The need for a large animal tumor model in experimental neuro-oncology led us to re-evaluate and to modify the transplantable canine glioma of Wodinsky and Walker. Successive passages of the original tumor brei were made in purebred beagles, from beagle to mongrel, and between various mongrel strains until an intracerebral injection of 0.1 cc on Days 1 to 3 of life produced a 93% incidence of tumor take in all breeds. The mean survival was 13.5 +/- 1.9 days after injection (range, 10 to 19 days) in 10 litters. The tumor was invariably fatal and possessed many of the histological characteristics of human glioblastoma (i.e., capillary proliferation, pseudopallisading, frequent mitotic figures, and multinucleated giant cells). The animals were large enough to be scanned on the Pfizer 450 scanner, and the tumors were visualized in vivo as typical "ring" lesions after the injection of contrast agent. Intravital staining with Evans blue outlined the areas of contrast enhancement observed in the same tumors by computed tomography. The apparent defect in the blood-brain barrier could be explained in part by the absence of endothelial tight junctions on electron microscopy. Stability in the histology and activity of the tumor could be demonstrated after more than 14 months of storage at -70 degrees C. The transplantable canine glioma model has many advantages including low cost, reproducible morphology, a short survival time, and relative safety for the investigator. The large size of the animal preparation allows the use of complex surgical instrumentation and radiographic study, as well as repeated sampling of cerebrospinal and other fluids.
In a series of 120 head-injured patients, recovery rates (rr) were calculated separately on the basis of either Glasgow come scale (GCS) scores or Maryland coma scale (MCS) scores; the latter contains the three variables of the GCS, excludes unevaluable responses, and provides more information concerning the status of brain stem reflexes and motor lateralization. The early (Day 3/4 vs. Day 1) and late (Day 8/14 vs. Day 1) recovery rates from the two scales generally agree (r = 0.76; r = 0.79), but in 39 of 94 patients the MCSrr and GCSrr disagreed by more than 10%. When the MCSrr was greater than the GCSrr, it more accurately reflected a favorable outcome. Graphic representations of clinical courses through serial plots of raw scores were more reliable when unaffected by intubation, sedation, swollen eyelids, casts, etc.; this was more often achieved with serial plots of MCS scores, which are graded as percentages of testable function. Final outcomes (good/disabled vs. vegetative/dead) were well predicted by Day 1 MCS scores above or below 35% (chi 2 = 27.63; p less than 0.001) and Day 1 GCS scores above or below 7 (chi 2 = 23.21; P less than 0.001). However, in 57 very sick patients (Day 1 GCS less than or equal to 7), the GCS did no better than chance (26 good, 31 bad outcomes), whereas 20 of 26 patients with a Day 1 MCS score of less than or equal to 35% had bad outcomes. In patients with severe multiple injuries, the Maryland coma scale may provide a more sensitive index of clinical course; a Day 1 MCS raw score of less than or equal to 35% is of grave prognostic significance.
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