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Biomedical subjects

K Boer

Publications and source records attributed to K Boer.

At least 19 recordsLinked to original sources

[Timely recognition and treatment of hypothyroidism in pregnant women: benefit for the child].

Three women aged 36, 34 and 33 years, with primary hypothyroidism were euthyroid whilst on levothyroxine treatment. Two women had previously received 131iodine therapy due to Graves' disease. During pregnancy the levothyroxine dose required to maintain a normal TSH level increased. The serum TSH-binding inhibiting immunoglobulins (TBII) activity was still very high (188 U/l) in one of the women, but decreased to 26 U/l in the last trimester. Foetal or neonatal thyrotoxicosis was not observed. The levothyroxine dose was decreased after delivery and none of the women experienced any adverse effects as a result of this. It is recommended that all women taking levothyroxine should have their serum TSH activity measured during the first trimester. The daily dose of levothyroxine required will usually increase by 50 micrograms during pregnancy. The determination of serum TBII activity is indicated in the case of Graves' disease; serum TBII values of > 40 U/l constitute a risk of foetal or neonatal thyrotoxicosis.

Adult↗

[Pregnancy (conception) in hyper- or hypothyroidism].

Pregnancy is accompanied by changes in thyroid function. Due to the increased synthesis of thyroid binding globulin and the thyroid-stimulating effect of human chorionic gonadotrophin (hCG), serum concentrations of thyroid hormones will increase in the first trimester of pregnancy (total T4, T3). Free T4 levels decrease during the latter half of pregnancy. Hyperthyroidism during pregnancy is usually due to Graves' disease. Definitive therapy may be considered for cases prior to pregnancy, although a medical management as would be given during pregnancy is an equally good option. The medical management of hyperthyroidism consists of a monotherapy with thyreostatics in which the recommended dose needs to be adjusted on the basis of free T4 in the high-normal and thyroid stimulating hormone (TSH) in the low-normal area so as to minimise the risk of foetal hypothyroidism. The transplacental passage of maternal TSH receptor stimulating antibodies may cause foetal hyperthyroidism. Another cause of maternal hyperthyroidism during pregnancy is 'gestational transient thyrotoxicosis', which is associated with high hCG levels during the first trimester of pregnancy. It is nearly always accompanied by hyperemesis gravidarum. Hypothyroidism in pregnancy has negative consequences for the foetus. If the hypothyroidism is apparent prior to pregnancy, it should be corrected before conception (target TSH value of 1 mU/l). If discovered during pregnancy, treatment with levothyroxine should be started as soon as possible. In the case of a pre-existing hypothyroidism a 25-50% increase in the levothyroxine dosage is often needed during the first trimester of pregnancy. This is possibly due to an increased requirement. An adequate serum concentration of T4 is necessary for foetal brain development.

Adult↗

Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders.

BACKGROUND: Animal studies demonstrated that early exposure to phenobarbital decreases reproductive function. This study investigates whether prenatal exposure to these anticonvulsants affects human genital tract development. METHODS: Genital anomalies at birth were studied retrospectively in 90 phenobarbital-exposed, 108 phenobarbital plus phenytoin-exposed, and 198 matched control infants. Of this group, 72 drug-exposed males, 75 drug-exposed females, and 147 matched control subjects participated in a follow-up and were interviewed at age 19-35. Differences between groups were tested by chi-square and t-tests. RESULTS: A total of 15% of the phenobarbital-exposed boys versus 2.8% control boys had undescended testes at birth. More anticonvulsant-exposed (24%) than control males (11%) had received medical treatment for genital anomalies. Anticonvulsant-exposed females more often had irregularities in menstrual cycles (31% vs. 17%) and bleeding (15% vs. 3%) and reported more problems during pregnancy. CONCLUSIONS: Prenatal exposure to anticonvulsants seems to induce minor genital anomalies and may affect reproductive function.

Adult↗

In vitro placental pressure-flow behaviour is non-linear and depends on the external pressure.

OBJECTIVE: To study pressure-flow behaviour of in vitro placentas under normal simulated conditions and during raised external pressures, to simulate in vivo placental hemodynamic function, and as a model for polyhydramnios and the supine hypotension syndrome. DESIGN: Eleven normal term human singleton in vitro placentas were perfused under optimal physiologic conditions. Perfusion pressures varied between 5 and 90 mmHg, external pressures between 4 and 30 mmHg. Venous-external pressure (mmHg) combinations included 10-4, 10-10, 20-20, 25-25, 30-30 and 10-20. RESULTS: Pressure-flow curves varied markedly among the 11 placentas, but all showed a non-linear, perfusion pressure-dependent resistance. The in vitro placental resistances were significantly higher than estimated in vivo values. All placentas showed inevitable leakage at the maternal side due to damage during delivery. Increased external pressures increased the placental resistance at lower perfusion pressures. CONCLUSION: Placental damage reduces the number of perfused cotyledonic capillaries. This increases the placental resistance but preserves circulatory properties. Our findings therefore, represent in vivo placental function. They may explain why polyhydramnios often persists and that polyhydramnios and the supine hypotension syndrome are likely to be more detrimental in hypotensive than in normotensive or hypertensive fetuses.

Adult↗

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↗