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Biomedical subjects

M Fleisher

Publications and source records attributed to M Fleisher.

At least 19 recordsLinked to original sources

An evaluation of a non-isotopic homogeneous enzyme immunoassay (CEDIA assay) for cortisol and its clinical utility.

Serum cortisol is one of the more frequently requested steroid hormone assays. Its use is important in evaluating diseases of the adrenal cortex and pituitary. We briefly review the biochemistry of cortisol synthesis, the pathophysiology resulting from adrenal and pituitary abnormalities and the more specific immunochemical procedures which have replaced colorimetric chemical assays for cortisol. We also report our results on the evaluation of the analytical performance of the non-isotopic homogeneous CEDIA Cortisol assay and compare the advantages of this assay to state-of-the-art immunoassays.

Addison Disease

Glucosephosphate isomerase as a CSF marker for leptomeningeal metastasis.

Glucosephosphate isomerase (GPI), also known as phosphohexoisomerase, is a glycolytic enzyme whose activity is elevated in serum and CSF of patients with primary and metastatic CNS tumors. To improve the diagnostic accuracy of leptomeningeal metastasis (LM), we measured GPI levels in CSF of 66 patients with CNS or systemic malignancies with suspected LM. We determined GPI kinetically using a coupled enzyme reaction assay. There were 31 males and 35 females, aged 1 to seventy-six. Thirty-one had primary brain tumors, and 35 had systemic cancer with suspected CNS metastasis. We analyzed 95 samples; GPI values ranged from 0.85 to 329.0 U/l (normal, less than 20 U/l). Compared with positive CSF cytology and myelography, GPI sensitivity was 53.5% and specificity 92.1% for the group as a whole. There was a highly significant association between elevated CSF GPI (greater than 20 U/l) and LM. The results were similar for both primary CNS and systemic malignancies. Although not very sensitive, an elevated CSF GPI strongly suggests LM and may aid in early diagnosis of this serious complication of cancer.

Adolescent

Fatal thrombocytopenia and liver failure associated with carboplatin therapy.

A patient with fatal severe thrombocytopenia and acute hepatic necrosis complicating carboplatin (JM8, CBDCA, NSC 241240) therapy is described. The patient, an 18-year-old man with acute lymphocytic leukemia, was given high-dose carboplatin as a part of a phase I trial of this agent for the treatment of leukemia. Carboplatin (270 mg/m2/day) was administered as an intravenous infusion on five consecutive days, and the patient died 10 days after his last dose of carboplatin from complications of thrombocytopenia and acute liver necrosis. Autopsy revealed hemorrhage into the substance of the myocardium and hemorrhagic centrilobular liver necrosis. The temporal relationship between the initial rise in this patient's liver function tests and treatment with carboplatin suggests that this patient's liver failure was in part due to carboplatin. The autopsy findings of hemorrhage into the substance of the myocardium and centrolobular liver necrosis suggest that, in addition to its direct effects, carboplatin may have also contributed indirectly to this patient's liver failure through the complications of thrombocytopenia.

Adolescent

Comparison of assays for prostatic and total acid phosphatase.

Total and tartrate inhibited acid phosphatase was determined on the Technicon Chem 1 and evaluated against a Cobas-Bio centrifugal analysis procedure and an immunochemical method. Precision and reference range studies were performed for the Chem 1 acid phosphatase procedure and correlation was established with the other methods. The Chem 1 method for measuring total and prostatic acid phosphatase is a sensitive method with good correlation to the centrifugal analysis and the immunochemical method. The assay is fully automated and requires no manual off-line sample preparation.

Acid Phosphatase

Strategies of organization and service for the critical-care laboratory.

Critical-care medicine requires rapidity of treatment decisions and clinical management. To meet the objectives of critical-care medicine, the critical-care laboratory must consider four major aspects of laboratory organization in addition to analytical responsibilities: specimen collection and delivery, training of technologists, selection of reliable instrumentation, and efficient data dissemination. One must also consider the advantages and disadvantages of centralization vs decentralization, the influence of such a laboratory on patient care and personnel needs, and the space required for optimal operation. Centralization may lead to workflow interruption and increased turnaround time (TAT); decentralization requires redundancy of instrumentation and staff but may shorten TAT. Minimal TAT is the hallmark of efficient laboratory service. We surveyed 55 laboratories in 33 hospitals and found that virtually all hospitals with 200 or more beds had a critical-care laboratory operating as a satellite of the main laboratory. We present data on actual TAT, although these were available in only eight of the 15 routine laboratories that provided emergency service and in eight of the 40 critical-care laboratories. In meeting the challenges of an increasing workload, a reduced clinical laboratory work force, and the need to reduce TAT, changes in traditional laboratory practice are mandatory. An increased reliance on whole-blood analysis, for example, should eliminate delays associated with sample preparation, reduce the potential hazards associated with centrifugation, and eliminate excess specimen handling.

Centralized Hospital Services

Neuron-specific enolase and retinoblastoma. Clinicopathologic correlations.

Neuron-specific enolase (a glycolytic, ubiquitous, intracellular enzyme) has recently been reported to be detectable in the aqueous humor of eyes containing retinoblastoma. Aqueous humor from 17 patients with histologically proven retinoblastoma was assayed for the presence of neuron-specific enolase (NSE). NSE was detectable in 17 out of 17 patients with levels between 619 and 60,000 ng/ml. A multitude of clinocopathological parameters were examined for statistically significant correlations with levels of aqueous humor NSE. This investigation demonstrated that only two parameters, the presence of tumor invasion into the anterior chamber, and inflammation significantly correlated with aqueous NSE levels. Histological parameters which did not correlate with aqueous NSE levels included tumor necrosis, calcification, Flexner-Wintersteiner rosettes, exophytic/endophytic tumor type, tumor extent relative to the equator, and optic nerve/choroidal invasion. Clinical parameters which showed no correlation included patient sex (M/F), enucleation age, presentation age, family history, laterality, prior treatment, and presence of metastatic disease. Neuron-specific enolase is present in the anterior chamber of eyes enucleated for retinoblastoma, but additional testing is necessary to determine the normal levels of neuron-specific enolase in children's eyes and the levels in eyes with lesions simulating retinoblastoma.

Anterior Chamber

Cerebrospinal fluid beta 2 microglobulin in patients infected with human immunodeficiency virus.

We prospectively evaluated CSF concentrations of beta 2 microglobulin (beta 2M) in 65 human immunodeficiency virus type 1 seropositive patients. The highest concentrations occurred in those with lymphoma, neurologic opportunistic infections, and acquired immune deficiency syndrome dementia complex (ADC). There was a high correlation between the CSF beta 2M concentration and ADC severity, suggesting that CSF beta 2M may be useful as a marker for the development, progression, and perhaps response to treatment of ADC. Elevated CSF beta 2M was not due to CSF pleocytosis and was usually independent of blood-brain barrier dysfunction.

Acquired Immunodeficiency Syndrome

Two whole-blood multi-analyte analyzers evaluated.

We evaluated two multi-analyte analyzers, the NOVA Stat Profile 1 (SP 1) and the NOVA Stat Profile 5 (SP 5). The SP 1 measures pH, pCO2, pO2, sodium, potassium, ionized calcium, and hematocrit in heparinized whole blood; the SP 5 determines all these analytes, plus chloride (not evaluated because it was unavailable at the time this study was initiated) and glucose. Interassay precision for pH, pCO2, pO2, sodium, potassium, ionized calcium, and hematocrit (all on the SP 1) and glucose (on the SP 5) was excellent, the respective CVs (%) being: less than 0.006, 2.1, less than or equal to 3.0, less than or equal to 0.5, less than or equal to 1.7, less than or equal to 2.1, less than or equal to 3.9, and less than or equal to 1.2. Correlation with results obtained with Corning's Model 178, NOVA Biomedical's Model 6, Beckman's Astra 8, and Roche's Cobas-Bio was also excellent (r greater than 0.975 for all analytes, r for hematocrit 0.865). Temperature-stability studies on whole-blood specimens maintained at 1 degree C indicated that results for all measured analytes were essentially uncharged for at least 2 h, except for potassium, which increased by 13% in 2 h. At 22 degrees C, values for pH, pCO2, pO2, and glucose changed significantly within 2 h. Advantages of the NOVA Stat Profile series include decreased specimen requirements (250 microL), analysis time (72-90 s), turnaround time (about 4.5 min), and overall cost of operation.

Autoanalysis

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

The clinical utility of plasma and urinary carcinoembryonic antigen in patients with genitourinary disease.

Carcinoembryonic antigen was measured in the urine and plasma of 108 patients with several types and various stages of genitourinary cancer. The value of the carcinoembryonic antigen assay as an early indicator of neoplastic disease was evaluated and a correlation was made between the extent of disease and the concentration of urinary and plasma carcinoembryonic antigen. Patients were classified according to stage of tumor involvement as follows: no evidence of disease, non-malignant disease, non-invasive disease, no known metastasis, regional metastasis and disseminated metastasis. The urinary carcinoembryonic antigen levels more closely paralleled the extent of disease than did the plasma carcinoembryonic antigen levels in patients with bladder cancer. Neither urinary nor plasma carcinoembryonic antigen levels were useful in assessing the extent of disease in patients with prostatic or testicular cancer. Studies related to microbiological interference in the carcinoembryonic antigen assay indicated that bacterial counts up to 10(5) organisms per ml. did not interfere. Cytological studies indicated that the presence of white blood cells, atypical cells and malignant cells could result in elevated urinary carcinoembryonic antigen levels.

Carcinoembryonic Antigen

Carcinoembryonic antigen in colonic lavage.

Colonoscopic lavage was performed for assay of carcinoembryonic antigen (CEA) concentration in patients with small and large colonic adenomas, in patients with adenocarcinoma of the colon, and in normal controls. CEA concentration was considerably higher in colonoscopic lavage as compared to plasma. CEA concentration in normal controls and in patients with colonic adenomas less than 1 cm in size were not significantly different. CEA concentrations in patients with colonic adenomas greater than 1 cm in size and in patients with adenocarcinoma of the colon were significantly higher than those observed in patients with small adenomas and in the normal controls. In all except 2 patients, plasma CEA concentrations were normal. Assay of CEA concentrations in colonic lavage may have potential application in the further assessment of the mucosa at risk for colon adenomas and for colon cancer. It does not appear to be accurate enough for diagnosis of colon cancer in individual patients.

Adenocarcinoma