Bioengineering methods were useful in evaluating multiple characteristics during wound healing: (i) reflectance colourimetry for skin colour, (ii) evaporimetry to measure transepidermal water loss as an indicator of barrier function, (iii) laser Doppler perfusion imaging to assess cutaneous blood flow, and (iv) ballistometry to measure the mechanical properties of skin hardness and elasticity. Perhaps the most useful method was evaporimetry, as a restored barrier function was the best indicator of healed wounds. The use of reflectance colourimetry and ballistometry will continue in future wound healing studies for their contributions in judging cosmetic and functional outcomes. While useful, laser Doppler perfusion imaging was found to be rather time consuming. This methodology will be limited in the future to burn depth estimation prior to treatment, and for evaluation of pharmaceuticals specifically designed to improve or sustain blood flow into damaged areas.
The study supports the pulmonary and systemic safety of aerosolized CIS at expected lung dose levels/kg of up to 12 times greater than the average dose patients are receiving in the CYCLIST trial.
Introduction: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment.Methods: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure.Results: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean Ͻ2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal.Conclusions: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.
Incisional hernias occur in up to 11 per cent of patients undergoing abdominal surgery. Up to 50 per cent of these patients with hernias will require repeat operative procedures. Management of these hernias have focused primarily on tensile strength of the mesh material, have not addressed currently used materials, and have not compared the strength of these repairs with each other. Forty-nine adult Sprague–Dawley rats had an incisional hernia created by removing a portion of their abdominal wall that was then repaired primarily, using either a composite mesh, Dual mesh (Gore-Tex), or polypropylene mesh. Six weeks after the repair, the rats were euthanized. Hydrostatic distension of the abdominal cavity was performed to compare bursting strength of each repair. Wound tensile strength was assessed and compared. Tissue samples were also taken to compare repair types for incorporation of prosthetic materials. The gross weight of the animals subjected to hydrostatic distention was equivalent between groups, as was the volume required prior to failure of the repair. There was a trend toward improved tensile strength of the Prolene mesh repair, which had a lower average inflammatory and fibrosis score on histology. Overall, the type of mesh used for repair does not seem to impact significantly the strength of the repair when assessed 6 weeks postoperatively. Choice of prosthetic material to repair the hernia should be made based on economics and handling characteristics alone. Prolene mesh has satisfactory strength with the least amount of inflammation and fibrosis.
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