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B L Webber

Publications and source records attributed to B L Webber.

At least 19 recordsLinked to original sources

Part-of relations in anatomy ontologies: a proposal for RDFS and OWL formalisations.

Part-of relations are central to anatomy. However, the definition, formalisation and use of part-of in anatomy ontologies is problematic. This paper surveys existing formal approaches, as well as the use of part-of in the Open Biological Ontologies (OBO) anatomies of model species. Based on this analysis, we propose a minimal ontology for anatomy which is expressed in the Semantic Web languages RDFS and OWL-Full. The paper concludes with a description of the context of this work in capturing cross-species tissue homologies and analogies.

Animals↗

An objective analysis of process errors in trauma resuscitations.

OBJECTIVE: A computer-based system to apply trauma resuscitation protocols to patients with penetrating thoracoabdominal trauma was previously validated for 97 consecutive patients at a Level 1 trauma center by a panel of the trauma attendings and further refined by a panel of national trauma experts. The purpose of this article is to describe how this system is now used to objectively critique the actual care given to those patients for process errors in reasoning, independent of outcome. METHODS: A chronological narrative of the care of each patient was presented to the computer program. The actual care was compared with the validated computer protocols at each decision point and differences were classified by a predetermined scoring system from 0 to 100, based on the potential impact on outcome, as critical/noncritical/no errors of commission, omission, or procedure selection. RESULTS: Errors in reasoning occurred in 100% of the 97 cases studied, averaging 11.9/case. Errors of omission were more prevalent than errors of commission (2. 4 errors/case vs 1.2) and were of greater severity (19.4/error vs 5. 1). The largest number of errors involved the failure to record, and perhaps observe, beside information relevant to the reasoning process, an average of 7.4 missing items/patient. Only 2 of the 10 adverse outcomes were judged to be potentially related to errors of reasoning. CONCLUSIONS: Process errors in reasoning were ubiquitous, occurring in every case, although they were infrequently judged to be potentially related to an adverse outcome. Errors of omission were assessed to be more severe. The most common error was failure to consider, or document, available relevant information in the selection of appropriate care.

Abdominal Injuries↗

Undifferentiated sarcomas of children: pathology and clinical behavior--an Intergroup Rhabdomyosarcoma study.

Undifferentiated soft tissue sarcoma (UND-STS) is the most poorly defined tumor eligible for intergroup Rhabdomyosarcoma Studies (IRS). Recent IRS UND-STS experience was reviewed to assess the histologic characteristics and clinical behavior of undifferentiated sarcomas. Of the 1,527 patients entered on IRS-III and IRS pilot-IV, 96 had tumors classified by the IRS Pathology Committee as UND-STS. Of these, 52 had adequate histologic material for this study. After application of immunohistochemistry, 18 tumors were reclassified, mostly as embryonal rhabdomyosarcomas (RMS), primitive neuroectodermal tumors, and intraabdominal desmoplastic small found cell tumors. The remaining 34 UND-STS had a diffuse hypercellular histologic pattern made up of sheets of medium-sized cells. The tumor cells had a minimal to moderate amount of cytoplasm and a variable nuclear morphology, predominately vesicular with finely granular chromatin. Except for reactivity with antibodies against vimentin, most tumors had a negative immunohistochemical profile. The 5 year Kaplan-Meier survival estimate for patients with non-metastatic disease was 72%, a significant improvement when contrasted with patients diagnosed to have UND-STS in IRS-I and IRS-II.

Adolescent↗

On-line quality [corrected] assurance in the initial definitive management of multiple trauma: evaluating system potential.

The TraumAID system has been designed to provide on-line decision support throughout the initial definitive management of injured patients. Here we describe its retrospective evaluation and the use we subsequently made of judges comments on the validation data to evaluate TraumaTIQ, a new critiquing interface for TraumAID, investigating the question of whether, with timely recording of information, a system could produce commentary in line with that of human experts. Our results show that (1) comparable commentary can be produced, and (2) validation studies, which take great time and effort to conduct, can produce useful data beyond their original design goals.

Evaluation Studies as Topic↗

Simulated casualties and medics for emergency training.

The MediSim system extends virtual environment technology to allow medical personnel to interact with and train on simulated casualties. The casualty model employs a three-dimensional animated human body that displays appropriate physical and behavioral responses to injury and/or treatment. Medical corpsmen behaviors were developed to allow the actions of simulated medical personnel to conform to both military practice and medical protocols during patient assessment and stabilization. A trainee may initiate medic actions through a mouse and menu interface; a VR interface has also been created by Stansfield's research group at Sandia National Labs.

Computer Simulation↗

Herpes virus-like sequences are specifically found in Kaposi sarcoma lesions.

AIM: To detect the prevalence of herpes virus-like DNA sequences in AIDS associated Kaposi sarcoma (KSHV) lesions and normal tissue. METHODS: KSHV detection was performed by polymerase chain reaction (PCR) using four different sets of primers. PCR products were cloned, sequenced, and analysed. RESULTS: All of four biopsies of Kaposi sarcoma lesions and all of three paraffin embedded Kaposi sarcoma tissues were positive for KSHV, while normal tissue from the same patients was negative. Sequence analysis of amplification products revealed polymorphisms that result in amino acid changes of the predicted sequence. CONCLUSIONS: KSHV is prevalent in tissues from Kaposi sarcoma, suggesting a role in the development of the tumour. On this basis, anti-herpes virus agents should be considered to control Kaposi sarcoma.

Acquired Immunodeficiency Syndrome↗

Casualty modeling for real-time medical training.

We present a model for simulating casualties in virtual environments for real-time medical training. It allows a user to choose diagnostic and therapeutic actions to carry out on a simulated casualty who will manifest appropriate physiological, behavioral, and physical responses. Currently, the user or a "stealth instructor" can specify one or more injuries that the casualty has sustained. The model responds by continuously determining the state of the casualty, responding appropriately to medical assessment and treatment procedures. So far, we have modeled four medical conditions and over 20 procedures. The model has been designed to handle the addition of other injuries and medical procedures.

Computer Simulation↗

Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study.

BACKGROUND: There is a need to develop a single prognostically significant classification of rhabdomyosarcomas (RMS) and other related tumors of children, adolescents, and young adults which would be a current guide for their diagnosis, allow valid comparison of outcomes between protocols carried out anywhere in the world, and should enhance recognition of prognostic subsets. METHOD: Sixteen pathologists from eight pathology groups, representing six countries and several cooperative groups, classified by four histopathologic classification schemes 800 representative tumors of the 999 eligible cases treated on Intergroup Rhabdomyosarcoma Study II. Each tumor was classified according to each of the four systems by each of the pathologists. In addition, two independent subsamples of 200 of the 800 patients were reviewed according to the new system, so that 343 distinct patients were reviewed once, and 57 of these twice. RESULTS: A study of the survival rates of all subtypes in the sample of 800 patients led to the formation of a new system. This was tested on two independent subsets of 200 of the original cases and found to be reproducible and predictive of outcome by univariate analysis. A multivariate analysis of the 343 patients classified according to the new system indicated that a survival model including pathologic classification and known prognostic factors of primary site, clinical group, and tumor size was significantly better at predicting survival than a model with only the known prognostic factors. CONCLUSION: This new classification, termed International Classification of Rhabdomyosarcoma (ICR) by the authors, was reproducible and predictive of outcome among patients with differing histologies treated uniformly on the Intergroup Rhabdomyosarcoma II protocols. We believe it should be utilized by all pathologists and cooperative groups to classify rhabdomyosarcomas in order to provide comparability among and within multi-institutional studies.

Adolescent↗

Use of monoclonal antibody 1H1, anticortactin, to distinguish normal and neoplastic smooth muscle cells: comparison with anti-alpha-smooth muscle actin and antimuscle-specific actin.

In preliminary experiments, we found that 1H1, a monoclonal antibody directed against the v-src substrate cortactin, reacts with smooth muscle, myoepithelium, myofibroblasts, and macrophages in formaldehyde-fixed human tissues. To evaluate the use of this antibody as a diagnostic reagent, we tested the immunohistochemical distribution of cortactin in 61 mesenchymal neoplasms, 11 neuroectodermal neoplasms, and eight embryonal epithelial neoplasms. The results were compared with those obtained using antibodies against alpha-smooth muscle actin and muscle-specific actin on a similar set of tissues. With the exception of positive staining in rhabdomyosarcoma, in this series only tumors with smooth muscle differentiation appeared to contain cortactin (16 of 19 leiomyosarcomas, one infantile fibrosarcoma, one malignant fibrous histiocytoma). Immunoelectron microscopy localized cortactin to the actin-associated dense bodies of the microfilament network. We conclude that cortactin may be a useful adjunct to alpha-smooth muscle actin and muscle-specific actin as a marker for the study and diagnosis of smooth muscle neoplasms and related lesions.

Actins↗

Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma.

Cytogenetic analysis has defined specific translocations associated with two of the most common small round cell tumors of childhood, t(11;22) in Ewing's sarcoma and t(2;13) in alveolar rhabdomyosarcoma. We and others have previously demonstrated the diagnostic utility of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for the detection of the t(11;22) encoded EWS/FLI-1 chimeric message in Ewing's sarcoma. More recently, we have cloned the t(2;13)(q35;q14) translocation and have shown that it results in the fusion of the PAX3 gene on chromosome 2 to FKHR, a novel member of the fork-head family of transcription factors on chromosome 13. To define the morphological spectrum of childhood sarcomas that express the t(2;13) encoded PAX3/FKHR chimeric message, we have performed RT-PCR analysis on samples from 44 primary pediatric sarcomas and 8 sarcoma cell lines. PAX3/FKHR chimeric messages were detected in 24 of 27 alveolar, 2 of 12 embryonal, and 0 of 1 pleomorphic rhabdomyosarcoma and in 1 of 2 ectomesenchymomas. In contrast, none of 8 Ewing's sarcomas or 2 undifferentiated sarcomas expressed this message. Chimeric transcripts were detected in all cases with cytogenetic evidence of the (2;13) translocation, and in each case the chimeric PAX3/FKHR message had the identical junction sequence, suggesting that genomic chromosome breaks were clustered in a single intron in both genes. By combining the PAX3/FKHR RT-PCR assay with primers for detection of the Ewing's sarcoma t(11;22) encoded EWS/FLI-1 chimeric transcript, we have developed a multiplex RT-PCR reaction that allows the rapid and accurate identification of either translocation in a biopsy sample.

Base Sequence↗

Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading.

Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas, it is difficult to test standardized treatment protocols for individual tumor entities. Grading has been used successfully to predict outcome of adult sarcomas, but pediatric soft tissue tumors display a notable difference in clinical behavior when compared to older patients. To test systematically a standardized treatment strategy for pediatric nonrhabdomyosarcomastous soft tissue sarcomas devised by the Pediatric Oncology Group, the authors devised a grading schema using concepts of adult grading systems and integrating the unique clinical and morphologic features of pediatric sarcomas. Three grading tiers were devised: Grade I, which includes certain pediatric tumors with little propensity for malignancy; Grade II, which is composed of tumors excluded from Grades I or III by virtue of histologic diagnosis and having <5 mitoses/10 high-power fields or <15% geographic necrosis; and Grade III, which comprises certain tumors known to be clinically aggressive by virtue of histologic diagnosis and non-Grade I tumors with >4 mitoses/10 high-power fields or > 15% necrosis. An initial retrospective analysis on a series of lesions treated at a single institution indicated a strong predictive value for grading. Subsequent prospective studies by the Pediatric Oncology Group continue to verify the prognostic value of pediatric nonrhabdomyosarcomatous soft tissue sarcoma grading, and studies on individual pediatric nonrhabdomyosarcomatous soft tissue sarcomas, such as synovial sarcoma, also indicate the relatively poor outcome of higher grade lesions. Grade can be used to predict outcome of pediatric nonrhabdomyosarcomatous soft tissue sarcomas and to devise treatment strategies for experimental protocols.

Adolescent↗

Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.

BACKGROUND: An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to patho-new subtypes were used as a basis for selection of a proposed new pathologic classification. METHODS: A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions. A 20% sample of the 800 patients was then reviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system, and the cytohistologic system. RESULTS: Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. CONCLUSIONS: There was a general similarity between the agreement reached within the modified conventional, STOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibilty and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems.

Adolescent↗

Solid alveolar rhabdomyosarcomas with the t(2;13). Report of two cases with diagnostic implications.

Two patients having rhabdomyosarcomas with the recently described "solid variant" pattern of alveolar rhabdomyosarcoma are reported. Both tumors had aggressive cytologic features with monotonous sheets of round nuclei, but without fibrous septa, and both had been initially classified as embryonal rhabdomyosarcomas. Cytogenetic analyses of tumor explants from both cases revealed the t(2;13) chromosomal aberration typical of alveolar rhabdomyosarcoma. Both patients died of metastases, despite aggressive surgical and adjuvant therapy. This report represents the first karyotypic analyses of solid alveolar rhabdomyosarcomas and supports the inclusion of these tumors in the alveolar category despite the lack of fibrous septa.

Adolescent↗

Renal tumors in childhood.

A great variety of tumors and tumor-like lesions affect the kidneys in childhood. We have discussed the practical aspects of the examination of tumors because the pathologist's role is becoming more critical to the staging and management of these patients. The use of newer techniques shows promise in renal tumors, and flow cytometry with DNA ploidy analysis may prove useful in more precisely identifying high-risk patients. Invaluable data continue to be generated from the large cooperative groups, particularly the National Wilms' Tumor Study, which helps refine our understanding of the renal tumors and their proper management. Close collaboration between the oncologist, the radiologist, the surgeon, the pathologist, and the radiation oncologist is the mainstay in providing the best possible outcome for these patients.

Adolescent↗

Rhabdomyosarcoma. A new classification scheme related to prognosis.

We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.

Adolescent↗

Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma.

Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.

Adolescent↗

Development and characterization of pediatric osteosarcoma xenografts.

Of 33 surgical specimens of osteosarcoma obtained from 24 patients, eight were established as transplantable tumor lines in immune-deprived CBA/CaJ inbred mice. Each line retained the histological characteristics of the corresponding primary tumor and produced human lactate dehydrogenase isozymes. Volume doubling times, which ranged from a mean of 12.3 +/- 5.6 to 39.3 +/- 9.8 days, were stable for individual lines over multiple passages. Flow cytometric analysis indicated similar cellular DNA content values in the primary human tumors and established xenograft lines; the presence of two separate stem lines, as in the original tumors, was observed in the laboratory models. Comparison of two methods of immune deprivation indicated that thymectomy, whole-body irradiation, and bone marrow reconstitution was associated with a higher rate of successful engraftment than was thymectomy, 1-beta-D-arabinofuranosylcytosine treatment, and whole-body irradiation. Bone marrow-reconstituted mice also showed less variability in tumor volume doubling time. We conclude that osteosarcoma can be heterotransplanted into bone marrow-reconstituted mice with a relatively high success rate and that the xenografts retain features characteristic of the tumors of origin. The availability of these models should prove useful in the development of new therapeutic regimens and in understanding the biology of osteosarcoma.

Animals↗