Studies of natural allele effects in mice can be used to identify genes causing common human obesity

Although genes causing rare Mendelian forms of human obesity have provided much useful information about underlying causes of obesity, these genes do not explain significant proportions of common obesity. This review presents evidence that animal models can be used to uncover subtle genetic effects on obesity and can provide a powerful rigorous compliment to human association studies. We discuss the advantages of animal models of obesity, various approaches to discovering obesity genes, and the future of mapping and isolating naturally occurring alleles of obesity genes. We review evidence that it is important to map naturally occurring obesity genes using quantitative trait locus (QTL) mapping, instead of mutagenesis and knockout models because the latter do not allow study of interactions and because naturally occurring obesity alleles can interfere with cloning from mutagenesis projects. Because a substantial percentage of human obesity results from complex interactions, the underlying genes can only be identified by direct studies in humans, which are still very difficult, or by studies in mice that begin with QTL mapping. Finally, we emphasize that animal model studies can be used to prove that a specific gene, only associated with obesity in humans, can indeed be the underlying cause of obesity in mammals.     

Hematuria in the burned child

Hematuria is a frequent complication in burn patients, but its clinical significance has not been reported. The incidence, etiologies, treatment, and outcome of hematuria in 1,785 burn patients treated from 1964 to 1983, have been reviewed. Ninety-one patients had hematuria (greater than 15 RBC/HPF with unspun urine). There were five main causes: urinary infections (UTI), 50 cases; renal calculi (RC), 14 cases, including 3% and 5% total body surface area burn patients; catheter trauma, 7 cases; renal vein thrombosis (RVT), 5 cases; and acute renal failure (ATN), 4 cases. Ten patients died in the UTI group, five with Candida as the infecting organism. No RC patients died, but two required surgical extraction of their stones. This incidence of RC may be due to large intake of dairy products and antacids and to prolonged immobilization. The catheter trauma group had no deaths and was the youngest group. One RVT patient was diagnosed clinically and successfully treated surgically. The other three were diagnosed at necropsy. The ATN patients all developed renal failure late as part of multiple organ system failure and all died. We conclude hematuria is a serious finding in burn patients and prompt diagnosis of its etiology and treatment are essential for maintaining renal function and patient survival.     

Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006' +/- .002' compared to .013' +/- .018' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.     

Surgical correction of burn scar contractures of the foot in children

The results of reconstructive procedures for the treatment of burn scar contractures of the feet in 55 children undergoing 90 operations were reviewed. The patients were treated in all but one case by release of the contracture band with placement of a skin graft in the resulting defect. There was an overall recurrence rate of 15 per cent that was not affected by the use of split-thickness versus full-thickness grafts. The time delay from the thermal injury to the reconstructive procedure was also found not to affect the outcome. Postoperative immobilization by the use of either a dynamic or an adynamic splint was found to be important both for preventing graft loss and for decreasing the rate of contracture recurrence.