[The vestibular craniovertebral joints]. / Die vestibulären Kopfgelenke.

INTRODUCTION: The significance of cervical proprioception for human balance has thus far not been sufficiently elucidated. The aim of this study was to provoke selective cervico-vestibular stimulation using the trunk excursion test (TET) we ourselves constructed. This chair is designed to enable evaluation of cervico-ocular reactions during isolated trunk excursion and possible effects of aging. METHODS: The previously used head excursion test (HET) was statistically compared to the TET. In both methods, 100 healthy subjects of two age groups (group(26): median age = 26 years, n = 50; group(50): median age = 50 years, n = 50) were randomized for comparison of similar neck-to-trunk-positions. RESULTS: HET enabled detection of significant nystagmus modulation in horizontal and vertical dimensions; whereas in pure cervical stimulation using the new TET, this was only evident in the horizontal dimension and only during trunk torsion. Comparison of the two methods confirmed significantly stronger nystagmus modulation through head excursion. In terms of the HET, group(50) showed significantly more vertical nystagmus activity than group(26). However, no significant difference was found between the groups in terms of their reactions to trunk excursion in the TET. In a group-specific comparison of the methods, group(26) showed a significant increase in horizontal nystagmus in head compared to trunk excursion, whereas group(50) generally displayed a significantly greater response to provocation by head excursion in HET. Analysis of the significant vertical nystagmus modulation produced with the TET method showed predominance of upbeat- (UBN) over downbeat-nystagmus (DBN). Through head excursion with the HET, DBN was more frequently evoked in group(50) than in group(26). No significant age-dependent difference could be derived in UBN. CONCLUSION: The results of the pilot study indicate that head-to-trunk provocation is a suitable means of evaluating cervicotonic provocation nystagmus. Only by evaluation of adequate excursion limits and consistent analysis of patients with cervical deficiency can the effects of the method be further assessed.

Predictive binding of beta-carboline inverse agonists and antagonists via the CoMFA/GOLPE approach.

The synthesis and affinities of six new 3-substituted beta-carbolines (6-10, 12) for the benzodiazepine receptor (BzR) are described. These analogs were used both to probe the dimensions of the hydrophobic pocket in the benzodiazepine receptor and to test the predictive ability of a previously reported 3D-QSAR regression model. Of the new analogs synthesized, the gamma-branched derivatives (isobutoxy, 7, IC50 = 93 nM; isopentoxy, 9, IC50 = 104 nM) display significantly higher affinity for the BzR than either the beta-branched (sec-butoxy, 6, IC50 = 471 nM; tert-butyl ketone, 12, IC50 = 358 nM) or delta-branched (isopentoxy, 8, IC50 = 535 nM) analogs. An exception to this rule is the gamma-branched 3-benzyloxy derivative 10 (IC50 > 1000 nM) which appears to have a chain length that is too long to be accommodated by the BzR. The standard error of prediction for these six new beta-carbolines using the original regression model is significantly lower than the standard error estimate of the cross validation runs on the training set, hence the predictions made using this model are much better than expected. In order to obtain more credible predictions, a new procedure called GOLPE (generating optimal linear PLS estimates) was used to eliminate irrelevant electrostatic and steric descriptors from the regression equation. A substantial reduction in the standard error estimate resulted. The predictions from this new regression equation were somewhat less accurate than the ones obtained with the original regression equation; however the standard error of prediction and the standard error estimate are in much closer agreement. Finally, to probe the effect that the quality of the steric and electrostatic potentials has on 3D-QSAR analyses, the semiempirical MNDO parallel PRDDOE geometries and Mulliken charges used in the original analyses were replaced with ab initio 3-21G parallel 6-31G* geometries and electrostatic potential fit charges. A modest decrease in the standard error estimate and increase in cross validated R2 resulted.