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Biomedical subjects

Dominic Kelly

Publications and source records attributed to Dominic Kelly.

6 recordsLinked to original sources
PubMed2007

Myotrophin is a more powerful predictor of major adverse cardiac events following acute coronary syndrome than N-terminal pro-B-type natriuretic peptide.

Myotrophin is a 12 kDa protein initially isolated from hypertrophied hearts of spontaneously hypertensive rats and acts by modulating NF-kappaB (nuclear factor kappaB) activity. We have reported previously the presence of myotrophin in patients with human systolic heart failure; however, its role as a predictor of MACE (major adverse cardiac events) in patients with ACS (acute coronary syndrome) is unclear. In the present study, we sought to investigate this and compared myotrophin with NTproBNP (N-terminal pro-B-type natriuretic peptide), a marker of MACE. We studied 356 patients with ACS {276 men; mean age, 63.0+/-12.8 years; 80.6% STEMI [ST segment elevation MI (myocardial infarction)]; and 19.4% NSTEMI (non-STEMI)}. Blood measurement was made at 25-48 h after the onset of chest pain. The plasma concentration of myotrophin and NTproBNP was determined using in-house non-competitive immunoassays. Patients were followed-up for the combined end point of death, MI or need for urgent revascularization. Over the median follow-up period of 355 (range 0-645) days, there were 28 deaths, 27 non-fatal MIs and 73 patients required urgent revascularization. Myotrophin was raised in patients with MACE compared with survivors [510.7 (116.0-7445.6) fmol/ml compared with 371.5 (51.8-6990.4) fmol/ml respectively; P=0.001; values are medians (range)]. Using a Cox proportional hazards model, myotrophin {HR (hazard ratio), 1.64 [95% CI (confidence interval), 0.97-2.76]; P=0.05} and Killip class above 1 [HR, 1.52 (95% CI, 0.93-2.42); P=0.10] were the only independent predictors of MACE. A Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with myotrophin below the median compared with those with myotrophin above the median (log rank, 7.63; P=0.006). In conclusion, after an ACS, levels of myotrophin are more informative at predicting MACE than NTproBNP and may be useful to risk stratify patients.

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PubMed2006

Myeloperoxidase aids prognostication together with N-terminal pro-B-type natriuretic peptide in high-risk patients with acute ST elevation myocardial infarction.

BACKGROUND: Inflammation plays a critical role in acute myocardial infarction (MI). One such inflammatory marker is myeloperoxidase (MPO). Its role as a predictor of death or MI in patients with ST segment elevation myocardial infarction (STEMI) is unclear. AIM: To investigate the role of MPO as a predictor of death or MI in patients with STEMI and to compare it with N-terminal pro-B-type natriuretic peptide (NT-BNP). METHOD: 384 post STEMI patients were studied. Patients were followed up for the combined end point of death or readmission with non-fatal MI. RESULTS: There were 40 deaths and 37 readmissions with MI. Median MPO was raised in patients experiencing death or MI than in survivors (median (range), 50.6 (15.3-124.1) ng/ml vs 33.5 (6.6-400.2) ng/ml, p = 0.001). Using a Cox proportional hazards model, log median MPO (HR 6.91, 95% CI 1.79 to 26.73, p = 0.005) and log median NT-BNP (HR 4.21, 95% CI 1.53 to 11.58, p = 0.005) independently predicted death or non-fatal MI. MPO had predictive power in both below and above median NT-BNP levels (log rank 5.60, p = 0.020 and log rank 5.12, p = 0.024, respectively). The receiver-operating curve for median NT-BNP yielded an area under the curve (AUC) of 0.72 (95% CI 0.65 to 0.79, p<0.001); for median MPO, the AUC was 0.62 (95% CI 0.55 to 0.69, p = 0.001). The logistic model combining the two markers yielded an AUC of 0.76 (95% CI 0.69 to 0.82, p<0.001). CONCLUSION: MPO and NT-BNP may be useful tools for risk stratification of all acute coronary syndromes, including patients with STEMI at higher risk.

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PubMed2006

Effectiveness analyses may underestimate protection of infants after group C meningococcal immunization.

BACKGROUND: Group C meningococcal conjugate-vaccine effectiveness in the United Kingdom declines from ~90% in the first year to 0% between 1 and 4 years after immunization in infants immunized at 2, 3, and 4 months of age and to 61% in toddlers given a single dose. Confidence intervals are wide, and the extent of protection is uncertain. METHODS: Serum samples were obtained from children 3-5 years of age who were participants in a preschool booster-vaccine trial. Serum bactericidal activity was measured with human complement. Group C anticapsular antibody concentrations were measured by a radioantigen binding assay. Passive protection was analyzed in an infant rat bacteremia model. RESULTS: Serum samples from UK children who had been immunized 2-3 years earlier as infants or toddlers had higher levels of radioantigen binding, bactericidal activity, and passive protection than did historical control serum samples from unimmunized children (P<.05). A higher proportion of children immunized as infants had serum bactericidal activity titers > or =1 : 4 (considered to be protective) than those immunized as toddlers (61% vs. 24%; P<.01), but there were no significant differences in the proportion of serum samples conferring passive protection (50% and 41%, respectively; P=.4). CONCLUSIONS: We found no evidence of lower immunity in children immunized as infants than as toddlers. On the basis of serum bactericidal activity and/or passive protection, 40%-50% of both age groups are protected at 2-3 years after immunization, which was significantly greater than in unimmunized historical controls (<5%).

Antibodies, Bacterial↗
PubMed2006

Cardiotrophin-1 predicts death or heart failure following acute myocardial infarction.

BACKGROUND: Cardiotrophin-1 (CT-1) is an important inflammatory cytokine; its presence has been documented in patients after acute myocardial infarction (AMI). However, its role as a predictor of death or heart failure is unclear. We sought to investigate this and compared it with N terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of death or heart failure. METHODS AND RESULTS: We studied 291 post-AMI patients. The plasma concentration of CT-1 and NT-proBNP was determined using in-house noncompetitive immunoassays and patients followed for death or heart failure. There were 27 deaths and 19 readmissions with heart failure. CT-1 was raised in patients with death or heart failure compared with survivors (median [range] fmol/mL, 0.9 [0.1-392.2] vs. 0.67 [0-453.3], P = .019). Using a multivariate binary logistic model CT-1 (OR 1.8, 95% CI: 1.1-3.2, P = .031) and NT-proBNP (OR 2.4, 95% CI: 1.1-5.2, P = .026) predicted death or heart failure independently of age, sex, previous AMI, serum creatinine, and Killip class. The receiver-operating curve for CT-1 yielded an area under the curve (AUC) of 0.62 (95% CI: 0.53-0.70, P = .017); for NT-proBNP the AUC was 0.77 (95% CI: 0.69-0.86, P < .001); the logistic model combining the 2 markers yielded an AUC of 0.84 (95% CI: 0.78-0.91, P < .001). CONCLUSION: After an AMI, combined levels of CT-1 and NT-proBNP are more informative at predicting death or heart failure than either marker alone.

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