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Biomedical subjects

R C Rock

Publications and source records attributed to R C Rock.

At least 19 recordsLinked to original sources

Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.

To evaluate the usefulness of serum prostate specific antigen in the preoperative staging of prostate cancer we examined tumor volume and differentiation, as well as benign prostatic hyperplasia volume to determine their influence on serum antigen levels. Serum prostate specific antigen was measured in 350 men with clinically localized prostate cancer and preoperatively in 72 men with documented benign prostatic hyperplasia. Although the mean antigen levels increased with advancing pathological stage, the usefulness of prostate specific antigen to predict pathological stage for an individual patient was limited: 1 of 102 men (0.9%) with prostate specific antigen levels of less than 2.8 ng./ml. had positive lymph nodes and 5 of 5 men with levels of greater than 100 ng./ml. had either seminal vesicle or lymph node involvement. However, for the majority of men (greater than 70%) with prostate specific antigen values between these 2 extremes the antigen levels did not accurately predict pathological stage. Because serum prostate specific antigen levels correlated with morphometrically determined tumor volume (r equals 0.535, p less than 0.01) they should, in fact, be predictive of pathological stage. However, most men with prostate cancer also have varying degrees of benign prostatic hyperplasia tissue in the gland producing prostate specific antigen. We have found that serum prostate specific antigen does not correlate with the volume of benign hyperplasia within the gland (r equals 0.21, p greater than 0.05). In addition, immunohistochemical studies have suggested that the lack of correlation between pathological stage and serum prostate specific antigen might be explained by a decrease in the production of antigen with increasing histological grade. Our findings of a negative correlation (r equals -0.37, p less than 0.01) between serum prostate specific antigen levels and Gleason score adjusted for tumor volume confirmed this suggestion. Consequently, serum prostate specific antigen levels do not reflect tumor burden and pathological stage accurately in individual patients for 2 reasons: 1) the unpredictable contribution from the benign prostatic hyperplasia component of the gland and 2) the decreasing production of prostate specific antigen by higher grade lesions as tumor volume increases.

Adenocarcinoma

The value of prostate-specific antigen in the management of localized prostatic cancer.

Prostate-specific antigen has proven to be a new useful marker for the evaluation of men with prostatic cancer. In addition to its proven value for immunohistochemical staining and for the followup evaluation of men treated with hormonal therapy, the monoclonal immunoradiometric assay for PSA has proven to be a unique, sensitive, and specific marker for the followup evaluation of men who have undergone radical prostatectomy.

Adenocarcinoma

Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy.

The usefulness of prostate specific antigen to predict final pathological stage was studied in 178 consecutive patients. Prostate specific antigen was determined preoperatively in all patients by a monoclonal immunoradiometric assay. All pathological specimens were examined for capsular penetration, seminal vesicle involvement and lymph node involvement. Prostate specific antigen correlated directly with capsular penetration (p less than 0.002), seminal vesicle involvement (p less than 0.02) and lymph node involvement (p less than 0.05). However the diagnostic accuracy of an elevated serum antigen level on an individual basis was only 55 per cent for capsular penetration and 50 per cent for seminal vesicle involvement and lymph node involvement. With a log-linear regression model, the half-life of prostate specific antigen was calculated to be 3.15 +/- 0.09 days. From the equation PSA (t) equals PSA (2) e[-0.2197(t-2)], prostate specific antigen can be used to detect residual cancer on day t in the immediate postoperative period. With respect to long-term followup, 127 patients have been monitored for longer than 2 months postoperatively with prostate specific antigen (mean followup 2 years, range 2 months to 8.6 years). Of the 101 patients who had favorable pathological findings at operation (organ-confined cancer or capsular penetration only) 92 (91 per cent) had a followup antigen concentration in the female range (0.0 to 0.2 ng. per ml.), whereas only 5 of 26 men (19 per cent) with either seminal vesicle involvement or lymph node involvement had an antigen value that was less than 0.2 ng. per ml. All patients with a documented clinical recurrence (8 of 127, 6 per cent) had an elevated followup serum prostate specific antigen concentration. These findings suggest that preoperative levels of prostate specific antigen are not sufficiently reliable to predict final pathological stage on an individual basis in patients with early prostatic cancer, and that the antigen is a sensitive tumor marker for the detection of residual disease after radical prostatectomy and subsequent recurrence of tumor on long-term followup.

Adenocarcinoma

A new biomarker in monitoring breast cancer: CA 549.

Serum biomarkers are not very reliable in assessing outcome or predicting recurrence of breast cancer. Clinically, carcinoembryonic antigen (CEA) is widely used and is elevated in a majority of patients with metastatic breast cancer. However, it is falsely elevated in a wide range of nonmalignant conditions and correlates poorly with disease progression. We evaluated a newly described monoclonal antibody, CA 549, in an immunoradiometric assay which uses two monoclonal antibodies directed against tumor and milk fat globule membranes. CA 549 and CEA were studied in 682 patients, 331 of whom had breast diseases and 99 of whom were followed with multiple serum samples. Of 69 patients with benign breast diseases, 1.5% had elevated CA 549, 0% of 30 pregnant women had elevated CA 549, and 26% of patients with nonmalignant liver disease had CA 549 elevation. In metastatic cancer of prostate, ovary, endometrium, colon, and lung CA 549 was elevated in 12% to 50% of cases with levels less than 120 U/mL. In breast cancer, CA 549 was elevated in 11% of 88 patients who received adjuvant chemotherapy and had no evidence of metastasis; in 23% of 16 patients in complete remission after chemotherapy; in 63% of 52 patients in partial remission after therapy; and in 83% of 106 patients with progression of breast cancer compared with 63% with elevated CEA (P = .001). In diseases of the breast, CA 549 has a sensitivity In diseases of the breast, CA 549 has a sensitivity and specificity of 77% and 92% v 61% and 92% for CEA. Of 99 patients serially monitored with clinically documented breast cancer progression, regression, or stability of disease, CA 549 was statistically significantly superior to CEA in monitoring a greater than 25% change in those patients with metastatic progression (P = .03). CA 549 is a new serum marker that should be control tested in prospective clinical trials alone or in conjunction with other markers.

Adenocarcinoma

Monitoring hepatocellular carcinoma by using a monoclonal immunoenzymometric assay for alpha-fetoprotein.

A monoclonal immunoenzymometric assay for alpha-fetoprotein (M-AFP) was evaluated with respect to its utility in monitoring hepatocellular carcinoma (HCC) patients. Earlier (Clin Chem 1986;32:1318-22), we found this immunoassay to demonstrate abilities similar to polyclonal AFP assays, and we suggested that changes in M-AFP correlated with changes in intrahepatic tumor volume in most HCC patients. In the present study, 107 HCC patients were evaluated between 1978 and 1986. Patient demographics characterized this study population as being similar to those seen in regions with low incidence of HCC. Changes in serum M-AFP concentration correlated moderately (r = 0.55) with changes in intrahepatic tumor volume. The AFP concentration in serum was found to be a statistically significant independent predictor of survival; patients with above-normal M-AFP (AFP[+]) at presentation demonstrated a median survival time of 10 months, compared with 16 months for patients with "normal" values for M-AFP (AFP[-]) (P = 0.008). This prognostic pattern persisted when adjusted for serum bilirubin concentration (AFP[+] 12 months vs AFP[-] 29 months, P = 0.01).

Adolescent

Monitoring breast cancer with CA 549.

CA 549, a new marker for breast cancer, was measured in serum of 719 patients by an immunoradiometric assay involving two monoclonal antibodies: BC4E 549, developed against a breast-tumor cell line, and BC4N 154, developed against milk fat-globule membrane. The reference interval for healthy women was 0-11 kilo-units/L. The percentages of patients with CA 549 greater than 11 kilo-units/L for benign conditions are: 0% pregnancy, 1% breast, 26% liver; and for nonbreast metastatic cancers: 12% endometrial, 33% lung, 40% prostatic, and 50% ovarian. In women with breast cancer who were receiving or had completed adjuvant therapy with no evidence of disease there was an 11% increase in CA 549. For patients with metastatic breast cancer, 19% of those in complete remission, 63% of those in partial remission, and 88% of those with systemic progression had increased CA 549. CA 549 is a more specific marker than carcinoembryonic antigen (CEA) in nonmalignant disease, nonbreast malignancies, and adjuvant breast-cancer patients, and it is more sensitive in breast-cancer patients with progressive disease than is CEA. We could show CA 549 to be superior to CEA for detecting active breast cancer in patients with malignant or nonmalignant breast diseases. In monitoring 19 adjuvant-treated patients, CA 549 correlated more closely with the clinical course than did CEA values and, when increased, predicted a clinical recurrence. In 18 breast-cancer patients with metastasis, monitored for two to three years, the change of CA 549 values paralleled disease courses more often than did CEA values.

Adult

Prostate-specific antigen as a marker for prostatic cancer: a monoclonal and a polyclonal immunoassay compared.

We evaluated the clinical utility of prostate-specific antigen (PSA) in diagnosis and management of prostatic cancer, using a monoclonal immunoradiometric assay (M-PSA) and a polyclonal radioimmunoassay (P-PSA). Assay CVs ranged from 1.3% to 4.9% (M-PSA) and from 5.1% to 8.0% (P-PSA). Detection limits were 0.1 microgram/L (M-PSA) and 0.2 microgram/L (P-PSA). Reference intervals established for healthy men were: 0-2.8 micrograms/L (M-PSA) and 0-4.2 micrograms/L (P-PSA). The regression equation for the PSA concentrations (0-100 micrograms/L) measured in normal men, men with primary prostatic cancer, and men with benign prostatic hypertrophy (BPH) was: P-PSA = 1.603 M-PSA - 0.120 microgram/L (r = 0.9923, n = 201). The P-PSA calibrators yielded one-half their assigned values when analyzed by the M-PSA assay. With either assay there were proportional increases in PSA values with advancing cancer. The proportion of PSA values exceeding the reference interval was 50% for patients with stage A prostatic cancer, 80% (stage B), 100% (stages C and D), and 65% for men with BPH. After radical prostatectomy, the follow-up PSA values for most patients were within the reference intervals for women (0-0.2 microgram/L for M-PSA, 0-0.8 microgram/L for P-PSA). Most patients with above-normal PSA values have clinically detectable disease.

Antibodies

Evaluation of a monoclonal immunoradiometric assay for prostate-specific antigen.

We evaluated the analytical performance of a new monoclonal immunoradiometric assay ("M-PSA") for prostate-specific antigen ("Tandem"; Hybritech Inc.) in comparison with a monoclonal immunoradiometric assay ("M-PAP") for mass measurement of prostatic acid phosphatase ("Tandem") and with a conventional enzyme-activity assay ("E-PAP") for prostatic acid phosphatase (EC 3.1.3.2). For M-PSA, the CVs were 1.3-3.0% within-run and 3.0-4.9% between-run. The minimum detectable mass concentration was 0.10 microgram/L, and linearity extended to 100 micrograms/L. The reference interval for M-PSA in 178 healthy men was 0-2.8 micrograms/L. Serum specimens from men with prostatic disease (primarily prostatic carcinoma and benign prostatic hypertrophy) were assayed by the three methods. Correlation was best between mass measurement (M-PAP) and enzyme activity (E-PAP) for prostatic acid phosphatase (r = 0.958). Results for PSA did not correlate well with those for either M-PAP (r = 0.629) or E-PAP (r = 0.387). PSA was increased in a higher percentage of specimens from men with earlier (clinical stage B) prostatic carcinoma than were results from either assay for PAP.

Acid Phosphatase

Assuring quality of care under DRG-based prospective payment.

The implementation of the Medicare Prospective Payment System (PPS) has sparked growing concern that economic pressures on hospitals may adversely affect quality of care. Potential problems include: premature hospital discharge, inter-hospital transfers of severely ill patients, and increased performance of high-risk procedures on an outpatient basis. Quality assurance efforts by Peer Review Organizations (PROs) and by individual institutions should help keep these forces in check. It will be necessary, however, to develop better monitoring systems containing both clinical and financial "markers" to assure the medical appropriateness of inpatient, as well as ambulatory, services offered under PPS.

Diagnosis-Related Groups

Interpreting thyroid tests in the elderly: updated guidelines.

T4 determinations by themselves have been reported to be cost-effective as a screening test to identify patients with unsuspected thyroid disease. The most consistent finding in healthy older subjects, that of a decrease in circulating T3, means that reference intervals for T3 need to be adjusted downward by as much as 25%.

Aged

Monitoring therapeutic drug levels in older patients.

Reduced renal function is the most important variable to consider in reducing dosage of drugs that are excreted largely unchanged in the urine, eg, cardiac glycosides and aminoglycoside antibiotics. Generally, therapeutic concentrations listed for specific drugs are equivalent for both younger and older adults. The major change in treatment of the elderly is lowering the customary dose to compensate for decreases in metabolism or clearance.

Absorption

Serum creatine kinase isoenzyme MB activity: evaluation of a kit employing agarose-gel electrophoresis with overlay paper fluorescence scanning.

A commercial kit for determining serum creatine kinase isoenzyme MB activity was evaluated. The kit employed agarose-gel electrophoresis followed by incubation of overlay paper on the agarose and then fluorescnece scanning of the paper. Within-day coefficients of variation ranged from 24.9% for a specimen with no elevation of MB activity of 6.6% for a specimen with moderately elevated MB activity. The kit appeared to demonstrate MB in all sera and showed higher than expected values in recovery studies. The kit performed in a relatively linear fashion from 50 to 500 I.U./l total creatine kinase activity. Hemolysis appeared to lower measured MB. For comparison with another method, specimens were also analyzed by microcolumn chromatography, which was found to incompletely separate isoenzymes. The kit produced lower values than microchromatography for specimens with low MB activities and higher values for specimens with elevated MB activities. Patients without corroborative evidence of myocardial injury showed a somewhat hyperbolic relationship between per cent MB and total creatine kinase activity, but MB activity was generally 4 I.U./l or less. Although the kit had serious laboratory shortcomings, it may be as clinically useful as other methodologies.

Chromatography, Ion Exchange

Lipoprotein X and alkaline phosphatase as indicators of cholestasis.

Lipoprotein X is considered to be an indicator of cholestasis, but its clinical usefulness is unclear owing to different methods of measurement in use and varying definitions of cholestasis. We investigated the reliability of the qualitative determination of lipoprotein X in predicting cholestasis, defined here as the presence of stainable bile in tissue sections. Liver tissue and serum were collected from 42 patients. Patients were divided into those who did and those who did not have stainable bile in tissue sections. Lipoprotein X was demonstrated by electrophoresis and polyanion precipitation. Lipoprotein X in serum correlated with the presence of stainable bile (p = 0.0006). A normal range of alkaline phosphatase values correlated with the absence (p = 0.04), but elevated values did not correlate with the presence of stainable bile. In patients known to have elevated alkaline phosphatase, the presence of lipoprotein X still correlated with the presence of bile (p = 0.008). We conclude that lipoprotein X is a reliable indicator of cholestasis and that it is more useful than alkaline phosphatase in this application.

Alkaline Phosphatase

Creatine kinase and lactate dehydrogenase in type 2 glycogenosis (Pompe disease).

At least three varieties of type 2 glycogenosis (Pompe disease) have been described, the most severe of which is an infantile form. The relationship between clinical manifestations, glycogen accumulation, and tissue damage has not been established. Serum levels of creatine kinase (CK [EC 2.7.3.2 adenosine triphosphate:creatine phosphotransferase]) lactate dehydrogenase (LDH [EC 1.1.1.27 L-lactate:NAD oxidoreductase]) and their isoenzyme fractions were used to identify and monitor myocardial damage in this study of an infant with type 2 glycogenosis diagnosed by light microscopy and tissue enzyme assay.

Creatine Kinase

A semi-automated fluorometric method for total estrogens in pregnancy urine.

We report a continuous-flow fluorometric method for total urinary estrogens that involves the Kober reaction, with extraction of the reaction product into dichloroethane containing trichloroacetic acid as described by Hahnel and Jones [Clin. Chim. Acta 16, 185 (1967)]. The dichloroethane extraction gives greater stability to the Kober color and sharper separation of aqueous and organic phases. The analytical system is adjusted to give maximum response to estriol 16alpha,beta-D-glucuronide, the principal estrogen conjugate in urine from late pregnancy, when calibrated with estriol standards. An initial 20-fold dilution of the sample with water increased analytical recovery of estriol conjugates from urine while maintaining adequate fluorescent response. Glucose interference was reduced by dilution and eliminated by treatment with sodium borohydride. Urinary protein up to 20 g/liter did not interfere. Total estriol, as determined by gas-liquid chromatography, comprises about 70% of total urinary estrogens in late pregnancy as measured by our continuous-flow fluorometric method. A reference range is presented based on 209 randomly collected urine specimens in which total urinary estrogens are expressed as a ratio to creatinine.

Chromatography, Gas