Familial expansile osteolysis: a morphological, histomorphometric and serological study.

Biopsies from the diseased bones of patients with familial expansile osteolysis (FEO) were examined by light and electron microscopy. Focal concentrations of multinuclear osteoclasts were present, and these contained viral-like microcylindrical inclusions which appeared exclusive to their nuclei. No consistent relationship was found between osteoclast size and the number of osteoclast nuclei containing microcylindrical inclusions. Quantitative histomorphometry showed evidence of increased bone remodelling with high bone cell densities and a decrease of the reversal period in bone remodelling. The lesions contained prominent woven bone and fibrovascular tissue, together with mononuclear cells and adipocytes. Little bone was found in the most radiolucent lesions, which were almost totally occupied by adipocytes and fibrovascular tissue. Serology did not reveal any significant differences between the viral antibody titres of patients and their age- and sex-matched controls. The present study suggests that intranuclear viral-like microcylindrical inclusions of osteoclasts are not a specific feature of Paget's disease, and are found in other disorders of osteoclast function, including pycnodysostosis, osteopetrosis, giant cell tumours, and familial expansile osteolysis.     

Prokinetic benzamides stimulate peristaltic activity in the isolated guinea pig ileum by activation of 5-HT4 receptors.

Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlying mechanism is unclear. To clarify this, the effect of some substituted benzamides on gut motility was investigated in the isolated guinea pig ileum using the Trendelenburg technique, in which pressure-induced peristaltic contractions are measured. All benzamides stimulated the peristaltic reflex with the rank order of potency: renzapride greater than cisapride greater than BRL 20627 greater than (+/-)-zacopride greater than metoclopramide. ICS 205-930, granisetron and 2-methyl-5-HT did not change the peristaltic response. 5-HT and 5-methoxytryptamine potently mimicked the effect of the benzamides. The effect of 5-HT was not blocked by ICS 205-930 (10(-7) M). These results indicate that the Trendelenburg preparation is suitable for the investigation of intestinal prokinetic effects of the substituted benzamides. Furthermore, the results suggest that the intestinal effect of benzamides results from activation of 5-HT4 receptors rather than from blockade of 5-HT3 receptors.