Search

Osteonecrosis of the jaw induced by administration of bisphosphonates (BPs), BP-related osteonecrosis (BRONJ), typically develops after tooth extraction and is medically challenging. As BPs inhibit oral mucosal cell growth, we hypothesized that suppression of the wound healing-inhibiting effects could prevent BRONJ onset after tooth extraction. Since basic fibroblast growth factor (bFGF) promotes wound healing, but has a short half-life, we examined whether the initiation of BRONJ could be prevented by applying a bFGF-containing gelatin hydrogel over the extraction sockets of BRONJ model rats. Forty-three rats, received two intravenous injections of zoledronic acid 60 μg/kg, once per week for a period of 2 weeks, underwent extraction of a unilateral lower first molar. The rats here were randomly assigned to the bFGF group (n = 15 rats, gelatin hydrogel sheets with incorporated bFGF applied over the sockets); the phosphate-buffered saline (PBS) group (n = 14 rats, gelatin hydrogel sheets without bFGF applied over the sockets); or the control group (n = 14 rats, nothing applied over the sockets). One rat in the bFGF group was sacrificed immediately after tooth extraction. Twenty-one rats were sacrificed at 3 weeks, and the remaining 21 rats were sacrificed at 8 weeks after tooth extractions. The harvested mandibles were analyzed using micro-computed tomography and sections were evaluated qualitatively for mucosal disruption and osteonecrosis. The incidence of osteonecrosis at 8 weeks after tooth extraction was 0% in the bFGF group, 100% in the PBS group, and 85.7% in the control group. The frequency of complete coverage of the extraction socket by mucosal tissue was significantly greater in the bFGF group than in the other groups. These results suggest that application of bFGF in the extraction socket promoted socket healing, which prevented BRONJ development. The growth-stimulating effects of bFGF may have offset the inhibition of wound healing by BP.

To estimate the accuracy of cardiac output measured by continuous wave Doppler echocardiography from the suprasternal notch and the utility of this method for evaluating left ventricular function during dynamic exercise, simultaneous thermodilution and Doppler cardiac output were measured in 34 patients with coronary artery disease during multistage ergometer exercise in the supine position. Cardiac output was measured at rest and during each stage of exercise. Twenty-five of the 34 patients whose thermodilution curves were adequate for analysis were studied during exercise. The correlation coefficient for the two methods was 0.85 at rest and 0.84 during exercise. Differences between the two methods were not significant at rest but were significant during exercise, with the thermodilution method giving the higher values. Underestimation by the Doppler method is probably due to technical problems and changes in aortic diameter during exercise.The 25 patients were classified into two groups according to pulmonary artery wedge pressure at peak exercise. There were 11 patients in Group 1 pressure (≥20 mm Hg at peak exercise) and 14 in Group 2 pressure (