Radiation-induced craniofacial bone growth inhibition: development of an animal model.

Craniofacial deformities caused by therapeutic radiation-induced bone growth inhibition can occur in up to 100% of survivors of childhood head and neck cancers. The mechanism of radiation-induced craniofacial bone growth inhibition is poorly understood. The objective of this study is to establish a model of radiation-induced craniofacial bone growth inhibition to study the pathophysiology of radiation on growing membranous bone. Seven-week-old male New Zealand white rabbits were randomized into 4 groups (n = 10/group) and received a single dose of orthovoltage radiation (0, 15, 25, or 35 Gy) to the right orbital-zygomatic complex. Serial radiographs and computed tomography scans were performed for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Statistically significant ( P < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were found after radiation with 25 or 35 Gy compared with nonirradiated control animals. A significant ( P < 0.05) decrease in orbital-zygomatic complex volume was noted after 15-Gy radiation but there were no significant effects on linear bone growth as assessed by cephalometric analysis at this dose. This study establishes the rabbit orbital-zygomatic complex as a suitable model for the study of radiation-induced craniofacial bone growth inhibition and will permit investigation into the underlying cellular and molecular basis of this injury.

The role of Mepitel silicone net dressings in the management of fingertip injuries in children.

Forty-five children with isolated fingertip injuries were randomized for treatment with either Mepitel silicone net dressings or paraffin gauze dressings. Over a 4 week period, the objective adherence of the dressing, and the perceived level of stress caused to the child by the dressing change were scored by linear analogue scales. The wounds were also assessed for the progress of healing and presence of infection. Twenty children received Mepitel dressings and 25 had paraffin gauze dressings. There was no difference in duration of healing or complication rates between the two groups. Statistically lower scores were seen for the Mepitel group for the first 3 weeks in both adherence and stress scores. These results suggest that silicone net dressings may be a less adherent and less painful method of dressing fingertip injuries in children.

Alpha-1-antichymotrypsin is an effective inhibitor of pancreatitis-induced lung injury.

BACKGROUND: Pancreatitis-induced adult respiratory distress syndrome (ARDS) may result from an imbalance between leucocyte proteases, produced by infiltrating neutrophils, and endogenous protease inhibitors. OBJECTIVE: The aim of this study was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P3-P3'), an endogenous serine protease inhibitor, in ameliorating lung injury associated with pancreatitis. DESIGN: Sprague-Dawley rats were randomly divided into control (saline infusion) and pancreatitis groups, which were treated immediately with saline or rACT P3-P3' (50 mg/kg body weight). METHODS: Myeloperoxidase (MPO) was employed as a monitor of neutrophil traffic in the lung, and wet-dry lung weights as a measure of pulmonary endothelial permeability. Lungs were also evaluated histologically. RESULTS: Caerulein (5 micrograms/kg body weight/h) induced pancreatitis in all animals, with an increase in serum amylase from 1851 +/- 208 IU (control) to 5198 +/- 924 IU (pancreatitis), P < 0.05. Pancreatitis caused a significant increase in MPO activity (7.8 +/- 1.1 units compared with 2.08 +/- 0.5 units in controls, P < 0.001) and wet-dry lung weight ratios (12.8 +/- 3.3 compared with 3.2 +/- 0.1 in controls, P < 0.001), indicating significant pulmonary neutrophil influx and microvascular leakage, respectively. These increases in MPO activity and wet-dry ratios were decreased in the pancreatitis group treated with rACT P3-P3' (MPO 4.68 +/- 0.7 units, wet-dry ratio 4.2 +/- 0.5, P < 0.05 compared with the untreated pancreatitis group). CONCLUSION: These data support the hypothesis that deficient endogenous protease inhibition may be responsible for the neutrophil-mediated lung injury observed in pancreatitis and suggest that there may be a therapeutic role for recombinant protease inhibitors such as alpha-1 antichymotrypsin.

Role of nitric oxide in lung injury associated with experimental acute pancreatitis.

This study evaluated the effect of varying the synthesis of nitric oxide with sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAME) in a pancreatitis-lung injury model. Rats (n = 45) were randomized to control or caerulein-induced pancreatitis groups, treated with saline, sodium nitroprusside (0.4 micrograms/kg) or L-NAME (10 mg/kg). Myeloperoxidase activity was used as a measure of neutrophil infiltration. Wet to dry (W:D) lung weight and bronchoalveolar lavage (BAL) protein concentrations were used to assess vascular leakage. Pancreatitis was shown to induce pulmonary neutrophil influx: mean(s.e.m.) myeloperoxidase activity 6.79(0.5) units/g in caerulein-treated animals versus 2.08(0.5) units/g in controls (P < 0.001). Animals with pancreatitis showed increased microvascular leakage compared with controls (mean(s.e.m.) W:D lung weight 7.01(0.5) versus 2.85(0.2), P < 0.001; BAL protein concentration 2539(222) versus 347(32) micrograms/ml, P < 0.001). Compared with the saline-treated pancreatitis group, these changes were reduced by sodium nitroprusside (mean(s.e.m.) myeloperoxidase activity to 2.5(0.4) units/g, P < 0.001; W:D lung weight to 3.8(0.37), P < 0.001; BAL protein concentration 1389(182) micrograms/ml, P < 0.05). L-NAME exacerbated the pancreatitis-induced pulmonary oedema (W:D lung weight increased to 11.96(0.6), P < 0.001), protein leakage (BAL protein concentration rose to 3707(309) micrograms/ml, P < 0.05) and neutrophil infiltration (myeloperoxidase activity increased to 9.01(0.3) units/g, P < 0.05). These data suggest that, in vivo, nitric oxide inhibits pancreatitis-induced lung injury, possibly in part by inhibiting pulmonary neutrophil influx.