Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation.

Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P < 0.001). The pathologic analysis demonstrated P values of < 0.001 when comparing histopathology with age and MRI results. All severely degenerated discs seen by MRI were in baboons 14 years of age or older.

Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation of intracerebral injection in nonhuman primates.

This study examined the safety of intracerebral inoculation of G207, an attenuated, replication-competent herpes simplex virus type 1 (HSV-1) recombinant, in nonhuman primates. Sixteen New World owl monkeys (Aotus nancymae [karyotype 1, formerly believed to be A. trivirgatus]), known for their exquisite susceptibility to HSV-1 infection, were evaluated. Thirteen underwent intracerebral inoculation with G207 at doses of 10(7) or 10(9) PFU, two were vehicle inoculated, and one served as an infected wild-type control and received 10(3) PFU of HSV-1 strain F. HSV-1 strain F caused rapid mortality and symptoms consistent with HSV encephalitis, including fever, hemiparesis, meningitis, and hemorrhage in the basal ganglia. One year after G207 inoculation, seven of the animals were alive and exhibited no evidence of clinical complications. Three deaths resulted from nonneurologic causes unrelated to HSV infection, and three animals were sacrificed for histopathologic examination. Two animals were reinoculated with G207 (10(7) PFU) at the same stereotactic coordinates 1 year after the initial G207 inoculation. These animals were alive and healthy 2 years after the second inoculation. Cerebral magnetic resonance imaging studies performed both before and after G207 inoculation failed to reveal radiographic evidence of HSV-related sequelae. Despite the lack of outwardly observable HSV pathology, measurable increases in serum anti-HSV titers were detected. Histopathological examination of multiple organ tissues found no evidence of HSV-induced histopathology or dissemination. We conclude that intracerebral inoculation of up to 10(9) PFU of G207, well above the efficacious dose in mouse tumor studies, is safe and therefore appropriate for human clinical trials.

Posterior sacroiliac fixation using a sacral pedicle targeting device: an anatomical study.

This study compares the accuracy of posterior sacroiliac (SI) screw placement using a "free-hand" method, without the use of fluoroscopy, versus a specially developed targeting device. Posterior SI screws were inserted after exposing the iliac wing in five cadavers on one side, and inserted percutaneously with a unique targeting device on the opposite side. Fluoroscopy was not used for screw or pedicle placement on either side. Computed tomography and dissection results were then used to grade screw placement for both sides. A statistically significant difference between the sides was found. More importantly, three screws on the free-hand side violated major neurovascular structures. The regional anatomy was defined: structures most at risk are the iliac vein ventrally and the sacral canal dorsally. A highly variable "safe zone" (mean arc 43 degrees at the S1 level and 30 degrees at the S2 level) was established. Inclination of the SI joint was also defined (mean 29 degrees at the S1 level and 17 degrees at the S2 level). SI screw placement using the specially developed targeting device is technically less demanding, requires less soft tissue dissection, allows variable placement, and poses minimal risk to major neurovascular structures. Our limited clinical experience with the device is encouraging. The potential application of this technique to unstable vertical shear fractures is appealing.

Age-related disk degeneration: preliminary report of a naturally occurring baboon model.

Anteroposterior and lateral radiographs of 126 adult baboons were reviewed. The mean age was 15.7 years (range 6-30 years). Evidence of disk degeneration, to include disk-space narrowing, osteophyte formation, endplate changes, and facet joint arthropathy, was noted, and a grading scale, grades 0-3, was used to assign each animal an overall grade for degree of disk degeneration. Lateral radiographs were measured in the area of maximal sagittal plane curvatures. Radiographic review demonstrated a strongly positive correlation between the age of the baboons and the degree of degenerative change (p less than 0.0001), between the degree of kyphosis and the degree of degenerative change (p less than 0.0001), and between the age of the animal and the degree of kyphosis (p less than 0.001). This pilot study demonstrates plain radiographic confirmation of a naturally occurring primate model of disk degeneration, the first such model described, and is the basis for further investigation into magnetic resonance imaging and histopathologic confirmation of this model.