Metabolic correlates of theophylline therapy: a concentration-related phenomenon.

OBJECTIVE: To determine the relationship of serum theophylline concentration with electrolyte and glucose abnormalities across a broad range of theophylline concentrations. DESIGN: Retrospective review of a computerized laboratory database between June 1, 1984 and June 1, 1986. SETTING: A midwestern university medical center. PATIENTS: Eight hundred sixty-nine patients with serum theophylline concentrations of > 5.5 mumol/L and a random unmatched sample (control group) of 350 in- and outpatient adults and children with no history of reactive airways disease or theophylline exposure. RESULTS: Patients with measurable theophylline had a higher risk of hypokalemia, hyponatremia, hyperglycemia, hypophosphatemia, and hypomagnesemia compared with the unexposed control group. Unadjusted odds ratios (OR) were: (1) hypokalemia OR = 4.2 (95 percent CI 2.2 to 7.9); (2) hyponatremia OR = 5.4 (95 percent CI 2.0 to 12.9); (3) hypomagnesemia OR = 1.6 (95 percent CI 1.0 to 2.5); (4) hyperglycemia OR = 2.3 (95 percent CI 1.7 to 3.0); and (5) hypophosphatemia OR = 2.7 (95 percent CI 1.2 to 5.3). A linear concentration-response relationship was documented between serum theophylline concentration and all metabolic disturbances. CONCLUSIONS: Measurable theophylline was associated with increased risk for glucose and electrolyte abnormalities in a concentration-related fashion across a broad range of theophylline concentrations from 5.5 to > or = 110 mumol/L.

Routine serum magnesium determination: a contemporary clinical imperative.

Identification of hypomagnesaemia or hypermagnesaemia is presently the most expeditious method of clinically identifying perturbations in Mg metabolism. Clinicians may overlook as much as 90% of clinical hypomagnesaemia and hypermagnesaemia when serum Mg is determined on order versus on a routine basis. Routine serum Mg determination will facilitate management of digitalis toxicity in patients who are not currently identified as being hypomagnesaemic as well as preventing the occurrence of refractory K repletion. In our opinion routine serum Mg determination represents a clinical need which has not been addressed to date.

Frequency of hypomagnesemia and hypermagnesemia. Requested vs routine.

This study was designed to assess the effectiveness of identifying serum magnesium abnormalities by comparing physician-initiated requests for this analyte with routine magnesium determinations. Because magnesium abnormalities frequently accompany other electrolyte abnormalities, we measured magnesium in 1033 serum specimens submitted for electrolyte analyses. Physician-initiated requests for magnesium measurements were received for 81 (7.4%) of these specimens. Serum magnesium abnormalities were identified in 546 of the 1033 specimens (hypomagnesemia [less than 0.74 mmol/L], 487; hypermagnesemia [greater than 0.99 mmol/L], 59). Only 10% of the hypomagnesemic patients (48/487) and 13% of the hypermagnesemic patients (7/59) were identified by physician-initiated requests for this analyte. Fifty-three patients were both hypomagnesemic/hypokalemic and 30 patients were both hypomagnesemic/hyponatremic, but only 8 (15%) and 3 (10%), respectively, had physician-initiated requests for magnesium. Because magnesium abnormalities in significant numbers of patients are not being detected, we recommend routine measurement of this analyte when analyses of electrolytes are required for the care of patients.

Unreliable visual estimation of the incidence and amount of turbidity, hemolysis, and icterus in serum from hospitalized patients.

We examined the frequency of occurrence for turbidity, hemolysis, or icterus in 2599 serum samples submitted for chemistry testing in an acute-care general hospital. Each specimen was compared visually with full-color photographs of adulterated serum, and designated as either "0" (containing no interferent), or trace, 1+, 2+, 3+, 4+, or 5+. Visible interferents (1+ or greater) were thought to be present in 838 (31%) of the specimens (icterus, 525; hemolysis, 244; lipemia, 69). To assess the accuracy of such visual grading, we determined the concentration of triglycerides, hemoglobin, or bilirubin in the specimens considered to be contaminated. There was little agreement between the actual concentration of each interferent and the assigned grade of turbidity, hemolysis, or icterus, confirming the unreliability of human visual estimation of these potentially interfering substances.

An enzyme immunoassay procedure for cancer antigen 125 evaluated.

The performance of a new enzyme immunoassay (EIA) procedure (Abbott Labs.) for cancer antigen 125 (CA 125) met or exceeded the manufacturer's claims for all analytical variables examined. Overall correlation with results obtained with a radioimmunoassay (RIA) were good. However, near the decision thresholds typically chosen to define a positive result for ovarian carcinoma, EIA results were 10 to 20 arbitrary units/mL less than the RIA results. At specific decision thresholds, therefore, the sensitivities and specificities of the EIA and RIA procedure differed. Adjusting the decision thresholds gave a similar optimum efficiency for each procedure: EIA, 82.9% (decision threshold, 35 units/mL); RIA, 83.4% (decision threshold, 54 units/mL). Receiver-operating characteristic curves showed that the two procedures' ability to distinguish patients with active ovarian carcinoma from those with disease in remission was the same.

Effect of storage temperature and shaking rate on pH and blood-gas results for two quality-control products.

Directions for pre-analytical handling of ampules of two commercially available aqueous quality-control products (contrlL and G.A.S.) contain vague instructions such as "store at room temperature" and "shake vigorously" before analysis. We examined the effect of different storage temperatures (25, 31, and 38 degrees C) and shaking rate (one, two, and four shakes per second) on pH and blood-gas results. For both products, increasing the storage temperature significantly decreased pO2 results, the magnitude of the bias being greatest for those solutions with the highest O2 tensions. However, increasing the shaking rate partly offset this bias. Increasing storage temperature also decreased results for pCO2 and increased results for pH for both manufacturers' ampules with the highest CO2 tensions, and this bias was not offset by increasing the shaking rate. We conclude that both storage temperature and shaking rate must be precisely defined and carefully monitored before these products are used in a quality-control program.

Analytical systems ranked by freedom from interferences.

We determined the effect of hemolysis, lipemia, and bilirubinemia on clinical-chemical analytical results under standardized conditions, for serum specimens prepared by us. Our purpose was to assess results obtained with 22 commonly available analytical systems. The quantitative rating scheme described is derived from the observed interference(s) divided by the number of analytical methods evaluated. The combined ranking reveals which chemistry analyzers are least affected and which are most affected by the added substances. Generally, systems that incorporate physical barriers or protein-separation steps perform better than those without thin-film layers, glass-fiber barriers, or dialysis membranes. Among the "direct" analyzers, fewer interferences are seen if appropriate "blanking" wavelengths are used, especially if a "specimen blank" absorbance is used appropriately in the analytical system. Centrifugal analyzers tended to perform poorly, according to the criteria presented here.

The effect of thioridazine on the Automatic Clinical Analyzer serum tricyclic anti-depressant screen.

A patient who had ingested thioridazine and flurazepam was brought to the authors' emergency department. Initial laboratory evaluation included a positive result for a serum screening test for tricyclic anti-depressants performed with the DuPont Automatic Clinical Analyzer. This false positive test result caused considerable unnecessary treatment and expense for the patient. The authors have found that a serum thioridazine concentration of 125 ng/mL (within the usual therapeutic range for this drug) will produce a false positive automatic clinical analyzer serum tricyclic anti-depressant screen result. Because thioridazine is the most widely used phenothiazine and is prescribed more frequently than the most widely used tricyclic anti-depressant, it is important to recognize this cause of a false positive result.

Emergency screening for ethylene glycol in serum.

We have exploited the "interference" of ethylene glycol in the Du Pont aca triglyceride method to develop a convenient and rapid screening method for detecting ethylene glycol in serum. Pretreatment of patient's serum with lipase, glycerol kinase, and other cofactors usually added for triglyceride analysis removes triglycerides and glycerol, but not ethylene glycol, from the sample. The aca triglyceride method may then be used to estimate the ethylene glycol concentration in serum.

The effect of skin cleansing agents on ethanol results measured with the Du Pont automatic clinical analyzer.

The effect of various prepackaged skin cleansers on the results of serum ethanol analyses performed with the Du Pont automatic clinical analyzer has not been previously reported. When added directly to serum in concentrations of either 0.625 or 1.56% (v/v), neither polyvinyl-pyrrolidone iodine nor benzalkonium chloride affected the ethanol results. The cross-reactivity of isopropanol with the automatic clinical analyzer ethanol procedure was 3.9%. The greatest interference in the measured ethanol concentration was from the addition of green soap tincture, which contained 30% ethanol. The effect of improper phlebotomy technique on ethanol measurements was also investigated by performing venipunctures through a pool of 100% ethanol on the skin. No ethanol was detected in these samples unless an ethanol-soaked sponge was pressed over the venipuncture site while the needle was withdrawn from the skin. When correct phlebotomy technique is used, skin cleansing agents should not affect the results of ethanol measurements determined with the Du Pont automatic clinical analyzer.

Graphical comparisons of interferences in clinical chemistry instrumentation.

Instrument- and analyte-specific interferences can be produced by adding known concentrations of potentially interfering substances to serum from healthy volunteers. Analytical results are expressed as a percentage of the original (unaffected) result. Graphical displays of the transformed data document the conditions under which erroneous results would be probable for specimens containing the additive. If several analytical systems are available, one can make an informed choice of which to use for a particular analysis by comparing the appropriate graphical information. Comparisons of such displays of data from newer systems being considered for purchase may facilitate decisions regarding laboratory instrumentation.

Serum angiotensin converting enzyme activity in patients with psoriasis.

Serum angiotensin converting enzyme activity is frequently increased in patients with active sarcoidosis. In spite of a reported association between sarcoidosis and psoriasis, serum angiotensin converting enzyme activities have not been reported for patients with psoriasis. We found the mean (SD) angiotensin-converting enzyme activity for 51 healthy subjects was 18.6 (5.8) kU/l, but for 52 patients with psoriasis without coexisting sarcoidosis, it was 28.3 (6.7) kU/l. There is a significant difference between these means (p less than 0.01). Forty-two percent (22/52) of the psoriasis patients had an increased serum angiotensin converting activity. Other diseases sometimes associated with an increased serum angiotensin converting enzyme activity were excluded as possible causes of a elevated activity in our patients with psoriasis. We conclude that almost half of the patients with psoriasis will have an elevated serum angiotensin converting enzyme activity, even when coexisting sarcoidosis is absent.

Predictors of myocardial infarction in emergency room patients.

To develop a decision rule to aid in the diagnosis of myocardial infarction, we evaluated clinical and ECG data on 540 adults treated in an urban hospital emergency room for acute chest pain. Of 62 (11.5%) patients who had acute infarctions, 54 were admitted to intensive care (sensitivity 87%); 103 of 478 patients without infarctions were also admitted to intensive care (specificity 78%). Thirty-four percent of all patients admitted had infarctions. Multivariate analysis identified only four clinical variables which carried independent information predicting infarction: two from the ECG and two from the clinical history. A predictive model based on these four variables had significantly greater specificity (86% vs. 78%, p = .003) and accuracy of overall patient classification (88% vs. 79%, p = .013) but somewhat lower sensitivity (81% vs. 87%, p = .46) than physician judgments. However, a decision rule which would have admitted to intensive care those patients with a high probability of infarction who were not admitted by the emergency room physicians, would have increased the sensitivity for detecting infarction to 95% with no appreciable decrease in specificity or yield of infarctions among patients admitted to intensive care.

Radioimmunoassay for arylsulfatase A in urine.

Purified arylsulfatase A (EC 3.1.6.1) from human urine was radioiodinated under conditions that caused no significant loss of antigenic activity. We used this labeled arylsulfatase A (specific radioactivity 4-7.5 Ci/g) together with nonlabeled enzyme and rabbit antiserum produced against homogeneous enzyme to develop a radioimmunoassay for arylsulfatase A in urine. A solid-phase, second-antibody technique (Immunobead Second Antibody; Bio-Rad Laboratories) was used to separate free enzyme from antigen-antibody complexes. The working range of the assay was 0.1-4.0 ng of enzyme; within- and between-assay CVs were around 10%, and the analytical recovery was 105.5% (SD 7.7%). The lower limit of detection was 0.08 ng of arysulfatase A per assay, substantially less than that of typical activity-based assays. Over a wide range of urinary arylsulfatase A activities, results by this method agreed well (r = 0.99) with those obtained by activity assays. We measured the enzyme in urines of 59 healthy volunteers and 92 patients with different diseases, including a group of colorectal cancer cases, to determine whether this could serve as a reliable marker for cancer of the colon; however, urinary excretion of arylsulfatase A by most patients with colon cancer was within normal limits.