Are you using a HUB or plugging directly into the PC?
Here are the things I generally start with.
1. Battery pull.
2. No HUB connection
3. Delete/Reinstall DM
4. Try connecting to AppLoader via the DOS Command Prompt
Read this post for tips and help to connect your device to Desktop Manager, you might pull some from there: Tips for getting BlackBerry Desktop Manager to det... - BlackBerry Support Community Forums
Also, for a clean uninstall of Desktop Manager KB02206-How to perform a clean uninstall of the BlackBerry Desktop Software