Molecular markers in prognosis of colorectal cancer and prediction of response to treatment

Colorectal cancer is the third most common human malignancy. Direct observation and biopsy sampling by colonoscopy have provided unique opportunities to study the natural history of the disease. As a consequence, advances in the understanding of colorectal cancer pathogenesis have evolved more rapidly than with most other solid tumours. Numerous molecular events arising during the development of colorectal cancer have been sorted out over the past two decades. Despite these advances, predicting outcome and response to therapy is still a major challenge in the management of patients with colorectal cancer. Molecular and biochemical markers of colorectal cancer are greatly needed for diagnosis and prognosis as well as for the selection and monitoring of treatments. The purpose of this chapter is to provide a critical assessment of the usefulness of markers in the prognosis and prediction of response to treatment in colorectal cancer.     

Assessment of oxidative metabolism in adults with hepatocellular carcinoma in the Sudan.

The hypothesis that an increased rate of oxidative metabolism may be an initiator or promoter of hepatocellular carcinoma was tested in vivo. Elimination of antipyrine (phenazone) was used as an index of the activity of microsomal mixed function oxidative enzymes. Plasma antipyrine kinetics were examined in 10 patients with hepatocellular carcinoma and in 10 normal Sudanese adults. The half life, volume of distribution and clearance of antipyrine in patients were 18.8 +/- 7.9 hours (mean +/- SD), 33.8 +/- 7.7 litres and 23.7 +/- 10.1 ml/min, respectively; and in normal adults were 20.3 +/- 8.8 hours, 40.1 +/- 10.4 litres and 25.7 +/- 12.0 ml/min, respectively. These differences were not significant. Antipyrine plasma clearance when corrected for weight was similar in the two groups. This study suggests that in a population at risk for hepatocellular carcinoma, the overall activity of mixed function oxidative enzymes is not an important determinant in selectively increasing this risk.     

Pulse wave analysis of the aortic pressure waveform in patients with vasovagal syncope

Vascular reflex mechanisms contribute to vasovagal syncope. However, the alterations in central haemodynamics in patients with vasovagal syncope are unknown. 30 consecutive patients (36.5 ± 15 years, 14 females) with recurrent vasovagal syncope (VVS) and a positive tilt table test were compared to 39 age- and sex-matched controls (36.9 ± 16 years, 15 females) with a negative tilt table result and no history of syncope. Central aortic pressure parameters including augmentation index and central pulse pressure as markers of aortic stiffness were generated non-invasively by applanation tonometry of the radial artery and use of a validated mathematical transfer function. No difference in aortic augmentation index was observed between groups. (VVS 9 ± 2.6 vs. Control 11 ± 2.4, p = 0.8). However, in patients with vasovagal syncope the aortic pressure waveform significantly differed from healthy controls. A prolonged time to the peak of aortic pressure wave (aortic T2) was observed in patients with vasovagal syncope (226 ± 24 vs. 208 ± 21 ms, p = 0.001). Furthermore time to the first shoulder of the aortic pressure wave (aortic T1) was slightly shorter compared to healthy controls, but did not reach statistical significance (106 ± 22 vs. 110 ± 12 ms, p = 0.33). Patients with vasovagal syncope have an altered aortic pressure waveform at rest, but no signs of elevated aortic stiffness. The underlying mechanisms for these findings may potentially result from a complex imbalance of the autonomic nervous system with a continuous deregulation of the sympathetic and parasympathetic reflex arcs.     

Methodology to develop a geometric modeling process according to collaborative constraints

A product design goes through a Digital Mock-Up which is based on the product geometric model. This latter has an important role in the design project whose exploitation mainly depends on how it has been established (DELPHI Automotive Systems, Delphi met á plat ses arborescences, CADReport no. 192, février, 2004). Furthermore, the growing competitive context hardly encourages firms to implement new working methods like collaborative engineering. However, its implementation in combination with product geometric data generates many problems in terms of project and data management. For this purpose, this article proposes a methodological solution to the problem at hand. Moreover the problem gets complicated as the project progresses. As a result, the detailed design phase becomes critical particularly in the face of this problem. Therefore, the current article focuses on this phase of the product design process through an example.     

The effect of orlistat-induced weight loss on interleukin-6 and C-reactive protein levels in obese subjects

OBJECTIVE: Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients. METHODS AND RESULTS: Thirty-six obese (BMI: 36.1 +/- 3.4 kg/m2) and II non-obese (BMI: 22.9 +/- 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels. CONCLUSION: In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistat-induced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.     

The diabetes-obesity-hypertension nexus in Qatar: evidence from the World Health Survey

Background

As countries develop economically, an “epidemiological transition” occurs whereby a set of chronic diseases increasingly becomes a country’s health challenge. Against this background, this paper examines the most common conditions associated with the prevalence of diabetes in Qatar, with a specific focus on the diabetes-obesity-hypertension nexus.

Methods

We analyzed data from the World Health Organization’s World Health Survey conducted in the State of Qatar in 2006. The survey included demographic, anthropometric, and blood chemistry measurements. Using multivariate logistical regression analysis, we assessed the most common conditions associated with diabetes, using both objective and subjective measures of diabetes. The objective measures relied on random blood sugar tests, and the subjective measure included respondents who affirmatively answered the question on diabetes diagnosis. We repeated our analysis on respondents who had blood glucose levels high enough to be considered diabetic/glucose intolerant but did not answer affirmatively on the question of diabetes diagnosis.

Results

When using the objective measure of diabetes, the following conditions appeared significant: obesity (OR?=?1.5, 95% CI?=?1.2 – 1.9), higher income (OR?=?1.4, 95% CI?=?1.0 – 1.9), high cholesterol (OR?=?1.4, 95% CI?=?1.0 – 1.9), having Qatari origin (OR?=?1.3, 95% CI?=?1.0 – 1.7), and increasing systolic blood pressure (SBP) 120–139 mmHg (OR?=?1.5, 95% CI?=?1.2 – 2.0), SBP 140–159 mmHg (OR?=?2.2, 95% CI?=?1.6 – 3.1), SBP?>?160 mmHg (OR?=?3.2, 95% CI?=?2.0 – 5.3). Similar results were obtained using the subjective measure of diabetes as a dependent variable. When applied to the group of respondents that included pre-diabetics and those who did not know they were diabetic, obesity and hypertension appeared as the only statistically significant explanatory variables.

Conclusion

High prevalence of diabetes, hypertension, and especially obesity is documented among residents of Qatar. Further steps are required to tackle the most common conditions associated with the rising diabetes epidemic in the country, which might also pose significant fiscal challenges in the future.