An accurate equation of state for fluids and solids.

A simple functional form for a general equation of state based on an effective near-neighbor pair interaction of an extended Lennard-Jones (12,6,3) type is given and tested against experimental data for a wide variety of fluids and solids. Computer simulation results for ionic liquids are used for further evaluation. For fluids, there appears to be no upper density limitation on the equation of state. The lower density limit for isotherms near the critical temperature is the critical density. The equation of state gives a good description of all types of fluids, nonpolar (including long-chain hydrocarbons), polar, hydrogen-bonded, and metallic, at temperatures ranging from the triple point to the highest temperature for which there is experimental data. For solids, the equation of state is very accurate for all types considered, including covalent, molecular, metallic, and ionic systems. The experimental pvT data available for solids does not reveal any pressure or temperature limitations. An analysis of the importance and possible underlying physical significance of the terms in the equation of state is given.

Structural and dynamical properties of ionic liquids: The influence of charge location.

The properties of ionic liquids depend on the chemical structure of the constituent ions. An important difference between molten inorganic salts and room temperature ionic liquids (RTILs) is that in RTILs the charge is frequently not located at the center of mass. This paper describes a molecular dynamics investigation of the influence of charge location on the structure and transport properties of ionic liquids. The model considered consists of univalent spherical ions with the cation charge moved away from its center of mass. It is shown that the charge location has an important influence on the liquid properties. As the charge is moved off center, the electrical conductivity initially increases, and the shear viscosity decreases. However, when the charge exceeds a certain displacement, this behavior is reversed. With further charge displacement, the conductivity decreases sharply and the viscosity increases rapidly. This behavior reversal can be traced to the formation of directional ion pairs that are present in sufficient numbers, and have lifetimes sufficiently long to strongly influence the liquid properties. We suggest that the influence of directional ion pairing can explain what appear to be anomalously low conductivities and high viscosities observed for some RTILs. The rotational and reorientational motions of the cations are examined, and shown to be strongly influenced by ion-pair formation when the charge is far off center. The temperature dependence of the transport properties is considered for selected systems, and deviations from Arrhenius behavior are found to be most important for the conductivity. Based on our results, this possibly indicates that directional ion pairs create an additional "barrier" to charge transport in some ionic liquids.

Structural and dynamical properties of ionic liquids: the influence of ion size disparity.

The influence of ion size disparity on structural and dynamical properties of ionic liquids is systematically investigated employing molecular dynamics simulations. Ion size ratios are varied over a realistic range (from 1:1 to 5:1) while holding other important molecular and system parameters fixed. In this way we isolate and identify effects that stem from size disparity alone. In strongly size disparate systems the larger species (cations in our model) tend to dominate the structure; the anion-anion distribution is largely determined by anion-cation correlations. The diffusion coefficients of both species increase, and the shear viscosity decreases with increasing size disparity. The influence of size disparity is strongest up to a size ratio of 3:1, then decreases, and by 5:1 both the diffusion coefficients and viscosity appear to be approaching limiting values. The conventional Stokes-Einstein expression for diffusion coefficients holds reasonably well for the cations but fails for the smaller anions as size disparity increases likely due to the neglect of strong anion-cation correlations. The electrical conductivity is not a simple monotonic function of size disparity; it first increases up to size ratios of 2:1, remains nearly constant until 3:1, then decreases such that the conductivities of the 1:1 and 5:1 systems are similar. This behavior is traced to the competing influences of ion diffusion (enhancing) and ion densities (reducing) on conductivities at constant packing fraction. The temperature dependence of the transport properties is examined for the 1:1 and 3:1 systems. In accord with experiment, the temperature dependence of all transport properties is well represented by the Vogel-Fulcher-Tammann equation. The dependence of the diffusion coefficients on the temperature/viscosity ratio is well described by the fractional Stokes-Einstein relation D proportional to (T/eta)(beta) with beta approximately = 0.8, consistent with the exponent observed for many molten inorganic salts.

Characterization of the first supernumerary tricentric ring chromosome 1 mosaicism by conventional and molecular cytogenetic techniques.

We report on the conventional cytogenetic and fluorescence in situ hybridization (FISH) results obtained for a 3.5-year-old girl with developmental and language delay and a supernumerary ring chromosome mosaicism in 8% of T-lymphocytes analyzed. Using different conventional and molecular cytogenetic techniques as YAC hybridization and comparative genomic hybridization, we could show that the extra tricentric ring chromosome consists of three heterochromatic blocks with inserted euchromatic material. Additionally, chromosome microdissection followed by FISH analysis demonstrated that the small tricentric ring chromosome consisted of material from the pericentromeric region of chromosome 1q21. Thus, the patient has a mosaic of normal cells and cells with partial pentasomy of the pericentromeric region of chromosome 1. So far, 19 cases with single supernumerary marker chromosome 1 have been published, but no tricentric ring chromosome 1 is, to our knowledge, reviewed in the literature. In this study, we compare the clinical features of our patient with cytogenetically comparable cases described in the literature. We introduce a hypothesis for the formation of a tricentric ring chromosome: starting with a monocentric ring, sister chromatid exchange leading to the formation of a tetracentric ring, which underwent intrastrand recombination generating the tricentric ring.

Sex differences in cocaine-stimulated motor behavior: disparate effects of gonadectomy.

Sex differences in biological substrates of drug use and addiction are poorly understood. The present study investigated sexual dimorphisms in motor behavior following acute cocaine administration (10, 20, or 40 mg/kg, i.p.). Cocaine increased stereotypy rating, horizontal and vertical activity in both sexes, and effects were always greater in females than males. A population analysis using data from multiple experiments indicated that horizontal activity scores were normally distributed in males but not in females. Gonadectomy induced disparate effects on cocaine-stimulated motor behavior. Population analysis indicated that castrated males exhibited more horizontal activity and stereotypy than shams. Ovariectomy did not affect cocaine-stimulated stereotypy but did attenuate horizontal activity in a subset of rats that had not been vaginally lavaged. In summary, gonadectomy effects were sex and behavioral topography specific and indicate that activational effects of gonadal hormones partially mediate the robust sex differences in cocaine-stimulated open-field behavior.

Long-term follow-up study of vigabatrin in pretreated children with West syndrome.

A multicentre, long-term, open-label, add-on study of vigabatrin was undertaken in 23 pretreated children with infantile spasms. After 3 months of vigabatrin therapy 11 of the 23 patients had become seizure-free. At this time two-thirds of these 11 children still received other antiepileptic drugs (AEDs) in addition to vigabatrin (mostly valproic acid and/or dexamethasone). After a mean follow-up time of 5 1/4 years (range: 4 1/4-6 1/2) 72% of 18 evaluable patients (two children died, three were lost to follow-up) revealed seizure freedom for at least 1 year. The mean duration of vigabatrin therapy had been 2 1/2 years (range: 2 weeks to 4 3/4 years). Two-thirds of the 18 children continued to take AEDs, three of them undergoing vigabatrin monotherapy. Relapses of infantile spasms had occurred in 14% of the children. The rate of vigabatrin side effects (10%) was low. At follow-up, the EEG of 13 and the 18 patients demonstrated focal or multifocal epileptic discharges. Fifty-five percent had developed another epilepsy (focal epilepsy, secondary generalized epilepsy or myoclonic-astatic epilepsy). With respect to mental functions, three children were normal or slightly retarded, four showed moderate retardation and 11 revealed severe or very severe retardation. This long-term result is comparable to that in ACTH studies with unselected patients. The conclusions are: (1) vigabatrin is an effective drug for the short-term and long-term treatment of refractory infantile spasms; (2) the relapse rate is low; (3) vigabatrin is well tolerated; (4) with respect to secondary epilepsies and mental functions the long-term outcome in these pretreated children is similar to that in earlier studies with ACTH or corticosteroids.

Long-term outcome of children with fetal alcohol syndrome: psychopathology, behavior, and intelligence.

Within an interdisciplinary research project, the long-term outcome of children with fetal alcohol syndrome was studied. Methods for the assessment of psychopathology, behavior, and intelligence included psychiatric interviews, behavior checklists for parents and teachers, and intelligence tests. The children were assessed during preschool age, early school age (6 to 12 years), and late school age (> or =13 years). An excess of psychopathology, (including hyperkinetic disorders, emotional disorders, sleep disorders, and abnormal habits and stereotypes) with a strong persistence over time was found. Cognitive functioning was marked by a large proportion of mentally retarded children and also did not change considerably over time. This long-term outcome study reflects the handicapping effects of fetal alcohol syndrome.

Antiepileptic drugs alter endogenous retinoid concentrations: a possible mechanism of teratogenesis of anticonvulsant therapy.

The major antiepileptic drugs used for the control of seizures can induce developmental toxicity when administered during pregnancy. Vitamin A and retinoids are thought to control many processes of embryonic development including growth, differentiation and morphogenesis. We have therefore studied if the teratogenic action of antiepileptic agents could be mediated via alteration of the endogenous vitamin A--retinoid metabolism. Retinol and its oxidative metabolites all-trans-, 13-cis- and 13-cis-4-oxo-retinoic acid were measured in the plasma of 75 infants and children treated with various antiepileptic drugs for the control of seizures, and in 29 untreated controls of comparable age. Retinol levels increased with age, while the concentrations of retinoic acid compounds did not exhibit age-dependency. Valproic acid monotherapy increased retinol levels in the young age group and a trend toward increased retinol concentrations was also observed in all other patient groups. The plasma levels of the oxidative metabolites 13-cis- and 13-cis-4-oxo-retinoic acids were strongly decreased in all patient groups treated with phenytoin, phenobarbital, carbamazepine and ethosuximide, in combination with valproic acid, to levels which were below 1/3rd and 1/10th of corresponding control values, respectively. Little changes were observed with all-trans-retinoic acid except in one patient group treated with valproic acid/ethosuximide cotherapy where increased levels of this retinoid were found. Our study indicates that therapy with antiepileptic agents can have a profound effect on the endogenous retinoid metabolism. Because of the importance of retinoids for the signaling of crucial biological events during embryonic development, such altered retinoid metabolism may be highly significant in regard to antiepileptic drug teratogenesis.

The fetal alcohol syndrome in adolescence.

At present, alcohol is recognized as the leading teratogenic agent in long-lasting CNS dysfunction. Little is known about the long-term development and outcome of children with fetal alcohol syndrome (FAS). Forty-four FAS patients who were diagnosed in early childhood were followed up for 10-14 years. This study documents the developmental changes of the manifestations of FAS from childhood to adolescence and describes a characteristic "juvenile" pattern of FAS, which may help to identify this syndrome even in adolescence. This is especially relevant for patients who were not diagnosed earlier.

[Intervertebral disk-induced diseases (BK Nr. 2108, 2109, 2110). The so-called exacerbation and assessment of work disability]. / Die bandscheibenbedingten Erkrankungen (BK Nr. 2108, 2109, 2110). Die sog. Verschlimmerung und die Einschätzung der MdE.

Two problems are discussed from a multitude of problems arising with the assessment of the "new" occupational diseases classified under the heading "Vertebral Column" which are of essential importance in determining the amount of compensation payment under German statutory health insurance legislation. One problem concerns differentiation of damage from already existing damage or dividing the total disease into preliminary i.e. already existing damage on the one hand and worsening or exacerbation on the other. Pathogenesis of disk-related disease does not usually allow splitting the disease into an already existing damage that is not job-conditioned and an exacerbation caused by the insured exposure to job-conditioned risk: compensation must be based on the "all-or-nothing" principle. The second problem is to assess the reduction in ability to cope with gainful employment stress. Preventive considerations will decisively influence the number of working places that can be offered as alternatives if a person has been suffering from intravertebral disk disease. Not only those jobs that require heavy physical work are barred, but also those where the worker has to remain in the same position for a prolonged time. Such disease-specific preventive considerations result in a rejection of the usual assessment criteria for intervertebral disk diseases.

Correlates of psychopathology and intelligence in children with fetal alcohol syndrome.

After documenting the wide range of psychopathology and impairment of intellectual functioning in earlier contributions, the present report from long-term observations of an extended cohort of children with Fetal Alcohol Syndrome (FAS) deals with correlates of psychopathology and intelligence in these children. At preschool age, severity of morphological damage, the type of milieu, sex and IQ were significant predictors of psychopathology. In another subgroup of school-aged children, these associations were less strong; only severity of morphological damage and IQ still correlated to some extent significantly with psychopathology. Intelligence was significantly impaired in those children with severe morphological damage who were raised in institutions.

Long-term psychopathological and cognitive outcome of children with fetal alcohol syndrome.

OBJECTIVE: The long-term outcome of a large cohort of children suffering from fetal alcohol syndrome was studied. METHOD: Structured psychiatric interviews, behavior checklists for parents and teachers, and intelligence tests were used. Assessments took place during preschool age, early school age (6 to 12 years), and late school age (> or = 13 years). RESULTS: There was an excess of psychopathology with a wide variety of psychiatric syndromes in this cohort. Hyperkinetic disorders, emotional disorders, sleep disorders, and abnormal habits and stereotypes persisted over time. Interview findings were largely in accordance with parents' and teachers' questionnaire findings. Intelligence test findings included a large proportion of mentally retarded children and displayed high stability at follow-up. CONCLUSIONS: The development of children suffering from fetal alcohol syndrome is jeopardized by a high rate of persistent psychiatric and cognitive impairments.

["Extent of damage, previous damage, previous condition, previous disability"--definition of concepts for the legal expert]. / "Schadensanlage, Vorschaden, Vorzustand, Vorinvalidität"--Begriffsdefinition für den ärztlichen Gutachter.

Several examples are discussed to explain the most important legal definitions of social and private accident insurance. The importance of disciplined and lucid language in expert opinions is emphasised. Typical cases are described.

Prenatal alcohol exposure and long-term developmental consequences.

Fetal alcohol syndrome (FAS) is a leading cause of congenital mental retardation but little is known about the long-term development and adolescent outcome of children with FAS. In a 10-year follow-up study of 60 patients diagnosed as having FAS in infancy and childhood, we investigated the long-term sequelae of intrauterine alcohol exposure. We found that the characteristic craniofacial malformations of FAS diminish with time, but microcephaly and, to a lesser degree, short stature and underweight (in boys) persist; in female adolescents body weight normalises. Persistent mental retardation is the major sequela of intrauterine alcohol exposure in many cases, and environmental and educational factors do not have strong compensatory effects on the intellectual development of affected children.

[Expert assessment of so-called post-thrombotic syndrome in compulsory accident insurance]. / Die Begutachtung des sogenannten postthrombotischen Syndroms in der gesetzlichen Unfallversicherung.

Expertising a late damage after thrombosis requires most careful investigation of the findings, a detailed description of the damage, and a definition of the impairment of functions. This is imperative for arriving at an administrative decision to implement the conclusions arrived at by the expert without committing a legal error by such implementation. Estimation and determination of the damage and of awarding a reasonable compensation requires a detailed consideration of the circumstances of each case and observance of the legal principle of equal rights.

[Alcohol drinking and intrauterine dystrophia. Effects and significance in infancy]. / Alkoholkonsum und intrauterine Dystrophie. Auswirkungen und Bedeutung im Säuglingsalter.

In a prospective study intrauterine growth retardation (IUGR) (less than 10. growth percentile at birth) was used as a predictor to diagnose intrauterine alcohol exposure. An interview about maternal alcohol consumption was performed prenatally--when IUGR was diagnosed by ultrasound--or postnatally. The children were followed up to 18 months of age. In 6/47 children we diagnosed various degrees of the Fetal Alcohol Syndrome FAS, with only one patient showing a full blown syndrome at birth. 5 patients could not be identified until the pediatric reexamination at the age of 8-18 months. IUGR and a maternal history of even moderate drinking during pregnancy should emphasize the possibility of an intrauterine alcohol damage, even in a normal child at birth.

[GM2 gangliosidosis, O variant (Sandhoff disease): suspected diagnosis of a storage disease by ultrasound]. / GM2-Gangliosidose, Variante O (M. Sandhoff): Verdachtsdiagnose einer Speicherkrankheit durch Ultraschall.

We report on a 3.6 year old boy who suffers from Sandhoff disease. The diagnosis was suspected because of striking ultrasound findings: Parts of the thalamus were more echogenic, the cortical gyri were sharp and accentuated. The CT- and MRI features were similar to the US-findings. The diagnosis was confirmed by demonstrating the typical enzyme deficiency in leucocytes.

Angelman ("happy puppet") syndrome--seven new cases documented by cerebral computed tomography: review of the literature.

We report on seven children with Angelman syndrome presenting with psychomotor retardation during the 1st year of life. Seizures developed in six patients, and computed tomography (CT) scanning showed diffuse atrophy of the brain in five patients. We conclude that diagnosis is difficult in the first years of life. A review of the literature is given.

Therapy of infantile spasms with valproate: results of a prospective study.

In a prospective study, 22 children with recently manifested infantile spasms (18 patients with symptomatic and 4 with idiopathic infantile spasms) were treated with sodium valproate (VPA). Before VPA was instituted, a loading test was performed to exclude abnormal patterns of VPA metabolites by gas chromatography and mass spectroscopy of serum and urine. This test was repeated during VPA therapy; an abnormal pattern of VPA metabolites was not observed. VPA was started in increasing dosage until infantile spasms were controlled or a maximum dose of 100 mg/kg/day was reached. If VPA did not control seizures or at least reduce frequency significantly after a trial of 4-6 weeks, dexamathasone was added to VPA. If focal seizures occurred in association with localized epileptogenic EEG discharges, carbamazepine (CBZ) was added to VPA. After 4 weeks of VPA monotherapy, infantile spasms were controlled in 11 children. After 3 months of therapy, 16 children were free of seizures (14 patients VPA monotherapy), and 4 children had reduction of seizure frequency to less than 25%. VPA doses varied between 40 and 100 mg/kg/day (mean 74). The mean plasma concentration was 113 micrograms/ml (range 46-177). After 6 months of therapy, total seizure control was achieved in 20 of 22 patients (16 children VPA monotherapy). The mean observation time was 16 1/2 months (range 6-36 months). There were seven relapses in six children during the first 7 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Expert assessment of reduced earning capacity in legal accident insurance following traumatic loss of the spleen]. / Uberlegungen zur gutachterlichen Beurteilung der MdE in der gesetzlichen Unfallversicherung nach traumatischem Milzverlust.

For legally binding assessment of reduced earning capacity after loss of spleen in adolescents and adults--in accordance with the Federal German compulsory accident insurance regulations--the article offers a brief review of expertising practice and then proceeds to examine dogmatically which of the cases of subsequent damage after loss of spleen are relevant according to German social security laws. The risk covered by Federal German compulsory accident insurance is critically discussed while bearing in mind that assessment of reduced earning capacity is done exclusively under the viewpoint of objectifiable functional losses.