Lupus‐like disease and high interferon levels corresponding to trisomy of the type I interferon cluster on chromosome 9p

Objective

Systemic lupus erythematosus (SLE) is associated with type I interferons (IFNs) and can be induced by IFNα treatment. This study looked for evidence of autoimmunity in a pedigree consisting of 4 family members with a balanced translocation 9;21 and 2 members with an unbalanced translocation resulting in trisomy of the short (p) arm and part of the long (q) arm of chromosome 9. These latter 2 subjects had 3 copies of the IFN gene cluster.

Methods

Subjects were evaluated clinically and serologically for autoimmune disease. Expression levels of IFNα4, IFNβ, the type I IFN–inducible gene Mx1, the type I IFN receptor, interleukin‐6, and tumor necrosis factor α were determined by real‐time polymerase chain reaction. Circulating plasmacytoid dendritic cells, the main IFN‐producing cells, were quantified by flow cytometry.

Results

Both subjects with trisomy of chromosome 9p had a lupus‐like syndrome with joint manifestations and antinuclear antibodies: one had anti‐RNP and antiphospholipid autoantibodies, and the other had anti–Ro 60. The 3 family members with a balanced translocation 9;21 had no clinical or serologic evidence of autoimmunity, similar to that in relatives who were unaffected by the chromosomal translocation. In the 2 subjects with trisomy of 9p, high levels of IFNα/β (comparable with those found in patients with SLE), increased signaling through the IFN receptor (as indicated by high Mx1 expression), and low levels of circulating plasmacytoid dendritic cells (as observed in patients with SLE) were evident. These abnormalities were not seen in individuals with a balanced translocation.

Conclusion

Trisomy of the type I IFN cluster of chromosome 9p was associated with lupus‐like autoimmunity and increased IFNα/β and IFN receptor signaling. The data support the idea that abnormal regulation of type I IFN production is involved in the pathogenesis of SLE.

     

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.     

Wearing the F-Scan mobile in-shoe pressure measurement system alters gait characteristics during running

This study investigated the influence of wearing an F-Scan mobile in-shoe pressure measurement system on running characteristics. Six subjects ran on a treadmill at three speeds (3.5 ms(-1), 4.5 ms(-1) and 5.4 ms(-1)) with and without wearing the F-Scan system while kinematic data were collected at 240 Hz using a motion capture system. Six gait cycles were selected for analysis, with touchdown and toe-off visually identified based on foot markers displacement. Spatio-temporal gait parameters including stride frequency, stride length, stride length relative to height, and stance time were determined. A 2x3 ANOVA with repeated measures (alpha=0.05) was performed to identify differences in each gait parameter between running with and without the F-Scan system at different speeds. Wearing the F-Scan system did not affect the stance time but lead to an increase in stride frequency (P<0.05) and a decrease in stride length (P<0.05) and relative stride length (P<0.05). As speed increased, stance time decreased while stride frequency, stride length and relative stride length increased (all P<0.001). These results imply that wearing the F-Scan system alters gait characteristics and therefore data obtained may not represent those in a real life setting, at least in the case of running. One should take into account the potential risk of the movement of interest being altered when interpreting data obtained while subjects were wearing the F-Scan system. Future instrumentation should minimize the potential influence a measurement device may have on natural movement.     

Neck-shoulder muscle activity in general and task-specific resting postures of symptomatic computer users with chronic neck pain

Past research on work-related musculoskeletal disorders (WMSD) has frequently examined the activity of neck-shoulder muscles such as upper trapezius (UT) and cervical erector spinae (CES) during typing tasks. Increased electromyographic activity in these postural stabilising muscles has been consistently found in chronic neck pain patients under different physically stressful conditions. The present study compared muscle activity when female office workers with chronic neck pain (n=39) and asymptomatic controls (n=34) adopted two resting postures: (1) with hands on laps versus; and (2) hands on a keyboard. Resting hands on keyboard elicited significantly increased muscle activity in the right UT of subjects with high discomforts (n=22), similar to that observed during actual typing. In contrast, the asymptomatic controls showed no difference in muscle activity between the resting postures. This result suggested that altered muscle activation patterns were triggered by some anticipatory task demand associated with a task-specific position in some individuals.     

乳腺不典型增生组织中H—ras基因突变的检测

目的：探讨H-ras基因在乳腺癌发生早期的作用。方法：用PCR-RFLP和PCR-SSCP方法检测30例乳腺癌、36例单纯性增生、31例不典型增生组织中H-ras基因第12密码子的突变,用免疫组化技术检测乳腺癌和乳腺增生病组织中H-ras蛋白的表达。结果：73.3%的乳腺癌和48.4%的乳腺导管不典型增生组织有H-ras蛋白表达,单纯性增生上皮中无表达,所检测的增生病和乳腺组织中均未见到H-ras基因第12密码子突变。结论：H-ras蛋白过表达出现于乳腺癌发生的早期阶段,但这种过表达与H-ras基因第12密码子突变无关。     

A meta-analysis of anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer

Fulvestrant is a highly active systemic therapy in patients with metastatic hormone receptor positive breast cancer. Preclinical work suggested potential synergy of fulvestrant in combination with aromatase inhibitor therapy and delayed development of endocrine resistance. The purpose of this meta-analysis is to evaluate the effectiveness of fulvestrant plus anastrozole, compared to anastrozole alone, as first line treatment of postmenopausal stage IV hormone receptor positive, HER2-negative breast cancer. The literature search was performed using PubMed, Google Scholar, Embase, ASCO, and ESMO to search for abstracts published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of anastrozole plus fulvestrant versus anastrozole alone. Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95 % prediction intervals (PIs) for study-specific hazard and odds ratios. Pooled hazard ratio for progression-free survival is 0.88 (95 % CI 0.72–1.09, 95 % PI 0.65–1.21), overall survival 0.88 (95 % CI 0.72–1.08, 95 % PI 0.68–1.14) and pooled odds ratio for response rate is 1.13 (95 % CI 0.79–1.63, 95 % PI 0.78–1.65). A non-significant trend was observed with anastrozole plus fulvestrant being only marginally better than anastrozole alone in the endpoints of: progression-free survival, overall survival, and response rates. Based on these data, there is not solid evidence that the addition of fulvestrant at a dose of 250 mg monthly is better than anastrozole alone as first line therapy in women with postmenopausal hormone receptor positive breast cancer.