Computers in otorhinolaryngology; new horizons

There has been an explosion in the computers and information technology in the past couple of years. Otorhinolaryngology has also seen a number of new applications of computers. This article aims to familiarize the reader with different uses of computers as applied to the field of Otorhinolaryngology. It deals with the role in medical literature search, patient and doctor education, medical record keeping telemedicine, internet and E-mail, creating virtual environments and its role in FESS. skull base tumours and plastic surgery.     

Nicotinic Receptor Mutation in a Mildly Dysmorphic Girl with Duane Retraction Syndrome

Background: To evaluate possible monogenic and chromosomal anomalies in a patient with unilateral Duane retraction syndrome and modest dysmorphism.

Materials and Methods: Clinical evaluation, sequencing of candidate genes, and array comparative genomic hybridization (array CGH).

Results: The proband had unilateral Duane retraction syndrome (DRS) with low-set ears bilaterally, a high arched palate, and clinodactyly. Motor development and cognitive function were normal. Parents were first cousins, but no other family member was similarly affected. No mutations were detected in the HOXA1. KIF21A. SALL4, TUBB3, and CHN1 genes. Array CGH revealed a 16?Kb de novo deletion at chromosome 8p11.2 that encompassed a portion of only one gene, the Cholinergic Receptor, Nicotinic, Beta-3 (CHRNB3, Neuronal). This gene encodes a protein that is involved in the nicotinic acetylcholine receptor on neurons. It interacts functionally with other genes that code components of the acetylcholine receptor.

Conclusions: This patient’s chromosomal abnormality affected only one gene that is highly expressed in the brainstem and brain, involved in neurotransmission, and could be related to her Duane retraction syndrome.     

Interspecies plasmid transfer appears rare in sequential infections with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae

From a cohort of 1836 Swedish patients infected with ESBL-producing Enterobacteriaceae (EPE) during 2004–2014, 513 patients with recurrent EPE infection were identified. Only in 14 of the 513 patients was a change of species (ESBL-E. coli to ESBL-K. pneumoniae or vice versa) found between the index and subsequent infection. Eleven sequential urine isolates from 5 of the 14 patients were available for further analysis of possible transfer of ESBL-carrying plasmids. The plasmid content was studied using optical DNA mapping (ODM), PCR-based replicon typing, and ESBL gene sequencing. ODM allowed us to directly compare whole plasmids between isolates and found similar ESBL-carrying plasmids in 3 out of the 5 patients. The ODM results and the rarity in shift of species between ESBL-E. coli and ESBL-K. pneumoniae imply that in recurrent EPE infections interspecies plasmid transfer is uncommon.     

基于3D Slicer应用程序构建大鼠小脑外形微细结构信息数据库

目的:建立大鼠小脑外形三维重构的可视化数据集,为小脑中央核团的三维重建摸索一个可行的方案。方法:实验于2003-03/2005-05在首都医科大学解剖教研室实验室完成。取SD大鼠5只,麻醉后处死取小脑,固定后进行冰冻连续切片、贴片,后经尼氏染色,用扫描仪对各切片进行投射扫描,图像大小为(1868×1491),获取原始图像数据库,并通过首都医科大学生物工程学院开发的配准软件及图像处理软件photoshop7.0对数据库中的数据进行半自动配准及人工分割,应用哈佛大学开发的图像处理专业软件3DSlicer对分割后的数据库进行三维重建。并应用牙科Cad-cam仪器对小脑外形进行扫描,获取完整的小脑外形图像。结果:①小脑尼氏染色获得的原始图像共159张,图像边缘清晰,可见深染的皮质和浅染的白质部分,白质间的小脑中央核深染,边界清晰。②共获得159个小脑外形的三维表面模型数据库(.vtk文件)。在3DSlicer应用程序上可选择小脑外形的三维表面模型数据进行三维显示,并构建了它们的动画显示文件(.gif),使用WindowsMediaPlayer应用软件即可以播放;与应用牙科Cad-cam仪器对小脑表面扫描获取的小脑表面的图像比较,信息更饱满,图像更真实,层次感强。结论:通过切片、配准、分割等方法获得了大鼠小脑外形微细结构信息的数据库,此法更适用于组织微细结构的三维重建。     

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.     

A CYP21A2 gene mutation in patients with congenital adrenal hyperplasia: Molecular genetics report from Saudi Arabia

Objectives:

The aim of this study is to determine congenital adrenal hyperplasia (CAH) with the pattern of CYP21A2 gene-mutations in Saudi children.

Methods:

Between January 2011 and March 2014 at King Fahad Military Complex, Dhahran, Saudi Arabia, we thoroughly examined 11 patients with CAH and 2 asymptomatic individuals with a history of affected siblings. Additionally, we sequenced the full coding regions of the CYP21A2 gene and screened the gene for deletion(s)/duplication(s) using the multiplex ligation-dependent probe amplification (MLPA) technique.

Results:

Nine patients had classic CAH and presented with ambiguous genitalia and/or salt losing crisis. Two patients had the non-classic form of CAH and presented with precocious puberty. The remaining 2 subjects were asymptomatic. Screening the CYP21A2 gene, we detected p.Gln318X mutation in 4 patients, c.290 -13 C>G (IVS2-13C>G) in another 4, and a common deletion, involving exons 6 and 8 in 3 patients.

Conclusion:

Our strategy of Sanger sequencing followed by MLPA was very successful in detecting CYP21A2 mutations in all patients with CAH.Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition caused by a deficiency of one of 5 enzymes involved in the steroidogenesis pathway.1 The most common is 21-hydroxylase deficiency. This enzyme deficiency is caused by mutations in the CYP21A2 gene.2 The level of residual enzyme activity determines the clinical phenotype that ranges from mild virilization to salt losing life threatening crisis.1Worldwide, the classic forms of 21-hydroxylase deficiency occur in one in 10,000 to 20,000 newborns.1,2 While the prevalence of the non-classical form of 21-hydroxylase deficiency is estimated to be one in 1,000 individuals.1 The recently introduced universal screening for CAH in Saudi Arabia reported an incidence of one in 6400 births.3 The prevalence of both classic and non-classic forms as well as their mutation pattern varies among different ethnic populations.4 Recent studies showed that an IVS2 AS -13 (A/C to G) mutation is prevalent in the Iranians while p.Q319X is common in Turkey, Tunisia, and East India.4-7 Different mutations result in variable deficiency of cortisol and aldosterone together with increased synthesis of androgen.8-10 The genotype/phenotype correlation of CAH has been reported in different populations and ethnic groups.4-7 Although the clinical presentations of CAH have been studied in Saudi children, literature review revealed no molecular report of 21-hydroxylase.3 Therefore, the aim of this study was to determine the pattern of CYP21A2 gene-mutations in Saudi children with CAH, and to describe the clinical phenotype of these patients.     

A Novel CYP1B1 Mutation with Congenital Glaucoma and Total Aniridia

Purpose: Primary congenital glaucoma is a common disorder in the Middle East mainly caused by mutations in the the CYP1Bl gene. We report a family with three siblings that presented with recalcitrant childhood glaucoma, aniridia in two siblings with a novel CYP1B1 gene mutation.

Materials and methods: Review of pedigree, clinical history and clinical course of the family. Genetic testing in the affected family members.

Results: Three sisters presented with clinical findings of severe congenital glaucoma and a positive family history. Clinical examination of two of sisters revealed corneal scarring, bilateral aniridia with severe glaucoma that required multiple surgical procedures to control intraocular pressure. The third sibling presented with garden-variety primary congenital glaucoma. Genetic analysis revealed a novel CYP1B1 gene mutation (g.8291 C?>?T; p.S485F).

Conclusion: CYP1B1 mutation related congenital glaucoma can present with an extreme form of anterior segment dysgenesis that includes recalcitrant glaucoma, corneal opacification and aniridia.     

Acute leukemia in idiopathic sideroblastic anemia: response to combination chemotherapy

Three patients with idiopathic sideroblastic anemia of variable duration developed acute leukemia. In two the leukemia was morphologically and histochemically myeloblastic, in one lymphoblastic. With combination chemotherapy remission was achieved in all three. The remission inductions were complicated by long periods of bone marrow suppression and the duration of remissions was brief (3, 2 and 3 months). Survival after diagnosis was 13, 10 and 9 mo, respectively. The ring sideroblast abnormality persisted during the leukemic and remission phases and transfusion requirements remained unaltered in the two patients with transfusion dependent anemia throughout their courses.