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Showing papers by "David G. Greenhalgh published in 1999"


Journal ArticleDOI
TL;DR: Nf1 is a key regulator of fibroblast responses to injury, and Nf1 mutation in mouse fibroblasts causes abnormalities characteristic of human neurofibromas, as well as abnormal response of mutant fibro Blasts to wound cytokines.

103 citations


Journal ArticleDOI
TL;DR: It is concluded that little matrix metalloproteinase‐9 activity (the gelatinase involved in early tissue repair) is present in keloids and hypertrophic scars, while matrix meetallop proteinase‐2 activity ( the gelatin enzyme involved in prolonged tissue remodeling) ispresent in donor skin and is significantly increased in hypertrophic scar levels.
Abstract: Keloids and hypertrophic scars are characterized by excessive deposition of collagen, which may result from insufficient protein degradation. Little is known about the levels of two gelatinases, matrix metalloproteinase-2 (72 kD type IV collagenase) and matrix metalloproteinase-9 (matrix metalloproteinase-9; 92 kD type IV collagenase) in these abnormal scars. The purpose of this study was to determine levels of these proteinases in tissue from hypertrophic scars, keloids, and donor skin. Ten hypertrophic scar samples, 9 keloid samples, and 10 donor skin samples were frozen, pulverized, homogenized, clarified by centrifugation, and analyzed for matrix metalloproteinases by quantitative zymography. Identity of matrix metalloproteinases was determined using a conditioned media reference standard, molecular weight ladders, and Western blotting. Levels of matrix metalloproteinase-9 activity were very low or undetectable in all samples. However, matrix metalloproteinase-2 activity was significantly elevated in keloids and hypertrophic scars vs. donor samples: 2.6 and 3.9-fold increases for latent matrix metalloproteinase-2, 7.8 and 6.9-fold increases for active matrix metalloproteinase-2, respectively. We conclude that little matrix metalloproteinase-9 activity (the gelatinase involved in early tissue repair) is present in keloids and hypertrophic scars, while matrix metalloproteinase-2 activity (the gelatinase involved in prolonged tissue remodeling) is present in donor skin and is significantly increased in hypertrophic scars and keloids.

93 citations


Journal ArticleDOI
TL;DR: Cutaneous wounding produces a HSP response in inflammatory cells, and expression of inducible HSP70 is delayed in diabetic mice, and this delay may be related to the impaired inflammatory response of diabetics, and may contribute to impaired wound healing.

63 citations


Journal ArticleDOI
TL;DR: Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance and its role in scar maturation also needs to be investigated.
Abstract: Objective The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. Methods The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. Results Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. Conclusion Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.

43 citations


Journal ArticleDOI
TL;DR: For this population, burn injury did not appear to impact outcome negatively as it related to a child's return or function in school, and these children returned to school rather rapidly after discharge and functioned as well or better after injury.
Abstract: Outcome measures have become an important tool to assist with monitoring the efficacy of burn care. One such measurement for children is the time required for them to return to school, as well as their behavior and academic performance in school after a burn injury. The purpose of this study was to relate demographic data with return-to-school time and school performance. Through medical record review and interviews with patients, parents, and school teachers, information was obtained regarding the patient's burn injury, as well as home and school status before and after the burn injury. School information before the burn injury was obtained after patient admission. Schools were contacted 6 months after hospital discharge for data after the burn injury. Thirty-four patients aged 6 to 16 years had their outcomes evaluated from September 1993 to June 1995. Average total body surface area burned was 25.9%; the mean area of full-thickness burn was 17.5%. Length of stay averaged 30.8 days. Sixty-five percent of patients were discharged with splints, and all were discharged with a pressure program. Children returned to school an average of 7.4 days after discharge, and the average number of missed school days was 22. Thirty-four percent of the children had a school reentry visit, and either a phone call, written material, or both were provided in lieu of a visit to the other schools. For this population, burn injury did not appear to impact outcome negatively as it related to a child's return or function in school. These children returned to school rather rapidly after discharge and functioned as well or better after injury. Little loss of grade was noted, and only those children with problems in school before the burn injury had problems after the burn injury. Contact with the child's school before reentry might have assisted with the smooth transition.

41 citations


Journal ArticleDOI
TL;DR: It was found that 12 patients (mean age, 30.3 months; range 6 to 69 months) were placed on ECLS because of profound pulmonary failure that was unresponsive to aggressive ventilatory support and the overall survival was 67%.
Abstract: Extracorporeal life support (ECLS) for pediatric burn patients is a viable option for respiratory failure that is unresponsive to maximal conventional therapy. No criteria have been identified that are predictive of the success of the use of ECLS for these patients. This article presents a retrospective review of the pediatric burn patients placed on ECLS at a single pediatric medical center. It was found that 12 patients (mean age, 30.3 months; range 6 to 69 months) were placed on ECLS because of profound pulmonary failure that was unresponsive to aggressive ventilatory support. The mean size of the burns of these patients was 50.2% of the total body surface area (average size of full-thickness burns, 41.8% total body surface area), with 6 patients having scald burns and 6 having flame burns. The overall survival was 67% (8 of 12). Nonsurvivors had greater positive end-expiratory pressure, mean airway pressure, peak inspiratory pressure, and oxygenation index before ECLS. It is felt that ECLS is a life-saving therapy for pediatric patients with thermal injury. Greater ventilator requirements before ECLS are associated with nonsurvival. Early institution of ECLS in pediatric burn patients with severe respiratory failure may prevent excessive barotrauma and thus discourage the onset of irreversible lung injury.

34 citations


Journal ArticleDOI
TL;DR: Two SIR models for the spread of infectious diseases are considered but with a time delay in the vaccination term, and numbers indicate that for diseases in human populations Hopf bifurcation is unlikely to occur at realistic parameter values if the death rate is a concave function of the population size.
Abstract: Two SIR models for the spread of infectious diseases which were originally suggested by Greenhalgh & Das (1995, Theor. Popul. Biol. 47, 129-179; 1995, Mathematical Population Dynamics: Analysis of Heterogeneity, pp. 79-101, Winnipeg: Wuerz Publishing) are considered but with a time delay in the vaccination term. This reflects the fact that real vaccines do not immediately confer permanent immunity. The population is divided into susceptible, infectious, and immune classes. The contact rate is constant in model I but it depends on the population size in model II. The death rate depends on the population size in both models. There is an additional mortality due to the disease, and susceptibles are vaccinated and may become permanently immune after a lapse of some time. Using the time delay as a bifurcation parameter, necessary and sufficient conditions for Hopf bifurcation to occur are derived. Numerical results indicate that that for diseases in human populations Hopf bifurcation is unlikely to occur at realistic parameter values if the death rate is a concave function of the population size.

32 citations


01 Jan 1999
TL;DR: In this paper, the authors present a retrospective review of the pediatric burn patients placed on ECLS at a single pediatric medical center and the overall survival was 67% (8 of 12).
Abstract: Extracorporeal life support (ECLS) for pediatric burn patients is a viable option for respiratory failure that is unresponsive to maximal conventional therapy. No criteria have been identified that are predictive of the success of the use of ECLS for these patients. This article presents a retrospective review of the pediatric burn patients placed on ECLS at a single pediatric medical center. It was found that 12 patients (mean age, 30.3 months; range 6 to 69 months) were placed on ECLS because of profound pulmonary failure that was unresponsive to aggressive ventilatory support. The mean size of the burns of these patients was 50.2% of the total body surface area (average size of full-thickness burns, 41.8% total body surface area), with 6 patients having scald burns and 6 having flame burns. The overall survival was 67% (8 of 12). Nonsurvivors had greater positive end-expiratory pressure, mean airway pressure, peak inspiratory pressure, and oxygenation index before ECLS. It is felt that ECLS is a life-saving therapy for pediatric patients with thermal injury. Greater ventilator requirements before ECLS are associated with nonsurvival. Early institution of ECLS in pediatric burn patients with severe respiratory failure may prevent excessive barotrauma and thus discourage the onset of irreversible lung injury.

28 citations


Journal ArticleDOI
TL;DR: The impact of general asymmetry in sexual behaviour between the sexes, subject to this group contact constraint, on the transient and long term behaviour of a HIV epidemic is examined.

13 citations


Journal ArticleDOI
TL;DR: A statistical method for identifying whether there are likely to be individuals repeatedly represented in the resulting data set, which is considered by birth year, using a partial ordering method that is especially useful for years where the number of birth years in the sample is too small for x2 tests to be used.
Abstract: Summary. Diagnoses of HIV infection are reported to the Public Health Laboratory Service (PHLS) AIDS Centre under a voluntary surveillance scheme. Names are not held in the data set, but the date of birth of the individual concerned is usually available. This paper describes a statistical method for identifying whether there are likely to be individuals repeatedly represented in the resulting data set, which is considered by birth year. A partial ordering method is used that is especially useful for years where the number of birth years in the sample is too small for x2 tests to be used. At the 5% level, one of the five birth years tested in the data supplied to us by the PHLS shows evidence of more replication than would be expected from independent random sampling from the population. The results are compared with an alternative maximum-likelihood-based test that reaches the same conclusions. Maximum likelihood methods are further used to estimate the percentage of overcounting of individuals in the sample at 2.7%.

3 citations


Journal ArticleDOI
TL;DR: A statistical method to detect repeated counting of individuals in HIV infection data and similar data based on the number of matching pairs in the sample is discussed.
Abstract: Diagnoses of HIV infection are reported to the Public Health Laboratory Service (PHLS) by microbiologists through a voluntary confidential surveillance scheme. Names are not recorded on the database but the date of birth of the individual concerned is usually available. This paper discusses a statistical method to detect repeated counting of individuals in these and similar data based on the number of matching pairs in the sample. The test is based on the theoretical result that the null hypothesis of all birth dates equally likely and all individuals distinct minimizes the expected number of matching pairs in the sample. Five of the 16 birth years in the sample taken in 1991 show evidence of more replication than would be expected by chance using a 5 per cent level test. When the test is repeated taking into account a small but statistically significant seasonal variation in the birth rate, the results are very similar.