Homozygous nonsense mutation in SCHIP1/IQCJ‐SCHIP1 causes a neurodevelopmental brain malformation syndrome

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria‐cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C‐terminal region shared by the Schwanomin‐Interacting Protein1 (SCHIP1) isoforms including the IQCJ‐SCHIP1. The in vitro expression of SCHIP1 and IQCJ‐SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full‐length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ‐SCHIP1 point mutation in humans associated with a neurological‐developmental phenotype.     

Volumetry and Analysis of Anatomical Variants of the Anterior Portion of the Petrous Apex Outlined by the Kawase Triangle Using Computed Tomography

Background Anterior petrosectomy has become an increasingly used approach for petroclival lesions. This study measures the volume and the anatomical variants of the anterior portion of the petrous apex outlined by the Kawase triangle using computed tomography (CT). Methods This was a transversal retrospective study. We assessed the anterior petrous apex portion outlined by the Kawase triangle in consecutive patients > 18 years of age from CT scans of temporal bone stored in an archive system. The volumetry was performed on a workstation. Results A total of 154 petrosal apex were analyzed in 77 patients (36 men). The average volume of the region outlined by the Kawase triangle was 1.89 ± 0.52 cm³. The volume average in men was 2.01 ± 0.58 cm³, and the average in women was 1.79 ± 0.41 cm³. Intra- and interobserver agreement were both excellent, and there was little variance. Nineteen petrous apex demonstrated anatomical variations. In 18 cases it was pneumatized, and in one case a vascular or nerve-like structure was identified, a report we did not find in the literature. Conclusion The volumetry of the petrous apex anterior portion outlined by the Kawase triangle can be made by CT with excellent intra- and interobserver agreement and reproducibility. There are anatomical variants in this region that are relevant to surgery.     

Unusual manifestation of the yellow nail syndrome - Case report

The yellow nail syndrome is a rare disorder characterized by the classic triad of yellow and dystrophic nails, lymphedema and pleural effusion. We report in this paper a case of yellow nail syndrome, presenting the classic triad of the disease, associated with an unusual lymph accumulation in the abdomen region.     

Importance of slow vital capacity in the detection of airway obstruction

OBJECTIVE:

To investigate the presence of airway obstruction by determining the FEV₁/FVC and FEV₁/slow vital capacity (SVC) ratios.

METHODS:

This was a quantitative, retrospective cross-sectional study. The sample comprised 1,084 individuals who underwent spirometry and plethysmography in a central hospital in Lisbon, Portugal. The study sample was stratified into six groups, by pulmonary function.

RESULTS:

The analysis of the FEV₁/FVC ratio revealed the presence of airway obstruction in 476 individuals (43.9%), compared with 566 individuals (52.2%) for the analysis of the FEV₁/SVC ratio. In the airway obstruction, airway obstruction plus lung hyperinflation, and mixed pattern groups, the difference between SVC and FVC (SVC − FVC) was statistically superior to that in the normal pulmonary function, reduced FEF, and restrictive lung disease groups. The SVC − FVC parameter showed a significant negative correlation with FEV₁ (in % of the predicted value) only in the airway obstruction plus lung hyperinflation group.

CONCLUSIONS:

The FEV₁/SVC ratio detected the presence of airway obstruction in more individuals than did the FEV₁/FVC ratio; that is, the FEV₁/SVC ratio is more reliable than is the FEV₁/FVC ratio in the detection of obstructive pulmonary disease.     

Successful use of plasmapheresis for granulomatosis with polyangiitis presenting as diffuse alveolar hemorrhage

Diffuse alveolar hemorrhage (DAH) is uncommon in pediatric patients and is a rare presenting sign of granulomatosis with polyangiitis (GPA). We present the case a 14‐year‐old girl who presented with respiratory failure secondary to DAH as the initial presenting sign of GPA. Her clinical course improved after initiation of plasmapheresis therapy and she is now in clinical remission. Pediatr Pulmonol. 2013; 48:614–616. © 2012 Wiley Periodicals, Inc.     

Immunogenicity and safety of pneumococcal conjugate polysaccharide and free polysaccharide vaccines alone or combined in HIV-infected adults in Brazil

Background

Streptococcus pneumoniae is a leading cause of hospitalization in HIV-infected adults therefore pneumococcal vaccine is recommended. The ideal antipneumococcal vaccine and effective vaccination regimen remain controversial and needs further evaluation.

Methods

To assess the efficacy of pneumococcal vaccines alone and combined, a randomized, blinded clinical trial was conducted in Brazil with 331 HIV-patients aged 18–60, with CD4-T cell count ≥200 cells/mm³. Two interventions 60 days apart were done in three schedules: 23-valent pneumococcal polysaccharide vaccine (PPV23)/placebo; 7-valent pneumococcal conjugate vaccine (PCV7)/placebo; and PCV7 plus PPV23. Safety and reactogenicity were evaluated, and immunogenicity was assessed by an IgG enzyme-linked immunosorbent assay to S. pneumoniae serotypes 6B, 9V and 14, performed at baseline, 60 and 180 days after first intervention. Comparison of immunogenicity was based on geometric mean concentration (GMC), percentages of individuals with serotype-specific IgG ≥ 0.35 μg/mL and ≥1.0 μg/mL and proportion of individuals with ≥4-fold increase in specific antibody concentrations for each serotype.

Results

Demographic and HIV conditions were similar, and both vaccines were well tolerated across vaccine groups. Significant increase in IgG-antibodies was observed to all serotypes evaluated. A greater proportion of PCV7 recipients reached and sustained IgG antibody concentrations at least four times as high as those at baseline, for serotypes 6B and 9V. A PPV23 dose after PCV7 did not enhance immunogenicity.

Conclusions

In this first trial conducted with HIV-infected immunologically stable adults in South America, both PPV23 and PCV7 were safe and immunogenic. Evidence suggesting PCV7 was more immunogenic than PPV23, as it elicited higher and persistent ≥4-fold increase of antibodies for 6B and 9V serotypes in a greater proportion of HIV-patients is noteworthy. Despite current recommendation of schedules combining PCV7 and PPV23, there is little evidence to support this practice and we did not observe benefits in this combination.     

Obstetric vesicovaginal fistula: reporting two cases in France

Obstetric vesicovaginal fistula is nowadays rare in developed countries. We are reporting two cases of patients with obstetric vesicovaginal fistula that occurred after operative vaginal deliveries performed in a French hospital. Early postpartum symptoms were vaginal urine leakage and infectious syndrome. The fistula has been cured by vaginal surgery one case and combined (laparotomy and vagina surgery) in the other case. Patients were totally healed a few months following the surgery.