Asunto(s)
Dolor en el Pecho/etiología , Unión Esofagogástrica , Migración de Cuerpo Extraño/diagnóstico , Migración de Cuerpo Extraño/etiología , Reflujo Gastroesofágico/terapia , Ganglios Linfáticos , Polivinilos/efectos adversos , Adulto , Dolor en el Pecho/diagnóstico , Contraindicaciones , Control de Medicamentos y Narcóticos , Estudios de Seguimiento , Reflujo Gastroesofágico/diagnóstico , Humanos , Inyecciones Intralesiones , Intestino Delgado , Hígado , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Masculino , Polivinilos/uso terapéutico , Recurrencia , Índice de Severidad de la Enfermedad , Bazo , Tomografía Computarizada por Rayos X , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Interferon alpha (IFN-alpha) can be effective therapy for patients with chronic kidney disease who have chronic hepatitis C (HCV). However, acute allograft rejection has been reported in association with IFN-alpha following kidney transplantation, and therefore IFN therapy is recommended prior to, rather than after, kidney transplantation whenever feasible. The special case of repeat allograft recipients who contract HCV after the first transplantation presents special difficulties. This report features the case of a repeat allograft recipient who presented with neutropenic fevers after 5 months of pegylated IFN-alpha therapy, initiated 6 months following the functional loss of his third graft and the reinitiation of hemodialysis (HD). Physical exam, radiographic and laboratory findings led to allograft nephrectomy. The pathologic findings supported a diagnosis of acute-on-chronic rejection. This represents a rare case of IFN-alpha induced rejection following allograft failure and return to HD in a repeat allograft recipient. It also calls attention to the need for a high index of suspicion for the development of allograft rejection, which may require allograft nephrectomy even after allograft 'failure'.
Asunto(s)
Hepacivirus/efectos de los fármacos , Hepacivirus/fisiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Interferón-alfa/uso terapéutico , Trasplante de Riñón/patología , Diálisis Renal , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/patología , Hepatitis C Crónica/complicaciones , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Polietilenglicoles , Radiografía , Proteínas Recombinantes , Tomógrafos Computarizados por Rayos X , Trasplante HomólogoRESUMEN
We report a case of amyloidosis associated with K light chain multiple myeloma in a 42-year-old African American man. The patient initially had mild dyspepsia, which rapidly progressed to include anorexia, fulminant hepatic failure, and death within 9 weeks. This is only the fourth reported case of hepatic failure from myeloma-associated amyloidosis and the second reported case of light chain myeloma with amyloidosis resulting in a progressive clinical course of hepatic failure. Our patient was unique in that, despite severe disease, he had mild symptoms without laboratory abnormalities until 2 weeks prior to death.
Asunto(s)
Amiloidosis/etiología , Fallo Hepático/etiología , Mieloma Múltiple/complicaciones , Adulto , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Resultado Fatal , Humanos , Fallo Hepático/patología , Masculino , Mieloma Múltiple/patologíaRESUMEN
Benzodiazepine discontinuation is characterized by a syndrome of increased activity and reduced seizure threshold that is similar to effects mediated by the glutamatergic system. To elucidate the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation, we administered lorazepam, the NMDA antagonist CPP, and the combination of these compounds either concomitantly or consecutively to mice via osmotic pumps and evaluated pentylenetetrazole-induced seizure threshold, open-field activity, and benzodiazepine receptor binding during and after chronic administration. Animals receiving lorazepam alone developed partial tolerance at 7 days and complete tolerance at 14 days to the anticonvulsant effects of lorazepam. This effect was partly attenuated by CPP coadministration with lorazepam. This combination produced only partial tolerance. A reduction in seizure threshold was observed 4 days after discontinuation of lorazepam alone. This effect was abolished by coadministration of CPP with lorazepam and by CPP administration during the withdrawal period. Benzodiazepine binding in most structures examined was significantly reduced at 14 days during chronic lorazepam administration (versus 1 day), and coadministration of CPP did not alter this decrement. After lorazepam discontinuation, binding was increased at 4 and 7 days versus chronically treated animals and versus vehicle within the cerebral cortex. This effect was abolished by coadministration of CPP as well as by CPP administration during the lorazepam withdrawal period. These data support the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Lorazepam/toxicidad , Piperazinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Síndrome de Abstinencia a Sustancias/fisiopatología , Animales , Corteza Cerebral/metabolismo , Interacciones Farmacológicas , Tolerancia a Medicamentos , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Hipocampo/metabolismo , Lorazepam/administración & dosificación , Lorazepam/farmacocinética , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Pentilenotetrazol/toxicidad , Piperazinas/administración & dosificación , Receptores de GABA-A/metabolismo , Convulsiones/inducido químicamente , Convulsiones/fisiopatologíaRESUMEN
Prenatal benzodiazepine exposure is associated with behavioral and neurochemical alterations in the early postnatal period. To determine the persistence of these effects, we evaluated pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake in mice at 6 and 12 months of age after prenatal lorazepam exposure. Seizure threshhold was reduced after acute lorazepam pretreatment in mice exposed to lorazepam prenatally, compared to control groups, at 6 and 12 months of age. Maximal GABA-dependent chloride uptake was also reduced in exposed mice at 6 and 12 months of age. These data indicate that behavioral and neurochemical alterations persist well into maturity after prenatal lorazepam exposure.
Asunto(s)
Cloruros/metabolismo , Lorazepam/farmacología , Pentilenotetrazol , Efectos Tardíos de la Exposición Prenatal , Convulsiones/fisiopatología , Ácido gamma-Aminobutírico/fisiología , Animales , Química Encefálica/efectos de los fármacos , Cloro , Femenino , Ratones , Muscimol/farmacología , Embarazo , Radioisótopos , Convulsiones/inducido químicamenteRESUMEN
1. Chronic administration of benzodiazepines is associated with the development of tolerance and discontinuation effects in humans and in a mouse model. 2. Co-administration of compounds active at the "peripheral" benzodiazepine site may alter chronic benzodiazepine effects. 3. During chronic lorazepam administration, addition of the peripheral site antagonist PK11195 attenuates behavioral tolerance and receptor downregulation. 4. In mice treated with both lorazepam and PK11195, discontinuation effects were also attenuated compared to lorazepam alone. 5. Specificity of the action of PK11195 was confirmed by antagonism of its action by the peripheral-site agonist Ro5-4864.
Asunto(s)
Benzodiazepinas/farmacocinética , Encéfalo/metabolismo , Sistema Nervioso Periférico/metabolismo , Receptores de GABA-A/metabolismo , Síndrome de Abstinencia a Sustancias/metabolismo , Animales , Benzodiazepinas/efectos adversos , Benzodiazepinas/antagonistas & inhibidores , Tolerancia a Medicamentos , Humanos , Ratones , Receptores de GABA-A/efectos de los fármacosRESUMEN
Chronic cocaine administration has been associated with sensitization (an increase in drug effect) rather than the tolerance observed with many psychotropic compounds. Because cocaine acts at the presynaptic dopamine transporter, we evaluated sensitization and striatal dopamine transporter binding in vivo in several mouse strains. All strains of mice evaluated showed increased activity after cocaine compared with after saline injections. BALB/cByJ, DBA/2J, B6AF1/J and C57BL6/J mice exhibited sensitization when assayed 72 hr after five daily injections of cocaine at 20 and 40 mg/kg/day, whereas B6AF1/J mice showed sensitization at 20 but not at 40 mg/kg/day. CD-1 mice did not exhibit sensitization at either dose. Striatal dopamine transporter binding in vivo was increased in DBA/2J and B6AF1/J mice when determined 72 hr after five injections of 40 mg/kg/day cocaine. In contrast, a continuous infusion of cocaine at the same dose and duration did not produce sensitization or binding changes in DBA/2J mice. The time course of transporter binding alterations after intermittent cocaine exposure indicated no change at 1 day, increased binding at 3 days, a return to control levels at 7 days and decreased binding at 14 days. These data indicate that both sensitization and alterations in dopamine transporter binding occur after chronic cocaine injection but that these changes are unlikely to be directly related.
Asunto(s)
Conducta Animal/efectos de los fármacos , Proteínas Portadoras/efectos de los fármacos , Cocaína/farmacología , Cuerpo Estriado/efectos de los fármacos , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso/metabolismo , Animales , Proteínas Portadoras/metabolismo , Cocaína/administración & dosificación , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Masculino , Ratones , Ratones Endogámicos , Unión Proteica/efectos de los fármacos , Factores de TiempoRESUMEN
Prior studies indicate that prenatal cocaine exposure can alter dopamine transporter binding in mature mice. To determine the persistence of these effects, pregnant mice were treated with cocaine, 10 mg/kg/d, during days 13 to 20 of gestation and dopamine transporter binding was evaluated in offspring at 3 and 6 months of age. In contrast to prior studies, binding in striatum was significantly increased at both time points in cocaine-exposed mice compared to controls.
Asunto(s)
Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/metabolismo , Cocaína/farmacología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Femenino , Ratones , EmbarazoRESUMEN
Pregnant mice were treated with cocaine, 10 mg/kg/day, during days 13 to 20 of gestation. Cocaine sensitization and dopamine transporter binding were evaluated in offspring at 6 weeks of age. Sensitization, defined as the increase in activity after 5 injections of cocaine compared to 1 injection, was reduced in cocaine-exposed mice. Dopamine transporter binding in striatum was also significantly reduced in cocaine-exposed mice compared to controls.