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Biomedical subjects

Ariel Roguin

Publications and source records attributed to Ariel Roguin.

At least 55 records · Page 3Linked to original sources

Nikola Tesla: the man behind the magnetic field unit.

The magnetic field strength of both the magnet and gradient coils used in MR imaging equipment is measured in Tesla units, which are named for Nikola Tesla. This article presents the life and achievements of this Serbian-American inventor and researcher who discovered the rotating magnetic field, the basis of most alternating-current machinery. Nikola Tesla had 700 patents in the United States and Europe that covered every aspect of science and technology. Tesla's discoveries include the Tesla coil, AC electrical conduction, improved lighting, newer forms of turbine engines, robotics, fluorescent light, wireless transmission of electrical energy, radio, remote control, discovery of cosmic radio waves, and the use of the ionosphere for scientific purposes. He was a genius whose discoveries had a pivotal role in advancing us into the modern era.

Electricity↗

Stereotactic magnetic resonance guidance for anatomically targeted ablations of the fossa ovalis and the left atrium.

INTRODUCTION: Targets for radiofrequency ablation (RFA) of atrial fibrillation are increasingly being selected based on anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures, we evaluated whether stereotactic catheter guidance might facilitate anatomical catheter navigation and RFA to the great vessels, the fossa ovalis and the left atrium (LA). METHODS AND RESULTS: An electromagnetic catheter's position system was superimposed on three-dimensional (3D) MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MRI in real-time. To assess the reproducibility of RFA, repeat ablations were created at the identical anatomic site in the inferior vena cava (IVC) in 5 swine. Average distance of the repeated ablations was 4.4 +/- 2.4 mm.In five swine the catheter was anatomically guided with the MRI to the fossa ovalis and a single RFA was performed. On the pathological specimen all ablation sites were located within the fossa ovalis with an average distance of 3.9 +/- 2.1 mm from its center. In two of the experiments the ablation catheter was passed into the left atrium and anatomically targeted ablation performed in the lateral wall of the left atrial appendage. Catheter location and ablation site were confirmed by autopsy and histology. CONCLUSION: Real-time display of the catheter position on 3D-MRI allows anatomically targeted catheter navigation and RFA in the IVC, the fossa ovalis, and the left atrium. This may facilitate anatomically based interventions like septal puncture or pulmonary vein ablation and decrease fluoroscopy times.

Animals↗

Misdiagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

INTRODUCTION: Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has major implications for the management of patients and their first-degree relatives. Diagnosis is based on a set of criteria proposed by the International Task Force for Cardiomyopathies. We report our experience in providing a re-evaluation for patients who previously have been diagnosed with ARVD/C. METHODS AND RESULTS: We studied 89 patients who requested a re-evaluation for diagnosis of ARVD/C at our center. Each of these patients had been diagnosed with ARVD/C at their initial evaluation. Each patient was re-evaluated with clinical history, physical examination, and noninvasive testing at our center. Invasive testing, which included electrophysiologic testing, right ventricular angiography, and endomyocardial biopsy, was performed when clinically indicated. Sixty (92%) of the 65 patients who had undergone magnetic resonance imaging (MRI) at an outside institution were reported to have an abnormal MRI consistent with ARVD/C. Among these patients, the only abnormality identified was the qualitative finding of intramyocardial fat/wall thinning in 46 patients. On re-evaluation, these qualitative findings were not confirmed. None of these 46 patients ultimately were diagnosed with ARVD/C. Among the entire patient group, only 24 (27%) of the 89 patients met the Task Force criteria for ARVD/C. CONCLUSION: This study demonstrates that the high frequency of "misdiagnosis" of ARVD/C is due to over-reliance on the presence of intramyocardial fat/wall thinning on MRI, incomplete diagnostic testing, and lack of awareness of the Task Force criteria. Diagnosis of ARVD/C cannot rely solely upon qualitative features on MRI.

Adolescent↗

A new method for inducing hypothermia during cardiac arrest.

OBJECTIVE: It has been shown that hypothermia induced after successful resuscitation of comatose survivors of ventricular fibrillation cardiac arrest improves survival and neurologic function. Recent studies also suggest that earlier induction of hypothermia may yield even more improvement. We sought to determine if a new pump system, in addition to vigorous external chest compression, could rapidly induce hypothermia during cardiopulmonary resuscitation in a porcine model of cardiac arrest. METHODS: Nine pigs (25-37 kg) were instrumented with micromanometers and thermocouple probes. Two 8-Fr catheters were placed into the femoral veins. Cardiac arrest was induced with 60-Hz current. After 5 mins of no support, chest compression was performed by a circumferential pneumatic bladder (vest-cardiopulmonary resuscitation). Blood was withdrawn from one catheter by a pump system that maximized flow by servo-control of inlet pressure, was cooled, and was returned through the other catheter. Four dogs were instrumented similarly, and cooling was performed during normal circulation. RESULTS: In the pigs, baseline temperatures were (mean +/- SEM) 37 +/- 1 degree C. With blood cooling in the external chiller to 10 degrees C, cerebral and right atrial temperatures were reduced by 0.49 +/- 0.09 and 0.67 +/- 0.21 degrees C/min, respectively, for 10 mins. With blood cooling in the external chiller to 4 degrees C, cerebral and right atrial temperatures were reduced by 0.61 +/- 0.18 and 1.56 +/- 0.33 degrees C/min, respectively. Cerebral cooling lagged behind right atrial cooling. There was a strong correlation between coronary perfusion pressure (aortic to right atrial mean decompression-phase pressure) and cerebral cooling rate (r = .79; p < .022). Rates of cooling during normal circulation in dogs were similar. CONCLUSIONS: Rapid induction of mild hypothermia is feasible with a system that uses venous access, standard access techniques, and external chest compression. Induction of mild hypothermia during cardiac arrest in the field appears feasible and may allow the benefit of very early induction of hypothermia to be determined in patients.

Animals↗

Percutaneous coronary interventions in diabetic patients: is complete revascularization important?

BACKGROUND: The long-term prognosis of diabetic patients with multivessel coronary artery disease (CAD) treated by surgical or percutaneous coronary revascularization is significantly worse as compared to non-diabetics. Lower rates of complete revascularization may be one factor that influences the poor long-term outcome in the diabetic population. Our study assessed the impact of complete revascularization on the long-term prognosis in diabetic patients with CAD treated by percutaneous coronary intervention (PCI). The study included 658 consecutive diabetic patients (mean age, 60.9+/-10.1 years) who underwent PCI. Multivessel disease was present in 352 patients (53.5%). Revascularization was complete in 94 (26.7%) and incomplete in 258 (73.3%) patients with multivessel disease. Reasons for incomplete revascularization included angioplasty of only the culprit lesion (43.4%); small vessel size (22.8%); moderate lesion, defined as diameter stenosis 50-69% (18.6%); chronic total occlusion of the non-intervened vessel (6.6%); and others (8.5%). Overall survival rate at 5 years was 87.4%. Patients who underwent complete revascularization had a 94.5% survival rate, compared to 83.0% for those with incomplete revascularization (p<0.001). Similarly, the rates of myocardial infarction-free survival were significantly higher in patients with complete versus incomplete revascularization (92.9% versus 79.9%, respectively). Incomplete revascularization was the most powerful independent predictor of mortality at follow-up (relative risk 95% confidence interval, 1.54-7.69; p=0.003). Our data suggest that complete myocardial revascularization may improve the long-term prognosis after PCI of diabetic patients with multivessel CAD.

Adult↗

Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model.

BACKGROUND: Angiogenic therapy with vascular endothelial growth factor (VEGF) has been proposed as a treatment paradigm for patients suffering from an insufficiency of collateral vessels. Diabetes is associated with increase in the production of VEGF and therefore additional VEGF may not be beneficial. Accordingly, we sought to determine the efficacy of VEGF therapy to augment collateral formation and tissue perfusion in a diabetic mouse ischemic hindlimb model. METHODS: Diabetic and non-diabetic mice were studied in parallel for the efficacy of VEGF administration. Diabetes was induced with streptozotocin. Hindlimb ischemia was produced by severing the left iliac artery. An outlet tube from an osmotic infusion pump with placebo/500 micrograms of plasmid-DNA encoding VEGF was fenestrated and tunneled into the left quadriceps muscle. RESULTS: VEGF induced more rapid and complete restoration of blood flow in normal mice. However, in the setting of diabetes there was no difference between VEGF vs. placebo in the rate or adequacy of flow restoration. There was a significant increase in smooth muscle actin and Factor-VIII antigen densities in diabetic animals and in animals which received VEGF. CONCLUSIONS: Angiogenic therapy with VEGF in the setting of diabetes does not appear to have the beneficial effects seen in the absence of diabetes.

Journal Article↗

Restoration of blood flow by using continuous perimuscular infiltration of plasmid DNA encoding subterranean mole rat Spalax ehrenbergi VEGF.

The optimal vector, regulatory sequences, and method of delivery of angiogenic gene therapy are of considerable interest. The Spalax ehrenbergi superspecies live in subterranean burrows at low oxygen tensions and its tissues are highly vascularized. We tested whether continuous perimuscular administration of Spalax vascular endothelial growth factor (VEGF) DNA could increase tissue perfusion in a murine hindlimb ischemia model. Placebo or VEGF +/- internal ribosome entry site (IRES) was continuously administrated perimuscularly in the ischemic zone by using an infusion pump. None of the mice in the VEGF-treated group (>50 microg) developed visible necrosis vs. 33% of the placebo group. Microscopic necrosis was observed only in the placebo group. Spalax VEGF muscular infiltration resulted in a faster and more complete restoration of blood flow. The restoration of blood flow by VEGF was dose-dependent and more robust and rapid when using the VEGF-IRES elements. The flow restoration using continuous perimuscular infiltration was faster than single i.m. injections. Vessel density was higher in the VEGF and VEGF-IRES (-) groups compared with the placebo. Continuous perimuscular administration of angiogenic gene therapy offers a new approach to restore blood flow to an ischemic limb. Incorporation of an IRES element may assist in the expression of transgenes delivered to ischemic tissues. Further studies are needed to determine whether VEGF from the subterranean mole rat Spalax VEGF is superior to VEGF from other species. If so, 40 million years of Spalax evolution underground, including adaptive hypoxia tolerance, may prove important to human angiogenic gene therapy.

Animals↗

Haptoglobin genotype is predictive of major adverse cardiac events in the 1-year period after percutaneous transluminal coronary angioplasty in individuals with diabetes.

OBJECTIVE: The goal of this study was to determine whether the haptoglobin (Hp) genotype was predictive of restenosis and major adverse cardiac events (MACEs) after percutaneous transluminal coronary angioplasty (PTCA) in individuals with diabetes. RESEARCH DESIGN AND METHODS: A consecutive series of 935 diabetic patients treated with oral agents and/or insulin were followed for 1 year after PTCA. The primary study end point was angiographic restenosis, MACEs and secondary study end points were defined as target vessel revascularization, myocardial infarction, and death. Two alleles exist at the Hp gene locus, denoted 1 and 2. The Hp genotype (Hp 1-1, Hp 2-1, or Hp 2-2) was determined by PCR. RESULTS: In multivariate analysis controlling for all known determinants of outcome after PTCA, we found that the Hp genotype was a highly significant independent predictor of MACEs in the 1-year period after PTCA in individuals with diabetes. This was predominantly due to differences in the risk of myocardial infarction during that period: Hp 1-1, 0 of 129 (0%); Hp 2-1, 20 of 424 (4.7%); and Hp 2-2, 32 of 382 (8.4%); P < 0.0001. CONCLUSIONS: The Hp genotype seems to be highly predictive of adverse cardiac events, particularly myocardial infarction, in the 1-year period after PTCA. Determination of the Hp genotype may be useful in the evaluation of new therapies to reduce cardiovascular risk after PTCA.

Aged↗

Haptoglobin phenotype and the risk of restenosis after coronary artery stent implantation.

We recently demonstrated that an allelic polymorphism in the haptoglobin gene is a major determinant of susceptibility to a number of vascular disorders. We set out to determine if haptoglobin phenotype was predictive of the development of restenosis in a consecutive series of patients, all of whom underwent stent implantation followed by repeat angiography with quantitative coronary angiography analysis 6 months later. This study included 214 consecutive patients undergoing stent implantation for de novo lesions between 1998 and 1999 in Aalst, Belgium. All underwent follow-up quantitative coronary angiography analysis 6 months after the procedure. The haptoglobin phenotype was determined by electrophoresis. No significant differences were found between patients segregated by phenotype with respect to clinical, procedural, and angiographic factors previously suggested to influence the development of restenosis. None of the diabetic patients homozygous for the haptoglobin 1 allele developed restenosis compared with a >50% restenosis rate for diabetic patients with at least 1 haptoglobin 2 allele (p <0.02). In all patients (diabetic and nondiabetic), we observed a trend toward a lower incidence of restenosis in patients homozygous for the 1 allele (21% vs 33%, p <0.09). Moreover, we found a graded risk relation to the number of haptoglobin 2 alleles. The risk of developing restenosis was greater in subjects with 2 haptoglobin 2 alleles (36%) than in those with 1 haptoglobin 2 allele (31%) or no haptoglobin 2 alleles (21%). Thus, knowledge of the haptoglobin phenotype may be useful in assessing and utilizing new therapies that attempt to reduce restenosis, and may have important implications for the risk stratification algorithm used in managing diabetic patients with coronary artery disease.

Aged↗

Stenting very small coronary narrowings (< 2 mm) using the biocompatible phosphorylcholine-coated coronary stent.

Published data regarding stenting very small arteries are still limited. The BiodivYsio stent is a new stent coated with phosphorylcholine, a biocompatible molecule designed to reduce the formation of thrombus and potentially the risk of restenosis. The feasibility, safety, and efficacy of implantation of the 2.0 mm coated coronary stent were prospectively studied. We studied 97 patients from three centers who underwent elective, urgent, or bailout implantation of 106 BiodivYsio mini-stents (2.0 mm) in 101 lesions. Forty percent of lesions had unfavorable characteristics (type B2 or C) and 16% had thrombus and/or chronic total occlusion. Successful stent deployment was achieved in 100/101 lesions (99%). MLD increased from 0.49 +/- 0.31 mm to 1.89 +/- 0.41 mm and diameter stenosis decreased from 89% +/- 7% to 5.6% +/- 6%. Small vessel stenting was the only procedure in 71% patients. There was one acute stent thrombosis case. During 6-month follow-up, none died, one had MI, and one was referred to CABG due to nontarget lesion progression. Angiographic restenosis that required target lesion revascularization was performed in 8/18 that had catheterization due to chest pain or significant ischemia. Most patients improved in their clinical symptoms. The rate of major adverse cardiac events was 4.1% at 30-day and 10.3% at 6-month follow-up. This initial clinical experience indicates that the implantation of 2.0 mm stents coated with phosphorylcholine appears to be safe and efficacious in the treatment of complex coronary lesions and is associated with low target vessel revascularization rate in spite of the very small vessel diameter.

Adult↗

A prospective single-center registry for the use of intracoronary gamma radiation in patients with diffuse in-stent restenosis.

Based on single-center prospective registry data, the study evaluates short- and long-term results of intracoronary gamma radiation in patients with diffuse in-stent restenosis in the reality of routine clinical practice. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 84 vessels (81 patients) with diffuse in-stent restenosis. Repeat coronary angiography was performed in 35 patients with clinical restenosis. With a mean follow-up of 12.0 +/- 0.5 months, major adverse cardiac events were observed in 29 (34.5%) patients, including 2 cases of cardiac death, 3 myocardial infarctions, 21 target lesion revascularizations, and 4 target vessel revascularizations. Five of six patients with total occlusion of the target vessel at baseline developed target lesion restenosis. Late total occlusion of the target vessel was observed in four patients. The 1-year event-free survival rate was 69.8%. Total occlusion of the target vessel at baseline was the single independent predictor of cardiac events at 1-year follow-up (P < 0.001). In patients with a target lesion in the left anterior descending artery, predictors of cardiac events also included female sex (P = 0.014), current smoking (P = 0.014), stenting during brachytherapy session (P = 0.02), and smaller reference vessel diameter at baseline (P = 0.01). The results of our registry are similar to those of randomized trials. As applied in routine clinical practice, intracoronary gamma radiation is a feasible, safe, and effective tool in the treatment of diffuse in-stent restenosis. Late events in the entire group were predicted by total occlusion at baseline.

Aged↗

Haptoglobin phenotype and coronary artery collaterals in diabetic patients.

Cross-cultural epidemiological studies of incident cardiovascular disease in the diabetic patient have demonstrated marked differences in susceptibility that may be due to a genetic factor. The coronary artery collateral circulation is the chief determinant of the size of a myocardial infarction and is highly variable between patients. We recently demonstrated that a functional allelic polymorphism in the haptoglobin gene is correlated with a number of diabetic vascular complications. We thus set out to test the hypothesis that haptoglobin phenotype is associated with collateral formation in the setting of diabetes. We correlated the Hp phenotype (1-1, 2-1 or 2-2) as determined by polyacrylamide electrophoresis with the presence or absence of coronary collaterals by angiography in 82 consecutive diabetic patients and 138 consecutive non-diabetic patients undergoing catheterization. We found that diabetic patients with the Hp phenotype 2-1 were more likely to have collaterals than diabetic patients with the Hp phenotype 2-2 (P=0.007). There was no correlation between Hp phenotypes and the presence of collaterals in non-diabetic patients. Hp phenotype thus appears to be associated with the development of the coronary collateral circulation in diabetic patients with coronary artery disease. Haptoglobin 2-2 may predispose to less compensation for coronary artery stenosis in diabetic patients, and thereby portend a worse prognosis.

Aged↗

Staged versus one-step approach for multivessel percutaneous coronary interventions.

BACKGROUND: Percutaneous coronary interventions (PCIs) in patients with multivessel coronary artery disease (CAD) may be staged or performed in a single session. No data exist about the relative safety and efficacy of these 2 strategies. Our aim was to compare short-term and long-term outcomes of patients with multivessel CAD who underwent PCI in 1 versus 2 sessions. METHODS AND RESULTS: The study included 264 consecutive patients who underwent treatment in our center during 1997 and 1998. PCI was conducted in a single session in 129 patients and was staged in 135 patients. The mean interval between the sessions in the staged group was 45.6 +/- 22.3 days. The rates of major adverse cardiac events (MACEs) during in-hospital stay did not differ significantly between the staged (combined for both stages) and nonstaged groups (2.2% vs 4.6%; P =.28). A trend for lower event rates at 30-day (2.9% vs 6.9%; P =.13) and 1-year follow-up (26.1 vs 35.9; P =.08) favored the staged arm. Diameter stenosis > or =50% was found in 17% of patients in the staged group in the second session and was successfully retreated in most of them. No MACE occurred between the sessions. Multivariate analysis identified staging of the procedure as a single independent predictor of MACE at 1-year follow-up (P =.05). CONCLUSION: Our results suggest that a practical staging strategy within 4 to 8 weeks is safe and allows for identification and treatment of potential excessive proliferative response in the previously intervened lesions during the second procedure.

Angina Pectoris↗

Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR.

BACKGROUND: A genetically defined molecular heterogeneity of haptoglobin, characterized by the major phenotypic forms Hp 1-1, Hp 2-1, and Hp 2-2, has been associated with distinct clinical manifestations. To enable the use of DNA samples for the study of this polymorphism, we established a haptoglobin genotyping method based on PCR. METHODS: Taking advantage of the selectivity of PCR, we amplified DNA segments specifically representing haptoglobin alleles Hp 1 and Hp 2 from genomic DNA. The products were analyzed by agarose gel electrophoresis. Haptoglobin phenotyping of plasma samples was performed by polyacrylamide gel electrophoresis and peroxidase staining. RESULTS: Exploiting the known size difference between Hp 1 and Hp 2, we amplified allele-specific DNA molecules with one pair of oligonucleotide primers. As an alternative, we used separate primer pairs to generate amplification products indicative of alleles Hp 1 and Hp 2. Because of the primer design, genotype determination was not compromised by sequence variations specifying haptoglobin allele subtypes S and F. For the same reason, the sequence similarity between the haptoglobin gene and the haptoglobin-related gene did not interfere with the accuracy of genotyping. Analysis with restriction enzymes demonstrated the authenticity of the allele-specific DNA products. Haptoglobin DNA genotyping and protein phenotyping, performed in parallel, yielded fully corresponding results. In a group of 249 individuals, the haptoglobin genotype distribution was as follows: 14.5% Hp 1-1, 48.2% Hp 2-1, and 37.3% Hp 2-2. CONCLUSION: The new method can be used for genotyping of a common haptoglobin polymorphism.

DNA↗