Using a combination of cytochrome P450 1B1 and β-catenin for early diagnosis and prevention of colorectal cancer

Background: Although fecal occult blood test and invasive endoscopic examination are common used to detect colorectal adenomas and cancers, non-invasive and specific biomarkers are still under investigation. The objective is to evaluate the biomarker CYP1B1 alone or in combination with aryl hydrocarbon receptor (AhR), nuclear β-catenin, p53 or bcl-2 for early diagnosis and prevention of colorectal cancer. Methods: These biomarkers were analyzed semi-quantified across 231 colonic tissues including 97 adenocarcinomas, 85 adenomas and 49 non-neoplastic colons using immunohistochemistry. In order to differentiate non-neoplastic colons from colorectal neoplasms (adenoma and carcinoma), the values for CYP1B1, AhR, nuclear β-catenin, p53 and bcl-2 expressions were subjected to discrimination analysis, then the cross-validation, sensitivity and specificity of these models were calculated. Results: Expressions of CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly associated with colorectal carcinogenesis (p < 0.01 for the trend test). The overexpression rates for CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly higher in the adenoma and carcinoma groups than in the non-neoplastic colon group (p < 0.05). The discrimination models showed that a combination of two biomarkers was better than a single biomarker, and provided specificity ranging from 39% to 100% and sensitivity ranging from 43% to 82% for colorectal carcinoma. Conclusions: The increase in expression of CYP1B1 occurred not only in colorectal carcinoma and but also in adenoma. Moreover, a screening panel of CYP1B1 in combination with nuclear β-catenin was the most suitable marker pair to screen for colorectal carcinoma based on this study.     

Pulmonary Regurgitation: Determining Severity by Echocardiography and Magnetic Resonance Imaging

Objective. Pulmonary regurgitation (PR) is common after repair of congenital heart disease involving the right ventricular outflow tract. Because PR results in chronic right ventricular volume overload and associated morbidity and mortality, accurate assessment of its severity is important. The aim of this study was to compare echocardiography with the gold standard of PR quantitation by magnetic resonance imaging (MRI) in a young population with repaired congenital heart disease. Design/Methods. Patients with congenital heart disease who had undergone right ventricular outflow tract reconstruction and/or pulmonary valve replacement and had an MRI within 3 months of an echocardiogram formed the study group. Echocardiographic indices were compared with MRI‐determined pulmonary regurgitant fraction (PRF) to determine the most accurate measurements to quantitate PR. Results. Of the 69 MRI/echocardiography pairs in 64 patients, 53 data sets were complete and used in the analysis. For the prediction of MRI PRF ≥20%, PR jet width/annulus ratio ≥0.5 demonstrated excellent sensitivity (94%), specificity (100%), positive predictive value (PPV 100%), and negative predictive value (NPV 82%). For the prediction of MRI PRF ≥40%, jet width/annulus ratio ≥0.7 and diastolic flow reversal in the branch pulmonary arteries showed useful sensitivity (92%), specificity (68%), PPV (76%), and NPV (88%). Conclusion. Pulmonary regurgitation jet width/annulus ratio combined with diastolic flow reversal is the most valuable echocardiographic measure for assessing PR severity after right ventricular outflow tract reconstruction or pulmonary valve replacement; however, this surrogate measure does not replace the importance of MRI evaluation.     

Fentanyl and Morphine, but not Remifentanil, Inhibit Acetylcholine Release in Pontine Regions Modulating Arousal

Background: Opioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF.

Methods: Nine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl.

Results: Compared with dialysis of Ringer's solution, micro-dialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh.     

Telomere length and risk of Parkinson's disease

We investigated whether telomere length was associated with the risk of Parkinson's disease (PD) in a case‐control study (96 cases and 172 age‐matched controls) nested within the Health Professionals Follow‐up Study. Relative ratio of telomere repeat copy number to single‐gene copy number in peripheral blood leukocytes was determined by quantitative real time PCR. Men with shorter telomeres had a lower PD risk (multivariate adjusted relative risk for the lowest vs. the highest quartile 0.33; 95% confidence interval: 0.12–0.90). Our results suggest that, contrary to telomere attrition observed in several aging‐related diseases, shorter telomeres are not associated with an increased risk of PD. © 2007 Movement Disorder Society