Corpus callosum and limbic system: neuroanatomic MR evaluation of developmental anomalies

Agenesis of the corpus callosum is a complex malformation of the brain that has been associated with varying degrees of limbic system maldevelopment. We retrospectively reviewed the records of 11 patients with callosal agenesis (seven total, four partial) who underwent magnetic resonance (MR) imaging, with particular attention to the associated malformations of the limbic system. Comparison was made with selected images from MR examinations of healthy volunteers and with necropsy specimens from other patients with callosal agenesis. Ten of 11 patients demonstrated limbic anomalies (severe motion artifact precluded evaluation of these structures in one patient). MR depicted not only the abnormalities intrinsic to callosal agenesis but also the frequently associated malformations of the limbic system.     

Occult cerebral vascular malformations: high-field MR imaging

Occult cerebral vascular malformations (OCVMs) have characteristic appearances on high-field magnetic resonance (MR) images. These consist of circumscribed regions of low intensity, most prominent on T2-weighted images and representing hemosiderin deposits. Interspersed within most of these lesions are multiple areas of various signal intensity patterns, which correspond to hematomas in different stages of evolution and to fibrous regions containing calcium as well as hemosiderin. Forty-six lesions were found in 19 patients (34 supratentorial and 12 infratentorial). The supratentorial lesions tended to be subcortical or periventricular. Computed tomography depicted 24 of the 46 lesions demonstrated by high-field MR. Comparison of images obtained with both low-field MR (0.12 T and 0.35 T) and high-field MR (1.5 T) revealed that high-field MR imaging was superior in depicting OCVMs. High-field MR appears to be both sensitive and specific for OCVMs and may obviate the need for possible biopsy of these lesions.     

Anxiety in patients undergoing MR imaging

To determine and quantify the major sources of anxiety for patients undergoing magnetic resonance (MR) imaging and to suggest means by which to eliminate or diminish their negative effects, the authors studied anxiety in 46 subjects. Of these, 20 randomly selected subjects who successfully completed the examination participated in exit interviews. Six subjects who terminated the examination before completion also completed exit interviews. Pre-imaging and postimaging questionnaires (state-trait anxiety inventory) were administered to measure anxiety in the 20 other subjects. Anxiety was associated with the constrictive dimensions of the magnet bore, examination duration, coil noise, and temperature within the bore. Preparation at the point of referral was consistently absent, incomplete, or misleading. Patients used identifiable strategies to cope with the examination: blinding, breathing relaxation techniques, visualization of pleasant images, and performance of mental exercises.     

Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line

Using specific radioimmunoassays, 8 day cultures of Hep G2 cells were shown to contain in their supernatants 16, 74, and 828 ng/mL and in their cell lysates, 8, 55, and 48 ng/2 X 10(8) cells of factor VII, protein C, and protein S, respectively. These proteins and the protein C inhibitor were functionally active, and each of these activities was neutralized by their respective polyclonal antibodies. Although vitamin K had a modest effect, warfarin decreased the activity of secreted factor VII, protein C, and protein S by 50% to 90%. Protein C and protein S antigens were reduced three- to fourfold by warfarin. The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment. Intrinsic labeling and immunoprecipitation indicated that factor VII, protein S, and the protein C inhibitor were secreted as 52,000, 77,000, and 58,000 molecular weight (mol wt) proteins, respectively. Protein C was secreted as a single-chain protein of about 65,000 mol wt, indicating that all of the vitamin K- dependent proteins are translated and secreted as single-chain molecules. Each of the four proteins studied represented their plasma protein counterparts structurally, functionally, and immunochemically. Thus, all of the known soluble components of the protein C pathway are produced by liver parenchymal cells.     

Ghosal syndrome – genetics unveiled

Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)
Geneviève et al. (2008)
Nature Genetics 40(3):284–286     

A short-lived mRNA linked to blindness

Age-related macular degeneration is associated with an unstable ARMS2 ( LOC387715 ) mRNA
Fritsche et al. (2008)
Nature Genetics 40 (7): 892–896     

Factors associated with virological success with raltegravir-containing regimens and prevalence of raltegravir-resistance-associated mutations at failure in the ARCA database

Raltegravir (RAL) is the only licensed human immunodeficiency virus (HIV) integrase inhibitor. The factors associated with the virological response to RAL-containing regimens and the prevalence of integrase mutations associated with RAL failure deserve further investigation. From the Antiretroviral Resistance Cohort Analysis database, we selected triple-class-experienced subjects failing their current treatment with complete treatment history available. Selection criteria included HIV-RNA, CD4 count and HIV genotype within 3 months of RAL initiation. Factors associated with 24-week response were analysed; genotypic sensitivity scores (GSS) and weighted-GSS were evaluated. Virological response was achieved in 74.3% of 105 subjects. Mutations associated with RAL failure were detected in 12/24 subjects with an integrase genotype, with the prevalence of Q148H + G140S. Each extra unit of GSS (p 0.05, OR 2.62; 95% CI 1.00–6.87). was found to be a associated with response. Weighted-GSS had borderline statistical significance (p 0.063, OR 2.04; 95% CI 0.96–4.33) When stratifying for different cut-offs (< 1 as reference, 1–1.49, ≥ 1.5), a borderline significant increase in the probability of response appeared for GSS ≥ 1.5 (p 0.053, OR 4.00; 95% CI 0.98–16.25). GSS ≥ 1 showed the highest sensitivity, 82.6%. Receiver operating characteristic curves depicted the widest area under the curve (0.663, p 0.054) of GSS ≥ 1. Unresponsiveness to RAL-containing regimens among triple-class-experienced subjects was low. The activity of the background regimen was strongly associated with response. Although few integrase genotypes were available at failure, half of these were without integrase resistance mutations. The substantial rate of RAL failure in the absence of known RAL-resistance mutations may be associated with adherence issues and this issue warrants further analysis in longer observations.