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Fetal assessment based on fetal biophysical profile scoring: experience in 12,620 referred high-risk pregnancies. I. Perinatal mortality by frequency and etiology.

Fetal biophysical profile scoring was used as a method for antepartum fetal risk assessment in 12,620 high-risk patients referred in a 55-month interval. A total of 26,257 tests were performed on these patients (range, one to 18 tests per patient). Ninety-three perinatal deaths occurred (gross perinatal mortality rate, 7.37 per 1000) of which 62 (66.6%) were due to a major anomaly, seven were due to Rh disease (7.5%), and the remaining 24 deaths (25.8%) occurred in structurally normal fetuses. The corrected perinatal mortality rate was 1.90 per 1000. Eight structurally normal fetuses died within 1 week of a normal test result (corrected false negative rate, 0.634 per 1000). These data suggest fetal biophysical profile scoring is an accurate method for identification of the fetus at risk for perinatal death.

Amniotic Fluid↗

Prognostic components of computerized fetal biophysical testing.

Fetal biophysical testing with arbitrary scores for fetal heart rate (FHR), breathing movements, body movements, tone, and amniotic fluid volume has not proved to be highly sensitive or significantly better than FHR testing alone. Using a computerized analysis system for simultaneously acquired biophysical variables, we studied 200 high-risk fetuses near term. The dynamic parameters obtained for each fetus were compared with established nomograms, and overall test results correlated with the presence or absence of perinatal mortality, fetal distress, a 5-minute Apgar score less than 7, and intrauterine growth retardation for those delivered within 7 days of the last test. A test was considered abnormal if two or more parameters fell more than 2 standard deviations from the population mean. A decreased incidence of fetal body movements, amniotic fluid volume, and frequency of FHR acceleration were the most common individual test abnormalities. Test sensitivity (86%), specificity (89%), positive predictive value (75%), and negative predictive value (93%) exceeded those of the "standard" scoring approach and correctly identified all fetuses with malformation, perinatal death, and 19 of 22 fetuses with intrauterine growth retardation.

Amniotic Fluid↗

Fetal assessment based on fetal biophysical profile scoring. IV. An analysis of perinatal morbidity and mortality.

The relationship between the last biophysical profile score result and perinatal outcome was determined among a large referred population of high-risk pregnancies. A highly significant inverse linear correlation was observed for fetal distress, admission to neonatal intensive care unit, intrauterine growth retardation, 5-minute Apgar score less than 7, and umbilical cord pH less than 7.20 but not for the incidence of meconium or major anomaly. A highly significant inverse exponential (log 10) relationship was observed for perinatal mortality in total and by component parts and cause. These data strongly suggest the biophysical profile scoring method of fetal risk assessment is accurate and also provides insight into the extent of fetal compromise.

Female↗

Biophysical mechanisms for morphogenetic progressions at the shoot apex.

Leaf primordia, first visible as small bumps, are produced in a cyclical pattern at the edges of the shoot apex, a smooth region at the top of the stem. Their formation is a biomechanical process. This review first considers hypothetical construction mechanisms and then summarizes research that provides information about how and where the primordia are made. Studies of growth at the primordium site indicate the importance of growth parallel to the surface in generating the forces for primordium emergence. The symmetry of the pattern of reinforcement by cellulose microfibrils correlates with the subsequent pattern of primordium production. Finite element models of the apex reveal that lateral bulging of the apex results in a gradient of shear stress, with high shear at the future primordium site. In contrast, tension parallel to the surface is lowest at the primordium site. Response of apical surface tissue to punctures indicates that an existing primordium can exert a pulling force tangential to its base and a compressive force perpendicular to its base. These observations lead to identification of a continuous biophysical cycle for apex morphogenesis, in which most of the steps are direct physical consequences of the previous step. Biophysical processes, subject to input from genetic, hormonal, and environmental sources, are thus involved in the construction and patterning of leaf primordia.

Computer Simulation↗

Fetal biophysical profile and vibratory acoustic stimulation in high-risk pregnancies.

OBJECTIVES: To determine the influence of the non-stress test (NST) on the efficiency of the fetal biophysical profile (FBP) and to test the clinical usefulness of the FBP and its combination with vibratory acoustic stimulation (VAS) in managing high-risk pregnancies. METHODS: One hundred twenty fetuses of preeclamptic patients were included in a prospective study. Five standard variables of the FBP were observed ultrasonically following NST. In cases of non-reactive NST, external VAS was applied and the FBP score calculated and compared with the FBP score before VAS. RESULTS: Of 120 calculated FBPs, 102 (85%) had normal profile scores before VAS and 104 (86.7%) after VAS. No statistically significant difference was found. The sensitivity, specificity, and positive and negative predictive values of the FBP score in predicting poor perinatal outcome were 94.7%, 94.4%, 75% and 99%, respectively. VAS produced a high conversion (58.8%) of non-reactive NST to reactive fetal heart rate pattern. The false-negative rate of the FBP score was 9.8 per 1000, which did not increase after VAS. CONCLUSIONS: The efficiency of the FBP score was not significantly improved by VAS, although a high conversion of non-reactive to reactive NST was produced. The FBP with its three 'acute biophysical variables' was found to be an accurate method of antepartum assessment even without an NST. The low incidence of perinatal complications among patients with normal FBP scores, permits the conservative management of preterm high-risk pregnancies.

Acoustic Stimulation↗

Specificity of biophysical and biochemical alterations in erythrocyte membranes in neurological disorders--Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and duchenne muscular dystrophy.

Previous studies in our laboratory had demonstrated alterations in the physical state of membrane proteins in erythrocytes in Huntington's disease. In order to assess the specificity of our findings, the results of electron spin resonance studies of protein and lipid components, scanning electron-microscopic studies, enzymatic analyses of membrane-bound sodium plus potassium stimulated, magnesium-dependent adenosine triphosphatase and protein kinase, and cell deformability studies of erythrocyte membranes have been performed in the neurological disorders, Huntington's disease, Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and myotonic and Duchenne muscular dystrophy. Comparison of the results revealed that alterations in the biophysical and biochemical states of erythrocyte membranes in each disorder are specific to the particular disease state with the exception of those in Friedreich's ataxia and Alzheimer's disease. In the latter instance, the clinical and pathological alterations suggest that these two diseases have different primary defects. Our studies suggest that the molecular basis of each disease is different. In addition, the results suggest that biophysical and biochemical investigations of extraneural tissue in Huntington's disease and other neurological disordes have the potential of clarifying the molecular mechanisms by which these diseases arise.

Alzheimer Disease↗

Umbilical artery waveform analysis and biophysical profile. A comparison of two methods to identify compromised fetuses.

Sixty-nine singleton high-risk pregnancies were assessed with both umbilical artery flow velocity waveform analysis and fetal biophysical profile within 10 days of delivery. An abnormal outcome, as defined as either small for gestational age at birth (SGA) or fetal distress during labour, was found in 30 babies. The peak systolic/end diastolic (A/B) ratio from the umbilical artery had a higher sensitivity (37%), specificity (92%), positive predictive value (79%) and negative predictive value (66%) than the fetal biophysical profile (27%, 82%, 53%, and 59%, respectively) in the diagnosis of abnormal outcome. Additional information from a real-time ultrasound assessment, such as the diagnosis of malformations and oligohydramnios could justify a combination of the two methods in antenatal monitoring of high-risk pregnancies.

Blood Flow Velocity↗

Umbilical flow waveforms versus fetal biophysical profile in hypertensive pregnancies.

The pulsatility index (PI) of the umbilical arteries was measured in 40 hypertensive pregnancies. Doppler-velocimetric data were kept unknown to the clinical staff. An abnormal PI was found in 79% of cases in which an abnormal fetal growth in utero had been diagnosed by ultrasonographic measurements. Serial PI findings showed worsening figures in most of the cases with an abnormal fetal growth, irrespective of the last absolute value. Amniotic fluid estimation and PI data were significantly correlated. PI values were markedly abnormal in fetuses with non-reactive heart-rate tracings. A high sensitivity and an optimal specificity were found for umbilical PI versus the diagnosis of fetal growth retardation made by the coexistence of different biophysical criteria. However, false normal results may occur. 62% of the newborns weighed below the 5th percentile. The sensitivity of abnormal PI values to detect these light fetuses resulted to be only 67%. However the prevalence of neonatal morbidity in fetuses with abnormal PI values was 74%, while morbidity occurred only in 14% of cases with normal PI values. In hypertensive pregnancies, this simple velocimetric parameter proved to correlate with abnormal biophysical monitoring and complicated neonatal outcomes.

Birth Weight↗

Biological and biophysical techniques to assess radiation exposure: a perspective.

Biological dosimeters measure biologically relevant effects of radiation exposure that are in some sense an estimate of effective dose, whereas biophysical indicators serve as surrogates of absorbed dose in a manner analogous to conventional thermoluminescent dosimeters (TLD). The biological and biophysical dosimeters have the potential to play an important role in assessing unanticipated or occupational radiation exposures. For example, where the exposure is large and uncertain (i.e. radiation accidents), accurate dose information can help in deciding the most appropriate therapy and medical treatment. Another useful area is that of lifetime accumulated dose determination, and the ability to distinguish between and integrate the exposures from natural and anthropogenic (medical X-rays, indoor radon, natural background radiation, occupational and non-occupational exposures). Also, the possibility to monitor individual response and differences in inherent or induced radiation sensitivity may have important implications for radiation protection. More commonly, this type of dosimetry could be used for routine monitoring to detect and quantify unsuspected exposure, for regulatory purposes or for epidemiological studies of the long-term effects of radiation exposure (e.g. in Japanese A-bomb survivors or in the population surrounding Chernobyl). This review is a comparative study of the existing techniques and their future prospects. It summarizes the sensitivity, reproducibility, limiting dose, dose-rate, energy, LET response, sources of variability and uncertainty, and other practical aspects of each bio-indicator. The strengths and weaknesses of each approach are evaluated on the basis of common criteria for particular applications, and are summarized for each assay both in the text and in tabular form, for convenience. It is clear that no single indicator qualifies to reliably measure occupational exposures at the current levels of sensitivity conventional dosimetry services provide. Most of the bio-techniques are applicable to the detection of relatively high radiation exposures at relatively short times after exposure. Some of the bio-indicators have been identified that are, or offer future prospects for becoming, appropriate bio-indicators for dosimetry needs. However, all methods are subject to biological and other variables that are presently uncontrolled, and represent a major source of uncertainty. These include variations in background signals not directly associated with radiation exposure, inter- and intra-individual variability of radiation response, and genetic and environmental effects. Although these factors contribute to the lack of confidence in biological dosimetry, promising bio-indicators may be applied to large populations to establish the inherent variability and confounding factors that limit quantitative data collection and analysis, and reduce reliability and reproducibility.

Biological Assay↗

Nonspecific cytotoxic cells in fish (Ictalurus punctatus). III. Biophysical and biochemical properties affecting cytolysis.

Nonspecific cytotoxic cells (NCC) from the catfish (Ictalurus punctatus) may comprise a population of cells that are responsible for cellular immunity in the fish. NCC kill a wide variety of transformed target cells, and previous studies have indicated that NCC share properties with mammalian natural killer cells. In the present study, many biophysical and biochemical properties of NCC were defined. NCC were nylon wool nonadherent and adherent. NCC activity was also enriched in plastic nonadherent cells. NCC were nonphagocytic (for carbonyl iron), and they did not bind to Sephadex G-10. Characterization of NCC by density gradient centrifugation indicated that they comprise a relatively homogenous population of cytolytic cells that band at 45.5% Percoll. Moderate to high doses (500-2500 R) of X-irradiation produced a stimulatory effect on NCC lysis of labeled target cells. Additional studies indicated that a soluble suppressor protein in catfish serum (CFS) regulated NCC activity. This S. aureus protein A binding component isolated from CFS suppressed NCC activity. Analysis by SDS-PAGE indicated that the soluble regulatory protein had properties similar to immunoglobulin. These data indicate that NCC share some biophysical properties with mammalian natural killer cells. In addition, NCC appear to be under partial cell regulation by a radiation sensitive suppressor cell and also by a soluble regulator serum immunoglobulin component.

Animals↗

Biophysical characterization of mucin components HTM-1 and HTM-2 from tracheobronchial secretions of cystic fibrosis patients.

Mucins present in the tracheobronchial secretions are responsible for the viscoelastic properties of the mucus. Any changes in the mucin structure may alter the physical properties of mucus and hence its function. Previous studies from this laboratory have reported the isolation and characterization of a major mucin component (HTM-1) and a minor, novel mucin component (HTM-2) from the tracheobronchial secretions of cystic fibrosis (CF) individuals. In the present study, the macromolecular properties of the CF mucin components HTM-1 and HTM-2 were further investigated using biophysical methods. Dynamic light scattering studies showed that CF HTM-1 and HTM-2 had a greater extended structure in buffer containing 0.10 and 0.15 M NaCl than that observed in the presence of 0.03 M NaCl. Also, CF HTM-1 had a compact configuration in the presence of 5 and 10 mM Ca2+, while under similar experimental conditions, the structure of CF HTM-2 was unaffected, indicating differences in the macromolecular properties of CF mucin components. Fluorescent probe binding studies revealed that CF HTM-1 had more hydrophobic probe binding domains than those observed for CF HTM-2. In summary, both biochemical and biophysical characterization suggests structural differences between the CF HTM-1 and HTM-2 components.

Bronchi↗

Selective resolution of plaques and treatment of atherosclerosis by biophysical alteration of "cellular" and "intracellular" properties.

Presenting a totally new approach to the effective treatment of Atherosclerosis through the alteration of biophysical properties both "intracellularly" and "extracellularly." The experimental data is preliminary but the results obtained indicate that by allowing the atherosclerotic lesions to take up the magnetically excitable submicron particles and then applying an external alternating electromagnetic field, the atherosclerotic lesions may be selectively resolved without damaging normal blood vessels. This concept suggests many areas of investigation since there are a variety of means of biophysically altering the atherosclerotic plaques, and many substances may be utilized to enhance the process. This new technology and this initial experimentation introduces a "new era" in the effective treatment of Atherosclerosis.

Animals↗

Renal tolerance to nonhomogenous irradiation: comparison of observed effects to predictions of normal tissue complication probability from different biophysical models.

PURPOSE: A patient series was analyzed retrospectively as an example of whole organ kidney irradiation with an inhomogenous dose distribution to test the validity of biophysical models predicting normal tissue tolerance to radiotherapy. METHODS AND MATERIAL: From 1969 to 1984, 142 patients with seminoma were irradiated to the paraaortic region using predominantly rotational techniques which led to variable but partly substantial exposure of the kidneys. Median follow up was 8.2 (2.1-21) years and actuarial 10-year survival (Kaplan-Meier estimate) 82.8%. For all patients 3-dimensional dose distributions were reconstructed and normal tissue complication probabilities for the kidneys were generated from the individual dose volume histograms. To this respect different published biophysical algorithms had been introduced in a 3-dimensional-treatment planning system. RESULTS: In seven patients clinical manifest renal impairment was observed (interval 10-84 months). An excellent agreement between predicted and observed effects was seen for two volume-oriented models, whereas complications were overestimated by an algorithm based on critical element assumptions. CONCLUSIONS: Should these observations be confirmed and extended to different types of organs corresponding algorithms could easily be integrated into 3-dimensional-treatment planning programs and be used for comparing and judging different plans on a more biologically oriented basis.

Adult↗

[Biophysical membrane correlates of tolerance and dependence on alcohol].

A large number of studies have given clear indications that ethanol does affect the physicochemical properties of the membrane. Membrane reorganization and adaptation can develop against the acute disordering effect of ethanol during chronic intoxication. Nevertheless, there has been so far no direct evidence of correlations between functional tolerance or dependence and membrane physical states. Membrane physical state can be assessed by fluorescence polarization of DPH in the absence (measure of membrane 'fluidity') or presence (measured of membrane sensitivity) of ethanol added in vitro. Functional tolerance has been already correlated with a reduced synaptic membrane sensitivity to ethanol (membrane tolerance). Behavioural dependence was shown to be quantifiable by measurement of alcohol intake in a free choice situation (water/alcohol) solution). This dependence model allowed us to define a membrane dependence which consists in an increased membrane rigidity (or decrease in 'fluidity') persistent after withdrawal, and which was correlated to the intensity of the behavioural dependence. This biophysical expression of dependence seems rather independent of the biophysical membrane tolerance (resistance to the acute ethanol fluidizing effect), which was found to be rapidly reversible after withdrawal and re-induced by alcohol re-intake, requiring recent periods of current abuse to be expected.

Alcoholism↗

Studying biophysical barriers to DNA delivery by advanced light microscopy.

Advanced light microscopy (ALM) has been intensively employed by biophysicists to reveal cellular mechanisms. As described in this review, ALM clearly has potential to enhance our understanding of the mechanisms that affect macromolecular therapeutics or nanoscopic drug vectors in biological environments. However, while in recent years confocal microscopy and related techniques became rather routinely used in drug delivery it remains challenging to extract reliable information on the biophysical behaviour of drug delivery systems from ALM measurements. This review discusses studies in which confocal imaging, fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS) and fluorescence energy transfer were employed to reveal biophysical properties of DNA and DNA containing nanoparticles in extra- and intracellular media.

DNA↗

A biophysical model of atrial fibrillation to define the appropriate ablation pattern in modified maze.

OBJECTIVE: The surgical Maze III procedure remains the gold standard in treating atrial fibrillation (AF); however due to clinical difficulties and higher risks, less invasive ablation alternatives are clinically investigated. The present study aims to define more efficient ablation patterns of the modified maze procedure using a biophysical model of human atria with chronic AF. METHODS: A three-dimensional model of human atria was developed using both MRI-imaging and a one-layer cellular model reproducing experimentally observed atrial cellular properties. Sustained AF could be induced by a burst-pacing protocol. Ablation lines were implemented in rendering the cardiac cells non-conductive, mimicking transmural lines. Lines were progressively implemented respectively around pulmonary veins (PV), left atrial appendage (LAA), left atrial isthmus (LAI), cavo-tricuspid isthmus (CTI), and intercaval lines (SIVC) in the computer model, defining the following patterns: P1=PV, P2=P1+LAA, P3=P2+LAI, P4=P3+CTI, P5=P3+SIVC, P6=P5+CTI. Forty simulations were done for each pattern and proportion of sinus rhythm (SR) conversion and time-to-AF termination (TAFT) were assessed. RESULTS: The most efficient patterns are P5, P6, and Maze III with 100% success. The main difference is expressed in decreasing mean TAFT with a correlation coefficient R=-0.8. There is an inflexion point for 100% success rate at a 7.5s TAFT, meaning that no additional line is mandatory beyond pattern P5. CONCLUSIONS: Our biophysical model suggests that Maze III could be simplified in his right atrial pattern to a single line joining both vena cavae. This has to be confirmed in clinical settings.

Atrial Fibrillation↗

Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF. Anesthesia unmasked Brugada syndrome.

BACKGROUND: Brugada syndrome is an inherited disease associated with sudden cardiac death. The electrocardiographic pattern associated with Brugada syndrome has been linked to the use of sodium channel blockers, including antiarrhythmics, trycyclics and anesthetics. OBJECTIVE: We report a case of bupivacaine-induced Brugada syndrome, in which we investigated the genetic, biophysical and path physiological mechanism involved. METHODS AND RESULTS: The patient developed a Brugada-like electrocardiographic pattern twice under the influence of bupivacaine. The first occurrence was accompanied by ventricular tachycardia (VT) which subsided after withdrawal of the anesthetic. The VT was also observed during co-administration of diltiazem and isosorbide-5-mononitrate, agents thought to facilitate ST segment elevation in the Brugada syndrome. Genetic analysis revealed a missense mutation in the alpha subunit of the cardiac sodium channel, SCN5A. Biophysical analysis by whole-cell patch-clamping revealed a reduction in sodium current as a result of the mutation. The study of bupivacaine in the wedge model revealed use-dependent changes in conduction, heterogeneous loss of the action potential dome in RV epicardium and phase 2 re-entry when the preparations were pretreated with low concentrations of the calcium channel blocker verapamil. CONCLUSION: Our findings indicate that bupivacaine may induce the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in silent carriers of SCN5A mutations. The data have important implications in the management of patients who develop ST segment elevation when under the influence of anesthetics such as bupivacaine.

Anesthesia, General↗