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Biomedical subjects

R S Galen

Publications and source records attributed to R S Galen.

At least 19 recordsLinked to original sources

Changes in serum CK-MB mass after coronary artery bypass surgery.

We assessed the release of creatine kinase MB as both mass and activity during the postoperative period following cardiac surgery. CK-MB mass was determined by enzyme immunoassay using reagents obtained from Hybritech. CK-MB activity was determined both by agarose electrophoresis and by an immunochemical method. Fifty-five patients who underwent coronary artery bypass surgery and 52 control subjects who had orthopedic surgery were selected for study. Serial serum samples were collected following surgery and total LD, CK, AST, LD-1, CK-MB mass, and CK-MB activity determined. Results were compared to each other and to surgical parameters. All patients exhibited significant CK-MB mass and activity after surgery and peak serum levels were 6-94 micrograms/L and 12-84 U/L, respectively. CK-MB mass correlated with CK-MB activity on paired samples (r = 0.94). Total AST and CK activities correlated with CK-MB mass (r = 0.60, and 0.63, respectively). Peak levels of CK-MB mass correlated significantly with peak MB activity (r = 0.88), peak LD-1 (r = 0.62), peak AST (r = 0.71), and time on pump (r = 0.54). Similar correlations were also seen between peak CK-MB activity and these parameters. No relationship could be identified between extent of CK-MB mass release and number of grafts, degree of hypothermia, or minimum PaO2. The time course of CK-MB mass release exhibited 85% concordance with CK-MB activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Application of the EXPERT consultation system to accelerated laboratory testing and interpretation.

The EXPERT consultation system-building tool, a knowledge-based artificial intelligence program developed at Rutgers University, has been applied to the development of a laboratory consultation system facilitating sequential laboratory testing and interpretation. Depending on the results of a basic panel of laboratory tests, the system requests that specific secondary tests be performed. Input of these secondary findings can result in requests for tertiary testing, to complete the database necessary for interpretation. Interpretation of all results is based upon final inferences from the collected findings through a series of rules, a hierarchical network that yields an efficient production system not easily obtained through conventional programming. The rules included in this model are based upon initial results for total protein, calcium, glucose, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, thyroxin, hemoglobin, mean corpuscular volume, and the concentrations of four drugs. Pertinent clinical history items included are jaundice, diabetes, thyroid disease, medications, and ethanol. Implementing this system in a laboratory-based accelerated testing program involving outpatients maximized the effective use of laboratory resources, eliminated useless testing, and provided the patient with low-cost laboratory information.

Adolescent

Urinary magnesium loss in aging diabetic mellitus rats.

Past studies on urinary loss of magnesium (Mg) have focused on young diabetic rats. The aims of the present study were to determine the rapidity at which glycosuria and magnesuria occur after the induction of diabetes mellitus (DM) in old male rats, and the maximal amount of Mg and glucose (Glu) loss in the urine and whether or not the loss is persistent and (3) the most sensitive means of correlating the Mg and Glu loss in the urine. Three methods of expressing urinary Mg and Glu concentrations were selected: Method A: mg/24 h; Method B: mg/24 h/kg body weight (BW), and Method C: ratio of Mg to creatinine (Mg/Crea) or ratio of Glu to Crea (Glu/Crea). Our study indicated a maximal and rapid loss of Mg and Glu occurring within 1 week after induction of DM (by streptozotocin injection) and remained in effect for 6 weeks, the end of the study. The urinary Mg loss due to DM correlated best with urinary Glu when expressed as mg/24 h/kg BW. In addition, the increase in urinary Mg concentration paralleled the degree of glycosuria and reached a maximum of 5-12 times baseline values when expressed by Method B. This was 4-10 times when expressed by Method A, and 2-6 times when expressed by Method C. Since polyuria is a feature of DM, we also correlated the relationship between these two factors, and found a significantly positive correlation (r = 0.735) particularly when Mg was expressed as mg/24 h. In summary, rapid and significant urinary Mg loss is observed in old rats made diabetic with streptozotocin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

The assessment of laboratory tests in the diagnosis of acute appendicitis.

A comparison of laboratory tests was undertaken in 106 patients admitted to the emergency room with the tentative diagnosis of acute appendicitis and who subsequently underwent appendectomy. The tests examined included the total white blood cell count, manual differential count, cytochemical differential count, and C-reactive protein. The sensitivity, specificity, efficiency, and predictive value of these tests in the diagnosis of acute appendicitis were calculated. The cytochemically determined neutrophil count, when greater than the upper limit of the reference interval of either 75% or 7.88 X 10(9)/L, and the total white blood count greater than the upper limit of the reference interval of 10.5 X 10(9)/L were the single best tests for the diagnosis of acute appendicitis with the highest sensitivities of all tests examined (81-84%). The manual differential count and C-reactive protein showed significantly lower sensitivities. Test combinations also were examined. The combinations consisted of two or more tests joined by an "or" rule, i.e., if any one of the individually linked tests of the combination is above the reference interval, the combination is considered as indicating acute appendicitis. When either of the following test combinations were utilized--(1) total white count greater than 10.5 X 10(9)/L or cytochemical neutrophils greater than either 75% or 7.88 X 10(9)/L or CRP greater than 1.2 mg/dL; (2) total white count greater than 10.5 X 10(9)/L or manual bands greater than either 11% or 1.15 X 10(9)/L or CRP greater than 1.2 mg/dL--the sensitivity of the combination in the diagnosis of acute appendicitis approached 100% with a specificity in the range of 50%. We suggest that these test combinations may be useful in deciding which patients need further observation and reexamination prior to surgery. We also suggest the need for further studies to assess the usefulness of these tests in other types of acute inflammation and infection.

Acute Disease

Application of the predictive value model in the analysis of test effectiveness.

There are four levels at which laboratory tests and procedures can be evaluated relative to their effectiveness: 1. Analytical analysis of laboratory test: precision, accuracy, analytical sensitivity, and analytical specificity. 2. Diagnostic analysis of laboratory test: diagnostic sensitivity, diagnostic specificity, Youden index, likelihood ratio, and ROC curve. 3. Operational analysis of laboratory test: predictive value of positive result, predictive value of negative result, efficiency, discriminant function, and so forth. 4. Medical decision-making analysis of laboratory test: threshold probability, cost-benefit analysis, and solving the decision tree. Laboratory test selection can occur at any level, without knowledge of the test's evaluation and performance at the other levels. Alternatively, the development of new laboratory tests can proceed from level 1 to level 4, or vice versa. Unfortunately, the former is usually the case and most of the tests in use today have never been evaluated at the medical decision-making level. In evaluating clinical laboratory tests, it is essential that the laboratory have at its disposal simple ways to analyze sets of data. The predictive value model has proven to be effective in designing test strategies and evaluating the usefulness of laboratory tests. The widespread use of computers in laboratory medicine should permit this approach to data analysis to become routine in the next few years.

Acid Phosphatase

Diagnosis of hemolytic disease by electrophoresis of erythrocyte lactate dehydrogenase isoenzymes on cellulose acetate or Agarose.

We determined the LD-1/LD-2 isoenzyme ratio in hemolysates of erythrocytes by electrophoresis on cellulose acetate and on agarose. A ratio exceeding 1.0 was found with the former but not the latter. Results were similar for in vitro models of hemolytic disorders. Using cellulose acetate electrophoresis, we determined the predictive value of data on total LD activity and of the LD-1/LD-2 ratio in diagnosis of hemolytic disease in 100 patients. The sensitivity of the "flipped" LD-1/LD-2 ratio was only 58%, the specificity was 93%, and the predictive value was 74% for diagnosis of hemolytic disease. A normal total LD activity is highly predictive (92%) for ruling at the presence of hemolytic disease.

Anemia

The predictive value theory redefines quality assurance.

Performing laboratory tests that are unreliable or diagnostically meaningless is costly, time-consuming, and wasteful. The Predictive Value Model provides a means to eliminate this wastefulness and increase the utility of laboratory testing. This paper describes the way in which data regarding a test's predictive value, and efficiency may be used to determine which tests are of maximum utility in specific situations.

Clinical Laboratory Techniques

The predictive value of serum haptoglobin in hemolytic disease.

Using a rapid, highly sensitive immunoprecipitin nephelometric technique, a retrospective study was undertaken to evaluate the clinical usefulness of determining serum haptoglobin in the diagnosis of hemolysis. Haptoglobin assays were performed shortly after admission in 100 patients with a variety of hematologic and nonhematologic conditions and the results correlated with the clinical diagnosis. An ad hoc boolean computer program allowed for the separation of hemolytic from nonhemolytic disorders with a haptoglobin limit of 25 mg/dL or less. The sensitivity and specificity of the test are high (83% and 96%, respectively), providing 87% probability of predicting hemolytic disease when the serum haptoglobin level falls below this limit. These data support the routine use of serum haptoglobin determinations in the diagnosis of hemolytic disease.

Adult

Predictive value and efficiency of laboratory testing.

Literature on determining reference values and reference intervals on "normal" or "healthy" individuals is abundant. It is impossible, however, to evaluate a data set of reference values and select a suitable reference interval that will be meaningful for the practice of medicine. The reference interval, no matter how derived statistically, tells us nothing about disease. This is the main reason the concepts of "normal values" have failed us and why "reference values" will prove similarly disappointing. By studying these same constituents in a variety of disease states as well, it will be possible to select "referent values" that will make the test procedure meaningful for diagnostic purposes. In order to obtain meaningful referent values for predicting disease, it is necessary to study not only the "healthy" reference population, but patients with the disease in question, and patients who are free of the disease in question but who have other diseases. Studies of this type are not frequently found for laboratory tests that are in common use today.

Clinical Laboratory Techniques

Predictive value and efficiency of hematology data.

Laboratory test results and procedures can be evaluated at four levels:1. Analytic analysis of laboratory test: precision, technical sensitivity, technical specificity; 2. Diagnostic analysis of laboratory test: diagnostic sensitivity, diagnostic specificity, Youden index, likelihood ratio, etc.; 3. Operational analysis of laboratory test: predictive value of positive result, predictive value of negative result, efficiency, discriminant function, etc.; 4. Medical decision-making analysis of laboratory test: threshold probability, cost-benefit analysis, solving the decision tree. Analysis of results or selection of tests can occur at any level, without knowledge of the test's evaluation or performance at the remaining levels. Alternatively, the development of new laboratory tests can proceed from level 1 to level 4, or vice versa. Unfortunately, the former is usually the case and most of the tests in use today have never been evaluated at the medical decision-making level (level 4). Recent efforts at developing automated WBC differential counters represent a disproportionate amount of time and energy expended at level 1, and typify our backward approach to laboratory medicine. In thinking about the development of new diagnostic tests, we should begin at level 4 to characterize the properties and specifications that the test must meet. As an example, an in vitro test for the diagnosis of pulmonary embolism could be characterized in this fashion with criteria specified at each of the lower levels. Returning to the question of "How good should a laboratory test be?", we can see that the answer must come from an analysis of the benefit-cost equation (level 4). Figure 2 is a plot of the net benefit and cost of treatment versus the threshold probability. Since the threshold probability defines how certain one must be of the diagnosis before proceeding with treatment, it serves as a minimum probability which should be exceeded by the predictive value of the test. When the benefit--cost ratio is low, a test with a very high predictive value is required to exceed the threshold probability. On the other hand, when the benefit--cost ratio is high, even a test with a low predictive value would be of use to the physician in making the decision to treat the patient. Within this framework, a number of clinical situations could be evaluated and problems requiring the development of highly predictive laboratory tests (low benefit--cost ratios) could be identified. Too much emphasis in laboratory medicine has been placed on the "laboratory" and not enough on the "medicine". How important is the coefficient of variation when the benefit--cost ratio is high? Tests can not be developed or selected appropriately in a therapeutic vacuum.

Adolescent

Laboratory test selection.

One of the most frequent and perhaps frustrating problems in laboratory medicine today relates to the appropriate selection of laboratory tests. We all know that many laboratory tests are not always selected with care and results are not used to benefit the patient. If unnecessary tests are performed, then the laboratory is providing little or no new information to the clinician. This is costly and time consuming for the laboratory and wasteful of health care resources. In addition, unnecessary tests will serve to complicate the diagnostic process and adversely affect medical decision making. While precision and accuracy have been long standing concerns for the laboratorian, it is clear that our perspective about the tests we perform must be broadened if we are going to keep up with the changing pace of health care. The selection, interpretation and evaluation of laboratory tests can be facilitated by the use of some newer concepts in laboratory medicine They include sensitivity, specificity and predictive value. These concepts will be introduced together with examples of their application.

Analysis of Variance

Evaluation of a nephelometric assay for haptoglobin and its clinical usefulness.

Serum haptoglobin has been advocated as an indicator of intravascular hemolysis. We have evaluated a nephelometric determination of serum haptoglobin. The assay is sensitive and exhibits within-run precision in the range of 2.5-7.4% coefficient of variation (CV) and between-run precision of 7.0% (CV). In addition, when haptoglobin values determined with the nephelometric assay were compared with hemoglobin-binding capacity determined by electrophoresis, the correlation coefficient was 0.968. The assay is essentially independent of phenotype and free of significant interference by hemolysis. The clinical correlation of haptoglobin values obtained for 100 selected patients with the nephelometric technique correlated well, if less than 250 mg/L, with the presence of hemolytic disease.

Anemia, Hemolytic