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Biomedical subjects

T A Mustoe

Publications and source records attributed to T A Mustoe.

At least 91 records · Page 5Linked to original sources

Animal models of human tissue expansion.

Although tissue expansion is being used extensively in humans, many fundamental scientific questions remain to be addressed which can best be answered using an animal model. Presently, no single animal has been identified for research of this kind which is comparable both subjectively and objectively to humans. This study evaluates the skin of the rat, guinea pig, pig, and dog and identifies the dog as the best model based on biomechanical and practical considerations.

Animals↗

Physical, biomechanical, histologic, and biochemical effects of rapid versus conventional tissue expansion.

Clinical tissue expansion has been quite successful but takes 2 to 3 months. This study compares the effects of a conventional tissue expansion regimen of 6 weeks with an accelerated regimen of 2 weeks in the dog model, which is biomechanically similar to the human. In 22 dogs, the skin expanded 34.4 percent in the 2-week and 35.8 percent in the 6-week protocol, excluding stretch and recruitment. There was thinning of the panniculus carnosus in the 6-week group and otherwise no significant decrease in dermal thickness in either group. The biomechanical properties of elasticity and creep did not differ in expanded skin from both groups, while stress/relaxation mildly decreased from a control value of 53.5 percent to 48.8 percent in the 6-week group (p less than 0.05). Collagen activity was increased in both the 6-week and the 2-week groups (p less than 0.001) over nonexpanded skin, and immunohistochemical staining with a monoclonal procollagen antibody demonstrated collagen synthesis by dermal fibroblasts in both groups. We conclude that rapid tissue expansion did not demonstrate any deleterious effects when compared with a conventional regimen.

Animals↗

Topical silicone gel: a new treatment for hypertrophic scars.

A prospective, controlled clinical trial was designed to assess the efficacy of a new treatment of hypertrophic scars. Silicone gel sheeting was applied to 14 hypertrophic scars in 10 adults for 8 weeks. The treated scars and untreated, mirror-image or adjacent control scars were photographed, biopsy specimens were taken, and they were measured elastometrically before and after treatment. Photography and elastometry were repeated 4 weeks after treatment was discontinued. All the scars that had been treated for at least 12 hours a day were improved clinically after 4 weeks. There was further clinical improvement during the second 4 weeks of treatment. Elastometrically, the treated scars were improved significantly at 4, 8, and 12 weeks, compared with both their own treatment value and the control scars (p less than 0.05). Control scars were unchanged elastometrically. Clinical improvement persisted for at least 4 weeks after treatment was discontinued. The silicone gel sheeting was well tolerated, except for occasional transient rashes or superficial maceration--both of which resolved promptly when treatment was withdrawn. There was no histologic evidence of inflammation or foreign body reaction suggesting that silicone had entered the treated tissues. We conclude that this simple method of treating hypertrophic scar is efficacious, even in relatively chronic cases. The mechanism of action of silicone gel, which is apparently not related to compression, remains to be determined.

Administration, Topical↗

In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins.

Human platelet-derived growth factor (hPDGF) is likely to be important in stimulating tissue repair, based upon its in vivo chemotactic and stimulatory activities for inflammatory cells and fibroblasts and upon the presence of PDGF and related proteins in platelets, macrophages, and activated fibroblasts, cell types that make up the milieu of the healing wound. Recombinant human c-sis (rPDGF-B), homodimers of the B chain of PDGF, were compared with hPDGF in vitro. rPDGF-B was immunologically similar to hPDGF and, at identical concentrations, similar to hPDGF in stimulating fibroblast mitogenesis and chemotaxis of polymorphonuclear leukocytes, monocytes, and fibroblasts. Purified hPDGF and rPDGF-B were also tested in vivo for potency in a model of tissue repair using a linear incision wound through rat dermis. A single application of hPDGF or rPDGF-B (2-20 micrograms/wound) in a slow release vehicle at the time of wounding resulted in a dose-dependent, statistically highly significant increase of breaking strength of treated wounds. Wound healing in animals treated with rPDGF-B was 170% stronger and accelerated by 2 d during the first week over control wounds and by 4-6 d over the next 2 wk. Histologic evaluation of growth factor-treated wounds correlated the in vitro chemotactic activity and the accelerated healing of wounds with a striking inflammatory cell infiltrate early after wounding, markedly increased formation of granulation tissue by 4-d, and increased fibrosis by 14 d in comparison to control wounds. The results thus demonstrate that rPDGF-B is fully active in in vitro tests of mitogenesis and chemotaxis and, for the first time, demonstrate directly that PDGF significantly advances wound healing in incisional wounds of experimental animals.

Animals↗

Rapid tissue expansion in the treatment of myelomeningocele.

In 2 patients undergoing spinal fusion for correction of kyphoscoliosis secondary to myelomeningocele skin coverage was achieved with rapid tissue expansion. Tissue necrosis caused by overly rapid expansion in the first patient was prevented by rapid, but more controlled, expansion in the second patient. Rapid tissue expansion in the paraplegic in a carefully controlled setting is useful and can be done without unduly prolonging hospitalization. This technique has potential uses in other clinical situations as well.

Adolescent↗

Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta.

The role of polypeptide growth factors in the processes of inflammation and repair was investigated by analyzing the influence of transforming growth factor-beta (TGF-beta), applied directly to linear incisions made through rat dorsal skin. A dose-dependent, direct stimulatory effect of a single application of TGF-beta on the breaking strength of healing incisional wounds was demonstrated. An increase in maximum wound strength of 220 percent of control was observed at 5 days; the healing rate was accelerated by approximately 3 days for at least 14 days after production of the wound and application of TGF-beta. These increases in wound strength were accompanied by an increased influx of mononuclear cells and fibroblasts and by marked increases in collagen deposition at the site of application of TGF-beta. TGF-beta is thus a potent pharmacologic agent that can accelerate wound healing in rats.

Animals↗

Voice rehabilitation following laryngectomy. Myomucosal tracheoesophageal shunt.

Surgical procedures for speech rehabilitation following laryngectomy lack wide support owing to tumor recurrence, aspiration, stenosis of the fistula, and multiple surgical stages of limited usefulness in irradiated patients. The recent prostheses and their modifications have approximately a 70% success rate but similarly remain limited by the requisite maintenance and soilage. A mucosa-lined tracheoesophageal fistula with a functioning proximal muscle sphincter, created in one stage at laryngectomy, is described. This myomucosal unit can function with or without a prosthesis and potentially eliminates aspiration. Evolution of the flap design in an animal model is delineated and the clinical trial in six patients high-lighted. Five of the six have an excellent vocal quality without an associated air leak on phonation. Three function without a prosthesis.

Adult↗

[Reconstruction of the cervical esophagus by the free transfer of a jejunal loop. An experimental study in dogs].

A study was performed in twenty dogs in order to evaluate the chronic effects of free jejunal transfer and possible subsequent radiation therapy. Ten dogs were sacrificed within one week after surgery, three survived twelve to twenty days, and seven survived longer than six weeks with only one completing a full course of radiation equivalent to 6,000 rads to the jejunal flap. Fistulization was the most frequent complication in short-term and intermediate survivors. Inanition due to a functional rather than anatomic stenosis and dysmotility was observed in the long-term survivors. Interval oesophagoscopy and biopsy was of no additional value in evaluating flap survival. The jejunum of the animal receiving radiation showed a greater submucosal inflammatory response when compared to the other animals. Attempts at intraoperative cooling of the jejunal segment did not increase bowel survival or diminish the rate of fistulization.

Animals↗

Osteosclerotic plasmacytoma of maxillary bone (orbital floor).

Plasma cell neoplasms have been classified as multiple myeloma, solitary plasmacytoma and extramedullary plasmacytoma. They are usually considered as osteolytic lesions of bone except for the rare occurrence of osteosclerotic lesions. This paper describes the first reported osteosclerotic plasmacytoma of the maxillary bone and orbital floor. The difficulties in establishing a diagnosis and the relationship to other plasma cell neoplasms are discussed. Osteosclerotic plasmacytomas are a rare variant of plasma cell tumors which usually produce osteolytic lesions rather than bony sclerosis. Sixty-eight patients with the osteosclerotic variant have appeared in the world literature, with an overall incidence of about 1 per cent in a large series of plasma cell neoplasms (Dreidger and Pruzanski, 1979). There have been only six previous cases of solitary osteosclerotic plasmacytomas reported (Morley and Schweiger, 1964; Roberts et al., 1974; Rodriguez et al. 1976; Rushton, 1965; Schneinker, 1938; Brigham Medical Review, 1961) involving spine, sternum, or rib. None have previously been reported in the head and neck area. Plasma cell tumors have been classified into multiple myeloma, solitary plasmacytomas of bone, and extramedullary plasmacytomas. Multiple myeloma is a disseminated plasma cell malignancy characterized by the production of homogeneous immunoglobulins (whole or fragments) which appear in the serum and urine. Plasma cell tumors can also occur as solitary plasmacytomas, usually in bone, but also in soft tissue. With time, most solitary plasmacytomas develop disseminated disease with all the characteristics of multiple myeloma (Wiltshaw, 1976). Extramedullary plasmacytomas arise in soft tissue rather than bone, and primarily occur in the head and neck region. Clinically, they remain localized and less frequently develop into disseminated myeloma.

Female↗

Microvascular free tissue reconstruction following Mohs' micrographic surgery for advanced head and neck skin cancer.

Seven consecutive patients from 1986 through 1989 for 8 extensive recurrent and/or irradiated skin cancers of the face and scalp are retrospectively evaluated. One patient was treated by conventional surgical margins, and the limitations of this method in sampling margins are compared to the Mohs' micrographic surgery (MMS) used for the other 6 patients. All were treated with free flaps without flap loss or major complications in spite of advanced age. The advantages of an interdisciplinary approach to achieve maximum cure rates, optimal reconstruction, and minimizing anesthesia time are discussed.

Aged↗

Desmoplastic squamous cell carcinoma of the tongue simulating myositis or fasciitis.

An unusual form of squamous cell carcinoma of the tongue is reported, the "de novo" submucosal evolution of which is unique. Histologic definition of this malignancy and its distinction from clinically similar benign and malignant conditions are detailed through a brief review of the relevant differential diagnoses. The importance of circumspect diagnostic reassessment when the clinical behavior of a lesion contradicts apparent histologic benignancy is emphasized and treatment inferences are drawn.

Adult↗

Effects of insulin-like growth factor-I and insulin-like growth factor binding protein-1 on wound healing in a dermal ulcer model.

The effects on wound healing of insulin-like growth factor-I with and without insulin-like growth factor binding protein-1 were studied in a rabbit ear dermal ulcer model under both nonischemic and ischemic conditions. Wounds 6 mm in diameter were made on the ventral surface of rabbit ears for a total of 272 wounds in the nonischemic group and 77 wounds in the ischemic group. Insulin-like growth factor-I in varying doses (1 to 43 microg) and in combination with varying molar ratios of the binding protein were added at time of wounding to each wound. Wounds were analyzed histomorphometrically on day 7 after wounding. We found that insulin-like growth factor-I or binding protein alone at varying doses did not have any effects on wound healing parameters. Low to moderate doses (1 microg and 4 microg, respectively) of the combination of insulin-like growth factor-I with the binding protein in a molar ratio of 5:1 or 11:1 showed a 52% increase (p < 0.05) in new granulation tissue in the nonischemic model compared with controls but did not significantly augment new granulation tissue formation in the ischemic wound model. A high dose (43 microg) at a 10:1 molar ratio of growth factor to binding protein was required to elicit significantly enhanced wound healing in ischemic wounds. These results indicate that insulin-like growth factor binding protein-1 modulates the effects of insulin-like growth factor-I in promoting wound healing in vivo and that the combination is a highly effective vulnerary compound with effects comparable in magnitude with other growth factors previously tested in this model.

Journal Article↗