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Biomedical subjects

D Herndon

Publications and source records attributed to D Herndon.

At least 19 recordsLinked to original sources
PubMed2003

Statistical approach to DNA chip analysis.

Statistical methods for analyzing data from DNA microarray experiments are reviewed. Specifically, we discuss common experimental setups, methods for data reduction and clustering, and analysis of time-course experiments. While early microarray studies focused mainly on the basic methodological and technical aspects of DNA arrays, emphasis has shifted to biological, medical, and clinical applications. We mention several of these and present results from our recent research as illustrative examples. New developments in this ever-growing field are outlined.

Algorithms↗
PubMed2000

Insulin-like growth factor-I cDNA gene transfer in vitro and in vivo.

Our hypothesis is that gene transfer of an IGF-I CMV-cDNA with cholesterol containing cationic liposomes is an efficient tool for transient transfection of growth factors in vitro and in vivo. In vitro, we transiently cotransfected IGF-I cDNA with a CMV construct and a Lac Z beta-galactosidase cDNA/CMV construct using cholesterol containing cationic liposomes and measured beta-galactosidase and IGF-I mRNA and protein. In vivo, we subcutaneously injected 3-month-old male Sprague-Dawley rats with IGF-I cDNA and beta-galactosidase cDNA into rat skin. After IGF-I and beta-galactosidase were cotransfected into PC12 cells, Northern blot analysis showed that the peak time of IGF-I expression was 2 days for mRNA and 5 days for protein. In vivo, a cDNA/liposome ratio of 1:2 was most effective. IGF-I protein expression in IGF-I-transfected skin resulted in significant transfection from day 5 to day 7. In situ determination of beta-galactosidase activity confirmed that transfections resulted in a restricted expression area.

Animals↗
PubMed2000

beta-adrenergic desensitization after burn excision not affected by the use of epinephrine to limit blood loss.

BACKGROUND: Burn patients have impaired myocardial function and decreased beta-adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic beta-adrenergic response. METHODS: Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta-adrenergic receptor density. RESULTS: Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor content was not changed. CONCLUSIONS: Topical epinephrine to limit blood loss during burn excision resulted in significant systemic absorption and increased plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic cascade was induced by the administration of epinephrine reflected by increased cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h after the use of epinephrine or thrombin, indicating that epinephrine administration was not a causative factor.

Administration, Topical↗
PubMed1998

Long-term psychosocial adaptation of children who survive burns involving 80% or greater total body surface area.

OBJECTIVE: To examine the psychosocial adjustment of survivors of massive pediatric burn injuries, the change in adjustment across time, and the impact on parents. BACKGROUND: Patients/parents were assessed at regular intervals postburn using standardized tests of adjustment. Patients who could not be included in standardized longitudinal assessments were administered questionnaires by mail/telephone. METHODS: The Child Behavior Checklist, the Teacher Report Form, the Youth Self Report Form, and the Parenting Stress Index were utilized to assess adjustment. RESULTS: On all objective measures, the group of survivors and their parents were within normal limits. Adjustment neither improved nor deteriorated over time. CONCLUSION: Children who survive massive burn injuries can achieve positive psychosocial adaptation.

Activities of Daily Living↗
PubMed1997

Applying what burn survivors have to say to future therapeutic interventions.

Statements by caregivers can be beneficial to paediatric burn patients, facilitating their psychological adaptation. However, the concerns of the burned child are not always obvious, and caregivers may flounder, not knowing how to elicit the concerns of the patient. The purpose of this paper is to examine whether universal concerns of the postburn survivor can be detected through one type of psychological assessment tool, a sentence completion task. Sixty paediatric burn survivors, ages 6-19, were administered a 30-item Incomplete Sentences measure. Five major aspects of postburn life were identified and proscribed the following descriptive labels: (1) preoccupation with health; (2) the struggle for internal acceptance; (3) reconstruction of one's life map; (4) changing relationships; and (5) redefining the world. These five dimensions of postburn life are discussed, as well as applications for each.

Adaptation, Psychological↗
PubMed1997

Adjunctive methods of pain control in burns.

Opiates remain the most common form of analgesic therapy in the burn patient today. Because of increased opiate requirements, optimal relief of burn pain continues to be a problem for these patients. The purpose of this article is to summarize those alternative pain control methods that appear in the literature. For instance, in minor burns acetominophen continues to be a useful first line analgesic. Non-steroidal anti-inflammatory drugs (NSAID) and benzodiazepine are generally combined with opiates while entonox seems to be used commonly in the adolescent patients to relieve procedural pain. Antidepressants appear to enhance opiate-induced analgesia while anticonvulsants are useful in the treatment of sympathetically maintained pain following burns. Ketamine has been extensively used during burn dressing changes but its psychological side-effects have limited its use. Clonidine, however, has shown promise in reducing pain without causing pruritus or respiratory depression. Other forms such as transcutaneous electrical nerve stimulation (TENS), psychological techniques, topical and systemic local anaesthetics are also useful adjuncts.

Analgesia↗
PubMed1996

Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and burns.

OBJECTIVE: To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma. DESIGN: Retrospective study. SETTING: Teaching hospitals, USA and Germany. SUBJECTS: Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points. INTERVENTIONS: Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10). MAIN OUTCOME MEASURES: Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns. RESULTS: High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma. CONCLUSION: Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.

Adolescent↗
PubMed1988

Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006'' +/- .002'' compared to .013'' +/- .018'' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.

Adolescent↗
PubMed1988

Beta endorphin, a vasoconstrictor during septic shock.

UNLABELLED: A relationship between increased peripheral resistance (TPRI) and decreased cardiac index (CI) and mortality from sepsis has been suggested. The relationship between endogenous opiates and this response was evaluated. METHODS: Chronically instrumented sheep were given E. coli endotoxin (LPS, 1.5 mcg/kg x 30 minutes). In one study, survivors (n = 9) and nonsurvivors (n = 11) of LPS were compared along with survivors (n = 8) of half the dose of LPS. In a second study, two groups of animals received naloxone: one (n = 11) had a bolus of 2 mg/kg followed by a 2 mg/kg/hr continuous infusion started 30 minutes before LPS while the other had the bolus and infusion started 1 hour after LPS was begun. RESULTS: Both vasoconstrictive and vasodilative phases were seen. Vasoconstriction was associated with elevated beta endorphin levels, a pattern sustained until death in the nonsurvivors. Both pre- and posttreatment with naloxone lessened the maximum increase in total peripheral resistance index compared with untreated sheep. DISCUSSION: The vasoconstrictive aspects of the response to LPS correlated with elevated beta endorphin levels and with mortality. This vascular response is attenuated with naloxone blockade.

Animals↗
PubMed1988

Cardiopulmonary changes with intermittent endotoxin administration in sheep.

Chronic sepsis was induced by administering endotoxin (lipopolysaccharide--LPS) at 12-hr intervals to sheep. The animals (n = 7) responded to the first dose of LPS with increased pulmonary arterial pressure (PAP), systemic vascular resistance, plasma and lymph thromboxane B2 (TxB2) concentrations, and lung lymph flow rate concurrent with a reduction in the cardiac index (CI). Subsequent doses of LPS produced an elevation of PAP and TxB2 which was progressively attenuated and eventually disappeared. With LPS the lung lymph flow was markedly elevated and CI increased. This latter was transient and associated with a reduction in systemic vascular resistance. Concomitant with the cardiopulmonary changes prekallikrein levels were not diminished, but there was a statistically significant reduction in C1-esterase inhibitor. The administration of LPS was discontinued after 5 days and the cardiopulmonary variables rapidly returned to baseline levels. Chronic endotoxemia appears to be associated with an elevated pulmonary microvascular permeability and a tendency toward a hyperdynamic circulation but with an appreciable degree of refractoriness associated with regional hemodynamics and eicosanoid biosynthesis.

Animals↗
PubMed1988

Ibuprofen reduces the lung lymph flow changes associated with inhalation injury.

Inhalation injury was produced in sheep which were chronically prepared for study. The injury was induced by insufflating them with smoke from burning cotton cloth. One group of animals was treated with the cyclooxygenase inhibitor ibuprofen and another group was untreated. Eight hr following the administration of smoke, there was an elevation of lung lymph flow in both groups. These changes were not as severe in the animals which were treated with ibuprofen. The pulmonary changes which occur following smoke inhalation injury are associated with elevations of the metabolites of arachidonic acid, especially those generated by the cyclooxygenase pathway. These metabolites in some way contribute to the pathophysiological changes induced by the inhalation of smoke, since they are reduced by the administration of a cyclooxygenase inhibitor.

Animals↗
PubMed1985

A model of ovine endotoxemia characterized by an increased cardiac output.

High cardiac output sepsis is a major clinical problem. We have designed a sheep endotoxin model to simulate this condition and have evaluated how closely it approximates the clinical situation. The animals were prepared for chronic study by the implantation of cardiopulmonary catheters. One week later, endotoxin (0.75 microgram/kg/30 min) was administered following baseline measurements, and the animals were studied for an additional 15 hr. From 6-15 hr after the administration of endotoxin, there was a statistically significant twofold increase in cardiac output. Simultaneously, the total peripheral vascular resistance and mean arterial pressure was reduced. Eicosanoid measurements made at this time indicated that the vasodilator prostanoid, prostacyclin, was not elevated. A high cardiac output (hyperdynamic) model of sepsis has thus been established by the 30 min infusion of a small quantity of endotoxin. Prostacyclin is not a mediator of this response.

Animals↗
PubMedDate not supplied

Time course of alterations in lung lymph and bronchial blood flows after inhalation injury.

The effects of inhalation injury on the pulmonary microvascular fluid flux and bronchial blood flow were examined in a long-term study of sheep (N = 13). They were insufflated with either 48 breaths of cotton smoke (n = 8) or air (n = 5) while they were deeply anesthetized with halothane. After injury, anesthesia was discontinued and the animals were mechanically ventilated throughout the experimental period (24 hours). Bronchial blood flow increased significantly at all time points recorded and reached its peak 20 minutes after the inhalation trauma (11 +/- 1 ml/hr to 106 +/- 18 ml/hr; p less than 0.05). Thereafter, bronchial blood flow decreased to a value that was six to eight times above the baseline measurement for the remainder of the study period. With these changes in blood flow, there was a concomitant increase in lung lymph flow. This variable gradually increased and was 633% of the baseline value (6 +/- 1 ml/hr to 44 +/- 8 ml/hr) 24 hours after the challenge with smoke. The control animals showed little or no change in cardiopulmonary function during the experimental period. There is no correlation between the increase in bronchial blood flow and lung lymph flow patterns after cotton smoke inhalation injury.

Animals↗
PubMedDate not supplied

Cold stress response in patients with severe burns after beta-blockade.

Adrenergic receptor blockade has been shown to be of benefit in the treatment of adverse cardiovascular changes in patients with burns during the hypermetabolic phase. This article examines the stress response to cold exposure in adults and children with 33% to 95% total body surface area burns with and without beta-blockade. Resting energy expenditures were measured by indirect calorimetry; the test subjects were exposed to mean temperatures of 27.5 degrees C (room temperature) or 24.6 degrees C (cold). The mean resting energy expenditure at ambient room temperature in patients with burns without beta-blockade was 1411 +/- 70 kcal/m2/day (mean +/- SEM). This value was 142% of that predicted for normal control subjects without burns. When placed in a cold temperature, patients with burns significantly increased their resting energy expenditures by 160% of predicted values, whereas patients with similar burns and beta-blockade increased their resting energy expenditures by 156%. Adults with septic burns had a mean resting energy expenditure 198% of the predicted value. These patients did not significantly increase their resting energy expenditures when they were exposed to cold either with or without beta-blockade. Data suggest that patients with septic burns already have a maximal metabolic response and that cold stress does not further increase this response. Males, ages 17 to 54 years, were found to increase their resting energy expenditures by 11.4 kcal/m2/day for each percent total body surface area burn. We conclude that beta-blockade with propranolol in therapeutic doses may be used in patients with burns without adversely affecting the cold stress response.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Social competence and behavioral problems of pediatric survivors of burns.

Sixty children (35 boys, 25 girls) with burns were surveyed at least 1 year after burn injury to assess the behavior problems and difficulties with competency that they were having. The Child Behavior Checklist, the Youth Self Report, and the Teacher Report Form developed by Achenbach were administered to obtain standardized measures of behavior and competence. The mean values for these scales were in the normal range for each age and sex. However, the Child Behavior Checklist revealed a statistically significant (p < 0.05) increase in problems and decrease in competency for most age groups and both sexes when compared with the reference population. In contrast, the Teacher Report Form and the Youth Self Report revealed very few differences from the reference population. The burn size (15% to 20% total body surface area, 35% to 50% total body surface area, and > 70% total body surface area) did not account for any of the group differences. Further studies involving detailed clinical interviews and other standardized measures are needed to understand the discrepancies between the Child Behavior Checklist and the other scales.

Adolescent↗
PubMedDate not supplied

Psychosocial sequelae of pediatric burns involving 80% or greater total body surface area.

Important questions for pediatric burn care specialists relate to the quality of life for those children who survive the most severe burn injuries. This study examines the psychological adjustment of 25 children who survived injuries > or = 80% total body surface area and the impact of such injury on the families. Data were analyzed from the most recent assessment, with the Child Behavior Checklist, Teacher Report Form, Piers-Harris Children's Self-Concept Scale, Parenting Stress Index, and a parental questionnaire designed by the authors. As a group, the children's behavioral problems as reported by both parents and teachers were within normal limits. Measures of parental stress, however, clearly differentiated the burn population. These parents attributed more stress to characteristics of their children. Children with > or = 80% TBSA burns develop positive feelings about themselves and appear no more troubled than a comparable group of nonburned children. The impact on the families is significant, however, and must be considered of consequence in the rehabilitation of the burned child.

Adaptation, Psychological↗