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Fred S. Apple, Ph.D


Professor
612-873-3324
apple004@umn.edu

Dr Apple is Professor of Laboratory Medicine in the Department of Laboratory Medicine and Pathology, as well as Medical Director of Clinical Laboratories and the Clinical Chemistry and Toxicology Laboratories at Hennepin County Medical Center. In addition, he serves as the Forensic Toxicology Consultant to the Hennepin County Medical Examiner's Office. Dr. Apple instructs residents and fellows during their chemistry and toxicology rotations, as well as directs the Ph.D. Clinical Chemistry Fellowship program.

Educational Background

  • Rensselaer Polytechnic Institute, Troy, NY (1975), B.S.
  • University of Minnesota, Minneapolis MN (1979) Ph.D. (Bioorganic Biophysical Chemistry)
  • Washington University School of Medicine, Barnes Hospital, St. Louis, MO (1982) Fellowship (Clinical Chemistry)

Board Certification

  • American Board of Clinical Chemistry, Clinical Chemistry (1985)
  • American Board of Clinical Chemistry, Toxicological Chemistry (1988)

Professional Background

  • Visiting Assistant Professor, Department of Chemistry, University of Wisconsin - River Falls, River Falls, WI, 1979
  • NIH Research Training Fellow, Washington University School of Medicine, St. Louis, MO, 1980 - 1982
  • Assistant Professor, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, 1982 - 1988
  • Associate Professor, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, 1988 - 1995
  • Associate Professor, Department of Kinesiology, University of Minnesota, Minneapolis, MN, 1992 - 1995
  • University of Minnesota Graduate School Faculty Member, Minneapolis, MN: Clinical Laboratory Science, 1985 - present; School of Kinesiology and Leisure Studies, 1992 - present
  • Associate Director, Department of Pathology Residency Program, Hennepin County Medical Center, Minneapolis, MN, 1993 - 2000
  • Medical Director, North Central (formerly Regional Kidney Disease Program) Renal Laboratory of Total Renal Care (Davita), Minneapolis, MN, 1992 - 2001
  • Medical Director, HFA Clinical Laboratories, Minneapolis, MN, 2001 - present
  • Professor, Department of Kinesiology, University of Minnesota, Minneapolis, MN, 1995 - present
  • Forensic Toxicology Consultant, Hennepin County Medical Examiner's Office, Minneapolis, MN, 1982 - present.
  • Medical Director Point of Care Testing, Hennepin County Medical Center, Minneapolis, MN, 1995 - present.
  • Medical Director of Clinical Chemistry and Toxicology Laboratories, Hennepin County Medical Center, Minneapolis, MN, 1982 - present
  • Professor, University of Minnesota Medical School, Department of Laboratory Medicine and Pathology, Minneapolis, MN, 1995 - present
  • Medical Director of Clinical Laboratories, Hennepin County Medical Center, Minneapolis, MN, 1996 - present.

Professional Memberships/Honors

  • Young Investigator Award, International Society for Clinical Enzymology, 1983
  • Fellow, American College of Sports Medicine, FACSM, 1986
  • Visiting Professor, Karolinska Institute, Physiology III, Stockholm Sweden, November 1989; Recipient of Swedish National Council for Sports Research Award
  • Visiting Lecturer, Danish Society Clinical Chemistry, Copenhagen Denmark, September 1991
  • AACC Outstanding Speaker Award, 1995, 1996, 1997, 1998, 2001, 2002, 2003, 2004
  • Canadian Society of Clinical Chemists Traveling Lectureship, 1997
  • Visiting Professor, Emory University School of Medicine, Department of Pathology and Laboratory Medicine; December 2005
  • American Chemical Society, 1977 - present
  • American Association for Clinical Chemistry, 1980 – present, Associate Editor, Clinical Chemistry, 2001 - present
  • American College of Sports Medicine, 1981; Fellow 1986 - present
  • International Society of Clinical Enzymology, 1983- present
  • American Academy of Forensic Sciences, 1986 - present
  • Academy of Clinical Laboratory Physicians and Scientists, 1991 – present; President 2003-2004
  • National Committee for Clinical Laboratory Standards (NCCLS); Clinical Chemistry, 1991-1993
  • American Board of Clinical Chemistry, Board of Directors, 1992-1998
  • Society of Forensic Toxicology (SOFT), 2000 - present
  • IFCC, Committee Standardization of Markers of Cardiac Damage, 1998 – present; Chair 2004 - present
  • FDA Clinical Chemistry and Clinical Toxicology Devices Panel of the Medical Devices. Advisory Committee, Center for Devices and Radiological Health, 2004-2005
  • Canadian Society of Clinical Chemists, 2000
  • United States Anti-Doping Agency Anti-Doping Review Board, 2003-2006
  • Global Task Force for Redefinition of Myocardial Infarction; 2004 to present.

Research Activities

Dr Apple has been actively involved in NIH, VA, and industry sponsored research studies involving application of cardiac, vascular inflammatory, and ischemia biomarkers for the detection of myocardial cell damage, ischemic, inflammatory and reperfusion injury, as well as risk stratification and outcomes research. In addition, he has directed research in sports medicine – biochemistry of exercise involving the dynamics of protein and mRNA alterations in human and animal heart and skeletal muscle in response to exercise and muscle disuse. Dr Apple is also an active participant in research studies addressing forensic /postmortem analysis of drugs and alcohol in tissues, blood, vitreous humor, medical legal ethanol pharmacokinetics, and drugs of abuse testing.

Publications

  1. Potts KT, Dunlap WC, Apple FS.  Photodimerization of some 1,2,4-triazo (4,3-a) quinoline and 1,2,4-triazolo (3,4-a) -isoquinoline derivatives.  Tetrahedron 1977; 33: 1263-7.
  2. Ladenson JH, Apple FS, Koch DD.  Misleading hyponatremia due to hyperlipemia:  a method dependent error.  Ann Intern Med 1981; 95: 707-8.
  3. Apple FS, Koch DD, Graves S, Ladenson JH.  Relationship between direct potentiometry and flame photometric measurement of sodium in blood.  Clin Chem 1982; 28: 1931-5.
  4. Apple FS, Greenspan N, Dietzler DN.  Elevation of creatine kinase BB in hospitalized patients:  importance of distinguishing BB CK from MB CK.  Ann Clin Lab Sci 1982; 12: 398-402.
  5. Ladenson JH, Apple FS, Aguanno JJ, Koch DD.  Sodium measurements in multiple myeloma:  two techniques compared. Clin Chem 1982; 28: 2383-6.
  6. Apple FS, McGue MK. Serum changes during marathon training. Am J Clin Path 1983;79:716-9.
  7. Apple FS, Walker FC, Dietzler DN.  Serum creatinine concentrations and the discrepancy between EMIT and GLC phenytoin levels.  Ann Clin Lab Sci 1983; 13: 385 - 92.
  8. Ladenson JH, Apple FS, Aguanno JJ, Koch DD.  Natriumbestimmung bei multiplem myelom; ein vergleich zweier techniken.  G T Lab Med 1983; 6: 176 - 81 (In German).
  9. Apple FS, Rogers MA, Sherman WM, Ivy JL.  Creatine kinase isoenzyme patterns in gastrocnemius muscle obtained from marathon runners.  Selected Topics in Clinical Enzymol 1984; 2: 419 - 28.
  10. Apple FS, Rogers MA, Sherman WM, Ivy JL.  Comparison of elevated serum creatine kinase MB activities post marathon race and post myocardial infarction.  Clin Chim Acta 1984; 138: 111 - 8.
  11. Apple FS, Rogers MA, Sherman WM, Costill D, Hagerman F, Ivy JL.  Profile of creatine kinase isoenzymes in skeletal muscles of marathon runners.  Clin Chem 1984; 30:413 - 6.
  12. Yasmineh WG, Lewis L, Apple FS.  Chromatographic behavior of immunoglobulin - creatine kinase on DEAE - Sephadex A - 50. Clin Chim Acta 1984; 144: 29-37.
  13. Apple FS, Rogers MA, Sherman WM, Casal DC, Ivy JL.  Creatine kinase MB isoenzyme adaptations in stressed human skeletal muscle.  J Appl Physiol 1985; 59: 149-53.
  14. Coe JI, Apple FS.  Variation in vitreous chemical values due to instrumentation.  J Forens Sci 1985; 30: 828-35.
  15. Rogers MA, Apple FS.  Creatine kinase isoenzyme activities in men and women following a 42.2 Km race.  Med Sci Sports Exer 1985; 17: 679-82.
  16. Lampe JW, Slavin JL, Apple FS. Poor iron status of women runners training for a marathon.  Intl J Sports Med 1986; 7: 111-4.
  17. Apple FS, Rogers MA.  Creatine kinase isoenzyme MM in skeletal muscle and plasma from marathon runners.  Clin Chem 1986; 32: 41-4.
  18. Apple FS, Bandt C, Prosch A, Erlandson G, Holmstrom V, Scholen J, Googins MK.  Creatinine clearance:  enzymatic vs Jaffe determinations of creatinine in plasma and urine.  Clin Chem 1986; 32: 388-90.
  19. Apple FS, Rogers MA.  Skeletal muscle lactate dehydrogenase isozyme alterations in men and women runners.  J Appl Physiol 1986; 61: 477-81.
  20. Apple FS, Rogers MA.  Mitochondrial creatine kinase activity alterations in skeletal muscle during long distance running. J Appl Physiol 1986; 61: 482-5.
  21. Lampe JW, Slavin JL, Apple FS.  Elevated serum ferritin concentrations in master runners after a marathon race. Internat J Vit Nutr Res 1986; 56: 395-8.
  22. Lampe JW, Slavin JL, Apple FS.  Effects of moderate iron supplementation on the iron status of runners with low ferritin levels.  Nut Report Intl 1986; 34: 959-66.
  23. Clarkson PM, Apple FS, Byrnes WC, McCormick KM, Triffletti P. Creatine kinase isoforms following isometric exercise.  Muscle and Nerve 1987; 10: 41-4.
  24. Apple FS, Rogers MA, Casal DC, Lewis L, Ivy JL, Lampe JW. Skeletal muscle creatine kinase MB alterations in women marathon runners.  Eur J Appl Physiol 1987; 56: 49-52.
  25. Apple FS, Sharkey SW, Werdick M, Elsperger J, Tillbury RT. Analysis of creatine kinase isoenzymes and isoforms in serum to detect reperfusion after acute myocardial infarction.  Clin Chem 1987; 33: 507-11.
  26. Schneider C, Stull GA, Apple FS.  Kinetic characterization of human heart and skeletal muscle CK isoenzymes.  Enzyme 1988; 39: 220-6.
  27. Apple FS, Bandt CM.  Liver and blood postmortem tricyclic antidepressant concentrations.  Am J Clin Path 1989; 89: 794-6.
  28. Apple FS, Hellsten Y, Clarkson PM.  Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise.  Clin Chem 1988; 34: 1102-04.
  29. Apple FS, Rhodes MD.  Enzymatic estimation of skeletal muscle damage by analysis of changes in serum creatine kinase.  J Appl Physiol 1988; 65: 2598-2600.
  30. Sharkey SW, Apple FS, Elsperger KJ, Tilsury RT, Miller S, Fjeldos K, Asinger RW.  Early peak of creatine kinase - MB in acute myocardial infarction with a non-diagnostic electrocardiogram.  Am Heart J 1988; 116:1207-11.
  31. Apple F, Preese L, Bennett R, Fredrickson A.  Clinical and analytical evaluation of two immunoassays for direct measurement of creatine kinase MB with monoclonal anti-CK-MB antibodies.  Clin Chem 1988; 34: 2364-6.
  32. Sharkey SW, Elsperger KJ, Murakami M, Apple FS.  Canine myocardial creatine kinase isoenzyme response to coronary artery occlusion.  Am J Physiol 1989; 256: H508-14.
  33. Eastep SJ, Benson PJ, Preese LM, Apple FS.  Factitiously high sodium activities on the Ektachem 400 owing to interferences by high gamma-globulin concentrations.  Clin Chem 1989; 35: 333-4.
  34. Apple FS, Abraham PA, Rosono TG, Halstenson CE.  Assessment of renal function by inulin clearance:  comparison with creatine clearance as determined by enzymatic methods.  Clin Chem 1989; 35: 312-14.
  35. Apple FS, Tesch PA.  CK and LD isoenzymes in human single muscle fibers in athletes.  J Appl Physiol 1989; 66: 2717-20.
  36. Apple FS.  Postmortem tricyclic antidepressant concentrations: assessing cause of death using parent drug to metabolite ratio.  J Analyt Tox 1989; 13: 197-8.
  37. Apple FS, Roe SJ.  Cocaine-associated fetal death in utero. J Analyt Tox 1990; 14:259-60.
  38. Apple FS, Preese LM, Riley L, Gerken KL, VanLente F.  Clinical and financial impact of a rapid CK-MB specific immunoassay on the diagnosis of myocardial infarction.  Arch Path Lab Med 1990; 114: 1017-1020.
  39. Sjodin B, Westing YH, Apple FS.  Formation of oxygen free radicals during exercise.  Sports Med 1990; 10: 236-54. 
  40. Lampe JW, Slavin JL, Apple FS.  Iron status in active women: the effect of running a marathon on bowel function and gastrointestinal blood loss.  Int J Sport Med 1991; 12:173-9.
  41. Sharkey SW, Murakami MA, Smith S, Apple FS.  Canine myocardial creatine kinase isoenzyme redistribution three weeks after coronary occlusion: biochemical and ultrastructural correlates.  Circulation 1991; 84: 333-40.
  42. Apple F, Benson, P, Preese L, Eastep S, Heiler G, Bilodeau L. Lipase and pancreatic amylase activities in tissues and in patients with hyperamylasemia.  Am J Clin Path 1991; 96: 610-4.
  43. Apple FS, Hyde JE, Ingersoll AM, Stone J, Theologides A. Geographic distribution of xanthine oxidase, free radical scavenger, creatine kinase and lactate dehydrogenase enzyme systems in rat heart and skeletal muscle.  Am J Anat 1991; 192: 319-23.
  44. Apple FS.  Acute myocardial infarction and coronary reperfusion: serum cardiac markers for the 1990s.  Am J Clin Path 1992; 97: 217-26. 
  45. Nosaka K, Clarkson PM, Apple FS.  Time course of serum protein changes after strenuous exercise of the forearm flexors.  J Lab Clin Med 1992; 119: 183-8.
  46. Apple FS.  The creatine kinase system in overtrained runners. Clin Physiol 1992; 12: 1-6.
  47. Bilodeau L, Grotte DA, Preese LM, Apple FS.  Glycerol interference in serum lipase assay falsely indicates pancreas injury.  Gastroenterology 1992; 103: 1066-7.
  48. Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton J, Vercellotti GM.  Ferritin:  a cytoprotective antioxidant strategem of endothelium.  J Biol Chem 1992; 267: 18148-53.
  49. Schneider CM, Rogers MA, Lampe JW, Rhodes MC, Apple FS. Serum creatine kinase isoenzyme measurements in master male and female marathon runners.  Sports Med Train Rehab 1992; 3: 237-242.
  50. Adams JE, Bodor GS, Davila-Roman VG, Delmez JA, Apple FS, Ladenson JH, Jaffe AS.  Cardiac troponin I: A marker with high specificity for cardiac injury. Circulation 1993; 88:101-6. 
  51. Wu AHB, Valdes R, Apple FS, Gornet T, Stone MA, Mayfield-Stokes S, Ingersoll-Stroibos AM, Wiler B. Cardiac troponin-T immunoassay for diagnosis of acute myocardial infarction. Clin Chem 1994; 40:  900-907.
  52. Apple FS, Billadello JJ.  Creatine Kinase M and B subunit mRNA levels in exercise trained rat skeletal muscle.  Life Sci 1994; 55: 585-92.
  53. Apple FS, Preese LM. Creatine kinase MB:  detection of AMI and monitoring reperfusion.  J Clin Immunoassay 1994; 17:  24-29.
  54. Theologides A, Ingersoll-Stroubos AM, Apple FS.  TNF - effect on oxygen free radical scavenging and generating enzymes in rat liver.  Biochem Mol Biol Internal 1994; 33:  205-210.
  55. Apple FS, Bilodeau L, Preese LM, Benson P.  Clinical implementation of a rapid, automated assay for assessing fetal lung maturity.  J Reprod Med 1994; 39: 883 - 7.
  56. Apple FS, Voss E, Lund L, Preese L, Berger CR, Henry TD. Cardiac troponin, CK-MB and myoglobin for early detection of acute myocardial infarction and monitor of reperfusion following thrombolytic therapy.  Clin Chim Acta 1995; 237: 59-66.
  57. Apple FS. Glycogen phosphorylase BB and other cardiac proteins: challenges to creatine kinase MB as the marker for detecting myocardial injury. Clin Chem 1995; 41: 13 - 5.
  58. Voss EM, Sharkey SW, Gernert A, Murakami MA, Johnston RB, Hsieh CC, Apple FS.  Human and canine cardiac troponin T and CK-MB distribution in normal and diseased myocardium: infarct sizing using serum profiles.  Arch Path Lab Med, 1995; 119:799-806.
  59. Apple FS, Sharkey SW, Henry TD. Early serum cardiac troponin I and T concentrations following successful thrombolysis for acute myocardial infarction. Clin Chem 1995; 41: 1197-8.
  60. Bodor GS, Porterfield D, Voss E, Smith S, Apple FS. Cardiac troponin I is not expressed in fetal and adult human skeletal muscle tissue. Clin Chem 1995; 41: 1710 - 5.
  61. Apple FS, Henry TD, Berger CR, Landt YV.  Early monitoring of coronary reperfusion following thrombolytic therapy by measurement of cardiac troponin I, creatine kinase MB and myoglobin.  Am J Clin Path 1996; 105: 6-10.
  62. Apple FS, Wu AHB, Valdes R. Serum cardiac troponin T concentrations in hospitalized patients without acute myocardial infarction. Scand J Clin Lab Invest 1996; 56: 63-8.
  63. McLaurin M, Apple FS, Henry TD, Sharkey SW.  Cardiac troponin I and T levels in patients with cocaine associated chest pain. Ann Clin Biochem 1996; 33: 183-6.
  64. Hellsten Y, Apple FS, Sjodin B. The effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle. J Appl Physiol 1996; 81: 1484-7.
  65. Apple FS, Lowe MC, Googins MK, Kloss J. Serum thiocyanate concentrations in normal and renal impaired patients receiving nitroprusside. Clin Chem 1996; 42: 1878-9.
  66. Tucker JF, Collins RA, Anderson AJ, Hauser J, Kalas J, Apple FS. Early diagnostic efficiency of cardiac troponin I and cardiac troponin T for acute myocardial infarction. Acad Emerg Med 1997; 4:13-21.
  67. Apple FS, Sharkey SW, Hoeft P, Skeate R, Voss EM, Dahlmeier BA, Preese LM. Prognostic value of serum cardiac troponin I and T in chronic dialysis patients: a one year outcomes analysis. Am J Kid Dis 1997; 29: 399-403.
  68. Bodor GS, Survant L, Voss EM, Smith S, Posterfield D, Apple FS. Cardiac troponin-T composition in normal and regenerating human skeletal muscle. Clin Chem 1997;43:476-84.
  69. McLaurin MD, Apple FS, Voss EM, Herzog CA, Sharkey SW.  Serum cardiac troponin I, cardiac troponin T, and CK MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle.      Clin Chem 1997; 43: 976 - 82.
  70. Ricchiuti V, Zhang J, Apple FS. Cardiac troponin I and T alterations in hearts with severe left ventricular remodeling. Clin Chem 1997; 43: 990-5.
  71. Hoang CD, Zhang J, Payne RM, Apple FS. Post-infarction left ventricular remodeling induces changes in creatine kinase mRNA and protein subunit levels in porcine myocardium. Am J Pathol 1997; 151: 257-64.
  72. Apple FS, Falahati A, Paulson PR, Miller E, Sharkey SW. Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I. Clin Chem 1997; 43: 2047-51.
  73. Christenson RH, Apple FS, Morgan DL, Alonsozana GL, Mascotti K, Olson M, McCormack RT, Wians FH, Keffer JH, Duh SH. Cardiac troponin I measurement on the Access immunoassay system: analytical and clinical performance characteristics. Clin Chem 1997; 44: 52-60.
  74. Apple FS, Sharkey SW, Falahati A, Murakami MA, Mitha N, Christenson D. Assessment            of left ventricular function using serum cardiac troponin I measurements following           myocardial infarction. Clin Chim Acta 1998; 272: 59-67.
  75. Henderson AR, Gerhardt W, Apple FS. Summary with extrapolations of a roundtable on the use of biochemical markers in the diagnosis and theory of monitoring of patients with ischemic heart disease. Clin Chim Acta 1998; 272: 93-100.
  76. Wu AHB, Feng YJ, Moore R, Apple FS, McPherson PH, Buechler KF, Bodor G. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. Clin Chem1998; 44:1198-1208.
  77. Ricchiuti V, Sharkey SW, Murakami MA, Voss EM, Apple FS. Cardiac troponin I and T alterations in dog hearts with myocardial infarction: correlation with infarct size. Am J Clin Path 1998; 110: 241-7.
  78. McLaurin MD, Apple FS, Falahati A, Murakami MA, Miller EA, Sharkey SW. Cardiac troponin I and creatine kinase MB mass to rule out myocardial injury in hospitalized patients with renal insufficiency. Am J Cardiol 1998; 82: 973-5.
  79. Ricchiuti V, Voss EM, Ney A, Odland M, Anderson PAW, Apple FS. Cardiac troponin T isoforms skeletal muscle of renal diseased patients will not cause false positive serum results by the second generation cardiac troponin T assay. Eur Heart J 1998; 19 (suppl N): N30-3.
  80. Apple FS, Ricchiuti V, Voss EM, Ney A, Odland M, Anderson PAW. Expression of cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false positive results by the second generation cardiac troponin T assay by Boehringer Mannheim. Clin Chem 1998; 44: 1919-24.
  81. Falahati A, Sharkey SW, Christensen D, McCoy M, Miller E, Murakami MA, Apple FS. Implementation of cardiac troponin I for detection of acute myocardial injury in an urban medical center. Am Heart J 1999; 137: 332-7; letter to editor correction 1999; 138: 798-800.
  82. Apple FS, Christenson RH, Valdes Jr R, Andriak AJ, Duh SH, Feng YJ, Koplen B, Jortani SA, Johnson NA, Berg A, Mascotti K, Wu AHB. Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the Triage Cardiac Panel for detection of myocardial infarction. Clin Chem 1999; 45: 199-205.
  83. Apple FS, Maturen AJ, Mullins RE, Painter PC, Pessin-Minsley MS, Webster RA, Flores JS, DeCresce R, Fink DJ, Buckley PM, Marsh J, Ricchiuti V, Christenson RH. Multicenter clinical and analytical evaluation of the AxSYM troponin I immunoassay to assist in the diagnosis of myocardial infarction. Clin Chem 1999; 45: 206-12.
  84. Sheng WS, Lin YC, Apple FS, Hy S, Peterson PK, Chao CC.  Brain energy stores in C57BL/6 mice after c. parvum injection. Neuroreport 1999; 10: 177-181.
  85. Wu AHB, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes Jr R. National academy of clinical biochemistry standards of laboratory practice: recommendations for use of cardiac markers in coronary artery diseases. Clin Chem 1999; 45: 1104-21.
  86. Apple FS. Biochemical markers of thrombolytic success. Scand J Clin Lab Invest 1999; 59 (suppl 230) 60-6.
  87. Panteghini M, Apple FS, Christenson RH, Dati F, Mair J, Wu AH. Proposals from IFCC committee on standardization of markers of cardiac damage (C-SMCD): recommendations on use of biochemical markers of damage in acute coronary syndrome. Scand J Clin Lab Invest 1999; 59 (suppl 230) 103-12.
  88. Dati F, Panteghini M, Apple FS, Christenson RH, Mair J, Wu AH. Proposals from IFCC committee on standardization of markers of cardiac damage (C-SMCD): strategies and concepts on standardization of cardiac marker assays. Scand J Clin Lab Invest 1999; 59 (sup 230) 113-23.
  89. Apple FS. Tissue specificity of cardiac troponin I, cardiac troponin T, and creatine kinase MB. Clin Chim Acta 1999; 284: 151-9.
  90. Christenson RH, Vaidya H, Landt Y, Bauer RS, Green SF, Apple FS, Jacob A, Magneson GR, Nag S, Wu AHB, Azzazy HME. Standardization of creatine kinase MB (CK MB) mass assays: the use of recombinant CK MB as a reference material. Clin Chem 1999; 45: 1414-23.
  91. Ricchiuti V, Apple FS. RNA expression of cardiac troponin T isoforms in diseased human skeletal muscle. Clin Chem 1999; 45: 2129-35.
  92. Apple FS. Clinical and analytical standardization issues confronting cardiac troponin I. Clin Chem 1999; 45: 18-20.
  93. Siegel AJ, Sholar MB, Mendelson JH, Lukas SE, Kaufman MJ, Renshaw PF, McDonald JC, Lewandrowski KB, Apple FS, Stec JJ, Lipinski I, Tofler GH, Ridker PM. Cocaine induced erthrocytosis and increase in von Willebrand factor. Arch Intern Med 1999; 159: 1925-30.
  94. Wu AHB, Holtman V, Apple FS, Ricchiuti V, DiBello PM, Jacobsen D. Multicenter analytical evaluation of the automated IMx assay for total plasma homocysteine. Ann Clin Lab Sci 2000; 30: 185-90.
  95. Apple FS. The specificity of biochemical markers of cardiac damage: a problem solved. Clin Chem Lab Med 2000; 37: 1085-9.
  96. Apple FS, Koplen B, Murakami MA.  Preliminary evaluation of the Ortho ECi cardiac troponin I immnuodiagnostic assay. Clin Chem 2000; 46: 572-4.
  97. Mackey-Bojack S, Kloss J, Apple FS. Cocaine, cocaine metabolites, and ethanol concentrations in postmortem blood and vitreous humor. J Anal Tox 2000; 24: 59-65.
  98. Chen YJ, Serfass RC, Apple FS. Alterations in the expression and activity of creatine kinase-M and mitochondrial creatine kinase subunits in skeletal muscle following prolonged intense exercise in rats. Eur J Appl Physiol 2000; 81: 114-9.
  99. Chen YJ, Serfass RC, Mackey-Bojack SM, Kelly KL, Titus JL, Apple FS. Cardiac troponin T alterations in myocardium and serum of rats following stressful, prolonged intense exercise. J Appl Physiol 2000, 88: 1749-55.
  100. Chen YJ, Serfass RC, Apple FS. Loss of myocardial CK-MB into the circulation following 3.5 hours of swimming in a rat model. Int J Sports Med 2000; 21: 1-5.
  101. Stelow EB, Johari VP, Smith SA, Crosson JT, Apple FS. Propofol-associated rhabdomyolysis with cardiac involvement in adults: chemical and anatomic findings. Clin Chem 2000: 46: 577-81.
  102. Jaffe AS, Ravkilde J, Roberts R, Naslund U, Apple FS, Galvani M, Katus H. It’s time for a change to a troponin standard. Circulation 2000, 102: 1216-20.
  103. Apple FS, Anderson FP, Collinson P, Jesse RL, Kontos MC, Levitt MA, Miller EA. Clinical evaluation of the First Medical whole blood, point of care testing device for detection of myocardial infarction. Clin Chem 2000, 46: 1604-9.
  104. Joint European Society of Cardiology/American College of Cardiology Committee (Apple FS member Biochemistry section). Myocardial infarction redefined – a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000; 36: 959-69.
  105. Joint European Society of Cardiology/American College of Cardiology Committee (Apple FS member Biochemistry section). Myocardial infarction redefined – a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Europ Heart J 2000; 21: 1502-13.
  106. Miller R, Callas DD, Kahn SE, Ricchiuti V, Apple FS. Evidence of myocardial damage in mummified human tissue. JAMA 2000; 284: 831-2.
  107. Ricchiuti V, Shear W, Henry TD, Paulson PR, Miller EA, Apple FS. Monitoring plasma cardiac troponin I for the detection of myocardial injury after percutaneous transluminal coronary angioplasty. Clin Chim Acta 2000; 302: 161-70.
  108. Burt M, Anderson DC, Kloss J, Apple FS. Evidence based implementation of free phenytoin therapeutic drug monitoring. Clin Chem 2000; 46: 1132-5.
  109. Beuerle JR, Azzazy H, Apple FS, Duh SH, Tan A, Christenson RH. Performance characteristics of a new myoglobin microparticle immunoassay: a multicenter evaluation. Clin Biochem 2000; 33: 595-8.
  110. Apple FS, Murakami M, Panteghini M, Christenson RH, Dati F, Mair J, Wu AH. International survey on the use of cardiac markers. Clin Chem 2001; 47: 587-9.
  111. Christenson RH, Duh SH, Apple FS, Bodor G, Bunk D, Dalluge J, Panteghini M, Potter J, Welch M, Wu AHB, Kahn S. Standardization of cardiac troponin I assays: round robin performance of ten candidate reference materials. Clin Chem 2001; 47: 431-7.
  112. Burt MJ, Kloss J, Apple FS. Postmortem blood free and total morphine concentrations in medical examiners cases. J Forensic Sci 2001; 46: 1138-42.
  113. Christenson RH, Duh SH, Sanhai W, Wu AHB, Holtman V, Painter P, Branham E, Apple FS, Murakami MA, Morris DL. Characteristics of an albumin cobalt binding test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 2001; 47: 464-70.
  114. Apple FS, Wu AHB. Myocardial infarction redefined: role of cardiac troponin testing. Clin Chem 2001; 47: 377-9.
  115. Davis GK, Labugger R, Van Eyk JE, Apple FS. Cardiac troponin T is not detected in Western blots of diseased renal tissue. Clin Chem 2001; 47: 782-4.
  116. Panteghini M, Gerhardt W, Apple FS, Dati F, Ravkilde J, Wu AH. Quality specifications for cardiac troponin assays. Clin Chem Lab Med 2001; 39:175-9.
  117. Davis G, Park K, Kloss J, Apple FS. Tricyclic antidepressant fatality: role of measuring postmortem tissue concentration. J Toxicology 2001; 39: 44-5.
  118. Apple FS. Cardiac troponin assays: analytical issues and clinical reference range cutpoints. Cardiovas Tox 2001; 1: 93-8.
  119. Herzog CA, Apple FS. Cardiac biomarkers in the new millennium. Seminars Dial 2001; 14: 322-3.
  120. Wu AHB, Morris DL, Fletcher DR, Apple FS, Christenson RH, Painter PC. Analysis of the albumin cobalt binding (ACB) test as an adjunct to cardiac troponin I for the early detection of myocardial infarction. Cardiovas Tox 2001; 1: 147-52.
  121. Frantz CR, Powell C, Karon B, Parvin CA, Hankins K, Dayal M, Sadovsky Y, Johari V, Apple FS, Gronowski AM. Assesment of the diagnostic efficiency of the TDx-FLM II to predict fetal lung maturity. Clin Chem 2002; 48: 761-5.
  122. Uettwiller-Geiger D, Wu AHB, Apple FS, Jevans AW, Venge P, Olson MD, Darte C, Woodrum DL, Roberts S, Chan S. Analytical performance of Beckman Coulter’s Access AccuTnI (troponin I) in a multicenter evaluation. Clin Chem 2002; 48: 869-76.
  123. Apple FS, Wu AHB, Jaffe AS. European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: how to use existing assays clinically and for clinical trials. Am Heart J 2002; 144: 981-6.
  124. Apple FS, Quist WE, Mathews WE, Otto A, Murakami MM. Release characteristics of cardiac biomarkers and ischemia modified albumin as measured by the albumin cobalt binding test following a marathon race. Clin Chem 2002; 48: 1097-1100.
  125. Knoblock R, Lehman C, Smith R, Apple FS, Roberts WL. False positive AxSYM cardiac troponin I result in a 59 year old woman. Arch Path Lab Med 2002; 126: 606-9.
  126. Apple FS, Murakami MM, Jesse RL, Levitt MA, Collinson P. Risk assessment of patients with acute coronary syndromes utilizing a near bedside whole blood cardiac troponin I assay. Clin Chem 2002; 48: 1784-7.
  127. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end stage renal disease. Circulation 2002; 106: 2941-5.
  128. Fishbein MC, Wang T, Matijaevic M, Hong L, Apple FS. An immunohistochemical study in experimental models of myocardial ischemia. Cardiovas Path 2003; 12: 65-71.
  129. Apple FS, Trinity E, Steen J. Prawer S, Wu AHB. BNP test utilization in CHF in community hospital practice. Clin Chim Acta 2003; 328: 191-3.
  130. Gagajewski A, Apple FS. Methadone related deaths in Hennepin County, 1992-2002. J Forens Sci 2003; 48: 668-71.
  131. Apple FS, Johari V, Hoybook KJ, Weber-Shrikant E, Davis GK, Murakami MM. Operationalizing cardiac troponin I testing along ESC/ACC consensus guidelines for defining myocardial infarction. Clin Chim Acta 2003; 331: 165-6.
  132. Apple FS, Quist HE, Doyle PJ, Otto AP, Murakami MM. Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations. Clin Chem 2003; 49: 1331-6.
  133. Apple FS, Murakami MM, Quist H, Pearce LA, Wieczorek S, Wu AHB. Prognostic value of the Ortho Vitros Troponin I assay in patients with symptoms of myocardial ischemia: risk stratification using ESC/ACC recommended cutoff values. Am J Clin Path 2003; 120: 114-20.
  134. Gagajewski A, Apple FS. Amphetamines: role of toxicology testing for assisting in medical examiner cases. J Clin Lig Assay 2003; 26: 25-9.
  135. Yeo KTJ, Wu ANB, Apple FS, Kroll MH, Christenson RH, Lewandrowski KB, Sedor FA, Butch AW. Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite BNP assay.  Clin Chim Acta 2003; 338: 107-15.
  136. Gagajewski A, Murakami MM, Kloss J, Edstrom M, Hiller M, Peterson GF, Amatuzio J, Apple FS. Measurement of chemical analytes in vitreous humor: stability and precision studies. J Forens Sci 2004; 49: 371-4.
  137. Aslan D, Apple FS, Ischemia modified albumin: clinical and analytical update. Lab Med 2004;35: 1-5.
  138. Luepker RV, Apple FS, Christenson RH, Crow RS, Fortmann SP, Goff D, Goldberg RJ, Hand MM, Jaffe AS, Julian DG, Levy D, Manolio T, Mendis S, Mensah G, Pajak A, Prineas RJ, Reddy KS, Roger VL, Rosamond WD, Shahar E, Sharrett AR, Sorlie P, Tunstall-Pedoe H. Case definitions for acute coronary heart disease in epidemiology and clinical research studies. Circulation 2003; 108: 2543-9.
  139. Apple FS, Quist H, Murakami MM. Diagnostic and prognostic value of Ortho Vitros Troponin I and Beckman Access AccuTnI assay in patients admitted with symptoms suggestive of acute coronary syndrome. Arch Path Lab Med 2004; 128: 430-4.
  140. Lin JC, Apple FS, Murakami MM, Luepker RV. Rates of positive cardiac troponin I and creatine kinase MB among patients hospitalized for suspected acute coronary syndromes. Clin Chem 2004; 50: 333-8.
  141. Panteghini M, Pagani F, Yeo KT, Apple FS, Christenson RH, Dati F, Mair J, Ravkilde J, Wu AHB. Evaluation of the imprecision at low range concentrations of the assays for cardiac troponin determination. Clin Chem 2004; 50: 327-32.
  142. Panteghini M, Linsinger T, Wu AHB, Dati F, Apple F, Christenson RH, Mair J, Schimmel H. Standardization of immunoassays for measurement of myoglobin in serum. Phase I: evaluation of candidate reference materials. Clin Chim Acta 2004; 341; 65-72.
  143. Apple FS, Kleinfeld AM, Adams III J. Unbound free fatty acid concentrations are increased in cardiac ischemia. Clin Proteomics 2004; 1: 169-72.
  144. Ricchiuti V, Voss EM, Ney A, Odland M, Apple FS. Skeletal muscle expression of creatine kinase–B in end stage renal disease. Clin Proteomics 2004; 1: 161-7.
  145. Apple FS, Murakami MM, Christenson RH, Campbell JL, Miller CJ, Hock KG, Scott MG. Analytical performance of the i-STAT cardiac troponin I assay. Clin Chim Acta 2004; 345: 123-7.
  146. Wu AHB, Smith A, Apple FS. Optimum blood collection intervals for B-type natriuretic peptide testing in heart failure patients. Am J Cardiol 2004; 93: 1562-3.
  147. Wu AHB, Smith A, Christenson RH, Murakami MM, Apple FS. Evaluation of a point of care assay for cardiac markers for patients suspected of acute myocardial infarction. Clin Chim Acta 2004; 346: 211-9.
  148. Jaffe AS, Apple FS, Babdin L. Why we don’t know the answer may be more important than the specifics (re: BNP). Clin Chem 2004; 50: 1495-7.
  149. Apple FS, Murakami MM. Serum 99th percentile reference cutoffs for seven cardiac troponin assays. Clin Chem 2004; 50: 1477-9.
  150. Apple FS, Murakami MM, Pearce LA, Herzog CA. Prognostic value of high sensitivity C-reactive protein, N-terminal proBNP, and cardiac troponin T and I in end stage renal disease for subsequent death over two years.  Clin Chem 2004; 50: 2279-85.
  151. Rosalki S, Roberts R, Katus HA, Giannitsis E, Ladenson JH, Apple FS. Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present. Clin Chem 2004; 50: 2205-13.
  152. Apple FS. Analytical issues for cardiac troponin. Prog Cardiovas Dis 2004; 47: 189-95.
  153. Apple FS, Murakami MM. Cardiac troponin and creatine kinase MB monitoring during in-hospital myocardial reinfarction. Clin Chem 2005; 51: 460-3.
  154. Apple FS, Panteghini M, Ravkilde J, Mair J, Wu AHB, Tate J, Pagani F, Christenson RH, Jaffe AS. Quality specifications for B-type natriuretic peptide assays. Clin Chem 2005, 51: 486-93.
  155. Apple FS, Wu AHB, Mair J, Ravkilde J, Panteghini M, Tate J, Pagani F, Christenson RH, Mockel M, Danne O, Jaffe AS. Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clin Chem 2005; 810-24.
  156. Slack JA, McGuirk SM, Erb HN, Lien L, Coombs D, Semrad SD, Riseberg A, Marques F, Darien B, Murakami MM, Apple FS, Peek SM. Biochemical markers of cardiac injury in normal and surviving versus non-surviving septicemic neonatal foals. Vet Med 2005; 19: 577-580.
  157. Apple FS. Standardization of cardiac markers. Scand J Clin Lab Invest 2005; 65 (suppl 240): 107-111.
  158. Apple FS, Parvin CA, Buechler KF, Christenson RH, Wu AHB, Jaffe AS. Validation of the 99th percentile cutoff independent of assay imprecision (%CV) for cardiac troponin monitoring for ruling out myocardial infarction. Clin Chem 2005; 51: 2198-2200.
  159. Apple FS, Ler R, Chung AY, Berger MJ, Murakami MM. Point-of –care i-STAT cardiac troponin I for assessment of patients with symptoms suggestive of acute coronary syndrome. Clin Chem 2006; 52: in press.
  160. Apple FS. Point of care cardiac troponin testing: process improvements for detection of acute myocardial infarction. Point of Care 2006; 5: In press.

 

 

 

 

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