15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia.

Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia. We also show that the deletion associates with a smaller left fusiform gyrus. Moreover, tailored functional magnetic resonance imaging experiments using phonological lexical decision and multiplication verification tasks demonstrate altered activation in the left fusiform and the left angular gyri in carriers. Thus, by using convergent evidence from neuropsychological testing, and structural and functional neuroimaging, we show that the 15q11.2(BP1-BP2) deletion affects cognitive, structural and functional correlates of both dyslexia and dyscalculia.

Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents.

AIMS/HYPOTHESIS: The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. METHODS: Blood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). RESULTS: At type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p < 0.0001). GADA was positively associated with TPOAb (p < 0.001) and with TGAb (p < 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p c) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p c = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. CONCLUSIONS/INTERPRETATION: GADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.

Efficient use of automatic exposure control systems in computed tomography requires correct patient positioning.

BACKGROUND: Image quality and radiation dose to the patient are important factors in computed tomography (CT). To provide constant image quality, tube current modulation (TCM) performed by automatic exposure control (AEC) adjusts the tube current to the patient's size and shape. PURPOSE: To evaluate the effects of patient centering on tube current-time product (mAs) and image noise. MATERIAL AND METHODS: An oval-shaped acrylic phantom was scanned in various off-center positions, at 30-mm intervals within a 500-mm field of view, using three different CT scanners. Acquisition parameters were similar to routine abdomen examinations at each site. The mAs was recorded and noise measured in the images. The correlation of mAs and noise with position was calculated using Pearson correlation. RESULTS: In all three scanners, the mAs delivered by the AEC changed with y-position of the phantom (P<0.001), with correlation values of 0.98 for scanners A and B and -0.98 for scanner C. With x-position, mAs changes were 4.9% or less. As the phantom moved into the y-positions, compared with the iso-center, the mAs varied by up to +70%, -34%, and +56% in scanners A, B, and C, respectively. For scanners A and B, noise in two regions of interest in the lower part of the phantom decreased with elevation, with correlation factors from -0.95 to -0.86 (P<0.02). In the x-direction, significant noise relationships (P<0.005) were only seen in scanner A. CONCLUSION: This study demonstrates that patient centering markedly affects the efficacy of AEC function and that tube current changes vary between scanners. Tube position when acquiring the scout projection radiograph is decisive for the direction of the mAs change. Off-center patient positions cause errors in tube current modulation that can outweigh the dose reduction gained by AEC use, and image quality is affected.

[Migraine-related stroke. Two case-reports.].

Migraine is the cause of 3-25% of strokes in young adults. Each year we can expect 9-10 cases of migraine-related stroke in Iceland. The most common symptom is hemianopia but other common symptoms include hemiparesis, hemianesthesia, dysphasia and various brain stem symptoms. The stroke must occur during a typical migraine attack and other causes have to be excluded. Here we describe two cases of migraine-related stroke.

Vertebral bone density in Icelandic women using quantitative computed tomography without an external reference phantom.

Vertebral trabecular bone mineral density (BMD) was measured in 187 healthy Icelandic women, age 35-64 years, by quantitative computed tomography (QCT) with the use of internal references (muscle and subcutaneous fat) instead of the traditional external references (phantoms). We found a mean 2.4 mg/cm3 (1.8%) bone loss per year in the age range 35-64 years. There was an accelerated phase (exponential) after menopause, with 4% loss per year for the first 1-5 years after menopause or 5-fold trabecular bone loss compared with the subsequent 11-15 years after menopause. Reproducibility was found to be 1.9%. This method thus compares with traditional QCT measurements and is highly reproducible. We find QCT using internal references a promising method for assessing fracture risk in perimenopausal women and for follow-up in osteoporotic patients.

Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results.

Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%). The median duration of response was 34 months. Stable disease was noted in 14 of 36 patients (39%), all presenting mid-gut carcinoids. The median duration of stable disease was 25 months. Progressive disease from the start of IFN therapy was seen in five patients (14%). All responders except one had a greater than 50% reduction of urinary 5-hydroxyindoleacetic acid or alpha-human chorionic gonadotropin, whereas four patients also had a significant reduction of tumor size on computerized tomographic scan or at laparotomy. Two patients achieved complete remission. Improvement of clinical manifestations of the carcinoid syndrome was seen in all patients with objective response. Adverse effects including influenza-like syndrome, reduction of blood cells, chemical signs of liver dysfunction, and disturbed lipid metabolism occurred but were reversible or could be circumvented by dose reduction. Autoimmune phenomena were also noted such as development of thyroid autoantibodies with thyroiditis, SLE syndrome with antinuclear factors, and parietal cell antibodies with pernicious anemia. IFN therapy seems to be very effective in controlling tumor-secreted substances and thus giving relief of clinical symptoms. It also arrests tumor growth for extended time periods (median, 2 years). The adverse effects are surmountable and less severe than with cytotoxic therapy.