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The objective of this study was to determine if increased alcohol exposure is associated with greater use of health services among older veterans. A total of 129 older veterans (> or =65 years old), receiving longitudinal care in a Veterans' Administration primary care clinic, were followed retrospectively for up to 42 months. Subjects were screened at baseline for problem drinking with the CAGE or the quantity-frequency questions from the Alcohol Use Disorders Identification Test (QF-AUDIT), and stratified by exposure into three categories: abstainers, social drinkers, and problem drinkers. Outcomes included total outpatient clinic visits, laboratory tests, radiologic and other technologic procedures, as well as acute care hospitalizations. For all subjects (N = 129), no association was found between alcohol exposure and use of any outpatient services. Among CAGE-screened (n = 62) abstainers, social drinkers, and problem drinkers, significant differences were found in the median number of laboratory tests (7.3 vs. 3.4 vs. 7.1, P = 0.004) and hospitalizations (0.3 vs. 0.0 vs. 0.3, P = 0.001) per patient year of follow-up. No exposure-outcome associations were present, however, among QF-AUDIT-screened subjects (n = 67). We were unable to demonstrate a consistent relationship between alcohol exposure and health services utilization. The effects of alcohol on older veterans' use of health services varied with the method used to measure alcohol exposure. Additional studies are needed to determine whether multiple, or possibly new, measures can more precisely define the health effects of alcohol in older populations.

Because of possibly better activity against colorectal cancer of 5-fluoro-2'-deoxyuridine [floxuridine (FUdR)] compared to 5-fluorouracil (5-FU), and because of improved therapeutic results of leucovorin (LV) modulation of 5-FU, we carried out a phase II study of systemic FUdR and LV in 5-FU-treated patients with metastatic colorectal cancer. Weekly regimens consisted of a 4-hour infusion of LV, 200 mg/m2, and at 2 hours, a 2-hour infusion of FUdR, 30 mg/kg, with weekly dose escalation, as tolerated, to a maximum of 60 mg/kg. Twenty-nine patients were treated; they had a median age of 66, most had good performance status, and all had measurable disease. All had received 5-FU, although three had received it as adjuvant therapy only. Two patients had partial responses (6.9% response rate, 95% confidence interval, 1.9-21.9%) lasting 29 and 19 weeks, and five had stable disease. Median time to progression was 8 weeks and median survival was 36.5 weeks. The median number of courses was 6.5; escalation of FUdR was carried out in 27 patients. Hematologic toxicity was minimal and gastrointestinal toxicity was most frequent, although mild. This regimen, although well tolerated, is minimally effective in previously 5-FU-treated patients with metastatic colorectal cancer.

A clinicopathologic study of 153 cases of thyroid follicular Hurthle cell tumor (HCT) is presented. Follow-up, available in all cases, ranged from 5 to 26 years (median, 9 years). These neoplasms were divided into three categories on the basis of presence and degree of capsular and vascular invasion, pattern of growth (follicular, trabecular, or solid), nuclear atypia, and necrosis. The categories were benign (90 cases), indeterminate (35 cases), and malignant (28 cases). All the tumors classified histologically as benign or indeterminate behaved in a clinically benign fashion. Of the 28 tumors classified histologically as malignant, 20 had a clinically malignant behavior. At survival analysis, no clinical or pathologic feature among the carcinomas was found to correlate with a fatal outcome. It is concluded that histologic criteria alone can distinguish benign from malignant HCT and that clinical or pathologic feature cannot predict behavior among the malignant tumors.

A series of 183 cases of primary endometrial carcinomas were immunohistochemically stained for estrogen receptors (ERs) and progesterone receptors (PRs) using formalin-fixed, paraffin-embedded sections. All specimens were obtained from uterine curettages performed at the time of the initial diagnosis or initial therapy. The ER and PR content in the malignant and benign components (benign epithelium, stroma, and myometrium) was evaluated separately for positivity and divided into three groups according to the percentage of positive cells and the intensity of the nuclear stain. Endometrioid-type adenocarcinoma had the highest degree of positivity for both receptors, followed by adenosquamous carcinoma, serous carcinoma, and clear cell carcinoma. The positivity for ERs and PRs of the malignant component was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P less than 0.01), FIGO grade (P less than 0.001), and nuclear grade (P less than 0.0001) of the tumors. The degrees of ER and PR positivity of the malignant component correlated with each other (P less than 0.0001). There was no association between the depth of myometrial tumor invasion and either receptor status of the malignant component. There was a significant association between the presence of lymph vessel invasion and the positivity for PR. Positivity for PR correlated negatively with the patients' ages (P less than 0.004). The results of this study indicate that immunohistochemical analysis of sex steroid receptor status on formalin-fixed, paraffin-embedded tissue offers an excellent alternative to the standard biochemical procedure.

One hundred eighty-three patients with endometrial carcinoma had both immunohistochemical and biochemical analysis of estrogen receptor (ER) and progesterone receptor (PR) content of the tumor. Biochemical analysis was done on a homogenate of uterine curettings; immunohistochemical stainings were done on formalin-fixed, paraffin-embedded sections. The biochemical method was scored quantitatively and the immunohistochemical, in a semiquantitative way. There was a significant correlation between the immunohistochemical categories of the malignant component of the tumor and the biochemical levels of receptor content (P = 0.0001). The sensitivity of the immunohistochemical method for the ER content was 78.5% and the specificity was 58.2%. The sensitivity for the PR was 52.5% and the specificity was 92.8%. Changing cut-off levels for positivity of the biochemical analysis changed the sensitivity and specificity. Survival was predicted by the immunohistochemical status of the ER (P = 0.001) and PR (P = 0.01). Similarly, it was predicted by the biochemical receptor status. Multivariate analysis of the immunohistochemical receptor status and the biochemical receptor status showed that the immunohistochemically determined estrogen status was the most significant predictor of survival (P = 0.001). The immunohistochemical analysis of sex steroid receptor status on formalin-fixed, paraffin-embedded tissue is not only possible and practical, but also predicts survival.

Seventeen patients with presumed advanced ovarian cancer were treated initially with platinum-based chemotherapy. All patients had either cytologic or histologic findings consistent with an ovarian adenocarcinoma. Eight patients subsequently had surgery: one patient had a complete pathological response and one patient had microscopic disease; both are alive without evidence of disease. Five patients were surgically debulked to less than 1 cm, and one patient had large residual disease after surgery. Four of these patients are alive with disease and one died of disease. Nine patients did not have surgery; two patients had no response to chemotherapy and four patients had stabilization of disease. These six patients have died. Two patients had initial partial responses and are alive with disease. One patient with a complete clinical response at autopsy was without evidence of disease. The follow-up ranged from 7 to 109 months; the median survival was 15 months. Comparison of these 17 patients with 21 patients with stage IV disease and 38 suboptimally debulked patients with stage III disease treated during the same period with aggressive surgery followed by chemotherapy revealed no statistical difference in overall survival between these 17 patients and the two groups of patients. The postoperative hospital stay and complication rate were significantly lower for the 9 patients who had surgery than for the 21 patients with stage IV disease. This report suggests that in patients with presumed ovarian cancer and significant medical problems or with a priori nondebulkable tumor, initial chemotherapy and then surgery should be considered.

A computerized system for the management of a clinical research database has been developed with several attractive features. This relational database management system allows for screen-driven data entry, data checking, system security, and report generation in a timely manner. In addition, the system is cost-effective in a number of ways: (1) development time is considerably reduced due to the inherent programming features of the software, (2) once developed the system can be maintained by nontechnical personnel thereby reducing personnel costs, (3) the system can be developed and maintained on a microcomputer system, and (4) the commercial software used in our system is periodically updated thereby assuring the user of state-of-the-art technology. Beyond the initial expenditures for hardware and software, no additional system costs are incurred. While this system, currently adopted by the Yale Comprehensive Cancer Center, represents an effective approach to handling the data-management needs of a large, single-institution cancer research center, the design and programming methodology can be readily adapted to other research settings.

One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.

Examination of the kinetic parameters for the hydrolysis, by acid proteinases, of a single peptide bond (between p-nitro-L-phenylalanyl and L-phenylalanyl) in a series of oligopeptides has shown that secondary interactions are important factors in determining the catalytic efficiency. Comparison of the action of highly purified pepsinlike enzymes (Rhizopus proteinase, Mucor proteinase, rennin) with that of swine pepsin A indicates significant differences among them, either in the binding of the substrate (as estimated by K(m)), or in the catalytic efficiency (as measured by k(cat)), or both. It may be concluded from these data that, in their action on oligopeptide substrates, the specificity of proteinases operating by a similar catalytic mechanism cannot be explained solely in terms of the amino acid residues flanking the sensitive peptide bond; in addition, the specificity includes significant contributions from secondary interactions arising from complementary relations between parts of the substrate and of the enzyme at a distance from the catalytic site. Data are also presented for the effect of urea (about 1 M) on the kinetic parameters of several acid proteinases; under the conditions of these studies, the binding of the substrate is affected to a much lesser degree than is the catalytic efficiency.