All what settings are gone? All user profile settings? Could someone have set a mandatory user profile?
Have him search the hard drive for "ntuser.man" he could change it back to ntuser.dat so that changes are saved.
If it isn't a mandatory profile, could someone have removed NTFS write permission for the profile? The default place to find it should be C:\Documents and Settings\Administrator have him look there for ntuser.dat and right click the file and check the security tab to look if the Administrators Group has NTFS write permission to file (if it isn't a FAT partition)
Or, he could delete the profile and he'll get the default profile next time he boots...then maybe he'll be able to make changes and they'll stick.