Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults.

INTRODUCTION: Propranolol, a nonselective ß-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. METHODS: Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge. RESULTS: Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P < 0.05). The average number of days between skin grafting procedures was also lower in propranolol patients (10 ± 5 days) than in control patients (17 ± 12 days; P = 0.02), indicative of a faster donor site healing time in the propranolol group. Packed red blood cell infusion was similar between groups (control 5.3 ± 5.4 units vs. propranolol 4.4 ± 3.1 units, P = 0.89). Propranolol was associated with a 5 to 7% improvement in perioperative hematocrit during grafting procedures of 4,000 to 16,000 cm(2) compared to control (P = 0.002). CONCLUSIONS: Administration of propranolol during the acute hospitalization period diminishes blood loss during skin grafting procedures and markedly improves wound healing in severely burned adults. As burn patients require serial surgical interventions for motor and cosmetic repair, restricting blood loss during operative intervention is optimal.

Distal metaphyseal radius fractures in children following closed reduction and casting: can loss of reduction be predicted?

PURPOSE: The aim of this study was to identify factors which contribute to loss of reduction (LOR). METHODS: Outpatient records and initial, post-reduction (PR) and follow-up radiographs of patients with a distal radial metaphyseal fracture were reviewed to determine demographic factors; fracture characteristics (obliquity, comminution, intact ulna); three-point cast index (3PI); and initial, PR, and follow-up displacement (angulation and translation in the sagittal and coronal planes). Univariate and multivariate regression were used to identify significant risk factors for LOR. RESULTS: A total of 161 patients were included in our series (119 boys and 42 girls). Fifty-seven (35%) patients met the criteria for LOR. Multivariate logistic regression revealed that patients over 14 years old were 4.8 times more likely (p=0.01) to lose reduction, and those with more than 10% PR translation in the sagittal plane were four times more likely (p=0.03) to lose reduction. In younger patients, initial coronal translation and PR sagittal translation were independent risk factors. Patients with over 10% initial translation in the coronal plane were 2.4 times more likely (p=0.01) to lose reduction, and those with over 10% PR translation in the sagittal plane were 2.7 times more likely (p=0.03) to lose reduction. Three point cast index was not found to be a significant risk factor (1.64 vs. 1.57, p=0.43). CONCLUSION: Our study, the largest dedicated series of distal radial metaphyseal fractures, indicates that loss of reduction is common. Our analysis suggests that an anatomical reduction, which minimises residual translation, is the most important variable in preventing a loss of reduction.

Impact of the lectin chaperone calnexin on the stress response, virulence and proteolytic secretome of the fungal pathogen Aspergillus fumigatus.

Calnexin is a membrane-bound lectin chaperone in the endoplasmic reticulum (ER) that is part of a quality control system that promotes the accurate folding of glycoproteins entering the secretory pathway. We have previously shown that ER homeostasis is important for virulence of the human fungal pathogen Aspergillus fumigatus, but the contribution of calnexin has not been explored. Here, we determined the extent to which A. fumigatus relies on calnexin for growth under conditions of environmental stress and for virulence. The calnexin gene, clxA, was deleted from A. fumigatus and complemented by reconstitution with the wild type gene. Loss of clxA altered the proteolytic secretome of the fungus, but had no impact on growth rates in either minimal or complex media at 37°C. However, the ΔclxA mutant was growth impaired at temperatures above 42°C and was hypersensitive to acute ER stress caused by the reducing agent dithiothreitol. In contrast to wild type A. fumigatus, ΔclxA hyphae were unable to grow when transferred to starvation medium. In addition, depleting the medium of cations by chelation prevented ΔclxA from sustaining polarized hyphal growth, resulting in blunted hyphae with irregular morphology. Despite these abnormal stress responses, the ΔclxA mutant remained virulent in two immunologically distinct models of invasive aspergillosis. These findings demonstrate that calnexin functions are needed for growth under conditions of thermal, ER and nutrient stress, but are dispensable for surviving the stresses encountered in the host environment.

Isolated distal radial metaphyseal fractures with an intact ulna: risk factors for loss of reduction.

PURPOSE: The purpose of this study was to determine the risk factors for loss of reduction in patients with an isolated distal radius fracture and intact ulna. METHODS: Outpatient records and initial, post-reduction, and follow-up radiographs of children with displaced distal radial metaphyseal fractures and intact ulnas that required closed reduction and casting at our institution were reviewed for demographic factors, body mass index (BMI), initial fracture displacement, residual displacement after reduction, and 3-point cast index. Loss of reduction was defined as angulation ≥15° in the coronal plane for all ages and/or angulation ≥20° in the sagittal plane for patients ≥11 years of age and ≥30° for children <11 years of age. Additionally, all patients who were remanipulated and/or pinned were considered to have lost reduction. RESULTS: Thirty-five of the 76 patients in our series met the criteria for loss of reduction (46%). Multivariate logistic regression revealed that initial angulation in the coronal plane and post-reduction translation in the coronal plane were independent predictors for loss of reduction. Patients with >11° of initial angulation in the coronal plane were 6.3 times as likely to lose reduction (confidence interval [CI]: 1.43-28.3, P = 0.015) and those with any amount of residual translation in the coronal plane after closed reduction were 7.8 times as likely to lose reduction (CI: 2.5-24.0, P < 0.001). CONCLUSION: Our study, the largest dedicated series of distal radial metaphyseal fractures with intact ulnas, indicates that loss of reduction is common, and that risk factors include initial angulation in the coronal plane and post-reduction translation in the coronal plane.

Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI of fetal brain development in pregnant baboons.

The global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (PG; weeks 17-25 of 26 weeks total gestation). Studying pregnant baboons using high-resolution MRI in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of 10 primary cortical sulci. Seven normally developing fetuses were imaged in two animals longitudinally and sequentially. We compared these results to those on PG that from the ferret studies and analyzed them in the context of our recent studies of phylogenetics of cerebral gyrification. We observed that in both primates and non-primates, the cerebrum undergoes a very rapid transformation into the gyrencephalic state, subsequently accompanied by an accelerated growth in brain volume and cortical surface area. However, PG trends in baboons exhibited some critical differences from those observed in ferrets. For example, in baboons, the growth along the long (length) axis of cortical sulci was unrelated to the growth along the short (depth) axis and far outpaced it. Additionally, the correlation between the rate of growth along the short sulcal axis and heritability of sulcal depth was negative and approached significance (r = -0.60; p < 0.10), while the same trend for long axis was positive and not significant (p = 0.3; p = 0.40). These findings, in an animal that shares a highly orchestrated pattern of PG with humans, suggest that ontogenic processes that influence changes in sulcal length and depth are diverse and possibly driven by different factors in primates than in non-primates.