Lower extremity article.doc
Vol. 10 •Issue 3 • Page 32 Wound Care
Evaluation & Management of Lower Extremity Ulcers
Adherence to Prescribed Therapy Can Save Limbs
By Susie Seaman, NP Lower extremity ulcers may affect up to 2.5 million people in the United States and are a source of significant morbidity and expense.1 Most leg ulcers are a result of chronic venous insufficiency, peripheral arterial disease or diabetes.2 Many patients with these chronic conditions present with vascular, neurological or skin changes in the lower extremities long before an ulcer develops. Early recognition of these changes permits preventive measures to avoid ulceration. When a leg ulcer develops, identification and management of the underlying disease process are paramount to successful wound healing. Other aspects of chronic wound care include the management of systemic factors that affect wound healing, use of appropriate topical therapy, debridement of nonviable tissue, and identification and treatment of infection (Table 1). Many providers adequately address these factors, but miss the underlying disease process.
Table 1: Principles of Chronic Wound Management
1. Nutritional and fluid support — especially important with large wounds such as pressure
ulcers, post-operative abdominal wounds and severe traumatic injuries
Diet history Weight loss > 15% total body weight Laboratory in dices: -Albumin -Transferrin -Pre-albumin -Total lymphocyte count
30-35 calories/kg/day 1.25-1.5 grams of protein/kg/day
Vitamin and mineral supplementation 2. Control systemic conditions that affect wound healin g
• Medications (corticosteroids, chemotherapy): check with prescribing provider to see if meds can be adjusted to improve healing • Altered tissue perfusion 2º local or systemic factors: improve blood flow, address cardiopulmonary issues
1. Sharp: the use of instruments to remove necrotic tissue
• Fast, aggressive management, the only method that works to remove
• May be painful (requires local anesthesia), contraindications include bleeding tendency, severe PAD 2. Mechanical: the use of physical forces to remove necrotic tissue. Examples include wet -to-dry gauze dressings, whirlpool, scrubbing the wound with gauze
• Provides non-selective debridement (removes viable and nonviable tissue), leading to further tissue trauma. Whirlpool can result in maceration of intact skin, cross-contamination, and burns. There is no evidence supporting whirlpool in chronic wound care. 3.Enzymatic — the use of prescription enzymes to digest necrotic tissu e; papain — or collagenase -based
• Easy to use, provides selective debridement (does not harm viable tissue)
• Costly pharmaceutical, slower than sharp debridement, possible sensitivity reactions
4. Autolytic — the debridement of necrotic tissue by white cells and naturally occurring enzymes that are present in wound fluid. Occurs optimally under occlusive dressings • Painless, selective debridement, easy to use in home care and long term care settings
• Slow debridement, occlusive dressings contraindicated in infected wounds
1. Differentiate between colonization and infection
• Colonization is the presence of multiplying microbes in a wound without invasion into viable tissue. Evidenced by: Odor prior to cleansing Multiple organisms on swab culture
• Infection is the invasion and multiplication of microbes into viable tissue, causing a host reaction as evidenced by: Erythema Tissue necrosis (with necrotizing infections) Induration Fever Pain Leukocytosis Increased exudate
• Colonization is treated with debridement and wound cleansing. Infection requires systemic antibiotics. 2. Obtain cultures appropriately; the purpose of the culture is to identify the infecting organism. Only culture when an infection is diagnosed and treatment is being initiated.
• Thoroughly debride and irrigate wound prior to culturing to remove colonizing bacteria
• Only swab over viable tissue, not necrotic tissue (the bacteria that have invaded viable tissue is what is required for identification)
• Saline irrigation preferred — 35cc syringe and 19g needle = 8 psi of pressure, sufficient to decrease bacterial counts and remove debris from wound
• Commercial wound cleansers — contain nontoxic cleansers, very convenient for home use 2. Avoid topical antiseptics such as betadine, hydrogen peroxide, Dakin's solution, acetic acid. These chemicals harm healthy cells and can impair wound healing. If bacterial colonization is a concern, use topical antibiotics instead, after saline irrigation 3. Utilize dressings that maintain a moist wound environment
• Advantages of moist wound healing Prevention of tissue dehydration and cell death Accelerated wound healing
Autolytic debridement Reduced pain Better cosmetic effect • Characteristics of an ideal dressing41 Does not damage or dessicate wound Provides thermal insulation Provides moist environment Serves as barrier to microorganisms Absorbs excess exudate Allows atraumatic removal • Basic rules of dressing selection High exudate
Ischemic ulcers fail to heal due to impaired blood flow to the wound. This may be due to a disruption in microvascular blood flow, which
occurs with disorders such as vasculitis, microthrombosis, Raynaud's phenomenon and sickle cell anemia. More commonly,
macrovascular flow is disrupted by atherosclerosis.
Atherosclerosis, caused by deposits of cholesterol, lipids and calcium in the lumen of vessels, may affect any artery in the body and
lead to impaired arterial flow.3,4 Peripheral arterial disease (PAD) is atherosclerosis of the large and medium -sized vessels of the lower
extremities.5 The patient with PAD may present with a his tory of coronary artery disease, cerebrovascular disease, hyperlipidemia,
diabetes, hypertension or cigarette smoking.6 He may have undergone prior revascularization procedures or amputation. A history of
vascular disease suggests that PAD may be the underlying disorder causing the chronic leg ulcer.
Ischemic ulcers from PAD are typically the result of trauma. When blood flow is insufficient to meet the metabolic demands of tissue
repair in the presence of severe PAD, a chronic wound results.
Symptomatically, the patient with PAD may complain of intermittent claudication or rest pain.2 Claudication is ischemic pain in the
muscles of the legs (calves, thighs, buttocks) that occurs with exercise and abates promptly with rest. Rest pain, which indicates severe
PAD, typically occurs at night and affects the feet. The pain may diminish when the patient suspends his legs over the side of the bed.
Patients with limb-threatening PAD may report the need to sleep with legs dependent to reduce pain. The patient with an ischemic ulcer
secondary to PAD may also complain of severe tenderness at the wound site, and may not tolerate aggressive cleansing.
An ischemic ulcer secondary to PAD occurs on the distal extremities and has a deep, punched-out appearance with regular wound
edges.5,7 The wound bed appears pale and may have necrotic tissue, but no healthy granulation tissue. Associated manifestations may
include femoral bruits; absent or diminished peripheral pulses; thin, shiny, dry skin; thickened toenails, absence of hair, decreased skin
temperature; or dependent rubor. Doppler examination of the pedal pulses may reveal monophasic or absent sounds.
If you suspect PAD as the etiologic factor of a leg ulcer, order further testing to obtain qualitative and quantitative data. Order
noninvasive vascular testing (NIVT), including segmental pressures, toe pressures, Doppler waveform analysis, and duplex scanning.8,9
Depending on availability, transcutaneous oxygen monitoring or skin perfusion pressures may be obtained.10,11 Table 2 describes these
tests and their significance. Order a lipid panel to rule out hyperlipidemia. Radiographic films can rule out osteomyelitis and provide
baseline films for future comparison.
Table 2: Noninvasive Vascular Testing
BP cuffs placed on the proximal thigh, distal thigh,
proximal calf and ankle. SBP is obtained at each
level using a Doppler. SBP is also obtained from
between two cuffs. -Ankle pressure < 40 mm Hg is associated with ischemic rest pain. -Calculate ABI by dividing the ankle SBP by the brachial SBP. -normal: 1.0 -1.2 -claudication: 0.5-0.9 -rest pain/impaired healing: < 0.5
Doppler probe is held over the artery at the level of
the femoral, popliteal, dorsalis pedis and posterior
tibial vessels. A printout is provided of the
Small pneumatic cuff is placed around the toe.
Using a photoelectrode on the tip of the toe,
photoplethysmograph. The cuff is inflated until the
waveform is flat. During deflation of the cuff, SBP is
recorded at the first return of a waveform.
-Toe/brachial index < 0.65 indicates decreased blood flow.
A transducer is held over the vessels to be
examined and ultrasound technology (B -mode and
pulsed doppler) is used to provide anatomic and
A sensor, placed on the skin, is heated to cause
local vasodilitation, and the oxygen level at the skin
A pneumatic cuff with a laser Doppler flow sensor is
placed around the toe, foot, ankle, calf, or thigh.
This is attached to a monitor that records capillary
blood flow. As the cuff is inflated, pressure is
exerted on the skin, which causes capillary flow to
cease. As the cuff is deflated, the sensor notes the
point at which flow returns. This is the skin
SBP = systolic blood pressure PAD = peripheral arterial disease Reprinted with permission. From: Seaman S. Considerations for the global assessment and treatment of patients with recalcitrant wounds. Ostomy/Wound Management
. 2000;46(Suppl 1A):10S-29S. The key to the successful treatment of ischemic ulcers secondary to PAD is restoration of blood flow. Refer the affected patient to a vascular surgeon, who may order arteriography to provide a definitive anatomic map of the arterial disease. Based on the test results, the surgeon will plan a revascularization procedure, which may include bypass surgery, angioplasty or placement of an intravascular stent.6,12 PAD in patients unaffected by diabetes (occurring most commonly in the larger aortic, iliac and femoral arteries) is amenable to each of the three latter procedures. PAD in diabetes patients (occurring in the smaller vessels between the knee and the ankle) may be best treated with bypass surgery, but endovascular procedures are sometimes performed.13 Many providers incorrectly believe that diabetes patients are not good candidates for revascularization. However, the majority of diabetes patients with PAD can undergo successful distal bypass surgery to the pedal vessels, which are frequently patent.14,15 LoGerfo
et al demonstrated that extreme distal bypass surgery to the pedal vessels in patients with diabetes was inversely related to amputation
rate (r = -.91, P <.001).16 With this same procedure, Pomposelli et al demonstrated a 3-year patency rate of 87%, and a limb salvage
rate of 92%.17 All patients with severe PAD that affects wound healing, regardless of diabetes status, should be evaluated for
Nonsurgical approaches to PAD include risk factor modification and pharmacologic therapy. Target serum LDL for a patient with
documented vascular disease is < 100 mg/dL.18 In diabetes, target HbA1c is < 7.0%.19 Hypertension should be controlled, and the
patient should stop smoking and lose weight if needed. Refer the patient to ancillary programs to assist with lifestyle changes as
necessary. Pharmacologic therapy includes platelet inhibitors, such as aspirin, ticlopidine (Ticlid) or cilostazol (Pletal), and
hemorrheologic agents such as pentoxifylline (Trental).20,21
Topical therapy for an ischemic ulcer depends on vascular supply. If NIVT indicates adequate blood flow to support healing, or if the
patient has been successfully revascularized, debridement and provision of a moist wound healing environment is recommended to
promote tissue repair. When NIVT suggests severe ischemia and the patient is not a candidate for revascularization, dry eschars
should be left intact. Debridement of intact eschar on an extremity with little potential to heal exposes the underlying tissue to possible
contamination and infection. Debridement into viable tissue causes further tissue damage, which, in the presence of severe ischemia,
may lead to extension of the necrosis. The eschar should simply be kept dry and protected.
Chronic venous insufficiency (CVI) is the etiologic factor in the majority of leg ulcers.22 CVI is the result of damage to the valves of the
leg veins, which results in impaired venous return and abnormally high venous pressure at rest and with ambulation. This leads to
edema and altered microcirculation in the skin, which causes impaired healing.22,23 Risk factors for CVI include a history of deep-vein
thrombosis, obesity, lower leg trauma (crush injury, fracture or surgery), congenital venous abnormality, limited mobility with impaired
calf muscle pump (arthritis, paralysis, muscular disorders), and pregnancy.24 The presence of these risk factors in a patient who has a
leg ulcer should cue you to think about CVI as an etiologic factor in wound chronicity.
Venous ulcers are frequently precipitated by trauma. The patient may have traumatized the leg weeks to months earlier, and the wound
never healed. The patient may also report that he had a pruritic rash and that the ulcer started after the skin was scratched. Finally, a
spontaneous blister may form in the presence of severe edema and, following rupture, result in a chronic wound.
Venous ulcers generally occur on the lower calf, above the malleoli.25 The ulcers are superficial and have irregular wound edges and
ruddy granulation tissue. Necrotic tissue is not present unless there is coexisting PAD or a severe infection.
The presence of fibrin, a pale yellow gelatinous material that commonly accumulates in venous ulcers, should not be confused with
necrotic tissue. Venous ulcers have high amounts of exudate due to the edema in the surrounding tissue. Patients complain of low to
moderate pain, especially with leg dependence, which is relieved by leg elevation. Associated manifestations include normal pulses (in
the absence of coexisting PAD), edema, hyperpigmentation of the skin (due to hemosiderin deposits), stasis dermatitis, and dilated
superficial veins. In late CVI, lipodermatosclerosis (fibrosis of the skin and subcutaneous tissue in the lower leg) may be present. If
pulses are not palpable due to edema, a Doppler exam reveals biphasic or triphasic sounds in the absence of PAD. If the pulses are
abnormal, noninvasive vascular testing should be done prior to treatment.
Compression therapy is the mainstay of treatment for venous ulcers. Table 3 lists various compression devices and their advantages
and disadvantages.26,27 Compression can be safely applied with an ankle-brachial index (ABI) > 0.9, and caution should be used with
an ABI between 0.7 and 0.9. Compression is contraindicated if the ABI is 0.7.28 Essential to the prescription of compression therapy is
the patient's device preference. It does not matter if a particular device is best for a patient if he will not wear it! Typically, Unna boots or
multi-layer wraps are used for ulcer treatment. Once the ulcer is healed, stockings, wraps or leggings are used for long-term
compression. The key to prevention of ulcer recurrence is lifelong compression therapy.
Table 3: Compression Modalities
Wraps that are applied from the toes to the knee.
Elastic hosiery with graduated compression that decreases from
Compression varies at the ankle from 20-60 mmHg.
Gauze imp regnated with variety of substances including calamine,
zinc oxide, gelatin or glycerine. Applied as a wrap from the toes to
the knee. For sustained compression, a self-adherent elastic wrap
(eg., Coban) should be applied over the paste bandage. With the
latter, provides approx. 30-40 mm at the ankle.
health care provider -Does not handle heavy exudate
Multiple layers of wraps that are applied dry. The first la yer is a
soft cotton wrap. Subsequent layers provide compression that is
cannot manage wraps or stockings, or are allergic to paste bandages
Inelastic system of straps that are applied from the toes to the
knee. Straps are secured with velcro. Separate ankle-foot wrap
that actively pumps out fluid; also provides low resting pressure
-After training, easy to apply, even for patients with poor strength -Provides sustained compression -Best choice for morbidly obese patients and patients with lymphedema
Adapted with permission. From: Seaman S. Considerations for the global assessment and treatment of patients with recalcitrant wounds. Ostomy/Wound Management.
2000;46(Suppl 1A):10S-29S. Pharmacotherapy, bioengineered tissue or surgery may be indicated for patients with ulcers that are unresponsive to optimal care. Stanozolol (Winstrol), an anabolic steroid with fibrinolytic properties, can reduce pain and induration associated with lipodermatosclerosis, although enhanced ulcer healing has not been demonstrated.29 Pentoxifylline (Trental), which has multiple effects including increased cell deformability, decreased blood viscosity, increased fibrinolysis and decreased platelet aggregation and adhesion, has demonstrated improved venous ulcer healing.30 Apligraf, a bi-layered skin equivalent consisting of human keratinocytes and fibroblasts derived from neonatal foreskin, may expedite wound closure in chronic venous ulcers.31 Apligraf is not a skin graft; it delivers living cells to the wound bed that produce extracellular matrix proteins, as well as growth factors that stimulate wound healing. Surgical options include ligation of affected perforating veins, stripping (removal) of the saphenous vein or reconstruction of the deep veins with valvuloplasty. A less invasive procedure involves the endoscopic ligation of perforators (subfascial endoscopic perforator surgery). Studies have demonstrated that each of these procedures is effective at improving venous hemodynamics and promoting healing of recalcitrant venous ulcers.32,33 Topical therapy of venous ulcers consists of providing a moist wound healing environment. Use caution when introducing any new topical treatment such as creams, ointments or adhesive dressings, since patients with venous ulcers tend to have multiple contact allergies. A 48-hour patch test with the product is advised to prevent widespread contact dermatitis. Dermatitis (whether from a sensitivity reaction or from CVI) should be treated with corticosteroid ointments, which have fewer preservatives that may cause sensitivity reaction, rather than creams. Fluocinolone ointm ent 0.025% (Synalar, etc.) is an example of a medium -potency corticosteroid that has no preservatives, and thus is appropriate for the treatment of stasis or contact dermatitis associated with venous ulceration.
Table 4: Other Causes of Lower Extremity Ulcers
Vasospastic disorders (e.g., Raynaud's)
Thromboangiitis obliterans (Buerger's disease)
Marjolin's ulcer (malignant transformation of chronic ulcer or scar)
Diabetic Foot Ulcers
An estimated 15% of people with diabetes develop a foot ulcer at some point, and up to 24% require amputation because of foot
ulcers.34 It is critical to understand the primary cause of diabetic foot ulcers, because early intervention aimed at primary prevention
may prevent at least half of all amputations. Many providers mistakenly believe that the primary etiologic factor in the development of a
diabetic foot ulcer is peripheral arterial disease. While 20% of diabetic foot ulcers are due to PAD, at least 60% are secondary to
peripheral neuropathy alone. Another 20% of diabetes patients with foot ulcers have both PAD and neuropathy.35
Diabetic foot ulcers due to peripheral neuropathy occur as a result of repetitive trauma from pressure and shear.36-38 Sensory
neuropathy results in an insensate foot that causes the patient to not feel traum a. Motor neuropathy causes atrophy of the foot muscles
that support the joints, leading to foot deformities and abnormal bony prominences subject to repeated mechanical stress during
A thick, hard callus forms over the bony prominence in response to this repetitive trauma. Due to lack of sensation, the patient is
unaware of the callus, and continues to walk on it. This results in pressure to underlying tissue, which is compressed between the callus
and the bony prominence and results in tissue damage. A blister or hematoma forms under the callus, which eventually ruptures as the
exposure to pressure continues. The patient may be unaware that a problem has occurred and may finally present to you after noting
blood on his sock. Unfortunately, many patients present to the emergency department with foot infection as the first sign of a problem.
The diabetic foot ulcer that is secondary to neuropathy has a characteristic appearance. It occurs over a bony prominence, typically on
the plantar surface of the foot, and is punched out, with a clean, pink wound bed (in the absence of infection or PAD) and surrounding
callus. Loss of sympathetic tone from autonomic neuropathy impairs sweating and results in very dry skin with possible fissures. To
help achieve early recognition and prevention of such ulcers, regularly inspect feet and treat callus formation with debridement,
appropriate shoe gear and patient education. The patient who understands why the ulcers form will tend to be more compliant with foot
care and shoe gear recommendations.
Prior to initiating treatment for a diabetic foot ulcer, further assessments are needed.34,37 Perform a complete neurovascular exam.
Patients with neuropathic diabetic foot ulcers exhibit loss of protective sensation (as evidenced by an inability to feel a Semmes -
Weinstein monofilament on the plantar foot) and a decrease in vibratory sensation, proprioception and deep tendon reflexes. The
majority of patients with diabetic foot ulcers have adequate arterial flow, so puls es are usually palpable.
If they are not palpable, perform noninvasive vascular testing, keeping in mind that the ankle-brachial index tends to be falsely elevated
in people with diabetes.
Assess glucose control via HbA1c levels. Radiographs of the affected foot can rule out foreign bodies and osteomyelitis, and provide
baseline data for later comparison. Routine assessment of the wound should include gentle probing to check for bone exposure.
Grayson et al demonstrated a positive predictive value of 89% for osteomyelitis when infected diabetic foot ulcers were probed to
Finally, the unaffected foot should be thoroughly assessed for deformities, calluses and unrecognized trauma.
Goals of wound management include identification and treatment of infection, ongoing callus debridement, provision of a moist wound
environment, and off-weighting to reduce pressure and normalization of blood glucose.34,37 Patients with severe PAD should be
revascularized as previously discussed.
Infection is a leading cause of amputation and must be addressed promptly.40 Treatment is based on the risk for limb loss. Non-
threatening limb infections include those with no systemic symptoms, absence of abscess, osteomyelitis and gangrene, and peri-wound
cellulitis less than 2 cm.34 These wounds may be treated on an outpatient basis with oral antibiotics. The patient should be reassessed
in 1 to 3 days, depending on the severity of the infection and the patient's ability to monitor his own condition.
Limb-threatening infections are associated with advancing cellulitis, a deep abscess or osteomyelitis. Gangrene may be present,
especially with coexisting PAD. A patient with a plantar ulcer with dorsal cellulitis should be considered as having a deep space
Patients with limb-threatening infection require urgent hospitalization, intravenous antibiotics and surgical debridement.34,38 Infection is
a potentially serious consequence of foot ulceration and may require a multidisciplinary approach to resolve it.
Local wound care involves the regular sharp debridement of any nonviable tissue and peri-wound callus. The presence of nonviable
tissue in the wound increases the risk for infection, since it is a culture medium for bacteria. The peri-wound callus is a source of
ongoing pressure (not a problem if the patient is compliant with off-weighting), impairs epithelialization from the wound margins, and
creates a ledge in which bacteria can become trapped. As long as the patient does not have severe PAD, aggressive debridement is
essential for wound healing to occur. Additionally, local care includes the provision of a moist wound healing environment using gels or
creams for low draining wounds and absorptive fillers for high draining wounds.41
Off-weighting is the key to s uccessful treatment of these ulcers.34 Because diabetic foot ulcers occur secondary to repetitive trauma, the
source of the trauma should be removed. The patient must
be completely non-weightbearing on the affected foot. Refer patients to a
physical therapist for instruction in crutch-walking, to an orthotist or podiatrist for an off-weighting device, and order a wheelchair.
Several types of off-weighting devices exist, from special shoes and removable boots to total contact casts. The goal is to mold the
device to the foot, thus dispersing pressure away from the bony prominence where the wound is located. The multidisciplinary team, in
consultation with the patient, should decide on the most appropriate device. The device should be worn at all times, except when
sleeping (the contact cast stays on 24 hours per day).
Patients with diabetic foot ulcers that do not heal despite optimal care may require the use of advanced technologies such as growth
factors or bioengineered tissue, or possibly surgical intervention. Human recombinant platelet-derived growth factor (Regranex Gel) can
improve wound healing rates in diabetic foot ulcers compared to placebo.42 This prescription gel is easily applied to the wound on a
daily basis. Both Apligraf and Dermagraft have demonstrated enhanced healing of diabetic foot ulcers compared to controls.43,44
Providers apply these devices in the clinical setting. Impaired wound healing or recurrence of diabetic foot ulcers may result from
underlying osseous deformities. Surgical intervention to correct structural abnormalities may be a viable alternative for treatment and
long-term prevention of recurrence.45,46 Refer patients with significant foot deformities who are unresponsive to optimal care to a
podiatrist or orthopedic surgeon experienced in foot reconstruction.
Once the wound is healed, an orthotist should fit the patient for appropriate long-term shoe gear. Edmonds et al reported only a 26%
recurrence rate of foot ulceration in patients with healed diabetic foot ulcers that were placed in special shoes.47 Patients who wore their
own regular shoes had an 83% recurrence rate.
Educate patients that prevention of recurrence requires meticulous foot care for life. This includes daily foot inspection and prompt
reporting of any callus formation. A callus should be recognized as a pre-ulcerative condition that requires both prompt debridement
and referral back to the orthotist for shoe adjustment.
Patient Education Essential
Nurse practitioners play an essential role in educating patients about leg ulcers and how to prevent them. Writing a prescription for
compression stockings or a pair of custom shoes is not enough; the patient must acknowledge and accept the need for these devices.
Lastly, just as blood pressure is checked at each clinical visit, the patient with a history of a lower extremity ulcer should be checked for
compliance with the medical regimen, including compression therapy for venous disease, risk factor modification for peripheral arterial
disease, or proper foot care and shoe gear for diabetic peripheral neuropathy.
1. Phillips T, Stanton B, Provan BA, Lew R. A study of the impact of leg ulcers on quality of life: financial, social, and psychologic
implications. J Am Acad Dermatol.
2. Donayre CE. Diagnosis and management of vascular ulcers. In: Sussman C, Bates -Jensen BM, eds. Wound Care: A Collaborative
Practice Manual for Physical Therapists and Nurses.
2nd ed. Gaithersburg, Md.: Aspen Publishers; 2001:390-402.
3. Federman DG, Trent JT, Froelich CW, Demirovic J, Kirsner RS. Epidemiology of peripheral vascular disease: a predictor of systemic
vascular disease. Ostomy/Wound Management.
4. Creager MA, Dzau VJ. Vascular diseases of the extremities. In: Fauci AS, ed. Harrison's Principles of Internal Medicine
. 14th ed. New
5. Rubano JJ, Kerstein MD. Arterial insufficiency and the vasculitides. J WOCN.
1998;25:147-157. 6. O'Brien SP, Mureebe L, Lossing A, Kerstein MD. Epidemiology, risk factors, and management of peripheral vascular disease.
7. Sibbald RG. An approach to leg and foot ulcers: a brief overview. Ostomy/Wound Management.
1998;44(9):28-55. 8. Gahtan V. The noninvasive vascular laboratory. Surg Clin North Am.
1998;78:507-518. 9. Ligush J, Reavis SW, Preisser JS, Hansen KJ. Duplex ultrasound scanning defines operative strategies for patients with limb
threatening ischemia. J Vasc Surg.
10. Padberg FT, Back TL, Thompson PN, Hobson RW. Transcutaneous oxygen (TcPO2) estimates probability of healing in the
ischemic extremity. J Surg Res.
11. Castronuovo JJ, Adera HM, Smiell JM, Price RM. Skin perfusion pressure measurement is valuable in the diagnosis of critical limb
ischemia. J Vasc Surg
12. Wisselink W, Panetta TF. Endoluminal treatment of vascular occlusive disease. Surg Clin North Am.
1998;78:863-879. 13. Hu MY, Allen BT. The role of vascular surgery in the diabetic patient. In: Bowker JH, Pfeifer MA, eds. The Diabetic Foot.
6th ed. St.
14. da Silva AF, Desgranges P, Holdsworth J, et al. The management and outcome of critical limb ischemia in diabetic patients: results
of a national survey. Diabetic Med.
15. Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg.
1998;176(Suppl 2A):5S-10S. 16. LoGerfo FW, Gibbons GW, Pomposelli FB, et al. Trends in the care of the diabetic foot: expanded role of arterial reconstruction.
17. Pomposelli FB, Jepsen SJ, Gibbons GW, et al. Efficacy of the dorsal pedal bypass for limb salvage in diabetic patients: short term
observations. J Vasc Surg.
18. Ginsberg HN, Goldberg IJ. Disorders of lipoprotein metabolism. In: Fauci AS, ed. Harrison's Principles of Internal Medicine
. 14th ed.
New York, NY: McGraw-Hill; 1998: 2138-2149.
19. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care.
20. McNamara DB, Champion HC, Kadowitz PJ. Pharmacologic management of peripheral vascular disease. Surg Clin North Am.
21. Eberhardt RT, Coffman JD. Drug treatment of peripheral vascular disease. Heart Dis.
2000;2(1):62-74. 22. Falanga V. Venous ulceration. J Dermatol Surg Oncol.
1993;19:764-771. 23. Rudolph DM. Pathophysiology and management of venous ulcers. J WOCN.
1998;27:248-255. 24. Scott TE, LaMorte WW, Gorin DR, Mensoian JO. Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc
25. Sibbald RG. Venous leg ulcers. Ostomy/Wound Management.
1998;44(9):52-64. 26. Partsch H. Compression therapy of the legs. J Dermatol Surg Oncol.
1991;17:799-805. 27. Fletcher A, Cullum N, Sheldon TA. A systematic review of compression treatment for venous leg ulcers. BMJ.
1997;315:576-580. 28. McGuckin M, Stineman MG, Goin JE, Williams SV. Venous Leg Ulcer Guidelines
. Wayne, Pa: Health Management Publications Inc;
29. McMullin GM, Watkin GT, Coleridge-Smith PD, Scurr JH. Efficacy of fibrinolytic enhancement with stanozolol in the treatment of
venous insufficiency. Aust N Z J Surg.
30. Falanga V, Fujitani RM, Diaz C, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a
randomized, placebo-controlled trial. Wound Rep Reg.
31. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured
human skin equivalent. Arch Dermatol.
32. DePalma RG, Kowallek DL. Venous ulceration: a cross-over study from nonoperative to operative treatment. J Vasc Surg.
33. Padberg FT, Pappas PJ, Araki CT, Back TL, Hobson RW. Hemodynamic and clinical improvement after superficial vein ablation in
primary combined venous insufficiency with ulceration. J Vasc Surg.
34. American Diabetes Association. Consensus development conference on diabetic foot wound care. Diabetes Care.
35. Levin M. Preventing amputation in the patient with diabetes. Diabetes Care.
1995;18:1383-1394. 36. Shaw JE, Boulton AJM. The pathogenesis of diabetic foot problems: an overview.
37. Boulton AJ, Meneses P, Ennis WJ. Diabetic foot ulcers: a framework for prevention and care. Wound Rep Reg.
1999;7:7-16. 38. Caputo GM, Cavanaugh PR, Ulbrecht JS, et al. Assessment and management of foot disease in patients with diabetes. N Eng J
39. Grayson ML, Gibbons GW, Balogh K, et al. Probing to bone in infected pedal ulcers. A clinical sign of underlying osteom yelitis in
diabetic patients. JAMA.
40. Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation: basis for prevention. Diabetes Care.
41. Seaman S. Dressing selection in chronic wound management. J Am Podiatr Med Assoc.
2002;92(1):24-33. 42. Wiemen TJ, Smiell JM, Su Y. Efficacy and safety of a topical formulation of recombinant human platelet-derived growth factor-BB
(becaplermin) in patients with chronic neuropathic diabetic ulcers. Diabetes Care.
43. Falanga V. Bioengineered skin. WOUNDS.
2000;12(Suppl B):99B-105B. 44. Gentzkow GD, Jensen JL, Pollack RA. Improved healing of diabetic foot ulcers after grafting with a living human dermal
45. Catanzariti AR. Prophylactic foot surgery in the diabetic patient. Adv Wound Care.
46. Giacalone VF, Krych SM, Harkless LB. The University of Texas Health Science Center at San Antonio: experience with foot surgery
in diabetics. J Foot Ankle Surg.
47. Edmonds ME, Blundell MP, Morris ME, et al. Improved survival of the diabetic foot: the role of a specialised foot clinic. Q J Med.
48. Seaman S. Considerations for the global assessment and treatment of patients with recaltricant wounds. Ostomy/Wound
. 2000;46(Suppl A):105-295.
"Tegon" glows bright green under ultraviolet light in a feat that could eventually help scientists track diseases. A genetically modified female beagle named Tegon glows bright fluorescent green under ultraviolet light, according to a paper published in the journal Genesis. In the scientific record books, Tegon joins a red fluorescent puppy named Ruppy and Mr. Green Genes the cat as al
Definition 1. The standard definition is that a mould is a function on “a variable number of variables”. To flesh out this definition, in the general case, let A, B be sets and K be an algebra. A mould , M • = ( M •, A, K ) , is a map from the free monoid A∗ into K and a bimould is defined as a function on the free monoid of the Cartesian product of two sets, ( A × B ) ∗: w