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Biomedical subjects

C A McNulty

Publications and source records attributed to C A McNulty.

At least 19 recordsLinked to original sources
PubMed2002

Characterisation of adhesion receptors mediating lymphocyte adhesion to bronchial endothelium provides evidence for a distinct lung homing pathway.

BACKGROUND: The lung is an important tertiary lymphoid organ and many lung diseases are associated with disordered lung immunity. Unlike the gut (alpha4beta7 binding to MAdCAM-1) and skin (CLA+ve T cells binding to E-selectin) where the adhesion receptors involved in organ specific homing of T cells have been identified, the molecular pathways controlling lymphocyte migration to the lung are unclear. Using a modified version of the Stamper-Woodruff assay we have investigated the receptors mediating adhesion of peripheral blood lymphocytes to airway endothelium. METHODS: Longitudinal frozen sections of bronchus (8 micro m) obtained from lung resection specimens were incubated with T cell enriched peripheral blood mononuclear cells for 30 minutes under shaking conditions in the presence of a fluorescently labelled polyclonal anti-von Willebrand antibody to identify blood vessels. After fixation the percentage of blood vessels supporting adhesion was measured. Blocking monoclonal antibodies were used to determine the role of individual adhesion receptors in lymphocyte binding. RESULTS: Specific cation dependent binding of lymphocytes to bronchial endothelium was observed which was significantly inhibited by antibodies against P-selectin, PSGL-1, L-selectin, LFA-1, ICAM-1 and ICAM-2 but not E-selectin, VLA-4, VCAM-1 or Mac-1. This was consistent with the pattern of endothelial expression of these receptors with strong expression of P-selectin and ICAM-1, but negligible expression of E-selectin on bronchial endothelium. CONCLUSION: This study suggests an important role for PSGL-1/P-selectin in T cell migration into the bronchi and provides further evidence for a pattern of recirculation for respiratory tract homing T cells distinct from the gut and skin.

Bronchi↗
PubMed2002

Survey of public health laboratory protocols for reporting the antibiotic susceptibility of urinary isolates submitted from general practice.

This study set out to investigate the variation in laboratory reports of the antibiotic susceptibility of urinary isolates from specimens received from primary care. A questionnaire survey was conducted across Public Health laboratories in England and Wales, and 38 out of 47 questionnaires were returned. Seventy-nine percent of laboratories had community antibiotic guidelines for the management of urinary tract infections, and trimethoprim was the most common first-line antibiotic recommendation. Trimethoprim and nitrofurantoin were the most commonly tested antibiotics, and the oral cephalosporins were the most frequent second-line antibiotics tested. A wide variation in reporting was demonstrated, with 47% of laboratories reporting on the combination of trimethoprim, amoxycilline and an oral cephalosporin. In view of the increasing concern about antibiotic prescribing in the community, it may be useful to review local laboratory policies so that antibiotic susceptibility reporting is consistent with primary care antibiotic guidance.

Anti-Bacterial Agents↗
PubMed2001

Optimising antibiotic prescribing in primary care.

Prudent antimicrobial prescribing in the community may help to prevent the relentless increase in resistance, highlighted worldwide by numerous parliamentary documents. Antibiotic guidance, developed by primary care professionals and disseminated locally with outreach workshops, helps to reduce the use of broad-spectrum antimicrobials. Computerised guidance, audit of antibiotic use and restricted laboratory sensitivity reporting moves the prescriber towards the selection of recommended drugs. Educational campaigns and patient leaflets given at the consultation help to modify patients' expectations. Primary care physicians need to consider how much pharmaceutical representatives and free samples influence their prescribing. This multi-faceted approach needs to be backed up with a research programme developing the evidence base for management guidance of antimicrobial use in primary care.

Anti-Bacterial Agents↗
PubMed2001

A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide. Steam-distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy. MATERIALS AND METHODS: In this pilot study dyspeptic patients with positive serology for H. pylori confirmed by 13C urea breath test (UBT), at 0 and 2 weeks, were enrolled. Treatment consisted of one 4 mg garlic oil capsule with a meal four times per day for 14 days. H. pylori eradication was defined as a negative UBT at both follow-up appointments. Suppression was defined as a 50% fall in 13C excess between baseline and follow-up 1. RESULTS: Five patients completed the study. There was no evidence of either eradication or suppression of H. pylori or symptom improvement whilst taking garlic oil. CONCLUSION: These negative results show that, within the gastric milieu, garlic oil at this dose does not inhibit H. pylori. A higher dose administered for a longer time-period may be effective. Antibiotics are usually combined with a proton-pump inhibitor or bismuth salt, as the only antibiotic with any in vivo activity against H. pylori in monotherapy is clarithromycin. A proton pump inhibitor raises gastric pH and, by increasing bacterial division, may increase the in vivo activity of garlic oil. This may be worth pursuing in a future trial.

Adult↗
PubMed2001

The significance of cagA(+) Helicobacter pylori in reflux oesophagitis.

BACKGROUND: Helicobacter pylori is a gastroduodenal pathogen associated with ulceration, dyspepsia, and adenocarcinoma. Recent preliminary studies have suggested that H pylori may be protective for oesophageal adenocarcinoma. In addition, strains of H pylori identified by the presence of the cytotoxin associated gene A (cagA) are shown to have a significant inverse association with oesophageal adenocarcinoma. Given that cagA(+) H pylori may protect against oesophageal carcinoma, these strains may be protective for oesophagitis, a precursor of oesophageal carcinoma. AIMS: The aim of this study was to investigate the association between cagA(+) H pylori and endoscopically proved oesophagitis. PATIENTS: The study group included 1486 patients attending for routine upper gastrointestinal tract endoscopy. METHODS: At endoscopy the oesophagus was assessed for evidence of reflux disease and graded according to standard protocols. Culture and histology of gastric biopsy specimens determined H pylori status. The prevalence of cagA was identified by an antibody specific ELISA (Viva Diagnostika, Germany). RESULTS: H pylori was present in 663/1485 (45%) patients and in 120/312 (38%) patients with oesophagitis. Anti-CagA antibody was found in 499/640 (78%) H pylori positive patients. Similarly, anti-CagA antibody was found in 422/521 (81%) patients with a normal oesophagus and in 42/60 (70%) with mild, 24/35 (69%) with moderate, and 11/24 (46%) with severe oesophagitis. The risk of severe oesophagitis was significantly decreased for patients infected with cagA(+) H pylori after correction for confounding variables (odds ratio 0.57, 95% confidence interval 0.41-0.80; p=0.001). CONCLUSIONS: These results suggest that infection by cagA(+) H pylori may be protective for oesophageal disease.

Adult↗
PubMed2001

Role of screening agar plates for in vitro susceptibility testing of Helicobacter pylori in a routine laboratory setting.

BACKGROUND: Resistance of Helicobacter pylori to the more frequently used antibiotics (metronidazole and clarithromycin) reduces eradication rates even with triple treatment. Determining the antibiogram profile of H pylori can take up to 14 days and delays appropriate treatment. AIMS: To determine the role of screening agar plates for more rapid in vitro susceptibility of H pylori to metronidazole, amoxicillin, and clarithromycin. METHODS: Routine gastric biopsy specimens from 507 dyspeptic patients were inoculated on to 10% lysed blood agar plates containing metronidazole (8 microg/ml), clarithromycin (2 microg/ml), or amoxicillin (0.5 microg/ml). The minimum inhibitory concentration (MIC) of the 90 isolates was determined using the E test. RESULTS: Metronidazole resistance was detected in 28 of 90 isolates by E test and nine of 98 by screening agar. The screening agar detected none of the four clarithromycin resistant isolates detected by the E test. CONCLUSIONS: The screening agar method is not sufficiently sensitive to be used alone.

Adult↗
PubMed2001

PHLS primary care consultation--infectious disease and primary care research and service development priorities.

In 1999 for the first time the PHLS undertook a questionnaire survey of general practitioners' views of the burden of infectious disease and the priorities for research and development of infectious disease services within the PHLS. Three hundred and seventy-one (38%) of 979 questionnaires mailed to chairs of primary care groups in England, and general practitioners in research networks, were returned. Service areas: computer transfer of laboratory results was considered of greatest priority. Guidance on antibiotic usage, guidance on infectious diseases and education for general practitioners were ranked two, three and four. Burden of infectious disease in primary care: upper respiratory tract infections, tonsillitis/pharyngitis, otitis media/externa and acute cough were placed one, three, four and seven respectively. Urinary tract infections were ranked second and dyspepsia/Helicobacter pylori fifth. Leg ulcers, diarrhoea, genital chlamydia infection and vaginal discharge were other diseases considered to cause a large burden of ill-health. Genital chlamydia, tuberculosis, Helicobacter pylori and meningococci were ranked one, two, three, and five in the NHS opportunity to affect the burden of ill-health. Priorities for improvements to diagnostic tests, evidence on which to base treatment and guidance: chronic fatigue/ME was ranked top in these areas. The other top ten syndromes ranked in order were genital chlamydia infections, antibiotic resistance surveillance, vaginal discharge, leg ulcers, sinusitis, otitis media/externa, dyspepsia/Helicobacter pylori, Creutzfeld Jacob Disease, and tonsillitis. This consultation exercise has highlighted broad areas for future PHLS involvement in primary care. In order to make progress, further consultation is needed with groups of GPs, and other relevant bodies. Particularly for the areas ranked in the top ten, the type of further PHLS involvement needs to be defined. For some syndromes (chronic fatigue and leg ulcers) this may be writing guidance and for others (respiratory tract infections) more treatment trials are required. The purposes and possible methods of communicable disease surveillance in general practice should be the subject of additional consultation.

Attitude of Health Personnel↗
PubMed2000

Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow.

Selective eosinophil accumulation is a hallmark of diseases such as asthma. In a model of chronic eosinophilic inflammation, we have previously shown that the tethering step in eosinophil adhesion is mediated by PSGL-1 binding to P-selectin. The Th2-associated cytokine IL-13 is of potential importance in allergic disease. We have therefore investigated whether IL-13 can mediate eosinophil binding to human umbilical vein endothelial cells (HUVEC) through P-selectin. IL-13 caused dose- and time-dependent increases of P-selectin expression, as assessed by flow and laser scanning cytometry. A similar degree of expression was observed with IL-4. There was no effect on E-selectin or ICAM-1 expression. Tumor necrosis factor-alpha induced the expression of VCAM-1, E-selectin, and ICAM-1 but had no effect on P-selectin expression. IL-13 increased the production of mRNA for surface and soluble variants of P-selectin. Under flow conditions, eosinophils, but not neutrophils, showed enhanced binding to IL-13 and to IL-4-stimulated HUVEC compared to medium-cultured cells. Eosinophil adhesion was completely inhibited by a blocking monoclonal antibody against PSGL-1 and P-selectin. Anti-VLA-4 and anti-VCAM-1 antibodies inhibited binding to a lesser extent. Thus, at physiologic levels of expression induced by Th2 cytokines, P-selectin/PSGL-1 supported eosinophil but not neutrophil adhesion. This mechanism is likely to be a key event leading to the selective accumulation of eosinophils in allergic inflammation.

Animals↗
PubMed2000

Primary care workshops can reduce and rationalize antibiotic prescribing.

We describe a controlled study comparing the effects on primary care prescribing in west Gloucestershire, UK, where antibiotic workshops were offered, with those in east Gloucestershire, where microbiology tutorials were given. The year-on-year changes in quantity and costs of antibiotics dispensed following general practice prescriptions were measured. There was no significant difference in the number of antibiotic items prescribed across the county, but the number of prescriptions for broad-spectrum agents (quinolones, cephalosporins and co-amoxiclav) declined by 15.4% in west Gloucestershire, compared with a 6.5% increase in east Gloucestershire (P: = 0.002). Use of narrow-spectrum antibiotics (penicillin V, trimethoprim and nitrofurantoin), whose use was encouraged, did not change in west Gloucestershire practices, but decreased by 12% in east Gloucestershire practices (P: = 0.003). There was increased use of clarithromycin and azithromycin in both groups of practices. Antibiotic workshops held in the primary care setting can rationalize antibiotic prescribing. This can reduce prescribing costs and selection pressure by broad-spectrum antimicrobial agents and, perhaps, go some way to reducing the development of resistance.

Anti-Bacterial Agents↗
PubMed2000

PHLS works towards effective interaction with primary care.

The PHLS primary care initiative was set up to develop and maintain links with primary care professionals, including researchers, GP research networks, and primary care groups in order to prioritize research and laboratory service developments. Such collaboration has spawned the development of antibiotic guidance, which has been posted on the Internet, and participation of the PHLS in other infectious disease guidance (for example, Prodigy). The implementation of the NHS information strategy will further facilitate the development of and access to local and national primary care guidance, laboratory reporting, and participation in surveillance. Primary care professionals identified several main research priorities in an exercise that facilitated collaboration in the development of research projects and grant applications. These priorities are the natural history of infections presenting to GPs, antibiotic resistance, the role of clinical scores and the laboratory in the diagnosis of infection, the importance of patient and professional attitudes in modifying antimicrobial prescribing, and the role of health professionals in community infection control. Current rapid changes in primary care in the new NHS--such as NHS Direct and the establishment of walk-in centres--may affect the surveillance of communicable disease by offering opportunities for improved data collection but also by posing threats to current systems of surveillance.

Communicable Disease Control↗
PubMed1999

P- and L-selectin mediate binding of T cells to chronically inflamed human airway endothelium.

The inflammatory process that underlies allergic diseases such as asthma is characterized by tissue infiltration of eosinophils and T cells. We have used the Stamper-Woodruff frozen-section assay to characterize the receptors involved in adhesion of human peripheral blood T cells to nasal polyp endothelium (NPE) as a model of T cell migration in allergic disease. T cells bound specifically to NPE in a temperature-, cell concentration- and shear stress-dependent fashion. Adhesion was inhibited by approximately 70% by antibodies against P-selectin and its counter-receptor P-selectin glycoprotein-1 (PSGL-1). In addition, a blocking monoclonal antibody (mAb) against L-selectin caused significant although lesser inhibition. Cells adhering to NPE were primarily of the CD45RO+ memory subset. Although only a minority subset of peripheral blood T cells expressed functional PSGL-1, as determined by binding of a P-selectin Fc chimera, the majority of the P-selectin chimera-binding cells were found to be CD45RO+. This is consistent with the observation that memory T cells bind to NPE via P-selectin. Using blocking mAb we also investigated which integrins and their counter-structures were involved in T cell binding. A combination of anti-beta1 and beta2 mAb was able to inhibit adhesion by almost 50%. An antibody against intercellular adhesion molecule (ICAM)-2 gave an inhibition similar to that by anti-CD18 mAb, suggesting ICAM-2 was the major counter-receptor involved for the beta2 integrin component. This study suggests that P-selectin, and to a lesser extent L-selectin, may be acting as specific homing receptors for the airway mucosa in the context of chronic allergic disease.

Cell Adhesion↗
PubMed1999

Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium.

We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (beta1), CD49d (alpha4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and the two IL-8 receptors IL8RA and IL8RB (C-X-CR1 and -CR2). In contrast, eosinophil adhesion was unaffected by PT, WEB 2086, or anti-IL8R mAbs. mAbs against CCR-3, IL-3, IL-5, and GM-CSF also had no effect. This study demonstrates that eosinophil and neutrophil adhesion to NPE in the FSA conforms to the multistep paradigm for leukocyte adhesion and can be used to model the molecular basis for adhesion to endothelium in the context of chronic inflammatory disease. Using this assay, we have observed significant differences in integrin usage between eosinophils and neutrophils and a striking difference in the mechanism of integrin activation. These differences could explain, in part, the preferential accumulation of eosinophils in diseases such as asthma.

CD11 Antigens↗
PubMed1999

A comparison of six commercial kits for Helicobacter pylori detection.

The British Society of Gastroenterologists suggests that dyspeptic patients under 45 years of age should be screened serologically for Helicobacter pylori infection, to reduce endoscopy workload. We have compared the sensitivity, specificity, and predictive value of six commercial serological kits intended for pre-endoscopy screening for H. pylori with histopathology and culture in 82 dyspeptic patients, 35 of whom were H. pylori positive. The kits' sensitivities were as follows: Bio-Rad GAP 100%, Helico-G 100%, Premier 97%, and Pyloriset EIA-G 94%. Poor specificity of the ELISA kits--Bio-Rad GAP 67%, Helico-G 67%, Premier 85%, and Pyloriset EIA-G 76%--was due to previous treated or cleared H. pylori infection. Allowing for previously documented H. pylori infection or peptic ulcer improved specificity--Bio-Rad GAP 84%, Helico-G 84%, Premier 100%, and Pyloriset EIA-G 90%. The Pyloriset Dry latex kit had a higher specificity (86%) but a lower sensitivity (75%) than the Oxoid latex kit (specificity 70%, sensitivity 94%). The qualitative Premier Launch kit had the best overall results (and was the easiest ELISA to perform). Reliable serological diagnosis of H. pylori is now suitable for screening dyspeptic patients.

Adult↗
PubMed1999

Meningococcal disease in siblings caused by rifampicin sensitive and rifampicin resistant strains.

Two brothers presented with meningococcal infection in a five day period, the first with a rifampicin sensitive strain and the second, who had received rifampicin chemoprophylaxis, with a resistant strain. Secondary cases of meningococcal disease can occur despite chemoprophylaxis, and may be rifampicin resistant. Close contacts should be informed of the early symptoms of meningococcal disease and of the need to seek medical advice urgently if they occur.

Antibiotic Prophylaxis↗
PubMed1999

A prospective study of central venous hemodialysis catheter colonization and peripheral bacteremia.

BACKGROUND: Sepsis as a consequence of central venous hemodialysis catheter colonization is a major cause of morbidity in the hemodialysis population. We have previously shown that the majority of catheters become colonized and that this is associated with peripheral bacteremia. The time period over which this colonization occurs is unknown. METHOD: A prospective study of 31 central venous hemodialysis catheters was performed. Central venous blood cultures were taken from the catheter weekly after insertion. When the central cultures became positive, indicating catheter colonization, peripheral venous blood cultures were taken during dialysis to detect peripheral bacteremia. RESULTS: Twenty-one catheters (68%) became colonized before their removal for reasons other than infection (mean time to colonization 27 days, range 5-115 days). Eleven patients (35%) developed peripheral bacteremia with the same organisms (mean time from colonization to bacteremia 32 days, range 5-26 days). Bacteremia only occurred when blood drawn from the catheter cultured more than 3000 colony forming units per ml. CONCLUSIONS: Bacterial colonization of central venous catheters often leads to bacteremia. The time between insertion and colonization is very variable, but is universally present after 16 weeks. The risk of subsequent bacteremia is related not only to time left in situ, but also the degree of colonization. Surveillance cultures would allow clinicians to detect colonization before bacteremia occurs and take preventative measures.

Bacteremia↗
PubMed1998

Radon measurements and mitigation at a fish hatchery.

Groundwater radon concentration of 83 Bq L(-1) generated indoor radon levels exceeding 3,300 Bq m(-3) at a commercial fish hatchery. Passive and active mitigation strategies to reduce the waterborne radon levels included a packed column, a waterfall through perforated grates, surface aeration, and bottom bubblers. Waterborne concentrations were reduced up to 83% using a combination of mitigation procedures, but a comparable reduction in indoor radon concentrations was not observed. A diurnal cycle showed that indoor radon levels peaked in early afternoon, probably as a result of warmer air being dissolved in the water during mitigation. Reduction of indoor radon levels below 148 Bq m(-3) was seldom achievable with both water mitigation and direct air ventilation at 23 room air changes hourly.

Air Pollutants, Radioactive↗