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P Wolters

Publications and source records attributed to P Wolters.

15 recordsLinked to original sources

Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics?

Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects.

Acquired Immunodeficiency Syndrome↗

Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease.

The relationships between viral load in plasma and cerebrospinal fluid (CSF) and computed tomography (CT) brain scan abnormalities were studied in 39 children between 0.5 and 13 years of age with symptomatic HIV-1 disease. Quantitative RNA PCR was used to determine HIV-1 RNA levels and a semiquantitative analog rating technique was used to evaluate non-contrast CT brain scans. CSF HIV-1 RNA copy number correlated significantly with CT brain scan ratings for severity of cortical atrophy (r = 0.36; P < 0.05) but not with ratings of intracerebral calcifications (r = -12; NS). The difference between these two correlations was significant (P < 0.05). Plasma HIV-1 RNA copy number did not correlate significantly with any CT brain scan ratings or with CSF viral load (r = 0.05; NS). Severity of cortical atrophy appeared to reflect the level of viral load in the CSF, supporting the notion that active HIV-1 replication in the CNS is at least in part responsible for such brain abnormalities in children. The lack of correlation of intracerebral calcifications with other CT brain scan abnormalities as well as with CSF viral load suggests that this lesion is relatively independent and may reflect a different neuropathologic process.

AIDS Dementia Complex↗

A preliminary study of factors associated with psychological adjustment and disease course in school-age children infected with the human immunodeficiency virus.

This study consisted of a longitudinal examination (baseline and approximately 2-yr follow-up) of factors associated with psychological adjustment in a sample of 24 school-age children infected with the human immunodeficiency virus (HIV). Measures of depression, anxiety, and self-concept were administered to the children, and measures of behavioral problems, social functioning, and negative life events were administered to the parents. Generally, psychological adjustment seemed stable, though a decrease in positive social self-concept over time was observed. Negative life events were significantly associated with greater adverse psychological and behavioral outcomes at both baseline and follow-up. An additional component to the study investigated factors associated with survival. Examination of an additional five children who died within 12 months of baseline indicated that they experienced significantly more adverse life events, were less resilient, and had greater disease progression. The sample size was small and requires that these findings be considered as preliminary and suggestive rather than conclusive.

Adaptation, Psychological↗

Chronic blockade of glutamate-mediated bioelectric activity in long-term organotypic neocortical explants differentially effects pyramidal/non-pyramidal dendritic morphology.

Dendritic/axonal growth has been examined in long-term organotypic neocortical explants taken from neonatal rat pups and grown either as isolated slices or as co-cultures. The quantitative light microscopic measurement of dendritic and axonal branching patterns within both types of explants was carried out on Golgi-stained materials. Spontaneous bioelectric activity (SBA) was blocked within both types of explants using a combination of APV and DNQX, NMDA and non-NMDA receptor antagonists, respectively. No extracellularly measurable SBA was observed to occur in the silenced explants in the presence of both antagonists but reappeared following wash-out with control medium. In both control and silenced explants, the overall cellular organization of the slice was maintained throughout the culturing period, with distinguishable pyramidal and non-pyramidal neurons located within the same layers and with the same orientations as observed in situ. The major findings of the present study show the following. (i) Pyramidal neurones chronically exposed to APV/DNQX exhibited no basal dendritic growth in co-cultured explants, while growth of apical dendritic lengths was similar to control values in the absence of SBA. (ii) Pyramidal neurones, nonetheless, exhibited significant terminal segment growth under SBA blockade which was correlated with a concomitant decrease in number of basal dendrites. (iii) Axonal growth in co-cultures was not sustained in silenced pyramidal neurones. (iv) Non-pyramidal neurones showed significant total dendritic and axonal growth in co-cultures following APV/DNQX treatment. (v) Non-pyramidal cells in co-cultures experienced an increase in terminal segment length at 2 weeks which declined in the third week. This increase-decrease was correlated with a decrease-increase in the total number of dendritic segments during the second and third weeks, respectively. (vi) In isolated explants the only departure from control growth curves was a significant increase in terminal segment length which was offset by a similar decrease in number of dendritic segments under APV/DNQX growth conditions. Thus the chronic loss of glutamate-mediated SBA differentially effected pyramidal and non-pyramidal neurones in isolated and co-cultured explants, with pyramidal neurones experiencing the more pronounced effects. We conclude that SBA effects the dynamics of neuritic elongation and branching and that these changes are most dramatically seen in co-cultures which cross-innervate one another, presumably via pyramidal axons. We hypothesize that the activity-dependent changes associated with reduction in pyramidal dendritic and axonal growth may be associated with neurotrophin receptor production/maturation.

Animals↗

Spontaneous eye blinking, a measure of dopaminergic function, in children with acquired immunodeficiency syndrome.

OBJECTIVE: To investigate possible alterations in dopaminergic function in children with acquired immunodeficiency syndrome by evaluating spontaneous eye blink rate, a putative measure of central dopaminergic function. DESIGN: Evaluation of previously videotaped test sessions of a consecutive case series of 50 children (mean age, 5.2 years; range, 2-12 years) with acquired immunodeficiency syndrome. SETTING: Government medical research center. RESULTS: Intrarater reliability was high, expected co-variation of blink rate with age and concurrent mental activity were confirmed, and obtained rates were similar to published data. Higher blink rates, suggestive of increased dopaminergic function, were associated with more severe cortical atrophy (P < .05) and white matter abnormality (P < .05) on computed tomographic brain scans. The presence or severity of basal ganglia calcifications did not seem to influence blink rate. In addition, higher blink rates were associated with higher ratings of depressed affect (P < .05) and lower ratings of hyperactive behaviors (P < .05) during other test activities. CONCLUSIONS: The higher blink rates in human immunodeficiency virus-infected children with more severe cortical abnormalities suggest increased central dopamine activity compared with that in children without cortical computed tomographic brain scan abnormalities. Thus, as a result of structural brain abnormalities, neurotransmitter levels in children with acquired immunodeficiency syndrome may vary and this may be reflected in their socioemotional functioning.

AIDS Dementia Complex↗

Correlation between computed tomographic brain scan abnormalities and neuropsychological function in children with symptomatic human immunodeficiency virus disease.

OBJECTIVE: To evaluate the clinical significance of computed tomographic brain scan abnormalities observed in children with symptomatic human immunodeficiency virus disease. PATIENTS: Eighty-seven previously untreated children with symptomatic human immunodeficiency virus type 1 disease. METHODS: General levels of cognitive functioning, obtained from age-appropriate intelligence tests, and social-emotional behavior were correlated with computed tomographic brain scan abnormality ratings. RESULTS: A significant relation between computed tomographic brain scan abnormalities and cognitive dysfunction as well as aberrant behavior was found, which appeared stronger in (younger) vertically infected children compared with transfusion-infected patients. Calcifications, independent from the degree of brain atrophy, were associated with significantly greater delays in neurocognitive development. CONCLUSION: Computed tomographic brain scan abnormalities, even when mild, were of clinical significance, suggesting that human immunodeficiency virus-associated central nervous system compromise is a continuous process and that scans may be helpful at baseline in defining patients at risk and for monitoring them during therapy.

Brain↗

Effect of continuous-infusion zidovudine therapy on neuropsychologic functioning in children with symptomatic human immunodeficiency virus infection.

Neuropsychologic function was assessed in 13 children with symptomatic human immunodeficiency virus disease (Centers for Disease Control Class P2), ranging in age from 14 months to 12 years. Before the initiation of treatment, eight patients were classified as having encephalopathy. Psychologic tests were administered both before and after 6 and 12 months of continuous-infusion azidothymidine (AZT; zidovudine) treatment. After 6 months of treatment a significant increase of 15.5 (+/- 3.3) IQ points was demonstrated in general cognitive functioning (p less than 0.001). Follow-up for 10 of these patients indicated that after 12 months of AZT therapy, they had maintained their gains in IQ points. Improvements in adaptive behavior after 6 months of therapy, assessed with a standardized interview, paralleled the findings on the IQ data. No significant differences in the amount of change was observed for the different subgroups. The magnitude of these improvements could not be explained by practice effects, environmental changes, or general improvement in physical state. We conclude that neuropsychologic function was significantly improved with continuous infusion AZT treatment.

AIDS Dementia Complex↗

[Public health sciences graduate study at the Bielefeld University in the framework of comparative endeavours].

Beginning with the summer term 1989 the University of Bielefeld offers-for the first time in the FRG-an interdisciplinary graduate program on health sciences which follows the American School of Public Health model. The association of the university with regional medical institutions guarantees teaching, research and practice in the core disciplines of public health.

Curriculum↗

Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection.

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.

Acquired Immunodeficiency Syndrome↗

Quantitative light microscopic autoradiographic localization of binding sites labelled with [3H]vasopressin antagonist d(CH2)5Tyr(Me)VP in the rat brain, pituitary and kidney.

Binding sites for the vasopressin (VP) antagonist d(CH2)5Tyr(Me)VP, were located in various brain areas (e.g. the lateral septum, amygdala, choroid plexus and nucleus of the solitary tract) using light microscopic autoradiography. A number of areas (e.g. suprachiasmatic and arcuate nucleus, pineal gland) which previously showed no VP binding were labelled in the present study. The olfactory nucleus and ventromedial hypothalamic nucleus were not labelled. It therefore appears that d(CH2)5Tyr(Me)VP is capable of discriminating between VP and oxytocin binding sites and a more sensitive means of detecting VP binding sites than VP alone.

Animals↗

Light microscopic autoradiographic localization of [3H]oxytocin binding sites in the rat brain, pituitary and mammary gland.

An autoradiographical oxytocin (OXT) labeling procedure using frozen, unfixed tissue sections resulted in very dense labeling of the mammary gland. Binding sites for OXT were also found in various forebrain areas, including the hippocampus, especially the ventral subiculum and taenia tecta, central amygdala, posterior part of the anterior olfactory nucleus, claustrum, nucleus accumbens, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, and the posterior pituitary. The ependyma of the lateral ventricle and/or the chorioid plexus near the lateral septum was labeled as well. These data support the hypothesis that OXT plays a role in a number of centrally regulated processes.

Animals↗

Light microscopic autoradiographic localization of [3H]arginine-vasopressin binding sites in the rat brain and kidney.

Specific binding sites for arginine-vasopressin (VP) were demonstrated in various major target areas of VP in the rat brain and kidney by light microscopic autoradiography. In the kidney moderate and intense labelling was found in the cortical and medullar areas, respectively. Within the brain intense labelling was shown in the lateral septum, which lends further support to the hypothesis that VP acts as a neurotransmitter. In the hypophysis moderate and heavy labelling was found in the anterior and neural lobes, respectively, which is in agreement with the idea that VP influences hypophyseal functioning.

Animals↗