Search PubMed⌕ Search

Biomedical subjects

Katherine A Barsness

Publications and source records attributed to Katherine A Barsness.

8 recordsLinked to original sources
PubMed2004

IL-1beta induces an exaggerated pro- and anti-inflammatory response in peritoneal macrophages of children compared with adults.

Children have a lower incidence of acute lung injury (ALI) compared with adults. Because ALI appears to be the end result of systemic hyperinflammation, children may either have 1) an attenuated pro-inflammatory response or 2) an augmented anti-inflammatory response compared with adults. The purpose of this study was to determine the IL-1-induced pro- and anti-inflammatory response of pediatric vs. adult peritoneal macrophages (PMs). We hypothesized that pediatric PMs would have an enhanced anti-inflammatory response compared with adult PMs. Human PMs were collected during elective laparoscopic procedures, cultured, and stimulated with IL-1beta. IL-6, IL-8, IL-10, and TNFalpha production were determined by ELISA. Statistical analyses were by ANOVA; a P <0.05 was significant. Our results showed that IL-1beta induced an 11-fold increase in IL-10 production in pediatric PMs (659+/-103 vs. 60+/-25 control, P <0.05). There was no IL-10 production in IL-1beta-stimulated adult PMs. IL-1beta-induced TNF production was greater in children compared with adults (2152+/-166 vs. 592+/-188, P <0.05). Similarly, IL-1beta-induced IL-6 production was greater in pediatric PMs compared with adults (532+/-3 vs. 444+/-52, P <0.05). There was no difference in IL-1beta-induced IL-8 production in children compared with adults. The IL-10:TNFalpha ratio after IL-1beta stimulation was 0.306+/-0.056 in pediatric macrophages and 0.020+/-0.015 in adult macrophages ( P<0.01). In conclusion, IL-1beta-induced IL-6 and TNFalpha production were greater in pediatric than adult PMs. Furthermore, pediatric PMs had an 11-fold increase in IL-1beta-induced IL-10 production, while adult PMs did not produce IL-10. Therefore, IL-1beta induces both a pro- and an anti-inflammatory response in pediatric PMs, whereas adult PMs produce only pro-inflammatory cytokines in response to IL-1beta. The exaggerated anti-inflammatory IL-10 response in children may be an important factor in the observed differences in ALI between children and adults.

Adult↗
PubMed2004

Hemorrhage-induced acute lung injury is TLR-4 dependent.

Toll-like receptor 4 (TLR-4), initially identified as an LPS receptor, is critical to the signaling of a variety of danger signals, including heat shock protein 60, fibrinogen, and fibronectin. Recent data also suggest that TLR-4 plays a role in determining survival in both endotoxemia and hemorrhagic shock. We hypothesized that a functional TLR-4 would be required for hemorrhage and endotoxin-induced acute lung injury. Hemorrhage- and endotoxin-induced lung TNF-alpha mRNA and protein production, neutrophil accumulation, and protein permeability were dependent on a functional TLR-4. Hemorrhage-induced nuclear factor (NF)-kappaB activation was independent of functional TLR-4, whereas endotoxin-induced activation of NF-kappaB requires a functional TLR-4 for full response. Therefore, we conclude that 1) hemorrhage-induced acute lung injury is TLR-4 dependent and 2) hemorrhage has a different and distinct TLR-4-dependent intracellular activation mechanism compared with endotoxemia.

Acute Disease↗
PubMed2004

Endotoxin induces an exaggerated interleukin-10 response in peritoneal macrophages of children compared with adults.

BACKGROUND: Children have a lower incidence of postinjury multiple organ failure (MOF) compared with adults with equivalent injury severity. Because MOF appears to be the end result of systemic hyperinflammation, children may have either an attenuated proinflammatory response or an augmented antiinflammatory response compared with adults. The purpose of this study was to determine the lipopolysaccharide (LPS)-induced pro- and antiinflammatory cytokine response of pediatric versus adult peritoneal macrophages (PM). The authors hypothesized that pediatric PMs would have an enhanced antiinflammatory response compared with adults. METHODS: Human PMs were collected during elective laparoscopic procedures and stimulated with LPS. (Pediatric cohort: n = 9 [mean, 5.4 years], adult cohort: n = 8 [mean, 41.6 years]). P less than.05 was accepted as significant. RESULTS: LPS-induced a 50-fold increase in interleukin-10 (IL-10) antiinflammatory cytokine production in pediatric versus adult PMs. LPS-induced tumor necrosis factor-alpha (TNF-alpha) production was also increased in pediatric versus adult PMs. The anti-proinflammatory cytokine ratio (IL-10 to TNF-alpha) was 20-fold higher in pediatric versus adult PMs. CONCLUSIONS: LPS-induced macrophage production of both IL-10 and TNF-alpha was increased in children. The anti-proinflammatory cytokine ratio (IL-10 to TNF-alpha) was strikingly higher in pediatric versus adult PMs. These data suggest that the age-related balance of anti- and proinflammatory cytokines in resident macrophages is different in children compared with adults.

Adult↗
PubMed2004

Blunt diaphragmatic rupture in children.

BACKGROUND: Although several series of blunt diaphragmatic rupture in adults have been published, this injury remains largely uncharacterized in the pediatric population. METHODS: We queried our trauma registry for all children admitted with blunt diaphragmatic rupture over a 10-year period at a Level I pediatric trauma center. RESULTS: Six children (aged 2-15 years; mean, 7 years) were identified with blunt diaphragmatic rupture (three right, two left, one bilateral), representing 0.4% of admissions. All of the children had associated injuries (4.5 per child), with a mean Injury Severity Score of 32. Four diaphragmatic injuries were identified during the initial evaluation. The two missed injuries were diagnosed at postinjury days 5 and 8. There were no deaths and all children were eventually discharged without sequelae. CONCLUSION: Blunt diaphragmatic rupture occurs in children with a frequency and severity commensurate with that observed in adults. Our data suggest improved survival compared with adults with this injury.

Adolescent↗
PubMed2004

Renovascular injury: an argument for renal preservation.

BACKGROUND: Renovascular injury is uncommon among children. This study hypothesized that preservation of the severely injured kidney can be achieved safely without renal insufficiency, postinjury hypertension, or the need for hemodialysis. METHODS: Retrospective chart review of renal injuries seen between 1997 and 2001 at a level 1 pediatric trauma center was conducted. Severity of injury was graded by the American Association for the Surgery of Trauma Organ Injury Severity Scale. The outcome variables included the need for hemodialysis, impaired renal function (creatinine), and postinjury hypertension. RESULTS: In this study, 34 children presented with grade 1, 2, or 3 injury (74%), whereas 13 children presented with grade 4 or 5 renovascular injury (28%). The children with unilateral renovascular injury who underwent either nephrectomy or renal preservation had comparable outcomes with no hypertension, hemodialysis, or renal insufficiency in either group. CONCLUSIONS: The treatment outcomes were not different between the patients who underwent renal preservation and those who had immediate nephrectomy. The authors conclude that renal preservation should be attempted for all children with grade 4 or 5 renovascular injury.

Analysis of Variance↗
PubMed2003

The positive predictive value of rib fractures as an indicator of nonaccidental trauma in children.

BACKGROUND: Rib fractures have a strong association with nonaccidental trauma (NAT) and severe trauma. The purposes of this study were to evaluate rib fractures in children to determine (1) the positive predictive value of a rib fracture in defining NAT and (2) the frequency of rib fractures as the only skeletal manifestation of NAT. METHODS: We reviewed the medical records and imaging of all children with rib fractures over a 6-year period. NAT was determined by the Child Advocacy and Protection team. RESULTS: In children younger than 3 years of age, the positive predictive value (PPV) of a rib fracture as an indicator of NAT was 95%. The positive predictive value increased to 100% once historical and clinical circumstance excluded all other causes for rib fractures. CONCLUSION: In this study, rib fracture(s) were the only skeletal manifestation of NAT in 29% of the children.

Adolescent↗
PubMed2002

Cytokines for surgeons.

All cells maintain continuous communication. Hormones derive constitutively from specialized cells to effect total body homeostasis. Conversely, cytokines are produced sporadically from almost all nucleated cells in response to surgical ischemia/septic challenge. Surgical patients are a stew of pulsating cytokines, which serve as the language between all surgically stressed somatic and myeloid cells. Therapeutic manipulation of cytokines has already generated some exhilarating success stories and some crushing disappointments. This introduction to surgically relevant cytokines is presented with the conviction that cytokine-based therapies of surgical patients will (in the future) prove as beneficial to our patients as antibiotics have in the past.

Chemokines↗