Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.
Background and Purpose: We recently described an autosomal dominant syndrome characterized mainly by recurrent strokes and neuroimaging evidence of leukoencephalopathy. We now report the pathological findings in one of the affected subjects.Case Description: A 40-year-old woman experienced her first grand mal seizure in 1971. From 1983 on she suffered recurrent strokes, seizures, and psychiatric disturbances with depressions, manic episodes, and dementia. In 1988, after her fourth stroke, she became tetraplegic with a severe pseudobulbar palsy,
Objective: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. Methods: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media-intima junction or in the media. Results: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age ,50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of ,0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples >0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). Conclusions: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.T he diagnosis of giant cell arteritis is most solidly established by the demonstration of granulomatous inflammation in a temporal artery biopsy (TAB). For between 7% and 44% of cases of giant cell arteritis, however, TAB examination is unremarkable 1 and it is unclear to what extent these non-informative specimens reflect false negative histological findings. One of several factors that has been advanced to explain false negative TAB results is that, because of the ''skipping'' nature of the inflammatory involvement in giant cell arteritis, 2 3 histological changes may be missed in a TAB taken in an arteritis-free segment.The resultant widely accepted dogma is that a long TAB segment should be excised to maximise the chance of visualising disease components. Although it is most commonly recommended that samples of 2-3 cm 4 or 3-5 cm 5 length be taken, the TAB length yielding optimal diagnostic sensitivity remains unknown. We therefore undertook this study in an attempt to determine the relation between TAB length and diagnostic sensitivity for giant cell arteritis. METHODSWe reviewed the written histological TAB reports from four pathology departments in three university hospitals (centres 1-3), each having internal medicine, rheumatology, and ophthalmology units, and one public ophthalmology hospital (centre 4). These departments customarily measured the lengths of formalin fixed TAB samples on macroscopic examination and recorded them in their reports. Using those departments' computerised databases, we retrieved all consecutive TAB reports that had been generated during well defined periods. Selected time periods covered either the entire interval from computerisation of histological reports unti...
Muscle biopsy specimens were obtained from 48 human immunodeficiency virus-infected patients suffering from various neuromuscular symptoms. Microscopic examination by conventional and electron microscopy revealed a characteristic structural myopathy associated with mitochondrial changes in 13 patients, all of whom had received long-term zidovudine therapy. The mean cumulative dose they had received (498 +/- 145 gm) was significantly higher than that of the other 14 zidovudine recipients of the study. They suffered from a progressive, usually painful, proximal myopathy with pronounced wasting, normal-to-moderately elevated creatine kinase levels, and a myopathic electromyographic pattern. The condition usually improved after withdrawal of the drug. Assay of mitochondrial enzymes, including succinate-cytochrome c reductase, cytochrome c oxidase, and citrate synthase, showed a decline in respiratory chain capacity. Southern blot analysis of mitochondrial DNA showed no abnormality. It is likely that mitochondrial dysfunction, probably resulting from drug-induced inhibition of the mitochondrial DNA polymerase, is implicated in the pathogenesis of this complication of zidovudine therapy.
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