AMENDMENT NO. 1 TO STOCKHOLDERS AGREEMENT

   1
                                                                    Exhibit 4.22


                                 AMENDMENT NO. 1
                                       TO
                             STOCKHOLDERS AGREEMENT

         This Amendment No. 1 dated July 25, 2000, to the Stockholders Agreement
(the "Agreement") by and among (1) Ampersand Medical Corporation (as successor
by merger to Xxxx National Corporation); (2) Xxxxxxxxx X. Xxxxxx, Xxxxxx X.
Xxxx, Xxxxxx Corporation, a Massachusetts corporation, Xxxxxx Management
Incorporated, a Delaware corporation and Winchester National, Inc., a Delaware
corporation; and (3) Xxxxx X. Xxxxxxxx, as an individual and as Trustee of the
InPath, LLC Voting Trust; Xxxxxxxx X. Xxxxxx, as Trustee of each of The EAG
Trust, The CMC Trust, The MDG Trust and The MSD Trust; Xxxxxxx X. Xxxxxx;
AccuMed International, Inc., a Delaware corporation; Northlea Partners Ltd., a
Colorado limited partnership, Xxxx X. Xxxxxxx, as Trustee of Xxxx X. Xxxxxxx'x
Trust; Xxxxxx Xxxxxx, as Trustee of the Xxxxxx Xxxxxx Trust; and Monroe
Investments, Inc., and Illinois corporation.

                                   WITNESSETH:

         WHEREAS, the parties to the Agreement all agree that the Agreement
shall be terminated;

         NOW, THEREFORE, in consideration of the foregoing, the parties,
intending to be legally bound, agree the Agreement shall be terminated as of
July 25, 2000, and that it shall thereafter be of no further effect.

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