A comparison of the predictive value and diagnostic efficiency of FHAP and CEA as cancer markers.

Previous studies have shown that fast homoarginine-sensitive alkaline phosphatase (FHAP) is roughly equivalent to CEA (Roche) as a marker in colon cancer. The present study compares FHAP with CEA-EIA (Abbott) as a marker in cancer of the colon, breast, lung, ovary, uterus, skin, and lymph nodes. Comparison is made with regard to sensitivity, specificity, predictive value of a positive test, and diagnostic efficiency. It was determined that FHAP and CEA-EIA were comparable as markers for cancers of the colon, breast, and lung. FHAP was more sensitive and specific and had a higher predictive value and diagnostic efficiency for cancers of the ovary, uterus, skin, and lymph nodes.

Quantitation of cimetidine and cimetidine sulfoxide in serum by solid-phase extraction and solvent-recycled liquid chromatography.

A high performance liquid chromatographic method for the simultaneous determination of cimetidine and its major metabolite, cimetidine sulfoxide, was developed. These compounds and the internal standard, ornidazole, were extracted from 0.5 mL of serum using a solid phase Bond Elut C18 analytical column with detection at 229 nm. Absolute recoveries were 94 to 103%, 93 to 104%, and 95 to 105% for cimetidine, cimetidine sulfoxide, and ornidazole, respectively. The minimum detection limit for cimetidine was 0.1 mg/L and for cimetidine sulfoxide was 0.05 mg/L when the concentrating step was used. Cimetidine and cimetidine sulfoxide demonstrated linearity up to 10 mg/L and 7.5 mg/L respectively, with the between-run precision of less than a 5% coefficient of variation for both compounds. Interferences from other drugs tested or endogenous substances in serum were not detected. The mobile phase was recycled to maintain better long term column stability and to minimize solvent cost. The instability of the drugs in solution was circumvented with a reduced-pressure drying process that produced working standards possessing longterm stability. The problem of drug interconversion observed during sample storage and with concentrating steps was controlled also. In addition, a resolution test mixture was chromatographed daily to control chromatographic quality.

A comparison of fast homoarginine-sensitive alkaline phosphatase and carcinoembryonic antigen as markers in colon carcinoma.

The diagnostic value of a recently described cancer marker, fast homoarginine-sensitive alkaline phosphatase ( FHAP ), was compared with the established marker, carcinoembryonic antigen (CEA), in the diagnosis of colon cancer. Comparisons were made with respect to sensitivity, specificity, predictive value of a positive result, and efficiency. An upper limit of normal of 2.1 units/L was assumed for FHAP , based on earlier studies. Two values for the upper limit of normal for CEA were tested: 2.5 ng/mL and 5.0 ng/mL. When 2.5 ng/mL was used as the upper limit of normal for CEA, FHAP was less sensitive, more specific, and had a higher predictive value. The diagnostic efficiency was not significantly different. When the upper limit of normal for CEA was set at 5.0 ng/mL, the two tests were roughly equal in sensitivity, specificity, predictive value, and diagnostic efficiency.

Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer.

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.

Increased activity in serum of an alkaline phosphatase isoenzyme in cancer: analytical method and preliminary clinical studies.

Serum of cancer patients often contains high activities of a homoarginine-sensitive isoenzyme of alkaline phosphatase with high electrophoretic mobility, which is present in relatively low activities in sera from most normal persons and persons with benign disease. In earlier studies of this isoenzyme, in a semi-quantitative assay, electrophoresis was used in the separation step. This report describes a column separation procedure, which provides quantitative data. We tested the revised procedure by assaying a mixed panel of 192 sera (cancer, benign disease, and normal). The organ sites of cancer and benign disease in this study were: lung, pancreas, uterus, and ovaries. The isoenzyme showed moderate sensitivity for lung (0.6) and pancreas (0.8) cancer and high specificity for all cancers tested. Thus the assay may be useful for discriminating between cancer sera and non-cancer sera for these cancer types.

DuPont aca III performance as tested according to NCCLS guidelines.

We evaluated the analytical performance of 10 representative channels on the new microprocessor-controlled DuPont aca III according to the guidelines (draft documents PSEP-2, 3, and 4) proposed by the Instrument Evaluation Subcommittee of the National Committee for Clinical Laboratory Standards. These guidelines were used for the experimental design and data analysis for the precision and accuracy testing, the latter by comparison with an aca II, with results of atomic absorption spectroscopy for calcium, and with the National Glucose Reference Method. From a 20-day replication study, we estimated within-run, between-run/within-day, between-run/between-day, and total standard deviations at three concentrations for each method. From duplicate analyses of 100 samples on the aca III, aca II, and other methods, we estimated the bias from the regression line at specific concentrations and total error from a tolerance limit about the regression line. Analytical performance of the aca III was judged acceptable because these estimated errors were small.

Computer-controlled instrument system for sequential chemical testing III. Application to liver assessment.

We used the previously described [Clin. Chem. 19, 1114 (1973)] and evaluated [Clin. Chem. 19, 1122 (1973)] computer-controlled instrument system for sequential chemical testing to select and perform tests of hepatic status, to aid the clinician in the diagnosis of liver disease. Results for total bilirubin, aspartate aminotransferase, and alkaline phosphatase obtained from the continuous-flow analysis (SMA 12/60) admission screen were used by the instrument system to determine selectively the values for gamma-glutamyltransferase, alanine aminotransferase, creatine kinase, and total and direct bilirubin. Kit methods for the latter four tests were evaluated on the system; results were similar to manual procedures. A software, enzymatic ratemeter was found to be better than the previously described hardware ratemeter. The follow-up tests of serum prescribed by the system are compared to clinician-prescribed follow-up tests and discharge diagnoses. In 10 of 19 cases, the system and clinician ordered similar follow-up tests; in three cases follow-up differed, and in six cases, the system ordered follow-up tests and the clinician ordered none.

A cancer-associated, fast, homoarginine-sensitive electrophoretic form of serum alkaline phosphatase.

Serum from patients with a variety of cancers often (p = 70%) contains a characteristic electrophoretic form of alkaline phosphatase detectable by cellulose polyacetate electrophoresis. The lower prevalence of this electrophoretic form in presumably healthy individuals (p = 7%) and noncancer hospitalized patients (p = 30%) suggests that it may be useful as a diagnostic or monitory marker.