Manipulating prefabricated flaps: An experimental study examining flap viability

As flap prefabrication becomes a more commonly used clinical tool, it is necessary to investigate the limitations of this technique. Reconstructive procedures of the face often require “custom fitted” flaps to satisfy esthetic demands. This study examines and compares the safety of manipulating thin prefabricated skin flaps versus established axial pattern skin flaps. Twenty-seven New Zealand white rabbits were used to determine if prefabricated flaps can be folded 180° around the edge of the rabbits' ears. The survival of these folded prefabricated flaps was compared with the survival of axial pattern flaps sutured into an identically recipient site. In addition, flaps prefabricated in the same manner were sutured onto a straight recipient bed to evaluate the viability of the newly vascularized tissue. The folded prefabricated flaps had reduced survival (56%) compared to equivalent folded axial pattern flaps (85%), P<0.005. The nonmanipulated prefabricated flaps and axial pattern flaps survived completely. © 1994 Wiley-Liss, Inc.     

A comparison of two data analyses from two observer performance studies using Jackknife ROC and JAFROC

The authors compared two methodological approaches, Jackknife ROC and JAFROC, in analyzing data ascertained during FROC (free-response receiver operating characteristics) type studies. Observer rating data obtained from two observer performance studies were analyzed. During the first study, seven radiologists interpreted 120 mammography examinations depicting 57 masses under five different conditions with and without the results of computer-aided detection (CAD). In the second study, eight radiologists interpreted 110 examinations depicting 51 masses under six different display conditions with and without CAD results. Readers rated the detection task in a FROC type response. Jackknife ROC (using the software of LABMRMC with the highest rating per case) and JAFROC were used to compute differences, if any, in summary performance levels among all reading modes in each study as well as for all paired data sets. The results of the different analytical approaches are compared. The overall results for all modes were significantly different for the first study (p < 0.05) and not significant (p > 0.05) for the second study using either analytical approach. In the first study, the performance levels represented by three paired data sets were significantly different (p < 0.05) when computed using LABMRMC and four pairs were significantly different (p < 0.05) using JAFROC. In eight of ten pairs, JAFROC produced lower p values than LABMRMC. In the second study, LABMRMC showed no significant differences for any paired data sets and JAFROC showed a significant difference for one pair. In 15 of 16 pairs, p values computed by JAFROC were lower than those computed by LABMRMC.     

Joint Photographic Experts Group (JPEG) compatible data compression of mammograms

We have developed a Joint Photographic Experts Group (JPEG) compatible image compression scheme tailored to the compression of digitized mammographic images. This includes a preprocessing step that segments the tissue area from the background, replaces the background pixels with a constant value, and applies a noise-removal filter to the tissue area. The process was tested by performing a just-noticeable difference (JND) study to determine the relationship between compression ratio and a reader's ability to discriminate between compressed and noncompressed versions of digitized mammograms. We found that at compression ratios of 15∶1 and below, image-processing experts are unable to detect a difference, whereas at ratios of 60∶1 and above they can identify the compressed image nearly 100% of the time. The performance of less specialized viewers was significantly lower because these viewers seemed to have difficulty in differentiating between artifact and real information at the lower and middle compression ratios. This preliminary study suggests that digitized mammograms are very amenable to compression by techniques compatible with the JPEG standard. However, this study was not designed to address the efficacy of image compression process for mammography, but is a necessary first step in optimizing the compression in anticipation of more elaborate reader performance (ROC) studies.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.