RESUMO
BACKGROUND/PURPOSE: Patients with spina bifida represent the highest risk group for hypersensitivity to latex. Recognized risk factors for these patients are repeated surgery and an atopic disposition. Little is known about children operated on in the first year of life for reasons other than spina bifida. METHODS: Eighty-six patients (mean age, 10.2 years) with gastrointestinal or urologic surgery were investigated for the number, type, and date of surgical interventions. Additionally, skin prick tests and provocation tests were performed to classify sensitized and symptomatic latex-allergic individuals. RESULTS: Twenty-seven patients were regarded as sensitized to latex (31.4%). Twenty patients were classified as being atopic (25.6%). Atopic patients were significantly more often sensitized and provocation positive compared with nonsensitized and provocation-negative ones (P <.01). Children already operated on in the first year of life (n = 44) with a positive provocation showed significantly higher latex-specific IgE-values than individuals with a negative outcome (P <.0001). The total number of operations and degree of sensitization showed a significant correlation; more than 8 surgical interventions during the first year of life significantly increased the risk of clinically relevant allergy to latex. CONCLUSION: This study emphasizes that individuals undergoing surgical interventions during infancy should be handled latex free from the very beginning of life.
Assuntos
Hipersensibilidade ao Látex/etiologia , Procedimentos Cirúrgicos Operatórios , Adolescente , Adulto , Criança , Pré-Escolar , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Imunoglobulina E/imunologia , Lactente , Hipersensibilidade ao Látex/imunologia , Masculino , Reoperação , Fatores de Risco , Disrafismo Espinal/imunologia , Disrafismo Espinal/cirurgia , Procedimentos Cirúrgicos UrológicosAssuntos
Calcinose/etiologia , Doença das Coronárias/etiologia , Terapia de Substituição Renal/efeitos adversos , Adolescente , Adulto , Calcinose/diagnóstico por imagem , Criança , Doença das Coronárias/diagnóstico por imagem , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Hormônio Paratireóideo/sangue , Diálise Peritoneal/efeitos adversos , Radiografia , Diálise Renal/efeitos adversosRESUMO
Treatment with recombinant human GH (rhGH), alone or in combination with the anabolic steroid oxandrolone (OX), has been recommended for girls with Turner's syndrome to improve final height. Several cardiovascular risk factors have been described in patients with Turner's syndrome, but the effect of therapy with rhGH and OX on lipoprotein(a) [Lp(a)] has not been investigated. Lp(a) serum levels and apolipoprotein(a) phenotypes were determined in 46 girls with Turners syndrome (aged 6-15 yr) during treatment with different combinations of rhGH and OX for 24-36 months (median, 27 months). Lp(a) serum levels showed little variation during 30 months of treatment in all treatment groups. Lp(a) levels showed no significant change in 25 patients receiving only rhGH and in 21 patients receiving rhGH and OX in combination. Treatment effects were independent of apolipoprotein(a) phenotypes and were not influenced by pubertal status. These data indicate that long term administration of rhGH has no significant impact on serum Lp(a) levels in girls with Turner's syndrome.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Lipoproteína(a)/sangue , Síndrome de Turner/sangue , Síndrome de Turner/tratamento farmacológico , Adolescente , Apolipoproteínas A/sangue , Apolipoproteínas A/genética , Criança , Combinação de Medicamentos , Feminino , Humanos , Oxandrolona/uso terapêutico , Fenótipo , Puberdade/sangue , Proteínas Recombinantes , Fatores de TempoRESUMO
Phospholipase D (PLD) activity in human embryonic kidney (HEK) cells is stimulated by phorbol-ester-activated protein kinase C (PKC) and by membrane receptors, the latter apparently acting via the GTP-binding proteins, ADP-ribosylation factor (ARF) and Rho. In the present study, performed in cell-free preparations, we have characterized and compared the regulation of HEK cell PLD activity by the stable GTP analogue, guanosine 5'-O-[gamma-thio]triphosphate (GTP[S]), and the phorbol ester, phorbol 12-myristate 13-acetate (PMA). In digitonin-permeabilized HEK cells, prelabeled with [3H]oleic acid, GTP[S] and PMA caused an approximately threefold concentration-dependent increase in the formation of [3H]phosphatidylethanol, measured in the presence of ethanol. Neomycin, which is known to complex with the PLD cofactor, phosphatidylinositol 4,5-bisphosphate, decreased basal and GTP[S]- or PMA-stimulated PLD activities with similar sensitivity. GDP and its analogue, guanosine 5'-O-[beta-thio]diphosphate, inhibited the stimulatory effect of GTP[S], whereas the PMA response was prevented by the nonselective PKC inhibitor, staurosporine, but not vice versa. PLD stimulation by GTP[S], but not by PMA, was markedly reduced upon cytosol depletion and reconstituted by purified recombinant ARF1. In HEK cell membranes, addition of purified recombinant ARNO, a guanine-nucleotide-exchange factor for ARF1. potentiated the GTP[S]-stimulated PLD activity. PLD stimulation by PMA in HEK cell membranes required MgATP and was largely prevented by the selective PKC inhibitors Goe 6976 and bisindolylmaleimide I. Immunoblot analysis demonstrated that both conventional PKC (alpha, beta, gamma) and atypical PKC isozymes (zeta, tau) were present in HEK cell membranes. The results indicate that phorbol ester stimulation of PLD activity in HEK cells apparently occurs by a phosphorylation-dependent mechanism involving membrane-associated PKC isozymes but not ARF proteins, the major targets of GTP[S]' action.
Assuntos
Proteínas de Ligação ao GTP/metabolismo , Proteínas Ativadoras de GTPase , Fosfolipase D/metabolismo , Proteína Quinase C/metabolismo , Fator 1 de Ribosilação do ADP , Fatores de Ribosilação do ADP , Linhagem Celular , Digitonina/farmacologia , Guanina/análogos & derivados , Guanina/farmacologia , Guanosina 5'-O-(3-Tiotrifosfato)/análogos & derivados , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Humanos , Isoenzimas , Rim/citologia , Rim/embriologia , Rim/metabolismo , Neomicina/farmacologia , Permeabilidade/efeitos dos fármacos , Fosfolipase D/efeitos dos fármacos , Proteína Quinase C/efeitos dos fármacos , Estaurosporina/farmacologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Activation of phospholipase D (PLD) is a cellular response to a wide variety of extracellular ligands. However, the exact mechanisms that link cell surface receptors to PLD remain unclear. In this study, we report the involvement of the small-molecular-mass guanine-nucleotide-binding protein, ADP-ribosylation factor (ARF), in the activation of PLD by the muscarinic acetylcholine receptor (mAChR) in human embryonic kidney cells stably expressing the human m3 subtype. PLD stimulation in permeabilized cells by guanosine 5'-O-[gamma-thio]triphosphate (GTP[S]) was dependent on a cytosolic factor and reconstituted by purified recombinant ARF 1. Brefeldin A, a known inhibitor of the ARF guanine-nucleotide-exchange-factor activity in Golgi membranes, inhibited mAChR-stimulated PLD, whereas basal PLD activity and stimulation by GTP[S] were not affected. Upon cell permeabilization without the addition of stimulus, ARF proteins were released. However, the addition of GTP[S] during permeabilization and mAChR activation before permeabilization caused an almost complete and partial (about 60%) inhibition, respectively, of ARF release, indicating that ARF proteins are activated and thereby translocated to membranes. The results indicate that ARF proteins and their nucleotide-exchange factor are apparently involved in the signalling pathway leading from mAChR activation to PLD stimulation in human embryonic kidney cells.