Kevin D Murphy

University of Texas Medical Branch at Galveston, Galveston, TX, United States

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Publications (11)26.98 Total impact

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    ABSTRACT: Ideal tendon repair materials combine minimal donor-site morbidity and ready availability with excellent healing and postoperative function. Bioengineered porcine small-intestinal submucosa (SIS) was compared with tendon autografts as a potential human flexor tendon graft substitute. Rabbit zone II flexor digitorum profundus segments were excised in 40 rabbits. Randomized tendon repair consisted of either interposition reversed autograft or SIS, passed beneath the A2 and A4 pulleys. Forepaws were statically splinted for 3 weeks followed by unrestricted motion. Animals were killed at 7, 14, 28, and 56 days. Specimens were analyzed for hydroxyproline content (absorption spectroscopy) and tensile strength. Hematoxylin-eosin and Movat-stained sections of the central graft and distal repair site were semiquantitatively scored for total cellularity, inflammatory cell content, foreign-body reaction, vascularity, mature collagen content, and new collagen deposition. Transforming growth factor-beta (TGF-beta1) and TGF-beta1 receptor immunostaining was performed. At week 1, SIS hydroxyproline content was significantly reduced compared with autograft hydroxyproline content. However, week 2 SIS hydroxyproline content increased to equivalent values. Collagen deposition was evident in SIS by week 1 but negligible in autograft. More rapid total and inflammatory cell increases occurred in SIS by 4 weeks. A stronger early inflammatory reaction also occurred. More rapid SIS neovascularization occurred despite a greater foreign-body reaction. Small-intestinal submucosa vascularity was markedly greater at weeks 1 and 2 and equivalent thereafter. At week 4, SIS intrinsic tensile strength (suture removed) exceeded that of both autograft and suture material. Preoperative TGF-beta1 immunostaining in SIS was less than that of autograft but greater during weeks 2 and 4. Earlier neovascularization, increased TGF-beta1 levels, and increased collagen deposition, along with greater intrinsic repair strength relative to both autograft and suture strength at week 4, make SIS a promising flexor tendon graft substitute. Future studies examining tendon excursion are planned.
    The Journal of hand surgery 10/2008; 33(7):1168-78. · 1.33 Impact Factor
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    ABSTRACT: Growth hormone (GH) improves wound healing and ameliorates pediatric postburn tissue catabolism associated with deficient endogenous GH/IGF-1 levels. Expense, parenteral administration, and compliance have limited widespread usage. Gammahydroxybutyrate (GHB), an upstream neuromodulatory gamma-amino butyric acid (GABA) derivative, is known to increase slow wave sleep and stimulate endogenous GH secretion. In this study, improvement in GH levels in turn has been shown to accelerate wound healing. Body composition in male Sprague-Dawley rats with > or =40% total body surface area scald burn, receiving incremental GHB doses orally, was assessed by Dual Energy X-Ray Absorptiometry. Serum GH and IGF-1 levels were measured. Wound cross sections were scored semiquantitatively for wound healing variables. Incremental elevation in GH and IGF-1 were associated with significantly improved wound edge epithelialization and cell-layer thickness at high doses (p < 0.005). However, body composition was similar to that of burned controls. GHB sufficiently elevated serum GH and IGF-1 levels to significantly improve epithelialization rates and layer thickness at high doses. Substantially greater elevations of serum GH and IGF-1 levels are required in the rat burn model than for humans. GHB may improve postburn hypermetabolism in humans by elevating endogenous GH levels, though only improved epithelialization was demonstrated in this study.
    The Journal of trauma 11/2007; 63(5):1099-107. · 2.35 Impact Factor
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    ABSTRACT: The neuropsychological outcomes of children who suffered hypoxic episodes following their burns are not completely understood and vary depending on the nature and severity of the episode. A retrospective review of youth that were admitted to this acute burn care facility over the past 20 years was conducted to identify the extent of cognitive and affective difficulties. Thirty-nine children who sustained hypoxic injuries related to their burns were compared with 21 controls that were matched for age, TBSA, and time of injury. Approximately a third of the children who survived from the hypoxia group continued to have long-term cognitive and emotional difficulties. For those who recovered reasonably well, no differences were found from the matched burned controls. These results probably underestimate the true extent of neuropsychological difficulties experienced by these youth given that detailed cognitive testing was not routinely performed. Prospective studies are needed to further characterize the full nature of difficulties and outcomes associated with burn related hypoxic injuries.
    Burns 12/2005; 31(7):883-9. · 1.80 Impact Factor
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    ABSTRACT: Severe burns are typically followed by a hypermetabolic response that lasts for at least 9-12 months post-injury. The endocrine status is also markedly altered with an initial and then sustained increase in proinflammatory 'stress' hormones such as cortisol and other glucocorticoids, and catecholamines including epinephrine and norepinephrine by the adrenal medulla and cortex. These hormones exert catabolic effects leading to muscle wasting, the intensity of which depends upon the percentage of total body surface area (TBSA) involved, as well as the time elapsed since initial injury. Pharmacological and non-pharmacological strategies may be used to reverse the catabolic effect of thermal injury. Non-pharmacological strategies include early excision and wound closure of burn wound, aggressive treatment of sepsis, elevation of the environmental temperature to thermal neutrality (31.5+/-0.7 degrees C), high carbohydrate, high protein continuous enteral feeding and early institution of resistive exercise programs. Pharmacological modulators of the post-burn hypermetabolic response may be achieved through the administration of recombinant human growth hormone, low dose insulin infusion, use of the synthetic testosterone analogue, oxandrolone and beta blockade with propranolol. This paper aims to review the current understanding of post-burn muscle proteolysis and the effects of clinical and pharmacological strategies currently being studied to reverse it curb these debilitating sequelae of severe burns.
    The International Journal of Biochemistry & Cell Biology 11/2005; 37(10):1948-61. · 4.15 Impact Factor
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    ABSTRACT: Severe burn injuries are associated with growth delays a persistent hypermetabolic response and severe muscle catabolism and wasting. Growth hormone (GH), a potent anabolic agent and salutary modulator of post-traumatic metabolic responses has been shown to decrease muscle wasting, improve net protein synthesis and attenuate growth delays in burned children. In non-burned populations, GH has recently been shown to be of benefit in enhancing cardiac performance and improving cardiac contractility and efficiency. Yet, whether administration of GH will induce similar improvements in cardiac function in severely burned children is presently unknown. We therefore, investigated whether the administration of GH initiated upon hospital discharge (95% healed) and continued for 1-year post-burn would improve resting cardiac function in burned children. Severely burned children were randomized to receive either saline placebo (n = 37) or 0.05 mg/kg per day of GH (n = 39) from discharge until 12-month post-burn. Outcome variables included height, weight, lean body mass, resting energy expenditure, cardiac index, stroke-volume index, heart rate and left ventricular ejection fraction. Results: height, weight, lean body mass and ejection fraction showed a significant increase with GH. Our results indicate that severely burned children treated with long-term GH show a significant improvement in left ventricular ejection fraction.
    Burns 03/2005; 31(1):60-6. · 1.80 Impact Factor
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    ABSTRACT: Health care systems constantly struggle with ways to provide higher quality care in a cost-effective manner. Outcome measures serve to evaluate what works and what does not. Whether they are used for research or for the improvement of clinical practice, they are as such, efficiency markers and the first step in determining the consequences of health care. The accomplishments of the past decade have placed us in the midst of an exciting paradigm shift from what used to be primary concern (i.e. mortality), to areas that are more likely to enhance the quality of life of burn survivors. Optimal management of severely burned persons is enormously expensive, and even after survival is ensured, may require a protracted period of surgical, medical and psychological rehabilitative measures for many years. This article aims to review the outcome measures in the acute phase of burn management (mortality and morbidity from the post-burn hypermetabolic response). We further discuss long-term outcome measures (such as, quality of life measures, exercise tolerance and evaluation of return to pre-burn activities) that are now becoming of equal importance as the numbers of burn survivors increase.
    Burns 01/2005; 30(8):761-71. · 1.80 Impact Factor
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    ABSTRACT: A significant proportion of the mortality and morbidity of severe burns is attributable to the ensuing hypermetabolic response. This response can last for as long as 1 year after injury and is associated with impaired wound healing, increased infection risks, erosion of lean body mass, hampered rehabilitation, and delayed reintegration of burn survivors into society. Pharmacologic and nonpharmacologic strategies may be used to reverse the catabolic effect of thermal injury. Nonpharmacologic strategies include early excision and wound closure of burn wound, aggressive treatment of sepsis, elevation of the environmental temperature to thermal neutrality (31.5 +/- 0.7 degrees C), high carbohydrate, high protein continuous enteral feeding, and early institution of resistive exercise programs. Pharmacologic modulators of the postburn hypermetabolic response may be achieved through the administration of recombinant human growth hormone, low-dose insulin infusion, use of the synthetic testosterone analog, oxandrolone, and beta blockade with propranolol. This review article discusses these modulators of postburn metabolism.
    Journal of Burn Care & Rehabilitation 01/2005; 26(3):194-9. · 2.42 Impact Factor
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    ABSTRACT: Severe burns cause exaggerated catabolism of muscle protein and inhibit bone deposition. Weakness and bony growth arrest interfere with rehabilitation. The purpose of this study was to determine whether oxandrolone administration for 1 year after the burn reverses muscle and bone catabolism in hypermetabolic pediatric burn patients. Children with burns greater than 40% total body surface area were enrolled into a randomized controlled trial to receive oxandrolone as a long-term anabolic agent. All patients received similar clinical care. Subjects were studied at discharge (95% healed) and at 6, 9, and 12 months after the burn, after treatment with 0.1 mg/kg po bid or placebo. Serum hepatic transaminases were measured. Lean body mass (LBM), bone mineral content (BMC,) and bone mineral density (BMD) were measured by dual energy x-ray absorptiometry. Patients completed a safety questionnaire and were reviewed clinically at intervals. The groups were similar in age, weight, and total body surface area burned. LBM was significantly greater with oxandrolone at 6, 9, and 12 months after the burn (P < .001) and BMC at 12 months (P < .016). Age- and gender-matched BMD z scores were significantly better with oxandrolone (P < .039). Liver transaminases were unaffected. Long-term administration of oxandrolone safely improves LBM, BMC, and BMD in severely burned children.
    Surgery 08/2004; 136(2):219-24. · 3.37 Impact Factor
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    ABSTRACT: Acute phase protein production is a hallmark of severe burns. We wondered whether anabolic treatment with oxandrolone would affect these proteins. Thirty-five children with > or =40% total body surface area burns were randomized to receive either placebo or oxandrolone (0.1 mg/kg by mouth twice daily) from postoperative day 5 to 1 year postburn. Levels of constitutive proteins and acute phase proteins were measured at admission; at discharge; and at 6, 9, and 12 months after burn. Total albumin supplementation and hepatic transaminases were also assessed. Constitutive proteins such as albumin, prealbumin, and retinol-binding protein levels increased (p < 0.05), and acute phase proteins such as alpha 1-acid glycoprotein, C3 complement, alpha 2-macroglobulin, and fibrinogen levels significantly decreased in the oxandrolone group compared with placebo (p < 0.05). Albumin supplementation during the acute hospitalization was reduced in the oxandrolone group. Hepatic transaminases remained within normal levels. Treatment with oxandrolone in severe burns significantly increases constitutive protein and reduces acute phase protein levels.
    The Journal of trauma 01/2004; 56(1):37-44. · 2.35 Impact Factor
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    ABSTRACT: The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.
    Wound Repair and Regeneration 01/2004; 12(4):404-11. · 2.76 Impact Factor
  • Kevin D Murphy, Jong O Lee, David N Herndon
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    ABSTRACT: The pharmacotherapy of burn care has evolved from the first topical antibiotics instituted > 30 years ago. These have helped greatly to reduce the incidence of burn wound sepsis, but a better understanding of the principles of burn care has resulted in earlier burn wound excision and complete coverage with autograft, cadaver skin, synthetic dressings, and amnion. This has markedly reduced septic complications and ameliorated the hypermetabolic response to burn injury. The hypermetabolic response, which is mediated by hugely increased levels of circulating catecholamines, prostaglandins, glucagon and cortisol, causes profound skeletal muscle catabolism, immune deficiency, peripheral lipolysis, reduced bone mineralisation, reduced linear growth, and increased energy expenditure. Supportive therapy and pharmacological manipulation, acutely and during rehabilitation, with growth hormone, insulin and related proteins, oxandrolone and propranolol can ameliorate the hypermetabolic response, improving survival and long-term outcome. Despite judicious use of topical and systemic antibiotics, opportunistic nosocomial bacterial resistance threatens to annul the improved survival of patients with severe burns. Patterns of emerging resistance encountered in burn units need to be considered, in light of a decreasing antibiotic armamentarium. A holistic approach to pharmacotherapy of severely burned patients including current practice in antimicrobial control, analgesia, sedation, and anxiety management is required. Current therapy of frequently encountered problems, such as post-burn pruritus, prophylaxis of deep venous thrombosis and peptic ulceration, and pharmacological manipulation of inhalation injury in the burned patient is described. Current pharmacotherapy to ameliorate psychosocial problems associated with burns such as acute stress disorder, depression and post traumatic stress disorder are discussed. Better analgesics, newer antibiotics and immune stimulating drugs are required to reduce mortality and morbidity in large burns.
    Expert Opinion on Pharmacotherapy 03/2003; 4(3):369-84. · 2.86 Impact Factor