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L B Ellwein

Publications and source records attributed to L B Ellwein.

At least 73 records · Page 4Linked to original sources

Preparation methods for light microscopic and ultrastructural studies of fetal rat bladder.

Little is known about in utero urinary bladder embryogenesis and the development of the urothelium of laboratory animals. Previous scanning and transmission electron microscopy studies in rats and mice have indicated that the highly specialized superficial cells of the urothelium complete their differentiation at a very late stage of fetal development or shortly after birth. Limitations in methodology in the past have precluded extensive examination of earlier stages of bladder development. Innovations in preparatory procedures of the bladder of rat fetuses have been developed which make possible detailed scanning and transmission electron microscopic and light microscopic examination of cloaca and urinary bladder as early as day 11 of gestation.

Animals↗

A general probabilistic model of carcinogenesis: analysis of experimental urinary bladder cancer.

A theoretical model of two-stage carcinogenesis has been hypothesized. Variables that are modeled include the populations of normal, initiated, and transformed cells; mitotic rates of these cells; hyperplasia; and the probabilities of cell initiation and transformation during replication. The size of the cell populations can be estimated and mitotic rates determined directly from animal studies. Tumor occurrences at different time intervals following varying periods of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and sodium saccharin administration are known and are used in the indirect estimation of values for unobservable model variables. Model-based analyses suggest FANFT markedly increases the probability of cell initiation in addition to its experimentally verifiable effects on increasing the stem cell population and mitotic rates. Further, experimental results appear inconsistent with the hypothesis that FANFT increases the probability of cell transformation over background levels. Similarly, the effect of sodium saccharin was found to be attributable entirely to increases in stem cell populations and mitotic rates without influencing either the probability of initiation or the probability of transformation.

Animals↗

A decision-analysis methodology for consideration of morbidity factors in clinical decision-making.

An explicit and systematic means of incorporation of good medical practice plus individual patient preferences (utilities) for pretreatment and treatment options for a serious but curable neoplastic disease has been investigated. The methodology allows important quality-of-life information to be transmitted to patients, with the goal of providing an improved basis for informed consent. The example of Hodgkin's lymphoma staging and treatment selection is used. Individual patient utilities can be expressed and incorporated into a formal decision analysis for those who face the option of selecting MOPP chemotherapy or of pursuing the staging process in order to obtain a chance of being treated appropriately with irradiation. Equal survival probabilities for the two options are assumed, thus the short- and long-term toxicities (quality of Life) are the determinants of the decision. Patient-derived utilities can be developed for the 15 categories of anticipated toxicity. This, together with probabilistic inputs regarding toxicity severity and duration, will yield expected utilities for each of the decision options. Three physicians were studied and evaluated in the role of a patient. The physicians' toxicity preferences were different and because of this the management option of choice was different for each. This methodology allows explicit patient preferences to be incorporated into medical decisions without the requirement for detailed patient understanding of testing and/or treatment morbidity frequency and severity.

Adult↗

Comparison of treatments for symptomatic Hodgkin's lymphoma employing decision analysis.

A decision analysis methodology has been developed for addressing a comparison of immediate MOPP chemotherapy without staging to staging followed by medically indicated chemotherapy (MOPP) or radiotherapy (XRT). The patients would have symptomatic Hodgkin's lymphoma. Each test and therapy was previously described in terms of 15 toxicity categories. Each was assigned a probability of the occurrence over the five grades of toxicity. Each grade was assigned an expected duration of the toxicity for each test or therapy. Both actual probabilities and judgmental probabilities were used. Utilities for the 15 toxicity categories were solicited. The staging-test-morbidity outcomes only pertained to decision paths which were directed at a chance to receive XRT as the medically dictated therapy. Relative scalar weights were assigned to each grade IV toxicity of zero utility by three physicians. An additive (linear) model was used to compute composite utilities for the paths. There were three different outcomes for these individuals in the initial analysis: 1) MOPP immediately without staging; 2) MOPP immediately or if staging had proceeded to a negative bone marrow then further staging was preferred; and 3) Staging in order to have any change to receive XRT. When a lower toxicity program of presumed equal efficacy was substituted (ChlVPP) the decision changed so that all three participants now would receive ChlVPP instead of staging based on their personal preferences about morbidity outcomes. Decision analysis can contribute to selection between treatments based on differences in an individual's preferences in regard to varying degrees and spectra of toxicity.

Adult↗

An assessment of the impact of urine cytology screening using a computer-based model of bladder cancer.

Utilizing a computer-based model of bladder cancer, the applications of various urine cytology screening strategies are assessed. Outcomes for patients diagnosed by screening with respect to numbers of cases diagnosed, mean length of life, and numbers of cancer deaths are compared with a similar population of patients diagnosed after the development of symptoms. Diagnostic and treatment modality costs can be used to predict the cost per man-year of life extension afforded by a screening program.

Adult↗

Multistage carcinogenesis in the urinary bladder.

The induction of cancer of the urinary bladder is a multi-stage process involving multiple exogenous and endogenous factors. Based on the classical initiation-promotion model, we have used N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as initiator and sodium saccharin (SAC) or tryptophan as promoters. These latter chemicals have the properties expected of promoters: induction of hyperplasia, reversibility and nonmutagenicity. Also, tumors were induced whether the promoter was administered immediately after FANFT or beginning 6 weeks after FANFT was discontinued, but no tumors resulted if either promoter was given without initiation with FANFT. Factor(s) present in normal urine also are involved in the promotion process, in addition to the role of urine as a carrier of carcinogens. However, administration of SAC to animals with a rapidly proliferating bladder mucosa, induced by ulceration, pellet insertion, or in utero, resulted in bladder tumor induction, even without prior initiation with FANFT. To better understand the complex interaction of the multiple variables in bladder carcinogenesis, a stochastic computer model has been formulated based on long-term carcinogenicity and tissue kinetic studies in vivo. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis.

Animals↗

Quality of life assessment in blindness prevention interventions.

This article discusses the importance of self-reported visual function and quality of life (QOL) assessment in evaluating the effectiveness of eye care and prevention of blindness interventions. Traditional clinical measurements do not provide an adequate characterization of the burden of visual disability faced by the patient in day-to-day activities. The validity, reliability and responsiveness of QOL questionnaires should be demonstrated before general use of such instruments is advocated. A visual function questionnaire currently undergoing psychometric evaluation as part of a clinical study of cataract surgery in India is presented.

Blindness↗

Relationship of DNA adducts derived from 2-acetylaminofluorene to cell proliferation and the induction of rodent liver and bladder tumors.

Pharmacokinetic models have been developed to assist in extrapolating results from rodent bioassays. However, in numerous circumstances, it is necessary to combine such models with cellular response models to fully define interspecies and dose extrapolations. Interactions between pharmacokinetic target tissue end points (DNA adduct formation) and cellular proliferation in liver and urinary bladder carcinogenesis is illustrated with the results from the ED01 study involving 2-acetylaminofluorene administered to female mice. The interaction of genotoxic and cell proliferative effects are also illustrated in a co-carcinogenesis study with low doses of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and high doses of sodium saccharin. The application of such interactions to humans is illustrated for the case of cigarette smoke-induced bladder cancer.

2-Acetylaminofluorene↗

Urinary cytology screening: the decision facing the asymptomatic patient.

Voided-urine cytology as a screen for the early detection of urinary bladder cancer is analyzed to determine its potential in an asymptomatic population. Previous cost-effectiveness assessments predict that screening will extend life-span at a cost-per-detected-case that is comparable to those of other cancer screening efforts. The focus here is on investigating screening from the perspective of the individual contemplating the screening decision. The analysis is based on a computerized model of bladder cancer which integrates a Markov representation of the induction and progression of the disease with algorithms representing diagnostic and therapeutic intervention strategies, intervention effectiveness, and cost. It is shown that the utilities, as well as the probabilities, of true-positive, false-positive, and false-negative screening outcomes are affected by the particular testing regimen employed and the age at which screening takes place. Screening at age 55 or age 65 was analyzed for individuals of normal risk. Analyses predict that the predisposition of cytology screening to identify the high-grade, aggressive form of the disease will result in gains in life expectancy of more than three years for the asymptomatic true-positive case. Results support the decision to screen, and by requiring a repeatedly positive test result, the probability of a false-positive outcome will not exceed that of a true-positive outcome at age 65. Except for the risk of a false-positive outcome, cytology screening compares favorably with what could theoretically be obtained if a 100% accurate screening test were available.

Adult↗