A conserved tooth resorption mechanism in modern and fossil snakes.

Whether snakes evolved their elongated, limbless bodies or their specialized skulls and teeth first is a central question in squamate evolution. Identifying features shared between extant and fossil snakes is therefore key to unraveling the early evolution of this iconic reptile group. One promising candidate is their unusual mode of tooth replacement, whereby teeth are replaced without signs of external tooth resorption. We reveal through histological analysis that the lack of resorption pits in snakes is due to the unusual action of odontoclasts, which resorb dentine from within the pulp of the tooth. Internal tooth resorption is widespread in extant snakes, differs from replacement in other reptiles, and is even detectable via non-destructive µCT scanning, providing a method for identifying fossil snakes. We then detected internal tooth resorption in the fossil snake Yurlunggur, and one of the oldest snake fossils, Portugalophis, suggesting that it is one of the earliest innovations in Pan-Serpentes, likely preceding limb loss.

Convergent dental adaptations in the serrations of hypercarnivorous synapsids and dinosaurs.

Theropod dinosaurs are well known for having a ziphodont dentition: serrated, blade-shaped teeth that they used for cutting through prey. Serrations along the carinae of theropod teeth are composed of true denticles, a complex arrangement of dentine, enamel, and interdental folds. This structure would have supported individual denticles and dissipated the stresses associated with feeding. These particular serrations were previously thought to be unique to theropod dinosaurs and some other archosaurs. Here, we identify the same denticles and interdental folds forming the cutting edges in the teeth of a Permian gorgonopsian synapsid, extending the temporal and phylogenetic distribution of this dental morphology. This remarkable instance of convergence not only represents the earliest record of this adaptation to hypercarnivory but also demonstrates that the first iteration of this feature appeared in non-mammalian synapsids. Comparisons of tooth serrations in gorgonopsians with those of earlier synapsids and hypercarnivorous mammals reveal some gorgonopsians acquired a complex tissue arrangement that differed from other synapsids.

Caudal autotomy as anti-predatory behaviour in Palaeozoic reptiles.

Many lizards can drop a portion of their tail in response to an attack by a predator, a behaviour known as caudal autotomy. The capacity for intravertebral autotomy among modern reptiles suggests that it evolved in the lepidosaur branch of reptilian evolution, because no such vertebral features are known in turtles or crocodilians. Here we present the first detailed evidence of the oldest known case of caudal autotomy, found only among members of the Early Permian captorhinids, a group of ancient reptiles that diversified extensively and gained a near global distribution before the end-Permian  mass extinction event of the Palaeozoic. Histological and SEM evidence show that these early reptiles were the first amniotes that could autotomize their tails, likely as an anti-predatory behaviour. As in modern iguanid lizards, smaller captorhinids were able to drop their tails as juveniles, presumably as a mechanism to evade a predator, whereas larger individuals may have gradually lost this ability. Caudal autotomy in captorhinid reptiles highlights the antiquity of this anti-predator behaviour in a small member of a terrestrial community composed predominantly of larger amphibian and synapsid predators.

Developmental and evolutionary novelty in the serrated teeth of theropod dinosaurs.

Tooth morphology and development can provide valuable insights into the feeding behaviour and evolution of extinct organisms. The teeth of Theropoda, the only clade of predominantly predatory dinosaurs, are characterized by ziphodonty, the presence of serrations (denticles) on their cutting edges. Known today only in varanid lizards, ziphodonty is much more pervasive in the fossil record. Here we present the first model for the development of ziphodont teeth in theropods through histological, SEM, and SR-FTIR analyses, revealing that structures previously hypothesized to prevent tooth breakage instead first evolved to shape and maintain the characteristic denticles through the life of the tooth. We show that this novel complex of dental morphology and tissues characterizes Theropoda, with the exception of species with modified feeding behaviours, suggesting that these characters are important for facilitating the hypercarnivorous diet of most theropods. This adaptation may have played an important role in the initial radiation and subsequent success of theropods as terrestrial apex predators.

QT interval measurement and correction in patients with atrial flutter: a pilot study.

BACKGROUND AND PURPOSE: Measurement of QT intervals during atrial flutter (AFL) is relevant to monitor the safety of drug delivery. Our aim is to compare QT and QTc intervals in AFL patients before and after catheter ablation in order to validate QT measurement during AFL. METHODS: 25 patients suffering from AFL underwent catheter ablation; 9 were in sinus rhythm and 16 were in AFL at the time of the procedure. Holter ECGs were continuously recorded before, during and after the procedure. In AFL signals, flutter waves were subtracted using a previously-validated deconvolution-based method. Fridericia's QTc was computed before and after ablation after hysteresis reduction. RESULTS: Comparing QTc values obtained before and after ablation showed that (1) the intervention did not significantly affect QTc, and (2) the QTc during AFL was concordant with the QTc value in sinus rhythm. CONCLUSION: QTc can be reliably measured in patients with AFL using flutter wave subtraction and hysteresis reduction.

Automatic detection and classification of human epicardial atrial unipolar electrograms.

This paper describes an unsupervised signal processing method applied to three-channel unipolar electrograms recorded from human atria. These were obtained by epicardial wires sutured on the right and left atria after coronary artery bypass surgery. Atrial (A) and ventricular (V) activations had to be detected and identified on each channel, and gathered across the channels when belonging to the same global event. The algorithm was developed and optimized on a training set of 19 recordings of 5 min. It was assessed on twenty-seven 2 h recordings taken just before the onset of a prolonged atrial fibrillation for a total of 1593697 activations that were validated and classified as normal atrial or ventricular activations (A, V) and premature atrial or ventricular activations (PAA, PVA). 99.93% of the activations were detected, and amongst these, 99.89% of the A and 99.75% of the V activations were correctly labelled. In the subset of the 39705 PAA, 99.83% were detected and 99.3% were correctly classified as A. The false positive rate was 0.37%. In conclusion, a reliable fully automatic detection and classification algorithm was developed that can detect and discriminate A and V activations from atrial recordings. It can provide the time series needed to develop a monitoring system aiming to identify dynamic predictors of forthcoming cardiac events such as postoperative atrial fibrillation.

The effect of gender on autonomic and respiratory responses during sleep among both young and middle-aged subjects.

BACKGROUND AND OBJECTIVES: Sleep affects the control of circulation and respiratory function. Gender and age are also known to have a profound impact on the neural control of circulation. We investigated whether gender affects sleep-related cardiovascular and respiratory responses and whether these vary according to healthy subjects being young or middle-aged. METHODS: We studied 32 subjects: 8 women and 8 men aged 20-30 years (young), and 8 women and 8 men aged 50-60 years (middle-aged). Young women were under oral contraceptive therapy and middle-aged women were postmenopausal and not receiving hormonal replacement therapy. One-night polysomnography was used to assess RR variability during non-rapid eye movement (NREM) (stage 2) and rapid eye movement (REM) sleep. Low-frequency (LF) and high-frequency (HF) components, in normalized units (LFnu and HFnu) and LF/HF ratio were calculated on five-minute segments selected across the night and averaged for each sleep stage. The respiration frequency in NREM and REM sleep was also measured. Interaction between gender, age and sleep on autonomic and respiration variables was assessed by 2 x 2 x 2 analysis of variance (ANOVA). RESULTS: Compared to men, women had a greater NREM-to-REM increment in LFnu (gender-by-state interaction, p<0.01), a greater decrement in HFnu (interaction, p<0.01) and a greater increment in LF/HF (interaction, p<0.05). Women also showed a more pronounced increase in respiratory frequency during REM sleep compared to men in both groups of age (gender-by-state interaction, F=7.1, p<0.05). No gender-by-age-by-state interaction was observed to affect autonomic and respiration variables. CONCLUSION: NREM-to-REM excitatory cardiac and respiratory responses are more marked among women compared to men, regardless of their hormonal status and whether they are young or middle-aged.

The effect of compression on clinical diagnosis of glaucoma based on non-analyzed confocal scanning laser ophthalmoscopy images.

BACKGROUND AND OBJECTIVE: To evaluate the effect of different image compression formats of non-analyzed Heidelberg Retina Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) images on the diagnosis of glaucoma by ophthalmologists. MATERIALS AND METHODS: Thirty-three topographic and reflectance images taken with the HRT representing different levels of disease were transformed using nine different compression formats. Three independent ophthalmologists, masked as to contour line and stereometric parameters, classified the original and compressed HRT images as normal, suspected glaucoma, or glaucoma, and Kappa agreement coefficients were calculated. RESULTS: The Tagged Image File Format had the largest file size and the Joint Photographic Experts Group (JPEG) 2000 format had the smallest size. The highest Kappa coefficient value was 1.00 for all ophthalmologists using the Tagged Image File Format. Kappa values for JPEG formats were all in the range of good to excellent agreement. Kappa values were lower for Portable Network Graphic and Graphics Interchange Format compression formats. CONCLUSION: Image compression with JPEG 2000 at a ratio of 20:1 provided sufficient quality for glaucoma analysis in conjunction with a relatively small image size format, and may prove to be attractive for HRT telemedicine applications. Further clinical studies validating the usefulness of interpreting non-analyzed HRT images are required.

Wavelet time entropy, T wave morphology and myocardial ischemia.

Using wavelets, we computed the entropy of the signal at various frequency levels (wavelet time entropy) and, thus, find an optimal measure to differentiate normal states from ischemic ones. This new indicator is independent from the ST segment and yet provide a conclusive detection of the ischemic states.

Continuous ST-segment monitoring during coronary angioplasty using orthogonal ECG leads.

In order to characterize ST-segment shifts during transient coronary artery occlusion, 24 patients with single-vessel disease were continuously monitored during percutaneous transluminal coronary angioplasty by use of a computerized orthogonal lead system. Changes of ST-segment (J + 60 ms) in leads X, Y, and Z and of the ST vector magnitude were analyzed by using 20 microV as a threshold for significant ST-segment shift. The sensitivity and magnitude of this shift were compared among the left anterior descending, right coronary, and circumflex artery groups (11, 8, and 5 patients, respectively) during balloon inflation. Significant ST-segment shifts were seen in 22 patients (92%) in ST-VM, Y, and Z leads and all patients in lead X (100%). There was no significant difference in sensitivity of either the ST vector magnitude or the most sensitive lead for occlusion detection among the three groups. There was a significantly greater magnitude of ST shift during left anterior descending artery occlusion than during right coronary artery and circumflex artery occlusions in ST-VM. Analysis of the direction of ST shifts in the X, Y, and Z leads showed a characteristic pattern, which could distinguish among the three coronary groups in 21 patients (88%). The presence of collaterals was significantly associated with ST-segment depression in leads oriented toward ischemia (3 of 6 patients) as compared with ST-segment elevation in the absence of collaterals (all of 15 patients), P > .01. It is concluded that ST-segment shift in the orthogonal leads is a reliable marker for myocardial ischemia. It is equally sensitive to occlusion of each of the three major coronary arteries and can thus identify the occluded coronary. An ST-segment depression instead of an elevation was related to the presence of collaterals, which may reflect a lesser degree of ischemia.

A computer heart model incorporating anisotropic propagation. IV. Simulation of regional myocardial ischemia.

The main goal of this study was to simulate clinical body surface potential maps, recorded during percutaneous transluminal coronary angioplasty protocols, using a realistic geometry computer heart model. Other objectives were to address the question of reciprocal ST-segment changes observed in the 12-lead electrocardiogram during ischemia and to verify the hypothesis that the shortening of the QRS duration observed in left anterior descending (LAD) coronary artery occlusion may be explained by conduction delay in the septal His-Purkinje system. Simulation was achieved by first introducing into the heart model three transmural zones of mild, moderate, and severe ischemia for assumed occlusions in the LAD, left circumflex, and right coronary arteries. The heart model was then excited, in turn, with these three zones present for assumed occlusions in the LAD, left circumflex, and right coronary arteries. Myocardial conduction velocities in the regions of moderate and severe ischemia were assumed to be reduced to 75 and 50% of normal, respectively. Model action potentials in the mild, moderate, and severely ischemic zones were also altered to reflect known ischemic changes in these action potentials. Body surface potential maps and electrocardiograms were computed by placing the heart inside a numerical torso model. Simulated map patterns during both ST-segment and QRS were qualitatively similar to clinical maps. Reciprocal ST-segment depression was observed for all three occlusions in remote leads that did not overlie the ischemic zones. QRS shortening due to septal His-Purkinje conduction delay was verified. The simulation results attest to the model's ability to reproduce body surface potential distributions recorded following percutaneous transluminal coronary angioplasty protocols. The simulations also showed that reciprocal ST-segment changes occur as a natural consequence of the primary ischemic region and that there is no need to invoke a second region of ischemia. Finally, the model demonstrated that QRS shortening can occur in LAD occlusion despite a slowing of conduction down the septal His-Purkinje system.

Transfer function analysis of vagal control of heart rate during synchronized vagal stimulation.

Synchronized electrical stimulation was used to study the heart rate (HR) response to fluctuations in parasympathetic input to the sinus node in anesthetized dogs. This was obtained by varying the time interval (interpulse interval) between stimulatory vagal pulses. Spectral methods were used to estimate transfer functions between the excitatory signal and the resulting HR response for different intensities of vagal stimulation. The intensity of vagal stimulation was proportional to the number of pulses delivered in each cardiac cycle. From the estimated transfer functions, and based on a mathematical model of the time course of ACh concentration at the sinus node, filter models were derived by using a system identification approach. HR response was characterized by a combination of two different filter behaviors: a low-pass filter behavior of mean cut-off frequency of 0.065 Hz and an all-pass filter behavior. The magnitude of the low-pass filter gain decreased with increasing intensity of vagal stimulation. The magnitude of the all-pass filter gain increased and then decreased with increasing intensity of vagal stimulation. The all-pass filter characteristics of HR response during synchronized stimulation of the vagus nerves are specific to this mode of stimulation, because they were not observed in nonsynchronized modes of vagal stimulation. We can conclude that, during synchronized vagal stimulation, the HR response exhibits both a slow dynamic component and a fast component related to beat-to-beat variations.

Continuous ST segment recording during thrombolysis in acute myocardial infarction: a report on orthogonal ECG monitoring.

BACKGROUND: A noninvasive, real time method is needed to identify failures of thrombolysis and evaluate new treatments in acute myocardial infarction (MI). OBJECTIVE: To study XYZ monitored ST segment evolution during thrombolysis in acute MI and to examine the correlation of ST parameters to outcome. DESIGN: Thirty-five patients receiving tissue plasminogen activator (tPA) (n = 18) or streptokinase (SK) (n = 17) for acute MI were monitored by vector-cardiography during the first 12 h of thrombolytic therapy. Computer constructed ST vector magnitude (ST-VM) trends were analyzed for 0.5 or greater decline from the initial ST amplitude (IA) lasting for 10 mins or longer (ST response) and for ST re-elevation 0.75 IA or more following ST decline. The degree of ST response, time from treatment onset and ST-VM re-elevation were correlated to peak creatine phosphokinase (CPK), left ventricular ejection fraction (EF) and final ST-VM. RESULTS: The presence of an ST response correlated with a lower peak CPK (2691 +/- 1625 versus 4057 +/- 1622 U/L, P = 0.043) and tended to higher EF (0.48 +/- 0.11 versus 0.36 +/- 0.09, P = 0.057). The ST responder group had fewer patients with ST re-elevation than the group of nonresponders (13 of 30 versus five of five patients, P = 0.041). Moreover, ST response before 120 mins was associated with lower peak CPK (2089 +/- 1299 versus 3367 +/- 177 U/L, P = 0.02) and better EF (0.54 +/- 0.06 versus 0.41 +/- 0.12, P = 0.02) compared with later or no ST response. The degree of ST response correlated significantly with a lower ST-VM during the last hour (r = -0.744, P = 0.001). ST trends showed no significant differences between treatment groups (tPA versus SK). The tPA group, however, tended to an overall earlier ST response (117 +/- 75 versus 163 +/- 64 mins, P = 0.13). CONCLUSIONS: Early ST-VM trends are closely associated with electrocardiographic and clinical outcome and may provide a basis for clinical management, therapeutic comparisons and better insight into thrombolysis in MI.

Improved beat-to-beat timing measurements of His-bundle signal.

A simplified bioelectric model of the atrioventricular (AV) junction is proposed to better understand the underlying biophysical generation of intracardiac His-bundle signal and to analyze the effects of electrocatheter displacements on waveform morphology and estimation of AV node conduction time (AVCT). Based on this model, an inverse problem approach has been developed to estimate electrode displacements occurring in real recordings. A measurement correction method is proposed to improve estimation of AVCT. Results illustrate autonomic influences on AVCT, a phenomenon hardly measured with common techniques.

MD Concept: a model for integrating medical knowledge.

Many integrated clinical information systems depend on large knowledge bases containing dictionary of terms as well as specific information about each term and the relationships between terms. We propose a knowledge base model called MD Concept which is based on a semantic network and uses an object-oriented paradigm and relational tables. A prototype has been developed which integrates the Unified Medical Language System (UMLS) with other databases including the Systematized Nomenclature of Medicine (SNOMED II), the Diagnostic and Statistical Manual of Mental Disorders (DSM-IIIR) and a pharmaceutical database. We demonstrate how a user can easily navigate in this knowledge world using a browser.

Propagation in the AV node: a model based on a simplified two-dimensional structure and a bidomain tissue representation.

A model is proposed to explain mechanisms of propagation in the atrioventricular (AV) node of the heart. The model is based on a simplified two-dimensional anatomic description of the central node region and on a bidomain tissue model for the propagation. The central region is described as a three-tissue compartment model; the proximal tissue composed of ANL cells, the central tissue composed of N cells and the distal tissue composed of NH cells. The central N region is outlined as an unexcitable gap by forcing these cells to behave as depressed cells for which the fast ionic currents are inactivated. This model has allowed the authors to test the electrotonic gap hypothesis, which explains the time-delay properties of the AV node. Typical conduction curves have been obtained, as well as common patterns of Wenckebach blocks. Premature stimulus and resulting mapping of cell responses in the N region of the model show typical membrane potential dissociation in two components. The model has also been submitted to several programmed stimulation protocols in documented anterograde and retrograde conduction. The results show that the model is valid and covers several well known dynamic properties of the AV node.

Mapping of ventricular tachycardia induced by thoracic neural stimulation in dogs.

To investigate ventricular tachycardias produced in healthy canine myocardium by stimulation of sympathetic ganglia or cardiac nerves, we simultaneously recorded a surface ECG and 63 ventricular electrograms in anesthetized open-chest dogs. Isochronal and isopotential maps were generated off-line by computer. Ventricular tachycardia with uniform beat-to-beat morphology was induced in 13 or 22 dogs by electrical stimulation of the left stellate ganglion (five experiments), the left middle cervical ganglion (four experiments), the left caudal pole cardiopulmonary nerve (two experiments), or the ventrolateral cardiac nerve (eight experiments). It was not inducible by stimulation of the right-sided major cardiopulmonary nerves or ganglia. In most instances the earliest measured electrical excitation occurred on the posterior aspect of the ventricles. Isochronal maps demonstrated a radial spread of the impulse away from the area of earliest excitation. Changes in the region of earliest excitation and (or) activation pattern were accompanied by changes in QRS morphology. The potential gradients measured between areas displaying positive and negative T waves on the anterior and left lateral aspects of the ventricles were significantly increased by ventrolateral cardiac nerve stimulation. However, the ventricular regions where these potential gradients existed differed from the regions of earliest excitation during ventricular tachycardia. These results demonstrate that the thoracic autonomic nervous system can induce repetitive ventricular excitation originating from consistent loci.

Quantitative analysis of cardiac arrhythmias.

Quantitative analysis of cardiac arrhythmias has been the subject of intensive research during the last 10 years. Several systems have been designed to help in the processing of cardiac signals: single or multiple lead electrocardiograms (ECG), electrograms from intracardiac catheters, esophageal recordings, etc. The main objective of these developments was oriented toward positive identification of arrhythmias or rhythm-disturbance counts to imitate the cardiologist's interpretation in contexts such as routing ECG and ambulatory recordings. However, these systems were mainly measurement tools aimed at extracting auricular and ventricular depolarization timings plus gross morphology description. The domain of morphology analysis of beat-to-beat auricular depolarization on ECG has never been highly active due to poor signal conditions. For routine ECG, automatic interpretation was set as an objective to complement computer-assisted ECG interpretation of conduction problems (i.e., morphology analysis of a representative beat extracted or averaged from the dominant rhythm). The limitations of rhythm interpretation in this context are well known. In the ambulatory ECG context, the analysis procedures are relatively simple and are often summarized as trivial counts describing, most exclusively, the ventricular arrhythmic behavior of the heart over a relatively long duration. Waveform-detection and measurement have been the bottleneck of advancement in arrhythmia analysis since highly reliable detection of events on a beat-to-beat basis are necessary to perform a valid analysis. Rare approaches have proposed probabilistic definition of event detection. The present review puts emphasis on the potential of several methods which have been demonstrated as powerful in identifying short- or long-duration heartbeat patterns, mode of heartbeat initiation, mode of heartbeat coupling, etc. Globally, these methods are referred to as time series analysis, modeling of rhythm patterns, simulation, and pattern recognition. A delay in the advancement of the study of arrhythmogenesis and limiting the analysis of arrhythmias to textbook descriptions is not justified when put in perspective of the potential of implementing powerful techniques which have been more or less neglected or used in a narrow way.