Expression of TLR4-PTGE2 signaling genes in atherosclerotic carotid plaques and peripheral blood.

Toll-like receptor 4 (TLR4)/prostaglandine synthetase 2 (PTGS2) signaling plays a relevant role in atherosclerotic plaque vulnerability. The purpose of this study was to check the gene expression of 6 genes participating to TLR4/PTGS2 signaling (TLR4, PTGS2, ACSL4, PTGER3, PTGER4, and EPRAP) in carotid plaques and blood samples from the same individual and to evaluate these genes as biomarker of plaque progression. We investigated differential gene expression by qRT-PCR in 62 atherosclerotic patients' carotid plaques and corresponding blood sample. A very weak or no correlation was observed in the overall population or analyzing asymptomatic patients. These analyzed genes are most likely not suitable for inclusion in the clinical routine as biomarkers of plaque instability.

Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

INTRODUCTION: Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. PATIENTS AND METHODS: We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. RESULTS: Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. CONCLUSIONS: In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

Upregulated expression of Toll-like receptor 4 in peripheral blood of ischaemic stroke patients correlates with cyclooxygenase 2 expression.

OBJECTIVES: An inflammatory process following stroke in human brains and systemic inflammatory responses after stroke in humans have been reported by numerous investigators. The aim of the study was to investigate if genes involved in the cyclooxygenase 2 (COX-2) pathway are upregulated at peripheral level in patients after transient ischaemic attack (TIA) and stroke. DESIGN OF STUDY: Blood samples were obtained from two groups of patients undergoing carotid endarterectomy. The first group included 25 patients who presented TIA or ischaemic stroke. The second group included 35 patients who had an asymptomatic internal carotid artery stenosis. Total RNA was isolated and the expression of Toll-like Receptor 4 (TLR4), COX-2, membrane-associated Prostaglandin E synthase (mPGES-1), Prostaglandin E2 receptors (EP3 and EP4) was analysed by real time RT-PCR. RESULTS: Expression of COX-2 and TLR4 were significantly increased in symptomatic patients (p < 0.001). Correlation analysis showed that TLR4 expression significantly correlated with COX-2 expression (R = 0.65; p < 0.01) in ischaemic stroke patients. This correlation was not observed in TIA and asymptomatic patients. CONCLUSIONS: Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.

[Approach to juxtarenal inflammatory aneurysms]. / L'approccio agli aneurismi infiammatori iuxtarenali.

The incidence of inflammatory abdominal aortic aneurysm (IAAA) in a late review of the literature is estimated about 2-15% overall aortic aneurysms. In our data this type of aneurysm is 3.6 overall aortic aneurysms treated. In the majority of the cases, IAAA is juxtarenal or infrarenal. Ethiopathogenesis of IAAA till today is not certain. Recent hypothesis on IAAA attribute the same ethiopathogenesis in both atherosclerotic and inflammatory aneurysm. The interaction of genetic, environmental and infective factors should be able to determine an autoimmune inflammatory reaction of variable severity. 80% of the patients suffering from IAAA present abdominal or lumbar pain, loss of weight and increase of the RC sedimentation velocity. The IAAA's natural history goes to rupture. Entrapment of nearstanding organs totally involved in the fibrotic process is the most frequent complication. Usually there is a compression of the ureter and the duodenum with consequenced hydroureteronephrosis and bowel obstruction. Preoperative diagnosis is possible; CT scan and MRI guarantee and accuracy about 90%. Intraoperatively the external wall of IAAA appears whitish and translucent and always there are tenacious adhesion given by the avventital wounds inflammation. Confirm is given by the histological examination of the aneurysmatic wall and peravventitial tissues. Our experience and a late review of the literature concorde that surgical indication for the treatment of IAAA is the same for the atherosclerotic one. This conviction is supported by the fact that the diagnostic methodical evolution and the improvement in mininvasive surgical technique lowered perioperating morbility and mortaliy. We prefer, according with many authors, retroperitoneal approach to juxtarenal IAAA, instead of standardized transperitoneal access with xifo-pubical or transversal under costal incision. This approach offers some advantages as easier exposition of aorta, whose postero-lateral wall is hardly ever involved in inflammatory process, little duodenum's and left renal veins manipulation and low incidence of paralytic ileum and respiratory disease. Endovascular surgery hasn't in this moment any role in juxtarenal IAAA treatment because this type of aneurysm has inadequate proximal neck. In the future, probably, endovascular repair will be possible using a new type of endograft with renal legs. Often surgical treatment is inadequate to control retroperitorenal fibrosis and so surgeon has to use perioperating pharmacolocical therapy.

The Italian trial of endovascular AAA exclusion using the Parodi endograft.

PURPOSE: To report the outcome of the prospective 11-center Italian Parodi Trial using straight and tapered endografts for the endovascular exclusion of abdominal aortic aneurysms (AAA). METHODS: From April 1994 to July 1995, 27 patients were evaluated and selected for endovascular AAA exclusion. The Parodi devices were delivered through femoral arteriotomies using 18 to 22F introducers and deployed by balloon expansion of the terminal stents. RESULTS: Of 27 cases attempted, 24 endografts (15 tube, 9 aortomonoiliac) were implanted (1 deployment and 2 access failures [11.1%] were converted). Three endoleaks (12.5%) were treated intraoperatively with covered stents, two successfully, and the third sealed within 30 days. Three (12.5%) of the 24 treated patients died in-hospital of device-(n = 2) and procedure-related (n = 1) causes; the remaining 21 patients were discharged within 8 days. Of the 8 aortomonoiliac grafts in follow-up, only 1 (12.5%) failed in the mean 23-month (range 18 to 30) follow-up: however, 4 (31%) of 13 tube graft patients were converted to surgery within 18 months. Of the 16 (66.7%) surviving endografts at 2 years, 6 (38%) showed no change in the AAA diameter, while 10 (62%) had shrunk. CONCLUSIONS: The tube graft was applicable in only about 5% of cases, and accurate endograft sizing and distal fixation were problematic. The aortomonoiliac design was not appealing to surgeons but fared better in the long term. Given the advent of newer endograft models, the Italian Parodi Trial has been terminated.

[Carotid endarterectomy with placement of a PUR (polyurethane) patch]. / La TEA carotidea con posizionamento di patch in PUR.

In this study, 40 patients who underwent surgery for cerebro-vascular insufficiency were considered. Carotid endarterectomy was the procedure of choice in all of the patients; the arteriotomy was always closed using a PUR patch, a new material that, for its chemical and physical characteristics seems to be a good alternative to PTFE. All of the patients underwent surgery under loco-regional anesthesia, allowing a perioperative monitoring of the neurological status through the patient's active collaboration. During the postoperative period, non local or systemic pathology related to the use of the patch has been observed. During the short and half term follow-up, the patients underwent echo-Doppler of the supra-aortic trunks that didn't show either false aneurysms or thrombosis on the patch surface.

Arterial revascularization by laser angioplasty: first Italian experiences.

Eighty-seven laser angioplasty procedures were performed on 85 patients (73 men and 12 women). In the first phase (54 patients) a broad selection process included long occlusions (23.9 cm avg) and vessels with heavy calcification; in the second phase (31 patients) the authors treated vessels with shorter occlusions (10 cm avg) and less calcific. The primary success rate, based on number of procedures (73.5% overall) was 69% in the first phase but reached 81.3% in the second phase. There were 14 perforations (16%), 8 dissections (9.4%), and 4 peripheral emboli (4.7%). Six-month follow-up shows that the Winsor index maintained its initial improvement in 76.5% of all patients, or 62% in just the long occlusions. These data and a review of the cases suggest that no more of 10-20% of patients with claudication in lower extremities can be treated by laser angioplasty; the authors consider ideal candidates those patients who noncalcific lesions in the common iliac or superficial femoral arteries at the III medium level with obstructions shorter than 8 cm and good runoff.

[Evaluation of complications during laser angioplasty with a hot tip system in the treatment of peripheral arteriopathy]. / Valutazione delle complicanze durante laser angioplastica con sistema a punta calda nel trattamento delle arteriopatie periferiche.

"Hot tip" laser angioplasty has been used in the treatment of peripheral artery disease. The purpose of our study (the largest in Italy) is to evaluate the complications during the recanalization of stenotic and occluded iliac and femoro-popliteal arteries, using a hot tip laser system coupled to an Argon or Nd Yag laser. One hundred twenty-three patients have been treated. The complications were: arterial spasm in 2 patients; distal embolizations in 6 patients; arterial dissections in 35 patients; vessel wall perforations in 20 patients. Vessel wall perforation is the more severe complication and did never allow to complete the procedure. The presence of intravascular calcified deposits increases the risk of perforation, due to the loss of the coaxial position of the probe. Only the development of a guided laser system could allow a safer delivery of laser radiation, reducing the risk of arterial wall perforation.

Evolution of carotid atheromatous lesions in endarterectomized patients.

A noninvasive follow-up using duplex ultrasonography was conducted in 128 patients who had undergone carotid endarterectomy from January 1987 to December 1988. Repeated scans of the operated area revealed a distinct increase in thickened ultrasonographic features (32% vs 8%), and a stenosing lesion was detected in 8 patients. There was also a parallel increase in the number of subjects with thicknesses of the intima adjacent to the endarterectomy area exceeding 2.5 mm. In 7% of cases, dilatation was detected in the operated area and in 27% the margin of the area was raised. The study also dealt with the contralateral carotid artery, where a progression of atheromatous involvement was observed with an increased number of cases of hemodynamically significant stenosis and 3 cases of occlusion. Periodic duplex ultrasonography in endarterectomized patients proves useful for the early detection of hemodynamically significant stenoses or of structural features potentially capable of generating emboli.