Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids.

PURPOSE: To evaluate whether there is a relationship between steroid treatment and risk for osteonecrosis of the hip and knee in patients with severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: The hospital ethics committee approved the study, and all patients provided written informed consent. A total of 254 patients with confirmed SARS treated with steroids underwent evaluation with magnetic resonance (MR) imaging for osteonecrosis. Clinical profiles, joint symptoms, relevant past medical and drug history, steroid dose, and radiographic and MR imaging evidence of osteonecrosis and other bone abnormalities were evaluated. Mann-Whitney, Kruskal-Wallis, and Pearson exact chi(2) tests were performed, and univariate and multivariate logistic regression analyses were applied. RESULTS: One hundred thirty-four (53%) of 254 patients had recent onset of large joint pain, but 211 (80%) of 264 painful joints were not associated with abnormality on MR images. MR images in 12 (5%) of 254 patients showed evidence of subchondral osteonecrosis in the proximal femur (n = 9), distal femur (n = 2), and proximal and distal femora and proximal tibiae (n = 1). Additional nonspecific subchondral and intramedullary bone marrow abnormalities were present in 77 (30%) of 254 patients. Results of multiple logistic regression analysis confirmed cumulative prednisolone-equivalent dose to be the most important risk factor for osteonecrosis. The risk of osteonecrosis was 0.6% for patients receiving less than 3 g and 13% for patients receiving more than 3 g prednisolone-equivalent dose. No relationship was found between additional nonspecific bone marrow abnormalities and steroid dose. CONCLUSION: An appreciable dose-related risk was found for osteonecrosis in patients receiving steroid therapy for SARS. Additional nonspecific bone marrow abnormalities were frequent. Joint pain was common after SARS infection and was not a useful clinical indicator of osteonecrosis.

Clinicopathologic significance of loss of heterozygosity on chromosome 1 in cervical cancer.

OBJECTIVES: We studied the loss of heterozygosity (LOH) in chromosome 1 in squamous cell carcinoma (SCC) of the uterine cervix and evaluated its clinical and pathological significance. METHODS: Sixty-three highly polymorphic markers were used to study the LOH in 84 SCC. Microdissection was performed to enrich the tumor cells population before the alleotyping study. The findings were correlated with clinicopathologic findings. RESULTS: LOH was detected in all but one SCC. The number of loci showing LOH in each case ranged from 0 to 41. Five loci showed LOH in > or =30% SCC and 28 other loci had an LOH frequency between 20% and 30%. Six of the eight markers located at 1p36.21 to 1p36.33 had a frequency of LOH >20%. Shortened total survival was associated with LOH at 14 loci and shortened disease-free survival was associated with LOH at 11 loci while LOH at nine loci were associated with both. A high frequency of LOH was associated with stage as well as shortened total and disease-free survival. CONCLUSIONS: LOH is a common and early event in the development of cervical SCC. Tumor suppressor genes may be present at 1p36. The incidence of LOH increases as the tumor progresses but a high frequency of LOH is not an independent prognostic factor.

Epigenetic and genetic alternation of PTEN in cervical neoplasm.

OBJECTIVES: We studied the role of epigenetic and genetic changes of PTEN in the development of squamous cell carcinoma (SCC) of the uterine cervix and their value as a prognostic factor. METHODS: Ten high-grade cervical intraepithelial neoplasia (CIN-H) and 62 SCC tissues were used in this study. Microdissection was performed before loss of PTEN function through methylation of promoter CpG islands, deletion and mutation were studied. The findings were verified with PTEN protein expression and correlated with clinicopathologic information. RESULTS: PTEN mutation assessed by single-strand conformation polymorphism (PCR-SSCP) was not noted in any of the 62 SCC. Loss of heterozygosity (LOH) was only seen in eight SCC. PTEN promoter methylation was detected in 40% (4/10) of CIN-H and 58% (36/62) of SCC specimens. Loss of PTEN protein expression was associated with methylation of PTEN. PTEN methylation was not related to patient age, tumor grade or stage. Patients with persistent disease or who died of disease had a significantly higher percentage of PTEN methylation than those without evidence of recurrence. Multivariate Cox regression models confirmed PTEN was an important significant predictor both for total and disease-free survival after controlling age, pathologic grade and clinical stage. CONCLUSIONS: PTEN methylation and loss of PTEN expression are early events in the development of cervical cancer and may have prognostic significance.