Registry changes occur quite frequently. In trying to find a registry key that SFC.EXE uses to call for SP2 I found over 500 registry changes in the 10 to 15 seconds that I was scanning the registry.
And this wasn't while any program was being installed. The use of Total Uninstall will tell you how many registry entries were deleted, created, or modified. And the logfile will tell you which ones they were. Using it to uninstall will let you know if everything is removed - and if it's not, then it gives you a list so that you can go hunt the buggers down to kill them.
But a generic registry cleanup tool cannot anticipate the actions of each individual programmer. If the programmer adds key "x" to the registry - and the cleaner doesn't anticipate this - then there's a good chance that key "x" will be left on the system.
That being said, I'd consider the safest registry tool to be one that was made by the folks who made the registry - in this case it's Microsoft. They have a free online registry cleaner available here: http://safety.live.com/
The caveat here is that overuse of any registry cleaner can cause problems with your system. Because this effect seems to be cumulative, it's doubtful if a registry backup would enable you to recover from it.
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