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Biomedical subjects

R L McCauley

Publications and source records attributed to R L McCauley.

At least 19 recordsLinked to original sources

Gene expression profiles of giant hairy naevi.

BACKGROUND: Congenital neomelanocytic naevi appear in nearly 1% of newborns. Giant hairy naevi (GHN) are uncommon lesions covering large areas of the body. They are of concern because they have the potential to transform into malignant melanomas. AIMS: To describe gene expression profiles of GHN and nearby normal skin from patients with GHN and normal control skin (from patients with cleft lip/palate). METHODS: Tissues from three patients with GHN and two normal controls were studied for differences in gene expression profiles. Total RNA was isolated from normal skin near the hairy naevus, GHN, and skin from normal controls. The RNA samples were subjected to probe labelling, hybridisation to chips, and image acquisition according to the standard Affymetrix protocol. RESULTS: There were 227 genes affected across all samples, as determined by DNA microarray analysis. There was increased expression of 22 genes in GHN compared with nearby normal skin. Decreased expression was noted in 73 genes. In addition, there was increased expression of 36 genes in normal skin near GHN compared with normal control skin, and decreased expression of five genes. Categories of genes affected were those encoding structural proteins, proteins related to developmental processes, cell death associated proteins, transcription factors, growth factors, stress response modulators, and collagen associated proteins. Changes in mRNA expression were checked by reverse transcription polymerase chain reaction. CONCLUSIONS: Genetic profiles of GHN may provide insight into their pathogenesis, including their potential for malignant transformation. Such information may be useful in improving the understanding and management of these lesions.

Adolescent↗

Use of previously burned skin as random cutaneous local flaps in pediatric burn reconstruction.

Reconstruction after post-burn scarring remains a challenge. It is especially true in the severely burned patient, who normally presents with a paucity of donor sites. Healed skin from areas that had been burned and skin from grafted areas (termed as previously burned skin) have been occasionally used as flaps, but their safety is still in debate. We studied all patients undergoing burn reconstruction with normal skin flaps and previously burned skin flaps in the same operative procedure between April 1998 and October 1998 to determine the safety of flaps including burned and healed tissues. Patients served as their own controls. Three hundred and fifty-three local flaps were studied in 74 patients. These included 238 previously burned skin flaps and 115 normal skin flaps. There were no differences in complication rates between groups and only one previously burned skin flap suffered from complete necrosis. The use of local previously burned skin as flaps in burn reconstruction is safe. Reconstruction with flaps should be considered as first choice in burn reconstruction regardless of the quality of the local tissue.

Age Factors↗

Cadaveric allograft discards as a result of positive skin cultures.

INTRODUCTION: The availability of cadaveric allograft is often limited by potentially pathogenic microbial organisms. Little data exists on cadaveric allograft discard rates related to positive microbiology. The purpose of this retrospective review was to determine the cadaveric allograft discard rates related positive microbiology and the subsequent breakdown of those organisms involved. METHODS: From January 1995 to June 1997, 1112 donors were screened and procured after informed consent had been obtained. The procedures used were in accordance with American Association of Tissue Banks (AATB) standards and guidelines. The number of discards due to positive skin cultures was reviewed and analyzed for type of microbial organism. RESULTS: Fifty-four donors (4.9%) were discarded due to positive skin cultures. Methicillin resistant Staphylococcus epidermidis, (MRSE), was the most predominant organism (22.2%), followed by gram negative rods as a group (18.5%), with Aspergillus species being the least predominant isolate. CONCLUSION: Despite the strict adherence to AATB protocol, microbial contamination of cadaveric allograft skin does not reach zero. It is not surprising that S. epidermidis was the predominant isolate, since skin is one of its common habitats. Continued vigilance in microbial testing remains paramount to ensure the quality of the allograft.

Bacteria↗

Elevated interleukin-6 expression in keloid fibroblasts.

Keloids are characterized by a net accumulation of collagen. To date, the role of growth factors and various cytokines in the pathogenesis of these lesions has not been fully characterized. Interleukin-6 (IL-6) is an important immunoregulatory cytokine that has been implicated in a number of fibrotic autoimmune diseases such as scleroderma, interstitial nephritis, and pulmonary interstitial fibrosis. However, the role of IL-6 in the development of keloids has yet to be defined. This study demonstrates increased expression of the IL-6 gene in fibroblasts isolated from patients with keloids when compared with control fibroblasts using the ribonuclease protection assay. Subsequent detection of increased levels of IL-6 secretion by keloid fibroblasts is also demonstrated under unstimulated and stimulated conditions using serum and interferon gamma (IFN-gamma) (unstimulated: 0.3694 + 0.2499 pg/cell vs 0.0662 + 0.0786 pg/cell, P = 0.0137; serum: 1.066 + 0.513 pg/cell vs 0.233 + 0.231 pg/cell, P = 0.0027; serum and IFN-gamma: 1.286 + 0.395 pg/cell vs 0.244 + 0.199 pg/cell, P < 0.0001). These results suggest that IL-6 may play a significant role in the pathogenesis of keloids.

Blood Physiological Phenomena↗

Reconstruction of the pediatric burned hand.

It is clear that reconstruction of pediatric hand burns is a complicated task (Fig. 8), and attention to details during the acute phase of injury may be surgeons' greatest ally in subsequent functional rehabilitation of the hand. Reducing edema, maintaining digital circulation, limiting inflammation, and mobilizing the limb early are key parameters to assure return of function during the acute phase of injury. Although children may present with neglected contractures at a later date, even grade IV contractures can be surgically approached with hopes of improving hand function. Loss of the thumb in children with very large total body surface area burns can be approached reliably by lengthening of the thumb using first-to-second metacarpal transfers, as described by Littler. Although electrical injuries represent only a small fraction of patients admitted to our hospitals, children who present with viable insensate hands can have reliable sensory return more than 1 year after injury using nonvascularized cable nerve grafts if soft tissue coverage is adequate. As surgical procedures continue to evolve in delayed reconstruction of the hand, one would expect children to show better results than those seen in adult patients. A more aggressive surgical approach, with increased optimism, therefore is required when addressing children with complex hand burns requiring reconstruction.

Burns↗

Cadaveric skin allograft-associated cytomegalovirus transmission in a mouse model of thermal injury.

As a routine procedure to provide temporary coverage for burn wounds, cadaveric skin allografts have been used in patients with massive thermal injuries. In this study, CMV infection associated with skin grafting was investigated. Graft-associated CMV transmission was shown in a mouse model of thermal injury. Skins from mice 100 days after a nonlethal dose of murine CMV (MCMV) infection contained MCMV DNA and mRNA, although the virus was not isolated from these murine skins. When these skins were grafted to burned mice, the marked growth of MCMV was demonstrated in salivary glands. No viral growth was shown in the salivary glands of unburned mice or CMV sero(+) mice after grafting with these skins. When severe combined immunodeficient beige (SCID-beige) mice were used as recipients for CMV sero(+) skins, all mice died within 30 days after the grafting. Only 1 PFU/mouse of MCMV was shown to be 1 LD(50) in SCID-beige mice, while a 50% mortality rate was shown in normal unburned mice infected with 5 x 10(5) PFU/mouse of MCMV. This indicates that a very small amount of CMV contained in skins is sufficient to induce CMV infection in immunocompromised hosts. On the other hand, human CMV (HCMV) DNA and mRNA were detected by PCR analysis in 55% (DNA) and 33% (mRNA) of cadaveric skins, although the isolation of HCMV from cadaveric skin homogenates was not achieved in tissue cultures. CMV sero(-) patients with severe burn injuries may have a high risk for CMV infection associated with allografts of cadaveric skins.

Animals↗

Dural reconstruction of a class IV calvarial burn with decellularized human dermis.

Calvarial burns involving the brain (Class IV) are reported to be rare. They represent a treatment challenge. Wound coverage can be accomplished with serial debridement of bone and grafting over granulating tissue, local flaps and free tissue transfer. The former techniques are often not feasible in the young infant. We present a successful case of a six-week-old female patient affected of full thickness burns involving the skull and brain. The bone, dura mater and superficial brain were debrided and the defect covered with AlloDerm and split thickness grafts. The area engrafted completely and no complications or CSF leak occurred. An acellular human allogeneic dermis (AlloDerm) can be successfully used to replace dura mater in burn patients.

Brain Injuries↗

Increased physiological dead space/tidal volume ratio during exercise in burned children.

Exercise testing enables the simultaneous evaluation of the cardiovascular and respiratory systems' ability to perform gas exchange. The physiological responses to exercise have not been previously reported in the postburn child. This investigation was designed to evaluate residual cardiopulmonary impairment in patients convalescing from severe burns. Spirometry, lung volumes and exercise stress testing were completed on 40 children with a mean time postburn injury of 2.6 +/- 1.9 years and mean burn size of 44 +/- 22 per cent TBSA. Respiratory variables studied during exercise included expired volume, tidal volume and respiratory rate, and physiological dead space/tidal volume (VD/VT) ratios. Stress testing revealed an increased VD/VT ratio consistent with uneven ventilation-perfusion relationships. The data indicate that patients who survive thermal injury may not regain normal cardiopulmonary homeostasis.

Burns↗

Cytoprotection of human dermal fibroblasts against silver sulfadiazine using recombinant growth factors.

Topical antimicrobial agents, silver sulfadiazine (SSD) and mafenide acetate (MA), have been associated with delayed wound healing. Previous in vitro studies with human dermal fibroblasts (HDF) have shown progressive cellular cytotoxicity with increasing concentrations of SSD and MA. However, preexposure of HDF to epidermal growth factor, basic fibroblast growth factor, or platelet-derived growth factor has resulted in cytoprotection of HDF against 0.01 and 0.03% concentrations of SSD as determined by phase-contrast microscopy (PCM), hemocytometer cell counts, and total cellular protein content. PCM, however, showed slower destruction of HDF at the 0.05% concentration of SSD. These data suggest that cells activated by growth factors either take up less SSD or are more resistant to the direct cytotoxic effects of this drug.

Epidermal Growth Factor↗

Reconstructive management of patients with greater than 80 per cent TBSA burns.

With improving acute burn care, greater numbers of patients are surviving large burns. Meshed skin grafts or cultured epithelial autografts are often required to achieve rapid wound closure, even in areas such as the hands or face. This, plus the lack of suitable donor tissue for reconstruction, is mandating a change in reconstructive principles. Twenty-eight patients surviving > or = 80 per cent TBSA full skin thickness burns were evaluated using two specially devised instruments (Inventory of Potential Reconstructive Needs; Donor Tissue Surveillance). A total of 564 reconstructive needs were identified in the 28 patients, an average of 20.1 per patient. There were 265 defects in the head and neck, 143 in the upper extremities, and 156 in the torso/lower extremities. The injured anatomical units most frequently identified were the hand (74), trunk (60), nose/nasolabial fold (48), mouth (46), ankle/foot (42), neck (31) and check (28). The Donor Tissue Surveillance form revealed that the necessary donor tissue was frequently not available, and when available, was often of poor quality. These facts require a different set of priorities for reconstruction of the massively burned patient. No longer can a simple stepwise plan of active function, passive function, and aesthetic needs be followed. The patient and family desires must be combined with a realistic outlook by the entire burn team to determine the most judicious and efficient use of available donor tissue to meet the reconstructive needs.

Burns↗

Altered cytokine production in black patients with keloids.

The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha-interferon (IFN-alpha), beta-interferon (IFN-beta), gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta). The production of IFN-alpha, IFN-gamma, and TNF-beta were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-alpha, and IFN-beta. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation.

Black People↗

Differential inhibition of human basal keratinocyte growth to silver sulfadiazine and mafenide acetate.

The impact of topical antimicrobial agents on improving the survival of patients with major thermal injuries is significant. However, the effects of these agents on cells responsible for wound healing has only recently received attention. Fresh human basal keratinocytes were grown in serum-free modified MCDB 153 medium under standard tissue culture conditions. Cells were subsequently exposed to concentrations of silver sulfadiazine and mafenide acetate as low as 1/100 of that used clinically over a period of 5-7 days. Cellular responses documented with hemocytometer cells counts, cellular protein assays, phase-contrast microscopy, and transmission electron microscopy show only severe toxicity to mafenide acetate. Such data imply that inhibition of wound epithelialization is greater with the use of mafenide acetate than with the use of silver sulfadiazine.

Cell Count↗

Class C firework injuries in a pediatric population.

Class C fireworks are those which can be readily purchased by the public. Between July 1971 and August 1988, 23 patients were admitted to our institution with firework injuries. Fourteen patients (60.9%) sustained injuries related to Class C fireworks. All patients were males with a mean age of 9.0 +/- 3.6 years, with a total body surface area (TBSA) burn of 18 +/- 20% with 10 +/- 15% being full thickness. Thirteen of the 14 patients required hospitalization. Five patients were admitted acutely and eight patients were referred to our institution at least 3 days postinjury. All patients required operative intervention in order to obtain wound closure. Patients admitted acutely showed a decrease in length of hospital stay and patient morbidity when compared to referral patients. Our data suggest that class C firework injuries, although small in terms of TBSA burned, result in full-thickness wounds that warrant aggressive surgical management.

Burns↗

In vitro alterations in human fibroblast behavior secondary to silicone polymers.

The etiology of fibrous capsular contractures in patients with silicone prostheses is unclear. However, cellular responses to the silicone polymers of the prostheses have not been examined. The exposure of human dermal fibroblasts to the components of the silicone gel prosthesis results in a significant change in cellular configuration and a progressive reduction in cell proliferation as determined by total matrix protein assays and hemocytometer cell counts. Transmission electron microscopy, however, documents a twofold increase in the rough endoplasmic reticulum when cells are exposed to the silicone gel. These findings suggest significant alterations in the behavior of human fibroblast subpopulations in response to silicone polymers.

Cell Line↗

Frostbite. Methods to minimize tissue loss.

If frostbite is to be treated successfully, direct and indirect effects of injury must be understood. Rapid rewarming helps to preserve tissue by limiting the amount of direct cellular injury. Selective management of blisters helps protect the subdermal plexus, and application of Aloe vera cream (eg, Dermaide Aloe Cream) combats the local vasoconstrictive effects of thromboxane. Oral administration of ibuprofen decreases systemic levels of thromboxane.

Aloe↗

Tissue expansion in the correction of burn alopecia: classification and methods of correction.

Correction of burn alopecia using tissue expansion has recently gained acceptance. Yet, the technical approach to correction of this problem remains one of trial and error. Between January 1985 and December 1988, 102 children underwent placement of tissue expanders for correction of burn alopecia. Two hundred twenty-two expanders were placed during the 178 operative settings. Mean age was 9.1 +/- 4.3 years (range, 3-17 years). Forty-two patients previously underwent partial excisions or rotation of flaps to reduce or camouflage the initial burn alopecia. A review of our experience has dictated that proper classification of burn alopecia can influence operative planning and is essential for establishing guidelines for the correction of this problem. We have developed a classification scheme that addresses this problem. Patients are classified as type I, uniform alopecia; type II, segmental alopecia; type III, patchy alopecia; and type IV, total alopecia. The role of tissue expansion is reviewed in each group.

Adolescent↗

The scalp as a donor site: revisited.

The scalp cannot be used as skin graft donor site with impunity. A review of 2,620 charts identified 194 pediatric patients whose scalps served as donor sites for split-thickness skin grafts for the treatment of acute burns. The overall incidence of alopecia was 32%. However, the incidence of alopecia in unburned scalps was 13%. The occurrence of alopecia in this group was associated with larger burn area requiring more frequent use of the scalp and shorter intervals between graft harvests (p less than 0.05). Among this group of patients (n = 15), nine had mild spotty alopecia, four had surgically correctable alopecia, and two had global patchy alopecia not amenable to surgical correction. In the patients with concomitant burns to their scalps, the incidence of alopecia was 61%. Whether the burn or the graft harvest caused alopecia could not be established. Meticulous donor site care is mandatory in this latter group when the scalp donor site is indicated.

Adolescent↗