Verapamil is Less Effective than Triamcinolone for Prevention of Keloid Scar Recurrence After Excision in a Randomized Controlled Trial.

A double-blind randomized controlled trial with a paired split-scar design compared verapamil, an L-type Ca2+ channel antagonist, and triamcinolone for prevention of keloid recurrence after excision. Ca2+ channel blocking activity of verapamil in keloid cells was explored. One keloid was excised per subject and each wound half randomized to receive intralesional injections of triamcinolone (10 mg/ml) or verapamil (2.5 mg/ml) at monthly intervals (4 doses). Interim analysis was performed after 14 subjects were completed. Survival analysis demonstrated significantly higher keloid recurrence with verapamil compared to triamcinolone 12 months post-surgery (log-rank test, p = 0.01) and higher overall risk of recurrence with verapamil (hazard ratio 8.44, 95% CI 1.62-44.05). The study was terminated early according to the stopping guideline (p < 0.05). Verapamil is safe but not as effective as triamcinolone in preventing keloid recurrence after excision. Further study is necessary to determine if clinical response to verapamil is linked to modulation of intracellular Ca2+.

A vaccine against rumen methanogens can alter the composition of archaeal populations.

The objectives of this study were to formulate a vaccine based upon the different species/strains of methanogens present in sheep intended to be immunized and to determine if a targeted vaccine could be used to decrease the methane output of the sheep. Two 16S rRNA gene libraries were used to survey the methanogenic archaea in sheep prior to vaccination, and methanogens representing five phylotypes were found to account for >52% of the different species/strains of methanogens detected. A vaccine based on a mixture of these five methanogens was then formulated, and 32 sheep were vaccinated on days 0, 28, and 103 with either a control or the anti-methanogen vaccine. Enzyme-linked immunosorbent assay analysis revealed that each vaccination with the anti-methanogen formulation resulted in higher specific immunoglobulin G titers in plasma, saliva, and rumen fluid. Methane output levels corrected for dry-matter intake for the control and treatment groups were not significantly different, and real-time PCR data also indicated that methanogen numbers were not significantly different for the two groups after the second vaccination. However, clone library data indicated that methanogen diversity was significantly greater in sheep receiving the anti-methanogen vaccine and that the vaccine may have altered the composition of the methanogen population. A correlation between 16S rRNA gene sequence relatedness and cross-reactivity for the methanogens (R(2) = 0.90) also exists, which suggests that a highly specific vaccine can be made to target specific strains of methanogens and that a more broad-spectrum approach is needed for success in the rumen. Our data also suggest that methanogens take longer than 4 weeks to adapt to dietary changes and call into question the validity of experimental results based upon a 2- to 4-week acclimatization period normally observed for bacteria.

Surgeons and scars: differences between patients and surgeons in the perceived requirement for reconstructive surgery following burn injury.

BACKGROUND: Reconstruction of the burn patient presents a challenge to the burns surgeon. The variety of issues and the timing of surgery can be a daunting task. A group of 11 patients who were injured 1 year previously at the time of the Bali bomb blast were reviewed. METHODS: A customised assessment form was developed in order to quantify the patient's perceived need for reconstruction. Each patient was asked to prioritise, in order of preference any injured area they might consider for further surgery. These patients were then assessed independently by a consultant plastic and reconstructive surgeon and a senior trainee, using an identical form. The surgeons were asked to prioritise, in order of preference any area they might consider for further surgery and to indicate from a list the procedure they would employ. This list ranged from simple excision to free flap encompassing the entire reconstructive ladder. RESULTS: The patients all showed a strong reluctance to undergo further reconstruction. However there was a strong correlation between the surgeons, concurring on issues of function but there were discrepancies regarding "aesthetic" reconstruction. CONCLUSIONS: This study highlights the absolute need for secondary burns reconstruction to be a patient driven service.

Determinants of burn first aid knowledge: Cross-sectional study.

INTRODUCTION: This study investigated demographic factors, experience of burn/care and first aid course attendance as factors influencing burn first aid knowledge. METHODS: A cross-sectional study was undertaken using convenience sampling of members of sporting and recreation clubs. The main outcome measure was the proportion of correct responses to multiple-choice questions relating to four burn scenarios: (1) scald, (2) contact burn, (3) ignited clothing, and (4) chemical burn. RESULTS: A total of 2602 responses were obtained. Large gaps (30-50% incorrect answers) were identified in burn first aid knowledge across all scenarios. 15% more individuals gave correct answers if they had attended a first aid course compared to those who had not (p<0.0001); this proportion increased if the course was undertaken within the previous five years (p<0.0001) or contained a burns-specific component (p<0.0001). Males and younger (≤25 years) and older (≥65 years) age-groups had relatively lower levels of burn first aid knowledge. Gender and age were significant predictors of first aid course attendance, with males and younger (≤25 years) and older (≥65 years) age-groups less likely to have attended a first aid course. CONCLUSION: In this sample, first aid training undertaken within the last 5 years with a specific burns component was associated with enhanced burn first aid knowledge.

The effect of nano-scale topography on keratinocyte phenotype and wound healing following burn injury.

Topographic modulation of tissue response is an important consideration in the design and manufacture of a biomaterial. In developing new tissue therapies for skin, all levels of architecture, including the nanoscale need to be considered. Here we show that keratinocyte phenotype is affected by nanoscale changes in topography with cell morphology, proliferation, and migration influenced by the pore size in anodic aluminum oxide membranes. A membrane with a pore size of 300 nm, which enhanced cell phenotype in vitro, was used as a dressing to cover a partial thickness burn injury in the pig. Wounds dressed with the membrane showed evidence of advanced healing with significantly less organizing granulation tissue and more mature epidermal layers than control wounds dressed with a standard burns dressing. The results demonstrate the importance of nanoscale topography in modulating keratinocyte phenotype and skin wound healing.

A preliminary investigation of the reinnervation and return of sensory function in burn patients treated with INTEGRA®.

BACKGROUND: Loss of sensory function in scar after burn is common, although the basis for this loss is not clear. Additionally, little is known about the effects of different treatment modalities on sensory function and neuroanatomical outcomes in burn patients. Here, we investigated the effects of the use of the INTEGRA(®) dermal scaffold on neuroanatomy and sensory function in acute burn patients. HYPOTHESIS AND OBJECTIVES: We hypothesized that the use of artificial dermal templates would inhibit or reduce reinnervation after excision, since regrowth of nerves requires complex molecular interactions. Therefore the primary objective of this study was to identify whether there is regrowth of nerve fibres in the INTEGRA(®) dermal scaffold. The secondary objective was to identify whether the INTEGRA(®) dermal scaffold reduced nerve regrowth or limited sensory function outcomes in acute burn patients. METHODS: Five patients treated with INTEGRA(®), cultured epithelial autograft spray (prepared using ReCell(®) (CEA)) and split skin graft (SSG) were assessed for sensory function in scar and uninjured contralateral control skin. Neuroanatomy of scar and control sites was assessed using immunohistochemistry for PGP9.5, CGRP and substance P neuronal markers. Nerve density and sensory function was also assessed in a comparative group (n=8) treated with CEA and SSG only. RESULTS: Neuroanatomy was not significantly different in the INTEGRA(®) patients when compared to the CEA/SSG group only. The patients treated with INTEGRA(®) had worse sensory function than those with CEA/SSG only. CONCLUSIONS: Peripheral nerves do reinnervate the INTEGRA(®) dermal scaffold. There is no statistically significant reduction in reinnervation observed when compared to a control group. It is possible that the use of artificial dermal constructs, while permissive for nerve regrowth, limit functionality when compared to nerves that regrow through dermal tissue. Further research to understand the causes of this, and into enhancing reinnervation in dermal scaffolds may improve sensory outcome in the most severely burned patients.

Changes in cutaneous innervation in patients with chronic pain after burns.

BACKGROUND: Chronic pain is a common occurrence for burn patients and has significant impact on quality of life. However, the etiology is not well understood. Understanding the mechanisms underlying the restoration of sensory function and the development of chronic pain after burn is critical to improving long-term outcomes. OBJECTIVE: To determine whether cutaneous innervation in burn patients with chronic pain is altered when compared to patients without chronic pain. METHODS: Twelve patients with unilateral injury and who reported chronic pain were recruited. Each patient underwent sensory function testing and both scar and matched site uninjured skin biopsy. Biopsies were analyzed for total nerve density and nociceptive C-fiber density using immunohistochemistry. Results were compared to a control group of 33 patients with unilateral injury and no reported long-term pain. RESULTS: Sensory function was significantly diminished in scar compared to uninjured tissue in both study groups, but chronic pain patients did not have significantly diminished function when compared to control. Total nerve density was not significantly different between scar and uninjured sites in either group, or between groups. However, the density of nociceptive nerve fibers was significantly elevated in both uninjured (p=0.0193) and scar sites (p=0.0316) of the patients with chronic pain when compared to the control group. CONCLUSIONS: This data suggests that differences in cutaneous innervation may contribute to chronic pain after burn. There also appears to be a systemic difference in cutaneous innervation extending to distal uninjured sites. Therefore efforts to affect cutaneous reinnervation after burn may lead to less patients experiencing chronic pain.

Patterns of burn injury in the preambulatory infant.

INTRODUCTION: This study was undertaken after an increasing trend in young babies presenting with severe burns was observed in Princess Margaret Hospital (PMH) in Perth, Western Australia. The aim was to explore the patterns of these injuries with a view to identifying whether they could be prevented with better parent education. METHOD: Inclusion criteria was infants under 6 months of age who sustained a burns injury requiring admission or out-patient treatment in the Burns Unit of PMH between July 2005 and September 2007. RESULTS: Immobile infants are at significant risk of burns. In infants who are not yet mobile, environmental factors are commonly implicated, with the vast majority of burns sustained in the home. The mechanisms of injuries were scalds (43%), contact burns (39%), sunburn (11%) and TPN burns in premature infants in NICU (7%). TBSA ranged from <0.5% to 30%. CONCLUSION: Infants less than 6-month-old are at significant risk of burn; at this age the injury is usually caused by hazards in the home environment. These infants are vulnerable to inadequate first aid and require a large amount of follow-up care. Better parental education may help reduce the number of injuries we see in this age group.

Reponses of sheep to a vaccination of entodinial or mixed rumen protozoal antigens to reduce rumen protozoal numbers.

Two rumen protozoa vaccine formulations containing either whole fixed Entodinium or mixed rumen protozoa cells were tested on Merino sheep with the aim of decreasing the number and/or activity of protozoa in the rumen. Negative control (no antigen) and positive control (Tetrahymena corlissi antigens) treatments were also included in the experiment. Blood and saliva were sampled to measure the specific immune response. Protozoal numbers in the rumen were monitored by microscopic counts. Vaccination with protozoal formulations resulted in the presence of specific IgG in plasma and saliva, but saliva titres were low. Titres after secondary vaccination were higher (P 0.05) by the vaccination and there was also no difference (P>0.05) between treatments in rumen fluid ammonia-N concentration or wool growth. In vitro studies investigated the binding ability of the antibodies and estimated the amount of antibody required to reduce cell numbers in the rumen. The studies showed that the antibodies did bind to and reduced protozoa numbers, but the amount of antibody generated by vaccination was not enough to produce results in an in vivo system. It is suggested that the vaccine could be improved if specific protozoal antigens are determined and isolated and that improved understanding of the actions of protozoa antibodies in rumen fluid and the relationships between levels of antibodies and numbers of protozoa in the rumen is needed.