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Biomedical subjects

J P Heggers

Publications and source records attributed to J P Heggers.

At least 19 recordsLinked to original sources

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↗

Cadaveric allograft discards as a result of positive skin cultures.

INTRODUCTION: The availability of cadaveric allograft is often limited by potentially pathogenic microbial organisms. Little data exists on cadaveric allograft discard rates related to positive microbiology. The purpose of this retrospective review was to determine the cadaveric allograft discard rates related positive microbiology and the subsequent breakdown of those organisms involved. METHODS: From January 1995 to June 1997, 1112 donors were screened and procured after informed consent had been obtained. The procedures used were in accordance with American Association of Tissue Banks (AATB) standards and guidelines. The number of discards due to positive skin cultures was reviewed and analyzed for type of microbial organism. RESULTS: Fifty-four donors (4.9%) were discarded due to positive skin cultures. Methicillin resistant Staphylococcus epidermidis, (MRSE), was the most predominant organism (22.2%), followed by gram negative rods as a group (18.5%), with Aspergillus species being the least predominant isolate. CONCLUSION: Despite the strict adherence to AATB protocol, microbial contamination of cadaveric allograft skin does not reach zero. It is not surprising that S. epidermidis was the predominant isolate, since skin is one of its common habitats. Continued vigilance in microbial testing remains paramount to ensure the quality of the allograft.

Bacteria↗

The effects of hyperglycemia on skin graft survival in the burn patient.

The authors elected to determine the relative effects of hyperglycemia and/or elevated wound Gram-positive bacterial counts on success of skin graft survival in 74 burn patients. Results of serum glucose and quantitative wound biopsies on the day of admission and on postoperative day 4 were charted. Cases were separated into the following groups for analysis: normoglycemia plus normal bacterial counts, elevated bacterial counts only, hyperglycemia only, and hyperglycemia plus elevated bacterial counts. Successful graft "take" was defined as survival of 80% to 100% of the grafted area as assessed on postoperative day 4. Significant results included decreased incidence of graft take for groups with hyperglycemia only (62.5%), elevated bacterial counts only (63.3%), as well as hyperglycemia plus elevated bacterial counts (54.5%) when compared with the group with normoglycemia plus normal bacterial counts (92.8%; p = 0.020, p = 0.042, p = 0.012 respectively) for physiological parameters measured on postoperative day 4 only. Additionally, incidence of graft take was reassessed and found to be decreased significantly in groups with hyperglycemia (60.0%) vs. groups with normoglycemia (84.6%), regardless of Gram-positive bacterial counts (p = 0.034).

Burns↗

Angiotensin II inhibitor DuP753 attenuates burn- and endotoxin-induced gut ischemia, lipid peroxidation, mucosal permeability, and bacterial translocation.

OBJECTIVE: To investigate the role of angiotensin II as a mediator of burn- and sepsis-induced gut ischemia and reperfusion injury and to determine whether treatment with the angiotensin II inhibitor DuP753 can attenuate mucosal injury and bacterial translocation in a burn/endotoxemia porcine model. SUMMARY BACKGROUND DATA: Thermal injuries and endotoxemia have been shown to induce ischemia and reperfusion injury to the intestine, leading to increased mucosal permeability and bacterial translocation. Angiotensin II, the production of which has been reported to increase after burn, is thought to be one of the primary mediators of postburn mesenteric vasoconstriction. METHODS: An ultrasonic flow probe was inserted into the superior mesenteric artery and a catheter into the superior mesenteric vein in 21 female pigs. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. DuP753 was administered intravenously at 1 microg/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg Escherichia coli lipopolysaccharide (LPS) was intravenously administered. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Plasma conjugated dienes (PCDs), an index of lipid peroxidation, were measured every 6 hours. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures. RESULTS: Burn caused a significant decrease in mesenteric blood flow, to approximately 58% of baseline. Postburn endotoxemia significantly reduced the blood flow in the superior mesenteric artery to 53% of baseline. Treatment with DuP753 prevented postburn vasoconstriction and subsequently abrogated the impact of postburn endotoxemia on blood flow in the superior mesenteric artery. Mesenteric oxygen supply was significantly reduced after burn and endotoxin to 60% and 51% of baseline levels, respectively. DuP753 administration significantly improved mesenteric oxygen supply after both insults. Burn- and LPS-induced mesenteric hypoxia, as indicated by decreased mesenteric oxygen consumption, was also ameliorated by DuP753 treatment. PCD levels were significantly elevated 8 hours after burn. LPS caused a higher and prolonged increase in PCD levels. Treatment with DuP753 significantly reduced PCD levels after burn and after LPS. Intestinal permeability, as assessed by the lactulose/mannitol ratio, showed 6-fold and 12-fold increases after thermal injury and LPS, respectively. In contrast, the lactulose/mannitol ratio was only doubled in DuP753-treated animals. Bacterial translocation was significantly increased after burn and endotoxin. The incidence of bacterial translocation in the DuP753-treated animals was similar to that in the sham group. CONCLUSIONS: Angiotensin II appears to play a pivotal role in the burn- and endotoxin-induced intestinal ischemia and reperfusion injury, with subsequent increases in permeability and bacterial translocation. Postburn administration of the angiotensin II receptor antagonist DuP753 significantly reduces the extent of these events.

Angiotensin Receptor Antagonists↗

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Anti-Infective Agents, Local↗

The effect of denervation on leukocyte function in soft tissue infection.

BACKGROUND: The present study was undertaken to investigate the effect of denervation on leukocyte function in soft-tissue infection in an isolated in vivo ovine flap model. METHODS: Fifteen adult ewes were divided into three groups. An island pedicle flap was raised on the right buttock. In group I (no denervation), the cutaneous nerve remained intact, whereas in group II (acute denervation) the nerve was divided acutely. In group III (prolonged denervation) the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculation of 10(7) Staphylococcus aureus, and the animals were observed for 96 hours. RESULTS: In both groups II and III, the leukocyte chemiluminescence and chemotaxis were significantly decreased when compared with group I. Furthermore, there was profound impairment of leukocyte functions in group III compared with group II. Group III also had significantly higher bacterial counts, larger septic foci, lower viable leukocyte ratios, and decreased bacterial killing compared with group I. CONCLUSIONS: Denervation, particularly over a period of time, results in increased bacterial growth of soft-tissue septic foci. This appears to be due to decreased leukocyte function resulting in diminished bacterial killing.

Animals↗

Topical nystatin powder in severe burns: a new treatment for angioinvasive fungal infections refractory to other topical and systemic agents.

Angioinvasive fungal infections have a significant morbidity and mortality in the immunocompromised host. Massive burns produce a profound derangement in cellular immunity along with a loss of cutaneous barrier function. Treatment of fungal burn wound infections poses a difficult therapeutic challenge. We present a new method of treatment for angioinvasive fungal infections with nystatin powder at a concentration of 6,000,000 units/g. It proved to be efficacious in four consecutive severely burned patients affected by massive angioinvasive fungal infection. Both superficial and deep tissue infections were eradicated without any other therapeutic interventions or adverse effects on wound healing.

Administration, Topical↗

Modified Dakin's solution for cutaneous vibrio infections.

Vibrio species, specifically Vibrio vulnificus, are known to be endemic to warm saltwater environments. As a human pathogen they are capable of causing severe, progressive, necrotizing infections. The lesions are bullous in nature and often require wide surgical debridement due to the aggressiveness of this organism. The literature supports prophylactic antibiotic therapy for those with preexisting hepatic dysfunction or immunocompromise. The authors routinely implement prophylactic antibiotic coverage with doxycycline 100 mg every 12 hours for vibrio in patients with wounds exposed to or acquired in saltwater. In addition, they institute topical therapy with 0.025% sodium hypochlorite solution (modified Dakin's), based on their in vitro study of vibrio sensitivity to antimicrobials. Over the past 2 years, the authors have treated 10 patients with this protocol for cutaneous vibrio infections confirmed by quantitative cultures. None of these patients experienced progression of infection requiring operative debridement-contrary to the aggressive nature of this organism documented in other reports.

Adolescent↗

The use of a modified Dakin's solution (sodium hypochlorite) in the treatment of Vibrio vulnificus infection.

We report the first clinical use of a modified Dakin's solution (0.025% sodium hypochlorite [NaOCl]) to halt the progress of severe cutaneous Vibrio vulnificus infection in a critically ill patient. The regimen used arose from an initial in vitro study designed to examine the sensitivity of Vibrio species to topical antimicrobial agents. Twenty-eight wound isolates were tested against the following eight topical preparations: silver sulfadiazine (Silvadene), nitrofurazone, mupirocin ointment (Bactroban), polymyxin B/bacitracin, mafenide acetate (Sulfamylon), nystatin/Silvadene, nystatin/polymyxin B/bacitracin, and 0.025% NaOCl solution. The results showed that V vulnificus, along with the other 18 Vibrio species tested, was most sensitive to the modified NaOCl solution.

Administration, Cutaneous↗

Ciprofloxacin as a therapeutic modality in pediatric burn wound infections: efficacious or contraindicated?

BACKGROUND: Food and Drug Administration regulations state that ciprofloxacin hydrochloride may cause arthropathies. For this reason, such therapy is contraindicated in the pediatric population. However, several studies in children with cystic fibrosis have found the drug to be efficacious. Our hypothesis was that ciprofloxacin treatment is justified in the case of multiresistant organisms in burn populations. DESIGN: During a 4-year period (January 1, 1993, to December 31, 1997) we treated 56 of our pediatric burn patients with ciprofloxacin when cultures proved resistant to other antibiotics. The burn area was 65% of the total body surface area. The average patient age was 8.4 years. Of the 56 patients who received ciprofloxacin, 50 received the recommended dose. Biopsy specimens were assessed for quantitative bacteriology and antibiotic sensitivity. Radiologic review was conducted to examine for arthropathy. RESULTS: All patients showed unequivocal reduction in quantitative bacterial counts, and susceptibility to ciprofloxacin remained stable without the development of resistance. Of the 56 patients treated, 42 had a major reduction in their quantitative wound biopsies from 10(6) to less than 100 colonies per gram of tissue, while the remaining 14 were observed to have a 2- to 3-log decrease. No arthropathy was detected in any of the 56 patients receiving ciprofloxacin. Review of the patients' charts showed no documented adverse events associated with the use of ciprofloxacin. All patients survived their thermal injury and the complications associated with it without any untoward problems or complications of arthropathy. CONCLUSION: On the basis of these data, ciprofloxacin therapy in the treatment of immunosuppressed pediatric burn patients is efficacious and does not cause arthropathy.

Adolescent↗

Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy.

BACKGROUND: The relationship of the burn wound flora to microbial pathogens in the tracheobronchial tree has important implications for antimicrobial therapy in the severely burned patient. Management of septic complications is bolstered by surveillance quantitative wound cultures (QWC) and bronchial lavage fluid (BLF) cultures. OBJECTIVES: To compare the organisms present in BLF with those found in QWC and to determine if QWC can predict BLF results. DESIGN: Results of BLF cultures from all patients who underwent bronchial lavage from January 1, 1996, to December 31, 1996, at our institution were compared with QWC data from the same date. Criteria for a positive match included an identical antibiotic susceptibility pattern and biotype. Match rates were calculated qualitatively and quantitatively. RESULTS: In 30 (48%) of the 62 BLF cultures, there was a match between the organism identified in the BLF and the QWC. When strict quantitative criteria were applied, the match rate was only 9 (14%) of 62. Burn size and inhalation injury had no significant effect on match rate. CONCLUSIONS: Whereas the microbial pathogens were similar in the QWC and BLF, linear regression showed no value of QWC in predicting BLF culture results. The difference between qualitative and quantitative match rates suggests cross-colonization between the burn wound and tracheobronchial tree, but little to no cross-infection. The QWC and BLF cultures must be performed independently in determining antimicrobial specificity in the burned patient.

Adolescent↗

Protection against exotoxin A (ETA) and Pseudomonas aeruginosa infection in mice with ETA-specific antipeptide antibodies.

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and sometimes fatal infections in the compromised host, especially in patients with major trauma or thermal injuries. Exotoxin A (ETA) is the major and most lethal virulence factor produced by this ubiquitous microorganism. In a recent study (H. S. Elzaim, A. K. Chopra, J. W. Peterson, R. Goodheart, and J. P. Heggers, Infect. Immun. 66:2170-2179, 1998), we identified two major epitopes, one within the translocation domain (amino acid [aa] residues 289 to 333) of ETA and another within the enzymatic domain (aa 610 to 638), by using a panel of antipeptide antibodies. Synthetic peptides representing these two epitopes induced ETA-specific antibodies which were able to abrogate the cytotoxic activity of ETA, as measured by incorporation of [3H]leucine into 3T3 fibroblasts. In the present study, these antibodies were tested for the ability to provide protection against ETA and infection with a toxin-producing strain of P. aeruginosa in a mouse model. Antibodies to either of the synthetic peptides conferred protection against ETA. Also, when used for immunization, both peptides induced active immunity to ETA in mice. Antibodies to the peptide representing a region within the enzymatic domain of ETA, in combination with the antibiotic amikacin, enhanced the survival of mice infected with a toxin-producing strain of P. aeruginosa. Thus, antipeptide antibodies specific for ETA might be paired with antibiotic treatment for passive immunization of patients suffering from P. aeruginosa infection.

3T3 Cells↗

Generation of neutralizing antipeptide antibodies to the enzymatic domain of Pseudomonas aeruginosa exotoxin A.

Burn patients suffer a break in the physical barrier (skin), which, when combined with their generalized state of immunodeficiency, creates an open window for opportunistic infections, mainly with Pseudomonas aeruginosa. Infection of the burn wound has always been a major factor in retardation of wound healing, and sepsis remains the leading cause of death in burn patients. Because studies have shown that topical treatment with antiexotoxin A (ETA) antibodies significantly increases survival in rats infected with toxin-producing strains of P. aeruginosa, we examined 11 synthetic peptides encompassing 12 to 45 amino acid (aa) residues, representing what were predicted by computer analysis to be the most hydrophilic and antigenic regions of ETA. These synthetic peptides were injected into rabbits for antibody production. Different groups of rabbits were immunized with a combination of peptides, with each combination representing one of the three distinct domains of ETA. Animals immunized with various peptide combinations produced peptide-specific antibodies that exhibited cross-reactivity to ETA. Two major epitopes were identified on the ETA molecule by experiments with peptide-specific antibodies in enzyme-linked immunosorbent assay and immunoprecipitation. One of these epitopes was located in the translocation domain (II) (aa 297 to 310), while the other was mapped to the last 13 aa residues at the carboxy-terminal end of the enzymatic domain (III) (aa 626 to 638). Of these two regions, the epitope in the enzymatic domain induced a much higher level of neutralizing antibodies that abrogated the cytotoxic activity of ETA in vitro. Antibodies to this epitope blocked the ADP-ribosyltransferase activity of ETA and appeared to interfere with binding of the substrate elongation factor 2 to the enzymatic active site of the ETA molecule. We conclude that polyclonal, as well as monoclonal, antibodies to short peptides, representing small regions of ETA, may have therapeutic potential in passive immunization or topical treatment of burn patients infected with toxin-producing strains of P. aeruginosa.

3T3 Cells↗

The use of aztreonam as an alternate therapy for multi-resistant Pseudomonas aeruginosa.

The emergence of multi-resistant Gram-negative bacteria has created a most alarming clinical situation. The armamentarium of antibiotics used against this group of organisms is rapidly being depleted. Our routine therapeutic approach to control and prevent these Gram-negative bacteria from gaining a foothold was the empirical use of an aminoglycoside combined with piperacillin. However, aminoglycoside resistance is now routine rather than unusual. We evaluated the role of the monobactam aztreonam in burn wound infections and compared it to the aminoglycosides amikacin and gentamicin as well as piperacillin for the Enterobacteriacae and Pseudomonas aeruginosa. A total of 1274 Gram-negative isolates including P. aeruginosa were evaluated for susceptibility to the above-mentioned antibiotics from January 1995 to August 1995 (Table I). Among the Enterobacteriacae, aztreonam was more effective than amikacin and piperacillin (58.4 per cent vs. 45.8 per cent, respectively). However, it still fluctuated among the Enterobacteriacae as did the aminoglycosides. One major significant finding was that while susceptibility to aztreonam was variable for the Enterobacteriacae, P. aeruginosa remained 90 per cent susceptible to aztreonam and 90 per cent susceptible to piperacillin, whereas it was 79 per cent resistant to the aminoglycosides. Consequently, when choosing an antimicrobial in a suspected P. aeruginosa burn wound infection, aztreonam and piperacillin should be considered as the first line of defense.

Aminoglycosides↗

Containment of a multiresistant Serratia marcescens outbreak.

A 3-year-old male from Bolivia who sustained a full-thickness 80 per cent TBSA burn complicated by smoke inhalation on the 28 March 1995 was admitted to our burn centre on 6 April 1995. On 11 April the patient's wounds were colonized with a Serratia marcescens sensitive only to ciprofloxacin and imipenem. Sputum cultures revealed the same phenotypic S. marcescens. Two patients who were admitted days later had the same phenotypic S. marcescens. Their TBSA burns ranged from 54 to 80 per cent. Both were injured in early April. Sputum and wound cultures were also positive for S. marcescens. Precautionary measures were instituted immediately. All potential reservoirs were cultured. Cultures were negative for S. marcescens. Patient therapy was maintained via strict isolation. The first patient died on 17 May. The two remaining patients survived and were discharged colonized with S. marcescens. However, the biotype of the initial S. marcescens was different from the latter two. Early recognition of a multiresistant S. marcescens resulted in negating the spread of this agent to other patients.

Adolescent↗

Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model.

PURPOSE: Many systemic and topical therapeutic agents such as growth hormone, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF) have been used as vulnerary agents. However, the role of nitric oxide (NO) as a wound-healing stimulant has been received with mixed reviews. NO is a potent vasodilator that is thought to be an endothelium-dependent relaxing factor, and a regulator of blood pressure and regional blood flow. It affects vascular smooth muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Therefore we compared the effects of several topical substances that have similar or reverse properties. METHODS: Using the excisional rat wound model, we evaluated the topical effects of Dermaide Aloe (D-Aloe, Dermaide Research Corp, Palos Heights, IL), nitroglycerin, Aquaphor (Beuersdorf, Inc., Norwalk, CT) alone, with D-Aloe with nitroglycerin, 2%, and L-NAME (NO inhibitor) with Aquaphor, and L-NAME with Aquaphor and D-Aloe for a 21-day period. All wounds were measured by planimetry at 1, 7, 10, 13, 16, 18, and 21 days. RESULTS: At day 1, all wounds had an average wound size of 2.27 cm2 (SD +/- 0.372) with no significant difference in wound size among the groups. Topically applied D-Aloe appeared to promote wound healing faster than the remaining other topicals (p < .05, Student-Newman-Keuls and Dunn's Method) over the study period. However, topicals combined with D-Aloe, the vehicle Aquaphor, and L-NAME improved the wound healing process when compared with nitroglycerin alone (p < .05). CONCLUSIONS: D-Aloe appears to have a wound-healing advancement factor that can reverse the effects of petrolatum- and nitroglycerin-based products as observed in the remaining groups when compared with nitroglycerin alone. It appears that D-Aloe's effect of preventing dermal ischemia by reversing the effects of thromboxane synthetase (TxA2) may act synergistically with NO or could be an oxygen radical scavenger.

Administration, Topical↗