21-Hydroxylase Genotyping in Australasian Patients with Congenital Adrenal Hyperplasia

Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, 12 G splice and 1172N the most common. Five patients with a 1172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.

Clinical decision-making to facilitate appropriate patient management in chiropractic practice: 'the 3-questions model'

Background A definitive diagnosis in chiropractic clinical practice is frequently elusive, yet decisions around management are still necessary. Often, a clinical impression is made after the exclusion of serious illness or injury, and care provided within the context of diagnostic uncertainty. Rather than focussing on labelling the condition, the clinician may choose to develop a defendable management plan since the response to treatment often clarifies the diagnosis. Discussion This paper explores the concept and elements of defensive problem-solving practice, with a view to developing a model of agile, pragmatic decision-making amenable to real-world application. A theoretical framework that reflects the elements of this approach will be offered in order to validate the potential of a so called '3-Questions Model'; Summary Clinical decision-making is considered to be a key characteristic of any modern healthcare practitioner. It is, thus, prudent for chiropractors to re-visit the concept of defensible practice with a view to facilitate capable clinical decision-making and competent patient examination skills. In turn, the perception of competence and trustworthiness of chiropractors within the wider healthcare community helps integration of chiropractic services into broader healthcare settings

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Hungarian Scientific Research Fund (OTKA, PD100648 (AP)) Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010). AP is the recipient of a “Lendület” grant from the Hungarian Academy of Sciences

Artifacts In Magnetic Resonance Imaging and Computed Tomography Caused By Dental Materials

BACKGROUND: Artifacts caused by dental restorations, such as dental crowns, dental fillings and orthodontic appliances, are a common problem in MRI and CT scans of the head and neck. The aim of this in-vitro study was to identify and evaluate the artifacts produced by different dental restoration materials in CT and MRI images. METHODS: Test samples of 44 materials (Metal and Non-Metal) commonly used in dental restorations were fabricated and embedded with reference specimens in gelatin moulds. MRI imaging of 1.5T and CT scan were performed on the samples and evaluated in two dimensions. Artifact size and distortions were measured using a digital image analysis software. RESULTS: In MRI, 13 out of 44 materials produced artifacts, while in CT 41 out of 44 materials showed artifacts. Artifacts produced in both MRI and CT images were categorized according to the size of the artifact. SIGNIFICANCE: Metal based restoration materials had strong influence on CT and less artifacts in MRI images. Rare earth elements such as Ytterbium trifluoride found in composites caused artifacts in both MRI and CT. Recognizing these findings would help dental materials manufacturers and developers to produce materials which can cause less artifacts in MRI and CT images

Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency

<p>Abstract</p> <p>Background</p> <p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in <it>CYP21A2 </it>gene. The human gene is located at 6p21.3 within a <it>locus </it>containing the genes for putative serine/threonine Kinase <it>RP</it>, complement <it>C4</it>, steroid 21-hydroxylase <it>CYP21 </it>tenascin <it>TNX</it>, normally, in a duplicated cluster known as RCCX module. The <it>CYP21 </it>extra copy is a pseudogene (<it>CYP21A1P</it>). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric <it>CYP21A1P/A2 </it>genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular <it>C4/CYP21 locus</it>. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.</p> <p>Methods</p> <p>We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of <it>CYP21A1P/A2 </it>chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with <it>C4/CYP21 </it>30-kb deletion were included in the study.</p> <p>Results</p> <p>An allele carrying a <it>CYP21A1P/A2 </it>chimeric gene was found unusually associated to a <it>C4B/C4A </it><it>Taq </it>I 6.4-kb fragment, generally associated to <it>C4B </it>and <it>CYP21A1P </it>deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in <it>CYP21A1P </it>of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.</p> <p>Conclusions</p> <p>This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying <it>CYP21A1P/A2 </it>chimeric genes in Brazil.</p

3.0 T cardiovascular magnetic resonance in patients treated with coronary stenting for myocardial infarction: evaluation of short term safety and image quality

Purpose To evaluate safety and image quality of cardiovascular magnetic resonance (CMR) at 3.0 T in patients with coronary stents after myocardial infarction (MI), in comparison to the clinical standard at 1.5 T. Methods Twenty-five patients (21 men; 55 ± 9 years) with first MI treated with primary stenting, underwent 18 scans at 3.0 T and 18 scans at 1.5 T. Twenty-four scans were performed 4 ± 2 days and 12 scans 125 ± 23 days after MI. Cine (steady-state free precession) and late gadolinium-enhanced (LGE, segmented inversion-recovery gradient echo) images were acquired. Patient safety and image artifacts were evaluated, and in 16 patients stent position was assessed during repeat catheterization. Additionally, image quality was scored from 1 (poor quality) to 4 (excellent quality). Results There were no clinical events within 30 days of CMR at 3.0 T or 1.5 T, and no stent migration occurred. At 3.0 T, image quality of cine studies was clinically useful in all, but not sufficient for quantitative analysis in 44% of the scans, due to stent (6/18 scans), flow (7/18 scans) and/or dark band artifacts (8/18 scans). Image quality of LGE images at 3.0 T was not sufficient for quantitative analysis in 53%, and not clinically useful in 12%. At 1.5 T, all cine and LGE images were quantitatively analyzable. Conclusion 3.0 T is safe in the acute and chronic phase after MI treated with primary stenting. Although cine imaging at 3.0 T is suitable for clinical use, quantitative analysis and LGE imaging is less reliable than at 1.5 T. Further optimization of pulse sequences at 3.0 T is essential

Environment, Migratory Tendency, Phylogeny and Basal Metabolic Rate in Birds

Basal metabolic rate (BMR) represents the minimum maintenance energy requirement of an endotherm and has far-reaching consequences for interactions between animals and their environments. Avian BMR exhibits considerable variation that is independent of body mass. Some long-distance migrants have been found to exhibit particularly high BMR, traditionally interpreted as being related to the energetic demands of long-distance migration. Here we use a global dataset to evaluate differences in BMR between migrants and non-migrants, and to examine the effects of environmental variables. The BMR of migrant species is significantly higher than that of non-migrants. Intriguingly, while the elevated BMR of migrants on their breeding grounds may reflect the metabolic machinery required for long-distance movements, an alternative (and statistically stronger) explanation is their occupation of predominantly cold high-latitude breeding areas. Among several environmental predictors, average annual temperature has the strongest effect on BMR, with a 50% reduction associated with a 20°C gradient. The negative effects of temperature variables on BMR hold separately for migrants and non-migrants and are not due their different climatic associations. BMR in migrants shows a much lower degree of phylogenetic inertia. Our findings indicate that migratory tendency need not necessarily be invoked to explain the higher BMR of migrants. A weaker phylogenetic signal observed in migrants supports the notion of strong phenotypic flexibility in this group which facilitates migration-related BMR adjustments that occur above and beyond environmental conditions. In contrast to the findings of previous analyses of mammalian BMR, primary productivity, aridity or precipitation variability do not appear to be important environmental correlates of avian BMR. The strong effects of temperature-related variables and varying phylogenetic effects reiterate the importance of addressing both broad-scale and individual-scale variation for understanding the determinants of BMR

High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

BACKGROUND: The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1:25 to 1:10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling METHODOLOGY AND FINDINGS: CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. CONCLUSIONS: As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling

Cervical intramedullary schwannoma: a case report and review of the literature

Intramedullary schwannomas unrelated with neurofibromatosis are uncommon tumors, but if correctly diagnosed and properly treated they may have a good prognosis