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Biomedical subjects

A A Meyer

Publications and source records attributed to A A Meyer.

At least 19 recordsLinked to original sources
PubMed2004

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.

Adolescent↗
PubMed2001

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.

Animals↗
PubMed2000

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.

Acute Disease↗
PubMed2000

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.

Abdominal Injuries↗
PubMed2000

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.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Animals↗
PubMed1999

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.

Adult↗
PubMed1998

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.

Animals↗
PubMed1998

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.

Animals↗
PubMed1998

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.

Animals↗
PubMed1997

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.

Animals↗
PubMed1996

Immediate burn wound excision restores antibody synthesis to bacterial antigen.

Although burn wound excision and grafting have been shown to improve patient survival, the effects on immune function, especially humoral immunity, are not completely understood. The purpose of this study was to investigate the effect of immediate and early wound excision on antibody synthesis and B-cell proliferation, specifically, antibody response to PGPS, a ubiquitous bacterial cell wall antigen. Thirty-six male BALB/c mice were divided into four groups. Sham mice received no burn, and remaining mice received a 30% body surface area full-thickness burn. Under general anesthesia, excision and grafting was performed either 6 or 72 hr after injury (BE&G6 and BE&G72 groups). A fourth control group received burn but did not undergo excision and grafting (Burn group). Splenocytes were isolated 8 days postburn and stimulated with 2.5 microgram/ml lipopolysaccharide. Anti-PGPS IgM, total IgM, and total IgG levels were determined by ELISA. B-cell proliferation, measured by [3H]-thymidine uptake, was expressed as stimulation index. All B-cell functions were significantly suppressed by burn injury. Immediate excision and grafting (BE&G6) restored anti-PGPS IgM synthesis to normal, while nonspecific B-cell functions did not change significantly. Early excision and grafting (BE&G72), however, failed to significantly improve any B-cell functions. Immediate but not early BE&G restored antibody synthesis to the bacterial cell wall antigen (PGPS). Immediate BE&G may therefore lead to a decrease in bacterial infection after burn injury.

Animals↗
PubMed1996

Evaluation of persistent cough in children.

Persistent or chronic cough is defined as a cough lasting more than 3 weeks. A systematic approach to the diagnosis and treatment of chronic cough involves a detailed history. The age of the child, descriptive qualities of the cough, and environmental exposures are particularly important. A thorough physical examination, looking for evidence of growth retardation and failure to thrive in addition to more specific signs, is essential. When further investigation is necessary, a complete blood count, chest radiograph, and PPD are indicated. Additional testing is guided by findings in the history and physical examination to rule out the less common but more serious causes.

Adolescent↗