Valproate-induced eosinophilia in children with epilepsy: role of interleukin-5

Interleukin-5 contributes both in eosinophilopoiesis and neural development. Serum interleukin-5 levels were measured with enzyme-linked immunosorbent assay technique in 68 children with epilepsy receiving sodium valproate monotherapy and compared with the levels of 60 healthy controls and 14 children with epilepsy receiving carbamazepine. Eosinophilia was observed in 35.3% of children receiving valproate. Interleukin-5 in valproate users was significantly higher compared with children receiving carbamazepine and controls. Valproate users who exhibited eosinophilia had higher interleukin-5 levels compared with those without eosinophilia. However, the interleukin-5 level was also elevated, although to a lesser degree, in children without eosinophilia. The majority of valproate responders had high interleukin-5 levels. A positive correlation between interleukin-5 levels and the eosinophil count was also noted. We postulate that valproate contributes to the pathogenesis of eosinophilia, probably inducing interleukin-5 production. The finding that serum interleukin-5 was significantly elevated in valproate responders and even in valproate users without eosinophilia suggests that the increase in interleukin-5 might represent one of valproate's antiepileptic mechanisms.     

Tissue Plasminogen Activator (tPA) Inhibits Human Neutrophil Superoxide Anion Production in Vitro

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide ( ) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil production.     

Solitary central osteoma of the jaws: a diagnostic dilemma

Osteomas are relatively rare benign osteogenic neoplasms, characterized by the proliferation of compact and/or cancellous bone. Osteomas can develop as peripheral (periosteal) masses attached to the cortical plates or as central lesions arising from endosteal bone surfaces. Although multiple osteomas of the jaws are a hallmark of Gardner syndrome (familial adenomatous polyposis), nonsyndromic cases are typically solitary. A search of the literature identified 91 well documented cases of solitary osteoma of the jaws published since 1955: 93.4% were peripheral and only 6.6% central, a ratio of 14:1 in favor of peripheral osteomas. Solitary central osteomas of the jaws seem to be very rare, with only 6 such cases reported since 1955. Adding the 4 new cases described here brings the total to 10 central osteomas, 30% occurring in the maxilla and 70% in the mandible. Whereas peripheral osteomas are fairly easy to diagnose, central osteomas pose a more challenging diagnostic problem and need to be differentiated from other similar lesions of the jaws, such as central ossifying fibroma, condensing osteitis, idiopathic osteosclerosis, osteoblastoma, cementoblastoma, and complex odontoma. With such a low number of cases of central osteoma reported, the objectives of the present report are to describe 4 new cases, analyze the clinical and radiographic characteristics, and discuss the features which distinguish these lesions from other similar lesions of the jaws.