Biomedical subjects
D Thompson
Publications and source records attributed to D Thompson.
How to develop and use a Bayesian Belief Network.
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Analysis of the capillary architecture in the precursors of prostate cancer: recent findings and new concepts.
OBJECTIVE: To report on recent findings and new concepts in the remodeling of the capillary architecture in the precursors of prostate cancer. METHODS: Immunohistochemical methods have been adopted in prostate cancer and in its precursors (prostatic intra-epithelial neoplasia) to investigate capillary pattern changes-which were mainly analyzed as capillary frequency- and the degree of endothelial cell proliferation. Several features related to the capillary architecture have been considered. Manual, semiautomatic, and automatic (machine vision) types of evaluation have been used to quantify the features. RESULTS: The data available indicate that: (1) Going from normal prostate through prostatic intra-epithelial neoplasia up to invasive adenocarcinoma, an increasing proportion of capillaries becomes shorter, with open lumen and undulated external contour and with greater proliferation of the endothelial cells and greater expression of type IV collagenase. The highest proportion of touching capillaries is seen in normal prostate, while the lowest is found in invasive adenocarcinoma, being intermediate in prostatic intra-epithelial neoplasia. (2) When total androgen ablation is induced, there is no proliferation of the endothelium, whereas the capillaries are reduced in frequency and represented by small vessels lined by flat endothelial cells and with an open lumen. (3) Automation in the evaluation of the capillary architecture is feasible with a machine vision system. CONCLUSIONS: The progression in prostate carcinogenesis is associated with changes in the capillary architecture. There are some preliminary data indicating that total androgen ablation can inhibit the angiogenesis in precursors of prostate cancer.
Automated reasoning system in histopathologic diagnosis and prognosis of prostate cancer and its precursors.
OBJECTIVE: This article presents the rationale and options offered to diagnostic and prognostic decision support systems for prostate pathology by automated reasoning capabilities. METHODS: The symbolic information used in diagnostic decision-making is systematically ordered, compared, numerically assessed in its probability, and combined such that a conclusion can be drawn. The framework for the processing of such symbolic information may be an expert system, an inference network or a case-based reasoning system. Automated reasoning is implemented by the use of a rule base and information flow control modules. RESULTS: Automated reasoning allows decision support systems to follow highly adaptive decision sequences, capable of handling contradictory evidence, exceptions in diagnostic clue expression, and nonmonotonic decision-making. CONCLUSIONS: Automated reasoning capability in diagnostic and prognostic decision support systems allows highly flexible decision development, very close to human decision procedures.
Knowledge-based image analysis in the precursors of prostatic adenocarcinoma.
OBJECTIVES: It is the objective of this study to present the use of knowledge-guided procedures in quantitative image analysis and interpretation in histopathology. METHODS: The knowledge-guided procedures were implemented in the form of N-gram encoding methods for the search and detection of areas of atypicality or abnormality in histopathologic sections; they were implemented as expert system for automated scene segmentation based on an associative network with frames at each node. The extraction of histometric features from the basal cell layer of prostatic lesions is presented as an example of automated image interpretation. RESULTS: Rapid search algorithms for lesion detection were able to identify approximately 90% of areas labelled as atypical or abnormal by visual assessment, in lesions of colon, prostate and breast. Automated segmentation of very complex histopathologic imagery was possible with a success rate of approximately 80-90%, in sections of prostatic and colonic lesions. Histometry of the deterioration of the basal cell layer in prostatic lesions provided a monotonic trend curve suitable for the measurement of progression or regression. CONCLUSIONS: Knowledge-guided procedures bring external information, not offered by the imagery itself, to bear on image processing and image analytic methods. This has enabled automated analysis and interpretation of very complex imagery, such as from cribriform glands, resulting in quantitative diagnostic information.
Androgen-deprived prostate adenocarcinoma: evaluation of treatment-related changes versus no distinctive treatment effect with a Bayesian belief network. A methodological approach.
OBJECTIVE: To develop and test a Bayesian belief network (BBN) for the identification of prostatic adenocarcinomas (PACs) with combination endocrine therapy (CET) changes from PACs with poor to no treatment CET effect and from untreated PACs. METHODS: A network was designed with a decision node containing three diagnostic alternatives (PAC with CET effect, PAC with poor to no treatment effect, and untreated PAC) and seven first-level evidence nodes for the diagnostic features: nuclear enlargement; frequency of prominent nucleoli; cell cytoplasm vacuolization; shrunken acini; individual infiltrating tumor cells; WHO prostate cancer pattern recognition, and amount of interstitial tissue stroma. Three prototype cases, one for each diagnostic alternative, were used to develop the BBN. The BBN performance was then evaluated in 40 prostatectomies for PAC, consisting of 20 CET treated and 20 untreated cases. RESULTS: The results obtained with the three prototypes showed that the network can identify the diagnostic alternatives with certainty when seven features are polled. When the performance was evaluated in the 40 PACs, the belief values were 1.0 or close to it in most of the cases (the value range is 0.0-1.0; the closer to 1.0, the greater the belief). Moreover, the BBN allowed an identification with high certainty of PACs with treatment-related changes from those either with poor to no treatment effect or untreated. CONCLUSIONS: A BBN for the evaluation of androgen-deprived PAC offers a descriptive classifier which is readily implemented and allows the use of descriptive, linguistic terms.
Business planning in Hong Kong hospitals: the emergence of a seamless health care management process.
This paper examines the progress made by public hospitals in Hong Kong in implementing a business planning approach. A review of available literature suggests two main exploratory themes. The first establishes the key features of business planning in the private sector. The second theme discusses the problems of adapting this approach to the distinctive requirements of the public sector. The literature also suggests three dimensions for evaluating planning: incremental-developmental; reactive-proactive; ends-means. Qualitative data were collected by scrutinizing relevant organizational documentation and by discussions with focus groups formed by participants in the planning process. The data were analyzed against eight key elements of a business plan identified from the literature and from panels of business experts. These elements were found to be present in the Hospital Authority's plans but were less evident in hospital level plans. Because of the unitary nature of hospital organization in Hong Kong, it has been difficult for hospitals to break out of a reactive, incremental and ends-based pattern to a more imaginative identification of the distinctive business and market that they may be in. This is, however, changing rapidly and it is clear that there is in place a robust and 'seamless' health care management process.
Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone.
Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.
Subacute providers measure success.
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Use of intracranial pressure monitoring in the management of childhood hydrocephalus and shunt-related problems.
Although the clinical and radiological diagnosis of hydrocephalus in children is usually straightforward, there exists a minority of patients in whom the decision to shunt can be extremely difficult. Similarly, although the diagnosis of shunt malfunction usually presents little difficulty in the context of an acute blockage, a child can present with a confusing and unpredictable constellation of symptoms that might be caused by conditions separate from shunt malfunction. Continuous intraparenchymal intracranial pressure (ICP) monitoring was used to assess 41 patients with hydrocephalus, either as part of the initial diagnostic evaluation of ventriculomegaly (18 patients) or in the assessment of presumed shunt malfunction (23 patients). In 9 of 18 patients with ventriculomegaly, the ICP was within normal limits and surgical insertion of shunts was avoided. Of the 23 patients being assessed for shunt malfunction, the change in ICP profile indicated a siphoning or overdrainage process in 13. In no patient was there significant attendant morbidity, and the process was well tolerated and simple to perform. Clinical and radiological criteria alone can afford insufficient information in the initial evaluation and the subsequent management of the child with hydrocephalus. ICP monitoring provides a safe means of investigating such patients and provides valuable information upon which to base surgical management.
Knowledge-guided histometry of the basal cell layer in prostatic intraepithelial neoplasia.
OBJECTIVE: To define a procedure for the fully automated evaluation of histopathologic sections of prostatic intraepithelial neoplasia. STUDY DESIGN: The design is based on expert system-guided scene segmentation, the construction of a knowledge file and the defining of histometric measures for assessment of the basal cell layer. RESULTS: A knowledge file specifying a total of 263 entities was constructed. Of 73 multimegapixel-sized images of cribriform glands, 71 were correctly and completely processed. A histometric measure allowing precise indexing of the degree of lesion progression, based on the deterioration of the basal cell layer, was derived. CONCLUSION: The combination of image analytic and immunohistochemical procedures and fully automated processing provides a quantitative measure for evaluating prostatic intraepithelial neoplasia lesion progression and the effects of intervention.
An interactive decision support system for breast fine needle aspiration cytology.
OBJECTIVE: To develop a computerized system to assist in the diagnosis of malignancy in breast fine needle aspiration cytology. STUDY DESIGN: A Bayesian belief network was designed to control uncertainty and allow a diagnostic decision to be reached based on the sequential collection of cytologic information. Ten cytologic features were defined as clues that contribute to the diagnostic discrimination of benign and malignant aspirates. The impact of each feature on the diagnostic decision was quantified by a conditional probability matrix. RESULTS: For the assessment of a new case, the computer guides the user through the diagnosis, prompting him or her for information on each of the diagnostic features in turn. For each feature, the user is presented with a series of digitally stored color microscopic images that have been selected to represent good examples of the different feature grades-e.g., pleomorphism: none, mild, moderate and severe. Each image is mapped to an overlapping curve, and by positioning a line on the spectrum where the user feels the case lies, a membership function vector is calculated and entered as evidence into the network. This results in an update in the belief in the diagnostic alternatives. After all the clues have been assessed, a final diagnostic probability is reported. In addition, a cumulative belief curve can be drawn that maps the change in the diagnostic probabilities after each piece of evidence has been submitted, providing unique insight into the diagnostic process. CONCLUSION: Systems like this represent an important step forward in the use of descriptive classifiers. They impose consistency in terminology, improve reproducibility in the grading of cellular abnormalities and remove subjectivity in interpreting the significance of pvisual clues to diagnosis. As such, they represent a necessary tool in pathologic decision making.
Bone alkaline phosphatase in rheumatoid arthritis: a longitudinal study.
OBJECTIVE: To determine whether the raised total alkaline phosphatase (TAP) found in patients with active rheumatoid arthritis (RA) is derived primarily from an increase of the bone or liver isoenzyme, and to evaluate the treatment effect of steroids and disease modifying antirheumatic drugs (DMARD) on bone alkaline phosphatase (BAP) in serial analyses. METHODS: 58 patients with RA were treated with the DMARD gold sodium thiomalate (n = 22), D-penicillamine (n = 18), or sulfasalazine (n = 18) over a 24 week period with regular assessment of disease activity and measurement of BAP using a newly developed specific double monoclonal radioimmunometric assay. RESULTS: In the RA group as a whole, BAP correlated with TAP at all time points (e.g., Week 0 rs = 0.50, p < 0.0001). In contrast, no correlation was found between the intraindividual change of BAP and TAP between Weeks 4 and 24. TAP was correlated with disease activity (assessed by plasma viscosity rs = 0.33, p < 0.02 for the whole RA group and rs = 0.48, p < 0.0002 for intraindividual change from Weeks 4 to 24). Similarly, gamma-glutamyltranspeptidase was correlated with disease activity (rs = 0.56, p < 0.0001, and rs = 0.50, p < 0.0001, respectively). In contrast, BAP was not correlated with disease activity. Low dose steroids and the 3 DMARD studied had no significant effect on the time course of BAP. CONCLUSION: In the majority of patients with active RA, any increase of TAP is not mirrored by an increase of BAP. This supports the hypothesis that inflammatory reactions result in an increase in the plasma concentration of the membrane bound enzymes of the hepatobiliary system, including gamma-glutamyltranspeptidase and the liver isoenzyme of alkaline phosphatase, which is likely to be responsible, at least in part, for the increase of TAP. Since BAP is not correlated with disease activity, BAP measurements are not useful in monitoring response to treatment.
Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). A methodologic approach.
OBJECTIVE: To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two simple prostatectomy specimens from patients with clinical diagnoses of benign prostatic hyperplasia and treated with finasteride for six months. The feasibility of PIN diagnosis and grading based on "diagnostic distance" was investigated. It is a measure of the "extent" to which the observed features are different from those of the untreated prototypes representing the following diagnostic categories: normal prostate, low and high grade PIN and prostatic adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN diagnosis and grading was dealt with by means of a Bayesian belief network (BBN). RESULTS: The distance measure values of the three PIN foci from the prototype of untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative, arbitrary units. Their distance from the two prostate cancer patterns (large acinar and cribriform) was as high as 8-10. The distance of these foci from either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4, respectively. BBN produced the highest belief values for PIN, thus confirming the morphology-based and diagnostic distance-supported diagnosis; however, the belief values were low for both grades. CONCLUSION: The results provided by BBN analyses and diagnostic distance measures support the conclusion that this methodology is applicable to assessing the efficacy of finasteride treatment of PIN.
Periodontal innovations. Keys to a creative future.
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Improved diagnostic decision-making in pathology: do inference networks hold the key?
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Prostatic intraepithelial neoplasia (PIN). Performance of Bayesian belief network for diagnosis and grading.
Prostatic intraepithelial neoplasia (PIN) diagnosis and grading are affected by uncertainties which arise from the fact that almost all knowledge of PIN histopathology is expressed in concepts, descriptive linguistic terms, and words. A Bayesian belief network (BBN) was therefore used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependences between elements in the reasoning sequence. A shallow network was used with an open-tree topology, with eight first-level descendant nodes for the diagnostic clues (evidence nodes), each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives (decision node). One of the evidence nodes was based on the tissue architecture and the others were based on cell features. The system was designed to be interactive, in that the histopathologist entered evidence into the network in the form of likelihood ratios for outcomes at each evidence node. The efficiency of the network was tested on a series of 110 prostate specimens, subdivided as follows: 22 cases of non-neoplastic prostate or benign prostatic tissue (NP), 22 PINs of low grade (PINlow), 22 PINs of high grade (PINhigh), 22 prostatic adenocarcinomas with cribriform pattern (PACcri), and 22 prostatic adenocarcinomas with large acinar pattern (PAClgac). The results obtained in the benign and malignant categories showed that the belief for the diagnostic alternatives is very high, the values being in general more than 0.8 and often close to 1.0. When considering the PIN lesions, the network classified and graded most of the cases with high certainty. However, there were some cases which showed values less than 0.8 (13 cases out of 44), thus indicating that there are situations in which the feature changes are intermediate between contiguous categories or grades. Discrepancy between morphological grading and the BBN results was observed in four out of 44 PIN cases: one PINlow was classified as PINhigh and three PINhigh were classified as PINlow. In conclusion, the network can grade PIN lesions and differentiate them from other prostate lesions with certainty. In particular, it offers a descriptive classifier which is readily implemented and which allows the use of linguistic, fuzzy variables.