Fulminant multiple system atrophy in a young adult presenting as motor neuron disease.

A 34-year-old man demonstrated rapidly progressive motor neuron disease and, late in his 9-month clinical course, exhibited ophthalmoplegia and dysautonomic symptoms. Neuropathology showed spinal and bulbar motor neuron disease with severe involvement of extraocular motor nuclei, degeneration of spinal sympathetic and bulbar parasympathetic nuclei, striatonigral degeneration, and early olivopontocerebellar atrophy. This case underscores the diversity of multiple system atrophy and demonstrates an unusually rapid course in a young patient.

Neural network analysis of serial cardiac enzyme data. A clinical application of artificial machine intelligence.

There has been a recent resurgence of interest in the study and application of computerized neural networks within the broad field of artificial intelligence. These "intelligent machines" are modeled after biological nervous systems and are fundamentally different from the many computerized expert systems that previously have been introduced as clinical decision-making aids. The authors describe a neural network designed and trained to predict the probability of acute myocardial infarction (AMI) based on the analysis of paired sets of cardiac enzymes. The neural network predicted 24 of 24 (100%) AMIs and 27 of 29 (93%) No-AMIs when compared with a pathologist's interpretation of the patient's laboratory data (P less than 0.000001). The authors attempted to validate the network's diagnoses by two independent methods. When compared with echocardiogram and EKG for diagnosis of AMI, the neural network agreed with the cardiologist's interpretation in 12 of 14 (86%) AMIs and 1 of 3 (33%) No-AMIs, but the correlation was not statistically significant. Using autopsy outcome for validation, the neural network agreed with the anatomic evidence in 24 of 26 (92%) AMIs and 4 of 6 (67%) No-AMIs (P = 0.001). The authors conclude that neural networks can be successfully applied to the analysis of cardiac enzyme data and suggest that broader applications exist within the domain of clinical decision support.

Relative prognostic significance of DNA flow cytometry and histologic grading in endometrial carcinoma.

Flow cytometric analyses of the DNA content of neoplastic cells were performed in 60 cases of endometrial carcinoma using formalin-fixed, paraffin-embedded tissues. Each tumor was graded histologically prior to flow cytometry. Aneuploidy was found in almost half of the tumors, including those of moderate and high degrees of differentiation, although the poorly differentiated tumors were more commonly aneuploid. The cytometric and histologic results were then compared with prognosis (5-year survival). In general, survival was greater with diploid than with aneuploid tumors. With well-differentiated tumors, patients with both diploid and aneuploid lesions had a favorable prognosis, but with moderately and poorly differentiated tumors those with diploidy had a more favorable prognosis than those with aneuploidy. We conclude that flow cytometry is of principal prognostic value in poorly differentiated endometrial carcinomas.

Fine needle aspiration cytology of metastatic dermatofibrosarcoma protuberans. A case report.

Report is made of the fine needle aspiration (FNA) cytologic detection of a rare pulmonary metastasis of dermatofibrosarcoma protuberans, a locally aggressive tumor with a low metastatic potential but a high propensity for recurrences. The cytologic findings paralleled those seen on tissue sections and were characterized by tissue fragments displaying a storiform pattern and slender, spindle-shaped cells. Histiocytic differentiation and mitotic figures were also detected in the cytologic preparations. It is concluded that metastatic dermatofibrosarcoma may be accurately diagnosed by FNA cytology.

Assessment of chemically induced DNA repair in primary cultures of human bronchial epithelial cells.

A procedure has been developed to assess chemically induced DNA repair in freshly isolated, primary cultures of human bronchial epithelial (HBE) cells. HBE cells were isolated from eight samples of autopsy material or surgical specimens and incubated with test chemicals and [3H]thymidine. Viability as measured by trypan blue exclusion averaged 90%. Chemically induced DNA repair was assessed as unscheduled DNA synthesis (UDS) by quantitative autoradiography. The direct-acting agent methyl methanesulfonate induced DNA repair in HBE cells in all eight cases studied, indicating that the cultures were viable and capable of DNA repair in response to DNA damage. Benzo(a)pyrene induced DNA repair in all cultures whereas dimethylnitrosamine failed to induce UDS in any culture, suggesting an organ-specific pattern of metabolic activation. 1,6-Dinitropyrene was positive in cultures prepared from autopsy material but negative in cultures prepared from surgical specimens. Formaldehyde did not induce UDS in any sample examined. This system may be useful in assessing the genotoxic potential of environmental chemicals in human bronchial epithelial cells, give an indication of interindividual variability, and provide valuable information for comparison to proposed animal models for the human bronchus.

A new extracorporeal reactor-dialyzer for enzyme therapy using immobilized L-asparaginase.

Depletion of circulating L-asparagine has proved beneficial in the treatment of some acute lymphoyctic leukemias. To avoid the immunologic sequelae of administering L-asparaginase parenterally, we have covalently attached the enzyme to the outside of the fibers of a conventional hollow fiber hemodialyzer. This provides ready access of the substrate to the enzyme, while simultaneously isolating the foreign protein from the immune system. Such reactor-dialyzers perform well, both in vitro and in vivo. Circulating L-asparagine in the healthy dog is reduced from about 50 micrometer to less than 2 micrometer within 30 min of connecting the reactor-dialyzer and the reduction persists for at least 4 hr after cessation of treatment.