Urinary symptoms and natural history of urinary continence after first-ever stroke--a longitudinal population-based study.

BACKGROUND: there are limited population-based data on urinary symptoms and the natural history of urinary incontinence after a first stroke. AIM: to study the prevalence of urinary symptoms, and the natural history and factors associated with urinary incontinence after first-ever stroke. METHODS: we administered a standardised urinary symptom questionnaire at 3 and 12 months after stroke to patients enrolled in the North-East Melbourne Stroke Incidence Study. Urinary symptoms and evolution of urinary incontinence were recorded. Logistic regression was used to model associations between baseline factors and incontinence at 12 months. RESULTS: more than 80% of survivors reported one or more abnormal urinary symptoms at 3 or 12 months, with nocturia most frequent. Incontinence was present in 43.5% of patients at 3 months, and 37.7% at 12 months, with urge incontinence being most common. Pre-stroke continence (P < 0.001) and female sex (P < 0.001) were independently associated with incontinence at 12 months, whereas the effect of greater stroke severity was magnified with advancing age (P for interaction = 0.05). CONCLUSION: the majority of survivors reported abnormal urinary symptoms early and late after stroke. Around a third of patients had incontinence at 12 months, with pre-stroke UI, age, female sex and stroke severity predicting its presence.

Incontinence improves in older women after intensive pelvic floor muscle training: an assessor-blinded randomized controlled trial.

AIMS: To test the hypotheses that high intensity pelvic floor muscle training (PFMT) is effective in relief of stress urinary incontinence in community dwelling older women, and that intense PFMT improves stress urinary incontinence more than bladder training (BT) in this population. METHODS: A two-center, assessor-blinded randomized controlled trial of 20 weeks duration with two active intervention arms: PFMT and BT. Assessments and interventions were undertaken at two metropolitan tertiary hospitals. Participants were community dwelling women over 65 years of age with urodynamic stress incontinence. Primary outcome measure was urinary leakage during a cough stress test. Secondary outcome measures included symptoms and bother (ICIQ-UI SF), participant global perception of change, leakage episodes (7-day accident diary), degree of "bother" (VAS) and health related quality of life (AQoL). RESULTS: Eighty-three Caucasian women, 71.8 (SD 5.3) years participated in the study. Both groups improved over the intervention period; however, the PFMT group reported significantly lower amounts of leakage on the stress test [PFMT median 0.0 g, 95% CI: 0.2-0.9; BT median 0.3 g, 95% CI: 0.2-1.7, P=0.006], improved symptoms and bother [PFMT mean 5.9, 95% CI: 4.8-7.1; BT group mean 8.5, 95% CI: 7.1-9.9 and greater perception of change [PFMT 28 (73.6%); BT 12 (36.4%) (P=0.002)] after 5 months than the BT group. CONCLUSIONS: High intensity PFMT is effective in managing stress urinary incontinence and is more effective than BT in healthy older women.

The phagocytic capacity of neurones.

Phagocytosis is defined as the ingestion of particulates over 0.5 microm in diameter and is associated with cells of the immune system such as macrophages or monocytes. Neurones are not generally recognized to be phagocytic. Using light, confocal, time-lapse and electron microscopy, we carried out a wide range of in-vitro and in-vivo experiments to examine the phagocytic capacity of different neuronal cell types. We demonstrated phagocytosis of material by neurones, including cell debris and synthetic particles up to 2.8 microm in diameter. We showed phagocytosis in different neuronal types, and demonstrated that debris can be transported from neurite extremities to cell bodies and persist within neurones. Flow cytometry analysis demonstrated the lack of certain complement receptors on neurones but the presence of others, including integrin receptors known to mediate macrophage phagocytosis, indicating that a restricted set of phagocytosis receptors may mediate this process. Neuronal phagocytosis occurs in vitro and in vivo, and we propose that this is a more widespread and significant process than previously recognized. Neuronal phagocytosis may explain certain inclusions in neurones during disease, cell-to-cell spread of disease, neuronal death during disease progression and provide a potential mechanism for therapeutic intervention through the delivery of particulate drug carriers.

Effects of microinjected small GTPases on the actin cytoskeleton of human neutrophils.

This paper describes a method for microinjection of proteins (Rho GTPases) into neutrophils and observations on the responses of the cells to these injections. Neutrophils are extremely difficult to inject because of their small size, complex morphology and fragility. To allow microinjections they must be cultured on a substrate that enables them to settle, adhere and spread. We determined that fibronectin- and/or collagen-coated coverslips are the best substrates and we used very fine needles and short microinjection times to minimize cell damage. These methods permitted us to inject up to 100 cells in a single preparation over a period of 30 min. Effects of microinjection were assessed by using tetramethylrhodamine isothiocyanate (TRITC)-phalloidin to label F-actin filaments, and observation by fluorescence and confocal scanning microscopy. Microinjection alone resulted in cell rounding and some changes in the F-actin cytoskeleton but injected cells remained adherent at the substrate, were able to respond to microinjected GTPases (V12Rac, V14RhoA, V12Cdc42) and continued to be responsive to activation by exposure to fMet-Leu-Phe (fMLP) or O-tetradecanoylphorbal 13-acetate (TPA). V12Rac caused an increase in neutrophil membrane ruffling and short protrusions from the cell membrane, whereas V14RhoA induced a large increase in punctate F-actin structures. V12Cdc42 produced focal condensation of F-actin and induced the formation of small microspikes. The differences between these responses of neutrophils and those of other similarly treated cell types are discussed. Our findings demonstrate that microinjection is a valuable technique for studying the role of individual proteins in neutrophils.

The outgrowth response of the axons of developing and regenerating rat retinal ganglion cells in vitro to neurotrophin treatment.

BDNF and NT-4 (but not NT-3 or CNTF) significantly enhanced the outgrowth of early embryonic and adult regenerating RGC axons when provided with a supportive substrate in vitro. BDNF and NT-4 treatment transiently increased RGC axon outgrowth from E15 rat retinas but not from retinas at older embryonic ages. The transient effect of BDNF and NT-4 and the inability of the neurotrophins to promote outgrowth from older embryonic retinal explants suggests a time frame of neurotrophin action and that other chemical factors (target-derived or otherwise) may be necessary for the continued maintenance of developing RGC axons. BDNF and NT-4 also enhanced the outgrowth of regenerating axons from adult retinal explants, but appeared to have a more subtle effect on axon outgrowth, in that the growth-promoting effects of BDNF and NT-4 appeared continuous throughout the incubation period. The suppression of RGC axon outgrowth from embryonic and adult retinae cultured in trkB-IgG-containing medium suggests that the response of developing and regenerating axons, to BDNF and NT-4 are likely to occur through trkB signalling.

Distribution of GAP-43, beta-III tubulin and F-actin in developing and regenerating axons and their growth cones in vitro, following neurotrophin treatment.

Brain derived neurotrophic factor (BDNF) when added to explant cultures of both embryonic and adult retinal ganglion cell (RGC) axons exerted a marked effect on their growth cone size and complexity and also on the intensity of GAP-43, beta-III tubulin and F-actin immunoreaction product in their axons. GAP-43 was distributed in axons, lamellipodia, and filopodia whereas beta-III tubulin was distributed along the length of developing and adult regenerating axons and also in the C-domain of their growth cones. BDNF-treated developing RGC growth cones were larger and displayed increased numbers of GAP-43 and microtubule-containing branches. Although filopodia and lamellipodia were lost from both developing and adult RGC growth cones following trkB-IgG treatment, the intensity of the immunoreaction product of all these molecules was reduced and trkB-IgGs had no effect on the axonal distribution of betas-III tubulin and GAP-43. BDNF-treated growth cones also displayed increased numbers of F-actin containing filopodia and axonal protrusions. This study demonstrates, for the first time, that trkB-IgG treatment causes the loss of F-actin in the P-domain of growth cone tips in developing and regenerating RGC axons. Although microtubules and F-actin domains normally remained distinct in cultured growth cones, beta-III tubulin and F-actin overlapped within the growth cone C-domain, and within axonal protrusions of adult RGC axons, under higher concentrations of BDNF. The collapse of RGC growth cones appeared to correlate with the loss of F-actin. In vitro, trkB signalling may therefore be involved in the maintenance and stabilisation of RGC axons, by influencing F-actin polymerisation, stabilisation and distribution.