We present data correlating the time courses of hydroxyl radical (.OH) production, lipid peroxidation, and blood-brain barrier (BBB) damage following unilateral head injury in the rat. Using a controlled cortical impact device to inflict head injury, we have directly measured brain .OH levels via the salicylate trapping method, and phosphatidylcholine hydroperoxide (PCOOH) levels via the HPLC-chemiluminescence technique, at 5, 30, and 60 min postinjury. These results were then correlated with the time course of BBB disruption, as measured by the extravasation of Evans blue dye (EB) into the injured cortex, over the same time period. In the present study, .OH levels were 62% higher than sham at 5 min postinjury, 25% higher at 15 min (both p < or = 0.05), and no different from sham at 60 min. PCOOH, on the other hand, increased linearly between 5 and 60 min postinjury. Whereas PCOOH levels were 25% greater than sham at 5 min, they were 35% and 52% higher than sham at 30 and 60 min, respectively (both p < or = 0.05 vs sham). Blood-brain barrier disruption followed a similar time course to PCOOH generation, except that the magnitude of the effect was much greater. Whereas EB extravasation was only slightly elevated in the injured cortex at 5 min postinjury, there was nearly an 8-fold increase at 30 min and an 11-fold increase at 60 min (all p < or = 0.05 vs sham). An additional experiment demonstrated that BBB damage can be attenuated by treatment with the 21-aminosteroid lipid peroxidation inhibitor, tirilazad mesylate (U-74006F). Rats were given a single i.v. injection of 3 or 10 mg/kg of U-74006F 5 min postinjury and killed 30 min postinjury. The 10 mg/kg dose of U-74006F reduced EB extravasation 52% (p < 0.025) in comparison to vehicle-treated controls. This is the first study to correlate the time courses of .OH formation, lipid peroxidation, and BBB disruption in injured brain. The results suggest that there is an immediate, posttraumatic burst in .OH formation, followed by a progressive increase in lipid peroxidation and a similar, although slightly delayed, time-related opening of the BBB. The attenuation of BBB damage by U-74006F suggests that this chain of events can be interrupted by administration of an antioxidant/lipid peroxidation inhibitor.

The levels of hydroxyl radicals and oxidized GSH have been examined as indices of oxidative stress in young (3 months), middle-aged (15 months), and old (20-24 months) gerbil brain hippocampus, cortex, and striatum. The hydroxyl radical stress was estimated by measuring the salicylate hydroxyl radical trapping products 2,5- and 2,3-dihydroxybenzoic acid. The stress was significantly higher in all three brain regions in middle-aged and old gerbils versus young animals (< or = 66.0%). Regional comparisons showed that the stress was significantly higher in cortex than in either the hippocampus or striatum of the middle-aged and old gerbils (< or = 32.0%). The ratio of oxidized to total GSH also increased progressively in middle-aged and old animals in all three brain regions (p < 0.05, < or = 41.1%), further indicating a general age-related increase in oxidative stress. Parallel to this age-related increase in oxidative stress, a significant, albeit slight (8%), decrease in neuronal number in hippocampal CA1 region was observed in both the middle-aged and old animals. Possible differences in antioxidant levels were also examined. Total GSH levels were similar across age groups (variance < 12%). However, the regional comparison showed that it was highest in striatum in all age groups. The levels of alpha-tocopherol (vitamin E) were significantly higher in the middle-aged and old animals in all three regions (< or = 70.4%). Vitamin E was highest in the hippocampus and the differences between the hippocampus and the cortex and striatum increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)

With the advent of modern therapy, the differences in prognoses and treatment regimens among different subtypes of Hodgkin lymphoma (HL) have largely vanished. Stage and the presence of systemic symptoms are much more important than histologic subtypes as predictive factors. The current (2001) WHO classification markedly de-emphasizes spatial relationships as critical to the diagnosis of lymphoma and emphasizes cell morphology, immunophenotype, genetic features, and clinical information to define the disease states. This classification, thus, greatly enhances the capability of fine-needle aspiration (FNA) to accurately diagnose HL. We searched all the FNA cases in our institute in years 1999 through 2004 and found 42 cases, for which 13 were primarily diagnosed (31.0%), 2 were recurrent (4.8%), 5 were highly suspicious (11.9%), and 22 were suspicious (52.3%) for HL. On follow-up tissue biopsy, all the primarily diagnosed, recurrent, and highly suspicious cases were confirmed to be HL (100% agreement). For the 22 suspicious cases, 13 were HL (59.1%), 5 were other lymphomas (22.8%), 1 was lymphoma unclassifiable (4.5%), and 3 were reactive processes (13.6%). The effect of immunostains on the diagnosis of HL was examined, and its importance was emphasized. Analysis of demographic data and the distribution of HL subtypes demonstrate that the study sample is representative of the general HL patient population. On the basis of these results, we propose: (1) If the FNA diagnosis of HL is confirmed both by morphology and immunostains, no further tissue confirmation, subclassification and grading is necessary, and appropriate treatment regimens should follow. (2) The nodular lymphocyte predominant HL and classical HL can be differentiated by adequate immunostaining. (3) If a definitive diagnosis cannot be achieved by FNA, a second FNA or a tissue biopsy should be recommended.

INTRODUCTIONOxygen-free radicals have been postulated to play a role in the acute pathophysiology of blunt head injury.14. Much of this work points to the cerebral microvasculature as a major target of oxygen radical-mediated damage. Moreover, free-radical scavengers such as superoxide dismutase' and lipid antioxidants, including methylprednisolone,h U-72099E,' U-74006F,X and U-78517F: which block free radical damage to membrane polyunsaturated fatty acids (i.e., lipid peroxidation), have been reported to attenuate posttraumatic pathophysiology and/or to promote survival and recovery in experimental head injury. However, a firm association of oxygen radicals and lipid peroxidation with pathophysiological events has been hindered by the lack of analytical methodology that will directly measure cerebral tissue levels of specific radicals or lipid hydroperoxides.In recent studies in both the mouse concussive and the rat controlled cortical impact head injury models, we have directly measured brain hydroxyl radical (.OH) levels via the salicylate trapping method in which the production of 2,3-and/or 2,5-dihydroxybenzoic acid (DHBA) in brain, 15 min after salicylate administration was used as an index of .Ou formation.'" In the mouse model, we have also examined the brain levels of enzymatically derived eicosanoids (e.g., PGFZa, PGE2, TXB2, 6-keto PGFI,, LTC.,). Additionally, in the rat model, we have employed the highpressure liquid chromatographic-chemiluminescence (HPLC-CL) method" to measure the lipid peroxidation product, phosphatidylcholine hydroperoxide (PCOOH), and its time course in relation to that of .OH generation. Finally, to provide a pathophysiological correlation, we have further compared the time course of bloodbrain barrier (BBB) disruption in both models as an index of microvascular damage by oxygen radical-induced lipid peroxidation. These studies have shown a clear association between posttraumatic -OH generation, membrane lipid peroxidation, and subsequent increases in cerebral microvascular permeability.

We report 2 cases of toxic anterior segment syndrome (TASS) resulting from impurities in generic trypan blue that was administered intracamerally to improve visualization of the capsule. Histology of the corneal buttons revealed foci of inflammatory response and complete loss of endothelial cells. Cell culture analysis showed that the generic trypan blue was approximately twice as toxic to the endothelium as a proprietary trypan blue. Ophthalmologists should be aware that any substance administered intraocularly can be a source of complications, and they should know the source of all material used in surgery.