Periodontal innovations. Keys to a creative future.
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Diffusion of Innovation↗
Biomedical subjects
D Thompson
Publications and source records attributed to D Thompson.
Improved diagnostic decision-making in pathology: do inference networks hold the key?
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Bayes Theorem↗
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.
Adenocarcinoma↗
Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides.
Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.
Amino Acid Oxidoreductases↗
Functional bowel disorders. A multicenter comparison of health status and development of illness severity index.
In a multicenter study of patients with painful functional bowel disorders (FBD), we compared the demographic, health status, and diagnostic features of patients with FBD and developed a functional bowel disorder severity index (FBDSI) for research and clinical care. Two hundred seventy patients with FBD in the United States, England, and Canada were surveyed on symptoms and health status, and their physicians made a diagnosis and rated illness severity as mild, moderate, or severe. Comparisons of 22 demographic and clinical variables were made by study site in addition to physicians' severity ratings. To develop the FBDSI, multiple regression analysis used the demographic and clinical variables to predict the physician's rating of severity. We found that most health status measures of patients with FBD across study sites are comparable and the derived and validated FBDSI scoring system uses three easy to obtain variables: FBDSI = [current pain by visual analog scale (0-100)] + [diagnosis of chronic functional abdominal pain (0 if absent and 106 if present)] + [number of physicians visits over previous six months x 11]. The FBDSI can be used to select patients for research protocols and/or follow their clinical outcome or response to treatments over time.
Abdominal Pain↗
Prostatic intraepithelial neoplasia. Quantitation of the basal cell layer with machine vision system.
The aim of this paper is to report on a fully automated procedure to quantify the epithelial cell components in prostatic intraepithelial neoplasia with particular emphasis on the basal cell layer (BCL). Scene segmentation was guided by a knowledge-based system of digitized images recorded from histological section immunostained against high molecular weight keratin and counterstained with hematoxylin and eosin. Scene segmentation involved two major stages. First, the system located and identified the duct and segmented the scene, resulting in "intermediate segmentation products." This stage was followed by a reconstruction process in which the segmentation products (i.e., the lumen and the darkly and lightly stained epithelial cell components) were assembled to form the microscopic structure to achieve working unity. Following this, histometric measurements were made of the reconstructed scene. Computed were the percentage of the duct contour with BCL (90%), and the number and length of gaps in the BCL (19, ranging from 10 to 90 microns). Automated analysis of the BCL is accurate and provides information not readily identified by human examination.
Basement Membrane↗
Machine vision-based histometry of premalignant and malignant prostatic lesions.
The implementation of knowledge-guided control of the processing and segmentation of histopathologic images of prostatic lesions has made automated analysis and interpretation possible. To establish correspondence between histopathologic concepts, terms and diagnostic criteria, and computed histometric entities, "interpretive transforms" are introduced. Scene segmentation is controlled by an expert system following a model-based reasoning process. The expert system is structured as an associative network with frames at each node, which controls a knowledge file and a large library of image processing algorithms.
Expert Systems↗
Diagnostic decision support for prostate lesions.
The diagnostic evaluation of premalignant and malignant lesions of the prostate may benefit from the application of an inference network. Used as a diagnostic decision support system, an inference network provides standardized assessment of diagnostic clues which is supported by computer graphics and comparison imagery, uncertainty management by possibility and probabilistic schemes and the systematic combination of different pieces of diagnostic evidence. This assessment results in a numeric measure of belief in the final diagnosis.
Diagnosis, Computer-Assisted↗
Effects of transforming growth factor-beta on bone marrow macrophage Ia expression induced by cytokines.
The initiation of the immune response is regulated, in part, by the effect of cytokines on the level of expression of major histocompatibility complex (MHC) class II antigens on antigen-presenting cells (APC). The expression of class II antigens on B cell and macrophage APC is induced by IFN-gamma and IL-4, and GM-CSF induces class II expression on macrophages (M phi). Our results show that transforming growth factor-beta (TGF-beta) inhibits IL-4- and GM-CSF-induced Ia gene expression on bone marrow macrophages but enhances IFN-gamma-induced gene expression. Nuclear run-on experiments demonstrated that the inhibitory effects of TGF-beta on GM-CSF- and IL-4-induced Ia antigen expression were primarily posttranscriptional and augmentation of IFN-gamma by TGF-beta was largely transcriptionally regulated.
Animals↗
Sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) in eyedrops improves the tolerability of a topically applied pilocarpine prodrug in rabbits.
The effects of a novel, modified beta-cyclodextrin (SBE4-beta-CD; a variably substituted sulfobutyl ether with an average degree of substitution of four) on eye irritation and miotic response of an ophthalmically applied pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, in albino rabbits were studied. Compared to the commercial pilocarpine eyedrop solution (163 mM, equivalent to 3.4% pilocarpine), 12-24 mM pilocarpine prodrug solutions (equivalent to 0.5-1.0% pilocarpine, respectively) decreased peak miotic intensity (Imax) and increased the time to reach peak (tmax), but did not significantly affect values for the area under the miosis versus time curves (AUC), i.e. 12-24 mM pilocarpine prodrug appeared to be equivalent to 163 mM pilocarpine. Ocularly applied 12-24 mM pilocarpine prodrug solutions, however, were more irritating than a commercial pilocarpine eyedrop solution. Coadministered SBE4-beta-CD significantly decreased the eye irritation of the pilocarpine prodrug solutions. Coadministered SBE4-beta-CD did not affect the miotic response of prodrug solution when the molar ratio of SBE4-beta-CD to prodrug was low. However, increasing the molar ratio of SBE4-beta-CD to prodrug decreased the Imax and AUC values. The results show that eye irritation of the pilocarpine prodrug is prevented by levels of SBE4-beta-CD that do not affect the apparent ocular absorption of the prodrug.
Absorption↗
Developing a corporate-level performance assessment system.
Monmouth Medical Center (Long Branch, New Jersey) developed a corporate-level performance assessment system to provide information to external customers and to use as an internal management tool. In this article, we recount the process used to develop the measurement system and describe some of the indicators included in it.
Efficiency, Organizational↗
From paradigms lost to paradigms regained? The MILTON approach to health care reform.
Proposes the MILTON model of health care policy and management as a framework within which debates about the future reform of the UK National Health Service may be conducted. Reviews the economic, political, social and technological forces which have shaped health care policy and management. Suggests that, at the macrolevel, the paradigm has changed from one based on assessment of needs to one based on securing value for money. At the microlevel, there have been equally profound changes in the nature and availability of work. A theme common to both levels is that of rapid and continuous change. Claims the MILTON model offers a way for the protagonists in the health care debate to locate their arguments about policies of health care provision and the implications for the management of work in a changing world in four planes of the model. The benefits are that the differing positions may be seen more clearly and, arguably more important, that a wider range of options is appreciated when, all too often in the past, arguments have become polarized on a single plane.
Decision Making, Organizational↗
The acute phase protein response in patients receiving subcutaneous IL-6.
IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based on in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of these cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an extensive range of positive and negative acute phase proteins. It was part of a larger investigation to assess the value of IL-6 in the management of chemotherapy-induced thrombocytopenia. IL-6 was administered by a daily subcutaneous injection for 7 days at a dose level of 1, 3, or 10 micrograms/kg/day. Increases in the positive acute phase proteins, serum amyloid A, C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, haptoglobin, alpha 1-antitrypsin, fibrinogen, complement component C3, and caeruloplasmin, were observed, with the greatest incremental changes and fastest responses being seen for C-reactive protein and serum amyloid A protein. The negative acute phase proteins transferrin, transthyretin and retinol binding protein all fell to a nadir within 48-96 h after the first IL-6 injection. Increases in complement component C4 were only found in two patients, which may be related to the increase in circulating TNF-alpha concentrations found only in these patients. This study has therefore shown that IL-6 is capable of causing changes in the majority of acute phase proteins in vivo. Although secondary induction of TNF-alpha was not observed in the majority of patients examined, it is still possible however that other cytokines involved in regulation of the acute phase response, such as IL-1, may have been induced and contributed to the overall response.
Acute-Phase Proteins↗
Bone alkaline phosphatase in rheumatic diseases.
A double monoclonal immunoradiometric assay specific for bone alkaline phosphatase (BAP) was used to determine whether the raised total alkaline phosphatase (TAP) often found in patients with active rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is derived from bone or liver. Fifty-eight patients with RA were compared to 14 with AS and 14 with non-inflammatory rheumatic diseases (NI). None had clinical liver disease and only one had a slightly elevated aspartate transaminase activity. Elevated BAP concentrations were found in seven patients (5 RA, 1 AS, 1 NI), only two of whom also had abnormal TAP. Abnormal TAP activities were found in only three patients (all RA). BAP did not correlate with disease activity in RA or AS. In contrast, TAP correlated with disease activity (assessed by plasma viscosity) in RA (P < 0.002) and gamma-glutamyl transferase (GGT) also correlated with plasma viscosity in RA (P < 0.01). Both TAP and BAP were significantly correlated with GGT in RA (P < 0.001 and P < 0.02, respectively). These findings are discussed, together with possible reasons for the conflicting nature of some of the observations.
Adult↗
In vitro translation using rabbit reticulocyte lysate.
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Acetates↗
Knowledge-guided segmentation and morphometric analysis of colorectal dysplasia.
The histopathologic grading of colorectal adenomatous dysplasia is a subjective process. In this study, automated image analysis using knowledge-guided software was used to quantitatively assess colorectal glandular characteristics. Cases of histologically normal mucosa and of low, moderate and high grade dysplasia were examined using the technique. A total of 19 morphometric and densitometric features were measured on each gland. These included gland shape, epithelial area, nuclear stratification and nuclear optical density. Discriminant analysis of the data revealed those morphometric features which provided the best discrimination between the various histologic groups. The area of epithelium occupied by nuclei was the strongest discriminating variable, and this, in combination with a discriminant function derived from the remaining variables, was used to plot cases in bivariate sample space. The plots revealed that the data for normal glands were consistently well separated from dysplastic gland data. Data sets belonging to the various grades of dysplasia showed varying degrees of separation, depending which two histologic groups the discriminant function was based on. This study showed that automated image analysis of complex histologic scenes is possible using knowledge-guided segmentation and that it can provide useful data for the objective classification of colorectal dysplasia.
Adenoma↗
A hybrid neural and statistical classifier system for histopathologic grading of prostatic lesions.
Neural network and statistical classification methods were applied to derive an objective grading for moderately and poorly differentiated lesions of the prostate, based on characteristics of the nuclear placement patterns. A partly trained multilayer neural network was used as a feature extractor. A hybrid classifier system using a quadratic Bayesian classifier applied to these features allowed grade assignment consensus with visual diagnosis in 96% of fields from a training set of 500 fields and in 77% of 130 fields of a test set.
Humans↗