D N Herndon

Shriners Hospitals for Children, Tampa, Florida, United States

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Publications (530)1657.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Propranolol attenuates post-burn hypermetabolism and reverses muscle-protein catabolism. In a small study (n<40), propranolol reduced the appearance of scar severity. This randomised, controlled trial aimed to study the effects of propranolol on post-burn scars in a larger group of patients. Methods: childrenwere randomised to receive propranolol (n=90) or a control (n=89) for up to 12 months post-injury. Vancouver Scar Scale (VSS) assessmentswere carried out on leg scars at 6, 9, 12, 18 and 24months follow-up by one assessor blinded to treatments received. Statistical analysis was performed on an intention-to-treat-basis using t-tests and theWilcoxin 2-sample rank sum test. Results: Participants had a mean age of 7.01 with burns covering a mean of 56.6% of their total burn surface area (TBSA). The groups were similar in demographics, TBSA and mechanism of burn. At 9 and 12 months followup, the propranolol group had significantly lower VSS scores than controls (p<0.05). There were no differences in VSS scores at other time-points; at 18 and 24 months we predict this was due to loss of follow-up. Conclusions: These data suggest that propranolol improves scar appearance up to 12 months post-injury. Planimetric data is needed to provide an objective measure of this improvement. Enrolment of more patients beyond 18 months is necessary to determine whether the reduction in scarring by propranolol is sustainable. Take-home message: Propranolol is not only beneficial in ameliorting the hypermetabolic response to burns but may also improve cosmetic outcomes of
    SARS; 01/2013
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    ABSTRACT: Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients. Retrospective, single-center study. In all, 592 severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ≥85th percentile (n=277) and normal (n=315) weight groups based on body mass index (BMI) percentiles. Patients stratified below (normal) and ≥85th percentile had similar age, gender distribution and total burn size. No significant differences were detected in the incidence of sepsis (11% for obese vs 10% for normal), the incidence of multiple organ failure (MOF) (21% for obese and 16% for normal) or mortality (11% for obese vs 8% for normal). Compared with the normal group, the ≥85th percentile group had low levels of constitutive proteins (α2macroglobulin and Apolipoprotein A1) (P<0.05 for both) as well as high levels of triglycerides and the acute-phase protein, C-reactive protein (P<0.05 for both) up to 60 days after injury. Patients ≥85th percentile showed a significant higher loss of bone mineral density and lipolysis compared with normal individuals. Stepwise logistic regression analysis revealed that BMI had a positive predictive value towards the maximum DENVER2 score, an index of organ failure (P<0.001). BMI≥85th percentile altered the post-burn acute phase and catabolic response but did not increase the incidence of sepsis, MOF or mortality in pediatric burn patients. Our results suggest that impaired metabolism and an altered inflammatory response already exists in patients starting at the 85th percentile BMI.
    International journal of obesity (2005) 12/2011; 36(4):485-90. · 5.22 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2011; 165(2):183-183.
  • Journal of Surgical Research - J SURG RES. 01/2011; 165(2):317-317.
  • N. Rodriguez, D. N. Herndon, G. L. Klein
    Bone 01/2011; 48. · 3.82 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2011; 165(2):332-332.
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    ABSTRACT: Liposomal gene transfer effectively enhances dermal and epidermal regeneration in burned rodents. To advance this treatment to clinical studies, we investigated the efficacy of liposomal gene transfer in a clinically relevant porcine wound model. Mimicking the clinical scenario, six female Yorkshire pigs (40-50 kg) received up to 12 burns of 50 cm(2) area that were fully excised and covered with skin autograft meshed at 4:1 ratio 24 h post-burn. Animals received control injections (empty liposomes), liposomes (DMRIE-C) containing 1 mg LacZ-cDNA, or liposomes (DMRIE-C) with 1 mg of platelet-derived growth factor (PDGF)-cDNA, or the naked PDGF gene. Serial biopsies were taken from different wound sites at multiple time points up to 12 days post-wounding. Transfection efficacy and transfection rate of LacZ and localization of beta-gal were determined by immunohistochemical and immunofluorescent techniques. RT-PCR and multiplex protein analysis (ELISA) were used to measure levels of growth factor mRNA transcribed and growth factor protein translated. Wound re-epithelialization and graft adhesion was evaluated using planimetric analysis and clinical scores. We found that peak transfection of liposomal beta-galactosidase occurred on day 2, with a fluorescence increase of 154% to baseline (P<0.001). Transfection intensity dropped to 115% above baseline on day 4 (P<0.001) and 109% on day 7. Immunohistochemistry showed a maximum transfection rate of 34% of cells in wound tissue. Gene transfer of liposomal PDGF-cDNA resulted in increased PDGF-mRNA and protein expression on days 2 and 4, and accelerated wound re-epithlialization as well as graft adhesion on day 9 (P<0.05). In this study, we showed that liposomal cDNA gene transfer is possible in a porcine wound model, and by using PDGF-cDNA we further showed that dermal and epidermal regeneration can be improved. These data indicate that liposomal gene transfer can be a new therapeutic approach to improve wound healing in humans.
    Gene therapy 04/2010; 17(6):770-8. · 4.75 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):352. · 2.02 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):353. · 2.02 Impact Factor
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    ABSTRACT: This review article describes the pathophysiological aspects of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), induced by combined burn and smoke inhalation and examines various therapeutic approaches. The injury results in a fall in arterial oxygenation as a result of airway obstruction, increased pulmonary transvascular fluid flux and loss of hypoxic pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated by reactive oxygen and nitrogen species. Nitric oxide (NO) is generated by both inducible and constitutive isoforms of nitric oxide synthase (NOS). Recently, neuronal NOS emerged as a major component within the pathogenesis of ARDS. NO rapidly combines with the oxygen radical superoxide to form reactive and highly toxic nitrogen species such as peroxynitrite. The control of NO formation involves poly(ADP-ribose) polymerase and its ability to up-regulate the activity of nuclear transcription factors through ribosylation. In addition, present data support a major role of the bronchial circulation in the injury, as blockage of bronchial blood flow will also minimize the pulmonary injury. Current data suggest that cytotoxins and activated cells are formed in the airway and carried to the parenchyma.
    Der Anaesthesist 07/2009; 58(8):805-12. · 0.85 Impact Factor
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):300-301.
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):291-291.
  • R. Kraft, J. Song, D. N. Herndon, M. G. Jeschke
    Journal of Surgical Research - J SURG RES. 01/2009; 151(2):291-291.
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):212-212.
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):292-292.
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    Critical Care 01/2009; 13. · 4.93 Impact Factor
  • C. Pereira, D. N. Herndon, M. G. Jeschke
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    ABSTRACT: Introduction: Growth factors have been shown to affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study we determined the interaction between keratinocyte growth factor (KGF), an epidermal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors and collagen types I, III, and IV synthesis in an acute wound.Method: Adult male Sprague-Dawley rats received 30% total body surface area scalds under general anesthesia. They were then divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac Z gene (0.2 μg, vehicle), or liposomes plus the KGF cDNA (2.2 μg) and Lac Z gene (0.2 μg), for 4 weeks. Immunological assays, histological, and immunohistochemical techniques were used to determine growth factor concentrations and different types of collagen (I, III, and IV), rate of reepithelialization and dermal morphology, after KGF cDNA gene transfer.Results: KGF cDNA transfer significantly increased IGF-I (Insulin-like Growth Factor-I), IGFBP-3 (Insulin-like Growth Factor Binding Protein-3), and FGF (Fibroblast Growth Factor) and decreased TGF-β(Transforming Growth Factor–beta) levels (p < 0.05). KGF had no effect on PDGF (Platelet-Derived Growth Factor). KGF cDNA significantly increased collagen type IV (p < 0.02) at the wound edge as well as the wound bed, while it had no effect on collagen type I and III. KGF cDNA significantly increased reepithelialization compared to the control group.Conclusion: Exogenous KGF cDNA increases IGF-I, IGF-BP3, FGF expression and decreases TGF-β concentration in an acute wound. It accelerates re-epithelialization, improves dermal morphology and increases basement membrane formation, without a concomitant increase in inflammation or scarring.Acknowledgments: Clayton Foundation for Research
    Wound Repair and Regeneration 01/2008; 13(2). · 2.76 Impact Factor
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    ABSTRACT: Introduction: Early excision and closure is standard for severe burn management. Cadaver skin is generally used as temporary coverage if autograft donor sites are inadequate. However, it is associated with an inherent risk of antigenicity and infection and has a limited shelf life and availability. Use of Integra™, a dermal substitute, is well established for postburn reconstruction, but its efficacy as primary coverage for severe burns it is not well documented. Therefore the aim of the present study was to determine the short- and long-term efficacy of Integra™ as an acute cover.Method: Twenty children with >40 total body surface area (TBSA) burn, were randomized to be grafted with Integra™ or with the autograft-allograft technique. Short-term outcome measures such as length of hospital stay, mortality, incidence of infection/sepsis, cardiac, respiratory, and metabolic indexes were compared between and within groups before and after Integra™/graft application. Long-term outcome measures such as number of reconstructive procedures and blinded scar scoring were performed up to 2 years postinjury. Statistical analysis was performed using paired and unpaired t-test. Values are expressed as Mean ± SEM and significance accepted at p < 0.05.Results: There were no significant differences between groups, in burn size (Controls 74 ± 4% and Integra™ 70 ± 5%), mortality (Control 30%, Integra™ 40%), length of hospital stay (Control 39 ± 4 days, Integra™ 41 ± 4 days), and metabolic rates. In addition, there was no significant incidence of infection or sepsis in the Integra™ group compared to controls. Long-term follow-up (Integra n = 5, control n = 5) revealed a significantly improved scar, in terms of height, thickness, vascularity, and maturity, in the Integra™ group compared to the control group, at 12 months and 18–24 months postburn, (p < 0.01).Conclusion: Integra™ can be safely used for immediate wound coverage in children with severe burns, with better functional and aesthetic outcomes up to 2 years postinjury.
    Wound Repair and Regeneration 01/2008; 13(2). · 2.76 Impact Factor
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    M G Jeschke, D N Herndon
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    ABSTRACT: Insulin-like growth factor-I (IGF-I) and keratinocyte growth factor (KGF) cDNA gene transfer individually improves dermal and epidermal regeneration. The aim of the present study was to determine whether the combination of IGF-I plus KGF cDNA further improves wound healing and by which mechanisms these changes occur. Rats received an acute wound and were divided into four groups to receive weekly subcutaneous injections of liposomes plus Lac Z cDNA, liposomes plus IGF-I cDNA, liposomes plus KGF cDNA, or liposomes plus IGF-I/KGF cDNA. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine IGF-I, KGF, platelet-derived growth factor, fibroblast growth factor (FGF), transforming growth factor-beta and vascular endothelial growth factor (VEGF) expression and different types of collagen (I, III and IV). IGF-I, KGF and their combination cDNA treatment significantly (P<0.05) accelerated re-epithelization, increased IGF-I, KGF, FGF, VEGF and collagen type IV expression, while it had no effect on collagen type I and III expression. The combination of IGF-I plus KGF cDNA increased (P<0.05) neovascularization and VEGF expression when compared to IGF-I cDNA, KGF cDNA groups and controls. In conclusion, exogenous administration of liposomal IGF-I plus KGF cDNA enhanced dermal and epidermal regeneration which is due to increased neovascularization.
    Gene Therapy 08/2007; 14(16):1235-42. · 4.32 Impact Factor
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    ABSTRACT: Delayed gastrointestinal transit is common in patients with severe burn. Ghrelin is a potent prokinetic peptide. We aimed at testing the effect of ghrelin on burn-induced delayed gastrointestinal transit in rats. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) studies were performed in male Sprague-Dawley rats. Rats were randomized into two main groups as follows: sham injury and ghrelin-treated burn injury with doses of 0, 2, 5, and 10 nmol/rat ip 6 h after burn. Sham/burn injury was induced under anesthesia. Rats received a phenol red meal 20 min following ghrelin injection. Based on the most effective ghrelin dose, 1 mg/kg sc atropine was given 30 min before the ghrelin in one group of rats for each study. The rats in each group were killed 30-90 min later; their stomachs, intestines, and colons were harvested immediately, and the amount of phenol red recovered was measured. Percentage of gastric emptying (GE%) and geometric center for IT and CT were calculated. We found 1) severe cutaneous burn injury significantly delayed GE, IT, and CT compared with sham injury (P < 0.05); 2) ghrelin normalized both GE and IT, but not the CT; 3) the most effective dose of ghrelin was 2 nmol/rat; and 4) atropine blocked the prokinetic effects of ghrelin on GE% and IT. In conclusion, ghrelin normalizes burn-induced delayed GE and IT but has no effect on CT in rats. The prokinetic effects of ghrelin are exerted via the cholinergic pathway. Ghrelin may have a therapeutic potential for burn patients with delayed upper gastrointestinal transit.
    AJP Regulatory Integrative and Comparative Physiology 02/2007; 292(1):R253-7. · 3.28 Impact Factor

Publication Stats

10k Citations
1,657.66 Total Impact Points

Institutions

  • 1993–2011
    • Shriners Hospitals for Children
      Tampa, Florida, United States
  • 1983–2011
    • University of Texas Medical Branch at Galveston
      • • Department of Surgery
      • • Department of Anesthesiology
      • • Department of Pediatrics
      Galveston, Texas, United States
  • 1987–2006
    • Texas A&M University - Galveston
      Galveston, Texas, United States
  • 2003
    • Middlemore Hospital
      Окленд, Auckland, New Zealand
    • Hannover Medical School
      • Department of Plastic, Hand and Reconstructive Surgery
      Hannover, Lower Saxony, Germany
  • 2001–2002
    • Universität Regensburg
      • Department of Surgery
      Ratisbon, Bavaria, Germany
    • University of Illinois Springfield
      Спрингфилд, Florida, United States
    • Loma Linda University
      Loma Linda, California, United States
  • 1998
    • University of Texas Medical School
      Houston, Texas, United States
  • 1996
    • State University of New York
      New York City, New York, United States
  • 1987–1994
    • University of Münster
      • Department of Anaesthesiology and Intensive Care
      Münster, North Rhine-Westphalia, Germany
  • 1990
    • Northeast Ohio Medical University
      Ravenna, Ohio, United States
    • Ludwig-Maximilian-University of Munich
      • Cardiac Surgery Clinic
      München, Bavaria, Germany
  • 1988–1989
    • University of California, Davis
      • Department of Surgery
      Davis, California, United States
    • Ludwig Boltzmann Institute for Experimental and Clinical Traumatology
      Wien, Vienna, Austria
  • 1986
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States