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Biomedical subjects

D P Orgill

Publications and source records attributed to D P Orgill.

At least 19 recordsLinked to original sources
PubMed2005

The relative thermal stability of tissue macromolecules and cellular structure in burn injury.

When tissue is subjected to higher than physiological temperatures, protein and cell organelle structures can be altered resulting in cell death and subsequent tissue necrosis. A burn injury can be stratified into three main zones, coagulation, stasis and edema, which correlate with the extent of heat exposure and thermal properties of the tissue. While there has been considerable effort to characterize the time-temperature dependence of the injury, relatively little attention has been paid to the other important variable, the thermal susceptibility of the tissue. In the present study, we employ a standard physical chemistry approach to predict the level of denaturation at supraphysiological temperatures of 12 vital proteins as well as RNA, DNA and cell membrane components. Melting temperatures and unfolding enthalpies of the cellular components are used as input experimental parameters. This approach allows us to establish a relation between the level of denaturation of critical cellular components and clinical manifestations of the burn through the characteristic zones of the injury. Specifically, we evaluate the degree of molecular alteration for characteristic temperature profiles at two different depths (Mid-Dermis and Dermis-Fat interface) of 80 degrees C; 20s contact burn. The results of this investigation suggest that the thermal alteration of the plasma membrane is likely the most significant cause of the tissue necrosis. The lipid bilayer and membrane-bound ATPases show a high probability of thermal damage (almost 100% for the former and 85% for the latter) for short heat exposure times. These results suggest that strategies to minimize the damage in a burn injury might focus on the stabilization of the cellular membrane and membrane-bound ATPases. Further work will be required to validate these predictions in an in vivo model.

Burns↗
PubMed2001

Reduction of abdominal adhesions using composite collagen-GAG implants for ventral hernia repair.

Structural biomaterials can restore abdominal wall integrity but may cause adhesions to the underlying viscera. Collagen-glycosaminoglycan (CG) matrices induce the formation of connective tissue and may reduce adhesion formation to permanent biomaterials such as polypropylene (PP) mesh. Composite implants were created by interposing PP mesh within a porous CG matrix created composite implants. The implants were cross-linked with glutaraldehyde one group (CG-G/PP) or left untreated (CG-nG/PP) and compared to PP mesh. At 4 weeks, the abdominal wall was assessed for the degree of adhesions. The composite implants developed a nascent connective tissue-like structure that reduced adhesions to the bowel. The thickest connective tissue developed in the CG-G/PP group (0.7 +/- 0.1 mm) and thinnest in the PP mesh (0.05 +/- 0.01 mm). The surface area covered with adhesions was greatest in the PP group (72 +/- 17%) compared with the CG-G/PP group (28 +/- 15%) or the CG-nG/PP group (21 +/- 8%). Bowel preferentially adhered to the PP mesh, whereas omentum had some adherence to all constructs. Integrating a biodegradable extracellular matrix analog with a permanent structural biomaterial reduced adhesions in this animal model. Alterations in cross-linking of the CG matrix altered the biological response. This technology may be useful in reconstructive surgery by reducing adhesion formation, while maintaining the strength of permanent structural biomaterials.

Abdominal Muscles↗
PubMed2000

The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury.

PURPOSE: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. MATERIALS AND METHODS: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 +/- 9 days. RESULTS: Mean burn size was 49 +/- 8% for placebo and 53 +/- 9% of total body surface for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 +/- 3.1 kg in the placebo group compared with 3 +/- 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 +/- 4 g in placebo treated compared with 4 +/- 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 +/- 3 days to 9 +/- 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. CONCLUSION: We found the anabolic agent, oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of oxandrolone.

Adult↗
PubMed1999

Functional reconstruction following electrical injury.

Worldwide, high voltage electrical injury continues to cause significant morbidity, disability, and mortality despite improvements in electrical safety. Joule heating and cell membrane disruption are two mechanisms important in understanding the pathophysiology of electrical injury. The degree of tissue damage is often more extensive than initially perceived on clinical exam. Using modern reconstructive techniques, the functional outcome of electrical injury victims can be improved. The type of reconstruction selected for each injury can be selected from a number of options from the reconstructive ladder. Donor site considerations, risks of the surgery, team experience, and patient preference are important factors in this selection.

Accidents, Occupational↗
PubMed1999

The use of collagen-GAG membranes in reconstructive surgery.

Porous collagen-glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross-link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra, Integra Life Sciences, New Jersey) and available for clinical use. Because clinical outcomes have improved using these membranes for burn wound coverage, other skin reconstruction problems including scar resurfacing, keloids, treatment of donor sites, and treatment of chronic wounds can be considered as potential applications. This manuscript illustrates our early experience using Integra as a CG membrane for dermal replacement in reconstructive surgery. Our results indicate that CG membranes can lead to improved compliance and appearance compared to a meshed graft and may be sequentially placed in multiple layers to correct contour deformities. Also, in one case, we observed that, if placed on a wound bed with embedded skin epithelial cells, the PCG promotes epithelialization through the PCG matrix. The use of this material results in a supple integument with many similarities to normal skin.

Adult↗
PubMed1999

Comparison of cultured and uncultured keratinocytes seeded into a collagen-GAG matrix for skin replacements.

A well-characterised collagen-glycosaminoglycan (CG) matrix functions as an extracellular matrix analogue (ECMA) of dermis on full-thickness wounds. The epidermis can be reconstituted by seeding autologous uncultured keratinocytes into the matrix prior to grafting. We hypothesised that seeding the CG matrix with keratinocytes cultured to sub-confluence may provide the ECMA with more proliferating keratinocytes than with uncultured keratinocytes. Autologous cells were isolated from split-thickness skin grafts and cultured to sub-confluence. ECMAs were seeded by centrifuging cultured (n = 8) or uncultured (n = 8) autologous keratinocytes into a CG matrix at a density of 100,000 cells/cm2, then applied onto full-thickness wounds on Yorkshire pigs. Gross and histologic observations were made up to 21 days post-grafting. At 14 days, a fully differentiated epidermis was present on all graft sites, but the epidermis of the cultured-cell-seeded matrices was thicker, 180 (19) microns, than the uncultured-cell-seeded matrices, 110 (18) microns. The epidermis of cultured-cell-seeded matrices was acanthotic, containing 14 (4) cell layers, as compared to uncultured-cell-seeded matrices, 9 (1) cell layers. The number of subepithelial keratinocyte cysts/cm cross-section present in the neodermis was also greater in cultured-, 1.35 (0.37), than in uncultured-cell-seeded matrices, 0.47 (0.35). Epidermal confluence on day 14 was 96 (3)% on cultured-cell-seeded grafts and 50 (17)% on uncultured-cell-seeded grafts. These results are consistent with the hypothesis that the process of in vitro cell cultivation increases the proportion of dividing cells in preference to differentiated cells. This technology may be useful in reconstruction of specialised bilayer tissues with minimal donor sites.

Animals↗
PubMed1999

Vacuum-assisted closure in the treatment of degloving injuries.

Degloving injuries range from the occult, easily missed injury to obvious massive tissue damage. The serious nature of these wounds is exacerbated by mismanagement. It is generally accepted that the degloved tissue should be excised, defatted, fenestrated, and reapplied as a full-thickness skin graft. Dressings are required that provide gentle, evenly distributed pressure and avoid shear stress to the newly grafted skin. Numerous types of dressings have been devised but all are cumbersome and time-consuming. We have found the Vacuum-Assisted Closure device to be a rapid, effective, and easy-to-use alternative to traditional methods. The authors examine their experience using a vacuum-assisted closure device to treat nine degloving injuries in 5 patients and discuss the important aspects in using this technique.

Adult↗
PubMed1999

Flap prefabrication in the head and neck: a 10-year experience.

Tissue neovascularized by implanting a vascular pedicle can be transferred as a "prefabricated flap" based on the blood flow through the implanted pedicle. This technique potentially allows any defined tissue volume to be transferred to any specified recipient site, greatly expanding the armamentarium of reconstructive options. During the past 10 years, 17 flaps were prefabricated and 15 flaps were transferred successfully in 12 patients. Tissue expanders were used as an aid in 11 flaps. Seven flaps were prefabricated at a distant site and later transferred using microsurgical techniques. Ten flaps were prefabricated near the recipient site by either transposition of a local vascular pedicle or the microvascular transfer of a distant vascular pedicle. The prefabricated flaps were subsequently transferred as island pedicle flaps. These local vascular pedicles can be re-used to transfer additional neovascularized tissues. Common pedicles used for neovascularization included the descending branch of the lateral femoral circumflex, superficial temporal, radial, and thoracodorsal pedicles. Most flaps developed transient venous congestion that resolved in 36 to 48 hours. Venous congestion could be reduced by incorporating a native superficial vein into the design of the flap or by extending the prefabrication time from 6 weeks to several months. Placing a Gore-Tex sleeve around the proximal pedicle allowed for much easier pedicle dissection at the time of transfer. Prefabricated flaps allow the transfer of moderate-sized units of thin tissue to recipient sites throughout the body. They have been particularly useful in patients recovering from extensive burn injury on whom thin donor sites are limited.

Adolescent↗
PubMed1998

Design of an artificial skin. IV. Use of island graft to isolate organ regeneration from scar synthesis and other processes leading to skin wound closure.

Deep skin wounds in the adult mammal close spontaneously by epithelialization, wound contraction, and scar synthesis. In previous wound healing studies, it has been unsuccessfully attempted to separate from each other the natural processes that close wounds. In this study, we attempted to isolate skin regeneration from spontaneous processes of wound closure using "island" grafts. A porous analog of the extracellular matrix, composed of a graft copolymer of type I collagen and chondroitin 6-sulfate, was seeded with uncultured autologous keratinocytes and served to induce regeneration of the dermis and the epidermis. Grafts of the copolymer, measuring 1 x 2 cm, were placed in the center of 5 x 6-cm wounds in guinea pigs. By day 14, the edges of the island grafts were clearly separated from the host epidermis and dermis by a distinct bed of granulation tissue. Histologic study of island grafts on day 14 showed that the copolymer grafts had largely degraded and that a new epidermis and dermis had been synthesized in its place. The thickness of the new epidermis increased as the density of cells seeded into the graft increased. No synthesis of epidermis or dermis was observed in the granulation tissue outside the perimeter of the island grafts. We conclude that island grafting allows the study of early events in skin regeneration in isolation from epithelialization, contraction, and scar synthesis.

Animals↗
PubMed1998

Polyethylene glycol/microfibrillar collagen composite as a new resorbable hemostatic bone wax.

Although bone wax is effective at achieving hemostasis, it is nonresorbable, causes a foreign body reaction, and inhibits osteogenesis. We report development of a polyethylene glycol/microfibrillar collagen composite (PEG/MFC) that has inherent hemostatic qualities, is biodegradable, and is compatible with bone repair. PEG/MFC composite (n = 42) was placed in 5 mm cranial defects in New Zealand white rabbits. Hemostasis and healing were compared to unfilled defects (n = 32) and defects filled with standard bone wax (n = 10). Both PEG/MFC and bone wax handled well and stopped bleeding. The polyethylene glycol component was resorbed by 8 h, and the microfibrillar collagen was resorbed over 2 months, eliciting only a minor inflammatory response during the first month. Defects filled with the PEG/MFC composite showed similar amounts of bony regeneration as did unfilled control defects. At 4 weeks, healing bone accounted for 43 +/- 13% in those treated with PEG/MFC and 47 +/- 19% defect area in untreated holes. In contrast, less than 1% of the area was bone in defects filled with bone wax (p < 0.05). PEG/MFC composite provided excellent bony hemostasis and did not inhibit bone growth.

Animals↗
PubMed1998

Organized skin structure is regenerated in vivo from collagen-GAG matrices seeded with autologous keratinocytes.

A well-characterized collagen-glycosaminoglycan matrix (CGM) that has been shown to function as a dermal analog was seeded with freshly disaggregated autologous keratinocytes and applied to full-thickness wounds in a porcine model. CGM were impregnated with 50,000 keratinocytes per cm2, a seeding density that produces a confluent epidermis within 19 d post-grafting and affords a 60-fold surface expansion of the donor epidermis. In this study, the temporal sequence of events in epidermal and neodermal formation was analyzed histopathologically and immunohistochemically from 4 to 35 d post-grafting. The epidermis was observed to form from clonal growth of individual keratinocytes into epithelial cords and islands that gradually enlarged, coalesced, differentiated to form large horn cysts, and finally reorganized at the graft surface to form a fully differentiated, normally oriented epidermis with rete ridges. Simultaneously, a neodermis formed from migration of endothelial cells, fibroblasts, and macrophages into the CGM from the underlying wound bed, resulting in formation of blood vessels, the production of abundant extracellular matrix, and the degradation of the CGM fibers, respectively. Gradually, the stromal cellularity of the CGM decreased and collagen deposition and remodeling increased to form a neodermal connective tissue matrix beneath the newly formed epidermis. Complete dissolution of the CGM occurred, partly as a result of degradation by an ongoing foreign-body giant cell reaction that peaked at 8-12 d post-grafting, but neither acute inflammation nor evidence of immune stimulation were observed. Within 1 mo, many structural components of normal skin were reconstituted.

Animals↗
PubMed1998

Effect of keratinocyte seeding of collagen-glycosaminoglycan membranes on the regeneration of skin in a porcine model.

A collagen-glycosaminoglycan matrix, impregnated with autologous keratinocytes, was applied as island grafts onto full-thickness porcine wounds to determine whether complete epidermal coverage could be achieved in a single grafting procedure. Twenty-four grafts with seeding densities ranging from 0 to 3,000,000 cells/cm2 were used to determine the kinetics of epidermal coverage. The time sequence of epidermal formation was then studied between days 14 and 28 using four additional grafts, each seeded with a density of 500,000 cells/cm2. Autologous keratinocytes proliferated as the collagen-glycosaminoglycan matrix was vascularized to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2. The epidermal thickness and the number of keratinocyte cysts observed in the neodermis at 2 weeks increased linearly with the logarithm of the seeding density. Sequential analysis of neoepidermis showed the nascent epidermis to be hyperplastic, parakeratotic, and focally lacking in granular layer differentiation at 2 weeks. After 2 weeks, it underwent normal maturation and differentiation. Irrespective of seeding density at 2 weeks the collagen-glycosaminoglycan matrix was well vascularized, contained a dense cellular infiltrate, and was almost completely degraded. These studies demonstrate that seeded keratinocytes proliferate and differentiate to form a confluent epidermis by 2 weeks in matrices seeded with at least 100,000 cells/cm2.

Animals↗
PubMed1998

Vascularized collagen-glycosaminoglycan matrix provides a dermal substrate and improves take of cultured epithelial autografts.

Cultured epithelial autografts are an important adjunct in treating severely burned patients, greatly expanding the epidermis using a small donor site. Problems with cultured epithelial autografts include the time delay to culture cells to confluence and variable take on full-thickness wounds. Dermal allografts have been used as a substrate to improve the take of cultured epithelial autografts. This study examined the effect of a vascularized collagen-glycosaminoglycan matrix as a substrate for cultured epithelial autografts. The matrix was grafted onto 12 full-thickness wounds in Yorkshire pigs and allowed to vascularize for 10 days. The cultured epithelial autografts were applied over the vascularized collagen-glycosaminoglycan matrix (n = 12) or onto freshly excised full-thickness wounds (n = 10). Gross and histologic observations were made over a 3-week period. Gross observations at 7 days indicated cultured epithelial autografts to have nearly complete confluence when applied to wounds treated by collagen-glycosaminoglycan, whereas cultured epithelial autografts applied to freshly excised wounds did not take. Gross determination of epithelial confluence was verified by histologic analysis of randomly selected wounds. Histologic epithelial confluence of cultured epithelial autografts on collagen-glycosaminoglycan (98 +/- 4 percent) was significantly greater than that on full-thickness wounds (4 +/- 10 percent). Electron microscopy of the cultured epithelial autografts/collagen-glycosaminoglycan construct demonstrated anchoring fibrils at the dermal-epidermal junction at day 7. The neoepidermis of wounds treated by cultured epithelial autografts/collagen-glycosaminoglycan was hyperplastic at day 7 but developed a normal maturation sequence by 21 days. Results from this study suggest that vascularized collagen-glycosaminoglycan matrices produce a favorable substrate for cultured epithelial autografts and may improve cultured epithelial autografts take in burn patients.

Animals↗
PubMed1998

Salvage of externally exposed ventricular assist devices.

Although externally exposed ventricular assist devices are associated with extremely high mortality rates, salvage may be accomplished by early aggressive wound debridement, transposition of a well-perfused autologous tissue (such as omentum), dead space obliteration, and adequate external coverage using vascularized tissue. The temporary suppression rather than the total eradication of the infection should be the goal of these procedures.

Adult↗
PubMed1997

Management of a patient with advanced AIDS and toxic epidermal necrolysis using human growth hormone and G-CSF.

Toxic epidermal necrolysis (TEN) is a serious drug reaction that is occurring with increased frequency among those affected with HIV and AIDS. It carries a grave prognosis for those with advanced AIDS and massive skin involvement. We report a severe case of TEN treated with wound care, intravenous nutrition, human growth hormone (hgh), and granulocyte colony-stimulating factor (G-CSF).

Acquired Immunodeficiency Syndrome↗
PubMed1997

Tissue expansion in children: a retrospective study of complications.

We retrospectively reviewed 105 consecutive children in whom 191 tissue expanders were placed by the Plastic Surgical Service at The Children's Hospital from 1987 to 1995. The age range was 1 month to 28 years. The series included 68 females and 37 males. The indications for tissue expansion were congenital pigmented nevus (N = 55), craniofacial anomaly (N = 13), aplasia cutis congenita (N = 7), meningomyelocele (N = 7), posttumor resection (N = 5), unstable scar (N = 4), burn scar (N = 3), and miscellaneous disorders. The expanders were located in the scalp (N = 59), cervicofacial area (N = 23), back (N = 18), chest (N = 6), and extremities (N = 6). A single expander was used in 47 patients and the mean number of expanders per patient was 1.8. All patients were given preoperative intravenous antibiotics. There were 25 complications in 20 patients (19%), which comprised 13% of all expanders. The most common complications were infection (6%, N = 11), deflation (3%, N = 6), and exposure (2%, N = 5). These complication rates were not related to either the gender, site of implantation, number of expanders, use of closed suction drains, or the indication for expansion. The complications were related to age, being higher in children (age 1-12 years) compared with infants and adolescents. Tissue expanders can be successfully used in children to construct and reconstruct a variety of cutaneous defects, but there is an irreducible minimum for the three major complications.

Adolescent↗