AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The fi...AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The files of patients in our department with ALI between 2015 and 2017 were examined. In seven patients, the Rotarex~S catheter was used in the proximal segment of the crural arteries. Data related to the clinical examination, Doppler sonography, angiography and followup from these patients were further used for analysis.RESULTS Two patients(29%) had thrombotic occlusion of the common femoral artery, and the remaining five exhibited thrombosis of the superficial femoral artery and popliteal artery. Mechanical thrombectomy was performed in all cases using a 6F Rotarex~S catheter. Additional Rotarex~S catheter thrombectomy due to remaining thrombus formation with no reflow was performed in the anterior tibial artery in two of seven cases(29%), in the tibiofibular tract and posterior tibial artery in two of seven cases(29%) and in the tibiofibular tract and fibular artery in the remaining three of seven cases(43%). Ischemic symptoms resolved promptly in all, and none of the patients experienced a procedural complication, such as crural vessel dissection, perforation or thrombus embolization.CONCLUSION Mechanical debulking using the 6F Rotarex~S catheter system may be a safe and effective treatment option in case of thrombotic or thromboembolic occlusion of the proximal and mid-portion of crural arteries.展开更多
Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ...Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (1 5 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P〈0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.展开更多
BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new...BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE: To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor (HGF) into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN: Randomized occlusion modelled and verification animal study. SETTING: Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS: This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF (pUDKH) and occlusion model plasmid (pUDK) were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS: Grouping and model establishment: under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES: Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS: (1) Histopathological changes in the femoral nerve: tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. (2) Histopathological changes of the intramuscular nerve: large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION: Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.展开更多
Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have b...Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.展开更多
Objective To investigate the effect of H2S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, I...Objective To investigate the effect of H2S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NariS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NariS (0.78 mg/kg) as exogenous H2S donor and PPG (60 mg/kg) which can suppress endogenous H2S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP1), aquaporin-5 (AQP5) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.展开更多
Infective endocarditis (IE) occurs at a rate of approximately 1-7/100 000 people per year, and has a high morbidity and mortality despite advances in antibiotic and surgical treatments.
Acute limb ischemia is a urgent condition which occurs when there is an abrupt interruption of blood flow into an extremity usually because of either embolic or thrombotic vascular occlusion. Restoration of perfusion ...Acute limb ischemia is a urgent condition which occurs when there is an abrupt interruption of blood flow into an extremity usually because of either embolic or thrombotic vascular occlusion. Restoration of perfusion through early intervention can decrease amputation and mortality. Contemporary treatment includes both surgery and endovascular techniques. There is a rapid progress in endovascular intervention therapy. This article aims to make a comprehensive review of the endovascular intervention options of acute limb ischemia.展开更多
Delayed reperfusion of acute occlusive limb ischemia causes local and systemic serious consequences and is the main cause of morbidity and mortality in these patients. The aim of this study was to examine the outcome ...Delayed reperfusion of acute occlusive limb ischemia causes local and systemic serious consequences and is the main cause of morbidity and mortality in these patients. The aim of this study was to examine the outcome and risk factors of reperfusion injury in such cases. Patients and Methods: Retrospective review of all cases presented, to King Fahd Hospital of University, with acute occlusive limb ischemia more than 12 hours was performed between June 2004 and November 2012. Grades of ischemia, extremities, comorbidities, morbidities and mortality were recorded. Results: During the study period, 92 patients were included, 47 (51%) were embolic and the rest was thrombotic. On admission, 15 patients had grade III ischemia, 68 had grade IIb, 8 had grade IIa and 1 had grade I. Four patients died (4.3%) and 15 (16%) patients had amputation. The risk factors of amputation were age (p = 0.031), extremity (lower limb 21% vs. Upper limb 0%, p = 0.019), cause of ischemia (thrombotic 24% vs. embolic 8.5%, p = 0.049) and grade of ischemia (p = 0.001). Conclusion: Delayed reperfusion of acute occlusive ischemia carries acceptable morbidity and mortality and could be performed even in irreversible ischemia. The risk factors of amputation are age, lower limb ischemia, thrombosis and grade III ischemia.展开更多
Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservat...Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservation were reported in various consistency studies. Direct revascularization (DR) following the foot angiosomes distribution (whenever feasible) may afford better clinical results compared to angiosome indifferent, or indirect revascularization (IR), however without clear benefit on survival and for major adverse limb events (MALE). Inside this interrogation,?the notable influence of the remnant collaterals, the foot arches, the wound characteristics, and the type of revascularization (bypass versus endovascular) still remain ardent topics. Current evidence suggests that applying DR in daily vascular practice requires practitioners to be committed to every individual hemodynamic variable in a thorough macro- and micro-vascular evaluation of the ischemic foot. It becomes clearer nowadays that not all CLTI foot ulcers hold same ischemic burden and seemingly need specific DR. In the same setting,?a novel wound targeted revascularization (WTR) design was proposed assembling wider circulatory targets than genuine DR notion, as used by some authors. Beyond specific angiosomal artery reperfusion, WTR associates the available arches, the large- and medium-sized collaterals, and the arterial-arterial communicants, in an intentional “source artery” and “collateral” topographic foot revascularization. However,?up to date, the notion of angiosome wound-guided revascularization (DR and WTR) detains only a reserved level of confirmation. As for DR, the WTR equally needs higher levels of evidence allowed by standardized definition, uniform indications, and pertinent results from multicenter larger prospective analysis, before large application.展开更多
Introduction: Acute mesenteric ischemia due to an embolism of the superior mesenteric artery (SMA) is associated with a high mortality rate. Over twenty per cent of acute mesenteric embolism cases consist of multiple ...Introduction: Acute mesenteric ischemia due to an embolism of the superior mesenteric artery (SMA) is associated with a high mortality rate. Over twenty per cent of acute mesenteric embolism cases consist of multiple emboli. Case Presentation: We present a rare case of a 62-year-old man admitted with acute abdominal pain and signs of intestinal occlusion related to an acute mesenteric ischemia due to superior mesenteric arterial embolism. It was associated with a synchronous acute bilateral lower limb ischemia due to embolic arterial occlusion. He underwent an emergency explorative laparotomy with proximal jejunal resection, and the patient made an excellent recovery. As for the acute limb ischemia, it was treated by efficient anticoagulation allowing limb salvage. Conclusion: When treating a superior mesenteric arterial embolism, the possibility of recurrent or multiple arterial thromboembolic events should be considered. A prompt diagnosis, aggressive surgical treatment and intensive care could improve the prognosis.展开更多
BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patie...BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.展开更多
Objective To study of the effectiveness of using autologous mononuclear fraction of bone marrow for the treatment of chronic limb ischemia. Methods Results of autologous mononuclear fraction of bone marrow in 90 labor...Objective To study of the effectiveness of using autologous mononuclear fraction of bone marrow for the treatment of chronic limb ischemia. Methods Results of autologous mononuclear fraction of bone marrow in 90 laboratory Wistar rats on a background of creating chronic limb ischemia was presented. Sampling was carried out from the bone marrow of the femur of the animal. The mononuclear fraction of bone marrow autologous 4 × 106 cells in a volume of 200 microliter were injected into the ischemic limb of the two points,in each of which 100 microliter:(1)Paravessel directly below the inguinal ligament at the level of the sacroiliac joint in the area of the anatomical location of collaterals in the projection of the internal iliac artery and its branches;(2)Intramuscularly in gastrocnemius muscle anterior-lateral surface of the middle third of the leg. Results In the experimental group of rats treated with autologous mononuclear fraction of bone marrow,the level of microcirculation compared with the intact group of animals on day 21 was higher than 6. 1% by day 28% ~ 31. 2%; compared with the control group-day 10 increased by 111% at day 21,85. 7% on day 28% ~ 97%. Conclusion Proposed method of treating pathogenically justified and can be recommended for use in clinical practice in the treatment of patients with chronic obliterating diseases of lower limb arteries.展开更多
Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularizatio...Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.展开更多
AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elas...AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0,1,3,6,12 or 24 h. Ischemic post-conditioning,three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damage and the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD),xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays. RESULTS:Ischemic post-conditioning can reduce post-ischemic oxidative stress and the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA,SOD,XOD and MPO were regarded as indexes for mucosal injuries from ROS,and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions. CONCLUSION:ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore,ROS can regulate HIF-1α expression in gastric ischemia.展开更多
Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders im...Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".展开更多
As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant...As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.展开更多
文摘AIM To examine the efficacy and safety of the 6 French(6F) Rotarex~S catheter system in patients with acute limb ischemia(ALI) involving thromboembolic occlusion of the proximal and mid-crural vessels.METHODS The files of patients in our department with ALI between 2015 and 2017 were examined. In seven patients, the Rotarex~S catheter was used in the proximal segment of the crural arteries. Data related to the clinical examination, Doppler sonography, angiography and followup from these patients were further used for analysis.RESULTS Two patients(29%) had thrombotic occlusion of the common femoral artery, and the remaining five exhibited thrombosis of the superficial femoral artery and popliteal artery. Mechanical thrombectomy was performed in all cases using a 6F Rotarex~S catheter. Additional Rotarex~S catheter thrombectomy due to remaining thrombus formation with no reflow was performed in the anterior tibial artery in two of seven cases(29%), in the tibiofibular tract and posterior tibial artery in two of seven cases(29%) and in the tibiofibular tract and fibular artery in the remaining three of seven cases(43%). Ischemic symptoms resolved promptly in all, and none of the patients experienced a procedural complication, such as crural vessel dissection, perforation or thrombus embolization.CONCLUSION Mechanical debulking using the 6F Rotarex~S catheter system may be a safe and effective treatment option in case of thrombotic or thromboembolic occlusion of the proximal and mid-portion of crural arteries.
基金the Clinical Research Fund of Southwest Hospital at Third Military Medical University (SWH2005A109)
文摘Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (1 5 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P〈0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.
基金the Foundation of High-Tech Key Project of the National 863 Program, No. 2001AA217061
文摘BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE: To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor (HGF) into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN: Randomized occlusion modelled and verification animal study. SETTING: Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS: This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF (pUDKH) and occlusion model plasmid (pUDK) were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS: Grouping and model establishment: under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES: Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS: (1) Histopathological changes in the femoral nerve: tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. (2) Histopathological changes of the intramuscular nerve: large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION: Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.
文摘Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.
基金supported by the Military Health Care Foundation during the 12th Five-year Plan Period(11BZ21)the Military Scientific Research Foundation during the 12th Five-year Plan Period(BWS12J051)
文摘Objective To investigate the effect of H2S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NariS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NariS (0.78 mg/kg) as exogenous H2S donor and PPG (60 mg/kg) which can suppress endogenous H2S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP1), aquaporin-5 (AQP5) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-KB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NariS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-KB pathway, but PPG adjusted AO.PJAO.Ps and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.
文摘Infective endocarditis (IE) occurs at a rate of approximately 1-7/100 000 people per year, and has a high morbidity and mortality despite advances in antibiotic and surgical treatments.
文摘Acute limb ischemia is a urgent condition which occurs when there is an abrupt interruption of blood flow into an extremity usually because of either embolic or thrombotic vascular occlusion. Restoration of perfusion through early intervention can decrease amputation and mortality. Contemporary treatment includes both surgery and endovascular techniques. There is a rapid progress in endovascular intervention therapy. This article aims to make a comprehensive review of the endovascular intervention options of acute limb ischemia.
文摘Delayed reperfusion of acute occlusive limb ischemia causes local and systemic serious consequences and is the main cause of morbidity and mortality in these patients. The aim of this study was to examine the outcome and risk factors of reperfusion injury in such cases. Patients and Methods: Retrospective review of all cases presented, to King Fahd Hospital of University, with acute occlusive limb ischemia more than 12 hours was performed between June 2004 and November 2012. Grades of ischemia, extremities, comorbidities, morbidities and mortality were recorded. Results: During the study period, 92 patients were included, 47 (51%) were embolic and the rest was thrombotic. On admission, 15 patients had grade III ischemia, 68 had grade IIb, 8 had grade IIa and 1 had grade I. Four patients died (4.3%) and 15 (16%) patients had amputation. The risk factors of amputation were age (p = 0.031), extremity (lower limb 21% vs. Upper limb 0%, p = 0.019), cause of ischemia (thrombotic 24% vs. embolic 8.5%, p = 0.049) and grade of ischemia (p = 0.001). Conclusion: Delayed reperfusion of acute occlusive ischemia carries acceptable morbidity and mortality and could be performed even in irreversible ischemia. The risk factors of amputation are age, lower limb ischemia, thrombosis and grade III ischemia.
文摘Despite a lack of solid evidence in applying the angiosome concept (AC) in current chronic limb threatening ischemia (CLTI) treatment, several encouraging results for improved wound healing and less for limb preservation were reported in various consistency studies. Direct revascularization (DR) following the foot angiosomes distribution (whenever feasible) may afford better clinical results compared to angiosome indifferent, or indirect revascularization (IR), however without clear benefit on survival and for major adverse limb events (MALE). Inside this interrogation,?the notable influence of the remnant collaterals, the foot arches, the wound characteristics, and the type of revascularization (bypass versus endovascular) still remain ardent topics. Current evidence suggests that applying DR in daily vascular practice requires practitioners to be committed to every individual hemodynamic variable in a thorough macro- and micro-vascular evaluation of the ischemic foot. It becomes clearer nowadays that not all CLTI foot ulcers hold same ischemic burden and seemingly need specific DR. In the same setting,?a novel wound targeted revascularization (WTR) design was proposed assembling wider circulatory targets than genuine DR notion, as used by some authors. Beyond specific angiosomal artery reperfusion, WTR associates the available arches, the large- and medium-sized collaterals, and the arterial-arterial communicants, in an intentional “source artery” and “collateral” topographic foot revascularization. However,?up to date, the notion of angiosome wound-guided revascularization (DR and WTR) detains only a reserved level of confirmation. As for DR, the WTR equally needs higher levels of evidence allowed by standardized definition, uniform indications, and pertinent results from multicenter larger prospective analysis, before large application.
文摘Introduction: Acute mesenteric ischemia due to an embolism of the superior mesenteric artery (SMA) is associated with a high mortality rate. Over twenty per cent of acute mesenteric embolism cases consist of multiple emboli. Case Presentation: We present a rare case of a 62-year-old man admitted with acute abdominal pain and signs of intestinal occlusion related to an acute mesenteric ischemia due to superior mesenteric arterial embolism. It was associated with a synchronous acute bilateral lower limb ischemia due to embolic arterial occlusion. He underwent an emergency explorative laparotomy with proximal jejunal resection, and the patient made an excellent recovery. As for the acute limb ischemia, it was treated by efficient anticoagulation allowing limb salvage. Conclusion: When treating a superior mesenteric arterial embolism, the possibility of recurrent or multiple arterial thromboembolic events should be considered. A prompt diagnosis, aggressive surgical treatment and intensive care could improve the prognosis.
基金Supported by the Chang Gung Medical Foundation,Taiwan,No.CMRPD1J0101-0102。
文摘BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.
文摘Objective To study of the effectiveness of using autologous mononuclear fraction of bone marrow for the treatment of chronic limb ischemia. Methods Results of autologous mononuclear fraction of bone marrow in 90 laboratory Wistar rats on a background of creating chronic limb ischemia was presented. Sampling was carried out from the bone marrow of the femur of the animal. The mononuclear fraction of bone marrow autologous 4 × 106 cells in a volume of 200 microliter were injected into the ischemic limb of the two points,in each of which 100 microliter:(1)Paravessel directly below the inguinal ligament at the level of the sacroiliac joint in the area of the anatomical location of collaterals in the projection of the internal iliac artery and its branches;(2)Intramuscularly in gastrocnemius muscle anterior-lateral surface of the middle third of the leg. Results In the experimental group of rats treated with autologous mononuclear fraction of bone marrow,the level of microcirculation compared with the intact group of animals on day 21 was higher than 6. 1% by day 28% ~ 31. 2%; compared with the control group-day 10 increased by 111% at day 21,85. 7% on day 28% ~ 97%. Conclusion Proposed method of treating pathogenically justified and can be recommended for use in clinical practice in the treatment of patients with chronic obliterating diseases of lower limb arteries.
文摘Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.
基金Supported by Technology from the School of Basic Medical Sciences of Lanzhou University and the Animal Experimental Center, Gansu College of Traditional Chinese Medicine
文摘AIM:To investigate the relation of reactive oxygen species (ROS) to hypoxia induced factor 1α (HIF-1α) in gastric ischemia. METHODS:The animal model of gastric ischemia reperfusion was established by placing an elastic rubber band on the proximal part of the bilateral lower limb for ligature for 3 h and reperfusion for 0,1,3,6,12 or 24 h. Ischemic post-conditioning,three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were conducted before reperfusion. Histological and immunohistochemical methods were used to assess the gastric oxidative damage and the expression of HIF1-α in gastric ischemia. The malondialdehyde (MDA) content and superoxide dismutase (SOD),xanthine oxidase (XOD) and myeloperoxidase (MPO) activities were determined by colorimetric assays. RESULTS:Ischemic post-conditioning can reduce post-ischemic oxidative stress and the expression of HIF-1α of gastric tissue resulting from limb ischemia reperfusion injury. MDA,SOD,XOD and MPO were regarded as indexes for mucosal injuries from ROS,and ROS was found to affect the expression of HIF-1α under gastric ischemic conditions. CONCLUSION:ROS affects HIF-1α expression under gastric ischemic conditions induced by limb ischemia reperfusion injury. Therefore,ROS can regulate HIF-1α expression in gastric ischemia.
文摘Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".
文摘As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.