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Zoltán Papp

Publications and source records attributed to Zoltán Papp.

At least 73 records · Page 4Linked to original sources
PubMed2005

Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone.

We characterized the Ca2+-sensitizing and phosphodiesterase (PDE)-inhibitory potentials of levosimendan and enoximone to assess their contributions to the positive inotropic effects of these drugs. In guinea pig hearts perfused in the working-heart mode, the maximal increase in cardiac output (55%, P<0.05) was attained at 50 nM levosimendan. The corresponding value for enoximone (36%) was significantly smaller (P<0.05) and was observed at a higher concentration (500 nM). In permeabilized myocyte-sized preparations levosimendan evoked a maximal increase of 55.8+/-8% (mean+/-SEM) in isometric force production via Ca2+ sensitization (pCa 6.2, EC50 8.4 nM). Enoximone up to a concentration of 10 microM failed to influence the isometric force. The PDE-inhibitory effects were probed on the PDE III and PDE IV isoforms. Levosimendan proved to be a 1300-fold more potent and a 90-fold more selective PDE III inhibitor (IC50 for PDE III 1.4 nM, and IC50 for PDE IV 11 microM, selectivity factor approximately 8000) than enoximone (IC50 for PDE III 1.8 microM, and IC50 for PDE IV 160 microM, selectivity factor approximately 90). Hence, our data support the hypothesis that levosimendan exerts positive inotropy via a Ca2+-sensitizing mechanism, whereas enoximone does so via PDE inhibition with a limited PDE III versus PDE IV selectivity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Pharmacological mechanisms contributing to the clinical efficacy of levosimendan.

Acute decompensation of chronic heart failure is a direct life-threatening situation with short-term mortality approaching 30%. A number of maladaptive changes are amplified within the cardiovascular system during the progression of chronic heart failure that makes the decompensation phase difficult to handle. Levosimendan is a new Ca2+-sensitizer for the treatment of acutely decompensated heart failure that has proved to be effective during the decompensation of chronic heart failure and acute myocardial infarction. Levosimendan differs from other cardiotonic agents that are used for acute heart failure in that it utilizes a unique dual mechanism of action: Ca2+-sensitization through binding to troponin C in the myocardium, and the opening of ATP-sensitive K+ channels in vascular smooth muscle. In general, these mechanisms evoke positive inotropy and vasodilation. Clinical studies suggested long-term benefits on mortality following short-term administration. It may, therefore, be inferred that levosimendan has additional effects on the cardiovascular system that are responsible for the prolongation of survival. Results of preclinical and clinical investigations suggest that the combination of levosimendan-induced cardiac and vascular changes has favorable effects on the coronary, pulmonary and peripheral circulations. Redistribution of the circulating blood offers an improved hemodynamic context for the development of a positive inotropic effect through Ca2+-sensitization of the contractile filaments, without a proportionate increase in myocardial oxygen consumption or the development of arrhythmias. Activation of ATP-sensitive K+ channels, both on sarcolemma and mitochondria, may protect against myocardial ischemia, and decreased levels of cytokines may prevent the development of further myocardial remodeling. Collectively, these effects of levosimendan shift the disturbed cardiovascular parameters towards normalization, thereby halting the perpetuation of the vicious cycle of heart failure progression. This may contribute to stabilization of the circulation and improved life expectancy of patients with chronic heart failure.

Animals↗
PubMed2005

Trisomies and other chromosome abnormalities detected after positive sonographic findings.

OBJECTIVE: To evaluate the rate of trisomies and other chromosome abnormalities after positive ultrasound findings in thefirst and second trimester of pregnancy. STUDY DESIGN: The study investigated chromosome abnormalities detected in cases with prior abnormal ultrasoundfindings. During a 10-year period there were 1907 invasive interventions carried out with the purpose of chromosome analysis. The intervention was genetic amniocentesis in 1619 cases and chorionic villus sampling in 288. RESULTS: Karyotyping revealed 103 cases (5.4%) of chromosome abnormalities. Abnormalities with subcutaneous edema were examined: abnormal karyotype was found in 20% of cases with nonimmune hydrops, 48.1% of cases with cystic hygroma and 53.8% of cases with nonimmune hydrops and cystic hygroma together, 8.3% of cases with nuchal edema in the first trimester and 5.5% in the second trimester. The incidence of chromosome abnormalities in cases of cerebral anomalies was 6.3% of cases with ventricular dilatation, 3.6% of cases with choroid plexus cysts and 15.9% of cases with other cranial anomalies. Regarding abnormalities of the heart, isolated echogenic intracardiac focus and ventricular septal defects were not associated with chromosome abnormality, but, in conjunction with other positive ultrasound findings, the incidence of chromosome abnormalities was 7.9% and 26.7%, respectively. Other anomalies of the heart and large blood vessels showed an abnormal karyotype incidence of 18.2%. In cases of unilateral pyelectasis unassociated with other anomalies, the incidence of chromosome abnormalities was 1%. In cases of bilateral pyelectasis or pyelectasis associated with other anomalies, the incidence was 3%. In terms of anomalies of the abdominal wall and abdomen, the incidence of association with chromosome abnormalities was 9.5% in cases of omphalocele, 11.8% in cases of duodenal atresia and 5.7% in cases of echogenic bowel. In cases of short femur and humerus the rate of abnormal karyotypes was 16%. CONCLUSION: Ultrasound plays an important role in prenatal diagnosis. In cases of positive ultrasound findings, karyotyping is reasonable.

Amniocentesis↗
PubMed2004

[Diagnosis and treatment of haemodynamically significant fetal tachycardia--in 33 cases].

INTRODUCTION: Fetal tachycardia may lead to an increased pre- and postnatal morbidity and mortality rate particularly if it is complicated by cardial decompensation and hydrops fetalis. AIM AND METHODS: In this study 33 fetal tachycardia cases diagnosed and treated between 1993 and 2004 in the fetal echocardiography unit of the I. Department of Obstetrics and Gynecology of the Semmelweis University, Budapest are reviewed. The data of postnatal care of the newborns delivered in the author's department from these pregnancies, and the follow up data provided by the National Institute of Cardiology are examined as well. RESULTS: Mean gestational age at diagnosis of fetal tachycardia was 30 weeks (21-41 weeks). The tachyarrhythmias were classified into atrial flutter (n = 8), supraventricular tachycardia (n = 18), arrhythmia absoluta (n = 5), parasystole (n = 1) and brady-tachyarrhythmia (n = 1). Six cases were complicated by hydrops fetalis, 13 cases by cardial dysfunction. Transplacental antiarrhythmic therapy was applied in 22 cases, in 8 cases the newborns were delivered because of advanced gestational age, in 3 cases tachyarrhythmia resolved spontaneously or therapy was not indicated. The drug of first choice for transplacental therapy was digoxin, which was combined with amiodarone or verapamil (n = 10). Transplacental therapy led to cardioversion in 13/22 cases. The outcome of the 33 examined pregnancies was live birth in 27 cases, in utero death in 3 cases and 3 newborns were delivered elsewhere. The postnatal documentation of 24 newborns out of the 27 born in the author's department is available. At the time of birth 15/24 newborns were in sinus rhythm--out of whom 5 developed tachyarrhythmia later during the neonatal period--, 9/24 were tachycardic. Out of the 14 cases of tachyarrhythmia detected in the neonatal period altogether 3 resolved spontaneously, in 7 cases antiarrhythmic therapy was successful, in 4 cases unsuccessful. In 2 of these latter cases electrical cardioversion led to sinus rhythm. Neurological disorder was not detected in any case. In the early postnatal period 2 in utero severely decompensated newborns died. The follow-up data of 10 children is available, the follow-up period ranges between 6 weeks and 5 and a half years. All 5 children with history of supraventricular tachycardia are in sinus rhythm, 3 of them after suspending antiarrhythmic treatment, while the other 2 still on antiarrhythmic medication. Four out of 5 children with history of atrial flutter are in sinus rhythm, 2 of them left antiarrhythmic therapy, and 2 of them still take antiarrhythmic agents after electrical cardioversion. The atrial flutter of a 3 month old child could not be controlled yet permanently, despite several drug combinations applied. CONCLUSIONS: Survival and late prognosis of tachycardic fetuses treated in utero is good. A prospective study of even more cases is required to establish uniform therapeutic guidelines and to provide appropriate follow-up data.

Amiodarone↗
PubMed2004

[Isolation of free DNA from archived serum samples suitable for molecular genetic studies].

INTRODUCTION: Collected and archived serum samples could be important sources for genetic studies, once DNA suitable for molecular genetic studies could be obtained from them. METHODS: DNA was isolated from 54 archived sera samples, collected previously from the participants of a Hungarian allergy study, with commercially available isolation kit. The authors have determined the concentration of the isolated DNA (81.88 +/- 52.36 ng/ml) and the size of the isolated fragments was estimated using semiquantitative real-time PCR. Two primers were used producing two different fragment size, for the phospholipase 2A and the actin beta genes, and melting curve analyses was performed as quality control. RESULTS: The concentration of the phospholipase 2A product was 2.9798 +/- 5.4454 microg/microl and the actin beta gene was 0.0015 +/- 0.0011 microg/microl. The melting curve analysis served as a quality control for the determination of the size of PCR products. In the case of the phospholipase 2A all samples produced the 133 bp PCR fragments, except one, while in the case of actin beta gene only six sample showed the expected 178 bp product, all the others samples had smaller fragments. CONCLUSIONS: These results confirm the suitability of the DNA isolated from archived sera samples for further molecular biological studies (SNP analysis, mutation detection) and give an estimate for the product size of the isolated DNA. Sera samples have been collected years ago can be a good source of genetic information on different diseases.

Actins↗
PubMed2004

[Assessment of prognostic factors in common ovarian tumors of varying malignancy].

OBJECTIVE: The outcome and prognosis of apparently similar cases of epithelial ovarian cancers with the same histology and stage is highly variable. The objective was to compare survival and prognostic factors of patients treated at the 1st Department of Obstetrics and Gynecology of Semmelweis University between 1993-2003 with the similar data of the 25th Annual Report on the Results of Treatment in Gynecological Cancer of FIGO. In addition, the aim was to assess the prognostic value of MMP activities and fibronectin concentration in ovarian tumour patients. METHODS: The 25th Annual Report of FIGO included 5694 patients with ovarian tumours from 32 countries diagnosed and treated between 1995 and 1998. Hungary did not participate in this report. Between 1993 and 2003, 180 patients with common epithelial ovarian tumours had been treated at the 1st Department of Obstetrics and Gynecology of Semmelweis University. Treatment and survival data derived from medical record review and from the Population Register Office. In order to compare different prognostic factors, a multivariate Cox proportional regression analysis was performed. The authors measured MMP activities in 33 surgically removed ovarian tumours, serum and ascites by applying zymographic technique. Fibronectin content was determined by Western blot analysis and quantitated by densitometry. RESULTS: The 5-year survival was 90.0% and 30.9% in the case of ovarian tumours with low malignant potential and of epithelial ovarian cancers, respectively. Multivariate analysis identified adverse prognostic factors including advanced age (>60 years) and stage, high grade and suboptimal operation with residual macroscopic disease and the presence of ascites. However, the histological type was not identified to be an adverse prognostic factor in this study. No correlation could be seen between the histology of the ovarian tumours and the elevation of MMP-2/9 activity. More interestingly, however, MMP-9 expression and fibronectin concentration were significantly elevated and the activated forms of both MMP-9 and MMP-2 were more frequent in ovarian cancer patients who developed recurrent disease. CONCLUSION: A great deal of effort should be devoted to identification of further prognostic factors to improve treatment of ovarian cancer. These prognostic factors might help to identify those ovarian cancer patients at the time of diagnosis whose disease will have unfavourable outcome. Our data support the notion that high expression of MMP-9 and fibronectin indicates poor prognosis of ovarian cancer patients.

Adenocarcinoma, Clear Cell↗
PubMed2004

[First attempts of detecting fetal cells in the maternal circulation].

INTRODUCTION: In prenatal diagnosis there is great interest for noninvasive diagnostic methods. Authors report their first results in detecting fetal cells in the maternal circulation during pregnancy. OBJECTIVE: The aim of the study was to detect fetal gender from maternal peripheral blood samples during pregnancy. METHOD: Authors have analysed fetal nucleated red blood cells. In 12 cases after a double density Percoll gradient separation they labelled the surface antigens of the cells with anti-glycophorin-A and anti-CD45 fluorescent antibodies, did an intracellular staining of the epsilon haemoglobin chain, and analysed the cells with flow cytometry. The CD45 negative/glycophorin-A positive/epsilon-haemoglobin chain positive cells were considered as fetal cells. Having the results, in another 13 cases magnetic activated cell sorting with CD71 antibody were used as an enrichment step. Authors made an intracellular staining of the epsilon haemoglobin chain, the positive cells were isolated by micromanipulation, and analysed by single cell fluorescent polymerase chain reaction. Primers for the amelogenin gene were used to detect fetal gender. RESULTS: Only the Percoll enrichment step itself is not enough for using the samples for diagnostic molecular-biologic examinations, a following enrichment step is needed. For this the authors used magnetic activated cell sorting with CD71 antibody. With the help of this enrichment step, after the intracellular staining of the epsilon haemoglobin chain the direct micromanipulator isolation of the epsilon haemoglobin chain positive cells could be done. After analysing single cells by fluorescent polymerase chain reaction, in 8 out of the 11 comparable cases the results were similar to those, what was found during the genetic amniocentesis. In 2 cases from this 8, genetic amniocentesis proved Klinefelter syndrome, which they could also confirm with the examination of fetal cells in the maternal circulation. CONCLUSION: The results of the study suggest that the method described above can be useful in prenatal genetic diagnosis, and improving it could be useful to detect other genetic abnormalities (chromosomal abnormalities, single gene disorders) as well.

Antigens, CD↗
PubMed2004

[Cytogenetic exploration of fetal ultrasound anomalies].

AIMS: To evaluate the rate of trisomies and other chromosome abnormalities after positive ultrasound findings in first and second trimester. METHODS: In this study authors investigate the chromosome abnormalities detected in cases with prior abnormal ultrasound findings. During a ten-year period there were 1907 invasive interventions carried out with the purpose of chromosome analysis. The invasive intervention was genetic amniocentesis in 1619 cases and chorion villus sampling in 288 cases. RESULTS: Karyotyping revealed 103 cases (5.4%) with chromosome abnormalities. Abnormalities with subcutaneous oedema were examined: abnormal karyotype was found in 20% of cases with non-immune hydrops, 48.1% of cases with cystic hygroma, and 53.8% of cases with non-immune hydrops and cystic hygroma altogether, 8.3% of cases with nuchal oedema in the 1st trimester, and 5.5% in the 2nd trimester. The incidence rate of chromosome abnormalities in cases with cerebral anomalies was 6.3% of cases with ventricular dilatation, 3.6% of cases with choroid plexus cysts, and 15.9% of cases with other cranial anomalies. Regarding abnormalities of the heart; isolated echogenic intracardiac focus and ventricular septal defects were not associated with chromosome abnormality, but, in conjunction with other positive ultrasound findings the incidence rate of chromosome abnormalities were 7.9% and 26.7%, respectively. Other anomalies of the heart and large blood vessels showed an abnormal karyotype incidence rate of 18.2%. In cases of unilateral pyelectasis unassociated with other anomalies, the incidence rate of the chromosome abnormalities was 1%. In cases of bilateral pyelectasis, or pyelectasis associated with other anomalies, the incidence rate was 3%. In terms of anomalies of the abdominal wall and the abdomen; the incidence rate of association with chromosome abnormalities was 9.5% in cases with omphalocele, 11.8% in cases with duodenal atresia, and 5.7% in cases with echogenic bowel. In cases with short femur and humerus the rate of abnormal karyotype was 16%. CONCLUSIONS: Ultrasound plays important role in prenatal screening and diagnostics. In cases with positive ultrasound findings, the performance of karyotyping is reasonable.

Chromosome Aberrations↗
PubMed2004

[Elevated expression of matrix metalloproteinase-9, and fibronectin concentration in recurrent epithelial ovarian cancer].

INTRODUCTION: Ovarian cancer is the leading cause of mortality from gynecologic malignancies in developed countries. However, the outcome of apparently similar cases with regard to histology and stage is highly variable. In contrast to carcinomas of parenchymal organs such as the breast, lung, and colon, the spread of the epithelial ovarian carcinomas is characterized by transcoelomic dissemination of tumor cells into the peritoneal cavity. Matrix metalloproteinases, and fibronectin play an important role in this process. OBJECTIVES AND METHODS: The authors made an attempt to predict recurrence of ovarian cancer by comparing the clinico-pathologic characteristics, grading and biological behavior of the ovarian malignancies with the matrix metalloproteases activities and fibronectin expression. This study involved 17 patients with epithelial ovarian cancers, 5 patients with benign ovarian tumours, 5 patients with normal ovaries, 5 patients with ovarian tumours of low malignant potential, 4 patients with sex-cord stromal ovarian tumours and 2 patients with germ cell ovarian tumours. Matriolytic activity was detected in the surgically removed tumours, in serum and in ascites by gelatin zymography and quantitative assessment was performed by using densitometric scanning wih an Eagle Eye II (Stratagenic CA. USA). MMP-2 and MMP-9 activity was expressed in arbitrary units (U) per 10 g of ovarian cancer tissue. Fibronectin content was identified by Western blot analysis and quantity estimated by densitometric analysis. The-median follow-up period was 20.5 months. RESULTS: Activated forms of matrix metalloproteinase-2,-and-9 were not detected in normal ovaries. The expression levels of MMP-2 and MMP-9 were higher in epithelial ovarian cancers than in benign ovarian tumors, but the differences were not statistically significant. The MMP-9 activity was markedly elevated in advanced-stage and poorly-differentiated ovarian cancer compared to early-stage and well-differentiated ovarian malignancy. This relationship was not observed with regard to MMP-2 activity. The fibronectin concentration was significantly higher in ovarian cancers compared with benign ovarian tumors and normal ovaries. Fibronectin concentration significantly elevated in ovarian cancer patients with recurrent disease compared with ovarian cancer patients without recurrence. In patients with recurrent ovarian cancer the activated forms of MMP-9 were significantly higher compared to ovarian cancers without recurrence. CONCLUSION: In conclusion, our data support the hypothesis that the expression of tumor-derived matriolytic enzymes and fibronectin are important in the growth of ovarian tumours. The interaction of MMP-9 with fibronectin appears to be one of the key factors in the biology of epithelial ovarian cancers.

Adult↗
PubMed2004

Endotoxin-induced TNF-alpha production changes inversely to its plasma level during pregnancy.

OBJECTIVE: To study plasma TNF-alpha levels during normal pregnancy and the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells. STUDY DESIGN: In a longitudinal prospective study the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells and the plasma level of TNF-alpha in 18 women with uncomplicated pregnancies were determined at the 8th, 17th, 27th and 36th weeks of their pregnancy and 48 h and 6 weeks post-delivery. TNF-alpha levels were determined by ELISA technique. Data were analysed by Student's unpaired t-test. RESULTS: From the second trimester LPS-induced TNF-alpha production increased significantly (P<0.05) compared to non-pregnant values. In contrast, spontaneous TNF-alpha levels decreased with gestational age. Lowest values of plasma TNF-alpha levels and highest values of ex vivo endotoxin-induced TNF-alpha levels were detected at the 27th and 36th gestational weeks, respectively. Both parameters returned to non-pregnant levels after 6 weeks of delivery. CONCLUSION: Gestational age influences TNF-alpha production during normal pregnancy. The observed elevation of inducible TNF-alpha production may contribute to the immune defence of the mother against infections.

Female↗
PubMed2004

[Genetic amniocentesis in twin pregnancy--experience of eleven years].

AIMS: Genetic amniocentesis is the most commonly used method for the diagnosis of genetic disorders of the fetus. PATIENT AND METHODS: The authors give an account of their experiences on genetic amniocentesis performed in almost 200 cases of twin pregnancies in the last eleven years. They examined the outcome of the pregnancies, the fetal loss, the distribution of the deliveries, the perinatal mortality data and the technical aspects of the procedures. The control group included twin pregnancies not undergoing genetic amniocentesis. RESULTS: The authors found that the spontaneous fetal loss between the 18th and 24th gestation weeks is 2.39%. After genetic amniocentesis this rate is 3.87%. According to their results this light increase in fetal loss is non significant. CONCLUSIONS: The results suggest that beyond the 5th week after genetic amniocentesis the fetal loss can not be concluded as a result of the procedure. Regarding the outcome of the pregnancies they suggest, that the procedure should be done around the 18th gestation weeks. In their experience the procedure did not affect the perinatal mortality data.

Amniocentesis↗
PubMed2004

[Chorionic villus sampling and amniocentesis: invasive procedures and their risks in current prenatal diagnostic practice].

AIM: Since the two invasive diagnostic procedure, chorionic villus sampling and amniocentesis play important role in prenatal diagnosis, evaluation of their maternal and fetal risks is one of the most important part of genetic counselling. NEW DEVELOPMENTS: There are numerous factors that influence the specific risk of fetal aberrations or chromosomal abnormalities of the actual fetus. Risk factors and different conditions, modifying the procedure-related risk are discussed in the paper together with new chapters of prenatal diagnosis. CONCLUSION: The authors underline that individually tailored risk-assessment needs to be established during pre-procedure genetic counselling. This should take into account all the factors having impact on the specific risk in the actual pregnancy. Psychologic factors and recent scientific developments should also be discussed in order to give most information to the parents before they decide about taking any invasive procedure.

Amniocentesis↗
PubMed2004

The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig.

The concentration dependences of the Ca(2+)-sensitizing and the phosphodiesterase-inhibitory effects of levosimendan (the (-) enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile) and its active metabolite, OR-1896 (the (-) enantiomer of N-[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl] acetamide), were compared with their positive inotropic effects to reveal their mechanisms of action in guinea pig hearts. In Langendorff-perfused hearts, left ventricular +dP/dt(max) increased by 26+/-4% and 25+/-3% (mean+/-S.E.M.), with EC(50) values of 15+/-2 and 25+/-1 nM for levosimendan and OR-1896, respectively. In permeabilized myocyte-sized preparations, levosimendan and OR-1896 both increased isometric force production via Ca(2+) sensitization (at pCa 6.2), by 51+/-7% and 52+/-6%, with EC(50) values of 8+/-1 and 36+/-7 nM (P<0.05), respectively. Thus, the two molecules could be defined as Ca(2+) sensitizers and positive inotropes with very similar concentration dependences. However, major differences appeared when the phosphodiesterase-inhibitory effects of levosimendan and OR-1896 were probed on the two phosphodiesterase isoforms (phosphodiesterases III and IV) dominant in the left ventricular cardiac tissue. Levosimendan was a 40-fold more potent and a 3-fold more selective phosphodiesterase III inhibitor (IC(50) for phosphodiesterase III=2.5 nM, and IC(50) for phosphodiesterase IV=25 microM, selectivity factor approximately 10000) than OR-1896 (IC(50) for phosphodiesterase III=94 nM, and IC(50) for phosphodiesterase IV=286 microM, selectivity factor approximately 3000). Hence, our data support the hypothesis that levosimendan and OR-1896 both exert positive inotropy via a Ca(2+)-sensitizing mechanism and not via simultaneous inhibition of the phosphodiesterases III and IV isozymes in the myocardium at their maximal free plasma concentrations.

Acetamides↗
PubMed2004

Use of serum inhibin A and human chorionic gonadotropin measurements to predict the outcome of in vitro fertilization pregnancies.

OBJECTIVE: To assess the clinical value of maternal serum inhibin A measurements in early pregnancy in the prediction of outcome of IVF pregnancies and to compare the predictive accuracy of inhibin A concentrations with serum hCG concentrations. DESIGN: Retrospective study.University-based IVF program. PATIENT(S): One hundred fifty IVF pregnancies of 150 couples were studied during a 4-year period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association between pregnancy outcome and age, number of collected oocytes, number of transferred embryos, and serum hCG and inhibin A concentrations in early pregnancy was studied with logistic regression. Predictive accuracy of inhibin A and hCG concentrations was calculated by receiver-operating characteristic (ROC) analysis. RESULT(S): Lower serum concentrations of inhibin A and hCG were associated with increased odds for preclinical abortion and early pregnancy loss, whereas higher inhibin A and hCG concentrations were observed in multiple ongoing pregnancies. Inhibin A measurements were superior to hCG in the prediction of preclinical abortions; no significant difference was observed between the predictive value of hCG, inhibin A, or their combination in differentiating between ongoing pregnancies and early pregnancy losses. The discriminative potential of inhibin A for prognosticating multiple ongoing pregnancies was lower than that of hCG. CONCLUSION(S): Although serum inhibin A concentrations are more accurate than hCG levels for predicting preclinical abortion after IVF, they had no advantage in forecasting ongoing or multiple ongoing pregnancies, suggesting that routine assessment of serum inhibin A concentrations during follow-up of IVF pregnancies is unjustified.

Abortion, Spontaneous↗
PubMed2004

Human brain of preterm infants after hypoxic-ischaemic injuries: no evidence of a substantial role for apoptosis by using a fine-tuned ultrasound-guided neuropathological analysis.

Preterm birth may be associated with hypoxic-ischaemic encephalopathy (HIE) showing a well recognised number of patterns, including neuronal karyorrhexis/eosinophilia mostly at the diencephalon and brain stem and leukomalacia at the periventricular white matter. To investigate whether programmed cell death or apoptosis plays a role in HIE, we examined human brains of preterm infants. Brain tissue samples from 12 consecutive infants (24-34 weeks of gestation) were available at post-mortem examination (1998-2000) after approval of the Ethics Committee. Two tissue sections were stereologically localised after brain fixation, slice preparation, and comparison with ultrasound imaging. We studied the periventricular white matter and the corresponding cortical region in each brain. Conventional histological stains were used. In addition, apoptosis was detected using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labelling (TUNEL) method (NeuroTACS). A semiquantitative evaluation was performed to compare regions close to brain lesions with injury-free areas. Neuronal apoptosis was low in both cortical and in periventricular regions. No glial apoptosis was detected. Apoptosis in neurones was, however, detected in preterm brains with bacterial or mycotic infection. These results point out to the ambiguity of the TUNEL-reactive neurons in the diseased premature infants using fine-tuned ultrasound-guided neuropathological analysis, support the probable coexistence of neuronal TUNEL-reactivity and infection, and suggest that the association between apoptosis and HIE should overall be viewed with more caution.

Apoptosis↗
PubMed2004

Factors influencing parental decision making in prenatal diagnosis of sex chromosome aneuploidy.

OBJECTIVE: To evaluate factors influencing parental decisions toward continuing or terminating a pregnancy with prenatal diagnosis of sex chromosome aneuploidy. METHODS: We reviewed the records of patients with fetuses with sex chromosome aneuploidy between 1990 and 2001. A questionnaire survey of women who chose to terminate such pregnancies was designed to examine aspects of their decision-making process. RESULTS: Forty-nine of 89 pregnancies with sex chromosome aneuploidy were terminated (termination rate 0.55; 95% confidence interval 0.45-0.65). Pregnancies with abnormal ultrasound findings (14/16, 87%), with 45,X or 47,XXY karyotypes (26/36, 72%), and with nonmosaic karyotypes (30/48, 63%) were terminated significantly more often than pregnancies with normal ultrasound findings (35/73, 48%; P <.01), with 47,XXX or 47,XYY karyotypes (4/12, 33%; P <.05), and with mosaic karyotypes (5/25, 20%; P =.01). There was a trend (P =.136) toward a lower rate of termination from 67% to 36% across time, with a significant decrease from 67% to 7% in pregnancies with 47,XXX; 47,XYY; and mosaic karyotypes (P <.01), and no change in cases with 45,X and 47,XXY karyotypes (67% compared with 69%; P = 1.0). Abnormal sexual development and infertility were the greatest parental concerns related to termination. CONCLUSION: Fear of having a child with abnormal sexual development or infertility remains the major determinant of parental decision toward terminating pregnancy, resulting in consistently high termination rates across time in pregnancies with 45,X and 47,XXY karyotypes. In cases with 47,XXX; 47,XYY; and mosaic karyotypes, the declining termination rate across time is a consequence of recent studies reporting normal sexual development and fertility.

Abortion, Induced↗
PubMed2003

[Fetal sex determination with real time PCR of fetal DNA in maternal plasma].

INTRODUCTION: Non-invasive methods using maternal plasma and serum for molecular genetic diagnosis become an important field of interest in prenatal genetic diagnosis. Free fetal DNA in maternal plasma and serum has been shown to be useful for fetal gender determination, and seems to offer a new possibility to perform non-invasive prenatal genetic diagnosis. A possible application is fetal sex determination for couples at risk of X-linked diseases. The aim of this study was to control the reliability and reproducibility of the real-time PCR amplification of the SRY region. MATERIALS AND METHODS: Maternal serum before amniocentesis, and amnionic fluid samples were obtained from 56 pregnant women during the 11th to 22nd weeks of gestation. Real-time PCR analysis of the SRY region was performed in order to determine the fetal sex. Routine karyotyping of cultured amnionic cells was also performed on the samples. Six cases were excluded. RESULTS: In 26 of 50 pregnancies were found male fetuses by cytogenetic analysis. Real time PCR of maternal plasma has been positive for the SRY region in 27 cases. In 47 cases the cytogenetic gender and the real-time PCR result was correlating. In one case of 46,XY karyotype the PCR reaction for SRY region was negative, in two cases of SRY positivity the karyotype was 46,XX. In this study are presented the results of fetal sex determination in maternal plasma using real time PCR method. CONCLUSIONS: The real time PCR detection of fetal DNA in maternal plasma seems to be an easy non-invasive method to determine the fetal sex at this gestational age. Our experience is promising in terms of the specificity and sensitivity of the method.

Adult↗