CSF lactate in diseases of the CNS.

The usefulness of the CSF lactate concentration in the diagnosis of bacterial meningitis was studied in 109 adults and children with a variety of infectious and neurologic diseases. A positive correlation was found between elevated lactate levels and the presence of leukocytes in the CSF. Elevations of the CSF lactate concentration with concomitantly negative Gram's stains and cultures were found in patients with infections at anatomic sites other than the CNS, accidental or neurosurgical head trauma, subarachnoid hemorrhage, and seizures due to alcoholism. When performed routinely on CSF, the positive predictive value was 31%, indicating that a diagnosis other than bacterial meningitis is more likely. We conclude that the CSF lactate concentration does not contribute to the diagnosis in children or adults with suspected meningitis.

Reliability of amniotic fluid surfactant measurements.

A proficiency study designed to assess interlaboratory precision of amniotic fluid surfactant measurements is presented. A total of 31 laboratories participated in the study. The assays includes lecithin/sphingomyelin (L/S) ratio test, the measurement of phosphatidyl glycerol (PG), and the Lumadex-FSI test. L/S ratio values varied from "1.3" to over "5.0" on aliquots derived from the same pool. With only three exceptions, all PG values read as "positive." The interlaboratory agreement for the Lumadex-FSI assay was excellent. With the exception of two values of "46," all the other values were with "47" or "48."

Variations of cholesterol and total lipid concentrations in sera of healthy young men. Differentiating analytic error from biologic variability.

Three major sources of variation affecting serum cholesterol and serum total lipid concentration values were studied in a group of healthy men. The first source of variation, analytic error, was separated into pre-instrumental and instrumental components. The pre-instrumental component, which consisted of all uncertainties occurring from the instant of venipuncture to the entrance of the sample into the instrument, was statistically significant for total lipids. The second major source of variation-preparation of the subject-was evaluated for four major stresses: diet, exercise, posture prior to venipuncture, and duration of tourniquet application. Diet affected total lipids, while the specifics of posture and tourniquet application were statistically significant for both serum cholesterol and total lipids. The third source of variation considered was the within-day and the day-to-day changes. Within-day changes were divided into within-hour and hour-to-hour effects. Day-to-day changes occurred over a two-week period. The magnitude and statistical significance of the changes were evaluated using an ANOVA model. The C.V.'s of day-to-day changes for cholesterol and total lipids (biologic) were 5.3% and 10.2%, respectively while the hour-to-hour within-day C.V.'s were 3.8% for cholesterol and 10.4% for serum total lipids. In all cases the biologic variation was in far excess of the analytic variation. The significance of these factors affecting intraindividual variation in healthy subject is discussed.

Relationship of day-to-day variation of serum iron concentrations to iron-binding capacity in healthy young women.

Biologic intra-individual variations in concentrations of serum iron and serum iron-binding capacity were determined for nine healthy young women in a double experiment. In each of two series approximately one month in duration, venipunctures were performed three times per week. All serum specimens were assayed for iron concentration and iron-binding capacity. The average intra-subject day-to-day biologic variations for the group in terms of coefficient of variation (CV) were 29.3% for serum iron and 8.8% for iron-binding capacity. No significant difference in variances was found for any subject in serum iron concentrations from series I to series II. Only one subject had a significant positive correlation between iron concentrations and iron-binding capacity values. Percentage iron saturation was computed for each iron and iron-binding capacity combination, and the average intra-subject CV was of the same order of magnitude as the CV for serum iron. The clinical significance of an isolated serum iron result in view of the dramatic intra-subject day-to-day variability is discussed.

The acute effect of cigarette smoking on the concentrations of blood leukocyte types in healthy young women.

The acute effect of cigarette smoking on blood leukocyte values in four healthy young women is reported. In a cross-over experiment using the Hemalog-D automated differential system, the effect of smoking four to 12 cigarettes on the time course of the concentration of leukocyte types was studied. During each of two experiments lasting from 800 h to 1400 h, the subjects were in the supine position. Each subject abstained from smoking during one experimental day and started smoking at 930 h on the other experimental day. The values obtained during each experimental day were expressed for each subject as change from the baseline values measured before 930 h. The time course for the lymphocyte concentration changed significantly (P less than 0.05) on the day of smoking as compared with the day of not smoking, showing an initial elevation followed by a more prolonged depression. The eosinophil concentration was uniformly and significantly (P less than 0.05) depressed. The neutrophil concentration showed a delayed response, with an elevation starting at 1200 h. The latter effect, however, was of borderline significance (P = 0.07).

Serum caffeine half-lives. Healthy subjects vs. patients having alcoholic hepatic disease.

Results are presented describing serum caffeine half-lives for three healthy subjects and two patients having alcoholic hepatic disease. The mean serum caffeine half-life for the healthy subjects was 5.7 hours. One patient, a 35-year-old man who had alcoholic hepatic disease, had a serum half-life of 60 hours. The other patient, a 49-year-old woman having alcoholic hepatic disease had a serum half-life of 168 hours. The prolonged serum half-lives for the two patients are explained on the basis of compromised liver function. The serum half-life of caffeine was determined for the three healthy subjects when 25 mg diazepam was given one hour prior to the caffeine load. A significant difference was not found between the serum half-lives measured after diazepam was given and the serum half-life measured when diazepam was not given.

Serum enzyme alterations in polymyositis. Possible pitfalls in diagnosis.

We report serum enzyme patterns in three patients with polymyositis or dermatomyositis whose cases posed potential problems in distinguishing malignancy, hepatocellular damage, and myocardial infarction from myositis. The alanine aminotransferase showed five- to 16-fold elevations. The creatine kinase MB isoenzyme and a predominance of lactate dehydrogenase isoenzymes 2 and 3 were present in each of the three patients. However, none of the patients showed any evidence of hepatocellular damage, myocardial infarction, or malignancy. We suggest that, although the individual occurrences are indicative of other processes, the concurrence of elevated alanine aminotransferase, creatine kinase MB, and elevated lactate dehydrogenase isoenzymes 2 and 3 is consistent with the diagnosis of polymyositis.

Antithrombin III and plasminogen: a comparison of two synthetic substrate-based methods.

We have evaluated and compared the DuPont aca and the KABI/CentrifiChem synthetic substrate-based methods for the quantitation of plasma plasminogen (PLG) and antithrombin III (AT III). Method precision was evaluated using normal human pooled plasma (NHP) as sample. Within-day and day-to-day PLG assays generated a CV of 2.0% and 2.9%, respectively, for the aca method. For the KABI/CentrifiChem PLG method, within-run (within-rotor) analysis produced a CV of 1.7%, and day-to-day analysis produced a CV of 5.3%. The relationship between the aca (y axis) and the KABI/CentrifiChem (x axis) methods for PLG was found to be y = 0.99X - 1.4%, r = 0.979. Within-day precision for AT III by the aca method generated a CV of 4.6%, and day-to-day analysis produced a CV of 7.0%. The KABI/CentrifiChem AT III method generated a CV of 4.2% and 4.4% for within-run and day-to-day assays, respectively. The AT III correlation demonstrated a relationship of y = 0.84X + 15.2%, r = 0.952. The AT III and PLG reference ranges as established in our laboratory for healthy adults, pregnant women, and for cord blood specimens also are presented.

Assessing cost savings when unnecessary utilization of laboratory tests can be abolished.

The authors report on the theoretic cost savings that would be realized if presumed overutilization of selected laboratory tests could be eliminated. They limit the scope of this study to inpatients at the University Hospital and on a preselected subset of assays ordered in their institution. A baseline audit including the requests for 19 commonly ordered clinical chemistry tests made for all inpatients during three weekdays was performed at our 400-bed hospital. Eight of the 19 tests (the LYTES-Plus), were done on the ASTRA-8 selective multitest analyzer (Beckman Instruments Inc., Brea, CA 92621), while remaining 11 tests (MTA-11) were performed on the RA-1000 selective multitest system (Technicon Instruments Corp., Tarrytown, NY 10591). The average tests ordered per patient-day were 4.38 of the 19, and the average venipunctures were 0.67. The corresponding numbers for the intensive care patients were 16.6 tests and 2.45 venipunctures per patient-day. Although the intensive care units contributed approximately 8% of the patient days in the hospital, they represented more than 25% of the tests ordered. The authors noted that 5.89 of the eight possible LYTES-Plus assays were ordered per ASTRA-8 sample. The equivalent figure for MTA-11 was 4.55 of 11 possible tests. Using list prices of reagents and disposables, the savings in direct material costs resulting from implementing a number of rather conservative recommendations for decreasing overutilization was estimated to be $45,000 per annum or 31% of the total direct material costs.

The effects of time of venipuncture on variation of serum constituents. Consideration of within-day and day-to-day changes in a group of healthy young men.

Within-day and the day-to-day variations of serum constituents were evaluated in 11 healthy young men. Eighteen constituents, including electrolytes, metabolites, proteins, and enzymes, were assayed using the AutoChemist MultiChannel Analytic System. Venipunctures were performed at three hours of the day, 8 A.M., 11 A.M., and 2 P.M., on five separate experimental days. A three-factor analysis of variance model was employed to separate analytic variation from biological sources of variation. Statistically significant (p less than .05) group diurnal patterns (main effect of hour) during the six-hour period were found for serum lipids, iron, urea, albumin, total protein, and chloride. A unique individual diurnal pattern (subject-hour interaction) was statistically significant for serum potassium. Statistically significant main effect of month (main effect of day) for the group of subjects was seen for total lipids and potassium; however, the subject-day interaction term, which is an index of the day-to-day variation for the subjects, was significant (p less than .05) for all of the constituents except for sodium ion. The comparison of the variation expected within-day versus the variation seen day-to-day over four months was made by pooling the sources of within-day variation (main effect of hour + subject-hour interaction + subject-day-hour interaction) and by pooling the day-to-day variation terms (main effect of day + subject-month interaction). For serum cholesterol, potassium, acid phosphatase, and phosphate ion, the within-day variation was greater than the day-to-day variation occurring over four months, while the other constituents showed day-to-day variations of a greater magnitude than that experienced during the six-hour period.

The value of routine biochemical and surgical pathology quantities in predicting recurrence in high-risk patients following surgery for primary breast cancer.

The initial biochemical data (serum[S]-carcinoembryonic antigen, S-lactate dehydrogenase, S-gammaglutamyl transferase, S-alkaline phosphatase urine[U]-creatinine, and three urinary quantities related to collagen metabolism) and surgical pathology data (tumor size, grade of tumor anaplasia, number of positive lymph nodes, number of negative lymph nodes) were examined in 52 consecutive postmenopausal risk group II patients operated for primary breast cancer without metastatic disease (mastectomy + partial axillary resection) who participated in the Danish Breast Cancer Group's controlled clinical trial of radiation (RT) alone, and RT + levamisol. The follow-up (mean = 3.45 years, range = 3-4 years) included physical examination every three months, x-ray of chest, bone scan, and x-ray of axial skeleton every six months. Recurrence was defined as metastatic disease detected during the first three years of postoperative follow-up study. Twenty patients had recurrences. A stepwise discriminant analysis of the surgical pathology quantities showed that all quantities except tumor size contributed significantly (P less than 0.01) to the discrimination between controls (no recurrence after 3-4 years) and patients who had recurrences within three years. When each of the biochemical quantities was combined with the surgical pathology data it was found that only urinary total hydroxy-proline to creatinine ratio improved the discrimination significantly (P less than 0.05) and that the effect was marginal.

Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers.

The authors determined mean day-to-day (daily over five days), mean week-to-week (weekly over five weeks) and mean hour-to-hour (800 h, 1100 h, 1400 h) physiologic intra-individual variation of concentration values of leukocyte cell types, platelet count, and erythrocyte values (hematocrit, hemoglobin) for a group of 20 healthy adult volunteers. Total leukocyte counts and concentration values of leukocyte cell types were determined in duplicate on the Hemalong-DTM Automated Leukocyte Differential Cell Counter to minimize analytic variation. The data sets were analyzed according to an analysis of variance model. The mean physiologic hour-to-hour and week-to-week intra-individual variations in terms of % coefficient of variation included: hemoglobin, 2.5, 2.2; hematocrit, 2.6, 2.7; platelets, 1.6, 6.6; total leukocyte count, 9.4, 15.7; neutrophils, 12.9, 26.0; lymphocytes, 10.3, 13.2; monocytes, 18.6, 19.3; eosinophils, 19.9, 26.9; basophils, 7.4, 15.0; large unstained cells, 13.7, 16.0; "high-peroxidase" cells, 32.7, 25.7. Hour-to-hour variation was partitioned into random diurnal variation, group-consistent diurnal variation, and subject-specific unique individual variation. Subject-specific diurnal variation contributed greatly and statistically significantly to total diurnal variation for many of the leukocyte cell types--especially in the case of eosinophils, where it represented more than half of total diurnal variation.

Evaluation of the Yellow IRIS. An automated method for urinalysis.

The authors evaluated the Yellow IRIS automated urinalysis instrument (International Remote Imaging Systems, Chatsworth, CA 91311) in terms of its analytic performance as well as its ease of use. The Yellow IRIS is a system using automated intelligence microscopy (AIM), coupled with a dipstick reader and specific gravity module. The instrument can handle up to 30 specimens per hour in the authors' setting as compared with 10 specimens per hour using a full manual urinalysis coupled with microscopic examination. The authors conclude that the Yellow IRIS performed better than the manual method in terms of precision, linearity, and throughput. In addition, the diagnostic yield using this system in terms of abnormal results was higher than would have been picked up by manual analysis alone.

Evaluation of the Sysmex CC-800. An automated eight-parameter hematology instrument.

An evaluation of the Sysmex CC-800 hematology analyzer (TOA Medical Electronics, Kobe, Japan, and distributed by American Scientific Products, Chicago, IL) was performed at University Hospital at Boston University Medical Center to assess the analytic performance and ease of use of the instrument. The Sysmex CC-800 is the first self-contained, fully automated, eight-parameter hematology analyzer. It can handle as many as 100 whole blood specimens without constant operator intervention. Stat and predilute modes are also available. The optional PDA-410 (particle distribution analyzer) was not evaluated in this study. Precision, linearity, carryover, and reproducibility of values over time in the automode were well within the manufacturer's specifications. The correlation study was performed with the existing Coulter S-Plus (Coulter Electronics, Hialeah, FL). The Sysmex CC-800 allowed us to expand the linear range without dilution for white blood cells to 160 X 10(3)/microL, hemoglobin to 26 g/dL, and platelets to 2,000 X 10(3)/microL. The samples on the automode exposed to normal laboratory atmosphere for up to 120 minutes showed no significant difference from baseline. The two instruments correlated well (r greater than 0.99). The authors concluded that the Sysmex CC-800 would be a reliable and time saving instrument in their laboratory.

Chemical inhibition method for alkaline phosphatase isoenzymes in human serum.

The authors adapted a chemical inhibition procedure using L-phenylalanine and urea as specific inhibitors to quantitate the activities of bone, liver, and intestinal alkaline phosphatase (ALP) isoenzymes in human serum. The results of this assay were compared with electrophoretic separation, gamma-glutamyl transpeptidase (GGTP) activity, and the clinical setting in a group of patients with elevated total ALP activity. In addition, expected ranges of serum ALP isoenzymes for healthy young men and also for a geriatric population are presented.

Within-day physiologic variation of leukocyte types in healthy subjects as assayed by two automated leukocyte differential analyzers.

The physiologic within-day (700-2200 h) variation of leukocyte-type concentrations in blood as determined for 21 healthy young adults is reported. All blood specimens were obtained in duplicate such that the within-batch analytic variation, as well as the pertinent biologic sources of variation, was able to be determined. All specimens were analyzed on each of two automated leukocyte differential systems: Hemalog-D Differential System and the Hematrak-240 Analyzer. On the basis of a comparison of the performances of the two analyzers, it was decided to report the neutrophil and the lymphocyte values as measured on both systems, the monocyte values as measured on teh Hematrak only, and the eosinophil and basophil values as measured on the Hemalog-D only. The intrasubject within-day physiologic variations for the cell on the Hemalog-D and Hematrak, respectively, in terms of coefficient of variation wee as follows: neutrophils 19.4% and 19.6%; lymphocytes, 13.8% and 17.5%. For monocytes, as measured on the Hematrak, it was 13.4%. For eosinophils and basophils, as measured on the Hemalog-D, it was 27.2% and 8.3%, respectively. There was a consistent group-specific diurnal variance that amounted to more than 40% of the total within-day variance, both for lymphocytes and for eosinophils. The within-day physiologic variation of the cell type concentrations for eight of the volunteers was compared with that of the plasma cortisol concentrations, as determined on specimens derived from the same veni-puncture sessions. The decrease in plasma cortisol values was in most instances associated with decreases in eosinophils and increases in neutrophils. For total leukocytes and neutrophils, the mean concentration for smokers was significantly higher than that for nonsmokers.

Alterations in human serum alkaline phosphatase and its isoenzymes by hypolipidemic agents: colestipol and clofibrate.

Total serum alkaline phosphatase (TSAP) determinations were done as part of the biochemical screening in comparative studies of lipid lowering agents in type lla hyperlipoproteinemic patients. TSAP determinations were made by using a modification of the Bessey-Lowry method and the Statland method. Increases in TSAP following colestipol treatment of 20% (P less than 0.05) and 32% (P less than 0.005) were seen by using the respective methods. Isoenzymatic determinations were done by employing the Statland method and all fractions were increased from baseline levels during colestipol therapy. Clofibrate was associated with 34% (P less than 0.005) and 28% (P less than 0.005) reductions in TSAP activity by using the respective methods; significant reductions in both "bone" and "other" isoenzymatic components occurred. Gamma-glutamyltransferase (gamma GT) results did not consistently reflect TSAP or "liver" isoenzyme results.

Assessment of fetal pulmonary maturity by the Lumadex Foam Stability Index Test.

The authors describe the operational features and performance characteristics of a new commercial kit designed to measure the amount and functionality of amniotic fluid surfactant. This kit, the Lumadex-FSI Test, is based upon the manual foam stability index test. The test requires no more than 3.0 ml of centrifuged amniotic fluid. Initial experience based on 172 specimens, including 19 cases of neonatal respiratory distress syndrome (RDS), revealed the Lumadex-FSI Test to have excellent discriminating ability in predicting the likelihood of RDS. In 18 of 19 cases in which RDS was noted, the foam stability index was 46 or less. A foam stability index of 47 or above was associated in 133 of 134 cases with fetal pulmonary maturity. Based upon contamination studies with maternal serum and meconium, the authors observed that a 1% contamination with blood, or 4% contamination with meconium, would artifactually increase the Lumadex-FSI value. The Lumadex-FSI Test demonstrated a clinical reliability similar to that of the manual foam stability index procedure, in addition to making the test simpler, faster, and more accessible to the clinician, in whose hands this test will have unique input into the management of high-risk pregnancies.

Clinical evaluation of the quantitative foam stability index test.

The foam stability index (FSI) test for amniotic fluid is a quantitative test that uses ethanol as the antifoaming reagent; it presents values in terms of the highest ethanol volume fraction that will permit stable foam to occur. In this study the authors report on FSI tests results in terms of neonatal outcome in a total of 208 pregnancies in which fluids were obtained within 3 days of delivery. The authors noted a total of 27 cases of hyaline membrane disease (HMD) in their population. All 27 had FSI values of 0.47 or less, whereas 119 of the 181 patients without HMD had FSI values of 0.48 or above. The risk of HMD's occurring was calculated for 4 groups of FSI values. They were as follows: 1) FSI values less than or equal to 0.43 (62%); 2) FSI values of 0.44 and 0.45 (23%); 3) FSI values of 0.46 and 0.47% (14%); and 4) FSI values greater than 0.48 (0%). Comparable evaluations of the lecithin:sphingomyelin (L:S) ratio procedure performed on the same specimens revealed no apparently improved diagnostic reliability. In addition, in several cases of intrauterine growth retardation with normal neonatal respiratory status in which the L:S ratios were less than 1.5, the FSI test correctly predicted fetal lung maturity (FSI greater than or equal to 0.48). The authors conclude that the FSI test has sufficient diagnostic reliability to be considered as a sensitive and specific assay of fetal pulmonary maturation.

Identifying the small-for-gestational-age fetus on the basis of enhanced surfactant production.

The clinical utility of concurrent measurements of the fetal biparietal diameter, as measured by ultrasonography and fetal pulmonary maturity, as assessed by the amniotic fluid consisted of 57 cases in which pregnancy produced a low birth weight neonate (less than 2500 g). The combination of a small fetal biparietal diameter (less than 8.5 cm) and a mature foam stability index value (0.47 or greater) was associated with small-for-gestational-age neonates in 16 of 19 cases. In addition, the occurrence of an immature foam stability index value (less than 0.47) and a fetal biparietal diameter of less than 8.5 cm was associated with appropriate-for-gestational-age newborns in 16 of 16 cases. The discriminating ability of the foam stability index test in identifying the small-for-gestational-age infant was lost when the fetal biparietal diameter was 8.5 cm or more. Of clinical note was the fact that 14 cases in which the neonatal respiratory distress syndrome occurred were all associated with appropriate-for-gestational-age infants and foam stability index values of less than 0.47 (ie, immature). The results of this study suggest a potentially important clinical role for the concurrent measurement of fetal biparietal diameter and performance of the amniotic fluid foam stability index test in the prenatal evaluation of the high-risk, small, third-trimester fetus.