Intermittent versus continuous androgen suppression therapy: do we have consensus yet?

Androgen deprivation therapy (ADT) has been a cornerstone in the management of advanced prostate cancer for more than 50 years, but several aspects of the therapy remain controversial. Research since the mid-1980s has looked at the use of intermittent androgen suppression (IAS) as a way to reduce the side effects and costs of continuous androgen suppression. During that same time, testing for prostate-specific antigen resulted in forward stage migration both at diagnosis and at the time of treatment initiation. Earlier treatment has led to prolonged periods of ADT and increasing recognition of the resultant metabolic complications. With preclinical evidence suggesting a potential benefit for ias in terms of time to androgen independence, with phase II and III studies producing optimistic results, and with the potential for reductions in cost and complications, ias has become a popular modality of therapy around the globe. Large prospective randomized studies, currently ongoing, will ultimately determine the legitimate place of IAS in the treatment of prostate cancer.

Interferon-inducible factor 16 is a novel modulator of glucocorticoid action.

Previously, we used cDNA expression profiling to identify genes associated with glucocorticoid (Gc) sensitivity. We now identify which of these directly influence Gc action. Interferon-inducible protein 16 (IFI16), bone morphogenetic protein receptor type II (BMPRII), and regulator of G-protein signaling 14 (RGS14) increased Gc transactivation, whereas sialyltransferase 4B (SIAT4B) had a negative effect. Amyloid beta (A4) precursor-protein binding, family B, member 1 (APBB1/Fe65) and neural cell expressed developmentally down-regulated 9 (NEDD9) were without effect. Only IFI16 potentiated Gc repression of NF-kappaB. In addition, IFI16 affected basal expression, and Gc induction of endogenous target genes. IFI16 did not affect glucocorticoid receptor (GR) expression, ligand-dependent repression of GR expression, or the ligand-dependent induction of GR phosphorylation on Ser-211 or Ser-203. Coimmunoprecipitation revealed an interaction, suggesting that IFI16 modulation of GR function is mediated by protein crosstalk. Transfection analysis with GR mutants showed that the ligand-binding domain of GR binds IFI16 and is the target domain for IFI16 regulation. Analysis of human lung sections identified colocalization of GR and IFI16, suggesting a physiologically relevant interaction. We demonstrate that IFI16 is a novel modulator of GR function and show the importance of analyzing variation in Gc sensitivity in humans, using appropriate technology, to drive discovery.

Urban and rural patterns of bicycle helmet use: factors predicting usage.

OBJECTIVES: To document current bicycle helmet use in Winnipeg, Manitoba and nearby rural communities, and to identify target groups for a helmet promotion campaign. METHODS: Cyclist helmet use was observed between 28 May and 20 August 1996 at a sample of urban and rural locations. Age, gender, helmet use, riding companion(s), location type, correct helmet use, and use of headphones were recorded. Univariate and multivariate analyses were performed. Adjusted odds ratios with 95% confidence intervals were calculated from the final models. RESULTS: Altogether 2629 cyclists (70% male, 30% female) were observed: 2316 at 183 urban locations and 313 at 25 rural locations, with nearly equal numbers of children and adults observed. Overall helmet use was 21.3%, with lower use in males (18.9%) than females (26.3%), despite gender only being a significant variable on multivariate analysis for children under 8 years and adults. Urban helmet use was considerably higher (22.9%) than rural use (8.9%). Helmet use increased linearly as mean neighbourhood income increased, with a nearly fourfold difference in use between the highest and lowest income neighbourhoods. Children less than 8 years old and adults had the highest, and teenagers the lowest, use. Significant predictive variables were identified separately by age category to inform targeted programming. CONCLUSIONS: We documented low helmet use in our region, emphasizing the need for a regional helmet promotion campaign as well as future helmet legislation. A marked urban-rural difference in helmet use that has not been previously reported was also identified. Target groups for a future campaign include adolescents, males, rural cyclists, and those in lower income neighbourhoods.

An observational study of protective equipment use among in-line skaters.

OBJECTIVES: To describe the patterns of protective equipment use by in-line skaters in Winnipeg, Manitoba and nearby rural communities. METHODS: In-line skaters were observed for three months in 1996 at 190 urban and 30 rural sites selected using a formal sampling scheme. Age, gender, protective equipment use, skating companions, correct helmet use, and use of headphones were recorded. RESULTS: Altogether 123 in-line skaters were observed at 61 sites, including one rural site. No skaters were observed at the remaining sites. There were 37 adults and 86 children; 56% were male. Helmet use was 12.2% (95% confidence interval (CI) = 6.4% to 18.0%), wrist guard use was 16.3% (95% CI = 9.7% to 22.8%), knee pad use was 9.8% (95% CI = 5.2% to 16.4%), and elbow pad use was 7.3% (95% CI = 3.4% to 13.4%). Children were more likely to wear a helmet than teens 12-19 years of age (relative risk (RR) = 30, 95% CI = 4.01 to 225). Adults were more likely to wear wrist guards than children (RR = 4.32, 95% CI = 1.87 to 9.94). No gender differences were found. Incorrect helmet use was documented in four skaters; three skaters were wearing headphones. CONCLUSIONS: Low rates of protective equipment use were documented in our region, significantly lower than those reported in the literature. Barriers to equipment use are not known, and should be examined by further study. In-line skating safety programs should be developed, promoted, and evaluated. Teens should be targeted for future preventive efforts.

All terrain vehicle ownership, use, and self reported safety behaviours in rural children.

OBJECTIVES: To describe all terrain vehicle (ATV) ownership, access, use, and safety behaviours in rural Manitoba children. METHODS: Questionnaire administered to a convenience sample of grade 6 students attending an agricultural fair. RESULTS: 162 grade 6 children participated. The mean age was 11.4 years, and 46% were male. 125 students (77%) reported having access to ATVs, including 69 four wheeled, 24 three wheeled, and four both three and four wheeled ATVs. ATV experience was reported in 95 students, significantly more often in males and among those with a family owned ATV, with no difference between children living on a farm and in a town. Use of helmets and protective clothing was inadequate (10-40%), and dangerous riding habits common, with males and children living on a farm reporting significantly fewer desirable behaviours. CONCLUSIONS: ATVs are commonly used by children in rural Manitoba, with inadequate protective gear and dangerous riding habits. Mandatory rider training, consumer and dealer education, and legislation enforcement could improve ATV safety in this population.

Computer analysis of amino acid chromatograms.

A procedure is described for the automatic off-line analysis of amino acid chromatograms of protein hydrolysates, using a small computer. The data requirements are basic, and, unlike previous programs, the present system allows the separation and identification of bands, as well as the quantitative determination of composition. With minor modification, the program could be extended for use with most types of chromatographic data. The validity of the application of the program to experimental data is discussed.