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Biomedical subjects

M H Zweig

Publications and source records attributed to M H Zweig.

At least 37 records · Page 2Linked to original sources
PubMed1988

The potency of immunoglobulin G fragments for inhibition of interference caused by anti-immunoglobulin antibodies in a monoclonal immunoradiometric assay for thyrotropin.

Heterophile antibodies in patients' serum may produce false increases in apparent analyte concentrations in "sandwich"-type immunoassays. Using three patients with endogenous anti-mouse IgG antibodies and a two-site mouse monoclonal assay for thyrotropin, we studied the ability of IgG fragments to block this positive interference. Mouse whole IgG and IgG Fc fragment blocked the interference virtually completely; IgG F(ab')2 and Fab fragments did not. Rat and horse immunoglobulin fragments gave variable results. We suggest that sandwich assays formulated with IgG Fab or F(ab')2 fragments may be less susceptible to positive interference by heterophile antibodies. Unlike sera from the three patients, simulated human specimens containing heterologous anti-IgG antibodies showed little or no selectivity in inhibition by IgG fragments, and therefore are not useful to study this phenomenon.

Animals↗
PubMed1988

Evaluation of the clinical accuracy of laboratory tests.

Fundamental clinical performance of a laboratory test can be described in terms of accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Accuracy refers to the quality of the information provided by the classification device and should be distinguished from the efficacy, or practical usefulness, of the information. Receiver operating characteristic curves provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. If analytical imprecision is removed from the data, the resulting receiver operating characteristic curve represents the inherent biological variation that ultimately limits the clinical accuracy of the test.

Diagnostic Tests, Routine↗
PubMed1987

On the albumin-dependence of measurements of free thyroxin. II. Patients with non-thyroidal illness.

We studied the relation between thyroxin-binding proteins and free thyroxin (FT4) measurements by five radioimmunoassays (RIA) and an FT4 index (FT4I) in patients with non-thyroidal illness (NTI). The one-step FT4 RIAs and the FT4I frequently failed to identify the true FT4 status (as determined by equilibrium dialysis) of NTI patients. In these patients, falsely low FT4 results with one-step RIAs and FT4I were associated with decreasing total T3 and T4 concentrations, which, furthermore, paralleled decreasing serum albumin concentrations. All NTI patients with "low T3, low T4 syndrome" had subnormal albumin concentration. The two-step RIAs and equilibrium dialysis showed normal FT4 concentrations in most patients with NTI. However, sera from a subset of NTI patients with "low T3 syndrome" gave above-normal FT4 results with these methods. From their predictably poor performance in the presence of a subnormal albumin concentration, we conclude that the one-step FT4 RIAs and FT4I are inappropriate for testing the thyrometabolic status of NTI patients.

Diagnostic Errors↗
PubMed1987

Interference by anti-immunoglobulin G antibodies in immunoradiometric assays of thyrotropin involving mouse monoclonal antibodies.

"Sandwich"-type assays are subject to positive interference by the patient's "heterophile" antibodies. If present, these bind to the animal immunoglobulins in the assay reagents, forming artefactual sandwiches indistinguishable from those formed with the analyte itself. Immunoglobulins from non-immunized animals, added to the assay reagents, can diminish this effect by blocking the patient's antibodies. Elsewhere, we studied several patients with anti-mouse immunoglobulin activity, whose serum gave spuriously high results for thyrotropin (TSH) concentrations. Here we have studied this phenomenon by adding, to pooled zero-TSH serum, antibodies to mouse, goat, and horse immunoglobulins and then assaying TSH by several other sandwich-type assays involving mouse monoclonal antibodies. Assays not supplemented with blocking immunoglobulins from mice or other animals were more susceptible to this effect. When large amounts of antibody were added, the antibody excess diminished the interference. However, the presence of blocking immunoglobulins could reverse such antibody excess, actually enhancing, instead of diminishing, the positive interference. Users should be aware that blocking immunoglobulins may diminish but not necessarily eliminate this problem with such assays.

Animals↗
PubMed1986

Differential expression of neural isozymes by human medulloblastomas and gliomas and neuroectodermal cell lines.

For the determination of their possible utility as tumors markers, 2 neural-associated isozymes, neuron-specific enolase [(NSE) EC 4.2.1.11] and creatine kinase BB [(CK-BB) EC 2.7.3.2], were quantitated by radioimmunoassay in human neuroectodermal-derived cell lines, primary brain tumors, and sera and cerebrospinal fluid (CSF) from brain tumor patients. The NSE content of neuroblastoma cell lines was more than sixfold that of the glioma and medulloblastoma lines; the CK-BB content of neuroblastoma and medulloblastoma lines was fourfold to nineteen-fold that of the glioma and other lines. Expression of NSE in neuroblastoma cell lines was not related to time in culture and was cell line specific. NSE in ex vivo medulloblastomas was raised six to ten times that in astrocytomas and gliomas, although no significant differences were noted for the CK-BB content. Serum and CSF NSE levels were markedly raised above control values in 10 of 29 and 6 of 10 cases of astrocytoma, respectively. Raised CK-BB levels in serum (greater than 10 ng/ml) and CSF (greater than 12 ng/ml) were found in 9 of 18 and 2 of 10 patients, respectively. These data suggest that NSE is preferentially expressed by neuroblastoma lines and medulloblastomas and that NSE and CK-BB may have clinical utility as markers for prognosis, diagnosis, and monitoring of response to therapy.

Adolescent↗
PubMed1986

On the albumin dependence of measurements of free thyroxin. I. Technical performance of seven methods.

We evaluated three one-step (analog) and two two-step radioimmunoassay for free thyroxin (FT4), and a FT4 index calculated from the total T4 (TT4) and thyroxin-binding globulin (TBG) ratio for technical performance, for correlation with the reference FT4 method (equilibrium dialysis), and for dependence on TBG and albumin concentrations. The one-step methods (Amerlex, Coat-A-Count, and GammaCoat) showed greater precision than the two-step procedures (GammaCoat and Spiria). Results by the latter two techniques, however, correlated better with those by equilibrium dialysis than did those by the analog methods or by TT4/TBG. Only the GammaCoat two-step method had a slight but statistically significant (inverse) correlation with TBG concentration. All three analog methods and TT4/TBG showed a marked dependence on albumin concentration, whereas the Spiria technique showed only a slight dependence. Only equilibrium dialysis was independent of both the TBG and albumin concentration. Thus, despite their good precision, the analog (one-step) FT4 methods and the TT4/TBG approach cannot be expected to produce valid results when the concentration of albumin in serum is abnormally low or high.

Dialysis↗
PubMed1986

Ascorbic acid interference in reagent-strip reactions for assay of urinary glucose and hemoglobin.

Vitamin C (ascorbic acid), commonly taken as a dietary supplement and excreted in the urine, can interfere with peroxidase redox indicator systems such as those used in reagent-strip tests for urinary glucose and hemoglobin. We investigated whether the concentrations of ascorbic acid in urine after modest supplementary doses of vitamin C are high enough to interfere with such dipstick tests. After adding glucose or hemoglobin to urine collected from persons not taking vitamin C and from persons taking 350 to 1000 mg of vitamin C daily, we tested four reagent strips for interference and found that these commonly taken doses did frequently interfere with all test systems examined.

Ascorbic Acid↗
PubMed1985

Establishment and identification of small cell lung cancer cell lines having classic and variant features.

Using a chemically defined medium containing hydrocortisone, insulin, transferrin, 17 beta-estradiol and selenium, with or without serum supplementation (2.5% v/v), continuous cell lines can be established from 72% of all fresh biopsy specimens of small cell lung cancer (SCLC) containing tumor cells. No differences were observed in the rate of establishing cell lines from newly diagnosed untreated patients, or from patients who have relapsed from prior therapy, or from a variety of different organ sites. Biochemical characterization of 50 SCLC cell lines for the expression of L-dopa decarboxylase; bombesin-like immunoreactivity; neuron-specific enolase, and the brain isozyme of creatine kinase, revealed that SCLC cell lines can be subdivided into two distinct classes: classic SCLC cell lines (35 lines), which express elevated levels of all four biomarkers; and variant SCLC cell lines (15 lines) which have undetectable levels of L-dopa-decarboxylase and bombesin-like immunoreactivity, but continue to express neuron-specific enolase and the brain isozyme of creatine kinase. The presence of the latter two markers distinguishes variant lines fron non-SCLC cell lines. In addition, four distinct classes were identified morphologically. The biomedical differences among established SCLC cell lines may account for the differences in response rates to cytotoxic therapy observed in newly diagnosed SCLC patients. A prospective study of biomarker characterization of SCLC tumors will determine if clinical differences exist between classic and variant SCLC tumors.

Animals↗
PubMed1985

Assessment of serum radioimmune and enzymatic prostatic acid phosphatase and radioimmune creatine kinase BB for monitoring response to therapy in metastatic prostatic carcinoma.

Objective documentation of tumor response in patients with metastatic prostatic cancer is difficult. To evaluate a radioimmunoassay for creatine kinase BB, two commercial radioimmunoassays for prostatic acid phosphatase, and an enzymatic acid phosphatase measurement in monitoring the status of advanced prostatic carcinoma, we assayed sera from 34 patients with Stage D-2 disease prior to and during systemic treatment with combination chemotherapy or hormonal manipulation. Prior to treatment, the creatine kinase BB level was elevated less often (48%) than all three assays for acid phosphatase (83 to 91%). During therapy, all four test results both increased and decreased whether the patients were responding to or progressing on therapy. Test results usually declined when patients had documented responses to therapy, particularly when hormonal therapy was used. However, when patients progressed on therapy, test results also declined at least as often as they increased. No test was consistent enough to serve as a sole indication of tumor response. The three acid phosphatase assays performed similarly, with no evident advantage of radioimmunoassay over the enzymatic assay. Creatine kinase BB was generally inferior to all three acid phosphatase assays.

Acid Phosphatase↗
PubMed1984

Elevated serum creatine kinase BB levels in patients with small cell lung cancer.

Clinical tumor specimens and cultures of small cell lung cancer (SCLC) produce 10- to 100-fold higher quantities of the BB isoenzyme of creatine kinase (CK-BB) (EC 2.7.3.2) than did other types of lung cancer. Serum CK-BB levels were evaluated in 105 newly diagnosed, previously untreated patients with SCLC. All patients were thoroughly staged, including 42 patients with limited-stage and 63 patients with extensive-stage disease. Serum CK-BB was elevated (greater than 10 ng/ml) in 27 patients (26%) (range, 11 to 522 ng/ml; median, 40 ng/ml). Only 1 of 42 patients with limited disease had an elevated serum CK-BB, while 26 of 63 (41%) of patients with extensive disease did. When patients were subgrouped according to the number of metastatic sites detected in pretreatment staging, a significant association between the presence of an elevated serum CK-BB and the number of metastatic sites was observed (p less than 0.005). No association between the presence of metastatic disease in a specific site and an elevated serum CK-BB could be detected. After adjusting for the number of metastatic sites, survival among patients with a normal pretreatment CK-BB was significantly better than in patients with an elevated CK-BB (p = 0.014). Sequential serum CK-BB determinations in 33 patients revealed an excellent correlation between clinical response to therapy and serum CK-BB levels. Continuous SCLC cell lines established from 13 patients in this study all expressed high levels of CK-BB. These data suggest that serum CK-BB determinations may be of value in estimating the extent of tumor dissemination, assigning prognosis, and monitoring response to therapy in patients with SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Why we need better test evaluations.

A laboratory test is clinically useful only if it successfully answers a question of consequence to patient management. Unfortunately, the results and conclusions of many published test evaluations are misleading or of uncertain validity because common-sense principles of study design are overlooked. This is illustrated by examples from recent literature. We suggest that tests should be evaluated with prospective studies of patients representative of the population for which the test will ultimately be used. The clinical question to be addressed by the test should be clearly stated, and then answered for each patient by means independent of the test being evaluated. When comparing tests with each other, decision levels should be chosen to give either the same sensitivity or specificity for each. The use of soundly designed protocols for the clinical evaluation of tests provides the information needed to select the most effective tests.

Adult↗
PubMed1982

Comparison of the effectiveness of four clinical chemical assays in classifying patients with chest pain.

We compared the usefulness of four serum assays for classifying patients originally suspected of having an acute myocardial infarction. One of these is the long-used measurement of total creatine kinase (CK) activity. The other three are relatively new immunoassays: myoglobin by RIA, CK-BB by RIA, and CK-MB by immunoinhibition. When we evaluated test effectiveness with use of conventionally derived reference ranges, the results were misleading. However, by using receiver operating characteristic curves, we were able to effectively compare the four tests at all possible decision levels, rather than at only one. Multiple closely sequential serum specimens were obtained during the first four days after the onset of chest pain. Total CK, CK-MB, and CK-BB all behaved similarly, reaching peak diagnostic effectiveness at 18-20 h, when all three correctly classified 95% of the infarct patients, with a zero false-positive rate. However, total CK was more useful in identifying infarcts later in their courses than were the two CK isoenzyme tests. Myoglobin assay was most effective earlier in the course, at about 7 to 8 h. Our results indicate (a) that the tests for myoglobin and for CK or its isoenzymes are complementary and (b) that of the three CK tests, measurement of total CK activity provides the most information over the broadest segment of a patient's course.

Creatine Kinase↗
PubMed1981

Creatine kinase isozymes in the serum and CSF of schizophrenic patients.

Newly admitted psychotic patients often have elevations of serum creatine kinase (CK) enzymatic activity. Previous studies indicate that this increase consists of the muscle (MM) isozyme, and increases in the brain (BB) isozyme have not been observed. Using sensitive and specific radioimmunoassays that detect both active and inactive enzyme, we measured CK-MM and CK-BB in the serum and CSF of 100 patients with schizophrenia who were not newly admitted but whose conditions varied from acute to chronic to determine whether CK-MM or CK-BB appears in the CSF and whether CK-BB can be found in the serum of these patients. We found no unusual concentrations of either isozyme in CSF. We did observe a few elevations in serum CK-BB levels, but this test does not appear to be of diagnostic value for schizophrenic patients who are not newly admitted.

Adolescent↗
PubMed1981

Levels of creatine kinase and its BB isoenzyme in lung cancer specimens and cultures.

Small-cell carcinomas of the lung (SCCL) have properties of amine-handling cells, and high levels of the key amine-handling cell enzyme L-dopa decarboxylase (EC 4.1.1.28) distinguish SCCL from most other lung cancers. SCCL tumor specimens and continuous cultures also are characterized by high levels of creatine kinase (EC 2.7.3.2) and its BB isoenzyme (CK-BB). Electrophoretic analysis of creatine kinase isoenzymes indicated that creatine kinase levels in SCCL were quantitatively but not qualitatively different from those in normal lung and other lung cancers. Supernatant fluids of SCCL cultures contained relatively modest concentrations of CK-BB but lacked detectable L-dopa decarboxylase activity. Variant SCCL cultures with altered morphology lost their amine-handling properties, including L-dopa decarboxylase activity, but retained high levels of CK-BB, indicating discordant expression of the two enzymes. CK-BB levels were measured in the sera of 67 patients having SCCL. Elevated levels were present in 16 of 41 patients (39%) having extensive-stage disease but in none of 26 patients (0%) having limited-stage disease.

Carcinoma, Small Cell↗