Project-based transplant management as a research statistical support.

This paper proposes a transplant management method based on project management concepts applied to organ transplantation processes in all phases to provide statistical support for evidence based medicine (EBM) research. The transplant is viewed as a project composed by phases: (1) Initiation starts with the acknowledgement of transplant necessity. Also, the restrictions and hypothesis are determined thereby defining the medical protocols, the psychosocial attendance strategies, and performance criteria. (2) Planning formulates and revises transplant protocols that contain schedules, activities, risk identification, staff assignment, medication, examinations, evaluations, and operative interventions. Transplant requirements and stakeholders are identified to establish a resource management plan and transplant control. (3) Executing includes committing resources and coordinating implementation of transplant protocols and plans. The patient's progress is constantly evaluated in relation to quality assurance procedures. (4) Controlling performance measures and parameters with limits are used to take corrective actions subject to effectiveness evaluations that monitor transplant activities. (5) The closing reviews the collected documentation to avert potential problems with future transplants. Software was developed for transplant management based on the proposed methodology with a database and functional that statistically support primary and secondary studies, which provide parameters and definite variables for research focused on treatment, diagnoses, tracking, prognoses, and causality. The proposed methodology for transplant management gives statistical support for EBM research in the form of randomized clinical trials, cohort, case-controlled, transverse studies, and case reports. The software may be improved to provide a national/international database and research tool.

Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and present in all tissues investigated, affecting the cytosolic and the mitochondrial fumarase isoenzymes to the same degree. Analysis of fumarase cDNA demonstrated that both patients were homozygous for a missense mutation, a G-955-->C transversion, predicting a Glu-319-->Gln substitution. This substitution occurred in a highly conserved region of the fumarase cDNA. Both parents exhibited half the expected fumarase activity in their lymphocytes and were found to be heterozygous for this substitution. The present study is to our knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood.