Application of whole-exome sequencing for detecting copy number variants in CMT1A/HNPP.

Large insertions and deletions (indels), including copy number variations (CNVs), are commonly seen in many diseases. Standard approaches for indel detection rely on well-established methods such as qPCR or short tandem repeat (STR) markers. Recently, a number of tools for CNV detection based on next-generation sequencing (NGS) data have also been developed; however, use of these methods is limited. Here, we used whole-exome sequencing (WES) in patients previously diagnosed with CMT1A or HNPP using STR markers to evaluate the ability of WES to improve the clinical diagnosis. Patients were evaluated utilizing three CNV detection tools including CONIFER, ExomeCNV and CEQer, and array comparative genomic hybridization (aCGH). We identified a breakpoint region at 17p11.2-p12 in patients with CMT1A and HNPP. CNV detection levels were similar in both 6 Gb (mean read depth = 80×) and 17 Gb (mean read depth = 190×) data. Taken together, these data suggest that 6 Gb WES data are sufficient to reveal the genetic causes of various diseases and can be used to estimate single mutations, indels, and CNVs simultaneously. Furthermore, our data strongly indicate that CNV detection by NGS is a rapid and cost-effective method for clinical diagnosis of genetically heterogeneous disorders such as CMT neuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy in children: characterized by subacute, predominantly motor dominant polyeuropathy with a favorable response to the treatment.

OBJECTIVES: Chronic inflammatory demyelinating polyradiculopathy (CIDP) is less well-studied in children than in adults, probably due to its relative rarity. This study was performed in order to characterize the clinical features of CIDP in children. MATERIALS AND METHODS: Twenty-eight patients with CIDP who were followed up for more than 1 year were included, and were divided into a child (n = 7, age <16) and an adult group (n = 21, age >or=16). Then, we have assessed the initial progression pattern, clinical course, and serial nerve conduction findings in each patient. Finally, differential features in child and adult group were analyzed. RESULTS: Distinguishing features in the child group include subacute progression within less than 2 months, predominant motor system involvement in lower extremities, and marked improvement in response to immune modulating therapy. Our study also suggested that serial nerve conduction study may be useful in assessing the effectiveness of the treatment in children. CONCLUSIONS: Our study showed that children with CIDP have some distinguishing features from adults in terms of clinical course and response to treatment.

Association between unplanned readmission rate and volume of breast cancer operation cases.

This study was conducted to investigate the relationship between unplanned readmission and breast cancer operation cases, with the assumption that the rate of unplanned readmission within 30 days of surgery was solely due to postsurgical complications. We divided hospitals into three categories based on breast cancer operation cases: low-volume hospitals (< or =50 annual procedures), medium-volume hospitals (51-99 annual procedures) and high-volume hospitals (> or =100 annual procedures). The medical records of 1351 subjects in 24 hospitals were investigated. We found unplanned readmission rates were significantly higher in hospitals with a lower surgical volume. From these three groups, a sample consisting of 1351 patients was created and 17 unplanned readmission cases (1.2%) were reported. Of these 17 cases, 12 (70.59%) cases were from low-volume hospitals. The present results indicate that unplanned readmission within 30 days following discharge is an important adverse outcome in breast cancer surgery.

Freestanding and multiunit immediate loading of the expandable implant: an up-to-40-month prospective survival study.

STATEMENT OF PROBLEM: The subject of immediate loading of dental implants has received substantial attention, although it appears to conflict with the basic principles of dental implant therapies developed and established over the past 20 years. Clinicians would welcome the use of a reliable, immediate-loading implant system. PURPOSE: The purpose of this study was to evaluate the effectiveness of an expandable implant design for immediate and delayed loading and for freestanding and multiunit situations. MATERIAL AND METHODS: Two hundred eighty-six immediate-load Sargon implants were placed in 75 patients during a 40-month period. Of the 273 implants that survived, 81 were placed into fresh extraction sockets and immediately loaded, 162 were placed into healed sites and immediately loaded, and 30 were delay loaded. Some implants that had failed to remain stable after immediate loading became stable and osseointegrated after the load was removed and their expansion mechanisms were reactivated. RESULTS: The overall survival rate during the 40-month period was 96.0% in the maxilla and 94.8% in the mandible. Implants placed in fresh extraction sockets showed a 98.9% survival rate. Healed sites showed a 93.9% survival rate. Immediate loading of 52 fresh extraction socket implants in the maxilla showed a 100% survival rate during the evaluation period. CONCLUSION: Within the limitations of this study, it was shown that the feature of mechanical expandability may provide operators some control over implant stability during the vulnerable period after immediate loading of single, freestanding implants.

A study of the solar effect on actinic keratoses by quantification of elastic fibres using an image analysis system.

It is widely accepted that elastotic changes of the skin are primarily an indicator of cumulative sun exposure of the dermis and are a characteristic finding of actinic keratoses. To date, there have been few reports that measure the amount of elastic tissue objectively and quantitatively, especially in actinic keratoses. The computerized image analysis method has proved useful recently in determining the area of elastic fibres. Using this method, we objectively quantified the elastotic tissue in actinic keratoses and evaluated the relationship between the degree of dermal elastosis, epidermal atypia and histological types of actinic keratoses. Of the 28 actinic keratoses studied, the average percentage area of the elastic fibre was 40.48 +/- 14.48 (mean +/- SD) percentile. There was a 3.65-fold increase in the amount of elastic fibre in actinic keratoses compared with that of seborrhoeic keratoses occurring on the face (p < 0.00001). In addition, the more severe the atypia, the greater the area of elastic fibres in a representative section of the dermis. In conclusion, we observed that on quantitative assessment of elastic tissue in actinic keratoses, the percentage area of the elastic fibres in a representative section of the dermis ranges from 34.86 to 46.11%. This result may provide information for use in histological diagnosis of actinic keratoses and evidence for the possible role of sunlight in the pathogenesis of actinic keratosis.

Quantitative image analysis of hair follicles in alopecia areata.

We took biopsies from similar sites on the scalps of normal controls, normal looking and hair loss areas of patients with alopecia areata. The specimens were sectioned serially and horizontally. We measured morphological parameters, such as the diameter of the hair shaft, the thickness of the inner root sheath, the diameter of the outer root sheath, the irregularity of the outer root sheath and the ratio between the diameters of the hair shaft and the outer root sheath, using a computerized image analysis system. There were significant differences in 5 parameters between hair loss areas and normal controls. The proportions of vellus and telogen hair were significantly higher in the areata areas than in the controls. The 5 morphological parameters and most quantitative-measured parameters of normal-looking areas from patients with alopecia values intermediate between the other groups.