fumarates and Dementia

We report a case of a patient with a rapidly progressive dementing illness and gait disturbance, in whom initial screening demonstrated a high methylmalonic acid level only, suggestive of a functional vitamin B(12) deficiency. Despite B(12) replacement therapy, he continued to decline. Further investigations demonstrated extensive signal change on magnetic resonance imaging involving grey and white matter within the corpus callosum, deep grey matter, brainstem and cerebellar peduncles, and patchy post-contrast enhancement. Laboratory testing revealed a raised erythrocyte sedimentation rate, raised anti-nuclear, intrinsic factor and lupus anticoagulant antibody titres, and a IgG kappa paraprotein. Cerebrospinal fluid was unremarkable. Bone marrow trephine biopsy showed monoclonal gammopathy of unknown significance. The patient initially responded to steroids, and underwent a brain biopsy, which was uninformative. However, 3 weeks following admission, he died due to an aspiration pneumonia. Autopsy findings were consistent with a diffuse primary central nervous system small cell B-cell lymphoma. This has been rarely reported in the medical literature, but our case exhibits typical clinical features, although patchy enhancement on imaging and the high methylmalonic acid have not been previously described. We hypothesise that his functional B(12) deficiency may have resulted from rapid cell turnover, perhaps in conjunction with the presence of intrinsic factor antibodies.

Topics: Aged; Brain Neoplasms; Dementia; Fatal Outcome; Fumarates; Humans; Lymphoma, B-Cell; Magnetic Resonance Imaging; Male; Maleates

The aim of this study was to develop a pH-independent extended release matrix tablet of minocycline HCl for the treatment of dementia. The matrix tablets were prepared by wet granulation technique using Eudragit L and S as release modifiers at different w/w ratios (1:0, 1:1 and 0:1) and PEO as a matrix former. In the case of the matrix tablet without any release modifiers, the drug release rate at pH 1.2 was much higher than that of pH 7.4. By adding the release modifier, the drug release rate at pH 7.4 increased close to that of pH 1.2 and the pH-independent release was obtained. In addition, it was shown that lubricants containing a divalent cation such as Mg stearate inhibited minocycline release in basic medium. Therefore, the incorporation of Eudragit L and S (1:1 ratio) as release modifiers and Na stearyl fumarate as a lubricant into PEO-based matrix tablets effectively produced pH-independent minocycline release profiles.

Topics: Animals; Anti-Bacterial Agents; Delayed-Action Preparations; Dementia; Excipients; Fumarates; Humans; Hydrogen-Ion Concentration; Lubricants; Minocycline; Polyethylene Glycols; Polymethacrylic Acids; Tablets