Contribution of VANGL2 mutations to isolated neural tube defects

Kibar Z, Salem S, Bosoi CM, Pauwels E, De Marco P, Merello E, Bassuk AG, Capra V, Gros P. Contribution of VANGL2 mutations to isolated neural tube defects. Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non‐canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi‐ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

Dental caries status of Dai preschool children in Yunnan Province,China

Background

The Dai people, one of the ethnic minorities in China, have a population of 1,260,000. They have the same origin as one of the main ethnic groups of Laos and Thailand. Most of the Dai live in Yunnan province, which is located in the less-developed southwestern part of China. This study aimed to describe the oral health status of Dai preschool children in China and the factors that influence their oral health status.

Methods

An oral health survey was performed between 2011 and 2012 to select Dai five-year-old children using multi-stage stratified sampling in Yunnan. Their dental caries experience was measured using the “dmft” index, and severe caries was assessed using the “pa” index, which is modified from the “pufa” index. Oral hygiene status was assessed using the visual plaque index (VPI). A questionnaire to study the children’s socio-demographic background and oral health-related behaviours was completed by the children’s parents.

Results

A total of 833 children were examined. Their caries prevalence was 89% and 49% of the children had carious tooth with pulp involvement. The mean (SD) dmft score was 7.0 (5.3). Higher dmft scores were found among children who were girls, were currently bottle-fed, took daily sweet snacks, had higher VPI scores, and had visited a dentist within the last year.

Conclusions

The caries prevalence and experience of the five-year-old Dai children in Yunnan, China was high, and almost half had severe caries. The caries experience was associated with gender, snack habits, dental visit habits, and oral hygiene status.

     

Detection of the Philadelphia chromosome in acute lymphoblastic leukemia by pulsed-field gel electrophoresis

The Philadelphia (Ph1) chromosome is an acquired abnormality in the malignant cells of 10% to 25% of patients with acute lymphoblastic leukemia (ALL). Unlike chronic myelogenous leukemia (CML), where the molecular detection of the Ph1 chromosome is relatively straightforward using conventional Southern hybridization analysis, the detection of the Ph1 chromosome in ALL is complicated by the existence of several molecular subtypes, and the fact that translocation breakpoints are dispersed over a large genomic area. To circumvent these difficulties, we investigated pulsed-field gel electrophoresis (PFGE) to determine if this method could be used directly on clinical samples to detect the Ph1 chromosome in ALL. We report that, in a study of seven patients with Ph1-positive ALL, we could easily detect the Ph1 using only a single PFGE analysis, regardless of the Ph1 subtype, and we could confirm that the translocations occur either within or very near the BCR gene in all seven. We conclude that PFGE is a useful technique for the detection of the Ph1 in ALL, which ultimately may find wide applicability in the detection of other chromosomal abnormalities in other malignancies.     

Impact of a modified directly administered antiretroviral treatment intervention on virological outcome in HIV-infected patients treated in Burkina Faso and Mali

Objective

This study explores whether viral load measurements can be used in resource‐limited settings to target those in need of adherence assistance. It was hypothesized that high plasma viral loads (pVLs) (≥500 HIV‐1 RNA copies/mL) were the result of poor antiretroviral therapy adherence and amenable to improvement with adherence assistance.

Design

A single‐arm, multicentre pilot study was conducted from November 2003 to March 2004 on 606 treatment‐experienced patients who had initiated an antiretroviral regimen in Mali and Burkina Faso ≥6 months before study enrolment. In these patients, those whose pVL was ≥500 copies/mL were offered 1 month of modified directly administered antiretroviral treatment (mDAART) with weekly follow‐up visits from pharmacists or adherence counsellors.

Methods

An adherence questionnaire was given to all cohort patients and viral load was used to screen for patients with ≥500 copies/mL. mDAART participants included cohort patients with ≥500 copies/mL, who completed the adherence questionnaire. Genotypic analyses were conducted on samples taken prior to and after the intervention. The intervention was considered effective when there was a decrease of ≥1 log₁₀ in pVL.

Results

mDAART was effective in over one‐third of the intervention participants, while in two‐thirds no decrease in pVL was observed. The majority of mDAART participants had major resistance mutations.

Conclusions

pVL measurement was useful to identify patients who needed adherence assistance. However, because it was performed ≥6 months after starting treatment, mDAART came too late for most participants, as they had already developed important resistance mutations that might have been avoided with better laboratory monitoring.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

A Clinico-Bacteriological Study of Pyodermas at a Tertiary Health Center in Southwest Rajasthan

Background:

The spectrum of pyoderma changes constantly, and so does the antibiotic susceptibility pattern.

Aims:

This study was done to assess the magnitude and clinical patterns of pyodermas, their causative micro-organisms, and the antibiotic susceptibility patterns.

Materials and Methods:

Five hundred consecutive, clinically diagnosed and untreated cases of pyoderma, attending the Dermatology OPD of RNT Medical College and MB Government Hospital, Udaipur, from October 2010 to September 2011 were the subjects of this study. A detailed clinical examination, and relevant investigations including bacterial culture and sensitivity, were carried out and recorded.

Statistical Analysis:

For statistical analysis of data, the software ‘EPI-INFO Version 6’ was used, and Chi-square (χ²) test was applied.

Results:

Of 19576 cases attending skin OPD during the study period, pyoderma was seen in 500 patients; the incidence being 2.55%. Males outnumbered females. The highest number of cases (109; 21.8%) was observed in 1st decade. Lower extremities were the commonest site of predilection. Primary pyodermas outnumbered secondary pyodermas. Furuncle (136; 27.2%) and infectious eczematoid dermatitis (62; 12.4%) were the commonest entities among primary and secondary pyoderma respectively. Staphylococcus aureus was the commonest causative agent in both primary and secondary pyoderma. It showed high susceptibility to amoxycillin + sulbactam, aminoglycosides and cefoperazone, moderate susceptibility to linezolid, while low susceptibility to fluoroquinolones and cephalexin.

Conclusion:

Such studies help to assess the changing trend of bacterial infections, their causative organisms and antibiotic susceptibility pattern.     

The impact of maternal experience of violence and common mental disorders on neonatal outcomes: a survey of adolescent mothers in Sao Paulo,Brazil

Background  

Both violence and depression during pregnancy have been linked to adverse neonatal outcomes, particularly low birth weight. The aim of this study was to investigate the independent and interactive effects of these maternal exposures upon neonatal outcomes among pregnant adolescents in a disadvantaged population from Sao Paulo, Brazil.