Canadian results from the European Men-who-have-sex-with-men Internet survey (EMIS-2017).

BACKGROUND: In 2017, the international European Men-who-have-sex-with-men Internet Survey (EMIS-2017) collected data from 50 countries, including Canada for the first time. OBJECTIVE: To provide an overview of the Canadian EMIS-2017 data to describe the sexually transmitted and other bloodborne infection (STBBI) related needs of gay, bisexual and other men who have sex with men (gbMSM). METHODS: The EMIS-2017 questionnaire was an updated version of EMIS-2010. It included self-reported sociodemographic data, experience of discrimination, mental health and substance use, knowledge of preexposure prophylaxis (PrEP) for HIV, sexual practices and history of STBBI testing and diagnosis. Analysis was largely descriptive. RESULTS: Of the 6,059 respondents from Canada, 5,165 participants met the inclusion criteria for this analysis. The majority of participants were born in Canada (79.3%); and over half of the respondents (56.7%) were under the age of 39. In terms of discrimination related to their attraction to other men, participants reported high levels of intimidation (31.9%), verbal abuse (22.1%) and physical violence (1.5%) in the previous year. Regarding mental health, 23.9% had a moderate to severe depression/anxiety score. Almost two-thirds (64.1%) indicated substance use and one-fifth (21.5%) reported chemsex (or the use of stimulant drugs to make sex more intense or last longer). Only 8.4% of participants reported use of PrEP for HIV; however, 51.7% reported being likely to use PrEP if it was available and affordable. Sexual practices, such as condom use, varied by PrEP use with 91.3% of men using PrEP reporting condomless anal intercourse (CAI) compared with 71.5% of men not on PrEP. In terms of STBBI testing, 1.5% reported being diagnosed with hepatitis C and 9.0% reported an HIV diagnosis. Of those with an HIV diagnosis, most were on treatment (99.1%) and had an undetectable viral load (96.7%). CONCLUSION: gbMSM in Canada experienced stigma, discrimination and mental health problems; substance use was high as were high-risk sexual practices, such as CAI, among some groups of men. There was a gap between the proportion of men who were interested in PrEP and those who actually used it; and comprehensive STBBI testing was low.These findings can inform public health action and provide a baseline to examine the impact of current and new interventions.

A review of Human Immunodeficiency Virus (HIV) rapid testing.

BACKGROUND: In Canada, it is estimated that 71,300 persons were living with HIV at the end of 2011. Approximately 25% (14,500 to 21,500) of prevalent cases were unaware of their HIV infection. Expanded use of HIV rapid tests may increase the detection of undiagnosed infections, enable earlier treatment and support services and prevent the onward transmission of HIV. OBJECTIVE: To examine patient acceptability, impact (defined as receipt of test results and linkage to care) and cost-effectiveness of HIV rapid tests. METHODS: A search was conducted for systematic reviews on HIV rapid testing, with studies from both developed and developing countries, published in English and between 2000 and 2013. The Assessment of Multiple Systematic Review (AMSTAR) tool was used to assess the included systematic reviews for methodological quality. Results were summarized narratively for each of the outcomes. RESULTS: Eight systematic reviews were included. Acceptability of HIV rapid tests was generally high in medical settings (69% to 98%) especially among pregnant women and youth attending emergency rooms but was lower in non-medical settings (14% to 46%). The percentage of people who obtained their test results was variable. It was high (83% to 93%) in emergency rooms but was low in a rapid care setting with regular business hours (27%). Impact on linkage to care was limited. Only one systematic review examined cost-effectiveness of rapid testing and concluded that HIV rapid tests were cost-effective in comparison to traditional methods; however, results were all based on static models. CONCLUSION: Overall, HIV rapid tests demonstrated generally high acceptability, variability in receiving test results and limited impact on linkage to care. While these findings suggest that HIV rapid tests may be useful, further research is needed to confirm in whom, when and where they are best used and how to ensure better linkage to care.

BRIEF - SYNOPSIS OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV) SCREENING AND TESTING GUIDE.

BACKGROUND The Public Health Agency of Canada (PHAC) estimates that, in 2011, 25% of people living with HIV in Canada were undiagnosed. Hesitation to seek testing may arise from fear, stigma and discrimination associated with the HIV diagnosis and related risk behaviours. This guide is designed to complement existing efforts to support care providers involved in HIV testing, in order to reduce the number of undiagnosed HIV infections in Canada. APPROACH PHAC commissioned a literature review and consulted with provinces and territories, and key stakeholders, including people living with HIV/AIDS, academics, nurses, physicians, professional associations, non-governmental organizations, policy-makers, community workers, and legal and ethical experts. As a result, the recommendations outlined in the guide are based on the most up-to-date evidence and expert opinion. SCREENING AND TESTING GUIDE The consideration and discussion of HIV testing should be made a component of routine periodic medical care. Offering HIV testing routinely can help normalize testing, and address the multiple barriers to reducing the number of undiagnosed cases in Canada. Begin with a brief explanation to the client on how HIV is transmitted: through unprotected sex, the sharing of drug-use equipment, and from a pregnant mother to her child. Clients can then consider their own situation and indicate whether they would like to have an HIV test. Upon request, a risk assessment may be conducted. As with other tests, testing is voluntary and verbal consent is sufficient. Negative test results provide an opportunity to remind clients of those practices that can help them maintain an HIV-negative status. There are a range of referrals and resources available to assist clients in reducing at-risk activities and maintaining a negative status. Those who are part of a couple should be encouraged to discuss HIV testing with their partners so they're not unknowingly involved in a serodiscordant relationship. Positive test results should always be provided in person and ideally by the initial care provider who has information resources and support referrals at the ready. An HIV positive diagnosis can be difficult news; it is important to take the time to discuss the results and answer any questions the client might have. Focus on positive messages by highlighting advances in HIV care, treatment and support. Note that HIV is now considered a chronic illness, and people living with HIV can live long, active and healthy lives. Advise the client about strategies for managing HIV and link them to care. Provide risk reduction information to prevent transmission Make the client aware that positive test results will be shared confidentially with the local public health department, which can assist in notifying previous and current partners of the need to be tested while protecting the client's anonymity and privacy. Strategies for informing past, current and future partners can be reviewed. If not already completed with the HIV test, clients should be tested for other STIs, hepatitis B and C, and tuberculosis.

BRIEF - SYNOPSIS OF THE CURRENT EVIDENCE ON THE RISK OF HIV TRANSMISSION.

BACKGROUND: Knowledge of the risk of HIV transmission has evolved over the past decade as evidence on the impact of biological and behavioural co-factors, such as viral load, has come to light. We undertook a comprehensive review of the evidence on the risk of HIV transmission. METHODS: A search was conducted for literature published between January 2001 and May 2012. The search focused on systematic, meta-analytic, and narrative reviews. For topics where no reviews existed, primary research studies were included. RESULTS: The risk estimates for the sexual transmission of HIV, per sex act, ranged from 0.5% to 3.38% (with mid-range estimates of 1.4% to 1.69%) for receptive anal intercourse; 0.06% to 0.16% for insertive anal intercourse; 0.08% to 0.19% for receptive vaginal intercourse; and approximately 0.05% to 0.1% for insertive vaginal intercourse. For people who inject drugs, the risk of transmission from a contaminated needle, per injection, was estimated to be between 0.7% and 0.8%. A number of factors impact the risk, including viral load, the presence of other sexually transmitted infections (STIs), and male circumcision. CONCLUSIONS: Within each route of transmission, estimates of the risk of transmission varied widely, likely due to the role of behavioural and biological co-factors. Viral load appears to be an important predictor of transmission, regardless of the route of transmission. However, the evidence indicates that viral load is not the only determinant and that certain co-factors play a role in increasing (e.g., STIs) or decreasing (e.g., male circumcision) the risk of transmission.

Video-electroencephalography in conscious non human primate using radiotelemetry and computerized analysis: refinement of a safety pharmacology model.

INTRODUCTION: Electroencephalography (EEG) investigations are occasionally required as follow-up studies for safety pharmacology core battery (S7A). Video-EEG monitoring is a standard diagnostic tool in humans but limited data is available on its use in telemetered freely moving macaque monkeys for safety pharmacology investigations. While proconvulsant risk evaluations are routinely conducted in rodents, pharmacological or pharmacokinetic considerations lead to the use of non human primates in toxicology and safety pharmacology in some cases. METHODS: Cynomolgus monkeys were instrumented with telemetry implants. Placement of EEG electrode was based on the 10-20 system using three derivations (C3-O1, Cz-Oz and C4-O2). EEG trace analysis was carried out using NeuroScore software. After 24 h of continuous video-EEG monitoring, animals received pentylenetetrazole (PTZ, 10 mg/kg/15 min) until convulsions were noted. Convulsions were immediately treated with diazepam (1.0 mg/kg). A seizure detection protocol with a dynamic spike train threshold was used for the entire EEG monitoring period (total of 44 h) including periods when PTZ was administered. Spectral analysis was done to quantify the absolute and relative amplitude of EEG frequency bands (delta, theta, alpha, sigma and beta waves). Sleep stages were quantified and EEGs during seizures were analyzed using fast Fourier transformation (FFT) to assess dominant frequencies. RESULTS: Spike trains were detected by computerized analysis in all animals presenting PTZ-induced seizures while paroxysmal activities were systematically predictive (at least 4-min prior to generalized seizures). Beta activity increased with visual stimulation using monkey treats. Characteristics of EEG for all sleep stages (I, II, III and IV) were present in all animals. Delta activity was predominant in normal awake EEG as well as in all sleep stages. Seizure peak frequency was 3-6 Hz on FFT, corresponding to the discharge of the underlying generator. DISCUSSION: EEG-video monitoring can be useful when using non human primates to characterize neurological adverse effects with unpredictable onset. Computerized video-EEG analysis was a valuable tool for safety pharmacology investigations including proconvulsant risk assessment, spectral analysis of frequency bands and sleep stage determination.

EVA copolymer matrix for intra-oral delivery of antimicrobial and antiviral agents.

Biocompatible ethylene vinyl acetate copolymer (EVA) was utilized to study the release of an antiviral drug (acyclovir (ACY)) and an antimicrobial drug (doxycycline hyclate (DOH)). Release of both drugs from EVA was measured individually and in combination. The effect of drug combination of DOH and ACY is presented. Additionally, the release rate of DOH after coating of the matrix with a different copolymer, in drug-loading with increasing loads of DOH, and with increases in temperature are also presented. The drugs incorporated in EVA films were prepared from the dry sheet obtained by solvent evaporation of polymer casting solutions with drugs. Drug release from the films was examined for about 12 days in distilled water at 37 degrees C. Changes in optical density were followed spectrophotometrically. The combination of ACY and DOH resulted in an increased release of ACY by about three times (P < 0.001) while DOH showed a decrease in rate of about two times compared to the individual release rates (P = 0.008). Increases in drug levels of DOH resulted in increases in drug release rates (P = 0.001). The release rate of DOH increased with temperature (P = .001; 27, 32, 37 and 42 degrees C were studied) and the energy of activation (DeltaE ( not equal) = 56.69 kJ/mol) was calculated using the Arrhenius equation for the diffusion of DOH molecules. Thus, the release rates of drugs were influenced by many factors: drug combination, coating the device, drug-loading, and temperature variation. Therefore it is proposed that controlling these variables should make it possible to obtain therapeutic levels of drugs released from drug loaded polymer, which may be beneficial in treating oral infections.

An observational study of sun and heat protection during Canada Day outdoor celebration, 2003.

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.

Periodontal disease -- the emergence of a risk for systemic conditions: pre-term low birth weight.

This paper addresses the problem of adverse pregnancy outcome in relation to periodontal disease. There is compelling evidence that a link exists between pre-term low birth weight (PLBW) and periodontitis. Although 25% to 50% of PLBW deliveries occur without any known aetiology, there is increasing evidence that infection may play a significant role in pre-term delivery. A model explaining the plausible relationship is proposed based upon the concept of infection leading to a cascade of inflammatory reactions associated with pre-term labour and periodontal disease. Current evidence has pointed to an interest in dental intervention studies to control periodontal disease as one of the potential strategies to reduce pre-term labour. This paper reviews the potential association between periodontal infection and adverse pregnancy outcomes.

Clinical relevance of adjunctive minocycline microspheres in patients with chronic periodontitis: secondary analysis of a phase 3 trial.

BACKGROUND: A recent Phase 3 trial demonstrated that adjunctive treatment with minocycline microspheres resulted in significant reductions in patient mean probing depths as compared to scaling and root planing (SRP) alone. The objective of the present study was to evaluate clinical relevance of these changes within the trial using proposed site-based criteria. METHODS: A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multi-center trial and randomized to either: 1) SRP alone or 2) SRP plus minocycline microspheres. Subjects received complete probing examinations including the measurement of probing depths at baseline, and 1 and 3 months. Probing depth reductions were tabulated by treatment, examination time, and baseline depths, and inter-group differences were evaluated with logistic regression models for correlated data. RESULTS: Significantly more sites treated with adjunctive minocycline microspheres exhibited probing depths < 5 mm at 1 (P = 0.0009) and 3 (P = 0.01) months as compared to sites treated with SRP alone, both in the overall population and in smokers. In addition, significantly more sites decreased by 1, 2, or 3 mm in the adjunctive minocycline group than in the SRP alone group at 1 and 3 months, both overall as well as in smokers (P < 0.05). CONCLUSION: This secondary analysis indicates that treatment with SRP plus minocycline microspheres is consistently more effective than SRP alone in providing clinically relevant site-based responses in patients with chronic periodontitis.

Safety and clinical effects of topical histatin gels in humans with experimental gingivitis.

BACKGROUND: Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997). OBJECTIVES: The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design). MATERIAL AND METHODS: One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI < 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP. RESULTS: All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p < 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP < 15 or < 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p < 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using > 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p < 0.05). CONCLUSIONS: These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.

Evaluation of tuned aperture computed tomography (TACT) in the localization of simulated periodontal defects.

OBJECTIVES: To compare the diagnostic efficacy of tuned aperture computed tomography (TACT) with the application of the 'buccal object rule' (BOR) in the localization of simulated periodontal defects. METHODS: Thirty interproximal sites were selected in fifteen cadaver segments of maxillae and mandible. Artificial periodontal defects were created using round burs and 40% formic acid in the buccal, lingual or mid-buccolingual areas. Eight basis projections were obtained and TACT slices were reconstructed for each region of interest. Two of the basis images were used in application of BOR for localization of the defect. Eight observers scored the location of defects using TACT slices and the paired radiographs separately. Data were analysed using the kappa statistic and ANOVA. RESULTS: A mean weighted kappa of 0.14 for localization was obtained with both BOR and TACT. Using ANOVA, there was no significant difference between modality and observer. There was however, a significant difference (P=0.019) between different defect sizes. Both modalities performed better with larger defect sizes. TACT performed slightly better than BOR when the smaller lesions were included; however, with larger lesions, this trend was reversed. CONCLUSIONS: The results confirm the relationship between correlation distance (the resultant slice width) and object size in the application of TACT for localization. BOR remains a simple yet effective tool for localization. The clinical significance is not clear considering the low kappa scores obtained with both the modalities.

Toxicity of human adenovirus E4orf4 protein in Saccharomyces cerevisiae results from interactions with the Cdc55 regulatory B subunit of PP2A.

The E4orf4 protein of human adenovirus induces p53-independent apoptosis, a process that may promote cell death and viral spread. When expressed alone, E4orf4 kills transformed cells but not normal human cells. The only clear target of E4orf4 in mammalian cells is the Balpha (B55) subunit of protein phosphatase 2A (PP2A), a member of one of three classes of regulatory B subunits. Here we report the effects of E4orf4 in Saccharomyces cerevisiae, which encodes two PP2A regulatory B subunits, CDC55 and RTS1, that share homology with mammalian B and B' subunits, respectively. E4orf4 expression was found to be toxic in yeast, resulting in the accumulation of cells in G2/M phase that failed to grow upon removal of E4orf4. E4orf4-expressing yeast also displayed an elongated cell morphology similar to cdc55 deletion strains. E4orf4 required CDC55 to elicit its effect, whereas RTS1 was dispensable. The recruitment of the PP2A holoenzyme by E4orf4 was entirely dependent on Cdc55. These studies indicate that E4orf4-induced apoptosis in mammalian cells and cell death in yeast require functional interactions with B-type subunits of PP2A. However, some inhibition of growth by E4orf4 was observed in the cdc55 strain and with an E4orf4 mutant that fails to interact with Cdc55, indicating that E4orf4 may possess a second Cdc55-independent function affecting cell growth.

Short-contact topical tretinoin therapy to stimulate granulation tissue in chronic wounds.

BACKGROUND: The use of retinoids in wound healing is increasing. It has been shown that retinoic acid reverses the inhibitory effects of glucocorticoids on wound healing and accelerates the formation of healthy granulation tissue. Pretreatment with tretinoin before epidermal injury such as chemical peeling and dermabrasion has shown accelerated wound healing. Enhanced healing of full-thickness skin wounds has also been demonstrated in early wound healing studies. However, tretinoin therapy can be quite irritating. OBJECTIVE: Our purpose was to observe the clinical and histologic effects of topical tretinoin solution 0.05% applied directly to the wound beds of chronic leg ulcerations. METHODS: We report on the cases of 5 patients with long-standing leg ulcerations. All were treated with topical tretinoin solution 0.05% applied directly to the wound bed. The tretinoin solution was left in contact with the ulcer bed for a maximum of 10 minutes daily and then rinsed with normal saline. Punch biopsy specimens were obtained from the wound beds at baseline and mid therapy. Standard wound care was continued throughout the study. RESULTS: In this study we found that as early as 1 week after treatment with topical tretinoin solution 0.05%, there was increased granulation tissue first noted at the wound's edge. After 4 weeks of therapy with tretinoin, there was further stimulation of granulation tissue, new vascular tissue, and new collagen formation. CONCLUSION: Short-contact tretinoin therapy is a novel modality in which to treat chronic ulcers and stimulate the formation of granulation tissue.

Detection of specific antibodies using immunosubtraction and capillary electrophoresis instrumentation.

Solution-phase immunoassays based on capillary electrophoresis (CE) separations have been shown to be rapid and simple to perform. The potential for sample matrix interference and incompatibility with multiplexing conditions for antibody detection when dealing with real samples, however, has prompted the development of an assay that utilizes an immunosubtraction methodology. A model assay for the detection of specific antibodies that relies on solid-phase extraction, CE and laser-induced fluorescence (LIF) detection is described. The method, called immunocapture-immunosubtraction (ICIS), incorporates an antibody capture/purification protocol using magnetic particles. The detection of specific antibodies is achieved by CE-LIF analysis of a probe solution following incubation with the captured antibodies. As an example of the ICIS assay's capabilities, the relative quantification of anti-fluorescein in serum is presented.

A multicenter 12-month evaluation of single-tooth implants restored 3 weeks after 1-stage surgery.

The time-intensive, multi-step process of dental implant therapy limits patient acceptance. This 3-year prospective multicenter study sought to determine the safety of an expedited therapy that consisted of loading unsplinted maxillary anterior single-tooth implants 3 weeks after 1-stage surgical placement, and determination of the peri-implant cortical bone and mucosal responses to the expedited procedure. Fifty-two patients missing 1 or 2 maxilliary anterior teeth were enrolled in a study approved by the Institutional Committee on Human Subjects Research and based on strict inclusion and exclusion criteria. Astra Tech ST implants placed in a 1-stage procedure were restored 3 weeks later with ST abutments and a provisional crown (baseline); 7 to 9 weeks later, a porcelain-fused-to-metal or all-ceramic crown was cemented. Radiographic and clinical examinations were made at baseline and at 6 and 12 months. Implant survival was recorded. Cortical bone responses and peri-implant mucosal responses were evaluated. Fifty-eight implants were placed. During the 3-week period after implant placement, 4 patients were dismissed because of smoking cigarettes (a protocol deviation), and 1 patient was excluded because of deviation in loading time. Of the remaining 53 implants, 2 failed before definitive crown cementation. The resultant 96.2% survival rate was independent of implant length, tooth position, and bone quality/quantity. The mean change in marginal bone level was 0.4 mm at 12 months. The number of surfaces with plaque decreased from 3.4% at baseline to 0.5% at 12 months. The surfaces with inflammation also decreased. A mean gain in papilla length of 0.61 mm occurred, and a gain in buccal gingiva (x = 0.34 mm) was observed. A high success rate with positive tissue responses was achieved for maxillary anterior unsplinted single-tooth implants placed in a 1-stage surgery and restored at 3 weeks. This 2-component system is suited to a single-stage, rapid loading protocol for esthetic single-tooth replacement.

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Performance of screening mammography in organized programs in Canada in 1996. The Database Management Subcommittee to the National Committee for the Canadian Breast Cancer Screening Initiative.

BACKGROUND: The results of randomized trials show that breast cancer screening by mammography reduces breast cancer mortality by up to 40% in women aged 50-69 years. Because of these results, by 1998, 22 countries, including Canada, had established population-based organized screening programs. This paper presents the results of screening mammography in 1996 for 7 provincially organized breast cancer screening programs in Canada. METHODS: Analyses of interim performance indicators for screening mammography have been calculated from data submitted to the Canadian Breast Cancer Screening database. The data set consisted of data from 7 provincial programs and was limited to mammographic screens for women aged 50-69 years (n = 203,303). Screening outcomes and performance indicators were calculated for abnormalities detected by screening mammography only. RESULTS: The abnormal recall rate was 9.5% for first screens and 4.6% for subsequent screens, and the cancer detection rate per 1000 women screened was 6.9 for first screens and 3.8 for subsequent screens. The positive predictive value (i.e., the proportion of women who tested positive by mammography who were found to have breast cancer on screen-initiated diagnostic work-up) increased from 7.2% at the first screen to 8.2% at subsequent screens. Estimated participation rates within organized programs varied from 10.6% to 54.2%, depending on the province. INTERPRETATION: For 1996, organized breast cancer screening programs met or exceeded many of the interim measures used in international programs. It is possible to translate the benefits of breast cancer screening by mammography, as demonstrated in randomized trials, into population-based community programs. Screening mammography through organized programs should increase to allow more comprehensive monitoring in Canada.

Induction of p53-independent apoptosis by the adenovirus E4orf4 protein requires binding to the Balpha subunit of protein phosphatase 2A.

Previous studies have indicated that the E4orf4 protein of human adenovirus type 2 (Ad2) induces p53-independent apoptosis. We believe that this process may play a role in cell death and viral spread at the final stages of productive infection. E4orf4 may also be of therapeutic value in treating some diseases, including cancer, through its ability to induce apoptosis when expressed individually. The only previously identified biochemical function of E4orf4 is its ability to associate with the Balpha subunit of protein phosphatase 2A (PP2A). We have used a genetic approach to determine the role of such interactions in E4orf4-induced cell death. E4orf4 deletion mutants were of only limited value, as all were highly defective. We found that E4orf4 proteins from most if not all adenovirus serotypes induced cell death, and thus point mutations were introduced that converted the majority of highly conserved residues to alanines. Such mutants were used to correlate Balpha-subunit binding, association with PP2A activity, and cell killing following the transfection of appropriate cDNAs into p53-null H1299 or C33A cells. The results indicated that binding of the Balpha subunit is essential for induction of cell death, as every mutant that failed to bind efficiently was totally defective for cell killing. This class of mutations (class I) largely involved residues between amino acids 51 and 89. Almost all E4orf4 mutant proteins that associated with PP2A killed cancer cells at high levels; however, several mutants that associated with significant levels of PP2A were defective for killing (class II). Thus, binding of E4orf4 to PP2A is essential for induction of p53-independent apoptosis, but E4orf4 may possess one or more additional functions required for cell killing.

Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis.

The reported therapeutic benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) in slowing periodontal disease progression appear intimately linked to the effective inhibition of local prostaglandin synthesis. This randomized, partially double-blind, controlled trial was conducted to evaluate the pharmacodynamic effects of the NSAID, ketoprofen (KTP), on gingival crevicular fluid (GCF) prostanoids. 42 subjects, ages 35-57 years, with moderate to advanced adult periodontitis were recruited and monitored for 22 days. On day 1, subjects were randomized for 1 of 5 treatments: i) 0.5% KTP gel; ii) 1.0% KTP gel; iii) 1.0% KTP alternate gel; iv) 2.0% KTP gel; v) 25 mg KTP capsule (positive control). Subjects applied 1 ml of gel topically to their gingiva or administered one capsule p.o., b.i.d. for 14.5 days. GCF samples were collected from posterior, interproximal sites on days 1 (pre-dosing; 1, 2, 3, 6 h), 8 (pre-dosing; 2 h), 15 (pre-dosing; 2 h) and 22 (post-treatment). GCF levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were determined using RIA, and expressed in ng/ml and % reduction from baseline (%Effect). Neither a significant difference among groups nor a dose response in % effect for either prostanoid was evident, both overall and among cohorts with elevated baseline mediator levels ([PGE2]>34 ng/ml; [LTB4]>300 ng/ml). When data were combined from all groups, significant (p<0.01) % reductions in GCF PGE2 were noted at 1 and 2 h post-dosing (29% and 24% respectively). In comparing topical versus systemic formulations, all topical formulations were as equipotent as systemic dosing in altering local prostaglandin levels despite lower KTP exposures with gel treatments. These data indicate that both topical and systemic KTP therapies pharmacodynamically reduce GCF PGE2 levels in adult periodontitis subjects, allowing for potential inhibition of disease progression.

Selected topics related to occupational exposures.

The auditory and nonauditory effects of noise can be quite profound, affecting approximately 15 to 20 million Americans. As with most occupational toxins, recognition and careful assessment of noise exposure are the foundation on which preventive measures and treatment are based. Dosimeters can measure noise exposure over specific time periods. Pure tone air conduction audiometric monitoring should be performed on an annual basis in workers at risk for significant noise exposure. Occupational infectious disease involves far more than hepatitis and tuberculosis. Periodic fever, dermatologic manifestations and other symptoms peculiar to a specific disease may be important clues to an occupationally related exposure. Whereas strict attention to hand washing and isolation are cornerstones of prevention, use of protective gear is mandated in certain situations. Zoonotic disease, agriculture exposure, water transmission, and biologic contaminants in buildings can be important but subtle exposures sources. Recognition of these infections often depends on the alertness of the primary care giver.