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Biomedical subjects

M H Zweig

Publications and source records attributed to M H Zweig.

53 records · Page 3Linked to original sources

Assessment of radioimmunoassay of serum creatine kinase BB (CK-BB) as a tumor marker: studies in patients with various cancers and a comparison of CK-BB concentrations to prostate acid phosphatase concentrations.

The association between cancer and the BB isoenzyme of creatine kinase (CK-BB) was investigated, and the possibility of the role of CK-BB as a tumor marker was assessed. With the use of a specific radioimmunoassay, the concentration of CK-BB was measured in 524 sera (obtained from the National Cancer Institute-Mayo Clinic Serum Diagnostic Bank) from patients with a variety of benign and malignant disorders. In 79 of these sera, the results of radioimmunoassay for CK-BB were compared to those of three radioimmunoassays for prostate acid phosphatase. Abnormal CK-BB concentrations occurred in only about 11% of the 366 cancer patients. Some groups of cancer patients had higher rates; e.g., the CK-BB concentration was elevated in 29% of the prostate cancer patients. However, prostate acid phosphatase was abnormal in 65% of the patients with prostate carcinoma--a considerable higher fraction than that found with CK-BB. Findings in patients with benign and malignant gastrointestinal diseases indicate that CK-BB complements carcinoembryonic antigen data and might be useful as part of a tumor marker panel.

Acid Phosphatase↗

Use of receiver operating characteristic curves to evaluate the clinical performance of analytical systems.

The usefulness of an analytical system in patient care is ultimately judged not by its analytical performance but by its clinical performance, i.e., its ability to separate apparently similar patients into two subgroups, one of which has a particular clinically important condition and another subgroup which does not. This clinical performance can be studied with the tools of signal detectability theory, originally developed to analyze the performance of radar and data-transmission systems. Each classification made by an analytical system may be categorized as a true-positive, true-negative, false-positive, or false-negative decision. For laboratory tests the proportion of decisions in each category depends on the biological overlap between the two subgroups, the analytical performance of the system, and the decision level chosen. The clinical performance of the analytical system for all possible decision levels is represented by the receiver operating characteristic curve, which plots the true-positive rate against the false-positive rate. The use of these curves permits comparison of alternative analytical techniques at equal true-positive rates and at all possible decision levels. These comparisons show the effect of analytical improvements on clinical performance.

Chemistry, Clinical↗

The presence of creatine kinase BB isoenzyme in patients with prostatic cancer.

Creatine kinase BB isoenzyme (CK-BB) was detected in abnormal amounts in serum samples from 11 of 46 patients with Stage D carcinoma of the prostate by electrophoresis. Thirteen of 46 Stage D patients had elevated acid phosphatase values and 10 of these 13 had elevated CK-BB. CK-BB elevations were less frequent in earlier stages of prostatic cancer; Stage C: 0 of 35, Stage B: 1 of 26, Stage A: 0 of 3 and none in a group of 35 with BPH, prostatitis and bladder cancer. Results of CK-BB by a specific radioimmunoassay correlated well with those obtained by electrophoresis in most cases. Several patients were followed over time and data on CK-BB is presented for this interval. The origin of the CK-BB is still unclear. The BB isoenzyme predominates in prostatic tissue and CK-BB is the fetal form of the enzyme in human muscle and myocardium. The increase in serum CK-BB may be related to increased release of the isoenzyme, either from the prostate itself or from a metastatic lesion, or may represent a release of the fetal form of the enzyme from dedifferentiated tumor tissue.

Acid Phosphatase↗

Serum creatine kinase BB and MM concentrations determined by radioimmunoassay in neuromuscular disorders.

We measured the MM and BB isoenzymes of serum creatine kinase (CK) by radioimmunoassay in 89 patients with neuromuscular disorders and 44 definite or possible carriers of Duchenne muscular dystrophy (DMD). The CK-MM isoenzyme was closely associated with total CK enzymatic activity. CK-BB was not as closely correlated with total CK but was usually increased in the inflammatory myopathies and DMD and normal in myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis as well as in neuropathies in which CK is usually normal. In myopathies, CK-BB may be useful for assessing the level of disease activity or the regenerative component. More study is necessary to assess the role of CK-BB in detection of DMD carriers.

Child↗

Lot-to-lot variation in three thyroid-related radioimmunoassay kits.

We examined lot-to-lot variation in triiodothyronine, thyroxine, and thyrotropin radioimmunoassay kits over 14-20 months. For the thyroxine assay, less than 20% of the overall variation was attributable to lot-to-lot changes. In contrast, for the triiodothyronine and thyrotropin assays half to two-thirds of the overall variation was attributable to lot-to-lot differences. The shifts seen in control results were also observed in results for patients. These shifts produced disturbing deviations on quality-control charts but did not appear to compromise the clinical utility of the results. We conclude that lot-to-lot variation can account for a major part of the long term variability of radioimmunoassay kit results and should be considered in evaluating kits and monitoring their performance.

Humans↗

Distribution of serum concentrations of creatine kinase MM and BB isoenzymes measured by radioimmunoassay.

Because of the recent interest in measuring serum enzyme concentration as opposed to catalytic activity, we measured the serum concentration of creatine kinase isoenzymes BB and MM by radioimmunoassay and the total creatine kinase enzymatic activity in healthy adults. For sex-race subgroups we report mean values and the 2.5, 5, 25, 50, 75, 90, 95 and 97.5 percentiles. Differences among average values of the subgroups were highly significant. Results within subgroups frequently departed from a gaussian distribution.

Black People↗

Increased CK-BB concentrations in serum following cardiac surgery.

We measured the BB isoenzyme of creatine kinase by a specific radioimmunoassay in the serum of 47 patients following cardiac surgery. A sharp increase in CK-BB occurred immediately after surgery, with rapid return to baseline by the fourth post-operative day. This data, along with other reports in the literature, suggest that CK-BB is released into the circulation following myocardial insult.

Cardiac Surgical Procedures↗

Creatine kinase BB: a new tumor-associated marker.

Creatine kinase isoenzyme BB (CK-BB) is found in the serum of patients with various types of cancer. Using both radioimmunoassay and agarose electrophoresis, we found abnormal amounts of this isoenzyme in the serum of 15 of 17 patients with untreated prostatic carcinoma. Among patients with other types of adenocarcinomas and metastatic disease, serum CK-BB was increased in most of those who were unresponsive to therapy. In benign or malignant prostate tissue and in malignant pleural effusions, cytoplasmic CK-BB as determined by immunoperoxidase staining was found in epithelial cells. Prostatic fluid had high concentrations of CK-BB, as did malignant, but not benign, pleural fluid supernates. We conclude that glandular epithelial cells contain CK-BB, which is released in benign and malignant states and may appear in higher concentrations in the circulation in malignant states. These conclusions are consistent with predictions we have made from a model experimental system concerning characteristics of possible tumor markers. The observations indicate a role for CK-BB as a tumor marker, particularly for adenocarcinoma of the prostate.

Adenocarcinoma↗

Radioimmunoassay of creatine kinase isoenzymes in human serum: isoenzyme MM.

Measurement of the mass concentration of serum enzymes by radioimmunoassay provides direct quantitation of specific isoenzymes and may be less subject to some of the limitations of traditional assay procedures for enzymes. We describe the development of a sensitive and specific radioimmunoassay for the muscle isoenzyme of creatine kinase, CM-MM, in human serum. CK-MM, purified from human skeletal muscle, was used to raise high-titer antisera and for iodination by the Chloramine T method. The radioimmunoassay required 50 microliter of sample, utilized a double-antibody separation method, and was completed in 24 h. Cross reactivity with CK-BB was virtually zero, 3--17% with CK-MB. The mass concentration of CK-MM in the serum of healthy subjects ranged from 36 to 1668 microgram/liter and correlated closely with total CK enzymatic activity. Serum concentrations of CK-MM from casually selected patients correlated less well with total CK enzymatic activity, suggesting the existence of other CK isoenzymes or the presence of inactive forms.

Adult↗

Radioimmunoassay of creatine kinase isoenzymes in human serum: isoenzyme BB.

We describe a sensitive, specific radioimmunoassay for the BB isoenzyme of creatine kinase (CK-BB) in serum. A sequential saturation assay was used to achieve sufficient sensitivity to detect the isoenzyme in 100-microliter serum samples of all healthy persons and patients tested. Bound and free antigen were separated by a second antibody system. Large excesses of purified isoenzyme MM did not react in the assay. Cross reactivity of two preparations of CK-MB was only 1 to 7+. The 95th percentile of serum CK-BB in 208 healthy adults was 6.2 microgram/liter. Within-assay and between-assay precision ranged from 5.5 to 11.9% and 9.7 to 13.6%, respectively.

Adult↗

Influence of methotrexate on results by three methods for determining protein in cerebrospinal fluid.

Because high intravenous and intrathecal doses of methotrexate are used in treatment for various neoplasms, this drug can reach high concentrations in cerebrospinal fluid. At those encountered clinically, it produced significant positive interference with values for cerebrospinal fluid protein as determined with the du Pont aca. A small interference was found with the Folin-Lowry method, and virtually no interference with an automated immunochemical procedure.

Cerebrospinal Fluid Proteins↗