Biomedical subjects

Jay Wunder

Publications and source records attributed to Jay Wunder.

5 recordsLinked to original sources

PubMed2006

Application of reliability coefficients in cDNA microarray data analysis.

Gene expression microarray technology has been widely used in areas such as human cancer research to identify molecular characteristics of sample specimens. The microarray study, however, is a very complicated procedure which involves numerous sources of variability that may be either systematic or random. Systematic variation is often eliminated by applying normalization procedures, but at present there are no standard criteria available to evaluate the performance of a particular normalization approach. In this paper, we propose a reliability-type coefficient as a criterion to assess the effectiveness of normalization procedures in eliminating systematic variation. Simulation studies show that this criterion performs reasonably well in a range of settings. The proposed method is illustrated using a subset of an ongoing microarray study of soft-tissue sarcoma.

Computer Simulation↗

PubMed2005

Dysregulation of hedgehog signalling predisposes to synovial chondromatosis.

Synovial chondromatosis is a condition affecting joints in which metaplastic cartilage nodules arise from the synovium, causing pain, joint dysfunction, and ultimately joint destruction. Because dysregulation of hedgehog signalling is a feature of several benign cartilaginous tumours, expression of the hedgehog target genes PTC1 and GLI1 was examined in this study in samples from human synovial chondromatosis. Significantly higher expression levels were found in synovial chondromatosis than in the synovium, from which it arises. To determine if hedgehog-mediated transcription predisposes to synovial chondromatosis, the extra-toes mutant mouse, which harbours a heterozygous mutation in the hedgehog transcriptional repressor, Gli3, resulting in decreased expression of Gli3 protein, was studied. The extra-toes mutant mouse has a phenotype consistent with overactive hedgehog signalling, suggesting that Gli3 acts as a transcriptional repressor of limb development. Eighty-five per cent of Gli3 mutant mice developed synovial chondromatosis at 18 months of age, compared with 30% of wild-type littermates (p < 0.05). Three of the ten Gli3 mutant mice treated with triparanol, which blocks hedgehog signalling upstream of the Gli transcription factors, developed synovial chondromatosis, compared with eight of ten control mice. These data demonstrate that hedgehog signalling plays an important role in the development of synovial chondromatosis and suggest that blockade of hedgehog signalling may be a potential treatment for this disorder.

Animals↗

PubMed2005

Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma.

BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities evaluated included fibrosis, joint stiffness and edema at 2 years following treatment. The impact of morbidity on patient function as measured by the Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated. Toxicity rates were compared by treatment arm using the Fisher's exact test. Function scores by toxicity were analyzed using the Wilcoxon rank sum test. Multivariate logistic regression was used to evaluate the joint effect of treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater fibrosis (P = 0.07). Although not statistically significant, edema was more frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73 (17.8%). Patients with significant fibrosis, joint stiffness or edema had significantly lower function scores on both measures (all P-values < 0.01). Field size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients treated with postoperative radiotherapy tended to have greater fibrosis. Fibrosis, joint stiffness and edema adversely affect patient function.

Adolescent↗

PubMed2003

Obturator externus bursa: anatomic origin and MR imaging features of pathologic involvement.

PURPOSE: To investigate the anatomy of the obturator externus bursa of the hip and describe the magnetic resonance (MR) imaging features of pathologic involvement. MATERIALS AND METHODS: The authors dissected eight cadaver hemipelvises to assess for the presence of periarticular bursae of the hip and bursal communication with the fascial plane of the obturator externus muscle. In addition, 10 consecutive patients with obturator externus bursa enlargement were prospectively identified with MR imaging. A bursa was considered present when a fluid collection was seen extending along the obturator externus muscle, continuous with the posterior inferior hip joint. The direction, extent, contour, and thickness of the bursa and hip capsule were recorded. Surgical findings were available for eight of the 10 patients, with histopathologic correlation between the bursal lining and hip capsule. RESULTS: At cadaveric dissection, one specimen showed a bursa communicating with and extending from the posteroinferior aspect of the hip joint deep to the obturator externus tendon. In all 10 patients, MR images showed a hip joint effusion with a continuous bursa extending medially and displacing the obturator externus inferiorly. At surgery, a bursa was seen displacing the obturator externus muscle inferiorly and originating from the posteroinferior aspect of the hip joint in all eight patients. Results of pathologic analysis confirmed disease identical to the primary hip abnormality in all eight patients. CONCLUSION: The obturator externus bursa is a potential posteroinferior communication of the hip joint capsule, can be a site of disease spread from the hip joint, and can be accurately identified with MR imaging.

Adult↗

PubMed2002

Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.

BACKGROUND: External-beam radiotherapy (delivered either preoperatively or postoperatively) is frequently used in local management of sarcomas in the soft tissue of limbs, but the two approaches differ substantially in their potential toxic effects. We aimed to determine whether the timing of external-beam radiotherapy affected the number of wound healing complications in soft-tissue sarcoma in the limbs of adults. METHODS: After stratification by tumour size (< or = 10 cm or >10 cm), we randomly allocated 94 patients to preoperative radiotherapy (50 Gy in 25 fractions) and 96 to postoperative radiotherapy (66 Gy in 33 fractions). The primary endpoint was rate of wound complications within 120 days of surgery. Analyses were per protocol for primary outcomes and by intention to treat for secondary outcomes. FINDINGS: Median follow-up was 3.3 years (range 0.27-5.6). Four patients, all in the preoperative group, did not undergo protocol surgery and were not evaluable for the primary outcome. Of those patients who were eligible and evaluable, wound complications were recorded in 31 (35%) of 88 in the preoperative group and 16 (17%) of 94 in the postoperative group (difference 18% [95% CI 5-30], p=0.01). Tumour size and anatomical site were also significant risk factors in multivariate analysis. Overall survival was slightly better in patients who had preoperative radiotherapy than in those who had postoperative treatment (p=0.0481). INTERPRETATION: Because preoperative radiotherapy is associated with a greater risk of wound complications than postoperative radiotherapy, the choice of regimen for patients with soft-tissue sarcoma should take into account the timing of surgery and radiotherapy, and the size and anatomical site of the tumour.

Aged↗