Analysis of 1 year virtual histology changes in coronary plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold

Serial intravascular ultrasound virtual histology (IVUS-VH) after implantation of metallic stents has been unable to show any changes in the composition of the scaffolded plaque overtime. The everolimus-eluting ABSORB scaffold potentially allows for the formation of new fibrotic tissue on the scaffolded coronary plaque during bioresorption. We examined the 12?month IVUS-VH changes in composition of the plaque behind the struts (PBS) following the implantation of the ABSORB scaffold. Using IVUS-VH and dedicated software, the composition of the PBS was analyzed in all patients from the ABSORB Cohort B2 trial, who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA), immediately post-ABSORB implantation and at 12?month follow-up. Paired IVUS-VH data, recorded with s5i system, were available in 17 patients (18 lesions). The analysis demonstrated an increase in mean PBS area (2.39?±?1.85?mm(2) vs. 2.76?±?1.79?mm(2), P?=?0.078) and a reduction in the mean lumen area (6.37?±?0.90?mm(2) vs. 5.98?±?0.97?mm(2), P?=?0.006). Conversely, a significant decrease of 16 and 30% in necrotic core (NC) and dense calcium (DC) content, respectively, were evident (median % NC from 43.24 to 36.06%, P?=?0.016; median % DC from 20.28 to 11.36%, P?=?0.002). Serial IVUS-VH analyses of plaque located behind the ABSORB struts at 12-month demonstrated an increase in plaque area with a decrease in its NC and DC content. Larger studies are required to investigate the clinical impact of these findings.     

Epidemiological studies on pulmonary pathogens in HIV-positive and -negative subjects with or without community-acquired pneumonia with special emphasis on Mycoplasma pneumoniae

The prevalence of Mycoplasma pneumoniae among HIV-positive patients with community-acquired pneumonia (CAP) remains unclear. We investigated 300 HIV-positive adults (200 with CAP and 100 with no respiratory illness) and 75 HIV-negative adults with CAP for the prevalence of respiratory pathogens using culture and serology. A growth inhibition test was employed to confirm the isolates of M. pneumoniae using species-specific typing sera. The prevalence of M. pneumoniae in HIV-positive subjects was 17% by induced sputum and 11.3% by throat swab culture. The seroprevalence of anti-M. pneumoniae IgM was 11.7% by ELISA and 14.3% by the gelatin microparticle agglutination test. The prevalence of M. pneumoniae among HIV-negative cases was relatively low. Streptococcus pneumoniae was predominant (28%) among subjects with lower respiratory disease, whereas Staphylococcus aureus (15%) was common among upper respiratory symptomatic cases. Rales (P=0.001), pharyngeal erythema (P=0.02), cervical adenopathy (P=0.004), skin rash (P=0.001), and crepitations (P=0.001) were each significantly related to M. pneumoniae positivity. Statistical significance was observed in relation to total lymphocyte count (P=0.02) and erythrocyte sedimentation rate (P=0.04), as well as M. pneumoniae positivity. This study shows that the prevalence of M. pneumoniae in HIV-positive subjects is comparatively higher than in HIV-negative subjects with pulmonary symptoms, and concords with previous pilot studies carried out in Chennai, South India.     

Natural genetic variation caused by small insertions and deletions in the human genome

Human genetic variation is expected to play a central role in personalized medicine. Yet only a fraction of the natural genetic variation that is harbored by humans has been discovered to date. Here we report almost 2 million small insertions and deletions (INDELs) that range from 1 bp to 10,000 bp in length in the genomes of 79 diverse humans. These variants include 819,363 small INDELs that map to human genes. Small INDELs frequently were found in the coding exons of these genes, and several lines of evidence indicate that such variation is a major determinant of human biological diversity. Microarray-based genotyping experiments revealed several interesting observations regarding the population genetics of small INDEL variation. For example, we found that many of our INDELs had high levels of linkage disequilibrium (LD) with both HapMap SNPs and with high-scoring SNPs from genome-wide association studies. Overall, our study indicates that small INDEL variation is likely to be a key factor underlying inherited traits and diseases in humans.     

A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal‐recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13–12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.     

Haplotype analysis of two X-chromosome STR clusters in the Pakistani population

Haplotype analysis of closely associated markers has proven to be a powerful tool in kinship analysis especially when X-chromosome short tandem repeats fail to resolve uncertainty in relationship analysis. Microsatellites located on the X chromosome show stronger linkage disequilibrium compared with autosomal microsatellites; hence, it is necessary to estimate the haplotype frequencies directly from population studies as linkage disequilibrium is population-specific. Here, we describe five markers residing in two clusters; cluster I harboring three STR markers DXS6801–DXS6809–DXS6789 and cluster II harboring two STR markers DXS7424–DXS101. A total of 302 male DNA samples of Pakistani descent were analyzed. Theoretically, 847 and 160 different combinations of haplotypes are possible in clusters I and II, but genotyping identified only 129 and 75 haplotypes, respectively. No evidence of linkage disequilibrium was detected, except for the pair (DXS6801–DXS6789), consistent with results obtained with the cluster I in a German population. Our results demonstrate that 83% haplotypes of cluster I and 65% haplotypes of cluster II show <1% frequency in the Pakistani population. This strongly suggests that haplotypes of these two clusters provide a powerful tool for kinship testing and relationship investigations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was supported in part by Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan.     

Secondary neoplasms of the esophagus

A review of 62 cases of esophageal involvement by secondary neoplasms is reported. The common routes of esophageal involvement are by direct extension of the tumor from the contiguous or adjacent organs (45.2%), via mediastinal nodes (35.5%), and hematogenous spread from a distant primary (19.3%). In the first 2 modes of esophageal involvement, the diagnosis is usually obvious but hematogenous metastases to the esophagus usually pose a diagnostic challenge. Radiologically, hematogenous metastases show a spectrum of features consisting of a short segment of progressive stricture with normal to minimally irregular mucosa, a submucosal mass with or without ulceration, a polypoid mass or masses, and defects in esophageal motility including secondary achalasia. Since endoscopy and biopsy have limited diagnostic yield, radiologic diagnosis plays a key role in the diagnosis of secondary neoplasms of the esophagus irrespective of their mode of spread to the esophagus.     

Assessing the complications and effectiveness of open carpal tunnel release in a tertiary care centre in a developing country

INTRODUCTION

Open surgical release for carpal tunnel syndrome is not devoid of complications and its quantitative assessment with the Boston questionnaire in a developing country had not been conducted, where, lack of facilities and surgical technique can influence the outcome.

PRESENTATION OF CASE

This was a prospective study in which all cases of carpal tunnel syndrome undergoing open release between June 2007 and June 2012 and who returned for follow up were included. Each patient was requested to fill out the Boston questionnaire twice both pre and post op at 3 months. All complications were recorded as well as bio-data of patients and co morbidities. Follow up was at 2 weeks and at 3 months. Those reporting complications at 3 months were further followed up until 6 months. 373 patients were included in the study. Twenty four patients developed complications. Of these, 12 experienced pain resulting from reflex sympathetic dystrophy. Three patients developed wound dehiscence, 2 cases acquired infections, 4 patients developed immediate post-operative haemorrhage and in 3 patients there was late recurrence of median nerve compression. The symptom severity score pre-operatively was 3.30 (±0.60) and it improved to 1.65 (±0.75) post-operatively indicating a significant change (p < 0.0001). The preoperative functional status score was 2.58 (±0.75) and post-op it became 1.60 (±0.80) again implying a good improvement with an effect size of 1.3.

DISCUSSION

All of the complications produced were well managed. The complication incidence was low. The open release procedure produced good improvement in hand function and in decreasing the symptom severity.

CONCLUSION

Conducting open release for carpal tunnel syndrome in a tertiary referral centre in a developing country offers a good outcome.