PubMed Health⌕ Search

Biomedical subjects

J G Koppe

Publications and source records attributed to J G Koppe.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

Decreased lung function associated with perinatal exposure to Dutch background levels of dioxins.

UNLABELLED: Perinatal exposure to Dutch background dioxin levels is rather high. Studies of calamities have shown that dioxins negatively influence the respiratory system. It was hypothesized that perinatal exposure to background dioxin levels leads to lung suboptimality, probably through developmental interference. This study aimed to assess lung function in relation to perinatal dioxin exposure. Spirometry was performed in 41 healthy children (aged 7-12 y. mean 8.2 y) with known perinatal dioxin exposure. The ratio of forced expiratory volume in I s to forced vital capacity (FEV1/FVC ratio) was determined. A complete medical history was taken. The prenatal exposure ranged from 8.74 to 88.8 (mean 34.6) ng TEQ dioxin kg fat(-1), measured in breast milk. The postnatal exposure ranged from 4.34 to 384.51 (mean 75.4) ng TEQ dioxin. Twelve children had to be excluded. A significant decrease in lung function in relation to both prenatal (p = 0.045) and postnatal (p = 0.0002) dioxin exposure was seen in the 29 non-excluded children. A clinical association between chest congestion and perinatal dioxin exposure was seen. CONCLUSION: Perinatal background dioxin exposure may be inversely associated with the FEV1/ FVC ratio.

Adult↗
PubMed2000

Predictive value of neonatal neurological tests for developmental outcome of preterm infants.

BACKGROUND: There is a need to identify, as early as possible, infants who are at risk for long-term neurological morbidity. METHODS: To predict neurodevelopment outcome of preterm infants <30 weeks' gestation in a population of 100 infants, we used several neonatal and neurobehavioral tests, including cranial ultrasonography, the Prechtl neurological test, quality of spontaneous general movements, and quality of sleep-wake organization. RESULTS: The Prechtl test at corrected term age and findings on cranial sonograms both had high specificity, but the Prechtl test had better overall positive predictive power for normal neurological and developmental outcomes at 2 years' corrected age. Developmental changes in sleep and the amount of indeterminate sleep did not correlate with outcome. Scoring general movement quality did not predict outcome and did not augment the positive predictive power of the Prechtl test. CONCLUSIONS: The Prechtl test at corrected term age (independent of the other tests) is the best positive predictor of normal neurological outcome and Bayley test results at 2 years' corrected age.

Developmental Disabilities↗
PubMed2000

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↗
PubMed2000

Twenty-year follow-up of antenatal corticosteroid treatment.

OBJECTIVE: To study late side effects of antenatal corticosteroid treatment on health and sexual development in subjects 20 to 22 years old. METHODS: A follow-up study among young adults whose mothers had, because of a threatening delivery, participated in a randomized, double-blind, placebo- controlled trial of betamethasone to prevent neonatal respiratory distress syndrome. Measurements were taken on general health, growth, development in puberty, reproductivity, genital or gynecological complaints, gender development, sexual orientation, sex-specific cognitive functioning, and psychoneuroticism. In addition, some measurements were performed on family diseases, socioeconomic status, and education. RESULTS: No differences were found between the corticosteroid-treated and placebo groups as to medical or psychological variables. In general, the subjects were healthy and had normal intellectual capacities. Groups did not differ on gender development, sexual orientation, sex-specific cognitive functioning, and psychoneuroticism. Systolic blood pressure was significantly lower in the corticosteroid group, but the groups did not differ as to diastolic blood pressure. CONCLUSIONS: Our 20-year follow-up study indicates that 1 course of antenatally administered corticosteroid to prevent respiratory distress syndrome does not have adverse effects up to adulthood.

Adult↗
PubMed1999

Validation of a high-performance liquid chromatography assay for quantification of caffeine and paraxanthine in human serum in the context of CYP1A2 phenotyping.

In this study the validation of a reversed-phase high-performance liquid chromatography (HPLC) method, with UV-detection, for both caffeine and paraxanthine in human serum is described. This method is feasible for cytochrome P450 1A2 (CYP1A2) phenotyping, according to the results of a pilot study. With this HPLC method caffeine and paraxanthine can be determined selectively and specifically. In the expected concentration range, caffeine recoveries were 98-108% (within-run variation 4.0-6.4%, between-run variation 6.4-8.8%), paraxanthine recoveries were 96.6-97.5% (within-run variation 5.0-7.2%, between-run variation 7.2-10.8%). The limits of detection for caffeine and paraxanthine using this HPLC system were 0.3 and 0.1 mg/L, respectively. Linear calibration curves for both caffeine and paraxanthine were obtained in the concentration range 0.5-30 mg/L (r > 0.9999. Serum samples were stable for a week, when stored at -20 and +4 degrees C.

Caffeine↗
PubMed1999

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'-hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female WAG/Rij-rats.

Newborns are susceptible to hemorrhages (hemorrhagic disease of the newborn or HDN) due to vitamin K deficiency. Induction of cytochrome P450 in the fetal liver by maternal anticonvulsant therapy such as phenobarbital or phenytoin is considered to be a major cause. An observed increase in late hemorrhagic disease (LHD) in breast fed neonates gave rise to the hypothesis that PCBs and dioxins, P450-inducing contaminants present in human milk, might effect vitamin K-dependent blood coagulation. This hypothesis was studied in rats. Administration of a single oral dose of 0.003, 0.03, 0.3, 3 or 30 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) per kg bodyweight or 0.75, 4, 20, 100 or 500 micromol 2,2',4,4',5,5'-hexachlorobiphenyl/kg bw (HxCB) to female and male rats resulted in dose-related reductions of the vitamin K-dependent coagulation factor VII. The highest factor VII reduction in female rats was 44%, observed after TCDD exposure. The Lowest Observed Adverse Effect Level (LOAEL) of TCDD on female factor VII levels was 0.3 nmol/kg bw (96 ng/kg). There was a significant inverse correlation between Factor VII levels and induction of hepatic ethoxyresorufin O-deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. HxCB had no effect on female coagulation factors. In contrast, in male rats only exposure to HxCB, which induces mainly CYP2B1 and 2B2, decreased both coagulation factors dramatically up to 88%. The LOAEL of HxCB on factor VII in male rats was 100 micromol/kg bw (36 mg/kg). In general, effects on coagulation factors in male rats exceeded those in females. In addition, sex-dependent differences of TCDD and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female and male rats. Vitamin K-dependent (gamma-glutamyl carboxylase activity was mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was induced 1.7-fold by the highest dose of HxCB. KO-reductase activity in female rats was also increased by TCDD, however, less pronounced than the carboxylase activity. Concluding, the hepatic vitamin K cycle still functions and is not blocked by TCDD or HxCB, thus explaining the observed reduction in factor VII. Finally, the possible role of P450 in vitamin K deficiency is discussed. Based on these results it is suggested to investigate the possible role of PCBs and dioxin-like compounds in LHD in more detail.

Animals↗
PubMed1999

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↗
PubMed1997

The impact of surfactant replacement therapy on cerebral and systemic circulation and lung function.

UNLABELLED: The influence of surfactant administration on cerebral and systemic circulation and on lung function was evaluated in 12 premature mechanically ventilated infants (mean birth weight 1,560 +/- 770 g, mean gestational age 30.0 +/- 3.2 weeks) with respiratory distress syndrome (RDS) receiving surfactant replacement therapy. We measured mean cerebral blood flow velocity (MCBFV), heart rate (HR), mean arterial pressure (MAP), static compliance (Crs), resistance of respiratory system (Rrs), functional residual capacity (FRC) and fraction of inspired oxygen (FiO2). In addition to a very low compliance and a moderately elevated resistance of the respiratory system a significant drop in MAP, HR, MCBFV and FiO2 was noticed after surfactant administration. After 30 min HR, MAP and MCBFV values returned to baseline levels. We postulate that the drop in MCBFV, MAP, HR and FiO2 with a minor, though not significant improvement of the FRC can most likely be explained by a "relative" hypovolaemia in other organs and parts of the body due to expansion of the lung vascular bed. Compensation for the redistribution of circulatory volume occurred within several minutes. Blood pressure control and treatment of hypovolaemia is mandatory before surfactant is administered. CONCLUSION: In RDS patients there is a significant drop of MAP, HR, MCBFV and FiO2 after bolus surfactant administration.

Airway Resistance↗
PubMed1996

Missing effects of background dioxin exposure on development of breast-fed infants during the first half year of life.

Fetal exposure to higher levels of PCBs can result in low birth weight and neurological disorders of the newborn. In this study the effects of exposure to the highly toxic dioxins and dibenzofurans, structurally related to PCBs, was investigated in a population of 38 healthy infants. The infants were divided into two groups, according to concentrations of dioxins and dibenzofurans in their mothers milk fat. Neonatal body weight, length, Quetelet index and liver size were determined at different time points during the first half year of life. Additionally neurological development was determined. Comparing these items between the high and low exposure groups did not show any statistically significant differences. The results of this study do not reveal any effect of exposure to background levels of dioxins and dibenzofurans, but in utero exposure to these toxic agents may result in symptoms later in life. Therefore follow-up study of this well defined group will be performed.

Adult↗
PubMed1996

Signs of enhanced neuromotor maturation in children due to perinatal load with background levels of dioxins. Follow-up until age 2 years and 7 months.

We investigated psychomotor development (Bayley-test) and neuromotor functioning (Hempel-test) in a group of children with known perinatal load with background levels of dioxins. Bayley-test (n = 32) at 2 years, and additionally investigated growth, medical history, physical condition, TT4, TT4/TBG, TSH, AST and ALT at the age of 2.5 years did not reveal abnormalities, or differences between the high- and the low-exposure group. Although the Hempel-test was normal in all children (n = 31), we found in 22 out of 29 items less suboptimal scores in the high-exposure group; in five items this difference reached significance (p < 0.05). Total-score and subtotal-score (posture of legs and feet excluded) revealed lower "suboptimality-scores" with a wider range in the high-exposure group in comparison to the low-exposure group (total-score p = 0.008 mean 6.7 SD 3.6 and mean 9.3 SD 1.8 respectively and subtotal-score p = 0.06 mean 4.5 SD 2.9 and mean 6.1 SD 1.6 respectively (Mann-Whitney or Wilcoxon Two-Sample Test). Similar signs of enhanced maturation have been described in the tadpole due to low dosis of TCDD. Reflexes were higher (p = 0.02), with a wider range of findings in the high-exposure group. Our hypothesis is that these findings may be due to thyroxine agonistic action of dioxins, which is in accordance with the earlier described signs of relatively high thyroid function in the first 11 weeks of life in this high-exposure group.

Child, Preschool↗
PubMed1995

Nutrition and breast-feeding.

In the western industrialized world, malnutrition of the lactating mother is not a problem any more. However, new problems, the chemical pollutants in breastmilk, have given rise to concern. Since the seventies, pollution of breastmilk with PCBs and dioxins has taken place. After World War II, more and more PCBs and dioxins entered the environment. Because of the low half-life of these chemicals, persistence leading to accumulation in animal and human fat has taken place. The baby, before birth and when breast-fed, is the highest animal in the food chain, consuming the most concentrated amount of PCBs and dioxins in his/her daily fat intake. Exposure before and after birth has given rise to subtle abnormalities in approximately 10% of the newborns in the Netherlands. These subtle abnormalities are a disturbed cognitive development and a delayed motor-development. Severe vitamin K deficiency can be caused by these contaminants as well. Because of the very threatening situation, a study was performed to look for the possibilities of prevention by influencing the diet of the lactating mother. Two diets were tested for their ability to reduce concentrations of dioxins in human milk. The diets were a low-fat/high-carbohydrate/low-dioxin diet (about 20% of energy intake derived from fat) and a high-fat/low-carbohydrate/low-dioxin diet. Despite significant influences of these diets on the fatty acid profiles, no significant influence on the dioxin concentrations in breast milk could be found. We conclude that short-term dietary measures will not reduce dioxin concentrations in human milk. A lowering of intake of these chemicals must take place years before the mother becomes pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗