Feasibility of measuring memory response to increasing dexmedetomidine sedation in children.

BACKGROUND: The memory effect of dexmedetomidine has not been prospectively evaluated in children. We evaluated the feasibility of measuring memory and sedation responses in children during dexmedetomidine sedation for non-painful radiological imaging studies. Secondarily, we quantified changes in memory in relation to the onset of sedation. METHODS: A 10 min bolus of dexmedetomidine (2 mcg kg-1) was given to children as they named simple line drawings every five s. The absence of sedation was identified as any verbal response, regardless of correctness. After recovery, recognition memory was tested with correct Yes/No recognitions (50% novel pictures) and was matched to sedation responses during the bolus period (subsequent memory paradigm). RESULTS: Of 64 accruals, 30 children (mean [SD]6.1 (1.2) yr, eight male) received dexmedetomidine and completed all study tasks. Individual responses were able to be modelled successfully in the 30 children completing all the study tasks, demonstrating feasibility of this approach. Children had 50% probability of verbal response at five min 40 s after infusion start, whereas 50% probability of subsequent recognition memory occurred sooner at four min five s. CONCLUSIONS: Quantifying memory and sedation effects during dexmedetomidine infusion in verbal children was possible and demonstrated that memory function was present until shortly before verbal unresponsiveness occurred. This is the first study to investigate the effect of dexmedetomidine on memory in children. CLINICAL TRIAL REGISTRATION: NCT 02354378.

Characterization of pigs transgenic for human decay-accelerating factor.

BACKGROUND: To prevent the central role played by complement activation in the hyperacute rejection of pig organs transplanted into primates, pigs transgenic for human decay-accelerating factor (HDAF) have recently been produced. The data presented here extend previous immunohistochemical findings by documenting the immunological characterization and the levels of expression of HDAF in these transgenic pigs. METHODS: Animals from 30 independently derived lines were included in this study. HDAF expression was characterized by immunoprecipitation and epitope mapping. Quantitative analysis was performed by radiometric assays followed by Scatchard analysis and by double-determinant radioimmunoassay. Deposition of iC3b on porcine aortic endothelial cells was determined by radioimmunoassay. DNA slot-blot analysis and densitometric scanning were used to evaluate HDAF transgene copy number. RESULTS: The integrity of HDAF expressed by these transgenic pigs could be demonstrated. HDAF was present in 72% of the organs analyzed, although considerable variation in expression occurred, both between animals and within the same pig. High levels of HDAF on porcine aortic endothelial cells resulted in iC3b deposition at levels as low as that detected on human endothelial cells. Twenty-six organs expressed levels of HDAF greater than those observed in the equivalent human tissue. HDAF expression did not correlate with the number of copies of the transgene incorporated into the porcine genome. CONCLUSIONS: Transgenic pigs, which express levels of functional HDAF even greater than those observed in humans, have successfully been produced. Pigs transgenic for human complement inhibiting molecules could represent a source of organs for future clinical xenotransplantation.

A phase II study of weekly edatrexate (10-EDAM) in metastatic melanoma. A National Cancer Institute of Canada Clinical Trials Group study.

BACKGROUND: Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Edatrexate (10-EDAM). The objective of this multicentre phase II study was to determine the efficacy and toxicity of this agent in patients with metastatic melanoma. PATIENTS AND METHODS: Sixteen previously untreated patients with metastatic melanoma received 10-EDAM, 80 mg/m2/week intravenously. Patients were evaluated for response and toxicity. RESULTS: There were no objective responses. The median dose intensity of 10-EDAM actually delivered was 56.25 mg/m2/week (70% of projected). Mucositis of any degree was encountered in 93.8% of patients. Grade 3 or 4 mucositis, skin rash, nausea, abdominal pain, neutropenia, thrombocytopenia, anemia and hyperbilirubinemia each were encountered in 1-2 patients. There was 1 toxic death due to 10-EDAM. CONCLUSION: 10-EDAM is an inactive agent in metastatic melanoma.