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Biomedical subjects

G C O'Brien

Publications and source records attributed to G C O'Brien.

5 recordsLinked to original sources

Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

Acute Disease↗

Ingested foreign bodies in the paediatric patient.

BACKGROUND: Paediatric foreign body (FB) ingestion is a common problem and while most can be managed conservatively, a sub-population require intervention. AIMS: To establish clear guidelines for management of paediatric FB ingestion. METHODS: A retrospective chart review analysing all paediatric admissions with FB ingestion over a 10-year period from 1990 to 1999. RESULTS: Of 339 patients presenting to the accident and emergency department with FB ingestion, 59 required admission. Ingestion was accidental in 93.0% of patients. The reasons for admission were as follows: large FBs; dangerous FBs; and living far from the hospital. Nineteen patients (32.2%) were discharged without intervention. Thirty-seven (62.7%) required endoscopic retrieval. In two, the FB was not identified at endoscopy. Only three (5%) required surgery. CONCLUSION: Conservative management of FB ingestion in the paediatric population is possible in the majority of cases. However, a minority require intervention. While guidelines for intervention are ill-defined, definitive indications include symptomatic patients, or dangerous objects.

Adolescent↗

Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.

BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness. METHODS: Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response. RESULTS: Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease. CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.

Adult↗