Endovascular popliteal aneurysm repair: are the results comparable to open surgery?

INTRODUCTION: The aim of this study was to review our experience of popliteal aneurysms using endovascular techniques. METHODS: Thirty popliteal aneurysms in 25 patients were treated over an 11-year period. Median aneurysm diameter was 26 (16-48) mm. Five were symptomatic and 25 asymptomatic. Patients were treated with the Haemobahn/Viabahn stent-graft (26), Passager (two), Aneurx (one), and PTFE homemade device (one). Data were assessed using life table analysis, and expressed as cumulative patency rates and standard error (SE). RESULTS: Median follow-up was 24 (range 1-95) months. Primary patency was 92.9% (SE 4.5%), 84.7% (SE 6.8%), 80% (SE 8.2%), 74.5% (SE 9.4%) and 74.5% (11.3%) at 1, 6, 12, 24 and 36 months, respectively. Cumulative secondary patency was 96.5% (SE 3.3%), 88.7% (SE 6.0%), 88.7% (SE 8.6%), 83.2% (SE 8.0%) and 83.2% (SE 9.8%) at 1, 6, 12, 24 and 36 months, respectively. CONCLUSION: Endovascular treatment of popliteal aneurysms in this series achieved patency rates similar to open surgery. Aneurysm repair was performed without peroperative deaths and the risks associated with open surgery.

Using CCM and DHPLC to detect mutations in the glucocorticoid receptor in atherosclerosis: a comparison.

Growing evidence suggests that restenosis may be caused by a failure in growth inhibitory and apoptotic systems that would normally mediate lesion regression. One such inhibitory system is the glucocorticoid receptor. This paper develops, assesses and compares chemical cleavage of mismatch (CCM) and denaturing high-performance liquid chromatography (DHPLC) for their utility in detecting mutations in this system. The results of the two methods correlated in 74% of cases in a cohort of endarterectomy patients studied by these two methods.

DNA 2000: International Symposium on the State-of-the-Art in Genetic Analysis, June 1-3, 2000, Boston, U.S.A.

DNA 2000, an international symposium on state-of-the-art genetic analysis, was held at the Back Bay Hilton in Boston, Massachusetts, on 1-3 June, 2000. Meeting highlights are described. The meeting was organized and sponsored by the California Separation Science Society (CaSSS; www.casss.org) and other co-sponsors including the Human Genome Organisation (HUGO). DNA 2000 brought together a group of specialists in DNA detection and analysis methods from around the world in a venue presenting not only new technologies but also their applications in candidate gene studies, molecular diagnosis, analysis of complex diseases, and even studying the origin and evolution of humans.

The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance.

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.

Glucocorticoid resistance caused by reduced expression of the glucocorticoid receptor in cells from human vascular lesions.

Mechanisms that control the balance between cell proliferation and death are important in the development of vascular lesions. Rat primary smooth muscle cells were 80% inhibited by low microgram doses of hydrocortisone (HC) and 50% inhibited by nanogram concentrations of transforming growth factor-beta1 (TGF-beta1), although some lines acquired resistance in late passage. However, comparable doses of HC, or TGF-beta1, failed to inhibit most human lesion-derived cell (LDC) lines. In sensitive LDC, HC (10 microg/mL) inhibited proliferation by up to 50%, with obvious apoptosis in some lines, and TGF-beta1 inhibited proliferation by more than 90%. Collagen production, as measured by [3H]proline incorporation or RIA for type III pro-collagen, was either unaffected or increased in the LDCs by HC. These divergent responses between LDC lines were partially explained by the absence of the glucocorticoid receptor (GR) and heat shock protein 90 mRNA in 10 of 12 LDC lines, but the presence of the mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II. Western blot analysis confirmed the absence of the GR protein in cells lacking GR mRNA. Immunohistochemistry of human carotid lesions showed high levels of GR in the tunica media, but large areas lacking GR in the fibrous lesion. Considering the absence of the GR in most lines, the effects of HC may be elicited through the mineralocorticoid receptor. Functional resistance to the antiproliferative and antifibrotic effects of HC may contribute to excessive wound repair in atherosclerosis and restenosis.

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-beta1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-beta1 (TbetaR-II), causing acquired resistance to TGF-beta1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A10 microsatellite within TbetaR-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in TbetaR-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-beta1. We propose that microsatellite instability in TbetaR-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions.

Vascular smooth muscle cell proliferation in SHR and WKY rats: evidence for specific differences in growth inhibitory regulatory mechanisms.

1. This study examined and compared the actions of transforming growth factor-beta 1 (TGF-beta 1), heparin, dexamethasone and interferon-gamma on platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferation of vascular smooth muscle cells (VSMC) from normotensive, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Heparin, dexamethasone and interferon-gamma all inhibited VSMC proliferation stimulated by PDGF-BB in both SHR and WKY rats. There was no difference (P > 0.05) in their inhibitory effects, which varied between 40 and 85% for the different agents. 3. Similarly, TGF-beta 1 inhibited PDGF-BB-stimulated VSMC proliferation in WKY rats by approximately 50%. In contrast, TGF-beta 1 potentiated growth factor action on cell proliferation in the SHR by approximately 40%. 4. Specific TGF-beta 1-stimulated regulatory mechanisms involved in the inhibition of proliferation are absent in SHR and this defect may contribute to the vascular hypertrophy which is apparent in genetic hypertension.

Quadrupole parameters of 11B in crystalline CaO.B2O3.

The quadrupole coupling constant (Qcc) and asymmetry parameter (eta) of 11B in crystalline CaO.B2O3 have been measured employing three different NQR and NMR methods: (1) 11B and 10B NQR; (2) 11B NQR and NMR; and (3) the 11B Zeeman NQR powder pattern. It is found that Qcc = 2594.3 +/- 0.5 kHz and eta = 0.515 +/- 0.001 at 77 K, and Qcc = 2573.5 +/- 0.5 kHz and eta = 0.511 +/- 0.002 at 300 K. These values are in agreement with, but far more accurate than, values obtained from a fourth procedure: measurement of the second-order quadrupolar effects evident in the m = + 1/2<-->m = - 1/2 transition of the 11B NMR spectrum.

A bi-symmetric square wave Zeeman modulator for nuclear quadrupole resonance.

A simple circuit has been designed to generate a bi-symmetric square wave Zeeman modulation for the detection of nuclear quadrupole resonance. The square waveform not only provides an optimum result among bi-symmetric modulation waveforms, but also allows the observation of the Zeeman perturbed NQR powder pattern without the need for an extra external magnetic field.

Correlation of carbonic anhydrase inhibitory activities of benzenesulfonamides with the data obtained by use of nitrogen-14 nuclear quadrupole resonance.

Nitrogen-14 nuclear quadrupole resonance (NQR) spectra of several benzenesulfonamides in their solid state are reported and analyzed in the framework of the Townes and Dailey theory. Satisfactory correlations between the (sigma NH--sigma NS) electron densities at the sulfamyl nitrogen and the in vitro carbonic anhydrase inhibitory activities of the sulfonamides have been found. The correlations are in accord with the results of other studies that show the carbonic anhydrase inhibitory activities to be largely influenced by the electronic property of the sulfamyl group.

Defibrination of normal human blood in vitro: a method giving a high recovery of untraumatized cells.

A new automatic apparatus is described for the defibrination of blood in vitro at laboratory temperature which results in only small (less than 10%) losses of white cells. Freshly-drawn blood is mixed smoothly at high speed (greater than 1200 rpm) and fibrin is removed rapidly as formed. The apparatus is designed to produce minimum mechanical trauma to the blood. Subsequent in vitro incubation of red cells, granulocytes and lymphocytes demonostrated their viability to be comparable with cells obtained by other methods of defibrination.

Metabolism of biliverdin. Biliary excretion of bile pigments after intravenous injection of biliverdin isomers.

14C-labelled biliverdins IX alpha, beta, gamma and delta have been prepared in vitro from haemoglobin obtained from duck erythrocytes incubated with 5-amino[4-14C]-laevulinic acid. When injected intravenously into rats with biliary fistulae, about 60% of the label was recovered in the bile in 24 h after the alpha isomer was given, while approximately 10% was recovered with injection of the beta isomer. The gamma and delta isomers gave intermediate values. In each experiment, most of the recovered isotope was found in association with conjugated bile pigment. Thus, the metabolic pathway for bile pigment excretion in the rat handles the IX alpha isomer preferentially but is not specific for it.