Detection and reporting of RB1 promoter hypermethylation in diagnostic screening

Background: RB1 gene screening aids clinical management and genetic counselling in retinoblastoma families. Here we present epigenetic changes identified during routine molecular RB1 screening of tumor and blood samples. Complications in interpreting RB1 methylation are discussed.

Materials and Methods: Screening for RB1 promoter hypermethylation was carried out by Methylation Specific PCR (MS-PCR) after bisulphite modification of DNA. The cohort consisted of 315 tumors, and 204 blood samples, from 497 retinoblastoma patients (22 patients had both blood and tumor screened).

Results: 11.4% of retinoblastoma tumors had promoter hypermethylation. It was not routinely detected in blood samples, or in tumors with two other oncogenic RB1 changes. One blood sample had promoter hypermethylation due to an X;13 translocation. One tumor had low level methylation as well as two other oncogenic changes. Histopathological analysis of a small subset of age-matched tumors was similar regardless of promoter hypermethylation status.

Conclusions: Promoter hypermethylation was detected in 11.4% of the retinoblastoma tumors and should be tested for in routine RB1 screening programmes. Constitutional samples are not expected to display RB1 hypermethylation. In a small proportion of cases it may not be possible to use this somatic change in patient management.     

Successful Therapeutic Hypothermia in Patients with Congenital Long QT Syndrome

Therapeutic hypothermia has been shown to improve neurological outcomes in patients who remain comatose following resuscitation from cardiac arrest. While there are numerous reports of patients who have had a successful course after induction of therapeutic hypothermia, such therapeutic intervention has not been described in patients with congenital long QT syndrome (LQTS). We report outcomes in two patients with LQTS who had therapeutic hypothermia following a ventricular fibrillation arrest. Careful and routine monitoring of the QT interval in this patient population is necessary due to the potential for worsening electrical instability during induced hypothermia. Ann Noninvasive Electrocardiol 2011;16(1):100–103     

A target site for template-based design of measles virus entry inhibitors

Measles virus (MV) constitutes a principal cause of worldwide mortality, accounting for almost 1 million deaths annually. Although a live-attenuated vaccine protects against MV, vaccination efficiency of young infants is low because of interference by maternal antibodies. Parental concerns about vaccination safety further contribute to waning herd immunity in developed countries, resulting in recent MV outbreaks. The development of novel antivirals that close the vaccination gap in infants and silence viral outbreaks is thus highly desirable. We previously identified a microdomain in the MV fusion protein (F protein) that is structurally conserved in the paramyxovirus family and constitutes a promising target site for rationally designed antivirals. Here we report the template-based development of a small-molecule MV inhibitor, providing proof-of-concept for our approach. This lead compound specifically inhibits fusion and spread of live MV and MV glycoprotein-induced membrane fusion. The inhibitor induces negligible cytotoxicity and does not interfere with receptor binding or F protein biosynthesis or transport but prevents F protein-induced lipid mixing. Mutations in the postulated target site alter viral sensitivity to inhibition. In silico docking of the compound in this microdomain suggests a binding model that is experimentally corroborated by a structure-activity analysis of the compound and the inhibition profile of mutated F proteins. A second-generation compound designed on the basis of the interaction model shows a 200-fold increase in antiviral activity, creating the basis for novel MV therapeutics. This template-based design approach for MV may be applicable to other clinically relevant members of the paramyxovirus family.     

Mean platelet volume may not have a predictive value for renal involvement in Henoch-Schönlein purpura secondary to Mycoplasma pneumoniae infection

Clinical Rheumatology -     

To what extent and why are COPD and Willis-Ekbom disease associated?

Aim

Willis-Ekbom disease (RLS/WED) is common in chronic obstructive pulmonary disease (COPD). Patients with RLS/WED have poorer quality of sleep and more fatigue and depressive symptoms. The prevalence of RLS/WED in patients with COPD has been reported to vary between 29.1 and 36.8 %. However, during exacerbation, the prevalence can increase up to 54 %. These rates are higher than those seen in general population. We have not enough knowledge regarding the association between RLS and COPD. In this study, we aimed to determine the frequency of RLS in patients with stable COPD without comorbid conditions. In addition, we also aimed to determine possible related causative factors.

Method

We included 80 COPD patients without comorbid conditions who presented to our outpatient clinic between April 2013 and September 2013 for RLS/WED evaluation. Three cases that have polyneuropathy and one case that refused undergoing electromyography (EMG) examination were excluded from the study. Demographic data, P-A chest X-rays, pulmonary function tests (PFT), biochemical parameters (including hemogram), and dyspnea scales were evaluated for each patient. In addition, the RLS/WED rating scale and Epworth Sleep Scale (ESS) were applied. Further, each patient diagnosed with RLS/WED underwent a detailed neurological examination (performed by a neurologist) and an EMG examination to rule out polyneuropathy.

Results

Out of 76 COPD cases included in our study, 26.3 % (n?=?20) were diagnosed with RLS/WED (mean age 60.4?±?7.5 years, 20 males). The cases with RLS/WED had significantly lower body mass index (BMI) than cases without RLS/WED (p?=?0.009). There were no significant differences between cases with and without RLS/WED with respect to PFT, dyspnea scales, and arterial blood gas values. However, ESS was significantly different (p?=?0.016). There were no significant differences in RLS/WED scores and mean hs-CRP levels between COPD stages (p?=?0.424; p?=?0.518, respectively), while ESS was significantly different (p?=?0.016). ESS was significantly higher in stage B COPD than in stages A and D (p?=?0.005, p?=?0.008, respectively). Based on our model, we found that exacerbations and iron binding capacity (UIBC) were predictive factors for RLS/WED (p?<?0.100)

Conclusion

RLS/WED is a common disease in cases with stable COPD. Despite our hypothesis suggesting that the prevalence of RLS/WED in COPD is related with systemic inflammation, we did not find a significant association between hs-CRP and COPD cases with RLS/WED. However, we did find that UIBC is a predictive factor for the development of RLS/WED. Nonetheless, further studies are needed to understand the relationships between UIBC, low BMI, and the development of RLS/WED in COPD.

     

Mediastinal ectopic thyroid diagnosed by endobronchial ultrasound‐guided transbronchial needle aspiration: Report of three cases

An ectopic thyroid gland results from the abnormal migration of the thyroid in the course of its development. Primary ectopic mediastinal thyroid is very rare and occurs in less than 1% of all goiters that can be surgically excised. Ectopic thyroid tissue has a characteristic sonographic appearance as smooth‐bordered, homogeneous, hypoechoic tissue with fine specular echoes. We report 3 cases of mediastinal ectopic thyroid diagnosed by endobronchial ultrasound‐guided transbrochial needle aspiration biopsy.     

Retinal vessel diameters and their correlation with retinal nerve fiber layer thickness in patients with pseudoexfoliation syndrome

AIM: To compare retinal artery-vein diameters (RAVDs) of patients with pseudoexfoliation (PSX) syndrome with healthy controls and investigate the correlations between retinal nerve fiber layer (RNFL) thickness parameters and RAVDs. METHODS: Seventeen eyes with PSX and 17 eyes of age-matched controls were included in the study. All participants underwent routine ophthalmological examination, Humphrey visual field and RNFL examination by using Stratus OCT. Retinal images were obtained by using a retinal camera (Topcon 501X). RAVDs were measured from inferior nasal, inferior temporal, superior nasal and superior temporal arcuates by using IMAGEnet software. Superior, inferior, nasal, temporal and average RNFL thicknesses were recorded. RAVDs and RNFL parameters in groups and correlations were analyzed by Mann-Whitney U and Spearmann correlation tests. RESULTS: Only inferior quadrant and average RNFL thickness were detected thinner in the PSX group compared with control group (P=0.009, P=0.038, respectively). No statistically significant difference regarding RAVDs was found between two groups. CONCLUSION: RAVDs seems to be comparable in the PSX and control group. RNFL is thinner in the inferior quadrant in the PSX group. RNFL thickness and RAVDs show significant correlations in both groups. This correlation doesn’t seem to be specific to PSX.