Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Myelin basic protein is necessary for the regulation of myelin-associated glycoprotein expression in mouse oligodendroglia.

Myelin-associated glycoprotein (MAG) has currently been proposed to be a possible igniter of myelination in the central nervous system. We propose here that myelin basic protein (MBP) is prerequisite, which is more diffusely expressed than MAG in early stages of myelination. MBP-deficient mice show significant reduction of MAG-positive immature oligodendroglia at early stages of myelination, although significant increase of such cells is noted in the adult. MBP/Fyn-double deficient adult mice also show moderate increase of the same type of immature glia, but to a lesser degree than MBP-deficiency alone. The present study suggests that MBP is required for the regulation of MAG expression in oligodendroglia, involving Fyn therein. We discuss the possibility that hitherto unknown molecule, not MAG, may be in responsible for the ignition of the myelination.

Thermal oxidative degradation studies of phosphate esters.

Five phosphate esters - tri-p-tolyl phosphate, tributyl phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(2,3-dibromopropyl)phosphate, and tris(2-chloroethyl)phosphate- were subjected to thermal oxidative degradation in air at 370 degrees C. Degradation mechanisms were postulated and the toxic hazards assessed based on the volatiles produced. Tri-p-tolyl phosphate was found to undergo only minimal degradation; the other compounds were decomposed extensively. Butene was the main product formed on tributyl phosphate decomposition; hydrogen halides and halogenated C2- and C3- species were the main products formed by the halogenated phosphate ester. In the case of tris(1,3-dichloro-2-propyl)phosphate acrolein, not hydrogen chloride, presented the major toxic hazard.

Thermal oxidative decomposition studies of neoprene compositions.

Four neoprene compositions--uncured gum, known cured rubber, cable insulation, and hose conduit, the latter two used in underground mining--were subjected to thermal oxidative degradation under static and dynamic environments, and the volatile products were quantitated on a milligrams-per-gram basis. In a quiescent system at 370 degrees C, no glow was observed, the extent of oxidation was low, up to 84% of the chlorine content was evolved as hydrogen chloride, and the sulfur present was released largely in the form of carbon disulfide. Under more drastic conditions (higher temperatures and flowing air), glow occurred in several instances resulting in an increased production oxidation products as represented by CO2, COS, SO2, HCOOH, and CH3COOH, among others. Thermogravimetric investigations of the neoprene compositions show the first weight loss to correlate closely with hydrogen chloride evolution; furthermore, the use of thermogravimetric curves as means of meterial differentiation appears to offer a definite promise.