Joseph Kitzmiller, M.D., Ph.D., F.C.P. is a Translational Scholar with the National Institutes of Health and a faculty member in the Colleges of Medicine and Engineering at the Ohio State University (OSU). He is an Associate Director of the OSU’s Center for Pharmacogenomics and Director of their Clinical Pharmacology Fellowship training program. He is a Clinical Supervisor and Consultant for Ohio Clinical Trials and a physician with the Ohio Association of Free Clinics. His completed his Ph.D. in Biomedical Engineering and received postdoctoral training in both Internal Medicine and Clinical Pharmacology. A Board-Certified Clinical Pharmacologist with the American Board of Clinical Pharmacology and a Certified Physician Investigator with the Association of Pharmaceutical Physician Investigators (APPI), he has focused his primary research efforts on investigating genetic influences on cardiovascular disease and pharmacotherapies. He also supervises implements early- and mid-phase drug-development research, with a special interest in cardiotoxicity.
Cardiotoxicty remains a paramount concern in drug development. The FDA mandates significant preclinical analyses of emerging pharmaceuticals, and findings from in vitro and animal models provide guidance regarding the necessary level of cardiotoxity monitoring during the early clinical phases of drug development. Assessments of cardiotoxicity can include serial electrocardiograms (ECGs), Holter-monitoring, telemetry, plasma or serum biomarker tests, or even advanced structural and functional imaging modalities. Thorough QTc studies may also be undertaken to examine the risk for arrhythmias. However, for presumed low-risk compounds, cardiac monitoring may be minimal.
Our recently established registry (n ~ 1,000) of study participants in early-phase clinical trials includes demographic information and ECG data (heart rate, intervals, segments, and overall interpretation) for all registrants and the Holter-report findings (numbers of pauses, accelerations, and decelerations in a 24-hour period and an overall interpretation) for nearly half of the registrants. Participants are considered normal healthy after evaluation of clinical laboratory tests, physical examination, and medical and medication histories. Standard statistical analyses of the ECG and Holter-reports of the individuals in our registry of normal healthy participants have been computed. These will be compared historically established normal ECG parameters. ECG parameters and findings will also be compared between individuals with normal and abnormal Holter-reports.
Alhomida has completed his Ph.D. in 1993 from the University of Akron, Ohio, USA and have joined King Saud University, Department of Biochemistry, College of Science, Riyadh, Saudi Arabia since 1994. In 2002-2006 he became the Chairman of the Department of Biochemistry and in 2010-2012 he became the Vice-Dean of Graduate Studies and Scientific Research. He has published more than 95 papers in reputed journals and has been serving as an Editor-in-Chief of Saudi Journal of Biological Sciences and as editorial board member of repute.
Background: Biomarkers specificity is an important factor for their reliable utilization. Known markers for acute myocardial infarction (AMI) including creatine kinase (CK) activity, C-reactive protein (CRP) level and blood cell counts are thought to be altered in other pathological conditions such as infections.
Methods: We recruited 15 AMI patients, 15 patients with bacterial infections (infected control group) and 35 normal Subjects. Peripheral blood samples were obtained for blood cell counts and biochemical analyses.
Results: We therefore compared these biomarkers in 15 AMI patients (troponin criteria > 0.100 ng/mL) and 15 infected controls with respect to 35 normal subjects. Only monocytes were significantly increased in AMI patients (0.793*109/L) than normal controls (0.497*109/L). Infected controls showed a significant increase in total WBC (11.50*109/L versus 6.149*109/L) and neutrophils (9.360 versus 3.223*109/L) counts and significant decrease in RBC (3.750 versus 5.105*1012/L) counts as compared to normal controls. Serum CK activity was significantly increased in AMI patients (313.20 ± 94.84 U/L) and decreased in infected controls (48.40 ± 10.35 U/L) as compared to normal controls (100.82 ± 8.86 U/L). The levels of CRP were significantly higher in infected controls (136.93 ± 34.83 mg/L) and non-significantly higher in AMI patients (38.53 ± 12.76 mg/L) than normal controls (3.48 ± 0.59 mg/L). Monocytes were significantly correlated with both CK activity and CRP level, however there was no correlation between CK activity and CRP level.
Conclusion: Differential trends of monocytes and CK activity in AMI and infective controls point towards their possible application in prognosis of AMI patients. (Supported by National Plan for Science and Technology, King Saud University Project No. 08-BIO571-02).