Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid—an Experimental Study

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20?±?0.12 vs 1.17?±?0.78,p?=?0.29), while AV calcification progressed in the placebo group (1.22?±?0.15 vs 1.53?±?0.23,p?=?0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.     

Pectoralis major transfer for the treatment of irreparable anterosuperior rotator cuff tears

The purpose of this study was to evaluate the outcome of subcoracoid pectoralis major transfer for the treatment of irreparable anterosuperior rotator cuff tears. This type of tear involves complete rupture of the subscapularis in combination with either the supraspinatus alone or the supraspinatus and infraspinatus. These ruptures are characterised by a poor quality of the rotator cuff that does not allow for a direct tendon-to-bone reconstruction. Between 2000 and 2006, 15 patients were treated using a deltopectoral approach and transfer of the clavicular part of the pectoralis major to the lesser tuberosity and to the anterior part of the greater tuberosity. After an average follow-up (follow-up rate 100%) of 37 months the average functional rating using the Constant and Murley score (CS) increased from 51.73 ± 16.18 to 68.17 ± 8.84 points (p = 0.005). The mean subcategories of the Constant score for pain (p = 0.005), activities of daily living (p = 0.008) but not for range of motion (p = 0.9), significantly improved. At follow-up 13 patients (87%) were available for magnetic resonance imaging (MRI) of the shoulder. Nine patients (70%) had an intact transferred pectoralis major muscle, two (15%) had one that was thin but intact and two patients a rupture (one complete). Two patients had postoperative haematoma and one patient developed cuff tear arthropathy. The good results confirm that pectoralis major transfer is a reliable treatment option for irreparable anterosuperior rotator cuff injuries with significant improvement in pain and function.     

Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies

BACKGROUND: Obesity is a major risk factor for breast cancer. We hypothesized that obesity-induced decreases in total and/or high-molecular-weight (HMW) adiponectin levels may underlie this association. METHODS: We measured serum total and HMW adiponectin in a hospital-based case-control study of 74 female breast cancer patients and 76 controls. In parallel, expression of adiponectin and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and protein expression of AdipoR1/R2 was localized and quantified using immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several breast cancer cell lines and studied adiponectin signaling and the effect of adiponectin on proliferation in the T47D breast cancer cell line in vitro. RESULTS: Women with the highest adiponectin levels had a 65% reduced risk of breast cancer (P = 0.04). This association became stronger after adjustment for age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling HMW instead of total adiponectin produced similar results and did not offer any additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue than both adjacent and control tissues. Exposure of T47D cells to adiponectin significantly inhibited the percentage of viable cells to 86% and proliferation to 66% but had no effect on apoptosis. These effects were associated with activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK. CONCLUSION: These studies suggest that adiponectin may act as a biomarker of carcinogenesis and may constitute a molecular link between obesity and breast cancer.     

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

OBJECTIVE: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). DESIGN: Hospital-based case-control study. METHODS: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. RESULTS: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. CONCLUSIONS: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.     

Quality of life in endometrial cancer survivors

Objective: The aim of this study was to evaluate the health-related quality of life in survivors of endometrial cancer (EC), and to identify common problems that they may encounter, in the hope of paving the way to improving their quality of life. Study design: We investigated and compared the health conditions and quality of life between EC survivors and the general population as a control group. There were 61 EC patients who were at clinical stage I–III and survived for 5–7 years after the primary treatments. The control group was composed of 527 healthy postmenopausal women. All of them completed a self-evaluated questionnaire pertaining to personal conditions, medical surveillance, individual well-being and quality of life. Results: The EC survivors were divided into two groups: an older group (n=34) and a younger group (n=27). The latter was compared with the controls. In general, most of the EC survivors were old, low-educated women. The majority of them were in a poor condition. They were inactive, received medical surveillance and had regular medication. The distribution of various complications was higher in the older EC group while the climacteric symptoms were more common in the younger EC group. In both EC groups, the quality of life was lower than in the controls. The prevalence of somatic symptoms was higher in the older EC survivors and psychological problems were a common complaint of the younger EC survivors. Conclusion: The quality of life was poor in the EC survivors. To improve their life quality, earlier psychological counseling should be offered to EC survivors, in particular to younger and single women, and hormone replacement therapy (HRT) should be recommended, but on a selective basis, to those patients at low risk of cancer recurrence.