Decompression of the brain stem and superior cervical spine for congenital/acquired craniovertebral invagination: an interdisciplinary approach.

A transoropharyngeal/transpalatal approach to the clivus and anterior cervical spine in association with a midline labiomandibular glossotomy has proved successful in the treatment of craniovertebral instability. Nine cases at this institution between 1978 and 1986 were retrospectively reviewed. A head-and-neck surgeon, along with a neurosurgeon and/or orthopedic surgeon collaborated on these procedures. The indications, methods, operative techniques, results and postoperative complications are presented.

The role of prion peptide structure and aggregation in toxicity and membrane binding.

Prion diseases are neurodegenerative disorders associated with a conformational change in the normal cellular isoform of the prion protein, PrP(C), to an abnormal scrapie isoform, PrP(SC). Unlike the alpha-helical PrP(C), the protease-resistant core of PrP(SC) is predominantly beta-sheet and possesses a tendency to polymerize into amyloid fibrils. We performed experiments with two synthetic human prion peptides, PrP(106-126) and PrP(127-147), to determine how peptide structure affects neurotoxicity and protein-membrane interactions. Peptide solutions possessing beta-sheet and amyloid structures were neurotoxic to PC12 cells in vitro and bound with measurable affinities to cholesterol-rich phospholipid membranes at ambient conditions, but peptide solutions lacking stable beta-sheet structures and amyloid content were nontoxic and possessed less than one tenth of the binding affinities of the amyloid-containing peptides. Regardless of structure, the peptide binding affinities to cholesterol-depleted membranes were greatly reduced. These results suggest that the beta-sheet and amyloid structures of the prion peptides give rise to their toxicity and membrane binding affinities and that membrane binding affinity, especially in cholesterol-rich environments, may be related to toxicity. Our results may have significance in understanding the role of the fibrillogenic cerebral deposits associated with some of the prion diseases in neurodegeneration and may have implications for other amyloidoses.

Predominance of HCV type 2a in saliva from intravenous drug users.

Paired serum and saliva samples were collected simultaneously from 50 intravenous drug users with serologically proven hepatitis C virus infection. The oral health of the volunteers was also assessed. Hepatitis C virus RNA was detected by nested PCR, employing primers from the 5' noncoding region. Positive PCR products were sequenced using the Sequenase PCR Product Sequencing Kit (Amersham Life Sciences). HCV RNA was detected in 33 (66%) of the 50 serum samples. HCV RNA was detected in 19 (57.6%) of the corresponding 33 saliva samples. There was no correlation between oral health status or HIV seropositivity and the detection of HCV in saliva. However, subjects with HCV in their saliva were significantly more likely to complain of xerostomia (P < 0.05). Isolate genotypes were identified in paired serum and saliva of 15 intravenous drug users. HCV genotypes 1, 2, 3 and 6 were detected in both specimens. In seven cases, a differing HCV genotype was found in serum compared to the paired saliva specimen. The distributions of genotypes in serum and saliva were very different, with genotype 2a more common in saliva than serum (P < 0.005). These data suggest that in some cases the source of salivary HCV may not be serum transudation along the periodontal membrane or across damaged mucosa, and that an alternative local source, possibly the salivary glands themselves, should be considered.

Detection of antibodies against hepatitis C virus in saliva: a marker of viral replication.

Hepatitis C surveillance has been restricted owing to the lack of a sensitive antibody assay for saliva. The aim of our study was to develop and evaluate a screening assay for hepatitis C antibody in saliva specimens. Serum/saliva pairs were collected from 115 hepatitis C-positive patients. A modified hepatitis C antibody assay for saliva was developed and linked to testing carried out in the diagnostic laboratory. Correlation between the presence of antibody in serum and in saliva was poor (100% vs 85%). However, of 98 patients who were saliva antibody positive, 96 (98%) were also serum hepatitis C RNA positive and two (2%) were serum hepatitis C RNA negative. Hence, the correlation between a positive salivary antibody test and the serum hepatitis C RNA status of intravenous drug users suggests that this test could be used as a surrogate marker for hepatitis C viraemia in epidemiological studies.