An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases

Introduction An automated procedure for the detection, quantification, localization and statistical mapping of white matter hyperintensities (WMH) on T2-weighted magnetic resonance (MR) images is presented and validated based on the results of a between-centre reproducibility study. Methods The first step is the identification of white matter (WM) tissue using a multispectral (T1, T2, PD) segmentation. In a second step, WMH are identified within the WM tissue by segmenting T2 images, isolating two different classes of WMH voxels – low- and high-contrast WMH voxels, respectively. The reliability of the whole procedure was assessed by applying it to the analysis of two large MR imaging databases (n = 650 and n= 710, respectively) of healthy elderly subjects matched for demographic characteristics. Results Average overall WMH load and spatial distribution were found to be similar in the two samples, (1.81 and 1.79% of the WM volume, respectively). White matter hyperintensity load was found to be significantly associated with both age and high blood pressure, with similar effects in both samples. With specific reference to the 650 subject cohort, we also found that WMH load provided by this automated procedure was significantly associated with visual grading of the severity of WMH, as assessed by a trained neurologist. Conclusion The results show that this method is sensitive, well correlated with semi-quantitative visual rating and highly reproducible.     

Sensitivity to acute insulin-mediated suppression of plasma free fatty acids is not a determinant of fasting VLDL triglyceride secretion in healthy humans

One important mechanism whereby obesity-associated insulin resistance leads to VLDL overproduction is thought to be by the increased flux of free fatty acids (FFAs) from extrahepatic tissues to liver, which arises as a direct consequence of impaired insulin action in adipose tissue and skeletal muscle. The aim of the present study was to address whether direct measures of peripheral tissue insulin sensitivity with regard to FFAs and glucose in the fasting state are good predictors of postabsorptive VLDL triglyceride secretion rate (VLDL-TG ASR) in humans, independent of obesity. Eighteen healthy control subjects, after an overnight fast, underwent three studies 3 weeks apart, in random order. Study 1: VLDL-TG levels, fractional clearance rate (per h), and VLDL-TG ASR were determined after an intravenous bolus of [1,1,2,3,3-(2)H(5)] glycerol. Study 2: Insulin sensitivity (S(I)), acute insulin response (AIR), and acute C-peptide response to glucose were assessed by frequently sampled intravenous glucose tolerance test using the minimal model approach. Study 3: Insulin-mediated suppression of plasma FFAs (k) and insulin clearance were assessed in response to a low-dose stepwise intravenous insulin infusion. BMI (R(2) = 0.54), AIR, and fasting insulin levels were positively and S(I) negatively correlated with VLDL-TG ASR, but there was no significant association with plasma FFAs or k. Only BMI remained significantly associated with VLDL-TG ASR in multivariate analysis. The best multivariate model for VLDL-TG ASR (R(2) = 0.61, P = 0.0008) included BMI (P = 0.0008) and S(I) (P = 0.12, inversely correlated). VLDL-TG secretion is predicted by BMI, independently of direct measures of insulin sensitivity. The sensitivity to insulin's acute suppressive effect on plasma FFA levels during fasting is not an important determinant of postabsorptive VLDL-TG secretion in humans.     

Immunoglobulin heavy chain transgenic mice expressing Galalpha(1,3)Gal-reactive antibodies

BACKGROUND: Natural antibodies that bind the carbohydrate antigen Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) mediate rigorous rejection of porcine xenografts and represent a major immunological hurdle to successful discordant xenotransplantation. However, little is known about how production of antibodies specific for alphaGal is regulated. METHODS: Transgenic mice expressing an IgM heavy chain isolated from a B-cell hybridoma that produces antibodies specific for alphaGal were constructed. These mice were bred to mutant mice that lack the alphaGal epitope (GT0 mice) or wild-type (GT+) mice to generate animals in which the transgene is expressed in the presence or absence of alphaGal as a "self"-antigen. Development of transgene-expressing B cells and production of alphaGal-specific serum antibodies were then analyzed in transgenic mice on GT0 and GT+ backgrounds. RESULTS: B cells expressing the transgenic heavy chain and transgene-encoded serum antibodies specific for alphaGal were readily detected in mice on the GT0 background. Most alphaGal-reactive antibodies in GT0 mice used the transgene rather than endogenous Ig heavy chains. In contrast, transgene-encoded serum antibodies specific for alphaGal were not detected in GT+ mice. In transgenic mice on the GT+ background, B cells expressing the transgene underwent deletion as a result of encountering alphaGal during their development, indicating that expression of alphaGal as part of self-mediated efficient negative selection of B cells expressing transgene-encoded alphaGal-specific antibodies. CONCLUSIONS: The development of transgenic mice expressing a B cell receptor specific for alphaGal provides a novel system to study developmental regulation of B cells making carbohydrate-specific antibodies. In addition, these mice may be useful for examining methods to prevent production of alphaGal-reactive antibodies.     

Reading abilities and cognitive functions of children with epilepsy: influence of epileptic syndrome

Children with epilepsy are at risk of developing learning disorders. To explore the influence of the epileptic syndrome on reading abilities, we have compared the neuropsychological profile of 12 children with benign idiopathic epilepsy with rolandic spikes, 10 with temporal lobe epilepsy and 12 with idiopathic generalized epilepsy. Children underwent a selection of standardised tests designed to assess: oral language, reading, short-term memory, attention and behavioural adjustment. Analysis of variance was adjusted according to age of onset of the epileptic syndrome, duration of the syndrome, and performance IQ for each group. Children with temporal lobe epilepsy (TLE) had significantly lower scores for reading speed and comprehension, but epileptic variables (the age of onset of epilepsy, duration and activity of epilepsy) had influenced academic performances. In the TLE group there was a clear effect of the topography of the epileptic foci (left-side TLE vs. right-side TLE) on reading profile. Furthermore, the effect of epileptic syndromes was found in phonological, semantic and verbal working memory deficits in the TLE group. To a lesser extent children with idiopathic generalized epilepsy (IGE) also exhibit cognitive deficit. The results of the present study lend support to epilepsy-specific patterns of neuropsychological dysfunction in children that should be considered to improve remediation of academic underachievement in these populations.     

Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.     

Increasing incidence of bilateral mastectomies: the patient perspective

Background

Numerous studies have reported increasing rates of contralateral prophylactic mastectomies (CPMs). Understanding patient rationale for the surgical choice may provide insight into this trend.

Methods

A questionnaire was mailed to 350 mastectomy patients identified from a community health system tumor registry.

Results

Two hundred fifty questionnaires were received; of these, 237 had undergone mastectomy. Fifty-two percent had unilateral mastectomy (UM), and 43% had bilateral mastectomies (BMs) (6% for bilateral disease). Women younger than 60 years of age were more likely to choose BM (P = .0046). Those who had CPM were significantly more likely to make the same surgical decision (P < .0001). Reconstruction was performed in 52%, with BM patients more likely to undergo reconstruction (P = .009). Twenty-three (19%) needed unanticipated reoperation for reconstruction complications. CPM had equivalent rates of unanticipated surgery versus UM (P = .64).

Conclusions

Patients choosing BMs are younger, have equivalent rates of reoperation because of reconstruction complications, and are significantly more satisfied with their decision than those who chose UM.     

Eleventh international Argos proceedings: critical decision making in degenerative spinal stenosis

The eleventh Argos international symposium was held on 25 and 26 January 2007 at Maison des Arts et Métiers, Paris. Regular attendees were present as well as newcomers from around the world.