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Biophysics of radiofrequency ablation using an irrigated electrode.

BACKGROUND: Previous reports have proposed that prevention of electrode-endocardial interfacial boiling is the key mechanism by which radiofrequency application using an irrigated electrode yields a larger ablation lesion than a non-irrigated electrode. It has been suggested that maximal myocardial temperature is shifted deep into myocardium during irrigated ablation. PURPOSE: To examine the biophysics of irrigated ablation by correlating electrode and myocardial temperatures with ablation circuit impedance and lesion morphology, and to perform a comparison with non-irrigated ablation modes. To assess the influence of irrigant rate, composition, temperature and blood flow velocity. METHODS: I. Ablation with and without electrode irrigation was performed in vitro utilizing a whole blood-superfused system. Electrode, electrode-endocardial interface, and intramyocardial temperatures were assessed, as were ablation circuit impedance, total delivered energy, and lesion and electrode morphology. Irrigants assessed were room temperature normal saline, iced normal saline, and dextrose. Irrigant flow rates assessed were 20 and 100 cc/min. Blood flow velocities assessed were 0 and 0.26 m/s. II. Finite element simulations of myocardial temperature during irrigated ablation were performed to further elucidate irrigation biophysics and provide a more detailed myocardial temperature profile. Two models were constructed, each utilizing a different core assumption regarding the electrode-tissue boundary: 1. electrode temperature measured in vitro; 2. interfacial temperature measured in vitro. Intramyocardial temperatures predicted by each model were correlated with corresponding temperatures measured in vitro. RESULTS: I. Ablation during electrode irrigation with normal saline was associated with greater ablation energy deposition and larger lesion dimensions than non-irrigated ablation. The mechanism underlying the larger lesion was delay or inhibition of impedance rise; this was associated with attenuation or prevention of electrode coagulum. Irrigation did not prevent interfacial boiling, which occurred during uninterrupted radiofrequency energy deposition and lesion growth. Irrigation using saline at 100 cc/min was associated with no impedance rise regardless of blood flow velocity, whereas during irrigation at 20 cc/min impedance rise was blood flow rate-dependent. Iced saline produced results equivalent to room temperature saline. Irrigation with dextrose was associated with curtailed energy application and relatively small lesions. II. The finite element simulation that used electrode-endocardial interfacial temperature as the core assumption predicted a myocardial temperature profile which correlated significantly better with in vitro than did the simulation which used electrode temperature as the core assumption. Regardless of irrigant and blood flow rates, maximal myocardial temperature was always within 1 mm of the endocardial surface. CONCLUSIONS: Radiofrequency energy application via a saline irrigated electrode resulted in a larger lesion due to attenuation or eradication of electrode coagulum, thus preventing an impedance rise. Irrigation did not prevent interfacial boiling, but boiling did not prevent lesion growth. The site of maximal myocardial temperature during irrigated ablation was relatively superficial, always within 1 mm of the endocardial surface. Irrigation with iced saline was no more effective than with room temperature saline; both were far more effective than dextrose. Higher irrigation rates immunized the electrode from the influence of blood flow. The biophysical effects of blood flow and irrigation were similar.

Animals↗

Biophysical vision model and learning paradigms about vision: review.

A learning paradigm of a new biophysical vision model (BVM) is presented. It incorporates anatomical and physiological evidence from micro- and macroscopic research on vision as reported in the literature during the past five years. Anatomical and physiological vision research tends to drift away from the technological foundations of encoding and reproducing size-defined images of real ongoing life scenarios. White and color light waves reflecting life scenarios are converted by the retina to encoded electrical train pulses with attached real information to be decoded by cortical vision neurons. The BVM paradigm is based on the ideas that: (1) cinema technology reproduces real-life scenes just as the human eye sees them; (2) virtual reality and robotics are computerized replications of categorized human vision faculties in operation. We believe that vision-related technology may extend our knowledge about vision and direct vision research into new horizons. The biophysical vision model has three prerequisites: (1) The faculties of human vision must be categorized. (2) Logic circuits of the 'hardware' of neuronal vision must be present. (3) Vision faculties are operated by self-induced 'software'. Vision research may be enhanced with devices constructed according to BVM that would enable biophysical vision experiments in both humans and animals.

Animals↗

Biophysical characterization of proteins in the post-genomic era of proteomics.

Proteomics focuses on the high throughput study of the expression, structure, interactions, and, to some extent, function of large numbers of proteins. A true understanding of the functioning of a living cell also requires a quantitative description of the stoichiometry, kinetics, and energetics of each protein complex in a cellular pathway. Classical molecular biophysical studies contribute to understanding of these detailed properties of proteins on a smaller scale than does proteomics in that individual proteins are usually studied. This perspective article deals with the role of biophysical methods in the study of proteins in the proteomic era. Several important physical biochemical methods are discussed briefly and critiqued from the standpoint of information content and data acquisition. The focus is on conformational changes and macromolecular assembly, the utility of dynamic and static structural data, and the necessity to combine experimental approaches to obtain a full functional description. The conclusions are that biophysical information on proteins is a useful adjunct to "standard" proteomic methods, that data can be obtained by high throughput technology in some instances, but that hypothesis-driven experimentation may frequently be required.

Biophysical Phenomena↗

The biophysical profile: antepartal assessment of fetal well-being.

The assessment of fetal well-being is a primary consideration for perinatal nurses. The biophysical profile is a clinical evaluation of the status of the fetus based on assessment of multiple discrete variables. This article describes current biophysical profile scoring systems, the physiologic basis of the fetal variables, and factors that may affect the variables. It also discusses issues related to future applications and refinement of the biophysical profile, as well as nursing implications of the technology.

Amniotic Fluid↗

Functional, biophysical, and structural bases for antibacterial activity of tigecycline.

Tigecycline is a novel glycylcycline antibiotic that possesses broad-spectrum activity against many clinically relevant species of bacterial pathogens. The mechanism of action of tigecycline was delineated using functional, biophysical, and molecular modeling experiments in this study. Functional assays showed that tigecycline specifically inhibits bacterial protein synthesis with potency 3- and 20-fold greater than that of minocycline and tetracycline, respectively. Biophysical analyses demonstrated that isolated ribosomes bind tigecycline, minocycline, and tetracycline with dissociation constant values of 10(-8), 10(-7), and >10(-6) M, respectively. A molecular model of tigecycline bound to the ribosome was generated with the aid of a 3.40-angstrom resolution X-ray diffraction structure of the 30S ribosomal subunit from Thermus thermophilus. This model places tigecycline in the A site of the 30S subunit and involves substantial interactions with residues of H34 of the ribosomal subunit. These interactions were not observed in a model of tetracycline binding. Modeling data were consistent with the biochemical and biophysical data generated in this and other recent studies and suggested that tigecycline binds to bacterial ribosomes in a novel way that allows it to overcome tetracycline resistance due to ribosomal protection.

Anti-Bacterial Agents↗

Quantitative measurement and prediction of biophysical response during freezing in tissues.

Cryopreservation and cryosurgery are important biomedical applications used to selectively preserve or destroy cellular systems through freezing. Studies using cryomicroscopy techniques, which allow the visualization of the freezing process in single cells, have shown that a drop in viability correlates with the extent of two biophysical events during the freezing process: (a) intracellular ice formation and (b) cellular dehydration. These same biophysical events operate in tissue systems; however, the inability to visualize and quantify the dynamics of the freezing process in tissues has hampered direct correlation of these events with freezing-induced changes in viability. This review highlights two new techniques that use freeze substitution and differential scanning calorimetry to provide dynamic freezing data in tissue. Characteristic dimensions and parameters extracted from these new data are then used in a predictive model of biophysical freezing response in several tissues, including liver and tumor. This approach promises to help guide improved design of both cryopreservation and cryosurgical applications of tissue freezing.

Animals↗

Invited review: biophysical properties and clinical applications of magnetic resonance imaging contrast agents.

Contrast enhanced magnetic resonance imaging (MRI) is a very versatile and effective technique for detecting and characterizing lesions, for identifying a variety of patho-physiological abnormalities, and for providing perfusion and functional information. The application of contrast enhanced MRI to many clinical and research indications has emerged because of the rapid evolution in imaging techniques, improved methodology, and the development of efficient and specific contrast agents. Problems related to optimizing parameters and dosage have been due to complex interplay of relaxation times, biophysical mechanisms and acquisition parameters. A knowledge of basic biophysical aspects is therefore essential for a full understanding of the results obtained for different organs under different conditions, and for optimizing the image parameters and dosage of contrast agents. This article underlines the biophysical basis of the effects of contrast agents in MRI, identifies the problems involved in optimizing the parameters for maximum efficiency, and presents a general overview of the clinical studies and research applications in the central nervous system, perfusion abnormalities, hepatobiliary system, musculoskeletal system and the gastrointestinal tract. The section on perfusion studies includes a discussion of quantitative analysis and kinetic models describing the effects of contrast agents. Finally, a critical evaluation of the scope and limitations of contrast enhanced MRI is presented.

Biophysical Phenomena↗

Use of dose-volume histograms and biophysical models to compare 2D and 3D irradiation techniques for non-small cell lung cancer.

For non-small cell lung cancer (NSCLC), unsatisfactory local control (LC) still remains an important cause of failure. It has been suggested that improved LC can be achieved with both higher radiation dosage and adequate target coverage. Modern three-dimensional treatment planning systems (3D-TPSs) offer many tools for planning optimization. Biophysical models, which estimate the normal tissue complication probability (NTCP), are gaining in importance in comparing plans. This study compares conventional two-dimensional (2D) with 3D irradiation techniques using parameters related to volumetric dose distribution and two different biophysical models predicting normal tissue tolerance to radiotherapy (RT). Nine patients with inoperable locally advanced NSCLC were treated with a beam's eye view-based 3D technique. For the same patients, a conventional treatment was simulated; the irradiation geometry and beam contour were fully defined at the simulator and then transferred to the 3D-TPS to calculate the dose distribution. Both techniques gave the same prescribed dose at the reference point. Dose-volume histograms (DVHs) and dose statistics of organs at risk (OARs) (heart, lung(s), parenchyma lung, spinal cord and oesophagus) were analysed. The probability of side effects was estimated using two different biophysical models: the integrated normal ("empirical") model and the relative seriality model. Apart from contralateral lung, the 3D irradiation technique significantly reduced the average mean doses to all OARs. The current analysis suggests that in the treatment of locally advanced NSCLC, the use of 3D irradiation techniques allows a large sparing of OARs; this advantage is confirmed by both dose statistics analysis and NTCP values.

Aged↗

The prediction of fetal compromise and acidosis by biophysical profile scoring in the small for gestational age fetus.

In a prospective blind study, 133 fetuses suspected of being small for gestational age (SGA), defined as an estimated fetal weight less than the 10th centile for gestation, were monitored by weekly biophysical profile assessment. Perinatal outcome was assessed by umbilical venous blood pH estimation and compared with the profile score determined within seven days of delivery. The positive and negative predictive values of the full biophysical profile score were not significantly better than combinations of two or three of the individual components in this group of fetuses. The use of amniotic fluid volume, non-stress testing and either fetal movement or breathing offers an acceptable alternative to full biophysical profile assessment in the fetus suspected of being small for gestation.

Acidosis↗

From autopoiesis to neurophenomenology: Francisco Varela's exploration of the biophysics of being.

This paper reviews in detail Francisco Varela's work on subjectivity and consciousness in the biological sciences. His original approach to this "hard problem" presents a subjectivity that is radically intertwined with its biological and physical roots. It must be understood within the framework of his theory of a concrete, embodied dynamics, grounded in his general theory of autonomous systems. Through concepts and paradigms such as biological autonomy, embodiment and neurophenomenology, the article explores the multiple levels of circular causality assumed by Varela to play a fundamental role in the emergence of human experience. The concept of biological autonomy provides the necessary and sufficient conditions for characterizing biological life and identity as an emergent and circular self-producing process. Embodiment provides a systemic and dynamical framework for understanding how a cognitive self--a mind--can arise in an organism in the midst of its operational cycles of internal regulation and ongoing sensorimotor coupling. Global subjective properties can emerge at different levels from the interactions of components and can reciprocally constrain local processes through an ongoing, recursive morphodynamics. Neurophenomenology is a supplementary step in the study of consciousness. Through a rigorous method, it advocates the careful examination of experience with first-person methodologies. It attempts to create heuristic mutual constraints between biophysical data and data produced by accounts of subjective experience. The aim is to explicitly ground the active and disciplined insight the subject has about his/her experience in a biophysical emergent process. Finally, we discuss Varela's essential contribution to our understanding of the generation of consciousness in the framework of what we call his "biophysics of being."

Autonomic Nervous System↗

A review of therapeutic ultrasound: biophysical effects.

Almost 2 decades ago, it was pointed out that physical therapists tended to overlook the tenuous nature of the scientific basis for the use of therapeutic ultrasound. The purpose of this review is to examine the literature regarding the biophysical effects of therapeutic ultrasound to determine whether these effects may be considered sufficient to provide a reason (biological rationale) for the use of insonation for the treatment of people with pain and soft tissue injury. This review does not discuss articles that examined the clinical usefulness of ultrasound (see article by Robertson and Baker titled "A Review of Therapeutic Ultrasound: Effectiveness Studies" in this issue). The frequently described biophysical effects of ultrasound either do not occur in vivo under therapeutic conditions or have not been proven to have a clinical effect under these conditions. This review reveals that there is currently insufficient biophysical evidence to provide a scientific foundation for the clinical use of therapeutic ultrasound for the treatment of people with pain and soft tissue injury.

Animals↗

The devil is still in the details--driving early drug discovery forward with biophysical experimental methods.

This review comments on some recent trends and insights in the field of lead identification and optimization with a bias toward the increased use of biophysical methods, particularly in combination with three-dimensional structural information. While high-throughput screening, combinatorial chemistry and, most recently, in silico virtual screening techniques have made well-resourced but only partially successful attempts to meet the challenge of identifying new drug candidates by playing 'the large numbers game', another group of technologies are now approaching the same challenge from what might be considered the opposite extreme. The common strategy of these technologies is to focus on a smaller set of low-molecular-weight compounds whose interactions with a target are characterized with the aid of sensitive assays, most often high-quality biophysical techniques such as biosensors, calorimetry, nuclear magnetic resonance spectroscopy and X-ray crystallography. The advantages of such an approach include more optimal and chemically attractive starting points, immediate access to reliable measurements of binding properties, the mapping of ligand interactions on the atomic level and, most importantly, a greater control of experimental errors at the initial stages of drug discovery where compounds are either discovered or lost. When correctly supported, this more careful approach appears to deliver quality leads, even for the so-called 'difficult' targets. As these techniques are complementary to traditional methods, companies should be less hesitant to invest in them. The biophysical methods that are used to drive this approach have made something of a return to drug discovery after having been discarded for being too slow, too expensive or too old-fashioned by the over-optimistic supporters of high-throughput and statistical/computational in silico methods.

Animals↗

Fetal biophysical profile score and the nonstress test: a comparative trial.

In this prospective blind study, 735 patients with high-risk pregnancies referred for antepartum testing of fetal well-being were randomly assigned to either a fetal biophysical profile scoring (375 patients) or a nonstress testing scheme (360 patients). Management was based on the results of antepartum tests, but the method of testing used was not disclosed. Fetal biophysical profile scoring resulted in a significantly higher positive predictive value in regards to low Apgar scores. Sensitivity, specificity, and accuracy, although higher with fetal biophysical profile scoring, did not demonstrate significant differences when compared with the nonstress test. The negative predictive value between the two methods was similar. All major anomalies were detected during ultrasound scanning, whereas none of these anomalies were detected by heart rate testing alone.

Apgar Score↗

Antenatal fetal assessment using biophysical profile score.

This prospective cross sectional study was conducted in a tertiary hospital in Northern India. The objective of the study was to investigate the utility of recording certain fetal biophysical variables at or near term in high risk pregnancy for predicting the fetal outcome. A fetal biophysical profile score was used for predicting the outcome. The scoring system utilized following variables: non stress test, fetal breathing movement, fetal movement, fetal tone and amniotic fluid volume. One hundred and fifty four pregnant women attending a high risk pregnancy clinic were consecutively included in the study. At a cut off score < or = 4, sensitivity of the scoring system was 12.5% and specificity 99.23%. At score < or = 8, corresponding figures were 70.83% and 91.53%. As compared to each individual variable, the positive predictive value for abnormal perinatal outcome improved considerably after combining all the variables. The negative predictive value for normal perinatal outcome did not improve. Though biophysical profile scoring is used as a valuable adjunct in caring high risk fetuses, a simple and more practical screening test should be sought for. The cost-benefit analysis of such tests should also be performed.

Adult↗

Fetal congenital malformations. Biophysical profile evaluation.

OBJECTIVE: To study the association between various fetal congenital malformations and the biophysical profile (BPP), we tested the following hypotheses: (1) a specific organ system malformation is associated with the absence of one or more BPP parameters, and (2) four BPP parameters are not affected by the advancement of fetal maturation. STUDY DESIGN: From 1985 to 1995, 316 fetuses with congenital malformations and 351 controls were identified in a high-risk population undergoing ultrasound examinations of anatomic structures and biophysical profile evaluations. For investigation of the influence of fetal maturity on biophysical profile evaluations, both the malformed fetuses and the controls were stratified into two gestational-age groups, 26-34 weeks and > 34 completed weeks. Four parameters of the BPP, including (1) fetal breathing, (2) gross fetal movements, (3) fetal muscle tone, and (4) quantitative amniotic fluid volume, were divided into low (0-6) and high (8) total score subgroups. Tests of significance were done using chi 2 analysis, Student's t test or Fisher's exact test, as appropriate. Level of significance was set at P < .05. RESULTS: When comparing malformed fetuses to controls, the malformed group had a statistically significantly higher percentage of low BPP scores due to absent fluid, tone or breathing. Fetuses with a musculoskeletal anomaly were statistically significantly more likely to lose points for fetal movement (P < .02); fetuses with a genitourinary system anomaly lost points for fluid (P < .001), tone (P < .005) and breathing (P < .005); fetuses with a central nervous system anomaly lost points for tone (P < .02) and breathing (P < .001); and fetuses with a thoracic anomaly lost points for breathing (P < .002). There was no statistically significant difference in BPP scores between fetuses at 26-34 weeks' gestational age and fetuses > 34 completed weeks' gestational age. CONCLUSION: The two hypotheses were confirmed by the study results.

Amniotic Fluid↗

Consistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neurons.

The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well-known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage-gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K-currents (with 4-aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell-specific and tightly regulated.

4-Aminopyridine↗

The hydration problem in solution biophysics: an introduction.

The background and purpose of the British Biophysical Society Discussion meeting, The Hydration Problem in Solution Biophysics, held at the University of Glasgow, 12 September 2000, is described, particularly in relation to previous meetings in this field. Whereas a study of the nature and dynamic properties of water associated with a molecule is an important topic by itself, the collection of papers based on this meeting focus mainly on its affect in interpreting biophysical data in terms of macromolecular shape in a solution environment, particularly under dilute and very dilute systems. The techniques considered are largely hydrodynamically or thermodynamically based and supplemented by molecular modeling strategies; but in the context of how these could be used in conjunction with techniques like X-ray crystallography, NMR and neutron scattering.

Biophysics↗

Protein ligation: an enabling technology for the biophysical analysis of proteins.

Biophysical techniques such as fluorescence spectroscopy and nuclear magnetic resonance (NMR) spectroscopy provide a window into the inner workings of proteins. These approaches make use of probes that can either be naturally present within the protein or introduced through a labeling procedure. In general, the more control one has over the type, location and number of probes in a protein, then the more information one can extract from a given biophysical analysis. Recently, two related approaches have emerged that allow proteins to be labeled with a broad range of physical probes. Expressed protein ligation (EPL) and protein trans-splicing (PTS) are both intein-based approaches that permit the assembly of a protein from smaller synthetic and/or recombinant pieces. Here we provide some guidelines for the use of EPL and PTS, and highlight how the dovetailing of these new protein chemistry methods with standard biophysical techniques has improved our ability to interrogate protein function, structure and folding.

Biophysics↗