Medical management of cervical spondylosis.

Medical management is often the initial management of cervical spondylitic syndromes, including radiculopathy, myelopathy, and neck pain. This includes pharmacological and rehabilitation treatment. Prospective studies comparing the efficacy of surgical versus medical management are lacking. The indications and efficacy of pharmacological and rehabilitative treatments are reviewed. The use of anti-inflammatory drugs, muscle relaxants, analgesics, antidepressants, anticonvulsants, steroids, facet joint ablation, and physical therapy are reviewed. A rationale for the medical management of acute neck pain, chronic neck pain, radiculopathy, and myelopathy is presented.

Synthesis and characterization of peptides containing a cyclic Val adduct of diepoxybutane, a possible biomarker of human exposure to butadiene.

1,3-Butadiene, a potential human carcinogen widely used in industry, is oxidized by cytochrome P450 to diepoxybutane (DEB), which is the most mutagenic of the known butadiene metabolites. Assessment of the toxicological significance of DEB formation in humans and animals requires identification of a biomarker uniquely associated with DEB for use in molecular dosimetry studies. We wished to develop a specific and sensitive assay for one such suitable marker, the cyclic adduct 2-(3,4-dihydroxypyrrolidin-1-yl)-3-methylbutyramide (pyr-V), which is formed from addition of DEB to the terminal Val of the alpha- and beta-chains of hemoglobin. We needed to prepare a pure, rigorously characterized DEB-modified N-terminal oligopeptide for raising antibodies both to use in an immunoaffinity purification step and to standardize the assay. In addition, we needed a pure isotopomer to serve as an internal standard for quantitation by LC-MS. Direct modification of the globin sequences by reaction with DEB in vitro proved to be unproductive. We therefore opted to synthesize the cyclic Val adduct and incorporate it by FMOC chemistry into the appropriate oligopeptide sequences. In vitro and in vivo, butadiene is oxidized to enantiomeric and meso forms of DEB. A priori, all three DEB isomers are expected to form pyr-V adducts, resulting in three diastereomeric N-terminal peptides. We therefore synthesized a mixture of the cyclic Val diastereomers as their methyl esters by reaction of DEB with l-Val methyl ester hydrochloride. After protection as the di-O-tert-butyl derivatives, the mixture of 2-(3,4-di-t-butoxypyrrolidin-1-yl)-3-methylbutyric acid diastereomers was incorporated as the N-terminal residue into the 1-11 human globin alpha-chain sequence VLSPADKTNVK. The presence of the three diastereomers was confirmed by two-dimensional correlation NMR spectroscopy and temperature-dependent (1)H NMR. This strategy enabled us to obtain pure, rigorously characterized haptens in quantity for the preparation of polyclonal antibodies. Use of FMOC-protected (2)H(3)-Leu in the automated oligopeptide synthesis provided the required isotopomers for use as internal standard.