Epinastine (WAL 801CL) inhibits the electrical field stimulation-induced cholinergic contraction in guinea pig and human airways in vitro.

Epinastine is an antihistamine drug with binding affinities at 5-hydroxytryptamine (5-HT) receptors. The current study was performed to investigate whether epinastine could modulate the cholinergic contraction in guinea pig and human airways in vitro. Isolated guinea pig and human airway preparations were suspended in organ baths containing modified Krebs-Henseleit solution. Electrical field stimulation was applied to elicit cholinergic contractions. Epinastine produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig airways and pretreatment with methysergide (5-HT1/2/7 antagonist) significantly attenuated these inhibitory effects of epinastine. Pretreatment with tropisetron (5-HT3/4 antagonist), ketanserin (5-HT2 antagonist), SDZ216-525 (5-HT1A antagonist) or phentolamine (alpha-adrenergic antagonist) had no effect. Epinastine did not displace the concentration-response curve to acetylcholine. These results suggest that epinastine inhibits the cholinergic contraction in guinea pig airways through stimulation of prejunctional 5-hydroxytryptamine receptors, located to postganglionic cholinergic nerves. Inhibitory effects of epinastine on the cholinergic contraction in human airways in vitro were also demonstrated, which suggests that a similar mechanism might be present in human airways. The pharmacological profile of epinastine, which shows binding affinity at the 5-hydroxytryptamine7 receptor but not at the 5-hydroxytryptamine1 receptor subtypes corroborates the hypothesis that the inhibitory prejunctional 5-hydroxytryptamine receptor on cholinergic nerves is of the 5-hydroxytryptamine7 subtype.

Pertrochanteric fractures in the elderly: are there indications for primary prosthetic replacement?

During a 10-year period (1978-1988), 565 patients, aged greater than or equal to 70 years, who sustained a fresh pertrochanteric fracture, were treated in the Department of Traumatology at the University Hospitals of Leuven, Belgium. Three hundred eighty-eight fractures were complex and unstable, according to the Evans-Jensen system and the AO system. Special attention was given to the 324 cases of type IC and ID in Evans' system, type A2 in the AO system. The method of treatment changed greatly during the period of study. All patients were followed prospectively during 1 year. Our study showed that for these unstable fractures, fixation with an angled plate or Ender nails should be forsaken. The overall results of the compression hip screw treatment were good (reoperation rate 2%, good functional results in 64%), but as this treatment has a risk for serious collapse and pain in about 80% of all type ID fractures, one could suggest treating these complex multifragment fractures primarily with an endoprosthesis. This treatment need no longer be considered severe intervention, as the danger of mechanical complications is minimal (less than 1%).