Benign (nonparoxysmal) familial chorea of early onset: an electroneurophysiological examination of two families

A nonparoxysmal nonprogressive autosomal dominant choreatic disorder of early onset is described in two families. Laboratory investigations of blood, urine and cerebrospinal fluid were normal. Extensive electroneurophysiological examinations did not reveal evident abnormalities. The contingent negative variation was also normal, except for a P500. These electroneurophysiological data are the opposite of what can be found in cases of Huntington's chorea.     

Partial cell fusion: a newly recognized type of communication between dedifferentiating cardiomyocytes and fibroblasts

OBJECTIVE: Fibroblasts have been shown to couple to neonatal cardiomyocytes in heterocellular cultures through functional gap junctions. Our objective was to provide evidence for an additional type of heterocellular communication between fibroblasts and adult cardiomyocytes in vitro and in vivo. METHODS: The contact areas in heterocellular co-cultures were evaluated by specific labeling and the intercellular communication was studied using preloading of fibroblasts with tracer molecules. Heterocellular fibroblast-cardiomyocyte contacts present in the in vitro setting and in the border zone of a rabbit myocardial infarction in vivo were further examined by electron microscopy. RESULTS: Addition of fibroblasts preloaded with the fluorescent low molecular weight tracer calcein-AM to cultured myocytes indicated early dye transfer via connexin 43 functional gap junctions. At a later time-period after co-culturing, dye transfer of fibroblasts preloaded with the high molecular weight tracer dextran 10,000 suggested partial cell fusion. The membrane continuity giving rise to this partial cell fusion was confirmed by electron microscopy, clearly showing areas of intercytoplasmic contacts between fibroblasts and phenotypically adapted (dedifferentiated) cardiomyocytes. Fluorescein-labeled annexin V affinity studies revealed transient exposure of phosphatidylserine at the contact sites, suggesting that phosphatidylserine mediates the fusion process. Close contacts between cardiac fibroblasts and dedifferentiated cardiomyocytes accompanied by disruption of the basal lamina were observed in the border zone of a rabbit myocardial infarction in vivo. CONCLUSION: Our results suggest that the partial cell fusion-type of heterocellular communication in our co-culture model and the contacts observed in vivo may lead to new insights in cardiovascular disease.     

Content validity,construct validity,and reliability of the WHOQOL-Bref in a population of Dutch adult psychiatric outpatients

In this study, the psychometric properties of a quality of life scale, the WHOQOL-Bref, were examined in a population of 533 Dutch adult psychiatric outpatients. Participants underwent two semistructured interviews in order to obtain Axis-I and II diagnoses, according to DSM-IV. Besides the WHOQOL-Bref they also completed questionnaires for measuring psychopathological symptoms (SCL-90) and perceived social support (PSSS). Scores on 25 of the 26 questions of the WHOQOL-Bref had a good distribution. Similar to previous findings, exploratory factor analysis revealed a four-factor structure. A priori expected associations were found between the domains of the WHOQOL-Bref, on the one hand, and dimensions of the SCL-90 and the PSSS-score, on the other hand, indicating good construct validity. The internal consistency of the four domains of the WHOQOL-Bref ranged from 0.66 to 0.80. Domain scores of the WHOQOL-Bref correlated around 0.92 with the WHOQOL-100 domain scores. Relatively low correlations were found between demographic characteristics (age and sex) and WHOQOL-Bref domain scores. It is concluded that the content validity, construct validity, and the reliability of the WHOQOL-Bref in a population of adult Dutch psychiatric outpatients are good. The WHOQOL-Bref, therefore, is an adequate measure for assessing quality of life at the domain level in a population of adult psychiatric outpatients.     

Flagella-mediated bacterial motility accelerates but is not required for Salmonella serotype Enteritidis invasion of differentiated Caco-2 cells

The relative contributions of the flagellum and the flagella-associated bacterial motility in the invasion of Caco-2 cells by Salmonella serotype Enteritidis were investigated using an fliC mutant defective in flagellin production and a motA mutant that carries flagella but is non-motile. Infection assays demonstrated that, at 1 h of infection, both the fliC and the motA mutants were severely impaired in bacterial invasion compared to the parental strain. Infection assays at 3 h infection demonstrated virtually equal invasion levels for both non-motile mutants and the parental strain. Together these data suggest that flagella-mediated bacterial motility accelerates the invasion of Salmonella but is not required for the invasion event per se.     

Validation of the Oxfordshire Community Stroke Project syndrome diagnosis derived from a standard symptom list in acute stroke

Background: The Oxfordshire Community Stroke Project (OCSP) classification allows distinction of stroke subtypes with different prognosis. OCSP classification inferred from clinical signs filled out on patient entry forms has been used to facilitate subgroup analysis in clinical trials. However, such procedure has not been validated against clinical diagnosis. In preparation for an acute stroke trial, we set out to perform such a validation. Methods: An OCSP syndrome diagnosis of 194 acute stroke patients in four hospitals was made within 24 h using a standard list with neurological signs, to be filled out by a stroke physician or neurological resident on duty. This was compared with OCSP diagnosis within 2 days of stroke onset by a (blinded) stroke neurologist (‘gold standard’). Results: The proportion of the OCSP syndromes was quite similar between standard list and clinical judgement. Sensitivity, specificity, positive and negative predictive values were respectively: LACS: 0.76, 0.88, 0.72, 0.90; TACS: 0.63, 0.93, 0.62, 0.88; PACS: 0.62, 0.76, 0.63, 0.75; POCS: 0.50, 0.98, 0.60, 0.97. Kappa for agreement was 0.63 (LACS), 0.37 (PACS), 0.50 (TACS). Neuro-imaging falsified stroke subtype diagnosis in 40 cases (20.6%) diagnosed using the standard list, and 42 (21.6%) diagnosed by stroke neurologists. Conclusion: A standard list-derived stroke syndrome diagnosis may be used as a clinical test to make an OCSP syndrome diagnosis in acute stroke. The use of such list in acute stroke trials may facilitate uniformity in early stroke subtype diagnosis. However, to increase such uniformity, ancillary methods such as acute MRI should be evaluated.     

The diagnosis of epileptic and non-epileptic seizures

The aim of this prospective population-based study was to systematically define a cluster of diagnostic items which can assist in the early identification and classification of epileptic and non-epileptic seizures. A cohort of patients aged > or =14 years, suspected with a first epileptic seizure, were included in this study. A team of neurologists evaluated and classified all cases. Diagnostic items for epileptic and non-epileptic seizures were identified using logistic regression analysis. Three hundred and fifty cases entered this study. Distinctive features for epileptic seizures were postictal confusion (OR 0.09), an epileptiform EEG pattern (OR 0.02), and abnormal neuroimaging findings (OR 0.07), whereas for non-epileptic seizures of organic origin there was a history of hypertension (OR 7.5), and provoking factors (OR 13.4) such as exercise and warmth. Diagnostic items for seizures of non-organic origin were a history of febrile seizures (OR 5.8), treatment by a psychologist or psychiatrist (OR 9.1), and presentiment of the seizure (OR 3.7) such as a feeling of choking and palpitations. A separate analysis for the patients who were systematically investigated provided some additional diagnostic items for the different subgroups of patients. For instance, back arching during the seizure for the patients with seizures of non-organic origin and female sex for the patients with non-epileptic seizures of organic origin.     

The costs of epilepsy in three different populations of patients with epilepsy

The purpose of this study was to estimate the costs of care in three different populations of patients with epilepsy (general practices (GP), University Hospital (UH), and Epilepsy Center (EC)), and to analyse the distribution of costs by type of services for each patient group. A cost diary was developed to obtain prospective information on epilepsy-attributable service use over a period of 3 months. Similar information over the previous 3 months was obtained from a cost questionnaire. In addition, a quality of life inventory (QOLIE-31) was used. Standard cost lists were applied for the valuation of the direct cost items. A sensitivity analysis was performed for certain cost items for which no reliable data were available. One hundred and sixteen patients with established epilepsy were included, and the mean costs per patient per month (in Euros) ranged from 52.08 to 357.63. Patients from GP appeared to have lower direct costs, spent less time in seeking or undergoing a treatment, and reported lower seizure frequencies and less severe seizure types than the patients from the other patient groups. Patients from the EC reported the highest productivity changes and unemployment rates and also had the lowest scores on the QOLIE-31. The cost items anti-epileptic drugs, hospital services, unpaid care, and transportation accounted for the majority of the total direct costs.     

Planning of syllables in children with developmental apraxia of speech

The aim of the present study was to investigate whether children with developmental apraxia of speech (DAS) show a deficit in planning syllables in speech production. Six children with DAS and six normally speaking (NS) children produced high- and low-frequency of occurrence syllable utterances, in which the syllable structure was systematically manipulated in an otherwise unchanging phoneme sequence. Anticipatory coarticulation, using second formant trajectories, and durational structure were analysed. The results showed stronger coarticulation in the children with DAS when compared to the normally speaking children. but in contrast to our expectations, in neither group was a systematic effect of syllable structure on the second format trajectory found. Effects of syllable structure did emerge for durational structure in that durational adjustments were found in the segments of the second syllable. These adjustments were less systematic in children with DAS when compared to normally speaking children. Furthermore, at the prosodic level, normally speaking children showed metrical contrasts that were not realized by the children with DAS. The latter results are interpreted as evidence for a problem in the planning of syllables in speech production of children with DAS, in particular concerning prosodic aspects, which is discussed in relation to the automation of speech production.     

Hepatitis B virus-specific T cell response in chronic hepatitis B patients treated with lamivudine and interferon-alpha.

AIMS: The goal of the present study was to assess the impact combination antiviral therapy has on immune responses in chronic hepatitis B. MATERIALS AND METHODS: T cell responses were studied in 16 chronically hepatitis B virus (HBV)-infected patients treated with sequential, partially overlapping, lamivudine-interferon (IFN)-alpha combination therapy. RESULTS: HBcAg-specific lymphoproliferative response (LPR) was transiently detected in four of five patients who achieved virus suppression (HBV DNA < 10(4) genome equivalents/ml) at end of dual therapy, and then reverted to pre-treatment viral load after therapy discontinuation. In contrast, no significant HBcAg-specific LPR was detected in 8 patients who did not attain profound HBV suppression, as well as in three patients who experienced no HBV DNA rebound after therapy discontinuation. CONCLUSIONS: This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.