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.

Which version of the Eysenck Personality Profiler is best? 6-, 12- or 20-items per scale

Data provided by 400 first year undergraduate students were analysed to develop two short forms of the Eysenck Personality Profiler (EPP) in which each of the 22 primary scales is assessed by a 6-item and a 12-item version instead of the usual 20-item per scale measure. In comparison with the 6-item per scale measure, the 12-item version retains more of the characteristics of the long version and seems a good compromise between quality of data and administration time. (C) 2004 Elsevier Ltd. All rights reserved.

Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells

Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at approximate to6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all bypass interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly in vivo, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (i) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (it) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.

Validation and patient acceptance of a computer touch screen version of the WOMAC 3.1 osteoarthritis index

Objectives: To validate the WOMAC 3.1 in a touch screen computer format, which applies each question as a cartoon in writing and in speech (QUALITOUCH method), and to assess patient acceptance of the computer touch screen version. Methods: The paper and computer formats of WOMAC 3.1 were applied in random order to 53 subjects with hip or knee osteoarthritis. The mean age of the subjects was 64 years ( range 45 to 83), 60% were male, 53% were 65 years or older, and 53% used computers at home or at work. Agreement between formats was assessed by intraclass correlation coefficients (ICCs). Preferences were assessed with a supplementary questionnaire. Results: ICCs between formats were 0.92 (95% confidence interval, 0.87 to 0.96) for pain; 0.94 (0.90 to 0.97) for stiffness, and 0.96 ( 0.94 to 0.98) for function. ICCs were similar in men and women, in subjects with or without previous computer experience, and in subjects below or above age 65. The computer format was found easier to use by 26% of the subjects, the paper format by 8%, and 66% were undecided. Overall, 53% of subjects preferred the computer format, while 9% preferred the paper format, and 38% were undecided. Conclusion: The computer format of the WOMAC 3.1 is a reliable assessment tool. Agreement between computer and paper formats was independent of computer experience, age, or sex. Thus the computer format may help improve patient follow up by meeting patients' preferences and providing immediate results.

Fixing the system? The experience of service users of the quasi-market in disability services in Australia

A qualitative study involving semi-structured interviews with 31 people with disabilities and 32 carers in the state of Queensland, Australia, found that their experience of supportive service delivery had not improved despite reforms of the service delivery system driven by a version of the quasi-market model. Instead of delivering increased consumer choice and improved efficiency in service delivery, service users experienced inadequate service supply, service cutbacks, and an increased emphasis on cost subsidisation and assessment processes. Additionally, few consumers felt that individualised funding arrangements had personally delivered the benefits which the quasi-market model and associated policy paradigm had indicated that they should receive. For many consumers, the notion of consumer 'choice' around service provision was fictitious and they felt that any efficiency gains were at the agency level, largely at the consumers' cost. It is concluded that there appears to be no particular benefit to service users of quasi-market reforms, particularly in policy contexts where service delivery systems are historically under-funded.

Differential regulation of suppressor of cytokine signaling-3 in the liver and adipose tissue of the sheep fetus in late gestation

Differential regulation of suppressor of cytokine signaling-3 in the liver and adipose tissue of the sheep fetus in late gestation. Am J Physiol Regul Integr Comp Physiol 290: R1044 - R1051, 2006. First published November 10, 2005; doi: 10.1152/ajpregu. 00573.2005. - It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3) intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher in the liver than in the pancreas, spleen, and kidney of the sheep fetus during late gestation. In the liver, SOCS-3 mRNA expression was increased (P < 0.05) between 125 (n < 4) and 145 days (n < 7) gestation and lower (P < 0.05) in growth-restricted compared with normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic agonist, bromocriptine (n < 7), or saline (n < 5), such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below similar to 20 ng/ml [y = 0.99 - (2.47/x) + (4.96/x(2)); r(2) = 0.91, P < 0.0001, n < 12]. No relationship was shown between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased (P < 0001) between 90 - 91 (n < 6) and 140 - 145 days (n < 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in key fetal tissues and may play an important and tissue-specific role in the regulation of cellular proliferation and differentiation before birth.

The role of the learning community in the development of discipline knowledge and generic graduate outcomes

In this paper we describe a study of learning outcomes at a research-intensive Australian university. Three graduate outcome variables (discipline knowledge and skills, communication and problem solving, and ethical and social sensitivity) are analysed separately using OLS regression and comparisons are made of the patterns of unique contributions from four independent variables (the CEQ Good Teaching and Learning Communities Scales, and two new, independent, scales for measuring Teaching and Program Quality). Further comparisons of these patterns are made across the Schools of the university. Results support the view that teaching and program quality are not the only important determinants of students' learning outcomes. It is concluded that, whilst it continues to be appropriate for universities to be concerned with the quality of their teaching and programs, the interactive, social and collaborative aspects of students' learning experiences, captured in the notion of the Learning Community, are also very important determinants of graduate outcomes, and so should be included in the focus of attempts at enhancing the quality of student learning.

How many glomerular profiles must be measured to obtain reliable estimates of mean glomerular areas in human renal biopsies?

The objective of this study was to investigate the number of glomerular profiles that are required for accurate estimates of mean profile area in a renal biopsy series. Slides from 384 renal biopsies from one center were reviewed. They contained a median of seven glomerular profiles or of four profiles without sclerosis. Profile areas were measured using stereologic point counting. The true individual mean for each biopsy was calculated and the true population mean for groups of biopsies derived. Individual and population random sample means then were calculated from a random sampling of profiles in each biopsy and were compared with true means for the same biopsies. The effect on the true population means of the entire group of biopsies was also assessed, as the minimum number of glomerular profiles that were required for inclusion was changed. In a single biopsy, random sampling of >= 10 profiles without exclusions and of eight profiles or more without sclerosis reliably estimated the true mean areas. In a group of 30 biopsies, random sampling of five or more glomeruli per biopsy reliably estimated the true population mean. In the aggregate series, inclusion of all 384 biopsies produced the most robust true population mean; the reliability of the estimates decreased as the numbers of eligible biopsies diminished with increasing requisite minimum numbers of profiles per biopsy. We conclude that, while >= 10 profiles might be needed for reliable area estimates in a single biopsy, far fewer profiles per biopsy can suffice when groups of biopsies are studied. In analyses of groups of biopsies, all available biopsies should be used without consideration of the number of glomerular profiles in each. Stipulation of a specific minimum number of glomeruli in each biopsy for inclusion reduces the power of analyses because fewer biopsies are available for evaluation.

Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Progressive supranuclear palsy (PSP):A quantitative study of the pathological changes in cortical and subcortical regions of eight cases

In eight cases of progressive supranuclear palsy (PSP), neurofibrillary tangles (NFT) were numerous in the substantia nigra (SN), red nucleus (RN), locus caeruleus (LC), pontine nuclei (PN), and inferior olivary nucleus (ION) and abnormally enlarged neurons (EN) in the ION, LC and PN. Loss of Purkinje cells was evident in the cerebellum. Tufted astrocytes (TA) were abundant in the striatum, SN and RN and glial inclusions ('coiled bodies') (GI) in the midbrain (SN, RN) and pons (LC). Neuritic plaques were frequent in one case. NFT, GI, and TA densities were uncorrelated in most areas. NFT and EN densities were positively correlated in the midbrain and surviving neurons and disease duration in several areas. These results suggest: 1) predominantly subcortical pathology in PSP with widespread NFT while TA and GI have a more localized distribution, 2) little correlation between neuronal and glial pathologies, and 3) shorter duration cases may be more likely to develop cortical pathology. © 2007 Springer-Verlag.

A quantitative study of the pathological changes in white matter in multiple system atrophy

The density and spatial distribution of the vacuoles, glial cell nuclei and glial cytoplasmic inclusions (GCI) were studied in the white matter of various cortical and subcortical areas in 10 cases of multiple system atrophy (MSA). Vacuolation was more prevalent in subcortical than cortical areas and especially in the central tegmental tract. Glial cell nuclei widespread in all areas of the white matter studied; overall densities of glial cell nuclei being significantly greater in the central tegmental tract and frontal cortex compared with areas of the pons. The GCI were present most consistently in the external and internal capsules, the central tegmental tract and the white matter of the cerebellar cortex. The density of the vacuoles was greater in the MSA brains than in the control brains but glial cell density was similar in both groups. In the majority of areas, the pathological changes were distributed across the white matter randomly, uniformly, or in large diffuse clusters. In most areas, there were no spatial correlations between the vacuoles, glial cell nuclei and GCI. These results suggest: (i) there is significant degeneration of the white matter in MSA characterized by vacuolation and GCI; (ii) the central tegmental tract is affected significantly more than the cortical tracts; (iii) pathological changes are diffusely rather than topographically distributed across the white matter; and (iv) the development of the vacuoles and GCI appear to be unrelated phenomena. © 2007 Japanese Society of Neuropathology.

Spatial patterns of the pathological changes in neuronal intermediate filament inclusion disease (NIFID):an α-internexin immunohistochemical study

Neuronal intermediate filament inclusion disease (NIFID) is characterized by α-internexin positive neuronal cytoplasmic inclusions (NCI), swollen achromatic neurons (SN), neuronal loss, and gliosis. This study tested: 1) whether the spatial patterns of the lesions was topographically organized in areas of the frontal and temporal lobe and 2) whether a spatial relationship exists between the NCI and SN. The NCI were distributed in regular clusters and in a quarter of these areas, the clusters were 400-800 μm in diameter approximating to the size of the cells of origin of the cortico-cortical pathways. Variations in the density of the NCI were positively correlated with the SN. Hence, cortical degeneration in NIFID appears to be topographically organized and may affect the cortico-cortical projections, the clusters of NCI and SN developing within the same vertical columns of cells. © 2007 Springer-Verlag.

Spatial topography of the neurofibrillary tangles in cortical and subcortical regions in progressive supranuclear palsy

Objective: To study the topography of neurofibrillary tangles (NFT) in cortical and subcortical areas in progressive supranuclear palsy (PSP). Methods: Pattern analysis was carried out on tau-positive NFT in eight PSP cases. Results: Of the areas studied, NFT were randomly distributed in 68%, regularly distributed in 3%, and clustered in 29%. A regular distribution of clusters was more frequent in cortical than subcortical areas. Conclusion: NFT topography in subcortical areas was similar to inclusions in the synucleinopathy multiple system atrophy (MSA) but in cortical areas was comparable to other tauopathies. © 2006 Elsevier Ltd. All rights reserved.

Spatial patterns of the pathological changes in the temporal lobe of patients with neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID) is a new neurodegenerative disease characterized histologically by the presence of neuronal cytoplasmic inclusions (NI) immunopositive for intermediate filament proteins, neuronal loss, swollen achromatic neurons (SN), and gliosis. We studied the spatial patterns of these pathological changes parallel to the pia mater in gyri of the temporal lobe in four cases of NIFID. Both the NI and SN occurred in clusters that were regularly distributed parallel to the pia mater, the cluster sizes of the SN being significantly greater than those of the NI. In a significant proportion of areas studied, there was a spatial correlation between the clusters of NI and those of the SN and with the density of the surviving neurons. In addition, the clusters of surviving neurons were negatively correlated (out of phase) with the clusters of glial cell nuclei. The pattern of clustering of these histological features suggests that there is degeneration of the cortico-cortical projections in NIFID leading to the formation of NI and SN within the same vertical columns of cells. The glial cell reaction may be a response to the loss of neurons rather than to the appearance of the NI or SN.

A quantitative study of the pathological changes in ten patients with multiple system atrophy (MSA)

The densities of the glial cytoplasmic inclusions (GCI), neuronal inclusions (NI), and abnormal neurons were studied in the frontal cortex, hippocampus, cerebellum, basal ganglia and areas of the pons and medulla in 10 cases of multiple system atrophy (MSA). GCI density was greater in the substantia nigra and globus pallidus compared with the frontal cortex and hippocampus. Abnormal neurons were most abundant in the frontal cortex, substantia nigra, and inferior olivary nucleus. NI and abnormal neuron densities were positively correlated in the globus pallidus but negatively correlated in the hippocampus. The NI and GCI were only positively correlated in the pons. GCI in the pons and inferior olivary nucleus, NI in the substantia nigra, and abnormal neurons in the frontal cortex varied significantly between cases. The MSA cases did not cluster according to disease subtype. The data suggest that: 1) the greatest densities of pathological changes occur in the substantia nigra and globus pallidus, 2) density of the GCI is unrelated to that of the NI, and 3) there is overlapping pathology between the various subtypes of MSA.