Does the dipstick meet medical needs for urine specific gravity?
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Biomedical subjects
Publications and source records attributed to J A Lott.
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We obtained enzyme data on normal individuals in conjunction with a large interlaboratory enzyme survey. For the 12 largest peer groups using unique methods, we found a simple relationship between the upper reference limits and the laboratories' results obtained from human-enzyme-supplemented survey serum. A conversion to a common base made possible the merging of data on the normal individuals and interconversion of results by diverse methods. We determined the upper reference limits for serum lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase for approximately 8000 adult men and women believed to be in good health. Using a technique described here, we believe that the results can be transformed to user-specific units, and that the large data base can be applied to the many diverse enzyme methods in current use. With these data, enzyme survey participants will be able to estimate appropriate reference intervals for their particular method.
We evaluated three commercially available methods for determining lipase (EC 3.1.1.3) in serum--the Du Pont aca, Boehringer Mannheim Diagnostics (BMD), and Kodak Ektachem (EK) procedures--for their analytical properties and diagnostic efficiencies. Titrimetry was used as the comparative method. The BMD and EK methods showed better agreement with the titrimetric method, owing to the presence of the necessary cofactor, colipase, in their reagents. Colipase also increased the analytical sensitivity of the BMD and EK procedures as compared with the aca method. Determinations of serum lipase, by all methods, had a clinical sensitivity in excess of 80% for acute pancreatitis; the specificity of the lipase test was about 60%, or twice that of serum amylase. Serum lipase determinations with the current, simpler technology are superior to total amylase in the diagnosis of patients with acute pancreatitis. When a colipase-supplemented method is used, a serum lipase value greater than 10-fold the upper reference limit appears to be pathognomonic for acute pancreatitis or inflammation of organs close to the pancreas.
Creatine kinase (CK), a widely distributed enzyme in the body, has its highest activities in skeletal muscle and myocardium; when serum CK activities are abnormally increased, injury to these organs must be part of the differential diagnosis. The isoenzyme CK-MB is the most important biochemical test in the diagnosis of acute myocardial infarction.
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Because of its sensitivity to disturbances of excretory liver function, gamma-glutamyltransferase (GGT; EC 2.3.2.2) assay has become one of the most important diagnostic tests for hepatobiliary disorders. However, its value in the differential diagnosis of liver diseases is limited. It is present in kidney, liver, pancreas, and intestine in electrophoretically distinct but not necessarily organ-specific forms. Much effort has been expended to relate diseases of these organs to isoenzyme findings in serum. Although the activities of GGT isoenzymes in disease differ from those in health, the existence of disease-specific patterns is controversial. Much is known about the biochemistry, structure, and immunochemistry of GGT, but more work is needed on methods, standardization of terminology, and correlation of isoenzyme findings with diseases. Further progress in the last area should improve the clinical applicability of the isoenzyme activities.
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A new bench-top analyzer from Du Pont, the "aca IV," was evaluated. To do so, we performed 10 different tests during an eight-week test period. The instrument is very precise (CVs less than 2%), results agree well with those obtained with the older acas (II and III), linearity is good in the clinically important ranges, and there is very little drift or carryover. From a medical-needs viewpoint, we found the analyzer satisfactory for all tests except possibly for calcium, for which the medical-needs criteria are so strict that few laboratories can meet them. We reached the latter conclusions by using a statistical model, described here, and from the predictive value of an abnormal test for populations with various prevalences of disease.
Serum CK-MB and LD-1 have proved extremely useful in the diagnosis and differential diagnosis of acute myocardial infarction. However, CK-MB is present in skeletal muscle and can be released during ischemic attacks; thus, abnormal serum CK-MB activities cannot be equated with myocardial injury. Even wider is the distribution of LD-1, which is found particularly in erythrocytes and renal cortex; hence, an abnormal LD-1 level also cannot be equated with myocardial injury. The method of choice and the final arbiter for the CK and LD isoenzymes is electrophoresis. The possibility of interpreting the results visually fulfills, in part, quality-control needs, and makes the technique suitable for small and large laboratories. Extreme analytic sensitivity is not needed, and electrophoresis provides clinically useful and acceptable results.
In myopathic disorders, abnormal serum enzyme activities are seen primarily in diseases of skeletal muscle where the condition involves the muscle fibers themselves. In denervation myopathies, serum enzyme activities are usually normal. The most dramatic increases of serum enzymes, particularly creatine kinase, are found in the dystrophic diseases, particularly Duchenne dystrophy. A review is given here of the many causes of abnormal serum enzyme activities where the source of enzymes is believed to be skeletal muscle. These include the dystrophies, various types of trauma, exercise, drug- and poison-induced causes including alcohol, malignant hyperthermia, inflammatory diseases, and miscellaneous causes. Tissue and serum activities are summarized for the commonly performed serum enzymes, i.e., CK, LD, AST, and aldolase. An extensive tabular and current description of the various types of dystrophies is given along with serum CK and pyruvate kinase activities.
Reactivation of serum creatine kinase isoenzyme BB (CK-BB) with 2-mercaptoethanol and EDTA increased the electrophoretic detection rate of CK-BB from 34% to 78% in 58 hospitalized patients with various malignancies. Patients with solid tumors showed the largest and patients with hematologic malignancies the smallest percentage increase in CK-BB after reactivation. For serum from 50 hospitalized patients without cancer, reactivation resulted in detectable CK-BB in two patients; the CK-BB band was never seen in 15 healthy adults. For reasons unknown, five of eight patients with senile dementia of the Alzheimer's type showed CK-BB in serum after reactivation, as did two of five patients suspected of having this disorder. Serum CK-BB may be a useful tumor marker if reactivation with a thiol and EDTA is used immediately after collection.
The College of American Pathologists' enzyme survey permits the evaluation of the quality of enzyme analyses in clinical laboratories. Animal source enzymes for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and creatine kinase are satisfactory as supplements for enzyme survey serum, since they give results equivalent to human source enzymes. This finding makes the interconversion of results by different methods possible, and the estimation of the upper limit of normal based on the results obtained for the enzyme survey serum.
The Coomassie Brilliant Blue G-250 method for protein in urine has been evaluated for analytical accuracy and clinical applicability. Extremely simple to perform, the test exhibits good precision and sensitivity. The color developed per gram of protein is protein-type dependent, so no single protein standard is completely satisfactory. Color intensity is linearly related to concentration up to 1500 mg/L when used with a manual bichromatic method. Accuracy was clinically acceptable for patients with a variety of protein-losing diseases, and for patients having received renal transplants; however, the method underestimates urinary light-chain proteins. In athletes and premature neonates, we observed increased protein excretion during periods of stress. The upper reference limit for protein excretion in healthy adults is about 120 mg/24 h.
The College of American Pathologists' Enzyme Survey continues to provide a valuable measure of the analytic quality of clinical enzymology for its participants and for the laboratory community. An updated reporting format for the participants simplifies the interpretation of Enzyme Survey data and should make it more valuable for detecting short- and long-term changes in accuracy and precision. A short-term CV of 3% and a long-term CV of 6% are recommended as analytic goals for the five enzymes described here. The upper limit of normal used by many laboratories is appropriate for a given enzyme yet remains as an area requiring urgent further study.
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