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Biomedical subjects

J H Kok

Publications and source records attributed to J H Kok.

At least 37 records · Page 2Linked to original sources

In vivo human corneal hydration control dynamics: a new model.

PURPOSE: To introduce a new model describing human in vivo corneal deswelling after hypoxic contact lens wear, based on a damped harmonic oscillator, which can describe an overshoot in corneal deswelling, to compare this new model with the currently used exponential model, and also to test whether a diurnal variation in baseline corneal thickness exists that would have to be taken into consideration when calculating corneal deswelling curves. METHODS: In nine healthy young adults, corneal thickness was measured every 30 minutes for 11.5 hours on average using modified optical pachometry (natural test). On another day, corneal deswelling was monitored for 11.1 hours on average after 2 hours of hypoxic contact lens wear (stress test). The damped harmonic oscillator model and the exponential model were used to calculate best-fitting deswelling curves. Natural test data were analyzed for the presence of a trend. Goodness of fit of the curves to the experimental data was analyzed using the F test. RESULTS: In 82% of the deswelling curves the new damped harmonic oscillator model provided a better fit to the data than the exponential model (P < 0.05). An average overshoot in corneal thickness recovery of 5 microm (range, 0-11 microm) was found. In 50% of the natural tests significant trends were found, without any consistent similarities. The overshoot could not be explained by these trends. CONCLUSIONS: The new damped harmonic oscillator model describes corneal deswelling after hypoxic contact lens wear more accurately than the exponential model. No consistent diurnal variation could be demonstrated.

Adult↗

Neurodevelopmental outcome at three years of age after fetal 'brain-sparing'.

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal 'brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.

Brain↗

Motor nerve conduction velocity in very preterm infants in relation to L-thyroxine supplementation.

BACKGROUND: Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity. It is still unknown whether L-thyroxine supplementation is required. During an L-thyroxine supplementation trial, motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity. METHODS: Two hundred infants < 30 weeks' gestational age were enrolled in a randomized, double-blind, placebo-controlled L-thyroxine supplementation trial. L-Thyroxine (8 micrograms/kg birthweight per day) or a placebo was administered during the first 6 weeks of life. Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth, at 2 weeks, at 40 weeks, and at 66 weeks postmenstrual age. RESULTS: At 2 weeks, the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group, although the difference was not statistically significant (difference between means: 0.8 msec; 95% CI: -0.13 to 1.80; p = 0.06). Later on, no effect of L-thyroxine supplementation on motor nerve conduction velocity was found. CONCLUSION: This study shows that in infants < 30 weeks' gestational age L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity.

Double-Blind Method↗

Outcome of very preterm small for gestational age infants: the first nine years of life.

OBJECTIVE: To determine the influence of intrauterine growth retardation of preterm infants on mortality and cognitive development. DESIGN: A nationwide study cohort of very preterm and/or small for gestational age infants (< 32 weeks and/or < 1500 g) born alive in 1983 in the Netherlands. Assessment on neuromotor and cognitive development at five years, and a parental questionnaire on school performance at nine years. Cognitive outcome is defined as handicap for mental and speech-language development, and need for special education. SAMPLE: 134 small for gestational age infants (< 10th centile) and 410 appropriate for gestational age infants (between 25th and 75th centile) of all infants between 25 and 32 weeks of gestational age were identified; infants with congenital malformations and not of caucasian race were excluded. MAIN OUTCOME MEASURES: Neonatal mortality, in-hospital and five years mortality; Cognitive outcome at five years; School performance at nine years. RESULTS: The mortality risk for small for gestational age compared with appropriate for gestational age infants was significantly higher, after adjustment for gestational age, sex, multiple pregnancy and mode of delivery (OR 2.56, 95% CI 1.26-5.26). Small for gestational age infants showed more often gross motor and minor neurological dysfunction, but less cerebral palsy than appropriate for gestational age infants. Cognitive outcome at five years in small for gestational age infants was significantly worse than appropriate for gestational age infants stratified for mode of delivery OR 2.44 (95% CI 1.05-5.55). At nine years of age significantly more small for gestational age infants (16.4%) needed special education than appropriate for gestational age infants (11.9%). CONCLUSION: Intrauterine growth retardation increases the risk of mortality and of cognitive disorders.

Child↗

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations.

OBJECTIVE: To investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants. DESIGN AND METHODS: Two hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T4) (at a fixed daily dose of 8 microg/kg birthweight) or placebo was started 12-24h after birth and discontinued 6 weeks later. Plasma concentrations of T4, tri-iodothyronine (T3), reverse T3 (rT3), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter. RESULTS: The T4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T4 and rT3 were significantly increased in the T4 group. TSH concentrations were depressed in the T4 group and T3 was significantly decreased, probably as a result of TSH depression. The T4/T3 and T4/rT3 ratios differed significantly between the two study groups. CONCLUSIONS: Daily T4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T4 and T3.

Depression, Chemical↗

Somatosensory evoked potentials in very preterm infants in relation to L-thyroxine supplementation.

OBJECTIVE: To study the effect of L-thyroxine supplementation on neurologic maturation in very preterm infants with transient hypothyroxinemia. DESIGN: Randomized, double-blind, placebo-controlled, L-thyroxine supplementation trial. SETTING: Level III neonatal intensive care unit. SUBJECTS: A total of 200 infants <30 weeks' gestational age. INTERVENTION: Subjects were randomly assigned to receive L-thyroxine (8 microg/kg birth weight per day) or a placebo during the first 6 weeks of life. METHODS: Median nerve somatosensory evoked potentials were recorded, measuring cortical N1 peak latency at 2 weeks of age, at term, and at 6 months (corrected) age. RESULTS: Cortical N1 peak latency was not decreased significantly in the L-thyroxine group compared with the placebo group throughout the study period. CONCLUSION: L-Thyroxine supplementation during the first 6 weeks of life did not decrease cortical N1 peak latency in infants of <30 weeks' gestational age.

Double-Blind Method↗

Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation.

BACKGROUND: Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction. Whether thyroxine treatment during this period results in improved developmental outcomes is not known. METHODS: We carried out a randomized, placebo-controlled, double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks' gestation. Thyroxine (8 microg per kilogram of birth weight) or placebo was administered daily, starting 12 to 24 hours after birth, for six weeks. Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth. Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6, 12, and 24 months of age (corrected for prematurity). RESULTS: Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups. At 24 months of age, 157 infants were evaluated. Overall, neither mental nor psychomotor scores differed significantly between the study groups at any time, nor was the frequency of abnormal neurologic outcome significantly different. In thyroxine-treated infants born at gestational ages of less than 27 weeks, the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group (P=0.01); for thyroxine-treated infants born at 27 weeks or later, the mental-development score was 10 points lower than that of their counterparts in the placebo group (P=0.03). There was no relation between the initial plasma free thyroxine concentration and the effect of treatment. CONCLUSIONS: In infants born before 30 weeks' gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.

Central Nervous System↗

Thyroid function in preterm newborns; is T4 treatment required in infants < 27 weeks' gestational age?

Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low T4 and FT4 values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomised, double-blind, placebo-controlled trial with T4 in 200 infants < 30 weeks' gestation. In the study groups as a whole (n = 100 in the T4 group, n = 100 in the Placebo group), no clear effect of T4 administration was found. In this study we examined whether gestational age influenced the effect of T4 administration. The T4- and placebo groups were subdivided into 4 groups according to gestational age. FT4-values during the first weeks after birth were lowest in the youngest gestational age group in the T4 as well as in the placebo group. In this group with infants < 27 weeks' gestation mental developmental outcome at 2 years of age was significantly better than in the placebo group of the same gestational age. There was also a trend towards a better psychomotor and neurological outcome. Beyond 27 weeks' gestation, no clear effect of T4 could be found; on the contrary, a possible harmful effect on mental developmental outcome might be the result. In conclusion. T4 treatment possibly improves developmental outcome in infants < 27 weeks' gestation, but seems not necessary beyond this gestational age.

Developmental Disabilities↗

Thyroid function in very preterm infants: influences of gestational age and disease.

It is not known how immaturity and disease influence postnatal thyroid function in infants <30 wk of gestational age. We performed serial measurements of plasma thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), TSH, and T4-binding globulin (TBG) in 100 infants of <30 wk of gestation, during the first 8 postnatal weeks, to investigate the influences of disease and gestational age on the time course of thyroid hormones. One hundred infants were divided twice into two groups: 1) in a group of 25-28 and of 28-30 wk of gestation; and 2) in a sick and a healthy group, with similar gestational ages. The time course of T4, FT4, T3, TSH, and TBG, but not rT3 differed significantly (p < 0.005) between the gestational age groups. T4 and FT4 decreased to levels below the cord blood value with a deeper FT4 nadir on d 7 in the youngest group. Disease decreased T4, FT4, T3, TSH, and TBG concentrations especially during the 1st wk after birth (p < 0.005). However, the FT4 nadir on d 7 was similar in sick and healthy infants. After 3 wk, T4, FT4, T3, and TBG were higher in the sick group compared with the healthy group. rT3 levels were not increased in sick infants. We conclude that the extent of the FT4 decrease after birth in infants of <30 wk gestation is mainly influenced by gestational age and probably reflects a transient depletion of thyroidal hormone reserves. rT3 cannot be used as a marker of nonthyroidal illness in very preterm infants.

Double-Blind Method↗

[Poor prognosis in children with ultrasonographically diagnosed abnormalities of the central nervous system].

OBJECTIVE: Long-term follow-up of children with a prenatally diagnosed malformation of the central nervous system. DESIGN: Descriptive study. SETTING: Department of prenatal diagnosis, Academic Medical Center, Amsterdam, the Netherlands. METHODS: Evaluation of all documented ultrasound examinations between 1985 and 1990 (6 years). These ultrasound examinations were performed in women with an increased risk for a foetal malformation, because of obstetrical complications or when a foetal malformation was suspected on ultrasound examination performed elsewhere. Paediatricians and general practitioners were asked to provide follow-up data on the children who were still alive. RESULTS: Seven out of 67 foetuses with a prenatally diagnosed malformation of the central nervous system lived longer than one month. Two out of these 7 children developed normally, one child died after several years and four children were severely retarded. The two children who developed normally both had mild hydrocephaly. CONCLUSION: Prognosis of children with a prenatally diagnosed malformation of the central nervous system is poor. Children with mild hydrocephaly may have a better prognosis.

Adult↗

Fetal brain sparing is associated with accelerated shortening of visual evoked potential latencies during early infancy.

OBJECTIVE: Our purpose was to assess the effects that fetal growth restriction exerts on the myelination of the developing brain. STUDY DESIGN: Fetal haemodynamic centralization, an adaptive strategy to growth restriction caused by placental insufficiency, was determined by Doppler ultrasonography. Infants with a raised ratio between umbilical artery pulsatility index and cerebral artery pulsatility index are severely growth restricted. Visual evoked potentials give information on the degree of brain myelination. Shortening of visual evoked potential latencies is a normal feature of myelination. In a consecutive series of 105 Neonates, visual evoked potentials were recorded at the corrected ages of 6 months and 1 years. Correction for possible confounders, such as cranial ultrasonographic findings, gestational age, and head circumference, was performed. RESULTS: At 6 months, infants with a raised umbilical artery/cerebral artery pulsatility index ratio have shorter visual evoked potential latencies. Opposite of neonates with a normal umbilical artery/cerebral artery ratio, they show no postnatal maturational shortening of visual evoked potential latencies. CONCLUSION: Accelerated neurophysiologic maturation, found in infants with a high umbilical artery/cerebral artery ratio, might be the result of a beneficial adaptive process to severe fetal growth restriction.

Brain↗

Corneal tattooing.

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Coloring Agents↗

The relation between neonatal thyroxine levels and neurodevelopmental outcome at age 5 and 9 years in a national cohort of very preterm and/or very low birth weight infants.

Transient neonatal hypothyroxinemia is very common in preterm infants. The literature on the effect of this hypothyroxinemia is, however, controversial, and large or long-term follow-up studies are not available. In a nationwide prospective follow-up study on very preterm and (or) very low birth weight infants (n = 717), we studied the relationship between thyroxine levels in the 1st wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age. Thyroxine concentrations from filter paper eluates were determined in 717 infants: 32% had levels of more than 3 SD below the mean (< 60 nmol/L). The percentage of infants with such low levels increased with decreasing gestational age. At the age of 5 y, 96% of survivors (n = 640) were available for extensive neurodevelopmental examination: 85 (13.3%) had a disability and 92 (14.3%) a handicap. At the age of 9 y, 83% of survivors (n = 552) answered a questionnaire on school performance: 300 (54.3%) were in mainstream education in a grade appropriate for age, 151 (27%) were in mainstream education with grade retention, and 101 (18.3%) were in special education. Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors (odds ratio, 1.3). Whether this relationship is causal should be investigated. If a causal relationship exists, substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities, both common sequelae of very preterm birth.

Birth Weight↗

Type II and type III deiodinase activity in human placenta as a function of gestational age.

Thyroid hormones are essential for fetal development. T4 can be activated by type I (ID-I) and type II (ID-II) iodothyronine deiodinase or inactivated by type III deiodinase (ID-III). The influence of placental ID-II and ID-III on the regulation of fetal thyroid hormone levels was investigated. Using [125I]T4 and [125I]T3, respectively, ID-II and ID-III activities were measured in homogenates of normal human placentas from 6-43 weeks gestational age and in placentas from five term neonates with a total thyroid hormone synthesis defect. ID-II and ID-III activities related to protein or DNA concentration decreased and total placental ID-III activity increased significantly during pregnancy, whereas the increase in total placental ID-II activity was not significant. Absolute placental ID-II activity was approximately 200 times lower than ID-III activity at all gestational ages. Therefore, fluctuations in ID-II activity were not likely to have a significant influence on fetal thyroid hormone concentrations, but may play a role in the regulation of intraplacental T3 generation. The high ID-III activity most likely influences the thyroid hormone economy of the fetus. Severely hypothyroid newborns showed strongly decreased serum T4 levels, but serum T3 and placental ID-III activities were similar to those in euthyroid newborns. These results suggest that placental ID-III activity is regulated by serum T3, but not by serum T4.

Female↗

Neonatal cerebral circulation in relation to neurosonography and neurological outcome: a pulsed Doppler study.

In the pathogenesis of neonatal intracranial pathology and adverse neurologic outcome, severe instability of the neonatal cerebral circulation might play an important role. To examine this hypothesis the relationship was explored between intracranial pathology as detected by neurosonography during the first week of life, changes in cerebral blood flow velocity (CBFV) as measured by Doppler ultrasound in the same period and neurologic outcome, as measured by standardized tests during the first year of life. A group of 128 infants born after a pregnancy duration between 25 2/7 and 32 6/7 weeks was studied. In 40% of the infants, the time of occurrence of both types of intracranial pathology was within 1 hour after birth. No relation could be demonstrated between this occurrence and CBFV. Also after the appearance of intracranial pathology no specific changes in CBFV were seen. CBFV was associated with neurological outcome at term age. However, CBFV did not predict outcome of neurological examination at 6 and 12 months of corrected age. Intracranial hemorrhages were associated with abnormal neurological outcome at all assessments. Ischemic lesions were only associated with adverse outcome at 12 months of age.

Blood Flow Velocity↗

Corneal eccentricity as a tool for the diagnosis of keratoconus.

Ninety-nine eyes with keratoconus of 64 patients were examined using the sagittal radii method to determine the corneal flattening and compared with 100 eyes of 50 healthy controls. To express the degree of this flattening, four numerical eccentricity (E) values for each eye were calculated. The highest E value of the four was chosen as a parameter for diagnosis of the disease. In keratoconus patients in whom the highest E values of keratoconus eyes were > or = 0.8, the specificity of the test was 98% and the sensitivity was 97%. This abnormal eccentricity was observed in keratoconus eyes with a visual acuity of 1.0, whereas slit-lamp examination showed no abnormalities. This study demonstrates that eccentricity can be helpful to diagnose keratoconus at an early stage.

Adolescent↗