Visually evoked blood flow responses and vasoneuronal coupling in partial epilepsy

OBJECTIVES: Increased metabolic demand is coupled with increased regional blood flow. The decreased vasoreactivity in epileptic patients however, prompts an impact of epileptic dysfunction on vasoneuronal coupling. MATERIAL AND METHODS: Blood flow velocities during visual stimulation were monitored by TCD in both posterior cerebral arteries in 20 epileptic patients and 20 control persons, response-amplitudes (RA) and pulsatility indices (PI) were analyzed. RESULTS: The RAs were significantly smaller in patients than in controls (28.4 +/- 5.7% vs 38.4 +/- 10.2%; P < 0.001). RAs were larger in the right side and these right-sided responses were significantly smaller in patients with right-sided vs left-sided epileptic foci (27.9 +/- 5.5% vs 36.1 +/- 4.5%; P < 0.005). The PI during stimulation was significantly larger in patients than in controls (0.92 +/- 0.11 vs 0.74 +/- 0.15; P < 0.001). CONCLUSION: Our data suggest an impaired vasoneuronal coupling in focal epilepsy, and support the view that the right hemisphere might be more important for color processing.     

Dynamic expression patterns of Robo (Robo1 and Robo2) in the developing murine central nervous system

The Robo family of molecules is important for axon guidance across the midline during central nervous system (CNS) development in invertebrates and vertebrates. Here we describe the patterns of Robo protein expression in the developing mouse CNS from embryonic day (E) 9.5 to postnatal day (P) 4, as determined by immunohistochemical labeling with an antibody (S3) raised against a common epitope present in the Robo ectodomain of Robos 1 and 2. In the spinal cord, midline-crossing axons are initially (at E11) S3-positive. At later times, midline Robo expression disappears, but is strongly upregulated in longitudinally running postcrossing axons. It is also strongly expressed in noncrossing longitudinal axons. Differential expression of Robo along axons was also found in axons cultured from E14 spinal cord. These findings resemble those from the Drosophila ventral nerve cord and indicate that in vertebrates a low level of Robo expression occurs in the initial crossing of the midline, while a high level of expression in the postcrossing fibers prevents recrossing. Likewise, Robo-positive ipsilateral axons are prevented from crossing at all. However, in the brain different rules appear to apply. Most commissural axons including those of the corpus callosum are strongly S3-positive along their whole length from their time of formation to postnatal life, but some have more complex age-dependent expression patterns. S3 labeling of the optic pathway is also complex, being initially strong in the retinal ganglion cells, optic tract, and chiasma but thereafter being lost except in a proportion of postchiasmal axons. The corticospinal tract is strongly positive throughout its course at all stages examined, including its decussation, formed at about P2 in the central part of the medulla oblongata.     

Differential localization of hamartin and tuberin and increased S6 phosphorylation in a tuber

In a tuberous sclerosis patient with a mutation in the TSC1 tumor suppressor gene, no second-hit mutation was found in a resected cortical tuber. Tuber giant cells showed predominantly nuclear hamartin, cytosolic tuberin, and hyperphosphorylation of S6. Differential accumulation of hamartin and tuberin in separate cellular compartments of giant cells may prevent formation of the hamartin-tuberin complex, resulting in increased S6 phosphorylation. These data provide an alternative mechanism for tuberogenesis.     

Acute and subacute intracerebral hemorrhages: comparison of MR imaging at 1.5 and 3.0 T--initial experience

PURPOSE: To assess and describe the appearance of intracerebral hemorrhage (ICH) at 3.0-T magnetic resonance (MR) imaging as compared with the appearance of this lesion type at 1.5-T MR imaging. MATERIALS AND METHODS: Sixteen patients with 21 parenchymal ICHs were examined. ICHs were classified as hyperacute, acute, early subacute, late subacute, or chronic. Patients underwent 1.5- and 3.0-T MR imaging with T2-weighted fast spin-echo, fluid-attenuated inversion-recovery (FLAIR), and T1-weighted spin-echo (1.5-T) and gradient-echo (3.0-T) sequences within 4 hours of each other. The central (ie, core) and peripheral (ie, body) parts of the ICHs were analyzed quantitatively by using contrast-to-noise ratio (CNR) calculations derived from signal intensity (SI) measurements; these values were statistically evaluated by using the Mann-Whitney U test. Two readers qualitatively determined SIs of the cores and bodies of the ICHs, degrees of apparent susceptibility artifacts, and lesion ages. The chi(2) test was used to determine statistically significant differences. RESULTS: With the exception of the bodies of late subacute ICHs at 3.0-T T2-weighted imaging, which had increased positive CNRs and SI scores (P .05). With the exception of minor susceptibility artifacts seen in acute and early subacute ICHs at 3.0-T T1-weighted gradient-echo imaging, no susceptibility artifacts were noticed. The ages of most lesions were identified correctly without significant differences between the two field strengths (P >.05), with the exception of the ages of acute ICHs, which were occasionally misinterpreted as early subacute lesions at 3.0 T. CONCLUSION: At 3.0 T, all parts of acute and early subacute ICHs had significantly increased hypointensity on FLAIR and T2-weighted MR images as compared with the SIs of these lesions at 1.5 T. However, 1.5- and 3.0-T MR images were equivalent in the determination of acute to late subacute ICHs.     

OPA1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina

PURPOSE: Autosomal dominant optic atrophy is a hereditary disorder characterized by progressive loss of vision and caused by mutations in a dynamin-related gene, OPA1, which translates into a protein with a mitochondrial leader sequence. In this study the OPA1 gene and its protein were localized in the rat and mouse retina, and its rat orthologue, rOpa1, was identified. METHODS: The rOpa1 cDNA was isolated by using reverse transcribed cDNA from total RNA obtained from a rat retinal ganglion cell line. The spatial and temporal expression patterns of OPA1 and its gene product were investigated by RNA in situ hybridization and immunohistochemistry in mouse and rat retinas. To characterize further the OPA1-positive neurons, retinal ganglion cells were retrogradely labeled by an immunogold fluorescent tracer or double labeled with OPA1 and choline acetyltransferase or calbindin antibodies. RESULTS: Protein sequence alignment revealed a 96% identity between rat and human OPA1 mRNA. OPA1 expression was found as early as postnatal day 3 in the developing rodent retina. In the mature retina, the OPA1 gene and its protein were found not only in retinal ganglion cells, but also in starburst amacrine cells and horizontal cells, both of which are involved in lateral signal processing within the retina. However, OPA1 was absent from mitochondria rich nerve fibers and photoreceptor indicating a specific role for OPA1 in signal processing rather than in the requirement of mitochondrial energy supply in the retina. CONCLUSIONS: The data suggest an important and specific function of the OPA1 protein, not only in the optic nerve forming ganglion cells but also in the intrinsic signal processing of the inner retina.     

A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety

To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac; Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac at 3 and 5 months with a booster at 12 months of age. Hexavac demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac provided immunity against six important childhood diseases with a single injection at each visit.     

Impact of worktime arrangements on work-home interference among Dutch employees

OBJECTIVES: This study examined the effects of different worktime arrangements on work-home interference while taking into account other work-related factors, private situation and health status, explored gender differences in this relation, and examined reciprocal effects between workhours and work-home interference. METHODS: Data from the Maastricht cohort study on fatigue at work were used with 8 months of follow-up (N=6947 at baseline). RESULTS: Worktime arrangements were related to work-home interference among the men and women, even after control for confounding. As compared with daywork, baseline shiftwork was associated with higher work-home interference over time. Within daywork, full-time work was prospectively related to higher work-home interference than part-time work was. For full-timers, baseline overtime work, hours of overtime work, change in number of workhours, and commuting time were related to higher work-home interference over time, whereas compensation for overtime work, familiarity with work roster, ability to take a day off, and a decrease in workhours at own request were associated with less work-home interference. For the part-timers, baseline overtime work and commuting time were related to higher work-home interference over time, whereas compensation for overtime, flexible workhours, and ability to take a day off were protective against work-home interference. Reciprocal relations between work-home interference and workhours were also found. CONCLUSIONS: Worktime arrangements are clearly related to work-home interference. Because reciprocal effects exist as well, important selection processes may exist. Nevertheless, specific characteristics of worktime arrangements could constitute useful tools for reducing work-home interference.