Jeffrey W. Shupp

Identification of a Transcytosis Epitope on Staphylococcal Enterotoxins

ABSTRACT Staphylococcal enterotoxins (SE) are exoproteins produced by Staphylococcus aureus that act as superantigens and have been implicated as a leading cause of food-borne disease and toxic shock. Little is known about how these molecules penetrate the gut lining and gain access to both local and systemic immune tissues. To model movement in vitro of staphylococcal enterotoxins, we have employed a monolayer system composed of crypt-like human colonic T-84 cells. SEB and SEA showed comparable dose-dependent transcytosis in vitro, while toxic shock syndrome toxin (TSST-1) exhibited increased movement at lower doses. Synthetic peptides corresponding to specific regions of the SEB molecule were tested in vitro to identify the domain of the protein involved in the transcytosis of SE. A toxin peptide of particular interest contains the amino acid sequence KKKVTAQELD, which is highly conserved across all SE. At a toxin-to-peptide ratio of 1:10, movement of SEB across the monolayers was reduced by 85%. Antisera made against the SEB peptide recognized native SEB and also inhibited SEB transcytosis. Finally, the conserved 10-amino-acid peptide inhibited transcytosis of multiple staphylococcal enterotoxins, SEA, SEE, and TSST-1. These data demonstrate that this region of the staphylococcal enterotoxins plays a distinct role in toxin movement across epithelial cells. It has implications for the prevention of staphylococcal enterotoxin-mediated disease by design of a peptide vaccine that could reduce systemic exposure to oral or inhaled superantigens. Since the sequence identified is highly conserved, it allows for a single epitope blocking the transcytosis of multiple SE.

Critical Review of Burn Depth Assessment Techniques: Part I. Historical Review

The assessment of burn depth, and as such, the estimation of whether a burn wound is expected to heal on its own within 21 days, is one of the most important roles of the burn surgeon. A false-positive assessment and the patient faces needless surgery, a false-negative one and the patient faces increased length of stay, risks contracture, and hypertrophic scar formation. Although many clinical signs can aid in this determination, accurate assessment of burn depth is possible only 64 to 76% of the time, even for experienced burn surgeons. Through the years, a variety of tools have become available, all attempting to improve clinical accuracy. Part 1 of this two-part article reviews the literature supporting the different adjuvants to clinical decision making is, providing a historical perspective that serves as a framework for part 2, a critical assessment of laser Doppler imaging.

Critical Review of Burn Depth Assessment Techniques: Part II. Review of Laser Doppler Technology

The judgment of which wounds are expected to heal within 21 days is one of the most difficult and important tasks of the burn surgeon. The quoted accuracy of 64 to 76% by senior burn surgeons underscores the importance of an adjunct technology to help make this determination. A plethora of techniques have been developed in the last 70 years. Laser Doppler imaging (LDI) is one of the most recent and widely studied of these techniques. The technology provides an estimate of perfusion through the burn wound, the assumption being that a lower perfusion correlates with a deeper wound and, therefore, a longer time to heal. Although some reports suggest accuracy between 96 and 100% and that it does this 2 days ahead of clinical judgment, others have questioned its applicability to clinical practice. This article, the second of a two-part series, has two objectives: 1) a review of the Doppler principle and how the LDI uses it to estimate perfusion; and 2) a critical assessment of the burn literature on the LDI. Part I provides a historical perspective of the different technologies used through the last 70 years to assist in the determination of burn depth. Laser Doppler has brought technology closer to provide a reliable adjuvant to the clinical prediction of healing, yet, caution is warranted. A clear understanding of the limitations of LDI is needed to put the current research in perspective to find the right clinical application for LDI.

An Open, Parallel, Randomized, Comparative, Multicenter Study to Evaluate the Cost-Effectiveness, Performance, Tolerance, and Safety of a Silver-Containing Soft Silicone Foam Dressing (Intervention) vs Silver Sulfadiazine Cream

An open, parallel, randomized, comparative, multicenter study was implemented to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (Mepilex Ag) vs silver sulfadiazine cream (control) in the treatment of partial-thickness thermal burns. Individuals aged 5 years and older with partial-thickness thermal burns (2.5–20% BSA) were randomized into two groups and treated with the trial products for 21 days or until healed, whichever occurred first. Data were obtained and analyzed on cost (direct and indirect), healing rates, pain, comfort, ease of product use, and adverse events. A total of 101 subjects were recruited. There were no significant differences in burn area profiles within the groups. The cost of dressing-related analgesia was lower in the intervention group (P = .03) as was the cost of background analgesia (P = .07). The mean total cost of treatment was

A polarized multispectral imaging system for quantitative assessment of hypertrophic scars.

309 vs

Novel application of a spatial frequency domain imaging system to determine signature spectral differences between infected and noninfected burn wounds.

513 in the control (P < .001). The average cost-effectiveness per treatment regime was

Catechol-O-Methyltransferase Genotype Predicts Pain Severity in Hospitalized Burn Patients

381 lower in the intervention product, producing an incremental cost-effectiveness ratio of

Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis

1688 in favor of the soft silicone foam dressing. Mean healing rates were 71.7 vs 60.8% at final visit, and the number of dressing changes were 2.2 vs 12.4 in the treatment and control groups, respectively. Subjects reported significantly less pain at application (P = .02) and during wear (P = .048) of the Mepilex Ag dressing in the acute stages of wound healing. Clinicians reported the intervention dressing was significantly easier to use (P = .03) and flexible (P = .04). Both treatments were well tolerated; however, the total incidence of adverse events was higher in the control group. The silver-containing soft silicone foam dressing was as effective in the treatment of patients as the standard care (silver sulfadiazine). In addition, the group of patients treated with the soft silicone foam dressing demonstrated decreased pain and lower costs associated with treatment.

Commercially available topical platelet-derived growth factor as a novel agent to accelerate burn-related wound healing.

Hypertrophic scars (HTS) are a pathologic reaction of the skin and soft tissue to burn or other traumatic injury. Scar tissue can cause patients serious functional and cosmetic issues. Scar management strategies, specifically scar assessment techniques, are vital to improve clinical outcome. To date, no entirely objective method for scar assessment has been embraced by the medical community. In this study, we introduce for the first time, a novel polarized multispectral imaging system combining out-of-plane Stokes polarimetry and Spatial Frequency Domain Imaging (SFDI). This imaging system enables us to assess the pathophysiology (hemoglobin, blood oxygenation, water, and melanin) and structural features (cellularity and roughness) of HTS. To apply the proposed technique in an in vivo experiment, dermal wounds were created in a porcine model and allowed to form into scars. The developed scars were then measured at various time points using the imaging system. Results showed a good agreement with clinical Vancouver Scar Scale assessment and histological examinations.

Outcomes from Burn Injury—Should Decreasing Mortality Continue to be Our Compass?

Complications of infection can increase burn-related morbidity and mortality. Early detection of burn wound infection could lead to more precise and effective treatment, reducing systemic complications and the need for long-term, broad-spectrum intravenous antibiotics. Quantitative cultures from biopsies are the accepted standard to determine infection. However, this methodology can take days to yield results and is invasive. This investigation focuses on the use of noninvasive imaging to determine the infection status of burn wounds in a controlled in vivo model. Full-thickness burn wounds were created on the dorsum of adult male rats (n = 6). Twenty-four hours after burn wound creation, wounds in the “Infected” group were inoculated with a vehicle containing 1 × 108 colony forming unit Staphylococcus aureus. “Control” group animals received vehicle alone. Subsequently, the wounds were imaged daily for a total of 10 days and the differences of skin optical properties were assessed using spatial frequency domain imaging at 16 different wavelengths from 500 to 700 nm. Regions of interest on the resulting images were selected and averaged at each time point. Statistically significant differences in average absorption and reduced scattering coefficients (&mgr;a and &mgr;s′) at 620 and 700 nm were observed between the two groups (P < .05). Differential optical properties were most evident by day 4 and persisted throughout the time course. Differential signature changes in optical properties are evident in infected burn wounds. This novel application of spatial frequency domain imaging may prove to be a valuable adjunct to burn wound assessment. Further work will be aimed at determining dose–response relationships and prokaryotic species differences.