>> We have 19 powerbulder applicaitons that are used by 450+ users (not all at once) so to put the
>>applicaiton on all PCs would not be feasible.
Got that. That was just a debugging step to determine if the network is the issue.
I think the next step would be to get in touch with your networking support people and tell them what the problem is. They may have tools to monitor the situation.
You might also use something like Process Monitor to monitor what the application is doing. When if fails, check to see what was happening when the failure occurred. I'd be willing to be that suddenly the application couldn't access files on the network that up until that point it didn't have trouble reaching.