Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays

Adult-rat-brain tissues display an unusually high resistance to necrosis when serially irradiated with parallel, thin slices of a microplanar (i.e., microscopically thin and macroscopically broad) beam of synchrotron-wiggler-generated, approx. 35–120 keV (median approx. 50 keV) Gd-filtered X rays at skin-entrance absorbed doses of 312 to 5000 Gy per slice. Such microplanar beams were used to irradiate young adult rats bearing right frontocerebral 9L gliosarcomas (approx. 4 mm diameter), through a volume of tissue containing the tumor and contiguous brain tissue, either in a single array or in 2 orthogonally crossed arrays of tissue slices. Each array included 101 parallel microplanar slices, 100 μm center-to-center distance, each slice being approx. 25 μm wide and 12 mm high, with skin-entrance absorbed doses of 312.5 Gy or 625 Gy per slice. Compared with unirradiated controls with a median survival time of 20 days after tumor initiation, the median survival time was extended in irradiated rats by 139 days (625 Gy, crossed arrays), 96 days (312.Gy, crossed arrays) or 24 days (625 Gy, single array). The tumors disappeared in 22 of the 36 irradiated rats, 4/ 11 even after unidirectional microbeam irradiation. The extent and severity of radiation damage to the normal brain in rats with or without tumor was graded histopathologically. Correlation of those grades with radiation doses shows that loss of tissue structure was confined to beam-crossing regions and that only minor damage was done to zones of the brain irradiated unidirectionally. Int. J. Cancer 78:654–660, 1998. © 1998 Wiley-Liss, Inc.     

Memantine-induced brain activation as a model for the rapid screening of potential novel antipsychotic compounds: exemplified by activity of an mGlu2/3 receptor agonist

Rationale

Schizophrenia is a severe, disabling chronic disorder affecting approximately 1% of the population. Improvements and development of more robust and hopefully predictive screening assays for this disease should enhance the identification and development of novel treatments. The present study describes a rapid and robust method for the testing of potential novel antipsychotics by utilising a simplified [¹⁴C]2-deoxyglucose (2-DG) autoradiography method following memantine-induced brain activation.

Methods

Male C57BL/6JCRL mice were given vehicle, ketamine or memantine (10, 20 and 30?mg/kg, subcutaneously (s.c.)) and sacrificed 45?min post-[^14?C]2-DG administration. In subsequent reversal studies, the memantine challenge was further validated with haloperidol (0.32?mg/kg, s.c.) and clozapine (2.5 and 10?mg/kg, s.c.) in parallel with the ketamine model (Duncan et al. 1998a). Lastly, the effects of an mGlu2/3 receptor agonist, LY404039 (10?mg/kg, s.c.), on both ketamine and memantine-induced brain activation was determined.

Results

Both N-methyl-d-aspartate (NMDA) antagonists dose-dependently induced significant region-specific increases in 2-DG uptake. Interestingly, memantine elicited a considerably greater brain activation signature with a larger dynamic window than ketamine. The ??atypical?? antipsychotic clozapine significantly reversed memantine-induced 2-DG uptake whilst the ??typical?? antipsychotic haloperidol was inactive. Pre-treatment with LY404039 fully reversed both the ketamine- and memantine-induced increase in 2-DG uptake without effects on basal 2-DG uptake.

Conclusion

This novel pre-clinical imaging methodology displays potential for the screening of compounds targeting the NMDA receptor hypofunction hypothesis of schizophrenia and should assist in developing compounds from the bench to clinic.     

Primary testicular mucinous neoplasms: case report and literature review

Testicular epithelial mucinous tumours are an extremely rare, but interesting form of testicular neoplasm. We reviewed the medical literature using PubMed search terms: testis, mucinous cystadenoma, mucinous cystadenocarcinoma, neoplasms and testicular neoplasms. We describe a case from our institution and provide a review of the literature. Only 11 previously reported cases of mucinous testicular tumours have been reported in the English literature. The natural history of these tumours is poorly understood, due to their rarity, but it appears that, like their ovarian counterparts, they have an excellent prognosis. Exclusion of metastasis is an important point for the urologist when encountering a mucinous testicular tumour, as metastatic cystic lesions may mimic a primary mucinous tumour. We describe a case of ossified testicular mucinous tumour of low malignant potential. Such tumours are common in the ovary, but arise very rarely in the testicle. The clinical and histological features of this tumour are presented, and previously reported cases are reviewed to highlight important clinical features.     

Clearance of the cervical spine in multitrauma patients: The role of advanced imaging

The cervical spine is injured in 3% of major trauma patients. Radiographic clearance for injury must be provided efficiently and accurately. There are numerous choices for clearance that are now in clinical practice: lateral radiograph only, 3-view or 5-view cervical-spine (c-spine) series, flexion-extension radiographs, computed tomography (CT) with multiplanar reformations, and magnetic resonance imaging (MRI). This article reviews the literature on methods of c-spine clearance, and emphasizes the pitfalls of each modality. Although lateral radiographs detect 60% to 80% of c-spine fractures, a significant number of fractures are not visible, even when three views of the spine are obtained. The sensitivity of plain radiographs can be improved by attention to several subtle features, which are discussed. Flexion-extension radiographs in the acute setting have an unacceptably high false-negative and false-positive rate. CT detects 97% to 100% of fractures, but its accuracy in detection of purely ligamentous injuries has not been documented. Furthermore, CT is limited in patients with severe degenerative disease. MRI is highly sensitive in the detection of ligamentous injury, but not all cases of injury may cause instability. MRI is also much less sensitive than CT to fractures of the posterior elements of the spine, and to injuries of the craniocervical junction. The causes of missed cervical spine injury and delayed instability are discussed and shown in this article. An algorithm for the use of advanced imaging is proposed.