Comparison of bare metal stents versus drug-eluting stents on clinical decision making in patients with previous percutaneous coronary intervention admitted for suspected acute coronary syndrome

To determine whether the decreased rate of restenosis observed with drug-eluting stents (DES) has changed the treatment of patients with recurrent symptoms after stent placement, we compared patients hospitalized with presumed cardiac symptoms within 1 year after placement of either a DES or a bare metal stent (BMS). In this retrospective, single-center study, cases were identified from consecutive patients who received a DES from March 2003 to July 2004 or a BMS from August 2001 to June 2002. No differences were noted in the rate of hospitalization, hospitalization for presumed cardiac symptoms, use of coronary angiography in patients hospitalized for presumed cardiac symptoms, or average interval to hospitalization. In contrast, restenosis and the need for additional revascularization procedures were higher in the BMS group. The primary indication for additional revascularization was restenosis in the BMS group and progression of coronary artery disease in the DES group. In the DES group, the need for revascularization was significantly higher in patients with multi- versus single-vessel coronary artery disease (26% vs 7%, p < 0.05). In conclusion, the rate of hospitalization and use of coronary angiography in patients with recurrent symptoms were similar in patients who received a BMS or DES, despite the decreased rates of restenosis and additional revascularization procedures observed with DESs.     

Role of nuclear Ca2+/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival

In response to biological and mechanical injury, or in vitro culturing, vascular smooth muscle cells (VSMCs) undergo phenotypic modulation from a differentiated "contractile" phenotype to a dedifferentiated "synthetic" one. This results in the capacity to proliferate, migrate, and produce extracellular matrix proteins, thus contributing to neointimal formation. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing cAMP or cGMP, are critical in the homeostasis of cyclic nucleotides that regulate VSMC growth. Here, we demonstrate that PDE1A, a Ca2+-calmodulin-stimulated PDE preferentially hydrolyzing cGMP, is predominantly cytoplasmic in medial "contractile" VSMCs but is nuclear in neointimal "synthetic" VSMCs. Using primary VSMCs, we show that cytoplasmic and nuclear PDE1A were associated with a contractile marker (SM-calponin) and a growth marker (Ki-67), respectively. This suggests that cytoplasmic PDE1A is associated with the "contractile" phenotype, whereas nuclear PDE1A is with the "synthetic" phenotype. To determine the role of nuclear PDE1A, we examined the effects loss-of-PDE1A function on subcultured VSMC growth and survival using PDE1A RNA interference and pharmacological inhibition. Reducing PDE1A function significantly attenuated VSMC growth by decreasing proliferation via G1 arrest and inducing apoptosis. Inhibiting PDE1A also led to intracellular cGMP elevation, p27Kip1 upregulation, cyclin D1 downregulation, and p53 activation. We further demonstrated that in subcultured VSMCs redifferentiated by growth on collagen gels, cytoplasmic PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas inhibiting nuclear PDE1A has the opposite effects. These suggest that nuclear PDE1A is important in VSMC growth and survival and may contribute to the neointima formation in atherosclerosis and restenosis.     

Human monoclonal IgG anticardiolipin antibodies induce nitric oxide synthase expression

OBJECTIVE: Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function. METHODS: Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels. RESULTS: Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS. CONCLUSION: Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.     

Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES)

The aim of this cross-sectional study was to assess the association of insulin resistance (IR) with inflammatory molecules C-reactive protein (CRP), interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic protein 1 (MCP-1) in urban South Indian subjects. The following groups were selected from the population-based Chennai Urban Rural Epidemiology Study: group 1 composed of 50 healthy subjects with normal glucose tolerance without IR; group 2 consisted of 50 normal glucose-tolerant subjects with IR as defined by homeostasis model assessment of IR (HOMA-IR); group 3 consisted of 50 subjects with impaired glucose tolerance (IGT); and groups 4 and 5 each comprised 50 newly diagnosed and known type 2 diabetic subjects, respectively. The inclusion criteria included nonsmokers; normal resting 12-lead electrocardiogram; and absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases, and not on statins or aspirin. Normal glucose tolerance without IR had the lowest values of CRP, IL-6, and VCAM-1 (CRP, 1.32 mg/L; IL-6, 12.56 pg/mL; VCAM-1, 277 pg/mL) followed by normal glucose tolerance with IR (CRP, 2.25 mg/L; IL-6, 20.97 pg/mL; VCAM-1, 289 pg/mL), impaired glucose tolerance (CRP, 2.37 mg/L; IL-6, 22.11 pg/mL; VCAM-1, 335 pg/mL), newly diagnosed diabetic subjects (CRP, 3.24 mg/L; IL-6, 23.21 pg/mL; VCAM-1, 568 pg/mL), and the highest levels were in the known diabetic subjects (CRP, 4.08 mg/L; IL-6, 29.44 pg/mL; VCAM-1, 577 pg/mL). This trend was statistically significant (P < .001). However, monocyte chemotactic protein 1 did not show such a trend and did not differ significantly between groups. In nondiabetic subjects, Pearson correlation analysis revealed that CRP (r = 0.299; P < .001) and IL-6 (r = 0.180, P = .025) had a significant correlation with HOMA-IR. Monocyte chemotactic protein 1 did not show any correlation with HOMA-IR. Multiple linear regression analysis revealed CRP to be significantly associated with HOMA-IR (beta = .229; P < .001) and this was unaltered by the addition of waist and IL-6 into the model (beta = .158; P = .028). In conclusion, this study shows that in Asian Indians, inflammatory markers (CRP, IL-6, and VCAM-1) increase with increasing degrees of glucose intolerance.     

Coronary heart disease in Asian Indians: perspectives of family members

Despite the high prevalence rate and significant mortality and morbidity from coronary heart disease in Asian Indians (irrespective of their religious background), very few studies have reported on family members' experiences of caring for a person with coronary heart disease. This paper reports on family members' experiences of coronary heart disease in Asian Indians residing in Australia, and is part of a larger study that explored the experiences and/or understanding of coronary heart disease in Asian Indians from the perspective of patients, family members and 'healthy' participants. Using a constructivist approach semi-structured in-depth interviews were conducted with five family members. Findings are represented under the following main categories: 1. A period of complexity for family members; 2. Indian Culture: Its influence on health/health behaviour & illness experience; 3. Impact of migration and societal discrimination; 4. Disappointment with health care services and the health system; and 5. Strategies to prevent cardiac illness and attain optimal health. Cultural factors had both positive and negative influences not only on the illness experience but also on health behaviour and attitude. The impact of Indian culture in relation to coronary heart disease needs to be understood not only at the cultural level by providing culturally sensitive health care, but also by educating Asian Indians to change their health attitude and behaviour and improve their lifestyle. Asian Indians need education and advice to become more resilient and adaptable to a Western society and also to become aware of the acculturative effects of a Western lifestyle.     

Monte Carlo study of photon fields from a flattening filter-free clinical accelerator

In conventional clinical linear accelerators, the flattening filter scatters and absorbs a large fraction of primary photons. Increasing the beam-on time, which also increases the out-of-field exposure to patients, compensates for the reduction in photon fluence. In recent years, intensity modulated radiation therapy has been introduced, yielding better dose distributions than conventional three-dimensional conformal therapy. The drawback of this method is the further increase in beam-on time. An accelerator with the flattening filter removed, which would increase photon fluence greatly, could deliver considerably higher dose rates. The objective of the present study is to investigate the dosimetric properties of 6 and 18 MV photon beams from an accelerator without a flattening filter. The dosimetric data were generated using the Monte Carlo programs BEAMnrc and DOSXYZnrc. The accelerator model was based on the Varian Clinac 2100 design. We compared depth doses, dose rates, lateral profiles, doses outside collimation, total and collimator scatter factors for an accelerator with and without a flatteneing filter. The study showed that removing the filter increased the dose rate on the central axis by a factor of 2.31 (6 MV) and 5.45 (18 MV) at a given target current. Because the flattening filter is a major source of head scatter photons, its removal from the beam line could reduce the out-of-field dose.     

Relation of external surface to internal tumor motion studied with cine CT

The accuracy of delivering gated-radiation therapy to lung tumors using an external respiratory surrogate relies on not only interfractional and intrafractional reproducibility, but also a strong correlation between external motion and internal tumor motion. The purpose of this work was to use the cine images acquired by four-dimensional computed tomography acquisition protocol to study the relation between external surface motion and internal tumor motion. The respiratory phase information of tumor motion and chest wall motion was measured on the cine images using a proposed region-of-interest (ROI) method and compared to measurement of an external respiratory monitoring device. On eight lung patient data sets, the phase shifts were measured between (1) the signal of a real-time positioning-management (RPM) respiratory monitoring device placed in the abdominal region and four surface locations on the chest wall, (2) the RPM signal in the abdominal region and tumor motions, and (3) chest wall surface motions and tumor motions. Respiratory waveforms measured at different surface locations during the same respiratory cycle often varied and had significant phase shifts. Seven of the 8 patients showed the abdominal motion leading chest wall motion. The best correlation (smallest phase shift) was found between the abdominal motion and the superior-inferior (S-I) tumor motion. A wide range of phase shifts was observed between external surface motion and tumor anterior-posterior (A-P)/lateral motion. The result supported the placement of the RPM block in the abdominal region and suggested that during a gated therapy utilizing the RPM system, it is necessary to place the RPM block at the same location as it is during treatment simulation in order to reduce potential errors introduced by the position of the RPM block. Correlations between external motions and lateral/A-P tumor motions were inconclusive due to a combination of patient selection and the limitation of the ROI method.