Repost of my entry on the JVM forum: 

I have been experiencing major noise issues with my Line 6 HD500 and the Marshall JVM 410C using a 4 cable method to hook it up.  On the high gain channels, I was getting some serious hum and a notchy cocked-wah resonance effect leading to feedback.  The indications were that this related to a ground loop somewhere in the hookup.

I managed to address the problem using a Behringer HD400 hum destroyer between the cables in/out of in the Amp FX Loop, thereby breaking the ground loop - very effective at getting rid of hum (but not hiss). However, I have been a bit concerned by the impact on my tone from putting this unit (effectible a transformer) inline.  This certainly causes a level drop and may be pulling on my tone too.

Santiago (the JVM's designer) had suggested in other posts that disconnecting the ground (shield) from one side of the patch cables used in the hookup could break the problem ground loops.  I have been reluctant to carve up my main performance cables but realised today that I didn't have to.

Instead. I went outand bought four 1/4" Mono Jack sockets and some short crocodile-clip cables (from my local Maplin store here in the UK).   I then improvised two cables, each using two 1/4" mono jacks and a croc clip cable linking the 'tip' connections only.  The ground tag on each socket was left unconnected.  I was left with a pair of 'ground lift' cables for testing with.

Next step:  I plugged short pedal hookup cables into the JVM 'Send' and 'Return' sockets and then plugged them into the jacks on one side of my home-made ground-lift cables.  Then I plugged the two leads that would normally go into the amp loop into the jacks on the other side of my home-made cables.  The upshot of this was that each cable in the amp loop wound up with a broken ground connection.

I then turned the master back up.  The result?   Hum gone - certainly as much as with the Hum Destroyer inline.  Hiss remained (as expected) but the gate on the MultiFx could now take care of that.  Anyone wanna buy a hum destroyer?

Next step is for me to go back and buy a (plastic/non-conductive) case for the jacks to go in.  I will then solder some wire in place of the croc cables and job done.

I have considered breaking the ground on cables themselves but I think it will be more flexible to use a box ... in case I run into some  unexpected circumstance where I am forced to put the grounds back.   Not sure why I would want to right now though.  If after a period I don't get any problems I will attack the cables and remove the grounds from those.

Thought this might be useful as information and a test procedure for anyone trying to fight with hum in a 4CM or similar setup.  You could try breaking grounds like this on any of the signal cables for testing - but keep the master volume down on HD500 and amp. If your master volume comes in before the FX Loop on the amp then all you can do is be careful that your test cables are not shorting .... or you will know noise !!!

Do NOT remove the ground on your speaker cable.  This could do damage.

Do NOT break the main ground connection into the amp as this is very dangerous.  If your amp has a ground lift switch, take it to a competent tech for evaluation and advice.

Do NOT break the ground on the cable that plugs into your guitar.  This will kill your connection and will not work.

This information is provided for use at your own risk.  There is always a degree of risk when working with electrical devices and I will not held liable for  personal injury or death as a result of actions taken as a consequence of this post.  OK ?

Edit 9-Oct-11:  I built a ground lift box that I now use to take care of this problem.  Details can be found over on jvmforum.com at http://jvmforum.com/phpBB3/viewtopic.php?f=7&t=5610