Transplant data: sources, collection and research considerations, 2004

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.     

Elevated concentrations of CRF in the locus coeruleus of depressed subjects.

Research evidence that corticotropin-releasing factor (CRF) plays a role in the pathophysiology of major depressive disorder (MDD) has accumulated over the past 20 years. The elevation of lumbar cerebrospinal fluid (CSF) concentrations of CRF decreased responsiveness of pituitary CRF receptors to challenge with synthetic CRF, and increased levels of serum cortisol in MDD subjects support the hypothesis that CRF is chronically hypersecreted in at least the endocrine circuits of the hypothalamic-pituitary-adrenal (HPA) axis and may also involve other CRF brain circuits mediating emotional responses and/or arousal. One such circuit includes the excitatory CRF input to the locus coeruleus (LC), the major source of norepinephrine in the brain. Furthermore, there are now reports of decreased levels of CRF in lumbar CSF from MDD patients after symptom relief from chronic treatment with antidepressant drugs or electroconvulsive therapy. Whether this normalization reflects therapeutic effects on both endocrine- and limbic-associated CRF circuits has not yet been effectively addressed. In this brief report, we describe increased concentrations of CRF-like immunoreactivity in micropunches of post-mortem LC from subjects with MDD symptoms as established by retrospective psychiatric diagnosis compared to nondepressed subjects matched for age and sex.