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Evolution of cytochrome C investigated by the maximum parsimony method.

Rates of evolution for cytochrome c over the past one billion years were calculated from a maximum parsimony dendrogram which approximates the phylogeny of 87 lineages. Two periods of evolutionary acceleration and deceleration apparently occurred for the cytochrome c molecule. The tempo of evolutionary change indicated by this analysis was compared to the patterns of acceleration and deceleration in the ancestry of several other proteins. The synchrony of these tempos of molecular change supports the notion that rapid genetic evolution accompanied periods of major adaptive radiations. Rates of change at different time in several structural-functional areas of cytochrome c were also investigated in order to test the Darwinian hypothesis that during periods of rapid evolution, functional sites accumulate proportionately more substitutions than areas with no known functions. Rates of change in four proposed functional groupings of sites were therefore compared to rates in areas of unknown function for several different time periods. This analysis revealed a significant increase in the rate of evolution for sites associated with the regions of cytochrome c oxidase and reductase interaction during the period between the emergence of the eutherian ancestor to the emergence of the anthropoid ancestor.

Animals↗

Noninvasive evaluation of the influence of aortic wave reflection on left ventricular ejection during auxotonic contraction.

To develop a noninvasive method for evaluating the influence of aortic wave reflection on left ventricular ejection, the carotid pulse wave and the pulsed Doppler wave in the left ventricular outflow tract were evaluated in 35 patients. Agreement between the pulsed Doppler waveform and the aortic flow velocity contour (obtained invasively) was verified by Fourier analysis. The carotid augmentation index was used to determine the magnitude of the aortic pressure wave reflection. A Doppler index named "DR1/3" was defined as the ratio of deceleration at the first one-third in the deceleration phase to the peak flow velocity of the pulsed Doppler. This index was validated by close correlation with the carotid augmentation index (n = 48, r = 0.70, P < 0.01). Both nitrates and nifedipine induced a significant decrease in DR1/3 (indicating an increase in left ventricular ejection flow) in relation to a reduction of the reflected pressure wave. The new noninvasive index, DR1/3, is useful in evaluating the influence of aortic wave reflection as part of the left ventricular afterload and in assessing the benefit of treatment aimed at reducing wave reflection.

Aorta↗

The spectrum of left ventricular filling in severe aortic stenosis.

To assess left ventricular diastolic filling in valvular aortic stenosis, pulsed Doppler echocardiography was used prospectively in 35 patients with severe aortic stenosis (valve area less than 1 cm2) and in 38 age-matched normal subjects. Twenty-seven patients had a normal left ventricular systolic function at rest (ejection fraction greater than 0.50) and a normal or only slightly increased mean pulmonary capillary wedge pressure (mean 11 +/- 4 mm Hg). Eight patients had a poor left ventricular systolic function (ejection fraction: 0.28 +/- 0.10) and an elevated mean pulmonary capillary wedge pressure (mean: 36 +/- 9 mm Hg). The Doppler derived filling parameters were correlated with hemodynamic data, left ventricular wall thickness derived from M-mode echocardiograms, heart rate and atrio-ventricular (A-V) conduction delay using stepwise multiple correlation. The data of this study suggest that left ventricular filling is significantly impaired in patients with severe aortic stenosis and left ventricular hypertrophy with an increase in late diastolic (A-wave) velocity, an increase in the A/E ratio, a decrease in the first one-half filling fraction and a prolongation of early diastolic deceleration time. These changes in filling hemodynamics are associated with alterations in mean pulmonary capillary wedge pressure, left ventricular wall thickness, heart rate and A-V conduction delay. When heart failure develops as a result of impaired left ventricular systolic function, an increase in left atrial filling pressure is associated with a shift of left ventricular filling towards early diastole with a 'normalisation' of the transmitral flow velocity curve. In extreme cases, a progression towards a 'restrictive' filling pattern is found with a marked shortening of the left ventricular early diastolic deceleration time. In the presence of high filling pressures, increased left atrial driving pressure (derived from the mean pulmonary capillary wedge pressure) is associated with changes in the left ventricular filling pattern irrespective of the presence and the degree of myocardial hypertrophy.

Adolescent↗

What stops the flow of blood from the heart?

The determinants of aortic pressure and flow are generally studied using impedance methods, the results of which indicate that reflected waves are important, particularly during aortic flow deceleration. An alternative analysis of measured aortic pressure and velocity, using the method of characteristics to calculate the energy flux per unit area of the waves, suggests a different conclusion. We suggest that aortic deceleration is caused by a discrete expansion wave propagating from the left ventricle, and that energy thus recovered by the ventricle may be coupled to early filling of the ventricle.

Aorta, Thoracic↗

Pharmacology of saccadic eye movements in man. 2. Effects of the alpha 2-adrenoceptor ligands idazoxan and clonidine.

The effects of alpha 2-adrenoceptor agonists and antagonists on saccadic eye movements were studied in normal volunteers using the agonist clonidine and the antagonist idazoxan. Changes in blood pressure, heart rate, and several psychological self-ratings were also recorded. Clonidine produced marked slowing of peak saccade velocity, acceleration and deceleration, with deceleration affected more than acceleration, but had no effect on saccade error or latency measurements. In contrast, most saccade parameters were not altered by idazoxan, although fatigue effects were eliminated. Blood pressure, heart rate, and self ratings of alertness were increased by idazoxan and reduced by clonidine, with opposite effects noted on sedation self-ratings. There were no correlations between the clonidine-induced changes in saccade parameters and changes in self-ratings. Although the slowing of some saccade parameters by clonidine may imply that alpha 2-adrenoceptors are involved in control of saccades, it may also be due to sedation. Although alpha 2-adrenoceptor antagonists may abolish fatigue effects, they cannot increase them over baseline values.

Adrenergic alpha-Antagonists↗

The course of the traumatising force in acceleration head injury: CT evidence.

Since brain damage in closed head injury of acceleration-deceleration type depends on the site of impact and on the course of the traumatising force, a reconstruction of these was attempted using CT. The study included 45 standard CT studies of adults with closed acceleration-deceleration head injuries. We selected 32 patients exclusively on the basis of CT findings of soft tissue contusion, skull fractures and cerebral contusions (coup and/or contrecoup, as well as other parenchymal lesions), while in the remaining 13 patients clinical findings were also used. On CT, the axial section of the skull was divided into 12 sections imitating the clock-face, to permit computerised graphic presentation of the direction of the traumatising force. Analysis of cerebral contusions on different CT studies in each case allowed location of "dominant coup" and "dominant contrecoup" lesions to be determined. The site of impact and the course of the traumatising force were reconstructed and graphically presented on the basis of these findings, supplemented with data on soft tissue contusions (present in 71% of cases), skull fractures (in 36%) and sometimes on other brain lesions. Comparison of the computerised graphic presentation of the site of impact and direction of the traumatic force and the location of lesions revealed a high correlation between them. In 80% of cases, the site of impact could be visualised only by CT. The acceleration force acted along the longer axis of the head (centroaxial or semioblique) in 87% and along the shorter axis in 13% of cases. Multiple lesions were found in 87% of cases. The lesions were most frequent in the frontal (51%) and temporal (26%) lobes. CT was very useful for reconstruction of the site of impact and of the course of the traumatising force in acceleration head injury. Data obtained by this procedure may have far-reaching prognostic and forensic implications.

Acceleration↗

A new method of fitting and analysis of simple uni-joint arm movements.

A new method for fitting and analysis of simple uni-joint arm movements is proposed. The method is based on a model which postulates that the acceleration-time profile of the movement can be described by a linear combination of two Gaussian functions (positive for acceleration and negative for deceleration). The method was tested on more than 21000 arm movements performed under different control conditions and showed high fitting precision. It allows to completely describe a movement using only five parameters of two Gaussian functions. The method is sensitive to differences between the acceleration and deceleration phases of movement as well as between subsequent movements because of the independent calculation of the Gaussian functions for accelerative and decelerative movement parts. Relationships between conventional kinematic and model parameters as well as areas of application of the method are discussed.

Algorithms↗

Suitability of artificial neural networks for feature extraction from cardiotocogram during labour.

Fetal condition during labour is inferred from a continuous display of fetal heart rate and uterine contractions called the cardiotocogram (CTG). The CTG requires a considerable expertise for correct interpretation, which is not always available. We are developing an intelligent system to support clinical decision-making during labour. The system's performance depends on its ability to classify features from the CTG similarly to experts. Artificial neural networks (NNs) can be taught by experts for such tasks, and so may be particularly suitable. We found NNs suitable for feature extraction when the problem was reduced to small well defined tasks, and numerical algorithms were used to pre-process the raw data before application to the NNs. A NN with optimised dimensions was used in this way to classify the magnitude of decelerations, a feature clinicians find particularly difficult. The NN was compared with the algorithm used in a commercial antenatal monitor and six reviewers which included two CTG experts. The experts were consistent (89.7% and 97.0%) and agreed well with each other (81.0%), whereas the non-experts were less consistent and agreed less well. The NN agreed well with the experts (75.0% and 81.9%) but the algorithm agreed poorly (56.5% and 68.9%). It was found that the algorithm's performance could be improved (72.1% and 76.7%) when modified to use additional information. Our earlier attempts to fully classify the raw CTG using a single NN were unsuccessful because of the large number of data patterns. A simplified approach to classify the magnitude and timing of decelerations was also unsuitable when contraction data was of poor quality or absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

A new electromechanical method for measuring intraocular pressure.

A new electromechanical method to measure intraocular pressure is presented. A light probe was made to collide with an eye (cornea or sclera) and to bounce back. The impact was registered by an acceleration sensor or the duration of contact with the eye was measured using the phenomenon of the electrical conductivity of biological objects. Laboratory experiments were carried out using pig eyes pressurized with water leveled to different heights. Preliminary clinical trials were carried out comparing the values obtained with those of the Goldmann applanation tonometer. The time of contact and the deceleration time decreases and the deceleration maximum increases in proportion with IOP. A new kind of tonometer can be constructed based on this principle. Measurement can be performed to cornea or sclera without an anesthetic drop. Further study is required to evaluate the accuracy and usefulness of this method.

Animals↗

Heart rate reactivity in attention deficit disorder subgroups.

Beat-to-beat heart rate (HR) was analyzed for 9 contiguous seconds in a warned reaction time (RT) paradigm. Imperative stimuli were tones of three intensity levels (55, 78, and 100 db); a visual warning signal occurred 5 sec before tone onset. Baseline and reward conditions were run. Normal controls were contrasted with three Attention Deficit Disorder (ADD) subgroups: ADD-only, ADD with hyperactivity (ADDH), ADD with hyperactivity and aggression (ADDHA). The ADD subgroups were predicted to show less deceleration in HR because of their problem sustaining readiness to respond. Significant sex x group differences in HR levels and change scores were found. Overall, girls had higher HR levels than boys and the ADD-only group (boys and girls) had lower HRs than the other ADD groups. But, the ADD-only boys had more marked deceleration to the warning signal and acceleration to the tones than the other ADD boys, whereas the ADD-only girls were no more reactive than the ADDH and ADDHA girls. Control girls had the highest HR levels and were the most reactive to stimuli. Control boys and ADD-only boys had similar HR levels and reaction patterns. ADD-only girls appear to be underaroused, whereas ADD-only boys do not. Results suggest that cardiac measures can provide external validation of disruptive and nondisruptive ADD subtypes.

Attention Deficit Disorder with Hyperactivity↗

Amnioinfusion in thick meconium.

OBJECTIVE: There are conflicting reports regarding the results of amnioinfusion in the management of meconium passage in utero. This study was done to evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labour. METHODS: 196 women at term in early labour with meconium were randomized to receive either transcervical intrapartum amnioinfusion with saline (96) or routine obstetrical care (100). Transcervical amnioinfusion of one liter saline infused over 30-45 minutes. End points were relief of decelerations, incidence of vaginal delivery, presence of meconium below the neonatal cords, and X-ray evidence of meconium aspiration. RESULTS: Amnioinfusion resulted in relief of decelerations in 75% of cases as compared to 7% in the control group. Eighty-eight percent of patients delivered vaginally as compared to 58% in the control group (p< 0.001). Neonatal outcome was significantly better in the infusion group. The incidence of meconium below the vocal cords was reduced from 48% to 17% (p< 0.004) using amnioinfusion with positive X-rays for meconium aspiration in only 12.5% versus 26% (p < 0.5). CONCLUSIONS: We concluded that transcervical intrapartum amnioinfusion is a safe, simple and inexpensive technique that reduces operative intervention and improves neonatal outcome, and is of tremendous relevance in developing countries.

Amniotic Fluid↗

Wave-intensity analysis: a new approach to left ventricular filling dynamics.

In order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks. Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to "diastolic suction". Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase. Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration. Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction. Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.

Aorta↗

Autonomic responsivity during visual search of hyperactive and reading-disabled children.

Heart rate and skin conductance measures, recorded during a visual search task, were compared for hyperactive, reading-disabled, hyperactive reading-disabled, and control elementary school boys. As shown in past work, basal autonomic levels did not statistically differentiate groups. In all groups, heart rate levels increased with task complexity, but more so on reward than on nonreward trials. In the intertrial interval, heart rate decelerated consistently when subjects were anticipating stimuli associated with reward, but when reward was uncertain, heart rate accelerated slightly or stayed the same. Control subjects exhibited anticipatory heart rate deceleration more consistently than did clinical subjects, especially the solely hyperactive ones. Skin conductance levels first decreased, then rose as task complexity increased, but the groups did not differ on this measure. A conditioning model is outlined to explain directional changes in heart rate.

Arousal↗

Effects of awareness and motor involvement on autonomic conditioning in chronic schizophrenics.

Chronic schizophrenics under neuroleptic medication were compared with normals, matched for age and education, in two conditioning experiments. Both experiments employed a differential paradigm with long conditional stimulus--unconditional stimulus (CS-UCS) intervals. Skin resistance (SR) and finger pulse or heart rate (HR) were recorded. In Experiment 1, half of the subjects were trained in categorizing the to-be conditional stimuli. In a further step, half of the subjects were informed about the CS-UCS contingency. The UCS was an electric shock. Information improved discrimination of SR responses only of normals, and discrimination training had no effect at all on autonomic responses. In Experiment 2, only electrodermal responders were included. Each subject was tested in two sessions, using a loud tone as UCS in one, and a reaction time signal in the other. Again, half of the subjects wee informed about the contingency. Information improved discrimination of SR responses of both diagnostic groups. Decelerations of HR following CS onset showed informed schizophrenics to discriminate better with the loud tone UCS than with the reaction time signal. General autonomic responsivity seems to determine not only discriminative conditioning of schizophrenic patients but also the reports of awareness and the effects of manipulations of awareness. However, when subjects are matched for electrodermal responsivity and are equivalent in terms of SR response conditioning, patients react to information about the contingency with enhanced HR deceleration to the CSs, possibly reflecting a heightened sensitivity of the cardiovascular system.

Adult↗

Improved epidural analgesia in the parturient in the 30 degree tilt position.

PURPOSE: To compare the incidence of incomplete analgesia when epidural local anesthetic is administered with the parturient supine in a 30 degree leftward tilt or in the left lateral decubitus position. METHODS: After placement of a multiorifice catheter 5 cm into the epidural space, 293 women in active labour were randomly positioned either to the left lateral decubitus position (lateral group) or supine with a 30 degree leftward tilt (tilt group) and then received 13 mL bupivacaine 0.25%. The success of the epidural block was determined by asking the patient if she required additional medication 15 min later. The incidence of complications (fetal heart rate decelerations, hypotension, and ephedrine usage) was noted. RESULTS: In the lateral group, 38% required additional medication compared with 24% in the tilt group (P = 0.006). There were no differences between groups in the incidence of maternal hypotension or fetal heart rate decelerations, but more women (10%) received ephedrine in the lateral than in the tilt group (4%), P = 0.035. CONCLUSIONS: Placing the parturient supine with a 30 degree leftward tilt is associated with a greater success rate of labour epidural analgesia without an increase in complications than in women in the left lateral decubitus position. This advantage should be considered when positioning the parturient after epidural catheter placement.

Adult↗

Arm and mouth coordination during the eating action in humans: a kinematic analysis.

The kinematic characteristics of the eating action in humans were assessed. Ten subjects were asked to bring to the mouth pieces of cheese of different sizes (0.7 cm and 2 cm). The pattern of mouth aperture with respect to the size of the food was similar to that found for grasping differently sized objects with the hand. Mouth aperture was appropriately scaled and the time of maximum aperture was reached earlier for the smaller than for the larger piece of cheese. The deceleration phase of the arm was prolonged when the small piece of cheese had to be brought to the mouth with respect to when the large piece of cheese had to be brought to the mouth. Temporal coupling between the time of maximum peak deceleration and the maximum mouth aperture was found in seven of the ten subjects. Taken together these preliminary results suggest that coordinated actions are subserved by the use of a common coordinating schema independently from the effectors involved.

Adult↗

Manual interception of moving targets. I. Performance and movement initiation.

We investigated the capacities of human subjects to intercept moving targets in a two-dimensional (2D) space. Subjects were instructed to intercept moving targets on a computer screen using a cursor controlled by an articulated 2D manipulandum. A target was presented in 1 of 18 combinations of three acceleration types (constant acceleration, constant deceleration, and constant velocity) and six target motion times, from 0.5 to 2.0 s. First, subjects held the cursor in a start zone located at the bottom of the screen along the vertical meridian. After a pseudorandom hold period, the target appeared in the lower left or right corner of the screen and traveled at 45 degrees toward an interception zone located on the vertical meridian 12.5 cm above the start zone. For a trial to be considered successful, the subject's cursor had to enter the interception zone within 100 ms of the target's arrival at the center of the interception zone and stay inside a slightly larger hold zone. Trials in which the cursor arrived more than 100 ms before the target were classified as "early errors," whereas trials in which the cursor arrived more than 100 ms after the target were classified as "late errors." Given the criteria above, the task proved to be difficult for the subjects. Only 41.3% (1080 out of 2614) of the movements were successful, whereas the remaining 58.7% were temporal (i.e., early or late) errors. A large majority of the early errors occurred in trials with decelerating targets, and their percentage tended to increase with longer target motion times. In contrast, late errors occurred in relation to all three target acceleration types, and their percentage tended to decrease with longer target motion times. Three models of movement initiation were investigated. First, the threshold-distance model, originally proposed for optokinetic eye movements to constant-velocity visual stimuli, maintains that response time is composed of two parts, a constant processing time and the time required for the stimulus to travel a threshold distance. This model only partially fit our data. Second, the threshold-tau model, originally proposed as a strategy for movement initiation, assumes that the subject uses the first-order estimate of time-to-contact (tau) to determine when to initiate the interception movement. Similar to the threshold distance model, the threshold-tau model only partially fit the data. Finally, a dual-strategy model was developed which allowed for the adoption of either of the two strategies for movement initiation; namely, a strategy based on the threshold-distance model ("reactive" strategy) and another based on the threshold-tau model ("predictive" strategy). This model provided a good fit to the data. In fact, individual subjects preferred to use one or the other strategy. This preference was allowed to be manifested at long target motion times, whereas shorter target motion times (i.e., 0.5 s and 0.8 s) forced the subjects to use only the reactive strategy.

Adult↗

Diastolic function in neonates after the arterial switch operation: effects of positive pressure ventilation and inspiratory time.

OBJECTIVE: To determine the effects positive pressure ventilation have on left ventricular diastolic function in neonates after the arterial switch operation. DESIGN: Prospective case series. SETTING: Pediatric cardiac and multidisciplinary intensive care units in two university-affiliated children's hospitals. PATIENTS AND PARTICIPANTS: The patient population consisted of 12 neonates weighing 2.5-4.2 kg with D-transposition of the great arteries (DTGA) who underwent arterial switch operation. INTERVENTIONS: All patients were mechanically ventilated in a volume-targeted mode with a square wave flow pattern. The positive end-expiratory pressure was held constant. A long inspiratory time was set by extending it over three cardiac cycles. MEASUREMENTS AND RESULTS: Pulsed Doppler measurements of left ventricular diastolic function were performed during the following cardiac cycles: (1) the last diastolic period of expiration (E(L)), (2) first, second and third diastolic periods of inspiration (I1, I2, I3) and (3) the first diastolic period of expiration (E(F)). Doppler measurements of peak E wave, peak A wave, E area/A area, E area fraction, A area fraction, 0.33 area fraction and the deceleration time were made. Doppler tracings were digitized and the data obtained from three sequential study periods were averaged. Data were statistically analyzed using the repeated measures analysis of variance procedure. During (I1), there was a 21% increase in the peak E wave (0.53+/-0.06 vs 0.64+/-0.08 m/s, p < 0.01) and 28% increase in peak A wave (0.47+/-0.07 vs 0.60+/-0.08 m/s, p < 0.01) compared to (E(L)). There was a 24% increase in total area under the E and A waves when I1 was compared to E(L) (0.059+/-0.008 vs 0.073+/-0.009, p < 0.01) and there was no change in mitral valve deceleration time. Compared to the initial diastolic period during inspiration (I1), the third diastolic period during inspiration (I3) had a 38% decrease in peak E (0.64+/-0.08 vs 0.40+/-0.05 m/s, p < 0.01) and 33% decrease in peak A (0.60+/-0.09 vs 0.40+/-0.05 m/s, p < 0.01). In addition, there was a 16% reduction in total area under the E and A waves (0.073+/-0.009 vs 0.061+/-0.008, p < 0.01). There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation. CONCLUSIONS: In neonates with transposition of the great arteries (TGA) after the arterial switch operation, positive pressure ventilation augments left ventricular filling during the early phase of inspiration. Prolonging the inspiratory time over three cardiac cycles results in a reduction in left ventricular filling during the third diastolic period. There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation.

Blood Pressure↗