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Biomedical subjects

S A Leon

Publications and source records attributed to S A Leon.

At least 19 recordsLinked to original sources

Development of anemia and recovery in prostate cancer patients treated with combined androgen blockade and radiotherapy.

BACKGROUND: The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined androgen blockade (CAB) and pelvic radiotherapy (XRT). METHODS: Four institutions treated 141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy) for 7-8 weeks. RESULTS: After the XRT, the patients were randomized to receive no further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70 patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/- SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or = 2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an additional 2 months of CAB with concurrent XRT. The decrease in Hb levels paralleled the decreased in testosterone levels. No evidence of blood loss or hemolysis was found. CONCLUSIONS: There was no association between incidence or rate of Hb decrease and race, age, or pretreatment prostate-specific antigen (PSA) levels. However, the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex alone, and approximately 6% with flutamide alone, in our study 81% showed mild to pronounced anemia. Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex, we conclude that the anemia was due to CAB. Recognition of this side effect should avoid unnecessary diagnostic evaluations.

Aged↗

Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy.

To evaluate the diagnostic usefulness of simultaneous determinations of 4 tumor markers (carcinoembryonic antigen, calcitonin, creatinine kinase-BB, and DNA), we studied 31 patients with lung cancer, 22 with benign lung disease, and 15 normal volunteers as control subjects. The measurements were made by radioimmunoassay in bronchoalveolar lavage (BAL) and in serum obtained on the same day. The results showed that in serum, only CEA levels were significantly higher in malignancy; in lavage fluids, all 4 markers were abnormally high in cancer patients when compared with control subjects (p less than 0.05); there was no correlation between the levels in lavage and those in the bloodstream. When the mean levels in lavage of the normal control subjects were designated as the limits for a positive test, significant association was found between malignancy and abnormally elevated marker concentration (p less than 0.01). The particular combination of CEA-BAL greater than 35 ng/mg, CEA-serum greater than 4 ng/ml, and calcitonin-BAL greater than 120 pg/mg taken together with the results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant and benign lung disease. The sensitivity of the bronchoscopy procedure increased from 50 to 89%, with at least 2 positive markers, and had a specificity of 71%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%. We conclude that tumor marker levels in lavage are a useful aid in the diagnosis of malignancy in patients undergoing bronchoscopy.

Adult↗

Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease.

Previous studies showed that patients with neoplasms of various types and origins have abnormally high concentration of DNA in their serum. The current work compares circulating DNA levels in patients with benign or malignant disease of the gastrointestinal tract and determines the diagnostic value of such measurements. DNA was quantitated by radioimmunoassay capable of detecting 25 ng/ml, and as a simple and noninvasive test, it could be a useful addition to other diagnostic procedures. The GI tract was chosen because it affords a comparison of benign, precancerous, and malignant lesions of the same organ. Of the 386 patients studied prospectively, 48% had benign disease and mean DNA levels (+/- SE) of 118 +/- 14 ng/ml, whereas 52% had malignant disease and 412 +/- 63 ng DNA/ml. The difference was statistically significant (P less than 0.001). The DNA assay showed the highest sensitivity for pancreas carcinoma: 90% of the patients had DNA levels above 100 ng/ml, chosen as the upper normal limit. Simultaneous measurements of both DNA and carcinoembryonic antigen (CEA) resulted in increased sensitivity and specificity, even when either marker alone had low sensitivity (gastric carcinoma). The results indicate that serum DNA concentration is markedly elevated in malignancy, and moderately elevated in benign disease, as compared with normal controls. These findings may have diagnostic and prognostic value.

Carcinoembryonic Antigen↗

Plasma and serum concentrations of DNA in pulmonary thromboembolism.

The value of circulating DNA concentrations in the diagnosis of pulmonary embolism (PE) was assessed in 68 consecutive patients, of which 36 (Group 1) had clinical symptoms suggesting PE. The diagnosis of PE was established in 13 patients on the basis of pulmonary angiography (PA) (8 patients) and high probability ventilation-perfusion lung scanning (VPS) (5 patients). Pulmonary embolism was ruled out in 23 patients (by PA, 9 patients; by VPS, 14 patients). We found abnormally high DNA concentrations in 26 of the 36 patients (72%) with suggested PE, but there was no significant differences between patients with and patients without PE (p less than 0.05). The results were compared with the DNA concentrations in the remaining 32 patients (16 medical and 16 surgical cases) who had no clinical evidence of PE (Group 2). Increased DNA concentrations were found in 21 of these (66%). There was no significant difference in mean DNA concentrations between Group 1 and Group 2 (p less than 0.05). We conclude that pulmonary angiography and high probability ventilation-perfusion scanning remain the most reliable methods for the diagnosis of PE.

Adrenal Cortex Hormones↗

DNA in synovial fluid and the circulation of patients with arthritis.

DNA levels were measured in synovial fluids and sera of 106 patients with rheumatoid arthritis (RA), osteoarthritis (OA), gout, pseudogout, and posttraumatic arthritis (TRA). In synovial fluids, the highest concentration was found in rheumatoid arthritis (mean +/- SE 18 +/- 3 microgram/ml for seropositive and 9 +/- 1 microgram/ml for seronegative variants), gout and pseudogout (17 +/- 3 microgram/ml). In contrast, the levels in patients with OA or acute TRA were very low: 0.8 +/- 0.1 microgram/ml an 1.1 +/- 0.2 microgram/ml, respectively. The differences between the means of the first disease group and OA or TRA is statistically significant. A similar pattern was observed for DNA levels in the circulation: in rheumatoid arthritis, the mean concentration was 135 +/- 28 ng/ml and 164 +/- 39 ng/ml for seropositive and seronegative RA, respectively. Again the levels in OA and TRA were much lower, 52 +/- 18 ng/ml and 0 ng/Ml, respectively. The latter are not significantly different from the mean levels of 95 normal, healthy controls (14 +/- 3 ng/ml), whereas the concentration of DNA in the serum of RA patients is significantly higher than in OA, TRA, or normal controls. Serial determinations of DNA and other criteria of disease activity (leukocytes and protein levels in synovial fluid, blood sedimentation rate) in individual patients revealed a strong correlation of elevated values with active episodes. THe results suggest that these parameters reflect tissue damage.

Arthritis↗

A comparison of antinuclear antibodies and DNA-binding antibodies in chronic open-angle glaucoma.

Antinuclear antibodies (ANA) were examined in the sera of 28 patients with chronic open angle glaucoma (COAG) and 24 normal volunteers by an immunoperoxidase technique. Unlike the results of a previous report, no significant difference in titers was found between the two groups. A highly objective radioimmunoassay for DNA antibody was also employed, giving similar results. The increased incidence of ANA at low dilutions in both COAG and normal groups in this study and its absence when measured by radioimmunoassay suggest that positive ANA reactions at such low dilutions are the result of nonspecific binding. The lack of demonstrable differences from normal in ANA- or DNA-binding antibody does not support the results of earlier studies suggesting a humoral immune or autoimmune mechanism in COAG.

Antibodies↗

Free DNA in the serum of cancer patients and the effect of therapy.

A radioimmunoassay for ng quantities of DNA was developed. [125l]lododeoxyuridine-labeled DNA was used as the antigen, and the serum of a lupus erythematosus patient served as the source of antibody. The level of free DNA in the serum of 173 patients with various types of cancer and in 55 healthy individuals was determined by this radioimmunoassay. DNA concentration in the normal controls had a range of 0 to 100 ng/ml with a mean of 13 +/- 3 ng/ml (S.E.). For comparison purposes, the range of 0 to 50 ng/ml was designated as normal, and 93% of controls were found in this range. In the cancer patients, the DNA concentration ranged from zero to mug levels with a mean of 180 +/- 38 ng/ml. Fifty % of the patients values were found in the range of 0 to 50 ng/ml; the other 50% were between 50 and 5000 ng/ml. No correlation could be seen between DNA levels and the size or location of the primary tumor. Significantly higher DNA levels, however, were found in the serum of patients with metastatic disease (mean of 209 +/- 39 ng/ml), as compared to nonmetastatic patients (mean 100 +/- 30, p less than 0.02). After radiation therapy in lymphoma, lung, ovary, uterus, and cervical tumors, the levels decreased in 66 to 90% of the patients, whereas in glioma, breast, colon, and rectal tumors, the DNA levels decreased only in 16 to 33% of the patients. Generally, the decrease in DNA concene of tumor size and reduction of pain. Conversely, when DNA levels either increased or remained unchanged, a lack of response to the treatment was noted. Of 17 patients who died within a year, 13 showed DNA levels that remained high or unchanged, whereas only 4 showed lower levels during treatment. Persistent high or increasing DNA levels in the circulation, therefore, may signal a relapse and are probably a poor prognostic sign. The relatively high percentage (50%) of cancer patients with apparently normal DNA levels would suggest that this test may have low diagnostic value. It should be pointed out, however, that all these patients represent a selected group considered for radiation therapy, usually after surgery and/or chemotherapy. It is possible that a better correlation between DNA levels and cancer will be obtained prior to the initiation of treatment. On the other hand, DNA in the serum may be an important tool for the evaluation of therapy or the comparison of different regimens.

Cell Survival↗

Free DNA in the serum of rheumatoid arthritis patients.

Seventy patients with classical or definite rheumatoid arthritis (RA) were studied in an attempt to correlate the serum levels of free DNA with other features. In 26 patients (37%), levels of DNA ranging from 100-540 ng/ml, with a mean of 187 ng/ml, were found. In additional seven patients with a mean of 257 ng/ml, low levels of anti-DNA-antibody were observed. The remaining of 37 patients (53%) had levels of 0-80 ng/ml in their sera, with a mean of 39 ng/ml. All three groups differed significantly (p less than 0.01) from the control group of 61 healthy individuals, who had levels of 0-80 ng/ml with a mean of 13 ng/ml. The high levels of free DNA were commonly found in patients with more severe symptoms who had active RA for less than 10 years, whereas patients with longer duration of disease showed lower levels of DNA. In addition, elevated DNA levels were found more commonly in patients seronegative for rheumatoid factor (RF). Other clinical features did not show significant differences among these patients. The implications of these findings to the pathogenesis of the disease are discussed.

Arthritis, Rheumatoid↗

Radioimmunoassay for nanogram quantities of DNA.

A direct competitive binding radioimmunoassay for DNA has been developed, using 125I-iododeoxyuridine-labelled DNA as the antigen and the serum from a patient with systemic lupus erythematosus. The assay is sensitive in the range of 25 to 1000 ng/ml of DNA. The sensitivity is determined by the affinity of the antibody: this SLE serum contains a component with an association constant of 9.6 X 10(-5) l/mol active at high dilution (1/10,000). Any biological material, such as serum, synovial fluid or tissue extracts can be tested directly. No interference has been found by DNAse in normal serum, or inhibition by mononucleotides or RNA. Native or denatured DNA from different sources (Escherichia coli, salmon sperm, calf thymus and human placenta) either purified or not, competes equally well for the antibody in this system.

Antibody Specificity↗