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Biomedical subjects

John Fitzpatrick

Publications and source records attributed to John Fitzpatrick.

7 recordsLinked to original sources
PubMed2006

Neutrophil transendothelial migration potential predicts rejection severity in human cardiac transplantation.

OBJECTIVE: Transplant rejection remains a clinical problem despite therapies that focus on lymphocyte suppression, with little attention focused on the neutrophil. Neutrophils are however the first leukocyte to infiltrate the allograft, are capable of causing myocardial damage and may facilitate lymphocytes recruitment. We hypothesised that an early allograft neutrophil infiltration influences rejection severity. METHODS: Myocardial neutrophil infiltration was assessed using CD15 and myeloperoxidase immunohistochemistry of rejection surveillance endomyocardial biopsy specimens from human cardiac transplant recipients (n=18). In patients undergoing cardiac transplantation (n=10), neutrophils were isolated from multiple perioperative blood samples using a ficoll-based density gradient centrifugation method. The expression of the neutrophil adhesion protein CD11b was then assessed using flow cytometry and compared to subsequent endomyocardial biopsy rejection grades. The effects of contemporary immunosuppressive agents on human neutrophil CD11b were also assessed using healthy control volunteers. RESULTS: Myeloperoxidase staining of endomyocardial biopsies from human heart transplant recipients demonstrated a positive correlation between the degree of neutrophil infiltration and rejection severity at the first postoperative biopsy. Rejection severity was unrelated to ischaemic time. Functional assessment of neutrophils obtained from recipients was then performed. Perioperative transplant sampling demonstrated a significant correlation between the preoperative expression of CD11b and rejection grade at the first postoperative biopsy. In addition, dynamic changes in CD11b expression in the first 24 h positively correlated with subsequent rejection severity. In vitro experiments showed that transplant immunosuppression did not alter neutrophil CD11b expression. CONCLUSION: This study demonstrates a potentially greater role for neutrophils in cardiac transplantation than previously recognised, and suggests that blockade of the early allograft neutrophil infiltration might prevent subsequent lymphocyte recruitment and attenuate rejection.

Adult↗
PubMed2002

Severe acute pancreatitis is related to increased early urinary levels of the activation Peptide of pancreatic phospholipase A(2).

BACKGROUND/AIM: In acute pancreatitis, it is believed that generalized activation of pancreatic zymogens leads to autodigestion of the pancreas and if excessive to systemic organ injury. Under physiological circumstances, secretory phospholipase A(2) type I (sPLA(2)-I) is activated by trypsinogen, but the extent of this activation in acute pancreatitis is unclear. The aim of this study was to assess time course and level of activation of sPLA(2)-I and trypsinogen in acute pancreatitis, relative to severity. METHODS: 246 patients were enrolled into a prospective European multicenter study. 137 patients had mild and 35 had severe acute pancreatitis, and there were 74 control patients. Urinary samples were taken on admission and at 6-hour intervals for 48 h, then every 12 h up to 72 h, and finally daily for at least 5 days for measurement of the activation peptide of sPLA(2)-I (pro-phosphatase A(2); PROP) and trypsinogen activation peptide. RESULTS: The median maximum PROP values were significantly elevated 48 h after symptom onset in patients with severe acute pancreatitis [1.52 (95% CI 0.8-2.9) nmol/l] as compared with patients with mild acute pancreatitis [0.72 (0.55-1) nmol/l, p = 0.002] and controls [0.49 (0.22-1.2) nmol/l, p = 0.001], but not before or after this time point. The best cutoff point for urinary PROP to predict overall severity was >1 nmol/l < or =48 h after symptom onset (negative predictive value = 88%), but the PROP levels failed to predict the development of multi-organ dysfunction. CONCLUSIONS: Activation of sPLA(2)-I is associated with the early pathogenesis of acute pancreatitis, but not in the development of distant organ damage. This observation raises questions as to the theory of generalized zymogen activation being a principle mechanism involved in the pathogenesis of distant organ damage in acute pancreatitis.

Acute Disease↗