Impact of metabolic syndrome on the outcomes of superficial femoral artery interventions

BackgroundMetabolic syndrome (MetSyn) is an epidemic in the United States and is associated with early onset of atherosclerosis, increased thrombotic events, and increased complications after cardiovascular intervention. MetSyn is found in ∼50% of patients with peripheral vascular disease. However, its impact on peripheral interventions is unknown. The aim of this study is to determine the outcomes of superficial femoral artery (SFA) interventions in patients with and without MetSyn.MethodsA database of patients undergoing endovascular treatment of SFA disease between 1999 and 2009 was retrospectively queried. MetSyn was defined as the presence of ≥3 of the following criteria: blood pressure ≥130 mm Hg/≥85 mm Hg; triglycerides ≥150 mg/dL; high-density lipoprotein ≤50 mg/dL for women and ≤40 mg/dL for men; fasting blood glucose ≥110 mg/dL; or body mass index ≥30 kg/m2. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. Factor analyses were performed using a Cox proportional hazard model for time-dependent variables.ResultsA total of 1018 limbs in 738 patients (64% male, average age 67 years) underwent endovascular treatment for symptomatic SFA disease with 45% of patients meeting the criteria for MetSyn. MetSyn patients were more likely to be female (P = .001), to present with critical ischemia (rest pain/tissue loss: 55% MetSyn vs 45% non-MetSyn; P = .001), have poorer ambulatory status (P = .001), and have more advanced SFA lesions (TransAtlantic Inter-Society Consensus II C/D: 51% vs 11%; P = .001) and worse tibial runoff (P = .001). MetSyn patients required more complex interventions (P = .0001). There was no difference in mortality and major adverse cardiac events, but systemic complications (4% vs 1%; P = .001) and major adverse limb events (12% vs 7%; P = .0009) were significantly higher in the MetSyn group. Immediate postprocedural hemodynamic improvement, resolved or improved symptoms, and restoration of impaired ambulation were equivalent in both groups. Early failure (<6 months) was more common in those with MetSyn. At 5 years, primary, assisted primary, and secondary patencies were not affected by the presence of MetSyn. The presence of MetSyn was associated with a decrease in clinical efficacy, decreased freedom from recurrent symptoms, and decreased freedom from major amputation at 5 years.ConclusionsMetSyn is present in nearly half of the patients presenting with SFA disease. These patients present with more advanced disease and have poorer symptomatic and functional outcomes compared with those patients without MetSyn

Phase Space Isometries and Equivariant Localization of Path Integrals in Two Dimensions

By considering the most general metric which can occur on a contractable two dimensional symplectic manifold, we find the most general Hamiltonians on a two dimensional phase space to which equivariant localization formulas for the associated path integrals can be applied. We show that in the case of a maximally symmetric phase space the only applicable Hamiltonians are essentially harmonic oscillators, while for non-homogeneous phase spaces the possibilities are more numerous but ambiguities in the path integrals occur. In the latter case we give general formulas for the Darboux Hamiltonians, as well as the Hamiltonians which result naturally from a generalized coherent state formulation of the quantum theory which shows that again the Hamiltonians so obtained are just generalized versions of harmonic oscillators. Our analysis and results describe the quantum geometry of some two dimensional systems.Comment: 26 pages, plain TeX; UBCTP 93-01

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Clinical significance of circulating anti-p53 antibodies in European patients with hepatocellular carcinoma

p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12–30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of the p53 gene nor the serum alpha-fetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative ‘good prognosis’ in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis. © 1999 Cancer Research Campaig