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Biomedical subjects

M R Conaway

Publications and source records attributed to M R Conaway.

10 recordsLinked to original sources

Factors contributing to patient satisfaction with breast reconstruction using silicone gel implants.

Recently, concerns have been raised about risks and benefits of silicone gel implants for breast reconstruction. Using a survey conducted during the silicone controversy that began in 1990, this study examines patient satisfaction in 174 women with silicone breast implants. Overall satisfaction was high; 43 percent indicated complete satisfaction, and only 3 percent stated they were "not at all" satisfied. Satisfaction was correlated with each woman's assessment of how reconstruction met her expectations, particularly expectations about clothes fitting better, feeling whole, looking normal, and having similar-appearing breasts. Higher levels of satisfaction also were associated with lower body mass index and absence of medical problems. While patients appeared satisfied with their reconstructions, 34 percent said they would be completely unlikely to choose silicone implants today. Further research is needed to understand the impact of the silicone breast implant debate on women who have had or may consider breast reconstruction.

Adult

Combinations of multiple serum markers are superior to individual assays for discriminating malignant from benign pelvic masses.

To determine whether measurement of the levels of multiple tumor markers in the preoperative serum of women presenting with a pelvic mass distinguished benign from malignant disease better than the assay of CA 125 alone, sera from 429 patients, 192 of whom had malignant histology, were assayed for 8 different markers: CA 125, macrophage colony-stimulating factor, OVX1, lipid-associated sialic acid (LASA), CA15-3, CA72-4, CA19-9, and CA54/61. The sensitivity and specificity of CA 125 alone (> 35 U/ml) was 78.1 and 76.8%, respectively. A panel consisting of CA 125, OVX1, LASA, CA15-3, and CA72-4 had a sensitivity of 83.3% and specificity of 84.0% when two or more markers were elevated. Using the concentrations of these five markers, logistic regression analysis had a sensitivity of 85.4% and a specificity of 83.1%. Considering the values of markers in different sequences, classification and regression tree analysis substantially improved the sensitivity to 90.6% and the specificity to 93.2%. When applied in clinical practice this approach could improve the management of women presenting with a pelvic mass and may also have application in screening for ovarian cancer.

Biomarkers, Tumor

Bivariate sequential designs for phase II trials.

In this paper we propose methods for designing group sequential phase II trials with two dependent binary endpoints. The emphasis is on the derivation of stopping rules for phase II trials which require the enrollment of a small number of patients. The methods are based on enumerating the exact distribution for the binary endpoints. We illustrate the methods with a recent study which required the use of group sequential design to monitor antitumor activity and toxicity.

Antineoplastic Agents

Overexpression of the protein tyrosine phosphatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression.

BACKGROUND: The p185c-erbB-2 growth factor receptor protein tyrosine kinase (PTK) is overexpressed in one third of human breast cancer patients and indicates a poor prognosis in these patients. Protein tyrosine phosphatases (PTPs) may balance PTK activity as part of normal growth-regulation pathways. PTP1B is an intracellular PTP that is involved in linkage between signal transduction pathways and may interface with inappropriate PTK activity in transformed cells. PURPOSE: The aim of this study was to determine if PTP1B is overexpressed in human mammary tumors and to determine if such overexpression is associated with the overexpression of the p185c-erbB-2 receptor PTK. METHODS: Our samples were frozen sections from 29 human mammary tumors (19 pure infiltrating, two pure intraductal, and eight combined intraductal and infiltrating) and nine sections from normal breast tissue. The sections were immunohistochemically stained for PTP1B and p185c-erbB-2, and the results were analyzed statistically for association between overexpression of the two proteins. Northern blot analysis was used to assess if PTP1B overexpression was coincident with increased transcription of the PTP1B gene. RESULTS: Overexpression of the PTP1B protein was observed in 72.4% of the tumor sections compared with normal epithelium, with maximal expression occurring in 37.9% of the tumors. All of the tumor subtypes, including the pure intraductal lesions, overexpressed PTP1B. Statistical analyses demonstrated a significant association between PTP1B overexpression and breast cancer (P < .038) and between the overexpression of PTP1B and the overexpression of p185c-erbB-2 (P < .006). PTP1B messenger RNA steady-state transcription was consistently increased in tumors versus normal tissues. CONCLUSIONS: PTP1B overexpression is a common phenotypic manifestation in human breast cancers and is associated with over-expression of p185c-erbB-2. Steady-state PTP1B transcription is increased in tumor tissue. IMPLICATIONS: Further studies are needed to determine if PTP1B overexpression balances or augments PTK activity. PTP1B overexpression might also be evaluated as a clinical prognostic factor in human breast cancers.

Blotting, Northern

Overexpression of the tyrosine phosphatase PTP1B is associated with human ovarian carcinomas.

OBJECTIVE: Our purpose was to determine whether protein tyrosine phosphatase 1B is overexpressed in ovarian cancers, possibly altering the balance of intracellular tyrosine phosphorylation. STUDY DESIGN: The expression of protein tyrosine phosphatase 1B was assayed in frozen sections from 54 human ovarian carcinomas and seven normal ovaries by immunochemical staining with monoclonal antibody AE4-2J, which is specific for protein tyrosine phosphatase 1B. The expression of protein tyrosine phosphatase 1B-specific messenger ribonucleic acid in tumors was determined by Northern analysis. The results were analyzed statistically by means of Fisher's exact test. RESULTS: Minimal staining was observed in normal ovarian epithelium. In contrast, 43 of 54 (79.6%) tumors displayed increased protein tyrosine phosphatase 1B expression, which is statistically associated with malignancy. Overexpression was associated with the expression of the p185c-erbB-2, p170EGFR, and p165mCSFR growth factor receptor protein tyrosine kinases. Protein tyrosine phosphatase 1B messenger ribonucleic acid expression was inconsistently increased in tumor cells. CONCLUSION: Increased expression of protein tyrosine phosphatase 1B in ovarian cancers that also express protein tyrosine kinases suggests that protein tyrosine phosphatase 1B may play a role in the growth regulation of ovarian cancers.

Female

Causal nonresponse models for repeated categorical measurements.

This paper uses causal models for nonresponse (Fay, 1986, Journal of the American Statistical Association 81, 354-365) to extend the conditional likelihood procedure for repeated categorical outcome variables to allow for nonrandomly missing data. The extension based on causal models is similar to the log-linear approach presented by Conaway (1992, Journal of the American Statistical Association, 87, 817-824), but has the advantage that the parameters are directly interpretable in terms of the distribution of the outcome variables. As with log-linear model approach, all of the computations can be done with standard statistical software. The methods are first described in terms of a simple example with three binary responses with no covariates and then are applied to a more complicated example. A simulation study evaluates the properties of the estimates based on the proposed method.

Adolescent

Evaluation of prognostic factors and staging in gestational trophoblastic tumor.

OBJECTIVE: To evaluate factors influencing survival and compare current classification systems in women treated for malignant gestational trophoblastic tumor. METHODS: A consecutive series of 454 women treated between 1968-1992 was reviewed retrospectively to identify potential clinical prognostic factors using univariate analysis of life tables. All patients were evaluated using clinical classification, World Health Organization, and recently modified International Federation of Gynecology and Obstetrics (FIGO) staging systems, applied retrospectively. Multivariate Cox regression analysis was used to model potential independent prognostic factors within subsets of the patient population. RESULTS: Factors identified by univariate analysis as potential prognostic influences included age, duration of disease, type of antecedent pregnancy, clinicopathologic diagnosis, site of metastases, number of metastatic sites and foci, tumor size, and prior therapy. The pre-therapy hCG level was not significantly associated with survival (P < .04). Multivariate Cox modeling consistently identified prior therapy, type of antecedent pregnancy, number of metastatic sites, and duration of disease as independent prognostic factors. Clinicopathologic diagnosis and hCG level were of borderline significance only in some models of the total patient population. All classification systems were able to identify low- and high-risk subsets of patients with approximately equal efficiency. The addition of FIGO substages enhanced discrimination between prognostic groups in patients with stage III disease. CONCLUSIONS: Existing systems for the classification of malignant gestational trophoblastic tumor are based in part on factors that are not independently prognostic, such as hCG level or tumor size. These systems discriminate between low- and high-risk patients with approximately equal efficiency. The clinical classification system is currently preferred for determining initial therapy in women with malignant gestational trophoblastic tumors.

Chorionic Gonadotropin

Impact of patient-controlled compression on the mammography experience.

The authors tested the hypothesis that giving women control over the compression portion of the mammography examination results in a less painful experience, greater overall patient satisfaction, and a radiographic image as good as that produced by means of technologist-controlled compression. One hundred nine women undergoing screening mammography at a hospital-based outpatient clinic were studied. Each underwent two-view, screen-film mammography performed in routine fashion except that, by random assignment, one breast was compressed by the technologist and the other breast, by the patient. Patient-controlled compression was significantly (P = .003) less painful than technologist-controlled compression. Overall patient satisfaction (96% [105 of 109]) and willingness to repeat the experience were extremely high. The majority of images (93.5% [202 of 216]) were rated as having good to excellent compression. With minimal patient education, self-compression resulted in an image at least as good as that produced with technologist-applied compression. Further study of this technique is warranted.

Adult

Pre-natal blood lead levels and learning difficulties in children: an analysis of non-randomly missing categorical data.

This paper presents an analysis of categorical variables subject to non-response. We incorporate the incomplete data into the analysis by modelling the distribution of the variables of interest and the non-response mechanism. We discuss issues of model selection and interpretation and the effect of discarding incomplete observations. In addition, we describe how to perform all of the computations with standard statistical software. We discuss the problem of incomplete categorical data within the context of a study of the effect of lead exposure on learning difficulties in children. In this study, many of the children are not observed on some of the variables of interest. It is particularly important in this study to incorporate the incomplete data, since there is evidence that non-response is related to the variables of interest. We reach different conclusions when we incorporate the incomplete data into the analysis than we reach when we discard the incomplete data. We also examine the sensitivity of our conclusions to the choice of a model for the non-response mechanism.

Algorithms