ABSTRACT. A 6-year-old boy presented with epilepsia partialis continua 6 months after diagnosis of type 1 diabetes. Anti-glutamic acid decarboxylase 65 antibodies were found in his serum and cerebrospinal fluid. Antiepileptic agents did not improve his seizures. High-dose steroids, plasmapheresis, and intravenous immunoglobulin resulted in decreased anti-glutamic acid decarboxylase 65 antibody levels and resolution of his seizures. Pediatrics 2002;109(3). URL: http://www.pediatrics.org/ cgi/content/full/109/3/e50; GAD65 antibody, type 1 diabetes mellitus, Rasmussen encephalitis, seizure, plasmapheresis, autoimmunity.ABBREVIATIONS. GAD, glutamic acid decarboxylase; GABA, ␥ amino butyric acid; SMS, stiff-man syndrome; EPC, epilepsia partialis continua.G lutamic acid decarboxylase 65 (GAD65) is a protein found both in the central nervous system, where it converts glutamic acid to ␥ amino butyric acid (GABA), and in the -cells of pancreatic islets. Antibodies to GAD65 are found in 70% to 80% of patients with new-onset type 1 (autoimmune) diabetes mellitus. 1 They are also found in patients with certain neurologic conditions, particularly, stiff-man syndrome (SMS); however, the antibody titers are 10-to 1000-fold higher than the titers usually seen in type 1 diabetes mellitus. 2 This is the first report of a patient with both type 1 diabetes mellitus and epilepsia partialis continua (EPC) associated with extremely elevated levels of anti-GAD65 antibodies. CASE REPORTThe patient is a previously healthy 6 1 ⁄2-year-old adopted black boy who developed simple partial seizures involving the right hand 6 months after receiving the diagnosis of type 1 diabetes. He progressed rapidly over 3 days to have continuous multifocal right-sided seizures involving the hand, the face, and the leg (EPC). He stabilized transiently after 1 week, but 2 weeks after the initial seizure he became aphasic and obtunded. An electroencephalogram revealed frequent left-sided epileptiform discharges and slowing. He was treated with continuous but changing antiepileptic medications for the first 17 days after onset of seizures, at which time high-dose corticosteroids (2 mg/kg/d intravenous prednisolone) were added. Acyclovir was used for 4 days at the time of presentation but was discontinued when herpes simplex virus polymerase chain reaction and cultures were negative. Intubation and midazolam coma were used between day 17 and day 25 after seizure onset. None of these modalities resulted in improvement of the seizures.His evaluation included cerebrospinal fluid studies that were negative for herpes simplex virus, tuberculosis, fungus, cryptococcal antigen, and routine viral and bacterial pathogens. Serology was negative for herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Mycoplasma. Coagulation studies, including protime, partial thromboplastin time, protein C and protein S, and antithrombin III, all were normal. Rheumatologic studies, including lupus anticoagulant, antinuclear antibodi...
Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-α-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-α was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-α, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.
Objective To assess depression in children with chronic kidney disease (CKD) and to determine associations with patient characteristics, intellectual and educational levels, and health related quality of life (HRQoL). Study design Subjects aged 6–17 years from the Chronic Kidney Disease in Children cohort study completed the Children’s Depression Inventory (CDI), Wechsler’s Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate (GFR) and time to renal replacement therapy. Results 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate 0.95; 95% CI 0.92, 0.99). Depression status was associated with lower IQ (99 versus 88, P= 0.053), lower achievement (95 versus 77.5, P<0.05), and lower HRQoL by parent and child reports (effect estimates −15.48; 95% CI −28.71, −2.24 and −18.39; 95% CI −27.81, −8.96, respectively). CDI score was not related to change in GFR. Conclusion Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means to improve the academic performance and HRQoL of children with CKD.
In preeclampsia, the placenta releases one or more factors promoting neutrophil-endothelial adhesion. The increased neutrophil-endothelial adhesion thereby induced is a PAF-mediated event. It is suggested that if preeclamptic placentas release toxic factors into the maternal circulation in vivo, these factors may contribute to the altered vascular endothelial cell function in preeclampsia.
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