sentence-interpretation strategies in monolingual German-learning children with and without specific language impairment

    Get PDF
    Previous research on sentence comprehension conducted with German-learning children has concentrated on the role of case marking and word order in typically developing children. This paper compares, the performance of German-learning children with language impairment (age 4-6 years) and without language impairment (aged 2-6, 8-9 years) in two experiments that systematically vary the cues animacy, case marking; word-order, and subject-verb agreement. The two experiments differ with regard to the choice of case marking: in the first it is distinct but in the second it is neutralized. The theoretical framework is the competition model developed by Bates and Mac Whinney and their collaborators, a variant of the parallel distributed processing models. It is hypothesized that children of either population first appreciate the cue animacy that can be processed locally, that is, "on the spot," before they turn to more distributed cues leading ultimately up to subject-verb agreement, which presupposes the comparison of various constituents before an interpretation can be established. Thus agreement is more "costly" in processing than animacy or the (more) local cue initial NP. In experiment I with unambiguous case markers it is shown that the typically developing children proceed from animacy to the nominative (predominantly in coalition with the initial NP) to agreement, while in the second experiment with ambiguous case markers these children turn from animacy to the initial NP and then to agreement. The impaired children also progress from local to distributed cues. Yet, in contrast to the control group, they do not acknowledge the nominative in coalition with the initial NP in the first experiment but only in support of agreement. However, although they do not seem to appreciate distinct case markers to any large extent in the first experiment, they are irritated if such distinctions are lacking: in experiment II all impaired children turn to. animacy (some in coalition with the initial NP and/or particular word orders). In the discussion, the relationship between short-term memory and processing as well as the relationship between production and comprehension of case markers and agreement are addressed. Further research is needed to explore in more detail "cue costs" in sentence comprehension

    Histone modifications associated with herpes simplex virus type 1 genomes during quiescence and following ICP0-mediated de-repression

    Get PDF
    In the current study, it was shown that repressed virus genomes in quiescently infected MRC5 cells adopt a repressed histone-associated structure marked by the enrichment of deacetylated histones at a wide variety of herpes simplex virus type 1 (HSV-1) promoters. In addition, it was shown that genome de-repression, mediated by HSV-2 superinfection or delivery of ICP0 using a recombinant adenovirus vector, resulted in the enrichment of acetylated histones on HSV DNA. These data indicate that ICP0-mediated genome de-repression is intimately linked to enrichment of acetylated histones at virus promoters. The fold change in association of pan-acetylated histone H3 following Ad.TRE.ICP0-mediated de-repression consistently revealed promoter-specific variation, with the highest fold changes (>50-fold) being observed at the latency-associated transcript promoter and enhancer regions. Chromatin immunoprecipitation analyses using an antibody specific to the C terminus of histone H3 as a surrogate measure of nucleosome occupancy revealed little variability in the total loading of histone H3 at the various HSV promoters. This observation suggests that acetylation of histone H3 in response to ICP0 expression is not uniformly targeted across the HSV-1 genome during ICP0-mediated de-repression

    Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

    Get PDF
    BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

    A case report of bilateral synovial chondromatosis of the ankle

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Synovial chondromatosis is a rare, generally benign condition which affects synovial membranes. It most commonly involves large joints such as the knee, hip, and elbow, but its presence in smaller joints has also been reported. The diagnosis of synovial chondromatosis is commonly made following a thorough history, physical examination, and radiographic examination. Patients may report pain and swelling within a joint which is often aggravated with physical activity.</p> <p>Case presentation</p> <p>A rare case of bilateral synovial chondromatosis of the ankle is reviewed. A 26 year-old male presented with chronic bilateral ankle pain. Physical examination suggested and imaging confirmed multiple synovial chondromatoses bilaterally, likely secondary to previous trauma.</p> <p>Conclusion</p> <p>The clinical and imaging findings, along with potential differential diagnoses, are described. Since this condition tends to be progressive but self-limiting, indications for surgery depend on the level of symptomatic presentation in addition to the functional demands of the patient. Following a surgical consultation, it was decided that it was not appropriate to pursue surgery at the present time.</p
    corecore