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Fetal assessment based on fetal biophysical profile scoring. III. Positive predictive accuracy of the very abnormal test (biophysical profile score = 0).

The relationship between complete absence of all components of the fetal biophysical profile score (biophysical profile score = 0) and adverse perinatal outcome was examined. Twenty-nine of 28,655 fetuses studied (0.092%) had a last biophysical profile score of 0; 48.3% of these perinates died (14 of 29 fetuses), the majority of whom (11 of 14) were stillborn, with death occurring as early as 30 minutes to as long as 11 days after the last test. Three asphyxia-related neonatal deaths occurred despite aggressive and immediate intervention. All survivors exhibited at least one of the five discrete markers used to assess perinatal morbidity. The positive predictive accuracy of a biophysical profile score of 0, with mortality and morbidity used as end points, was 100%. These data indicate the very abnormal fetal biophysical profile score to be a perinatal emergency.

Acidosis

Intracellular hyperthermia. A biophysical approach to cancer treatment via intracellular temperature and biophysical alterations.

This paper introduces a new multi-disciplinary "intracellular" biophysical treatment of cancer. The basic concept uses locally induced heat energy after tumor phagocytosis of submicron particles whose composition permits magnetic excitation. The key to this process is the utilization of the cancer cell membrane to contain the energy within the cancer cell. Any magnetic or electric dipole contained within or introduced into the cell, or that is capable of being produced by an external field, can be used. Submicron particles are colloidally suspended, injected intravenously and are phagocytized by cancer cells. Application of an external high frequency or pulsed electromagnetic field then raises the particles' temperature thus generating intracellular heat in precise increments. This results in selective thermal destruction of cancer cells with little effect on normal cells. Experimental evidence is presented showing tumor cell destruction in spontaneous mammary tumors in Sprague Dawley rats. In addition, we suggest that certain biophysical properties are altered within the cancer cells and could be used to enhance this effect. Specific radioisotopes or tumor specific antibodies bound to particles or chemotherapeutic microspheres increase cancer cell sensitivity and affinity for these particles. This "intracellular" treatment of cancer has a wide potential range of applications.

Animals

The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in preterm premature rupture of the membranes.

The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in 44 consecutive patients with preterm premature rupture of the membranes were determined. All patients were followed up with daily fetal biophysical profiles and systolic/diastolic ratios. After delivery, placental pathologic examination for histologic evidence of infection (umbilical vasculitis) was performed in all cases according to a standard protocol. The longitudinal trends of fetal biophysical profile scores and systolic/diastolic ratios were analyzed for patients with and without umbilical vasculitis. Analysis of the longitudinal trend during the period of 2 to 7 days before delivery showed that there were no differences of biophysical scores of systolic/diastolic ratios in either group. However, in the last examination, within 24 hours of delivery, patients with umbilical vasculitis had higher systolic/diastolic ratios and lower biophysical profile scores as compared with previous examinations. In addition, the biophysical profile score of the last examination 24 hours before delivery in patients with umbilical vasculitis was found to be significantly lower as compared with patients without umbilical vasculitis (mean +/- SD, 6.6 +/- 2.3 versus 8.2 +/- 2.4, respectively). These data suggest that subclinical stages of infection are associated with biophysical alterations of the fetoplacental unit (i.e., simultaneous decrease in fetal biophysical activities and increase in systolic/diastolic ratios). Daily umbilical artery systolic/diastolic ratios, in conjunction with biophysical profiles, may be useful to follow up patients with preterm premature rupture of the membranes.

Blood Flow Velocity

Biophysical profile as a predictor of amniotic fluid culture results.

The biophysical profile has been proposed as a noninvasive method of detecting fetal infection in patients with preterm premature rupture of membranes (PROM). The purpose of this study was to evaluate the biophysical profile as a rapid predictor of amniotic fluid (AF) culture results in women with PROM. Amniocentesis was performed on 111 patients with PROM at or before 34 weeks' estimated gestational age. Aerobic, anaerobic, Ureaplasma, and Mycoplasma cultures were performed on the AF. A biophysical profile was performed just before the amniocentesis. Women with positive AF cultures had a significantly lower total biophysical profile score, as well as significantly lower scores for nonstress test, fetal breathing movements, fetal movements, and AF volume, than those with negative AF cultures. However, neither the total biophysical profile score nor any of the individual components had sufficient sensitivity, specificity, or positive or negative predictive value to be useful clinically in predicting culture results. Although the incidence of positive AF cultures was inversely related to the biophysical profile score, 48% of patients with a score of 8 and 27% of those with a score of 10 had positive AF cultures. The results of this study do not support use of the biophysical profile as an early predictor of AF culture results in patients with PROM.

Amniotic Fluid

The relationship between fetal biophysical assessment, umbilical artery velocimetry, and fetal acidosis.

In a prospective study of 62 patients undergoing cesarean delivery before the onset of labor, fetal biophysical assessment and umbilical artery systolic-diastolic ratios (S/Ds) were performed within 3 hours of delivery. There was a significant relationship between the fetal biophysical profile score and cord arterial as well as cord venous pH. However, there was no identifiable relationship between S/D and cord arterial or venous pH. The efficacies of the biophysical components alone (nonstress test [NST] and fetal biophysical profile) and in combination with S/D to predict fetal acidosis were determined. The NST had the best sensitivity (100%) and negative predictive value (100%). The fetal biophysical profile had the best specificity (91%), positive predictive value (62%), and overall efficiency (90%). The S/D had the lowest sensitivity (66%), specificity (42%), positive predictive value (16%), negative predictive value (88%), and overall efficiency (45%). The addition of S/D to the NST or fetal biophysical profile did not improve diagnostic accuracy. These data suggest that the NST should be used as a primary test for the antepartum detection of fetal acidosis, whereas the fetal biophysical profile is a reasonable adjunct test. The umbilical artery S/D, as determined by continuous-wave Doppler velocimetry, has no value as a primary method or an adjunct in the antepartum detection of fetal acidosis.

Acidosis

Refining the biophysical profile with a risk-related evaluation of test performance.

OBJECTIVE: Our objective was to determine the ability of biophysical profile variables to predict bad perinatal outcome in high-risk third-trimester pregnancy. STUDY DESIGN: The outcomes of 1146 fetuses were correlated with abnormal single or multiple variables occurring in biophysical profile done within 72 hours of delivery. Theoretic risks of poor outcomes for different combinations of abnormal variables, calculated with Shortlife's formula, were compared with the actual risks observed (chi 2 tests). RESULTS: Two hundred forty-six fetuses had at least one abnormal biophysical profile variable with the risk of bad outcome, for a single abnormal variable, ranging from 8% (body movements) to 100% (tone) and increasing from 14% (any variable abnormal) to 63% (all variables abnormal). In most (57%) observed combinations of biophysical profile variables, significant differences between theoretic and actual risks of bad outcomes were found. By stepwise logistic regression the best predictive model contained all variables except fetal movement. CONCLUSIONS: Dynamic biophysical profile variables appear to be interdependent. Not all combinations of abnormal variables occur and specific combinations improve prediction of poor outcome. Risk-related scales for biophysical profile outcomes might prove superior to more conventional scoring systems.

Biophysics

The abnormal fetal biophysical profile score. V. Predictive accuracy according to score composition.

The relationship between last abnormal biophysical profile score, in total and by variable composition, and a spectra of abnormal perinatal outcome end points was examined in 525 fetuses. Highly significant inverse relationships between last test score and outcome were observed; relationships were linear for most end points and exponential for perinatal mortality end points. For biophysical profile scores less than or equal to 6, 25 of the 26 possible variable combinations were observed, at varying frequencies. For a biophysical profile score of 6, the positive predictive accuracy for some end points was significantly higher with either nonreactive nonstress test/fetal tone absent or nonreactive nonstress test/absent fetal breathing movement, and significantly lower with absent fetal breathing movement and decreased amniotic fluid volume. For a biophysical profile score of 4, the positive predictive accuracy for some end points was significantly higher with nonreactive nonstress test/absent fetal breathing movement/decreased amniotic fluid and was significantly lower with absent fetal movement/fetal breathing movement/fetal tone. No significant variation was observed for a biophysical profile score of 2. These data indicate that not all abnormal biophysical profile scores are equal.

Apgar Score

Comparative studies on the biophysical activities of the low-molecular-weight hydrophobic proteins purified from bovine pulmonary surfactant.

Two low-molecular-weight hydrophobic proteins with nominal molecular weights Mr = 15,000 and Mr = 3,500 have been isolated from the lipid extracts of bovine pulmonary surfactant by several methods, including (a) dialysis plus silicic acid chromatography, (b) elution from Waters SEP-PAK silica cartridges with a variety of solvent mixtures, and (c) ultrafiltration. As detailed in the text, these proteins have been designated surfactant-associated protein-BC (SP-BC) (15 kDa: nonreduced), and SP-C (3.5 kDa). The biophysical activities of reconstituted surfactant containing these proteins and the phospholipids present in lung surfactant have been compared with the biophysical activities of bovine lipid extract surfactant on a pulsating bubble surfactometer using a phospholipid concentration of 10 mg/ml. At this concentration, unmodified lipid extract surfactant reduces the surface tension of the pulsating bubble to near 0 within 10 pulsations at 20 cycles per min. Similar biophysical properties were observed with modified lipid extract surfactant in which the relative concentration of hydrophobic protein had been reduced from 1 to 0.4% (W/W) of the phospholipids by addition of dipalmitoylphosphatidylcholine (DPPC) or DPPC plus phosphatidylglycerol. Reconstituted surfactants, which contained partially delipidated SP-BC (15 kDa: nonreduced) obtained by method (a) at a relative concentration of 0.1%, were also capable of reducing the surface tension to near 0 mN/m. Preparations of SP-BC (15 kDa: nonreduced) obtained by method (b), which had been subjected to very low pH levels during isolation and were extensively delipidated, exhibited full biophysical activity only at higher protein concentrations and with prolonged pulsation. Extensively delipidated samples of SP-BC obtained by method (c) exhibited impaired biophysical activities, even when prepared with neutral organic solvents. Reconstituted surfactant samples containing SP-C (3.5 kDa) obtained by any of the methods listed above were only able to reduce the surface tension at minimum bubble radius to approx. 20 mN/m. The biophysical activity of SP-C (3.5 kDa) was not significantly affected by low pH or extensive delipidation. Reconstituted samples containing mixtures of SP-BC (15 kDa: nonreduced) and SP-C (3.5 kDa) were more effective than samples containing either protein alone. Furthermore, with samples containing both hydrophobic proteins the final surface tensions at maximum bubble radius were attained within a few bubble pulsations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Biophysical inhibition of synthetic lung surfactants.

The biophysical activity and inhibition of a series of synthetic surfactant mixtures was studied and correlated with physiological effectiveness in restoring pressure-volume (P-V) mechanics of excised lungs. Results showed that several simple mixtures of dipalmitoyl phosphatidylcholine (DPPC) with fatty acids or diacylglycerols could be formulated to give good adsorption facility and dynamic surface tension lowering to less than 1 mN/m in pulsating bubble measurements at 37 degrees C. However, although biophysical activity approached that of natural lung surfactant (LS) and a related surfactant extract (CLSE) under normal conditions, surface properties were sharply inhibited by relatively small amounts of the plasma protein albumin (2 mg/ml) with minimum surface tensions greater than 30 nM/m even at high surfactant concentrations (5-20 mg lipids/ml). This sensitivity to biophysical inhibition was markedly increased compared to LS and CLSE, and had direct consequences for physiological efficacy: in spite of initially high activity, synthetic surfactants did not exert beneficial effects on P-V mechanics when instilled into surfactant-deficient excised rat lungs. Endogenous protein material was shown to be present upon surfactant recovery by lavage, and bubble measurements confirmed surface activity well below pre-instillation levels. Moreover, full biophysical activity was restored when lavage fluid was extracted to separate the synthetic surfactants from endogenous inhibitors. These results show that it is important to define relative sensitivity to biophysical inhibition in the development of effective lung surfactant substitutes. In addition, the existence of inhibition effects can generate an apparent lack of correspondence between initial biophysical activity and ultimate physiological actions of exogenous surfactant mixtures.

1,2-Dipalmitoylphosphatidylcholine

Fetal biophysical profile and perinatal death.

Antepartum assessment of 5034 high-risk pregnancies to predict perinatal death included five biophysical variables (nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume) which combined to form a biophysical profile score. We assessed 4148 fetuses within seven days of delivery. The ability of each variable to predict perinatal death was expressed as the likelihood ratio, which incorporates sensitivity and specificity into one number. The predictive ability was most accurate with fetal movement (likelihood ratio 48.1) and the combined biophysical profile score (likelihood ratio 51.0). The biophysical profile score was more likely to predict perinatal death due to asphyxia (seven of eight) than lethal anomaly (six of 19). The overall perinatal mortality was 7.6 per 1000 total births. The perinatal mortality rate was 1.0 for a normal biophysical profile score, 31.3 for an equivocal score, and 200.0 for an abnormal score. The false-negative rate for the biophysical profile score was 0.7 per 1000.

Amniotic Fluid

Two-tier approach to biophysical assessment of the fetus.

The biophysical profile score is widely accepted as a superior predictor of acute-on-chronic fetal asphyxia over the nonstress test. Nevertheless, in the United Kingdom facilities for assessment of high-risk pregnancies by nonstress test are more widely available than with the biophysical profile score. After a retrospective review of 2038 biophysical assessments in 500 high-risk pregnancies, it is suggested that biophysical evaluation of the fetus can be rationalized on the basis of the clinical problem and fetal growth. Terminal acute-on-chronic fetal asphyxia can be excluded by a two-tier method of fetal assessment by initial nonstress test backed up by the biophysical profile score when the nonstress test is suboptimal.

Asphyxia Neonatorum

Antepartum fetal risk assessment: the role of the fetal biophysical profile score.

In the art of medicine we have always known that establishing an accurate diagnosis of health or disease is essential. An active search for the physical signs, both the time honoured and newly discovered, are a crucial step in achieving diagnostic accuracy, in monitoring disease progression, and in assigning prognosis. In extrauterine medicine it is common practice to gather together sets of biophysical data in order to determine immediate health, to monitor condition, and to estimate prognosis: witness the use of vital signs, and, in the newborn, the Apgar score. The providers of perinatal care have known since biblical days that fetal biophysical activities were a reflection of fetal condition (Luke: Chapter 1, Verses 44-45), yet lacked the ability to categorize these activities in an objective and complete manner. The introduction of dynamic ultrasound imaging methods to perinatal medicine at last create the window through which the principles of extrauterine medicine may now be applied to the intrauterine patient--the fetus. Fetal biophysical profile scoring is a method that utilizes this new wealth of information to differentiate the normal fetus from the fetus at risk for death or damage in utero. The method is based on the concept that the discrimination of fetal health and disease improves as more variables are considered. The now extensive clinical experience with the method, in which both overall (gross) and selected (corrected) perinatal death are reduced, while maintaining a remarkably low false negative predictive error, indicate the validity of the concept. Comparative studies lead us to believe that reliance upon single biophysical variables, such as fetal movement counts, or antepartum fetal heart rate monitoring, is no longer of sufficient accuracy to support its use as a sole measure of fetal condition. Looking forward, we anticipate that while the concept on which fetal biophysical profile scoring is based will remain unchanged, inclusion of additional variables is likely to occur. It seems likely that addition of new variables, as may be now measured using high-resolution dynamic ultrasound methods, both B-mode and Doppler, will improve diagnostic accuracy even more. We believe that the application of the current and future modified methods of composite fetal risk assessment will render the occurrence of the tragedy of perinatal loss even more infrequent. While the goal of complete elimination of perinatal deaths remain elusive, this method may be one step towards this goal.

Biophysical Phenomena