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1.
Burns ; 45(4): 772-782, 2019 06.
Article in English | MEDLINE | ID: mdl-30578048

ABSTRACT

INTRODUCTION: Split-thickness skin grafts (STSG) are the standard of care (SOC) for burns undergoing autografting but are associated with donor skin site morbidity and limited by the availability of uninjured skin. The RECELL® Autologous Cell Harvesting Device (RECELL® System, or RECELL) was developed for point-of-care preparation and application of a suspension of non-cultured, disaggregated, autologous skin cells, using 1cm2 of the patient's skin to treat up to 80cm2 of excised burn. METHODS: A multi-center, prospective, within-subject controlled, randomized, clinical trial was conducted with 30 subjects to evaluate RECELL in combination with a more widely meshed STSG than a pre-defined SOC meshed STSG (RECELL treatment) for the treatment of mixed-depth burns, including full-thickness. Treatment areas were randomized to receive standard meshed STSG (Control treatment) or RECELL treatment, such that each subject had 1 Control and 1 RECELL treatment area. Effectiveness measures were assessed and included complete wound closure, donor skin use, subject satisfaction, and scarring outcomes out to one year following treatment. RESULTS: At 8 weeks, 85% of the Control-treated wounds were healed compared with 92% of the RECELL-treated wounds, establishing the non-inferiority of RECELL treatment for wound healing. Control-treated and RECELL-treated wounds were similar in mean size; however, mean donor skin use was significantly reduced by 32% with the use of RECELL (p<0.001), establishing the superiority of RECELL treatment for reducing donor skin requirements. Secondary effectiveness and safety outcomes were similar between the treatments. CONCLUSIONS: In combination with widely meshed STSG, RECELL is a safe and effective point-of-care treatment for mixed-depth burns without confluent dermis, achieving short- and long-term healing comparable to standard STSG, while significantly decreasing donor skin use.


Subject(s)
Burns/therapy , Cell Transplantation/methods , Skin Transplantation/methods , Wound Healing , Adolescent , Adult , Aged , Child , Equivalence Trials as Topic , Female , Humans , Male , Middle Aged , Point-of-Care Systems , Skin/cytology , Transplantation, Autologous/methods , Treatment Outcome , Young Adult
2.
Anaesth Intensive Care ; 42(1): 97-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24471670

ABSTRACT

Heparin-induced thrombocytopenia is a serious complication of heparin use. Treatment includes discontinuation of heparin and initiation of alternative anticoagulation therapy. In extracorporeal membrane oxygenation anticoagulation is mandatory, and direct thrombin inhibitors (DTIs) have been approved in these cases. However, the use and monitoring of DTIs in extracorporeal membrane oxygenation patients is not well described. DTI use is also complicated by the imprecision of available monitoring tests and currently recommended dosing has been shown to result in a supratherapeutic anticoagulative state. This case report describes the successful use of the DTI argatroban as an alternative anticoagulant in a patient with heparin-induced thrombocytopenia requiring extracorporeal membrane oxygenation support.


Subject(s)
Antithrombins/administration & dosage , Extracorporeal Membrane Oxygenation , Heparin/adverse effects , Pipecolic Acids/administration & dosage , Thrombocytopenia/chemically induced , Adult , Arginine/analogs & derivatives , Female , Humans , Sulfonamides
4.
Ann Burns Fire Disasters ; 26(3): 115-20, 2013 Sep 30.
Article in English | MEDLINE | ID: mdl-24563636

ABSTRACT

Through the years, the burn injury has been described using a variety of labels. These labels have ranged from one word terms to phrases including degrees of injury or more descriptive terms. A search was conducted relying on a common general internet search engine. After multiple searches varying the keywords, the top 100 searches identified the most prevalent terms or phrases, ranging from the common to the more obscure. The search was repeated using the most prevalent terms or phrases identified in the common internet search engine, focusing on either the title or abstract for all papers indexed in PubMed. This process narrowed the attention to the most common terms or phrases used by the academics in their published work. This work therefore focused on measuring the specific terms being used today and their frequency of use in the peer reviewed papers indexed in the PubMed system. It is difficult to focus on the unique aspects of any given profession when there is confusion surrounding a common vocabulary. By identifying and noting in the academic literature the most commonly used labels, a point of reference can be created for future work. Furthermore, having a common and accurate set of labels that are uniformly applied across the profession is critical for academia to include in training and education programs for physicians, nurses, and paramedical staff.


Au fil des ans, la brûlure a été décrite en utilisant une variété d'étiquettes. Ces étiquettes ont oscillé entre un seul mot et des phrases, y compris degrés de blessures ou de termes plus descriptifs. Une recherche a été menée en s'appuyant sur un moteur de recherche internet. Après de multiples recherches variant les mots-clés, le top 100 des termes de recherche identifié ou expressions les plus courantes, allant de la commune à la plus obscure. La recherche a été répétée en utilisant des termes ou des expressions les plus fréquentes identifiées dans le moteur de recherche internet, en mettant l'accent soit sur le titre ou le résumé de tous les articles indexés dans PubMed. Ce processus réduit l'attention de termes ou expressions les plus courantes utilisées par les professeurs dans leur travail publié. Par conséquent, ce travail a porté sur la mesure des termes spécifiques qui sont utilisées aujourd'hui et leur fréquence d'utilisation dans les journaux évalués par les pairs indexées dans le système PubMed. Il est difficile de se concentrer sur les aspects spécifiques de chaque profession donnée quand il y a confusion entourant un vocabulaire commun. En identifiant et en notant dans la littérature académique les étiquettes les plus couramment utilisées, un point de référence peut être créé pour les travaux futurs. En outre, un ensemble commun et précis des étiquettes qui sont appliqués uniformément à travers la profession est essentiel pour les universités à inclure dans les programmes de formation et d'éducation pour les médecins, les infirmières et le personnel paramédical.

5.
J Int Med Res ; 39(3): 873-9, 2011.
Article in English | MEDLINE | ID: mdl-21819720

ABSTRACT

This report describes the epidemiology of burn injuries and quantifies the appropriateness of use of available interventions at Kamuzu Central Hospital, Malawi, between July 2008 and June 2009 (370 burn patients). Burns accounted for 4.4% of all injuries and 25.9% of all burns presenting to the hospital were admitted. Most patients (67.6%) were < 15 years old and 56.2% were male. The most frequent cause was scalding (51.4%). Burns occurred most frequently in the cool, dry season and in the evening. The mean burn surface area (second/third degree) was 14.1% and most burns (74%) presented within 8 h. The commonest procedure was debridement and/or amputation. The mean hospital stay was 21.1 days, in-hospital mortality was 27% and wound infection rate was 31%. Available interventions (intravenous fluids, nutrition therapy, physiotherapy) were misapplied in 59% of cases. It is concluded that primary prevention should address paediatric and scald burns, and secondary prevention should train providers to use available interventions appropriately.


Subject(s)
Burns/epidemiology , Adolescent , Amputation, Surgical , Burns/therapy , Child , Child, Preschool , Cross-Sectional Studies , Debridement , Dietetics , Female , Fluid Therapy , Humans , Malawi/epidemiology , Male , Physical Therapy Modalities , Retrospective Studies , Treatment Outcome
6.
J Trauma ; 51(5): 843-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11706329

ABSTRACT

BACKGROUND: The exact mechanism by which tracheostomy results in clinical improvement in respiratory function and liberation from mechanical ventilation remains unknown. Physiologic dead space, which includes both normal and abnormal components of non-gas exchange tidal volume, is a clinical measure of the efficiency of ventilation. Theoretically, tracheostomy should reduce dead space ventilation and improve pulmonary mechanics, thereby facilitating weaning from mechanical ventilation. METHODS: This study compares arterial blood gases (ABG), pulmonary mechanics, including minute ventilation (VE) and dead space ventilation (Vd/Vt) within 24 hours before and after tracheostomy in 45 patients admitted to a surgical intensive care unit. RESULTS: There was no difference noted in patients' ABG or VE. Pre- and posttracheostomy change in Vd/Vt was negligible (50.7 and 10 vs. 51.9 and 11; p = NS). On subgroup analysis, those patients that were weaned from mechanical ventilation with 72 hours of tracheostomy (T3) were compared with those patients weaned from mechanical ventilation 5 days or more after tracheostomy (T+5). Again, no difference was found in pulmonary mechanics or Vd/Vt pre- and posttracheostomy. CONCLUSION: There is minimal improvement in pulmonary mechanics after tracheostomy. The change in physiologic dead space posttracheostomy does not predict the outcome of weaning from mechanical ventilation. Tracheostomy does allow better pulmonary toilet, and easier initiation and removal of mechanical ventilation and control of the upper airway.


Subject(s)
Respiratory Dead Space , Respiratory Distress Syndrome/physiopathology , Tracheostomy , Ventilator Weaning , Adolescent , Adult , Aged , Aged, 80 and over , Blood Gas Analysis , Female , Humans , Intensive Care Units , Male , Middle Aged , Positive-Pressure Respiration , Prospective Studies , Pulmonary Gas Exchange , Respiratory Distress Syndrome/etiology , Respiratory Mechanics
7.
Obstet Gynecol ; 98(5 Pt 2): 895-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11704193

ABSTRACT

BACKGROUND: Primary pulmonary hypertension is a rare and dangerous entity in pregnancy. Previous studies have found a 35-50% maternal mortality rate in the peripartum period. To date, most reports have described treatment of these patients with diuretics, digoxin, and calcium-channel blockers. CASE: We describe the successful treatment of a primigravida with severe primary pulmonary hypertension. We used elective intubation before labor, inhaled nitric oxide therapy, and assisted vaginal delivery with epidural anesthesia that resulted in a viable infant and survival of the mother. CONCLUSION: Nitric oxide can be used to successfully treat primary pulmonary hypertension in pregnancy.


Subject(s)
Hypertension, Pulmonary/drug therapy , Nitric Oxide/therapeutic use , Pregnancy Complications, Cardiovascular/drug therapy , Vasodilator Agents/therapeutic use , Administration, Inhalation , Adult , Female , Humans , Intubation, Intratracheal , Nitric Oxide/administration & dosage , Pregnancy , Vasodilator Agents/administration & dosage
8.
Surgery ; 130(2): 210-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11490351

ABSTRACT

BACKGROUND: Previous studies suggest that CD8(+) T cells are immunosuppressive after burn injury, but recent reports indicate that CD8(+) T cells have several functions similar to CD4(+) T cells, including the secretion of cytokines. This study uses HY male antigen in transgenic HY female mice to determine the antigen-specific response of activated CD8(+) T cells after burn injury. METHODS: HY TCR transgenic female mice underwent burn or sham injury. Seventy-two hours after the burn, splenocytes were stimulated with 20 micromol/L HY peptide for 16, 48, and 64 hours; cellular proliferation, intracellular interferon-gamma and interleukin-2, and apoptosis were measured. RESULTS: Burn injury significantly impaired proliferation to HY antigen (P < or =.05). Activated CD8(+) T cells from burned mice showed increased intracellular interferon-gamma and interleukin-2 16 hours after stimulation compared with sham (P < or =.05) and at no time was less than control mice. The percent of CD8(+) T cells decreased with the time of stimulation but was not due to apoptosis by Annexin V staining. CONCLUSIONS: Activated CD8(+) T cells express a T(h1)-like phenotype after burn injury. This provides evidence that CD8(+) T cells are not simply suppressive and that is consistent with data that CD4(+) T cells are primed for a T(h1) response after burn injury.


Subject(s)
Burns/immunology , CD8-Positive T-Lymphocytes/immunology , Th1 Cells/immunology , Animals , Apoptosis/immunology , CD8-Positive T-Lymphocytes/cytology , Cells, Cultured , Female , Flow Cytometry , Immunophenotyping , Mice , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Spleen/cytology , Spleen/immunology , Th1 Cells/cytology
9.
J Burn Care Rehabil ; 19(4): 367-76; discussion 366-7, 1998.
Article in English | MEDLINE | ID: mdl-9710740

ABSTRACT

Child abuse and neglect continue to account for a significant number of pediatric burn injuries. Although the epidemiology of intentional burn injuries has been studied, this report compares victims of abuse with victims of neglect. Furthermore, we investigate the long-term fate of both victim and perpetrator. A retrospective search of the North Carolina Jaycee Burn Center database identified 21 abuse and 21 neglect patients among 238 pediatric admissions (mean age, 5.4 years, mean surface area 14%) from 1992 to 1994. The medical, social, and legal records of each patients were examined by two independent reviewers. History, hospital course, and disposition were compared between groups by chi-square analysis and Student's t test. Compared with victims of neglect, abused children were slightly younger (2.1 vs 2.7 years), had somewhat larger burns (12.3% vs 9.05 total body surface area), had inconsistent mechanisms of injury (90% vs 33%, p < 0.002) that were bathroom related (81% vs 29%, p < 0.001), were likely to have a history of abuse (57% vs 24%, p < 0.05) or stigmata of abuse on exam (43% vs 14%, p < 0.05), had longer lengths of stay (23.8 vs 14.1 days, p < 0.05), had similar complication rates, and were place more often in foster care (65% vs 15%, p < 0.01). Inpatient mortality was 5%. Mean follow-up was 108 days, during which time two children were readmitted for repeat abuse. Regarding the caregivers, 57% were single mothers, 36% had been investigated for abuse or neglect, and 12% had lost custody of other children. Of the perpetrators involved in abuse, 71% were charged with a felony, 43% were convicted, and 19% were incarcerated longer than 30 days. Victims of burn abuse and neglect differ considerably in terms of history and disposition but not hospital course. Children in both groups, however, remain at risk for abuse and neglect after discharge. We recommend that more aggressive efforts be made to secure safe environments for these children and that the perpetrator, if clearly identified, be dealt with in a fashion to prevent recurrence of the offense.


Subject(s)
Burns/epidemiology , Child Abuse , Burns/complications , Child , Databases, Factual , Female , Follow-Up Studies , Foster Home Care , Humans , Length of Stay , Male , Medical Records , North Carolina/epidemiology , Retrospective Studies , Single Parent
10.
Am Surg ; 62(11): 911-7, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8895712

ABSTRACT

Although splenectomy was the preferred method of treating the injured spleen in the past, the methods of splenorrhaphy and nonoperative management have appeared to gain in popularity. The purpose of this study was to determine whether the management of splenic injuries has changed over the course of time and if there has been any differences in the morbidity and mortality associated with different methods of treatment. We retrospectively examined the discharge records from 2627 patients with splenic injuries from the North Carolina Discharge Database. There were 2258 adults and 369 pediatric patients for evaluation. The rate of nonoperative therapy increased from 33.9 per cent to 46.3 per cent over the 5 years of the study, whereas the rate of splenectomy decreased from 52.9 per cent to 43.4 per cent over the same time period. Splenorrhaphy was used in approximately 10 per cent of the injuries over the course of the entire study period. Adults treated nonoperatively required late operation 6.0 per cent (49/811) of the time. The pediatric late operation rate for nonoperative management was 0.4 per cent(1/231). Reoperation after splenorrhaphy was 2.9 per cent (7/240) for adult patients and 4.3 per cent (2/47) for pediatric patients. The majority of adults (57.2%) with an Injury Severity Score (ISS) < or = 15 were able to be cared for via nonoperative methods, whereas the majority of adults (66.4%) with an ISS > 15 required splenectomy. The majority of pediatric patients were able to be cared for in a nonoperative fashion in both the ISS < or = 15 (83.4%) and ISS > 15 (45.5%).


Subject(s)
Spleen/injuries , Adult , Child , Female , Humans , Injury Severity Score , Length of Stay , Male , Medical Records Systems, Computerized , Middle Aged , North Carolina , Patient Discharge , Retrospective Studies , Spleen/surgery , Treatment Failure , Treatment Outcome , Wounds and Injuries/therapy
11.
J Trauma ; 41(1): 51-8; discussion 58-60, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8676424

ABSTRACT

INTRODUCTION: Cultured epidermal autografts (CEAs) have been used for wound coverage in patients with massive burns and other skin defects. However, CEAs often display late breakdown, which may be immunologically mediated and initiated by persistent foreign fibroblasts used as a feeder layer to optimize keratinocyte growth. This study investigates whether these fibroblasts, previously shown to persist in vitro, survive after grafting and induce host sensitization to alloantigen. METHODS: CEAs from CBA donors (H-2k) were grown on allogeneic NIH 3T3 (H-2q) or syngeneic LTK (H-2k) fibroblasts, which were removed by trypsinization 7 days later. CBA mice (n = 85) were flank-grafted with NIH allografts (positive control), CEA/3T3s, CEA/LTKs, or CBA autografts (negative control). Hosts were challenged with second set NIH tail allografts 3 weeks later. Median graft survival was compared between groups by Wilcoxon rank and chi 2 analysis. Additional CBA mice (n = 15) received CEAs that were biopsied 0, 4, and 8 days after grafting. The presence of allogeneic fibroblasts was determined by Western immunoblotting, using KL295, a monoclonal antibody that recognizes H-2q (but not H-2k) class II histocompatibility antigens. RESULTS: Allogeneic fibroblasts persisted after grafting but decreased over time, as determined by alloantigen expression on Western immunoblots. Accelerated tail graft rejection occurred in hosts primed by NIH allografts (9 days, p < 0.05), as well as by CEAs growth with an allogeneic (10 days, p < 0.05) but not a syngeneic feeder layer (12 days, NS). Mice receiving flank autografts rejected second set tail allografts at 12 days. CONCLUSIONS: Immunogenic fibroblasts used to grow CEAs survive in vivo and sensitize the graft recipient for accelerated second-set rejection. These persistent cells may initiate an inflammatory response that may result in late graft breakdown and limit the utility of CEAs grown with a foreign fibroblast feeder layer.


Subject(s)
Culture Techniques , Epidermis/transplantation , Fibroblasts/immunology , Graft Rejection/immunology , Transplantation Immunology , Animals , Blotting, Western , Cell Survival , Epidermal Cells , Epidermis/immunology , Female , Fibroblasts/cytology , Isoantigens , Keratinocytes/cytology , Keratinocytes/immunology , Mice , Mice, Inbred CBA , Skin Transplantation/immunology , Transplantation, Autologous , Transplantation, Homologous
12.
J Pediatr Surg ; 31(3): 329-33, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8708897

ABSTRACT

A 6-year retrospective review of burn victims hospitalized at a major burn center was conducted to determine the etiology and outcome of pediatric burns. Four hundred forty-nine patients under age 16 years were identified and stratified by age, sex, burn size, presence or absence of inhalation injury, cause of burn, and county of residence. The mean patient age was 4.3 +/- 0.2 years, and the male:female ratio was 1.9:1. There were 21 deaths overall (4.7%), the majority of which (18) were among children under 4 years of age. With respect to large burns, defined as > and = 30% total body surface area (TBSA), the mortality rate for children under age 4 was significantly higher than that for older children (46.9% v 12.5%; P < .01), despite the nearly identical mean burn size of the two groups. Except for burn incidence, there were no significant differences between males and females. The mean burn size was 15.1% +/- 0.7%, and was significantly larger for nonsurvivors than survivors (55.3% +/- 5.7 v 13.1% +/- 0.5%; P < .01). Inhalation injuries were strongly associated with large burns and were present in all 15 flame-burn fatalities. Scalds were the most common type of burn among children under 4 years of age; flame burns predominated in older children. There were 6 deaths related to scalds, all of which occurred in children under 4. Burn type, size, and mortality rate did not differ between children from urban and rural counties. Large burn size was the strongest predictor of mortality, followed by (in order) age less than 4 and the presence of inhalation injury. Infants and young children have the highest risk of death from burn injury. Burns smaller than 30% TBSA without an inhalation injury (such as small scald injuries) occasionally are lethal in infants and small children, despite modern therapy.


Subject(s)
Burns/etiology , Adolescent , Age Distribution , Burn Units , Burns/epidemiology , Burns/therapy , Cause of Death , Child , Child, Preschool , Female , Humans , Incidence , Infant , Logistic Models , Male , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Sex Distribution , Treatment Outcome
13.
J Burn Care Rehabil ; 16(6): 573-80, 1995.
Article in English | MEDLINE | ID: mdl-8582933

ABSTRACT

Burn injury impairs cellular immunity, increases the risk of viral infection, and delays allograft rejection, but little is known about its effect on antigen processing and cytotoxic T-lymphocyte (CTL) function. This study examined the effect of burn injury on alloantigen sensitization with an in vivo model of second-set rejection and in vitro assays of CTL alloreactivity. Anesthetized CBA mice (n = 95) received a 0%, 20%, or 40% full-thickness contact burn that was partially excised 3 days later and covered with autograft or C57BL/6 allograft. Two weeks after the burn was inflicted, mice were challenged with second-set tail allografts, which were observed for rejection. Median graft survival times were compared by Wilcoxon rank and chi-squared analysis. Additional CBA mice (n = 24) underwent similar burn injury, excision, and grafting. Splenocytes were harvested 2 weeks later and were used as CTL effectors against radiolabeled targets. Dilution curves of target lysis were compared by analysis of variance. Forty percent burn injury prolonged unprimed allograft survival from 13 to 15 days (p < 0.01) but had a greater effect on primed allograft survival, which increased from 9 to 12.5 days (p < 0.01). Furthermore, a 40% burn eliminated the influence of priming, resulting in second-set graft survival similar to that of mice in an unburned, unprimed control group (12.5 vs. 13 days, NS). Whereas 20% burn injury did not inhibit CTL priming, a 40% burn profoundly impaired CTL function (p < 0.001), which recovered only after 6 days of in vitro allostimulation. Burn injury inhibits both alloantigen priming and the immunologic memory of CTLs as a function of burn size. This impairment in alloantigen processing helps to explain defects in cellular immunity and suggests a mechanism for prolonged allograft survival and decreased viral resistance after burn injury occurs.


Subject(s)
Awards and Prizes , Burns/immunology , Isoantigens/immunology , T-Lymphocytes, Cytotoxic/immunology , Tissue Transplantation , Transplantation Immunology/immunology , Animals , Burns/therapy , Chi-Square Distribution , Disease Models, Animal , Female , Graft Survival/immunology , Histocompatibility Antigens/immunology , Mice , Mice, Inbred CBA , Tissue Transplantation/pathology , Tissue Transplantation/physiology
14.
Ann Surg ; 222(3): 384-9; discussion 392-3, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7677467

ABSTRACT

BACKGROUND: Cultured keratinocyte (CK) and cadaveric skin allografts have prolonged survival in patients with massive thermal injury. It is unclear if this delayed rejection is due to impaired host responsiveness or decreased graft immunogenicity. Although burn injury has been shown to decrease parameters of allograft response, no studies have examined the effect of burn injury on alloantigen expression. This study investigated the effect of burn size on class II antigen expression in CK allografts as well as on tissue levels of interferon-gamma (IFN-gamma), the principle regulator of alloantigen expression. METHODS: Anesthetized CBA mice (n = 64) received a 0%, 20% partial-thickness (PT), 20% full-thickness (FT), or 40% FT contact burn. Forty-eight hours later, wounds were partially excised and covered with CK allografts from C57BL/6 donors. Five days after burn injury, grafts were analyzed for donor-specific class II antigen. Protein expression was determined by Western immunoblotting and quantified with video densitometry. Wound, serum, and unburned skin levels of IFN-gamma were determined by enzyme-linked immunosorbent assay. Groups were compared by Fisher's analysis of variance. RESULTS: As burn size increased, class II antigen expression decreased (p < 0.001). This corresponded with decreased wound and skin levels of IFN-gamma after 40% burn (p < 0.05); however, wound IFN-gamma was significantly elevated after 20% PT and FT burns (p < 0.01). Serum IFN-gamma increased as burn size increased (p < 0.01). CONCLUSIONS: Burn injury decreases the antigenicity of CK allografts, which partly explains delayed allograft rejection after burn injury. Although wound IFN-gamma increases after minor thermal injury, the profound decrease in wound and skin IFN-gamma after a major burn corresponds with diminished class II antigen expression. The decreased availability of IFN-gamma after major thermal injury provides a mechanism for limited allograft tolerance.


Subject(s)
Burns/immunology , Genes, MHC Class II/immunology , Interferon-gamma/analysis , Keratinocytes/immunology , Animals , Female , Gene Expression , Humans , Keratinocytes/transplantation , Mice , Mice, Inbred CBA
15.
Transplantation ; 60(6): 584-9, 1995 Sep 27.
Article in English | MEDLINE | ID: mdl-7570955

ABSTRACT

Cultured keratinocyte (CK) allografts have limited antigenicity and have been used as a skin replacement in patients with massive thermal injury. Recent data indicate that CK grafts are more immunogenic than previously believed and could compromise wound healing in the immunocompetent host. The purpose of this study was to determine if the immunosuppression of burn injury might affect the alloantigen response and minimize sensitization to CK allografts. CBA mice received a 0%, 20%, or 40% burn that was partially excised three days later and grafted with a full-thickness (FT) skin allograft, CK allograft, or CK autograft. Two weeks postburn, mice received FT tail skin allografts, which were observed for rejection. We observed that FT and CK allografts primed the unburned host with equal efficacy. However, burn injury selectively minimized priming by CK allografts, resulting in delayed rejection of second-set allografts. With evidence that burn injury inhibits host sensitization to CK allografts, we then examined the effect of burn size on CTL alloreactivity. Additional CBA mice underwent burn injury, excision, and grafting as described above. Host splenocytes were harvested two weeks later and tested on radiolabeled targets for allospecific cytotoxicity. CTLs from unburned mice primed with FT allografts demonstrated the greatest CTL lysis, followed next by CTLs from unburned mice covered with CK allografts. Burn injury inhibited CTL activity as a function of wound size. Activity of CTLs from burned mice primed with CK allografts improved after in vitro allostimulation but remained below that of CTLs from unburned, unprimed mice. We conclude that burn injury selectively inhibits the allospecific response to CK allografts. The decreased immunogenicity of CK allografts, when used for burn wound coverage, may improve the long-term survival of allogeneic keratinocytes, enhancing their potential as a biologic skin replacement.


Subject(s)
Burns/immunology , Graft Rejection , Immunologic Memory , Keratinocytes/immunology , Skin Transplantation/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Cytotoxicity, Immunologic , Immunosuppression Therapy , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Time Factors
16.
Surgery ; 118(2): 421-9; discussion 429-30, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7638760

ABSTRACT

BACKGROUND: Cytotoxic lymphocytes (CTLs) are an important component of immune function, involved in antigen recognition and resistance to viral infection. Burn injury suppresses cell-mediated immunity, induces allograft tolerance, and increases the risk of viral infection, but the mechanisms are not well understood. This study analyzes the effect of burn size and burn wound excision on CTL activity. METHODS: Anesthetized CBA mice (n = 12) received a 0%, 20%, or 40% body surface area contact burn. Additional mice (n = 16) received a 40% burn that was totally, partially, or not excised 72 hours after burn. Excised areas were covered with normal, syngeneic skin. Two weeks later harvested splenocytes were cocultured with allogeneic stimulators. CTL activity was determined by a 51Cr release assay, in which CTL effectors were tested on allogeneic, radiolabeled targets. Dilution curves of CTL activity were compared by ANOVA: RESULTS: Both 20% and 40% burns significantly inhibited CTL activity (p < 0.05). Total but not partial excision of a 40% burn restored CTL activity (p < 0.01). Both total and partial wound excision also improved survival (p < 0.05). CONCLUSIONS: Burn injury inhibits CTL activity in a size-dependent manner, and total wound excision significantly improves both CTL function and survival after injury. This study suggests a mechanism for the immunosuppressive effects of burn injury and provides an immunologic rationale for early, complete burn wound excision.


Subject(s)
Burns/surgery , T-Lymphocytes, Cytotoxic/physiology , Animals , Burns/mortality , Burns/pathology , Female , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Postoperative Period , Survival Analysis , Time Factors
17.
J Trauma ; 39(1): 75-9; discussion 79-80, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7636913

ABSTRACT

Recent reports suggest that long-term graft take of cultured epidermal autografts (CEAs) is less than 50% when late graft loss is considered. The characteristics of late CEA loss suggest that it may occur as a result of an immunologic reaction to persistent xenogeneic cells and/or proteins used to grow CEA. In this study we examined whether immunologically reactive, mouse 3T3 fibroblasts used as feeder layers can persist in primary, secondary, and tertiary human CEA. We cocultured keratinocytes from 11 separate burn patients with growth-arrested 3T3 fibroblasts. After removing visible 3T3 fibroblasts from CEA with trypsinization, we allowed CEA to reach confluence. We then harvested CEA either as primary, secondary, or tertiary cultures. We detected mouse fibroblasts using fluorescence activated cell sorting (FACS) with a monoclonal antibody specific for mouse major histocompatibility (MHC) antigens. We detected mouse MHC class II antigens by performing Western immunoblotting with another mouse MHC-specific monoclonal antibody. By FACS we identified mouse fibroblasts in 100, 75, and 62.5% of primary, secondary, and tertiary passage CEAs, respectively. Similarly by immunoblotting we found mouse MHC class II antigen in 100, 80, and 66.7% of primary, secondary, and tertiary CEAs. These results demonstrate that xenogeneic fibroblast feeder layers capable of generating immunogenic transplantation antigens persist in CEAs. The persistence of these cells and their antigen expression may contribute to CEA loss.


Subject(s)
Epidermis/transplantation , Fibroblasts/immunology , Skin Transplantation/immunology , Animals , Blotting, Western , Cell Separation , Cells, Cultured , Epidermal Cells , Epidermis/immunology , Flow Cytometry , Humans , Major Histocompatibility Complex/immunology , Mice , Transplantation, Heterologous/immunology
18.
J Am Coll Surg ; 180(4): 394-401, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7719542

ABSTRACT

BACKGROUND: This study was done to examine the outcome of cardiopulmonary resuscitation (CPR) in the surgical intensive care unit (SICU) and to identify factors preceding cardiopulmonary arrest that could predict survival. STUDY DESIGN: We prospectively collected demographic, laboratory, diagnostic, and complications data in our SICU database on 5,237 consecutive patients and reviewed the charts of all patients receiving CPR. RESULTS: Cardiopulmonary resuscitation was performed upon 1.1 percent (55 of 5,237 patients) of patients in the SICU. Twenty-nine percent (16 of 55 patients) survived greater than 24 hours but died in the hospital, and 13 percent (seven of 55 patients) survived to discharge. No patient with a worsening Glasgow Coma Scale (GCS) score, acute physiology score (APS), or any acute organ failure who had cardiopulmonary arrest survived. Survival after CPR for patients with a stable or improving APS was 32 percent (p < 0.01). CONCLUSIONS: Patients in the SICU who survived CPR had a stable or improving clinical course as determined by APS and GCS score, and had not had acute organ failure. Patients who were critically ill with a declining clinical course did not survive after CPR.


Subject(s)
Cardiopulmonary Resuscitation/mortality , Critical Illness , Surgical Procedures, Operative , APACHE , Adolescent , Adult , Aged , Aged, 80 and over , Female , Glasgow Coma Scale , Heart Arrest/mortality , Heart Arrest/therapy , Humans , Intensive Care Units , Male , Middle Aged , Outcome Assessment, Health Care , Prospective Studies
19.
Ann Surg ; 221(3): 272-7, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7717780

ABSTRACT

OBJECTIVE: The management and outcome of 138 abdominal shotgun wounds were examined over a 5-year period. SUMMARY BACKGROUND DATA: It has been proposed that exploratory laparotomy may be unnecessary and even overused in a subset of patients with abdominal shotgun wounds. METHODS: Data on shotgun wound patients from October 1987 through March 1992 from a statewide trauma registry were examined. Patients with abdominal shotgun wounds were identified and compared with patients with nonabdominal shotgun wounds. RESULTS: Of 516 shotgun wound patients, 138 (26.7%) had abdominal wounds and 88 (63.8%) had exploratory laparotomies. Abdominal shotgun wounds resulted in significantly longer number of intensive care unit days (4.3 vs. 2.5, p < 0.05), a greater number of blood units transfused (7.8 vs. 2.4, p < 0.05), and a higher mortality (15.9% vs. 4.8%, p < 0.05) when compared with nonabdominal shotgun wounds. When stratified for trauma score, the mortality for abdominal shotgun wounds always was significantly greater than for nonabdominal shotgun wounds. All abdominal shotgun wound patients with trauma scores less than ten died. The negative laparotomy rate for abdominal shotgun wound patients with normal trauma scores was 9.4%. No patient with a negative laparotomy died. CONCLUSION: Abdominal shotgun wounds are a particularly lethal subset of shotgun wounds. Although some abdominal shotgun wound patients can be managed without laparotomy, the morbidity and mortality for these injuries are substantial, even in patients with normal trauma score. Clinical judgment is an excellent predictor of the need for laparotomy.


Subject(s)
Abdominal Injuries/surgery , Laparotomy , Wounds, Gunshot/surgery , Abdominal Injuries/mortality , Adult , Female , Humans , Male , Trauma Severity Indices , Treatment Outcome , Wounds, Gunshot/mortality
20.
J Burn Care Rehabil ; 15(6): 509-14, 1994.
Article in English | MEDLINE | ID: mdl-7852454

ABSTRACT

Dehydroepiandrosterone has been proposed as a means of restoring immune function after injury. In this study we examined the effect of dehydroepiandrosterone on the impaired immunoglobulin M synthesis and depressed lymphocyte mitogenic responses observed after burn injury. We divided BALB/c mice (n = 28) into four equal groups that received either a 25% total body surface area dorsal steam burn or a sham procedure. One hour later we injected mice subcutaneously either with 100 micrograms dehydroepiandrosterone or vehicle alone. Five days later we isolated splenocytes for assessment of immune function. We stimulated splenocytes with lipopolysaccharide and 5 days later measured immunoglobulin M synthesis specific for peptidoglycan polysaccharide, a ubiquitous bacterial antigen. We stimulated additional cultures with lipopolysaccharide or concanavalin A to measure B- or T-lymphocyte mitogenic response. Burn injury impaired peptidoglycan polysaccharide-specific immunoglobulin M synthesis compared with sham (p < 0.05), and this impairment was not restored by the administration of dehydroepiandrosterone (p < 0.05). Furthermore dehydroepiandrosterone did not correct the burn-induced impairments of B- and T-cell mitogenic responses (p < 0.05). Our study demonstrates that in this model the administration of dehydroepiandrosterone in vivo does not correct the impairments of humoral or cellular immunity induced by burn injury.


Subject(s)
B-Lymphocytes/immunology , Burns/immunology , Dehydroepiandrosterone/pharmacology , Immunoglobulin M/biosynthesis , Lymphocyte Activation/drug effects , T-Lymphocytes/immunology , Animals , B-Lymphocytes/drug effects , Burns/drug therapy , Concanavalin A/pharmacology , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Lymphocyte Activation/immunology , Male , Mice , Mice, Inbred BALB C , T-Lymphocytes/drug effects
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