Asunto(s)
Miocarditis/terapia , Miocarditis/virología , Adolescente , Fármacos Cardiovasculares/uso terapéutico , Niño , Preescolar , Diuréticos/uso terapéutico , Insuficiencia Cardíaca/etiología , Humanos , Inmunoterapia/métodos , Lactante , Recién Nacido , Miocarditis/complicaciones , Miocarditis/diagnóstico , Miocarditis/inmunología , PronósticoRESUMEN
BACKGROUND: Myocardial damage in myocarditis is mediated, in part, by immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki disease, as well as in murine myocarditis. Since 1990, the routine management of presumed acute myocarditis at Children's Hospital, Boston, and Children's Hospital, Los Angeles, has included administration of high-dose IVIG. METHODS AND RESULTS: We treated 21 consecutive children presenting with presumed acute myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive therapies. A comparison group comprised 25 recent historical control patients meeting identical eligibility criteria but not receiving IVIG therapy. Left ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3 weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation, the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor fractional shortening. Compared with the non-IVIG group, those treated with IVIG had a smaller mean adjusted left ventricular end-diastolic dimension and higher fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033, respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin-converting enzyme inhibitors, patients treated with IVIG were more likely to achieve normal left ventricular function during the first year after presentation (P = .03). By 1 year after presentation, the probability of survival tended to be higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no adverse effects of IVIG administration. CONCLUSIONS: These data suggest that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.
Asunto(s)
Inmunización Pasiva , Inmunoglobulinas Intravenosas/uso terapéutico , Miocarditis/terapia , Virosis/terapia , Enfermedad Aguda , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Miocarditis/epidemiología , Miocarditis/etiología , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Factores de Tiempo , Función Ventricular Izquierda/fisiología , Virosis/epidemiologíaRESUMEN
This study examined Schwann cell behavior during paranodal demyelination induced by beta,beta'-iminodipropionitrile (IDPN). The stimuli for Schwann cell proliferation, extensively studied in vitro, are less well understood in vivo. Most in vivo systems previously used to examine Schwann cell proliferation in disease are dominated by loss of internodal myelin sheaths. As used in this study, IDPN administration produces neurofilamentous axonal swellings and paranodal demyelination, without segmental demyelination or fiber degeneration. We asked whether Schwann cells would proliferate following the restricted paranodal demyelination that accompanies the axonal swellings, and if so what the sources and distributions of new Schwann cells might be. IDPN was given as a single large dose (2 ml/kg) to 21-d-old rats. Neurofilamentous axonal swellings formed in the proximal regions of motor axons, reaching their greatest enlargement in the root exit zone 8 d after IDPN administration. These swellings subsequently migrated distally down the nerves at rates approaching 1 mm/d. The axonal enlargement was consistently associated with displacement of the myelin sheath attachment sites into internodal regions, and consequent paranodal demyelination. This stage was associated with perikaryal changes, including nucleolar enlargement, "girdling" of the perikaryon, and formation of attenuated stalks separating the perinuclear region from the external cytoplasmic collar. Schwann cells proliferated abundantly during this stage. Daughter Schwann cells migrated within the endoneurial space (outside the nerve fiber basal laminae) to overlie the demyelinated paranodes of swollen nerve fibers. In these regions, local proliferation of Schwann cells continued, resulting in large paranodal clusters of Schwann cells. As the axonal calibers subsequently returned to normal, the outermost myelin lamellae of the original internodes returned to their paranodal attachment sites and the supernumerary Schwann cells disappeared. Formation of short internodes, segmental demyelination, and nerve fiber loss were rare phenomena. These results indicate that paranodal demyelination is a sufficient stimulus to excite abundant Schwann cell proliferation; neither internodal demyelination nor myelin breakdown is a necessary stimulus for mitosis. The 3H-thymidine incorporation studies indicated that the sources of new Schwann cells included markedly increased division of the Schwann cells of unmyelinated fibers and, as they formed, supernumerary Schwann cells. In addition, there were rare examples of 3H-thymidine incorporation by Schwann cells associated with myelinated nerve fibers.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Células de Schwann/citología , Animales , Axones/ultraestructura , División Celular , Movimiento Celular , Masculino , Vaina de Mielina/fisiología , Fibras Nerviosas/citología , Nitrilos/farmacología , Ratas , Ratas Endogámicas , Células de Schwann/fisiología , Células de Schwann/ultraestructura , Factores de TiempoRESUMEN
The question addressed in this study was whether exogenous insulin can enhance the rate of assimilation of blood glucose after prolonged hypovolemia when homeostasis is waning. Twenty-three well-fed mongrel dogs were maintained at a mean arterial blood pressure of 50 mm Hg by bleeding. Periodic analyses were made of arterial and venous plasma concentration of glucose, femoral blood flow, arterial plasma concentration of insulin, and hematocrit. At the onset of physiologic deterioration signaled by the need to reinfuse 50 ml of shed blood to maintain 50 mm Hg blood pressure, dogs received either 10 ml saline (control; n=15) or 10 ml saline containing 2 units insulin (treated; n=8). Administration of 2 units of insulin to eight of the dogs caused a significantly faster decline of blood glucose than that observed in saline-treated animals. Despite the more rapid decline in plasma concentration of glucose in animals that received insulin, there was no significant difference in glucose uptake between the two groups of animals. The hemoconcentration reflected by a rising hematocrit that develops when hypovolemia persists was accentuated by the administration of insulin without supplementary fluids. The absence of any effect of insulin on glucose uptake in the hindlimb in the late phase of hypovolemic shock suggests that the accelerated decline in arterial glucose levels may be due to inhibitory effects of insulin on hepatic glucose release. These results are not consistent with the resistance of plasma glucose to insulin in the late phases of hypovolemic shock.