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Biomedical subjects

Richard J Kagan

Publications and source records attributed to Richard J Kagan.

4 recordsLinked to original sources

Clinical effects of inhibiting leukocyte adhesion with monoclonal antibody to intercellular adhesion molecule-1 (enlimomab) in the treatment of partial-thickness burn injury.

BACKGROUND: A randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial was performed to determine whether inhibition of leukocyte adherence by administration of monoclonal antibody directed against intercellular adhesion molecule-1 would improve burn wound healing. METHODS: One hundred ten patients with burn injury ranging from 10% to 30% total body surface area were enrolled. Fifty-six patients received placebo (saline) and 54 patients received murine monoclonal antibody to the human intercellular adhesion molecule-1 (enlimomab). Treatment was initiated within 6 hours of injury. Patients had three distinct partial-thickness wound sites assessed. Laser Doppler flowmetry was used to stratify wounds on the day of injury. Wounds were assessed for healing status on day 21 postburn and categorized as healed, nonhealed, or grafted. RESULTS: Patients treated with enlimomab had a significantly increased percentage of wounds that healed spontaneously in less than 21 days overall and when stratified by burn wound laser Doppler blood flow readings for those wounds at greatest risk for nonhealing. CONCLUSION: These results support the concept that leukocyte adherence is involved in the pathogenesis of burn wound necrosis and suggest a therapeutic mechanism for modulating the inflammatory response after the burn injury that may improve wound healing.

Adult↗

Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns.

OBJECTIVE: Comparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results. METHODS: Qualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS. RESULTS: Measures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG. CONCLUSIONS: The requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.

Burns↗

Invited editorial.

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Biocompatible Materials↗

The 2002 Clinical Research Award. An evaluation of the safety of early vs delayed enteral support and effects on clinical, nutritional, and endocrine outcomes after severe burns.

Early enteral support is believed to improve gastrointestinal, immunological, nutritional, and metabolic responses to critical injury; however, this premise is in need of further substantiation by definitive data. The purpose of this prospective study was to examine the effectiveness and safety of early enteral feeding in pediatric patients who had burns in excess of 25% total body surface area. Seventy-seven patients with a mean percent total body surface area burn of 52.5 +/- 2.3 (range 26-91), percent full thickness injury of 44.7 +/- 2.8 (range 0-90), and age ranging from 3.1 to 18.4 (mean 9.3 +/- 0.5) were randomized to two groups: early (feeding within 24 hours of injury) vs control (feeding delayed at least 48 hours postburn). Nutrient intake was measured daily, indirect calorimetry was performed biweekly, and blood and urine samples were obtained for the assay of cortisol, glucagon, insulin, gastrin, epinephrine, norepinephrine, dopamine, triiodothyronine, tetraiodothyronine, albumin, transferrin, prealbumin, retinol-binding protein, glucose, nitrogen balance, and 3-methylhistidine throughout the study period. Three protocol violations occurred, and two patients were transferred to another hospital; these patients were excluded from the study. No patient in either group experienced tube feeding aspiration. No differences were evident in infection, diarrhea, hospital length of stay, or mortality outcomes. A higher incidence of reportable adverse events coincided with early feeding (22 vs 8%), but this was not statistically significant. The delayed feeding group demonstrated a significant caloric deficit during postburn week (PBW) 1 (P <.0001) and PBW2 (P =.0022). Serum insulin (P =.0004) and triiodothyronine (P =.0162) were higher in the early fed group during PBW1. A decrease in 3-methylhistidine output (suggesting a decrease in protein breakdown) was also evident during PBW1 (P =.0138). No other significant trends in study outcome variables were noted. In conclusion, provision of enteral nutrients shortly after burn injury reduces caloric deficits and may stimulate insulin secretion and protein retention during the early phase postburn. These data, however, do not necessarily reaffirm the safety of early enteral feeding, nor do they associate earlier feeding with a direct improvement in endocrine status or a reduction in morbidity, mortality, hypermetabolism, or hospital stay. Future studies are needed to establish precise feeding implementation times that maximize clinical benefit while minimizing morbidity in the critically injured burn patient.

Adolescent↗