insufficiency. In the case of ischemic ulcers, the classical appearance would involve an ulcer located on the 
toes, heel, or lateral aspect of the foot or in the distal lower limb, having a sharply demarcated border with 
necrotic edges and, in its center, pale, poorly formed granulation tissue; although the classic ischemic ulcer 
is extremely painful, local neurologic deficit (typically secondary to diabetes mellitus) may result in lack of 
pain. The development of apparent gangrene will be neither a requirement nor an exclusion criterion for the 
purposes of this study. To determine that simple conventional measures such as rest and therapeutic 
dressings will have been insufficient to acheive healing of the ulcer, a minimum duration of four weeks of 
conservative therapy without evidence of significant healing will be required for entry into the study. 
f. Non-invasive findings. Each patient will be required to have undergone non- 
invasive examination including, but not limited to, the following assessments: 
•Ankle-brachial index (ABI). Resting ABI in the affected limb must be <0.6 on two 
consecutive examinations performed at least 1 week apart. For patients with incompressible ankle arteries 
(due to calcific deposits with or without associated diabetes), the Great Toe Index (GTI) must be <0.6. 
•Excercise testing. It is assumed that the requirement for rest pain and/or ischemic 
ulcers will preclude excercise testing in most patients. Each patient, however, will be asked to excercise; if 
unable to do so, this will be noted. The basis for this consideration is that the ability to successfully 
complete any portion of an exercise protocol post-treatment will be evaluated in the event that rest pain is 
eliminated and/or ulcerations healed. 
g. Diagnostic angiography. Each patient will undergo selective diagnostic 
angiography of the involved extremity. A selective approach will be employed to optimally demonstrate 
distal runoff and pre-existing collateral arteries. The angiogram will be done via a contralateral or antegrade 
approach depending upon operator preference and patient anatomy, including the site of anatomic 
obstruction. To be eligible for entry into the study, diagnostic angiography must unequivocally 
demonstrate total occlusion in the affected limb of one or more of the following arteries: iliac, superficial 
femoral, popliteal, and/or one or more infrapopliteal arteries. Furthermore, the site of occlusion and 
associated anatomic findings must be such that selective angiography - and selective arterial transfection - 
is technically feasible. 
h. Medications. Patients will be included only if they agree to and judged appropriate to 
discontinue concomitant prostaglandin therapy and/or therapy with vasodilators, dextran, hetastarch, 
pentoxyfylline, L-camitine, and/or hyperbaric oxygen. Patients may continue to receive aspirin and 
coumadin, provided that these therapies have been used by the patient for a minimum of 6 months prior to 
entry into the study. 
II. B. 2 . Exclusion Criteria 
a. Aortic or lower extremity arterial surgery, angioplasty, or lumbar sympathectomy within 
2 months. 
b. Radiographic or radioisotopic evidence of concomitant osteomyelitis in ischemic 
extremity. 
c. Any concomitant disease process with a life expectancy of less than 1 year or which is 
sufficiently severe as to compromise clinical follow-up examinations. 
d. Significant history of alcohol or drug abuse within the past three months. 
e. Previous or current history of neoplasm 
f. Clinically significant abnormality in liver function or other laboratory tests, including 
PSA and CEA; moreover, patients will be excluded if there are even equivocal signs by chest radiograph, 
abdominal CT scan, mammography in the case of female, or prostate examination in the case of male of 
neoplasm. 
g. Clinical evidence of Type I diabetes mellitus, diabetic retinopathy, and/ or other 
ophthalmologic complications of diabetes. 
h. Patients who are pregnant, lactating, or if in whom childbearing capabilities are 
preserved, refuse to use barrier contraception. 
i. Refusal or inability to give informed consent. 
II. C. Patient Evaluation 
The following examinations will be performed prior to entry into the study (See Table 1). 
1) Medical history. The patient will be interrogated regarding the presence or absence of rest pain 
using a 10 cm visual analogue scale. The generic name and total daily dose of all analgesic or other drugs 
will be recorded. The date of any required surgery for extensive debridement, skin grafting or limb 
amputation will be recorded. A general and cardiovascular history will be recorded as well. 
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