48 research outputs found
Magnetic resonance imaging in the diagnosis of white matter signal abnormalities.
Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to 31 patients selected from patients attending the neurometabolic/neurogenetic/metabolic/neurology clinics at a tertiary care hospital. These patients varied in age from 5 months to 79 years old, and were reported to have WMSAs on cranial MRI scans. Twenty-one patients had confirmed WMA diagnoses and 10 patients had non-specific WMA diagnoses (etiology unknown). Two radiologists, blinded to confirmed diagnoses, used clinical abstracts and the WMSAs present on patient MRI scans to classify possible WMA diagnoses utilizing the algorithm. Results The MRI algorithm displayed a sensitivity of 100%, a specificity of 30.0% and a positive predicted value of 74.1%. Cohen\u27s kappa statistic for inter-radiologist agreement was 0.733, suggesting good agreement between radiologists. Conclusions Although a high diagnostic utility was not observed, results suggest that this MRI algorithm has promise as a clinical tool for clinicians and radiologists. We discuss the benefits and limitations of this approach
Apparent diffusion coefficient restriction in the white matter: going beyond acute brain territorial ischemia
BACKGROUND: Reduction of apparent diffusion coefficient (ADC) values in white matter is not always ischaemic in nature.
METHODS: We retrospectively analysed our MRI records featuring reduced ADC values in the centrum semiovale without grey matter involvement or significant vasogenic oedema.
RESULTS: Several conditions showed the aforementioned MR findings: moose-horn lesions on coronal images in X-linked Charcot-Marie-Tooth disease; small fronto-parietal lesions in Menkes disease; marked signal abnormalities in the myelinised regions in the acute neonatal form of maple syrup urine disease; strip-like involvement of the corpus callosum in glutaric aciduria type 1; persistent periventricular parieto-occipital abnormalities in phenylketonuria; diffuse signal abnormalities with necrotic evolution in global cerebral anoxia or after heroin vapour inhalation; almost completely reversible symmetric fronto-parietal lesions in methotrexate neurotoxicity; chain-like lesions in watershed ischaemia; splenium involvement that normalises in reversible splenial lesions or leads to gliosis in diffuse axonal injury.
CONCLUSION: Neuroradiologists must be familiar with these features, thereby preventing misdiagnosis and inappropriate management
Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring
This study was supported by the Finnish Academy (grant
127219), the European Foundation for the Study of Diabetes, the Novo
Nordisk Foundation, the Diabetes Research Foundation, the EVO
funding of the South Ostrobothnia Central Hospital from the Ministry
ofHealthand SocialAffairs (EVO1107), the BiomedicumHelsinki Foun-
dation, the Jalmari and Rauha Ahokas Foundation, the Yrjö Jahnsson
Foundation, the Suoma Loimaranta-Airila Fund, the Onni and Hilja
Tuovinen Foundation and the Juho Vainio Foundation
Biochemical effects of mutations in the gene encoding the alpha subunit of eukaryotic initiation factor (eIF) 2B associated with Vanishing White Matter disease
Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms
Evaluation of the genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO), a broad-spectrum pesticide, in multiple in vivo and in vitro short-term tests
The genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO) were evaluated in multiple in vivo and in vitro short-term tests preparatory to its potential wide use as a molluscicide in control of schistosomiasis. When tested in the rec assay in Bacillus subtilis, TBTO was not mutagenic and it did not induce reverse mutations in Klebsiella pneumoniae. Neither in the presence nor in the absence of rat liver activation system did TBTO produce point mutations in Salmonella typhimurium strains TA1530, TA1535, TA1538, TA97, TA98 or TA100. TBTO was mutagenic in strain TA100 in a fluctuation test, but only in the presence of rat liver S9 (Aroclor-induced). TBTO did not induce gene mutations in the yeast Schizosaccharomyces pombe, mitotic gene conversions in the yeast Saccharomyces cerevisiae, nor sister-chromatid exchange in Chinese hamster ovary cells in the presence or absence of rat or mouse liver S9. In the latter cells, structural chromosomal aberrations, endoreduplicated and polyploid cells were induced. TBTO did not induce gene mutations in V79 Chinese hamster cells (to 8-azaguanine-, ouabain- or 6-thioguanine-resistance) in the presence of a rat liver postmitochondrial fraction or in cell (hamster embryo cells and human and mouse epidermal keratinocyte)-mediated assays. In mouse lymphoma cells, TBTO did not induce 6-thioguanine- or BUdR-resistant mutations. As many tumour promoters inhibit metabolic cooperation between V79 Chinese hamster 6-thioguanine-resistant/-sensitive cells, TBTO was tested but showed no such activity. TBTO was examined for the induction of recessive lethal mutations in adult Berlin K male Drosophila melanogaster, either by feeding or by injection. Doses of 0.37 or 0.74 mM did not increase the number of X-linked recessive lethal mutations. An increased number of micronuclei was observed in the polychromatic erythrocytes of male BALB/c mice 48 h after a single oral dose of TBTO (60 mg/kg bw), while a lower dose (30 mg/kg bw) was ineffective. Neither of the two doses had induced micronuclei 30 h after treatment. The reproductive toxicity of TBTO was studied in NMRI mice. In a 10-day toxicity study, the LD50 and LD10 were 74 and 34 mg/kg bw, respectively. An increased frequency of cleft palates was seen in the fetuses of mice (compared with controls, 0.7%) treated orally during pregnancy with 11.7 mg/kg TBTO (7%), 23.4 mg/kg (24%) or 35 mg/kg (48%). The two highest doses of the drug also increased the frequencies of irregular ossification centres of sternebrae and of minor abnormalities, such as fusion of the bases of the os occipitalis. Doses of 6 mg of TBTO/kg bw do not produce teratogenic effects in mice. Teratogenic effects were only seen at TBTO doses that were toxic to the maternal organism. Electron microscopy 26 and 48 h after TBTO treatment showed no evidence that embryos were damaged. In contrast, the maternal liver was greatly affected. The tin contents of different organs of the maternal organism and of the whole fetus were determined after TBTO treatment. After a single oral treatment with 117 mg TBTO/kg bw, the total tin content in 11.5-day-old embryos 12 h after TBTO administration was 9.5 nmoles Sn/g wet weight - 70% greater than the normal value. The total concentration of tin in the maternal liver was increased to a similar extent (by approximately 60%) over the normal level between 6 and 24 h after treatment. No other organ studied showed similarly high increases in tin content. These results show that TBTO gives negative results in short-term tests using various genetic endpoints. However, at cytotoxic concentrations, it was mutagenic in one bacterial strain, clastogenic in CHO cells in vitro and produced micronuclei in mouse bone marrow cells in vivo. In view of these adverse biological effects, and its high capacity to interfere with morphogenetic differentiation processes in vitro careful evaluations must be made before TBTO is released in large quantities into the aquatic environment, and levels to which humans are exposed must be strictly controlled when it is used as a molluscicide