Nasopharyngeal cancer mimicking otitic barotrauma in a resource-challenged center: a case report

<p>Abstract</p> <p>Introduction</p> <p>Nasopharyngeal cancer commonly manifests with cervical lymphadenopathy, recurrent epistaxis and progressive nasal obstruction. Neuro-ophthalmic and otologic manifestations can also occur. Isolated otologic presentations of nasopharyngeal cancer are rare and the diagnosis of nasopharyngeal cancer may not be foremost in the list of differentials.</p> <p>Case presentation</p> <p>We present the case of a 29-year-old Nigerian woman with bilateral conductive hearing loss and tinnitus after air travel. There were no other symptoms. The persistence of the symptoms after adequate treatment for otitic barotrauma necessitated re-evaluation, which led to a diagnosis of nasopharyngeal cancer.</p> <p>Conclusion</p> <p>Isolated otologic manifestations of nasopharyngeal cancer are rare in regions with low incidence of the disease. There is a need for it to be considered as a possible differential in patients presenting with bilateral serous otitis media.</p

Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects

ABSTRACT Background Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD. Method A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT task with baseline and fast-incentive conditions. Results ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60-70%. Conclusions The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADH

Endoscopic procedures for removal of foreign bodies of the aerodigestive tract: The Bugando Medical Centre experience

<p>Abstract</p> <p>Background</p> <p>Foreign bodies in the aerodigestive tract continue to be a common problem that contributes significantly to high morbidity and mortality worldwide. This study was conducted to describe our own experience with endoscopic procedures for removal of foreign bodies in the aerodigestive tract, in our local setting and compare with what is described in literature.</p> <p>Methods</p> <p>This was a prospective descriptive study which was conducted at Bugando Medical Centre between January 2008 and December 2009. Data were collected using a structured questionnaire and analyzed using SPSS computer software version 15.</p> <p>Results</p> <p>A total of 98 patients were studied. Males outnumbered females by a ratio of 1.1:1. Patients aged 2 years and below were the majority (75.9%). The commonest type of foreign bodies in airways was groundnuts (72.7%) and in esophagus was coins (72.7%). The trachea (52.2%) was the most common site of foreign body's lodgment in the airways, whereas cricopharyngeal sphincter (68.5%) was the commonest site in the esophagus. Rigid endoscopy with forceps removal under general anesthesia was the main treatment modality performed in 87.8% of patients. The foreign bodies were successfully removed without complications in 90.8% of cases. Complication rate was 7.1% and bronchopneumonia was the most common complication accounting for 42.8% of cases. The mean duration of hospital stay was 3.4 days and mortality rate was 4.1%.</p> <p>Conclusion</p> <p>Aerodigestive tract foreign bodies continue to be a significant cause of childhood morbidity and mortality in our setting. Rigid endoscopic procedures under general anesthesia are the main treatment modalities performed. Prevention is highly recommended whereby parents should be educated to keep a close eye on their children and keep objects which can be foreign bodies away from children's reach.</p

Identification of QTL genes for BMD variation using both linkage and gene-based association approaches

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation

Complete Sequencing of pNDM-HK Encoding NDM-1 Carbapenemase from a Multidrug-Resistant Escherichia coli Strain Isolated in Hong Kong

BACKGROUND: The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited. METHODOLOGY: We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced. PRINCIPAL FINDINGS: The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla(TEM-1), bla(NDM-1), Δbla(DHA-1)), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively. SIGNIFICANCE: The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa

Fine Mapping of the NRG1 Hirschsprung's Disease Locus

The primary pathology of Hirschsprung's disease (HSCR, colon aganglionosis) is the absence of ganglia in variable lengths of the hindgut, resulting in functional obstruction. HSCR is attributed to a failure of migration of the enteric ganglion precursors along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Yet the reduced penetrance of RET DNA HSCR-associated variants together with the phenotypic variability suggest the involvement of additional genes in the disease. Through a genome-wide association study, we uncovered a ∼350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1). To identify the causal NRG1 variants contributing to HSCR, we genotyped 243 SNPs variants on 343 ethnic Chinese HSCR patients and 359 controls. Genotype analysis coupled with imputation narrowed down the HSCR-associated region to 21 kb, with four of the most associated SNPs (rs10088313, rs10094655, rs4624987, and rs3884552) mapping to the NRG1 promoter. We investigated whether there was correlation between the genotype at the rs10088313 locus and the amount of NRG1 expressed in human gut tissues (40 patients and 21 controls) and found differences in expression as a function of genotype. We also found significant differences in NRG1 expression levels between diseased and control individuals bearing the same rs10088313 risk genotype. This indicates that the effects of NRG1 common variants are likely to depend on other alleles or epigenetic factors present in the patients and would account for the variability in the genetic predisposition to HSCR

RET Mutational Spectrum in Hirschsprung Disease: Evaluation of 601 Chinese Patients

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial)

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity