Health-related quality of life assessment in euthymic and depressed patients with bipolar disorder. Psychometric performance of four self-report measures

The aim of this study was to determine the interaction potential of the new antiepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with three Ca2+ channel blockers (nicardipine, nifedipine, and flunarizine), one Ca2+ channel activator (Bay K 8644; 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid), and two methylxanthines (caffeine and aminophylline (theophylline2 . ethylenediamine)) which are all known to markedly change protective effects of conventional antiepileptic drugs. To do so, the maximal electroshock seizure test in mice (an experimental model predicting drug efficacy in the treatment of human generalized tonic-clonic seizures) was employed to (1) quantify changes in the protective efficacy and potency of felbamate produced by adjunct drugs and (2) assess the ability of aminophylline and caffeine to affect protective efficacy afforded by a submaximal protective dose of felbamate against maximal electroshock-induced seizures. Doses of adjunct drugs were selected based on their effects on the threshold for electroconvulsions and on appropriate literature. Nicardipine (10-30 mg/kg), nifedipine (5-20 mg/kg), flunarizine (2.5-10 mg/kg), Bay K 8644 (2.5-5 mg/kg), and aminophylline (50-75 mg/kg) did not change the protective efficacy and potency of felbamate against maximal electroshock-induced tonic convulsions. Aminophylline in the dose of 100 mg/kg, however, diminished the protective potency of felbamate as evidenced by a statistically significant increase in the protective ED50 value of felbamate (a dose, in mg/kg, predicted to protect 50% of mice against convulsive stimulus) from 79.6 to 118 mg/kg; P < 0.05). Aminophylline and caffeine only at high doses (100 and 161.7 mg/kg, respectively) significantly diminished the protective efficacy of felbamate (110 mg/kg) from 96% to 27% and 40% (P < 0.05), respectively. In conclusion, felbamate shows low interaction potential with Ca2+ channel modulators and methylxanthines. Such low interaction potential clearly differentiates felbamate from conventional antiepileptic drugs where protective effects are readily altered by the compounds tested in the present study.     

Recent developments in the hammerhead ribozyme field

Developments in the hammerhead ribozyme field during the last two years are reviewed here. New results on the specificity of this ribozyme, the mechanism of its action and on the question of metal ion involvement in the cleavage reaction are discussed. To demonstrate the potential of ribozyme technology examples of the application of this ribozyme for the inhibition of gene expression in cell culture, in animals, as well as in plant models are presented. Particular emphasis is given to critical steps in the approach, including RNA site selection, delivery, vector development and cassette construction.     

POEMS syndrome: an unusual cause of bilateral optic disk swelling

Four cases of acute ileal diverticulitis are presented wherein early diagnosis helped avoid emergent surgery. All patients did well initially with conservative medical management. Acute ileal diverticulitis, although uncommon, should be suspected when the clinical presentation indicates an inflammatory condition of the lower right abdomen. Surgery, when required for recurrent disease, can be reserved for the interval between acute episodes.     

Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells

Esophageal adenocarcinoma (SKGT-2, SKGT-4, and SKGT-5) and epidermoid carcinoma (HCE-4) cells containing variable retinoblastoma (Rb), cyclin D1, p16, and p53 expression patterns were exposed to the synthetic flavone, flavopiridol. The IC50 was approximately 100-150 nM for each of these cell lines. Exposure of esophageal carcinoma cells to 300 nM flavopiridol induced cell cycle arrest and apoptosis, resulting in a 90% inhibition of proliferation relative to that of nontreated cells after a 5-day exposure to the drug. Western blot analysis revealed diminution of cyclin D1, Rb, and p107 protein levels after flavopiridol exposure. Whereas cell cycle arrest and overall growth inhibition did not correlate in any obvious manner with the genotype of these cell lines, apoptosis seemed to be more pronounced in SKGT-2 and SKGT-4 cells that lack Rb expression. Pretreatment of esophageal cancer cells with 9-cis-retinoic acid did not substantially potentiate flavopiridol activity in these cell lines. Although the precise mechanism of flavopiridol-mediated cytotoxicity has not been fully defined, this drug is an attractive agent for molecular intervention in esophageal cancers and their precursor lesions; further evaluation of flavopiridol in this clinical context is warranted.     

Sacral hydatidosis: value of MRI in the diagnosis

We present a case of primary hydatid disease of the sacrum. The diagnosis was made on MR imaging obtained to evaluate the spine for recurrent disc disease. The patient had previously undergone laminectomy elsewhere for L4-5 radiculopathy. Ultrasound-guided aspiration and visualisation of scolices confirmed the diagnosis. No other site of involvement was found.     

Single units and conscious vision

Figures that can be seen in more than one way are invaluable tools for the study of the neural basis of visual awareness, because such stimuli permit the dissociation of the neural responses that underlie what we perceive at any given time from those forming the sensory representation of a visual pattern. To study the former type of responses, monkeys were subjected to binocular rivalry, and the response of neurons in a number of different visual areas was studied while the animals reported their alternating percepts by pulling levers. Perception-related modulations of neural activity were found to occur to different extents in different cortical visual areas. The cells that were affected by suppression were almost exclusively binocular, and their proportion was found to increase in the higher processing stages of the visual system. The strongest correlations between neural activity and perception were observed in the visual areas of the temporal lobe. A strikingly large number of neurons in the early visual areas remained active during the perceptual suppression of the stimulus, a finding suggesting that conscious visual perception might be mediated by only a subset of the cells exhibiting stimulus selective responses. These physiological findings, together with a number of recent psychophysical studies, offer a new explanation of the phenomenon of binocular rivalry. Indeed, rivalry has long been considered to be closely linked with binocular fusion and stereopsis, and the sequences of dominance and suppression have been viewed as the result of competition between the two monocular channels. The physiological data presented here are incompatible with this interpretation. Rather than reflecting interocular competition, the rivalry is most probably between the two different central neural representations generated by the dichoptically presented stimuli. The mechanisms of rivalry are probably the same as, or very similar to, those underlying multistable perception in general, and further physiological studies might reveal much about the neural mechanisms of our perceptual organization.