Retrospective post-authorisation safety study investigating the relationship of first-generation antihistamines with sedative effect and the risk of falls in older patients.

For patients at the age of 65 years or older an increased risk of falls in association with the intake of first-generation antihistamines with sedative effect is discussed. Currently, there are no valid data that can either confirm or disprove this risk. In this retrospective non-interventional safety study, the primary objective was to investigate a possible causal relationship between falls in patients ≥ 65 years of age and the intake of first-generation antihistamines. Secondary objectives were to investigate a possible causal relationship of falls after taking first-generation antihistamines for the subgroups < 65 years, 65-84 years and ≥ 85 years; to determine the fall rate of patients ≥ 65 years of age and of the subgroups < 65 years, 65-84 years and ≥ 85 years; and to identify causes of falls in patients ≥ 65 years. Out of the 13,866 physicians who were invited to participate in the study, 524 (3.8%) opened the link to the survey. The evaluation included verified data sets of 169 physicians who were either general practitioners or resident neurologists who had in total treated 313,046 patients within the previous six months. 9,922 patients had fallen at least once (total fall rate 3.2%). The rate of falls increased with age (< 65 years 1.1%; 65-84 years 3.9%; ≥ 85 years 9.9%). The fall rate of patients aged 65 years and older was 5.4%. Only a small proportion (2.9%, 8,942 patients) of the altogether 313,046 patients recorded had taken a first-generation antihistamine at any time within the previous six months. In the records of 9.5% (940 patients) of the 9,922 patients who had fallen the intake of first-generation antihistamines was documented. Detailed information was available for 379 of these patients with a total of 505 falls. The analysis of these cases indicates that in almost three quarters of falls (72.5%, 366 falls) there is no causal link between the intake of first-generation antihistamines and the fall. In almost 95% of the remaining 123 falls, the physicians suggested between one and seven possible alternative causes of falls (mainly underlying and concomitant diseases). This suggests that first-generation antihistamines do not play a relevant role in the fall incidents.

Export of ribosomal subunits from resealed rat liver nuclear envelopes.

We have previously described the rat liver resealed nuclear envelope model system for the study of the selective import of nuclear proteins, and the export of poly(A)-containing mRNA [Riedel, N., Bachmann, M., Richter, H. & Fasold, H. (1987) Proc. Natl Acad. Sci. USA 83, 3540-3544]. The vesicles still respond to the importin-ATP signal for the uptake of nuclear-location-sequence (NLS)-carrying proteins. During the preparation of the vesicles and extraction of the chromatin from nuclei in cold hypotonic heparin solution, ribosomal subunits may be introduced into these envelopes, and after resealing remain stably included. Efflux from the resealed nuclear envelopes is effected by a cytoplasmatic protein fraction, and strongly enhanced in the presence of ATP. The heterogeneous nuclear RNP (hnRNP) A1, the components of importin, or GTP showed no influence on this export. The ATP-dependent efflux of mRNA is not affected by these cytoplasmic proteins in this model system.