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D L Witte

Publications and source records attributed to D L Witte.

At least 37 records · Page 2Linked to original sources
PubMed1993

Medically relevant laboratory-performance goals: a listing of the complexities and a call for action.

This 1992 Clinical Chemistry Forum asks if accuracy and precision goals for the laboratory can be specified by reference to medical requirements, which are a function of the total laboratory testing process as well as the needs of patients, clinicians, and societal institutions. Furthermore, medical decisions and decisions about medical requirements must be made in situations of uncertainty and thus are subject to predictable cognitive errors. The interaction of all these factors must be considered by patients, laboratorians, and clinicians to identify practical and effective performance goals. Pathologists and clinical chemists are uniquely trained to identify thoughtful clinicians who are knowledgeable in quantitative judgment to participate in this goal-setting endeavor. It is time for these parties to accumulate the available data and engage in the synthesis of effective performance goals.

Bias↗
PubMed1993

Matrix effects in therapeutic drug monitoring surveys. Proposed protocol to identify error components and quality improvement opportunities.

Therapeutic drugs are not endogenous compounds. Therefore, differing reactivities between proficiency testing and patient samples have potential mechanisms beyond those attributable to alterations of the serum protein base, stabilizing materials, and other manufacturing components. The therapeutic drug monitoring proficiency sample is the ultimate in polypharmacy. Cross-reactivities may be uncovered that may or may not occur with any frequency in patient samples. Drugs are present in therapeutic drug monitoring proficiency samples in the absence of their metabolites, which may alter interactions with the assay systems. The CAP Therapeutic Drug Monitoring Resource Committee has contacted manufacturers when a specific method yields proficiency test results that differ from all other methods and/or the weighed-in target values. Only a few examples have been formally evaluated with the "matrix evaluation protocol." The protocol is very useful and has identified some matrix effects. A protocol is proposed using multiple samples containing survey base material. Data analysis using reciprocal plots will identify interference and corroborate calibration or recovery errors in the presence of survey base material. Data from 1987 through 1991 surveys for lithium and theophylline illustrate this data analysis and show interference from other drugs and suggest calibration errors. Weighted-in target values are the most rigorous method to provide accurate, transferable patient results and convince ourselves and our evaluators that we know what we are measuring. All of us need to be committed to improvement of laboratory procedures. I believe weighed-in target values are the appropriate and achievable goal for proficiency testing the majority of therapeutic drug monitoring analytes. Implementation of target values requires diligent and intricate collaboration among laboratorians, surveyors, manufacturers, and regulators.

Bias↗
PubMed1992

Insensitivity of rapid antigen detection methods and single blood agar plate culture for diagnosing streptococcal pharyngitis.

OBJECTIVE: To compare the sensitivity of five group A streptococcal antigen detection systems and single blood agar plate culture with a two-plate culture method for diagnosis of streptococcal pharyngitis. DESIGN: Two simultaneous throat swabs were obtained from consecutive patients with suspected streptococcal pharyngitis. One swab was tested for streptococcal antigen by physicians' office nurses and the other was cultured on both aerobic blood agar and anaerobic trimethoprim-sulfamethoxazole blood agar plates. SETTING: Community office practice and community hospital laboratory. PARTICIPANTS: Consecutive outpatients seen by one of four pediatricians or a family practice physician. MAIN OUTCOME MEASURES: Results of rapid streptococcal antigen tests were compared with culture results either on a single aerobic blood agar plate or on the two-plate culture method. RESULTS: On throat swabs from 755 consecutive outpatients, the two-plate culture method detected 261 cases (defined as 100%) of group A streptococcal pharyngitis. The anaerobic trimethoprim-sulfamethoxazole plate alone, read at 1 and 2 days, detected 245 cases (94%). The blood agar plate used alone detected 189 cases (72%) at 2 days and 151 cases (58%) at 1 day. Antigen detection test results were positive for 106 throat specimens (41%), with individual kit sensitivity ranging from 31% to 50% compared with the two-plate culture method. Antigen detection test sensitivity decreased with decreasing colony counts. Antigen kit false-positivity rates varied from 0 to 28%. CONCLUSIONS: We conclude that the single blood agar plate culture and the antigen detection tests are insensitive, possibly leading the physician toward undertreatment and risking immunologic, local, or distant sequelae. The two-plate culture method should be the standard of practice to rule out streptococcal pharyngitis.

Antigens, Bacterial↗
PubMed1988

Predicting bone marrow iron stores in anemic patients in a community hospital using ferritin and erythrocyte sedimentation rate.

Forty-three consecutive cases from a community hospital with concomitant bone marrow iron stain, serum ferritin, and erythrocyte sedimentation rate (ESR) were reviewed. Cases were classified as iron present or absent by the bone marrow iron stain. A two-dimensional linear graphic relationship between ferritin and ESR correctly identified six of nine iron-deficient patients and 32 of 34 iron-present patients. Four cases yielded indeterminate results. One complex iron-deficient case was incorrectly classified. This graphic method developed with data from tertiary care patients was correct in 88.4% of cases, incorrect in 2.3%, and indeterminate in 9.3%. When absent iron stores were graphically predicted, the predictive value was 100%. When iron deficiency was graphically excluded, the predictive value was 97%. The authors conclude the graphic method is useful in a community hospital practice for the confirmation or exclusion of iron deficiency.

Anemia↗
PubMed1988

Chemistry profiles in "wellness programs": test selection and participant outcomes.

Insurers, employers, and individuals create demands for laboratory testing in "wellness programs." Tests chosen to identify cases deserving intervention included routine automated chemical tests plus high-density lipoprotein cholesterol, ferritin, and thyroid tests. Participants' unwarranted concerns were addressed with a personalized reporting schema. We tested 1338 individuals, identified 224 (16.7%) with significant abnormalities, and made phone contact follow-up with 193 (86%) of these six to 14 months later. Cholesterol results suggesting increased risk of heart disease were frequent, and were not studied. Interventions were initiated in 55 of the 193 followup cases (49 by physician and six by participants), including prescription of iron or thyroid hormone, counseling on dietary or alcohol intake, and repeat testing. For 58, there was medical advice without intervention; abnormal results were ignored by 79. Noteworthy participant anxiety was manifested in two of the 193 cases, both of whom were treated with iron. We conclude that 4% of the original 1338 participants potentially benefitted from intervention. Ferritin and thyroid tests initiated 33 (61%) of these 55 specific therapeutic interventions.

Adult↗
PubMed1986

Prediction of bone marrow iron findings from tests performed on peripheral blood.

After evaluating multiple tests, the authors have devised a scheme to predict bone marrow iron findings from tests performed on peripheral blood. They examined bone marrows from 97 consecutive patients with anemia who were divided into five marrow morphologic groups: (1) iron deficiency; (2) anemia of chronic disease; (3) abnormal sideroblasts; (4) ring sideroblasts; and (5) other. Tests of peripheral blood included hemoglobin, hematocrit, red blood cell count and red blood cell indices, reticulocyte count, sedimentation rate or zetacrit, ferritin, iron, iron binding capacity, free erythrocyte protoporphyrin, and tests of hepatic and renal function. Cluster analysis, multidimensional scaling, and logistic discriminant analysis were used to derive a graph of serum ferritin with the sedimentation rate, allowing accurate confirmation or exclusion of iron deficiency in most patients. Percent saturation of serum transferrin and serum ferritin allowed identification of only 50 percent of patients with abnormal or ring sideroblasts while excluding 100 percent of patients without abnormal or ring sideroblasts. In three years of follow-up, two of 19 patients with abnormal or ring sideroblast have developed the dysmyelopoietic syndrome or ANLL, respectively. With the aid of the two parameter graphs described, the authors believe the differential diagnosis of the hypoproliferative anemias relating to iron metabolism can frequently be made without examination of the bone marrow.

Anemia↗
PubMed1985

Serum 5'-nucleotidase in patients receiving anti-epileptic drugs.

Alkaline phosphatase (ALP), 5'-nucleotidase (5NT), and gamma-glutamyltransferase (GGT) were measured in sera from 335 adult and 93 pediatric inpatients receiving anti-epileptic drugs (AEDs). Among adults, 18 took only phenobarbital, 39 only carbamazepine, 159 only phenytoin, and 99 phenytoin with other AEDs. Of 93 children, 49 took phenytoin, and 44 took another AED. Among the 335 adults, only 118 had normal enzymes, but 316 had 5NT and ALP, each less than two times and GGT less than five times normal limits. Of 19 patients outside these ranges, 14 had either historic, physical, or biochemical evidence of liver or severe multisystem disease. The authors observed that the frequency of enzyme elevations in adults receiving AEDs was lower for 5NT (23%) than for GGT (54%) but similar to ALP (27%). The degree of elevation was also lower for 5NT and ALP than for GGT. Phenytoin was associated with the most frequent and highest enzyme elevations in both adult and pediatric patients. Consideration of these data is necessary in the evaluation of liver function in patients receiving AEDs.

5'-Nucleotidase↗
PubMed1982

Single-stage automated assay for heparin.

We have developed a single-stage assay for heparin, using reagents modified from the two-stage Dade Protopath heparin synthetic substrate assay. The single-stage assay involves simultaneous mixing of a plasma sample, an antithrombin III source, alpha-thrombin, and the alpha-thrombin fluorogenic substrate. The synthetic substrate, antithrombin III, and heparin-antithrombin III complex compete for the alpha-thrombin active site. The alpha-thrombin is inactivated by the heparin-antithrombin complex while substrate is being hydrolyzed, so that total product formation decreases with heparin concentration. Day-to-day CV was 9.3% at a heparin concentration of 246 USP units/L. Comparison of results of the single-stage heparin assay with those of a two-stage esterolytic assay yielded the linear regression equation: esterolytic = 0.834 (single-stage)--7 USP units/L (r = 0.94, n = 47). Bilirubin interfered with the single-stage assay, resulting in an apparent increase in sample heparin concentration. The single-stage heparin assay can be automated for centrifugal analyzers capable of double-reagent addition and fluorometric detection, substantially decreasing reagent requirements and therefore costs.

Centrifugation↗
PubMed1981

Use of alpha cyclodextrin to eliminate interference by nonesterified fatty acids in calcium measurements.

This study shows that nonesterified fatty acids cause underestimation of serum calcium by some colorimetric methods. The underestimation of calcium occurs infrequently, but can be as large as 20-30 mg/l. Preincubation of the sample with alpha cyclodextrin will eliminate this interference. The procedure is simple, inexpensive, and applicable to most clinical laboratories.

Autoanalysis↗
PubMed1981

Esterolytic method for determination of heparin in plasma.

This assay for heparin is based on the heparin-accelerated rate of alpha-thrombin III. The rate or product formation from the residual active thrombin is inversely proportional to plasma heparin content. The assay can be performed manually, but our results were obtained with a discrete analyzer, the ABA-100. The assay is insensitive to concentrations of antithrombin III in plasma. Precision studies gave CVs of less than 10%. This assay was compared to the Dade Protopath heparin assay and a correlation coefficient of 0.90 was obtained (n = 62). The correlation between activated partial thromboplastin times and heparin concentrations (r = 0.67) was calculated frm results on 78 plasma specimens from 10 patients.

Antithrombin III↗
PubMed1980

The presence of creatine kinase BB isoenzyme in patients with prostatic cancer.

Creatine kinase BB isoenzyme (CK-BB) was detected in abnormal amounts in serum samples from 11 of 46 patients with Stage D carcinoma of the prostate by electrophoresis. Thirteen of 46 Stage D patients had elevated acid phosphatase values and 10 of these 13 had elevated CK-BB. CK-BB elevations were less frequent in earlier stages of prostatic cancer; Stage C: 0 of 35, Stage B: 1 of 26, Stage A: 0 of 3 and none in a group of 35 with BPH, prostatitis and bladder cancer. Results of CK-BB by a specific radioimmunoassay correlated well with those obtained by electrophoresis in most cases. Several patients were followed over time and data on CK-BB is presented for this interval. The origin of the CK-BB is still unclear. The BB isoenzyme predominates in prostatic tissue and CK-BB is the fetal form of the enzyme in human muscle and myocardium. The increase in serum CK-BB may be related to increased release of the isoenzyme, either from the prostate itself or from a metastatic lesion, or may represent a release of the fetal form of the enzyme from dedifferentiated tumor tissue.

Acid Phosphatase↗
PubMed1980

Enzymic inhibition assay for methotrexate with a discrete analyzer, the ABA-100.

We adapted an inhibition assay for methotrexate, involving dihydrofolate reductase from bovine liver, for use with a discrete analyzer (the ABA-100). The analyzer was used both for dilution and a 5-min pre-incubation of the sample with NADPH--enzyme reagent, and for the assay itself. The standard curve was linear between 10 and 120 microgram/L. Without pre-incubation the standard curve was nonlinear. The presence of albumin in the NADPH--enzyme reagent enhanced both enzyme activity and stability. Within-run precision (CV) was 2.0% (n = 24), run-to-run precision 7.1% (n = 49). Results obtained on patients' samples (29 sera, 15 urines, 18 cerebrospinal fluids) by the present method and a radioimmunoassay method did not differ statistically (p greater than 0.05) when the paired data were analyzed by use of the sign test and Wilcoxon's ranked sign test.

Albumins↗
PubMed1980

A coupled-enzyme equilibrium method for measuring urea in serum: optimization and evaluation of the AACC study group on urea candidate reference method.

We describe a coupled-enzyme equilibrium method for measuring urea in serum, which is performed on supernates prepared by treating each specimen with Ba(OH)2 and ZnSO4 (Somogyi reagent). Analytical recovery of [14C]urea added to a variety of matrices was essentially complete (mean, 100.6%) for the supernates after precipitation. Nine variables were univariately examined in arriving at the reaction conditions for the method: glutamate dehydrogenase, urease, 2-oxoglutarate, ADP, Tris . HCI, NADH, EDTA, pH, and temperature. The reagent is stable for at least 48 days at--20 degrees C and for 23 days at 4 degrees C. Mean analytical recovery of urea (14 mmol/L) added to seven different specimens (three different matrices) was 100.8%. The analytical linear range of the method extends to 30 mmol of urea per liter. Of 22 potential interferents, only bilirubin at 1 mmol/L (580 mg/L), hemoglobin at 10 g/L, and hydroxyurea at 6 mmol/L showed more than 2% interference. We discuss precision and effects of specimen dilution, and compare results for 100 human serum specimens with those measured for the same specimens with four other urea methods. We examined the effects of measuring a blank, consisting of sample and reagent without urease, with each specimen.

Animals↗
PubMed1979

Platelet and leukocyte counts in pregnancy.

Platelets and leukocytes in venous blood were counted with automated methodology in 23 women studied longitudinally throughout pregnancy and at six weeks after delivery. The average platelet count declined monotonically in a manner consistent with the gestational increase in blood volume. Total leukocyte count rose early in gestation and remained elevated, with neutrophils accounting for the changes. Absolute neutrophil counts during gestation were nearly twice those of the same women postpartum (5.76 vs 3.13/cu mm x 10(-3).) The monocyte count also tended to increase, whereas lymphocytes, eosinophils, and basophils declined in number.

Basophils↗