The value of clinical laboratory studies in acute pancreatitis.
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Biomedical subjects
Publications and source records attributed to J A Lott.
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Proficiency testing goals for serum enzymes have been set by statistical methods, by the ex cathedra statements of experts, based on the intraindividual variation of healthy people, and based on responses from the users of enzyme data, ie, clinicians in practice. Clinicians consider small changes in serum enzyme values to be medically unimportant. Medical-needs criteria are probably the most relevant in setting proficiency testing goals for enzymes. The enzyme values that most modern clinical analyzers are capable of producing are more precise than appears to be medically necessary. We surveyed clinicians for their perceived needs; based on their responses, we conclude that tight proficiency testing limits for enzyme tests are inappropriate.
BACKGROUND: A physician can obtain a patient's complete lipoprotein profile at the time of the office visit including assays of the total serum cholesterol, high-density lipoprotein cholesterol (HDL-C), and fasting triglyceride concentrations, and then calculate the low-density lipoprotein cholesterol (LDL-C). Until recently, this was not possible. Instruments are currently available that provide reliable rapid total serum cholesterol and fasting triglyceride measurements. METHODS: This study evaluated the accuracy and precision of a recently developed analytical method for the rapid measurement of HDL-C (Seralyzer Cholesterol System) as compared with a reference clinical laboratory method (Kodak Ektachem 700 XR). Blood specimens were taken from 90 participants and were analyzed in duplicate for HDL-C concentrations and total cholesterol using the Seralyzer and a standard Ektachem 700 XR. RESULTS: Nearly all (98.9%) of the initial Seralyzer HDL-C measures were within +/- 0.08 mmol/L (+/- 3 mg/dL) of the duplicate Seralyzer values. Most (98.3%) of the Seralyzer HDL-C results were within +/- 0.16 mmol/L (+/- 6 mg/dL) of the Kodak HDL-C values. CONCLUSIONS: The Seralyzer HDL-C test provides a reliable and accurate measure of the HDL-C concentration.
Graphical representation of laboratory data speeds up recognition of abnormalities. The Chernoff face is an excellent tool to represent patient data; the human eye and mind are exquisitely sensitive to subtle changes in facial appearances and expression. One of the best uses of the faces is in illustrating trends in the data, particularly in acutely ill patients where many laboratory studies are performed. The faces are especially useful if comparisons to a former or normal state are made. A very brief examination of adjacent faces suffices to identify changes in laboratory data.
We describe three patients with seizure disorders in whom pancreatitis or pancreatic injury was probably caused by valproic acid, a widely used anticonvulsant drug. Trivial or no increases of serum amylase (EC 3.2.1.1) but striking increases of serum lipase (EC 3.1.1.3) were common to all patients, as assayed in the Kodak Ektachem. In vitro, valproic acid does not cause any change in serum lipase. In patients with symptoms suggestive of pancreatitis and abnormal values for amylase and (or) lipase, treatment with valproic acid should be discontinued.
In 78 patients with likely pancreatitis, we used laparotomy, computerized tomography, ultrasonography and other information to make an objective diagnosis of pancreatitis. Laboratory studies included serum amylase, amylase isoenzymes and lipase. We found that both amylase and lipase are highly sensitive tests and P3 amylase by electrophoresis on agarose to be specific; a combination of these tests is recommended to assist in the diagnosis of pancreatitis. The frequent occurrence of an abnormal amylase and lipase in patients without pancreatitis is suggested as the cause of overdiagnosis of this disorder. A markedly increased amylase or lipase was always associated with pancreatic disease.
We evaluated the Seralyzer instrument for the assay of serum cholesterol and compared it to the Kodak Ektachem method. The Seralyzer showed good accuracy in the analysis of cholesterol in Abell-Kendall-verified serum pools, and the bias from the expected value was small in all cases but one. The Seralyzer exhibited CVs of less than 5% in all cases and good comparison with the Ektachem method. The Seralyzer is easy to use; however, some training in the proper pipetting technique is necessary. The Seralyzer meets medical needs criteria of total error greater than 5% from the true cholesterol value.
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Proficiency testing by State and Federal agencies is an ongoing activity of clinical laboratories and an occasional source of anxiety; strict statistical evaluations of "snapshot" laboratory values are inappropriate and medical-needs criteria should be used. The quality of laboratory results largely depends on available technology. Fortunately, for most of the common clinical chemistry analytes there has been a steady reduction of imprecision during the past 20 years. Proficiency testing may have been the stimulus for this improved performance. Medical-needs criteria differ, depending on the testing goal. For proficiency testing, population screening criteria are appropriate, e.g., the College of American Pathologists fixed criteria for the common tests. Stricter criteria are needed for short-term (inpatient) and long-term (outpatient) monitoring of laboratory data. Explicit proficiency-testing limits are given here for nine of the common clinical chemistry tests for each of the three medical-needs criteria described above. The limits consider total error--i.e., bias from the believed correct value, and imprecision. Rather broad limits are acceptable for the commonly performed enzyme tests when used for screening purposes.
For the diagnosis of myocardial injury, particularly AMI, CK-MB has become the gold standard. Changing CK-MB activities in serially collected blood from patients with suggestive signs and symptoms of AMI is almost pathognomonic for infarction. Nevertheless, an increased CK-MB cannot be equated with AMI owing to the many other types of inflammatory, traumatic, and miscellaneous forms of injury to the heart and the trace activities of CK-MB in skeletal muscle. Other enzyme tests for AMI are less efficient. In order of decreasing efficiency, the tests are CK-MB, CK, LD1 greater than LD2 or LD1/LD2 greater than 0.76, AST and LD; the latter two tests are not cost effective and add little or nothing when results for CK-MB, CK, and LD isoenzymes are available. The value of the isoforms of CK-MM and CK-MB remains to be established. Early evidence suggests that they could be helpful in the diagnosis of AMI; however, owing to the greater technical difficulties in performing these tests, their use is necessarily more restricted. Enzyme testing on admission and then every 12 hours for 2 days is sufficient and effective in making the initial diagnosis. In patients presenting early after an attack, CK and CK-MB are often normal. Decisions on AMI cannot be made on blood tests collected in the emergency department. Clot-lysing agents like streptokinase, urokinase, and tPA have changed the therapy of AMI dramatically. Enzyme tests clearly separate patients with and without successful therapeutic or spontaneous reperfusion. With successful reperfusion, the uniform finding has been a "washout" phenomenon with significantly earlier peaking times for CK and CK-MB. The isoforms of CK and myoglobin give the earliest peaks after successful reperfusion. With faster turnaround times for these tests, they may become important tools in patient management.
Protein in cerebrospinal fluid (CSF) was measured by a modified biuret procedure and in two automated instruments, the Du Pont aca and the Kodak Ektachem. The latter's dry-slide reagent was also evaluated for precision, linearity, and effect of potential interferents. In vitro, ampicillin and vancomycin increase the apparent value for CSF protein as measured with the Ektachem slides. We excluded patients with disorders of the central nervous system, and we estimated the central 95% percentile reference intervals for CSF protein for each of the three methods. We found no age or gender dependence of values. By the biuret procedure, the reference interval is 140 to 620 mg/L.
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The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.
When 14 "moderate" drinkers abstained from alcohol for four weeks, the activity of gamma-glutamyltransferase (GGT; EC 2.3.2.2) in their serum showed a large decrease. Immediately after the period of abstention, an orally given ethanol challenge of 1 g/kg produced a marked increase in serum GGT at 24 h, followed by a slow decline thereafter. Aspartate amino-transferase activity in serum was significantly increased at 24 h; however, alkaline phosphate, alanine aminotransferase, and lactate dehydrogenase showed much smaller or no changes. An abnormal increase in lactate dehydrogenase isoenzyme 5 was observed in seven subjects. In some of the moderate drinkers, liver biopsies showed mild chronic hepatitis or nonspecific changes. Eight nondrinking controls showed only slight increases in serum GGT following the same alcohol challenge; results for the other enzyme tests were unchanged. We consider it probable that pre-existing liver disease affects the response to ethanol, so that greater amounts of GGT are released from hepatic tissue; alternatively, drinkers may have a higher GGT activity in this tissue as a result of enzyme induction by ethanol. The alcohol challenge test was an effective discriminator between moderate drinkers and abstainers.
Mesenteric vascular occlusion and intestinal obstruction are difficult-to-diagnose medical emergencies. We evaluated a large panel of biochemical markers as diagnostic and prognostic indicators in a rat model of intestinal infarction and partial, complete, and strangulated intestinal obstruction. After intestinal infarction and obstruction, laboratory data are distinctly abnormal. Serum urea nitrogen dramatically increased in all groups, but most rapidly in the groups with infarction and strangulated obstruction. Inorganic phosphorus proved to be a sensitive indicator of infarction, but less so for any form of obstruction. While all members in the infarct group demonstrated significant increases in the aminotransferases, creatine kinase, and alkaline phosphatase, such increases in the groups with obstruction were less pronounced. Serum maltase assays revealed decreasing activities in all members of the groups with complete and strangulated obstruction, but in only 17% of the rats with partial obstruction. Serum maltase activity increased from abnormally low values after surgery to abnormally high values in the six animals that recovered from partial intestinal obstruction. The proportion of hexosaminidase A (of total beta-N-acetylhexosaminidase, EC 3.2.1.30) was generally abnormal in rats with complete and strangulated obstruction.
Laboratories participating in the College of American Pathologists Enzyme Survey (ES) and Comprehensive Chemistry Survey used diverse methods for the same analyte, resulting in a considerable range of values for the commonly performed enzyme measurements. Nevertheless, with the techniques developed for the ES, both the short-term (within-mailing) and long-term (between-mailings) coefficients of variation (CVs) can be determined. The ten-year experience of the ES has shown improvement in the short-term CV; however, long-term stability of enzyme testing requires more effort on the part of the instrument and reagent suppliers and participating laboratories. A reference material with an International Federation of Clinical Chemistry-established aspartate aminotransferase value, National Bureau of Standards RM 8430, is now available and was sent to three large peer groups as part of a special study. Correction of the results to the RM 8430 aspartate aminotransferase value resulted in reducing the range of data from peers using the duPont aca but not from those using the American Monitor KDA or Technicon SMAC. Based on our experience with the ES, goals of 5% for the short-term CV and 10% for the long-term CV are proposed; they are achievable by most laboratories and meet medical needs for biochemical screening. Fixed criteria for the evaluation of enzyme results appear to be appropriate given the way most enzyme data are used clinically.
Skeletal muscle is rich in creatine kinase (CK), lactate dehydrogenase (LD), and other enzymes. Many reports describe changes in serum CK and LD following exercise. In our study, 11 male international-class medium-distance runners were followed over a 10-month period prior to the 1984 US Olympic Trials. Cardiorespiratory fitness, evaluated through repetitive treadmill testing, was unchanged in our athletes. Total CK increased significantly during the course of training, and the CK-MB activity was higher than that of sedentary individuals; CK-MB never rose to more than 3% of the total CK. Total LD also rose following acute exercise; however, the proportions of the five isoenzymes were unaltered. There was no change in the LD-1/LD-2 ratio from normal. The origin of the increased serum enzymes was believed to be primarily skeletal muscle. A decrease of serum haptoglobin following acute stress was attributed to intravascular hemolysis and binding of hemoglobin. As expected, serum lactate was dramatically increased immediately postexercise.
The Coomassie Brilliant Blue G-250 method for urinary proteins underestimates urinary immunoglobulin light chains when albumin or pooled serum is used as the protein standard. The specific color yields of these and other proteins can be brought closer together by adding sodium dodecyl sulfate to the reagent; however, there is some loss of sensitivity. We found such a reagent to be satisfactory for assaying urinary proteins on studying 43 patients with light-chain proteinuria, 19 of whom had multiple myeloma and six possible multiple myeloma.