Improving rates for screening colonoscopy: Analysis of the health information national trends survey (HINTS I) data

Background Colonoscopy is an effective modality for colorectal cancer screening. The objectives of this study were to identify colorectal cancer knowledge and barriers to screening colonoscopy in the general US population. Methods Data was obtained from the health information national trends survey (HINTS I). The dataset (n = 6369) examined the influence of age, race, gender, education, income, media usage, and interactions with health care providers on knowledge, attitudes, and behavior regarding colonoscopic screening for colorectal cancer. Results The term ‘colonoscopy’ was recognized by 80% of participants (over the age of 35), however only 35% of respondents perceived it as a major method for colon cancer screening. Hispanics had the least awareness of colonoscopic screening (16% versus 39% non-Hispanic). Female gender, education, and income all correlated with knowledge and use of colonoscopic screening. There was a positive correlation between media usage and having a colonoscopy (r = 0.095, p < 0.01). Having a health care provider was strongly correlated with having undergone a colonoscopy (r = 0.249, p < 0.01). Reasons for not having a colonoscopy were ‘no reason’ (29%), ‘doctor didn’t order it’ (24%), and ‘didn’t know I needed the test’ (15%). Personalized materials were the preferred media for receiving cancer-related information. Conclusions Knowledge of and participation in screening colonoscopy is low in the US population, especially among Hispanics. The most important immediate action is to increase physician referral for screening colonoscopy. Education materials focused on specific sociodemographic segments and targeted communication campaigns need to be developed to encourage screening.     

Cancer resistance in transgenic mice expressing the SAC module of Par-4

Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-kappaB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.     

Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras

Ras is one of the most commonly mutated oncogenes in the array of human cancers. The mechanism by which Ras induces cellular transformation is, however, not fully elucidated. We present here evidence that oncogenic Ras suppresses the expression of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 (PTEN), and this action of oncogenic Ras is mediated by the Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway via up-regulation of c-Jun. Jun(+/+) cells undergo cellular transformation by oncogenic Ras, and restoration of wild-type PTEN, but not a phosphate-defective mutant of PTEN, induces apoptosis in these cells. Conversely, in Jun(-/-) cells, oncogenic Ras neither suppresses PTEN nor causes transformation, but rather it induces PTEN-dependent apoptosis. An apoptotic response to oncogenic Ras in Jun(-/-) cells can be prevented by suppressing PTEN expression. These findings imply that oncogenic Ras suppresses the apoptotic gene PTEN via the Raf-MEK-ERK-c-Jun pathway to induce antiapoptosis and cellular transformation. Together, our findings identify a novel molecular interface between the oncogenic and tumor suppressor pathways that regulates cellular transformation and survival.     

Consent Administrator Training to Reduce Disparities in Research Participation

Purpose: The aims for this paper are to summarize the current state of disparities in clinical research participation, discuss regulatory and interpersonal causes for these disparities, and to suggest an approach to address this problem by standardized training for consent administrators.
Organizing Construct: A program based on the Precede-Proceed model for training consent administrators is proposed and described.
Conclusions: The current process for informed consent for research is unstandardized and inadequate, and may contribute to racial and ethnic disparities. Researchers are urged to consider a formal training program for members of their research teams who will be obtaining participants' consent.
Clinical Relevance: An educational program for consent administrators may help to reduce disparities in research participation by improving communication between research staff and potential participants.     

Visual acuity in an Australian Aboriginal population

Background: Australia is a developed country, However; Aboriginal Australians have rates of blindness comparable to Third World countries. There have been well-funded eye health programs for 15 years in Central Australia. This paper examines if there has been an improvement in visual disability of one traditional group of Aboriginal Australians. Methods: Results from an eye health survey of the Anangu Pitjantjatjara of South Australia in 1990 are presented. These data are compared with results for ‘blindness’ and ‘poor vision’ from a national survey undertaken in 1976. The two surveys were comparable in design, both were cross-sectional population-based prevalence surveys. Prevalence rates were adjusted for the size of the source population. Results: Young rural Aboriginal Australians have good visual acuity. Low vision and blindness (WHO definitions) occur in 19.6% and 10.4% of 60+ year olds, respectively. Women were more likely than men to be blind or have low vision (OR= 1.93; 1.06-3.58). There was a decline in ‘poor vision’ between surveys (OR=2.86; 1.86-4.75) but not in ‘blindness’. Conclusion: Although there has been a reduction in the prevalence of visual disability in rural Aboriginal Australians, improvements in the provision of eye care for the elderly need to occur.     

Improvements in pelvic exenteration: Factors responsible for reducing morbidity and mortality

Background: Since pelvic exenteration for the treatment of recurrent gynecologic malignancy first was described, reported rates of morbidity and mortality have declined steadily. However, the factors responsible for this decline have never been clearly delineated. Methods: We reviewed the charts of 154 patients who underwent pelvic exenteration for gynecologic malignancy between 1954 and 1994. Charts were abstracted for details of the surgical procedure, pathologic findings, postoperative management, short- and long-term complications, time to recurrence, and overall survival. Results: Seventy-two patients (47%) experienced 95 identifiable postoperative complications, resulting in death in 22 patients (14%). The rate of infectious complications declined to a statistically significant degree between the first two decades and latter two decades of the study (odds ratio [OR] 0.28, 95% CI 0.11–0.69). The use of routine prophylactic antibiotics was associated with this decline in infectious complications (OR 0.25, 95% CI 0.07–0.83). The use of preoperative subcutaneous heparin was associated with a reduction in thrombotic complications from 5 of 100 patients to 0 of 54 patients (P=.11), as well as a significant reduction in overall risk of complications (OR 0.53, 95% CI 0.33–0.85) and risk of postoperative mortality (OR 0.19, 95% CI 0.05–0.80). There was a significant reduction in overall risk of postoperative complications with both intensive care unit monitoring postoperatively (OR 0.65, 95% CI 0.43–0.99) and routine postoperative monitoring with a pulmonary artery catheter (OR 0.61, 95% CI 0.38–0.98). Conclusions: Routine use of prophylactic antibiotics, prophylactic subcutaneous heparin, and intensive postoperative monitoring appear to have reduced morbidity from pelvic exenteration.     

Heat shock alters Alzheimer's β amyloid precursor protein expression in human endothelial cells

One of the pathological lesions in Alzheimer's disease (AD) is the amyloid or senile plaque. The plaque core is predominantly made up of amyloid beta peptide (Aβ), a 42–43 amino acid peptide derived from amyloid precursor protein (APP). APP is a membrane bound glycoprotein which is expressed ubiquitously is many cells. Although normal or pathological functions for APP are not well understood, several observations suggest that APP may play a role in cellular stress and inflammation at the endothelial cell/vascular barrier. APP is found in platelets and endothelial cells, it can inhibit a blood coagulation factor, and secreted APP can be neuroprotective. Changes in expression of APP during cellular stress or inflammation may contribute to pathological deposition of Aβ. In the present studies, expression of APP in human endothelial cells was examined following heat shock. In human umbilical vein endothelial cells (HUVECs) exposed to 42°C for 30 min, there was a five-to eight-fold increase in APP mRNA levels which peaked at 4 hr. The increase in APP mRNA was followed by an increase in APP protein immunoreactivity in the cytoplasm in a perinuclear Golgi-like region, and in discrete granular cytoplasmic structures. Immunoblot analysis of APP in the cell media found a transient increase in APP which peaked at 1 hr after heat shock. These results suggest that cellular stress induces the secretion of APP from endothelial cells followed by a subsequent increase in APP mRNA and protein synthesis. The upregulation of APP mRNA and protein supports a cellular stress role for APP. Wiley-Liss, Inc.