Lexical production in children with Williams syndrome: spontaneous use of gesture in a naming task.

This study investigates lexical organization and lexical retrieval in children with Williams syndrome (WS), by examining both naming accuracy and accompanying use of gestures in a picture-naming task. Ten children with the genetic disorder of Williams syndrome (age range: 9.5-12.9) were compared with 20 typically developing children, 10 matched for chronological age (CA) and 10 for mental-age (MA). Lexical production was measured by administering the Boston Naming test (BNT). Older typically developing children performed significantly better than the other two groups. No differences in accuracy were found between the children with WS and the typically developing children matched for mental-age. The overall distribution of error types displayed by children with WS indicate that the lexical-semantic organization is similar to that of typically developing children. However, compared to controls, the WS group produced more iconic gestures during the task, in patterns that suggest the existence of specific word-finding difficulties in these children. Results are discussed within the framework of recent theories on the role of gesture in speech production.

Language acquisition in special populations: a comparison between Down and Williams syndromes.

To investigate the relationship between language acquisition and cognition, we evaluated linguistic abilities in 12 Italian-speaking children with Williams syndrome (WS) and 12 with Down syndrome (DS) of comparable global cognitive level. Another control group included 12 typically developing (TD) children, matched for mental age. Linguistic measures included a parent questionnaire to assess vocabulary, a verbal comprehension test, a sentence repetition test and MLU calculated on spontaneous production. No dissociation was evident between lexical and cognitive abilities, but specific morphosyntactic difficulties emerged both in comprehension and production in children with DS. Individuals with WS, albeit less compromised than DS, also had difficulty in the phrase repetition task and, particularly, using content words. Our results demonstrate that the linguistic abilities of infants with WS are not above their cognitive level and that language development in these special populations is not only delayed, but follows a different developmental trajectory.

Analysis of reboxetine, a novel antidepressant drug, in pharmaceutical tablets by capillary electrophoresis and derivative spectrophotometry.

The recent antidepressant drug reboxetine was quantified in pharmaceutical tablets by derivative spectrophotometry and capillary zone electrophoresis. The feasible sample pretreatment consists of a single extraction with a pH 2.5 phosphate buffer, centrifugation and dilution. For the spectrophotometric assay, the fourth derivative of the absorbance was used which gave satisfactory results in terms of accuracy (mean recovery 99.7%) and precision (mean RSD 3.4%). The electrophoretic experiments were carried out using the shortest effective length of the capillary (8.5 cm) in order to obtain a very rapid separation of reboxetine and dibenzepine used as the internal standard. Using a pH 2.5, 50 mM phosphate buffer as the background electrolyte, each analysis lasted less than 2.5 min. Accuracy (101.3%) and precision (1.5%) were very good.

Rapid capillary electrophoretic method for the determination of clozapine and desmethylclozapine in human plasma.

A rapid and sensitive high-performance capillary electrophoretic method for the determination of clozapine and its main metabolite desmethylclozapine in human plasma was developed. The separation of the two analytes was carried out in an untreated fused-silica capillary [33 cm (8.5 cm effective length) x 50 microm I.D.] filled with a background electrolyte at pH 2.5 containing beta-cyclodextrin. Baseline separation of clozapine and desmethylclozapine was recorded in less than 3 min. An accurate sample pretreatment by means of solid-phase extraction and subsequent concentration allows for reliable quantitation of clozapine in the plasma of schizophrenic patients under treatment with the drug. The method showed good precision (mean RSD = 4.0%) as well as satisfactory extraction yields (approximately 88%) and a good sensitivity (limit of quantitation = 0.075 microg ml(-1), limit of detection = 0.025 microg ml(-1)).

Comparison of three analytical methods for quality control of clozapine tablets.

Three different analytical methods for the quality control of clozapine in commercial formulations were developed and compared: a liquid chromatographic (LC) method with UV detection, a capillary zone electrophoretic (CZE) method, and a linear scan voltammetric (LSV) method. The isocratic LC procedure used a C18 reversed-phase column; the CZE method used an uncoated fused-silica capillary and phosphate buffer containing polyvinylpyrrolidone as the background electrolyte; the LSV method analyzed clozapine solutions with acidic phosphate buffer as the supporting electrolyte. The 3 methods gave similar and satisfactory results, in terms of precision and accuracy. Repeatability and intermediate precision were good (RSD% < 2.2) and accuracy, resulting from recovery studies, was between 98 and 102%. The rapidity of analysis was high for all 3 methods, especially for the LSV.

A sensitive high-performance liquid chromatographic method using electrochemical detection for the analysis of olanzapine and desmethylolanzapine in plasma of schizophrenic patients using a new solid-phase extraction procedure.

A high-performance liquid chromatographic method with amperometric detection for the analysis of the novel antipsychotic drug olanzapine and its metabolite desmethylolanzapine in human plasma has been developed. The analysis was carried out on a reversed-phase column (C8, 150 x 4.6 mm I.D., 5 microm) using acetonitrile-phosphate buffer, pH 3.8, as the mobile phase. The detection voltage was + 800 mV and the cell and column temperature was 30 degrees C. The flow-rate was 1.2 ml min(-1). Linear responses were obtained between 5 and 150 ng ml(-1), with repeatability <3.3%. A careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE) on C8 cartridges. The method requires 500 microl of plasma for one complete analysis. Absolute recovery exceeded 97% for both olanzapine and desmethylolanzapine, and the detection limit was 1 ng ml(-1) for both analytes. Repeatability, intermediate precision and accuracy were satisfactory. This sensitive and selective method has been successfully applied to therapeutic drug monitoring in schizophrenic patients treated with Zyprexa tablets.

Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.

The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development. Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21). Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels. When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.

Development of acute psychotic disorders and HIV-1 infection.

OBJECTIVE: To gain more understanding about the relationship between human immunodeficiency virus type 1 (HIV-1) infection and new-onset psychosis, we compared clinical and immunological findings, psychiatric symptoms, global cognitive performance and, when available, computerized tomography (CT) findings between HIV-1-seropositive patients with new-onset psychosis and well-matched nonpsychotic HIV-1-seropositives. METHODS: Two groups of subjects: HIV-1-seropositives with new-onset psychosis (n = 12) and HIV-1-seropositives without psychosis (n = 15) were recruited through outpatient departments. Organic Delusional Syndrome and Organic Hallucinosis were clinically diagnosed using DSM-III-R diagnostic criteria. Of the baseline participants, twenty-two participated in the two-year follow-up examination. RESULTS: The prevalence of new-onset psychosis in HIV-1-infected subjects was 3.7 per 100 (95% C.I. = 1.6-5.7). HIV-1-seropositive persons with new-onset psychosis had more frequently a positive past psychiatric history, no antiretroviral therapy, and a lower global cognitive performance than did the nonpsychotic HIV-1-seropositives. CT was positive, showing generalized brain atrophy, in three out of nine patients. Remission of psychotic symptoms was observed only in two HIV-1-seropositive persons with new-onset psychosis. Death occurred in two psychic HIV-1-seropositives with simple loosely held delusions. Autopsy results showed that cortical sulci and ventricle size were graded as with moderate/severe enlargement. CONCLUSIONS: New-onset psychosis in HIV infected patients could raise considerable problems in deciding whether a presentation is organic or functional. An interaction of the disease or of psychologically "having" the disease with the presence of a psychotic reaction should also be considered. Interestingly, a protective effect of antiretroviral therapy for new-onset psychosis is suggested.

A rapid LC method for the identification and determination of CNS drugs in pharmaceutical formulations.

Antidepressant, neuroleptic and antiepileptic drugs were identified and determined in pharmaceutical formulations (tablets, capsules and oral solutions) by a rapid high-performance liquid chromatography method. The sample pretreatment consisted of a one-step extraction, filtration and dilution. The chromatographic conditions were: reversed-phase C8 column (150 x 4.6 mm i.d., 5 microm); acetonitrile-tetramethylammonium perchlorate aqueous solution (pH 2.8; 12.6 mM) (45:55, v/v) as the mobile phase; detection wavelength, 230 nm. Calibration curves were linear in the 100-1000 ng ml(-1) range for all tested drugs except for phenobarbital. The repeatability (or intra-day precision), expressed by the relative standard deviation, was better than 2.0%. The accuracy, resulting from recovery studies, was between 98.1 and 101.3%. The amount of drug found agreed with the declared content within the limits specified by United States Pharmacopeia and British Pharmacopeia.

Drawing abilities in Williams syndrome: a case study.

Children with Williams syndrome (WS) have been reported to exhibit an unusual cognitive profile characterized by marked preservation of linguistic abilities and poor visuospatial abilities against a backdrop of generalized mental retardation. Much of the data documenting this profile come from studies of older children and adults with WS. Very few studies have reported findings from the preschool and early school-age period. As a result, little is known about the early development of cognitive processes in children with WS. Capirci, Sabbadini, and Volterra (1996) reported data from a longitudinal case study of early language development in a young child with WS. This article presents the longitudinal profile of visuospatial abilities in this same child. Data on copying and free drawing collected over a period extending from late preschool to early school age are reported. It is clear from these data that this child does indeed exhibit deficits in visuospatial abilities. Her performance clearly improved with age, but deficits persist.

Visuo-spatial and linguistic abilities in a twin with Williams syndrome.

The present study reports a case of dizygotic twins, one boy with Williams syndrome (WS) and one typically developing girl, and compares their neuropsychological profiles. The goal of the present authors was to verify whether the child with WS displayed a cognitive profile which is unique to the syndrome. Several tests designed to assess visuo-perceptual, visuo-motor, linguistic and memory abilities were administered to both children when they were 10.9 years old. Compared to his sister, the boy with WS displayed a homogeneous developmental delay in both non-verbal and verbal abilities. He achieved a level of performance similar to his sister only in facial recognition, phonological word fluency and memory for phonologically similar words. Furthermore, despite the overall delayed performance of the boy, both the twins displayed a cognitive profile characterized by strength in lexical comprehension and relative weakness in visuo-motor abilities.

[Williams syndrome]. / La sindrome di Williams.

Williams syndrome (WS) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuospatial cognitive function and a relative preservation of linguistic abilities in general, and spoken language in particular. This syndrome also includes morphological anomalies, metabolic functional impairments, and likely deficits in the pattern of brain ontogenesis. The genetic basis of WS, recently identified, are presented. A cognitive profile of the WS individuals is defined and compared to Down syndrome (DS) and autism cognitive profiles. Neuroanatomical features of WS, including a reduction in brain volume, preservation of cerebellum and frontal lobes, and a reduction of posterior cortical systems, are described. The possible role of NGF (nerve growth factor)--a neurotrophin involved in the development of brain cholinergic systems and the associated behavioural functions--in the aetiology of the typical mental retardation of WS patients, is critically discussed. Future research avenues, including the identification of potential neurobiological markers in order to precociously diagnose this syndrome, are reviewed.

Determination of fluoxetine and norfluoxetine in human plasma by high-pressure liquid chromatography with fluorescence detection.

Fluoxetine is an atypical antidepressant drug, which selectively inhibits the neuronal reuptake of serotonin, and is widely used in the treatment of depressive disorders. The aim of this research is the development of an HPLC method with fluorescence detection for the monitoring of fluoxetine plasma levels. The determination requires no more than 250 microl of plasma, which undergo solid phase extraction (SPE), then are injected in the HPLC. For the analytical separation a reversed phase C8 column (150 x 4.6 mm I.D.) was used, while the mobile phase was a mixture of acetonitrile and water containing perchloric acid and tetramethylammonium perchlorate (flow rate: 1 ml min(-1)). The very low levels of analytes in plasma required the employment of a fluorescence detector (lambda(exc) = 230 nm, lambda(em)=290 nm), which also granted a good selectivity. Fluoxetine is revealed as a single peak at a retention time of 9.7 min, while norfluoxetine, the main metabolite of fluoxetine, is revealed at a retention time of 8.1 min. Linearity was obtained over the concentration range 8-200 ng ml(-1) for both substances. The method seems suitable, in accuracy and precision, for the determination of fluoxetine plasma levels of patients; furthermore, it is rapid and sensitive.

Analytical methods for the quality control of Prozac capsules.

Some analytical methods (two spectrophotometric and two chromatographic procedures) for the determination of fluoxetine in Prozac capsules are described. All of them are applied to the samples after extracting the drug with a methanol water mixture. The direct and derivative spectrophotometric methods are simple and reliable; the derivative method gives better recovery and lessens interference. Both methods show linearity in the 5-30 microg ml(-1) range of the fluoxetine concentration range. Both HPLC methods (spectrophotometric and spectrofluorimetric detection) use a tetramethylammonium perchlorate buffer-acetonitrile mixture as the mobile phase and a C8 reversed phase column. The UV detection is performed at 226 nm, while the fluorimetric detection is performed by exciting at 230 nm and revealing the emission at 290 nm. The HPLC method with UV detection is more precise, but the procedure with fluorimetric detection is more sensitive.

Teaching sign language to hearing children as a possible factor in cognitive enhancement.

We describe an educational experience designed to teach Italian Sign Language (LIS) to a group of hearing children. The hypothesis underlying this experience was that learning a visual-gestural language such as LIS may improve children's attentional abilities, visual discrimination, and spatial memory. To examine this hypothesis, we conducted two studies. The first involved an educational experience lasting two years with a group of hearing children attending a Sign Language class from first to second grade. The Raven PM 47 TEST was administered at the beginning and at the end of each school year to children attending the LIS classes and to a control group of children enrolled in the same school but not exposed to LIS. The second study involved an educational experience in first grade. The Raven PM 47 and Corsi's block tapping tests were administered at the beginning and at the end of the school year to the children attending the LIS classes, to children enrolled in the same school but at tending an English class, and to children not exposed to a second language. We found that in both studies the LIS group performed better than the other groups. These results suggest that learning a sign language may lead to a cognitive advancement in hearing children.

Written language abilities in deaf Italians.

Written texts produced by 10 Italian deaf native signers in four different writing tasks were analyzed. Data analysis focused on linguistic and orthographic nonstandard forms. The written production of deaf subjects with deaf parents (DD) was compared to the written production in two control groups: a group of 10 hearing subjects with deaf parents (HD) and a group of 10 subjects who have had no contact with deaf people or sign language (HH). The results duplicate findings from previous studies. Deaf subjects display a pattern of selective difficulty with Italian grammatical morphology, especially with free-standing function words. The four different writing tasks used in the present study yield results indicating that text type does influence our assessment of deaf writing abilities. A comparison of the texts written by deaf native signers with those of two hearing groups confirms the view that difficulties in the acquisition of written Italian are best explained by deafness itself, not by the influence of a previously acquired Sign Language, and that the specific difficulties with grammatical morphology displayed by our deaf subjects cannot be attributed solely to their limited experience with written Italian.

A story description task in children with Down's syndrome: lexical and morphosyntactic abilities.

A story description task was used to elicit short stories by 10 Italian children and adolescents with Down's syndrome and 10 normal children matched on mean length of utterance (MLU). Data analysis focused on a subset of lexical, morphological and syntactic aspects of language use. The results show that the subjects with Down's syndrome and their normal matches use a similar lexical repertoire. However, the two groups differ with respect to omissions of free morphemes, and some aspects of syntactic and pragmatic abilities. These data on Italian subjects corroborate and extend previous findings on other languages: despite an extensive repertoire of lexical and grammatical items, subjects with Down's syndrome seem unable to use such elements appropriately and consistently across contexts.

[Williams syndrome: a window to the development of cognitive and neural processes]. / La sindrome di Williams: una finestra aperta sullo sviluppo dei processi cognitivi e neurali.

Williams syndrome (SW) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuo-spatial cognitive function and a relative preservation of linguistic abilities. This syndrome also includes morphological anomalies and metabolic-functional impairments, likely deficits in the pattern of brain ontogenesis. Neuropsychological and somatic features of the SW individuals are illustrated, and the correspondent genetic bases, recently identified, are presented. The possible role of NGF (nerve growth factor), a particular neurotrophin involved in the development of brain cholinergic system and the associated behavioural functions, in the aetiology of the typical mental retardation of SW patients, is critically discussed. Prospect of researches, including the identification of potential neurobiological markers and the definition of appropriate cognitive profiles of the SW, in order to precociously diagnose this syndrome, and a more thorough investigation of factors affecting phenotypic expression of this genetically determined pathological condition, are reviewed.