A survey of current management of Benign Paroxysmal Positional Vertigo (BPPV) by physiotherapists' interested in vestibular rehabilitation in the UK.

OBJECTIVES: Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of dizziness. Extensive research has identified the best assessment and treatment manoeuvres for each subtype of BPPV. Education in vestibular rehabilitation (VR) is inconsistent. It is unclear if the evidence has been adopted by UK physiotherapists in clinical practice and no research has investigated this specifically. DESIGN: An online survey with closed- and open-text answers. PARTICIPANTS: A purposive sample of physiotherapists interested in VR. A response rate of 67% (100/150) was obtained, from which 20 responses were excluded. RESULTS: Participants had good evidence-based awareness in assessment (79/80, 99%) and treatment (72/80, 90%) of posterior BPPV. Horizontal BPPV assessment awareness was lower than treatment (37/80, 46% vs 60/80, 75%). Differential diagnosis was poor in subjective (20/80, 25%) and objective stages of assessment (34/80, 43%). Thirty six percent (29/80) were able to list ≥3 test precautions with all three nystagmus characteristics described by 29% (23/80). Eighty one percent (65/80) encourage activity restrictions post-treatment. Only 28% (22/80) were aware of practice guidelines or Cochrane reviews in BPPV. External courses were rated the top method for learning how to manage BPPV. Lack of peer support (26/77, 34%) was the main challenge faced whilst learning. Recommendations for improving BPPV education included more external courses (23/87, 26%) and competency guidelines (13/87, 15%). CONCLUSIONS: Good awareness of research evidence was observed in some aspects of BPPV management but many areas require development. Translation and implementation of evidence remains poor and suggests changes in education and knowledge dissemination are warranted.

Evidence of Long Term Benefit of Praziquantel Treatment Against Schistosoma mansoni in Kigungu Fishing Village of Entebbe, Uganda

Praziquantel (PZQ) is efficacious against all species of schistosome: Schistosoma mansoni; Schistosoma haematobium; Schistosoma japonicum and other parasites like the Taenia species. This cross-sectional cohorts study was carried out in Kigungu fishing village along Lake Victoria shore in Entebbe Uganda. Our analysis was based on examining microscopically three slides from a single stool specimen from each of base line cohorts 945.These included children and adults; participants from both sexes in Kigungu fishing village in Entebbe Uganda. Nine hundred and one (901) of the cohorts were re-examined after six months and 625 of the same cohorts who were examined at the baseline and after six months were re-examined 18 months later. The slides were prepared using modified Kato/Katz (Odongo-Aginya) method. The infection proportion with Schistosoma mansoni at baseline was 448 (47.5) but this was reduced to 244 (25.8) 18 months after treatment with a single oral dose of praziquantel at 40mg/kg. However 495 (52.5) were negative at the baseline study. The cure proportion after six was significant ///{(P=0.00); (OR4.63) CI at 95(3.53-6.06)///}. Similarly the cure proportion after 18 months was significant ///{(P=0.00); (OR2.2) CI at 95(1.87-3.34)///}. The force of re-infection after six months was significant ///{(P=0.0001); (OR 0.47) CI at 95(0.31-0.71)///}. Nevertheless the force of re-infection was not significant after 18 months ///{(P=0.766); (OR 0.95) CI at 95(0.68-1.34)///} eggs excretion did not reach the level of the pre-treatment intensity. The egg reduction was 69.3. This was associated with age and pre-treatment intensity 400 eggs per gram (epg) of faeces and age groups ? 30 years. The egg reduction also resulted in marked decrease in clinical symptoms in the participants. Our study suggests evidence of long-term benefit of praziquantel in Kigungu and that the re-infection occurred more commonly in younger age group than in the older patients

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study.

OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. PATIENTS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47·6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant. CONCLUSIONS: The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.

Polarized P-glycoprotein expression by the immortalised human brain endothelial cell line, hCMEC/D3, restricts apical-to-basolateral permeability to rhodamine 123.

P-glycoprotein (P-gp) expression at the blood-brain barrier prevents unwanted blood-borne toxins and signalling molecules from entering the brain. Primary and immortalised human brain endothelial cells (BECs) represent two suitable options for studying P-gp function in vitro. The limited supply of primary human BECs and their instability over passage number make this choice unattractive for medium/high throughput studies. The aim of this study was to further characterise the expression of P-gp by an immortalised human BEC line, hCMEC/D3, in order to evaluate their use as an in vitro human blood-brain barrier model. P-gp expression was stable over a high passage number (up to passage 38) and was polarised on the apical plasma membrane, consistent with human BECs in vivo. In addition, hCMEC/D3 cell P-gp expression was comparable, albeit slightly lower to that observed in primary isolated human BECs although P-gp function was similar in both cell lines. The P-gp inhibitors tariquidar and vinblastine prevented the efflux of rhodamine 123 (rh123) from hCMEC/D3 cells, indicative of functional P-gp expression. hCMEC/D3 cells also displayed polarised P-gp transport, since both tariquidar and vinblasine selectively increased the apical-to-basolateral permeability of hCMEC/D3 cells to rh123. The results presented here demonstrate that hCMEC/D3 cells are a suitable model to investigate substrate specificity of P-gp in BECs of human origin.

Gastric-type mucin and TFF-peptide expression in Barrett's oesophagus is disturbed during increased expression of MUC2.

AIMS: Barrett's oesophagus constitutes metaplastic epithelium, often diagnosed by mucin histochemistry. We determined the mucins and trefoil factor family (TFF)-peptides that were expressed in Barrett's oesophagus, in order to study changes in protein expression in early stages of Barrett's oesophagus development. METHODS AND RESULTS: Biopsy specimens of 71 Barrett's oesophagus patients were collected, and sections were stained for secretory mucins by histochemistry. Immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC, MUC5B, MUC6), TFFs (TFF1, TFF2, TFF3), and proliferation (Ki67). Protein expression in the tissue was measured semiquantitatively. MUC5AC and TFF1 showed high levels and strong colocalization in the surface epithelium, whereas MUC6, MUC5B and TFF3 were found in the deeper glandular structures. TFF2 was found in both surface and glandular epithelium. The co-ordinate expression patterns of these six markers were similar to gastric antrum epithelium. MUC2 expression was ubiquitously associated with goblet cells within intestinal metaplasia, occurring in 68% of patients, and was correlated with increasing proliferation in the epithelium. CONCLUSIONS: Virtually all cells in Barrett's oesophagus epithelium displayed a secretory phenotype, demonstrating a co-ordinate gastric-type MUC and TFF expression. When MUC2 expression was more pronounced, the expression patterns of the other MUCs and the TFFs were increasingly disturbed. MUC2 expression may constitute a marker for early change in the phenotype of Barrett's oesophagus as a precancerous lesion.

Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study.

Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. We obtained localised 1H magnetic resonance spectra from the left frontal lobe and left cerebellum of 15 boys with DMD (mean age 106 months+/-32) and 15 similarly aged control boys (mean age 115 months+/-31); all boys underwent a battery of neuropsychological tests. We found a significant (P<0.01) increase in the ratio of choline-containing compounds to N-acetylaspartate (Cho/NA) in the left cerebellum in boys with DMD compared with control boys. There was no change in the creatine/NA ratio and a significant increase (P=0.03) in the Cho/creatine ratio, suggesting that the change in Cho/NA ratio was due to an increase in choline-containing compounds; this increase has been previously observed in the brain of the murine model of DMD, the mdx mouse. No significant changes were observed in spectra obtained from left frontal lobe in DMD compared to controls. We also observed a significant association between Cho/NA in the left cerebellum, and the performance of DMD boys on the Matrix Analogies Test (MAT). The MAT is a test of visuo-spatial ability and non-verbal reasoning which requires neither manual dexterity nor a verbal response for an adequate performance. A comparison of DMD boys whose cerebellar Cho/NA fell within 2 standard deviations of the control norm (0.56+/-0.24) with DMD boys whose cerebellar Cho/NA was outside this range (i.e. >0.80) revealed a significant difference in ability on the MAT (P<0.05). DMD boys whose Cho/NA ratio is more than two standard deviations higher than controls perform significantly better on the MAT than DMD boys whose Cho/NA ratio is within the normal range. This finding suggests that the observed elevation in Cho/NA and Cho/creatine is not associated with intellectual deficit (as sampled by the MAT), and may represent a compensatory mechanism. The possible interpretations of these metabolic changes are discussed.

Serum somatomedin activity and cartilage metabolism in acutely fasted, chronically malnourished, and refed rats.

Serum somatomedin activity (SM-act) and cartilage metabolism were compared in acutely fasted, marasmic (M), and marasmic kwashiorkor (MK) rats. SM-act was estimated in the porcine bioassay. In vitro uptake of [35S]sulfate and [3H]methylthymidine in costal cartilage of the experimental animals during an incubation in medium immediately after sacrifice, called endogenous activity, and the effect of incubation in 20% normal human plasma after a preincubation of 22 h in medium only, called plasma responsiveness", were determined. Acutely fasted rats had lowered SM-act and a circulating heat-labile inhibitor. Endogenous activity and responsiveness of cartilage were depressed. MK rats (fed ad libitum a 0.5% casein, isocaloric food) showed a profound depression of growth and cartilage endogenous activity despite only partially reduced SM-act and increased responsiveness. M rats received normal food and were pair-fed with MK rats, consuming approximately 0.08 g/g BW . day. They showed very depressed SM-act and low endogenous activity, and responsiveness was increased, though less than in the MK rats. On refeeding M rats, SM-act and cartilage responsiveness increased, followed by an increase of endogenous activity. Catch-up growth was best related to [3H]methylthymidine incorporation by cartilage (endogenous activity). In conclusion, these two types of experimental chronic malnutrition induce a more diversified pattern than does acute fasting. During malnutrition, cartilage metabolism does not reflect bioassayable SM-act of serum but rather the other effects of the nutritional insult. On refeeding, the expected relationship of SM-act and cartilage metabolism is rapidly restored.