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PubMed1993

Ultrahigh resolution matrix-assisted laser desorption/ionization of small proteins by Fourier transform mass spectrometry.

Recent research has demonstrated that matrix-assisted laser desorption/ionization (MALDI) is feasible for Fourier transform mass spectrometric analysis of biomolecules with masses in excess of 50,000 Da. Here, the effects of electrostatic deceleration times and laser energy upon mass resolution are reported. It is demonstrated that optimum deceleration times for singly-charged MALDI-generated protein ions ranging in mass from 2627 to 29,000 Da are a linear function of m1/2 when a 9.5-V decelerating potential is used. Furthermore, higher resolution is obtained with laser fluences close to the threshold for MALDI. Slow metastable decay of molecular ions in the absence of co-matrix is demonstrated for melittin and bovine insulin. It appears that the resolution enhancing effect of co-matrix may result from slowing molecular ion unimolecular decomposition rates sufficiently to allow infrared emission to compete with metastable decay, thus providing the requisite population of long-lived ions for high mass resolution. A spectrum of bovine insulin molecular ion with mass resolution of 30,000 is presented, together with several spectra of lower mass proteins with mass resolution in excess of 100,000. Detection of a doubly-charged carbonic anhydrase trimer ion with a mass of 87,000 Da is reported.

Fourier Analysis↗
PubMed2004

Effect of streptavidins with varying biotin binding affinities on the properties of biotinylated gramicidin channels.

The pentadecapeptide gramicidin A, which is known to form highly conductive ion channels in a bilayer lipid membrane by assembling as transmembrane head-to-head dimers, can be modified by attaching a biotin group to its C-terminus through an aminocaproyl spacer. Such biotinylated gramicidin A analogues also form ion channels in a hydrophobic lipid bilayer, exposing the biotin group to the aqueous bathing solution. Interaction of the biotinylated gramicidin channels with (strept)avidin has previously been shown to result in the appearance of a long-lasting open state with a doubled transition amplitude in single-channel traces and a deceleration of the macroscopic current kinetics as studied by the sensitized photoinactivation method. Here this interaction was studied further by using streptavidin mutants with weakened biotin binding affinities. The Stv-F120 mutant, having a substantially reduced biotin binding affinity, exhibited an efficacy similar to that of natural streptavidin in inducing both double-conductance channel formation and deceleration of the photoinactivation kinetics of the biotinylated gramicidin having a long linker arm. The Stv-A23D27 mutant with a severely weakened biotin binding affinity was ineffective in eliciting the double-conductance channels, but decelerated noticeably the photoinactivation kinetics of the long linker biotinylated gramicidin. However, the marked difference in the effects of the mutant and natural streptavidins was smaller than expected on the basis of the substantially reduced biotin binding affinity of the Stv-A23D27 mutant. This may suggest direct interaction of this mutant streptavidin with a lipid membrane in the process of its binding to biotinylated gramicidin channels. The role of linker arm length in the interaction of biotinylated gramicidins with streptavidin was revealed in experiments with a short linker gramicidin. This gramicidin analogue appeared to be unable to form double-conductance channels, though several lines of evidence were indicative of its binding by streptavidin. The data obtained show the conditions under which the interaction of streptavidin with biotinylated gramicidin leads to the formation of the double-conductance tandem channels composed of two cross-linked transmembrane dimers.

Binding Sites↗
PubMed1997

Protection afforded by maltosyl-beta-cyclodextrin against alpha-chymotrypsin-catalyzed hydrolysis of a luteinizing hormone-releasing hormone agonist, buserelin acetate.

PURPOSE: The present study addresses how maltosyl-beta-cyclodextrin (G2-beta-CyD) impacts upon the alpha-chymotrypsin-catalyzed hydrolysis of buserelin acetate, an agonist of luteinizing hormone-releasing hormone with emphasis upon the direct effect of G2-beta-CyD on the activity of the protease. METHODS: Kinetic and solubility studies were performed in isotonic phosphate buffer (pH 7.4) at 25 degrees C and 37 degrees C. The interaction of alpha-chymotrypsin with G2-beta-CyD in the buffer solution was examined by differential scanning calorimetry. RESULTS: G2-beta-CyD decelerated the alpha-chymotrypsin-catalyzed hydrolysis of buserelin acetate to give the 1-3 tripeptide and the 4-9 hexapeptide fragments. This deceleration can be explained solely by a non-productive encounter between a complex of the substrate with G2-beta-CyD and the protease at relatively low CyD concentrations, while the direct inhibitory effect of G2-beta-CyD on the proteolytic activity made a considerable contribution to the overall deceleration of the hydrolysis at higher CyD concentrations. Calorimetric studies indicate the presence of intermediate states in the thermal unfolding of alpha-chymotrypsin, simultaneously accompanied by the autolysis. By contrast, a two-state thermal unfolding of alpha-chymotrypsin was observed in the presence of G2-beta-CyD, suggesting reduced proteolytic activity upon binding to G2-beta-CyD. CONCLUSIONS: These results suggest that G2-beta-CyD at higher concentrations inhibits the proteolytic action of alpha-chymotrypsin through direct interaction with the protease, as well as through the formation of a non-productive complex with the substrate.

Buserelin↗
PubMed1999

Effects of ventilatory pattern on exhaled nitric oxide in mechanically ventilated rabbits.

BACKGROUND: Nitric oxide [NOexp] is present in exhaled air in many species. During experiments on pressure-controlled inverse ratio ventilation (PCIRV) in rabbits, increased [NOexp] was observed during PCIRV. The present study was undertaken to clarify which component of PCIRV increased [NOexp]. METHODS: Three groups of six New Zealand White rabbits were anaesthetised and mechanically ventilated. Exhaled nitric oxide, lung mechanics and gas exchange were measured using an experimental protocol designed to assess the effects of variations in 1) flow profile, 2) inspiratory time and 3) time-weighted tidal volume. Ventilator settings used were volume and pressure control ventilation at I:E ratios of 1:2 and 4:1. RESULTS: Constant and decelerating flow gave comparable [NOexp] levels (20.0 +/- 6.4 vs. 21.9 +/- 7.7 ppb, n.s.) when time-weighted tidal volume was kept constant. Using conventional (I:E 1:2) or inverted (I:E 4:1) I:E ratios in combination with decelerating flow and constant time-weighted tidal volumes did not alter [NOexp] (26.0 +/- 3.6 vs. 24.0 +/- 5.8 ppb, n.s.). An increased time-weighted tidal volume produced by pressure control with an I:E ratio of 4:1 increased [NOexp] (29.6 +/- 7.4) in comparison to constant (19.3 +/- 4.1, P < 0.05) and decelerating flow ventilation (19.6 +/- 3.6, P < 0.05) with I:E ratios of 1:2. CONCLUSION: The exhaled NO concentration was affected by ventilator setting. Increased levels of [NOexp] were observed with increases in time-weighted tidal volume, whereas changes in flow pattern and inspiratory time did not seem to influence airway NO production or release.

Animals↗
PubMed1999

Speed, size, and edge-rate information for the detection of collision events.

In the present study an alternative analysis to tau was considered that was based on perceived speed and size and that assumed constant deceleration for the detection of collision events. Observers were presented with displays simulating a 3-D environment with obstacles in the path of observer motion. During the trial, observer motion decelerated at a constant rate and was followed by a blackout prior to the end of the display. Observers had to detect which trials resulted in a collision. The results indicate that collision detection varied as a function of the size of the obstacles, observer speed, and edge rate--findings not predicted by an analysis of tau. The results suggest that observers use an analysis based on speed and size information. A model that assumes constant deceleration is proposed for braking control.

Adult↗
PubMed1994

Fear potentiation of acoustic startle stimulus-evoked heart rate changes in rats.

The present study examined the extent to which heart rate changes evoked by acoustic startle stimuli are affected by the development of fear during startle testing. The phasic heart rate responses of rats elicited by a 120-dB startle stimulus were characterized by decelerations that habituated across trials and accelerations that developed across trials in a manner that paralleled the development of freezing behavior. A 92-dB stimulus evoked little freezing or tachycardia, yet evoked decelerations of similar magnitude to the 120-dB stimulus. Pharmacological blockade of autonomic activity was used to uncouple freezing from the heart rate accelerations and to show that the accelerations were not an artifact of the habituating decelerations. These results indicate that heart rate responses to nonsignal stimuli depend critically on a rat's previous experience with those stimuli.

Acoustic Stimulation↗
PubMed1996

Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing. A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment, the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R.N. Leaton, 1994) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli.

Acoustic Stimulation↗
PubMed2000

Involvement of differential efficiency of transcription by esigmas and esigma70 RNA polymerase holoenzymes in growth phase regulation of the Escherichia coli osmE promoter.

Transcription of the gene osmE of Escherichia coli is inducible by elevated osmotic pressure and during the decelerating phase of growth. osmE expression is directed by a single promoter, osmEp. Decelerating phase induction of osmEp is dependent on the sigmas (RpoS) factor, whereas its osmotic induction is independent of sigmas. Purified Esigmas and Esigma70 were both able to transcribe osmEp in vitro on supercoiled templates. In the presence of rpoD800, a mutation resulting in a thermosensitive sigma70 factor, a shift to non-permissive temperature abolished induction of osmEp after an osmotic shock during exponential phase, but did not affect the decelerating phase induction. Point mutations affecting osmEp activity were isolated. Down-promoter mutations decreased transcription in both the presence and the absence of sigmas, indicating that the two forms of RNA polymerase holoenzyme recognize very similar sequence determinants on the osmE promoter. Three up-promoter mutations brought osmEp closer to the consensus of Esigma70-dependent promoters. The two variant promoters exhibiting the highest efficiency became essentially independent of sigmas in vivo. Our data suggest that Esigmas transcribes wild-type osmEp with a higher efficiency than Esigma70. A model in which an intrinsic differential recognition contributes to growth phase-dependent regulation is proposed. Generalization of this model to other sigmas-dependent promoters is discussed.

Bacterial Proteins↗
PubMed2002

The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico.

Hypomorphic mutants affecting the Drosophila insulin/IGF signal pathway are reported to increase longevity in females but not in males. To understand this sex-difference, we conducted a large-scale demographic study with three new isogenic strains of alleles at chico, the insulin-receptor substrate homologue. We verify that female dwarf homozygotes (ch1/ch1) and normal-sized heterozygotes (ch1/+) are long-lived, as originally reported. We find for the first time that male heterozygotes are long-lived relative to wildtype, by about 50%. The life span of male ch1/ch1 is similar to that of wildtype but these dwarf males age at a slow demographic rate. The levels of demographic frailty and of age-independent mortality are elevated in ch1/ch1 males, counteracting the effect of slow aging upon life expectancy. Mortality deceleration occurs amongst the oldest-old wildtype adults, as seen in many organisms. Remarkably, in similarly sized cohorts of male and female ch1/ch1 and of male ch1/+ mortality deceleration is absent. Mortality deceleration is a phenotype of chico.

Aging↗
PubMed2002

Doppler-derived mitral and pulmonary venous flow variables are predictors of pulmonary hypertension in dilated cardiomyopathy.

This study assessed whether Doppler-derived mitral and pulmonary venous flow parameters were predictors of pulmonary artery hypertension in patients with left ventricular dysfunction. Doppler echocardiographic examinations were performed in patients (n = 100) with dilated cardiomyopathy in sinus rhythm either symptomatic or asymptomatic before and after optimized therapy with ACE inhibitors, diuretics, and vasodilators. In case of weak or poor Doppler signals, measurable tricuspid regurgitation and pulmonary venous flow tracings were obtained after intravenous administration of 2.5 grams of Levovist at 400 mg/ml. At baseline, left ventricular ejection fraction was 30% +/- 7% and pulmonary artery systolic pressure was 48 +/- 14 mmHg. At the follow-up study carried out after 6 +/- 2 months, reversibility of pulmonary artery hypertension was apparent only in those patients exhibiting favorable changes of mitral flow curve from the restrictive or pseudonormal to impaired relaxation pattern (53 +/- 7 mmHg vs 38 +/- 8 mmHg; P < 0.0001). Numerous variables correlated significantly with pulmonary artery systolic pressure at baseline, while the correlations were generally weaker at the follow-up study. The closest correlations were found with E wave deceleration rate (r = 0.73) at baseline and with the systolic fraction of pulmonary venous flow forward peak velocities (r = -0.67) at follow-up. The stepwise regression model showed that the E wave deceleration rate and the degree of mitral regurgitation were the strongest independent predictors of pulmonary hypertension at baseline, while the ratio between pulmonary venous flow reverse and mitral wave velocities at atrial systole and ejection fraction added minor contributions, leading to a cumulative r value of 0.81. The systolic fraction was the strongest at the follow-up study, with minor contributions provided by the E wave deceleration rate and the left atrial dimension index, leading to a cumulative r value of 0.71.

Aged↗
PubMed2000

Mitral flow derived Doppler indices of left ventricular diastolic function in a general population; the Tromso study.

AIMS: Left ventricular diastolic dysfunction has been proposed as the basis of heart failure in patients with normal left ventricular systolic function. Doppler indices of mitral inflow have been widely used to diagnose this condition and have been shown to correlate well with increased left atrial pressure in patients with cardiovascular disease. We wanted to establish age-specific criteria for normality of these indices in a large population and to determine the association of abnormal values to age and cardiovascular disease. METHODS AND RESULTS: In our sample of subjects aged 25-85 years, 3022 had pulsed Doppler measurements of mitral inflow velocities and early inflow deceleration time. The association of these indices to age and gender were established in a 'healthy' reference subsample of 949 subjects. Age-specific percentiles showed a significant decline with increasing age for peak early mitral inflow velocity and the ratio of peak early and atrial inflow velocities (E/A ratio), whereas early inflow deceleration time and peak atrial inflow velocity showed a significant increase with increasing age. According to current criteria for diastolic dysfunction, the prevalence of dysfunction decreases with increasing age in the general population, as well as in the subgroup with cardiovascular disease. Only 7% of the variance in deceleration time was explained by cardiovascular disease or risk factors. For the E/A ratio, however, 41 and 48% of the variance were explained for men and women, respectively. CONCLUSION: Age- and gender-specific criteria for normality are provided. Our data confirm the existence of a significant effect of age and gender on mitral Doppler indices of diastolic dysfunction. However, Doppler criteria for diastolic dysfunction based on these measurements need revision.

Adult↗
PubMed2002

Doppler echocardiographic evaluation of right ventricular diastolic function in hypertrophic cardiomyopathy.

AIMS: Left ventricular diastolic function in patients with hypertrophic cardiomyopathy has been adequately studied. In contrast there are few studies concerning right ventricular diastolic function in hypertrophic cardiomyopathy. We studied right ventricular diastolic function in patients with hypertrophic cardiomyopathy using Doppler echocardiography. METHODS AND RESULTS: We studied 20 patients with hypertrophic cardiomyopathy (mean age 43.6+/-13.8 years) and 20 healthy volunteers (control group, mean age 43+/-13.8 years). We calculated left ventricular and right ventricular diastolic indices using pulsed Doppler echocardiography. Hypertrophic cardiomyopathy patients compared with controls had significantly lower right ventricular-E/A ratio (1.01+/-0.40 vs 1.30+/-0.28, P<0.04), significantly prolonged right ventricular isovolumic relaxation time (170+/-72 vs 32+/-23 ms, P<0.001), and also significantly prolonged right ventricular deceleration time (160+/-58 vs 118+/-35 ms, P<0.01). There was also strong significant correlation between right ventricular deceleration time and left ventricular deceleration time (r=0.78), right ventricular-E/A ratio and left atrial filling fraction (r=-0.55) and between right atrial filling fraction and left atrial filling fraction (r=0.75). CONCLUSIONS: Right ventricular diastolic function in patients with hypertrophic cardiomyopathy is impaired, reflecting abnormal relaxation. Right ventricular diastolic indices correlate well with those of left ventricle.

Adolescent↗
PubMedDate not supplied

[3-dimensional image analysis of the shoulder joint--a new method for characterizing parameters of shoulder joint function].

OBJECTIVE: An exact assessment of shoulder movement is of special importance both in the diagnosis of and in the therapy for different shoulder diseases. Therefore, we developed a feasible method for the analysis of shoulder movement. METHODS: On the basis of an ELITE system and 6 skin markers (marker positions. acromion, humerus, olecranon, proc. styloideus ulnae, cervical and thoracic spine), movement analysis was performed during continuous abduction of the arm over 15 s. With the help of a purpose made software we determined the exact angle of abduction and, in addition, the acceleration (+aAC) and the deceleration (-aAC) of the acromion. We evaluated 12 normal subjects (10 male, 2 female, average age 29 yrs) without shoulder conditions and 8 patients (6 male, 2 female, average age 46 yrs.) with unilateral impingement syndrome stage II according to Neer. RESULTS: In addition to a significantly diminished abduction ability in patients with impingement syndrome, our results also revealed significantly decreased acceleration values for the acromion in impingement patients. In contrast, deceleration values for the acromion were not altered in patients with impingement syndrome. CONCLUSION: The presented method allows exact measurements of shoulder movement. In addition, measurements of acromion acceleration and deceleration seem to offer two parameters for the assessment of shoulder function in pathological conditions. Further investigations are required to prove the advantages and limitations of this method.

Adult↗
PubMed2002

[Computer-assisted analysis of intrapartum cardiotocodynagraphs].

OBJECTIVE: To develop a numerical index by quantifying characteristic cardiotocography parameters in order to determine the intrauterine state of the fetus sub partu with sufficient accuracy to improve the diagnostic potential of cardiotocography. This score is then computerized for offline and online analysis. METHODS: The last 120 minutes of 406 directly recorded intrapartal cardiotocograms (CTG) were evaluated with a magnifying glass on the basis of conventional criteria. The mean basal frequency, the amplitude and the oscillation frequency of each individual baseline minute, the decelerations with depth, duration and type classification as well as the accelerations were determined. The Apgar score and the measurements of blood gases in the umbilical arterial and venous blood served as outcome parameters. The actual pH in the umbilical artery (UA) was the key variable. The newly developed CTG score was converted into a complex programming language after meticulous statistical testing and prepared for offline and online use. RESULTS: A score which is based on the CTG characteristics basal frequency level, baseline fluctuation and total decelerations area was developed on the basis of about 40 000 baseline minutes and more than 8 000 analysed decelerations from 406 fetuses which were all vaginal deliveries with a rate of acidosis (pH,UA < 7.100) of 9.8 % (deliberate selection). This score correlates highly significantly (r = -0.5752) with the actual umbilical arterial pH (p < 0.001). The correlation with the Apgar score (1 min) is r = -0.398, p < 0.001. The positive likelihood ratio (score 9) is 11.0 (95 % confidence interval 7.4-16.5) indicating that the test is very reliable. The score could be prepared for offline analysis of electronically registered CTGs with the assistance of a mathematician, so that the obstetrician's "eye work" can be dispensed with entirely. This program written in "C" also enables online evaluation of fetal heart rate patterns over time and a representation of the output parameters with acoustic and optical warning display options appropriate for the delivery room. CONCLUSIONS: Quantitative registration of fetal heart rate phenomena during delivery can be accomplished successfully by means of a score. The score correlates highly significantly with the actual pH value (UA) and the Apgar score (1 min). It is suitable both for offline and online analysis of intrapartal CTGs, and offers the prospect of quantitative fetal online monitoring.

Apgar Score↗
PubMed2005

Recurrent antepartum compression of a single artery double nuchal cord necessitating emergency cesarean delivery.

Fetuses with a single umbilical artery are considered at increased risk for chromosomal and structural abnormalities, and increased adverse perinatal outcome. A young nulliparous patient was followed with weekly nonstress testing due to well-controlled gestational diabetes, a single umbilical artery, and a double nuchal cord. At 31 weeks gestation, following the occurrence of a severe prolonged variable deceleration of the fetal heart rate the patient was hospitalized for close fetal surveillance with consideration that the deceleration may represent recurring intermittent compression of the single umbilical artery. Continuous fetal monitoring depicted recurrent severe variable decelerations of the fetal heart rate. Thirty-six hours after admission, prolonged fetal bradycardia to 60 bpm necessitated emergency cesarean delivery of a nonhypoxic nonacidotic fetus, which subsequently did well. This case suggests that fetuses with a single umbilical artery nuchal cord(s) may be at increased risk of significant umbilical cord compression.

Adult↗
PubMed1998

The fetal admission test and intrapartum fetal death.

Our objective was to describe the admission and subsequent intrapartum fetal heart rate (FHR) patterns in 21 singleton term pregnancies with an intrapartum fetal death. Through a retrospective chart review, 21 pregnancies with a term intrapartum fetal death were divided into 2 groups based on the fetal admission test (FAT): Group I-reactive (one or more FHR accelerations of 15 bpm x 15 sec in the first 30 min of monitoring); and Group II-nonreactive (NR [the absence of accelerations]). The FAT was compared with the subsequent intrapartum FHR pattern. Of the 21 deaths, the FAT was reactive in 7 fetuses (33%) or NR in 14 fetuses (67%). While the demographic features of these groups were statistically similar, Group II had higher rates of meconium (12 out of 14 (86%) vs. 2 out of 7 [29%] p = 0.017) and admission FHR decelerations (9 out of 14 (64%) vs. 1 out of 7 [14%] p = 0.06). In Group I, a sudden catastrophic event such as a uterine rupture produced a prolonged FHR deceleration in six fetuses (86%). One (14%) fetus died after a Hon pattern. In Group II, four patients had a stair steps to death pattern. Intrapartum fetal death can occur after a reactive or NR FAT. With a reactive FAT, a catastrophic event appears necessary to cause fetal death. The higher rates of meconium, FHR decelerations, and stair steps to death patterns in the NR group suggest the underlying basis for the fetal demise was related to preadmission fetal compromise.

Adult↗
PubMed1991

Hyperstimulation contraction stress tests: an evaluation of outcome by test pattern.

Contraction stress tests (CSTs) interpreted as equivocal, with hyperstimulated contractions accompanied by late decelerations (hyperstimulation CSTs), were analyzed by test pattern and outcome and compared to a control group with negative CSTs. Outcome was evaluated for subsequent abnormal CST, low Apgar score, the presence of meconium, and cesarean section for fetal distress. Patients with hyperstimulation CSTs and solitary late decelerations, and the remainder of the test interpretable as a negative CST, had the least morbidity. In both the presence and absence of 10-minute negative windows, patients with more than one late deceleration were at significantly higher risk for cesarean section for fetal distress than controls. It would seem warranted in the presence of hyperstimulation CSTs, therefore, to repeat the CST within 24 hours regardless of the presence of a negative window.

Cesarean Section↗
PubMed1990

[Acute and chronic reduction of diastolic blood flow velocity in fetal umbilical arteries: a Doppler ultrasound study].

The significance of increased placental resistance for the development of fetal distress was examined in 800 pregnant women by pulsed Doppler flow velocimetry of the umbilical arteries. Moderately elevated resistance with reduced diastolic flow velocities with forward flow throughout the diastole, leads to an increased frequency of cesarean section for fetal distress and to a more negative fetal outcome. Severely elevated resistance of the fetal placental circulation shows absent diastolic velocities or even a diastolic reverse flow in the umbilical arteries. In 90% of 25 pregnancies this flow pattern leads to a premature delivery by cesarean section for fetal distress or to intrauterine fetal death. Standardised conditions of the Doppler signal measurement are required, before an absence of diastolic flow velocities is diagnosed. Acute changes in the resistance of the fetoplacental circulation were measured in 6 fetuses showing variable decelerations of the fetal heart rate (FHR). In 3 fetuses the flow curves showed a rapid change from normal to absent and to reverse diastolic flow during a period of time of 20-25 sec, which can indicate an acute resistance and a mechanical occlusion of the umbilical cord. Nevertheless, we found in 2 fetuses variable decelerations without any changes in the flow pattern of the umbilical arteries except for a frequency effect. One fetus showed both types of flow changes. Since two completely different sorts of flow changes exist, we conclude, that umbilical cord compression is not always the cause of variable decelerations of the FHR.

Asphyxia Neonatorum↗