How does a Belgian health care provider deal with a request for emergency contraception?

OBJECTIVE: To evaluate how Belgian health care providers deal with a request for emergency contraception. METHOD: In 2002-2003 we conducted 12 focus groups with pharmacists, general practitioners and school physicians. A skilled moderator accompanied by an observer conducted the focus groups using a semi-structured screenplay. RESULTS: All these health care providers agree with the free access to emergency contraception (EC), but experience considerable frustration with regard to the practical aspects and the legal framework. General practitioners (GPs) claim to spend a lot of time on requests for EC and they are concerned about the quality of the counselling provided in pharmacies. Pharmacists are creative when giving counselling in the pharmacy, but there is, nevertheless, a problem with a lack of privacy. School physicians are frustrated that there is no legal possibility to respond to a request for EC when they feel they are ideally placed to advise adolescents. CONCLUSION: The over-the-counter sale of EC offers women better access, but many barriers still interfere with optimal care. Pharmacists experience a lack of skills to communicate with adolescents and a lack of privacy to give counselling. GPs have good intentions, but are confronted with a lack of willingness on the part of the patients and also financial barriers. School physicians want more possibilities to help adolescents.     

Antioxidant defence during cardiopulmonary bypass surgery.

OBJECTIVE: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. METHODS: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. RESULTS: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. CONCLUSION: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.     

The profile of emergency contraception users in a chlamydia prevalence study in primary care in Belgium.

INTRODUCTION: We describe the use of emergency contraception (EC) and its association with sociodemographic, contraceptive and behavioural characteristics in a sample of family practice attendants in Belgium. METHODS: The study was part of a large Chlamydia trachomatis (CT) prevalence study in general practice. Sexually active women under 40 who consulted their general practitioner for routine gynaecological care were enrolled in the study. Participants completed a questionnaire on sociodemographic variables, urogenital symptoms, sexual history and sexual behaviour, and delivered a sample for CT testing. Logistic regression analysis was performed to identify determinants of a history of EC use in women in this sample. RESULTS: Of 815 questioned women, 23.5% had ever used EC. EC users were a heterogeneous group with respect to educational level, age and ethnicity. The use of emergency contraception was associated with the level of urbanisation, condom use, not having children yet, young age of first sexual intercourse, having had multiple partners in the past year, a history of unintended pregnancy, and current or previous STI. DISCUSSION: Information on availability and correct use of EC, and on the need for additional testing for STI, are necessary to help primary care attendees to preserve their future reproductive health.     

Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction

The plasminogen system plays an important role in the proteolytic degradation of extracellular matrices during wound healing. In the present study we investigated the impact of the plasminogen system on cardiac wound healing and function after myocardial infarction. Myocardial infarction was induced in plasminogen-deficient mice (Plg-/-) and in wild-type controls (Plg+/+). Structural analysis 1, 2, and 5 weeks after infarction revealed that infarct healing was virtually abolished in Plg-/- mice, indicating that the plasminogen system is required for the repair process of the heart after infarction. In the absence of plasminogen, inflammatory cells did not migrate into the infarcted myocardium. Necrotic cardiomyocytes were not removed and the formation of granulation tissue and fibrous tissue did not occur. In these non-healing infarcted hearts, LV dilatation was not altered. In addition, gelatinolytic activity of MMP-2 and MMP-9 was depressed in the Plg-/- infarcted hearts, suggesting that the plasmin effect on infarct healing may be mediated by MMPs. Surprisingly, cardiac function was only attenuated to a rather small extent in the Plg-/- infarcted mice when compared to the wild-types. This study provides direct prove that plasmin-mediated proteolysis plays a central role in cardiac wound healing after myocardial infarction in mice.     

The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts

The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this is lacking. Furthermore, invertebrate models point towards a key role of the ADAM 10 orthologues Kuzbanian and sup-17 in Notch signalling. In the mouse, this function is, however, currently attributed to ADAM 17/TACE, while the role of ADAM 10 remains unknown. We have created ADAM 10-deficient mice. They die at day 9.5 of embryogenesis with multiple defects of the developing central nervous system, somites, and cardiovascular system. In situ hybridization revealed a reduced expression of the Notch target gene hes-5 in the neural tube and an increased expression of the Notch ligand dll-1, supporting an important role for ADAM 10 in Notch signalling in the vertebrates as well. Since the early lethality precluded the establishment of primary neuronal cultures, APPs alpha generation was analyzed in embryonic fibroblasts and found to be preserved in 15 out of 17 independently generated ADAM 10-deficient fibroblast cell lines, albeit at a quantitatively more variable level than in controls, whereas a severe reduction was found in only two cases. The variability was not due to differences in genetic background or to variable expression of the alternative alpha-secretase candidates ADAM 9 and ADAM 17. These results indicate, therefore, either a regulation between ADAMs on the post-translational level or that other, not yet known, proteases are able to compensate for ADAM 10 deficiency. Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity.     

Transport,Uptake, and Metabolism of the Bis(pivaloyloxymethyl)-Ester Prodrug of 9-(2- Phosphonylmethoxyethyl)Adenine in an In Vitro Cell Culture System of the Intestinal Mucosa (Caco-2)

Purpose. To evaluate intestinal transport, uptake and metabolism characteristics of the bis(pivaloyloxymethyl)-ester [bis(POM)-ester] of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine [PMEA]. Methods. Intestinal transport, uptake and metabolism of bis(POM)-PMEA were studied using an in vitro cell culture system of the intestinal mucosa (Caco-2 monolayers). Concentrations of bis(POM)-PMEA and its metabolites mono(POM)-PMEA and PMEA were determined using a reversed-phase HPLC method. Enzymatic stability of bis(POM)-PMEA was evaluated by incubation with purified liver carboxylesterase, homogenates of Caco-2 cells and scraped pig small intestinal mucosa. Results. The use of bis(POM)-PMEA as a prodrug of PMEA resulted in a significant increase in transport of total PMEA [bis(POM)-PMEA, mono(POM)-PMEA and PMEA] across Caco-2 monolayers. While transepithelial transport of PMEA (500 M) was lower than 0.1% during a 3 hr incubation period, transport of total PMEA after addition of bis(POM)-PMEA (100 M) amounted to 8.8% over the same incubation period. Only 23% of the amount transported appeared as intact bis-ester at the basolateral side, while 33% of this amount was free PMEA and 44% was mono(POM)-PMEA, suggesting susceptibility of the prodrug to chemical and enzymatic degradation. Uptake studies revealed that only negligible amounts of bis(POM)-PMEA (< 0.2%) were present inside the cells. Very high intracellular concentrations of PMEA were found 1.2 mM, after a 3 hr incubation with 50 M bis(POM)-PMEA), which suggests that PMEA was trapped inside the cells probably due to its negative charge. This explains that efflux of PMEA was relatively slow (25% of the intracellular amount in 3 hr). Enzymatic degradation of the prodrug by carboxylesterase was confirmed by incubation of bis(POM)-PMEA with purified enzyme (K_m = 87 M and V_max = 9.5 M/min). Incubation of bis(POM)-PMEA (10 M) with cell homogenate of Caco-2 monolayers and pig small intestinal mucosa produced similar degradation profiles. Conclusions. The use of the bis(POM)-prodrug significantly enhances the intestinal permeability of PMEA. Intracellular trapping of PMEA in the intestinal mucosa may result in slow release of PMEA to the circulation after oral administration of bis(POM)-PMEA.     

Preoperative outpatient evaluation of young adults by anesthesiologist: anamnesis and physical examination are satisfactory--short questionnaire of Dutch Public Health Council is not

The report of the Netherlands Health Council 'Preoperatief onderzoek; een herijking van uitgangspunten' recommends that the health status of patients aged 16-39 years can be investigated preoperatively by the anaesthesiologist using a short questionnaire (6 questions). However, it is not clear whether such an abbreviated preoperative investigation will be informative enough for a safe and balanced anaesthesiologic management. An overview of relevant literature on the subject of preoperative investigation indicates that the preoperative physical status of patients as reflected by the American Society of Anesthesiologists (ASA) classification is a predictor of perioperative complications. Patients can be classified accordingly on the basis of an extended history and physical examination only: any routine additional investigation, such as ECG, chest X-ray or laboratory investigations, seem superfluous. Only blood group, rhesus factor and the presence of irregular antibodies may need to be determined if indicated by the kind of surgery. Currently, however, there is not sufficient evidence to demonstrate that the short questionnaire of the Netherlands Health Council is informative enough.     

Risk assessment of dietary acrylamide intake in Flemish adolescents.

Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate.     

Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes

PurposeModerate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol–biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown.MethodsIn a case–cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method.ResultsUsing the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41–243), whereas high-sensitivity C-reactive protein (?7.5%; ?36.4 to 1.8) or blood pressure (?6.9; ?26.3 to ?0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower.ConclusionsThe relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure–mediator interactions may result in bias. The difference and G-estimation methods provide similar results.