Promoting better use of the PSA test in general practice: Randomized controlled trial of educational strategies based on outreach visits and mailout

Background. Prostate-specific antigen (PSA) testing for prostate cancer is controversial. Demand for PSA testing is likely to rise in the UK, Australia and other western countries. Primary care needs to develop appropriate strategies to respond to this demand. Objectives. Our aim was to compare the effectiveness of educational outreach visits (EOVs) and mailout strategies targeting PSA testing in Australian primary care. Methods. A randomized controlled trial was conducted in general practices in southern Adelaide. The main outcome measures at baseline, 6 months and 12 months post-intervention were PSA testing rates and GP knowledge in key areas relating to prostate cancer and PSA testing. Results. The interventions were able to demonstrate a change in clinical practice. In the 6 months post-intervention, median PSA testing rate in the EOV group was significantly lower than in the postal group, which in turn was significantly lower than the control group (P < 0.001). Statistically significant differences were not, however, maintained in the 6-12 month post-intervention period. The EOV group, at 6 months follow-up, had a significantly greater proportion of 'correct' responses than the control group to questions about prostate cancer treatment effectiveness (P = 0.004) and endorsement of PSA screening by professional bodies (P = 0.041). Conclusions. Primary care has a central role in PSA testing for prostate cancer. Clinical practice in this area is receptive to evidence-based interventions.

Effect of inspiratory flow on methacholine challenge in children

Regulation of inspiratory flow alters the outcomes of the methacholine (MHC) challenge in adults and cough receptor sensitivity in children. The effect of inspiratory flow on the reproducibility of the MHC challenge in children is unknown. The aim of this study was to evaluate the effect of inspiratory flow alteration on the repeatabilty of the MHC challenge in children with and without asthma. Twenty-five children undertook the MHC challenge on three different days by using a dosimeter connected to a setup that allowed regulation of inspiratory flow and pattern. Children were randomized to commence the challenges at 20 or 60 L/min, and the last challenge was performed at 20 L/min. The within-subject standard deviation, 95% range for change, and doubling dose for the differing inspiratory flow (20 vs. 60 L/min) was more than twice that of when inspiratory flow was maintained at 20 L/min for both occasions. The range of the limits of agreement of the Bland and Altman plot was smaller when inspiratory flow was constant. For short-term comparative individual studies in children, inspiratory flow should be regulated. Laboratories and research measuring change in airway hyperrepsonsiveness to MHC should determine and report reproducibility indices of the challenge so airway hyperresponsiveness changes can be interpreted meaningfully.

Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet

Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring (ESTring) to that of a vaginal estradiol tablet (Vagifem®) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency. Quality of life and acceptability of treatment delivery were also assessed. Study design A prospective, randomized study in which women were assigned in a 2: 1 ratio to ESTring and Vagifem and followed for 12 months. The primary endpoint was endometrial safety, based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48. Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3, 12, 24, 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline, 12 and 48 weeks. In addition, pelvic floor strength, vaginal cytological evaluation and pH, bacteruria and patient acceptability were assessed. Quality of life was assessed using a menopause-specific quality-of-life questionnire and a 2-day bladder diary at baseline and 12 and 48 weeks. The comparability of the two groups was assessed using ANOVA, χ(2) or Fisher's exact tests. Results A total of 126 women were randomized to ESTring and 59 to Vagifem. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency. Maturation indices increased in both groups, from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks. After 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. A statistically smaller proportion of bleeding/spotting occurred in the ESTring group (n = 0) compared to the Vagifem users (n = 4). Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range. General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups. Bladder diary variables showed no differences between treatment groups. Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.

Involuntary glottal closure during inspiration in muscle tension dysphonia

Objective/Hypothesis: The purpose of this study was to examine respiratory function in a group of patients with muscle tension dysphonia (MTD) Design: Cross-sectional analytical study. Methods: Participants included 15 people with a diagnosis of MTD referred to speech pathology for management of their voice disorder, fiberoptic evidence of glottal or supraglottic constriction during phonation with or without posterior chink, or bowing combined and deviation in perceptual voice quality. A second group of 15 participants with no history of voice disorder served as healthy controls,. Baseline pulmonary function test measures included forced expiratory volume in the first second (FEV1), FVC, FEF25 to 75, FIF50, FEV1/FVC, ratio and FEF50/FIF50 ratio. Hypertonic saline challenge test measures included FEV1 and FIF50 after provocation, close response slope, and provocation dose. Results: Compared with healthy controls, participants with MTD demonstrated a higher prevalence of glottal constriction during inspiration after provocation with nebulized hypertonic saline as demonstrated by a reduction in FIF50 after the hypertonic saline challenge. There was no significant difference between the MTD and healthy control groups in baseline pulmonary function testing. Participants with MTD demonstrated a higher prevalence than healthy controls of abnormal glottic closure during inspiration similar to paradoxical vocal fold movement (PVFM). This suggests that they either had previously undiagnosed coexisting PVFM or that the condition of MTD could be expanded to include descriptions of aberrant glottic function during respiration. This study enhances the understanding of PVFM and MTD by combining research advances made in the fields of otolaryngology and respiratory medicine.

Evaluating the properties of a stage-specific self-efficacy scale for physical activity using classical test theory, confirmatory factor analysis and item response modeling

The purpose of this paper was to evaluate the psychometric properties of a stage-specific selfefficacy scale for physical activity with classical test theory (CTT), confirmatory factor analysis (CFA) and item response modeling (IRM). Women who enrolled in the Women On The Move study completed a 20-item stage-specific self-efficacy scale developed for this study [n = 226, 51.1% African-American and 48.9% Hispanic women, mean age = 49.2 (67.0) years, mean body mass index = 29.7 (66.4)]. Three analyses were conducted: (i) a CTT item analysis, (ii) a CFA to validate the factor structure and (iii) an IRM analysis. The CTT item analysis and the CFA results showed that the scale had high internal consistency (ranging from 0.76 to 0.93) and a strong factor structure. Results also showed that the scale could be improved by modifying or eliminating some of the existing items without significantly altering the content of the scale. The IRM results also showed that the scale had few items that targeted high self-efficacy and the stage-specific assumption underlying the scale was rejected. In addition, the IRM analyses found that the five-point response format functioned more like a four-point response format. Overall, employing multiple methods to assess the psychometric properties of the stage-specific self-efficacy scale demonstrated the complimentary nature of these methods and it highlighted the strengths and weaknesses of this scale.

Role of generalized and episode specific memories in the word frequency effect in recognition

Frequency, recency, and type of prior exposure to very low-and high-frequency words were manipulated in a 3-phase (i.e., familiarization training, study, and test) design. Increasing the frequency with which a definition for a very low-frequency word was provided during familiarization facilitated the word's recognition in both yes-no (Experiment 1) and forced-choice paradigms (Experiment 2). Recognition of very low-frequency words not accompanied by a definition during familiarization first increased, then decreased as familiarization frequency increased (Experiment I). Reasons for these differences were investigated in Experiment 3 using judgments of recency and frequency. Results suggested that prior familiarization of a very low-frequency word with its definition may allow a more adequate episodic representation of the word to be formed during a subsequent study trial. Theoretical implications of these results for current models of memory are discussed.

Sensitive and specific detection of Clavibacter xyli subsp. xyli, causal agent of ratoon stunting disease of sugarcane, with a polymerase chain reaction-based assay

A sensitive, specific polymerase chain reaction-based assay was developed for the detection of the causal agent of ratoon stunting disease of sugarcane, Clavibacter xyli subsp. xyli. This assay uses oligonucleotide primers derived from the internal transcribed spacer region between the 16S and 23S rRNA genes of the bacterial rRNA operon. The assay is specific for C. xyli subsp. xyli and does not produce an amplification product from the template of the closely related bacterium C. xyli subsp. cynodontis, nor from other bacterial species. The assay was successfully applied to the detection of C. xyli subsp. xyli in fibrovascular fluid extracted from sugarcane and was sensitive to approximately 22 cells per PCR assay. A multiplex PCR test was also developed which identified and differentiated C. xyli subsp. xyli and C. xyli subsp. cynodontis in a single PCR assay.

Season-specific directional movement in migratory Australian butterflies

Large numbers of adults of certain species of butterfly flying in an apparently 'purposeful' manner are often noted by entomologists and the general public. Occasionally, these are recorded in the literature. Using these records we summarise information regarding the direction of movement in Australian butterflies and test whether there are consistent patterns that could account for known seasonal shifts in geographical range. The data were analysed using contingency tables and directionality statistics. Vanessa itea, Vanessa kershawi, Danaus plexippus, Danaus chrysippus and Badamia exclamationis flew predominately south in the spring-summer and north in the autumn-winter. Tirumala hamata has a strong southern component to its flight in spring but, as in Euploea core, appears non-directional in the autumn. For many supposedly known migratory species, the number of literature records are few, particularly in one season (mainly autumn). Thus, for Appias paulina, four of seven records were south in the spring-summer, as were six of nine records for Catopsilia pomona, and three of five for Zizina labradus. For Belenois java, flight records were only available for the spring and these showed geographical differences; predominantly north-west in northern Australia (Queensland) and south-west in southern Australia (Victoria, New South Wales). There were too few records for Papilio demoleus in the literature (four only) to draw any conclusions. Major exceptions to the seasonal trend of south in the spring and north in the autumn were Junonia villida, which showed a predominant north-westward direction in both seasons, and Eurema smilax, with a predominant southern or western flight in both seasons. We discuss these species specific trends in migration direction in relation to seasonal shifts in suitable habitat conditions, possible cues used in orientation and in timing changes in direction.

Molecular characterization of the toxic cyanobacterium Cylindrospermopsis raciborskii and design of a species-specific PCR

Cylindrospermopsis raciborskii is a toxic-bloom-forming cyanobacterium that is commonly found in tropical to subtropical climatic regions worldwide, but it is also recognized as a common component of cyanobacterial communities in temperate climates. Genetic profiles of C. raciborskii were examined in 19 cultured isolates originating from geographically diverse regions of Australia and represented by two distinct morphotypes. A 609-bp region of rpoC1, a DNA-dependent RNA polymerase gene, was amplified by PCR from these isolates with cyanobacterium-specific primers. Sequence analysis revealed that all isolates belonged to the same species, including morphotypes with straight or coiled trichomes. Additional rpoC1 gene sequences obtained for a range of cyanobacteria highlighted clustering of C. raciborskii with other heterocyst-producing cyanobacteria (orders Nostocales and Stigonematales). In contrast, randomly amplified polymorphic DNA and short tandemly repeated repetitive sequence profiles revealed a greater level of genetic heterogeneity among C. raciborskii isolates than did rpoC1 gene analysis, and unique band profiles were also found among each of the cyanobacterial genera examined. A PCR test targeting a region of the rpoC1 gene unique to C. raciborskii was developed for the specific identification of C. raciborskii from both purified genomic DNA and environmental samples. The PCR was evaluated with a number of cyanobacterial isolates, but a PCR-positive result was only achieved with C, raciborskii. This method provides an accurate alternative to traditional morphological identification of C. raciborskii.

Antigen-specific suppression of inflammatory arthritis by dendritic cells

Purpose Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. We have shown that NF-κB inactivation in dendritic cells (modified DC) converts them into cells that tolerize rather than immunize to specific antigen [1]. Antigen-exposed modified DC prevent priming of immunity, and they suppress previously primed immune responses. Regulatory CD4+ T cells, which can transfer antigen-specific tolerance in an IL-10-dependent fashion, mediate the tolerance. We hypothesized that modified DC exposed to arthritogenic antigen would suppress clinical arthritis after disease onset. Methods Antigen-induced arthritis was induced in C57/Bl6 mice by priming to methylated bovine serum albumin (mBSA) antigen followed by challenge injection of mBSA to one knee. Knee swelling was apparent within 2 days, with peak clinical signs apparent at 5 days. Mice were treated with antigen-exposed modified DC between 2 and 6 days after mBSA challenge to the knee joint. Results Clinical arthritis was suppressed in each group receiving mBSA-exposed modified DC within 4 days compared with mice that received either no DC or keyhole limpet hemocyanin-exposed modified DC. Clinical improvement was associated with mBSA-specific tolerance in mice receiving mBSA-exposed modified DC. Tolerance induction was not impaired by concomitant administration of anti-tumor necrosis factor alpha monoclonal antibody. Subsequent rechallenge with intra-articular IL-1 induced flare of arthritis in all groups, which could be effectively suppressed by a second administration of mBSA-exposed modified DC. Conclusions The data indicate that modified DC induce antigen-specific immune suppression in this model of inflammatory arthritis, even after full clinical expression of the disease. These observations have important implications for antigen-specific therapy of autoimmunity.

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of the cancer, we determined levels of EBV-specific CTLp in peripheral blood from NPC patients, long-term survivors of the cancer and healthy subjects. CTLp levels of test subjects varied between 3-3,000/10(6) PBMCs. The plasma EBV burden increased when the CTLp level fell below 150, whereas the EBV burden of PBMCs was not correlated with CTLp level. Compared with healthy carriers, CTLp levels of patients were lower and varied over a wider range, between 3-1,500/10(6) PBMCs. The quantitative immune deficit was probably attributed to the tumor because, first, CTLp in survivors was restored to levels similar to those in healthy carriers after the tumor had been successfully treated. Second, the CTLp level changed as disease progressed, being lower in local disease, increased in locoregional disease and decreased again when the tumor metastasized. Based on these findings, 4 patients with advanced disease were infused with 5 x 10(7)-3 x 10(8) autologous EBV CTLs. The treatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the large tumor bulk. Nevertheless, the treatment regularly increased CTLp levels of patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plasma EBV burden. Taken together, these results provided a rationale to further explore EBV as a target of immune intervention of NPC. (C) 2001 Wiley-Liss, Inc.

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest(TM) Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest(TM) Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for >15 weeks in dry conditions up to 45degreesC and in humid conditions up to 37degreesC. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10

Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. ReIB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which ReIB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4(+) T cells induced by the DCs transfer antigen-specific Infectious tolerance to primed recipients in an interleukin10-dependent fashion. Thus CD40, regulated by ReIB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.

New fluorescence parameters for monitoring photosynthesis in plants - 1. The effect of illumination on the fluorescence parameters of the JIP-test

Chlorophyll fluorescence measurements have a wide range of applications from basic understanding of photosynthesis functioning to plant environmental stress responses and direct assessments of plant health. The measured signal is the fluorescence intensity (expressed in relative units) and the most meaningful data are derived from the time dependent increase in fluorescence intensity achieved upon application of continuous bright light to a previously dark adapted sample. The fluorescence response changes over time and is termed the Kautsky curve or chlorophyll fluorescence transient. Recently, Strasser and Strasser (1995) formulated a group of fluorescence parameters, called the JIP-test, that quantify the stepwise flow of energy through Photosystem II, using input data from the fluorescence transient. The purpose of this study was to establish relationships between the biochemical reactions occurring in PS II and specific JIP-test parameters. This was approached using isolated systems that facilitated the addition of modifying agents, a PS II electron transport inhibitor, an electron acceptor and an uncoupler, whose effects on PS II activity are well documented in the literature. The alteration to PS II activity caused by each of these compounds could then be monitored through the JIP-test parameters and compared and contrasted with the literature. The known alteration in PS II activity of Chenopodium album atrazine resistant and sensitive biotypes was also used to gauge the effectiveness and sensitivity of the JIP-test. The information gained from the in vitro study was successfully applied to an in situ study. This is the first in a series of four papers. It shows that the trapping parameters of the JIP-test were most affected by illumination and that the reduction in trapping had a run-on effect to inhibit electron transport. When irradiance exposure proceeded to photoinhibition, the electron transport probability parameter was greatly reduced and dissipation significantly increased. These results illustrate the advantage of monitoring a number of fluorescence parameters over the use of just one, which is often the case when the F-V/F-M ratio is used.