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Biomedical subjects

M K Schwartz

Publications and source records attributed to M K Schwartz.

At least 19 recordsLinked to original sources

Enzymes as prognostic markers and therapeutic indicators in patients with cancer.

An important question in the management of patients with cancer is early identification of the individual who following 'curative' primary therapy will develop recurrence. Another question is which of several alternative treatments is most appropriate. If the patient at risk can be identified early more aggressive and appropriate adjuvant chemotherapy can be initiated to insure remission or longer periods of disease free survival. In this review the role of tissue and/or serum enzyme activities in this regard is considered. Enzymes alone or in combination with tumor markers or other factors may be used. Lactic dehydrogenase (LDH) is perhaps the most common clinical enzyme used in cancer patients for prognostic purposes. It has an important role in germ cell tumors and in association with chorionic gonadotropin and can predict response to therapy and the prospects of remission. LDH is a valuable prognostic marker in lymphoma, leukemia and in colon cancer. Patients can be stratified into treatment protocols based on LDH activity. The stage of cellular proliferation can be evaluated by assay of thymidine kinase in the serum of patients with Hodgkins Disease and in Lymphoma. An important new marker, Cathepsin D in breast tissue may be useful in predicting women with breast cancer who are at risk for early recurrence.

Biomarkers, Tumor

Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

Aspirin

Sulfur amino acid metabolism in hepatobiliary disorders.

Sulfur amino acid metabolism was studied in patients with mild to severe forms of liver dysfunction and compared with that of healthy controls. Patients with mild liver dysfunction (for example, Gilbert's syndrome) had a normal sulfur amino acid metabolism. With increased inflammatory activity and cirrhosis (for example, chronic active hepatitis, alcohol-induced cirrhosis, and hepatic coma) a decreased ability to metabolize methionine (to cysteine, with cystathionine accumulation) and cysteine (to inorganic sulfate, with thiosulfate and N-acetylcysteine accumulation) was found. In contrast, transaminative metabolism of sulfur amino acids was preserved in patients with advanced forms of liver dysfunction, suggesting that transamination of sulfur amino acids is performed not only in the liver but also in extrahepatic tissues. Some implications of these findings are discussed.

Adolescent

Abbott IMx evaluated for assay of prostate-specific antigen in serum.

We evaluated a new fully automated procedure for quantitative measurement of prostate-specific antigen (PSA) by the Microparticle Enzyme Immunoassay (MEIA) technology developed for the Abbott IMx automated immunoassay system. The performance characteristics of the Abbott IMx PSA assay (y) were evaluated and compared with those of the Hybritech Tandem-E PSA assay (x), a solid-phase two-site immunoenzymometric assay. PSA values for both assays were well correlated (r = 0.99); regression analysis yielded the equation y = 0.92x - 0.23 micrograms/L. The Abbott assay proved reliable and reproducible, as shown by the intra- and interassay coefficients of variation (2.0-3.4% and 3.1-4.7%, respectively). The assay gave a linear standard curve up to 100 micrograms/L and was very sensitive (detected PSA < 0.1 microgram/L). This analytical sensitivity was comparable with that of the Tandem-E PSA assay. Overall, the IMx PSA assay demonstrated the accuracy, precision, linearity, and intermethod correlation required for monitoring patients with prostate cancer.

Autoanalysis

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

Cerebrospinal fluid beta 2-microglobulin in patients with AIDS dementia complex: an expanded series including response to zidovudine treatment.

OBJECTIVE: To determine the relationship between cerebrospinal fluid (CSF) beta 2-microglobulin (beta 2M) and severity of AIDS dementia complex (ADC), and between CSF beta 2M and response of ADC to zidovudine. DESIGN: A prospective study. SETTING: Tertiary referral hospital. PATIENTS, PARTICIPANTS: Seventy-eight patients with varying stages of ADC were selected from a subgroup of a cohort of HIV-seropositive patients who are being studied prospectively for the neurological complications of HIV-1 infection. To enter our study, patients had to have an ADC stage of at least 0.5 (equivocal symptoms or abnormal neurological signs in the absence of functional impairment). A control group of 11 HIV-1-seropositive, neurologically normal patients was chosen randomly from the patients followed in the Multicenter AIDS Cohort Study. INTERVENTIONS: Patients were assessed neurologically and neuropsychologically and computed tomography of the brain and CSF studies were performed. MAIN OUTCOME MEASURES: Patients were staged according to severity of ADC on clinical criteria. Neuropsychological test scores were converted to an impairment score. CSF beta 2M was quantified in both serum and CSF of all patients and in 10 patients with pre- and post-zidovudine assessments. RESULTS: There was a high correlation between CSF beta 2M concentration and severity of ADC (P less than 0.0001); treatment with zidovudine significantly reduced these concentrations (P = 0.013). CSF beta 2M concentration was independent of CSF white-cell count and blood-brain barrier impairment. Other CSF changes in the same patients (including blood-brain barrier permeability to albumin, intrathecal synthesis of immunoglobulin G and HIV-1-p24-antigen levels) were less useful as objective correlates of ADC severity and response to zidovudine therapy. CONCLUSIONS: CSF beta 2M may be a valuable marker of ADC severity and response to antiviral therapy.

AIDS Dementia Complex

The role of the laboratory in the prevention and detection of chronic disease.

Laboratory Initiative For The Year 2000 (LIFT), the laboratory response to the Healthy People 2000 program, includes the following in its definition of chronic disease: cancer, diabetes, hypertension, end-stage renal disease, stroke, and cardiovascular disease. All are priority health targets for which the laboratory must play an active support role if we are to achieve the goal of controlling these diseases by the year 2000. What are the laboratory procedures needed to assist in the prevention and detection of chronic disease? In this review I consider the traditional tests now used in these efforts, emphasize how and where screening for diabetes, cardiovascular disease, and cancer is now done, and describe the current status of the clinical laboratory in supporting these activities, including new and promising procedures that may be useful in identifying individuals at high risk for disease. It is important to initiate good clinical laboratory practice for these new tests as they are transferred from the research laboratory to the clinical laboratory. The laboratory will be required to provide for this need rapidly and at the same time comply with federal and state controls and regulations.

Cardiovascular Diseases

CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer.

The individual and combined value of CA 15-3 and carcinoembryonic antigen (CEA) as breast cancer tumor markers was investigated in longitudinal studies. Patients included women at high risk for recurrence after primary therapy or undergoing treatment for metastatic disease. During follow-up, recurrent disease was documented in 33 of 39 (85%) patients including 11 with local recurrence and 22 with distant metastases. At the time recurrence was first documented by objective criteria 23 of 33 (70%) of the patients presented with abnormal CA 15-3 levels (greater than 36.7 U/ml) compared with 19/33 (58%) with abnormal CEA levels (5 ng/ml). Tumor marker elevations predominated in patients with advanced disease indicating that CA 15-3 and CEA are not reliable for the detection of early breast cancer. Both markers were helpful in monitoring therapeutic response since antigen levels correlated closely with disease status.

Antigens, Neoplasm

Evaluation of CA M26, CA M29, CA 15-3 and CEA as circulating tumor markers in breast cancer patients.

The clinical utility of CA M26 and CA M29 was studied in 116 breast cancer patients and compared with results for CA 15-3 and carcinoembryonic antigen (CEA). The highest sensitivities for breast cancer detection were achieved with CA 15-3 (0.60) and CEA (0.56), but this was compromised by a relative lack of specificity (0.87 and 0.88 for CA 15-3 and CEA, respectively). Sensitivities attained with CA M26 (0.47) and CA M29 (0.53) were lower, but there was an excellent specificity (1.00) for each assay in this series of benign patients. Tumor marker elevations were appreciable with advanced disease such that 82 of 91 patients (90%) with active metastatic breast cancer exhibited at least one abnormal test value. Longitudinal studies demonstrated that CA M26, CA M29, CA 15-3 and CEA complement each other and combinations of these markers reflect disease status better than individual tests.

Adult

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

Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.

Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.

Administration, Oral

Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.

We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.

AIDS Dementia Complex

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

Enzymes used in predicting high risk to colon cancer.

Attempts have been made to use enzyme assays primarily in tissue, to predict risk of colon cancer in high risk colon cancer families, and in patients with polyposis. Efforts have also been made to predict recurrence in surgically "cured" cancer patients. The use of thymidine kinase, ornithine decarboxylase, LDH isoenzymes, and other enzymes for these purposes will be reviewed.

Animals