Effects of obesity on burn resuscitation.

The effects of obesity on resuscitation after severe burn are not well understood. Formulas to calculate 24-h resuscitation volumes incorporate body weight, which in obese patients often leads to excessive fluid administration and potential complications such as pulmonary edema, extremity or abdominal compartment syndrome, and longer mechanical ventilation. We evaluated the impact of obesity on 24-h fluid resuscitation after severe burn using a cohort of 145 adults admitted to the burn ICU from January 2014 to March 2017 with >20% total body surface area burns. Patients were divided into four groups based on body mass index: normal weight (index of <25), overweight (25-29.9), obese (30-39.9), and morbidly obese (>40). Median total body surface area burn was 39.4% (interquartile range: 23.5%-49.5%). Patients were 74.5% male and demographics and injury characteristics were similar across groups. Resuscitation volumes exceeded the predicted Parkland formula volume in the normal and overweight groups but were less than predicted in the obese and morbidly obese categories (p<0.001). No difference was found in 24-h urine output between groups (p=0.08). Increasing body mass index was not associated with increased use of renal replacement therapy. Only total body surface area burned, and age were independent predictors of hospital mortality (p<0.001). We conclude that using body weight to calculate resuscitation in obese patients results in a predicted fluid volume that is higher than the volume actually given, which can lead to over-resuscitation if rates are not titrated regularly to address fluid responsiveness.

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003-2008).

OBJECTIVES: To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. DESIGN: Retrospective study from December 2003 to December 2008. SETTING: Veterinary university teaching hospital. ANIMALS: Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). CONCLUSION: This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness.

Biological activity of gemcitabine against canine osteosarcoma cell lines in vitro.

OBJECTIVE: To evaluate in vitro biological activity of gemcitabine, alone and in combination with Pamidronate or carboplatin, against canine osteosarcoma (OSA) cell lines. SAMPLE POPULATION: In vitro cultures of OSA cell lines OSA8, OSA16, OSA32, and OSA36. PROCEDURES: Cell lines were treated with gemcitabine alone or in combination with pamidronate or carboplatin. Cell viability was assessed with the water soluble tetrazolium-1 (WST-1) assay, cell cycle distribution was evaluated by means of propidium iodide staining, and apoptosis was assessed by measuring caspase-3/7 activity. Synergy was quantified by use of combination index (CI) analysis. RESULTS: For all of the cell lines, treatment with gemcitabine induced growth inhibition, cell cycle arrest, and apoptosis. No synergistic or additive activity was identified when OSA cell lines were treated with gemcitabine in combination with pamidronate. However, when OSA cell lines were treated with gemcitabine in combination with carboplatin, a significant decrease in cell viability was observed, compared with treatment with carboplatin alone, and the drug combination was determined to be synergistic on the basis of results of CI analysis. For 3 of the 4 cell lines, this activity was greater when cells were treated with carboplatin prior to gemcitabine rather than with gemcitabine prior to carboplatin. CONCLUSIONS AND CLINICAL RELEVANCE: Gemcitabine exhibited biological activity against canine OSA cell lines in vitro, and a combination of gemcitabine and carboplatin exhibited synergistic activity at biologically relevant concentrations. Findings support future clinical trials of gemcitabine alone or in combination with carboplatin for the treatment of dogs with OSA.

System y+ arginine transport and NO production in peripheral blood mononuclear cells in pregnancy and preeclampsia.

Systemic inflammation and oxidative stress are features of normal pregnancy and, in excess, contribute to the pathogenesis of preeclampsia. Inflammatory cell activation stimulates uptake of arginine (the precursor for nitric oxide) by transport system y+, expression of one of its genes (CAT-2) together with inducible nitric oxide synthase, leading to nitric oxide production. We investigated whether these changes occur in peripheral blood mononuclear cells in normal pregnancy and are exaggerated in preeclampsia. Samples from matched trios of nonpregnant, normal pregnant, and preeclamptic women were studied. Arginine transport was characterized, and the expression of inducible nitric oxide synthase and cell-specific nitric oxide production were measured. Arginine uptake by system y+ was significantly increased (P<0.001) in peripheral blood mononuclear cells in normal pregnancy but not in preeclampsia. CAT-2 mRNA was not detected in cells from nonpregnant women but was detected in 3 of 10 normal pregnant and 8 of 10 of preeclamptic women (P<0.001). Inducible nitric oxide synthase protein expression was significantly increased in normal pregnant women (P<0.05) but not preeclamptic women. No significant differences in cell-specific nitric oxide production were observed. These changes confirm the predictions for normal pregnancy but not for preeclampsia in which, despite increases in CAT-2 expression, arginine uptake is not additionally increased. This may create a relative deficiency of arginine in PBMCs favoring superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia.