M. M. Thompson

Increased Matrix Metalloproteinase-9 Activity in Unstable Carotid Plaques A Potential Role in Acute Plaque Disruption

BACKGROUND AND PURPOSEnAcute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology.nnnMETHODSnPlaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA.nnnRESULTSnThe level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median <32 ng/mL for all other groups; P=0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (P=0.019) and those with histological evidence of plaque instability (P<0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate.nnnCONCLUSIONSnThe concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.

Subintimal angioplasty of isolated infragenicular vessels in lower limb ischemia: long-term results.

Purpose: To assess the outcome of subintimal angioplasty in treating isolated infragenicular arterial disease in patients with severe lower limb ischemia. Methods: A retrospective study reviewed 67 consecutive patients (39 men; mean age 76 years, range 41–96) who underwent infragenicular subintimal angioplasty between March 1997 and May 2000 for ischemia in 70 limbs. The median length of occlusion was 6 cm (range 1–10) in the below-knee popliteal arteries, 4 cm (range 1–4) in the tibioperoneal trunk, 21 cm(range 1–35) in the anterior tibial artery, 10 (1–30) in the posterior tibial artery, and 5 (range 1–20) in the peroneal artery. Results: The technical and clinical success rates were 86% and 80%, respectively. In the 10 (14%) patients with a technical failure, 3 underwent successful bypass, 4 had an amputation, 1 had a lumbar sympathectomy, and 2 were treated conservatively. Of the 4 (6%) limbs that did not achieve clinical success, 2 patients required femorodistal bypass and their ulcers improved; in the other 2, ulcerations did not heal completely. The cumulative limb salvage rate and freedom from critical limb ischemia (CLI) quantified by Kaplan-Meier life-table analysis were 94% and 84% at 36 months. Mortality rates were 19% at 1 year, 43% at 2 years, and 51% at 3 years. In a subgroup analysis, the rate of CLI was significantly lower in nondiabetics (4%) and than in diabetics (24%, p=0.02), but neither survival nor amputation rates were significantly different. Conclusions: Subintimal angioplasty is a safe and effective procedure for treating isolated crural vessels in patients with severe lower limb ischemia.

Subintimal and intraluminal recanalisation of occluded crural arteries by percutaneous balloon angioplasty

Advances in radiological techniques have allowed successful treatment of arterial stenoses situated in the distal arterial tree. This paper describes the experience at Leicester Royal Infirmary with percutaneous transluminal angioplasty (PTA) for the treatment of occluded crural arteries. Over a 27 month period, 21 patients with 24 ischaemic limbs have undergone PTA for crural artery occlusion. PTA was attempted in a total of 29 occluded crural arteries with a median length of occlusion of 6 cm (range 1-30 cm). Intraluminal recanalisation was used for short occlusions and the subintimal technique for long occlusions. Technical success with angiographic recanalisation of the artery was achieved in 25 out of 29 crural vessels (86%). Endovascular treatment of crural artery occlusion appears to be a safe and effective treatment which avoids the need for femorodistal surgery in patients with occluded calf vessels.

Surgical Management of 671 Abdominal Aortic Aneurysms: A 13 Year Review from a Single Centre

OBJECTIVEnTo audit the results for abdominal aortic aneurysm (AAA) repair from a single centre over a 13 year period.nnnDESIGNnRetrospective survey.nnnSETTINGnVascular unit of a major teaching hospital.nnnMATERIALSnSix hundred and seventy-one consecutive patients divided into two groups: group A (1981-87) and group B (1988-93).nnnCHIEF OUTCOME MEASURESnMortality rates, cause of death and major complications in patients undergoing elective, urgent and ruptured AAAs.nnnRESULTSnElective repair was performed in 313 (47%) patients, urgent repair in 80 (12%) and emergency repair for rupture in 278 (41%). A vascular surgeon performed the procedure in 94% of patients. The overall mortality was 21 patients in the elective group (6.7%), 13 in the urgent group (16%) and 148 in the ruptured group (53%). Mortality rates have not fallen during the study period but more patients in group B had ischaemic heart disease. Sixty patients (9%) required further operative procedures on 66 occasions: 24 elective cases (8%), 8 urgent cases (10%) and 28 ruptured cases (10%). There were 23 deaths in these 60 patients (38%) who underwent re-operation (5 elective, 2 urgent and 16 ruptured). Major postoperative complications included cardiac events in 212 (32%) patients, respiratory failure in 202 (30%) and renal failure in 90 (13%). Major causes of death included cardiac disease in 67 patients (37%), cardiac disease with coagulopathy in 22 (12%) and cardiac disease with respiratory failure in 16 (9%). Logistic regression analysis showed that in the elective group, cardiac or renal failure were significantly associated with death; and in the ruptured group cardiac, respiratory or renal failure were significantly associated with death.nnnCONCLUSIONSnMore high risk patients with ischaemic heart disease are undergoing AAA repair. Postoperative cardiac, respiratory or renal failure are significant causes of death in AAA patients.

Endovascular AAA Repair Attenuates the Inflammatory and Renal Responses Associated with Conventional Surgery

PURPOSEnTo quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs).nnnMETHODSnForty-three patients (41 men; ages 58-81 years) underwent endovascular or conventional aneurysm surgery according to aortic morphology. All patients received a standard general anesthetic and had 12 serial blood and urine samples collected during the perioperative period. Samples underwent analysis for the cytokines interleukin (IL) 1beta tumor necrosis factor-alpha (TNF-alpha), and IL-6. White cell and platelet activation were estimated indirectly by measuring sL-selectin and 11-dehydrothromboxane B2, respectively. The urinary albumin:creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase (NAG) activity were estimated to assess renal injury. Fibrinogen and fibrinogen degradation products were calculated to assess activation of the clotting cascade.nnnRESULTSnTwenty-three patients underwent endovascular AAA repair and 20 had conventional surgery. Concentrations of IL-6 (p < 0.002) and TNF-alpha (p < 0.0004) were significantly higher in the conventional group. The ACR (p < 0.002) and urinary NAGs (p < 0.0009) were also significantly higher in this group, suggesting greater renal injury. Platelet activity was significantly greater in the endovascular group (p < 0.01), perhaps indicating thrombus organization within the aneurysm sac.nnnCONCLUSIONSnThese data suggest that the inflammatory response associated with conventional aneurysm repair is largely obviated by endovascular techniques. This may potentially translate to a lower incidence of multiple organ failure after endovascular surgery.

Chronic critical leg ischaemia must be redefined.

The Second European Consensus Document on Chronic Critical Leg Ischaemia defines critical limb ischaemia in non-diabetic patients as rest pain or tissue necrosis (ulceration or gangrene) with an ankle systolic pressure (ASP) of less than or equal to 50 mmHg, or a toe pressure of less than or equal to 30 mmHg. The aim of this study was to investigate whether this definition is able to predict the outcome of patients with severe lower limb ischaemia and thus to determine the relevance of the definition in clinical practice. We have analysed 148 severely ischaemic limbs in 133 non-diabetic patients who presented with rest pain, tissue necrosis or a combination of these symptoms. Fifty-one percent of these limbs fulfilled the current definition with an ASP < or = 50 mmHg; 49% had an ASP > 50 mmHg and were thus not defined as critically ischaemic according to the current definition. We have compared actuarial limb salvage and mortality rates in patients with an ASP < or = 50 mmHg to those patients with an ASP > 50 mmHg. The 1 year limb salvage and mortality rates for ischaemic limbs fulfilling the European Consensus Document criteria were 78.7 and 36.7% respectively, compared to rates of 73.9 and 17.3% in patients who were not defined as critically ischaemic under the current definition. There were no significant differences between 1 year limb salvage or mortality rates between the two patients groups (p = 0.843, 0.078, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Selection of Patients with Critical Limb Ischaemia for Femorodistal Vein Bypass

The merits of an aggressive policy of distal reconstruction have been questioned by some observers. To determine the factors affecting graft patency and mortality, we analysed 78 consecutive infragenicular femorodistal vein grafts performed in 72 patients with critical limb ischaemia. The primary, primary assisted and secondary graft patency rates at 36 months were 29, 57 and 64%, respectively. The limb salvage and patient survival rates at 36 months were 67 and 74%, respectively. Univariate analysis (log-rank test) was performed to identify factors affecting graft patency, limb salvage and mortality at 1 month (perioperative) and 1 year. Independent variables of age, sex, diabetes, presentation, level of anastomosis and vein technique (reversed or in situ) did not affect graft patency. The ankle systolic pressure did not predict graft patency but was an independent variable affecting mortality (p = 0.047), as did diabetes (p = 0.019). These results show that excellent limb salvage can be successfully achieved in severely ischaemic patients by adopting an aggressive approach to femorodistal bypass, and that age, gender and poor medical condition are not contraindications to femorodistal bypass. The difference between the primary and primary assisted patency rates in this series is dramatic and reflects the impact of a vein graft surveillance programme in preventing graft occlusion.

Percutaneous Transluminal Angioplasty in the Treatment of Critical Limb Ischemia

Purpose: To assess the role of percutaneous transluminal angioplasty (PTA) to treat critical limb ischemia (CLI) and to relate the changing experience with endovascular treatment of this condition in a major vascular unit. Methods: A prospective study was performed involving 110 consecutive patients (57 women; mean age 76 years, range 57–99) undergoing balloon angioplasty for critical limb ischemia in 133 limbs. Outcome at 1 year was examined by case note review or questionnaire to determine survival, amputation-free survival, limb salvage, and CLI recurrence. Results: Technical success was achieved in 105 (79%) of 133 limbs; the overall complication rate was 20% (3.8% major, 16.2% minor). The median follow-up was 15 months (minimum 12). The 12-month limb salvage rate by life-table analysis was 88%. Patients with an initially successful angioplasty had an extremely good outcome (95% 1-year limb salvage). In contrast, the 28 patients with failed angioplasty fared very poorly; a major amputation was required in 10, and death occurred in another 9, leaving only 9 survivors with limbs intact at 1 year. Conclusions: The results of this study justify the continuing use of PTA as first-line treatment for critical limb ischemia.

Simple and reliable method of doxycycline determination in human plasma and biological tissues

Over recent years there has been a resurgence in the use of doxycycline in clinical practice, which does not depend on its antibacterial properties. This paper describes a method of determination of doxycycline in human plasma and atheromatous tissue using high-performance liquid chromatography (HPLC), and a cheap commercially available extraction system. Doxycycline is extracted in the mobile phase and injected directly into the HPLC system, avoiding time consuming drying up steps. A limit of detection of 0.125 microg/ml of plasma, and a relative standard deviation of 3% was achieved, making the method very reliable and useful for assays within the usual therapeutic range. The method has also been applied to the extraction of a mixture of tetracyclines from plasma and atherma with equal efficacy, making it useful for assays of this class of drugs in veterinary practice and assays of food contaminants.

Trends in Abdominal Aortic Aneurysms: a 13 year review

AIMnTo assess changing trends of abdominal aortic aneurysms 1979-1991.nnnDESIGNnRetrospective study from the Leicestershire Health Authority.nnnRESULTSn727 patients with abdominal aortic aneurysm were treated. Of these 56.4% were admitted for elective repair and 43.6% presented with rupture. There was a significant increase in the number of ruptured aortic aneurysms over this period despite an increase in the number of elective repairs. The overall 30-day mortality of elective repair (including patients with symptomatic but non-ruptured aneurysms) was 8.8%. The overall 30-day mortality of ruptured aneurysms (including patients who were deemed medically too unfit for surgery) was 57.7%. There has been no significant change in elective and ruptured mortality over the study period. There was a significant increase in the median age of patients (69.5 yrs in 1979 to 74 yrs in 1991).nnnCONCLUSIONnThe increasing incidence of abdominal aortic aneurysms may reflect better diagnostic methods, greater clinical awareness of the condition and increase in the proportion of elderly people in the population.