Growth and characterization of childhood rhabdomyosarcomas as xenografts.

Eleven surgical specimens of childhood rhabdomyosarcoma (RMS), two bone marrow samples, and cells from ascitic fluid from 1 patient were implanted sc into immune-deprived inbred CBA/CaJ mice. From these, seven lines of RMS were obtained as xenografts, each retaining the histologic characteristics of the tumor of origin and human lactate dehydrogenase isozymes; these represented 6 of the 11 surgical specimens, whereas one line originated from the transplanted cells from ascitic fluid. It was concluded that children RMS has a fairly high frequency of heterotransplantability in this system and that such a laboratory model may prove useful in the development of new therapeutic regimens in this disease.

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.

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.

Therapy for childhood soft-tissue sarcomas other than rhabdomyosarcoma: a review of 62 cases treated at a single institution.

The rarity and diverse characteristics of the nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) in children have hindered study of their clinical presentations and response to therapy. Here we describe the findings of a retrospective analysis of 62 cases of NRSTS seen in a single institution from 1962 through 1983. The most common histopathologic diagnosis was synovial sarcoma, occurring in 18 patients, followed by malignant schwannoma in 12. The median age at diagnosis was 11 years (range, 2 months to 20 years). Anatomic sites of primary tumors were the trunk (28), extremity (24), and head and neck (10). Of the 31 patients whose tumors were completely resected, 26 (84%) survive with no evidence of disease. Postoperative chemotherapy, administered to nearly one half of this group, did not produce any demonstrable gains in survival. Only one of the 26 patients with local or metastatic gross tumor after resection survives. We conclude that an aggressive surgical approach is imperative in patients with NRSTS and that the contribution of other treatment modalities needs to be defined in a collaborative group trial.

Diffuse fasciitis with eosinophilia. A clinicopathologic study.

Three cases of diffuse fasciitis with eosinophilia are presented, and their clinical, laboratory and histologic follow-up are outlined. Furthermore histologic comparison with scleroderma is attempted and the literature is reviewed. From our findings, we conclude that diffuse fasciitis with eosinophilia is a distinct clinicopathologic entity.

Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis.

In this restrospective study we review the clinical features of patients with the sicca syndrome in the presence and absence of rheumatoid arthritis. All patients were followed at the National Institutes of Health for at least five years after the diagnosis of sicca syndrome was established. Twenty-two patients had sicca syndrome alone, and 21 patients had definite rheumatoid arthritis and the sicca syndrome. Rheumatoid arthritis tended to precede the developement of sicca syndrome. The mean age at diagnosis of sicca syndrome is the same in both groups. No significant differences in serum innumoglobulins, the third component of complement (C3), rheumatoid factor titer and salivary histopathology were found. However, the clinical features were quite distinct. Patients with sicca syndrome alone had a significantly greater frequency of recurrent parotitis, Raynaud's phenomenon, purpura, lymphadenopathy, myositis and renal involvement. The clinical characteristics of these two groups coupled with the known serologic and genetic differences suggest that sicca syndrome alone is a distinct pathologic entity.

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.

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.

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.

Natural language generation in health care.

Good communication is vital in health care, both among health care professionals, and between health care professionals and their patients. And well-written documents, describing and/or explaining the information in structured databases may be easier to comprehend, more edifying, and even more convincing than the structured data, even when presented in tabular or graphic form. Documents may be automatically generated from structured data, using techniques from the field of natural language generation. These techniques are concerned with how the content, organization and language used in a document can be dynamically selected, depending on the audience and context. They have been used to generate health education materials, explanations and critiques in decision support systems, and medical reports and progress notes.

Prospective evaluation of aspiration needle, cutting needle, transbronchial, and open lung biopsy in patients with pulmonary infiltrates.

Twenty consecutive patients with pulmonary infiltrates undiagnosed by routine, noninvasive methods were entered into a prospective study designed to evaluate the diagnostic yield of four methods of lung biopsy. Percutaneous aspiration needle, cutting needle, transbronchial, and open (anterior thoracotomy) biopsy were performed synchronously on all patients. Specimens were evaluated by microbiological, virological, and pathological methods. The diagnostic yields of the four methods were as follows: aspiration needle, 29%; cutting needle, 53%; transbronchial, 59%; and open lung biopsy, 94%. Open lung biopsy was significantly better in yielding a diagnosis than aspiration needle (p less than 0.001), cutting needle (p less than 0.001), and transbronchial biopsy (p less than 0.04).

Acalculous parotid sialadenopathy.

Acalculous inflammation of the parotid gland has been regarded by some as a specific disorder that can be staged as to the severity of the disease process. A review of the literature, however, indicates a divergence of opinion. It is the purpose of this study to test this hypothesis by a retrospective double-blind analysis of clinical, sialographic and histopathologic findings. Forty-two patients who were seen by the Department of Otolaryngology, Washington University School of Medicine from 1961 to 1970 were evaluated by two separate teams. There were 20 sialograms and 30 pathologic specimens, and all were re-examined. Eleven patients had both sialographic studies and histopathologic examination. The clinical presentations and sialographic findings were reviewed. These findings were then compared to each other. Our results indicate that we could not evaluate the severity of the clinical disease by sialography or histopathology. There was no consistent method of staging the sialographic and pathologic findings. In addition, there was no correlation between these two parameters. They reflect neither the patient's clinical syndrome pattern nor the extent of disease. It appears that the parotid gland responds variable to inflammation. These observations are exemplified by case histories.

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.

The multiple sclerotic osteogenic sarcoma of early childhood.

Two cases of sclerosing osteogenic sarcoma that occurred in early childhood are reported. They and the similar cases reviewed are unusual in their development at an unusually early age, their multicentric presentation and their densely sclerotic nature. These are uncommon manifestations of osteogenic sarcoma and are considered due to proliferative metastatic osteoid formation in areas of rapid bone growth.

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.

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.

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.