Predictive value of technetium Tc 99m-labeled red blood cell scintigraphy for positive angiogram in massive lower gastrointestinal hemorrhage.

PURPOSE: This study was performed to evaluate whether the time interval from injection of technetium Tc 99m (99mTc)-labeled red blood cells to the time of a radionuclide "blush" (positive scan) can be used to improve the efficacy in predicting a positive angiogram. METHOD: A retrospective review revealed 160 patients who received 99mTc-labeled red blood cell scintigraphy for evaluation of massive lower gastrointestinal hemorrhage between 1989 and 1994. Patients were included who demonstrated signs of shock on admission, had an initial decrease in hematocrit of > or = 6 percent, or required a minimum transfusion of two units of packed red blood cells. Scanning duration was 90 minutes, with imaging every 2 minutes. Time interval from injection to a positive scan was analyzed to determine predictability of a positive angiography. RESULTS: Of 160 patients, 86 demonstrated positive scans, of whom 47 underwent angiography. These 47 patients were divided into two groups according to scan results. Group 1 (n = 33) had immediate appearance of blush; Group 2 (n = 14) had blush after two minutes. In Group 1, 20 of 33 patients had a positive angiogram, yielding a positive predictive value of 60 percent (P = 0.033). Of the 14 patients with negative angiograms (13 from Group 1, and 1 with a negative scan), 6 had radiographic occlusion of the inferior mesenteric artery and 1 had spasm of the right colic artery, with scans that blushed in the respective distributions. Excluding these seven patients yielded a positive predictive value of 75 percent (P = 0.0072) for angiography. In patients with a delayed blush (Group 2), 13 of 14 had negative angiograms, yielding a negative predictive value of 93 percent (92 percent excluding those with nonvisualization of the inferior mesenteric artery). Twenty of 21 (95 percent) positive angiograms occurred in Group 1 patients. Of the 27 patients with negative angiograms, 13 were Group 2 patients. CONCLUSION: Patients with immediate blush on 99mTc-labeled red blood cell scintigraphy required urgent angiography. Patients with delayed blush have low angiographic yields. These data suggest that patients with delayed blush or negative scans may be observed and evaluated with colonoscopy.

Sensitive prostate specific antigen measurements identify men with long disease-free intervals and differentiate aggressive from indolent cancer recurrences within 2 years after radical prostatectomy.

PURPOSE: Commonly available prostate specific antigen (PSA) assays have detection limits of greater than 0.05 ng/ml., limiting their ability to identify residual or recurrent prostate cancer after radical prostatectomy or to provide prognostic information within the first several years after surgery. We investigated the ability of a sensitive PSA assay to identify residual prostate cancer and men at risk for early recurrence after radical prostatectomy. MATERIALS AND METHODS: We measured PSA in 1,037 serum samples obtained serially from 127 men after radical prostatectomy using the IMMULITE third generation PSA assay. RESULTS: The IMMULITE PSA assay has an analytical sensitivity of less than 0.002 ng./ml. and a clinically useful decision threshold of 0.01 ng./ml. With this assay our patients were classified into 3 groups: 1) 50 with a postoperative baseline PSA of less than 0.01 ng./ml. that did not change during an average of 36 months postoperatively, 2) 66 with increasing PSA that exceeded 0.01 ng./ml. in all cases by 30 months postoperatively (20 with clinical cancer recurrences) and 3) 11 with slowly increasing PSA of greater than 0.01 but less than 0.02 ng./ml. at an average of 36 months postoperatively. CONCLUSIONS: The IMMULITE PSA assay provides clinically useful information not previously available from PSA assays with conventional sensitivity, which is highly predictive of cancer activity in patients within 2 years after radical prostatectomy.

Immunoassays for quantifying choriogonadotropin compared for assay performance and clinical application.

We examined calibration and accuracy, precision, sensitivity, specificity, and "hook" effects for recently revised automated choriogonadotropin (hCG) immunoassay systems (Baxter-Dade Stratus II, Abbott IMx intact hCG and total beta hCG) and compared them with a widely used immunoradiometric assay (Hybritech). We estimated hCG in pregnant women, women with trophoblastic disease, nonpregnant young and menopausal women, normal men, and men with testicular tumors. We found clinically unimportant differences in calibration (all calibrated to the 3rd International Standard). Detection of hCG by all four assays was limited by their responses in serum from nonpregnant women and men. Precision within-run was best for the automated instruments, but all four assays had similar between-run precision. The Hybritech, Stratus, and IMx intact assays are specific for intact hCG. The IMx total beta assay quantifies both free beta subunit and beta subunit present in intact hCG. There is a clinically important hook effect in the Hybritech assay but not the Stratus or IMx assays (to 1.2 x 10(6) int. units/L). Results for pregnant women were similar by all four assays. We measured "hCG" to 8 int. units/L in menopausal women, which weakly correlated with concentrations of lutropin and follitropin and was, in part, explained by crossreactivity. There was no sample-probe carryover in either instrument. We found the IMx diluting module as well as results at the extremes of the IMx calibration curves (less than 10, 800-1200 int. units/L) unreliable but encountered no such problems with the Stratus system. Both automated systems involve batch analyzers with limited throughput but provide hCG concentration estimates much more quickly than the Hybritech assay can.

Chemically blocked analog assays for free thyronines. II. Use of equilibrium dialysis to optimize the displacement by chemical blockers of T4 analog and T3 analog from albumin while avoiding displacement of T4 and T3 from thyroxin-binding globulin.

Chemical blockers used to displace thyronine analog from albumin in analog kits for assay of free thyroxin (FT4) or free triiodothyronine (FT3) may also displace thyroxin (T4) or triiodothyronine (T3) from thyroxin-binding globulin (TBG), resulting in an apparent TBG dependence of results of free hormone estimates. We used equilibrium dialysis and antibody binding to assess the displacement of thyronine analogs and thyronines from albumin and TBG by use of chemical blockers. We chose a combination of two chemical blockers, which eliminated thyronine analog-albumin binding but minimized thyronine displacement from TBG for use in FT4 and FT3 assays. These blocked-analog free-hormone assays yielded accurate clinical results in euthyroid patients, hypo- and hyperthyroid patients, and in pregnant women. FT4 results were not entirely normalized in all nonthyroidally ill patients, indicating that decreased analog-albumin binding is not the only factor resulting in low FT4 results. In current Diagnostic Products Corp. (DPC) FT4 and FT3 blocked-analog kits, the blocker concentrations are the same as we used in these assays.

Chemically blocked analog assays for free thyronines. I. The effect of chemical blockers on T4 analog and T4 binding by albumin and by thyroxin-binding globulin.

Analog assays for free thyroxin (FT4) produce inaccurate results because the T4 analog is sequestered by albumin. Diagnostic Products Corp. (DPC) introduced the concept of chemically blocking analog-albumin binding in 1982. While DPC succeeded in eliminating albumin dependence, their 1985 version of chemically blocked FT4 assay appeared to be "thyroxin-binding globulin" (TBG) dependent, producing inappropriately low FT4 results with low TBG concentrations and high results with high TBG concentrations. We examined the effects of chemical blockers on albumin and TBG binding, using equilibrium dialysis to measure free fractions of T4 analog and T4. We then created FT4 assays in which various concentrations of chemical blockers were used to demonstrate their effects on FT4 estimates in patients with low or increased TBG concentrations or who were pregnant. We found that chemical blockers do displace T4 analog from albumin, but also displace T4 from albumin and, in high concentrations, from TBG as well. It is this displacement of T4 from TBG by chemical blockers that resulted in "TBG dependence" of DPC FT4 estimates. This problem has been corrected in currently available versions of the DPC FT4 kit.

Heterophilic antibody as a source of error in immunoassay.

We describe our experience with a young woman believed to be hypothyroid and menopausal because of erroneously elevated TSH, LH, and FSH estimates. These errors were found to be due to the presence of antibodies to rabbit IgG in the patient's blood. We found that antibody-limited assays for TSH, LH, and FSH using antisera raised in rabbits were affected by this problem unless rabbit IgG was included, whereas antibody-excess assays were not. These problems were most simply detected by observing inappropriate results when measurements were made in dilutions of the patient's serum. The presence of endogenous antibody directed against antibodies used in immunoassays is a significant potential source of error requiring awareness on the part of both the clinician caring for such patients and the clinical laboratory making the measurements.

Estimation of thyroxin, triiodothyronine, thyrotropin, free thyroxin, and triiodothyronine uptake by use of magnetic-particle solid phases.

We evaluated solid-phase radioassays involving small, uniform magnetic particles (MAGIC, Corning Medical), obtaining data on total serum thyroxin (T4), triiodothyronine (T3), thyrotropin (TSH), free thyroxin (FT4), and T3 uptake for a total of 301 serum samples from euthyroid patients; patients receiving replacement thyroxin; patients receiving estrogen, or who were pregnant; hyperthyroid, hypothyroid, and nonthyroidally ill patients; and patients receiving salicylates, phenytoin, or heparin. We found each procedure to be technically simple and precise (between-assay CVs for T4 2.8-8.2%, T3 9-7.4%, TSH 2.9-4.5%, FT4 3.6-11%, T3 uptake 2.2-3.7%). The magnetic separations are rapid (2 to 5 min), reproducible, and complete. Each MAGIC assay produced clinically appropriate results. These assay systems offer the convenience associated with noncentrifugation assays and excellent analytical performance.

Estimation of free thyroxin with a new thyroxin analog and a porous-glass solid phase.

We evaluated a new thyroxin analog-based assay for free thyroxin (FT4) (Corning Medical), finding it technically simple and precise (between-assay CVs of 3.3 and 4.2% for FT4 concentrations of 12 and 25 ng/L, respectively). We measured FT4 in a total of 325 serum samples from euthyroid patients; patients receiving replacement thyroxin; patients receiving estrogens or who were pregnant; hyperthyroid, hypothyroid, and non- thyroidally ill patients; and patients receiving salicylates, phenytoin, or heparin. This assay clearly identified hyper- and hypothyroid patients, and produced similar results in euthyroid patients with above-normal, normal, or low concentration of thyroxin-binding globulin. Results in some non-thyroid-illness patients and patients receiving salicylates or phenytoin were low compared with euthyroid patients receiving no medications, but the diagnostic accuracy of the Corning FT4 assay exceeded that of another analog-based assay (Amersham) in these particular groups. We believe the new Corning analog FT4 assay offers an attractive alternative to other commercial FT4 systems.

Evaluation of an immunoextraction procedure for the estimation of free thyroxine concentration.

We have examined the performance of a commercial free-thyroxine assay in which a radiolabeled T4 derivative permits the competitive quantitation of extracted T4 in the presence of serum proteins. After the total T4 pool had been radiolabeled with either I-125 T4 or I-131 T4, the solid-phase antibody was found to be associated with 4-8% of the total T4 present in the assay tube. Of this, 15-60% was displaceable (antibody-bound). The assay estimated free T4 to be 0.6-1.8 ng/dl in euthyroid patients, and distinguished them from hyperthyroid (sensitivity 91%) and hypothyroid patients (sensitivity 91%) without apparent TBG dependence. In patients with severe nonthyroidal illnesses, the assay correctly quantitated a reduced extracted mass in some. In other patients, however, the assay results were inappropriately lower than the actual extracted mass, in agreement with the FTI but not with the measurements of free T4 by dialysis. This assay appears to produce clinically appropriate results in most patients. In some nonthyroidally ill patients however, the indicated free T4 is spuriously low.

Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure.

Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

Creatine kinase B subunit as measured with a radioimmunoassay kit in detection of acute myocardial infarction.

Results with a commercial radioimmunoassay (RIA) reagent kit for quantification of the creatine kinase B subunit (CK-B) (Nuclear-Medical Laboratories, Irving, TX 75061) were compared with results obtained by electrophoresis for patients consecutively admitted to our coronary care unit for suspected acute myocardial infarction. Analytical sensitivity, precision, and specificity of the RIA were satisfactory. Its clinical efficacy was assessed in 97 patients suspected of having had an acute myocardial infarction. Of 30 patients who had had an acute myocardial infarction, increased CK-B was detected by RIA in 30 and by electrophoresis in 27. The temporal relationship between CK-B by RIA and CK-MB by electrophoresis was similar. Of 66 admissions where infarction was not established, CK-B was negligibly increased in samples from four patients by RIA, and from one by electrophoresis. Although not abnormally increased (greater than 5 U/L), CK-MB was detected by electrophoresis in samples from another five of these 66 patients. We conclude that estimation of CK-B by this RIA is an excellent alternative to estimation of CK-MB by electrophoresis in patients suspected of having had an acute myocardial infarction.

Two radioimmunoassays compared with isoenzyme electrophoresis for the detection of serum creatine kinase-MB in acute myocardial infarction.

We have evaluated two commercial radioimmunoassay (RIA) reagent kits for the estimation of the MB isoenzyme of creating kinase (CK). Although both methods use CK-B antisera and radioiodinated CK-B, one ("M" for Mallinckrodt) uses hybridized CK-MB for calibration, while the other ("NMS" for Nuclear Medical Systems) uses CK-B. Both assays provide adequate sensitivity, precision, and specificity for the estimation of serum CK-MB. Ninety-nine patients admitted consecutively to our coronary care unit were studied. Apparent CK-MB was measured by both RIAs and results compared with CK-MB enzymatic activity after electrophoresis (E). CK-MB was elevated, as judged by E and by M, in all of 42 patients with acute myocardial infarction (AMI), and in 40 of the 42 by NMS. Of the 57 patients who did not have an AMI, eight had elevated CK-MB by E, 16 by M, and 25 by NMS. Patients with persistently elevated apparent CK-MB concentrations not associated with AMI were identified by M and by NMS, but not by E. The ability to differentiate AMI from no infarction in patients was best with E, and was not satisfactory by NMS. Although the detection of AMI by M equaled that by E, the large number of apparent false-positive results hindered the clinical application of RIA CK-MB measurements.

The triiodothyronine uptake test: an assessment of methods.

How well the free thyroxine index reflects thyroid functional status depends on the degree to which the triiodothyronine uptake test normalizes the effects of thyroxine binding protein concentrations on the total thyroxine concentration. We examined eight triiodothyronine uptake tests in which were used different secondary binders representative of those available in commercial kits. The relation between triiodothyronine uptake and thyroxine-binding globulin concentrations was established by use of sera from euthyroid individuals. We examined the effects of both high (greater than 20 mg/L) and low (less than 10 mg/L) thyroxine-binding globulin concentrations on triiodothyronine uptake. The precision of each assay, expressed as within- and between-run coefficient of variation, was calculated from multiple measurements on high, low, and midrange triiodothyronine uptake serum pools. The effects of variation in temperature and in exposure times were examined. The clinical most useful assays exhibited the ability to reflect a wide range of thyroxine-binding globulin concentrations and demonstrated little or no time or temperature effects.

An assessment of methods for the estimation of free thyroxine.

Three commercial kit methods for the estimation of free thyroxine (FT4) (Clinical Assays, Corning Medical, Damon Diagnostics) were evaluated. The effects of changes in thyroxine-binding globulin (TBG) and FT4 concentrations in these systems were assessed. Measurements were made in serum samples from hyperthyroid, hypothyroid, and euthyroid patients with different TBG concentrations, and results were correlated with functional thyroid status. The Clinical Assays and Damon Diagnostics assays were found to be essentially independent of binding-protein concentration effects and responded appropriately to changes in FT4 concentration. The method of Corning Medical does not measure FT4 directly but yields an FT4 index calculated from a TBG-dependent T4 uptake and the total T4 concentration. This corning index yields falsely elevated results in patients with marked elevation in TBG concentration.