A novel bFGF-GH injection therapy for two patients with severe ischemic limb pain
Tóm tắt
Severe ischemic pain is difficult to treat with a single therapy. Although modern angiogenic therapies have been used in patients with peripheral arterial occlusive diseases, a regimen combining novel angiogenic therapy and classic nerve blocks, including sympathectomy, has not been discussed to date. In this case report, we present two patients with peripheral arterial occlusive disease who were first treated with medication and lumbar sympathectomy, and then with a novel gelatin hydrogel drug-delivery system loaded with basic fibroblast growth factor. The gelatin hydrogel combined with recombinant basic fibroblast growth factor was injected intramuscularly into the ischemic limbs. In the first patient, with arteriosclerosis obliterans, a foot ulcer was healed, and the original score for resting pain (visual analogue scale, 5/10) was decreased to 0/10. In the second patient, with Buerger’s disease, a large toe ulcer was healed, and his resting pain (visual analogue scale, 8/10) was decreased to 1/10. Some other parameters, such as skin surface temperature, transcutaneous oxygen partial pressure, and pain-free walking distance, were also improved in both patients after the combined therapy. A multimodal approach is necessary to treat severe ischemic pain. Novel angiogenic therapy combined with nerve blocks seems to be a promising option in patients with severe pain.
Tài liệu tham khảo
Rosenfield K, Isner JM. Disease of peripheral vessels. In: Topol EJ, editor. Textbook of cardiovascular medicine. Philadelphia: Lippincott-Raven; 1998. p. 2597–2620.
Mills JL. Buerger’s disease in the twenty-first century: diagnosis, clinical features, and therapy. Semin Vascular Surg. 2003;16: 179–189.
Zhang WW, Harris LM, Shenoy SS, Hassett JM, Wall LP. Outcomes of patients with atherosclerotic upper extremity tissue loss. Vasc Endovascular Surg 2005;39:33–38.
Diehm DC. Non-invasive treatment of critical limb ischemia. Curr Drug Targets Cardiovasc Haematol Disord. 2004;4:241–247.
Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischemic limb. Lancet. 1996;348:370–374.
Isner JM, Baumgartner I, Rauh G, Schainfeld R, Blair R, Manor O, Razvi S, Symes JF. Treatment of thromboangiitis obliterans (Buerger’s disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg. 1998;28:964–973.
Morishita R, Aoki M, Hashiya N, Makino H, Yamasaki K, Azuma J, Sawa Y, Matsuda H, Kaneda Y, Ogihara T. Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease. Hypertension. 2004;44:203–209.
Lederman RJ, Mendelsohn FO, Anderson RD, Saucedo JF, Tenaglia AN, Hermiller JB, Hillegass WB, Rocha-Singh K, Moon TE, Whitehouse MJ, Annex BH; TRAFFIC Investigators. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial. Lancet. 2002;359:2053–2058.
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002;360:427–435.
Marui A, Tabata Y, Kojima S, Yamamoto M, Tambara K, Nishina T, Saji Y, Inui K, Hashida T, Yokoyama S, Onodera R, Ikeda T, Fukushima M, Komeda M. A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel. An initial report of the phase I-IIa study. Circ J. 2007;71:1181–1186.
Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997;26:517–538.
Pomposelli JJ, Gupta SK, Zacharoulis DC, Landa R, Miller A, Nanda R. Surgical complication outcome (SCOUT) score: a new method to evaluate quality of care in vascular surgery. J Vasc Surg. 1997;25:1007–1014.
Fontaine R, Tuchmann L. The role of thrombectomy in deep venous thromboses, indication and results. J Cardiovasc Surg (Torino). 1964;5:298–312.
Hirose K, Fujita M, Marui A, Arai Y, Sakaguchi H, Huang Y, Chandra S, Tabata Y, Komeda M. Combined treatment of sustained release basic fibroblast growth factor and sarpogrelate enhances collateral blood flow effectively in rabbit hindlimb ischemia. Circ J. 2006;70:1190–1194.
Young S, Wong M, Tabata Y, Mikos AG. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release. 2005;109:256–274.
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T. Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5:434–438.
Saito S, Nishikawa K, Obata H, Goto F. Autologous bone marrow transplantation and hyperbaric oxygen therapy for patients with thromboangiitis obliterans. Angiology. 2007;58:429–434.
Wu HM, Yuan Y, McCarthy M, Granger HJ. Acidic and basic FGFs dilate arterioles of skeletal muscle through a NO dependent mechanism. Am J Physiol. 1996;271(3Pt2):H1087–H1093.
Emmerich J. Current state and perspective on medical treatment of critical leg ischemia: gene and cell therapy. Int J Low Extrem Wounds. 2005;4:234–241.
Lei Y, Haider HKH, Shujia J, Sim ES. Therapeutic angiogenesis. Devising new strategies based on past experiences. Basic Res Cardiol. 2004;99:121–132.