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Biomedical subjects

M M Wagner

Publications and source records attributed to M M Wagner.

At least 37 records · Page 2Linked to original sources

Using belief networks to enhance sharing of medical knowledge between sites with variations in data accuracy.

Differences in data definition between sites are a known obstacle to sharing of reminder-system rule sets. We identify another data characteristic--data accuracy--with implications for sharing. We reviewed the literature on data accuracy and found reports of high error rates for many data classes used by reminder systems (e.g., problem lists). The accuracy of other, equally important, data classes had not been characterized. Wide variations in accuracy between sites has been observed, suggesting that such differences may pose a previously unrecognized barrier to sharing of reminder rules. We propose a belief-network model for encoding reminder rules that explicitly models site-specific data accuracy and we discuss how encoding knowledge in this format may lower the cost and effort required to share reminder rules between sites.

Artificial Intelligence↗

Evaluation of a belief-network-based reminder system that learns from utility feedback.

PRETRIEVE is a belief-network-based, unsolicited information-retrieval system that performs machine learning based on user feedback. We report here on the document-ordering and document-retrieval performance of PRETRIEVE. We developed a test collection of 410 judgments of document utility in a simulated medical order-entry context. We characterized the validity of these judgments, which were elicited from domain experts, by measuring interrater and intrarater reproducibility. We developed a measure of the quality of document orderings similar to the ROC-curve analysis used to evaluate document-retrieval systems. We found that the ordering performance of the PRETRIEVE system was (1) substantially better than random, (2) somewhat less than ideal, and (3) superior to that of versions of the PRETRIEVE system that used relevance feedback instead of utility feedback. Under a set of assumptions, which we make explicit, we found that the documents retrieved by a version of PRETRIEVE that modeled time cost were of higher utility than those retrieved by a similar rule-based system.

Artificial Intelligence↗

Decision-theoretic information pretrieval: a generalization of reminding.

Reminder systems and clinical medical librarian services often provide information to clinicians without requiring that a clinician actively seek information. This characteristic may explain in part the effectiveness and high clinician acceptance of these systems. We term systems with this characteristic "information pretrieval systems" to distinguish them from information retrieval systems, which require a clinician to articulate an information need in the form of a query. Because of the increasing importance of information pretrieval systems in medical care, we have developed a decision-theoretic model of an ideal information pretrieval system. In this paper, we present this model and suggest its use as an analytic framework for understanding existing approaches, and as a formal basis for a functioning pretrieval system.

Decision Support Techniques↗

Evaluation of a Meta-1-based automatic indexing method for medical documents.

This paper describes MetaIndex, an automatic indexing program that creates symbolic representations of documents for the purpose of document retrieval. MetaIndex uses a simple transition network parser to recognize a language that is derived from the set of main concepts in the Unified Medical Language System Metathesaurus (Meta-1). MetaIndex uses a hierarchy of medical concepts, also derived from Meta-1, to represent the content of documents. The goal of this approach is to improve document retrieval performance by better representation of documents. An evaluation method is described, and the performance of MetaIndex on the task of indexing the Slice of Life medical image collection is reported.

Abstracting and Indexing↗

An automatic indexing method for medical documents.

This paper describes MetaIndex, an automatic indexing program that creates symbolic representations of documents for the purpose of document retrieval. MetaIndex uses a simple transition network parser to recognize a language that is derived from the set of main concepts in the Unified Medical Language System Metathesaurus (Meta-1). MetaIndex uses a hierarchy of medical concepts, also derived from Meta-1, to represent the content of documents. The goal of this approach is to improve document retrieval performance by better representation of documents. An evaluation method is described, and the performance of MetaIndex on the task of indexing the Slice of Life medical image collection is reported.

Abstracting and Indexing↗

A novel, nonsteroidal inhibitor of androgen binding to the rat androgen binding protein: diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl]amino]methylene] propanedioate.

In vitro binding studies demonstrate the binding specificity of a series of 4-aryl-2,6-dimethylpyridines for the rat epididymal androgen binding protein (rABP). The compounds bound competitively to rABP but have very weak or no demonstrable affinity for rat ventral prostate androgen receptor and human sex hormone binding globulin. In particular, compound 11, diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorphenyl]amino]methylene] propanedioate, bound with high affinity to rABP (binding affinity about 1/3 that of the endogenous ligand 5 alpha-dihydrotestosterone). However, additional in vitro binding studies indicated that 11 did not bind to testicular or epididymal ABP from rabbit, rhesus monkey, and human. Nevertheless, the specificity and relatively high affinity of these nonsteroidal compounds make them unique and potentially ideal agents for the study of the role of ABP in spermatogenesis and sperm maturation in the rat.

Androgen-Binding Protein↗

The patient with abdominal injuries.

Pathology of blunt and penetrating abdominal trauma is presented in specific sections. Samples of a focused cue search, nursing diagnostic statements, and defining characteristics are included. Utilization of the aforementioned items are discussed within the context of a case involving victims of an accident resulting from a high-speed chase.

Abdominal Injuries↗

Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist.

Win 49596 is an orally active antiandrogen in the rat. This report describes a series of in vitro and in vivo studies which were performed to characterize the mechanism of action of this compound. In vitro competition and Lineweaver-Burk analyses indicate that Win 49596 binds competitively to the rat ventral prostate androgen receptor with a Ki of 2.2 +/- 0.4 microM. Similar to other androgen antagonists, the relative binding affinity (RBA) of Win 49596 was greater after 1 h of incubation with androgen receptor than after an 18 h incubation (RBA of 2.2 versus 0.05, respectively). Win 49596 did not bind to rat cytosolic uterine estrogen or progesterone receptors or thymus glucocorticoid receptors. Furthermore, Win 49596 did not inhibit rat ventral prostate 5 alpha-reductase or 3 alpha-oxidoreductase, rat adrenal 3 beta-hydroxysteroid dehydrogenase or human placental aromatase activity in vitro at concentrations as high as 10 microM. A series of in vivo studies demonstrated that Win 49596 inhibited the uptake of [3H]testosterone as well as testosterone-induced nuclear accumulation of androgen receptor in the rat ventral prostate. Collectively, these results support direct androgen receptor antagonism as the mechanism for the antiandrogenic effects of Win 49596.

Androgen Receptor Antagonists↗

Antiandrogens do not reverse androgen-induced inhibition of sex hormone-binding globulin levels in adult female rhesus monkeys.

Studies were done to determine if changes in plasma sex hormone-binding globulin (SHBG) levels could serve as a specific marker of androgenic and antiandrogenic activities in rhesus monkeys. Treatment of adult female monkeys for 11 days with 17 alpha-methyltestosterone (MeT) produced dose and time-dependent reductions in SHBG levels. However, the non-steroidal antiandrogen flutamide (80 mg/monkey.day) did not inhibit the reduction in SHBG levels when coadministered with MeT, nor did it have an effect on SHBG levels when given alone. In contrast, the steroidal antiandrogens Win 49596 (100 mg/monkey.day) and cyproterone acetate (80 mg/monkey.day) significantly (P less than 0.01) reduced SHBG plasma concentration to about 50% of pretreatment control values whether given alone or in combination with MeT. Furthermore, Win 49596 reduced SHBG levels at doses as low as 4 mg/monkey, whereas cortico-steroid-binding globulin levels were not affected. In ovariectomized monkeys, MeT treatment (4 mg/monkey.day for 15 days) reduced plasma SHBG levels to 42% of pretreatment values and delayed the onset of withdrawal menstrual bleeding compared to that in controls. When administered concurrently with MeT, flutamide (100 mg/monkey.day) antagonized the effect on withdrawal bleeding, but was without effect on SHBG levels. Therefore, plasma SHBG levels cannot be used as a specific indicator of androgenic or antiandrogenic activity and may not be regulated through the classical androgen receptor.

Androgen Antagonists↗

Pathophysiology related to peripheral vascular disease.

The problems of peripheral vascular diseases are varied and sometimes complex. The major and most common disease is arteriosclerosis obliterans. This problem will continue as the life expectancy increases. The severity of the disease compromises the quality of life. An understanding of the pathophysiologic process is necessary to enhance the quality of life and prevent the terrible and disfiguring complications which can arise as a result of insufficient knowledge.

Adult↗

Multipotential behaviour of cloned rat mesothelioma cells with epithelial phenotype.

Reference cultures derived from a transplantable rat mesothelioma were obtained by cloning cells three times in soft agar. Each line, designated "CARM-Lines", was selected on the basis of their epithelial or fibroblastic phenotype, and their uniform morphology. Three epithelial lines were used for more detailed in vitro studies comparing morphological and biological criteria at early and late passages. All three lines exhibited both epithelial and fibroblastic elements after 10-14 passages in vitro, demonstrating that the dimorphic histology of these tumours could be derived from a single aberrant cell. Morphology and growth characteristics of these cells were density-dependent. Anchorage dependent and independent clonogenic assays did not correlate. Anchorage dependent colony formation was the only parameter which differed markedly from the original parent line in the assays described. In vivo evidence of chondrogenesis and attempted ossification support the concept of a multipotential cell contributing to the diverse primary tumour morphology by cellular modulation or differentiation.

Animals↗

Cell population and histochemistry of asbestos related lesions of rat pleural cavity after injection of various inorganic dusts.

Rats injected intrapleurally with either crocidolite or chrysotile asbestos or silica or saline, were killed at intervals up to 2 years of age. The pleural cavities were washed out immediately after death and the washing used for enumerating cells. In addition tissue from granulomas and mesotheliomas was sectioned and stained for lysosomal enzymes. The total cellular response to silica found in the washout showed a pronounced increase when compared with either asbestos dust or controls; crocidolite gave a decreased response in an early group of the individual cells studied. The most important finding was a decrease in the number of mast cells found to be associated with the injection of both types of fibres. Crocidolite induced granulomas showed the presence of lysosomal enzymes and non-specific esterase in mononuclear cells and giant cells, even two years after injection. With chrysotile, giant cells were only present up to three to four months, and few positively staining cells were noted after 18 months. While the response of cells in the pleural cavity does not differ greatly between the two types of fibres, that in the granulomas highlights the longer lasting action of crocidolite.

Animals↗

Mast cells and inhalation of asbestos in rats.

Mast cell counts were performed on sections taken from the lungs of rats exposed by inhalation to different UICC samples of asbestos fibres for periods ranging from a few days to two years. A comparison of mast cell counts with grades of fibrosis showed that there is a sevenfold increase when there is interlobular linking of the fibrotic lesions (grade 5). Submesothelial mast cells showed a trend of increasing numbers with increasing exposure and with increasing subpleural thickening. Each type of asbestos produced a steady increase in mast cell numbers with increasing exposure. Two samples from animals exposed to chrysotile and two from animals exposed to amphiboles (crocidolite and amosite respectively) had 10 times as many cells as the control group after six and 24 months' exposure. Another amphibole, anthophyllite, produced 50 times more cells than were present in the control specimen appropriate for the heaviest exposure. These results are briefly discussed in relation to further exposure, smoking, and characteristics of the dusts.

Animals↗

HLA-A, B and DR antigens and properdin factor B allotypes in Caplan's syndrome.

Seventy-nine cases of Caplan's lung were typed for HLA-A and B antigens. The antigen Bw45 was present only in those patients with rheumatoid factor and was of significantly higher frequency (13.6%) when compared to a non-coal dust exposed population of 316 (1.0%). Those patients without rheumatoid factor showed an increase in HLA-A1 and B8 (58.6% and 51.7% respectively) when compared to the rheumatoid factor positive group (29.6% and 25.0% respectively). Clinical and radiological reassessment were performed on 49 of these patients who were also typed for HLA-DR antigens and properdin factor B allotypes. HLA-DR4 was raised in the rheumatoid factor positive group with rheumatoid arthritis (55.2% compared to 25.8% in the non-coal dust exposed group and 37.3% in coalworkers with normal radiographs). The HLA-DR results are comparable to those found in other studies of rheumatoid arthritis not associated with pneumoconiosis. The findings for HLA-A1, B8 and DR4, however, were not significant after correction was made for the number of antigens tested for. No particular Bf allotype was found to be associated with either the lung change or the arthritis. The induction of the pulmonary lesion in Caplan's syndrome is discussed in relation to the HLA findings.

Aged↗

Silica-induced malignant histiocytic lymphoma: incidence linked with strain of rat and type of silica.

It has already been established that a single intrapleural inoculation of crystalline silica (quartz) produces malignant lymphomas of histiocytic type (MLHT) in Wistar-derived rats. It has now been shown that after treatment with Min-U-Sil, rats of the Alderley Park strain have a tumour incidence of 35%, whereas the incidence in Agus rats is 5% and in PVG 8%. There was also a significant difference in the incidence of MLHT caused by injecting different samples of crystalline silica, particularly of tridymite. There was correlation between cytotoxicity to mouse peritoneal macrophages and tumour incidence, except for one dust (DQ12). Zeta potential, number of particles and their size range were considered, but the incidence does not show a clear correlation with these measurements. The results are discussed.

Animals↗