Cushing's syndrome in pregnancy: a case report and mini review of the literature.

Adrenal diseases in pregnant women are diagnosed relatively rarely. The main cause of hypercortisolemia during pregnancy is Cushing's syndrome related to adrenal adenoma. It is important to diagnose Cushing's syndrome in pregnant women because it can lead to significant maternal and foetal complications and morbidity. However, due to physiological endocrine changes and symptoms in pregnant women the diagnosis of this disorder can be a challenge. One current case describes a 38-year-old pregnant woman with hypertension, oedema and an adrenal tumour. At the beginning, Conn syndrome was suspected, but after careful analysis Cushing's syndrome (with an adenoma of the right adrenal gland) was diagnosed. After delivery and 5 weeks of pharmacological treatment the patient underwent right side adrenalectomy by laparoscopy.

Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure.

UNLABELLED: Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. RESULTS: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns' hair when compared to mothers'. The mean concentrations of diazepam in mothers' hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns' hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers' hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns' hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn's hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers' hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam and temazepam--were detected in very few cases, in low concentrations.

The significance of C3435T point mutation of the MDR1 gene in endometrial cancer.

The P-glycoprotein (P-gp) plays an important role in carcinogen distribution and is connected with cell differentiation and apoptotic processes leading to carcinogenesis. Interindividual differences in P-gp activity could modulate susceptibility to cancer development. The MDR1 gene, coding for P-gp, is highly polymorphic and some mutations modulate P-gp activity. Recently, association between the MDR1 C3435T polymorphism and the cancer susceptibility was shown. We have hypothesized that MDR1 polymorphism could influence endometrial cancer susceptibility. We have matched 198 women with endometrial cancer and 198 controls. An additional group of 488 healthy volunteers was investigated. The MDR1 C3435T polymorphism was tested by LightCycler assay. The distribution of MDR1 3435 genotypes was significantly different between cases and controls (P = 0.006). Genotypes containing at least one 3435T allele were statistically significant more frequent in the endometrial cancer group (86.8% vs 75.2%, OR 2.18, P = 0.004). Our observation suggests that MDR1 C3435T polymorphism is correlated with endometrial cancer susceptibility.

Limits of fetal viability and its enhancement.

According to Websters Encyclopedic Unabridged Dictionary of the English Language, viable of a fetus it means having reached such a stage of development as to be capable of living, under normal conditions, outside the uterus. Viability exists as a function of biomedical and technological capacities, which are different in different parts of the world. As a consequence, there is, at the present time, no worldwide, uniform gestational age that defines viability. Viability is not an intrinsic property of the fetus because viability should be understood in terms of both biological and technological factors. It is only in virtue of both factors that a viable fetus can exist ex utero and thus later achieve independent moral status. Moreover, these two factors do not exist as a function of the autonomy of the pregnant woman. When a fetus is viable, that is, when it is of sufficient maturity so that it can survive into the neonatal period and later achieve independent moral status given the availability of the requisite technological support, and when it is presented to the physician, the fetus is a patient. In the United States viability presently occurs at approximately 24 weeks of gestational age (Chervenak, L.B. McCullough; Textbook of Perinatal Medicine, 1998). In Portugal, the mortality increase significantly with GA<25 weeks. At 25 weeks mortality was 44.4% and at 26 weeks was 24.4% (I. Macedo et al. Matemidade Dr. Alfredo da Costa, Lisbon, 2000). In Poland during last years we observe also a very significant decrease of perinatal mortality. There are several aspects of fetal viability: ethical, social, psychological and medical. Ethical aspects There is a compelling conceptual and clinical reason to reject Primum non nocere as the primary principle of perinatal ethics; virtually all medical interventions involve unavoidable risks of harm, for example, amniocentesis. If Primum non nocere were to be made the primary principle of perinatal ethics, virtually all of perinatal medicine would be unethical. Social aspects Greatly increased advances in perinatal medicine lead on one hand to a high quality of care expected and demanded by both the health care professionals and patients, but on the other hand the resources available for responding to the expectations and demands are becoming increasingly stretched. Even in the high-income countries, the available resources are scarce in relation to these demands a high quality of care expected and demanded by both the health care professionals and patients, but on the other hand the resources available for responding to the expectations and demands are becoming increasingly stretched. Medical aspects During the preconceptional period the most important actions are: family planning, education, analysis of previous obstetrical miscarriages and prevention of congenital malformations (folic acid). Pregnancy presents several problems, which can significantly influence fetal viability. Proper management of these problems can improve perinatal outcome. Among others prevention of prematurity is the most important goal of contemporary perinatal medicine. Enhancement of fetal viability There are several possibilities to enhance fetal viability. The most important are: organization of perinatal care, introduction of new technologies to perinatal medicine, intensive fetal therapy and early detection of fetal distress. Three levels system of perinatal care, transport in utero, introduction and promotion of new methods, continues education of staff are characteristic for the modern organization of perinatal medicine. Echocardiography, Color Doppler Energy, 3D sonography, prenatal diagnosis (cordocentesis, analysis of fetal cells in maternal blood,.), fetal pulse oximetry, mathematical analysis of the signal are the methods which should be used at the highest level of perinatal care. Today, the prospect of survival is only about 1 in 10 at 23 weeks, and if the child lives it is more likely to be handicapped that not. At 24 weeks the chance of a normal survivor is about 50%, and after this the odds are in favor of a normal survivor. Considering this data, intensive care should be an optional choice for fetuses at 23 and 24 weeks of gestation and should be offered to every fetus at 25 weeks or more.

Blood velocity in the fetal vein of Galen and the outcome of high-risk pregnancy.

BACKGROUND: Pulsation in the flow velocity waveform in the umbilical vein is related to perinatal mortality but the flow velocity waveform in the fetal vein of Galen is normally even and without fluctuation. OBJECTIVES: To establish whether blood flow velocity pulsations in the vein of Galen in high-risk pregnancies are related to outcome. STUDY DESIGN: The vein of Galen was located by colour Doppler ultrasound in 102 pregnancies complicated by severe pregnancy-induced hypertension. The blood velocity waveform was recorded by pulsed Doppler within 2 days of delivery and the presence pulsations related to pregnancy outcome, including emergency operative intervention and neonatal distress. Umbilical artery and vein and uterine artery blood flow velocity waveform were also recorded at the same time. The clinicians managing the women were unaware of the venous flow results. RESULTS: Pulsation were present in the vein of Galen in 68 cases and in the umbilical vein in 21. Both were significantly related to adverse outcome. Pulsations in the vein of Galen were seen in all seven perinatal deaths. CONCLUSIONS: Since umbilical venous pulsation are a late sign of fetal compromise, and pulsations in the vein of Galen seem to appear earlier, thus being an intermediate sign of fetal compromise that might be of great value for fetal surveillance.

[Analysis of pulmonary venous blood flow in growth retarded fetuses above 30 weeks of gestation]. / Ocena przeplywu krwi w zylach plucnych plodu po 30 tygodniu ciazy powiklanej wewnatrzmacicznym ograniczeniem wzrostu plodu.

Abnormal spectra of blood flow are observed in many fetal vessels in pregnancy complicated by intrauterine growth restriction. Redistribution of blood flow to the most important organs causes a diminished perfusion of the others. The disturbances of lung perfusion in utero are related to abnormal growth and development of the fetal lung. The aim of this study was to describe blood flow velocity waveforms in fetal pulmonary veins in normally grown and growth restricted fetuses above 30 weeks of gestation. Doppler studies were performed in 53 normally grown and 39 growth restricted fetuses. The subjects of analysis were: peak systolic (VS), peak diastolic (VD), end-diastolic (VA), and pulsatility index for veins (PIV). Analysis was performed for two gestational intervals: 31-36, 37-41 wks. The pulmonary venous flow in growth retarded fetuses demonstrates the similar pattern to that observed in normally grown fetuses above 30 weeks of gestation. There were no statistically significant differences between normally grown and growth restricted fetuses in all analyzed indices in both gestational intervals.

[Lung hypoplasia and the application of Doppler ultrasonography in the assessment of fetal pulmonary circulation]. / Hipoplazja pluc a mozliwosci zastosowania technik dopplerowskich w ocenie plodowego krazenia plucnego.

The paper presents a review of literature concerning the use of Doppler technique in the evaluation of pulmonary blood flow. Especially, it is important to monitor the development of lung in suspicion of lung hypoplasia that closely correlates with abnormal development of pulmonary vessels. In the literature there are single reports pointing on its usefulness in the detection of lethal lung hypoplasia. It has been suggested that this technique may provide valuable information of the development of vascular bed in lung. Recent data concerning Doppler blood flow velocimetry in hypoplastic lung stimulate to further studies suggesting their significant value in the diagnosis and distinguishing the lethal form of pulmonary hypoplasia.

[Fetal breathing movements and onset of delivery at term]. / Ruchy oddechowe plodu a czas wystapienia porodu w ciazy donoszonej.

It has been studied the relation between fetal breathing activity and labor among 216 patients in uncomplicated pregnancies at term. It has been also described the value of fetal breathing movements in the evaluation of fetal well-being. Among patients where fetal breathing movements were absent 81.9% women delivered within 3 days since ultrasonographic examination. And among patients with visible fetal breathing activity only 25.0% delivered within this period. The analysis of newborn condition based on Apgar score in pregnant women with or without fetal breathing movements showed no significant statistical differences. The absence of fetal breathing movements has no prognostic value concerning the evaluation of fetal well-being in antepartum period. The cessation of fetal breathing activity facilitates to prognose the time of labor in mature pregnancies.

[Analysis of selected parameters of maternal and fetal status during stimulation of fetal lung maturation]. / Analiza wybranych parametrów stanu ciezarnej i plodu w trakcie stymulacji dojrzewania ukladu oddechowego.

At patients threatened with premature childbirth the influence of glicocorticoids on short and tong-term fetal heart rate variability and the occurrence of respiratory arrhythmia was evaluated. It has been ascertained statistical significant lowering of the incidence of fetal respiratory arrhythmia and short-term variability. Described changes had a temporary character and surrendered of normalization in the course 72 of hours after last use of glicocorticoids. The influence of glicocorticoids on select biochemical and biophysical parameters of state pregnant women was also studied. One specified occurrence of incidental symptoms in road drove of therapy. Pregnant women in road of treatment glicocorticoids have also observed a temporary weakness of feeling of fetal movements.

[Evaluation of fetal breathing movements in prognosis of preterm labor]. / Ocena aktywnosci oddechowej plodu w prognozowaniu porodu przedwczesnego.

The relationship between fetal breathing activity and preterm labor among patients with signs of preterm labor has been analyzed. The assessment concerned pregnant women admitted to the hospital because of regular uterine contractions, uterine contractility and bleeding or premature rupture of membranes. It has been found the significant correlation between the absence of fetal breathing movements and preterm labor.

[Twin-to-twin transfusion syndrome--case report]. / Zespól transfuzji plodowo-plodowej--opis przypadku.

Authors described a case of twin-to-twin transfusion syndrome that did not comply with a classic definition of syndrome. It has been presented possibilities of ultrasound screening regarding to Doppler blood flow velocimetry. It has been also shown the usefulness of these methods in the monitoring and assessment of fetal status. This is an example of Doppler blood flow velocimetry applying that yields information concerning fetal condition. This method seems to be very useful in these situations when fetal heart rate monitoring is difficult or even inapplicable.

[Intrauterine therapy of obstructive uropathy--case report]. / Terapia wewnatrzmaciczna uropatii zaporowej--opis przypadku.

The use of vesicoamniotic shunt in the case of obstructive uropathy was described. On the base of ultrasound screening it has been diagnosed urethral obstruction. This abnormality of urinary tract was found in male fetus. It has been diagnosed the posterior urethral valve. Qualification to intrauterine therapy was based on normal parameters of renal function. Under ultrasound guidance the vesicoamniotic shunt was installed. The normal drenage was observed within 6 weeks, until it was dislocated. In 36th week of gestation the cesarean section was performed. The indications were signs of urethral obstruction. The boy was born in whom posterior urethral valves were recognized. He was born in good condition without any biochemical features of renal damage as well as signs of hypoplastic lung.

[Fetal pulse oximetry in second stage of labor]. / Zastosowanie pulsoksymetrii plodowej w II okresie porodu.

OBJECTIVE: To compare the mean values of fetal oxygen saturation with fetal heart rate pattern in the second stage of labor (Melchior classification) MATERIAL AND METHODS: The study included 30 parturients in gestational age 37-41 weeks. Fetal oxygen saturation was recorded and averaged over the last 30 min of the second stage of labor Simultaneously, fetal heart rate and uterine contractions were monitoring. Fetal heart rate patterns were assessed according to Melchior's classification. At birth, the cord acid-base parameter (pH) was calculated. RESULTS: The lowest value of fetal oxygen saturation over the last 30 min of labor was 10%, the highest 60%, and the mean value 39.1 +/- 12.5%. Statistically, significant correlation between the mean value of oxygen saturation over the last 30 min of labor and pH arterial values (n = 25, p = 0.004, r = 0.42) was found. There was no statistically significant correlation between fetal oxygen saturation and pH venous values (n = 24, p. = 0.006, r = 0.49), but trend towards significance could be observed. Statistical analysis revealed that arterial pH was significantly correlated to Melchior's classification. The lowest pH and FSpO2 values coexisted with type 3 and 4 of FHR patterns according to Melchior's classification. CONCLUSIONS: The mean values of fetal oxygen saturation over the last 30 min of labor significantly correlate with arterial pH values. These values correlate with FHR abnormalities according to Melchior's classification. Fetal pulse oximetry seems to be an important, additional method assessing fetal well-being in the second stage of labor.

[Spectral analysis of fetal heart rate variability]. / Analiza spektralna zmiennosci czynnosci serca plodu.

OBJECTIVE: To assess power spectral densities and power spectrum of FHR variability in two categories of fetal activity, quiescence and breathing movements, in pregnancies complicated by diabetes mellitus or intrauterine growth retardation. MATERIAL AND METHODS: The study group included 70 women, 35 in uncomplicated pregnancies and 35 with above-mentioned complications. The spectral analysis of FHR variability in fetal quiescence or breathing activity was performed. The power spectrum was analyzed at frequencies 0-1.0 Hz. Successively, the power spectral density was calculated. It has been presented the plots of spectral densities of beat-to-beat variabilities well during breathing episodes as "no breathing". Subsequently, the power spectra were calculated in both analyzed activities and groups. RESULTS: The highest values of power spectral densities (0.118 +/- 0.025) at 0.6-0.8 Hz were found in uncomplicated pregnancies. In pregnancies complicated by diabetes mellitus (0.048 +/- 0.049) or IUGR (0.042 +/- 0.041) these values were statistically significantly. At 0.6 Hz and 0.8 Hz power spectra of FHR variability were lower in quiescence comparing to breathing activity, as well in uncomplicated as complicated pregnancies. At these frequencies power spectra during breathing movements were significantly lower in complicated pregnancies comparing to uncomplicated. COMMENTS: The results of this study confirm the usefulness of spectral analysis in the assessment of FHR variability. The observed disturbances may reflect an abnormal fetal reactivity. The evaluation of breathing and cardiovascular systems interaction allows to study indirectly the central nervous system that coordinates both activities.

Fetal adrenal and middle cerebral artery Doppler velocimetry in high-risk pregnancy.

OBJECTIVES: Animal studies have shown that hypoxic fetuses redistribute their blood flow, giving preferential supply to the brain, heart and adrenal glands. The aim of this study was to establish whether blood velocity waveforms in the human fetal adrenal artery and middle cerebral artery showed signs of redistribution of fetal circulation in high-risk pregnancy, and to analyze the relationship between signs of such redistribution and the outcome of pregnancy. METHODS: Fetal middle adrenal artery and middle cerebral artery waveforms were recorded between 27 and 41 weeks of gestation in 102 pregnancies complicated by pregnancy-induced hypertension. Signs of fetal adrenal-sparing were deemed present when the pulsatility index (PI) fell below the fifth percentile of the normal range. Signs of fetal brain-sparing were deemed present when the cerebral artery PI was below the mean -2 SD of the normal range and the cerebroplacental PI ratio was < 1.08. RESULTS: Signs of adrenal sparing were found in 64 cases and brain sparing in 32 cases. Fetal adrenal sparing was strongly associated with adverse perinatal outcome; all perinatal mortality cases showed signs of adrenal sparing. There was a significant positive correlation between the fetal adrenal artery PI and umbilical arterial and venous pH. CONCLUSIONS: Signs of adrenal sparing are frequent in high-risk pregnancies. Adrenal artery velocimetry may be a useful procedure for fetuses at risk for hypoxemia.

Fetal and placental power Doppler imaging in normal and high-risk pregnancy.

OBJECTIVE: Computer analysis of organ power Doppler (PD) imaging has recently become available. The aim of the study was to evaluate gestational trends in placenta-, fetal lung-, liver- and kidney-blood flow in normal pregnancies and relate it to signals in high-risk pregnancies. METHODS: PD signals were recorded in normal singleton pregnancies between 26 and 42 weeks of gestation. Signals were also recorded in 63 high-risk pregnancies. Fixed preinstalled PD system installations for each organ were used during examinations. Images from PD scan were recorded on video tape and off-line analysed by computer. Mean flow signal intensity was calculated for each organ. Umbilical and uterine artery Doppler velocimetry were also recorded in high-risk pregnancies. RESULTS: PD signals from the four organs indicated increasing organ blood flow until approximately 34 weeks of gestation, from where the organ signals seemed to decrease. High-risk pregnancies seemed to have lower PD signal intensity, which was more pronounced in cases with signs of placental vascular resistance. CONCLUSION: The results suggest that a decrease in fetal organ blood flow might indicate a centralisation of fetal circulation in normal pregnancy at term, as a physiological response to a decrease in placental perfusion. In the high-risk pregnancies the placental and fetal organ blood flow seem to be even further reduced, suggesting a more intense centralisation of circulation.

Ultrasound in the diagnosis of twin-to-twin transfusion syndrome--a preliminary report.

OBJECTIVE: The aim of this study was to show the diagnostic possibilities of ultrasound in twin-to-twin transfusion syndrome (TTTS), to demonstrate its usefulness in cases of hemoglobin difference < 5 g/dL in neonates as well as in cases complicated by intrauterine death of one or both twins. STUDY DESIGN: The study included 4 pairs of twins. In two cases 3 fetuses died in utero. In the other two the hemoglobin difference in newborn infants was < 5 g/dL. The ultrasound examination, evaluating the fetal anatomy and biometry, amniotic fluid volume, placentation, was performed. The special attention was paid to polyhydramnios/oligohydramnios, discordant fetal growth (fetal weight, abdominal circumference), the presence of fetal hydrops, ascites, pericardial effusion. Doppler blood flow velocimetry has been done in umbilical vessels, middle cerebral artery. The data was compared with normal reference values for singleton pregnancies. The waveforms from both uterine arteries were also evaluated to exclude placental insufficiency. Additionally the blood flow through the AV valves was measured to exclude or confirm its regurgitation. Postnatally the hemoglobin difference was evaluated if available and compared with sonographic findings. RESULTS: In all cases inter-twin difference in abdominal circumference was greater than 18 mm and inter-twin weight difference of more than 15%. We observed polyhydramnios/oligohydramnios in all twin pregnancies. It has been found decreased PI in middle cerebral artery in larger fetus (recipient) in all our cases (comparing to single pregnancy). PI values for this vessel in smaller fetuses were within normal range (for single pregnancy). PI values in umbilical arteries of recipients were abnormal (increased PI or absent end-diastolic flow). COMMENTS: The sonographic criteria seem to be very useful in diagnosis of twin-to-twin transfusion syndrome, especially in cases where the measurement of hemoglobin level is impossible. Doppler blood flow velocimetry in fetal vessels helps to explain the changes in fetal hemodynamics in TTTS.

Betamethasone treatment and fetal lung perfusion evaluated with color Doppler energy imaging.

The aim of this study was semiquantitative evaluation of tissue blood flow in the fetal lung before and after administration of betamethasone. This was carried out by means of computer analysis of ultrasound Doppler signals obtained by the color Doppler energy (CDE) technique. CDE signals were recorded in 20 singleton pregnancies with appropriate growth and imminent preterm delivery between 26 and 33 weeks of gestation. The CDE signal recordings were made before and after intramuscular administration of betamethasone 8 mg/day for 3 days. Fixed preset CDE system control settings for the fetal right lung were used during the examinations. Images from CDE scans were recorded on S-VHS videotape and transmitted for computer analysis of 8-bit images at 256 gray-scale levels. The mean flow signal intensity was recorded for the fetal lung before and after betamethasone administration. Additionally, blood velocity waveforms were measured in the intrapulmonary arteries and veins in the peripheral part of the lung. CDE signals from the fetal lung indicated increased energy values after corticosteroid treatment in 16 cases. In three cases there was no change in CDE signal values, and in one case a fall of the signal value was noted. Blood velocity waveforms from the intrapulmonary arteries showed decreased resistance to flow in 15 cases, increased resistance to flow in four cases and no change in one case. No significant differences in venous blood flow velocities were found. In conclusion, the results suggest that there is an increase in fetal lung blood perfusion after maternal corticosteroid administration.

[Statistical methods applied in retrospective risk assessment of endometrial adenocarcinoma occurrence]. / Metody statystyczne stosowane w retrospektywnej ocenie ryzyka wystapienia raka blony sluzowej macicy.

A retrospective study about frequency of occurrence of endometrial adenocarcinoma in postmenopausal women which are associated with diabetes mellitus, overweight and hypertension was performed. The aim of the study was to have risk factors for carcinoma of endometrium estimated. The nonparametric statistics such as: 2 x 2 table chi 2/Phi2 test, observed versus expected chi 2 test and estimation of relative risk were applicable. A retrospective study (from 1991 to 1993) of 2887 patients of Institute of Obstetrics and Gynecology University School of Poznan with pathological sign and symptoms was performed.