Thrombolytic therapy in arterial thrombosis producing acute ischemia of the lower limbs]

Efficiency of the thrombolytic therapy in the acute arterial thrombosis (producing an acute ischemia of the lower limbs) with streptokinase has been assessed in 35 patients treated in the selected departments of vascular surgery in Poland. Complete recovery has been noted in 9 patients (25.7%) in whom limb functioning with detectable peripheral pulse have been restored. An improvement has been achieved in 12 (34.3%) patients and moderate result in 4 (11.4%) patients. The limb has been amputated in 7 (20%) patients, and 3 patients (8.6%) died. Similar results have been observed in case of ischemia of duration period below 12 hours, between 12 and 24 hours, and between 24 and 72 hours. The results have been worse when thrombolytic therapy was introduced after 72 hours.     

Dissecting aneurysm as a cause of acute non-traumatic ischemia of the lower limbs]

The results of the treatment the acute non-traumatic ischemia of the lower limbs caused by dissecting aneurysm are discussed. Out of 726 analysed patients 8 of them suffered from dissecting aneurysm, i.e. 1.1%. Dissecting aneurysm was more frequent in male patients. All patients with lower limbs ischemia caused by the dissecting aneurysm were operated. Vascular prosthesis was used in 6 cases, and restoration of arterial patency in 2 cases. Seven patients died during the early postoperative period and one was released home with proper blood flow.     

Late results of surgical and conservative treatment for atheromatous ischemia of the lower limb in young patients]

The study was carried out within a multicenter program. Hundred fifty four patients under 40 years were treated (73 conservatively, and 81 surgically) for the atheromatous ischemia of the lower limbs in 14 Departments of Vascular Surgery in Poland within 5 years. The results of the treatment were evaluated according to the site of atheromatous lesions, type of surgery, and mainly according to the progress in pathologic process expressed by the degree of limb ischemia. It was found that surgery performed in the II period of the disease produces the best results. Surgery produces positively better results than conservative treatment in patients with the II period of the disease whereas both surgical and conservative therapy are ineffective in the III and IV degrees of ischemia. Sympathectomy may be effective in the occlusion of crural arteries even of the IV degree ischemia. In case of the II degree ischemia better results are produced by the operation of aorto-iliaco-femoral segment (transplantation or thrombendarterectomy) than that involving distal segment (sympathectomy) whereas the results of conservative therapy are better in peripheral and iliaco-femoral occlusion than those in aortofemoral and multisegmental arterial occlusion. An opinion of several authors on the specificity of atheromatous ischemia of the lower limbs in young patients was not confirmed.     

Neoplastic diseases of the hematopoietic system and ischemia of the lower limbs]

The possible interaction between hematopoietic neoplasms and ischemia of the lower limbs in patients with both pathologies was subjected to analysis. Anaemia, polycythemia, thrombocythemia, increased leucocytosis in the peripheral blood, and hyperuricemia exerted unfavourable effect on the blood flow through the arteries of the lower limbs. In some cases effective cytostatic treatment diminished the ischemia of the lower limbs. Interactions between various drugs used in the chronic treatment of both pathologies in the same patient was also examined.     

Early and late results of treating peripheral arterial injuries]

Forty six patients with injuries to the great peripheral arteries were treated at the III Department of Surgery, Medical Academy in Cracow in 1968-1987. An injury to the blood vessels was accompanied by bone fractures or joint dislocation in 9 (19.5%) patients whereas 35 (76%) patients suffered also from vein injuries and nervous trunks trauma. In 13 (28%) cases an accident took place when the victims were drunk. Favourable result of the treatment, i.e. return of peripheral pulse, was achieved in 33 (75%) patients, acceptable result, i.e. an increase in limb temperature, in 11 (23%) patients. Two patients underwent an amputation of the limb because of its necrosis. One patient died. Anti-thrombolytic agents were given intra- and postoperatively, and in 9 patients with extensive contusions fasciotomy proved successful. Late results were similar to early ones.     

Results of surgical and conservative treatment for multi-level atheromatous arterial occlusion of the lower limb after five years]

After 5 years of observation, materials of 239 patients treated operatively and 96 patients treated conservatively because of multisegmental arterial occlusion of lower limbs were obtained within the framework of multi-central programme of investigation. The results of the treatment with these methods have been evaluated according to the site of the atheromatous changes and the degree of ischemia of lower limbs. It has been ascertained, that after operative therapy, the percentage of good results and the percentage of death in the case of occlusion comprising the aorto-ilio-femoral segment is higher than in the case of occlusion of femoro-popliteal and peripheral segments, whereas in the case of conservative therapy, the situation is reverse. The results of therapy (operative and conservative) of multilevel arterial occlusion, in all kinds of location, depend upon blood supply in the limbs. The results are best (the highest percentage of good results and without improvement, the least number of amputation and death) in the II period of disease and they become worse when the degree of ischemia increases. It appears that the operative therapy is less effective than the conservative therapy in the case of atheromatous multilevel changes manifesting clinically in the form of intermittent claudication, whereas in the case of the IV degree of ischemia, only the operation can save the limb or even the patient's life.     

Free-tissue transfer in patients with peripheral vascular disease: a 10-year experience

Advances in free-tissue transfer have allowed for lower limb salvage in patients with significant peripheral vascular disease and limb-threatening soft-tissue wounds. The authors retrospectively reviewed their 10-year experience with free flaps for limb salvage in patients with peripheral vascular disease to assess postoperative complication rates and long-term functional outcome. They identified all patients undergoing free-tissue transfer with significant peripheral vascular disease and otherwise unreconstructible soft-tissue defects. Charts were reviewed for perioperative and long-term outcome. Parameters studied included perioperative morbidity and mortality, flap success, bypass graft patency, ambulatory results, and long-term limb and patient survival. Survival data were analyzed using life-table analysis, Kaplan-Meier survival analysis, and Cox testing. A total of 79 flaps were examined in 75 patients with peripheral vascular disease from July of 1990 to November of 1999. All patients would have required a major amputation had free-tissue transfer not been performed. Mean age was 60 years, average hospital stay was 32 days, and perioperative mortality was 5 percent. Within the first 30 days after operation, there were four cases of primary flap loss, and another two were lost as the result of bypass graft failure (8 percent); five of these cases resulted in amputation. There were no primary flap failures after 30 days. Follow-up ranged to 91 months (mean, 24 months). During this time, another 14 limbs were lost, most commonly because of progressive gangrene and/or infection in sites remote from the still-viable free flap. Using Kaplan-Meier survival analysis, 5-year flap survival was 77 percent, limb salvage 63 percent, and patient survival 67 percent. Sixty-six percent of patients were able to ambulate independently with the use of their reconstructed limb at least 1 year after hospital discharge, although some of these later went on to amputation. Free-tissue transfer for lower extremity reconstruction can be performed with acceptable morbidity and mortality in patients with peripheral vascular disease. Flap loss is low, and limb salvage, ambulation, and long-term survival rates in these patients are excellent.     

Transplantation of placenta‐derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice

Mesenchymal stem cell‐based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta‐derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation‐induced murine limb ischemia model was generated with fluorescent dye (CM‐DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia‐induced injury to mouse hind limbs by enhancement of angiogenesis.     

Erythropoietin augments the efficacy of therapeutic angiogenesis induced by allogenic bone marrow stromal cells in a rat model of limb ischemia

Transplantation of adult marrow stromal cells (MSCs) has been developed as a new method of treating severe ischemia diseases by therapeutic angiogenesis. Erythropoietin (EPO) is capable of inducing angiogenesis and inhibiting MSCs apoptosis. The effect of EPO on the therapeutic potency of MSCs transplantation in a rat model of limb ischemia was investigated in the current study. The results indicate that the combined treatment with MSC transplantation and EPO infusion is superior to MSC transplantation alone in the treatment of limb ischemia. MSCs transplantation and EPO infusion could enhance the angiogenic effect of each other to achieve a better therapeutic effect. This combination therapy may become a more effective approach for ischemia diseases of the limbs.     

A test with dexamethasone in acute leukemia.

A simple test with dexamethasone (DMS) in acute leukemia (AL) is described. In peripheral blood, blast cell count is determined before 8 mg DMS are given intravenously, and 2, 4 and 6 hours afterwards. The result is expressed as the lowest blast cell count after DMS in percentage of the initial value. This test was performed on 51 adult patients with AL. The results were correlated with the morphological and cytochemical classification. Only patients with clearly classified AL were evaluated. A statistically significant difference in blast cell response between acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) was observed. In 12 out of 16 cases of ALL, but in only 1 out of 19 cases of AML, the blast cell count decreased to 50 percent or less of the initial value. The results of the test were further correlated with the results of treatment. In 11 out of 12 patients with ALL, who showed a response to DMS, glucocorticoids were included in the treatment regimen. A complete remission was obtained in 7 out of 10 patients who were treated for the first time. In the remaining 4 patients with a poor response to DMS, a complete remission after the first treatment was obtained in only one case. The number of patients examined is to small for final conclusions on the value of this test for a discrimination between glucocorticoid-responsive and non-responsive cases of AL. Nevertheless, these preliminary results indicate that further trials seem to be warranted.     

Anticipated results of arterial surgery in chronic atherosclerotic ischemia of the lower limb]

In 1983-1988, the results of conservative and surgical treatment of patients with atherosclerotic ischemia of the lower limbs were assessed with the aid of a questionnaire. A possibility of prognosis was assessed with the use of mathematically processed data obtained with such approach. An effect of clinical symptoms (intermittent claudication distance, resting pain, necrosis) and stage of the disease (duration, K/R index) and risk factors (blood cholesterol, triglycerides, diabetes mellitus, ischemic heart disease, arterial hypertension) on the result of surgical treatment was analysed. The obtained results suggest that clinical symptoms and risk factors may predict the results of surgical treatment in the atherosclerotic ischemia of the lower limbs.     

Major limb malformations following intrauterine exposure to ethanol: two additional cases and literature review

Two children are reported in whom major limb malformations were identified and whose mothers had consumed large quantities of alcohol in the first trimester of pregnancy. In one there was complete amelia of the upper limbs, while the other had preaxial polydactyly of both hands. These cases, taken together with previously reported instances of major limb anomalies following intrauterine ethanol exposure, as well as animal investigations that have demonstrated virtually identical limb malformations following ethanol administration, suggest that maternal ethanol abuse may be casually related to these limb malformations. We suggest that interruption of blood supply to the developing limb may be caused by ethanol exposure and may result in all of the various limb malformations described.     

Free tissue transfer in patients with renal disease

Several authors have cited renal disease as a risk factor for free flap failure. The authors performed a retrospective analysis of all patients who underwent free tissue transfer with concomitant renal disease, including acute renal failure, end-stage renal disease, chronic renal insufficiency, and functional kidney transplants, to determine what effect renal disease has on flap survival and overall reconstructive outcome. More than 1053 free flaps were examined. Renal disease was identified in 32 patients who underwent 33 free tissue transfers. Average patient age was 57 years (range, 36 to 80 years). Twelve patients (38 percent) were on chronic dialysis (end-stage renal disease), 18 patients (56 percent) had chronic renal insufficiency, and three patients (9 percent) had the diagnosis of acute renal failure at the time of surgery. Three patients in the chronic renal insufficiency group had a functioning renal transplant. Average follow-up was 16 months. Immediate postoperative complications occurred in 14 patients (42 percent of the 33 flaps). Overall perioperative mortality was 3 percent. Within the first 30 days there were two cases (6 percent) of primary flap failure; an additional four legs were lost as the result of complications related to their bypass grafts. There were no primary flap failures after 30 days; however, within the first year after surgery an additional seven limbs were lost as the result of progressive ischemia or infection, and an additional three patients died. This resulted in a 52 percent incidence of major morbidity or mortality during the first year and a 55 percent reconstructive success rate in survivors at 1 year. No significant difference was seen in postoperative morbidity or mortality when comparing the end-stage renal disease group to the chronic renal insufficiency group; however, patients with renal disease and diabetes tended to have poorer outcomes. Renal disease, especially renal disease associated with diabetes and peripheral vascular disease, can be a strong indicator of possible reconstructive failure. The surgeon and patient should be aware of the medical and surgical complications associated with this procedure at the outset.     

纯化自体外周血CD34^＋细胞移植治疗肢体重度缺血的中期疗效

目的探讨纯化CD34^＋细胞移植治疗肢体重度缺血的中期疗效。方法自2009年5月至2011年12月录入30例肢体重度缺血患者,男性29例,女性1例,平均年龄43 ± 12岁（23 - 75岁）,均不具备外科血管重建条件,共治疗31条下肢和4条上肢。G-CSF（5-10μg/kg）动员,第5天采集外周血单个核细胞,分选获得纯化CD34^＋细胞,肢体肌肉局部注射。根据移植细胞数分为3组：低剂量组（105/kg）、中剂量组（5 × 105/kg）和高剂量组（106/kg）。结果随访16 - 48个月,1个月和2个月时Wong-Baker FACES疼痛评分由术前7 ± 2降到3 ± 3（P〈 0.001）和1 ± 2（P〈 0.001）。术后3个月和6个月：最长无痛步行时间由术前的（5 ± 3）min分别延长至（12 ± 6）min（P〈 0.001）和（19 ± 5）min（P〈 0.001）;踝肱指数由术前的0.44 ± 0.20提高至0.62 ± 0.18（P= 0.04）和0.66 ± 0.14（P〈 0.001）;经皮氧分压由术前（26 ± 11）mmHg分别上升至（42 ± 11）mmHg（P 〈 0.001）和（56 ± 12）mmHg（P〈 0.001）。16例溃疡患者愈合11例。Kaplan Meier生存分析法计算16个月保肢率为84﹪（95﹪可信区间为0.63 - 0.94）。3个不同剂量组之间的比较,治疗效果差异无统计学意义,除了1个月时WFPRSC检测结果显示：高剂量组明显优于低、中剂量组。结论纯化自体外周血CD34^＋细胞移植治疗肢体重度缺血性疾病安全、可行,能够较为持久地缓解缺血,挽救肢体,改善患者生活质量。     

Safety and efficacy of granulocyte–colony-stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia

Background aimsThe aim was to investigate the therapeutic effect of granulocyte–colony-stimulating factor (G-CSF) administration following implantation of autologous bone marrow mononuclear cells (BM MNC) for patients with lower limb ischemia.MethodsThe design was a randomized controlled trial. Fifteen patients with severe chronic limb ischemia were treated with autologous BM MNC [without G-CSF (MNC–G-CSF) or combined with G-CSF administration for 5 days following transplantation (MNC+G-CSF)].ResultsAll clinical parameters, including ankle brachial index, visual analog scale and pain-free walking distance, showed a mean improvement from baseline, which was measured at 4 and 24 weeks after transplantation in both groups. However, in three (20%) patients, the clinical course did not improve and limb salvage was not achieved. No significant difference was observed among the patients treated in the MNC–G-CSF and MNC+G-CSF groups. No severe adverse reactions were reported during the study period. No relationship was observed between both the numbers of viable MNC or CD34⁺ cells and the clinical outcome.ConclusionsAutologous transplantation of BM MNC into ischemic lower limbs is safe, feasible and efficient for patients with severe peripheral artery disease. However, the administration of G-CSF following cell transplantation does not improve the effect of BM MNC implantation and therefore would not have any beneficial value in clinical applications of such cases.     

Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease

BACKGROUND: Iloprost, a prostacyclin analogue, is used in the treatment of peripheral arterial occlusive disease at Leriche-Fontaine stages III-IV, through intravenous infusion for at least 21 days. Recently, iloprost has been shown to be safe and effective in critical limb ischemia patients when administered per 7 days. We investigated in patients at Leriche-Fontaine stages III-IV the effect of 1-week treatment with iloprost on plasma asymmetric dimethylarginine (ADMA), plasma and platelet serotonin, and on clinical response. METHODS AND RESULTS: Twenty-four critical limb ischemia patients (16 men and 8 women, mean age 76+/-9.7 years) were included in the study and treated with intravenous iloprost (titrated from 0.5 up to 1.5 ng/kg/min) for 16 h a day for seven consecutive days. Blood samples were drawn before infusion on days 1, 4 and 8 of treatment, under the same conditions. Clinical assessment was performed by clinical evaluation, ankle/brachial pressure index and treadmill exercise test. During treatment with iloprost patients clinically improved and plasma levels of ADMA significantly decreased (p<0.001). We also observed a significant increase of serotonin (p<0.01) in platelets and a significant decrease of serotonin (p<0.001) in plasma. Similar variations of ADMA and serotonin were found in two subgroups of patients, diabetics and non-diabetics. CONCLUSIONS: One-week treatment with iloprost in critical limb ischemia patients induced changes of peripheral markers of endothelial dysfunction and atherosclerosis, such as ADMA and serotonin, associated to a clinical improvement.     

Isotope limb blood flow measurement in patients undergoing peripheral laser angioplasty

A technique of isotope limb blood flow (ILBF) measurement employing Technetium-labelled human albumin and a gamma camera, was used to assess limb perfusion in 19 patients undergoing percutaneous laser angioplasty, both before and one month after treatment. Twenty-three limbs with femoro-poplited occlusions ranging in length from 3–35 cm (median 8cm) were recanalized using an Nd-YAG laser and sapphire tipped optical fibre. Primary angiographic success was achieved in 19 lesions of which 6 re-occluded within the first month, and 13 remained patent with relief of symptoms. Clinically successful procedures were associated with a large increase in ILBF. However, normal blood flow was restored in only 54% of limbs. There was a slight decrease in limb perfusion after failed laser angioplasty but this was not statistically significant in this small series. Furthermore, there was no clinically apparent circulatory compromise, or need for urgent surgical bypass in failed cases. We conclude that ILBF is a useful means of assessing patients undergoing laser angioplasty, particularly for detecting small flow changes in patients who are unable to complete a standard exercise test. Its use can be recommended for assessing blood flow changes following other forms of limb revascularization.     

FFU complex: an analysis of 491 cases

A study of 491 patients with femur-fibula-ulna (FFU) complex is presented. The term FFU complex has been proposed for cases in which the femur, fibula and/or ulna show defects, which tend to be associated. These cases are usually sporadic. Some rare anomalies of the arms which are present are particularly frequent in FFU complex. These are amelia, peromelia of humerus, humeroradial synostosis and defect of ulna. In our study, 491 patients were investigated for involvement of limb malformations. Our results, showing nearly equal proportions of the most common malformations in four analysed groups (with one, two, three and four limbs affected) supports the hypothesis that even if one arm or one leg only is affected, the cases may still be classifiable as FFU complex. There is a striking asymmetry in presence and in degree. All malformations are more often unilateral than bilateral. Upper limbs are affected more often than lower limbs. The right side and the male sex are preferentially affected. The limb malformations present in the FFU complex are different from those seen in most other types of limb defects, so there is virtually no overlap between FFU and other limb malformations. Some arguments in favour of early somatic mutation as a cause are discussed.     

Certain aspects of acute arterial thrombosis]

An analysis included 228 patients with the acute arterial thrombosis in the extremities. Over 33% of patients reported to the treatment later than 24 hours after the onset. This delay markedly worsened the results of therapy. Sixty two percent of limbs was saved. Mortality rate was 15%. The author analyse the results of therapy in relation to the localization of thrombi and type of the treatment--surgical, use of vasodilators with heparin or streptokinase. In case of thrombosis localized in the end segment of aorta the results were less promising than in case of more peripheral arterial involvement. Excellent and favourable results in this group amounted to 32%, the limb was amputated in 13% of patients and 28% of patients died. Hundred eighty patients were operated. Arteriosclerotic lesions to the arterial wall were detected in 97%. Excellent and favourable results of surgery were achieved in 45%, amputations amounted to 22%, and mortality rate was 16%. Vasodilators combined with heparin produced an improvement in 13% of patients in whom surgery could be postponed. The best results were achieved in patients treated with fibrinolytic agents with subsequent surgery or without it. In this group excellent and favourable results amounted to 57%, amputations--24%, and mortality rate--8%.     

脂肪干细胞治疗下肢缺血的研究进展

下肢缺血性疾病是临床常见的严重危害中老年人健康的疾病之一。目前，临床针对下肢缺血性疾病的治疗方法多样，但远 期疗效欠佳，对于肢体严重缺血的患者往往需要进行截肢处理。脂肪干细胞（adipose-derived stemcells, ADSCs）作为再生医学用 于治疗下肢缺血的种子细胞具有广阔的应用前景。本文将对ADSCs 治疗下肢缺血的研究进展进行综述。