Biomedical subjects

J Ojuel

Publications and source records attributed to J Ojuel.

18 recordsLinked to original sources

PubMed2000

Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity.

In human brain, nonartherosclerotic calcification is associated with normal aging and several pathological conditions without any clear significance. In all situations, calcification appears predominantly in the basal ganglia, but is also frequent in the hippocampus and cerebral cortex. alpha-Amino-(3-hydroxi-5-methyl-4-isoxazol-4-il)-propionic acid-induced lesion of the globus pallidus is associated in rats with the formation of calcium deposits similar to those observed in the human brain. To determine whether direct neuronal activation may induce calcification, N-methyl-d-aspartate (NMDA) was microinjected in rat hippocampus, globus pallidus, and lateral prefrontal cortex. Two months later, neuronal death was associated with calcium deposits that were characterized in terms of distribution and size. A unique population of deposits was present in the hippocampus and prefrontal cortex, whereas in the globus pallidus two main groups could be differentiated. Calcification was always associated with a significant microglial reaction as shown by the peripheral benzodiazepine receptor autoradiography. Monoamine oxidase B autoradiography, reflecting the astroglial reaction, was also significantly increased. Our results provide evidence that acute NMDA neuronal activation leads with time to calcification associated with a glial reaction and indicate that nonartherosclerotic calcification in the human brain may develop from an acute NMDA receptor activation. A key role of the metabotropic mGluR1 receptor is also suggested.

Animals↗

PubMed1999

First-trimester biochemical markers for Down syndrome.

The value of maternal serum pregnancy-associated protein A (PAPP-A), free and total beta human chorionic gonadotrophin (fbetahCG, betahCG) and alpha-fetoprotein (AFP) in screening for Down syndrome (DS) in early pregnancy has been assessed. To evaluate the different biochemical markers, 32 DS pregnancies and 267 controls were used for AFP, betahCG and PAPP-A. A subgroup of those (17 DS and 136 controls) were used to evaluate fbetahCG. All analytes were determined in fresh serum samples. Our results give support to the feasibility of maternal serum levels of PAPP-A as the best biochemical marker for DS in the first trimester, and either betahCG or fbetahCG as the second marker. No differences were found between betahCG and fbetahCG distribution levels as expressed as MoMs in normal and DS pregnancies in this study.

Adult↗

PubMed1998

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

Adult↗

PubMed1998

Fetal heart rate and nuchal translucency in detecting chromosomal abnormalities other than Down syndrome.

OBJECTIVE: To evaluate whether the combined use of fetal heart rate (FHR) and nuchal translucency measurements would be useful in the prediction of fetal chromosomal abnormalities at 10-13 weeks' gestation. METHODS: In a prospective study, 1053 (553 reported previously) consecutive singleton pregnancies between 10 and 13 weeks' gestation underwent chorionic villus sampling at our institution. Fetal heart rate and fetal nuchal translucency thickness were measured immediately before the invasive procedure. RESULTS: Thirty-five abnormal karyotypes were diagnosed, including 17 trisomy 21, seven trisomy 18, one trisomy 13, one trisomy 9, four unbalanced translocation, two Klinefelter syndrome, one Turner syndrome, one deletion of chromosome 18, and one true mosaicism. Using 95% of normal ranges as the cutoff for both measurements, the detection rate for all chromosomal anomalies was 77.1%, with a false-positive rate (1-specificity) of 7.7%, a positive predictive value of 25.7%, and a negative predictive value of 99.2%. Fetal heart rate improved the sensitivity of nuchal thickness in trisomies 21 and 18 (from 62.5% to 75%) and was particularly useful to detect other chromosomal anomalies (from 27.2% to 81.8%). CONCLUSION: Our findings suggest that there is an added role of FHR in ultrasound screening of chromosomal abnormalities, specifically for those other than trisomy 21 and 18. The value of a single measurement of fetal heart rate for screening purposes needs to be confirmed by further investigation in a low-risk population.

Adult↗

PubMed1997

Brachycephaly is ineffective for detection of Down syndrome in early midtrimester fetuses.

The aim of this study was to assess the value of fetal brachycephaly in the detection of Down syndrome at 13-18 weeks of pregnancy. The cephalic index (CI) was determined in 555 consecutive chromosomally normal fetuses, and in 38 chromosomal abnormalities, prior to amniocentesis. A CI > 0.85 was observed in 14% (2/14) of the fetuses with Down syndrome and in 11% of the normal fetuses. In conclusion, our data show that brachycephaly is not a useful marker for Down syndrome in early midtrimester fetuses.

Adolescent↗

PubMed1997

Umbilical Doppler velocimetry in fetuses with trisomy 18 at 10-18 weeks' gestation.

The aim of our study was to obtain measurements of the umbilical artery pulsatility index (PI) in pregnancies before invasive procedures for prenatal diagnosis, in order to investigate its potential prognostic value in predicting trisomy 18. We performed a prospective study including 1785 consecutive women from 10 to 18 weeks with singleton pregnancies undergoing chorionic villus sampling (n = 559) or genetic amniocentesis (n = 1226) in our unit. Doppler measurements were performed transvaginally (tenth to 13th week of gestation) or transabdominally (14th to 18th week of gestation) immediately before the invasive procedure. In 7 out of 10 fetuses subsequently diagnosed as trisomy 18, the PI was above the 95th centile, providing a detection rate of 70 per cent, a specificity of 95.1 per cent, a positive predictive value of 7.7 per cent, and a negative predictive value of 99.8 per cent. When the 90th percentile was assayed as a cut-off, the efficacy of PI as a marker of trisomy 18 yielded a sensitivity of 90 per cent and a specificity of 90.4 per cent, with a positive predictive value of 5.2 per cent and a negative predictive value of 99.9 per cent. We suggest that although the use of a single PI measurement for screening purposes needs to be confirmed by further investigation, trisomy 18 fetuses show an abnormal increase in umbilical PI in the first half of pregnancy, and its relation to the early onset of fetal growth retardation needs to be further explored.

Blood Flow Velocity↗

PubMed1997

Combining nuchal translucency with umbilical Doppler velocimetry for detecting fetal trisomies in the first trimester of pregnancy.

OBJECTIVE: The aim of our study was to evaluate whether the combined use of umbilical artery pulsatility index (UAPI) and nuchal translucency (NT) measurements would be useful in the prediction of fetal chromosomal abnormalities at 10 to 13 weeks of gestation. DESIGN: A prospective study. POPULATION AND METHODS: Five hundred and fifty-three consecutive women with singleton pregnancies between 10 and 13 weeks of gestation, who underwent chorionic villus sampling at our institution. UAPI and fetal NT thickness were measured immediately before the invasive procedure. Pregnancies in which structural malformations had been detected by ultrasound were excluded. RESULTS: Using the 95th centile and 3 mm as the cutoffs for UAPI and NT, respectively, the detection rate for all chromosomal anomalies was 84.2%, with a false positive rate (1-specificity) of 6.6%, a positive predictive value of 31.3%, and a negative predictive value of 99.4%. Out of the 553 tested pregnancies 502 had both parameters within the normal range and only three of them (0.6%) were chromosomally abnormal; in six of the eight cases (75%) in which both parameters were abnormal a chromosome anomaly was present. Of the 43 cases in which only one parameter was abnormal, 10 were chromosomally abnormal (23.2%). CONCLUSIONS: Our results suggest that the presence of chromosomal anomalies may be strongly suspected when an increased NT thickness (NT > or = 3 mm) is associated with an abnormally high UAPI at 10 to 13 weeks of gestation. The number of cases studied is small, however, and these conclusions are tentative and preliminary. The value of a single measurement of NT and UAPI for screening purposes needs to be substantiated by further investigation.

Adult↗

PubMed1996

Doppler assessment of umbilical flow after genetic amniocentesis.

The aim of our study was to evaluate the immediate changes on the fetal heart rate (FHR) and the fetal umbilical artery pulsatility index (UPI) after performing genetic amniocentesis. This was a prospective study including 431 consecutive singleton pregnancies between 14 and 18 weeks undergoing genetic amniocentesis in our institution. Doppler measurements were obtained transabdominally before and immediately after the procedure. Structural malformations detected by ultrasound were excluded. Student's t-test was performed for comparisons among different groups and observed mean changes. The results showed a significant decrease in FHR post-amniocentesis (mean 1.5 beats, t = 3.47, P < 0.01) and a non-significant elevation in UPI (mean -0.01, t = -0.29, P = 0.77) after the procedure. Differences in FHR could be found when analyzed by each gestational week. These preliminary data suggest that although acute fetal hemodynamic changes are detected after genetic amniocentesis, such changes are unlikely to have clinical relevance. However, it is reasonable to propose the use of Doppler as a method of assessing hemodynamic effects caused by prenatal invasive procedures in order to provide more accurate in vivo research on this issue.

Adult↗

PubMed1996

Immediate changes in umbilical blood flow after transcervical chorionic villus sampling performed by biopsy forceps.

Transvaginal ultrasonography with colour Doppler was used to evaluate the immediate changes on the fetal heart rate (FHR) and the fetal umbilical artery pulsatility index (PI) after chorionic villus sampling (CVS). This prospective study included 279 consecutive singleton pregnancies, between 10 and 13 weeks, of women who underwent transcervical CVS in our institution. All Doppler measurements were obtained transvaginally before and immediately after CVS. Structural malformations detected by ultrasound were excluded. Student's t- and Wilcoxon texts were performed for statistical analysis. The results showed no significant decrease in FHR (mean 1.04 beats, t = 1.68, P = 0.94) and a significant elevation of umbilical artery PI (mean 0.12, t = - 6.51, P < 0.001) post-CVS. This difference was only significant in procedures performed at less than 11 weeks' gestation, since there was no significant change for those procedures performed thereafter. These preliminary data suggest that acute fetal haemodynamic changes are induced by CVS and may have clinical effects. Hypotheses on possible vascular mechanisms are discussed. Colour Doppler could widen the possibilities for more accurate in vivo assessment and research on CVS-related placental injury.

Abortion, Spontaneous↗

PubMed1996

First-trimester biochemical screening for Down syndrome with the use of PAPP-A, AFP, and beta-hCG.

Biochemical screening for Down syndrome (DS) is well established in the second trimester of pregnancy, but there is little information available on its value in the first trimester. This study describes our preliminary results with biochemical screening for DS in the first trimester of pregnancy in order to evaluate its efficacy at this time. Our study population, including 19 DS pregnancies, was evaluated using maternal serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and pregnancy-associated plasma protein A (PAPP-A). At a false positive rate (FPR) of 5 per cent, the detection rate (DR) for DS is 9 per cent for beta-hCG, 18 per cent for AFP, and 66 per cent for PAPP-A when considering these parameters individually. With different combinations of the analytes, the best detection rates are obtained with the association of PAPP-A and AFP (85 and 82 per cent DR for a 10 and 5 per cent FPR, respectively). Our data support the value of first-trimester biochemical screening for DS and that of PAPP-A as a single marker.

Adult↗

PubMed1996

Fetal heart rate patterns in pregnancies with chromosomal disorders or subsequent fetal loss.

OBJECTIVE: To evaluate whether an abnormal fetal heart rate (FHR) is associated with chromosomal abnormalities in pregnant women undergoing an invasive procedure for prenatal diagnosis, and to investigate an abnormal FHR's potential value in predicting fetal loss in chromosomally normal pregnancies after the procedure. METHODS: This was a prospective study including 867 women, all consecutive singleton pregnancies at 10-18 weeks' gestation, who underwent chorionic villus sampling (n = 371) or genetic amniocentesis (n = 496) at our institution. Fetal heart rate, expressed as beats per minute, was measured before the invasive procedure. Structural malformations detected by ultrasound were excluded. RESULTS: Chromosomal abnormalities were diagnosed in 25 fetuses, including 11 with trisomy 21. In ten of 25 fetuses with chromosomal abnormalities, the FHR was between the fifth and 95th percentiles established before the procedure for the chromosomally normal group with normal outcome. Using the fifth percentile as a cutoff for trisomy 21, the detection rate was 63.6%, with a specificity of 96.2% and a positive predictive value of 17.9% (one in 5.5) in our population. Moreover, in six of the ten chromosomally normal miscarriages occurring within 4 weeks after the procedure, the FHR was above the 95th percentile. CONCLUSION: Although the value of a single measurement for screening purposes needs to be confirmed by further investigation, our preliminary data suggest that chromosomal anomalies, especially trisomy 21, may be suspected in fetuses with an abnormally low FHR in early pregnancy. In chromosomally normal fetuses, the detection of an abnormally high FHR in some degree may be predictive of fetal loss after the invasive procedure.

Adult↗

PubMed1996

Early midtrimester fetal nuchal thickness: effectiveness as a marker of Down syndrome.

OBJECTIVE: Our purpose was to assess the validity of nuchal thickness in the prediction of Down syndrome in early midtrimester fetuses. STUDY DESIGN: In 1543 consecutive pregnancies undergoing amniocentesis, primarily for advanced maternal age, nuchal thickness was prospectively measured between 13 and 18 weeks and then correlated with the karyotype obtained from amniotic fluid. RESULTS: With the cutoff value suggested in the literature (> or = 6 mm), 33.3% (6/18) of the cases of Down syndrome would be detected for a 0.1% (2/1424) false-positive rate, with a positive predictive value adjusted to a prevalence of Down syndrome in the general population of 1:3. To increase the sensitivity of the method, the threshold was lowered to 5 mm, achieving a sensitivity of 77.8% (14/18) for a 2.1% (30/1424) false-positive rate and an adjusted positive value of 1:19. CONCLUSIONS: In early midtrimester fetuses decreasing the nuchal thickness threshold to 5 mm substantially enhances the detection of Down syndrome with a reasonable false-positive rate.

Down Syndrome↗

PubMed1996

Reversed end-diastolic umbilical artery velocity in two cases of trisomy 18 at 10 weeks' gestation.

Doppler velocimetry of the umbilical artery was carried out during routine ultrasound examinations performed immediately before either chorionic villus sampling (n = 383) or genetic amniocentesis (n = 649) in 1032 women referred for prenatal diagnosis at our institution, between 10 and 18 weeks of gestation. Reversed end-diastolic flow was detected in only two cases (0.19%), both of which were affected by trisomy 18. The diagnosis was made at 10 weeks' gestation and, to our knowledge, these are the earliest records of this pathological Doppler pattern. Although a possible relationship with early abnormal placentation remains to be established, the finding of reversed end-diastolic velocities in the umbilical artery in the first trimester of pregnancy may be an early sign of karyotype abnormality.

Adult↗

PubMed1995

First-trimester nuchal edema as a marker of aneuploidy.

Targeted ultrasonographic screening for nuchal fluid accumulation during the first trimester (9-13 weeks) seems to be a recommendable method for the detection of Down's syndrome and other chromosomal anomalies in pregnant women. It compares favorably with current methods of maternal serum screening performed during the second trimester. Using a 4-mm cut-off value, the detection rate of aneuploidy among our population was found to be 57.1%, with a false-positive rate of 0.7% and a positive predictive value of 72.7%. Chromosomal analysis should be considered for fetuses with nuchal translucency equal to or greater than 4 mm in the first trimester.

Adolescent↗

PubMed1995

The influence of the site of Doppler recording on umbilical artery pulsatility index during the first trimester.

The aim of our study was to determine the pulsatility index (PI) of the umbilical artery velocity waveform obtained from the fetal insertion, the placental insertion and a free floating loop of the umbilical cord. This was a prospective study involving 60 consecutive singleton pregnancies undergoing ultrasound examination between 10 and 13 weeks' gestation. Doppler measurements were obtained transvaginally from the placental and the fetal abdominal insertion, and from a free floating loop of umbilical cord. Chromosomal abnormalities and structural malformations detected by ultrasound were excluded. A multi-way analysis of variance did not show significant differences between the measurements of umbilical PI at the different sites of the umbilical cord and Pearson's coefficient showed an excellent correlation between them. No significant intra- and interobserver differences were found. In conclusion, measurements of Doppler velocimetric indices of the umbilical artery during the first trimester are not influenced by the recording site and these recordings are reproducible at this stage of gestation.

Adult↗

PubMedDate not supplied

Biphasic and region-specific MAO-B response to aging in normal human brain.

Variations of monoamine oxidases (MAO) A and B were studied during aging in 27 human subjects (age range 17-93 years) in 18 brain structures of temporal cortex, frontal gyrus, hippocampal formation, striatum, cerebellum, and brainstem. [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. Postmortem delay or time of tissue storage did not affect MAO-A or MAO-B levels. There was, moreover, no evidence of sexual dimorphism. A marked age-related increase in MAO-B was observed in most structures. This increase started at the age of 50-60 years. Before this age, MAO-B levels were constant in all structures studied. MAO-B-rich senile plaques were observed in some cortical areas but they did not significantly influence the age-related MAO-B increase. Surprisingly, no age-related MAO-B changes were observed in the substantia nigra. In contrast to MAO-B, no clear age-related changes in MAO-A were observed, indicating an independent regulation of the two isoenzymes, also suggested by the cross-correlation analysis of these data.

Adolescent↗

PubMedDate not supplied

Limited effectiveness of femur and humerus shortening as markers of Down syndrome in early midtrimester fetuses.

This is a prospective screening study addressed to assess the value of femur and humerus shortening in the prenatal detection of Down syndrome. Prior to amniocentesis, 1,543 consecutive pregnancies between 13 and 18 weeks were studied. Femur and humerus shortening were assessed with the use of 6 different ratios, and then correlated with the karyotype obtained in amniotic fluid. Sensitivities achieved for Down syndrome with femur ratios were lower than those using humerus (17-22 vs. 43%) for similar false-positive rates (7-8 vs. 6-8%). The most effective ratio was the observed-to-expected humerus length with 43% sensitivity for a 6% false-positive rate. Combining femur and humerus measurements did not substantially improve the prediction obtained using the best humeral ratio. In conclusion, femur and humerus shortening appears to be of limited value in the detection of Down syndrome.

Adult↗

PubMedDate not supplied

[Alexithymia and verbal intelligence: a psychometric study].

INTRODUCTION: Alexithymia is a concept that describes the unability to put emotions into words ant that has been associated with somatization and psychosomatic disorders. METHODS: A sample of 124 outpatients attending the Psychosomatic Unit of a General Hospital was studied in order to test the hypothesis that alexithymic patients have a significantly lower verbal intelligence than nonalexithymics. Alexithymia was assessed by the Toronto Alexithymia Scale (TAS), and verbal, nonverbal and general intelligence were measured by the WAIS. RESULTS: TAS scores were not related to medical and psychiatric diagnoses, and alexithymic patients (n: 53) showed not only significantly lower scores in verbal intelligence than undifferentiated subjects (n: 37) and nonalexithymics (n: 34) but also significantly lower scores in nonverbal and general intelligence. CONCLUSION: The results do not confirm our hypothesis and are discussed in relation to theories that consider alexithymia as a consequence of cerebral asymmetry and interhemispheric dysfunctions.

Adult↗