A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.     

Thirteen year experience with aortic valve replacement

Two hundred forty-one patients (163 male, 78 female) underwent isolated aortic valve replacement at the Medical College of Georgia from 1963 to 1976. The mean age was 46 years (range 12 to 72). Thirty-seven percent had aortic stenosis, 39 percent aortic regurgitation and 24 percent mixed valve lesions. One hundred ninety-eight were in New York Heart Association functional class III or IV. Forty-three were in functional class I or II and underwent surgery for endocarditis, severe regurgitation with rapidly increasing heart size or appearance of angina or electrocardiographic signs of ischemia.     

Assessment of myocardial contractility in children and young adults from ventricular pressure recordings

The index V_pm (the actual or physiologic maximal shortening velocity of the contractile element) has been obtained from the analysis of left ventricular pressure recordings and then applied to the assessment of myocardial contractility in man. Pressures during the isovolumic period of ventricular systole were recorded during routine catheterization of 46 patients with a variety of cardiac lesions. The quantity V_pm, that is (dp/dt/kp)_max, was compared with the hemodynamic evaluation of each patient based on the left ventricular end-diastolic pressure, ejection fraction and left ventricular end-diastolic volume. V_pm was selected for this study since it appeared to be largely independent of load and does not require biplane angiocardiography and extrapolation analyses.     

Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators

INTRODUCTION: Ventricular oversensing (OS) of respirophasic noise transients may cause spurious detections and therapies and pacing inhibition among patients with implantable cardioverter defibrillators (ICDs). The incidence of OS and its relationship to clinical variables and ICD system design are unknown. METHODS AND RESULTS: Three hundred twenty-nine patients performed provocative respiratory maneuvers at rest during intrinsic rhythm and continuous ventricular pacing. OS resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329 patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise transients not recognized and marked as sensed events, but visually evident on the local endocardial ventricular electrogram, were provoked in an additional 23 (7.0%) of 329 patients. Multivariate logistic regression identified history of spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to 50.0), automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to 10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25), and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of provocable OS. Spontaneous OS resulting in spurious ventricular detections and therapies occurred in 12 (3.6%) patients during follow-up. Eleven of 12 spontaneous episodes occurred in male patients during ventricular pacing; 11 of 12 patients had automatic gain control devices and integrated bipolar leads. CONCLUSION: OS is commonly provoked in ICD patients during ventricular pacing and may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing inhibition. Differences in the incidence of spontaneous and provoked OS between ICD systems can be explained on the basis of unique features of automatic sensing systems and sensing lead design.     

Lack of association between skin tags and colon polyps in a primary care setting

Cutaneous skin tags (acrochordons) have recently been proposed as markers for adenomatous polyps of the colon among symptomatic patients referred for colonoscopy. To ascertain the utility of skin tags as a predictor of colonic polyps in a primary care setting, 492 patients, with a mean age of 58 +/- 13.3 years (241 with signs or symptoms and 251 for screening), were evaluated for the presence of skin tags and then examined using a 60-cm fiberoptic sigmoidoscope by an examiner "blinded" to the skin findings. Among patients with skin tags, 23 (10.2%) of 226 had polyps, whereas among patients without skin tags, 20 (7.5%) of 266 had polyps. The predictive value of the presence of a skin tag was 10.2%. Contrary to studies done in more selected populations with a higher prevalence of adenomatous polyps, the results using a 60-cm flexible sigmoidoscope in a primary care population suggest that cutaneous skin tags are not a marker for adenomatous polyps of the colon.     

Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.     

What evidence is there that adjustment for adult height influences the relationship between birth weight and blood pressure?

Background: The inverse association between birth weight and blood pressure may partly be the result of inappropriate adjustment for adult body size, but it remains unclear whether adjustment for adult height elicits this effect.

Aim: The study investigated the impact of adjustment for adult height on the relationship between birth weight and blood pressure.

Methods: A systematic search of Medline® from 1996 to 2006 was conducted using the terms ‘birth weight’, ‘blood pressure’ and ‘hypertension’, and any papers containing linear regression analyses of blood pressure on birth weight for populations with an average age of 25+ were eligible for inclusion in comparative meta-analyses.

Results: None of the 30 studies identified had published regression coefficients for blood pressure on birth weight before and after adjustment for adult height, and only two studies were found to adjust for adult height at all. Data from these studies were obtained, and it was found that adjustment for height made the association between birth weight and systolic blood pressure (SBP) more negative in one study but less negative in the other. When compared with meta-analyses of comparable models, it was found that both studies were substantially different from the combined estimate of the relationship between birth weight and SBP.

Conclusions: Both the differences between the two selected studies and their differences from the combined estimates obtained by meta-analysis are likely to be due to differences in the age of the participants. The relationship between birth weight and SBP tended to become more strongly inverse in studies with older participants. Additionally, the correlations between height and SBP were found to change from positive to negative with increasing age, which explained the differential impact of adjustment for height in the two selected studies. It therefore appears that adjustment for height may have little effect for older participants, but more so for younger participants.