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Biomedical subjects

D Jurkovic

Publications and source records attributed to D Jurkovic.

At least 73 records · Page 4Linked to original sources

The origin of alpha-fetoprotein in first-trimester anembryonic pregnancies.

OBJECTIVE: Our purpose was to evaluate the origin of alpha-fetoprotein in the maternal circulation and coelomic fluid of pregnancies with an empty gestational sac on first-trimester ultrasonographic examination. STUDY DESIGN: The alpha-fetoprotein level and the affinity of alpha-fetoprotein for concanavalin A Sepharose was measured between 8 and 11 weeks of gestation in the maternal serum and coelomic fluid of nine pregnancies complicated by an empty gestational sac and of 27 normal pregrancies. RESULTS: The maternal serum alpha-fetoprotein level in patients with an empty gestational sac was high in seven cases and normal in two cases. In these cases the median level was significantly (p < 0.01) higher in the serum and lower in the coelomic fluid compared with normal pregnancies. In eight cases of the nine pregnancies with an empty sac, > 50% of alpha-fetoprotein molecules in the coelomic fluid were of the concanavalin A nonreactive fraction, whereas in one case the coelomic fluid sample contained < 5% of this fraction. A similar distribution was found in the corresponding serum samples. CONCLUSION: Normal or high maternal serum AFP levels and alpha-fetoprotein molecules predominantly of yolk sac origin in the coelomic fluid of pregnancies with an empty gestational sac on ultrasonography provide further evidence that the most likely explanation for this feature is the early death of the embryo with persistence of the placental tissue.

Embryo, Mammalian↗

Three-dimensional ultrasound for the assessment of uterine anatomy and detection of congenital anomalies: a comparison with hysterosalpingography and two-dimensional sonography.

The purpose of this study was to investigate the potential value of three-dimensional ultrasound for the assessment of normal uterine anatomy and the diagnosis of congenital uterine anomalies. A total of 61 patients with a history of recurrent miscarriage or infertility and who had previously been investigated by hysterosalpingography were recruited into the study. They first underwent a conventional two-dimensional transvaginal ultrasound scan. At the end of the examination, three-dimensional ultrasound volumes were recorded and stored in the machine computer memory. The examination of planar reformatted sections was than used for the assessment of uterine morphology and the diagnosis of congenital anomalies. On three-dimensional scanning, the most useful plane was a transverse section through the whole length of the uterus from the fundus to the cervix. Hysterosalpingography showed a normal uterus in 44 (72.1%) patients, an arcuate uterus in nine (14.8%) and a major fusion defect in three cases (4.9%). Five patients (8.2%) had large fibroids which were distorting the uterine cavity. Good-quality two-dimensional ultrasound images were obtained in 60 (98.3%) and three-dimensional images in 58 (95.1%) cases. All poor images were caused by large uterine fibroids. Comparison between hysterosalpingography and ultrasound showed that five false-positive diagnoses of arcuate uterus and three of major uterine anomalies were made on two-dimensional scans. Three-dimensional ultrasound agreed with hysterosalpingography in all cases of arcuate uterus and major congenital anomalies. The ability to visualize both the uterine cavity and the myometrium on a three-dimensional scan facilitated the diagnosis of uterine anomalies and enabled easy differentiation between subseptate and bicornuate uteri.

Abortion, Habitual↗

Circadian variation in uterine artery blood flow indices during the follicular phase of the menstrual cycle.

We investigated for the presence of circadian variation in uterine artery blood flow indices during the late follicular phase of the menstrual cycle. Twenty women with regular menstrual cycles underwent transvaginal color Doppler assessment of blood flow in the uterine arteries on two occasions precisely 12 h apart on the same day in the follicular phase. Ultrasound examinations were performed between 06.00 and 10.00 and repeated between 18.00 and 22.00. Indices of uterine artery blood flow included the pulsatility index (PI) and the time-averaged maximum velocity (TAMX). The changes in PI and TAMX were related to variations in serum concentrations of estradiol and luteinizing hormone (LH). We noted a significantly higher PI and lower TAMX in the evening compared to the morning values, p < 0.001 and p = 0.01, respectively. There was no significant change in estradiol or LH concentrations between morning and evening (p > 0.05). There appears to be a circadian rhythm in uterine artery blood flow occurring independently of these hormonal parameters. The circadian changes in PI and TAMX may be larger than the previously described effects of hormones on these parameters. The accurate interpretation of uterine artery blood flow indices should take these time-related fluctuations into account.

Adult↗

Coelomic fluid chorionic gonadotrophin and protein concentrations in normal and complicated first trimester human pregnancies.

Coelomic fluid and maternal serum samples were collected from 43 normal pregnancies and 18 missed abortions between 7 and 12 weeks of gestation. The samples were analysed for the concentrations of intact human chorionic gonadotrophin (HCG), free alpha HCG, free beta HCG and total protein. The relationships between the biological findings and the ultrasound and pathological features were assessed by regression analysis. In normal pregnancies, intact HCG, free alpha HCG and free beta HCG concentrations were respectively 1.3, 185 and 33 times higher in coelomic fluid than in maternal serum. The coelomic concentrations of intact HCG and free alpha HCG decreased significantly with advancing gestation. No relationship was found between coelomic fluid and maternal serum concentrations of the different variables. These findings suggest that in normal pregnancies, the concentration of HCG in the coelomic fluid, as in maternal serum, is mainly influenced by cytotrophoblastic differentiation and that the metabolic clearance of HCG molecules is slower in the coelomic cavity than in maternal serum. In missed abortions, the serum concentrations of intact HCG, alpha HCG and free beta HCG and the coelomic concentration of total protein were significantly lower than in normal pregnancies. In three out of nine anembryonic pregnancies diagnosed by ultrasound, embryonic remnants were present at histological examination. The coelomic concentration of total protein was extremely low in all missed abortions with advanced trophoblastic necrosis whereas the HCG concentration was low when embryonic remnants were absent. These findings support the concept that embryonic and placental development are closely related in the first trimester of human pregnancy, placental biological functions persisting only for a limited period of time after embryonic demise.

Abortion, Missed↗

Luteinized unruptured follicle: morphology, endocrine function and blood flow changes during the menstrual cycle.

A case of spontaneous luteinized unruptured follicle syndrome is presented with full documentation of hormonal, morphological and haemodynamic changes. Changes in uterine blood flow were also noted. Growth of the leading follicle was slow during the follicular phase of the cycle. After the luteinizing hormone (LH) surge, growth of the follicle was more rapid. Concurrently, the follicle developed internal echogenicity with ultrasonic evidence of separation of the granulosa cell layer. The follicle was no longer visible 144 and 132 h after the LH rise and peak respectively. There was no primary progesterone rise associated with either the LH rise or peak, but a secondary progesterone rise occurred 42 h after the onset of the LH surge. Peri-follicular blood flow velocity was detected for the first time on cycle day 5 and appeared to rise after the onset of the LH surge. Peri-follicular blood flow velocity appeared to reduce after the LH surge to values associated with the follicular phase. These observations are consistent with an association of a primary granulosa cell defect with luteinized unruptured follicle syndrome which would account for the initial slow follicular growth, absent primary progesterone rise and reduction in blood flow in the wall of the follicle after the LH surge.

Adult↗

Induced tolerance and chimaerism in human fetuses using coelocentesis: a medical opportunity to avert genetic disease?

Coelocentesis offers a new opportunity for gaining access to the coelomic cavity of human embryos from 28 days post-fertilization (42 days menstrual age). With this technique, cells can be extracted from the cavity for the genetic typing of embryos in early pregnancy. Coelocentesis may also offer a unique opportunity of inducing tolerance to foreign grafts and chimaerism in these human embryos by replacing donor cells into the coelomic cavity. This cavity appears to be closely associated with the fetal haemopoietic system. The optimal age to inject stem cells designed to produce chimaerism may be at 5-6 weeks embryonic age, and these grafted cells may induce tolerance later in gestation. Two successive coelocenteses would be needed, the first to extract fetal cells to type the fetus, and a second within a few days to inject the donor cells into the coelomic cavity. Alternatively, non-invasive methods of diagnosis such as lower uterine pole extramembranous sampling of fetal trophoblast, or the extraction of fetal cells from maternal blood, could be combined with coelocentesis. If tolerance and chimaerism can be established, repeated tissue grafts could be carried out during fetal life and after birth, so that disorders caused by single or multiple gene defects in the haemopoietic system and other organs may be corrected.

Chimera↗

Materno-fetal immunoglobulin transfer and passive immunity during the first trimester of human pregnancy.

Passive transfer of immunity from the mother to the first trimester fetus is of particular interest because of the reported high incidence of serious fetal sequelae due to congenital infection. We have examined the relationship between maternal serum, coelomic fluid and amniotic fluid concentrations of immunoglobulin (Ig) and complement. Ig fractions G (IgG), A (IgA), and M (IgM) and complement factors 3 (C3) and 4 (C4) were measured in 34 normal pregnancies between 6 and 12 weeks of gestation. The concentrations of specific antibodies for Toxoplasma gondii, cytomegalovirus (CMV) and rubella were also measured on 21 matched samples from the same study group. IgG and IgA concentrations were detected in all coelomic fluid samples whereas IgG was only measurable in two amniotic fluid samples. IgG and IgA concentrations were respectively 28 and 128 times lower in coelomic fluid than in maternal serum and probably reflect fetal serum concentrations. Significant positive linear correlations were found between gestational age and the coelomic concentrations of IgG (P = 0.001) and IgA (P = 0.014). There was no obvious association between immunoglobulin concentrations in coelomic fluid and maternal serum suggesting increasing active transport across the placenta with advancing gestation. IgM, C3 and C4 were not detected in coelomic or amniotic fluid samples. Specific antibodies were found in 13 out of 63 samples of coelomic fluid and in 32 out of 63 samples of maternal serum. They were found in coelomic fluid only if they were present in maternal serum. These results suggest that maternal IgG and IgA are potentially available to the embryo as early as the 6th week of gestation. The presence in the coelomic fluid of the IgG fraction, both total and infectious agent-specific transferred via the placenta, indicates that they may provide limited protection against congenital infection in the first trimester.

Amniotic Fluid↗

Temporal relationship between the human chorionic gonadotrophin peak and the establishment of intervillous blood flow in early pregnancy.

The purpose of this study was to investigate the temporal relationship between the early pregnancy peak of circulating human chorionic gonadotrophin (HCG) concentration and the establishment of maternal blood flow in the placental intervillous space. The presence of blood flow echoes within intervillous space was determined by colour Doppler imaging from 44 women with clinically uncomplicated pregnancy between 6 and 18 weeks gestation. Circulating HCG, free alpha- and beta HCG subunits, oestradiol and progesterone concentrations were immunoassayed in blood samples collected at the time of Doppler examination. A continuous intervillous blood flow was detected in all cases with a gestational age > or = 11.7 weeks (n = 18) but never before this time. Circulating concentrations of free alpha HCG, oestradiol and progesterone were linearly or exponentially correlated with gestational age (r = 0.860, 0.903 and 0.538 respectively, all with P < 0.001), indicating steady increase of these hormones with advancing gestation. However, the best fitted lines were found to be parabolic for HCG (r = 0.771, P < 0.001) and beta HCG (r = 0.695, P < 0.001), their highest points corresponding to 11.24 and 10.74 weeks gestational age respectively. The close temporal relationship between the Doppler advent of intervillous maternal blood flow and the HCG peak suggests that the establishment of the intervillous blood flow is associated with the decline in circulating HCG concentrations.

Chorionic Gonadotropin↗

Detection of sickle gene by coelocentesis in early pregnancy: a new approach to prenatal diagnosis of single gene disorders.

Coelomic fluid, placental tissue and maternal blood were collected at 7-10 weeks gestation from each of 58 women undergoing elective termination of pregnancy for psychological indications. In all samples, a 364 bp fragment of the human beta-globin gene spanning positions -23 to 341 was amplified. The restriction endonuclease Ddel was used to detect the sickle mutation which abolishes its restriction site. beta-Globin DNA was successfully amplified from all samples. In 53 cases a normal maternal beta-globin genotype was detected. In three out of five cases, where the maternal haemoglobin phenotype was HbAS, heterozygosity for the sickle mutation was demonstrated on analysis of coelomic fluid. In the remaining two cases a normal beta-globin genotype was observed. Three further coelomic fluid samples were found to be heterozygous for the sickle mutation. In these instances the maternal haemoglobin phenotype was normal, indicating paternal transmission of the sickle gene. The results of the present study have established that the diagnosis of sickle cell anaemia, and potentially other human single gene disorders, is feasible by coelocentesis.

Amniocentesis↗

Description of circadian rhythm in uterine artery blood flow during the peri-ovulatory period.

Uterine artery blood flow was assessed by transvaginal colour and pulsed Doppler ultrasound prospectively in six women during the peri-ovulatory period. All patients had regular ovulatory menstrual cycles and a mid-luteal serum progesterone consistent with spontaneous ovulation in the preceding cycle. Each patient underwent serial transvaginal ultrasound examination and Doppler assessment of blood flow in the uterine arteries. When the mean follicular diameter was > 16 mm or day -2 from the estimated day of ovulation was reached, patients were scanned at 6 hourly intervals at 0600, 1200, 1800 and 2400 h until follicular rupture. The pulsatility index (PI) and time averaged maximum velocity (TAMX) were calculated as Doppler indices of impedance to blood flow and velocity respectively. A venous blood sample was taken at each visit for subsequent hormonal analysis. The mean uterine artery PI showed a marked daily fluctuation with a nadir occurring most commonly at 0600 h. A comparison between the mean PI values at 0600 and 1800 h showed significantly lower results at 0600 h in both dominant (P < 0.05) and nondominant (P < 0.02) uterine arteries. Furthermore, mean uterine artery TAMX showed daily fluctuations with peak values most commonly occurring at 0600 h with the nadir occurring during the afternoon and late evening. There was no temporal relationship between the fluctuations in PI and changes in luteinizing hormone, follicle stimulating hormone, oestradiol or progesterone concentrations. These observations suggest that there is a circadian rhythm in uterine artery blood flow during the peri-ovulatory period which appears to be independent from the hormonal changes.

Adult↗

Changes in the coelomic fluid composition following two different methods of cervical ripening.

We have evaluated the changes in maternal serum and coelomic fluid biochemical composition following two different methods of cervical ripening, i.e. mechanical and biochemical. Each study group included 20 women between 8 and 12 weeks of gestation who were requesting termination for psychosocial reasons. In the first group, a 3 mm hypan (synthetic hygroscopic dilator) was inserted into the cervix 12 h preoperatively. In the second group, two 1 mg pessaries of gemeprost (prostaglandin analogue) were inserted into the posterior fornix 6 and 2 h preoperatively. Coelomic fluid and maternal serum were obtained at the time of the surgical procedure and assayed for urea, total protein, potassium, sodium, human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Significantly higher coelomic fluid sodium (t = 4.72; P = 0.029) and significantly higher maternal serum AFP (t = 13.21; P < 0.001) concentrations were observed after gemeprost than after hypan. There was no difference in the concentration of potassium, urea, total protein and HCG between the two groups. These findings indicate that prostaglandin analogues, when used for cervical ripening, provoke a breakdown of the placental barrier resulting in an increase in AFP molecules transferred from the fetal fluid compartments into the maternal circulation. The results also suggest that these drugs increase the placental permeability to sodium with a secondary accumulation of this ion in the coelomic fluid.

Abortion, Induced↗

Ultrasound features of normal early pregnancy development.

Recent advances in ultrasound imaging have improved the assessment of early pregnancy development. The gestational sac can be detected within the uterine cavity as early as 4 weeks and 3 days after the last menstrual period. High resolution images of early embryos have enabled ultrasound studies of normal brain, abdominal wall or limb development. The definition of standard developmental morphological features may open the possibility of screening for structural defects early in the first trimester of pregnancy.

Crown-Rump Length↗

Biochemical composition of the coelomic fluid in anembryonic pregnancy.

OBJECTIVE: Our purpose was to investigate the biochemical composition of the coelomic fluid in first-trimester anembryonic pregnancies. STUDY DESIGN: Coelomic and maternal serum were obtained from 17 anembryonic pregnancies and 17 apparently normal pregnancies between 7 and 12 weeks of gestation that were matched for gestational age. Electrolytes, total proteins, urea, creatinine, lactate, and human chorionic gonadotropin concentrations and pH were measured. RESULTS: Significantly higher pH (p < 0.005) and bicarbonate levels (p < 0.001) and significantly lower total protein (p < 0.05), phosphate (p < 0.005), and human chorionic gonadotropin (p < 0.001) levels were found in coelomic fluid from anembryonic pregnancies compared with normal pregnancies. No difference was found for chloride, sodium, potassium, urea, creatinine, and lactate between the study and control groups. CONCLUSIONS: The fluid collected in anembryonic pregnancies is of exocoelomic origin and its biochemical characteristics reflect a failure of most placental biological mechanisms such as metabolic function, transport function, and endocrine activity.

Bicarbonates↗

Investigation of the acid-base balance of coelomic and amniotic fluids in early human pregnancy.

OBJECTIVE: The aim of our study was to analyze and compare the acid-base status of coelomic and amniotic fluids in early human pregnancy. STUDY DESIGN: Coelomic fluid, amniotic fluid, and maternal serum were obtained from 55 normal pregnancies between 7 and 14 weeks of gestation and assayed for pH, PCO2, bicarbonate, chloride, phosphate, total protein, glucose, and lactate concentrations. RESULTS: The coelomic fluid had a significantly lower pH and base excess and contained significantly lower glucose, total protein, and bicarbonate concentrations and higher PCO2, lactate, and phosphate levels than did maternal serum. In the amniotic fluid significantly higher pH, base excess, and lactate and bicarbonate levels and lower concentrations of chloride and phosphate were found compared with the coelomic fluid. Little variation was observed in the coelomic and amniotic fluid composition before 11 weeks of gestation. A significant increase in PCO2, total protein, and chloride levels and a decrease in pH, base excess, and bicarbonate concentrations were observed in the amniotic fluid between 11 and 14 weeks compared with 7 to 10 weeks. CONCLUSIONS: The coelomic fluid composition was indicative of an anaerobic metabolic acidosis probably related to the accumulation of acid compounds from placental metabolism. During the same period of gestation the composition of the amniotic fluid demonstrated a metabolic alkalosis that probably arises from the accumulation of basic substances through the unkeratinized embryonic skin and from the metabolism of organic anions in the embryonic tissues. The changes in the amniotic composition and acid-base balance at the end of the first trimester may correspond to the switch from the mesonephros to the metanephros and result from the excretion in the amniotic fluid of acid metabolic fetal bioproducts through the maturing kidneys.

Acid-Base Equilibrium↗

Relationship between protein concentrations in embryological fluids and maternal serum and yolk sac size during human early pregnancy.

Coelomic fluid (n = 57), amniotic fluid (n = 61) and maternal serum (n = 81) were obtained from normal pregnancies between 7.7 and 13.9 weeks and assayed for total protein, alpha-fetoprotein (alpha FP), albumin and pre-albumin. The mean concentration of total protein in matched samples was 18 times higher in maternal serum than in the coelomic fluid and 54 times higher in the coelomic fluid than in amniotic fluid. The concentrations of total protein, albumin and pre-albumin decreased and that of alpha FP increased in maternal serum with advancing gestation. The yolk sac volume and the concentrations of total protein in the coelomic and amniotic fluids increased with gestational age. No difference was found for the crown-rump length, yolk sac volume and protein concentration in the coelomic fluid between two groups presenting with low and high maternal serum pre-albumin concentrations. Before 11 weeks gestation, significant correlation was only found between yolk sac volume and coelomic fluid concentration of pre-albumin as evaluated by both electrophoresis and immunonephelometry. These results suggest that during the first trimester of normal pregnancy, the placental metabolism and transfer rate of proteins is not directly influenced by the concentrations of protein in the maternal circulation and that the transfer of proteins through the amniotic membrane is limited. These results also indicate that during that period the secondary yolk sac may contribute to the protein content of the exocoelomic cavity, and that the embryo and its yolk sac and subsequently the fetus are the main source of the proteins present in the amniotic fluid.

Adult↗

Comparison of colour Doppler features and pathological findings in complicated early pregnancy.

Resistance index (RI) and pulsatility index (PI) in the uterine and spiral arteries, uterine artery peak systolic velocity and intervillous blood flow were recorded by transvaginal colour Doppler imaging in 30 missed abortions and 30 normal pregnancies matched for menstrual age. Pathological examination was performed in both groups within 24 h of Doppler investigation. The mean uterine PI was significantly (P < 0.01) higher in missed abortions compared to normal controls, whereas the mean uterine RI and peak systolic velocity and spiral RI and PI did not differ. A continuous intervillous flow was found in 16 out of 23 (69.6%) of the complicated pregnancies before 12 weeks of gestation whereas it was not found in controls. In the missed abortion cases, the trophoblastic shell was fragmented or absent in 53% and trophoblastic infiltration and physiological changes in the spiral arteries were reduced or absent in 43 and 63%, respectively. These findings were not related to normal or abnormal Doppler indices. Extended dislocation of the trophoblastic shell and a massive infiltration of the intervillous space and placental bed by maternal blood was also found in cases presenting with a continuous intervillous blood flow before 12 weeks of gestation. These findings suggest that abnormal flow velocity waveforms in early pregnancies complicated by embryonic death are related to deficient placentation and dislocation of the trophoblastic shell that follows embryonic demise. The premature entry of maternal blood into the intervillous space disrupts the materno-embryonic interface and is probably the final mechanism causing abortion.

Abortion, Missed↗

Amino acid concentrations in human embryological fluids.

The concentrations of amino acids in samples of coelomic fluid (n = 15), amniotic fluid (n = 9) and maternal serum (n = 15) obtained from normal pregnancies between 7 and 12 weeks of gestation were measured using reversed-phase chromatography with pre-column derivatization. The total molar concentration of the 18 amino acids measured was 2.3 times higher in coelomic fluid than in maternal serum. All amino acids except serine and tryptophan were present in significantly higher concentrations in coelomic fluid than in maternal serum. Significant correlations between maternal serum and coelomic fluid were only found for proline, tyrosine, and tryptophan, suggesting that levels of the other amino acids are mainly influenced by placental synthesis and do not directly depend on maternal amino acid metabolism. Levels of all amino acids were significantly higher in coelomic fluid compared to amniotic fluid. Compared to maternal serum, the amniotic fluid contained significantly higher levels of arginine, lysine, alanine and tyrosine and lower levels of serine, glutamine and tryptophan. The total molar amino acid concentration decreased significantly with gestational age in both coelomic fluid and maternal serum. These results suggest that amino acids accumulate in coelomic fluid to support the metabolism of the secondary yolk sac, and that the exocoelomic cavity is the reservoir for most nutrients needed by the embryo and early fetus in the first trimester of human pregnancy.

Amino Acids↗