Lampros K. Michalis

Hydrodynamics of magnetic drug targeting

Among the proposed techniques for delivering drugs to specific locations within the human body, magnetic drug targeting surpasses due to its non-invasive character and its high targeting efficiency. Although the method has been proposed almost 30 years ago, the technical problems obstruct possible applications. It is the aim of the present work to classify the emerging problems and propose satisfactory answers. A general phenomenological theory is developed and a model case is studied, which incorporates all the physical parameters of the problem.

Automated Diagnosis of Coronary Artery Disease Based on Data Mining and Fuzzy Modeling

A fuzzy rule-based decision support system (DSS) is presented for the diagnosis of coronary artery disease (CAD). The system is automatically generated from an initial annotated dataset, using a four stage methodology: 1) induction of a decision tree from the data; 2) extraction of a set of rules from the decision tree, in disjunctive normal form and formulation of a crisp model; 3) transformation of the crisp set of rules into a fuzzy model; and 4) optimization of the parameters of the fuzzy model. The dataset used for the DSS generation and evaluation consists of 199 subjects, each one characterized by 19 features, including demographic and history data, as well as laboratory examinations. Tenfold cross validation is employed, and the average sensitivity and specificity obtained is 62% and 54%, respectively, using the set of rules extracted from the decision tree (first and second stages), while the average sensitivity and specificity increase to 80% and 65%, respectively, when the fuzzification and optimization stages are used. The system offers several advantages since it is automatically generated, it provides CAD diagnosis based on easily and noninvasively acquired features, and is able to provide interpretation for the decisions made.

Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes.

CONTEXT The effect of early menopause on indices of vascular function has been little studied. OBJECTIVE The objective of the study was to investigate the effect of early menopause on indices of subclinical atherosclerosis and identify predictors of those indices in early menopausal women. DESIGN, SETTING, AND PARTICIPANTS This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women. MAIN OUTCOME MEASURES Brachial artery flow-mediated dilation (FMD) and common carotid intima-media thickness (IMT) were studied. Estrogen receptor (ER)-alpha (rs2234693 T-->C and rs9340799 A-->G) and ERbeta (rs4986938 A-->G) polymorphisms were studied in menopausal women. RESULTS FMD was significantly lower in early menopausal women compared with controls (5.43 +/- 2.53 vs. 8.74 +/- 3.17%, P < 0.001), whereas IMT did not differ between groups (P > 0.8). Severity of hot flushes was the most important independent predictor for FMD (P < 0.001) in menopausal women. Women with moderate/severe/very severe hot flushes had impaired FMD in contrast to women with no/mild hot flushes or controls. Women with no/mild hot flushes did not differ compared with controls. Age and systolic blood pressure were the main determinants of IMT (both P = 0.004). ER polymorphisms were not associated with vascular parameters. CONCLUSIONS Impairment of endothelial function is present in the early menopausal years, whereas carotid IMT is not affected. Severity of hot flushes is the main determinant of endothelial dysfunction in early menopausal women. The studied ER polymorphisms do not offer important information on vascular health in early menopause.

An automated method for lumen and media-adventitia border detection in a sequence of IVUS frames

In this paper, we present a method for the automated detection of lumen and media-adventitia border in sequential intravascular ultrasound (IVUS) frames. The method is based on the use of deformable models. The energy function is appropriately modified and minimized using a Hopfield neural network. Proper modifications in the definition of the bias of the neurons have been introduced to incorporate image characteristics. A simulated annealing scheme is included to ensure convergence at a global minimum. The method overcomes distortions in the expected image pattern, due to the presence of calcium, employing a specialized structure of the neural network and boundary correction schemas which are based on a priori knowledge about the vessel geometry. The proposed method is evaluated using sequences of IVUS frames from 18 arterial segments, some of them indicating calcified regions. The obtained results demonstrate that our method is statistically accurate, reproducible, and capable to identify the regions of interest in sequences of IVUS frames.

Automated ischemic beat classification using genetic algorithms and multicriteria decision analysis

Cardiac beat classification is a key process in the detection of myocardial ischemic episodes in the electrocardiographic signal. In the present study, we propose a multicriteria sorting method for classifying the cardiac beats as ischemic or not. Through a supervised learning procedure, each beat is compared to preclassified category prototypes under five criteria. These criteria refer to ST segment changes, T wave alterations, and the patients age. The difficulty in applying the above criteria is the determination of the required method parameters, namely the thresholds and weight values. To overcome this problem, we employed a genetic algorithm, which, after proper training, automatically calculates the optimum values for the above parameters. A task-specific cardiac beat database was developed for training and testing the proposed method using data from the European Society of Cardiology ST-T database. Various experimental tests were carried out in order to adjust each module of the classification system. The obtained performance was 91% in terms of both sensitivity and specificity and compares favorably to other beat classification approaches proposed in the literature.

An ischemia detection method based on artificial neural networks

An automated technique was developed for the detection of ischemic episodes in long duration electrocardiographic (ECG) recordings that employs an artificial neural network. In order to train the network for beat classification, a cardiac beat dataset was constructed based on recordings from the European Society of Cardiology (ESC) ST-T database. The network was trained using a Bayesian regularisation method. The raw ECG signal containing the ST segment and the T wave of each beat were the inputs to the beat classification system and the output was the classification of the beat. The input to the network was produced through a principal component analysis (PCA) to achieve dimensionality reduction. The network performance in beat classification was tested on the cardiac beat database providing 90% sensitivity (Se) and 90% specificity (Sp). The neural beat classifier is integrated in a four-stage procedure for ischemic episode detection. The whole system was evaluated on the ESC ST-T database. When aggregate gross statistics was used the Se was 90% and the positive predictive accuracy (PPA) 89%. When aggregate average statistics was used the Se became 86% and the PPA 87%. These results are better than other reported.

A knowledge-based technique for automated detection of ischaemic episodes in long duration electrocardiograms

A novel method for the detection of ischaemic episodes in long duration ECGs is proposed. It includes noise handling, feature extraction, rule-based beat classification, sliding window classification and ischaemic episode identification, all integrated in a four-stage procedure. It can be executed in real time and is able to provide explanations for the diagnostic decisions obtained. The method was tested on the ESC ST-T database and high scores were obtained for both sensitivity and positive predictive accuracy (93.8% and 78.5% respectively using aggregate gross statistics, and 90.7% and 80.7% using aggregate average statistics).

The Effect of Shear Stress on Neointimal Response Following Sirolimus- and Paclitaxel-Eluting Stent Implantation Compared With Bare-Metal Stents in Humans

OBJECTIVES We aimed to explore the relationship of neointimal thickness (NT) to shear stress (SS) after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS). We then tested the hypothesis that drug elution attenuates the SS effect. BACKGROUND Neointimal thickness after BMS implantation has been associated with SS; pertinent data for drug-eluting stents (DES) are limited. METHODS Three-dimensional coronary artery and stent reconstruction was performed in 30 patients at 6-month follow-up after SES (n = 10), PES (n = 10), or BMS (n = 10) implantation. Baseline SS at the stent surface was calculated using computational fluid dynamics and NT at follow-up was computed in 3-dimensional space. RESULTS Neointimal thickness was lower in DES versus BMS (0.03 ± 0.07 mm vs. 0.16 ± 0.08 mm, p < 0.001) and maximum NT was reduced in SES versus PES (0.33 ± 0.13 mm vs. 0.46 ± 0.13 mm, p = 0.025). In the total population, both SS (slope: -0.05 mm/Pa, p < 0.001) and DES (coefficient for DES vs. BMS: -0.17 mm, p = 0.003) were independent predictors of NT. Subgroup analysis demonstrated a significant negative relationship of NT to SS in PES (slope: -0.05 mm/Pa, p = 0.016) and BMS (slope: -0.05 mm/Pa, p = 0.001). Sirolimus elution significantly attenuated the effect of SS on NT (interaction coefficient for SES vs. BMS: 0.04 mm/Pa, p = 0.023), whereas the SS effect remained unchanged in PES (interaction coefficient for PES vs. BMS: 0.01 mm/Pa, p = 0.71). CONCLUSIONS Neointimal thickness is significantly correlated (inversely) to SS in PES as in BMS. Sirolimus elution abrogates the SS effect on the neointimal response following stent implantation, whereas the SS effect is unchanged in PES.

A Prospective Randomized Trial Comparing the Safety and Efficacy of Three Commercially Available Closure Devices (Angioseal, Vasoseal and Duett)

Purpose: We compared the safety and efficacy of three closure devices (Angioseal, Vasoseal and Duett) used to close arterial puncture sites in patients who underwent coronary percutaneous procedures. Methods: A prospective randomized, single-center trial was carried out of consecutive patients who underwent coronary angiography [705 patients: Angioseal (243),Vasoseal (228) and Duett (234)] or angioplasty [146 patients:Angioseal (47), Vasoseal (52) and Duett (47)]. Results: In the angiography patients the device deployment rates were similar, with the Angioseal been significantly slower in achieving hemostasis (p = 0.0001) but resulting in earlier ambulation (p = 0.0001). In the coronary angioplasty patients the deployment rates were similar to those for angiography: time to hemostasis was longer for the Angioseal (p = 0.003), while ambulation times were not different, although prolonged compared with angiography (p = 0.0001). The three devices had similar major complication rates. The Vasoseal had a higher major complication rate after angioplasty than after angiography (p = 0.004). The incidence rate of peripheral embolization was lower when the Angioseal was utilized. Severe complications were mainly seen in patients who received abciximab. Conclusions: The three closure devices had high rates of successful deployment and were relatively safe. The Angioseal resulted in earlier ambulation after angiography. Utilization of closure devices after abciximab administration possibly increased the complications.

Hsp70 translocates to the nuclei and nucleoli, binds to XRCC1 and PARP-1, and protects HeLa cells from single-strand DNA breaks

For many years, there has been uncertainty concerning the reason for Hsp70 translocation to the nucleus and nucleolus. Herein, we propose that Hsp70 translocates to the nucleus and nucleoli in order to participate in pathways related to the protection of the nucleoplasmic DNA or ribosomal DNA from single-strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing (knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore, HeLa Hsp70 depleted cells were very sensitive in heat treatment and their DNA breaks were multiple compared to that of control HeLa cells. The molecular mechanism with which Hsp70 performs its role at the level of nucleus and nucleolus during stress was examined. Hsp70 co-localizes with PARP1 in the nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain of PARP1 as was revealed with protein–protein interaction assays. It was also found that Hsp70 binds simultaneously to XRCC1 and PARP-1, indicating that Hsp70 function takes place at the level of DNA repair and possibly at the base excision repair system. Making a hypothetical model, we have suggested that Hsp70 is the molecule that binds and interrelates with PARP1 creating the repair proteins simultaneously, such as XRCC1, at the single-strand DNA breaks. Our data partially clarify a previously unrecognized cellular response to heat stress. Finally, we can speculate that Hsp70 plays a role in the quality and integrity of DNA.