PubMed HealthSearch

Biomedical subjects

R Terinde

Publications and source records attributed to R Terinde.

At least 19 recordsLinked to original sources

In vitro studies on clonal growth of chondrocytes in thanatophoric dysplasia.

Thanatophoric dysplasia (TD) is characterized by a disorganized growth plate with markedly reduced proliferative and hypertrophic cartilage zones. Therefore, we studied in vitro the proliferation rates of articular chondrocytes from five TD patients and age-matched controls in response to bFGF, IGF-I, IGF-II, and TGF-beta 1. In human fetal controls bFGF was the most potent growth factor. Clonal growth the articular chondrocytes in response to bFGF was reduced in two of five TD patients and slightly below the range of controls in a third case. Stimulation of chondrocyte proliferation by IGF I and II was reduced in the patient whose response to bFGF was most markedly impaired. The effect of TGF-beta 1 ranged from normal to slightly elevated values in TD fetuses. These results indicate heterogeneity of the underlying defects in TD. Low proliferative responses of chondrocytes to bFGF and IGF-I/II are likely to play a key role in the pathogenesis of some cases. In two of five patients studied, the mechanisms of bFGF and IGF-signal transduction are candidates for the primary molecular defect.

Cartilage, Articular

Continuous-wave Doppler investigation of uteroplacental vessels in high-risk pregnancies as predictor of fetal growth retardation and pregnancy-induced hypertension.

Continuous-wave Doppler sonography of uteroplacental vessels and the umbilical artery was used as an additive method in the management of risk pregnancies. Its major advantage lies in permitting noninvasive access to placental perfusion. In a sample of 650 singleton pregnancies considered at risk, flow patterns of the right and left uterine and arcuate arteries and of the umbilical artery were obtained. Increased resistance in uteroplacental circulation alone (90th percentile of resistance index and/or notching) was seen in 62 of 100 patients with confirmed growth retardation, proving the key role played by uteroplacental perfusion disorders. Early diastolic notching as well as incomplete vascular flow patterns were also found significantly more often in the growth-retarded group compared to the controls, especially in pregnancies additionally beset by hypertensive disorders. Doppler study of both utero- and fetoplacental circulation increased the sensitivity to 76% in pregnancies with intrauterine growth retardation, and to 90% in those cases with an additional risk of pregnancy-induced hypertension, while the false-positive rate (100-specificity) remained acceptable (17%).

Female

Proliferation and collagen biosynthesis of osteoblasts and chondrocytes in short rib syndrome type beemer.

We report on a case of lethal short-limbed skeletal dysplasia with extremely short ribs, median cleft upper lip and palate, malrotation of intestine, lung hypoplasia with bilateral segmentation defect, atrial septum defect, union of distal urethra and vagina, and complex brain malformations. Based on radiological criteria and the pattern of associated abnormalities a short rib syndrome without polydactyly (Type Beemer) was diagnosed. Morphologically, the growth plate showed a reduced proliferation zone and an enlarged zone of hypertrophic cartilage. In addition, islands of persistent hypertrophic cartilage were present even in the metaphysis. In monolayer cell cultures supplemented with 10% fetal calf serum proliferation was normal in articular chondrocytes, reduced in costal chondrocytes, and elevated in osteoblasts from the patient. Clonal growth of costal and articular chondrocytes in methylcellulose could be stimulated normally by insulin-like growth factor-I (IGF-I), IGF-II, and human growth hormone (hGH). However, the response to transforming growth factor beta 1 (TGF-beta 1) was markedly elevated in articular chondrocytes of the patient compared to those of 3 fetal controls. Quantitative collagen synthesis in both osteoblasts and chondrocytes from the patient did not differ significantly from that of controls. Osteoblasts synthesized predominantly collagen I and minor amounts of collagen III, chondrocytes synthesized primarily collagen II. All collagen chains including CNBr-peptides of collagen II showed normal migration in PAA gel electrophoresis.

Cartilage

Evaluation of amniotic fluid cell filtration: an experimental approach to early amniocentesis.

Prior to a prospective application of amniotic fluid (AF) cell filtration to early amniocentesis, we tested the technique on a surplus from mid-trimester samples. By using the same sample size of 5 ml in experiments with a filter and in routine diagnostic procedures (control), we evaluated an optimal filter system. The prolonged culture time of filtered cells and the reduced number of clones are most probably due to mechanical stress (filtration pressure), whereas loss of the cells by adhesion to the filter system, and an AF-free culture medium (growth factors) are suggested to be less important. The AF cells are very sensitive to mechanical stress. Slow filtration (< or = ml AF/min) through filters with a high porosity and the largest possible pore size should be preferred. A mixed cellulose ester filter membrane with a pore size of 5.0 microns proved to be the most efficient, allowing harvest of the filtered cells after only a slight prolongation of the culture time (+2.4 days) compared with unfiltered aliquots. A filter set with a bypass connected by three-way taps allows cell filtration during either aspiration or reinjection of the AF. Cell filtration after amniocentesis and consecutive reverse flushing of the membrane with the appropriate amount of culture medium proved to be the best with regard to easy handling and reducing the risk of bacterial contamination.

Amniocentesis

A prospective cytogenetic study of third-trimester placentae in small-for-date but otherwise normal newborns.

Data in the literature suggest that confined placental mosaicism might be associated with intrauterine growth retardation. However, this association may be coincidental and due to bias of ascertainment. We therefore started a prospective study based on the cytogenetic evaluation of placentae derived from growth-retarded newborns. We further minimized possible bias by excluding those small-for-date infants displaying findings which already could explain intrauterine growth retardation (mothers who are smokers, multiple pregnancies, gestosis, dysmorphic infants). In a collection of 71 small-for-gestational age newborns, we did not see a single case of true confined placental mosaicism.

Cells, Cultured

Cytogenetic diagnoses after chorionic villus sampling are less reliable in very-high-or very-low-risk pregnancies.

An increasing number of cytogenetic prenatal diagnoses are performed on chorionic villus samplings. The accuracy of this method is influenced by chromosomal mosaicism, mostly confined to direct preparation methods. Especially those investigators who have experienced false-negative and false-positive findings propagate the combined use of direct and culture methods. Yet large collaborative studies have shown that in approximately two-thirds of diagnostic cases only one procedure is applied. Moreover, the accuracy of a cytogenetic investigation depends not only on the ontogenetic origin of the tissues investigated, but also on interacting factors such as the 'a priori risk' and the 'predictive value of a cytogenetic finding'. On this basis a differentiated prenatal diagnostic procedure is discussed, including either sole short-term culture (STC), combined STC and long-term culture (LTC), primary amniocentesis (AC), or primary percutaneous umbilical blood sampling (PUBS). The predictive value of the cytogenetic diagnosis from CVS varies significantly dependent on the a priori risk of a chromosome aberration and, in the case of an abnormal karyotype, on the specific chromosome involved. A non-mosaic and 'non-lethal' trisomy detected in STC is highly representative of the embryo/fetus, but there are exceptions of limited predictive value, e.g., trisomy 18. Guided by the strategy of an optional follow-up by LTC, AC, or PUBS in 1317 successive CV samplings, we are not aware of a false-negative diagnosis, but probably had one false-positive diagnosis: 47,XXY after STC; 46,XY after LTC. When referring to the rate of fetuses with an unbalanced karyotype expected in the different indication groups, a relative increase of false-positive findings in the very-low-risk group (maternal age < or = 35 years of age) and of false-negative findings in the very-high-risk group (abnormal ultrasonographic findings) of pregnant women when only performing CVS becomes obvious. Because of this dilemma, AC or--especially in the latter group--PUBS might be primarily offered to these indication groups instead of CVS.

Adult

[Discordant growth in twin pregnancy--value of Doppler ultrasound].

A 4 MHz continuous-wave Doppler device was used to study uterine and umbilical arterial wave forms in 91 pairs of twins between 18th and 40th week of gestation. Biometry and cord localisation were effected by real-time ultrasound. The results of 182 Doppler flow examinations showed that umbilical flow velocimetry may prove relevant for early identification of twin pregnancies with discordant growth. Depending on the interval between examination and delivery, sensitivity and specificity values between 44% and 66%, and 66% and 73%, respectively, were obtained. A high resistance index in umbilical arteries was indicative of intrauterine growth retardation, at a specificity of 69% and a sensitivity of 44%. For uteroplacental as well as foetoplacental flow velocity waveform assessment, singleton reference values may be used, whereas, by reason of its low sensitivity, Doppler flow velocimetry does not lend itself as a primary diagnostic tool for intrauterine growth retardation. It can signal pathologic blood flow profiles, which are often associated with added risks, such as pregnancy-induced hypertension, foetal acidosis and stillbirth and can contribute to early detection of twin pregnancies that require close clinical and cardiotocographic surveillance.

Blood Flow Velocity

Polynomial analysis of placental flow patterns in growth-retarded fetuses.

Correct interpretation of conspicuous blood flow velocity waveforms cannot rely solely on the evaluation of uteroplacental vascular Doppler flow patterns by means of angle-independent indices such as the resistance or pulsatility index. In addition to the degree of pulsatility, the waveform shape between the systolic and diastolic peak values is of considerable consequence. A subdivision of the total flow waveform into orthogonal polynomial components allows both pulsatility evaluation and notching to be registered, providing a higher sensitivity in identification of pathological vascular resistance. Accurate recording and assessment of the flow waveform is therefore an important qualitative criterion for the classification of Doppler flow patterns in pregnancies with reduced uteroplacental perfusion.

Blood Flow Velocity

[The value of continuous wave Doppler ultrasound in risk pregnancy-intrauterine growth retardation and pregnancy-induced hypertension].

To evaluate the frequency of abnormal doppler results in pregnancies complicated by placental insufficiency, flow waveforms of 100 patients with documented intrauterine growth retardation--birthweight below the 10th percentile--were analysed. Uterine, arcuate and umbilical artery velocimetry were performed by means of a continuous wave Doppler ultrasound. Neither the range of serial examination nor the interval between last prepartal doppler test und delivery showed influence on the doppler results. Compared to normal pregnancy, a significant increase of diastolic notching and incomplete registration of maternal vessels were found. Using 90th percentile as cut-off limit last doppler examination before delivery showed pathological results in 76% of all cases with growth retardation and 90% of pregnancies with an additional risk of pregnancy induced hypertension. As pathological waveforms in the maternal compartment contribute a major part to abnormal velocity waveforms, doppler study of utero-placental vessels plays an important role in the diagnose of impaired persuasion of the placenta.

Blood Flow Velocity

First trimester amniocentesis between the seventh and 13th weeks: evaluation of the earliest possible genetic diagnosis.

Amniocentesis performed at the 12th week and later gives reliable results. The procedure can be performed using regimens developed for mid-trimester amniotic fluid (AF) cells. Extension to the 10th-11th week is, in principle, feasible. However, the high cytogenetic failure rate is a difficulty and despite a high clone count, the culture time is prolonged. The problem of the relatively high loss of AF could be overcome by cell filtration techniques and replacement of the fluid. Because of the short turnover rate of the AF, this may be unnecessary or replacement with an isotonic solution may be sufficient. (Pseudo)mosaicism appears to occur more frequently in early than in late amniocentesis. As yet, data are too sparse to allow a comparison with chorionic villus sampling. There are no reliable follow-up data from which to estimate the abortion rate and the number of embryonic malformations.

Amniocentesis

Introduction of early amniocentesis to routine prenatal diagnosis.

With growing awareness of the problems associated with prenatal cytogenetic diagnoses after CVS, attempts have been made to provide early amniocentesis as an alternative to CVS. Since 1990, at our clinic the gestational age limit for routine diagnostic amniocentesis has been successively lowered, first to 14 and then to 13 weeks of gestation. Thus, 811 prenatal diagnoses were performed after early amniocentesis at 13 weeks (n = 217) and at 14 weeks of gestation (n = 594). No problems were encountered. Culture failure was never observed in the early samples. Using the criteria 'number of colonies' and 'culture duration until harvest', early samples taken at 14 weeks did not differ significantly from the controls after standard amniocentesis performed at 15 and 16 weeks, respectively, whereas a minority of samples taken at 13 weeks experienced some delay in culturing. However, in each group at least 85 per cent of samples led to a diagnosis fulfilling our standard criteria of a safe diagnosis (at least 20 metaphases of at least five colonies from at least one primary culture after trypsinization) within 15 days. Some differences between the different groups can be recognized: culture duration of less than 11 days tends to be increasing after standard amniocentesis, whereas long culture duration (more than 20 days) is more often associated with early amniocentesis. However, this trend is only minimal and did not result in an increased risk of missing a diagnosis.

Adult

[Comparison of different blood flow parameters for evaluating blood flow spectra in fetal growth retardation].

Uteroplacental and foetoplacental vascular resistance is generally high in pregnancies complicated by intrauterine growth retardation. Assessment of flow velocity curves using angle-independent indices as A/B ratio, resistance index (RI) or pulsatility index (PI) cannot classify all cases with pathological flow velocity profiles. Beneath the pulsatility the maximum frequency outline of the flow velocity waveform offers additional clinical information. The evaluation of flow velocity curves using polynome analysis (including III degrees) provides additional data including occurrence of diastolic notching and can be used as a more sensitive indicator of impaired uteroplacental blood flow. In such pregnancies accurate evaluation of the maximum flow velocity outline with polynome analysis has been shown to be an important qualitative criterion in the assessment of blood flow velocity waveforms.

Blood Flow Velocity

[Ultrasound studies in pregnancy: technical principles and clinical safety].

Ultrasound examinations in pregnancy were carried out worldwide for over 30 years with no proof of adverse effects on either, mother or child. However, to evaluate the clinical significance of the numerous studies dealing with questions of safety of obstetrical sonography, a basic knowledge of its physical and technical aspects is needed. The present paper aims to convey these basics and should provide a review of the major publications concerned with the clinical safety of the method. Below clearly defined intensity levels, ultrasound scanning in pregnancy can still be considered unhazardous for both mother and child. However, it must be borne in mind, that the safety margin of Doppler flow measurements is lower for duplex compared with B-mode equipment. Therefore, for the present, duplex sonography should not be routinely applied in the first trimester of pregnancy.

Blood Flow Velocity

Nuclear and chromosomal replication patterns in chorionic villi cells by bromodeoxyuridine labelling and DNA flow cytometry.

Cell kinetics of chorionic villi (CV) were studied by BrdUrd-incorporation detected by fluorescence-plus-Giemsa and BrdUrd-antibody techniques, and by DNA flow cytometry. Growth characteristics of long-term cultures of CV resembled fibroblasts with a total cell cycle time of 26 h, final S phase of 9 h, penultimate S phase of 16 h and G2/M phase of 3-4 h. Especially useful for a quick routine diagnostic approach, Ultroser RG, a commercially available serum supplement, significantly increased cell proliferation and stabilized cell cycle lengths to a total cell cycle time of 14 h, final S phase of 7 h, penultimate S phase of 6 h and G2/M phase of 4 h. Moreover, mitotic activity steadily increased in cultured CV, when studying six successive subculturings. This reflects adaptation to the culture conditions rather than an inherent response of cultured CV cells of increasing passage numbers. Native villi exposed to BrdUrd immediately after biopsy show lower rates of uptake than do aliquots after overnight incubation. As shown by BrdUrd-pulse labelling studies, more than 7 h are required to overcome the proposed 'biopsy stress'. This correlates with routine diagnostic techniques, in which many more metaphase cells are observed in short-term cultures than in direct preparations.

Bromodeoxyuridine

[Early diastolic incisures in uteroplacental blood vessels. Experiences in patients with uneventful pregnancy and labor].

The frequency of diastolic notching in uteroplacental arteries was examined in a collective of 510 patients with uneventful pregnancies and deliveries. Notching appeared to be more frequent in the uterine than arcuate artery. It was seen to increase as pregnancy progressed and was markedly higher in the third compared with the second trimester. Uteroplacental notching occurred more frequently unilaterally and mainly affected contralateral sites of the placenta. Bilateral and retroplacental notching was the exception in normal pregnancies.

Blood Flow Velocity

Reference values for resistance index and pulsatility index of uteroplacental Doppler flow velocity waveforms based on 612 uneventful pregnancies.

Using a 4-MHz continuous-wave Doppler device, standard rates were established for resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries of 612 patients with uneventful pregnancies and deliveries. From 18 to 41 weeks of gestation, neither RI nor PI of uterine or arcuate arteries proved to vary with gestational age, maternal heart rate, or maternal age. By contrast, a significant effect of placental location on the measurement results was found in both uterine and arcuate arteries. The differences between measurements on the placental or opposite site are more distinct in arcuate than in uterine arteries. Taking the 90th percentile as a localization gauge, cutoff levels of 0.52 (RI) and 0.98 (PI) were found in uterine arteries. In arcuate arteries, cutoff levels of 0.45 (RI) and 0.82 (PI) were found on the placental site or with a placenta without lateralization. On the nonplacental site of a lateralized placenta, the cutoff levels were 0.51 (RI) and 0.92 (PI).

Blood Flow Velocity