Biomedical subjects
Publications and source records attributed to D A Burd.
A 31 year old woman presented with a crusting lesion on the scar of her BCG vaccination. Histological examination showed it to be a basal cell carcinoma, which only rarely arises in vaccination scars, and is particularly unusual in BCG vaccination scars.
Clinical observations and experimental data suggest that fetal wound healing is very different from adult wound healing. An understanding of the biology of scarless fetal wound healing has tremendous clinical potential for modulating postnatal wound problems. In this study, the fetal lamb model was used to assess excisional fetal skin wound contraction in utero. Full-thickness 9-mm punch biopsy wounds were created on fetal lambs at 100 days' gestation (term, 145 days). Half of the wounds remained exposed to amniotic fluid, whereas the other half were covered by a silastic patch to exclude amniotic fluid. Wounds were harvested 3, 7, or 14 days later and wound areas were calculated. Exposure to amniotic fluid retarded wound contraction significantly at 3 days, but by 14 days all wounds had completely contracted and reepithelialized. Myofibroblasts are an important cellular element of wound contraction. The presence of wound myofibroblasts was documented by both transmission electronmicroscopy and immunocytochemistry with antimuscle actin antibody. It is concluded that fetal lamb wounds contract in utero and exposure to amniotic fluid appears to retard fetal skin wound contraction only during the early healing process.
Small proteoglycans (PGs), extracted from human keloid scar tissue with 4M guanidinium chloride and fractionated by DEAE-cellulose chromatography, were separated by ethanol precipitation into one L-iduronic acid-rich and one D-glucuronic acid-rich fraction. The size of the L-iduronic acid-rich PG was 102 kDa with a 27 kDa glycosaminoglycan chain, that of the D-glucuronic acid-rich PG was 90 kDa with a 26 kDa glycosaminoglycan chain, and the protein core of both PGs was 14.5 kDa. The two PGs carried sulfate groups mostly attached at C-4 of the 2-amino-2-deoxy-D-galactose units. The N-terminal amino acid sequence of both was similar to human bone PGII (decorin), normal and hypertrophic scar, and human dermal tissue PG.
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Foetal wound healing occurs without scarring. A scar is a collagen-rich repair tissue, and the absence of scarring in the foetus has raised questions concerning the presence and nature of collagen deposition in foetal wounds. Studies of collagen deposition in foetal wounds in small animals, performed late in gestation, have been equivocal. In this study, using a large animal with a long gestational period, the sheep, the deposition of collagen is confirmed.
Closure of full-thickness open wounds in loose-skinned animals is accomplished by wound contraction. Fibroblast-populated collagen lattice (FPCL) contraction is an in vitro model for studying wound contraction. Fibroblasts suspended in a collagen matrix reorient the surrounding collagen fibers, resulting in a reduction in the size of the FPCL. The organization of collagen fibers by fibroblast-generated forces produces lattice contraction. An open wound in a rat begins to show contraction by 3 days, and its size will be reduced by 50% at 7 days. Fluid from 3- and 7-day-old rat wounds was examined for its ability to affect in vitro lattice contraction. Wound fluid was found to inhibit lattice contraction. The fractions which inhibit lattice contraction had molecular weights ranging between 10,000 and 20,000, as revealed by molecular sieve chromatography, and a high positive charge, as demonstrated by ion exchange chromatography. The factor(s) was only slightly affected by added indomethacin in the FPCL contraction model. This suggests a mechanism independent of the generation of prostaglandins. The factor(s) was tested in an ATP-induced model of fibroblast contraction where it was shown to be ineffective at altering cell contraction. The factor(s) did, however, prevent cell spreading and elongation on glass surfaces. Wound fluid has a factor(s) which hinders fibroblast spreading and elongation and which inhibits FPCL contraction.
The ability of fetal skin wounds to heal without scar formation is remarkable. The mechanisms that endow the fetus with this unique healing ability remain unknown. We have developed an in vitro explant model using fetal sheep skin to investigate fetal wound healing. This model eliminates the complex systemic mechanisms that modulate in vivo wound healing. We demonstrated that using an enriched medium, midgestation fetal sheep skin explants following wounding reepithelialized within 4 days. By 7 days after wounding the confluent epidermis was thicker, but the dermal wound remained open. This model demonstrates that it is possible to achieve conditions in culture that maintain tissue viability and support reepithelialization. This model may allow us to resolve some of the individual components that participate in the process of scarless fetal skin healing.
Hyaluronan (HA) extracted from tissues has been demonstrated to have an enhancing effect on the process of wound healing; the question arises whether this effect is due to the HA or to associated collagen and other proteins. In this study, HA has been extracted from human skin and scar tissue under dissociative conditions and isolated by DEAE-cellulose chromatography followed by CsCl gradient and Sepharose CL-6B chromatography. This highly purified HA was found to contain between 4 and 28% protein, with collagen constituting 5% of the total protein. A functional association between HA and a collagen protein complex is proposed.
We have highlighted this problem as there are situations where skin staples have to be removed rapidly, for example where bleeding and subsequent respiratory distress develop following neck surgery. A survey of junior hospital staff showed that many doctors had never removed skin staples nor were aware how best to remove them in the event of an emergency. Using skin simulation we compared the time to remove sutures and staples, and found it takes 55% longer to remove skin staples. Where the standard staple remover is not immediately available, an artery forceps, correctly applied, is just as quick.
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A study of 153 preschool children admitted to a subregional burns unit over a 4-year period revealed 23 who had sustained scalds by pulling on kettle flexes. The dangers of dangling kettle flexes have been noted in the past. However, identifying problems and undertaking education programmes to warn against them has a limited effect on accident prevention. The recent introduction of 'curly' cables makes the prospect of active prevention considerably simpler.
The "tie-over" dressing is commonly used in plastic surgical practice. A simple, cheap and effective refinement of this established technique is described. This consists of a flanged disc over which can be slipped a "neoprene" sealing ring. The advantages of the device include the ease and speed of application: the facility to tighten and adjust the tie-over sutures once they are in place and the possibility of removing and replacing the device if early inspection of the graft is desired.
A case of a mixed dermal appendage tumour is described. The relevant literature is reviewed and problems with the histological diagnosis discussed.
This study looks at the remodelling of an in vitro system of foetal wound healing. Contraction is confirmed and the stimulatory role of amniotic fluid demonstrated.
Hyaluronan has long been associated with the remodelling extracellular matrix. Such remodelling occurs in development, growth and wound healing. This role has been thought to be related to the physical structure and chemical composition of the pure glycosaminoglycan chain. We question this proposition and present evidence which suggests that proteins associated with hyaluronan may be more critical determinants of tissue remodelling.