Mechanisms of radiosensitization in iododeoxyuridine-substituted cells.

The radiosensitization caused by iododeoxyuridine (IdU)-substitution of thymidine in V79-171 cells is decreased by the presence of acetone during irradiation. Acetone, at 1 mol dm-3, removes almost all the increase in double strand breaks (dsbs) caused by IdU substitution, but removes only about two-thirds of the enhancement in killing. Similar observations were made with BrdU-substituted cells. The decrease in cell radiosensitization coincides with the removal of the additional dsbs. The protection afforded by acetone is assumed to be due to its scavenging of hydrated electrons, thought to be the active species causing enhanced DNA damage in the presence of halogenated pyrimidines. The residual component of IdU radiosensitization, which could not be removed by treatment with acetone, is manifest largely as a shoulder effect (Dq) and may be due to either a subset of non-scavengable, lethal dsbs and/or the influence of IdU on the fixation of potentially lethal damage. This study further demonstrates that halogenated pyrimidine-mediated radiosensitization consists of at least distinct components each associated with a different phenomenon.

Mechanisms of radiosensitization in bromodeoxyuridine-substituted cells.

The radiosensitization of exponentially-growing V79-171 cells whose DNA has been substituted by bromodeoxyuridine (BrdU) in place of thymidine is decreased if acetone is present during irradiation. Acetone, at a concentration of 1 mol dm-3, removes the majority of the increase in double-strand breaks (dsbs) caused by BrdU substitution, but only removes approximately half of the increase in cell killing. The decrease in cell radiosensitization coincides with the removal of the additional dsbs. The protection afforded by acetone against dsbs is assumed to be due to its ability to scavenge hydrated electrons, thought to be the active species causing the increased DNA damage in the presence of BrdU. The residual component of BrdU radiosensitization which could not be removed by treatment with acetone may be due to either a subset of nonscavengable, lethal dsbs or the influence of BrdU on the fixation of potentially-lethal damage (Iliakis et al. 1992). Cells substituted with BrdU are not sensitized to hydroxyl radicals (from hydrogen peroxide). Also, the enhanced levels of single-strand break (ssb) and dsb production in cells substituted with BrdU arise from analogous events (i.e. increases in the yield of ssbs). These studies support the locally multiply damaged site theory of lesion (dsb) production (Ward 1981) and, in the case of BrdU-substituted cells, the increase in dsbs appears to be due to the production of additional ssbs by hydrated electrons at sites of multiple damage.

Spontaneous cerebral hypothermia diminishes focal infarction in rat brain.

BACKGROUND AND PURPOSE: Brain temperature during ischemia is known to strongly influence the extent of cellular injury. The objectives of the present study were to determine the effect of severe focal ischemia on brain temperature and to assess the influence of those changes on focal infarction. METHODS: Severe focal ischemia was produced in rats using permanent occlusion of the distal middle cerebral artery combined with transient (60-minute) bilateral carotid artery occlusion. The temperature of the ischemic focus was measured with a small subdural probe. Three groups of rats were studied. In the first group, brain temperature was permitted to decline spontaneously to 32 degrees C after occlusion. In the second, brain temperature was maintained at 37.5 degrees C during occlusion. In the third group, the brain temperature was maintained at 37.5 degrees C for 40 minutes postocclusion before cooling. After recovery for 24 hours, the volume of infarction was measured in histological sections. RESULTS: In the absence of cranial heating, the brain temperature fell to 33 degrees C by 10 minutes postocclusion, and infarct volume was 19 +/- 9 mm3 (mean +/- SEM; n = 6). Maintaining brain temperature at 37.5 degrees C increased the volume of infarction to 82 +/- 16 mm3 (n = 7; p < 0.001). Delayed cooling did not prevent the increase in infarct volume (75 +/- 16 mm3; n = 6). CONCLUSIONS: These results demonstrate that in the present model of transient focal ischemia, spontaneous cooling of the brain during ischemia diminishes the extent of focal infarction, relative to that observed when cerebral hypothermia is prevented or delayed for 40 minutes.

Anomalous arrangement of the origins of the anterior choroidal and posterior communicating arteries. Case report.

A case of anomalous origin of the anterior choroidal and posterior communicating arteries in a 36-year-old woman with aneurysmal subarachnoid hemorrhage is presented. Preoperative four-vessel angiography revealed a reverse relationship of these vessels, wherein the anterior choroidal artery origin was proximal to the origin of the posterior communicating artery. This arrangement is extremely rare; the only other reported case was in a patient undergoing angiography prior to acoustic neurinoma resection. It is believed that this is the first case reported in a patient with subarachnoid hemorrhage from rupture of an aneurysm arising from a vessel of such anomalous origin.

Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain.

In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.

Pseudoankylosis of the mandible after temporal bone attached craniotomy.

Mandibular hypomobility after intracranial surgical procedures is seldom encountered. A case of limited oral opening after temporal bone attached craniotomy is described. The condition is due to fibrosis of the temporalis muscle resulting in a pseudoankylosis of the temporomandibular joint. The appropriate operative intervention is transoral coronoidectomy, which restores normal joint function.

Problems in evaluation of penetrating foreign bodies with computed tomography scans: report of cases.

Computed tomography is the best radiologic modality available in the evaluation of penetrating injuries to the soft tissues. The technique is the best available when the foreign body has a density similar to the surrounding tissues. Limitations of CT scanning include difficulty in identifying small foreign bodies, objects with densities similar to surrounding structures, and detecting vascular injury. Interpretation of postoperative changes is also difficult. Two cases have been presented to illustrate the advantages, and limitations of CT scanning in penetrating soft tissue trauma.