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Biomedical subjects

D J Slymen

Publications and source records attributed to D J Slymen.

At least 37 records · Page 2Linked to original sources

Aquatic biomonitoring of reclaimed water for potable use: the San Diego Health Effects Study.

Highly treated reclaimed wastewater was evaluated as a possible supplement to raw water sources required to meet San Diego's growing need for potable water. Biomonitoring experiments employing fathead minnows (Pimephales promelas) were used to compare reclaimed water with the city's current raw water supply. Juvenile fish were exposed in flow-through aquaria in field laboratories located at the reclamation plant (AQUA II) and at a municipal potable water treatment facility (Miramar). Biomonitoring measurements were survival and growth, swimming performance, and trace amounts of 68 base/neutral/acid extractable organics, 27 pesticides, and 27 inorganic chemicals found in fish tissues after exposure. Biomonitoring revealed differences in survival, growth, and swimming performance only after 90- and 180-d exposure. Reclaimed water and raw water were not readily distinguishable in 28-d chemical bioaccumulation tests in terms of organic chemical contaminants in fish tissue except for pesticide levels, which tended to be higher in raw water. Similar inorganic species were found in samples from both waters, although there was greater evidence of bioaccumulation of certain contaminants from raw water. Based on biomonitoring parameters included in these experiments, the use of reclaimed water to supplement raw water supplies would appear to pose no major public health threats. The results of these studies will be combined with additional health effects information before final conclusions are reached about the suitability of reclaimed water for human consumption.

Animals↗

Mammography knowledge and intentions among insured women.

UNLABELLED: METHOD. A survey was conducted among 1,113 randomly selected insured state university employees to evaluate knowledge of the American Cancer Society mammography guidelines, awareness of insurance coverage for screening mammograms, previous guideline adherence, and future mammography intentions. RESULTS: The survey, which included two mailings with follow-up phone cells of nonresponders, had a refusal rate of 6%. Respondents were relatively more likely to know the guideline for older age groups; 77% knew the guidelines for women 50+. Over one-third of the responders were not aware that their insurance policy covered screening mammograms. For women who had never had a mammogram, insurance knowledge was significantly related to intentions to have a mammogram in the future. Previous screening adherence, as well as future intentions, was positively related to the age of the respondent. The results are contrasted with those of previous studies, and the implications for the content of future breast cancer screening campaigns are discussed.

Adult↗

Breast and cervical cancer screening in older women: the San Diego Medicare Preventive Health Project.

BACKGROUND. This study presents rates and correlates of cancer screening, including mammography, clinical breast exam, breast self-examination, and Pap tests, in older women. Age was the predictor of main interest. RESULTS. Among a sample of female Medicare beneficiaries ages 65 and older, who were members of a health maintenance organization, there was a significant, inverse relationship between age and mammography adherence, while controlling for health status, physician utilization, education, and income. The proportions of subjects ages 65-74 and 75+ never having had a mammogram were 17 and 32%, respectively, and the proportions having had annual mammograms were 40 and 28%, respectively. Pap test frequency showed a trend toward an inverse relationship with age, controlling for demographic and health-related variables. In the youngest age group (65-69), 52% had annual Pap tests, whereas in the oldest group (80+), only 36% had annual Pap tests. Age did not predict frequency of clinical breast exam, and the relationship of age to breast self-examination was inconclusive. The role of the physician in promoting cancer screening is discussed.

Age Factors↗

Functional status as an overall measure of health in adults with cystic fibrosis: further validation of a generic health measure.

We studied the validity of a generic health measure in a population with a chronic, life-shortening illness. Thirty-seven adults with cystic fibrosis (CF) and 46 of their healthy peers completed a questionnaire which included 12 questions on functional status from the RAND Health Insurance Study. For the CF group, the questionnaire and a medical chart review yielded data on 7 additional health variables, including pulmonary function. After data collection, members of the CF group were followed for 5 years, by which time 11 had died. The functional status of the CF group was significantly lower than that of the comparison group. Within the CF group, functional status correlated significantly with 6 of the 7 other health variables. Analysis using the Cox proportional hazards model showed that functional status alone was a significant (p less than 0.001) predictor of a CF subject's survival time; in a multivariate model a non-significant trend suggested that lowered functional status may be associated with an increased risk of early death even after adjustment for pulmonary function and percent ideal body weight. These results extend previous findings and suggest that functional status can be used as an overall measure of health in a wide variety of studies.

Activities of Daily Living↗

Compliance with a 12-month assessment in an elderly cohort participating in a preventive intervention study: the San Diego Medicare Preventive Health Project.

Non-compliance in long-term cohort studies contributes to bias in the estimation of study parameters and loss of power in hypothesis testing. This paper identifies baseline factors associated with non-compliance in a 12-month health assessment among elderly participants in the San Diego Medicare Preventive Health Project, a randomized preventive intervention study. A non-complier was defined as a study subject contacted by telephone by study personnel to schedule an appointment for the 12-month health assessment but who would not or could not attend. Of the almost 1600 contacted subjects, 14.1% did not participate in the evaluation. Using logistic regression, non-compliance was found to be associated with older age, intervention group assignment, nonsingle family residence, no alcohol use, and, to a lesser extent, depression. No interactions between group assignment and other baseline factors were detected. These results may be useful in designing cohort maintenance strategies where greater resources may be devoted to participants at higher risk of non-compliance and attrition.

Aged↗

Radiosensitivity of murine and human melanoma cells: a comparative study with different models.

The in vitro radiosensitivity of one murine melanoma cell line (Cloudman S91 CCL 53.1) and three human melanoma cell strains (C8146C, C8161, and R83-4) were studied. Cells were irradiated by single dose X-rays and plated either in agar or on plastic. The survival curves were fitted by the single-hit multitarget, two-hit multitarget, and quadratic models. Multiple comparisons of the residual sum of squares suggested that the two-hit model was clearly inferior to the single-hit and quadratic models. No statistically significant difference was suggested for either the single-hit or quadratic models. Furthermore, on examination of the differences in correlations between the observed and predicted values, the residual plots (observed minus predicted over dose) failed to suggest a clear advantage of either the single-hit multitarget or the quadratic models. Either model could be recommended for analysis of in vitro radiation data.

Animals↗

Immunobiologic factors predictive of clinical outcome in diffuse large-cell lymphoma.

The prognostic importance of immunobiologic factors in diffuse large-cell lymphoma (DLCL) is studied in 105 consecutive DLCL patients. Multivariate results using the Cox proportional hazards model clearly indicate that the Ki-67 index (P = .002), a marker of cell proliferation activity, and the presence or absence of human leukocyte antigen-DR (HLA-DR) (P = .007) are strong predictors of survival even in the presence of established clinical factors of stage (P = .015) and symptoms (P = .050). Using these four variables, prognostic groups were formed identifying patient groups with varying degrees of risk. The group of patients with three or four risk factors present at the time of diagnosis had a median survival of 4 months compared with a median survival of 59 months for the group with no risk factors. Similarly, prognostic groups for disease-free survival (DFS) were constructed based on the proportional hazards model that involved B versus T phenotype (P = .035) and HLA-DR (P = .054). Median DFS for the patient group with one or two risk factors present was 11 months compared with 43 months with no risk factors present. This study suggests immunobiologic parameters are important predictors of clinical outcome in DLCL patients and are of value in identifying subgroups of patients who have not responded to currently available therapy. The practical significance of this study is to identify parameters that may suggest specific changes in therapy of patient subgroups.

Aged↗

Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course.

Recent data from studies of experimental murine tumors and certain human tumors (primarily melanoma) suggest that tumor-infiltrating T-lymphocytes (T-cell TILs) represent a highly potent and specific host antitumor response. We conducted an immunohistochemical analysis of the T-cell TIL subpopulations in frozen tissue sections taken from 82 consecutive B-cell diffuse large cell lymphoma (DLCL) patients. Initially, we analyzed the relationship in these patients between relapse-free survival (RFS) and their T-cell TIL characteristics. Nineteen patients had a low percentage (less than 6% of Leu-2+ (suppressor/cytotoxic) T-cell TILs, and 63 patients had a high percentage (greater than 6%) of Leu-2+ TILs. We found that a low percentage of Leu-2+ TILs correlated with a reduction in RFS: at 20 mo follow-up, all 19 low Leu-2+ patients had relapsed, whereas 70% of the 63 high Leu-2+ patients remained relapse-free (P = 0.008). No significant correlations appeared between patients' T-cell TIL subsets and overall survival. The percentage of newly diagnosed tumors with low counts of Leu-4+ (pan-T) TILs was marginally greater among interleukin-2 (IL-2) receptor-positive tumors than among IL-2 receptor-negative tumors (50 versus 28%, P = 0.098), which suggests that specific phenotypic characteristics of B-cell DLCL may modulate the host T-cell TIL response. Our results indicate that the host's T-cell TIL response in B-cell DLCL can be quantitated from frozen tissue sections and that this response may be related to disease course. Further related TIL studies may lead to new immunorestorative therapeutic approaches for patients with deficient or aberrant cytotoxic T-lymphocyte host responses.

Adolescent↗

Low circulating T-helper cells in relapsing multiple myeloma.

Peripheral blood T-lymphocyte subsets were studied serially over a 6 year period in 50 patients with monoclonal gammopathy of unknown significance and multiple myeloma. The results were correlated with clinical status as measured by responsiveness to treatment (response vs. relapse). To allow assessment of the effects of treatment per se upon T-lymphocyte subset levels, patients were studied prior to as well as on and off therapy. After adjustment for treatment effects, the significant correlation (P less than 0.001) between low percentages of T4-bearing cells and relapse status persisted in all patients. Following multivariate analysis, beta 2-microglobulin and m-protein values correlated with relapse status, but these correlations were not unexpected since these parameters were often used in association with other clinical and laboratory findings to assess relapse status. The most striking finding of this study was the independent correlation between decreasing percent of T4 levels and increasing probability of relapse (P less than or equal to 0.003). Specifically, in this study the proportion of subjects with T4 levels less than 20% who relapsed was 67% regardless of other parameters. The strength of the correlation between the T4 values and relapse may provide insight into the biology of relapsing myeloma as well as adding a clinically useful test for disease assessment.

Adult↗

Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration.

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second-look laparotomy. As in many other investigations, several factors have been analyzed for predicting second-look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P less than 0.001) were significantly associated with the absence of disease at second-look laparotomy, and both were significant predictors of second-look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second-look laparotomy diminished, however. Actuarial survival after second-look laparotomy was associated with residual tumor size at second-look surgery (P = 0.02). According to second-look findings, the 3-year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% +/- 13.4% 3-year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% +/- 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% +/- 11.4% survival. We also examined the effect of extensive tumor resection at second-look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P less than 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second-look laparotomy.

Actuarial Analysis↗

Radiation survival of murine and human melanoma cells utilizing two assay systems: monolayer and soft agar.

The radiation response of murine and human melanoma cells assayed in bilayer soft agar and monolayer was examined. Cells from the murine melanoma Cloudman S91 CCL 53.1 cell line and three human melanoma cell strains (C8146C, C8161, and R83-4) developed in our laboratory were irradiated by single dose X-rays and plated either in agar or on plastic. D0 values were the same within 95% confidence intervals for cells from the human melanoma cell strains C8146C, C8161, and R83-4 but were dissimilar for the murine cell line CCL 53.1 Dq values were different for all cells studied. The shape of the survival curve for all four melanomas was not identical for cells assayed in soft agar versus cells grown on plastic. This would indicate that apparent radiosensitivity was influenced by the method of assay although there were no apparent consistent differences between the curves generated by monolayer or bilayer soft agar assays.

Animals↗

HLA-DR (Ia) immune phenotype predicts outcome for patients with diffuse large cell lymphoma.

The clinical utility for establishing the immune phenotype in patients with non-Hodgkin's lymphoma is controversial. To help resolve this dilemma, we studied 104 consecutive patients with diffuse large cell lymphoma, the most common subtype of potentially curable non-Hodgkin's lymphomas. The presence or absence of the human class II histocompatibility antigen was determined using the monoclonal antibody anti-HLA-DR (Ia), and the results correlated with pretreatment clinical features and survival. We found that eight HLA-DR negative patients had similar pretreatment clinical characteristics compared with 96 HLA-DR positive patients, but HLA-DR negative patients had a significantly shorter survival duration compared with HLA-DR positive patients (P = 0.003 log-rank). The median survival of the HLA-DR negative patients was 0.5 years compared to 2.8 yr for the HLA-DR positive patients. No HLA-DR negative patient survived beyond 1.5 yr. A multi-variate analysis, adjusting for prognostic factors of known clinical significance, confirmed the importance of HLA-DR as a prognostic factor (P = 0.016). We conclude that determining the presence of HLA-DR is a relatively simple pretreatment study that identifies a small but important group of patients who are not curable using currently available combination chemotherapy.

Aged↗

The aberrancy of immunophenotype and immunoglobulin status as indicators of prognosis in B cell diffuse large cell lymphoma.

To assess the prognostic significance of the immunophenotype in diffuse large cell lymphoma (DLCL), 105 DLCL patients were studied between 1978 and 1987 using a panel of 40 monoclonal antibodies applied to frozen tissue. Eighty-three patients were found to have B cell phenotypes, and 20 patients had T cell phenotypes. Focusing on markers relevant to clinical outcome among B cell LCL showed that lack of expression of the pan B antigens Leu14 and Leu16 were correlated with decreased survival (Leu14, P = 0.01; Leu16, P = 0.06; log-rank). HLA-DR activity also showed that lack of expression of this antigen correlated with poor survival (P = 0.004, log-rank). Kappa light chain immunoglobulin lack of expression showed predictive value for decreased survival as well (P = 0.005, log-rank). Multivariate analyses of known clinically important variables and the immune phenotypes confirm that the loss of HLA-DR and B cell aberrancy are independent factors predicting a poor clinical outcome. Losing some B activation/kappa antigens appears to be a broad biologic phenomenon linking surface antigen lack of expression with decreased survival. This suggests that aberrancy of immunophenotype and immunoglobulin status are key predictors of survival in B-LCL.

Antigens, Surface↗

Pharmacokinetics and metabolism of retinol administered at a chemopreventive level to normal subjects.

Thirteen subjects between the ages of 50 years and 70 years were administered a daily 25,000 IU dose of retinol for 9 months. Two subjects experienced mild skin dryness, headaches, and/or alopecia. There were no significant changes in serum chemistries. High performance liquid chromatography assays for plasma retinol revealed no evidence of drug accumulation; however, there was a significant increase in the plasma concentration-versus-time curve for retinyl palmitate concentrations between the first and subsequent sampling days (P = 0.009). The mean skin retinol and retinyl palmitate concentrations in 7 retinol-treated subjects (131.7 and 15.9 ng/g, respectively) were not significantly different from those observed in 13 age-matched controls (118.9 and 25.5 ng/gm, respectively).

Adipose Tissue↗

The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype.

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas is controversial. Therefore, we conducted the present study of 103 consecutively accrued diffuse large-cell lymphoma (DLCL) patients to define, independently of histologic subtypes, the prognostic importance of phenotyping. We used an extensive panel of monoclonal antibodies to T- and B-cell antigens to assign all patients immunologically into the T-cell (20 patients) or B-cell group (83 patients). The only significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of bulky disease (greater than 10 cm) in B-cell patients (P = .008) and more frequent skin involvement in the T-cell group (P less than or equal to .001). Multiagent doxorubicin-containing chemotherapy regimens were employed as initial therapy in over 83% of the patients in each group. Our study revealed that disease-free survival (DFS) was significantly shorter in the T-cell patients than in the B-cell DLCL patients (median DFS, 10.8 months for T-cell and 42.7 months for B-cell; P = .01, log rank). No patient with T-cell DLCL remained disease free for longer than 2 years, whereas 55% of the B-cell group were disease free at 2 years. Univariate and multivariate analyses of all major prognostic factors of DFS suggest that the T-cell phenotype indicates an incurable subset of DLCL patients. Although the B-cell group had a twofold advantage in median survival (35 months v 18 months), actuarial overall survival was not significantly different between the two patient groups (P = .23). Our results indicate the need for new approaches in the search for a curative treatment for T-cell DLCL.

Adolescent↗

Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67.

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki-67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.

Adolescent↗

Asymptomatic telephone ECG transmissions as an outpatient surveillance system of ventricular arrhythmias: relationship to quantitative ambulatory ECG recordings.

Although ambulatory ECG recordings provide quantitative information in the follow-up of patients with ventricular arrhythmias, they are performed infrequently, potentially missing serious arrhythmias in the unmonitored periods. Telephone ECG systems offer "real-time" ECG information, theoretically functioning as an arrhythmia surveillance system. Thus we incorporated frequent telephone ECG transmissions in two antiarrhythmic drug protocols. The first investigation was designed to show the relationship of telephone and ambulatory ECGs in patients with frequent ventricular tachycardia (VT). The second protocol selected patients with "nonlife-threatening" frequent premature ventricular complexes (PVCs) in whom a second placebo period was instituted to simulate the clinical situation of asymptomatic arrhythmia increase. In both drug trials there was a strong linear relationship between the log-transformed PVC counts of telephone ECG and concomitant PVC, couplet, and VT frequencies on ambulatory ECG. In the VT population, greater than or equal to 1 PVC on telephone ECG reflected the presence of VT on ambulatory ECG (sensitivity 87%; specificity 77%). In the second study, telephone ECG transmissions with PVCs on three consecutive transmissions reflected the change from less than or equal to 10 PVCs/hour to greater than or equal to 40 PVCs/hour on ambulatory ECG within 48 hours. These data support the concept that daily surveillance by means of telephone ECG provides arrhythmia information of qualitative clinical relevance.

Ambulatory Care↗