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Biomedical subjects

M Fleisher

Publications and source records attributed to M Fleisher.

At least 55 records · Page 3Linked to original sources

Solid-phase enzyme immunoassay of terminal deoxynucleotidyl transferase evaluated.

We evaluated a newly developed solid-phase immunoassay (EIA) of terminal deoxynucleotidyl transferase (TdT, EC 2.7.7.3) and compared it with the enzymatic assay of TdT involving DNA polymerase. We assessed the precision, performance characteristics, and clinical efficacy of the EIA procedure, using 249 specimens of peripheral blood and bone marrow and 118 specimens of whole blood. On linear regression analysis of results for these 249 samples as measured by the two procedures, the correlation coefficient was 0.87. Distribution of TdT in mononuclear cells isolated from whole blood and bone marrow of subjects in several disease categories indicated good concordance between the two assay procedures. The EIA procedure is precise, can be performed on whole blood without first isolating mononuclear cells, is nonisotopic, and shows potential as a quantitative indicator for the differential diagnosis and monitoring of human leukemia.

Bone Marrow↗

pH as a marker of breast cyst fluid biochemical type.

A previous study reported pH levels in human breast cyst fluid ranging from 7.00 to 7.80 with the cut off between Type I (high K+, low Cl-) and Type II (high Na+, high Cl-) cysts at pH 7.40. Our data indicate a wider range of pH levels in human breast cyst fluids with Type I cysts consistently having acidic levels below pH 7.0 while Type II cysts had pH levels greater than 7.0. Type I acidic cysts characteristically also contain greater amounts of organic acids than Type II cysts. Thus, the pH of breast cyst fluid appears to be related to the electrolyte profile.

Female↗

Acute high-dose methotrexate neurotoxicity in the rat.

Intravenous high-dose methotrexate chemotherapy may produce acute, subacute, or chronic neurotoxicity in patients with cancer. Acute encephalopathies following high-dose methotrexate treatment are recognized with increasing frequency. This study describes a model of acute high-dose methotrexate neurotoxicity in the rat characterized by a profound dose-dependent depression of cerebral glucose metabolism in association with behavioral and electroencephalographic abnormalities. Alterations in the amino acid profile, similar to those described in cancer patients after high-dose methotrexate treatment, were observed in the absence of biochemical evidence of systemic organ toxicity. This model facilitates the study of the biochemical mechanisms of antifolate neurotoxicity in humans and permits the evaluation of potential therapeutic interventions.

Amino Acids↗

Phase I/II trial of intravesical methotrexate for superficial bladder tumors.

Twenty-one patients with superficial transitional cell carcinoma of the bladder received a total of 121 doses of intravesical methotrexate (MTX) at 11 different concentrations of drug, ranging from 40 mg/m2 (mean concentration of 2.9 X 10(-3) M) to 500 mg/m2 (4.9 X 10(-2) M). Biochemical evidence of absorption was minimal in all cases. The maximum serum level was observed within 0.5-2 h in all patients and ranged from 1.8 X 10(-8) M to 5.0 X 10(-7) M. By 24 h the serum levels were negligible and ranged from 5.5 X 10(-9) M (the lowest limit detectable by the assay) to 4.4 X 10(-8) M in the patient who received the highest dosage of 500 mg/m2. Biologic evidence of absorption was minimal. Myelosuppression, mucositis, and nausea were not observed. Eighteen patients received six consecutive weekly doses ranging from 40 to 500 mg/m2. All patients had repeat cytoscopy performed within 2-4 weeks after six consecutive doses to evaluate local toxicity and efficacy. Flow cytometry was performed on the bladder washings of 22 patients, illustrating the use of flow cytometry, in conjunction with conventional cytology, as an additional means of objectively quantifying results. Despite MTX's established activity in systemic treatment of advanced bladder carcinoma, this study failed to demonstrate any clinical response to intravesically administered MTX, in doses of up to 500 mg/m2, and in concentrations of up to 4.9 X 10(-2) M.

Adult↗

Plasma steroid-binding proteins in the cysts of gross cystic disease of the breast.

Breast cyst fluids from 33 patients who underwent cyst aspiration were examined for their content of total protein, albumin, corticosteroid-binding globulin (CBG), and testosterone-estradiol-binding globulin (TeBG). Two distinct populations of cysts, based on their chloride concentration, were found. Both types of cysts had markedly reduced concentrations of the three plasma proteins compared to plasma levels. Concentrations of the proteins in the low chloride (less than 40 meq/liter) cysts were substantially lower than those in the high chloride (greater than 40 meq/liter) ones. Relative to albumin, both CBG and TeBG were excluded from low chloride cysts, whereas relative to one another, the ratios of these two steroid-binding proteins were the same as those in plasma. We conclude that there are specific mechanisms in breast cysts regulating the ingress and/or egress of CBG and TeBG.

Albumins↗

Roche RIA and Abbott EIA carcinoembryonic antigen assays compared.

We have evaluated Roche Diagnostics' RIA-CEA and Abbott Diagnostics' EIA-CEA methods for precision, normal reference interval, concordance, and correlation of malignant disease with increase in carcinoembryonic antigen (CEA) in plasma. In examining concordance, we used data on 138 patients with primary carcinomas of the breast, colon, lung, or pancreas, each further classified by extent of dissemination. We find the two methods to be comparably precise. The respective upper reference limits of normal for the Roche and Abbott methods were determined to be 5.0 micrograms/L and 4.6 micrograms/L. The regression equation for a log transformation of the 177 data points is y = 0.966x + 0.03, where x = Roche and y = Abbott, with a correlation coefficient of 0.948. According to the criteria we used, the concordance was 78.7%. The largest discordance was observed in widely disseminated disease states and in cancers of the colon and pancreas. Paired data analysis of discordance indicated greater increases in apparent CEA by the Abbott method in most colon cancers with liver involvement; six of the eight discordant pancreatic cancers had higher Roche-CEA values. CEA heterogeneity and the role of the liver in CEA metabolism appear to contribute to the observed differences. We show why the two methods should not be used interchangeably, and that baseline values for CEA must be established for each method.

Breast Neoplasms↗

Chemical and clinical evaluation of the random access analyzer "RA-1000".

In the RA-1000, a random-access discrete analyzer, an inert fluorocarbon fluid is used to prevent interaction and carryover. Production-model instruments were evaluated in two laboratories with respect to determination of glucose, creatinine, total protein, inorganic phosphorus, cholesterol, alkaline phosphatase, lactate dehydrogenase, creatine kinase, gamma-glutamyltransferase, and aspartate and alanine aminotransferases. Within-run, among-run, and day-to-day (for 15 days) precision was assessed, and results were correlated with those obtained by the methods routinely in use in our departments. Precision was excellent, correlation acceptable.

Autoanalysis↗

Lactic dehydrogenase isoenzymes in the cerebrospinal fluid of patients with systemic cancer.

Lactic dehydrogenase (LDH) isoenzymes were measured in the cerebrospinal fluid (CSF) patients suffering a variety of cancer-related neurologic problems. LDH-5 isoenzyme as a percentage of total LDH activity was abnormally elevated (above 10 to 15%) in leptomeningeal infiltration by carcinoma (breast carcinoma, lung carcinoma, and malignant melanoma) but not in other types of CNS metastases. Abnormal LDH isoenzyme patterns were also seen with CSF infections in which a granulocytic pleocytosis was present. In the absence of infection, an elevated LDH isoenzyme 5:1 ratio suggested leptomeningeal tumor and, when used with other CSF markers (beta-glucuronidase and CEA), LDH, isoenzymes aid in early detection of this metastatic neoplastic process. They may also help to differentiate leptomeningeal tumor from other chronic meningitides. Measurement of CSF markers also aids in assessing the effectiveness of treatment since marker levels often vary with the clinical course.

Brain Neoplasms↗

Steroid hormone accumulation in human breast cyst fluid.

Elevated concentrations of peptide hormones have been described previously in human breast fluid. In the current study, the levels of cortisol, progesterone, testosterone, dihydrotestosterone, androsterone, androsterone sulfate, dehydroisoandrosterone, dehydroisoandrosterone sulfate, estradiol, estrone, estradiol sulfate, and estrone sulfate were measured. The levels of the four 17-ketosteroids and the two estrogen sulfates were markedly elevated over the plasma level, while that of the other compounds was the same or only slightly higher than the plasma levels of the same compounds.

Androgens↗

Cerebrospinal fluid biochemical markers of central nervous system metastases.

beta-Glucuronidase and carcinoembryonic antigen (CEA) were measured in the cerebrospinal fluid of patients with cancer. Both substances were found to reliably detect the presence of leptomeningeal infiltration by carcinoma. Neither substance was reliable in the detection of leptomeningeal infiltration by lymphoma or of metastases to the brain parenchyma or spinal epidural space. beta-Glucuronidase was moderately elevated in chronic infectious meningitis, whereas CEA was not. Both markers approached control levels with favorable treatment of the leptomeningeal metastases, reflecting the effectiveness of treatment. Both beta-glucuronidase and CEA hold promise as indicators of early metastatic involvement of the leptomeninges by carcinoma.

Arachnoid↗

Accumulation of hormones in breast cyst fluid.

The concentration of some immunoreactive peptide hormones in breast cyst fluid and serum from a series of patients with cystic breast disease were compared. The concentrations of the two pituitary gonadotropins, LH and FSH, were consistently higher in serum than in cyst fluid, confirming earlier more limited observations. The mean PRL concentration, on the other hand, was elevated in cyst fluid though the variability was great. The cyst fluid serum ratio of hCG was elevated in the patient group as a whole. However, the results suggested the presence of two subpopulations; group I, in which the cyst fluid and serum hCG levels were essentially indistinguishable and in the range found in normal serum, and group II, in which the cyst fluid hCG concentration was consistently greater than the normal serum range. Analysis of hormone concentrations in multiple cysts aspirated at the same time showed a remarkable degree of agreement in the cyst hormone levels in most of the patients. The greatest variability in the levels was seen with hCG, were a small numer of subjects showed a very large spread in the values.

Breast Diseases↗