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Optimal diagnosis of myocardial infarction using only cardiac specific isoenzymes
632
ROYAL. COLLEGE OF PATHOLOGISTS OF AUSTRALASIA
Pathology (1981), 13, July
EVALUATION OF KIT METHODS FOR MEASUREMENT OF TOTAL PLASMA CHOLESTEROL LIXDSAY E. W'IxDtr4M. PACLS. BACHORIK 8: PETER0. KWITEROVICH. JR. Lipid Reseurch c h i c ,
T/IPJ o / m Hoipkitis C.tiirersitv. Bulriritore, M D . , LF.S.~4. The performance of 6 commercial kits for the measurement of total plasma cholesterol concentration. using enzymatic and chemical methods. was compared to the Lipid Research Clinics (LRC) method. Primary cholesterol standards. the purity of which was verified by spectrophotometry. thin-layer and gas chromatography by the Lipid Standardization Laborator!. Center for Disease Control. were used with thc L R C method. All kits were used according to the manufacturers' instructions and the standards recommended by each manufacturer were employed. Four frozen plasma pools (cholesterol range 1.8-9.0 mmol I ) were analysed in quadruplicate on 5 separate occasions. Accuracy and precision varied greatly amongst the kits. One enzymatic kit was consistently more accurate over the concentration range tested (reference value F 3""). Overall. the enzymatic kits were more precise than the chemical kits (coefficient of variation 0.7-4.4'<,,vs 2.6 51",). Fresh plasma sample, (n = 143-191: cholesterol range 4.9-12.5 minol 1) obtained by venepuncture were anallsed by each kit method and the LRC method. The mean difference in cholesterol concentration between each kit and the LRC method was uithin f 0.5 mmol 1. Two enzymatic kits produced mean differences within If: 0.1 minoi 1 of LRC value. In 4 kits the difference iaried with the cholesterol concentration ( P
THE DIAGNOSIS OF MYOCARDIAL INFARCTION USING CARDIAC-SPECIFIC ISOENZYME PROFILES
K. R. FATCHES Dirisiort o / Clinical Cher?ristrj~,The Pririce of Wales Hospiral, Sydney Crraiine kinase ( C K ) and lactate dehydrogenase ( L D ) isoenzyme activities uiere measured in 100 patients with suspected acute myocardial infarction (AMI). The method employed was electrophoresis on thin agarose films using the Corning-AC1 apparatus and reagents. The usefulness of this procedure as an aid to diagnosis and management \\as assessed. Specimens were collected at critical times on the enzyme release curve, the first on admission, then at intervals of 6 13 and 24-37 h. A comparison was made using significant elevations in total CK and r-Hydroxybutyrate dehydrogenase (z-HBDH) activities on specimens collected as part of the daily routine. In 34 patients there was an excellent correlation between both methods of analysis. However, the isoenzyme profile provided confirmation of AM1 in a further 7 patients. In these patients total CK remained within the reference range ( <80 p I ) or shoued borderline increases (80-160 p I), although r-HBDH remained normal. Among the remaining 48 patienis in which AM1 was ruled out. 4 showed elevations in total CK due to non-cardiac conditions. In a further 2 patients. in which total CK remained normal, trace amounts of CK-MB were detected. Both of these patients suffered episodes of atrial fibrillation, The individual assays for each collection period revealed that 61",, of the specimens were positive for CK-MB on the admission sample. whereas 937" were positive bq the second specimen Howexer elevdtions in total CK ( > 160 / I I) occurred in only 24", of patients on the first sperimen. uhereda 68",,were elevated b\ the second The ratio ot LDI LDZ > 1 occurred in 20",, on admission but 8 5 " , b\ 14 37 h This coincided with r-HBDH being ele\dted in 24',, and 78", of patients respectively Theiefore. the combination of CK and L D isoenzSme profiles probided a more rdpid and specific indication of AM1
OPTIMAL DIAGNOSIS OF MYOCARDIAL INFARCTION USING ONLY CARDIAC SPECIFIC ISOENZYMES
P. 7. FLET-I.N. D. H . BALAZS. A. SALKPS & P. DENNISDepartnietzts qfC'hemir,nl Pathology and C'tiI~liologj~. Pritiw fknr?.'s Hospital. .Mclhoitmr The routine serial measurenieiit of creatine kinase cardiac specific isoenzyme (CKMB) by a modified immunoinhibition method adapted to common discrete analysers (ABBOTT ABA 100 and Centrifichem 400) has been shown to be diagnostically accurate by a clinical trial involving 151 consecutive admissions to a coronary care unit. To minimize the possibility of missing a myocardial infarction (MI) due to the rapid clearance of CKMB
ABSTRACTS OF ANNUAL MEETING
1980 633
(36-48 h), heat stable lactate dehydrogenase (a cardiac specific isoenzyme having slow clearance) was measured if indicated. The predictive value (PV) of the measured enzymes was derived using the discharge diagnosis. PV positive gives the likelihood for the presence of the disease in a patient with a positive result. PV negative estimates the likelihood for freedom of disease in a patient with a negative result. Effectiveness is a measure of the overall diagnostic accuracy of a particular test. Predictive value of
PV positive PV negative Effectiveness
1
CKMB 0.90 1.00 0.99
1
CK 0.91 1.00 0.96
i
AST 0.76 1.00 0.87
1
CK&AST 0.91 1.00 0.87
Routine measurement of isoenzymes on discrete analysers leads to earlier and more accurate diagnosis of MI without increased laboratory costs. USE OF DIGOXIN ASSAYS IN A TEACHING HOSPITAL
S. J. BRYANT, F. BOCHNER & E. DELACEYDepartment of Pathology, Royal Brisbane Hospital This study was designed to determine the way in which plasma digoxin assays were used in a large teaching hospital. Clinical staff were interviewed 48 h after the report left the laboratory and were asked the indication for the investigation, iheir predicted outcome, whether the report had been sighted, how the level of digoxin was interpreted and any change in the management of the patient. Two hundred and eight assays were performed in the 4 wk of the study. Twenty-one inadequate responses and 15 assays performed for other hospitals were not included in the survey. 91036 of requests were on inpatients. The majority of requests (8 1:d) were originated by residents. Suspected toxicity or underdosage were suspected in 36'2, and 35% or requests respectively. When the requesting doctor was confident of his clinical judgement, he was more likely to becorrect if the patient was toxic. The clinical impression of underdosage was often not substantiated. However, 27% of patients in this study had subtherapeutic levels compared with the 12.5% in a study from Melbourne.' It may be that there is a large number of patients taking digoxin, who have subtherapeutic levels and who would not suffer if the drug were ceased. Of47 patients whose results were interpreted as toxic only 19 had plasma digoxin levels above 2.0 pg/l whereas 49 were said to be underdosed when 66 patients had levels less than 1.O pgil. Of the 56 patients who had a change in dose only 17 had a follow-up assay performed. The percentage ofassays which led to a management change (38%) is much greater than that (122,) following the performance of serum protein electrophoresis.' This may reflect the better understanding our medical graduates have of clinical pharmacology than of chemical pathology. References 1. GUEST, K. (1980): Med. J . Ausr. 1, 167-170. 2. BRYANT, S. J. & HICKEY,M. (1980): Aust. N . Z . J . Med. 10, 104106. RATIONALIZATION OF CLINICAL CHEMISTRY SERVICES IN THE SOUTHERN METROPOLITAN REGION OF NEW SOUTH WALES
M. MEERKIN, & L. WYNDHAMDivision of Clinical Chemistry, The Prince of Wales and Prince Henry Hospital Group, Randwick, N . S . W . In 1960 The Prince Henry Hospital, The Prince of Wales Hospital and the Eastern Suburbs Hospital amalgamated as a group of public hospitals to service a large section of the health care needs of the Eastern Suburbs of Sydney. The present bed allocation is 1300 excluding the newly acquired Randwick Chest Hospital. The policy of the Health Commission of N.S.W. and our Boards of Directors has been to rationalize where possible services pertaining to this hospital group. Since the inception of these hospitals there has been a Division of Clinical Chemistry at both Prince Henry and Prince of Wales. In late 1979 the Boards of Directors appointed a new Head of Division of Clinical Chemistry. This was to coincide with the wishes of the Health Commission of N.S.W. that there should be substantial re-equipping and upgrading of the Division. Upgrading of both sites was initially conceived but because of increased costs and
ROYAL. COLLEGE OF PATHOLOGISTS OF AUSTRALASIA
Pathology (1981), 13, July
EVALUATION OF KIT METHODS FOR MEASUREMENT OF TOTAL PLASMA CHOLESTEROL LIXDSAY E. W'IxDtr4M. PACLS. BACHORIK 8: PETER0. KWITEROVICH. JR. Lipid Reseurch c h i c ,
T/IPJ o / m Hoipkitis C.tiirersitv. Bulriritore, M D . , LF.S.~4. The performance of 6 commercial kits for the measurement of total plasma cholesterol concentration. using enzymatic and chemical methods. was compared to the Lipid Research Clinics (LRC) method. Primary cholesterol standards. the purity of which was verified by spectrophotometry. thin-layer and gas chromatography by the Lipid Standardization Laborator!. Center for Disease Control. were used with thc L R C method. All kits were used according to the manufacturers' instructions and the standards recommended by each manufacturer were employed. Four frozen plasma pools (cholesterol range 1.8-9.0 mmol I ) were analysed in quadruplicate on 5 separate occasions. Accuracy and precision varied greatly amongst the kits. One enzymatic kit was consistently more accurate over the concentration range tested (reference value F 3""). Overall. the enzymatic kits were more precise than the chemical kits (coefficient of variation 0.7-4.4'<,,vs 2.6 51",). Fresh plasma sample, (n = 143-191: cholesterol range 4.9-12.5 minol 1) obtained by venepuncture were anallsed by each kit method and the LRC method. The mean difference in cholesterol concentration between each kit and the LRC method was uithin f 0.5 mmol 1. Two enzymatic kits produced mean differences within If: 0.1 minoi 1 of LRC value. In 4 kits the difference iaried with the cholesterol concentration ( P
THE DIAGNOSIS OF MYOCARDIAL INFARCTION USING CARDIAC-SPECIFIC ISOENZYME PROFILES
K. R. FATCHES Dirisiort o / Clinical Cher?ristrj~,The Pririce of Wales Hospiral, Sydney Crraiine kinase ( C K ) and lactate dehydrogenase ( L D ) isoenzyme activities uiere measured in 100 patients with suspected acute myocardial infarction (AMI). The method employed was electrophoresis on thin agarose films using the Corning-AC1 apparatus and reagents. The usefulness of this procedure as an aid to diagnosis and management \\as assessed. Specimens were collected at critical times on the enzyme release curve, the first on admission, then at intervals of 6 13 and 24-37 h. A comparison was made using significant elevations in total CK and r-Hydroxybutyrate dehydrogenase (z-HBDH) activities on specimens collected as part of the daily routine. In 34 patients there was an excellent correlation between both methods of analysis. However, the isoenzyme profile provided confirmation of AM1 in a further 7 patients. In these patients total CK remained within the reference range ( <80 p I ) or shoued borderline increases (80-160 p I), although r-HBDH remained normal. Among the remaining 48 patienis in which AM1 was ruled out. 4 showed elevations in total CK due to non-cardiac conditions. In a further 2 patients. in which total CK remained normal, trace amounts of CK-MB were detected. Both of these patients suffered episodes of atrial fibrillation, The individual assays for each collection period revealed that 61",, of the specimens were positive for CK-MB on the admission sample. whereas 937" were positive bq the second specimen Howexer elevdtions in total CK ( > 160 / I I) occurred in only 24", of patients on the first sperimen. uhereda 68",,were elevated b\ the second The ratio ot LDI LDZ > 1 occurred in 20",, on admission but 8 5 " , b\ 14 37 h This coincided with r-HBDH being ele\dted in 24',, and 78", of patients respectively Theiefore. the combination of CK and L D isoenzSme profiles probided a more rdpid and specific indication of AM1
OPTIMAL DIAGNOSIS OF MYOCARDIAL INFARCTION USING ONLY CARDIAC SPECIFIC ISOENZYMES
P. 7. FLET-I.N. D. H . BALAZS. A. SALKPS & P. DENNISDepartnietzts qfC'hemir,nl Pathology and C'tiI~liologj~. Pritiw fknr?.'s Hospital. .Mclhoitmr The routine serial measurenieiit of creatine kinase cardiac specific isoenzyme (CKMB) by a modified immunoinhibition method adapted to common discrete analysers (ABBOTT ABA 100 and Centrifichem 400) has been shown to be diagnostically accurate by a clinical trial involving 151 consecutive admissions to a coronary care unit. To minimize the possibility of missing a myocardial infarction (MI) due to the rapid clearance of CKMB
ABSTRACTS OF ANNUAL MEETING
1980 633
(36-48 h), heat stable lactate dehydrogenase (a cardiac specific isoenzyme having slow clearance) was measured if indicated. The predictive value (PV) of the measured enzymes was derived using the discharge diagnosis. PV positive gives the likelihood for the presence of the disease in a patient with a positive result. PV negative estimates the likelihood for freedom of disease in a patient with a negative result. Effectiveness is a measure of the overall diagnostic accuracy of a particular test. Predictive value of
PV positive PV negative Effectiveness
1
CKMB 0.90 1.00 0.99
1
CK 0.91 1.00 0.96
i
AST 0.76 1.00 0.87
1
CK&AST 0.91 1.00 0.87
Routine measurement of isoenzymes on discrete analysers leads to earlier and more accurate diagnosis of MI without increased laboratory costs. USE OF DIGOXIN ASSAYS IN A TEACHING HOSPITAL
S. J. BRYANT, F. BOCHNER & E. DELACEYDepartment of Pathology, Royal Brisbane Hospital This study was designed to determine the way in which plasma digoxin assays were used in a large teaching hospital. Clinical staff were interviewed 48 h after the report left the laboratory and were asked the indication for the investigation, iheir predicted outcome, whether the report had been sighted, how the level of digoxin was interpreted and any change in the management of the patient. Two hundred and eight assays were performed in the 4 wk of the study. Twenty-one inadequate responses and 15 assays performed for other hospitals were not included in the survey. 91036 of requests were on inpatients. The majority of requests (8 1:d) were originated by residents. Suspected toxicity or underdosage were suspected in 36'2, and 35% or requests respectively. When the requesting doctor was confident of his clinical judgement, he was more likely to becorrect if the patient was toxic. The clinical impression of underdosage was often not substantiated. However, 27% of patients in this study had subtherapeutic levels compared with the 12.5% in a study from Melbourne.' It may be that there is a large number of patients taking digoxin, who have subtherapeutic levels and who would not suffer if the drug were ceased. Of47 patients whose results were interpreted as toxic only 19 had plasma digoxin levels above 2.0 pg/l whereas 49 were said to be underdosed when 66 patients had levels less than 1.O pgil. Of the 56 patients who had a change in dose only 17 had a follow-up assay performed. The percentage ofassays which led to a management change (38%) is much greater than that (122,) following the performance of serum protein electrophoresis.' This may reflect the better understanding our medical graduates have of clinical pharmacology than of chemical pathology. References 1. GUEST, K. (1980): Med. J . Ausr. 1, 167-170. 2. BRYANT, S. J. & HICKEY,M. (1980): Aust. N . Z . J . Med. 10, 104106. RATIONALIZATION OF CLINICAL CHEMISTRY SERVICES IN THE SOUTHERN METROPOLITAN REGION OF NEW SOUTH WALES
M. MEERKIN, & L. WYNDHAMDivision of Clinical Chemistry, The Prince of Wales and Prince Henry Hospital Group, Randwick, N . S . W . In 1960 The Prince Henry Hospital, The Prince of Wales Hospital and the Eastern Suburbs Hospital amalgamated as a group of public hospitals to service a large section of the health care needs of the Eastern Suburbs of Sydney. The present bed allocation is 1300 excluding the newly acquired Randwick Chest Hospital. The policy of the Health Commission of N.S.W. and our Boards of Directors has been to rationalize where possible services pertaining to this hospital group. Since the inception of these hospitals there has been a Division of Clinical Chemistry at both Prince Henry and Prince of Wales. In late 1979 the Boards of Directors appointed a new Head of Division of Clinical Chemistry. This was to coincide with the wishes of the Health Commission of N.S.W. that there should be substantial re-equipping and upgrading of the Division. Upgrading of both sites was initially conceived but because of increased costs and