[Macroscopic and histopathological changes in the fetal appendages as a factor in the pathogenesis of intrauterine fetal death ].

BACKGROUND: Intrauterine fetal death is an agonizing, often unpredictable event. Autopsies of stillborn fetuses, including placentas, umbilical cord and fetal membranes, are performed to clarify the cause of death. Autopsy results are not always easily understood by the patients and difficult to clarify by the specialists. OBJECTIVE: To evaluate the macroscopic pathological and histopathological changes in placenta, umbilical cord and fetal membranes as a factor in the pathogenesis of intrauterine fetal death. MATERIALS AND METHODS: Retrospective review of 129 autopsy reports of singleton stillborn fetuses and placentas from 23 to 41 weeks of gestation. RESULTS: Macroscopic and histopathological findings in the placenta, often in combination with inflammatory changes prevailing in premature cases, while macroscopic and histopathological findings in umbilical cord predominate in term stillborn. In 11% of cases there were no specific pathological findings. CONCLUSIONS: Pathological analysis of the placenta is essential for clarifying the pathogenesis of stillbirths. Simplifying the classification of pathological results of fetal appendages at autopsy categories--changes in the placenta, changes in the umbilical cord and inflammatory changes may contribute to easier interpretation and allows for comparison of results.

[Identification the risk of preterm labor :the role of fetal fibronectin].

UNLABELLED: Fibronectins represent a group of glycoproteins, which form "molecular glue" and are necessary in the interaction between a cell and a cell. The existence of fetal fibronectin in pregnant woman's vagina up to 22 g.w. is normal. In a normally proceeding pregnancy between 22 g.w. and 35 g.w. there is not supposed to be found fetal fibronectin in cervico-vaginal secretion. Its presence is a highly informative biological marker for the risk of premature birth. AIM: The aim of this research was to determine the risk for premature birth through applying fetal fibronectin test as a specific marker to pregnant women with or withthout symptoms of threatened birth. METHODS: A prospective longitudinal study has been carried out. The tests have been applied to hospitalized patients in University hospital "Majchin dom", Clinic of Pathologic pregnancy and Delivery room. Tests have been applied on 116 patients in totally). The pregnant have been separated in two groups depending on the fact of presence or absence of premature birth symptoms. The screening methods used were: the fFN test and the cervical length measurement by transvaginal according to an established protocol. CONCLUSION: From the total of 116 patients, in 78 we have received positive tests for fetal fibronectin; in 38 - negative test. With asymptomatic patients, having higher risk of preterm birth, the percent of positive tests has been lower (14%). With asymptomatic patients with higher percent of risk factors have been: short cervix (38%), multiple pregnancy (29%), followed by patients with diagnosis of preterm birth in the past (25%) and bleeding in earlier terms. Estimating positive and negative predictive rate, we have achieved following results: The test for fetal fibronectin has excellent predictive rate - 97%, which coincides with the great deal of research until this moment in the world. Referring to the positive predictive rate--it is not sufficient--only 19%.

[Causes of stillbirths according to the period of pregnancy].

INTRODUCTION: Stillbirths represent 50% of all perinatal mortality and remain significant and unanswered problem. OBJECTIVE: To investigate the causes of stillbirths in term and preterm fetuses and place of intrauterine growth retardation in the pathogenesis of antenatal death. MATERIALS AND METHODS: The study was retrospective for the period 2008 to 2013, covers 217 cases of stillbirths in University Hospital "Maichin dom" Sofia. Gestational age was from 23 to 41 weeks. Inclusion criteria for the study were: antenatal occurred dead and singleton pregnancy. Exclusion criteria: fetal malformations and multiple pregnancies. Thus number of enrolled cases was 153. RESULTS: The causes of stillbirths are different in different groups according gestational age. The cases of unknown cause, abruption of placenta and preeclampsia prevail in preterm group. The term stillborns headed with pathology of the umbilical cord, followed by cases of unknown cause, diabetes and infection. Overall, preterm group stillborn with mass below 10 percentile for the gestational age - 53 % predominate, compared with those born at term - 39%. CONCLUSIONS: The incidence of stillbirths is higher in preterm than term born fetuses. The causes of antenatal death in preterm is mainly abruption of placenta and preeclampsia, whereas in term - pathology of the umbilical cord. In premature stillborn intrauterine growth retardation is more common in comparison with those on term. Unexplained antenatal fetal death is more common in preterm fetuses.

[Tocolysis with nifedipin; its use in current practice].

AIM: The aim of the study is to establish the safety and efficacy of calcium channel blocker- Nifedipin as tocolytic agents. A wide range of tocolytics have been utilized for the management of preterm labor Calcium channel blockers, namely nifedipine, gained popularity as tocolytics due to the oral route of administration, availability of immediate- and slow-release preparations, the low incidence of maternal adverse effects associated with their use, and the fact that they are inexpensive. METHODS: 88 pregnant women in preterm labor participated in a prospective longitudinal study Inclusion criteria were: gestational age between 24 and 34 weeks gestation; uterine contractions in 10-15 min interval; single pregnancy, lack of contraindications for tocolysis. In all cases the calcium antagonist Nifedipine was used in dosage 4 x 10 mg per os. The clinical response to tocolysis, gestational age at delivery and potential side effects were analyzed. RESULTS: 91 pregnant women participated in the study. Three were excluded because they refused to participate. 88 pregnancies were finally analyzed. In nine of them maternal contractions persisted despite of treatment. The other 79 pregnancies were delayed 48 hours to receive antenatal corticosteroids. From all these 79 pregancies 66 delayed 7 days. The most common adverse effects were tachycardia, hypotonia, headache, dizziness, but they escape soon after the first dose. CONCLUSION: Nifedipine is an effective oral tocolytic with few maternal side effects.

[Perinatal mortality of IUGR neonates].

This study was conducted to evaluate the role of intrauterine fetal growth restriction (IUGR) in the perinatale mortality. A prospective study was designed, including 329 consecutive singleton pregnancies between 24 to 40 weeks' gestation, whose body weight is under 10th percentile for the gestational week. The control group consist of 530 appropriate for the gestational week (AGA) in the same period of gestation. The fetuses are without inborn malformations. The results show grater stillbirth rate in the group of hypotrophic than in the eutrophic neonates. In the group under 27th week of gestation is 2.6% forAGA and 8.3% for IUGR, for the group between 28-31 w.g. is 9.6% and 21.1% respectively and for 32-35 wg. is 2.3% against 13.1%. Perinatal mortality rate (stillbirth and demised before discharged) for the group before 27th w.g. is 65.8% for AGA and 72.2% for IUGR (P > 0.05). Between 28-31 w.g. is 28.4% and 50.0%, for 32-35 is 6.9% and 27.8% respectively (P > 0.01). After 37th w.g. perinatal mortality rate is less in AGA than in SGA fetuses. In conclusion the stillbirth rate is more frequent in IUGR fetuses than in AGA and frequencies is more pronounce in late preterm pregnancy. The fetal hypotrophy has deleterious effect on neonatal survival rate.

[Identification of preterm labor: the role of fetal fibronectin in parents with symptoms].

AIM: To determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery. Fetal fibronectin, a large molecular weight glycoprotein produced in the chorion, is expressed in cervical and vaginal secretions in women with disruption of the choriodecidual junction by labor or by inflammation. METHODS: A prospective observational longitudinal study from January 2013 till December 2013 was performed on patients between 24 and 32 weeks of gestation with symptoms of preterm labor, intact membranes, and cervical dilation < 4 cm (total patients = 86). The endpoint was the delivery at 34 weeks or more. The screening methods used were: the fFN test and the cervical length measurement by transvaginal according to an established protocol. CONCLUSION: The presence of FFN in vaginal or cervical secretions before 35 weeks is a is a strong predictor that preterm delivery is unlikely within the next 7 to 14 days. The predictive power of FFN is stronger at earlier gestation ages (24-29 wks) than it is later in pregnancy and is stronger for short-term prediction (7-14 d).

The spectral changes in EMG during a second bout eccentric contraction could be due to adaptation in muscle fibres themselves: a simulation study.

The mechanism of marked reduction in damage symptoms after repeated bout of similar eccentric contractions is still unknown. The neuronal adaptation leading to reduction of muscle fibre propagation velocity (MFPV) due to increased activation of slow-twitch motor units (MUs), decrease in activation of fast-twitch MUs, and/or increase in MU synchronization was suggested as a cause for lower EMG frequency characteristics. However, the repeated bout effect could occur also after electrically stimulated exercise. Prolonged elevation of cytoplasmic Ca(2+) due to the increased membrane permeability after eccentric contractions was reported. Elevated Ca(2+) induced peripheral changes that included alteration of intracellular action potential and MFPV reduction. We simulated and compared changes in EMG frequency characteristics related to effects of central nervous system (CNS) or to peripheral changes. The simulations were performed for different electrode arrangements and positions. The results showed that the peripheral effects could be similar or even stronger than the effects related to CNS. We hypothesised that the repeated bout effect was a consequence of the adaptation in muscle fibres necessary for avoiding Ca(2+)-induced protein and lipid degradation due to Ca(2+) overload resulting from the increased membrane permeability after eccentric contraction. The possibilities for noninvasive testing of this hypothesis were discussed.

Simulation analysis of interference EMG during fatiguing voluntary contractions. Part II--changes in amplitude and spectral characteristics.

Capabilities of amplitude and spectral methods for information extraction from interference EMG signals were assessed through simulation and preliminary experiment. Muscle was composed of 4 types of motor units (MUs). Different hypotheses on changes in firing frequency of individual MUs, intracellular action potential (IAP) and muscle fibre propagation velocity (MFPV) during fatigue were analyzed. It was found that changes in amplitude characteristics of interference signals (root mean square, RMS, or integrated rectified value, IEMG) detected by intramuscular and surface electrodes differed. RMS and IEMG of surface detected interference signals could increase even under MU firing rate reduction and without MU synchronisation. IAP profile lengthening can affect amplitude characteristics more significantly than MU firing frequency. Thus, an increase of interference EMG amplitude is unreliable to reflect changes in the neural drive. The ratio between EMG amplitude and contraction response can hardly characterise the so-called 'neuromuscular efficiency'. The recently proposed spectral fatigue indices can be used for quantification of interference EMG signals. The indices are practically insensitive to MU firing frequency. IAP profile lengthening and decrease in MFPV enhanced the index value, while recruitment of fast fatigable MUs reduced it. Sensitivity of the indices was higher than that of indices traditionally used.

Simulation analysis of interference EMG during fatiguing voluntary contractions. Part I: What do the intramuscular spike amplitude-frequency histograms reflect?

Decline in amplitude of EMG signals and in the rate of counts of intramuscularly recorded spikes during fatigue is often attributed to a progressive reduction of the neural drive only. As a rule, alterations in intracellular action potential (IAP) are not taken into account. To test correctness of the hypothesis, the effect of various discharge frequency patterns as well as changes in IAP shape and muscle fibre propagation velocity (MFPV) on the spike amplitude-frequency histogram of intramuscular interference EMG signals were simulated and analyzed. It was assumed that muscle was composed of four types of motor units (MUs): slow-twitch fatigue resistant, fast-twitch fatigue resistant, fast intermediate, and fast fatigable. MFPV and IAP duration at initial stage before fatigue as well as their changes differed for individual MU types. Fatigability of individual MU types in normal conditions as well as in the case of ischaemic or low oxygen conditions due to restricted blood flow was also taken into account. It was found that spike amplitude-frequency histogram is poorly sensitive to MU firing frequency, while it is highly sensitive to IAP profile lengthening. It is concluded that spike amplitude-frequency analysis can hardly provide a correct measure of MU rate-coding pattern during fatigue.

Positional distribution of fatty acids in rabbit lung phospholipids and triacylglycerols and effect of prolonged hyperoxy.

Investigations have been carried out for the determination of the effect of high oxygen concentration in inspired gas mixutre on the positional distribution of fatty acids in rabbit lung phospholipids and triacylglycerols. The following results were obtained: 1. In the phosphatidylcholine fraction, the high oxygen concentration caused a quantitative increase of palmitic acid (16 : 0) at the alpha-position, and of myristic (14 : 0), heptadecenic (17 : 1) and arachidonic (20 : 4) acids at the beta-position. 2. In t-e phosphatidylethanolamine fraction, the high oxygen concentration caused an increase of oleic acid (18 : 1) at the alpha-position, and of palmitoleic (16 : 1) and heptadecenic (17 : 1) acids at the beta-position. 3. In the triacylglycerol fraction such changes were not observed. In connection with these effects of oxygen, its possible influence on membrane structures in the lung has been discussed.

Simulation analysis of the performance of a novel high sensitive spectral index for quantifying M-wave changes during fatigue.

A high sensitive fatigue index is desired to improve stimulation strategy and to prevent muscle damage in functional electrical simulations. The great number of indexes used shows that there is no index that satisfies all investigators. A way to develop a high sensitive index for quantifying M-wave changes during fatigue and to estimate its performance was analyzed. The changes in M-wave and its frequency distribution due to variations of intracellular action potential (IAP) and muscle fibre propagation velocity (MFPV) with fatigue were simulated. It was found that the ratio between the spectral moments of order -1 and 2 was considerably more sensitive to peripheral muscle fatigue than the mean (the ratio between the spectral moments of order 1 and 0) and median frequency traditionally used. The sensitivity of the new index depended on the electrode arrangement and position in respect to the active fibres. The belly-tendon detection promised the highest index sensitivity. The length of the active fibres also affected the index sensitivity. The shorter the fibres the lower was the index sensitivity. The sensitivity of the new index could be relatively high even in the case of traditionally used high-pass cut-off frequencies that could distort the M-wave shape.

Intracellular action potential generation and extinction strongly affect the sensitivity of M-wave characteristic frequencies to changes in the peripheral parameters with muscle fatigue.

Changes in muscle fibre propagation velocity (MFPV) and shape of intracellular action potentials (IAPs) accompany peripheral muscle fatigue. We have shown through mathematical simulations that the effects of IAP generation and extinction reduced the sensitivity of the mean (fmean) and median (fmed) frequency of M-wave power spectra to individual changes in MFPV. Due to the differences in weighting of the spectral components used for calculation of the characteristic frequencies, the highest spectral components of the M-wave affected the fmean more than the fmed. These components are related to the M-wave leading edge that reflects the IAP depolarization phase. They reduced the sensitivity of the spectral moment of order 1 to individual changes in MFPV and increased its sensitivity to IAP changes. Since the changes of the IAP depolarization phase during the final stages of peripheral muscle fatigue affected the fmean more, the range of the relative reductions of the fmean and fmed were approximately the same under combined changes in IAP and MFPV. The sensitivities of M-wave characteristic frequencies depended also on the electrode arrangement and position as well as on the length of active muscle fibres.

Estimate of M-wave changes in human biceps brachii during continuous stimulation.

The purpose of the present study was to validate the capability of new fatigue indexes (in the time and frequency domain) applied to experimental recordings and thus, to test some assumptions made in previous simulations. The indexes were applied to M-waves detected non-invasively from human m.biceps brachii during repetitive slightly above threshold stimulations. It was found that distance between the motor point and middle of the end-plate region could be relatively large. Under identical conditions (signals detected by monopolar electrodes and high-pass filtered at 1 Hz), the relative changes of the indexes obtained in electrophysiological experiments and simulations were similar. Changes of the intracellular action potential profile during fatigue used in the simulations were consequently supposed to be close to the actual ones for the muscle analyzed. When the high-pass cut-off frequency was higher than 1 Hz, the sensitivity of the index in the time domain was higher, while that in the frequency domain was lower. If the normalizing spectral moment was of higher order, the sensitivity of the spectral index could be even 150-times greater than that of the fatigue indexes traditionally used. Thus, the spectral index promises high capability to assess fatigue during functional electrical stimulation.

Estimation of the muscle fibre semi-length under varying joint positions on the basis of non-invasively extracted motor unit action potentials.

Changes in muscle fibre length and surface electrode position with respect to the muscle fibres affect the amplitude and frequency characteristics of surface electromyography (SEMG) in different ways. Knowledge of changes in muscle fibre length would help towards a better interpretation of the signals. The possibility of estimating the length through SEMG during voluntary contractions was checked in this study. The fibres' semi-length was estimated from the product of the conduction velocity and conduction time during which the wave of excitation propagated from the end-plate region to the ends of the fibres. Short (10 s), moderate (30% of maximum voluntary contraction) isometric contractions were performed by 10 subjects at different elbow joint angles (80-140 degrees in steps of 20 degrees ). Monopolar signals were detected non-invasively, using a two-dimensional electrode array. High spatial resolution EMG and a decomposition technique were utilised to extract single motor unit activities for triggered averaging and to estimate conduction velocity. A significant increase with joint angle was found in conduction time and estimated fibre semi-length. Changes in conduction velocity with joint angle were found to be not significant. The methodology described allows the relative changes in fibres' semi-length to be estimated from SEMG data.

Retinal location and visual localization during pursuit eye movement.

Experiments were performed to measure the mislocation of a brief visual stimulus presented during pursuit eye movements in different places over the retina. The results obtained show that the mislocation for regions 5 degrees from fovea in the direction of motion is greater than in fovea. This fact shows that some kind of reorganization takes place in the visual localization mechanisms during pursuit eye movements. The results cast doubts on the concept of "perception time" which is often used to explain the visual mislocation phenomenon.

Temporal thresholds and reaction time to changes in velocity of visual motion.

A random dot pattern moved at a velocity V1. The velocity then increased or decreased abruptly to another value V2 for some time and again returned to V1. The temporal threshold, i.e. the duration of V2 that was necessary to detect the change was measured. Thresholds for the detection of the same velocity increment, V2 = 2 x V1, were shorter when the baseline velocity V1 increased from 1 to 8 deg/sec (Expt 1). The temporal threshold decreased as the velocity contrast (V2 - V1)/(V1 + V2) increased from 0.33 to 0.77. The thresholds for the detection of velocity decrements were in general longer than those for the detection of increments (Expt 3). In Expts 2 and 4 the random-dot pattern moved with velocity V1, which abruptly increased or decreased to V2, without returning to V1. The reaction time to the change was measured for the same velocity pairs as those used in the temporal threshold measurements. There was a good correspondence between changes in the reaction times and changes in the thresholds under the various conditions. The data are interpreted on the basis of two hypotheses: higher velocities are detected by mechanisms that respond more rapidly; and integration of velocities occurs when temporally-adjacent motions are presented.

The discrimination of abrupt changes in speed and direction of visual motion.

A random dot pattern that moved within an invisible aperture was used to present two motions contiguously in time. The motions differed slightly either in speed (Experiments 1 and 3) or in direction (Experiments 2 and 4) and the subject had to discriminate the sign of the change (e.g. increment or decrement). The same discrimination task was performed when the two motions were temporally separated by 1 s. In Experiments 1 and 2 discrimination thresholds were measured with motion durations of 0.125, 0.25, 0.5 and 1.0 s and mean speeds of 2, 4, 8, and 16 degrees/s. In Experiments 3 and 4 thresholds were measured with aperture widths of 5 and 20 cm. The discrimination of contiguous motions progressively deteriorated with decreasing duration and mean speed of motion. For the lowest value of duration the Weber fraction for contiguous speeds was more than three times as the Weber fractions for separate speeds. For the same low value of duration the thresholds for discrimination of direction of contiguous motions were only about 50% higher than the thresholds for separate motions. The Weber fraction for contiguous speeds was ca. three times higher with the smaller aperture than with the larger one, provided the ratio 'aperture width mean speed' (i.e. the lifetime of the moving dots) was less than 0.3 s. Aperture width did not affect the discrimination of direction of contiguous motions. The discrimination of contiguous motions is discussed together with the known data for detection of changes in speed and direction. It is suggested that both, detection of changes in speed and discrimination of the sign of speed changes, may be performed by a common visual mechanism.

Emission spectral analysis using photographic plates treated with a phenidone developer.

When spectral photographic plates are not treated in the conventional metol-hydroquinone developer, but in a phenidone developer, a strong increase in the sensitivity and a certain increase in the contrast are observed. With phenidone development, weak lines are intensified, permitting the lowering of the limits of detection and determination. The increase in the contrast increases the slope of the concentration-calibration curves and hence the concentrational sensitivity of the spectral analyses. This is illustrated in the curves for the determination of Si and Mn in low-alloy steels. Further sensitivity can be obtained by following the phenidone development by a chromium intensifying process.

Localization of brief visual stimuli during pursuit eye movements.

Experimental findings concerning the properties of the phenomenon of mislocation of brief visual stimuli during smooth eye tracking are described. One of these, which cannot be explained by existing hypotheses, is that under certain conditions the mislocation magnitude tends to have zero or even negative values. A model is developed for explanation of the mislocation phenomenon. It is suggested that localization is based on: (1) information about the current eye position and (2) information about the stimulus locus on the retina. They both arrive at the localization centre with non-zero delays. The mode of information processing in this centre leads to a magnitude of mislocation which is proportional to the difference between the two delays and which could be positive, zero or negative. Factors which influence either delay should also influence the mislocation magnitude.