Colorectal cancer, screening and survival: the influence of socio-economic deprivation

OBJECTIVES: To determine the extent to which socio-economic deprivation explains colorectal cancer prevalence, subject participation in screening, and postoperative survival and life expectancy. METHODS: Regression analyses of clinical data from a large randomized controlled trial, augmented by geographical-based indices of deprivation. RESULTS: Deprivation appears to exert no significant impact on colorectal cancer prevalence but is a major factor explaining subject participation in screening. Cancer detection at later stages reduces life expectancy at time of treatment. Females from more-deprived areas have poorer post-treatment life expectancies and survival prospects, independently of their screening behaviour. CONCLUSIONS: Screening increases the chances of having a cancer treated at an earlier stage, and treatment at an earlier stage is associated with longer subsequent life expectancy. However, those from more-deprived areas are less likely to accept an invitation to be screened.     

Mass population screening for colorectal cancer: factors influencing subjects' choice of screening test

OBJECTIVES: To identify socio-demographic, economic, medical and attitudinal factors that explain subjects' choice of test for screening for colorectal cancer (biennial faecal occult blood test versus once-only flexible sigmoidoscopy). METHODS: Data obtained from a questionnaire, administered by general practitioners and returned by approximately 2700 asymptomatic subjects. Thereafter, logistic regression modelling to explain willingness to participate in screening, whether or not a test preference is expressed, and the nature of the preference. RESULTS: An interest in undertaking screening is more probable if the subject is white, older, married and possesses a high health motivation. An intention to participate is more probable if the subjects are particularly worried about the disease, feel themselves to be particularly susceptible to it, and have already had experience of screening for colorectal and (if female) other cancers. Persons in receipt of a household income below 10,000 Pounds are less likely to express an interest in screening. Women are more likely to express a test preference and this preference is more likely to be for the faecal occult blood test. Subjects' worries and perception of risk are associated with reported experiences of cancer, stomach problems and depression. A positive attitude towards screening is positively associated with frequency of dental visits. CONCLUSIONS: Socio-demographic, economic and other factors evidently influence subjects' preferences for particular screening tests and, by implication, the likelihood of compliance with any future screening offer. The models support the view that participation in colorectal cancer screening has as much to do with a positive attitude towards health and health promotion generally as with any specific concern about the disease.     

Production of genetically stable high-titer retroviral vectors that carry a human gamma-globin gene under the control of the alpha-globin locus control region

The ability to generate stable high-titer vectors that give rise to high levels of expression of transduced globin genes in erythroid cells is a prerequisite for effective retroviral-mediated globin gene therapy. The human beta-globin gene with its immediate flanking sequences does not contain all the regulatory elements necessary for regulated high-level and position-independent expression in erythroid cells. The regulatory element known as the beta-globin locus control region (BetaLCR) can provide a linked Beta-globin gene with these properties. However, addition of BetaLCR sequences to a retrovirus carrying a beta-globin gene increases its genetic instability. We have developed a new generation of retroviral vectors in which a human gamma- globin gene is placed under the control of the alphaLCR, the major regulatory element of the alpha-globin gene cluster. We demonstrate that these retroviruses are genetically stable in producer cell lines and can be produced at high titers that exceed 5 x 10(6) colony-forming units (CFU)/mL. In addition, we show that the transduced gamma-globin gene can be expressed in the adult erythroid environment of mouse erythroleukemia (MEL) cells at a level comparable to that of a single endogenous Betamaj-globin gene. These retroviruses can also transduce primary murine bone marrow progenitor cells as efficiently as retroviruses that carry the neomycin resistance (neor) gene. This new generation of globin retroviral vectors may prove useful for gene therapy of human beta-globin gene disorders such as sickle cell disease and beta-thalassemia.     

Right hemisphere contributions to the comprehension of low-imagery words

A priming experiment, with normal university students as subjects, was used to investigate whether the right cerebral hemisphere contributes to the comprehension of low-imagery words. Each hemisphere's access to semantic representations of low-imagery words was gauged by comparing responses to low-imagery targets preceded by associated low-imagery primes (e.g., BELIEF-IDEAL) with responses to the same targets when they were preceded by unrelated primes (e.g., FATE-IDEAL). All primes and targets were independently projected to the left or right visual fields (LVF or RVF), and temporally separated by a stimulus onset asynchrony of 250 ms. There was a clear RVF advantage in response speed and accuracy measures, confirming the left hemisphere's advantage in processing low-imagery words. Nonetheless, the priming effects provided evidence that the right hemisphere contributes to the comprehension of low-imagery words, as primes projected to the RVF equally facilitated responses to associated targets subsequently appearing in either visual field. In contrast, primes directed to the LVF did not facilitate responses to associated targets projected to the LVF or RVF. The results suggest that low-imagery words projected to the left hemisphere activated low-imagery associates in both hemispheres to an equivalent degree, whereas low-imagery primes directed to the right hemisphere failed to activate low-imagery associates in either hemisphere. Like Kounios and Holcomb's (1994) study of event-related response potentials evoked by abstract and concrete words, the findings indicate that while the left hemisphere is the primary processor of low-imagery/abstract words, the right hemisphere plays a subsidiary role in the comprehension of these words.     

Compromised concentrations of ascorbate in fluid lining the respiratory tract in human subjects after exposure to ozone

OBJECTIVES: Ozone (O3) imposes an oxidative burden on the lung in two ways. Firstly, directly as a consequence of its oxidising character during exposure, and secondly, indirectly by engendering inflammation. In this study the second pathway was considered by ascertaining the impact of O3 on the redox state of the fluid lining the respiratory tract 6 hours after challenge. METHODS: Nine subjects were exposed in a double blind crossover control trial to air and 200 ppb O3 for 2 hours with an intermittent exercise and rest protocol. Blood samples were obtained and lung function (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1)) assessed before, immediately after, and 6 hours after exposure. Bronchoalveolar lavage (BAL) was performed 6 hours after challenge. Inflammation was assessed in BAL fluid (total and differential cell counts, plus myeloperoxidase concentrations), and plasma and BAL fluid redox state were determined by measuring concentrations of antioxidants and markers of oxidative damage. RESULTS: Neutrophil numbers in BAL fluid increased 2.2-fold (p = 0.07) 6 hours after exposure and this was accompanied by increased myeloperoxidase concentrations in BAL fluid (p = 0.08). On the other hand, BAL fluid macrophage and lymphocyte numbers decreased 2.5-fold (p = 0.08) and 3.1-fold (p = 0.08), respectively at this time. Of the antioxidants examined, only ascorbate in BAL fluid was affected by O3, falling in all subjects relative to air values (0.1 (0.0-0.3) v 0.3 (0.2-1.2) mumol/l (p = 0.008)). A marginal decrease in plasma ascorbate was also detected at this time (p < 0.05). Although the decrease in macrophage numbers seemed to be causally related to the increase in neutrophils (R = -0.79), myeloperoxidase concentrations (R = -0.93) and ascorbate concentrations (R = 0.6), no clear associations were apparent between ascorbate changes and neutrophils or myeloperoxidase concentration after O3. CONCLUSIONS: Ascorbate in the fluid lining the respiratory tract is depleted as a consequence of O3 exposure at 6 hours after exposure. This was contemporaneous with, although not quantitatively related to the increase in neutrophil numbers and myeloperoxidase concentrations. Decreased macrophage numbers 6 hours after O3 related to the degree of neutrophilic inflammation with populations conserved where ascorbate concentration in the fluid lining the respiratory tract were high after exposure. These results imply that ascorbate has a critical protective role against inflammatory oxidative stress induced by O3.

 

     

Biomarkers of periodontal inflammation in the Australian adult population

Background:  Several inflammatory biomarkers are implicated in the pathogenesis of periodontitis including interleukin-1β (IL-1β) and C-reactive protein (CRP). This study investigated the presence of these factors in gingival crevicular fluid (GCF) and their relationship to clinical and social determinants of periodontitis in the Australian population.
Methods:  Equal numbers of periodontitis cases and non-cases were sampled during oral epidemiologic examination in the National Survey of Adult Oral Health. GCF was sampled from four sites where probing pocket depth (PPD) and recession were recorded. From these, IL-1β and CRP were quantified by ELISA and the log amount of GCF IL-1β (pg) per person and the proportion of adults with detectable CRP was computed.
Results:  Periodontitis cases (n = 511) had significantly higher levels of IL-1β and CRP than non-cases (n = 562). PPD, clinical attachment loss, plaque and gingivitis indices were positively associated with elevated levels of both biomarkers. Levels of both were positively associated with age, low socio-economic position and non-Australian birth.
Conclusions:  The presence of IL-1β and CRP in GCF are associated with periodontal disease parameters within the Australian population. The levels of both biomarkers are influenced by age, education and eligibility for public dental care.     

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

The affinity of anti-HBc antibodies in acute and chronic hepatitis B infection.

Antibodies to hepatitis B core antigen (anti-HBc) are found in the sera of all individuals infected with hepatitis B virus. A role for these antibodies has been suggested in determining the outcome of infection. In this study, the affinity of anti-HBc antibodies in asymptomatic virus carriers was compared with that of antibodies present in the sera of patients with chronic liver disease. Persistently infected individuals with no evidence of clinical disease were found to have anti-HBc antibodies of greater affinity, compared with the chronic liver disease group. Sera from patients with chronic hepatitis contained high levels of low-affinity antibody whereas antibody levels in asymptomatic carriers were significantly lower. These findings are discussed in relation to the predicted role of anti-HBc antibodies in mediating hepatitis B virus-related hepatocellular injury.