RESUMO
Renal precipitation of uric acid associated with tumor lysis syndrome (TLS) is a major complication in the management of leukemia, lymphoma, and other drug-sensitive cancers. Management of hyperuricema has historically consisted of administration of allopurinol, hydration, alkalinization to maintain pH between 7.0 and 7.3, and in some cases diuresis. Allopurinol, a xanthine analogue, blocks xanthine oxidase and formation of uric acid. Urate oxidase converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. Homo sapiens cannot express urate oxidase because of a nonsense mutation. Urate oxidase was initially purified from Aspergillus flavus fungus. Treatment with this nonrecombinant product had been effective in preventing renal precipitation of uric acid in cancer patients, but was associated with a relatively high frequency of allergic reactions. This enzyme was recently cloned from A. flavus and is now manufactured as a recombinant protein. Clinical trials have shown this drug to be more effective than allopurinol for prevention and treatment of hyperuricemia in leukemia and lymphoma patients. This drug has been approved in Europe as well as the US and several clinical trials are in progress to further determine its clinical utility in other patient subsets. The purpose of this meeting was to discuss usefulness of recombinant urate oxidase, also known as rasburicase, Fasturtec, and Elitek, for the management of TLS in certain cancer patients.
Assuntos
Hiperuricemia/tratamento farmacológico , Síndrome de Lise Tumoral/complicações , Urato Oxidase/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Hiperuricemia/etiologia , Hiperuricemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome de Lise Tumoral/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controleRESUMO
Pulmonary inflammation is one of the risk factors associated with blood and marrow transplantation (BMT). To determine the potential role of T cells in pulmonary complications after transplantation, we analyzed the T-cell repertoire expressed in bronchoalveolar lavage fluids from eleven patients with graft-versus-host disease following BMT. A reverse transcriptase-polymerase chain reaction was used to amplify rearranged TCR transcripts in unfractionated, CD4+, and CD8+ T cells from bronchoalveolar lavage fluids. The relative expression of TCR variable (V) gene families and the diversity of junctional region lengths associated with different AV and BV gene families were analyzed. Nearly all TCR AV and BV gene families were detected in bronchoalveolar lavage cells from BMT recipients. Oligoclonal patterns of TCR junctional region lengths were observed in unfractionated, CD4+, and CD8+ bronchoalveolar T cells. The oligoclonal expansion of bronchoalveolar T cells in patients was confirmed by DNA sequencing. TCRV gene expression is almost completely restored in the lungs of BMT recipients as early as two weeks after transplantation. Increased oligoclonality among TCR gene families suggests either an incomplete restoration of TCR diversity or an antigen-driven expansion of T cells in the lungs of BMT recipients with graft-versus-host disease, not necessarily related to pulmonary infection.
Assuntos
Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/imunologia , Pneumopatias/imunologia , Pulmão/imunologia , Subpopulações de Linfócitos T/patologia , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Células Clonais/imunologia , Células Clonais/patologia , Feminino , Rearranjo Gênico do Linfócito T , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/patologia , Humanos , Pulmão/patologia , Pneumopatias/etiologia , Pneumopatias/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Transplante Autólogo/efeitos adversos , Transplante Autólogo/imunologia , Transplante Autólogo/patologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
OBJECTIVE: To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Eight intensive care units in four teaching hospitals. PATIENTS: Fifty-two patients with acute respiratory distress syndrome. INTERVENTIONS: Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa). MEASUREMENTS AND MAIN RESULTS: Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality. CONCLUSIONS: The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.
Assuntos
Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/terapia , Volume de Ventilação Pulmonar , Adulto , Gasometria , Peso Corporal , Protocolos Clínicos , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Respiração com Pressão Positiva/efeitos adversos , Estudos Prospectivos , Troca Gasosa Pulmonar , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/fisiopatologiaRESUMO
Encephalitis is a rare manifestation of adenovirus infection. We report the MR imaging findings of a patient with rhombencephalitis caused by adenovirus. Imaging findings included T2 signal abnormalities in the brain stem and cerebellum with mild patchy enhancement and mass effect.