Indium-111 labeled platelet deposition following transfemoral angiography

The incidence of thromboembolitic events in patients undergoing transfemoral angiography was examined using indium-111 labeled platelets. Twenty-seven patients received approximately 300 muCi of autologous labeled platelets at least 3 hours before angiography and were scanned with a gamma camera immediately before and after angiography. All patients were free of clinically obvious complications in the 1-2 day period after angiography. Our results showed evidence of platelet deposition at 21 sites other than the puncture site in 12 (44%) patients. Most platelet deposition (54%) occurred along the region between the puncture site and the aortic bifurcation; 24% occurred at sites not traversed by the catheter. At the puncture site itself, there was substantial platelet uptake in 44% of patients. This study indicates the need for further work in determining the most suitable catheter material and in assessing the efficacy of other measures such as anticoagulant or antiplatelet therapy.     

Incidence and mortality of venous thrombosis: a population-based study

Background: Estimates of the incidence of venous thrombosis (VT) vary, and data on mortality are limited. Objectives: We estimated the incidence and mortality of a first VT event in a general population. Methods: From the residents of Nord‐Trøndelag county in Norway aged 20 years and older (n = 94 194), we identified all cases with an objectively verified diagnosis of VT that occurred between 1995 and 2001. Patients and diagnosis characteristics were retrieved from medical records. Results: Seven hundred and forty patients were identified with a first diagnosis of VT during 516 405 person‐years of follow‐up. The incidence rate for all first VT events was 1.43 per 1000 person‐years [95% confidence interval (CI): 1.33–1.54], that for deep‐vein thrombosis (DVT) was 0.93 per 1000 person‐years (95% CI: 0.85–1.02), and that for pulmonary embolism (PE) was 0.50 per 1000 person‐years (95% CI: 0.44–0.56). The incidence rates increased exponentially with age, and were slightly higher in women than in men. The 30‐day case‐fatality rate was higher in patients with PE than in those with DVT [9.7% vs. 4.6%, risk ratio 2.1 (95% CI: 1.2–3.7)]; it was also higher in patients with cancer than in patients without cancer [19.1% vs. 3.6%, risk ratio 3.8 (95% CI 1.6–9.2)]. The risk of dying was highest in the first months subsequent to the VT, after which it gradually approached the mortality rate in the general population. Conclusions: This study provides estimates of incidence and mortality of a first VT event in the general population.     

High-resolution and accelerated multi-parametric mapping with automated characterization of vessel disease using intravascular MRI

Background

Atherosclerosis is prevalent in cardiovascular disease, but present imaging modalities have limited capabilities for characterizing lesion stage, progression and response to intervention. This study tests whether intravascular magnetic resonance imaging (IVMRI) measures of relaxation times (T₁, T₂) and proton density (PD) in a clinical 3 Tesla scanner could characterize vessel disease, and evaluates a practical strategy for accelerated quantification.

Methods

IVMRI was performed in fresh human artery segments and swine vessels in vivo, using fast multi-parametric sequences, 1–2 mm diameter loopless antennae and 200–300 μm resolution. T₁, T₂ and PD data were used to train a machine learning classifier (support vector machine, SVM) to automatically classify normal vessel, and early or advanced disease, using histology for validation. Disease identification using the SVM was tested with receiver operating characteristic curves. To expedite acquisition of T₁, T₂ and PD data for vessel characterization, the linear algebraic method (‘SLAM’) was modified to accommodate the antenna’s highly-nonuniform sensitivity, and used to provide average T₁, T₂ and PD measurements from compartments of normal and pathological tissue segmented from high-resolution images at acceleration factors of R ≤ 18-fold. The results were validated using compartment-average measures derived from the high-resolution scans.

Results

The SVM accurately classified ~80% of samples into the three disease classes. The ‘area-under-the-curve’ was 0.96 for detecting disease in 248 samples, with T₁ providing the best discrimination. SLAM T₁, T₂ and PD measures for R ≤ 10 were indistinguishable from the true means of segmented tissue compartments.

Conclusion

High-resolution IVMRI measures of T₁, T₂ and PD with a trained SVM can automatically classify normal, early and advanced atherosclerosis with high sensitivity and specificity. Replacing relaxometric MRI with SLAM yields good estimates of T₁, T₂ and PD an order-of-magnitude faster to facilitate IVMRI-based characterization of vessel disease.

     

The folding pathway of alpha1-antitrypsin: avoiding the unavoidable

Understanding the folding pathway of α(1)-antitrypsin is of interest from both biomedical and fundamental molecular biology perspectives. The native fold of α(1)-antitrypsin is metastable, and therefore does not represent the most stable conformation that its primary sequence can adopt. More stable conformations are formed when the reactive center loop inserts, as the fourth strand, into the A β sheet. The accessibility of these alternative low-energy folds renders α(1)-antitrypsin susceptible to mutations that can result in dysfunction and pathology. Here, I review some of the literature from the past 20 years, which has examined how α(1)-antitrypsin folds and preserves its native metastable state. In addition, I look at the relationship between α(1)-antitrypsin folding and misfolding, and its role in disease.     

Perilipin deficiency and autosomal dominant partial lipodystrophy

Perilipin is the most abundant adipocyte-specific protein that coats lipid droplets, and it is required for optimal lipid incorporation and release from the droplet. We identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein failed to increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue.