High-throughput copy number analysis of 17q23 in 3520 tissue specimens by fluorescence in situ hybridization to tissue microarrays

Analysis of allelic loss in archival tumor specimens is constrained by quality and quantity of tissue and by technical limitations on the number of chromosomal sites that can be efficiently evaluated in conventional analyses using polymorphic microsatellite markers. Newly developed array-based assays have the potential to yield genome-wide data from small amounts of tissue but have not been validated for use with routinely processed specimens. We used the Affymetrix HuSNP assay, composed of 1494 single nucleotide polymorphism sites, to compare allelic loss results obtained from both formalin-fixed and frozen breast tissue samples. Tumor cells were separated from normal epithelia and nonepithelial cells by dissection and bivariate cytokeratin/DNA flow sorting; normal breast cells from the same patient served as constitutive normal. Allele results from the HuSNP array averaged 96% reproducibility between duplicates and were concordant between the fixed and frozen normal samples. We also analyzed DNA from the same samples after whole-genome amplification (primer extension preamplification). Although overall signal intensities were lower, the genotype data from the primer extension preamplification material was concordant with genomic DNA data from the same samples. Results from genomic normal tissue DNA averaged informative single nucleotide polymorphism at 379 (25%) loci genome-wide. Although data points were clustered and some segments of chromosomes were not informative, our data indicated that the Affymetrix HuSNP assay could provide an efficient and valid genome-wide analysis of allelic imbalance in routinely processed and whole genome-amplified pathology specimens.     

Risk factors for antibiotic resistance in <Emphasis Type="Italic">Campylobacter</Emphasis> spp. isolated from raw poultry meat in Switzerland

Background  

The world-wide increase of foodborne infections with antibiotic resistant pathogens is of growing concern and is designated by the World Health Organization as an emerging public health problem. Thermophilic Campylobacter have been recognised as a major cause of foodborne bacterial gastrointestinal human infections in Switzerland and in many other countries throughout the world. Poultry meat is the most common source for foodborne cases caused by Campylobacter. Because all classes of antibiotics recommended for treatment of human campylobacteriosis are also used in veterinary medicine, in view of food safety, the resistance status of Campylobacter isolated from poultry meat is of special interest.     

Surgical treatment for scoliosis extending to main thoracic spine by keyvertebral-screws technique （KVST）

Objective ：To introduce a key-vertebral-screws technique （KVST） in the surgical treatment of scoliosis extending to main thoracic levels, and to find the role of fulcrum bending in predicting the result of surgical treatment for scoliosis by this technique. Methods： Seventeen consecutive patients with scoliosis extending to main thoracic spine, who underwent pure posterior fusion without anterior or posterior release by KVST between January 2004 and July 2005 were evaluated for fulcrum bending flexibility, surgical correction rate, fulcrum bending correction index （FBCI） in main thoracic curves. Universal Spine System （USS） instrumentation was used in 15 cases, Monarch in another 2 cases. The severity of the curves was measured by Cobb＇s method using RadWork 6.0 software. Preoperative standing AP radiographs, preoperative fulcrum bending anterioposterior （AP） radiographs, postoperative standing AP radiographs, and most recent follow-up standing AP radiographs for spine were measured and recorded. All the data were analyzed with two-sample paired t-test by Origin 7.0 software. Results： Infection and neurological complications were not noted. No major complications were found. Just one case had some axial back pain, which got a full recovery from physiotherapy for 2 weeks. In the X-ray, there was an average correction of 71.5 % of the fused main thoracic curves, which had no significant lose of correction in final follow-up. For the whole fused main thoracic curves, the fulcrum bending flexibility were lower to operation correction rate （P=0. 013）. The average FBCI was 123%. From the data, the more rigid curves （especially fulcrum bending flexibility 〈50%）, the more correction rate operation could get, compared with fulcrum bending flexibility. Conclusion： （1） KVST is a good method in the surgical treatment of thoracic scoliosis, which can get satisfying result with lower medical cost. （2） Fulcrum bending flexibility is lower than operative correction rate by KVST in main     

Acquisition of graphic communication by a young girl without comprehension of spoken language

Purpose: To describe a graphic-mode communication intervention involving a girl with intellectual impairment and autism who did not develop comprehension of spoken language. The aim was to teach graphic-mode vocabulary that reflected her interests, preferences, and the activities and routines of her daily life, by providing sufficient cues to the meanings of the graphic representations so that she would not need to comprehend spoken instructions. Method: An individual case study design was selected, including the use of written records, participant observation, and registration of the girl's graphic vocabulary and use of graphic signs and other communicative expressions. Results: While the girl's comprehension (and hence use) of spoken language remained lacking over a 3-year period, she acquired an active use of over 80 photographs and pictograms. Conclusions: The girl was able to cope better with the cognitive and attentional requirements of graphic communication than those of spoken language and manual signs, which had been focused in earlier interventions. Her achievements demonstrate that it is possible for communication-impaired children to learn to use an augmentative and alternative communication system without speech comprehension, provided the intervention utilizes functional strategies and non-language cues to the meaning of the graphic representations that are taught.     

Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases

This study describes the effects of two major treatment options, splenectomy and/or bone marrow transplantation, on the natural history of the Wiskott-Aldrich (WAS) syndrome. The records of 62 patients with the WAS evaluated at the National Institutes of Health Clinical Center from 1966 to 1992 were reviewed. Nineteen patients were treated with bone marrow transplantation (BMT) and the results were largely dependent on the source of the graft. Twelve of 12 patients receiving HLA-matched sibling marrow achieved satisfactory immunologic and hematologic reconstitution. By contrast, only 2 of 7 patients receiving haploidentical, parental, or matched unrelated marrow survived more than 1 year after BMT. Thirty-nine patients who lacked suitable bone marrow donors early in their course underwent splenectomy for management of their thrombocytopenia; most received prophylactic antibiotics to minimize the risk of sepsis. Nearly all these patients achieved normal platelet counts and the rate of serious bleeding was reduced nearly sevenfold. Median survival in the untransplanted splenectomy group was 25 years, compared with less than 5 years in unsplenectomized patients. We conclude that HLA-matched sibling donor BMT is the treatment of choice for patients with WAS and that splenectomy and daily prophylactic antibiotics provide a significant survival advantage to those boys without a matched sibling donor. Splenectomy should probably be used in preference to unmatched BMT until results with alternative donor BMT significantly improve or gene therapy becomes available.     

The PI-PLC inhibitor U-73122 is a potent inhibitor of the SERCA pump in smooth muscle

In this issue MacMillan and McCarron in 2010 demonstrated that the phospholipase C (PLC) inhibitor U-73122 can potently inhibit Ca²⁺ release from isolated smooth muscle cells independent of its effect on PLC. Their data suggest that the PLC inhibitor can block the sarcoplasmic/endoplasmic reticulum calcium ATPase pump in smooth muscle and cast doubt on the reliability of U-73122 as the main pharmacological tool to assess the role of the phosphotidyl inositol-PLC pathway in cellular signalling.     

Death in CHARGE syndrome after the neonatal period

Bergman JEH, Blake KD, Bakker MK, du Marchie Sarvaas GJ, Free RH, van Ravenswaaij‐Arts CMA. Death in CHARGE syndrome after the neonatal period. CHARGE syndrome is a multiple congenital anomaly syndrome that can be life‐threatening in the neonatal period. Complex heart defects, bilateral choanal atresia, esophageal atresia, severe T‐cell deficiency, and brain anomalies can cause neonatal death. As little is known about the causes of death in childhood and adolescence, we studied post‐neonatal death in patients with CHARGE syndrome. We collected medical data on three deceased children from a follow‐up cohort of 48 CHARGE patients and retrospectively on an additional four deceased patients (age at death 11 months to 22 years). We analyzed the factors that had contributed to their death. In five patients respiratory aspiration had most likely contributed to premature death, one died of post‐operative complications, and another choked during eating. From our findings and a literature review, we suggest that swallowing problems, gastro‐esophageal reflux disease, respiratory aspiration and post‐operative airway events are important contributors to post‐neonatal death in CHARGE syndrome. Cranial nerve dysfunction is proposed as the underlying pathogenic mechanism. We recommend every CHARGE patient with feeding difficulties to be assessed by a multidisciplinary team to evaluate cranial nerve function and swallowing. Timely treatment of swallowing problems and gastro‐esophageal reflux disease is important. Surgical procedures on these patients should be combined whenever possible because of their increased risk of post‐operative complications and intubation problems. Finally, we recommend performing autopsy in deceased CHARGE patients in order to gain more insight into causes of death.