[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%.

[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.

[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).

[Recurrent pyloric stenosis in a 7-year-old child with chronic granulomatous disease]. / Sténoses pyloriques récidivantes chez un enfant de 7ans atteint de granulomatose septique chronique.

Hypertrophic pyloric stenosis is a common affection in infants aged 3-8 weeks and typically does not affect older children. We report a case of pyloric stenosis that occurred recurrently at the ages of 3 and 7 years in a boy with X-linked chronic granulomatous disease. We emphasize the inflammatory origin of such stenosis, whose progression was favorable thanks exclusively to drug treatment with corticosteroids. We note that chronic granulomatous disease can affect the entire digestive tract, similar to inflammatory bowel disease in children.

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.

Reproductive outcome after hysteroscopic metroplasty in patients with infertility and recurrent pregnancy loss.

INTRODUCTION: Patients with uterine malformations have decreased reproductive potential and an unfavourable reproductive outcome starting even from the first pregnancy. Patients with untreated uterine malformations have a term delivery rate of 40%-65%. Hysteroscopic metroplasty is a standard, safe and minimally invasive method for treatment of uterine malformations, which provides a normal uterine cavity in patients with hysteroscopically correctible types of uterine malformations. The aim of the study was to analyse the variables associated with reproductive outcome before and after hysteroscopic metroplasty. MATERIAL AND METHODS: We analysed the variables determining reproductive outcome after 216 interventions with hysteroscopic metroplasty in 202 patients which were done at the University Obstetrics and Gynecology Clinic in Skopje during a three-year period, from 01.01.2006 to 31.12.2008. Patients were divided into three groups: patients with recurrent pregnancy loss, patients with secondary infertility and foetal loss and patients with primary infertility. The follow-up period lasted for two years (24 months). Statistical analysis was performed using the Chi-square test and p<0.05 was considered to be statistically significant. RESULTS: During the follow-up period of two years after hysteroscopic metroplasty there were a total of 113 pregnancies, of which 46 belonged to the group of primary infertility. Analysis of the reproductive outcome of those patients (compared before and after hysteroscopic metroplasty) showed a significant (p<0.05) decrease in the abortion rate from 89.6% to 12.4%, as well as an increase of term delivery rate from 1.4% to 74.4%. In the group of preterm deliveries there was a rise from 9% to 13.2%, which was not significant. The group of primary infertility had a pregnancy rate of 36%. CONCLUSION: Hysteroscopic metroplasty significantly improves the reproductive outcome in patients with surgically correctible uterine malformation.

Impact of body mass index (BMI) and age on the outcome of the IVF process.

BACKGROUND: The goal of this study was to examine the impact of body mass index (BMI) and age on the outcome of the IVF process. MATERIALS AND METHODS: This was a retrospective case-control study, of all patients undergoing IVF from 2008-2010 in the Re-Medika IVF Centre. A total of 1238 fresh, non-donor IVF cycles were analyzed, but to minimize the bias, only the first cycle for each patient in that period was analysed (N-920). The patients underwent standard protocols for COH and embryology treatment. In all retrieved oocytes, or in 100% of the cases, the process of fertilization was realized with the method of intracytoplasmic sperm insemination (ICSI). The primary end-point assessed was clinical pregnancy rate. Patients were initially grouped into four BMI categories. The data are presented as frequencies (qualitative data) and as mean±SD (quantitative data). Preliminary comparisons between groups with different BMI were made by the Chi-square and one-way ANOVA test. Because fertility declines with age, there is a Pearson-correlation coefficient to see if BMI depends on age, and the resulting value r=0.15 (p<0.05) showed that BMI is age-dependent, the relationship between them showed multicollinearity. However, the calculated error tolerance of 0.9 indicates stability of the model. Furthermore, to adjust the known fertility decline with age, every response or outcome is analysed by the method of multiple linear (continuous data) or logistic (qualitative data) regression, where the independent variables are taken: BMI, age and BMI interaction×age. RESULTS: Increased BMI significantly reduces the chance of clinical pregnancy (normal weight vs. overweight: clinical pregnancy rate: 49.2%, vs. 34.3%). Age, analysed as a single factor, significantly reduces clinical pregnancy rate. Interaction of BMI and age significantly affects clinical pregnancy rate. (BMI vs. BMI×Age vs. Age-p 0,01 vs. 0,001 vs. <0,0001). CONCLUSION: Increased body mass of patients entering IVF has a negative impact on the final outcome and certainly reduces the success of the process resulting in reduced clinical pregnancy. Interaction of BMI and age showed a strong significant impact on the outcome of IVF seen through the achievement of clinical pregnancy.

Fatigue analysis of interference EMG signals obtained from biceps brachii during isometric voluntary contraction at various force levels.

The aim of the present study was to test the applicability of indices of muscle fatigue to interference EMG signals detected at various distances from the end-plate region during isometric voluntary contractions at different force levels. Bar electrode with 12 leading off surfaces and 5mm inter-pole distance was used to detect EMG from human m. biceps brachii. The sensitivity of the new spectral indices to detect muscle fatigue was higher than that of mean or median frequencies. Considerable variations in the characteristic frequencies and values of spectral indices that could reflect recruitment and/or rotation of MUs were found under submaximal efforts. The increase of the indices was considered as a sign of peripheral muscle fatigue while their decreasing could be a sign of de-recruitment of fatigued or/and recruitment of new MUs reflecting central fatigue. The sensitivity of the indices to fatigue depended on the electrode arrangement and its longitudinal position in respect of the end-plate region and ends of the muscle fibres. It was larger for the electrodes placed in the middle of the semi-fibre. To overcome the problem with inappropriate position of the electrode, one could use an electrode whose longitudinal dimension would cover the entire semi-length of the analyzed fibres.

Elastic properties and structure of the radial artery in patients with type 2 diabetes.

Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.An echotracking system coupled to a plethysmograph was used to assess the morphologic and elastic properties of radial artery. Distensibility and compliance were evaluated using Langewouters' equations. Distensibility and compliance did not differ significantly in patients with diabetes compared with controls. In contrast, radial IMT and WCSA were significantly higher in patients with T2D than in controls. Multiple regression analyses revealed a significant association between SBP and IMT (r(2) = 0.40, p<0.001) as well as WCSA (r = 0.54; r(2) = 0.30; p<0.001 ) in individuals with diabetes. In conclusion, distensibility and compliance of the radial artery are not reduced in patients with T2D. In contrast, radial IMT and WCSA are significantly higher in patients with T2D than in controls.These modifications are chiefly and positively related to SBP.

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.

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.

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.