RESUMEN
BACKGROUND: Because prostaglandin (PG) E2 has been identified in the bone lesions of Langerhans cell histiocytosis (LCH), we speculated that indomethacin, a potent PG inhibitor, may be useful in patients with symptomatic LCH involving the bony skeleton. PROCEDURE: We used indomethacin to treat patients in whom we wanted to avoid steroids or chemotherapy, or in whom these treatments did not provide complete symptom relief. Ten children with bony LCH between 1984 and 1995 were treated; six had single-system bone disease and four had multisystem disease involving the bony skeleton and other organs. RESULTS: The dose of indomethacin ranged from 1 to 2.5 mg/kg/day (9-200 mg/day) in divided doses and was given for 1-16 weeks (mean, 6 weeks). Eight patients had a complete response to treatment, defined as complete resolution of symptoms for 4 weeks. One patient was withdrawn from treatment because of concern regarding the potential of indomethacin to induce seizures and a second patient, with suppurative skin lesions overlying a lytic skull defect, did not respond. CONCLUSIONS: Indomethacin is a useful therapy for LCH involving the bony skeleton and may have a role as first-line treatment in single-system bone disease. Whether it has a specific role in slowing disease progression or merely acts as an analgesic has not yet been established.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Indometacina/uso terapéutico , Antagonistas de Prostaglandina/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The identity of the primary in vitro translation products of fetal sheep nuchal ligament elastin mRNA was confirmed as two distinct polypeptides of 63 Kdal and 65 Kdal in both rabbit reticulocyte and wheat germ extract cell-free translation systems. Both polypeptides were co-translationally processed by a microsomal membrane signal peptidase, with the removal of 20-25 amino acid residues. A single (3,5 kb) RNA species encodes both tropoelastin polypeptides. Restriction endonuclease mapping of sheep genomic DNA by hydridization with two radiolabelled genomic DNA fragments containing sequences coding for sheep tropoelastin (pSE1-1,3 and pSE1-0.7,) indicated the presence of a single elastin gene. The elastin gene copy number was further quantitated by comparison of hybridisation of pSE1-1.3 and pSE1-0.7 to slot-blots and Southern transfers of sheep genomic DNA and to standard curves constructed with each clone. These results clearly demonstrate that each of these sequences is represented only once per haploid genome, suggesting that the two tropoelastin polypeptides are products of a single elastin gene.