Impact of after-treatment devices and biofuels on diesel exhausts genotoxicity in A549 cells exposed at air-liquid interface.

Using an air-liquid interface (ALI) device in dynamic conditions, we evaluated the efficiency of fuel after-treatment strategies (diesel oxidation catalysis, DOC, and diesel particulate filter, DPF, devices) and the impact of 7% and 30% rapeseed methyl esters (RME) blending on oxidative stress and genotoxicity induced in A549 lung cells after 3h exposure to whole Diesel exhausts. Oxidative stress was studied using assays of ROS production, glutathione level, catalase and superoxide-dismutase (SOD) activities. No oxidative stress and no clear differences on cytotoxicity patterns between biodiesel and standard Diesel exhausts were found. A weak but significant genotoxicity (8-oxodGuo adducts) and, for standard Diesel only, a DNA damage response (DDR) as evidenced by ƔH2AX foci, remained after DOC+DPF flowing. All together, these data could contribute to the improvement of the after treatment strategies and to health risk assessment of current diesel exhausts.

Provision of long-acting reversible contraception in HIV-prevalent countries: results from nationally representative surveys in southern Africa.

OBJECTIVE: To analyse the current provision of long-acting reversible contraception (LARC) and clinician training needs in HIV-prevalent settings. DESIGN: Nationally representative survey of clinicians. SETTING: HIV-prevalent settings in South Africa and Zimbabwe. POPULATION: Clinicians in South Africa and Zimbabwe. METHODS: Nationally representative surveys of clinicians were conducted in South Africa and Zimbabwe (n = 1444) to assess current clinical practice in the provision of LARC in HIV-prevalent settings. Multivariable logistic regression was used to analyse contraceptive provision and clinician training needs. MAIN OUTCOME MEASURE: Multivariable logistic regression of contraceptive provision and clinician training needs. RESULTS: Provision of the most effective reversible contraceptives is limited: only 14% of clinicians provide copper intrauterine devices (IUDs), 4% levonorgestrel-releasing IUDs and 16% contraceptive implants. Clinicians' perceptions of patient eligibility for IUD use were overly restrictive, especially related to HIV risks. Less than 5% reported that IUDs were appropriate for women at high risk of HIV or for HIV-positive women, contrary to evidence-based guidelines. Only 15% viewed implants as appropriate for women at risk of HIV. Most clinicians (82%), however, felt that IUDs were underused by patients, and over half desired additional training on LARC methods. Logistic regression analysis showed that LARC provision was largely restricted to physicians, hospital settings and urban areas. Results also showed that clinicians in rural areas and clinics, including nurses, were especially interested in training. CONCLUSIONS: Clinician competency in LARC provision is important in southern Africa, given the low use of methods and high rates of unintended pregnancy among HIV-positive and at-risk women. Despite low provision, clinician interest is high, suggesting the need for increased evidence-based training in LARC to reduce unintended pregnancy and associated morbidities.

Discrepancies in diagnosis of incident HIV infection between antibody- and DNA-based tests in a phase III prevention trial in southern Africa.

Dried blood spots (DBS) are widely used to test for HIV in a variety of research and service delivery settings; however, uniform guidelines regarding collection, storage and DNA extraction processes have neither been developed nor evaluated. Previously published reports suggested DBS may be stored at room temperature for up to 60 days, and intensive stability tests have shown that DBS can withstand high temperatures, humidity and freeze-thawing. During the implementation of a large randomized controlled trial (RCT) in southern Africa, with HIV acquisition as the primary endpoint, we observed 65 instances when DBS samples collected from the same day as a positive HIV antibody test yielded negative DNA polymerase chain reaction (PCR) results. The source of this discrepancy may have been due to inadequate specimen volume, filter paper or DNA extraction procedures, but were most likely due to storage conditions that have been reported as acceptable in other settings.

Sexual and reproductive health in Accra, Ghana.

OBJECTIVE: To describe sexual and reproductive health among women in Accra and explore the burden of sexual and reproductive ill health among this urban population. DESIGN: Cross-sectional study. METHODS: We analysed data from the WHSA-II (n=2814), a cross-sectional household survey on women's health, and supplemental data from an in-depth survey (n=400), focus groups discussions (n=22) and in-depth interviews (n=20) conducted among a sub-sample of women which focused specifically on reproductive health issues. RESULTS: Modern contraceptive use was uncommon. More than one third of women reported ever using abstinence; condoms, injectables and the pill were the most commonly reported modern methods ever used. The total fertility rate among this sample of women was just 2.5 births. We found a considerable burden of sexual and reproductive ill health; one in ten women reported menstrual irregularities and almost one quarter of women reported symptoms of a Sexually Transmitted Infection (STI) or Reproductive Tract Infection (RTI) in the past 6 months. Focus group results and in-depth interviews reveal misperceptions about contraception side-effects and a lack of information. CONCLUSION: In urban Ghana, modern contraceptive use is low and a significant proportion of women experience reproductive ill health (defined here as menstrual irregularity or RTI, UTI, STI symptoms). Increased access to information, products and services about for preventive care and contraception could improve reproductive health. More research on healthy sexuality and the impact of reproductive ill health on sexual experience is needed.

The value of ecologic studies: mercury concentration in ambient air and the risk of autism.

Ecologic studies of the spatial relationship between disease and sources of environmental contamination can help to ascertain the degree of risk to populations from contamination and to inform legislation to ameliorate the risk. Population risks associated with persistent low-level mercury exposure have recently begun to be of concern and current reports implicate environmental mercury as a potential contributor in the etiology of various developmental and neurodegenerative diseases including autism and Alzheimer's disease. In this demonstration of preliminary findings, we demonstrate for Bexar County Texas and Santa Clara County California, the hypothesis that the spatial structure of the occurrence of autism has a positive co-variation with the spatial structure of the distribution of mercury in ambient air. The relative risk of autism is greater in the geographic areas of higher levels of ambient mercury. We find that the higher levels of ambient mercury are geographically associated with point sources of mercury emission, such as coal-fired power plants and cement plants with coal-fired kilns. Although this does not indicate a cause, these results should not be dismissed, but rather seen as a preliminary step for generating a hypothesis for further investigation.

The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study.

We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55-2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77-11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01-15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8-39.3), for incident HSV-2 2.1% (95% CI: 0.6-3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5-5.8). Women's greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.

Cost-effectiveness analysis of alternative first-trimester pregnancy termination strategies in Mexico City.

OBJECTIVE: To assess the comparative health and economic outcomes associated with three alternative first-trimester abortion techniques in Mexico City and to examine the policy implications of increasing access to safe abortion modalities within a restrictive setting. DESIGN: Cost-effectiveness analysis. SETTING: Mexico City. POPULATION: Reproductive-aged women with unintended pregnancy seeking first-trimester abortion. METHODS: Synthesising the best available data, a computer-based model simulates induced abortion and its potential complications and is used to assess the cost-effectiveness of alternative safe modalities for first-trimester pregnancy termination: (1) hospital-based dilatation and curettage (D&C), (2) hospital-based manual vacuum aspiration (MVA), (3) clinic-based MVA and (4) medical abortion using vaginal misoprostol. MAIN OUTCOME MEASURES: Number of complications, lifetime costs, life expectancy, quality-adjusted life expectancy. RESULTS: In comparison to the magnitude of health gains associated with all safe abortion modalities, the relative differences between strategies were more pronounced in terms of their economic costs. Assuming all options were equally available, clinic-based MVA was the least costly and most effective. Medical abortion with misoprostol provided comparable benefits to D&C, but cost substantially less. Enhanced access to safe abortion was always more influential than shifting between safe abortion modalities. CONCLUSIONS: This study demonstrates that the provision of safe abortion is cost-effective and will result in reduced complications, decreased mortality and substantial cost savings compared with unsafe abortion. In Mexico City, shifting from a practice of hospital-based D&C to clinic-based MVA and enhancing access to medical abortion will have the best chance to minimise abortion-related morbidity and mortality.

Effectiveness of a three-day communication skills course in changing nurses' communication skills with cancer/palliative care patients: a randomised controlled trial.

This multi-centre, two-armed parallel-group pragmatic randomised controlled trial (RCT) evaluated the effectiveness of a 3-day communication skills course in changing nurses' communication skills. The primary outcome was the change in the nurses' communication skills score from pre-course to 12 weeks post-course. The main secondary outcome was the change in the nurses' level of confidence in communicating with patients. A total of 172 nurses were randomised to the course or control. The communication skills score for the intervention group increased by 3.4 points post-course but decreased in the control by 0.05 points (between-group difference in change: 3.41, 95% CI: 2.16-4.66, P < 0.001). Confidence scores increased by 18.16 points for the intervention group but decreased 0.7 points in the control (between-group difference in change: 18.86, 95% CI: 13.39-24.34, P < 0.001). This RCT contributes to the evidence base on the effectiveness of communication skills training in cancer and palliative care.

Reducing maternal mortality due to elective abortion: Potential impact of misoprostol in low-resource settings.

Over 99% of deaths due to abortion occur in developing countries. Maternal deaths due to abortion are preventable. Increasing the use of misoprostol for elective abortion could have a notable impact on maternal mortality due to abortion. As a test of this hypothesis, this study estimated the reduction in maternal deaths due to abortion in Africa, Asia and Latin America. The estimates were adjusted to changes in assumptions, yielding different possible scenarios of low and high estimates. This simple modeling exercise demonstrated that increased use of misoprostol, an option for pregnancy termination already available to many women in developing countries, could significantly reduce mortality due to abortion. Empirical testing of the hypothesis with data collected from developing countries could help to inform and improve the use of misoprostol in those settings.

A comparison of women's, providers' and ultrasound assessments of pregnancy duration among termination of pregnancy clients in South Africa.

OBJECTIVE: To compare providers' and women's estimates of duration of pregnancy with ultrasound estimates for determining medical abortion eligibility. DESIGN: Cross-sectional study. SETTING: Public termination of pregnancy (TOP) services in three provinces. SAMPLE: A total of 673 women attending the above services for TOP. METHODS: Women participating in a medical abortion feasibility study in South Africa provided estimates of pregnancy duration and date of last menstrual period (LMP). Each woman also had clinical and ultrasound exams. We compared estimates using the four methods, calculating the proportion of women in the 'caution zone' (< or = 8 weeks gestation by woman or provider estimate and > 8 weeks by ultrasound). MAIN OUTCOME MEASURES: Mean gestational age by each method; difference between provider and LMP estimates and ultrasound estimates; and percentage of women in the 'caution zone'. RESULTS: Women's estimates of pregnancy duration were 19 days fewer than ultrasound estimates (95% CI = -27 to 63). Mean provider- and LMP-based estimates were two (95% CI = -30 to 35) and less than one day(s) (95% CI = -46 to 51) fewer than ultrasound estimates. Comparing provider and ultrasound estimates, 15% of women were in the 'caution zone'; this fell to 12% if estimates of 9 weeks or fewer were considered acceptable. CONCLUSIONS: Provider estimates of gestational age were sufficiently accurate for determining eligibility for medical abortion. LMP-based estimates were also accurate on average, but included more extreme differences from ultrasound estimates. Medical abortion could be provided in TOP facilities without ultrasound or with ultrasound on referral.

Advance provision of emergency contraception for pregnancy prevention (full review).

BACKGROUND: Emergency contraception can prevent pregnancy when taken after unprotected intercourse. Obtaining emergency contraception within the recommended time frame is difficult for many women. Advance provision, in which women receive a supply of emergency contraception before unprotected sex, could circumvent some obstacles to timely use. OBJECTIVES: To summarize randomized controlled trials evaluating advance provision of emergency contraception to explore effects on pregnancy rates, sexually transmitted infections, and sexual and contraceptive behaviors. SEARCH STRATEGY: In August 2006, we searched CENTRAL, EMBASE, POPLINE, MEDLINE via PubMed, and a specialized emergency contraception article database. We also searched reference lists and contacted experts to identify additional published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials comparing advance provision and standard access, which was defined as any of the following: counseling which may or may not have included information about emergency contraception, or provision of emergency contraception on request at a clinic or pharmacy. DATA COLLECTION AND ANALYSIS: We evaluated all identified titles and abstracts found for potential inclusion. Two reviewers independently abstracted data and assessed study quality. We entered and analyzed data using RevMan 4.2.8. We calculated odds ratios with 95% confidence intervals for dichotomous data and weighted mean differences with 95% confidence intervals for continuous data. MAIN RESULTS: Eight randomized controlled trials met our criteria for inclusion, representing 6389 patients in the United States, China and India. Advance provision did not decrease pregnancy rates (OR 1.0; 95% CI: 0.78 to 1.29 in studies for which we included twelve month follow-up data; OR 0.91; 95% CI: 0.69 to 1.19 in studies for which we included six month follow-up data; OR 0.49; 95% CI: 0.09 to 2.74 in a study with three month follow up data), despite increased use (single use: OR 2.52; 95% CI 1.72 to 3.70; multiple use: OR 4.13; 95% CI 1.77 to 9.63) and faster use (weighted mean difference (WMD) -14.6 hours; 95% CI -16.77 to -12.4 hours). Advance provision did not lead to increased rates of sexually transmitted infections (OR 0.99; 95% CI 0.73 to 1.34), increased frequency of unprotected intercourse, nor changes in contraceptive methods. Women who received emergency contraception in advance were equally as likely to use condoms as other women. AUTHORS' CONCLUSIONS: Advance provision of emergency contraception did not reduce pregnancy rates when compared to conventional provision. Advance provision does not negatively impact sexual and reproductive health behaviors and outcomes. Women should have easy access to emergency contraception, because it can decrease the chance of pregnancy. However, the interventions tested thus far have not reduced overall pregnancy rates in the populations studied.

Gene amplification and associated loss of 5' regulatory sequences of CoAA in human cancers.

CoAA is an RRM-containing transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. We show that the CoAA gene is amplified at the chromosome 11q13 locus in a subset of primary human cancers including non-small cell lung carcinoma, squamous cell skin carcinoma and lymphoma. Analysis of 42 primary tumors suggests that CoAA amplifies independently from the CCND1 locus. Detailed mapping of three CoAA amplicons reveals that the amplified CoAA gene is consistently located at the 5' boundaries of the amplicons. The CoAA coding and basal promoter sequences are retained within the amplicons but upstream silencing sequences are lost. CoAA protein is overexpressed in tumors containing the amplified CoAA gene. RNA dot blot analysis of 100 cases of primary tumors suggests elevated CoAA mRNA expression. CoAA positively regulates its own basal promoter in transfection assays. Thus, gene amplification, loss of silencing sequence and positive feedback regulation may lead to drastic upregulation of CoAA protein. CoAA has transforming activities when tested in soft agar assays, and CoAA is homologous to oncoproteins EWS and TLS, which regulate alternative splicing. These data imply that CoAA may share a similar oncogenic mechanism with oncogene EWS and that CoAA deregulation may alter the alternative splicing of target genes.

Primary endoluminal stenting of transplant renal artery stenosis from cadaver and non-heart-beating donor kidneys.

This study evaluated the efficacy of primary endovascular stenting in cases of transplant renal artery stenosis (TRAS) from cadaver and non-heart-beating donor kidneys. Patients with TRAS (n = 13) from a single-centre transplant population (n = 476) were treated by primary percutaneous angioplasty and endovascular stenting. The short-term efficacy of this intervention is demonstrated in terms of serum creatinine, glomerular filtration rate (GFR) biochemical, anti-hypertensive medications and mean arterial blood pressure control. Stenting for TRAS was performed in male (n = 10) and female (n = 3) recipients. The median age at transplantation was 55 yr (range 10-67 yr). Stenting occurred at a median duration of 410 d post-transplantation (range 84-5799 d). Mean serum creatinine (pre, 247 micromol/L; post, 214 micromol/L; p = 0.002), GFR (pre, 82.6 mL/min; post, 100.9 mL/min; p < 0.001), arterial blood pressure (pre, 104 mmHg; post, 97 mmHg; p = 0.036) and the number of anti-hypertensive medications required (pre, 3.4; post, 3.0; p = 0.002) showed significant improvement after post-endovascular therapy. There were no serious complications encountered. Primary endovascular stenting of TRAS produces a significant improvement in biochemical parameters of renal graft function and in blood pressure stability, with the benefit of low patient morbidity and single arterial puncture. Primary endoluminal stenting of TRAS is a safe and effective procedure for the treatment of TRAS.

Postinfectious gastroparesis related to autonomic failure: a case report.

BACKGROUND AND AIM: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing and autopsy. HOSPITAL COURSE: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva manoeuvre although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteraemia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. CONCLUSION: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiological and autonomic studies with histological findings.

Phenolphthalein and bisacodyl: assessment of genotoxic and carcinogenic responses in heterozygous p53 (+/-) mice and syrian hamster embryo (SHE) assay.

Phenolphthalein (800 and 2400 mg/kg/day by gavage and 2400 mg/kg/day by diet) and bisacodyl (800-500, 4000-2000, and 8000 mg/kg/day by gavage) were administered to 15 male and 15 female and 20 male and 20 female p53(+/-) mice respectively for 26 weeks to investigate the potential carcinogenicity of each compound. Toxicokinetic analyses confirmed systemic exposure. p-Cresidine was administered by gavage (400 mg/kg/day) and served as the positive control agent in each study. Dietary phenolphthalein reduced survival in both sexes and early deaths were attributed to thymic lymphoma. No bisacodyl-related neoplasms were observed. Regardless of route of administration to p53(+/-) mice, phenolphthalein but not bisacodyl was unequivocally genotoxic, causing increased micronuclei in polychromatic erythrocytes. In the Syrian hamster embryo (SHE) cell transformation assay, phenolphthalein caused increases in morphologically transformed colonies, thereby corroborating NTP's earlier reports, showing phenolophthalein has potential carcinogenic activity. Bisacodyl was negative in the SHE assay. Results of these experiments confirm an earlier demonstration that dietary phenolphthalein causes thymic lymphoma in p53(+/-) mice and show that (1) phenolphthalein causes qualitatively identical results in this transgenic model regardless of route of oral administration, (2) phenolphthalein shows evidence of micronucleus induction in p53(+/-) mice for up to 26 weeks, (3) phenolphthalein induced transformations in the in vitro SHE assay, and (4) bisacodyl in p53(+/-) mice induces neither drug-related neoplasm, nor micronuclei in polychromatic erythrocytes, and did not induce transformations in the in vitro SHE assay.

Geography and geographic information systems in family medicine research.

Understanding spatial relationships between determinants and outcomes of health care is important as the concept of population-based health care gains acceptance. A wide range of tools for understanding these spatial relationships is available to the family medicine researcher through the use of Geographic Information Systems (GIS). The power of GIS lies in its ability to display the spatial distribution of a health-related predictor or outcome. These maps can then be used to either generate or test hypotheses that would not have otherwise occurred to the investigator without visualizing the spatial relationships. The type of GIS application used is dependent on the type of data the researcher has and the research question. The three most common types of data are point or event data, lattice data, and geostatistical data. Point or event data can be displayed using a technique known as geocoding. Lattice data is most commonly displayed as shaded or colored areas where the shading represents rates or counts. Geostatistical data provides counts or numbers at a given location. The analytic techniques used for analyzing spatial data depend on the type of data. Maps tell powerful stories and display relationships that may not be obvious using other techniques.

Misoprostol use in obstetrics and gynecology in Brazil, Jamaica, and the United States.

OBJECTIVES: To investigate current clinical use of misoprostol for the treatment of a range of reproductive health indications by providers in Brazil, Jamaica, and the United States. METHODS: Using a 'snowball' sampling technique, we surveyed 228 gynecologists and obstetricians in Brazil (n=123), Jamaica (n=52), and the United States (n=53). RESULTS: Providers use misoprostol for labor induction (46%), postpartum hemorrhage (8%), intra-uterine fetal death (61%), cervical priming (21%), missed abortion (57%), and incomplete abortion (16%) as well as first and second trimester abortion induction (27% and 13%, respectively). CONCLUSIONS: There is considerable variation in the regimens used; moreover, the regimens commonly used in clinical practice often differ from those recommended in the medical literature. While misoprostol is an appealing alternative for many reproductive health indications in developing countries, the varied regimens and lack of registration raise critical medical and policy questions.

Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA.

The Tg.AC transgenic mouse carries a v-Ha-ras transgene. Skin papillomas develop in Tg.AC mice upon repeated dermal application of tumor promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the >or= 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from papillomas when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC papillomas sampled. The transgene locus was hypomethylated in papillomas but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC mice, as shown by loss of resistance to digestion by HpaII. A cell line derived from a Tg.AC squamous cell carcinoma showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of papilloma growth.

Acceptability and feasibility of Micralax applicators and of methyl cellulose gel placebo for large-scale clinical trials of vaginal microbicides.

OBJECTIVE(S): To evaluate the feasibility and acceptability of the Micralax applicator and of methyl cellulose placebo gel for use in vaginal microbicide clinical trials. DESIGN: A two-centre prospective study following women for 2 months. SETTING: Two primary health care clinics in South Africa. PATIENTS, PARTICIPANTS: Female volunteers (n = 28) 18 years or older who were HIV negative and had no clinically detectable genital tract abnormalities or reproductive tract infections. INTERVENTIONS: Participants used pre-filled Micralax applicators to apply methyl cellulose gel every other day, as well as up to 1 h before to every episode of vaginal sex. MAIN OUTCOME MEASURE(S): Consistency in the weight of gel dispensed per application; side-effects attributed to applicator or gel use; and acceptability of the applicator and of the gel. RESULTS: Over a 2 month follow-up period the 22 women completing the study reported no adverse events related to gel or applicator use. The Micralax applicator proved acceptable. The gel was not too messy and did not reduce sexual frequency or pleasure. On average, the applicator dispensed 4.7 ml per use (close to the 4 ml planned). CONCLUSIONS: The Micralax applicator performs well as a delivery system for potential vaginal microbicides; and methyl cellulose is an appropriate placebo for future microbicide trials.

Women's willingness to participate in microbicide trials in Northern Thailand.

To assess women's interests and concerns regarding participation in trials of microbicides in Chiang Rai, Thailand, we administered structured questionnaires. Before answering the questionnaire, women attended an educational session on microbicides and clinical trials. Of 370 participants, 82% correctly answered 8 or more of the 11 overall comprehension questions, indicating an adequate knowledge base among the women from which to answer questions about attitudes toward microbicide trials. The most common motivations for participating in a trial were "getting tested for HIV" and "doing something good for women's health." The greatest barrier to participation was women's fear that if they proposed use of a microbicide, their husbands might feel protected and thereby have more sex partners. Overall, 6.2% said they would be "definitely willing to participate," and 66.8% said they wanted to participate but wanted to think about it. Most women previously unacquainted with the concept of microbicides or clinical trial design displayed adequate knowledge of these subjects after the short educational session. If women's initial reactions are validated by actual willingness, surveys could prove valuable for selecting sites for microbicide trials, estimating enrollment rates, and tailoring trials to make them most acceptable to women.