Meningococcal Disease in Northern Ireland - Past, Present & Future: MeningoNI Forum.

Meningococcal disease has had devastating consequences in Northern Ireland since its first description locally in 1859. The incidence of this disease has significantly declined in recent years, however it is important to understand reasons for this changing epidemiology and to acknowledge the diagnostic and clinical management developments that have been made locally. This review aims to examine the changing face of this disease in Northern Ireland over the years, with particular reference to local disease prevention, epidemiology, diagnosis, clinical treatment and management, post-disease sequelae and the role of meningitis charities locally, in terms of patient support and research.

A Survey of tooth morphology teaching methods employed in the United Kingdom and Ireland.

BACKGROUND: Tooth morphology is a central component of the dental curriculum and is applicable to all dental specialities. Traditional teaching methods are being supplemented with innovative strategies to tailor teaching and accommodate the learning styles of the recent generation of students. METHODS: An online survey was compiled and distributed to the staff involved in teaching tooth morphology in the United Kingdom and Ireland to assess the importance of tooth morphology in the dentistry curriculum and the methodologies employed in teaching. RESULTS: The results of the survey show that tooth morphology constitutes a small module in the dental curriculum. It is taught in the first 2 years of the dental curriculum but is applicable in the clinical years and throughout the dental career. Traditional teaching methods, lecture and practical, are being augmented with innovative teaching including e-learning via virtual learning environment, tooth atlas and e-books leading to blended learning. The majority of the schools teach both normal dental anatomy and morphologic variations of dental anatomy and utilise plastic teeth for practical and examination purposes. Learning the 3D aspects of tooth morphology was deemed important by most of the respondents who also agreed that tooth morphology is a difficult topic for the students. CONCLUSION: Despite being core to the dental curriculum, overall minimal time is dedicated to the delivery of tooth morphology, creating a reliance on the student to learn the material. New forms of delivery including computer-assisted learning tools should help sustain learning and previously acquired knowledge.

Evaluation of an animation tool developed to supplement dental student study of the cranial nerves.

INTRODUCTION: The structure/function of the cranial nerves is a core topic for dental students. However, due to the perceived complexity of the subject, it is often difficult for students to develop a comprehensive understanding of key concepts using textbooks and models. It is accepted that the acquisition of anatomical knowledge can be facilitated by visualisation of structures. This study aimed to develop and assess a novel cranial nerve animation as a supplemental learning aid for dental students. MATERIALS AND METHODS: A multidisciplinary team of anatomists, neuroscientists and a computer scientist developed a novel animation depicting the cranial nerves. The animation was viewed by newly enrolled first-year dental students, graduate entry dental students (year 1) and dental hygiene students (year 1). A simple life scenario employing the use of the cranial nerves was developed using a cartoon-type animation with a viewing time of 3.58 minutes. The animation was developed with emphasis on a life scenario. The animation was placed online for 2 weeks with open access or viewed once in a controlled laboratory setting. Questionnaires were designed to assess the participants' attitude towards the animation and their knowledge of the cranial nerves before and after visualisation. This study was performed before the delivery of core lectures on the cranial nerves. RESULTS: Our findings indicate that the use of the animation can act as a supplemental tool to improve student knowledge of the cranial nerves. Indeed, data indicate that a single viewing of the animation, in addition to 2-week access to the animation, can act as a supplemental learning tool to assist student understanding of the structure and function of cranial nerves. The animation significantly enhanced the student's opinion that their cranial nerve knowledge had improved. From a qualitative point of view, the students described the animation as an enjoyable and useful supplement to reading material/lectures and indicated that the animation was a useful tool in understanding the cranial nerves. CONCLUSION: Overall, these findings indicate that an animation demonstrating the cranial nerves in a simple, everyday functional scenario may act as a learning aid in the study of cranial nerves.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.

BACKGROUND: Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function. METHODS AND SETTING: 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >10(4) colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed. RESULTS: Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis (p=0.005). DISCUSSION AND CONCLUSIONS: This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

Mycoplasma hominis and Gardnerella vaginalis display a significant synergistic relationship in bacterial vaginosis.

Gardnerella vaginalis plays an important role in bacterial vaginosis (BV,) while the role of genital Mollicutes is less obvious. The diagnosis of BV by use of the current Gram stain Nugent score is also suboptimal for defining the role of Mollicutes that lack a cell wall. Since bacterial load and diversity is an important prerequisite for BV, real-time quantitative polymerase chain reaction (qPCR) assays enable these to be assessed. The purpose of this study was to define the role of genital Mollicutes and potential patterns of synergy with G. vaginalis in women with BV. Vaginal swabs from 130 women categorised by Nugent score as BV (n = 28), intermediate (n = 22) and non-BV (n = 80) were tested against four qPCR TaqMan assays targeting G. vaginalis, Mycoplasma hominis, M. genitalium, Ureaplasma urealyticum and U. parvum. Statistical analyses were used to compare bacterial prevalence and load between the three groups of women. Mycoplasma hominis and G. vaginalis co-infection was significantly more common in BV (60.7 %) compared to intermediate (36.4 %) and non-BV (8.8 %) Nugent scores (p < 0.001). Significantly higher loads of M. hominis (p = 0.001) and G. vaginalis (p < 0.001) were detected in women with BV and the respective loads in M. hominis and G. vaginalis co-infections displayed a significant positive correlation (p < 0.001; r = 0.60). No significant associations were seen with the other Mollicutes. The findings strengthen the evidence of a role for M. hominis in BV and a potential synergy with G. vaginalis. This synergy could be an important trigger of the condition and sexual contact the conduit for the transmission of an otherwise commensal bacterium that could initiate it.

Coxiella burnetii (Q fever) seroprevalence in cattle.

Human cases of Q fever appear to be common in Northern Ireland compared to the rest of the British Isles. The purpose of this study was to describe the seroepidemiology of Coxiella burnetii infection in cattle in Northern Ireland in terms of seroprevalence and determinants of infection. A total of 5182 animals (from a stratified systematic random sample of 273 herds) were tested with a commercial C. burnetii phase 2 IgG ELISA. A total of 6.2% of animals and 48.4% of herds tested positively. Results from a multilevel logistic regression model indicated that the odds of cattle being infected with Q fever increased with age, Friesian breed, being from large herds and from dairy herds. Large dairy herd animal prevalence was 12.5% compared to 2.1% for small beef herds. Preliminary seroprevalence in sheep (12.3%), goats (9.3%), pigs (0%) rats (9.7%) and mice (3.2%) using indirect immunofluorescence is reported.

Campylobacter spp. in conventional broiler flocks in Northern Ireland: epidemiology and risk factors.

Risk factors for Campylobacter infection in conventional broiler flocks in the time period up to the first removal of birds to slaughter were investigated over a maximum of five consecutive production cycles in a cohort of 88 broiler farms in Northern Ireland. Samples for Campylobacter culture, which consisted of 14 cloacal swabs per flock, were collected from one house on each farm prior to the first depopulation of birds. In total 388 flocks were sampled, of which 163 tested positive for Campylobacter spp. (42.0%; 95% CI 35.1-48.9%). Data on farm and flock variables were obtained from questionnaires and random-effects logistic regression modelling used to investigate the association between these and the Campylobacter status of flocks. Six variables, all of which were significant at p<0.05, were included in the final multivariable model. These included a combined variable on the presence of rodents on farms, which showed an increased odds of infection in flocks where the farmer reported having observed rodents during the production cycle (OR=2.1) and/or where rodent droppings were observed at the sampling visit (OR=2.9). Other variables that were significantly associated with an increased odds of infection included the age of the birds at sampling (odds ratio for its linear effect=1.16 for each day of increase in age), season (summer versus other seasons OR=2.0), farms with three or more broiler houses (OR=2.9 compared to those with one house), the frequency of footbath disinfectant changes (OR=2.5 for once weekly and OR=4.0 for less than once weekly compared to twice weekly changes) and a categorical variable on the standard of tidiness and cleanliness of the broiler house ante-room (OR=2.0 and OR=4.9 for flocks from houses with poorer standards). There was no significant evidence of direct carry-over of infection from one production cycle to the next, neither was there evidence of other farm species acting as a source of infection.

Survival of Campylobacter jejuni in waterborne protozoa.

The failure to reduce the Campylobacter contamination of intensively reared poultry may be partially due to Campylobacter resisting disinfection in water after their internalization by waterborne protozoa. Campylobacter jejuni and a variety of waterborne protozoa, including ciliates, flagellates, and alveolates, were detected in the drinking water of intensively reared poultry by a combination of culture and molecular techniques. An in vitro assay showed that C. jejuni remained viable when internalized by Tetrahymena pyriformis and Acanthamoeba castellanii for significantly longer (up to 36 h) than when they were in purely a planktonic state. The internalized Campylobacter were also significantly more resistant to disinfection than planktonic organisms. Collectively, our results strongly suggest that protozoa in broiler drinking water systems can delay the decline of Campylobacter viability and increase Campylobacter disinfection resistance, thus increasing the potential of Campylobacter to colonize broilers.

Antimicrobial susceptibility of Campylobacter spp. isolated from broiler chickens in Northern Ireland.

Between February 2000 and October 2001, cloacal swabs were collected from 387 broiler chicken flocks in Northern Ireland. Campylobacter isolates from the 262 positive flocks were tested with common antimicrobial agents using a disc diffusion method and by Etests. Resistance to erythromycin, gentamicin and chloramphenicol was <1%, whereas for ampicillin, nalidixic acid and tetracycline, resistance was 33%, 10% and 13%, respectively. Ciprofloxacin resistance was 3%, one of the lowest in recent reports from studies on human or poultry isolates. Sequence data of the quinolone resistance-determining region of the gyrA gene showed a mutation leading to Thr-86 to Ile substitution among highly resistant ciprofloxacin isolates. Only 0.8% of the isolates studied were resistant to four or more antibiotics.

Are higher doses of nicotine replacement more effective for smoking cessation?

This study determined whether higher dose nicotine patches are more efficacious than lower dose patches among heavy smokers. A randomized double-blind study compared 0, 21, 35, and 42 mg/day of a 24-h patch in 1039 smokers (> or = 30 cigarettes/day) at 12 clinical sites in the USA and one in Australia. Daily patches were used for 6 weeks followed by tapering over the next 10 weeks. Weekly group therapy occurred. Biochemically validated self-reported quit rates at 6, 12, 26, and 52 weeks post-cessation were measured. Quit rates were dose-related at all follow-ups (p < 0.01). Continuous, biochemically verified abstinence rates for the 0, 21, 35, and 42 mg doses at the end of treatment (12 weeks) were 16, 24, 30, and 39%. At 6 months, the rates were 13, 20, 20, and 26%. Among the 11 sites with 12 month follow-up (n = 879), the quit rates were 7, 13, 9, and 19%. In post-hoc tests, none of the active doses were significantly different from each other at any follow-up. The rates of dropouts due to adverse events for 0, 21, 35, and 42 mg were 3, 1, 3, and 6% (p = n.s.). Our results are similar to most prior smaller studies; i.e., in heavy smokers higher doses increase quit rates slightly. Longer durations of treatment may be necessary to show greater advantages from higher doses.

A comparison of the haemagglutinating and enzymic activities of Bacteroides fragilis whole cells and outer membrane vesicles.

The haemagglutinating and enzymic activities of the obligately anaerobic pathogenic bacterium Bacteroides fragilis were examined. Outer membrane vesicles are released from the surface of B. fragilis. They can be detected by electron microscopy in ultrathin sections and bacterial suspensions after negative staining. Electron microscopy and immunogold labelling with a MAb specific for surface polysaccharide of B. fragilis confirmed that the vesicles carried outer membrane associated epitopes. The haemagglutinating activity of whole cells from populations of B. fragilis strains NCTC9343, BE3 and LS66 enriched by Percoll density gradient centrifugation for a large capsule (LC), electron dense layer (EDL); non-capsulate by light microscopy) and outer membrane vesicles (OMV) which had been purified by centrifugation from EDL-enriched populations were compared using human and horse erythrocytes. The enzymic activity of OMV, LC- and EDL-enriched populations, as detected by the API ZYM kit, was compared for strains NCTC 9343 and BE3. Purified OMV from the strains examined exhibited both haemagglutinating and enzymatic activity. Haemagglutination by the EDL-enriched population was sensitive to treatment with sodium periodate. The LC-enriched population haemagglutinated only after ultrasonic removal of the capsule. This indicates that the LC masks a haemagglutinin. The results suggest a potential role for OMV in the virulence of B. fragilis.

Cigarette availability to minors.

Each year, more than 1 million children and adolescents begin smoking, and an average of 24% of high school students report smoking, despite existing laws that prohibit the sale of tobacco to minors. In this study, the authors observed an 11-year-old boy attempt to purchase cigarettes at 57 retail establishments in western Pennsylvania to determine if the existing laws do, indeed, limit children's access to buy cigarettes. This study took place between August 15, 1993, and October 2, 1993. The establishments included convenience stores, gas stations, liquor distributors, and restaurants. One of the researchers entered each establishment to look for the posting of the state law prohibiting the sale of cigarettes to minors after their underage subject had requested cigarettes from the salesclerks. The researcher also inquired of the salesclerks if they were aware of the state law. In 30 of the 57 attempts (53%), the 11-year-old student would have been able to purchase cigarettes. Of these attempts, 53% would have sold them on his first request, while 47% would have sold them to him if he indicated that the cigarettes were for his dad. Only 3 of the 57 establishments (5.2%) posted the law, and 54 of the 57 clerks (95%) were aware of the cigarette law.

The alpha isoform of protein kinase C inhibits histamine-stimulated adenylate cyclase activity in a particulate fraction of the human gastric cancer cell line HGT-1.

The isoform of protein kinase C responsible for the inhibition of histamine-stimulated adenylate cyclase by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), has been investigated in a particulate fraction prepared from the human gastric cancer cell line HGT-1. The alpha and epsilon isoforms of protein kinase C were detected in HGT-1 cells and in a 40,000 x g particulate fraction by immunoblotting procedures. The inhibitory effect of TPA on histamine-stimulated adenylate cyclase was enhanced by the presence of Ca2+, but decreased in a concentration-dependent manner by anti-peptide antibody to protein kinase C alpha, but not to protein kinase C epsilon. Addition of Ca2+ and TPA to the 40,000 x g particulate fraction stimulated the phosphorylation of the protein kinase C substrate myelin basic peptide 4-14. Protein kinase C alpha is probably the isoform responsible for inhibition of histamine-stimulated adenylate cyclase in HGT-1 cells.

Inhibition by Ro 31-8220 of acid secretory activity induced by carbachol indicates a stimulatory role for protein kinase C in the action of muscarinic agonists on isolated rat parietal cells.

The bisindolylmaleimide Ro 31-8220 is a selective inhibitor of protein kinase C. This compound was used to investigate the involvement of protein kinase C in the stimulation of gastric acid secretion by the muscarinic cholinergic receptor on rat isolated parietal cells. The accumulation of the weak base aminopyrine by both crude and enriched preparations of parietal cells was used as an index of secretory activity. Ro 31-8220 antagonized (IC50, 1.0 microM) the effect of the activator of protein kinase C,12-O-tetradecanoylphorbol 13-acetate (TPA), on histamine-stimulated aminopyrine accumulation. Ro 31-8220 (0.1-2.14 microM) inhibited the aminopyrine response to 0.1 mM carbachol (IC50, 0.78 microM; 49% inhibition at 2.14 microM Ro 31-8220) and shifted the dose-response curve for the effect of carbachol concentration of aminopyrine accumulation downwards and to the right. No inhibition of aminopyrine accumulation induced by histamine was found with Ro 31-8220 (0.1-2.14 microM). In a preparation containing > 80% parietal cells incubated with 0.1 mM carbachol, 2.14 microM Ro 31-8220 inhibited aminopyrine accumulation by 43%, but had no effect on the increase in intracellular Ca2+ which was measured by using the fluorescent probe FURA-2. In conclusion, Ro 31-8220 (0.1-2.14 microM) produced a selective reduction in secretory activity in parietal cells by inhibition of protein kinase C. The predominant role of protein kinase C in parietal cells activated with carbachol is not to cause feedback inhibition of the response but to facilitate stimulation of secretory activity.