Citations

Abstract To determine if bone cells produce interleukin-1β (IL-1β), a potent bone resorption-stimulating agent, we studied well-characterized, nearly homogeneous cultures of normal human osteoblast-like (hOB) cells. With four strains of such cells, vehicle-treated cultures produced minimal IL-1β (mean ± SEM, 1.3 ± 0.3 pg/ml per 106 cells per 24 h) and showed dose-dependent (r = 0.99) increases to 2.2 ± 0.7, 5.0 ± 0.9, or 17.8 ± 6.7 pg/ml, respectively, after treatment with lipopolysaccharide (LPS) at 3, 10, or 30 μg/ml (for increases after 10 and 30 μg/ml treatments, P < 0.05). After treatment with tumor necrosis factor α (TNF-α at 10 U/ ml, IL-1β increased to 16.2 * 3.7 pg/ml (P < 0.05). Neither 17β-estradiol nor bovine parathyroid hormone(1–34) (each at 10 nM), alone or in combination with LPS or TNF-α, affected IL-1β release. Northern blot analysis of total cellular RNA preparation revealed a single hybridization band at 1.9 kb when probed with a partially deleted cDNA for human IL-1β. The steady-state IL-1β mRNA levels showed a significant increase with LPS treatment and a lesser increase with TNF-α treatment in hOB cells. Moreover, TNF-α produced an even greater increase in IL-1 mRNA in HOBIT cells, a well-differentiated clonal cell line derived from normal hOB cells transfected with the SV40 large T antigen. We conclude that human cells of the osteoblast lineage produce IL-Iβ in response to well-recognized stimuli for IL-1 release from responsive tissue. Therefore, IL-1 may play an important role in the local regulation of bone remodeling.

Abstract A quality control (QC) program for bone mineral measurements at the proximal femur by dual-energy x-ray absorptiometry (DXA) was designed for the osteoporosis component of the Third National Health and Nutrition Examination Survey (NHANES III). Major elements of the QC program are (1) a QC center for review of all scans, (2) setup procedures for and continuous monitoring of daily QC procedures, (3) reference standards for cross-calibration, (4) longitudinal studies for assessment of instrument stability, (5) monitoring of technologist performance, and (6) training. This report describes the results of the QC program of the first half of this 6 year study, which began in 1988. Measurements were performed on 7376 subjects in three mobile examination centers, which traveled to a new location about every 3 months, a total of 44 locations. A small percentage (3.5%) of all scans were rejected, mostly because of patient motion during scanning, but 33% of the remaining scans required reanalysis at the QC center to refine the location of the regions of interest. Precision in spine and hip phantoms was below 1% at all ROIs. In 535 subjects with duplicate scans, age 20–91 of both sexes, examined in a blinded review, precision for BMD at the femur neck ROI was 3.2% (CV) and 5.1% for Ward's triangle BMD. The central review improved scan quality, increased the number of usable scans, and reduced significantly the range of the mean percentage difference in the duplicate scans. Minor alterations in machine function were observed and corrected. QC results on phantoms were similar to those obtained with stationary instruments in dedicated laboratories. Retrospective analysis of the regression slopes from QC records did not show a need for correction of the data base, indicating that the instruments were stable during the course of the study.

Abstract Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988–1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20–29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34–50% in four different femur regions, which corresponds to ∼12–17 million women. The prevalence with osteoporosis (BMD >2.5 SD below the mean of young NHW women) ranged from 17–20%, or ∼6–7 million women. Prevalences were 1.3–2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8–1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10–15 million, 800,000–1.2 million, and 300,000–400,000, respectively; corresponding figures for osteoporosis were 5–6 million, 200,000–300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD. The majority of these women are white, but the number of minority women with low BMD is not trivial.

Bilateral oophorectomy at the time of hysterectomy for benign disease is commonly practiced in order to prevent the subsequent development of ovarian cancer or other ovarian pathology that might require additional surgery. At present, bilateral oophorectomy is performed in 78% of women aged between 45 and 64 years having a hysterectomy, and a total of approximately 300,000 prophylactic oophorectomies are performed in the USA every year. Estrogen deficiency resulting from pre- and post-menopausal oophorectomies has been associated with higher risks of coronary heart disease, stroke, hip fracture, Parkinsonism, dementia, cognitive impairment, depression and anxiety in many studies. While ovarian cancer accounts for 14,800 deaths per year in the USA, coronary heart disease accounts for 350,000 deaths per year. In addition, 100,000 cases of dementia may be attributable annually to prior bilateral oophorectomy. At present, observational studies suggest that bilateral oophorectomy may do more harm than good. In women who are not at high risk of developing ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution.

Background The American College of Cardiology released a scientific advisory that included a recommendation to delay elective of noncardiac surgery (NCS) for 1 yr after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods This single-center, retrospective study examined the risk for complications of NCS performed within 2 yr after DES placement and examined whether this risk changed based on the time between procedures. The primary endpoint was major adverse cardiac events (MACEs) during the hospitalization for NCS. Bleeding events were analyzed as a secondary endpoint. Results From April 22, 2003, to December 31, 2006, a total of 520 patients underwent NCS within 2 yr after PCI with a DES at Mayo Clinic. The majority, 84%, of the DES placed were Cypher stents. The frequency of MACE was not found to be significantly associated with the time between PCI and NCS (rate of MACEs 6.4, 5.7, 5.9, and 3.3% at 0-90, 91-180, 181-365, and 366-730 days after PCI with DES, respectively; P = 0.727 for comparison across groups). Characteristics found to be associated with MACEs in univariate analysis were advanced age (P = 0.031), emergent NCS (P = 0.006), shock at time of PCI (P = 0.035), previous history of myocardial infarction (P = 0.046), and continuation of a thienopyridine (ticlopidine or clopidogrel) into the preoperative period (P = 0.040). The rate of transfusion did not seem to be associated with antiplatelet therapy use. Conclusions The risk of MACEs with NCS after DES placement was not significantly associated with time from stenting to surgery, but observed rates of MACEs were lowest after 1 yr.

Background The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. Methods This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. Results From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. Conclusions The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS.

Abstract Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (103–109 TCID50). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54–277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3–38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients. Cancer Res; 70(3); 875–82