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D N Herndon

Publications and source records attributed to D N Herndon.

At least 19 recordsLinked to original sources
PubMed2006

Ghrelin improves burn-induced delayed gastrointestinal transit in rats.

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.

Animals↗
PubMed2006

Gene therapy in wound healing: present status and future directions.

Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.

Animals↗
PubMed2006

[Treatment strategies for acute smoke inhalation injury].

Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases such as carbon monoxide and cyanide. As a wide variety of synthetic materials is used in buildings, such as insulation, furniture, carpeting, electric wiring covering as well as decorative items, the potential for poisoning from inhalation of products of combustion is continuously increasing. The present review describes the pathophysiologic effects from smoke inhalation injury as well as strategies for emergency treatment on scene and in the intensive care setting.

Carbon Monoxide Poisoning↗
PubMed2005

Lactate: early predictor of morbidity and mortality in patients with severe burns.

A severe burn results in a devastating and unique derangement called burn shock. Historically, resuscitation has been guided by a combination of basic laboratory values, invasive monitoring and clinical findings, but the optimal guide to the endpoint of resuscitation remains controversial. One-hundred sixty-six patients, who were admitted to our Burn Unit, were enrolled in this prospective study. Resuscitation of these patients was undertaken according to the current standard of care. Parkland formula was used as a first approximation of acquired fluid administration rates and fluid administration was adapted in order to meet clinical needs. The aim of this study was to evaluate if plasma lactate is a useful parameter to estimate the severity of a burn shock. One of the main objectives was to evaluate, if the lactate clearance adds additional information. The results of this study indicate that the initial lactate level (Day 0) is a useful parameter to separate survivors from non-survivors. Moreover, a significant marker of shock and resuscitation was observed in evaluating the lactate clearance on Day 1. A better chance of survival occurs when resuscitation results in a lactate clearance to normal values within 24h (survival was 68% if the lactate reached normal values, compared to 32% if the lactate level remained supra-normal). In summary, we believe that measuring lactate and lactate clearance may help to detect critically injured patients either for adequacy of treatment, or selection of other therapeutic options.

Biomarkers↗
PubMed2005

Effects of endotoxin on serum chemokines in man.

AIM: Endotoxin is known to be a primary initiator of sepsis and septic shock. Migration of immunocompetent cells due to chemotactic attraction plays a central role in the initiation of the immune response. Two major groups of chemokines can be distinguished: C-x-C chemokines like Interleukin-8 attract mainly neutrophils, C-C chemokines (e.g. RANTES) attract monocytes and T-cells. The aim of this study was to get further insight into chemokine profiles after a single endotoxin bolus in man. MATERIALS AND METHODS: We investigated the effect of systemically administered endotoxin (4ng/kg BW i.v.) in 8 healthy volunteers. Clinical data (heart rate, mean arterial pressure, temperature), serum levels of IL-8, and RANTES, as well as white blood cell count were obtained before and hourly for five hours after endotoxin administration. RESULTS: Heart rate and MAP showed significant changes (p<0.05) after 2-3 hours. All volunteers presented with low-grade fever after 2 hours. WBC was elevated 43% and 63% after 4 and 5 hours, respectively. Both chemokines were significantly different from baseline two hours after endotoxin challenge: While IL-8 was significantly increased RANTES serum levels were diminished. CONCLUSION: From our data we conclude that this endotoxin model was effective to mimic the clinical appearance of sepsis. Chemokines like IL-8 and RANTES are integrated in the early immune response to endotoxin challenge in man.

Adult↗
PubMed2005

The structure and composition of liposomes can affect skin regeneration, morphology and growth factor expression in acute wounds.

Liposomal gene transfer is an effective therapeutic approach to improve dermal and epidermal regeneration. The purpose of the present study was to define whether the biological or chemical structure of a liposome influences cellular and biological regeneration in the skin, and to determine by which mechanisms possible changes occur. Rats were inflicted a full-excision acute wound and divided into three groups to receive weekly subcutaneous injections of DMRIE liposomes plus the Lac Z gene, or DOTAP/Chol liposomes plus the Lac Z gene, or saline. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine cellular responses after gene transfer, protein expression, dermal and epidermal regeneration. DOTAP/Chol increased IGF-I and KGF protein concentration and caused concomitant cellular responses, for example, by increasing IGFBP-3, P<0.05. DOTAP/Chol liposomes improved epidermal regeneration by exhibiting the most rapid area and linear wound re-epithelization compared to DMRIE or control, P<0.001. DOTAP/Chol and DMRIE exerted promitogenic and antiapoptotic effects on basal keratinocytes, P<0.05. Dermal regeneration was improved in DOTAP/Chol-treated animals by an increased collagen deposition and morphology, P<0.001. DOTAP/Chol liposomes increased vascular endothelial growth factor concentrations and thus neovascularization when compared with DMRIE and saline, P<0.001. In the present study, we showed that different liposomes have different effects on intracellular and biological responses based on its chemical and molecular structure. For gene transfer in acute wounds, the administration of DOTAP/Chol liposomes appears to be beneficial.

Animals↗
PubMed2005

Immunological control of methicillin-resistant Staphylococcus aureus (MRSA) infection in an immunodeficient murine model of thermal injuries.

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns. In this study, an immunological regulation of MRSA infection was attempted in a mouse model of thermal injury. SCIDbg mice were resistant to MRSA infection, while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mphi)) were susceptible to the same infection. Also, thermally injured SCIDbg mice were shown to be susceptible to MRSA infection. On the other hand, the resistance of SCIDbgMN mice to the infection was completely recovered after an inoculation with Mphi from normal mice. However, anti-MRSA resistance was not shown in SCIDbgMN mice inoculated with Mphi from thermally injured mice. Mphi from MRSA-infected thermally injured mice were identified as alternatively activated Mphi, and Mphi from MRSA-infected unburned mice were characterized as classically activated Mphi. Mphi from thermally injured SCIDbg mice previously treated with 2-carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA infection. Ge-132 has been described as an inhibitor of alternatively activated Mphi generation. These results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti-MRSA effector cells and elimination of burn-associated alternatively activated Mphi, which are cells that inhibit the generation of classically activated Mphi.

Animals↗
PubMed2003

[Toxic epidermal necrolysis. A case for the burn intensive care unit].

Toxic epidermal necrolysis is a rare but life-threatening exfoliating disease of the skin and mucous membranes, commonly considered a drug sensitivity reaction. In this review of the literature we discuss the epidemiology, etiology, and pathology. We show diagnostic problems and current treatment strategies. Many of the problems associated with the disease, such as wound infection, sepsis, nutritional support, and pain management, are similar to problems in severely burned patients. Burn centers provide optimal logistics and knowledge to diagnose and treat this serious disease entity.

Biological Dressings↗
PubMed2003

Skin toxicity induced by wet heat.

Pieces of human skin from the skin bank were heated in an autoclave for 1 or 5 min at temperatures 80, 90, 100, 110 and 135 degrees C. The pieces were then homogenized and the homogenates were injected intraperitoneally into groups of mice. The amount injected was either a quantity equivalent to 50 or 75% of the mouse body surface area. Fourteen separate experiments were carried out, each one with a variety of temperatures. Mortality in the groups of mice was recorded by the 8th day. Control mice received homogenates of skin heated to no more that 38 degrees C and out of a total of 104 control mice there were only 4 deaths. In contrast homogenates of skin heated to 135 degrees C killed from 80 to 100% of the mice in different groups, averaging 92%. Skin heated to 110 degrees C killed from 33 to 90% of the mice in different groups, averaging 63%. Skin heated to 100 degrees C killed from 0 to 80% of the mice in different groups, averaging 33%. Temperatures of 80 and 90 degrees C killed no more than 10% of the mice in any group, averaging less than 3%. One minute of heating seemed to be sufficient to induce the toxic effect in the skin. These findings indicated that wet heat application to skin was capable of inducing toxicity in a fashion similar to that demonstrated many years ago with hotter dry temperatures applied to skin for 15s. That application was shown to induce polymerization of skin cell membrane lipid proteins rendering them toxic. In this study, increasing toxicity appeared similarly to depend on the quantity of wet heat input as illustrated by the range of increasing temperatures. The relatively lower temperatures of scalding versus flame burns can accomplish similar dangerous effects; it is simply a quantitative matter of heat input.

Animals↗
PubMed2003

Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin.

Inhibition of wound contraction by topical anti microbial agents has been described. The purpose of this study was to further investigate that phenomenon and to explore the effect that other agents such as Aloe vera might have on this process. Full-thickness excised wounds were created on the dorsum of Sprague-Dawley rats under anaesthesia. The wounds were treated with topical agents three times daily for fourteen days, then observed until healed. Groups were: saline control, placebo (aqueous cream) control, silver sulphadiazine (SSD) cream 1%, SSD 0.5%, SSD 1% with Aloe vera, SSD 1% with nystatin, nystatin. Wound surface areas were measured each three days. Time to 50% and 90% healing was compared using ANOVA. Wound half-life and healing times were shortest in the SSD/Aloe vera and nystatin groups (P<0.05) and longest in the 1% SSD and saline control groups. The placebo group (aqueous cream) healed in a significantly shorter time (P<0.05) than the control (saline) group. Wound contraction was delayed by saline and SSD. Nystatin and Aloe vera, when added to SSD, reversed that effect. These data suggest that a dry wound (saline) heals slowly. Infection control without delay of wound healing is most appealing and clinical trials are planned.

Administration, Topical↗
PubMed2003

Nutritional and pharmacological support of the metabolic response to injury.

Severe burn incites metabolic disturbances which last up to one year post injury. Persistent profound catabolism after severe burn hampers rehabilitative efforts delaying meaningful return of individuals to society. The simplest effective anabolic strategies for severe burn injuries are early excision and grafting of the burn wound, prompt treament of sepsis, maintenance of environmental temperature at 30-32 inverted exclamation mark C, continuous enteral feeding of a high carbohydrate, high protein diet, early institution of vigorous resistive and aerobic resistive exercise programs. To further minimize erosion of lean body mass administration of recombinant human growth hormone, insulin, oxandrolone or propranolol are all reasonable approaches. Exogenous continuous low dose insulin infusion, beta blockade with propranolol and the use of the synthetic testosterone analog, oxandrolone are the most cost effective and least toxic pharmaco therapies to date.

Burns↗
PubMed2002

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↗
PubMed2002

Non-viral liposomal keratinocyte growth factor (KGF) cDNA gene transfer improves dermal and epidermal regeneration through stimulation of epithelial and mesenchymal factors.

Keratinocyte growth factor (KGF) stimulates epithelial cell differentiation and proliferation, which are of major importance for wound healing. Local protein administration, however, has been shown to be ineffective due to enzymes and proteases in the wound fluid. We hypothesized that delivering KGF as a non-viral liposomal cDNA gene complex is a new approach that would effectively enhance dermal and epidermal regeneration. Twenty-two rats were given an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus the LacZ gene (0.2 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and LacZ cDNA (0.2 microg). Transfection was confirmed by histochemical assays for beta-galactosidase. Planimetry, histological and immunohistochemical techniques were used to determine protein expression, dermal and epidermal regeneration. Transfection and subsequent KGF expression was found in diving cells in the granulation tissue. Epidermal regeneration was improved by 170% in rats receiving the KGF cDNA constructs by exhibiting the most rapid area and linear wound re-epithelialization, P < 0.0001. KGF improved epidermal cell net balance by increasing skin cell proliferation and decreasing skin cell apoptosis, P < 0.0001. Dermal regeneration was further improved in KGF cDNA treated animals by an increased collagen deposition and morphology, P < 0.0001. KGF cDNA increased neo-vascularization and concomitant VEGF concentrations when compared with vehicle, P < 0.01. KGF cDNA did not only stimulate epithelial cells, but also mesenchymal cells through increases in IGF-I concentration, P < 0.005. Liposomes containing the KGF cDNA gene constructs were effective in improving epidermal and dermal regeneration. KGF gene transfer to acute wounds may represent a new therapeutic strategy to enhance wound healing.

Animals↗
PubMed2002

The effect of prolonged euglycemic hyperinsulinemia on lean body mass after severe burn.

BACKGROUND: The hypermetabolic response to burn increases protein catabolism. Euglycemic hyperinsu-linemia with exogenous insulin maintains muscle protein by continued stimulation of net protein synthesis. Our aim was to determine the effect of euglycemic hyperinsulinemia over the entire hospitalization on muscle anabolism by investigating lean body mass (LBM) as the primary endpoint. METHODS: Eighteen subjects between the ages of 2 and 18 with burns of more than 40% were prospectively randomized into 2 groups, a control (n = 9) and a treatment group (n = 9). The treatment group was given continuous intravenous insulin at a rate of at least 1.5 microU/kg/min to maintain serum glucose levels between 100 to 140 mg/dL. Treatment was instituted 24 to 48 hours after arrival and continued until the patient's injury was 95% healed. All patients received continuous enteral feeding. Patients underwent body composition studies by dual-energy x-ray absorptiometry (DEXA) scan on postoperative day 6 after initial burn excision and when 95% healed. RESULTS: Nutritional intakes were not different between groups. In the control, subjects continued catabolism resulted in peripheral muscle wasting and centripetal obesity with diminished truncal LBM. The treatment group had improvement in lean body mass (P =.004) and bone mass (P =.025). The treatment group also had less peripheral muscle wasting with overall increases in upper/lower extremity LBM (P =.005). Hospital length of stay in days per percent of total body surface area burned was decreased in the insulin group (control = 1.03 +/- 0.1 vs 0.7 +/- 0.9 for insulin patients; P <.05). CONCLUSIONS: Euglycemic hyperinsulinemia throughout the hospital course mitigates muscle catabolism and preserves lean body mass.

Adult↗
PubMed2002

Modulating the hypermetabolic response to burn injuries.

A huge rise in metabolic rates occurs following a burn injury. Practitioners can alleviate this problem by controlling the patient environment and providing appropriate nutritional support. Drug therapy is likely to be a future option.

Adolescent↗
PubMed2001

Reversal of catabolism by beta-blockade after severe burns.

BACKGROUND: The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of beta-adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns. METHODS: Twenty-five children with acute and severe burns (more than 40 percent of total body-surface area) were studied in a randomized trial. Thirteen received oral propranolol for at least two weeks, and 12 served as untreated controls. The dose of propranolol was adjusted to decrease the resting heart rate by 20 percent from each patient's base-line value. Resting energy expenditure and skeletal-muscle protein kinetics were measured before and after two weeks of beta-blockade (or no therapy, in controls). Body composition was measured serially throughout hospitalization. RESULTS: Patients in the control group and the propranolol group were similar with respect to age, weight, percentage of total body-surface area burned, percentage of body-surface area with third-degree burns, and length of time from injury to metabolic study. Beta-blockade decreased the heart rates and resting energy expenditure in the propranolol group, both as compared with the base-line values (P<0.001 and P=0.01, respectively) and as compared with the values in the control group (P=0.03 and P=0.001, respectively). The net muscle-protein balance increased by 82 percent over base-line values in the propranolol group (P=0.002), whereas it decreased by 27 percent in the control group (P not significant). The fat-free mass, as measured by whole-body potassium scanning, did not change substantially in the propranolol group, whereas it decreased by a mean (+/-SE) of 9+/-2 percent in the control group (P=0.003). CONCLUSIONS: In children with burns, treatment with propranolol during hospitalization attenuates hypermetabolism and reverses muscle-protein catabolism.

Adrenergic beta-Antagonists↗
PubMed2001

Glycyrrhizin restores the impaired IL-12 production in thermally injured mice.

Mice 6 days after thermal injury (TI-mice) did not respond to lipopolysaccharide (LPS) stimulation for production of serum interleukin 12 (IL-12; 2 h after LPS stimulation, <20 pg/ml in TI-mice; 1091+/-162 pg/ml in normal mice). However, 2 h after LPS stimulation, 1456+/-118 pg/ml of IL-12 were demonstrated in sera of TI-mice previously treated with a 10 mg/kg i.p. dose of glycyrrhizin (GR). IL-12 was not induced by LPS in sera of normal mice inoculated with burn-associated type 2 T cells (IL-4/IL-10-producing CD8+CD11b+TCRgamma/delta+T cells isolated from spleens of TI-mice). However, IL-12 production was induced by LPS in sera of these mice previously treated with GR or a mixture of monoclonal antibodies (mAbs) for type 2 cytokines. Also, IL-12 production was induced by LPS in TI-mice inoculated with CD4+T cells from spleens of GR-treated normal mice (GR-CD4+T cells, 5x10(6)cells/mouse). Since GR-CD4+T cells have been shown to be antagonistic cells against production of type 2 cytokines by burn-associated type 2 T cells, these results indicate that IL-12 unresponsiveness shown in TI-mice is recovered by GR through the regulation of burn-associated type 2 T cell responses.

Adoptive Transfer↗