The objective is to study the neuropsychiatric (NP) manifestations in pediatric onset systemic lupus erythematosus (SLE) at a tertiary care hospital of northwestern India applying American College of Rheumatology (ACR) case definitions in the context of occurrence of antiphospholipid antibodies (APLA). Data of 53 children with SLE were analyzed for NP syndromes. Tests for detection of APLA were performed as per international standards for quality control. Twenty-seven of the 53 (50.94%) children with lupus had at least one NP manifestation. The male to female ratio of our cohort of pediatric lupus was 1:2.8. However, there was significant male preponderance in patients with NPSLE as compared to patients without NPSLE (1:1.25 vs. 1:12; P < 0.0001). Majority of children with NPSLE (15/27, 55.5%) already had NP manifestations at the time of diagnosis and most of them (81.5%) had experienced more than one NP symptom. Headache was the commonest NP manifestation and was seen in 39.6% children with SLE followed by seizure disorder (35.8%) and cognitive dysfunction (16.9%). Tests for APLA were carried out in 37 of 53 (69.8%) patients with SLE and in 24 of 27 (88.8%) patients with NPSLE. While anticardiolipin antibodies were seen more frequently in children with NPSLE as compared to those without NPSLE (57.8 vs. 23%), lupus anticoagulant was more frequent in children without NPSLE (53.8 vs. 34.7%). However, these differences were statistically not significant. Eleven of the 27 children with NPSLE succumbed to their illness, primarily due to uncontrolled disease activity. Mean duration of follow-up of patients with NPSLE who are alive was 65.4 +/- 36.9 months. NP manifestations are common in pediatric onset lupus and contribute to significant morbidity. As compared to previously published literature, a significantly greater proportion of boys were affected. APLA were frequently detected in children with NPSLE. There is paucity of literature pertaining to NP manifestations of pediatric lupus in the context of APLA, especially with regard to antibodies to beta-2 glycoprotein I. To the best of our knowledge, this is the first detailed study on NP manifestations in childhood lupus from a developing country applying ACR case definitions.
Purpose: Novel therapeutic regimens are needed to improve the dismal outcomes of patients with anaplastic thyroid cancer (ATC). Oncolytic herpes simplex virus have shown promising activity against human ATC. We studied the application of oncolytic herpes simplex virus (G207 and NV1023) in combination with currently used chemotherapeutic drugs (paclitaxel and doxorubicin) for the treatment of ATC. Experimental Design and Results: All four agents showed dose-response cytotoxicity in vitro for the human ATC cell lines KAT4 and DRO90-1. G207, combined with paclitaxel, showed synergistic cytotoxicity. Chou-Talalay combination indices ranged from 0.56 to 0.66 for KAT4, and 0.68 to 0.74 for DRO90-1at higher affected fractions. Paclitaxel did not enhance G207 viral entry and early gene expression or G207 viral replication. Paclitaxel combined with G207 compared with single-agent treatment or controls showed significantly increased microtubule acetylation, mitotic arrest, aberrant chromatid separation, inhibition of metaphase to anaphase progression, and apoptosis. A single i.t. injection of G207 combined with biweekly i.p. paclitaxel injections in athymic nude mice bearing KAT4 flank tumors showed significantly reduced mean tumor volume (74 F 38 mm ) groups at 16 days. There was no morbidity in vivo attributable to therapy. Conclusions: Mechanisms of paclitaxel antitumoral activity, including microtubule acetylation, mitotic block, and apoptosis, were enhanced by G207, which also has direct oncolytic effects. Combination of G207 and paclitaxel therapy is synergistic in treating ATC and holds promise for patients with this fatal disease.
Regions of high (124)I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with (124)I-IAZGP PET is optimal 6 hours after injection.
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