The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality', the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50-59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies.
This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments.
Occasionally, a dog-bite is complicated by a systemic overwhelming infection. We report four consecutive patients who were admitted to our intensive care unit because of sepsis syndrome following dog-bites. The history of these patients did not reveal any immunocompromising conditions. Capnocytophaga canimorsus (C. canimorsus) was cultured from the blood culture of 2 patients. Our data illustrate that in patients with lack of immune-deficiency severe sepsis may develop.
#6052 Introduction: The combination of Computed Tomography (CT) and [18F] Fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) scanning technologies provides a more complete picture of disease activity than CT alone. Circulating tumor cell (CTC) levels were shown to be more predictive than standard imaging (CT) when used to monitor disease progression in women with metastatic breast cancer (MBC). We performed a retrospective study to compare the ability of combined FDG-PET/CT to CTC to predict clinical outcomes in patients treated for MBC.
 Methods: One hundred and two MBC patients with either measurable or evaluable disease starting a new line of therapy had CTC counts and FDG-PET/CT scans done at baseline (BL) and at mid-therapy. CTC: 7.5mL of blood collected in CellSave tubes at both time points was assayed for CTC using the FDA approved CellSearch® System. Patients were categorized as having a favorable (<5CTC) or unfavorable (≥5CTC) outcome. Imaging: non-contrast-enhanced CT images were acquired first, then FDG-PET/CT scans were performed after administering a mean dose of 555 MBq FDG (range 444-740 MBq) to fasting patients. CT, PET, and co-registered CT-PET images were reviewed independently by 2 radiologists. The highest recorded FDG uptake was semi-quantitatively analyzed and maximum standardized uptake value (SUV) calculated with response = SUV of <50% in target lesions and no response = SUV of >50%. Changes in CTC and SUV at mid-therapy were compared to progression free survival (PFS) and overall survival (OS).
 Results: CTC: 50% (51/102) patients had ≥5 CTC at baseline (BL). At mid-therapy (median 2.5 months from BL), 21/102 progressed (≥5CTC) with a median PFS of 2.8 months vs. 7.8 months for those with no progression (<5CTC) (p<0.0001). OS was 10.0 months for patients with ≥5CTC at mid-therapy vs. 29.6 months for those with <5CTC (p<0.0001). PET/CT: 48% (49/102) patients showed no response at mid-therapy with median OS = 17.4 months vs. 29.6 months for those responding (p=0.0020). Overall, there was approximately 75% concordance in predicting outcomes between imaging and CTC assay changes [Table 1]. The majority of patients with discordant results had more advanced aggressive disease, i.e., >2nd line chemotherapy and triple-negative disease.
 
 Conclusion: ≥5 CTC and/or no response at FDG-PET/CT at mid-therapy accurately predicted significantly shorter OS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6052.
BackgroundAnkle-brachial blood pressure index (ABI) is a noninvasive indicator of peripheral arterial diseases (PAD) in older individuals, but information in this regard in young adults is limited. This study examined the limitation of ABI for diagnosis of PAD in asymptomatic young and middle-age adults.MethodsABI was measured by dividing ankle systolic blood pressure by brachial systolic blood pressure obtained from a Collin machine in 867 black and white subjects (aged 24-44 years; 72% white, 44% male) enrolled in the Bogalusa Heart Study. Individuals in the bottom (ABI # 0.99; n = 44) versus top 5th (ABI $ 1.27; n = 50) percentile distribution of ABI were compared for traditional cardiovascular (CV) risk factors profile. Univariate analysis compared the two groups; t-tests and chi-square tests were performed.ResultsThere were only 6 (0.7%) individuals having clinically cut point ABI of # 0.9. Females, especially black females, had lower ABI than males (p < .0001). Blacks had lower ABI compared to whites (p < .0001). The bottom versus top 5th percentiles of ABI did not differ significantly with respect to age, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, non-HDL cholesterol, HDL cholesterol, triglycerides, glucose, insulin, cigarette smoking status, and femoral and carotid intima-media thickness (IMT). In terms of prevalence of clinically defined traditional risk factors, individuals at the bottom vs top 5th percentile of ABI distribution had not had significantly higher prevalence of high LDL cholesterol, non-HDL cholesterol, triglycerides, low HDL cholesterol, high blood sugar, and high blood pressure. Further, these individuals had not had significantly higher prevalence of high BMI, waist circumference, femoral IMT, abnormal ECG, and higher smoking status. Subjects with ABI # 0.99 did not display significantly higher prevalence of multiple risk factors compared to ABI $ 1.27.ConclusionsThe prevalence of abnormal ABI in this population is extremely low because of the relatively younger study population. The lack of association of traditionally cardiovascular risk factors with the lower ABI indicates that using ABI as a screening tool for diagnosis of PAD is not useful and cost-effective in younger and middle-age adults.
A 42-year-old man presented to his primary care provider office with symptoms of upper respiratory tract infection and episodic dull chest pain for 3 days. Chest pain was located over anterior precordium and retrosternum, increased in intensity with inspiration and body movement. On examination his vitals were stable except for pulse of 115 beats per minute. Physical examination was otherwise unremarkable. Electrocardiogram performed in the office revealed diffuse ST-segment elevation of 1-2 mm and diffuse PR-segment depression. Portable chest x-ray was unremarkable without mediastinal widening. He was diagnosed with acute pericarditis. However due to suspicion of acute coronary syndrome he was referred to emergency room for possible admission to coronary care unit for observation. In the emergency room on re-examination he is alert but uncomfortable. Blood pressure was 140/82 mm Hg in all extremities; pulse was 103 beats per minute and regular. His chest is clear and careful cardiac examination revealed a 2/6 early diastolic murmur in aortic region. First set of cardiac enzymes was negative. Repeat ECG was similar to previous one. Incidentally ordered CT scan of chest was reported as Stanford Type-A thoracic dissection. He was immediately started on IV labetolol drip and admitted to intensive care unit. Emergent cardiothoracic surgery consultation was placed. Patient successfully underwent aortic repair without complication. Thoracic aortic dissection is a life-threatening condition associated with high rates of morbidity and mortality. It is the most common acute aortic condition requiring emergent surgical therapy. The incidence of aortic dissection has been estimated at from 5 to 30 per 1 million people per year. Dissection is a dynamic process that can occur anywhere within the aorta and is characterized by separation of the layers within the aortic wall.Thoracic aortic dissection has long been known to mimic multitude of clinical conditions. It is usually associated with severe chest pain and or back pain and is the most frequent fatal condition in the spectrum of chest pain syndromes. We present a young patient with cystic medial necrosis who presented with atypical clinical symptoms and ascending thoracic aortic dissection was diagnosed by CT imaging. Patients with cystic medial necrosis and aortic dissection may not present with a classic acute chest pain syndrome. Due to variable clinical presentation, dissection of thoracic aorta can be a diagnostic challenge for physicians. Therefore a high clinical index of suspicion is necessary.
A 22 year old African immigrant female student who is otherwise well and fit was incidentally found to have an elevated blood pressure during a physical examination for evaluation of headache. She denied frequent use of over the counter medication, intravenous drug or recreation drug use. There is no family history of HTN, diabetes, coronary artery disease, sudden cardiac death, polycystic kidney disease or other polyglandular autoimmune endocrine disease. On initial examination blood pressure was 190/90 mm Hg in both upper extremities. On fundoscopic examination there was no papilledema; the rest of the examination was otherwise unremarkable. ECG and C-x-ray was essentially unremarkable. A cardiology consultation was placed; on reassessment, there was ejection click over aortic area, a continuous harsh murmur over interscapular space and radio-femoral delay of the pulse. Doppler echocardiography showed a bicuspid aortic valve with mild aortic regurgitation. Head CT was negative for aneurysm or bleeding. Careful review of the frontal chest radiographs revealed rib notching along the inferior aspect of the third to the eighth ribs. Diagnosis of aortic coarctation was suspected and a spiral CT of the thoracic aorta with three-dimensional reconstruction confirmed postductal coarctation. A cardiothoracic surgery consultation was obtained and the patient underwent successful repair. Coarctation of the aorta is an acyanotic congenital heart disease. Most patients are identified accidentally during routine medical examination. Coarctation accounts for approximately 5% of all congenital heart diseases. Coarctation is a discrete infolding of the posteriolateral wall of the aorta, which results in an obstructing membrane at the level of the ductus arteriosus. There are several classifications of the coarctation; it is most commonly classified into adult (postductal) type and infantile (preductal) type. However, many patients with preductal lesions do not present until adulthood. The age of the patient at presentation is dependent on the severity rather than the site of obstruction. Usually those with severe obstruction or associated cardiac anomalies present early, as a result of cardiac failure or occasionally cerebrovascular accident, aortic dissection, or endocarditis. 25-50% of patients will also have a bicuspid aortic valve. Patent ductus arteriosus, ventricular septal defects and Turner syndrome are other common associations with aortic coarctation. This case emphasizes the importance of a careful history and physical examination, which remain the cornerstones of diagnosis of coarctation.
Background Transforming growth factor (TGF)-b1 has pleiotropic effects in cancer. In the early stages of breast cancer, TGF-b may be responsible for immune tolerance through the activation of T-Regulatory cells (TR). On the other hand, in the late stages of disease, it may induce angiogenic factors [vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) (in Bonnomet J Mammary Gland Biol Neoplasia 2010); and IL-17 (Pickens J Immunol 2010)], and epithelial to mesenchymal transition (EMT) which may lead to an increase in the number of circulating tumor cells (CTC) (Kim, Cell 2009). Therefore, we investigated the possible correlation between TGF-b1, CTC count, angiogenic factors and T-cell function of patients with locally advanced or metastatic breast cancer. Methods As an interim analysis of an on-going prospective study, sera and peripheral blood mononuclear cells (PBMC) were collected from breast cancer patients starting a new line of therapy. At analysis, study enrollment included 78 patients with breast cancer [19 with locally advance disease (LABC), 23 with non-metastatic inflammatory breast cancer (IBC), and 32 with metastatic disease (MBC) including 19 with IBC features], and 28 healthy donors (HD). Serum TGF-b1, VEGF, and IL-8 levels were measured by Milliplex Luminex kits (Millipore, Billerica, MA). CD4+CD25+CD127dim TR cells were enumerated in whole blood by FACS (BD Biosciences, San Jose, CA). PBMC were used to study the ability of T cells to synthesize cytokines following activation of the T-cell receptor by immobilized anti-CD3 antibodies. CTC were enumerated by CellSearch (Veridex, Raritan, NJ). The Spearman Rho was calculated for nonparametric correlations and the Mann-Whitney U test was used to determine significant differences between median values. Results LABC patients and HD had a median serum TGF-b1 that was significantly higher than that of MBC patients (P = 0.042). There were statistically significantly positive correlations between serum TGF-b1 and the number of CD4+ T cells (rho = .226, P = .029) and IL-10 produced by %CD4+ (rho = .388, P = .002) and %CD8+ (rho = .459, P < .001) T cells. Furthermore, there was a positive correlation between serum TGF-b1 and the % of CD8+, but not CD4+, T cells that produced IL-17 (rho = .250, P = .022). Serum TGF-b1 levels did not correlate with either % or number of TR cells. Although serum TGF-b1 level of MBC patients was independent of CTCs (24.4 ng/mL vs. 24.0 ng/mL, P = .317), MBC patients with CTC had significantly higher serum levels of angiogenic factors such as VEGF (530 ng/mL vs. 240 ng/mL, P=0.037) and IL-8 (45.6 pg/ml vs. 20.0 pg/ml P= .006) than those of patients with no CTC. Even so, MBC patients with or without CTC have similar % of CD4 and CD8 T-cell subsets that could be activated to produce IFN-g, IL-2, TNF-a, IL-17, or IL-10. Conclusion: The concomitant presence of elevated serum TGF-ß1 levels and IL-10 producing T cells suggest immune suppression could facilitate disease progression of breast cancer. T-cell function is independent of CTC in MBC patients; however, serum VEGF and IL-8 levels were significantly elevated in MBC patients with CTC suggesting that vascular changes can facilitate tumor dissemination. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-07.
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