26 research outputs found

    Pyogenic spondylitis

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    Pyogenic spondylitis is a neurological and life threatening condition. It encompasses a broad range of clinical entities, including pyogenic spondylodiscitis, septic discitis, vertebral osteomyelitis, and epidural abscess. The incidence though low appears to be on the rise. The diagnosis is based on clinical, radiological, blood and tissue cultures and histopathological findings. Most of the cases can be treated non-operatively. Surgical treatment is required in 10–20% of patients. Anterior decompression, debridement and fusion are generally recommended and instrumentation is acceptable after good surgical debridement with postoperative antibiotic cover

    Defining the Functional Domain of Programmed Cell Death 10 through Its Interactions with Phosphatidylinositol-3,4,5-Trisphosphate

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    Cerebral cavernous malformations (CCM) are vascular abnormalities of the central nervous system predisposing blood vessels to leakage, leading to hemorrhagic stroke. Three genes, Krit1 (CCM1), OSM (CCM2), and PDCD10 (CCM3) are involved in CCM development. PDCD10 binds specifically to PtdIns(3,4,5)P3 and OSM. Using threading analysis and multi-template modeling, we constructed a three-dimensional model of PDCD10. PDCD10 appears to be a six-helical-bundle protein formed by two heptad-repeat-hairpin structures (α1–3 and α4–6) sharing the closest 3D homology with the bacterial phosphate transporter, PhoU. We identified a stretch of five lysines forming an amphipathic helix, a potential PtdIns(3,4,5)P3 binding site, in the α5 helix. We generated a recombinant wild-type (WT) and three PDCD10 mutants that have two (Δ2KA), three (Δ3KA), and five (Δ5KA) K to A mutations. Δ2KA and Δ3KA mutants hypothetically lack binding residues to PtdIns(3,4,5)P3 at the beginning and the end of predicted helix, while Δ5KA completely lacks all predicted binding residues. The WT, Δ2KA, and Δ3KA mutants maintain their binding to PtdIns(3,4,5)P3. Only the Δ5KA abolishes binding to PtdIns(3,4,5)P3. Both Δ5KA and WT show similar secondary and tertiary structures; however, Δ5KA does not bind to OSM. When WT and Δ5KA are co-expressed with membrane-bound constitutively-active PI3 kinase (p110-CAAX), the majority of the WT is co-localized with p110-CAAX at the plasma membrane where PtdIns(3,4,5)P3 is presumably abundant. In contrast, the Δ5KA remains in the cytoplasm and is not present in the plasma membrane. Combining computational modeling and biological data, we propose that the CCM protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3

    Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

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    Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed

    Seizure Outcome in Adult Patients with Supratentorial Cavernomas

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    Background Cavernomas are usually found in the supratentorial area, and epileptic seizures are one of the presenting symptoms. Objective This study aims to provide the seizure outcome in adult patients who underwent surgical excision of single supratentorial cavernomas. Materials and Methods A total of 23 patients with single supratentorial cavernomas were operated between May 2011 and January 2019. Pre- and postoperative seizure semiology, clinical, and radiological findings were collected from medical records. At the last follow-up, each patient was seen during regular visits and clinical variables were noted. Results The mean age was 37.08 10.5 years, and 11 (57.8%) and 12 (52.2%) were females and males, respectively. Headache (43.5%) and seizure (43.5%) were the most common presenting symptoms. Cavernomas were located on the right side in 13 and on the left side in 10 patients. The most common locations were the frontal (43.5%) and temporal (43.5%) lobes. The mean follow-up in this series was 41.4 +/- 30.8 months. Our results showed that surgery was effective in seizure outcome, as almost 70% of patients who had seizure before surgery was seizure free after surgery, and the difference between those who had seizure pre- and postoperative periods was statistically significant (p=0.0001)
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