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Biomedical subjects

C Abraham

Publications and source records attributed to C Abraham.

At least 19 recordsLinked to original sources

Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial.

OBJECTIVE: To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. DESIGN: Follow-up of cluster randomised trial 4.5 years after intervention. SETTING: NHS records of women who had attended 25 secondary schools in east Scotland. PARTICIPANTS: 4196 women (99.5% of those eligible). INTERVENTION: SHARE programme (intervention group) v existing sex education (control group). MAIN OUTCOME MEASURE: NHS recorded conceptions and terminations for the achieved sample linked at age 20. RESULTS: In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval -33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, -13 to 42) between ages 16 and 20. CONCLUSIONS: This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers. TRIAL REGISTRATION: ISRCTN48719575 [controlled-trials.com].

Abortion, Induced↗

Why don't young people volunteer to give blood? An investigation of the correlates of donation intentions among young nondonors.

BACKGROUND: In the past decade, the number of blood donors has steadily declined in the Netherlands, and young adults are underrepresented among registered donors. An understanding of the correlates of donation intentions among nondonors could facilitate targeting psychological prerequisites of donation decisions in recruitment campaigns. STUDY DESIGN AND METHODS. A cross-sectional study with self-administered questionnaires based on an extension of the Theory of Planned Behavior (TPB; a social cognition model to study the determinants of volitional behavior) was conducted to assess potential cognitive determinants of willingness to donate blood in a student sample. A response rate of 50.5 percent yielded a sample of 311. RESULTS: Just over 7 percent of participants were registered blood donors but most (61.7%) had never seriously considered becoming donors. Self-efficacy (confidence in performing the behavior), attitude (the overall evaluation of the behavior), and personal moral norm (the perceived personal responsibility to perform the behavior) regarding blood donation were the most important correlates of the intention to become a blood donor. In total, 43 percent of the variance in the intentions toward blood donation could be explained by a TPB-based model. CONCLUSION: Among students, determinants of the intention to become a blood donor include self-efficacy, attitude, personal moral norm regarding blood donation, and subjective norm (perceived social support). Future research could establish whether campaigns targeting these psychological prerequisites would be more effective than current strategies.

Adolescent↗

Making psychological theory useful for implementing evidence based practice: a consensus approach.

BACKGROUND: Evidence-based guidelines are often not implemented effectively with the result that best health outcomes are not achieved. This may be due to a lack of theoretical understanding of the processes involved in changing the behaviour of healthcare professionals. This paper reports the development of a consensus on a theoretical framework that could be used in implementation research. The objectives were to identify an agreed set of key theoretical constructs for use in (1) studying the implementation of evidence based practice and (2) developing strategies for effective implementation, and to communicate these constructs to an interdisciplinary audience. METHODS: Six phases of work were conducted to develop a consensus: (1) identifying theoretical constructs; (2) simplifying into construct domains; (3) evaluating the importance of the construct domains; (4) interdisciplinary evaluation; (5) validating the domain list; and (6) piloting interview questions. The contributors were a "psychological theory" group (n = 18), a "health services research" group (n = 13), and a "health psychology" group (n = 30). RESULTS: Twelve domains were identified to explain behaviour change: (1) knowledge, (2) skills, (3) social/professional role and identity, (4) beliefs about capabilities, (5) beliefs about consequences, (6) motivation and goals, (7) memory, attention and decision processes, (8) environmental context and resources, (9) social influences, (10) emotion regulation, (11) behavioural regulation, and (12) nature of the behaviour. CONCLUSIONS: A set of behaviour change domains agreed by a consensus of experts is available for use in implementation research. Applications of this domain list will enhance understanding of the behaviour change processes inherent in implementation of evidence-based practice and will also test the validity of these proposed domains.

Evidence-Based Medicine↗

Once-a-day controlled-release dosage form of divalproex sodium II: development of a predictive in vitro drug release method.

During formulation design of a once-daily controlled release matrix system of divalproex sodium, the in vitro dissolution test (USP II, 100 rpm, pH 6.8 buffer) was found to result in release rates that were slower than in vivo absorption. The test method also did not sufficiently discriminate formulations with different in vivo absorption rates. To develop an in vitro method that is directly correlated with in vivo absorption, statistically designed studies were carried out to investigate the effects of various in vitro testing variables on drug release using USP dissolution apparatuses. The variables studied included agitation intensity, apparatus, pH, surfactant and ionic strength of the dissolution medium. Experimental data were analyzed using ANOVA. In vitro/in vivo correlation was tested based on the hypothesis that the same linear regression equation holds for three formulations with different release rates. A mixed effects model was used in which the dependence among observations from the same subject was taken into account. Factorial studies indicated that higher pH, addition of sodium lauryl sulphate (SLS) to the dissolution medium, and higher agitation intensity increased the release rate from the matrix tablet. Use of SLS not only lead to increased release rates that are more comparable to in vivo absorption rates, but also improved differentiation among formulations with varying release rates. Furthermore, drug release was also affected by interactions among the variables studied. Statistical analysis indicated that a combination of higher SLS concentration and lower pH provided enhanced differentiation between release profiles of the fast and slow releasing formulations. Based on the above findings, a new set of testing conditions was identified and demonstrated to be predictive of in vivo drug absorption for various controlled release formulations of divalproex sodium. The new method uses USP Apparatus II operating at 100 rpm in 500 mL of 0.1 N HCl for 45 min followed by 900 mL of 0.05 M phosphate buffer containing 75 mM SLS, pH 5.5, 37 +/- 0.5 degrees C. In conclusion, adjusting dissolution testing conditions to match the behavior of the formulations in vitro with that in vivo is a useful approach in identifying a predictive method in development of in vitro-in vivo correlation.

Anticonvulsants↗

Molecular mechanisms of IL-2 gene regulation following costimulation through LFA-1.

The integrin LFA-1 serves as an accessory molecule in T cell activation. In addition to its well-known role as an adhesion molecule, LFA-1 can contribute to T cell activation and up-regulation of IL-2 gene expression. However, the specific mechanisms by which LFA-1 influences T cell activation have not been elucidated. Therefore, we examined the impact of LFA-1:ICAM-1 interactions on transcriptional and posttranscriptional IL-2 gene regulation, using a costimulation-negative cell line transfected with MHC class II alone, or in combination with ICAM-1 or B7-1. IL-2 transcription was assessed utilizing transgenic mice expressing an IL-2 promoter luciferase reporter construct crossed to DO11.10 TCR-transgenic mice, and IL-2 mRNA stability was evaluated by real-time RT-PCR. Comparison of naive and previously activated T cells demonstrates a dramatic increase in IL-2-luciferase transcription in activated T cells that can, in part, be attributed to downstream signaling events. Costimulation through LFA-1 enhances transcription of the transgenic reporter construct across a wide Ag dose range, but does not affect IL-2 mRNA stability. In contrast, CD28 costimulation is clearly mediated through up-regulation of IL-2 transcription and through enhancement of mRNA stability. These results indicate that the primary pathway whereby engagement of LFA-1 through its ligand ICAM-1 up-regulates IL-2 gene expression is through enhanced IL-2 transcription, in the absence of any effect on IL-2 mRNA stabilization.

CD28 Antigens↗

Effective approaches to persuading pregnant women to quit smoking: a meta-analysis of intervention evaluation studies.

OBJECTIVES: The study aimed to: (1) assess the effectiveness of prenatal smoking cessation interventions, (2) clarify whether the psychological changes targeted by interventions are related to their effectiveness, (3) identify specific intervention components associated with greater effectiveness, and (4) establish whether aspects of evaluation methodology are associated with a greater effectiveness. DESIGN: Differences in proportions of women quitting and odds ratios were calculated for the intervention and control groups. Interventions were categorized in relation to the main intervention target (i.e. cognitive preparation versus increased threat perception), use of follow-up contact, use of individual cessation counselling and other characteristics. Methodological approaches to evaluation were also categorized. METHODS: A systematic literature review generated 36 controlled evaluations, including one unpublished study. A meta-analysis was used to relate study classifications to effectiveness. This involved univariate analyses and a multivariate model of the relationship between observed univariate effects. RESULTS: A weighted mean odds ratio of 1.93 indicated a good overall effectiveness. Cognitive preparation interventions achieved higher quit rates (6.5%) compared to interventions focusing on threat perception (2.2%). However, this effect was not maintained in the multivariate analysis. CONCLUSION: Interventions should employ follow-up, but further research is required to assess the impact of one-to-one counselling. Clarification of the psychological change processes underlying the observed effectiveness of these interventions is required. Future research should seek to identify the active ingredients and cognitive mediators of successful interventions.

Journal Article↗

Hormone replacement therapy and 24-hour blood pressure profile of postmenopausal women.

Menopause is associated with an increase in blood pressure (BP) and a decrease in physiologic nocturnal BP fall. These factors may play a role in the increased risk of cardiovascular events after menopause. Some studies indicate that transdermal estrogen replacement therapy may help restore the 24-h BP profile, but data on the effect of oral conjugated estrogens are lacking. We compared 24-h ambulatory BP profiles of 42 postmenopausal women not receiving hormone replacement therapy (HRT) and 20 women receiving HRT. HRT was associated with a significant increase in the proportion of dippers (50% in women not receiving HRT and 80% in women receiving HRT, P = .048). Increase in nocturnal dipping may account, in part, for the beneficial cardiovascular effects of HRT.

Aged↗

Clinical benefits of oral irrigation for periodontitis are related to reduction of pro-inflammatory cytokine levels and plaque.

BACKGROUND: Although a growing body of evidence indicates that oral irrigation with water has therapeutic benefits in periodontitis, the mechanisms of action have not been elucidated. The aims of this study were: (1) to analyze the effects of oral irrigation (Water Pik Oral Irrigator) on the clinical signs of adult periodontitis (AP) and on the levels of interleukin-1 beta (IL-beta), prostaglandin-E2 (PGE2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) in GCF, and (2) to analyze the influence of the periodontitis-related IL-1 genotype (IL-1GT) on these variables. METHOD: A single-center, blinded study in otherwise healthy humans (n= 52) with localized mild to moderate AP was carried out, using the following groups: group A (n= 12), no oral hygiene for 14 days; group B (n=20), routine oral hygiene (ROH) for 14 days; group C (n=20), supra-gingival oral irrigation plus ROH for 14 days. Group A patients were crossed-over to group C for 14 days (=day 28) after a professional prophylaxis. Group assignment was randomized by a coin toss, with the exception of group A subjects, who were self-selected as per recommendations of the internal review board for human subjects. GCF was sampled from 3 study teeth per patient and analyzed for IL-1 beta, PGE2, IL-10 and IFN gamma by ELISA on days 0, 7, 14 and 28. Probing pocket depths (PPD), clinical attachment levels (CAL), bleeding on probing (BOP), gingival index (GI) and plaque index (PI) were measured by a calibrated examiner (TWS) on days 0, 14 and 28. Analysis of covariance was performed using SAS 6.12 and Proc Mixed with group and IL-1GT as the factors and the baseline levels as the covariate, with output being least squares means and least significant difference (LSD). Significant differences were declared if the p-value for the F-statistic was < or =0.05. RESULTS: Oral irrigation plus ROH resulted in a significant reduction in PPD, BOP, GI and PI, as well as IL-beta levels by 7 days and PGE2 levels by 14 days, relative to ROH or no oral hygiene. Interestingly, decreased IL-1 beta levels in patients using oral irrigation plus ROH was accompanied by a trend for increased levels of the "anti-inflammatory" cytokine IL-10. ROH reduced GI, BOP and PI, and PGE2 levels by 14 days, but had no effect on IL-1 beta or IL-10 levels relative to no oral hygiene. The effects of no oral hygiene were reversed by a prophy followed by oral irrigation plus ROH for 14 days. No clinical differences were evident between IL-1 GT (+) patients (n= 1) and GT (-) patients (n=40), but the former had significantly elevated levels of GCF IL-10 and borderline increases in IL-1 beta (p=0.07). CONCLUSIONS: Oral irrigation with water for 14 days had an improved therapeutic benefit for AP over that of routine oral hygiene alone and this improvement was accompanied by a down-modulation of the pro-inflammatory cytokine profile in GCF.

Adult↗

From psycho-social theory to sustainable classroom practice: developing a research-based teacher-delivered sex education programme.

This paper describes the development of a theoretically based sex education programme currently undergoing a randomized controlled trial in the UK. It considers some of the practical difficulties involved in translating research-based conclusions into acceptable, replicable and potentially effective classroom lessons. The discussion acknowledges that the implications of social psychological research and the requirements of rigorous evaluation may conflict with accepted principles inherent in current sex education practice. It also emphasizes that theoretical ideas must be carefully embedded in lessons which are informed by an awareness of classroom culture, and the needs and skills of teachers. For example, the use of same-sex student groups to reflect on the gendered construction of sexuality may be problematic. Materials must be tailored to recipients' circumstances, which may require substituting for limited experience with the use of detailed scripts and scenarios. Furthermore, role-play techniques for sexual negotiation that work elsewhere may not be effective in the UK. The use of trigger video sessions and other techniques are recommended. Finally, the problems involved in promoting condom-related skills are discussed. The paper concludes that, if an intervention is to be sustainable beyond the research stage, it must be designed to overcome such problems while remaining theoretically informed.

Adolescent↗

A vitamin D3 analog induces a G1-phase arrest in CaCo-2 cells by inhibiting cdk2 and cdk6: roles of cyclin E, p21Waf1, and p27Kip1.

Previous studies by our laboratory have shown that a noncalcemic fluorinated analog of 1alpha,25-dihydroxyvitamin D3, 1alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholcal ciferol (F6-D3), significantly reduced the frequency of colonic adenomas and completely abolished the development of colonic adenocarcinomas in rats treated with azoxymethane. The mechanisms involved in this analog's chemopreventive actions, however, remain unclear. In the present study, we now show that although both 1alpha,25-dihydroxyvitamin D3 and F6-D3 inhibited the proliferation of CaCo-2 cells, a human colonic adenocarcinoma cell line, by increasing their doubling times, only F6-D3 caused an arrest of these cells in the G1 phase of their cell cycle. This arrest was accompanied by an increase in the expression of the cyclin-dependent kinase (cdk) inhibitor proteins, p2Waf1 and p27Kip1, which served to decrease the activity of cyclin-dependent kinase 2 and cyclin-dependent kinase 6, whereas the expression and phosphorylation of pRB were unchanged. In contrast to the increased expression of these cdk inhibitors, the expression of cyclin E was decreased, which further inhibited the activity of cyclin-dependent kinase 2. Collectively, the inhibition of these cyclin-dependent kinases served to arrest the CaCo-2 cells, independent of changes in pRB. Furthermore, antibody neutralization studies suggest that transforming growth factor-beta may mediate the coassociations between cdk2 and p27Kip1 and cyclin E induced by F6-D3. These data indicate that cell cycle arrest may, at least in part, underlie the chemopreventive actions of F6-D3 observed in the azoxymethane model of colon cancer. Furthermore, if the antiproliferative action observed in CaCo-2 cells also occurs in human colonic epithelium, F6-D3 may have chemopreventive potential against human colon cancer, as well.

Anticarcinogenic Agents↗

The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand.

The leukocyte-specific integrin, LFA-1, can enhance T cell activation. However, it is unclear whether the binding of LFA-1 to its ligand, ICAM-1, functions through intercellular adhesion alone, resulting in an augmentation of the TCR signal, or involves an additional LFA-1-mediated cellular signal transduction pathway. We have previously shown that naive CD4+ lymph node T cells, isolated from DO11.10 TCR transgenic mice, are activated by increasing doses of exogenous OVA peptide presented by transfectants expressing both class II and ICAM-1, but not by cells expressing class II alone. To determine whether LFA-1/ICAM-1 interactions were simply enhancing the presentation of low concentrations of specific MHC/peptide complexes generated from exogenously added peptide, we transfected cells with class II that is covalently coupled to peptide, alone or in combination with ICAM-1. These cells express 100-fold more specific class II/peptide complexes than can be loaded onto class II-positive cells at maximum concentrations of exogenous peptide. Despite this high density of TCR ligand, activation of naive CD4+ T cells still requires the coexpression of ICAM-1. LFA-1/ICAM-1 interactions are not required for effective conjugate formation and TCR engagement because presentation of class II/peptide complexes in the absence of ICAM-1 does induce up-regulation of CD25 and CD69. Thus, high numbers of engaged TCR cannot compensate for the lack of LFA-1/ICAM-1 interactions in the activation of naive CD4+ T cells.

Animals↗

Streptozotocin dose-response curve in tilapia, a glucose-responsive teleost fish.

Streptozotocin (STZ) causes beta cell necrosis and insulin-dependent diabetes in many species. The specificity of this beta cell toxin relates to its structure as an alkylating agent with an attached glucose moiety. STZ uptake by rodent beta cells appears to be via the GLUT-2 glucose transporter. Teleost fish, in general, are severely glucose intolerant. The effects of STZ were examined in tilapia, a teleost fish with highly glucose-responsive islets. Fasted tilapia were given 0, 100, 150, 200, 250, 300, or 350 mg/kg STZ iv. Plasma glucose levels were followed for 72 h and the fish autopsied. Histological sections of islets were stained by immunoperoxidase for tilapia insulin. Severe hyperglycemia was seen in 20, 80, and 100% of fish receiving 250, 300, and 350 mg/kg doses; however, sections of islets showed only partial degranulation with no evidence of beta cell necrosis. Another group of fish receiving the highest dose were followed longer to determine whether beta cell necrosis and permanent hyperglycemia ensued. All fish died or were killed within 9 days because of severe hepatic failure characterized by hepatic necrosis, jaundice, and ascites; islet morphology was relatively normal suggesting, even in a glucose-sensitive species, that fish islets either do not take up STZ or are highly resistant to its "diabetogenic" effects. Tilapia may thus be a useful model to elucidate mechanisms of action of STZ. Furthermore, STZ may provide important insights into differences in glucose uptake and metabolism by mammalian and piscine beta cells.

Animals↗

Progression of steroid-associated osteoporosis after heart transplantation.

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.

Adult↗

Cognitive predictors of adherence to malaria prophylaxis regimens on return from a malarious region: a prospective study.

Cases of 'imported malaria' into countries where malaria is not endemic are increasing and evidence suggests that non-use of malaria prophylaxis and lack of adherence are contributing to this increase. Non-adherence may be especially likely because chemoprophylaxis regimens require travellers to continue to take medication for 4 weeks after their return from a malarious region. This study investigated the extent to which cognition measures specified by the theory of planned behaviour and the health belief model could distinguish between those who reported greater or lesser adherence after their return. Cognitions were measured using a brief questionnaire on the day of departure from the malarious region and reports of adherence were collected between 5 and 7 weeks later. Data from two longitudinal samples of UK tourists returning from The Gambia were analysed; 106 mefloquine users and 61 chloroquine and proguanil users. Results suggested that malaria prophylaxis adherence could be improved. 22.5% of mefloquine users and 31% of chloroquine and proguanil users reported adherence for 3 weeks or less. A model based on the theory of planned behaviour explained approximately 50% of the variance in reported adherence amongst mefloquine users and 40% amongst chloroquine and proguanil users, comparing favorably with other published applications of the theory. Findings suggest that targeting key cognitions could enhance adherence on return from malarious regions. Enhancing perceived control over adherence may be important as well as emphasising susceptibility to malaria infection. Reassuring mefloquine users concerning potential side effects of the drug may also encourage adherence on return. Implications for future research are discussed.

Adult↗

Psychosocial correlates of heterosexual condom use: a meta-analysis.

Despite increasing incidence of HIV/AIDS, there has been no systematic review of correlates of condom use among heterosexual samples. To rectify this, the present study used meta-analysis to quantify the relationship between psychosocial variables and self-reported condom use. Six hundred sixty correlations distributed across 44 variables were derived from 121 empirical studies. Variables were organized in terms of the labeling, commitment, and enactment stages of the AIDS Risk Reduction Model (Catania, Kegeles, & Coates, 1990). Findings showed that demographic, personality, and labeling stage variables had small average correlations with condom use. Commitment and enactment stage variables fared better, with attitudes toward condoms, behavioral intentions, and communication about condoms being the most important predictors. Overall, findings support a social psychological model of condom use highlighting the importance of behavior-specific cognitions, social interaction, and preparatory behaviors rather than knowledge and beliefs about the threat of infection.

Acquired Immunodeficiency Syndrome↗