Venous Ulcers: Pathophysiology and Treatment Options—Part 2
- Wed, 9/3/08 - 10:25am
- 0 Comments
- 6809 reads
Grafting
When dressings and medical management fail or when rapid healing is essential, skin grafting is an excellent alternative. The first recorded skin grafts were performed in India and Egypt. More recently, skin grafting has been used to treat recalcitrant venous leg ulcers as well as large or slow-healing wounds. Currently, several types of grafts are available for venous ulcers. These grafts can be categorized based on the source of the donor tissue, the thickness of the donor tissue, and whether the graft is cultured in a laboratory.2
Grafts are categorized as autografts or allografts depending on the source of the donor tissue. Autografts are grafts taken from the patient’s own skin, usually from the thigh, abdomen, or buttocks.2 Autologous skin grafts are not rejected, and donor tissue is usually readily available.
Allografts are taken from the skin of another person; of these, cadaveric allografts are the most commonly used.102 These grafts must be changed frequently because of rejection — periodic removal of the allografts debrides the wound bed. In addition, allografts promote healing and reduce the possibility of surface infection. These grafts are chemically treated to prevent bacterial contamination, but the possibility of viral contamination exists.103
Grafts also may be categorized as either full- or partial- (split) thickness.2 Full-thickness skin grafts (FTSG) consist of all the epidermis and all the dermis; split-thickness skin grafts (STSG) contain all the epidermis and part of the dermis. Compared to STSG, FTSG are thicker, more durable, prevent wound contracture, and offer better cosmetic results. They make poorer grafts for leg ulcers because more tissue is necessary to re-vascularize, which decreases the graft’s chance for survival.
Conversely, split-thickness skin grafts (STSG) require less tissue to re-vascularize and, therefore, the chance for graft survival is greater.2 Types of STSG include pinch grafts, punch grafts, and shave grafts, which are harvested freehand, as well as dermatome-harvested grafts. The advantage of using a dermatome is the production of uniformly sized grafts.104
Split-thickness skin grafts are typically expanded via a meshing technique (see Figures 5 and 6).2,105 By creating interstices in the original graft, the graft’s size may be expanded by 1.5 to nine times the original size; therefore, less tissue needs to be harvested and larger areas can be treated. These interstices also allow blood and exudates to escape from the wound; thus, improving graft survival. Split-thickness skin grafts adhere well to the graft bed and give reasonable cosmetic results.106,107
Numerous reports cite use of STSG for venous ulcers. Millard et al108 grafted 41 venous ulcers with pinch skin grafts; 74% of the ulcers healed after grafting. The authors proposed that this approach is a simple, inexpensive, and effective way to treat ulcers, which also offers long-term benefits. Ahnlide et al’s109 study of pinch grafting for venous ulcers also showed healing, although at a lower rate than Millard’s study.
1. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994;130:489–493.
2. Kirsner RS, Eaglstein WH, Kerdel FA. Split-thickness skin grafting for lower extremity ulceration. Dermatol Surg. 1997;23:85–91.
3. Picascia DD, Roenigk HH. Surgical management of leg ulcers. Adv Dermatol Surg. 1987;5:303–312.
4. Samson HS, Showalter DP. Stockings and the prevention of recurrent venous ulcers. Dermatol Surg. 1996;22:373–376.
5. Vanhoutte PM, Corcaud S, De Montrion C. The demographics of venous disease of the lower limbs. Angiology. 1997;48:557–558.
6. Ruckley CV. Socioeconomic impact of chronic venous insufficiency and leg ulcers. Angiology. 1997;48:67–69.
7. Colgan MP, Dormandy JA, Jones PW, et al. Oxypentifylline treatment of venous ulcers of the leg. BMJ. 1990;300:972–975.
8. Coon WW, Willis PW III, Keller JB. Venous thromboembolism and other venous disease in the Tecumseh Community Health Study. Circulation. 1973;58:839–846.
9. Alguire PC, Mathes BM. Chronic venous insufficiency and venous ulceration. JGIM. 1997;12:374–383.
10. Dalen JE, Paraskos JA, Ockene IS, et al. Venous thromboembolism: scope of the problem. Chest. 1986;89:370S-373S.
11. Callam MJ, Ruckley CV, Harper DR, Dale JJ. Chronic ulceration of the leg: extent of the problem and provision of care. BMJ. 1985;290:1855–1856.
12. Chaetle TR, Scott HJ, Scurr JH, Coleridge Smith PD. White cells, skin blood flow and venous ulcers. Br J Dermatol. 1991;125:288–290.
13. Scott TE, LaMorte WW, Gorin DR, Menzoian JO. Risk factors for chronic venous insufficiency: a dual case-control study. J Vasc Surg. 1995;22:622–628.
14. Olin JW, Beusterien KM, Childs MB, Seavey C, McHugh L, Griffiths RI. Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med. 1999;4:1–7.
15. Dinner MI, Peters CR. Surgical management of the ulcers on the lower limbs. J Dermatol Surg Oncol. 1978;4:696–699.
16. Welch HJ, Young CM, Semegran AB, et al. Duplex assessment of venous reflux and chronic venous insufficiency: the significance of deep venous reflux. J Vasc Surg. 1996;24:755–762.
17. White JV, Katz ML, Cisek P, Kreithen J. Venous outflow of the leg: anatomy and physiologic mechanism of the plantar venous plexus. J Vasc Surg. 1996;24:819–824.
18. Norgren L. Chronic venous insufficiency — a well known disorder with many question marks. Angiology. 1997;48:23–26.
19. Ruffieux PH, Hommel I, Saurat JH. Long-term assessment of chronic leg ulcer treatment by autologous skin grafts. Dermatology. 1997;195:77–80.
20. Lawrence MB, McIntire LV, Eskin SG. Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. Blood. 1987;70:1284–1290.
21. Coleridge Smith PD, Scurr JH, Dormandy JA. Causes of venous ulceration: a new hypothesis. Br Med J. 1988;296:1693–1727.
22. Scott HJ, Coleridge Smith PD, Scurr JH. Histologic study of white blood cells and their association with lipodermatosclerosis and venous ulceration. Br J Surg. 1991;78:210–211.
23. Browse NL, Burnand KG. The cause of venous ulceration. Lancet. 1982;ii:243–254.
24. Franzeck UK, Bollinger A, Huch R, Huch A. Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous incompetence. Circulation. 1984;70:806–811.
25. Landis EM. Microinjection studies of capillary blood pressure in human skin. Heart. 1930;15:404–453.
26. Pietra GG, Szidon JP, Leventhal MM, Fishman AP. Hemoglobin as a tracer in hemodynamic pulmonary edema. Science. 1969;166:1643–1646.
27. Burnand KG, Whimster I, Naidoo A, Browse NL. Pericapillary fibrin in the ulcer bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration. BMJ. 1982;285:1071–1072.
28. Danielpour D, Sporn MB. Differential inhibition of transforming growth factor beta-1 and beta-2 activity by alpha-2 macroglobulin. J Biol Chem. 1990;265:6973–6977.
29. Falanga V, Eaglstein WH. The “trap” hypothesis of venous ulceration. Lancet. 1993;341:1006–1008.
30. Malanin K. About the pathophysiology of venous leg ulceration. JAAD. 2002;47:157–158.
31. Labropoulos N, Giannoukas AD, Nicolaides AN, et al. The role of venous reflux and calf muscle pump function in nonthrombotic chronic venous insufficiency. Arch Surg. 1996;131:403–406.
32. Labropoulos N, Delis K, Nicolaides AN, et al. The role of the distribution and anatomic extent of reflux in the development of signs and symptoms in chronic venous insufficiency. J Vasc Surg. 1996;23:504–510.
33. Subcommittee on Reporting Standards. Classification of CVI. 1994. Available at: www.phlebology.com.
34. Phillips TJ, Machado F, Trout R, Porter J, Olin J, Falanga V. Prognostic indicators in venous ulcers. JAAD. 2000;43:627–630.
35. Margolis DJ, Berlin JA, Strom B. Risk factors associated with the failure of a venous ulcer to heal. Arch Dermatol. 1999;135:920–926.
36. Skene AI, Smith JM, Dore CJ, Charlett A, Lewis DJ. Venous leg ulcers: a prognostic index to predict time to healing. Br Med J. 1992;305:1119–1121.
37. Mayberry JC, Moneta GL, Taylor LM, Porter JM. Fifteen years’ results of ambulatory compression therapy. Surgery. 1991;109:575–581.
38. Valencia IC, Falabella A, Kirsner RS, Eaglstein WH. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol. 2001;44:401–421.
39. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of leg ulcers on quality of life: Financial, social, and psychological implications. J Am Acad Dermatol. 1994;31(1):49–53.
40. Freidman SA. The diagnosis and medical management of vascular ulcers. Clin Dermatol. 1990;8(3/4):30–48.
41. Nelzen O, Bergqvist D, Lindhagen A. Leg ulcer etiology- a cross sectional population study. J Vasc Surg. 1991;14:557–564.
42. Browse NL, Clemenson G, Lea Thomas M. Is the postphlebitic leg always postphlebitic? Relation between phlebographic appearances of deep vein thrombosis and late sequelae. Br Med J. 1980;281:1167–1170.
43. Sibbald RG. An approach to leg and foot ulcers: a brief overview. Ostomy Wound Manage. 1998;44:28-32.
44. Falanga V. Venous ulceration. J Dermatol Surg Oncol. 1993;19:764–771.
45. Falanga V. Venous ulceration. WOUNDS. 1996;8(3):102–108.
46. Maessen-Visch MB, Koedam MI, Hamulyak K, Neuman HAM. Atrophie blanche. Int J Dermatol. 1999;38:161–172.
47. Kirsner RS, Pardes JB, Eaglstein WH, Falanga V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol. 1993;28:623–627.
48. Phillips TJ, Dover JS. Leg ulcers. J Am Acad Dermatol. 1991;25(6, Pt.1):965–987.
49. Phillips TJ. Successful methods of treating leg ulcers: the tried and true plus the novel and new. Postgrad Med. 1999;105:159–179.
50. McGee SR, Boyko EJ. Physical examination and chronic lower-extremity ischemia. A critical review. Arch Intern Med. 1998;158:1357–1364.
51. Scriven JM, Hartshorne T, Bell PR, et al. Single visit venous ulcer assessment clinic: the first year. Br J Surg. 1997;84:334–336.
52. Lopez A, Phillips TJ. Venous ulcers. WOUNDS. 1998;10149–157.
53. McGukin M, Stineman M, Goin J, et al. Draft guideline: diagnosis and treatment of venous leg ulcers. Ostomy Wound Manage. 1996;42:48–78.
54. Labropoulos N, Leon M, Geroulakos G, et. Al. Venous hemodynamic abnormalities in patients with leg ulceration. Am J Surg. 1995;169:572–574.
55. Thibault PK. Duplex examination. Dermatologica. 1995;21:77–82.
56. Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW. Probing to bone in infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients. JAMA. 1995;273:721–723.
57. Ackroyd JS, Young AE. Leg ulcers that do not heal. Br Med J. 1983;286:207–208.
58. Hansson C, Andersson E. Malignant skin lesions on the legs and feet at a dermatological leg ulcer clinic during five years. Acta Derm Venereol. 1997;78:147–148.
59. Kramer SA. Compression wraps for venous ulcer healing: a review. J Vasc Nurs. 1999;17:89–97.
60. Cherry GW, Hoffman D, Cameron J, Poore SM. Bandaging in the treatment of venous ulcers: an European view. Ostomy Wound Manage. 1996;42:13S–18S.
61. Partsch H. Compression therapy of the legs. J Dermatol Surg Oncol. 1991;17:799–805.
62. Fletcher A, Cullum N, Sheldon TA. A systematic review of compression treatment for venous leg ulcers. BMJ. 1997;315:576–560.
63. Staudinger P, Weiss RA. Compression therapy: low or short stretch bandage and graduated compression stockings for leg edema. Dermatol Surg. 1995;106.
64. Hafner J, Botonakis I, Burg G. A comparison of multilayer bandage systems during rest, exercise, and over 2 days of wear time. Arch Dermatol. 2000;136:857–863.
65. Spence RK, Cahall E. Inelastic versus elastic leg compression in chronic venous insufficiency: a comparison of limb size and venous hemodynamics. J Vasc Surg. 1996;24:783–787.
66. Maune J, Giordano J. Experience with open-heeled Unna boot application technique. J Vasc Nurs. 1997;15:63–72.
67. Trent JF, Kirsner RS. Tissue engineered skin: Apligraf, a bi-layered living skin equivalent. International J Clin Pract. 1998;52:408–413.
68. Gould DJ, Campbell S, Newton H, Duffelen P, Griffin M, Harding EF. Setopress vs. Elastocrepe in chronic venous ulceration. Br J Nursing. 1998;7:66–73.
69. Williams C. Profore four-layer bandage system. Br J Nurs. 1996;5:1075–1076.
70. Falanga V. Venous ulceration. In: Krasner D, Kane D, eds. Chronic Wound Care, Second Edition. Wayne, Pa.: Health Management Publications, Inc.;1997:165–171.
71. Falanga V, Eaglstein WH. Compression. In: Falanga V, Eaglstein WH. Leg and Foot Ulcers: A Clinician’s Guide. UK: Martin Dunitz Ltd;1995:144–165.
72. Partsch H. Compression therapy of the Legs. J Dermatol Surg Oncol. 1991;17:799–805.
73. Richmond DM, O’Donnell TF, Zelikovski A. Sequential pneumatic compression for lymphedema. Arch Surg. 1985;120:1116–1119.
74. Cullum N, Nelson EA, Fletcher AW, Sheldon TA. Compression for venous leg ulcers (Cochrane Review). Cochrane Database Syst Rev. 2000;3:CD000265.
75. Johnson G, Kupper C, Farrar DJ, Swallow RT. Graded compression stockings. Arch Surg. 1982;117:69–72.
76. Sigel B, Edelstein AL, Savitch L, et al. Type of compression for reducing venous stasis. Arch Surg. 1975;110:173–175.
77. Sigel B, Edelstein AL, Felix WR, et al. Compression of the deep venous system of the lower leg during inactive recumbency. Arch Surg. 1973;106:38–43.
78. Lewis CE, Antoine J, Mueller C, et al. Elastic compression in the prevention of venous stasis. Am J Surg. 1976;132:739–743.
79. Scurr JH, Ibrahim SZ, Faber RG, et al. The efficacy of graduated compression stockings in the prevention of deep vein thrombosis. Br J Surg. 1977;64:371–373.
80. Holford CP. Graded compression for preventing deep venous thrombosis. Br Med J. 1976;2:969–970.
81. Barnes RW, Brand RA, Clarke W, et al. Efficacy of graded compression anti-embolism stockings in patients undergoing total hip arthroplasty. Clin Orthop Rel Res. 1978;132:61–67.
82. Wilkins RW, Stanton JR. Elastic compression stockings in the prevention of pulmonary embolism. NEJM. 1953;248:1087–1090.
83. Nielsen PG, Madsen SM, Stromberg L. Treatment of chronic leg ulcers with a hydrocolloid dressing. Acta Derm Venerol. 1989;152 (suppl):1–12.
84. Eaglstein WH, Falanga V. Chronic wounds. Surg Clin North Am. 1997;77:689–700.
85. Mulder GD, Reis TM. Venous ulcers: pathophysiology and medical therapy. Am Fam Physician. 1990;42:1323–1330.
86. Fitzpatrick TB, Johnson RA, Wolff K, Polano MK, Suurmond D. Leg ulcers. Color Atlas and Synopsis of Clinical Dermatology. 1997;486–491.
87. Layton AM, Ibbotson SH, Davies JA, Goodfield MJD. Randomised trial of oral aspirin for chronic venous leg ulcers. Lancet. 1994;344:164–165.
88. Puchmayer V. Modern therapeutic trends in the conservative treatment of ischemic disease of the lower extremities. Vnitrni Lekarstvi. 1995;41:204–206.
89. Ratner D. Skin grafting. Dermatol Clinics. 1998;16:75–90.
90. Angelkort B, Kiesewetter H. Influence of risk factors and coagulation phenomenon on the fluidity of blood on chronic arterial occlusive disease. Scand J Clin Lab Invest. 1984;41:185–188.
91. Ambrus JL, Stadler S, Kulaylat M. Hemorrhagic effects of metabolites of pentoxifylline (Trental). J Med. 1995;26:65–75.
92. Belcaro G,Cesarone MR, Nicolaides AN, DeSanctis MT, Incandela L, Geroulakos G. Treatment of venous ulcers with pentoxifylline: a 6-month, randomized, double-blind, placebo-controlled trial. Angiology. 2002;53:45–48.
93. 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 Repair Regen. 1999;7:208–213.
94. DeSanctis MT, Belcaro G, Cesarone MR, et al. Treatment of venous ulcers with pentoxifylline: a 6-month randomized, double-blind, placebo controlled trial. Angiology. 2002;53:49–52.
95. Jull A, Waters J, Arroll B. Pentoxifylline for treatment of venous leg ulcers: a systematic review. Lancet. 2002;359:1550–1554.
96. Ibbotson SH, Layton AM, Davies JA, Goodfield MJD. The effect of aspirin on haemostatic activity in the treatment of chronic venous leg ulceration. Br J Dermatol. 1995;132:422–426.
97. Lyseng-Williamson KA, Perry CM. Micronized purified flavonoid fraction. Drugs. 2003;63:71–100.
98. Bergan JJ, Schmid-Schonbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon® 500 mg. Angiology. 2001;52:43–50.
99. Ramelet AA. Clinical benefits of Daflon® 500 mg in the most severe stages of chronic venous insufficiency. Angiology. 2001;52:49–64.
100. Guilhou JJ, Fevrier F, Debure C. Benefits of a 2-month treatment with a micronized purified flavonoidic fraction on venous ulcer healing: a randomized double blind controlled versus placebo trial. Int J Microcirc Clin Exp. 1997;17:21–26.
101. Glinski W, Chodynicka B, Roszkiewicz J. The beneficial augmentative effect of micronized purified flavonoid fraction on the healing on leg ulcers: an open multicenter controlled randomized study. Phlebology. 1999;14:151–157.
102. Morris PJ, Bondoc C, Burke JF. The use of frequently changed skin allografts to promote healing in the nonhealing infected ulcer. Surgery. 1966;60:13–19.
103. Kealey GP. Disease transmission by means of allograft. J Burn Care Rehab. 1997;18:10S–11S.
104. Skouge JW. Techniques for split thickness skin grafting. J Dermatol Surg Oncol. 1987;13:841–849.
105. Kirsner RS, Falanga V. Techniques of split-thickness skin grafting for lower extremity ulcerations. J Dermatol Surg Oncol. 1993;19:779–783.
106. Davison PM, Batchelor AG, Lewis-Smith PA. The properties and uses of non-expanded machine meshed skin grafts. Br J Plastic Surg. 1986;39:462–468.
107. Fatah MF, Ward CM. The morbidity of split-skin graft donor sites in the elderly: the case for mesh-grafting the donors. Br J Plastic Surg. 1984;37:184–190.
108. Millard LG, Roberts MM, Gatecliffe M. Chronic leg ulcers treated by the pinch graft method. Br J Dermatol. 1977;97:289–295.
109. Ahnlide I, Bjellerup M. Efficacy of pinch grafting in leg ulcers of different aetiologies. Acta Derm Venereol. 1997;77:144–145.
110. Kirsner RS, Mata SM, Falanga V, Kerdel FA. Split-thickness skin grafting of leg ulcers. Dermatol Surg. 1995;21:701–703.
111. Schmeller W, Gaber Y, Gehl HB. Shave therapy is a simple, effective treatment of persistent venous leg ulcers. JAAD. 1998;39:232–238.
112. Limova M, Mauro T. Treatment of leg ulcers with cultured epithelial autografts: clinical study and case reports. Ostomy Wound Manage. 1995;41:48–50.
113. Hefton JM, Caldwell D, Biozes DG, Balin AK, Carter DM. Grafting of skin ulcers with cultured autologous epidermal cells. JAAD. 1986;14:399–405.
114. Phillips TJ. New skin for old: developments in biological skin substitutes. Arch Dermatol. 1998;134:344–349.
115. Leigh IM, Purkis PE, Navsaria HA, Phillips TJ. Treatment of chronic venous ulcers with sheets of cultured allogenic keratinocytes. Br J Dermtol. 1987;117:591–597.
116. Bolivar-Flores YJ. Kuri-Harcuch W. Frozen allogeneic human epidermal cultured sheets for the cure of complicated leg ulcers. Dermatol Surg. 1999;25:610–617.
117. Teepe RGC, Roseeuw DI, Hermans J, et al. Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers. JAAD. 1993;29:982–988.
118. Phillips TJ, Manzoor J, Rojas A, et al. The longevity of a bilayered skin substitute after application to venous ulcers. Arch Dermatol. 2002;138:1079–1081.
119. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic human skin equivalent. Arch Dermatol. 1998;134:293–300.
120. Falanga V, Sabolinski M. A bilayered living skin construct (Apligraf®) accelerates complete closure of hard to heal venous ulcers. Wound Rep Reg. 1999;7:201–207.
121. Brem H, Balledux J, Sukkarieh T, Carson P, Falanga V. Healing of venous ulcers of long duration with a bilayered living skin substitute: results from a general surgery and dermatology department. Dermatol Surg. 2001;11:915–919.
122. Kirsner RS, Fastenau J, Falabella A, Valencia I, Long R, Eaglstein WH. Clinical and economic outcomes with Graftskin for hard to heal venous leg ulcers: a single center experience. Dermatol Surg. 2002;28:81–82.
123. Martin LM, Kirsner RS. Use of a meshed bilayered cellular matrix to treat a venous ulcer. Adv Skin Wound Care. 2002;15:260–264.
124. Orcel® press release December 2003. Ortec International. Data on file.
125. Takeda Y, Agui T, Tanaka K, Okuzawa M, Tanigawa N. Sclerotherapy with a ligation of incompetent veins for a stasis ulcer due to varix cruris: minimal invasive therapy for varix cruris. Surg Today. 1999;29:1154–1157.
126. Queral LA, Criado FJ, Lilly MP, Rudolphi D. The role of sclerotherapy as an adjunct to Unna’s boot for treating venous ulcers: a prospective study. J Vasc Surg. 1990;11:572–575.
127. Murray JD, Bergan JJ, Riffenburgh RH. Development of open-scope subfascial perforating vein surgery: lessons learned from the first 67 cases. Ann Vasc Surg. 1999;13:372–377.
128. Gloviczki P. Subfascial Endoscopic perforator vein surgery: indications and results. Vasc Med. 1999;4:173–180.
129. Lee QWH, Chan ACW, Lam YH, et al. Early outcomes after subfascial endoscopic perforator surgery (SEPS) and saphenous vein Surgery in chronic venous insufficiency. Surg Endosc. 2001;15:737–740.
130. Rhodes JM, Gloviczki P, Canton L, Heaser TV, Rooke TW. Endoscopic perforator vein division with ablation of superficial reflux improves venous hemodynamics. J Vasc Surg. 1998;28:839–847.
131. Kolvenbach R, Ramadan H, Schwierz E. Redone endoscopic perforator surgery: feasibility and failure analysis. J Vasc Surg. 1999;30:720–726.
132. Gloviczki P, Bergan JJ, Rhodes JM, Canton LG, Harmsen S, Ilstrup DM. Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group. J Vasc Surg. 1999;29:489–502.
133. Proebstle TM, Bethge S, Barnstedt S, Kargl A, Knop J, Sattler G. Subfascial endoscopic perforator surgery with tumescent local anesthesia. Dermatol Surg. 2002;28:689–693.
134. Rhodes JM, Gloviczki P, Canton LG, Rooke T, Lewis BD, Lindsey JR. Factors affecting clinical outcome following endoscopic perforator vein ablation. Am J Surg. 1998;176:162–167.
135. Bianchi C, Ballard JL, Abou-Zamzam AM, Teruya TH. Subfascial endoscopic perforator vein surgery combined with saphenous vein ablation: results and critical analysis. J Vasc Surg. 2003;38:67–71.
136. Reutter H, Bort S, Jung MF, et al. Questionable effectiveness of autologous platelet growth factors (PDWHF) in treatment of venous ulcers of the leg. Hautarzt. 1999;50:859–865.
137. Coerper S, Koveker G, Flesch I, Becker HD. Ulcus cruris venosum: surgical debridement, antibiotic therapy and stimulation with thrombocytic growth factors. Langenbecks Arch Chir. 1995;380:102–107.
138. Stacey MC, Mata SD, Trengove NJ, Mather CA. Randomized double-blind placebo controlled trial of topical autologous platelet lysate in venous ulcer healing. Eur J Vasc Endovasc Surg. 2000;20:296–301.
139. Krupski WC, Reilly LM, Perez S. A prospective randomized trial of Autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. J Vasc Surg. 1991;14:526–536.
140. Senet P, Bon FX, Benbunan M, et al. Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers. J Vasc Surg. 2003;38:1342–1348.
141. Jaschke E, Zabernigg A, Gattringer C. Recombinant human granulocyte-macrophage colony stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers. Int J Dermatol. 1999;38:380–386.
142. Borbolla-Escoboza JR, Maria-Aceves R, Lopez-Hernandez MA, Collados-Larumbe MT. Recombinant human granulocyte-macrophage colony stimulating factor as treatment for chronic leg ulcers. Rev Invest Clin. 1997;49:449–451.
143. Da Costa RM, Ribeiro Jesus FM, Aniceto C, Mendes M. Randomized, double-blind, placebo-controlled, dose-ranging study of granulocyte-macrophage colony stimulating factor in patients with chronic venous leg ulcers. Wound Repair Regen. 1999;7:17–25.
144. Robson MC, Phillips TJ, Falanga V, et al. Randomized trial of topically applied Repifermin (recombinant human keratinocyte growth factor 2) to accelerate wound healing in venous ulcers. Wound Rep Reg. 2001;9:347–352.
145. Brown GL, Nanney LB, Griffin J, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. NEJM. 1989;321:76–79.
146. Falanga V, Eaglstein WH, Bucalo B, Katz MH, Harris B, Carson P. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. J Dermatol Surg Oncol. 1992;18:604–606.
147. Limat A, French LE, Blal L, Saurat JH, Hunziker T, Salomon D. Organotypic cultures of autologous hair follicle keratinocytes for the treatment of recurrent leg ulcers. JAAD. 2003;48:207–214.
148. Badiavas EV, Abedi M, Butmarc J, Falanga V, Quesenberry P. Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol. 2003;196:245–250.
149. Badiavas EV, Falanga V. Treatment of chronic wounds with bone marrow derived cells. Arch Dermatol. 2003;139:510–516.






Post new comment