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Biomedical subjects

K Boer

Publications and source records attributed to K Boer.

At least 37 records · Page 2Linked to original sources

A placental diploid cell line is not essential for ongoing trisomy 13 or 18 pregnancies.

Viable trisomy 13 or 18 pregnancies may be supported by the presence of a diploid cell line, confined to the outer layer of the placenta (cytotrophoblast). To establish the presence of diploid cells we investigated five random biopsies from placentas of trisomy 13 (n = 8) and trisomy 18 cases (n = 6) of newborn infants and terminated pregnancies by means of fluorescence in situ hybridisation on interphase nuclei (n = 100). In 12 of these 14 placentas (including all five liveborns) 80% or more of the analysed nuclei showed three spots, suggestive of the presence of a full trisomy. In the other two placentas (both cases of trisomy 18) mosaicism was detected at most investigated sites. Thus, in contrast with earlier studies, these results show that a significant diploid cell line present in the placenta, confined to the trophoblast, is not a pre-requisite for intrauterine survival in the investigated cases.

Adult↗

Polyhydramnios and arterio-arterial placental anastomoses may beneficially affect monochorionic twin pregnancies.

Our objective was to appraise whether an increased amniotic fluid pressure by polyhydramnios can beneficially affect monochorionic twins that are haemodynamically connected by arterio-venous plus arterio-arterial placental anastomoses. We assessed the effects of polyhydramnios in monochorionic twin placentas, combining (a) data from previous in vitro placental perfusion experiments in singleton term placentas under simulated normal and increased amniotic fluid pressures with (b) logical deduction from observations made in monochorionic twins. Our hypothesis is that in monochorionic placentas, an increased amniotic fluid pressure increases the placental microvascular resistance but not the resistance of placental chorionic plate arteries. Hence, an increased amniotic fluid pressure increases the microvascular resistance of the joint cotyledon, the arterio-venous resistance, but not the arterioarterial resistance. This proposed mechanism reduces arterio-venous but not oppositely directed arterio-arterial transfusion. Therefore, reversal of the normal direction of net foeto-foetal transfusion may develop, which will reduce the circulatory imbalance that evolved between the monochorionic foetal twins. In contrast, in monochorionic twins connected by unidirectional or bidirectional arterio-venous anastomoses reversal of the normal direction of net foeto-foetal transfusion will not occur. In conclusion, reversal of the normal direction of net foeto-foetal transfusion, induced by polyhydramnios, is protective against the onset and severity of twin-twin transfusion syndrome in monochorionic twins connected by arterio-venous plus arterio-arterial anastomoses, but not by unidirectional or bidirectional arterio-venous anastomoses.

Amniotic Fluid↗

Endothelial function in myometrial resistance arteries of normal pregnant women perfused with syncytiotrophoblast microvillous membranes.

OBJECTIVE: To investigate the effects of syncytiotrophoblast microvillous membranes (STBM) in concentrations, found in vivo in women with pre-eclampsia, on endothelial function in isolated resistance arteries. SETTING: Department of Obstetrics and Gynaecology, Huddinge University Hospital, Stockholm. SAMPLE: Twenty-nine myometrial resistance arteries isolated from biopsies of healthy term pregnant women, obtained during caesarean section. METHODS: The myometrial arteries were mounted in a pressure arteriograph and perfused intraluminally for three hours with STBM (20 to 2000ng/mL) or with erythrocyte membranes or physiological salt solution as controls, all substituted with 0.5% bovine serum albumin. Bradykinin concentration-response curves were performed before and after perfusion. MAIN OUTCOME MEASURES: The bradykinin concentrationresponse curves were fitted to the Hill equation and maximal dilation and the pEC50 values were determined from these fits. Differences within groups were analysed with a paired Student's t test. Electron microscopic evaluation of the endothelium was performed. RESULTS: Neither STBM nor erythrocyte membrane perfusion affected maximal dilation or the pEC50 values of the bradykinin concentration-response curves at any concentration. Examination by electron microscopy showed no obvious damage to the endothelium after perfusion with STBM or erythrocyte membranes. CONCLUSION: Perfusion with STBM in concentrations up to 100 times those reported in pre-eclampsia has no significant effect on bradykinin-mediated dilation in isolated myometrial arteries.

Adult↗

Impaired vascular function in women with pre-eclampsia observed with orthogonal polarisation spectral imaging.

OBJECTIVE: To investigate in vivo the function of the microcirculation of the skin in pregnancy and pregnancy complicated with pre-eclampsia. DESIGN: Case-control study. SETTING: Academic Medical Centre. PARTICIPANTS: A group of 10 women with pre-eclampsia and a healthy control group of 10 pregnant women. METHODS: The microcirculation of the skin of the finger at rest and during venous occlusion was studied with laser Doppler fluxmetry and orthogonal polarisation spectral imaging. By inflating a cuff around the upper arm to a pressure of 50 mmHg, causing venous occlusion, the local sympathetic veno-arteriolar reflex was provoked. With laser Doppler fluxmetry the blood flow of the skin at a depth of 1-2mm was measured at rest and during venous occlusion. Orthogonal polarisation spectral imaging was used to assess red blood cell velocity at rest and during venous occlusion of the nutritive capillaries of the skin. RESULTS: Laser Doppler fluxmetry showed no significant difference between the normotensive group and the group with pre-eclampsia. Using orthogonal polarisation spectral imaging, venous occlusion produced a significantly greater decrease in red blood cell velocity in the control group than in the women with pre-eclampsia: (84% (81-88)(median and interquartile range) vs 58% (45-88), P = 0.0029). No differences in absolute red blood cell velocities were observed between groups either at rest or during venous occlusion. CONCLUSION: This study shows an impaired local veno-arteriolar reflex in pre-eclampsia at the nutritive, but not at the therrmoregulatory, level of the microcirculation of the skin.

Adult↗

Comparison of OPS imaging and conventional capillary microscopy to study the human microcirculation.

Orthogonal polarization spectral (OPS) imaging is a new clinical technique for observation of the microcirculation of organ surfaces. For validation purposes, we compared OPS images of the nailfold skin with those obtained from conventional capillary microscopy at rest and during venous occlusion in 10 male volunteers. These images were computer analyzed to provide red blood cell velocity and capillary diameters of the same nailfold capillaries at rest and during venous occlusion. Results showed that OPS images provided similar values for red blood cell velocity and capillary diameter as those obtained from capillary microscopy images. OPS imaging, however, provided significantly better image quality, as shown by comparison of image contrast between OPS imaging and capillary microscopy. This made image analysis better and easier to perform. It is anticipated, therefore, that OPS imaging will become a new and powerful technique in the study of the human microcirculation in vivo because it can be used on human internal organs.

Adult↗

Vascular function in preeclampsia.

Preeclampsia is a multisystem disorder peculiar to human pregnancy. It occurs in 4-5% of all pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The pathophysiology of this syndrome is not fully understood. Two stages of vascular dysfunction seem to be involved. In the early stage suboptimal development of the placenta and a hemodynamic maladaptation to pregnancy exist. At this stage maternal constitutional factors such as genetic and immunological factors and pre-existing vascular diseases may play a role. Due to this defective placentation a factor is released from the placenta, supposedly under the influence of ischemia. This factor then results in the late vascular dysfunction characterised mainly by a generalised endothelial dysfunction, leading to the clinical syndrome of preeclampsia. This review attempts to unravel the mechanisms that may contribute to preeclampsia-associated changes in vascular function and to indicate the research needed to improve our understanding of this disease.

Adult↗

Prenatal HLA-matching to determine suitability for allogeneic bone marrow transplantation.

For several haematological malignancies, allogeneic stem cell transplantation is the treatment of choice. In most cases an HLA-identical sibling is required. If the mother of a patient is pregnant, cord blood from a related donor, which can be used for stem cell transplantation, might be obtainable in the near future. For the patient, knowledge of the foetal HLA-type can be important since it might influence choice of treatment and timing of transplantation. If the foetus is HLA compatible, as would be the situation in 25% of cases, the delivery has to be arranged in such a way that cord stem cells can be collected. As a result, in the other 75% of cases (spontaneous) delivery can take place in the home/local setting. Here we report four cases in which amniocentesis was performed and HLA-typing influenced treatment of the patient and delivery of the sibling.

Amniocentesis↗

Intra- and interoperator repeatability of the nuchal translucency measurement.

OBJECTIVE: The aim of this study was to assess the repeatability of nuchal translucency measurement by well-trained sonographers either experienced or inexperienced with the measurement. METHODS: The nuchal translucency was measured three times by two out of nine operators in 161 pregnant women attending two teaching hospitals. Intra-operator and inter-operator variation was assessed by calculating the standard deviation (SD). Intraclass Correlation Coefficients (ICC) with a 95% lower confidence limit (95% CL) were calculated for each operator and for pairs of operators. Intra- and inter-operator kappa statistics were calculated, after dichotomising the results into a nuchal translucency smaller or larger than 3 mm. RESULTS: The SD of intra-operator difference was 0.35 mm. The intra-operator repeatability showed ICCs varying from 0.83 to 0.95 for the experienced operators and from 0.47 to 0.83 for the inexperienced. The SD of inter-operator differences was 0.56 mm, 0.46 mm and 0.44 mm, based on one, two and three measurements, respectively. The inter-operator repeatability showed a variation in ICC from 0.74 to 0.95 in pairs of experienced sonographers to 0.51 in one pair inexperienced with the measurement. The kappa value expressing the intra and inter-operator repeatability as being > 3 mm or < 3 mm was 0.88 and 0.85, respectively. CONCLUSION: This study supports the finding that the nuchal translucency measurement is reproducible, as long as it is performed by sonographers well trained in the technique of this measurement.

Down Syndrome↗

Lack of relationship between diurnal rhythms in fetal heart rate and maternal cortisol concentration.

In 9 pregnancies complicated by intrauterine growth restriction, 24-hour fetal heart rate recordings were made before and after betamethasone treatment to study the influence of cortisol on diurnal fetal heart rate rhythms. Maternal and fetal rhythms were correlated and did not change after betamethasone administration. We conclude that diurnal fetal heart rate rhythms are synchronized by the mother through a mechanism other than adrenal control.

Betamethasone↗

Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems.

UNLABELLED: Small head size has been observed in prenatally anticonvulsant-exposed neonates. In infancy, cognitive impairments were revealed. It is presently unknown whether these impairments are permanent or disappear after puberty. We studied the link between the prenatal influence of anticonvulsants on brain development and cognitive functioning in adulthood: a retrospective study on head size and a follow-up assessing cognitive capacities among adults who had been included in the retrospective study. The retrospective study comprised 172 exposed and 168 control neonates, matched with respect to age, sex and their mothers' age. Prenatally phenobarbital + phenytoin-exposed neonates had a significantly smaller occipitofrontal circumference (OFC) than prenatally phenobarbital-monotherapy-exposed and control neonates (mean difference of 0.7 cm). In the follow-up, no difference in cognitive functioning was found between the exposed and the control groups. Most of the prenatally anticonvulsant-exposed subjects had normal intellectual capacity. However, 12% of the exposed subjects versus 1% of the controls had persistent learning problems. In addition, more of the exposed subjects were mentally retarded. There was no clear relationship between learning problems and small OFC, maternal epilepsy or unfavourable family climate. CONCLUSIONS: We conclude that the combination of phenobarbital + phenytoin affects the fetal OFC. The smaller OFC does not seem to be related to cognitive functioning in adulthood, but learning problems and mental retardation proved to be more prevalent among exposed subjects. Phenobarbital and phenytoin may therefore affect cognitive capacity but only in infants who are susceptible to this particular influence of the drugs.

Adult↗

Neurologic development of the newborn and young child in relation to maternal thyroid function.

A prospective observational study was performed in pregnant women with known thyroid disease. We studied the effect of maternal thyroid function in the first half of pregnancy on the neurologic development of the infant in the first 2 y of life. Clinical and thyroid function data were collected from 20 pregnant women with known thyroid disease and their newborn children. Infants were divided into three groups according to their maternal thyroid function within the first half of pregnancy: Group A (n = 7): maternal subclinical hypothyroidism, Group B (n = 6): maternal euthyroidism, and Group C (n = 7): maternal hyperthyroidism or subclinical hyperthyroidism. Neurophysiologic, i.e. motor nerve conduction velocity and somatosensory evoked potentials and neurologic and developmental (Bayley scales) assessments were done. One infant, born to a mother with Graves' disease, developed transient hyperthyroidism. At the age of 6 and 12 mo, the mean mental developmental index (MDI) score was 16 points lower for infants in Group A than for those in Group B (p = 0.03 and 0.02, respectively). At the age of 24 mo, the mean MDI score was 6 points lower, which was not statistically significant. Neurophysiologic and neurologic assessments and the mean Psychomotor Developmental scores did not differ among the three groups. In conclusion, maternal subclinical hypothyroidism in the first half of pregnancy was associated with a lower mean MDI score in their infants during the first year of life.

Developmental Disabilities↗

[No consensus on the definition, diagnosis and treatment of habitual abortion in the Netherlands].

OBJECTIVE: To review the current policy in diagnosis and treatment of recurrent miscarriage in the Netherlands. DESIGN: Cross-sectional survey. METHOD: A printed questionnaire was sent in 1996 to all 125 departments of gynaecology in the Netherlands with questions about definition, investigation and therapy of recurrent miscarriage. RESULTS: The response rate was 90% (n = 112). Twenty-nine per cent of the respondents defined recurrent miscarriage as having two or more abortions and 71% as three or more abortions. In 42% of the departments a diagnostic protocol for recurrent miscarriage was present. Diagnostic investigations most frequently performed were vaginal ultrasound (79%), parental chromosome analysis (78%), thyroid-stimulating hormone (72%), lupus anticoagulant (69%), blood glucose (65%), hysterosalpingography (56%) and anticardiolipin antibodies (IgG, IgM) (56%). Therapy most frequently applied was prescription of folic acid (53%). CONCLUSION: The definition of recurrent miscarriage differed. Uncertainty about a rational diagnostic approach was evident from the large number of tests requested by 20-50% of the respondents. Some diagnostic tests like immunological investigation and search for infectious factors were not followed by a therapeutical intervention.

Abortion, Habitual↗

[Preeclampsia not (yet) predictable from the blood platelet count].

Platelet activation plays an important role in the pathogenesis of pre-eclampsia as demonstrated by reduced platelet count, increased mean platelet volume and elevated plasma concentrations of beta-thromboglobulin and platelet factor 4 in pre-eclamptic patients. Thrombocytopenia precedes the onset of clinical symptoms of pre-eclampsia. Possibly an enhanced activation state of the platelets in the circulation is present some time before the onset of pre-eclampsia: platelet activation might then be used to predict pre-eclampsia. Flow cytometry is considered the most sensitive technique at this moment to measure the activation of platelets. Fluorescent-labelled antibodies are used to detect antigens that appear on the platelet surface or change their conformation upon activation. During the first and second trimester of pregnancy pre-eclamptic patients have an increased expression of some antigens on the surface of their platelets, such as CD63. There is no reliable platelet test yet to predict the onset of pre-eclampsia.

Adult↗

Clinical outcome and follow-up of sonographically suspected in utero urinary tract anomalies.

PURPOSE: We determined the outcome of pregnancy and long-term renal function in cases of sonographically detected fetal urinary tract anomalies (UTAs). METHODS: This was a retrospective cohort study done at an academic hospital (tertiary referral center). All records of prenatal sonographic examinations done between January 1985 and October 1994 that indicated a suspicion for UTA were examined for perinatal mortality, postnatal confirmation of sonographic diagnosis, postnatal management, and calculated creatinine clearance to determine the ultimate renal function. RESULTS: Of 99 cases with suspected UTAs, 28 pregnancies were terminated because the UTA was considered fatal, and 32 fetuses died perinatally. Twenty-one children are alive with good renal function, 4 with moderate renal function, and 2 with poor renal function. The prenatal diagnosis was not confirmed after birth in 12 children, all of whom are alive with good renal function. The prognosis for prenatally suspected UTA was worse in cases of bilateral involvement and in cases with associated multiple malformations. CONCLUSIONS: The prognosis of prenatally diagnosed UTAs depends on the specific anomaly suspected. Abnormal karyotype, other associated malformations, and bilateral involvement are unfavorable determinants of the prognosis in individual cases.

Cohort Studies↗

Prenatal exposure to anticonvulsants and psychosexual development.

Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in humans were investigated. A follow-up study was carried out in phenobarbital- and phenytoin-exposed subjects and control subjects matched for age, sex, and the mothers' ages. Subjects were born in the Academic Medical Center between 1957 and 1972. Out of 243 exposed and 222 control subjects who were asked to volunteer, 147 exposed subjects (72 male, 75 female) and equal numbers of their matched control subjects participated in the follow-up study. They were interviewed and were asked to fill out questionnaires on gender role behavior, gender development, and sexual orientation. As a group, exposed and control subjects did not differ with respect to gender role behavior, although higher numbers of prenatally anticonvulsant-exposed subjects reported current or past cross-gender behavior and/or gender dysphoria. Three prenatally anticonvulsant-exposed subjects were transsexuals and had undergone sex reassignment surgery, a remarkably high rate given the rarity of transsexualism. In addition, two exposed males had exclusively homosexual experiences, whereas none of the control males reported exclusive homosexual behavior. The groups did not differ in attainment of pubertal psychosexual milestones.

Anticonvulsants↗

Two trials of antenatal thyrotrophin-releasing hormone for fetal maturation: stopping before the due date. Antenatal TRH Trial and the Thyroneth Trial Groups.

OBJECTIVES: To determine whether the addition of antenatal thyrotrophin-releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity. DESIGN: Two concurrent multicentre, double blind, randomised, placebo-controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial. SETTING: Hospital maternity units. POPULATIONS: Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation. INTERVENTIONS: Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo. MAIN OUTCOME MEASURES: Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects. RESULTS: The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5-1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo. CONCLUSIONS: These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta-analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials.

Adrenal Cortex Hormones↗