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Biomedical subjects

J A Baker

Publications and source records attributed to J A Baker.

At least 37 records · Page 2Linked to original sources

Effect of patient history data on the prediction of breast cancer from mammographic findings with artificial neural networks.

RATIONALE AND OBJECTIVES: The authors evaluated the contribution of medical history data to the prediction of breast cancer with artificial neural network (ANN) models based on mammographic findings. MATERIALS AND METHODS: Three ANNs were developed: The first used 10 Breast Imaging Reporting and Data System (BI-RADS) variables; the second, the BI-RADS variables plus patient age; the third, the BI-RADS variables, patient age, and seven other history variables, for a total of 18 inputs. Performance of the ANNs and the original radiologist's impression were evaluated with five metrics: receiver operating characteristic area index (Az); specificity at given sensitivities of 100%, 98%, and 95%; and positive predictive value. RESULTS: All three ANNs consistently outperformed the radiologist's impression over all five performance metrics. The patient-age variable was particularly valuable. Adding the age variable to the basic ANN model, which used only the BI-RADS findings, significantly improved Az (P = .028). In fact, replacing all history data with just the age variable resulted in virtually no changes for Az or specificity at 98% sensitivity (P = .324 and P = .410, respectively). CONCLUSION: Patient age was an important variable for the prediction of breast cancer from mammographic findings with the ANNs. For this data set, all history data could be replaced with age alone.

Adult↗

Sonography of solid breast lesions: observer variability of lesion description and assessment.

OBJECTIVE: The purpose of this study was to measure the level of inter- and intraobserver agreement and to evaluate the causes of variability in radiologists' descriptions and assessments of sonograms of solid breast masses. MATERIALS AND METHODS: Sixty sonograms of solid masses were evaluated independently by five radiologists. Observers used the lexicon of a recently published benchmark report on sonographic appearances of breast masses to determine mass shape, margin, echogenicity, echo texture, presence of echogenic pseudocapsule, and acoustic transmission. Final diagnostic assessments were determined by applying the rule-based model of the same benchmark report to the radiologists' descriptions. In addition, one observer interpreted each case twice to evaluate intraobserver variability. Inter- and intraobserver variability were measured using Cohen's kappa statistic. We also investigated causes of variability in radiologists' descriptions. RESULTS: Interobserver agreement ranged from lowest for determining the presence of an echogenic pseudocapsule (kappa = .09) to highest for determining mass shape (kappa = .8). Intraobserver agreement was lowest for mass echo texture (kappa = .24) and greatest for mass shape (kappa = .79). Variability in descriptions of lesions contributed to interobserver (kappa = .51) and some intraobserver (kappa = .66) inconsistency in assessing the likelihood of malignancy. CONCLUSION: Lack of uniformity among observers' use of descriptive terms for solid breast masses resulted in inconsistent diagnoses. The need for improved definitions and additional illustrative examples could be addressed by developing a standardized lexicon similar to that of the Breast Imaging Reporting and Data System.

Adolescent↗

Predictive model for the diagnosis of intraabdominal abscess.

RATIONALE AND OBJECTIVES: The authors investigated the use of an artificial neural network (ANN) to aid in the diagnosis of intraabdominal abscess. MATERIALS AND METHODS: An ANN was constructed based on data from 140 patients who underwent abdominal and pelvic computed tomography (CT) between January and December 1995. Input nodes included data from clinical history, physical examination, laboratory investigation, and radiographic study. The ANN was trained and tested on data from all 140 cases by using a round-robin method and was compared with linear discriminate analysis. A receiver operating characteristic curve was generated to evaluate both predictive models. RESULTS: CT examinations in 50 cases were positive for abscess. This finding was confirmed by means of laboratory culture of aspirations from CT-guided percutaneous drainage in 38 patients, ultrasound-guided percutaneous drainage in five patients, surgery in five patients, and characteristic appearance on CT scans without aspiration in two patients. CT scans in 90 cases were negative for abscess. The sensitivity and specificity of the ANN in predicting the presence of intraabdominal abscess were 90% and 51%, respectively. Receiver operating characteristic analysis showed no statistically significant difference in performance between the two predictive models. CONCLUSION: The ANN is a useful tool for determining whether an intraabdominal abscess is present. It can be used to set priorities for CT examinations in order to expedite treatment in patients believed to be more likely to have an abscess.

Abdominal Abscess↗

Synthesis, chromatographic resolution and chiroptical properties of carboxyibuprofen stereoisomers: major metabolites of ibuprofen in man.

The chromatographic resolution of the four stereoisomers of carboxy-ibuprofen, a major metabolite of ibuprofen in man, was achieved using a Chiralpak AD chiral stationary phase (CSP) (J.T. Baker, Milton, Keynes, UK). The elution order of the stereoisomers was determined to be 2'S,2R;2'R,2R;2'R,2S;2'S,2S by a combination of stereoselective synthesis of diastereoisomeric mixtures and analysis of the two diastereoisomers isolated from human urine following the administration of (S)-ibuprofen. The individual stereoisomers were isolated by semipreparative chiral phase chromatography and characterized by circular dichroism spectroscopy.

Anti-Inflammatory Agents, Non-Steroidal↗

A mechanistic investigation of the microbial chiral inversion of 2-phenylpropionic acid by Verticillium lecanii.

Previous investigations have described the development of nongrowing suspensions of Verticillium lecanii as a microbial model of the mammalian chiral inversion of the 2-arylpropionic acids (2-APAs). Mechanistic studies in mammals have shown that inversion involves loss of the alpha-methine proton but retention of the original atoms at the beta-methyl position, and a mechanism has been proposed involving enzymatic epimerisation of acyl-CoA thioester derivatives of the substrate. Inversion of the 2-APAs by V. lecanii exhibits extensive intersubstrate variation in the presence, rate, extent, and direction of inversion, which are different from those observed in mammalian systems, possibly indicating differences in the mechanism of inversion between mammalian and microbial cells. This study involved the investigation of proton/deuterium exchange by 1H-nuclear magnetic resonance following incubation of deuterated derivatives of 2-phenylpropionic acid (2-PPA), a model compound, in cell suspensions of V. lecanii and incubation of undeuterated 2-PPA in cell suspensions containing D2O. The results indicated that the inversion of 2-PPA by V. lecanii also involved exchange of the alpha-methine proton but complete retention of the original atoms at the beta-methyl position. No kinetic deuterium isotope effect was observed, indicating that loss of the alpha-methine proton is not the rate-limiting step of the inversion process. This suggests that the observed differences between microbial and mammalian systems probably involve the stereoselective acyl-CoA thioester formation step and not the subsequent epimerisation of the resultant diastereomers.

Buffers↗

Fractal texture analysis in computer-aided diagnosis of solitary pulmonary nodules.

RATIONALE AND OBJECTIVES: The authors investigated the use of fractal texture characterization to improve the accuracy of solitary pulmonary nodule computer-aided diagnosis (CAD) systems. METHODS: Thirty chest radiographs were acquired from patients who had no pulmonary nodules. Thirty regions were selected that were considered remotely suspicious-looking for nodules. Artificial nodules of multiple shapes, sizes, and orientations were added at subtle levels of contrast to 30 non-suspicious-looking regions of the radiographs. Fractal dimensions of the 60 "nodule candidates" were calculated to quantify the texture of each region. Four radiologists also interpreted the images. RESULTS: The fractal dimension of each possible nodule provided statistically significant (P < .05) differentiation between regions that contained an artificial nodule and those that did not. The area under the receiver operating characteristic curve for the fractal analysis was significantly better (P < .05) than that for the radiologists. CONCLUSION: Fractal texture characterization provides useful information for the classification of potential solitary pulmonary nodules with CAD algorithms.

Diagnosis, Computer-Assisted↗

Predicting breast cancer invasion with artificial neural networks on the basis of mammographic features.

PURPOSE: To evaluate whether an artificial neural network (ANN) can predict breast cancer invasion on the basis of readily available medical findings (ie, mammographic findings classified according to the American College of Radiology Breast Imaging Reporting and Data System and patient age). MATERIALS AND METHODS: In 254 adult patients, 266 lesions that had been sampled at biopsy were randomly selected for the study. There were 96 malignant and 170 benign lesions. On the basis of nine mammographic findings and patient age, a three-layer backpropagation network was developed to predict whether the malignant lesions were in situ or invasive. RESULTS: The ANN predicted invasion among malignant lesions with an area under the receiver operating characteristic curve (Az) of .91 +/- .03. It correctly identified all 28 in situ cancers (specificity, 100%) and 48 of 68 invasive cancers (sensitivity, 71%). CONCLUSION: The ANN used mammographic features and patient age to accurately classify invasion among breast cancers, information that was previously available only by means of biopsy. This knowledge may assist in surgical planning and may help reduce the cost and morbidity of unnecessary biopsy.

Biopsy↗

Open reading frame 176 in the photosynthesis gene cluster of Rhodobacter capsulatus encodes idi, a gene for isopentenyl diphosphate isomerase.

Isopentenyl diphosphate (IPP) isomerase catalyzes an essential activation step in the isoprenoid biosynthetic pathway. A database search based on probes from the highly conserved regions in three eukaryotic IPP isomerases revealed substantial similarity with ORF176 in the photosynthesis gene cluster in Rhodobacter capsulatus. The open reading frame was cloned into an Escherichia coli expression vector. The encoded 20-kDa protein, which was purified in two steps by ion exchange and hydrophobic interaction chromatography, catalyzed the interconversion of IPP and dimethylallyl diphosphate. Thus, the photosynthesis gene cluster encodes all of the enzymes required to incorporate IPP into the ultimate carotenoid and bacteriochlorophyll metabolites in R. capsulatus. More recent searches uncovered additional putative open reading frames for IPP isomerase in seed-bearing plants (Oryza sativa, Arabidopsis thaliana, and Clarkia breweri), a worm (Caenorhabditis elegans), and another eubacterium (Escherichia coli). The R. capsulatus enzyme is the smallest of the IPP isomerases to be identified thus far and may consist mostly of a fundamental catalytic core for the enzyme.

Amino Acid Sequence↗

Artificial neural network: improving the quality of breast biopsy recommendations.

PURPOSE: To evaluate the performance and inter- and intraobserver variability of an artificial neural network (ANN) for predicting breast biopsy outcome. MATERIALS AND METHODS: Five radiologists described 60 mammographically detected lesions with the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) nomenclature. A previously programmed ANN used the BI-RADS descriptors and patient histories to predict biopsy results. ANN predictive performance was compared with the clinical decision to perform biopsy. Inter- and intraobserver variability of radiologists' interpretations and ANN predictions were evaluated with Cohen kappa analysis. RESULTS: The ANN maintained 100% sensitivity (23 of 23 cancers) while improving the positive predictive value of biopsy results from 38% (23 of 60 lesions) to between 58% (23 of 40 lesions) and 66% (23 of 35 lesions; P < .001). Interobserver variability for interpretation of the lesions was significantly reduced by the ANN (P < .001); there was no statistically significant effect on nearly perfect intraobserver reproducibility. CONCLUSION: Use of an ANN with radiologists' descriptions of abnormal findings may improve interpretation of mammographic abnormalities.

Biopsy↗

Breast imaging reporting and data system standardized mammography lexicon: observer variability in lesion description.

OBJECTIVE: The American College of Radiology has recommended the Breast Imaging Reporting and Data System (BI-RADS) as a standardized scheme for describing mammographic lesions. The objective of this study was to measure inter- and intraobserver variabilities of radiologists' descriptions of mammographic lesions with the BI-RADS standardized lexicon. MATERIALS AND METHODS: Sixty mammographic studies with abnormal findings were independently evaluated by five radiologists. Readers described each lesion by selecting a single term from the BI-RADS lexicon for each of eight morphologic categories: calcification distribution, number, and description; mass margin, shape, and density; associated findings; and special cases. Additionally, each reader assessed the significance of each lesion on a five-point scale. One observer read each case twice. Inter- and intraobserver variabilities for each description and interpretation category of the BI-RADS lexicon were determined with Cohen's kappa statistic. Radiologists' specific use of calcification descriptors was evaluated in detail. RESULTS: Substantial agreement was observed between readers for choosing terms to describe masses and calcifications (kappa value range, 0.50 +/- 0.02-0.77 +/- 0.03). Intraobserver agreement for these categories was similar (kappa value range, 0.57 +/- 0.07-0.84 +/- 0.09). Considerable inter- and intraobserver variabilities were noted for the "associated findings" and "special cases" categories (kappa value range, -0.02 +/- 0.14-0.38 +/- 0.12), a result that in part reflected the small number of cases to which these categories were assigned. Moderate interobserver variability and little intraobserver variability in the interpretation of lesion significance were noted when an assessment classification similar to that of BI-RADS was used. Use of terms to describe calcifications did not always conform to BI-RADS-defined levels of suspicion. CONCLUSION: BI-RADS is moderately successful in providing a standardized language for physicians to describe lesion morphology. Efforts to reevaluate specific terms and the diagnostic significance assigned to calcification descriptors may prove useful in maintaining the promise of improved quality with the BI-RADS standardized mammography lexicon.

Adult↗

Evaluation of the Arkansas Medicaid primary care physician management program.

Arkansas implemented a primary-care case-management program in February 1994. This study evaluates the program during its first 17 months. Using quarterly data collected for the Health Care Financing Administration (HCFA), a pooled cross-sectional time series analysis (1991:4-1995:2) estimates the effect of eligibles' program enrollment on expenditure (total, inpatient hospital, outpatient hospital, physicians, prescription drugs, laboratory and X-ray) and utilization measures (outpatient visits, physician visits, prescription drugs). The Arkansas Medicaid managed care program appears to have somewhat reduced growth in total vendor payments and also appears to have improved access to primary medical services.

Aid to Families with Dependent Children↗

Computer-aided diagnosis of breast cancer: artificial neural network approach for optimized merging of mammographic features.

RATIONALE AND OBJECTIVES: An artificial neural network (ANN) approach was developed for the computer-aided diagnosis of mammography using an optimally minimized number of input features. METHODS: A backpropagation ANN merged nine input features (age plus eight radiographic findings extracted by radiologists) to predict biopsy outcome as its output. The features were ranked, and more important ones were selected to produce an optimal subset of features. RESULTS: Given all nine features, the ANN performed with a receiver operator characteristic area under the curve (Az) of .95 +/- .01. Given only the four most important features, the ANN performed with an Az of .96 +/- .01. Although not significantly better than the ANN with all nine features, the ANN with the four optimized features was significantly better than expert radiologists' Az of .90 +/- .02 (p = .01). This four-feature ANN had a 95% sensitivity and an 81% specificity. For cases with calcifications, the radiologists' performance dropped to an Az of .85 +/- .04, whereas a specialized three-feature ANN performed significantly better with an Az of .95 +/- .02 (p = .02). CONCLUSION: Given only four input features, the ANN predicted biopsy outcome significantly better than did expert radiologists, who also had access to other radiographic and nonradiographic data. The reduced number of features would substantially decrease data entry efforts and potentially improve the ANN's general applicability.

Breast Neoplasms↗

Breast cancer: prediction with artificial neural network based on BI-RADS standardized lexicon.

PURPOSE: To determine if an artificial neural network (ANN) to categorize benign and malignant breast lesions can be standardized for use by all radiologists. MATERIALS AND METHODS: An ANN was constructed based on the standardized lexicon of the Breast Imaging Recording and Data System (BI-RADS) of the American College of Radiology. Eighteen inputs to the network included 10 BI-RADS lesion descriptors and eight input values from the patient's medical history. The network was trained and tested on 206 cases (133 benign, 73 malignant cases). Receiver operating characteristic curves for the network and radiologists were compared. RESULTS: At a specified output threshold, the ANN would have improved the positive predictive value (PPV) of biopsy from 35% to 61% with a relative sensitivity of 100%. At a fixed sensitivity of 95%, the specificity of the ANN (62%) was significantly greater than the specificity of radiologists (30%) (P < .01). CONCLUSION: The BI-RADS lexicon provides a standardized language between mammographers and an ANN that can improve the PPV of breast biopsy.

Adult↗

Selenium-based digital radiography of the chest: radiologists' preference compared with film-screen radiographs.

OBJECTIVE: A new digital thoracic radiography system (Thoravision; Philips Medical Systems, Hamburg, Germany), which uses selenium as a detector material, was evaluated for observer preference. The system has been shown to have higher detection efficiency than conventional film-screen systems and thus could provide an image with reduced noise. The hypothesis tested in this study was that the selenium-based digital system would provide an image appearance for conventional thoracic imaging that would be equal or superior to that provided by a conventional film-screen system. MATERIALS AND METHODS: Fifty-three patient volunteers were imaged at 120 kV with both the selenium-based system and a thoracic film-screen combination system (InSight HC; Kodak, Rochester, NY). Posteroanterior and lateral images were acquired with both systems, for a total of 212 images. Both imaging systems included a stationary 12:1 antiscatter grid. Exposures were the same for both imaging systems, and the digital images were printed to film. Images for the same patient were compared by six observers--three specialized chest radiologists and three general radiologists. Images included both normal chest radiographs and radiographs with abnormal findings. Each pair of images was ranked on a scale from 1 to 5 for preference of technique, with a score of 3 indicating no preference. Eleven anatomic features were evaluated in the posteroanterior views, and six features were evaluated in the lateral views. Statistical significance of preference was evaluated with Student's t test. RESULTS: The chest radiologists had a statistically significant preference for the selenium-based system for all 17 features (p < .001). The general radiologists had a statistically significant preference for the selenium-based system for visualization of 10 of the 17 features (p < .05). Neither group had a statistically significant preference for the conventional images in any category. CONCLUSION: The selenium-based system provided an image appearance that was significantly preferred by all radiologists, more strongly by those specializing in chest radiography. This study demonstrates that a digital thoracic imaging system can routinely produce images that are perceived as equal or superior to conventional images.

Artifacts↗

Identification of Cys139 and Glu207 as catalytically important groups in the active site of isopentenyl diphosphate:dimethylallyl diphosphate isomerase.

Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (EC 5.3.3.2) catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP). Active-site thiols at C138 and C139 were recently identified by covalent modification using active-site-directed irreversible inhibitors [Street, I. P., & Poulter, C. D. (1990) Biochemistry 29, 7531-7538; Lu, X. J., Christensen, D. J., & Poulter, C. D. (1992) Biochemistry 31, 9955-9960]. Kinetic studies were conducted with site-directed mutants of IPP isomerase (IPPIase) to evaluate the roles of these amino acids. C138S and C138V mutants were active catalysts with V/K values only 10-fold lower than that of wild-type IPPIase. In contrast, the C139S mutant was a poor catalyst, and the C139A and C139V mutants were inactive. Treatment of the C139S mutant with 3-(fluoromethyl)-3-butenyl diphosphate, an electrophilic active-site-directed irreversible inhibitor, resulted in inactivation of the enzyme by covalent modification of E207. The E207Q and E207V mutants were inactive, suggesting a role for the E207 carboxylate moiety in catalysis.

Amino Acid Sequence↗

Restoration of cognitive abilities by cholinergic grafts in cortex of monkeys with lesions of the basal nucleus of Meynert.

Three groups of marmosets were trained to perform a series of visual discrimination tasks in a Wisconsin General Test Apparatus. Two groups then received bilateral lesions of the basal nucleus of Meynert using the excitotoxin N-methyl-D-aspartate and were found to be severely impaired on relearning a visual discrimination first learnt prior to surgery. One lesioned group then received grafts of acetylcholine-rich tissue dissected from the basal forebrain of fetal marmosets. Three months later the marmosets with lesion alone remained impaired on a number of retention and reversal tasks whereas the transplanted animals were no longer significantly impaired. Histological examination of the brains indicated that all lesioned animals had sustained substantial loss of the cholinergic neurons of the basal nucleus of Meynert (assessed by nerve growth factor receptor immunoreactivity) and that the lesion-alone animals showed marked loss of the cholinergic marker acetylcholinesterase in the dorsolateral frontal and parietal cortex. All transplanted animals had surviving graft tissue (visualized by Cresyl Violet staining, dense acetylcholinesterase staining and the presence of a limited number of nerve growth factor receptor-immunoreactive neurons) in the neocortex and 5/6 transplanted animals showed near complete restitution of acetylcholinesterase staining in frontal and parietal cortex. Examination of individual animal data showed that the animal without this restitution performed very poorly. The performance of the remaining transplanted animals was significantly better than that of the animals with lesion alone. There was a significant positive correlation between the degree of acetylcholinesterase staining and good performance on tasks sensitive to frontal lobe damage. These results demonstrate that acetylcholine-rich tissue transplanted into the neocortex of primates with damage to the cholinergic projections to the neocortex can produce substantial restitution of function provided that an appropriate level of interaction between graft and host tissue is achieved.

Acetylcholine↗