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Biomedical subjects

David G Greenhalgh

Publications and source records attributed to David G Greenhalgh.

At least 37 records · Page 2Linked to original sources
PubMed2003

Alterations in the expression and modification of histones in the liver after injury.

Chromatin remodeling plays a key role in the transcriptional activation of regulatory factors in the liver in response to a variety of stress signals. The effects of burn injury on histone expression and its modification were investigated in this study. Liver tissues collected after a flame burn injury were subjected to RT-PCR and Western blot analyses of histone regulation. There was a marked induction of histone H3-D variant mRNA at 3 and 6 h. In contrast, histone H2A.2 variant mRNA had a downregulation at 3 days. No apparent changes were noted in other histone variants examined. Western blot analysis revealed a downregulation of all 5 histone subtypes (H1, H2A, H2B, H3, and H4) at 1 day and there was a subsequent induction of H1 and H2A subtypes at 3 days after injury. There was an induction of modified forms (phospho-, acetyl-, and dimethyl-) of histone H3 subtype at day 3. Furthermore, a transient elevation in PCNA (proliferating cell nuclear antigen) levels was apparent in the liver at day 3, which parallels the induction of phospho-histone H3, which is a mitosis marker. These findings suggest that histones participate in a cascade of events associated with phenotypic alterations in the liver after injury.

Animals↗
PubMed2003

Wound healing and diabetes mellitus.

Diabetes mellitus is one of the major contributors to chronic wound healing problems. When diabetic patients develop an ulcer, they become at high risk for major complications, including infection and amputation. The pathophysiologic relationship between diabetes and impaired healing is complex. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. Despite treatment of these chronic wounds, which involves tight glucose control and meticulous wound care, the prognosis for their healing is quite poor. Newer modalities that deliver natural or engineered growth factors show a great deal of promise. All of the studies clearly show the continued need for well-controlled clinical trials.

Chronic Disease↗
PubMed2003

Burn injury-mediated alterations in cell cycle progression in lymphoid organs of mice.

A key event in the cellular and molecular pathogenesis of multiple organ failure (MOF) after burn injury may be the change in profiles of the cell cycle progression in affected organs. We investigated the effects of burn injury on cell cycle progression in immune organs. Cell cycle analysis in the lymphoid tissues of mice after 18% burn injury revealed that S phase entry was temporarily arrested in the thymus 1 day after injury, whereas the spleen had substantially increased S phase entry at day 8. This mode of cell cycle regulation was reproduced in different age groups and strains of mice. Furthermore, the reactivity to the Ki-67 antibody (indicative of proliferation) was markedly reduced in the thymic cortex at day 1. There was a distinct pattern of hematopoietic foci formation and increased reactivities to the Ki-67 antibody in myelogenous cells in the red pulp of spleen at day 7, consistent with the elevated S phase entry. These data suggest that differential regulation of cell cycle progression may play a crucial role in the phenotypic changes in immune organs after burn injury.

Animals↗
PubMed2002

Burn-induced thymic apoptosis corresponds with altered TGF-beta(1) and Smad 2/3.

Immune suppression is a common complication of injury. Transforming growth factor-beta(1) (TGF-beta(1)), a cytokine with diverse anti-inflammatory and anti-apoptotic effects, may play an important role. Smad 2 and Smad 3 are transcription factors that mediate the effects of TGF-beta(1). We hypothesized that burn-induced immunosuppression would be accompanied by increased apoptosis in lymphoid organs, a change likely associated with changes in TGF-beta(1) and Smad 2/3 expression. Mice were subjected to 18% body surface area flame burn. Lymph nodes, spleen, and thymus were harvested at multiple time points after injury. TGF-beta(1) and Smad 2/3 expression and levels of apoptosis were determined in whole tissue and in sorted T-cells by flow cytometry, RT-PCR, ELISA, and Western blot. TGF-beta(1) protein expression in the thymus increased from 1 to 7 days. Smad 2/3 protein expression was decreased at the same time points. This down-regulation was more dramatic in the non-T-cells than in the T-cells themselves. RT-PCR confirmed down-regulation of Smad 3 mRNA in the thymus from 3 to 6 h. Apoptosis in the thymus doubled at 1 day (6.4% control vs 12.8% burned), which corresponded with a marked decrease in thymus mass on subjective assessment. No changes were observed in other lymphoid organs. Burn injury in mice increases TGF-beta(1) expression in the thymus, while suppressing expression of its intracellular mediator, Smad 2/3. This response is most pronounced in the non-T-cell tissue, which suggests the thymic epithelial cells may be responsible for the increased thymic apoptosis. This TGF-beta(1) and Smad 2/3 counterregulation in response to injury may represent a potential mechanism for postinjury immune suppression.

Animals↗
PubMed2002

Induction of murine AIDS virus-related sequences after burn injury.

To better understand the molecular signaling events leading to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF), changes in gene expression profiles after burn injury were investigated by differential display. C57BLKS/J mice were subjected to 18% total body surface area (TBSA) full-thickness burn and various tissues were harvested at multiple time points after injury. Initial differential display revealed that retroviral transcripts similar to the envelope sequence of murine AIDS (MAIDS) virus were rapidly and transiently up-regulated after injury. Subsequent RT-PCR and DNA sequencing analyses confirmed the transient up-regulation of retroviral sequences similar to those of the MAIDS virus. In addition, the presence and induction of the subgenomic envelope transcripts of these MAIDS virus-related sequences, including a novel double spliced message, were identified after burn injury. These data suggest that the transcriptional efficiency of the integrated retroviral DNA and reactivation of defective MAIDS virus-related sequences may be affected by pathophysiological signals, such as burn injury. The elevated expression of these MAIDS virus-related retroviral sequences may affect the transcriptional activities of the flanking genes at the integration sites and may be a cause of altered local and systemic immune responses to burn-related stress.

Animals↗
PubMed2002

Increased incidence of heater-related burn injury during a power crisis.

HYPOTHESIS: Recent power shortages in California resulted in rolling blackouts and increased utility prices. Residents turned to alternative heating devices, such as space heaters, to decrease utility bills. Our hypothesis is that the incidence of heater-related injuries increased owing to the use of alternative heating methods during the power crisis. DESIGN: Retrospective case-series database and medical record review of all burn admissions for the 4 months of November through February for the period 1998-2002. SETTING: Regional pediatric and adult burn unit in northern California. PATIENTS: Patients admitted during the study interval with burn injury. MAIN OUTCOME MEASURES: Parameters recorded included patient demographics, cause of burn, total body surface area burn, number of operative procedures, and hospital length of stay during each of the 4 months in the interval. RESULTS: A total of 512 patients were admitted during all 4-month intervals. During the power crisis there were significant increases in the number of hospital admissions (151 in 2000-2001 vs 117 in 1998-1999, 124 in 1999-2000, and 152 in 2001-2002) and heater-related burn admissions (36 in 2000-2001 vs 25 in 1998-1999, 26 in 1999-2000, and 29 in 2001-2002). The percentage total body surface area burn (mean +/- SEM, 24.0% +/- 4.6% in 2000-2001 vs 16.5% in 1998-1999, 12.3% in 1999-2000, and 12.0% in 2001-2002), hospital length of stay (15.0 days in 2000-2001 vs 9.9 days in 1998-1999, 12.3 days in 1999-2000, and 7.0 days 2001-2002), and the number of operations (55 in 2000-2001 vs 7 in 1998-1999, 18 in 1999-2000, and 19 in 2001-2002) also increased during the crisis. CONCLUSIONS: The number of heater-related burn admissions, as well as their magnitude, increased during the energy crisis, resulting in increased resource use and health care costs. The economic stresses of the power shortage had societal costs that extended far beyond the price of electricity.

Adult↗
PubMed2002

Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus.

Background. Patients with diabetic sensory neuropathy have significant risk of chronic ulcers. Insufficient nerve-derived mediators such as substance P (SP) may contribute to the impaired response to injury. Mutant diabetic mice (db/db), which develop neuropathy and have delayed healing, may provide a model to study the role of nerves in cutaneous injury.Methods. Skin from human chronic nonhealing ulcers and age-matched control skin was immunohistochemically evaluated for nerves. Nerve counts were also compared in murine diabetic (C57BL/KsJ-m+/+ Lepr(db); db/db) and nondiabetic (db/-) skin. Excisional wounds on the backs of db/db and db/- mice were grouped as: (a) untreated db/- mice; (b) untreated db/db mice; (c) db/db mice with polyethylene glycol (PEG); (d) db/db mice with PEG and SP 10(-9) M; or (e) db/db mice with PEG and SP 10(-6) M.Results. We demonstrated fewer nerves in the epidermis and papillary dermis of skin from human subjects with diabetes. Likewise, db/db murine skin had significantly fewer epidermal nerves than nondiabetic littermates. We confirmed increased healing times in db/db mice (51.7 days) compared to db/- littermates (19.8 days; P </= 0.001). SP 10(-6) M (44 days; P = 0.02) and SP 10(-9) M (45 days; P = 0.03) shortened time to closure compared to PEG treatment alone (68 days). Since there was no difference in the percentage contraction in these treatment groups, SP may favorably promote wound epithelization.Conclusions. Our data support the use of db/db murine excisional wounds to evaluate the role of nerves in healing. We have demonstrated that exogenous SP improves wound healing kinetics in an animal model.

Aged↗
PubMed2002

Direct quantification of autologous serum albumin leakage after burn injury in mice.

The current technique determining the extent of capillary leakage after injury is to measure the leakage of dye-labeled foreign albumin. A recent report, however, demonstrated that albumin leakage is dependent upon the type of fluorescent dye used for labeling. We chose to develop and test a technique for determining the extent of vascular albumin leakage after burn injury without the use of dyes. Skin and blood samples were harvested at 3h and 7 days after burn injury in mice. Total skin lysates and extracts as well as sera were analyzed for albumin leakage. Coomassie staining and Western blot analyses of skin preparations followed by the densitometric measurement revealed increased levels of albumin, suggesting that the leakage of serum albumin started within 3h after burn injury. Instead of employing dye-labeled foreign albumin, the use of SDS-polyacrylamide gel electrophoresis of tissue extracts followed by Coomassie staining will allow for a simple and direct quantification of autologous albumin leakage due to burn as well as other types of injury.

Animals↗
PubMed2002

Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns.

OBJECTIVE: Comparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results. METHODS: Qualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS. RESULTS: Measures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG. CONCLUSIONS: The requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.

Burns↗
PubMed2002

Benefits of early tracheostomy in severely burned children.

OBJECTIVE: The role of tracheostomy in burn patients is controversial. Previous studies, primarily in adults, suggested that severely burned patients with tracheostomies have a higher incidence of tracheostomy site infections, mortality, and pneumonia. The purpose of this study is to determine the safety and efficacy of early tracheostomy in severely burned children. DESIGN: Case series study analyzing mechanical ventilation and sedation requirements before and 24 hrs after tracheostomy. SETTING: Regional pediatric burn center. PATIENTS: All children admitted to a regional pediatric burn center requiring tracheostomy from March 1, 1998, to October 1, 2001. METHODS: Data were recorded on patients' demographics, extent of burn, presence of inhalation injury, and mortality. Mechanical ventilation variables measured pretracheostomy (pre) and posttracheostomy (post) and included mode of ventilation, ventilator settings, peak inspiratory pressures, and arterial blood gases (Pao2, Paco2, pH, and oxygen saturation). Calculated variables included compliance, Pao2:Fio2 ratio, and minute ventilation. Tracheostomy-related variables recorded included the interval to tracheostomy insertion, the duration of tracheostomy, and tracheostomy complications. MAIN RESULTS: A total of 38 patients (with a mean age of 4.7 +/- 0.6 yrs and a mean total body surface area involvement of 54% +/- 4%, 63% with inhalation injury) underwent tracheostomy a mean of 3.9 +/- 0.7 days after admission. Overall mortality was 21%. There were no tracheostomy site infections, tracheostomy-related deaths, or tracheal stenoses in survivors. Peak inspiratory pressures were lower after tracheostomy (30.4 +/- 1.4 [pre] vs. 27.6 +/- 1.5 cm H2O [post]; p <.05), ventilatory volumes were higher (190 +/- 22 mL [pre] vs. 225.5 +/- 25 [post]; p <.05), compliance improved (10.5 +/- 1.4 [pre] vs. 15.1 +/- 2.3 mL/cm H2O [post]; p <.05), and the Pao2:Fio2 ratio improved (300.6 +/- 20 [pre] vs. 348.6 +/- 16 [post]). There was no difference in oxygenation, ventilation, minute ventilation, or pH after tracheostomy. CONCLUSIONS: Early tracheostomy in severely burned children is safe and effective. It provides a secure airway and may result in improvement in ventilator management for these children.

Adolescent↗
PubMed2002

Release of abdominal compartment syndrome improves survival in patients with burn injury.

BACKGROUND: Abdominal compartment syndrome (ACS) has rarely been described as a complication of burn injury. This study describes cases of ACS in patients with burn injury and the physiologic results of abdominal release. METHODS: Charts for all patients admitted to two major burn center intensive care units from January 1998 through August 2000 were reviewed for ACS. Physiologic parameters were compared before and after abdominal release. RESULTS: Ten of 1,014 patients developed ACS. Abdominal release improved peak inspiratory pressures and Acute Physiology and Chronic Health Evaluation II scores (p < 0.03). The amount of fluid required to maintain adequate urine output also decreased substantially. Forty percent of patients with ACS survived to discharge. CONCLUSION: Abdominal release for patients with ACS and severe burn injury results in physiologic improvement and a 40% survival rate. We recommend bladder pressure monitoring for all patients with severe burn injuries and abdominal decompression in any patient who develops pressures greater than 30 mm Hg if they have signs of physiologic compromise. Aggressive expectant management can effect a 40% survival rate in this group of severely injured patients.

Abdomen↗
PubMed2002

Topical treatment of pediatric patients with burns: a practical guide.

Over 440 000 children receive medical attention for burn injuries each year in the US. Burn wound infections are a major source of morbidity and mortality in these patients. Infected wounds not only heal more slowly, but also may lead to systemic infections. The factors that contribute to wound complications are both the size and depth of the wound. Burn depth is usually categorized into first-degree (superficial, involving only the epidermis), second-degree (partial thickness, involving both epidermis and dermis), and third-degree (full thickness, through the epidermis, dermis, and into fat). Burns that will not heal within 2 weeks are at least second-degree and should generally be referred to a burn surgeon for possible excision and grafting, due to the increased risk of infection and scarring. The burn wound is dynamic. Proper treatment minimizes the extent of the burn injury, whereas improper treatment (lack of proper wound-care, edema formation, lack of resuscitation) may actually increase the size and/or depth of the wound. Topical antimicrobial agents have been shown to decrease wound-related infections and morbidity in burn wounds when used appropriately. The goal of topical antimicrobial therapy is to control microbial colonization, thus preventing development of invasive infections. A wide variety of agents are available for treatment of burn wounds, including ointments, creams, biological and nonbiological dressings. Topical antimicrobials of choice include bacitracin, neomycin, silver sulfadiazine and mafenide.

Anti-Infective Agents, Local↗
PubMedDate not supplied

Burn injury induces an inhibitory signal in the lung Smad pathway.

Smad signaling mediates the cellular response to transforming growth factor-beta (TGF-beta). We hypothesize that variations in Smad signaling modify the response to TGF-beta signaling in the lung after injury. C57BLKS/J mice were subjected to an 18% surface area burn injury, sacrificed at specific time points and their lung tissue was harvested. Lung TGF-beta1 expression, as determined by RT-PCR, ELISA and PAI/Luciferase assay, was not affected by injury. Western blots for Smad2/3 and Smad4 on nuclear fractions revealed decreased Smad2, Smad3, and Smad4 protein levels at 3h, while their total cellular levels did not differ from control mice. Smad7 protein increased transiently at 3 h. Correlating with Smad inhibition, transcription in type I alpha-2 collagen was also transiently depressed. By RT-PCR, Smad3 and Smad7 mRNAs decreased at 3 h, while Smad2 and Smad4 mRNA levels remained constitutive. Burn injury did not alter lung TGF-beta1 expression but caused Smad inhibition through decreased nuclear translocation of Smad2, Smad3, and Smad4, and upregulated Smad7. Transcription was not the key regulatory step in Smad protein expression, as transient decreases in Smad3 and Smad7 mRNA did not correlate with protein levels. It appears that Smad activity may in part attenuate TGF-beta activity after burn injury.

Animals↗
PubMedDate not supplied

Alterations in functional movement after axillary burn scar contracture: a motion analysis study.

Children with axillary burns often develop scar contractures that restrict shoulder movement. Objective data on functional movement patterns after contracture formation is sparse. The purpose of this study was to determine how axillary contractures affect shoulder movement during activities of daily living (ADLs). This was a prospective study of children with axillary contractures scheduled for surgical release. Three-dimensional upper extremity kinematic analysis was used to assess shoulder, elbow, and trunk motion during two ADLs: high reach and hand to back pocket. Results were compared with a pool of 49 normal age-matched controls. Eleven children with axillary contractures were compared with controls. During high reach, significant decreases in shoulder flexion, shoulder internal rotation, arm pronation, and trunk extension occurred. Elbow flexion increased significantly. In the hand to back pocket task, shoulder extension and elbow flexion decreased and shoulder abduction increased. Axillary contractures result in quantifiable movement changes during ADLs. Aggressive rehabilitation is required to prevent contracture formation. Three-dimensional motion analysis is a unique tool for the quantification of functional limitations and provides an objective method to evaluate treatment efficacy in patients with axillary contractures.

Activities of Daily Living↗
PubMedDate not supplied

The media glorifying burns: a hindrance to burn prevention.

The media have a profound influence on the actions of children and adults. Burns and burn prevention tend to be ignored or even mocked. The purpose of this presentation is to reveal the callousness of the media in its dealings with burns and burn prevention. Printed materials with a relationship to burns, risk of burning, or disrespect for the consequences of burns were collected. The materials were tabulated into four categories: comics, advertisements (ads), articles that made light of burns, and television shows that portrayed behavior that would risk burn injury. Most burn-related materials were found in comics or advertisements. Several comics made light of high-risk behavior with flames, scald injury, contact injury, or burns. In addition, several advertisements showed people on fire or actions that could easily lead to burns. Several articles and televisions shows portrayed high-risk behavior that, in some instances, led to copycat injuries. Flames are frequently used to sell items that target adolescent boys or young men. The high incidence injuries that frequent this population parallel the high-risk behaviors portrayed by the media. The media portrays flames and high-risk behavior for burn injury as being cool, funny, and without consequence. The use of flames on clothing and recreational equipment (skateboards, hot rods) particularly targets the high-risk adolescent male. The burn community should make the media aware of the harm it causes with its callous depiction and glorification of burns.

Accident Prevention↗
PubMedDate not supplied

Playing with fire: images of fire on toy packaging.

Despite prevention efforts designed to teach children that fire is not a toy, each year hundreds of children, primarily male, are injured while playing with fire. Mass-produced toys and games shape children's behaviors, and the fire images on toy packaging may send the message that fire is fun rather than dangerous. The purpose of this study was to determine the frequency of male fire-related injuries at our burn center and to investigate the use of fire images in toy packaging. An aisle-by-aisle search was conducted at a national toy store. Toys with fire images on their packaging were identified. Target gender and the setting in which the fire was displayed also were recorded. Only toys with clearly visible flames on their packaging were included. We reviewed our TRACS database from April 1997 to May 1999 for fire-related injuries to children admitted to our institution as a result of playing with fire. Review of toy stores revealed 404 toys with packaging containing fire images. Of these, 97% (393 of 404) were targeted to males. Video games were the leading category of flame-related packaging (208 of 404), followed by toy car/truck displays (84 of 404). Packaging for girls' toys had safe and contained settings, whereas boys' toys used settings that were uncontrolled and associated with speed and weapons. A total of 59 children, 52 males and 7 females, with a mean age of 10 +/- 0.6 years and mean TBSA burn of 12.3 +/- 2.1% were admitted to our facility with fire-related injuries during the study interval. Children imitate life with toys and use play to experiment with new behavior. Boys are receiving a powerful, consistent message from images of fire on toy packaging. These advertisements may help to contribute to the higher incidence of fire-related injuries in boys.

Accident Prevention↗