The distribution of homogeneously grafted nanoparticles in polymer thin films and blends.

Polymer nanocomposites are an important and growing class of materials where nanoparticles are mixed in a polymer matrix. Much of the interest in polymer nanocomposites is derived from the nanoparticles' ability to impart properties to the polymer not commonly found in polymer materials, such as tunable optical, electrical, and mechanical properties. Grafting polymer chains to the surface of a nanoparticle is one of the most common routes towards promoting dispersion of nanoparticles in a polymer matrix. However, we only understand the thermodynamics of grafted nanoparticles in a polymer matrix in the simplest of cases, and this problem is exacerbated by the lack of theoretical and computational tools capable of efficiently predicting the structure of phase separated grafted nanoparticle/polymer blends. In this work, we extend a recently developed field theoretic framework to study the distribution of homogeneously grafted nanoparticles in homopolymer thin films and blends. We demonstrate that our method reproduces trends observed experimentally in homopolymer thin films, and then we examine how the nanoparticle size, grafting density, and the length of the grafted chains relative to the matrix chains affects the distribution of the grafted nanoparticles in phase separated polymer blends. We find that position of the nanoparticles relative to the interface in the blends is sensitive to the brush conformation, even when the nanoparticles are miscible in one of the two homopolymer phases.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

Adaptive behavior in stressful situations and stroke incidence in hypertensive men: results from prospective cohort study "men born in 1914" in Malmö, Sweden.

BACKGROUND AND PURPOSE: Although hypertension is a major risk factor for stroke, many hypertensive persons remain healthy. The aim of the present study was to analyze whether adaptation in a stressful situation was associated with the incidence of stroke in hypertensive men. METHODS: Two hundred thirty-eight hypertensive men were followed from baseline in 1982/1983 until first stroke, death, or December 31, 1996. Adaptation to stress was studied with the serial Color-Word Test. In the Regression dimension, 4 patterns of adaptation could be distinguished according to mastering of the test. Successful mastering of the test was shown in stabilized patterns, increasing difficulty in cumulative patterns, fluctuating difficulty in dissociative patterns, and fluctuating difficulty that increased during testing in cumulative-dissociative patterns. The patterns were compared regarding stroke incidence. RESULTS: Forty-three men experienced a stroke during follow-up. Stroke rates per 1000 person-years were 12.6 for men with stabilized patterns, 14.3 for men with cumulative patterns, 16.2 for men with dissociative patterns, and 31.2 for men with cumulative-dissociative patterns. Multivariate analysis, adjusted for relevant cerebrovascular risk factors, showed that the cumulative-dissociative pattern of the Regression dimension was associated with an increased risk of stroke during follow-up (relative risk 3.00, 95% CI 1.32 to 6.81). CONCLUSIONS: The specific behavior pattern, characterized by the greatest difficulties in managing the test, was associated with incidence of stroke in hypertensive men. One interpretation is that hypertensive men who chronically fail to find successful strategies in stressful situations are vulnerable to the damaging effects of stress and thereby at an increased risk of a future stroke.

Segregation analysis of the X-chromosome in a family with Rett syndrome in two generations.

We report on the first family in which Rett syndrome (RTS) appeared in two consecutive generations. The index case is a 12-year-old girl (classical RTS); her maternal aunt, age 44 years, has mild RTS. Clinically, the family illustrates the wide phenotypic variability between cases, particularly in severity of neurological manifestations. We have analyzed the short arm of the X-chromosome of the family with gene technology. This did not uncover any genetic marker for diagnosis, but it did suggest how the syndrome might have segregated in the family. A cytogenetic analysis gave no information about chromosome abnormalities.

Rett syndrome: a search for gene sources.

A series of 77 Swedish females with classical Rett syndrome were genealogically traced as far back as possible, in most cases to 1720-1750, or 7-10 generations. Details were collected concerning approximately 8,000 ancestors. Common ancestry was seen in 2 pairs of females with Rett syndrome. Thirty-nine of the 77 Rett females were traced to 9 small and separate rural areas, and 17 pairs even came from the same farm or homestead. The common origin was found equally often among descendants of the father as of the mother. In 9 cases, the father came from one and the mother from another of the 9 specific "Rett areas." These observations, combined with the finding of a raised rate of consanguineous marriages in the paternal as well as in the maternal ancestry, point to a genetic transmission. Analyses of parental ages at birth and of birth order gave normal results.

Intravenous physostigmine treatment of Alzheimer's disease evaluated by psychometric testing, regional cerebral blood flow (rCBF) measurement, and EEG.

Ten patients with Alzheimer's disease were treated with intravenous infusion of physostigmine for 2 h. The acute effects on cognitive function, regional cerebral blood flow, and EEG were compared to placebo (isotonic glucose) using a double-blind cross-over design. Physostigmine causes a limited improvement of psychomotor performance and EEG and an increase of blood flow in the most severely affected cortical areas, predominantly in an early phase of Alzheimer's disease.

Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents.

Autopsy material from three patients with Rett syndrome and six control cases (frontal, temporal and motor cortical areas) were studied. Pyramidal and non-pyramidal neurones, 100-200 in each specimen, were visualized by Lucifer Yellow microinjection. 3-D reconstructions and rotations were computed using the VoxelView/GT program. Various types of abnormalities in 3-D dendritic architecture of pyramidal neurones in different cortices were observed. Some pyramidal cells in layers II-III had a subnormal number of dendrites. The normally occurring specializations in pyramidal architecture in different cortical areas were absent. Decreased numbers and regional loss ('naked' areas) of dendritic spines were found. Widely distributed cortical afferents were shown by the carbocyanine dye (DiI) tracing method. PAD showed no microdysgenesis, in contrast to the observations in epilepsy.

3-Methylglutaconic aciduria in two infants.

We studied two children who developed normally for the first 3-4 months of life and then displayed a failure-to-thrive syndrome, regression in psychomotor development, pronounced muscular hypotonia, and liver damage. At the age of about 1-2 years, optic atrophy and spastic parapareses were evident. One child died at the age of 2.5 years the other at an age of 4 years. Both children excreted 3-methylglutaconic acid, 0.1-0.4 mol/mol creatinine and 3-methylglutaric acid, 0.02-0.05 mol/mol creatinine. The excretion of 3-hydroxy-3-methylglutaric acid was not increased. One of the children was available for further biochemical studies. The activity of hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4) was moderately reduced in leucocytes and fibroblasts. During a 21-h fast there was a normal formation of ketone bodies and we conclude that the cause of the syndrome is not a deficiency of hydroxymethylglutaryl-CoA lyase. Normal formation of 14CO2 from [1-14C]isovaleric acid and [2-14C]leucine in fibroblasts and leucocytes apparently excludes a deficiency of methylglutaconyl CoA-hydratase (EC 4.2.1.18).

Cerebrospinal fluid gangliosides in patients with Rett syndrome and infantile neuronal ceroid lipofuscinosis.

Concentrations of the four major brain gangliosides, GM1, GD1a, GD1b and GT1b, biochemical markers of neuronal membranes, were determined in cerebrospinal fluid from a large series of patients with classical Rett syndrome, aged 1.5-21 years at sampling, and from 11 patients with infantile neuronal ceroid lipofuscinosis, aged 1.5-11 years. The results were compared with age-matched healthy controls. Compared with fluid from the control group, the cerebrospinal fluid samples from Rett patients contained significantly reduced levels of gangliosides GD1a and GT1b. In cerebrospinal fluid of the infantile neuronal ceroid lipofuscinosis patients, even the very young ones, all four major brain gangliosides were significantly reduced compared with controls and the concentration levels also differed significantly from those in patients with Rett syndrome. The ganglioside pattern in the brain is reflected in the cerebrospinal fluid early in the course of the disease in Rett syndrome and infantile neuronal ceroid lipofuscinosis.

Infantile hydrocephalus epidemiology: an indicator of enhanced survival.

The epidemiology of infantile hydrocephalus in the birth years 1973-90 was investigated in west Sweden. The study revealed a significant increase in prevalence from 1973-8 and 1979-82 considered due to the enhanced survival of very and extremely preterm infants. The increase did not continue from 1983-90. This could indicate an improved outcome in preterm survivors as the neonatal survival rate continued to increase. The striking predominance of a perinatal/neonatal aetiology in very preterm hydrocephalic infants could be confirmed: 89% born from 1983-90 had suffered a confirmed postpartum intraventricular haemorrhage. In infants born at term, prenatal origins, mainly maldevelopments, dominated. The outcome in very preterm surviving infants with infantile hydrocephalus was poor: 73% had cerebral palsy, 52% epilepsy, 22% severe visual disability, and 55% were mentally retarded. Despite the increased survival resulting in a majority of healthy infants, there is an accumulating cohort of hydrocephalic children.

Rett syndrome and the autistic disorders.

Rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy. In addition to gait difficulties, stereotypic hand movements, and loss of communication and purposeful hand skills, autistic-like behavior is an early sign that often results in misdiagnosis. Despite these significant clinical abnormalities, neuropathologic features are modest, and no consistent laboratory abnormality or diagnostic marker has been identified. The current status of research in RS is considered within the context of autism and other disorders in which autistic features may occur, such as the fragile X syndrome. The concept of autism as neurobiologically based behavior is developed. As such, autism is regarded as an umbrella category containing an ever-expanding list of specific disorders.

The Rett syndrome: an introductory overview 1990.

The position at the end of 1990 of clinical experiences and research in the Rett syndrome (RS) is summarized. Aspects on clinical and pathogenetic heterogeneity are given. Supports for RS as a developmental neuronal disconnection condition, with early infantile brain growth arrest, are emphasized. In trying to explain origin a two step process is hypothetically suggested: 1) an age dependent genetic deficiency, or transient dysfunction, as a basic predisposing factor; 2) a superimposed trigger factor which might differ in type and between groups of cases.

Rett syndrome: Swedish approach to analysis of prevalence and cause.

The prevalence of the Rett syndrome was found to be approximately 1:15,000 in south-western Sweden. About 40 cases have now been traced in this country, the majority during the last 2 yrs. Experiences of over 20 yrs in efforts to obtain information on the etiology and pathogenesis are summarized. The neurobiological approach used in Gothenburg today to try to reveal the origin is described. A plea is made for developmental screening of deteriorating hand skill as a tool for early identification of potential cases of the Rett syndrome.

The changing panorama of infantile hydrocephalus and cerebral palsy over forty years--a Swedish survey.

The time trends and background of infantile hydrocephalus (IH) and cerebral palsy (CP) are surveyed. The changes in live birth prevalence, disability patterns, associated neuroimpairments and distribution of etiologies are analysed. Both the risk of IH and that of CP sharply increase with decreasing birth weight and gestational age. It is concluded that the remarkably enhanced survival of particularly very preterm infants, those at the highest risk of long-term morbidity, implies an increasing number of impaired children as long as the outcome of survivors is not drastically improved. The data presented are thought to be of relevance as to reconsideration of the effectiveness of perinatal care for preterm babies.

Rett syndrome: update of a 25 year follow-up investigation in Western Sweden--sociomedical aspects.

Through 1998-1999 the Swedish research team have systematically mapped 45 of 54 females with Rett syndrome (RS) aged 5-57 years (Berg M. Uppföljning av flickor med Rett syndrom i Västsverige. Socialmedicinsk kartläggning, Stencilerad rapport, Sahlgrenska universitetssjukhuset, Göteborg, 1999; Läkartidningen (Swedish Medical Journal) 96 (1999) 5488). The emphasis is on the RS females' adjustment to grown-up living. At an adult age the large majority moved over to a Swedish type of small group home. We visited these girls in their group homes and got information about their adaptation to this special home situation. We noted their behaviour and contact with the staff and interviewed their parents. The results showed that the young women usually had adjusted well. The adjustment seemed to depend on the degree of planning before the girls moved from their parents to special group homes. These seem to provide a good environment for the RS females, in respect of both physical and social aspects. Although neuropaediatrics in Sweden today has advanced in RS knowledge, the result from this research shows that in Swedish society there is still a great ignorance of RS, even among medical professionals. In particular there is a gap of knowledge when the medical responsibility had to be transferred over to adult medicine. Many of the parents emphasized the great importance of how they were listened to by professionals in public medical and social services. It is essential that professionals always listen to information from parents and personal assistants.

Epidemiology of mental retardation--a Swedish survey.

ecent epidemiological studies in Swedish school age children revealed a prevalence of severe mental retardation (SMR = IQ less than 50) of 0.3% and of mild mental retardation (MMR = IQ 50-70) around 0.4%. In SMR prenatal causes were found in 55%, perinatal in 15-20%, no traceable brain pathology in 18%. Corresponding figures for MMR were 23%, 18% and 55%, respectively. Down syndrome was the largest single cause of SMR and polygenic subcapacity considered to be that of MMR. Chromosomal errors were detected among 29% SMR and 4% MMR school children. Fragile X accounted for 4% SMR and 10% MMR in boys. Fetal alcohol syndromes constituted 8% of urban MMR. The contribution of inborn errors of metabolism was 4-5% and less than 1%, in SMR and MMR, respectively. Perinatal (28th prenatal week-28th postnatal day) brain damage was implicated in 15% of SMR and 18% of MMR. Pathogenetic data are considered for potential preventive measures.

Rett syndrome: epidemiology and nosology--progress in knowledge 1986--a conference communication.

Recent progress from pooled clinical experience is reviewed. The approximate number of documented cases of Rett syndrome (RS) as of October 1986 was 1,100. Three sister pairs, 3 monozygotic twin pairs (both twin girls affected), 3 dizygotic twin pairs (one twin girl affected) are known. Genetics are discussed based on these and other known occurrences. Early seizure-onset variants have been reported in a dozen cases representing various countries. Approximately 20 incomplete RS related cases, also termed "formes frustes," are documented as of October 1986. An actual Swedish series of 66 classical RS, 4 "formes frustes," 2 early seizure-onset variants and 9 other clinically near related atypical cases is summarized. A suggested late stage IV spinal cord impairment is discussed, as well as the whole adult multifacetted complex neurological pattern. Gastrointestinal pathology is discussed with reference to possible generalized neuropeptide disturbances.

Early stages of the Rett syndrome and infantile neuronal ceroid lipofuscinosis--a difficult differential diagnosis.

The Rett syndrome (RS) and infantile neuronal ceroid lipofuscinosis (INCL) are known clinically to present with quite similar manifestations in the very first stages of disease. Ten girls, born 1982-85, from the Swedish series of RS, were compared with 6 children with biopsy-confirmed INCL, deriving from 4 families, as to neurodevelopmental, neurological, ophthalmological, neurophysiological, and CT data. The rapid regression at 1-2 years of age with loss of acquired fine motor skill, learned words, and communication were found to be inseparable between the diseases, as were the successively developing hand and finger stereotypies. Early clues for differential diagnosis were the appearance of transient drop spells, loss of head control, and irregular myoclonias in INCL, flattening of the EEG, early cortical atrophy indicated at CT, and particularly abnormal ERGs. For accurate diagnosis of INCL a biopsy with characteristic EM findings of "snowball" aggregates is a necessity. After 2 3/4-3 years of age, a clinical differentiation was possible in all cases, with visual failure and rapidly decreasing motor ability, head control deterioration, hyperexcitability, and trunk-limb extension tonus being characteristic for INCL.

The Rett syndrome: gross motor disability and neural impairment in adults.

Profile and variation of gross motor disability and neural impairments were studied in a series of 30 women, aged 22-44 years, fulfilling the diagnostic criteria for the Rett syndrome (RS). The sequential development of neurological signs and a movement disorder causing immobility in 80% were found. On the basis of acquired and sustained walking ability, the women could be divided into three groups: one comprising those 20% still walking (group III), one those 60% previously walking (group IVA) and the third those 20% who had never developed walking ability (group IVB). Spastic signs, seldom prominent, were found in all the three groups, while dystonic signs were most common in those previously walking, and weakness and wasting in the group that never acquired that skill. Early progressive scoliosis, peroneal weakness and excavated feet, interpreted as lower motor neuron signs mainly due to spinal tract impairment, were most extensive among those never able to walk. Loss of walking was considered a consequence of deranging combinations of weakness and dystonia. The patterns of neuromotor disturbances are discussed in relation to other manifestations of RS.

A "new" chromosome marker common to the Rett syndrome and infantile autism? The frequency of fragile sites at X p22 in 81 children with infantile autism, childhood psychosis and the Rett syndrome.

Chromosomes from 46 autistic, 20 psychotic and 15 Rett syndrome children were cultured in a folic-acid-depleted medium. Nine percent of the autistic, 20% of the psychotic and 40% of the Rett syndrome cases showed a "new" chromosomal anomaly, viz a fragile site at the (X) (p22) location. It is suggested that in some cases of autism/psychosis and the Rett syndrome, there might be a common biological marker for the common type of psychiatric disturbance. However, as the population frequency of the chromosome marker is not yet known, conclusions must be drawn with great caution.