Background: An attempt was made to visualize minute intraductal lesions using helical CT in patients with abnormal nipple discharge.Methods: Galactography was performed, immediately followed by CT (ductal CT examination). Based on the image data obtained, ductal images were constructed on a workstation using a Pegasus viewer (ductal CT imaging). Since no criteria for diagnosis by this method are available, ductal CT images were diagnosed by reference to the known ductal fiberscopic findings 1, 2) .Results: Ductal CT examination was performed in 10 cases, in 9 of whom ductal CT images were successfully constructed. Pathological examination was performed in 8 cases. It was possible to observe the structure of the luminal surface on the constructed ductoscopic images from all directions, but the color tone or the presence or absence of hemorrhage could not be observed.Conclusions: In the examination for abnormal nipple discharge, ductal CT examination was useful for intraductal observation. Currently, it is a method that allows for observation of the most minute intraductal lesions. However, some issues still remain unresolved. The results of this study suggest that further studies with more cases hold the promise of making ductal CT imaging a useful examination method.

Laboratory rabbits are fed foods rich with cationic metals, and while fasting cannot empty gastric contents because of their coprophagic habits. This implies that, in rabbits, the oral bioavailability of chelating drugs could be modulated by the slow gastric emptying rates and the interaction (chelation, adsorption) with gastric metals. In the present study, we tried to develop a rabbit model with low amounts of cationic metals in the stomach for preclinical oral bioavailability studies of chelating drugs. The elimination of gastric metals was achieved by preventing food intake and coprophagy and administering a low concentration of EDTA 2Na solution one day before experiments. Control rabbits were fasted but coprophagy was not prevented. The efficacy of rabbits treated with EDTA 2Na was evaluated by comparing the gastric contents, gastric metal contents and gastric pH between EDTA-treated and control rabbits. The treatment with more than 10 mL of 1 mg/mL EDTA 2Na solution decreased the amounts of gastric contents, cationic metals and gastric pH, without causing mucosal damage. The absolute oral bioavailabilities (mean values) of levofloxacin (LFX), ciprofloxacin (CFX) and tetracycline hydrochloride (TC), chelating antibiotics, were significantly higher in EDTA-treated rabbits than those in control rabbits as follows: 119.0 vs. 87.2%, 9.37 vs. 13.7%, and 4.90 vs. 2.59%, respectively. The oral bioavailabilities of these drugs were significantly decreased when Al(OH)3 was administered concomitantly in both control and EDTA-treated rabbits. In contrast, the absolute oral bioavailabilities of ethoxycarbonyl 1-ethyl hemiacetal ester (EHE) prodrugs of LFX and CFX (LFX-EHE, CFX-EHE), which are non-chelating prodrugs at least in in vitro condition, were comparable between control and EDTA-treated rabbits irrespective of the presence of Al(OH)3, although some variation was observed among rabbits. The oral bioavailabilities of LFX and CFX from their EHE prodrugs were comparable with LFX and CFX alone, respectively, even in the presence of Al(OH)3. In conclusion, LFX, CFX and TC exhibited higher oral bioavailabilities in EDTA-treated rabbits than in control rabbits, indicating that the oral bioavailabilities of these chelating drugs are reduced in untreated rabbits. In conclusion, EDTA-treated rabbits were found to exhibit low gastric contents including metals and low gastric pH, without causing mucosal damage. Ester prodrug of CFX was effective in preventing chelate formation with Al(OH)3 in vitro and in vivo, as well as in the case of ester prodrugs of LFX. EDTA-treated rabbits are expected to provide great advantages in preclinical oral bioavailability studies of various drugs and dosage formulations. However, a marked interspecies difference was still observed in the oral bioavailability of CFX and TC between EDTA-treated rabbits and humans, possibly due to the contribution of adsorptive interaction in rabbits. Further study is necessary to seek out the usefulness of the EDTA-treated rabbit with less gastric contents and metals as an experimental animal.

In the examination for abnormal nipple discharge, ductal CT examination was useful for intraductal observation. Currently, it is a method that allows for observation of the most minute intraductal lesions. However, some issues still remain unresolved. The results of this study suggest that further studies with more cases hold the promise of making ductal CT imaging a useful examination method.