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  1. As reported in Infection Control Today, 3/2002. Available at: http://www.infectioncontroltoday.com/articles/231feat3.html Accessed March 25, 2005.

    2. Clinical Care/Treatment Protocols

  2. Brem H, Lyder C. Protocol for the successful treatment of pressure ulcers. Am J Surg. 2004 Jul;188(1A Suppl):31-5.
  3. Brem H, Kirsner RS, Falanga V. Protocol for the successful treatment of venous ulcers. Am J Surg. 2004 Jul;188(1A Suppl):1-8.
  4. Brem H, Sheehan P, Boulton AJ. Protocol for treatment of diabetic foot ulcers. Am J Surg. 2004 May;187(5A):1S-10S.

    5. Clinical Care/Treatment Protocols/Diabetic Foot Ulcer

  5. Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg 1998;176:5S-10S.
  6. Steed DL. Foundations of good ulcer care. Am J Surg 1998;176:20S-25S.
  7. Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation. Basis for prevention. Diabetes Care 1990;13:513-21.
  8. Boulton AJ. The diabetic foot: a global view. Diabetes Metab Res Rev 2000;16 Suppl 1:S2-5.
  9. Frykberg RG, Armstrong DG, Giurini J, Edwards A, Kravette M, Kravitz S, Ross C, Stavosky J, Stuck R, Vanore J. Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons. J Foot Ankle Surg 2000;39:S1-60.
  10. Brandeis GH, Morris, J. N., Nash, D. J., Lipsitz, L. A. The epidemiology and natural history of pressure ulcers in elderly nursing home residents. JAMA 1990;264:2905-9.
  11. Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton AJ, Harkless LB. Off-loading the diabetic foot wound: a randomized clinical trial. Diabetes Care 2001;24:1019-22.
  12. Millington JT, Norris TW. Effective treatment strategies for diabetic foot wounds. J Fam Pract 2000;49:S40-8.
  13. Boulton AJ, Meneses P, Ennis WJ. Diabetic foot ulcers: A framework for prevention and care. Wound Repair Regen 1999;7:7-16.
  14. Piaggesi A, Baccetti F, Rizzo L, Romanelli M, Navalesi R, Benzi L. Sodium carboxyl-methyl-cellulose dressings in the management of deep ulcerations of diabetic foot. Diabet Med 2001;18:320-4.
  15. Brunner U, Eberlein T. Experiences with hydrofibres in the moist treatment of chronic wounds, in particular of diabetic foot. Vasa 2000;29:253-7.
  16. Bowering CK. Diabetic foot ulcers. Pathophysiology, assessment, and therapy. Can Fam Physician 2001;47:1007-16.
  17. Eibl N, Spatz M, Fischer GF, Mayr WR, Samstag A, Wolf HM, Schernthaner G, Eibl MM. Impaired primary immune response in type-1 diabetes: results from a controlled vaccination study. Clin Immunol 2002;103:249-59.

    18. Clinical Care/Treatment Protocols/Pressure Ulcer

  18. Eckman KL. The prevalence of dermal ulcers among persons in the U.S. who have died. Decubitus 1989;2:36-40.
  19. Allman RM. Pressure ulcer prevalence, incidence, risk factors, and impact. Clin Geriatr Med 1997;13:421-36.
  20. Brandeis GH, Morris JN, Nash DJ, Lipsitz LA. The epidemiology and natural history of pressure ulcers in elderly nursing home residents. Jama 1990;264:2905-9.
  21. Walter JS, Sacks J, Othman R, Rankin AZ, Nemchausky B, Chintam R, Wheeler JS. A database of self-reported secondary medical problems among VA spinal cord injury patients: its role in clinical care and management. J Rehabil Res Dev 2002;39:53-61.
  22. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130:489-93.
  23. Dale MC, Burns A, Panter L, Morris J. Factors affecting survival of elderly nursing home residents. Int J Geriatr Psychiatry 2001;16:70-6.
  24. Xakellis GC, Frantz R. The cost of healing pressure ulcers across multiple health care settings. Adv Wound Care 1996;9:18-22.
  25. Dwyer FM, Keeler D. Protocols for wound management. Nurs Manage 1997;28:45-9; quiz 50.
  26. Reuler JB, Cooney TG. The pressure sore: pathophysiology and principles of management. Ann Intern Med 1981;94:661-6.
  27. Brem H, Nierman DM, Nelson JE. Pressure ulcers in the chronically critically ill patient. Crit Care Clin 2002;18:683-94.
  28. Russell L. The importance of patients' nutritional status in wound healing. Br J Nurs 2001;10:S42, S44-9.
  29. Hoek T, Suski H. Proceedings of the European Tissue Repair Society 1997
  30. Galvin J. An audit of pressure ulcer incidence in a palliative care setting. Int J Palliat Nurs 2002;8:214-21.

    31. Clinical Care/Treatment Protocols/Sickle Cell Ulcer

  31. Eckman, J. Sickle Cell Information Center Guidelines: Introduction. Atlanta: The Sickle Cell Information Center 2002.
  32. Clair, B. Sickle Cell Disease: An Overview, Epidemiology. Augusta, Ga.: Medical College of Georgia Sickle Cell Center, 2002.
  33. Diallo, D., and Tchernia, G. "Sickle Cell Disease in Africa," Current Opinion in Hematology 9(2):111-16, March 2002.
  34. Gill, F.M., et al. "Clinical Events in the First Decade in a Cohort of Infants with Sickle Cell Disease. Cooperative Study of Sickle Cell Disease,' Blood 86(2):776-83, July 1995.
  35. Mohan, J.S., et al. "Abnormal Venous Function in Patients with Homozygous Sickle Cell (SS0 Disease and Chronic Leg Ulcers," Clinical Science 98(6):667-72, June 2000.
  36. Koshy, M., et al. "Leg Ulcers in Patients with Sickle Cell Disease," Blood 74(4):1403-408, September 1989.
  37. Gofrit, O.N., et al. "Segmental Testicular Infarction Due to Sickle Cell Disease," Journal of Urology 160(3 Pt 1:835-36, September 1998.
  38. De Chadarevian, J.P., et al. "Splenic Arteries and Veins in Pediatric Sickle Cell Disease," Pediatric and Developmental Pathology 4(6):538-44, November-December 2001.
  39. Sullivan, K.J., et al. "Low Exhaled Nitric Oxide and a Polymorphism in the NOS I Gene is Associated with acute Chest Syndrome," American Journal of Respiratory Critical Care Medicine 164(12)"2186-90, December 2001.
  40. Charache, S., et al. "'Acute Chest Syndrome' in Adults with Sickle Cell Anemia. Microbiology, Treatment, and Prevention," Archives of Internal Medicine 139(1):67-69, January 1979.
  41. Charache, S. et al. "One View of the Pathogenesis of Sickle Cell Diseases," Bulletin Europeen de Physiopathologie Respiratoire 19(4):361-66, July-August 1983.
  42. Bruno, D., et al. "Genitourinary Complications of Sickle Cell Disease," Journal of Urology 166(3):803-11, September 2001.
  43. Moser, F.G., et al. "The Spectrum of Brain MRI Abnormalities in Sickle Cell Disease: A Report from the Cooperative Study of Sickle Cell Disease," International Orthopaedics 17(6):397-99, December 1993.
  44. Onuba, O. "Bone Disorders in Sickle-Cell Disease," International Orthopaedics 17(6):397-99, December 1993.
  45. Teixeira, A.L., et al. "Sickle Cell Disease: A Clinical and Histopathologic Study of the Liver in Living Children," Journal of Pediatric Hematology Oncology 24(2): 125-29, February 2002.
  46. Woods, K.F., et al. "Helicobacter pylori Infection in Sickle Cell Disease," Journal of the National Medical Association 92(7):361-65, July 2000.
  47. Billett, H.H., et al. "Venous Insufficiency is not the Cause of Leg Ulcers in Sickle Cell Disease," American Journal of Hematology 37(2): 133-34, June 1991.
  48. "Leg Ulceration and Abnormalities of Calf Blood Flow in Sickle-Cell Anemia," European Journal of Haematology 37(2):133-34 June 1991.
  49. Reed, W., and Vichinsky, E.P. "New Considerations in the Treatment of Sickle Cell Disease," Annual Review of Medicine 49:461-74, 1998.
  50. Guidelines for the Management of Acute and Chronic Pain in Sickle Cell Disease. Glenview, IL: American Pain Society, 1999.
  51. Ballas, S.K. "Treatment of Painful Sickle Cell Leg Ulcers with Topical Opioids," Blood 99(3):1096, February 2002.
  52. Bolton, L. "The Science of Wound Healing," Continuing Education Lecture: Theory and Practice in Wound Healing. New York: New York University, 2002.
  53. Weinzweig, N., et al. "simultaneous Reconstruction of Extensive Soft-tissue Defects of Both Lower Limbs with Free Hemiflaps Harvested from the Omentum," Plastic Reconstructive Surgery 99(3):757-62, March 1997.

    54. Clinical Care/Treatment Protocols/Venous Ulcer

  54. Falanga V. Venous ulceration. J Dermatol Surg Oncol 1993;19:764-71.
  55. Hume M. Venous ulcers, the vascular surgeon, and the Medicare budget. J Vasc Surg 1992;16:671-3.
  56. Weingarten MS. State-of-the-art treatment of chronic venous disease. Clin Infect Dis 2001;32:949-54.
  57. Hjelmstedt A. Pressure decrease in the dorsal pedal veins on walking in persons with and without thrombosis. A study of a fracture series. Acta Chir Scand 1968;134:531-9.
  58. Lees TA, Lambert D. Patterns of venous reflux in limbs with skin changes associated with chronic venous insufficiency. Br J Surg 1993;80:725-8.
  59. 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;70:806-11.
  60. Mourad MM, Barton SP, Marks R. Changes in endothelial cell mass, luminal volume and capillary number in the gravitational syndrome. Br J Dermatol 1989;121:447-61.
  61. Butler CM, Coleridge Smith PD. Microcirculatory aspects of venous ulceration. J Dermatol Surg Oncol 1994;20:474-80.
  62. 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. Br Med J (Clin Res Ed) 1982;285:1071-2.
  63. Arnoldi CC, Greitz T, Linderholm H. Variations in cross sectional area and pressure in the veins of the normal human leg during rhythmic muscular exercise. Acta Chir Scand 1966;132:507-22.
  64. Smith JJ, Guest MG, Greenhalgh RM, Davies AH. Measuring the quality of life in patients with venous ulcers. J Vasc Surg 2000;31:642-9.
  65. Orsted HL, Radke L, Gorst R. The impact of musculoskeletal changes on the dynamics of the calf muscle pump. Ostomy Wound Manage 2001;47:18-24.
  66. Patel GK, Llewellyn M, Harding KG. Managing gravitational eczema and allergic contact dermatitis. Br J Community Nurs 2001;6:394-406.
  67. Danielsen L, Balslev E, Doring G, Hoiby N, Madsen SM, Agren M, Thomsen HK, Fos HH, Westh H. Ulcer bed infection. Report of a case of enlarging venous leg ulcer colonized by Pseudomonas aeruginosa. Apmis 1998;106:721-6.
  68. Hansson C, Hoborn J, Moller A, Swanbeck G. The microbial flora in venous leg ulcers without clinical signs of infection. Repeated culture using a validated standardised microbiological technique. Acta Derm Venereol 1995;75:24-30.
  69. Baldursson BT, Beitner H, Syrjanen S. Human papillomavirus in venous ulcers with and without squamous cell carcinoma. Arch Dermatol Res 2000;292:275-8.
  70. Baldursson B, Sigurgeirsson B, Lindelof B. Venous leg ulcers and squamous cell carcinoma: a large-scale epidemiological study. Br J Dermatol 1995;133:571-4.

    71. Clinical Care/Wound Bed Preparation

  71. Steed DL, Donohoe D, Webster MW et al. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. J Am Coll Surg 1996; 183:61-64.
  72. Falanga V, Margolis D, Alvarez O, Auletta M et al. Healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Arch Dermatol 1998; 134:293-300.
  73. Falanga V, Sabolinski M. A bilayered skin construct (Apligraf) accelerates complete closure of hard-to-heal venous ulcers. Wound Rep Reg 1999; 7:201-207.
  74. Falanga V. Venous ulceration. In: Krasner D, Kane D (eds) Chronic Wound Care: A Clinical Source Book for Health Care Professionals. Wayne, PA: Health Management Publications, 1997: 165-171.
  75. Hasan A, Murata H, Falabella A, Ochoa S et al. Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-"d1. J Dermatol Sci 1997; 16:59-66.
  76. Katz MH, Alvarez AF, Kirsner RS, Eaglstein WH et al. Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. J Am Acad Dermatol 1991; 25:1054-1058.
  77. Bucalo B, Eaglstein WH, Falanga V. Inhibition of cell proliferation by chronic wound fluid. Wound Rep Reg 1993; 1:181-186.

    78. Clinical Care/Chronic Wounds in The Elderly

  78. National Pressure Ulcer Advisory Panel. Consensus Conference, 1989.
  79. Knight CL. The chronic wound management decision tree: a tool for long-term care nurses. J Wound Ostomy Continence Nurs 1996 Mar;23(2):92-9.
  80. Walker N, Rodgers A, Birchall N, et al. Leg ulcers in New Zealand: age at onset, recurrence and provision of care in an urban population. N Z Med J. 2002 Jun 21;115(1156):286-9.
  81. Boulton AJ. The diabetic foot: from art to science. The 18th Camillo Golgi lecture. Diabetologia. 2004 Aug;47(8):1343-53.
  82. Angus DC, Linde-Zwirble WT, Lidicker J. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303-10.
  83. CDC National Diabetes Fact Sheet 2003. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf Accessed March 25, 2005.
  84. CDC Data and Trends, National Diabetes Surveillance System, Hospitalizations for Non-traumatic Lower Extremity Amputation 1980-2002. Available at: http://www.cdc.gov/diabetes/statistics/lea/byAgetable1_2.htm. Accessed March 19, 2005.
  85. Axelrod DA, Upchurch GR, Jr., DeMonner S, et al. Perioperative cardiovascular risk stratification of patients with diabetes who undergo elective major vascular surgery. J Vasc Surg 2002; 35: 894-901.
  86. Brem H, Vileikyte L, Boulton AJ, et al. Wound-healing protocols for diabetic foot and pressure ulcers. Surg Technol Int. 2003;11:85-92

    87. Clinical Care/Pain Management

  87. Phillips T, Stanton B, Provan A. A study of the impact of leg ulcers on the quality of life: financial, social, and psychologic implications. J Am Acad Dermatol 1994; 31:49-53.
  88. Freedman G, Cean C, Brem H, Tarnovskaya A, Duron V. Pathogenesis and treatment of pain in patients with chronic wounds. Surg Tech Int 2003; 11:168-179.

    89. Clinical Care/Human Skin Equivalent

  89. Veves A, Falanga V, Armstrong G. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multi-center clinical trial. Diabetes Care 2001; 24:290-5.
  90. Falanga V, Sabolinski M. A bilayered living skin construct (Apligraf) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen 1999; 7:201-7.
  91. Brem H, Balledux J, Bloom T. Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing. Arch Surg 2000; 135:627-34.
  92. Bitar MS, Labbad ZN. Transforming growth factor-beta and insulin-like growth factor-I in relation to diabetes-induced impairment of wound healing. J Surg Res 1996; 61:113-9.
  93. Werner S, Breeden M, Hubner G. Induction of keratinocyte growth factor expression is reduced and delayed during wound healing in the genetically diabetic mouse. J Invest Dermatol 1994; 103:469-73.
  94. Fahey TJ 3rd, Sadaty A, Jones WG 2nd. Diabetes impairs the late inflammatory response to wound healing. J Surg Res 1991; 50:308-13.
  95. Brem H, Tomic-Canic M, Young J. Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers. Surg Technol Int. 2003;11:23-31.

    96. Research/Angiogenesis

  96. Brem H, Ehrlich HP, Tsakayannis D. Delay of wound healing by the angiogenesis inhibitor TNP-470. Surgical Forum 1997; 48:714-6.

    97. Research/Angiogenesis/
    Impaired Angiogenesis In The Elderly

  97. Bach MH, Sadoun E, Reed MJ. Defects in activation of nitric oxide synthases occur during delayed angiogenesis in aging. Mech Ageing Dev. 2005 Apr;126(4):467-73.
  98. Cohen BJ, Danon D, Roth GS. Wound repair in mice as influenced by age and antimacrophage serum. J Gerontol 1987; 42:295-301.
  99. Rivard A, Berthou-Soulie L, Principe N. Age-dependent defect in vascular endothelial growth factor expression is associated with reduced hypoxia-inducible factor 1 activity. J Biol Chem 2000; 275:29643-7.
  100. Rivard A, Fabre JE, Silver M. Age-dependent impairment of angiogenesis. Circulation 1999; 99:111-20.
  101. Holt DR, Kirk SJ, Regan MC. Effect of age on wound healing in healthy human beings. Surgery 1992; 112:293-7; discussion 297-8.
  102. Gilchrest BA, Stoff JS, Soter NA. Chronologic aging alters the response to ultraviolet-induced inflammation in human skin. J Invest Dermatol 1982; 79:11-15.
  103. Wicke C, Wagner S, Trabold O. Age-dependency of insulin-like growth factors, insulin-like growth factor-binding proteins, and acid labile subunit in plasma and wounds of surgical patients. Wound Repair Regen 2002; 10:360-5.
  104. Brem H, Tomic-Canic M, Ehrlich HP, et al. Healing of elderly patients with diabetic foot ulcers, venous stasis ulcers, and pressure ulcers. Surg Technol Int. 2003;11:161-7.

    105. Research/Gene Array Technology

  105. Tomic-Canic M, Brem H. Gene array technology and pathogenesis of chronic wounds. Am J Surg. 2004 Jul;188(1A Suppl):67-72.

    106. Research/Growth Factors

  106. Walter DH, Cejna M, Diaz-Sandoval L, et al. Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis. Circulation. 2004 Jul 6;110(1):36-45.
  107. Holland TA, Tabata Y, Mikos AG. Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering. J Control Release. 2005 Jan 3;101(1-3):111-25.
  108. Royce SM, Askari M, Marra KG. Incorporation of polymer microspheres within fibrin scaffolds for the controlled delivery of FGF-1. J Biomater Sci Polym Ed. 2004;15(10):1327-36.

    109. Research/Statistical Models Of Healing Rates

  109. Wallenstein S, Brem H. Statistical analysis of wound-healing rates for pressure ulcers. Am J Surg. 2004 Jul;188(1A Suppl):73-8.
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