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Biomedical subjects

M Fleisher

Publications and source records attributed to M Fleisher.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antifolate analogs: mechanism of action, analytical methodology, and clinical efficacy.

Antifolates have demonstrated effective antineoplastic activity in the treatment of disorders of cell proliferation, e.g., acute lymphocytic leukemia, breast cancer, and mycosis fungoides. The enzymatic pathways involved in DNA biosynthesis, specifically dihydrofolate reductase and thymidylate synthetase, are the biochemical targets of antifolates. Methotrexate (MTX) and its analogs, 10-ethyl-10-deazaaminopterin (edatrexate), and trimetrexate (TMT) are paradigms for cytotoxicity at the biochemical level. Understanding the cellular pharmacology of MTX and other antifolates has provided a strong rationale for the use of high-dose MTX with leucovorin (LV) rescue. The combination of MTX and LV prevents severe toxicity without diminishing the antitumor activity of the drugs. The efficacy of antifolate drugs is related to the extent of intracellular polyglutamation in normal and cancer cells. Since toxicity in patients is difficult to predict, monitoring drug concentrations is critical. Antifolates, specifically MTX and edatrexate, are among a growing class of chemotherapeutic agents that require assiduous and rapid monitoring to help prevent severe systemic toxicity. Chemical and physical properties, mechanism of chemotherapeutic activity, and analytical methodology for measurement of serum concentrations of antifolates will be discussed.

Animals↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Proteases in cyst fluid from human gross cyst breast disease.

Cyst fluid from women with gross cystic breast disease was found to contain protease activity when assayed against [14C]albumin. At least six different proteases were detected when the fluid was fractionated by a combination of S-300 Sephacel, hydroxylapatite, and DEAE-Sephacel chromatographic techniques. The distribution of the proteases appeared to be related to the ionic composition of the fluids. A major protease component, found in both high Na and high K fluids, was isolated. It showed chymotryptic cleavage characteristics against the beta-chain of insulin. It was partially inhibited by alpha 2-macroglobulin, N-tosyl-L-phenylalanine chloromethyl ketone, and benzamidine but not by leupeptin, pepstatin, N-tosyl-L-lysine chloromethyl ketone, or alpha 1-protease inhibitor. The protease has an apparent molecular weight of 110,000 with Mr 24,000 subunits. This protease may be identical or closely associated with Haagensen's GCDFP-24 progesterone binding protein which was isolated in a similar manner. An imbalance between protease and protease inhibitors in cyst fluid may account for gross cyst formation and may be involved in the tumorigenic process. The accumulation of poorly diffusible peptide fragments, as a result of protease activity, would increase the oncotic pressure leading to enlargement of the cyst cavity as water enters to reestablish osmotic equilibrium.

Female↗
PubMed1988

Blunt bladder trauma: manifestation of severe injury.

Twenty-nine patients with bladder injuries requiring operative treatment as a result of blunt trauma are presented. Motor vehicle accidents accounted for 86 per cent of the injuries. Hypotension and gross hematuria were the most prevalent clinical features, 68 per cent and 97 per cent, respectively. All patients had multiple associated injuries requiring operative treatment, average 2.9 per patient. Pelvic fractures occurred in 93 per cent and intra-abdominal injuries in 48 per cent of patients. The majority of ruptures (72%) were intraperitoneal. Mortality, related to associated injuries, was high (34%), attesting to the magnitude of injury sustained by the victim.

Abdominal Injuries↗
PubMed1988

Massive solitary tophus containing calcium pyrophosphate dihydrate crystals at the acromioclavicular joint.

A massive solitary tophus containing calcium pyrophosphate dihydrate (CPPD) crystals was resected from the distal clavicle and proximal acromion of a 62-year-old man who presented with a painful shoulder mass. The diagnosis was confirmed histologically and by X-ray diffraction. CPPD crystal deposition was found within bone, however, the articular cartilage was not involved. Other unusual features of the case include the size of the lesion, the monoarticular presentation and a peculiar discoloration of the overlying skin. The clinical presentation and radiographic features were initially consistent with a malignant process; thus the case demonstrates that CPPD arthropathy should be included in the differential diagnosis of periarticular tumors.

Acromioclavicular Joint↗
PubMed1987

Phase I and clinical pharmacology study of trimetrexate administered weekly for three weeks.

Trimetrexate, a new antifolate compound, was administered by 30-min infusions weekly for 3 weeks to 29 patients with solid tumors in a Phase I study. Thrombocytopenia was dose limiting, but highly variable among patients at a given dose level; other toxicity was mild and uncommon. Twenty-three patients participated in pharmacokinetic studies and five patients participated in a study of the effects of trimetrexate on [6-3H]-deoxyuridine incorporation into hematopoietic cell DNA. The median total body clearance of trimetrexate for each dose level was independent of dose but the total body clearance varied widely among patients at a given dose level. The magnitude of the fall in platelet count in individual patients correlated well with the amount of exposure to trimetrexate, but not with the extent of prior therapy. The amount of [6-3H]deoxyuridine incorporation into hematopoietic cell DNA at 72 h after drug administration correlated with the total body clearance of trimetrexate. The total body clearance of trimetrexate was reduced in patients with impaired hepatic synthetic function, as judged by low pretreatment serum albumin concentrations. The recommended Phase II starting dose on this schedule is 130 mg/m2 weekly for 3 weeks; patients with hypoalbuminemia should be treated at lower doses.

Adenocarcinoma↗
PubMed1987

The genitourinary system in patients with imperforate anus.

The incidence and significance of associated genitourinary abnormalities was reviewed in a series of 484 infants with imperforate anus encountered over a 17-year period. Fourteen percent of the entire series had significant bilateral upper tract urinary abnormalities (either asymmetric or symmetric). Of 67 such patients only 14 had combinations of renal agenesis and hypoplasia-dysplasia representing uncorrectable renal pathology. A high incidence of vesicoureteral reflex and neurovesical dysfunction represent additional important sources of preventable renal deterioration.

Anus, Imperforate↗