RESUMEN
Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.
Asunto(s)
Anticuerpos/inmunología , Citotoxicidad Inmunológica , Linfocitos T Citotóxicos/inmunología , Animales , Células CHO , Cricetinae , Femenino , Humanos , Tolerancia Inmunológica , Isoanticuerpos/inmunología , Prueba de Cultivo Mixto de Linfocitos , Complejo Mayor de Histocompatibilidad , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Modelos Inmunológicos , Multimerización de Proteína , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Proteínas Recombinantes/inmunología , Bazo/inmunología , TransfecciónRESUMEN
The old saying about the squeaky wheel is true in politics. If physicians are not heard from, our share of the reimbursements will certainly be diminished or cut out.
Asunto(s)
Atención a la Salud/economía , Honorarios Médicos , Economía Médica , Humanos , Política , Estados UnidosAsunto(s)
Accesibilidad a los Servicios de Salud/economía , Medicaid/economía , Indigencia Médica/economía , Presupuestos/legislación & jurisprudencia , Accesibilidad a los Servicios de Salud/legislación & jurisprudencia , Indigencia Médica/legislación & jurisprudencia , Missouri , Sociedades Médicas , Estados UnidosAsunto(s)
Medicare/economía , Defensa del Paciente , Rol del Médico , Sistema de Pago Prospectivo , Rol , Anciano , Control de Costos , Honorarios Médicos , Humanos , Estados UnidosRESUMEN
The pharmacokinetics of fentanyl were determined in seven elderly (71-82 yr) and seven younger adults (18-41 yr) anaesthetized with thiopentone, nitrous oxide in oxygen and morphine. Fentanyl was administered as a 2-min i.v. infusion at doses of 15 micrograms kg-1 for elderly patients and 20 micrograms kg-1 for the younger patients. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Fentanyl concentration, per microgram kg-1 administered, was higher in elderly than in young patients at 2 min (7.73 +/- 3.14 v. 4.54 +/- 1.83 ng ml-1 (mean +/- SD), respectively) and at 4 min after the start of infusion (3.26 +/- 1.44 v. 1.78 +/- 0.72 ng ml-1, respectively). Concentrations were similar at all other sampling times. Pharmacokinetic variables were determined by non-compartmental techniques. Total plasma clearance was similar for the two age groups. Volume of distribution at steady-state (VDss) was smaller in elderly patients (1.36 +/- 0.44 v. 2.27 +/- 0.82 litre kg-1). Despite age-related changes in VDss, plasma fentanyl concentrations for the two groups were similar throughout the 4-h sampling period except immediately following administration. These results suggest that, if there are age-related differences in response to fentanyl, the likely pharmacokinetic explanation is the higher concentration of fentanyl in the elderly immediately following its administration.
Asunto(s)
Envejecimiento/metabolismo , Fentanilo/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Anestesia General , Fentanilo/administración & dosificación , Fentanilo/sangre , Humanos , Infusiones IntravenosasRESUMEN
To evaluate whether there are age-related differences in the plasma concentration-vs-time course of fentanyl, the authors administered fentanyl to seven infants (3-10 months), seven children (1-9 years) and seven adults (18-41 years). Anaesthesia was induced with thiopentone, nitrous oxide, and pancuronium; following tracheal intubation, fentanyl (approximately 30 micrograms X kg-1 for infants and children, 20 micrograms X kg-1 for adults) was administered as a 2-min IV infusion. Anaesthesia was maintained with nitrous oxide, pancuronium, and morphine sulphate as clinically indicated. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Plasma concentrations per microgram X kg-1 fentanyl administered were lowest in infants 4-10 and 60-240 min after the start of the 2-min infusion; values for children were lower than those for adults 4, 180 and 210 min after the start of the 2-min infusion. These findings are consistent with the authors' clinical observation that infants tolerate larger doses of fentanyl than do adults.