Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation.

AIMS: Increased cardiovascular morbidity is manifested a long time after the repair of aortic coarctation (CoA). By way of impaired flow-mediated vasodilation (FMD) and increased intima media thickness (IMT), surrogate parameters of atherosclerosis, cardiovascular risk factors (RFs) can be correlated with early vascular wall changes in children. This study investigated whether changes in arterial wall function and morphology are detectable in children after coarctation repair. METHODS AND RESULTS: We examined 28 children after successful repair of CoA vs. 30 control subjects. All children underwent identical screening, with a broad RF profile and FMD/IMT measurements. CoA-children presented significantly (P < 0.001) impaired FMD (4.87 +/- 2.6 vs. 10.2 +/- 3.1%) and higher IMT values (P < 0.001) than the controls (0.48 +/- 0.08 vs. 0.38 +/- 0.05 mm). The blood pressure during rest and exercise and the left ventricular mass were significantly elevated, but no additional RF could be identified in CoA-children. Only a remaining pressure gradient related significantly to FMD. CONCLUSION: This study documents early vascular wall changes in children after successful coarctation repair. Arterial hypertension and a resting pressure gradient are the major contributing factors to early atherosclerotic development and should be primary targets for therapy. Vascular status should be monitored regularly by FMD and IMT.

CD8(+) T cells express a T-helper 1--like phenotype after burn injury.

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.

Accuracy of administrative data in trauma: splenic injuries as an example.

BACKGROUND: Accurate data are needed to evaluate clinical outcomes, therapeutic modalities, and quality of care in trauma. Administrative data, usually used for billing, have been used to evaluate performance and assess therapy in other medical specialties. This study was performed to determine whether administrative databases are accurate in the recording of information about trauma patients with splenic injuries. METHODS: Patients who had blunt splenic injuries were identified using a state trauma registry. The medical records of those patients were reviewed. The data collected by chart review were compared with data in the statewide administrative database of patients who had splenic injuries at the same four Level I and II trauma centers in the same 5-year period. Age, sex, admission date, and hospital were matched to assure comparison of the identical cohort. chi2 analysis was used to compare dichotomous data and Student's t test continuous data. RESULTS: The administrative database identified 641 and the trauma registry identified 529 patients with a diagnosis of splenic injury. A total of 401 patients were found in both databases. Of these, 120 (22.7%) patients were not recorded in the administrative database. Injury Severity Score was underreported by the administrative database (25.74 +/- 14.7 vs. 19.52 +/- 11, p < 0.0001). The administrative database underreported orthopedic, chest, and head injuries (317 vs. 215, 325 vs. 228, and 234 vs. 155, respectively; all p < 0.0001). Use of abdominal computed tomographic scan and diagnostic peritoneal lavage were also underreported (260 vs. 56 and 104 vs.17, both p < 0.0001). The number of operations on the spleen and number of orthopedic procedures were underreported (259 vs. 225, p < 0.014 and 147 vs. 94, p < 0.0001). Complications were markedly underreported by the administrative database (200 vs. 47, p < 0.0001) CONCLUSION: This study shows that administrative data lack accuracy in the recording of associated injuries, injury severity, diagnostics, procedures, and outcomes data in patients with splenic injuries. Whether these data should be used to evaluate treatment modalities or quality of care in trauma is questionable.

Occupation-related burn injuries.

Unlike household burn injuries, the characteristics of burn injuries in the workplace have not been well described. In an effort to understand the causes and effects of occupation-related burn injuries and to aid in prevention, we sought to describe work-related burn injuries by frequency, burn type, age of the patients, body parts burned, and occupation of the patients. This was a statewide, cross-sectional study of all burns that occurred in the workplace during 1994. Data on fatal injuries were obtained from the National Census of Fatal Occupational Injuries. Survey data from the North Carolina Department of Labor were used for nonfatal injuries. Burns caused 34 deaths (15.3%) and 1720 injuries in the workplace in 1994. Of the nonfatal injuries, 1363 (79.2%) were caused by exposure to caustic substances or hot objects or substances. The head and upper extremities were the most frequently injured body parts (936 injuries; 57.6%). The average age of those burned was 30.7 years; most of the patients ranged from 25 to 35 years old. High-risk occupations included vehicle and equipment cleaners, food service personnel, and millwrights (11.3%, 5.3%, and 5.2% of burn injuries, respectively). Unlike the flame burns that occur in homes, exposure to caustics and hot objects and substances caused the majority of on-the-job burn injuries. Protective gear for the head and upper extremities may prevent a significant number of burns. Education and prevention programs may best be directed at workers with high-risk occupations and workers in the 25- to 35-year age range.

Diagnosis and management of blunt small bowel injury: a survey of the membership of the American Association for the Surgery of Trauma.

BACKGROUND: Blunt small bowel injury (SBI) may be difficult to diagnose accurately. Diagnostic delays are associated with increased morbidity and mortality. METHODS: A cross-sectional survey of members of the American Association for the Surgery of Trauma was conducted. A Likert-type multiple-choice scale was used to evaluate use and usefulness of diagnostic and laboratory tests. Data were analyzed by using univariate and multivariate techniques. RESULTS: A total of 461 of the 702 members (68%) surveyed responded, of which 133 members (29%) were excluded because they did not currently manage adult SBI. Of the remaining 328 respondents, 244 members (74%) reported prior experience as the most important influence on their current practice of diagnosing blunt SBI. None of the standard laboratory tests were reported as useful. Seventy-seven percent of respondents use computed tomographic (CT) scan most or all of the time for diagnosis (p < 0.05 compared with other modalities). Most respondents estimated their annual incidence of SBI at 5% with a >15% frequency of delay in diagnosis. Forty-four percent of the respondents estimated the mortality associated with a delay in diagnosis at < or =5%. Respondents varied significantly in their management of the patient with an unreliable abdominal exam and a CT scan finding of isolated free fluid. In patients with head injuries, 28% observe, 12% repeat the CT scan, 42% perform diagnostic peritoneal lavage, and 16% operate. For intoxicated patients, 51% observe, 11% repeat the CT scan, 26% perform diagnostic peritoneal lavage, and 10% operate. A more aggressive approach with diagnostic and operative intervention was significantly (p < 0.05) advocated by respondents practicing without residents, more than 15 years out from residency, or by those with a perception of higher morbidity and mortality from delays in diagnosis. CONCLUSION: There is significant variation in the diagnostic approach to the patient with suspected SBI. The perceived mortality of delayed diagnosis is much less than reported. Those surgeons with more experience or perception of greater morbidity and mortality from a delayed diagnosis are more aggressive. Further investigation into the diagnosis and treatment of this injury is needed.

Impact of burn injury on hepatic TGF-beta1 expression and plasma TGF-beta1 levels.

BACKGROUND: The liver plays a critical regulatory role in the acute inflammatory response to injury, although the mechanisms of this regulation are not well understood. transforming growth factor-beta1 (TGF-beta1) is induced after burn injury and may contribute to an inhibitory or fatal effect on hepatocytes. We investigated the association over time between plasma concentration of TGF-beta1, expression of TGF-beta1 m-RNA in liver tissue, and histologic analysis of liver apoptosis after burn injury. METHODS: Male BALB/c mice were anesthetized and randomized to receive 0% (sham), moderate (approximately 25%) (M), or large (approximately 50%) (L) body surface area full-thickness contact burn, followed by resuscitation and analgesia. Animals were killed over a time course from 15 minutes to 24 hours after burn injury, and liver tissue and peripheral blood were collected. Plasma levels of TGF-beta1 (nanograms per milliliter) were measured by enzyme-linked immunosorbent assay. TGF-beta1 m-RNA was extracted from liver and measured by reverse transcription-polymerase chain reaction. Histology of liver apoptosis was examined after fixation and staining with TdT-mediated dUTP nick-end labeling (TUNEL) method. RESULTS: The plasma concentration of TGF-beta in burn group L was significantly increased at 4 hours after burn when compared with sham and M burn groups. This rise in plasma TGF-beta1 was preceded by an increase in hepatic TGF-beta1 m-RNA expression at 30 minutes, 1, 2, and 4 hours after burn in the L group. Histologic analysis found greater hepatocyte death in the L group than in the M group at 8 hours after burn. CONCLUSION: The levels of induced TGF-beta1 and TGF-beta1 m-RNA after L burn injury are higher and peak earlier than after M burn injury. Elevated TGF-beta1 may be associated with cell death in hepatocytes. The TGF-beta1 rise may be associated with hepatocyte injury and systemic response to massive burn.

Transforming growth factor-beta1 and splenocyte apoptotic cell death after burn injuries.

Transforming growth factor (TGF)-beta1 is a multifunctional cytokine that mediates apoptotic cell death in human lymphocytes in vitro. To better understand the mechanism through which TGF-beta1 exerts its apoptotic effect, we investigated the role of TGF-beta1 in the relationship between burn injury and cell death of splenocytes in a mouse model of either 0%, 25%, or 40% full-thickness burns. Mice were killed and spleens were harvested at 15 and 30 minutes and at 1, 2, 4, 8, 12, and 24 hours after the burn. The spleens were divided and used for both histologic analyses with H-E stain and TUNEL stain and for total messenger RNA isolation and reverse transcriptase-polymerase chain reaction amplification. Amplified polymerase chain reaction products were analyzed for signal strength by electrophoresis. TGF-beta1 RNA expression was highest at 2 hours after the burn injuries in the 40% full-thickness burns and at 4 hours after the burn injuries in the 25% full-thickness burns. The relative increase in TGF-beta1 RNA was 3 times greater with the larger burn than with the smaller burn. In histologic analysis, splenocyte apoptotic cell death was observed at 4 to 24 hours after the burn in the 40% full-thickness burns but at only 4 to 12 hours in the 25% full-thickness burns. TGF-beta1 RNA peak expression was observed at different times after the burn in 25% and 40% full-thickness burns. Histologic analysis showed apoptotic cell death in proportion with respective messenger RNA expressions. This suggests that TGF-beta1 may be associated with apoptosis of splenocytes in vivo and that the effect of TGF-beta1 after a burn injury may be important in the immune system.

Gene expression and cytokine and enzyme activation in the liver after a burn injury.

The liver plays a critical role in the inflammatory response to injury; however, the mechanisms by which the liver is affected and how it influences the rest of the immune system are not well understood. Partial hepatectomy is a direct injury to the liver, whereas a burn is an indirect injury to liver, but both injuries appear to produce damage to the liver. In this study, we used a mouse model of 25% total body surface area and 40% total body surface area full-thickness burns to investigate the mechanism of liver damage and response to burn injury by measuring levels of c-Jun messenger (m)RNA, NFkappaB nuclear protein, interleukin-6, transaminases, and liver tissue histology over time. c-Jun and NFkappaB are 2 transcription factors that are induced by partial hepatectomy and related to hepatocyte injury and growth. In both groups of mice with burns, expression of c-Jun mRNA and NFkappaB nuclear protein was activated within 30 minutes after the burn injury, followed by increased levels of interleukin-6 and, finally, elevated enzyme levels. Liver injuries were similar in both groups despite the magnitude of the burns. We believe that these gene products are initiated in the hepatocyte injury after a burn and that they precede other inflammatory responses such as cytokine release, plasma transaminase levels, and histologic changes.

Accuracy of administrative data in trauma.

BACKGROUND: Accurate data are needed to evaluate outcomes, therapeutics, and quality of care. This study assesses the accuracy of administrative databases in recording information about trauma patients. METHODS: Patients with thoracic aorta injury were identified with a state trauma registry, and the medical records were reviewed. Data collected were compared to administrative data on patients with thoracic aorta injuries, at the same hospitals in the same time period. RESULTS: Fifteen patients (16.3%) with thoracic aorta injury were not recorded in the administrative database, and 23 patients (18.7%) were misdiagnosed. Ninety-one patients were found in both data sources. The administrative database significantly (P < .05) underrecorded abdominal injuries (50 vs 35), orthopedic injuries (117 vs 75), and chest injuries (77 vs 48). The number of aortograms (78 vs 8), type of operative procedures (use of graft; 70 vs 30), use of bypass (35 vs 16), and complications (77 vs 33) were underreported (P < .05). The Injury Severity Score was underestimated by the administrative database (38.65 +/- 12.41 vs 25.66 +/- 9.53; P < .05). CONCLUSIONS: Administrative data lack accuracy in the recording of associated injury, injury severity, diagnostic, and procedural data. Whether these data should be used to evaluate treatment or quality of care in trauma is questionable.

Percutaneous drainage of pancreatic pseudocysts is associated with a higher failure rate than surgical treatment in unselected patients.

OBJECTIVE: The primary aim was to compare directly the effectiveness of percutaneous drainage versus surgical treatment of pancreatic pseudocysts in unselected patients. The authors also wished to identify factors that may predict a successful outcome with percutaneous drainage. SUMMARY BACKGROUND DATA: Pancreatic pseudocysts are a common complication of pancreatitis, and recent data suggest that many pseudocysts may be observed or treated successfully by percutaneous drainage. Failures with percutaneous drainage have been recognized increasingly, and a direct comparison of percutaneous and surgical treatment was initiated to identify factors that may affect outcome with these approaches. METHODS: A computerized index search of the medical records of patients with a diagnosis of pancreatic pseudocyst was performed from 1984 to 1995. One hundred seventy-three patients were identified retrospectively and assigned to treatment groups: observation (n = 41), percutaneous drainage (n = 66), or surgical treatment (n = 66). Data on demographics, clinical presentation, pseudocyst etiology and characteristics, diagnostic evaluation, management, and outcome were obtained. Treatment failure was defined as persistence of a symptomatic pseudocyst or the need for additional intervention other than the original treatment. RESULTS: The etiology of pancreatitis, clinical presentation, and diagnostic evaluation did not differ between groups. Twenty-seven percent had documented chronic pancreatitis, and the etiology of pancreatitis was alcohol in 61% of patients. Mean pseudocyst size was 4.2 +/- 1 cm, 8.2 +/- 1.1 cm, and 7.4 +/- 1.3 cm in the observed, percutaneously treated, and surgically treated groups, respectively. Expectant treatment was successful in 93% of patients. Percutaneous drainage was successful in 42% of patients, whereas surgical treatment resulted in a success rate of 88%. Patients treated by percutaneous drainage had a higher mortality rate (16% vs. 0%), a higher incidence of complications (64% vs. 27%), and a longer hospital stay (45 +/- 5 days vs. 18 +/- 2 days) than patients treated by surgery. Eighty-seven percent of patients in whom percutaneous drainage failed required surgical salvage therapy. Multiple logistic regression analysis failed to reveal any factors significantly associated with a successful outcome after percutaneous drainage. CONCLUSIONS: Percutaneous drainage results in higher mortality and morbidity rates and a longer hospital stay than surgical treatment of pancreatic pseudocysts. The clinical benefit of percutaneous drainage of pancreatic pseudocysts in unselected patients has not been realized, and the role of this treatment should be established in a clinical trial.

Transforming growth factor-beta impairs postburn immunoglobulin production by limiting B-cell proliferation, but not cellular synthesis.

BACKGROUND: Transforming growth factor-beta (TGF-beta) has been shown to be an inhibitor of immunoglobulin (Ig) synthesis and may contribute to decreased Ig synthesis after burn injury. This study investigated the relationship between TGF-beta and Ig synthesis after burn injury. METHODS: Twenty-four BALB/c mice received either a 30% body surface area full-thickness contact burn or no burn. Splenocytes were isolated 8 days after burn and were cultured with 0, 0.05 or 0.5 ng/mL TGF-beta. After culture, total IgG and total IgM were measured by enzyme-linked immunosorbent assay. The number of IgM-secreting cells per 10(5) cells was measured by enzyme-linked immunoabsorbent spot forming assay. Total IgM per IgM-secreting cell (pg/cell) was calculated. RESULTS: Total IgG, IgM, IgM-secreting cells, and B-cell number after culture were decreased by burn injury, and the decrease was exacerbated by the presence of TGF-beta. The total IgM per IgM-secreting cells, however, was significantly increased by TGF-beta at 0.5 ng/mL. CONCLUSION: These data demonstrates that TGF-beta does not specifically impair IgM secretion by committed IgM B cells but appears to decrease B-cell proliferation or clonal expansion.

Host priming, not target antigen type, decides rejection rate in mice primed with MHC II "knockout" cultured keratinocytes.

BACKGROUND: Lack of skin for autograft continues to be problematic in patients with large burns. Allograft and xenograft have been used, but are prone to rapid rejection. Use of cultured keratinocytes (CK) and major histocompatibility complex (MHC) II "knockout" grafts leads to prolonged graft survival compared to allograft. Whether this prolongation is secondary to decreased priming efficacy or target recognition is unknown. Whether a combination of these techniques would generate a less immunogenic allograft remains to be determined. METHODS: CBA mice (n = 100) were flank-grafted with full thickness C57BL/6 (B6 FT), B6 cultured keratinocytes (B6 CK), B6 major histocompatibility complex II "knockout" full thickness (KO II FT), B6 major histocompatibility complex II "knockout" cultured keratinocytes (KO II CK), or a full thickness autograft (Auto). Three weeks after priming flank grafting, B6, MHC I (KO I), and KO II full thickness tail grafts were placed on each mouse. Tail graft rejection was assessed daily by an observer blinded to flank and tail-graft type. A 4-point grading system for graft color, hair loss, and texture was used. RESULTS: Animals primed with KO II CK flank grafts had increased survival of tail grafts over B6 FT flank grafted controls (12.3 +/- 1.05 vs 10.1 +/- 1.00, P < 0.05). Within flank graft groups, however, B6, KO I, and KO II tail graft survival was similar. CONCLUSIONS: KO II CK allografts decrease host priming compared to normal B6 FT allograft. MHC deletion (KO I or KO II) does not protect a target graft from rejection in a primed host. CK and KO techniques may offer a less immunogenic allograft and a readily available source of wound coverage in patients with extensive burns.

Return to jeopardy: the fate of pediatric burn patients who are victims of abuse and neglect.

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.

Immunogenicity of cultured keratinocyte allografts deficient in major histocompatibility complex antigens.

BACKGROUND: Full-thickness (FT) and cultured keratinocyte (CK) allografts have been used as temporary skin replacements in patients with massive burns, but these grafts are ultimately rejected after restoration of host immunocompetence. Genetic engineering has permitted the creation of knockout (KO) mice deficient in class I or class II major histocompatibility antigens. This study examines the immunogenicity of such grafts to determine if these genetically modified keratinocytes could be used for permanent wound coverage. METHODS: Host sensitization to alloantigen was assessed by second-set rejection. CBA mice (n = 111) were primed with flank grafts consisting of FT and CK allografts from normal C57BL/6 donors, FT and CK class I KO allografts, FT and CK class II KO allografts, and CK autografts. Three weeks later, hosts were challenged with normal tail allografts and observed for second-set rejection. Median graft survival was analyzed by chi2 and Wilcoxon rank tests. In the second experiment, cytotoxic T lymphocytes (CTLs) were harvested from CBA mice (n = 28) 3 weeks after flank grafting. CTL effectors were tested on radiolabeled targets at various ratios in a 51Cr release assay. Dilution curves of CTL activity were compared by analysis of variance. RESULTS: Hosts primed with CK or FT allografts demonstrated accelerated rejection of second-set tail grafts compared with hosts covered with CBA autografts. CK knockout grafts were less immunogenic than FT knockout skin; class II KO allografts were considerably less immunogenic than class I KO allografts. CTL activity against the knockout CK allografts was negligible compared with that of hosts primed with normal allografts or FT knockout allografts. CONCLUSION: Although full-thickness knockout skin retains substantial immunogenicity, cultured keratinocytes deficient in class II antigens fail to prime for accelerated second-set rejection and do not elicit a CTL response in the graft recipient. This lack of immunogenicity may permit the indefinite survival of allogeneic knockout keratinocytes in patients requiring massive wound excision and coverage.

The effector component of the cytotoxic T-lymphocyte response has a biphasic pattern after burn injury.

INTRODUCTION: Burn injury delays allograft rejection and impairs the host defense against infection. These functions are mediated via the cytotoxic T-lymphocyte (CTL) response. The CTL response is divided into antigen recognition/processing and effector phases. Presensitization allows selective analysis of changes, induced by burn injury, in the effector limb of the CTL response in relation to time and burn size. METHODS: Anesthetized CBA mice were primed with either a flank allograft from C57BL/6 (B6) mice or an autograft (negative control). Five weeks after grafting, animals were anesthetized and received either a 0, 20, or 40% burn. Spleens were harvested 3, 7, 10, and 14 days after burn injury (n = 96), cocultured with B6 stimulator splenocytes, and assessed for CTL response to radiolabeled allogeneic targets in a 51Cr release assay. In experiment 2, spleens were harvested from unburned and 40% burned animals on Postburn Days 3 and 14. After triple staining, cells were analyzed by flow cytometry for CD4, CD8, and CD25 antigens. In experiment 3, splenocytes from 0 and 40% burned animals on Postburn Days 3 and 14, were cocultured with B6 stimulators for 5 days. Supernatants were evaluated for interleukin (IL)-2, IL-5, and interferon-gamma (IFN-gamma) using ELISA: RESULTS: The CTL response for 20 and 40% burned animals decreased 3 days postburn (-11.9 and -30.1%, P < 0.05), returned to baseline in 7-10 days, and was increased by 14 days postburn (15.8 and 22.6%, P < 0.05). The T-helper lymphocyte population (CD4) from 40% burn animals was significantly decreased on Postburn Days 3 and 14 (10.12 +/- 0.45% vs 11.78 +/- 0.29% and 10.19 +/- 0.24% vs 14.21 +/- 0.97%, respectively, P < 0.05). The CTL effector (CD8) splenocyte population was significantly higher in the burned animals on Postburn Day 14 (4.55% vs 3.71%, P < 0.05). On Postburn Day 3, average IL-5 production was higher in the burned animals (1.80 pg/ml vs 0.59 pg/ml, respectively, P < 0.05). The burn group, on Postburn Days 3 and 14, showed a decrease in mean IL-2 production (212.81 pg/ml vs 263.6 pg/ml and 342.7 pg/ml vs 421.4 pg/ml, respectively, P < 0.05). Mean IFN-gamma production on Postburn Days 3 and 14 was decreased in burned mice (263.75 pg/ml vs 285.57 pg/ml and 218.16 pg/ml vs 263.42 pg/ml, P < 0.05). CONCLUSIONS: Burn injury impairs the effector limb of the CTL response as a function of burn size in the immediate postburn period. CTL activity returns to baseline within 7-10 days postburn and has a rebound increase by Day 14. Early CTL suppression, after burn injury, may be due to a decrease in the T-helper subpopulation. The late increase in cytotoxicity may be secondary to an increase in the effector CTL population in the late postburn period. Burn injury causes a T-helper-2 phenotype as demonstrated by depressed IL-2 and IFN-gamma production and increased IL-5 production.

Pentoxifylline alters class-specific immunoglobulin synthesis in resuscitated burn injury.

Pentoxifylline (PTXF) is a hemorheologic agent that can attenuate microvascular alterations induced by injury, resulting in improved microcirculatory flow. Burn injury-induced immunologic suppression may be caused by alterations in microvascular flow. We studied the effects of PTXF on humoral immunity in resuscitated burn injury. Male AKR mice (n = 80) were randomized to four groups: SHAM, BURN, PTXF-BURN, and NS-BURN (saline burn). Animals were resuscitated with Ringer's lactate and morphine sulfate and put to death at days 1 and 4 after injury. PTXF-BURN animals received PTXF (50 mg/kg intraperitoneally) at the time of resuscitation. Splenic lymphocytes (1 x 10(6) cells/well) were cultured with lipopolysaccharide (LPS) (2.5 and 10 micrograms/ml)). LPS-stimulated in vitro class-specific immunoglobulin (Ig) production was determined by enzyme-linked immunosorbent assay from splenic cell culture supernatants. Burn injury induced a reduction in immunoglobulin (Ig) M synthesis on postburn day 4. PTXF treatment was associated with an increase in IgG production, but a greater depression in IgM synthesis than burn injury alone. PTXF administration during resuscitation in burn injury does not ameliorate the burn-induced depression in IgM synthesis and results in significant potential adverse modulation of humoral immune function.

Early but not late burn wound excision partially restores viral-specific T lymphocyte cytotoxicity.

OBJECTIVE: Early burn wound excision restores immunocompetence and improves patient survival, but the exact mechanisms have not yet been defined. Burn injury impairs cytotoxic T lymphocyte (CTL) activity as a function of burn size, increasing the risk of infection. The purpose of this study was to determine if early wound excision improved viral-specific CTL function. METHODS: Anesthetized C57BL/6 mice (n = 20) received 0%, 20%, or 40% total body surface area full-thickness contact burns and were inoculated 3 days later with intraperitoneal lymphocytic choriomeningitis virus. Eight days after infection, or 11 days after burn, CTL effectors (E) were harvested and tested against infected, radiolabeled L-Dh targets (T) in a 51Cr-release assay, at varied E:T ratios. Dilution curves of CTL activity were compared by analysis of variance. In the second experiment, mice (n = 18) underwent a 30% burn that was totally excised and grafted on postburn days (PBDs) 0, 3, and 7. Control groups included sham burn and no excision of a 30% burn. In the third experiment, mice (n = 22) received a 30% burn that was partially, completely, or not excised on PBD 3. Control groups included sham burn with and without excision. All groups were infected with intraperitoneal lymphocytic choriomeningitis virus on PBD 3. Viral-specific CTL activity was determined on PBD 11. RESULTS: Both 20% and 40% burn injury impaired viral-specific CTL function. Wound excision on PBDs 0 and 3, but not on PBD 7, partially restored CTL function. Total excision of the 30% burn improved CTL activity to a greater extent than did partial excision. CONCLUSION: Burn injury inhibits viral-specific CTL activity. Early, complete wound excision augments CTL function. Improved CTL activity after burn may reduce the risk of infection, providing an immunologic rationale for expeditious wound excision.