In general that would be a "random access" type of traffic,

and best practice on Isilon is to use mirroring rather than striping

for those files, and to set the access pattern to "random" rather than default/concurrent.

Easily done with SmartPools, otherwise see the docs for "isi set".

You might also check wether settings for oplocks and secure packet signing

are the same as with the windows server before.

If it's stills slow, see here for general performance troubleshooting,

but in case the cluster is busy at large, don't expect wonders for random I/O

https://emc--c.na5.visual.force.com/apex/KB_BreakFix_1?id=kA1700000000QXC

(KB article 88844)

In addition,  this helps identifying the individual latencies

for reads and writes per each client:

isi statistics -nall --long

With slow random reads predominant for the clients in question,

test loading the complete Excel or Access DB files into the Isilon's cache.

(e.g. copy the file to local temp and remove the copy, before opening the

original server file in the application.)

With slow random writes, also consider upgrading to 7.0 or 7.1,

there are significant improvements over 6.5 for write latencies!

hth

-- Peter