Beat averaging alternatives for transmitral Doppler flow velocity images.

To characterize diastolic function from transmitral Doppler data, the image's maximum velocity envelope (MVE) is fit by a model for flow velocity. To reduce the physiologic beat-to-beat variability of best-fit determined model parameters, averaging of multiple cardiac cycles is indicated. To assess variability mathematically, we modeled physiologic noise as a random (normally-distributed) process and evaluated three methods of averaging (1, averaging model parameters from single images; 2, averaging images; and 3, averaging MVEs) using clinical datasets (50 continuous beats from 5 subjects). Method 2 generates a positive bias because low-velocity beats will not contribute to the composite MVE. The difference between Methods 3 and 1 is less than 2.0 E-5 (m/s)2 for uncorrelated model parameters. Input having 10% beat-to-beat variation yields a bias of <4% for model parameter mean. Hence, Method 1 was, in general, more robust than Method 3.

Evaluation of model-based processing algorithms for averaged transmitral spectral Doppler images.

In an effort to characterize more fully diastolic function using Doppler echocardiography, we have previously developed an automated method of model-based image processing for spectral Doppler images of transmitral blood flow. In this method, maximum velocity envelopes (MVEs) extracted from individual Doppler images are aligned and averaged over several cardiac cycles. The averaged waveform is fit by the solution of a kinematic model of diastolic filling. The results are estimates of the model parameters. As expected, the mean and standard deviation of the model parameter estimates depend on many factors such as noise, the number of cardiac cycles averaged, beat-to-beat variation, waveform shape, observation time and the processing methods used, among others. A comprehensive evaluation of these effects has not been performed to date. A simulation was developed to evaluate the performance of three automated processing methods and to measure the influence of noise, beat-to-beat variation and observation time on the model parameter estimates. The simulation's design and a description and analysis of the three automated processing methods are presented. Of the three methods evaluated, using the inflection point in the acceleration portion of the velocity contour as the first data point to be fit was found to be the most robust method for processing averaged E-wave MVE waveforms. Using this method under nominal conditions, the average bias was measured to be < 3% for each of the model parameters. As expected, the biases and standard deviations of the estimates increased as a result of increased noise levels, increased beat-to-beat variation and decreased observation time. Another important finding was that the effects of noise, beat-to-beat variation and waveform observation time on the parameter estimates are dependent on the location in model parameter space.

Echo machine-imposed limit on transmitral spectral Doppler velocity-profile analysis.

We have previously developed a kinematic model of ventricular filling. Its application to in vivo transmitral Doppler velocity profiles provides a quantitative characterization of filling. However, the model parameters computed by solving the "inverse problem" may depend on ultrasound machine type and setting (e.g., gain, baseline filter, dynamic range). To determine machine-based effects on the computed model parameters, we performed a flow phantom study using Acuson and HP echocardiography machines at various settings. We compared maximum velocity envelopes (MVEs), as well as the model fit to these MVEs, for 3 simulated waveforms imaged by both machines. For all 3 waveforms, the machines generated comparable MVEs, fit by the model within a mean-square difference of 5E-5 (m/s)2. The associated variations in model parameters for the 3 waveforms were not uniform. Two waveforms showed slight variation between machines, with model parameters varying by less than 6%. The shortest duration waveform showed model parameter variations of 10-15%. Analysis of the parameter space for this waveform showed a constant mean-square error contour that was larger than that for the other two, causing similar small variations in measured MVEs to result in larger differences in the parameter estimates for this waveform. Because this method completely eliminates inter- and intraobserver variability, we conclude that, within the limits established, the slight contour variations due to machine type and setting should not affect this method's applicability in clinical Doppler-flow analysis.

Relationship of the third heart sound to transmitral flow velocity deceleration.

BACKGROUND: The third heart sound (S3) occurs shortly after the early (E-wave) peak of the transmitral diastolic Doppler velocity profile (DVP). It is thought to be due to cardiohemic vibrations powered by rapid deceleration of transmitral blood flow. Although the presence, timing, and clinical correlates of the S3 have been extensively characterized, derivation and validation of a causal, mathematical relation between transmitral flow velocity and the S3 are lacking. METHODS AND RESULTS: To characterize the kinematics and physiological mechanisms of S3 production, we modeled the cardiohemic system as a forced, damped, nonlinear harmonic oscillator. The forcing term used a closed-form mathematical expression for the deceleration portion of the DVP. We tested the hypothesis that our model's predictions for amplitude, timing, and frequency of S3 accurately predict the transthoracic phonocardiogram, using the simultaneously recorded transmitral Doppler E wave as input, in three subject groups: those with audible pathological S3, those with audible physiological S3, and those with inaudible S3. CONCLUSIONS: We found excellent agreement between model prediction and the observed data for all three subject groups. We conclude that, in the presence of a normal mitral valve, the kinematics of filling requires that all hearts have oscillations of the cardiohemic system during E-wave deceleration. However, the oscillations may not have high enough amplitude or frequency to be heard as an S3 unless there is sufficiently rapid fluid deceleration (of the Doppler E-wave contour) with sufficient cardiohemic coupling.

Comparison of diastolic filling models and their fit to transmitral Doppler contours.

Anatomic/physiologic and kinematic mathematical models of diastolic filling which employ (lumped) parameters of diastolic function have been used to predict or characterize transmitral flow. The ability to determine model parameters from clinical transmitral flow, the Doppler velocity profile (DVP), is equivalent to solving the "inverse problem" of diastole. Systematic model-to-model and model-to-data comparison has never been carried out, in part due to the requirement that DVPs be digitized by hand. We developed, tested and verified a computerized method of DVP acquisition and reproduction, and carried out numerical determination of model-to-model and model-to-data goodness-of-fit. The transmitral flow velocity of two anatomic/physiologic models and one kinematic model were compared. Each model's ability to fit computer-acquired and reproduced transmitral DVPs was assessed. Results indicate that transmitral flow velocities generated by the three models are 'graphically indistinguishable and are able to fit the E-wave of clinical DVPs with comparable mean-square errors. Nonunique invertibility of the anatomic/physiologic models was verified, i.e., multiple sets of model parameters could be found that fit a single DVP with comparable mean-square error. The kinematic formulation permitted automated, unique, model-parameter determination, solving the "inverse problem" for the Doppler E-wave. We conclude that automated, quantitative characterization of clinical Doppler E-wave contours using this method is feasible. The relation of kinematic parameters to physiologic variables is a subject of current investigation.

Automated method for characterization of diastolic transmitral Doppler velocity contours: late atrial filling.

We develop an automated method of characterizing the late atrial filling phase of diastole by fitting a kinematic model for diastolic filling to the clinical Doppler A-wave contour. The result is a set of model parameters which completely characterizes the contour. We have previously derived a parameterized diastolic filling (PDF) model, which predicts the time-dependent transmitral blood flow velocity obtained by Doppler echocardiography. An automated method to determine the PDF model parameters for early rapid filling from the clinical Doppler E-wave has also been developed and validated. The method consists of digitizing the acoustic Doppler waveform, recreating the Doppler velocity profile, extracting the maximum velocity envelope, and fitting the PDF model for early filling to the envelope. In the current work, we apply the same general approach for PDF parameter determination for the late atrial filling phase of diastole. To assess the presence and significance of near-degeneracies in the model parameter set, numerical experiments (consisting of fitting the model to a model-generated contour to which Gaussian noise was added) were performed. These revealed a two-dimensional degeneracy in four-dimensional parameter space which could be removed by using two kinematic simplifications: critical damping and resonant forcing. We show that these degeneracy-eliminating approximations do not limit the ability of the model to predict clinical A-wave contours.

Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age.

Head injury in the youngest age group is distinct from that occurring in older children or adults because of differences in mechanisms, injury thresholds, and the frequency with which the question of child abuse is encountered. To analyze some of these characteristics in very young children, the authors prospectively studied 100 consecutively admitted head-injured patients 24 months of age or younger who were drawn from three institutions. Mechanism of injury, injury type, and associated injuries were recorded. All patients underwent ophthalmologic examination to document the presence of retinal hemorrhages. An algorithm incorporating injury type, best history, and associated findings was used to classify each injury as inflicted or accidental. The results confirmed that most head injuries in children younger than 2 years of age occurred from falls, and while different fall heights were associated with different injury types, most household falls were neurologically benign. Using strict criteria, 24% of injuries were presumed inflicted, and an additional 32% were suspicious for abuse, neglect, or social or family problems. Intradural hemorrhage was much more likely to occur from motor vehicle accidents and inflicted injury than from any other mechanism, with the latter being the most common cause of mortality. Retinal hemorrhages were seen in serious accidental head injury but were most commonly encountered in inflicted injury. The presence of more serious injuries associated with particular mechanisms may be related to a predominance of rotational rather than translational forces acting on the head.

Dual action of anti-sporozoite antibodies in vitro.

With the use of a double staining technique that permits localization of the sporozoite during the process of entering a host cell, we studied the biologic effects of three mAb directed against determinants contained in the circumsporozoite of Plasmodium yoelii. These mAb, which included one IgM and two IgG3, were studied in primary cultures of rodent hepatocytes inoculated with sporozoites of P. yoelii. These results confirm previous reports of the extended action of antibodies on Plasmodium falciparum after entering hepatocytes by producing a strong intrahepatocyte inhibitory effect in addition to the inhibitory effect on sporozoite entry. As with P. falciparum the intracellular effects on P. yoelii liver stages are only observed when the antibodies are present at the time the sporozoite enters the cell. While carrying out experiments on this phenomenon, it was discovered that, at lowered antibody concentrations, an increase in number of maturing liver schizonts occurs, with the increase or enhancement of infection reaching up to 150% of that of controls. It was also observed that there was an inverse relationship between the antibody concentration that was inhibitory and that which enhanced parasite infectivity.

Resting metabolic rate in lean and obese children: relationship to child and parent weight and percent-overweight change.

Two studies were conducted to assess differences in metabolic rate as a function of child weight (study I); and the interaction of child and parent weight (study II). In both studies obese children had higher resting metabolic rates (RMRs) than lean children (p less than 0.05). Child weight accounted for 72 and 78% of the variance in RMR in studies 1 and 2, respectively. Including parental weight did not improve the prediction of RMR. After 6 mo of treatment, obese children decreased percent overweight, whereas lean children showed no change (p less than 0.01). RMR in both groups remained unchanged after 6 mo. These results indicate that the RMR is higher in obese than in lean children, that changes in percent overweight that result from increases in height and no change in weight do not decrease RMR over 6 mo, and parent weight does not improve the prediction of child RMR.

Physiological characteristics of Culex pipiens populations in the Middle East.

We determined whether exposure to a short day-light regime of 14 h 15 min induces ovarian diapause in Culex pipiens L. mosquitoes from Israel and whether differences occur in certain morphological, physiological and behavioural traits. Samples from nineteen localities in Israel, from 33 degrees 05' N to 29 degrees 35' N latitude, conformed to the morphological criteria of Cx pipiens, sensu stricto (i.e. wider spread of dorsal than of ventral arms of the aedeagus) as determined by negative DV/D ratios of the male. Autogenous females occurred at frequencies of 4-55% in all areas of Israel throughout the breeding season. No mating barriers were detected between individuals of autogenous and anautogenous genotypes. Autogenous females were no more prevalent from polluted or enclosed breeding sites than from others with various degrees of openness. In general, Cx pipiens females fed equally well on human (35% engorgement) and avian (22% engorgement) hosts (P less than 0.01). Although females from the southern part of the study region appeared to be incapable of ovarian diapause, at least some of those from the north experienced diel-mediated diapause. We conclude that, in the Middle East, the 33rd parallel provides a southern limit to the range of Cx pipiens with capability for diel-mediated ovarian diapause, but that non-diapausing Cx pipiens s.l. are present at least as far south as Elat (20 degrees 25' N) on the coast of the Gulf of Aquaba.

Pre-erythrocytic stages of plasmodia. Role of specific and nonspecific factors.

Protection against pre-erythrocytic stages of malaria is possible as demonstrated by the generation of resistance after immunization with irradiated sporozoites. However, mechanisms involved are more numerous and intricate than previously believed and it progressively appears that the role of the presumed target, the sporozoite, might be negligible compared with that of the hepatic stage. The comparative use of in vivo and in vitro models clearly demonstrates that the intrahepatocytic parasite can be the target of antibodies, cytokines, phagocytic and cytotoxic cells, nonspecific factors--mechanisms in part induced by the previous or subsequent developmental stages.

Purinergic reception by culicine mosquitoes.

1. Adult female Culex pipiens and Culiseta inornata have purinergic receptors that respond to extracellular ADP and related compounds. Stimulation of these receptors caused ingestion of artificial diets. Addition of bicarbonate to the saline solvent enhanced the phagostimulatory effect. Saline-bicarbonate was as effective a solvent as blood plasma for Cx. pipiens, and was used in the dose-effect determinations. Ranking of the potencies was: ADP greater than AMP-PNP greater than ATP = AMP greater than AMP-PCP much greater than 2'dAMP greater than 2'dADP greater than 2'dATP. At 1 mM concentration, ITP, GTP, CTP, UTP, c-AMP, 2'AMP, 3'AMP, DPG, or GSH + glucose caused fewer than 50% of the insects to gorge, as did 2'3'dd-ATP, A tetra P, and AMP-CPP at 100 microM. 2. The potency ranking for Cu. inornata was: ADP greater than AMP-PNP greater than ATP greater than AMP-PCP much greater than AMP much greater than AMP-S. The concentrations required to produce the ED50 response (inducing 50% of the test insects to gorge) were much higher than those required for Cx. pipiens; however, saline, not saline-bicarbonate, was used as the solvent. With the exception of the very low potency of AMP for Cu. inornata, the ADP potency index values for the other chemicals tested on both species are similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe nonimmune fetal hydrops with fetal survival. A case report.

A case of severe idiopathic nonimmune fetal hydrops spontaneously resolved after delivery with only basic supportive therapy. This case emphasizes that natural occurrences occasionally are responsible for successes attributed to invasive intrauterine treatments.

Digital subtraction angiography of peripheral vascular bypass procedures.

Without premedication or special preparation, digital video subtraction angiography, also known as photoelectronic intravenous angiography, was effectively used for evaluating patients who had undergone peripheral vascular reconstructive procedures. Thirty-eight studies in 20 patients were performed using computer contrast enhancement after an intravenous injection. Patency of arterial grafts was thereby evaluated, thus obviating further routine angiography. Graft patency, even of small complex graft sites, was easily recognized. Occlusions were also readily identified. Patient acceptance was excellent since the procedure is almost painless and can be done on an outpatient basis. The technique is fast, safe, and less expensive than routine angiography.