From cholera to burns: a role for oral rehydration therapy.

According to the practice guidelines of the American Bum Association on burn shock resuscitation, intravenous (i.v.) fluid therapy is the standard of care for the replacement of fluid and electrolyte losses in burn injury of > or = 20% of the total body surface area. However, in mass burn casualties, i.v. fluid resuscitation may be delayed or unavailable. Oral rehydration therapy (ORT), which has been shown to be highly effective in the treatment of dehydration in epidemics of cholera, could be an alternate way to replace fluid losses in burns. A prospective case series of three patients was carried out as an initial step to establish whether oral Ceralyte 90 could replace fluid losses requiring i.v. fluid therapy in thermal injury. The requirement of the continuing i.v. fluid therapy was reduced by an average of 58% in the first 24 hours after the injury (range 37-78%). ORT may be a feasible alternative to i.v. fluid therapy in the resuscitation of burns. It could also potentially save many lives in mass casualty situations or in resource-poor settings where i.v. fluid therapy is not immediately available. Further studies are needed to assess the efficacy of this treatment and to determine whether the present formulations of ORT for cholera need modification.

Specimen Collection for Translational Studies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

Epidermal aquaporin-3 is increased in the cutaneous burn wound.

INTRODUCTION: Aquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing. However, the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We sought to assess the expression of AQP-3 in patients with burn wounds. METHODS: A fresh full thickness biopsy sample was taken from the center of the burn wound, the burn wound edge, and the graft donor site in 7 patients (n=21), approximately 3-7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3 specific antibody and examined by immunofluorescence. Fresh samples were processed to quantify AQP-3 protein expression with Western blot analysis. RESULTS: The central portion of the burn wound revealed destruction of the epidermis and dermis with no AQP-3 present. Along the burn wound edge where the epidermal architecture was disrupted, there was robust AQP-3 staining. Western blot analysis demonstrated deeper staining along the burn wound edge compared to unburned skin (control). Quantification of the protein shows a significant amount of AQP-3 expression along the burn wound edge (3.6±0.34) compared to unburned skin (2.1±0.28, N=7, *p<0.05). There is no AQP-3 expression in the burn wound center. CONCLUSION: AQP-3 expression is increased in the burn wound following injury. While its role in wound healing has been defined, we report for the first time the effect of cutaneous burns on AQP-3 expression. Our data provides the first step in determining its functional role in burn wounds. We hypothesize that development of AQP3 targeted therapies may improve burn wound healing.

Calcitonin gene-related peptide improves skin flap survival and tissue inflammation.

The effects of systemic administration of calcitonin gene-related peptide (CGRP) on survival and inflammation of experimental skin flaps subjected to prolonged arterial ischemia were studied. An island groin flap was elevated in the rat. The femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a group of 10 sham-operated control animals, the femoral artery was not occluded. After ischemia, blood flow was restored and flap survival evaluated at day 7. Following 12 h of ischemia, three flaps (30%) survived, compared with 100% survival of the control group. In the second part of the study the effects of CGRP on flap survival were assessed. Eighty flaps were rendered ischemic for 12 h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or saline (control) at the end of the ischemia period. Administration of CGRP (10(-7) M) significantly increased the number of flaps surviving compared with the control. The effect of systemic pretreatment of the animals with the CGRP receptor antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Flap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected to arterial ischemia for 12 h, and received systemic CGRP (10(-7) M), or saline at the end of the period of ischemia. The animals were sacrificed at 24 h and flap tissue samples were obtained. Myeloperoxidase (MPO) analysis was used as marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h MPO accumulation in the flap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increase of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on survival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.

Reduced antimicrobial peptide expression in human burn wounds.

Severely burned skin ceases to perform its natural protective role and surrenders itself as a nidus and portal for bacterial invasion. Antimicrobial peptides are part of a non-specific chemical defence system, separate from cellular and humoral immunity. Two of these peptides, human beta-defensins 1 and 2 have been recently found in skin and are produced by keratinocytes. Beta defensins have potent bactericidal activity against a wide spectrum of bacterial and fungal organisms commonly responsible for burn wound infections. To date, expression of beta defensins has not been examined in the human burn wound. Our findings demonstrate that expression of hBD-2 is greatly decreased in the burn wound whereas hBD-1 appears to be preserved. These results may have important implications in the pathogenesis and treatment of invasive burn sepsis.

Human beta defensin is absent in burn blister fluid.

Defensins are a family of cationic antimicrobial peptides that participate in innate host defence. Human beta defensin-2 (HBD-2) is produced by human keratinocytes, and has a potent bactericidal activity against a wide spectrum of microorganisms. We have recently shown that expression of HBD-2 is present in normal skin and lost in the full-thickness burn wound. Defensins have been found in the blister fluid of chronic wounds. Our study was designed to examine blister fluid from partial-thickness burns for defensin content. Fluid from five patients was collected from partial-thickness burn blisters, and then analysed by sandwich Enzyme-Linked Immunosorbent Assay (ELISA) with a monoclonal antibody and rabbit polyclonal antibody to HBD-2. The assay was validated against a Western blot assay for HBD-2 in samples of bronchoalveolar lavage fluid from patients with inflammatory lung disease. No HBD-2 was detectable in any of the burn blister fluids analysed. HBD-2 is lost in the full-thickness burn wound, and we have now demonstrated its absence in burn blister fluid. This finding represents evidence of a host defence defect within the burn wound and suggests a possible therapeutic role for antimicrobial peptides in the management of burn wounds.

The Burn Wheel: a practical guide to fluid resuscitation.

During preparation for mass casualties of burn victims in the Gulf War (1990-91), a 'Battlefield Burns Table' was devised to allow rapid calculation of fluid replacement. By standardizing weights and using only Hartmann's Solution BP, a regimen could be prescribed by the non-specialist without resort to mathematical calculations. By means of a revolving disc, this has now been refined for use in a civilian setting where expert burn advice may not be immediately available.

Inducibility of HBD-2 in acute burns and chronic conditions of the lung.

The respiratory tract produces a number of molecules that act in the first line of host defense to protect against pathogenic colonization and tissue invasion. Most of the innate antimicrobial activity can be attributed to airway fluid proteins, such as lysozyme, lactoferrin, and secretory leukoproteinase inhibitor, and peptides, such as defensins. Human beta-defensins are cationic antimicrobial peptides with broad and potent microbicidal activity that have been shown to play a role in protecting the healthy lung from infection. To determine the effect of thermal injury on the production of the inducible beta-defensin, human beta-defensin-2 (HBD-2), we measured the concentration of HBD-2 by Western blot analysis in bronchoalveolar lavage samples from the lungs of burned patients with and without inhalation injury. Our data demonstrates an increased amount of HBD-2 in the pulmonary airways with thermal injury compared to normal lung. A further substantial increase in levels was noted in chronic lung conditions.

Venous ulcers: improved healing by iontophoretic administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide.

A study on the effects of iontophoretic administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide on the healing of venous stasis ulcers of the extremities was carried out on 66 patients. Two randomized groups of patients were compared, one receiving standard treatment plus iontophoresis of calcitonin gene-related peptide and vasoactive intestinal polypeptide, and the other receiving standard treatment plus placebo iontophoresis. Calcitonin gene-related peptide and vasoactive intestinal polypeptide were administered locally by iontophoresis for 20 min three times weekly for 12 weeks. To determine the effects of the two treatments, the percentage surface area of ulcer healed and the number of healed ulcers were compared after 2, 4, 6, 8, and 12 weeks of treatment. The results demonstrate that there were significant improvements of the healing process in the group treated with calcitonin gene-related peptide and vasoactive intestinal polypeptide when compared with placebo iontophoresis, and support the use of iontophoresis administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide in the treatment of venous ulcers.

A comparison of two different 2400 mOsm solutions for resuscitation of major burns.

The reduction of burn edema is a common goal in the resuscitation of patients with thermal injury. Initial infusion of a 2400 mOsm hypertonic 7.5% NaCl 6% dextran (HSD) has been shown to reduce volume needs, but elevated serum sodium levels limit the dose that can be safely used. This study tested the hypothesis that a 2400 mOsm solution of NaCl, amino acids, glucose, and 6% dextran (Isosal-D) would reduce similar volume requirements while maintaining normal plasma sodium levels. Hemodynamics, plasma sodium, fluid balance, and tissue water content were measured after an initial baseline period and during resuscitation of a large scald injury in 21 anesthetized sheep. Resuscitation was begun 30 minutes after the scald with infusion of 10 ml/kg of either lactated Ringer's (LR), Isosal-D, or HSD and was continued with LR to restore and maintain baseline oxygen delivery throughout the 8-hour period. Oxygen delivery, cardiac output, and mean arterial pressure were rapidly reestablished by all three solutions, although a persistent tachycardia was noted with Isosal-D. Net fluid requirements of both HSD (35 +/- 13 ml/kg) and Isosal-D (72 +/- 13 ml/kg) were significantly lower than in the LR group (203 +/- 39 ml/kg). Mean serum sodium increased 11 mEq with HSD to a peak after 4 hours of 152 +/- 5 mEq, whereas with LR sodium fell 7 mEq to 132 +/- 4. Isosal-treated animals had minimal change in serum sodium. HSD significantly decreased tissue water content in colon, liver, pancreas, and nonburned skin compared with LR, whereas Isosal-D reduced edema only in the colon. It is concluded that in this protocol Isosal-D was not as effective as HSD at reducing volume needs and edema and had unexpected chronotropic effects.

Field surgery on a future conventional battlefield: strategy and wound management.

Most papers appearing in the surgical literature dealing with wound ballistics concern themselves with wound management in the civilian setting. The pathophysiology of modern war wounds is contrasted with ballistic wounds commonly encountered in peacetime, but it should be noted that even in peacetime the modern terrorist may have access to sophisticated military weaponry, and that patients injured by them may fall within the catchment area of any civilian hospital. Management problems associated with both wound types are highlighted; areas of controversy are discussed. The orthodox military surgical approach to ballistic wounds is expounded and defended.

Emergency cricothyrotomy.

The indications for the ruling for the Gulf Forces that emergency cricothyrotomy is to be performed where the airway is thought to be compromised are reviewed. The advantages of this procedure are outlined and some of the likely consequences regarding the incidence of complications and their management predicted.

Management of service personnel with a history of penicillin allergy: discussion paper.

A false label of penicillin allergy may have important consequences for wartime medical evacuation. This article outlines the antibiotic protocol for war wounds, the current status of tests to diagnose true penicillin allergy and suggests a strategy for the management of personnel with a history of such allergy.

Acetic acid used for the elimination of Pseudomonas aeruginosa from burn and soft tissue wounds.

Acetic acid was used topically at concentrations of between 0.5% and 5% to eliminate Pseudomonas aeruginosa from the burn wounds or soft tissue wounds of 16 patients. In-vitro studies indicated the susceptibility of P. aeruginosa to acetic acid; all strains exhibited a minimum inhibitory concentration of 2 per cent. P. aeruginosa was eliminated from the wounds of 14 of the 16 patients within two weeks of treatment. Acetic acid was shown to be an inexpensive and efficient agent for the elimination of P. aeruginosa from burn and soft tissue wounds.

Liposarcoma of the cord presenting at vasectomy counselling.

A case of liposarcoma of the cord is reported in a patient presenting for vasectomy. This paper discusses such tumours and illustrates the importance of a careful clinical examination during counselling.

PIP: A case of liposarcoma, a rare malignancy of lipoblasts derived from mesenchyme, in a 36-year old man applying for vasectomy is described. The subject reported nagging scrotal pain for 14 years. Examination revealed a soft mass above the left testis, thought to be an epididymal cyst. During exploration under general anesthesia, a partly encapsulated fatty lesion was found encircling the testis and the cord. The tumor was dissected and excised. Some parts of the tumor resembled a vascular lipoma, others contained multivesiculated primitive cells and hyperchromatic multi-nucleated and granular lipoblasts. The man was treated with left radical orchidectomy with high ligation of the cord 10 days later, and biopsies of lymph nodes, retroperitoneal fat and skin were taken for examination. He has remained recurrence free for 4 years by CT scans. This case dramatizes the need to consider paratesticular tumors in any case of a mass found in a vasectomy candidate.

Current Insights into the role of HIF-1 in cutaneous wound healing.

Hypoxia Inducible Factor-1 (HIF-1) is considered the major coordinator of the cellular adaptive response to hypoxia. Over recent years, its activity in the context of wound healing has been the object of increasing investigation. On the molecular level, HIF-1 transcriptional target products have been shown to regulate the process of endothelial cell survival, migration and proliferation (VEGF, ANGPT-1, ANGPT-2, ANGPT-4, FGF-2, PlGF, PDGF-B, RGC-32), vascular smooth muscle cell migration and proliferation (FGF-2, EGF, PDGF, thrombospondin) and mobilization of Circulating Angiogenic Cells to the periphery (SFD-1/CXCR4). Studies on the effect of HIF-1 on the expression and activity of extracellular cell matrix modifying enzymes, such as MMPs and prolidase, have been conducted in the context of tumor angiogenesis and metastasis, and have resulted in controversial findings. A growing body of evidence suggests that HIF-1 also affects reepithelialization of the wound bed, through increasing keratinocyte migration, but decreasing their proliferation. Diminished HIF-1 levels and activity have been documented in conditions of impaired wound healing, such as wound healing in aged and in diabetic mice. The increasing number of studies on the role of HIF-1 in wound healing, apart from answering certain questions, has also raised an equal number, if not more. Clarifying the topics that still remain unclear could introduce a new era of HIF-1 targeted management of a wide range of problematic wounds.