Biomedical subjects

K B Bamford

Publications and source records attributed to K B Bamford.

At least 19 recordsLinked to original sources

PubMed2005

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Bacteria↗

PubMed2001

Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody.

BACKGROUND: The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue. METHODS: Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR. RESULTS: C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG. CONCLUSIONS: We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland.

Adult↗

PubMed2001

Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion.

The majority of humans infected with Helicobacter pylori maintain a lifelong infection with strains bearing the cag pathogenicity island (PAI). H. pylori inhibits T cell responses and evades immunity so the mechanism by which infection impairs responsiveness was investigated. H. pylori caused apoptotic T cell death, whereas Campylobacter jejuni did not. The induction of apoptosis by H. pylori was blocked by an anti-Fas Ab (ZB4) or a caspase 8 inhibitor. In addition, a T cell line with the Fas rendered nonfunctional by a frame shift mutation was resistant to H. pylori-induced death. H. pylori strains bearing the cag PAI preferentially induced the expression of Fas ligand (FasL) on T cells and T cell death, whereas isogenic mutants lacking these genes did not. Inhibiting protein synthesis blocked FasL expression and apoptosis of T cells. Preventing the cleavage of FasL with a metalloproteinase inhibitor increased H. pylori-mediated killing. Thus, H. pylori induced apoptosis in Fas-bearing T cells through the induction of FasL expression. Moreover, this effect was linked to bacterial products encoded by the cag PAI, suggesting that persistent infection with this strain may be favored through the negative selection of T cells encountering specific H. pylori Ags.

Antigens, Bacterial↗

PubMed2000

Infection with virulent strains of Helicobacter pylori is not associated with ischaemic heart disease: evidence from a population-based case-control study of myocardial infarction.

BACKGROUND: Although the majority of evidence does not support association between Helicobacter pylori infection and ischaemic heart disease, the nature of this relationship may differ when virulence of the infecting strains are examined. METHODS AND RESULTS: The prevalence of IgG antibody evidence of infection with CagA positive stains of H. pylori was investigated in stored plasma samples from 259 cases of myocardial infarction (aged 25-70 years, 74 males) and 259 population based controls from the same area in Northern Ireland. Two-hundred and seventy (52.1%) subjects were seropositive for anti-CagA IgG. CagA seropositivity was more common in cases than in controls: 56.4 vs 47.9%, odds ratio for seropositivity in cases (95% CI) 1.41 (1.00, 1.99). Substantial attenuation of this relationship occurred on adjustment for age, sex, number of siblings, smoking and measures of socio-economic status: odds ratio (95% CI) 1.16 (0.79, 1.70). A similar pattern was seen for seropositivity for all H. pylori strains. CONCLUSION: Infection with the more virulent strains of H. pylori, as with all strains, is not associated with myocardial infarction.

Adult↗

PubMed1999

Epidemiology of Chlamydia pneumoniae infection in a randomly selected population in a developed country.

This cross-sectional study of 400 sera from a randomly selected adult population in Northern Ireland, using a microimmunofluorescence assay, demonstrated high overall seropositivity (70%) for IgG Chlamydia pneumoniae antibodies in developed populations. Seropositivity was shown to be unrelated to gender, age or smoking but there was an inverse trend between infection and educational level achieved as a measure of socio-economic status. IgG levels were also higher during the winter months suggesting seasonal variation of Chlamydia pneumoniae infection. The high prevalence of evidence of exposure to Chlamydia pneumoniae as described in this study may have implications for prevention of cardiovascular disease if further evidence conclusively determines that infection with this organism is a risk factor for cardiovascular disease.

Adult↗

PubMed1999

The rise in circulating gastrin with age is due to increases in gastric autoimmunity and Helicobacter pylori infection.

To assess the effect of increasing age on circulating gastrin, we surveyed serum gastrin, Helicobactor pylori seroantibody status and gastric autoimmunity in 366 hospitalized patients aged 15-90 years. Data were subjected to multivariate analysis, using logarithmic transformation to normalize the distribution of gastrin concentrations (presented as geometric means and 95% CIs). The frequency of H. pylori-positive antibody status increased with age from 28% in the second decade to > 70% beyond the fourth decade. Fasting gastrin concentrations rose significantly from 44 ng/l (41-48) in the second decade to 95 ng/l (67-131) by the eighth decade (p = 0.001) in the total group. Twenty-seven patients (6.8% of the total) tested positive for gastric auto-antibodies: 2% of patients in the second decade, rising to 15.9% in the eighth decade. These patients formed a distinct group with respect to circulating gastrin concentrations. Excluding these 27, fasting gastrin concentrations still rose significantly, from 44 ng/l (41-48) in the second decade, to 67 ng/l (50-89) in the eighth decade (p = 0.003) in the remaining 341 patients. Fasting gastrin concentrations were significantly higher in patients who were H. pylori-seropositive (59 ng/l, 54-64 vs. sero-negative 41 ng/l, 37-46) (p = 0.002), and there was no increase in circulating gastrin concentrations with increasing age in either the H. pylori-positive or the H. pylori-negative group. The increase in circulating fasting gastrin observed with increasing age is due to an increased incidence of gastric antibodies associated with auto-immune atrophic gastritis, and an increased incidence of H. pylori infection.

Adolescent↗

PubMed1999

Chronic gastrointestinal inflammation.

Chronic gastrointestinal inflammation is one of the most common types of inflammatory process which affects humans. It is diverse in aetiology, pathogenesis and manifestation. There are also features of chronic inflammation at different sites within the gastrointestinal tract which provide a common thread in terms of the approaches which may be used in investigating these intriguing processes. This paper provides an overview of the mucosal changes in chronic gastrointestinal inflammation. Conserved and variable features of inflammation at different sites extending from the oral cavity to the rectum are highlighted. The involvement of different inflammatory cell types within any diagnostic entity is considered and the progression from an acute to chronic inflammatory condition explored. Important issues in the maintenance of a chronic inflammatory state are the balance between pro- and anti-inflammatory pressures, the driving force behind the inflammation and immune response that is occurring and the mechanisms for curtailment of unwanted or harmful responses which may damage the host. Thus inflammation is likely to result when there is persistence of a driving force and/or imbalance in the pro- and anti-inflammatory mechanisms in the tissue involved.

Animals↗

PubMed1999

A prospective randomised trial of a "test and treat" policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic.

BACKGROUND: Management of dyspepsia remains a controversial area. Although the European Helicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial. AIMS: To compare a "test and treat" eradication policy against management by OGD. PATIENTS: Consecutive subjects were prospectively recruited from open access OGD and outpatient referrals. METHODS: H pylori status was assessed using the carbon-13 urea breath test. H pylori positive patients were randomised to either empirical eradication or OGD. Symptoms and quality of life scores were assessed at baseline and subsequent reviews over a 12 month period. RESULTS: A total of 104 H pylori positive patients aged under 45 years were recruited. Fifty two were randomised to receive empirical eradication therapy and 52 to OGD. Results were analysed using an intention to treat policy. Dyspepsia scores significantly improved in both groups over 12 months compared with baseline; however, dyspepsia scores were significantly better in the empirical eradication group. Quality of life showed significant improvements in both groups at 12 months; however, physical role functioning was significantly improved in the empirical eradication group. Fourteen (27%) in the empirical eradication group subsequently proceeded to OGD because of no improvement in dyspepsia. CONCLUSIONS: This randomised study strongly supports the use of empirical H pylori eradication in patients referred to secondary practice; it is estimated that 73% of OGDs in this group would have been avoided with no detriment to clinical outcome.

Adult↗

PubMed1999

Chlamydia pneumoniae antibodies are associated with an atherogenic lipid profile.

OBJECTIVE: To determine, within a representative population group of men and women, whether alteration of the lipid profile might underlie the reported association between Chlamydia pneumoniae and ischaemic heart disease. DESIGN AND SETTING: Cross sectional survey in an area with a high incidence of ischaemic heart disease. SUBJECTS: 400 randomly selected participants in the World Health Organisation MONICA project's third population survey in Northern Ireland. MAIN OUTCOME MEASURES: Stored sera were examined by microimmunofluorescence for IgG antibodies to C pneumoniae at a dilution of 1 in 64. Mean total and high density lipoprotein (HDL) cholesterol were compared between seropositive and seronegative individuals with adjustment for age, measures of socioeconomic status, smoking habit, alcohol consumption, body mass index, and the season during which blood had been taken. RESULTS: In seropositive men, adjusted mean serum total cholesterol and HDL cholesterol were 0.5 mmol/l (9.2%) higher and 0.11 mmol/l (9.3%) lower, respectively, than in seronegative men. Differences in women did not achieve statistical significance, but both total cholesterol and HDL cholesterol were higher (3.6% and 5.8%, respectively) in seropositive than in seronegative individuals. CONCLUSIONS: There is serological evidence that C pneumoniae infection is associated with an atherogenic lipid profile in men. Altered lipid levels may underlie the association between C pneumoniae and ischaemic heart disease.

Adult↗

PubMed1999

Regulation of the mucosal immune response.

Infectious diseases continue to exact an extensive toll on populations living closest to the equatorial regions of the globe. A substantial proportion of these infections gain access to the host via the mucosal tissues. Thus, the development of new vaccines that enhance mucosal immunity is considered to be of paramount importance in order to prevent or limit the impact of these infections. Mucosal immune responses must discriminate between commensal flora within the lumen and potential pathogens. These responses are highly adapted to induce protection without excessive amounts of inflammation. The balances that regulate mucosal immune and inflammatory responses have to be understood if effective mucosal immunity is to be induced through local immunization. This review will summarize some of the unique properties of mucosal immune responses and focus on recent advances that have significantly influenced our understanding of the regulation of immune and inflammatory responses following infection.

Animals↗

PubMed1998

Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype.

BACKGROUND & AIMS: Studies have shown that gastric T cells are increased during Helicobacter pylori infection. The purpose of this study was to characterize the human gastric T-cell responses in the presence or absence of H. pylori. METHODS: T-cell surface antigens were examined by immunohistochemistry or after isolation for evaluation of surface antigens and cytoplasmic cytokines using flow cytometry. RESULTS: CD4+ and CD8+ T cells were increased in situ during infection with H. pylori. Freshly isolated gastric T cells expressed cytoplasmic interferon gamma (IFN-gamma) and interleukin (IL)-2 after a brief stimulation. Simultaneous four-color flow cytometry demonstrated that both CD8+ and CD4+ T cells expressed IFN-gamma. Because stimulation through CD30 favors the induction of IL-5 and Th2 cells, gastric and colonic T cells were examined for CD30 expression. Consistent with the notion that Th2 cells are found in the intestine, CD30 was evident throughout the lamina propria of the colon but was virtually absent in the stomach. Furthermore, freshly isolated gastric T cells produced little IL-4 and virtually no IL-5 or tumor necrosis factor beta. CONCLUSIONS: These observations show that gastric T cells resemble the Th1 type, which may explain their failure to induce immunity to H. pylori and their ability to contribute to the pathogenesis of gastric disease.

Adult↗

PubMed1998

Nested primers improve sensitivity in the detection of Helicobacter pylori by the polymerase chain reaction.

To investigate potential routes of spread of infection by the polymerase chain reaction (PCR) it is important that the technique is effective in the types of specimen to be investigated. To establish the limits of detection of Helicobacter pylori by PCR in clinical material from the gastric mucosa, faeces, dental plaque and oral rinses, samples were seeded with known numbers of bacteria. DNA extraction was followed by amplification with primers from the urease C gene. Nested primers were used to amplify the PCR product which was detected using a digoxigenin-labelled probe. Faeces or plaque inhibited the single reaction 10(2)-10(6) fold. A second amplification using nested primers and probing increased the sensitivity to a level similar to that obtained with pure culture. This method is potentially useful with less likelihood of false negative results when trying to detect H. pylori by PCR in highly contaminated, clinical material.

DNA Primers↗

PubMed1998

A prospective study of the management of the young Helicobacter pylori negative dyspeptic patient--can gastroscopies be saved in clinical practice?

BACKGROUND: Helicobacter pylori status has been suggested as a means of selecting young dyspeptic patients for gastroscopy as patients who are H. pylori negative and do not exhibit alarm symptoms or ingest non-steroidal anti-inflammatory medication have a low risk of serious organic disease. AIM: To determine if young patients with ulcer-like dyspepsia and found to be H. pylori negative on non-invasive testing could be reassured by this knowledge and not proceed to gastroscopy. PATIENTS: One hundred and sixty-one consecutive attendees aged 45 years or less with a presenting complaint of epigastric pain or discomfort were prospectively recruited from open access gastroscopy referrals and gastroenterology clinics. METHODS: Patients who were H. pylori negative on 13-carbon urea breath test were reassured of the likelihood of a normal gastroscopy, given lifestyle advice and also advised to take symptomatic therapy as required. Patients were reviewed at 6 weeks, 3 months and 6 months when symptoms and quality of life were reassessed. Patients proceeded to gastroscopy if at any review their dyspepsia score stayed the same or worsened. RESULTS: Fifty-five H. pylori negative patients were recruited (30 male, mean age 31 years), two patients did not attend subsequent review. Thirty-two (58%) came to gastroscopy. Endoscopic diagnoses included 25 which were normal, three with gastro-oesophageal reflux disease, three with peptic ulcer disease and one with gastric erosions. Dyspepsia and quality of life scores showed significant improvement over 6 months. CONCLUSIONS: This management strategy resulted in a 42% reduction in gastroscopies in H. pylori negative patients. Whilst the majority of patients endoscoped had normal findings, seven patients (22%) had pathology. Overall there were significant improvements in dyspepsia and quality of life at 6 month follow-up.

Adult↗

PubMed1997

Epidemiology of Helicobacter pylori infection among 4742 randomly selected subjects from Northern Ireland.

BACKGROUND: Despite the widespread prevalence and serious clinical sequelae of infection with Helicobacter pylori, there have been few large population-based studies, using randomly selected subjects, examining the epidemiology of this infection. AIM: To examine the distribution and determinants of H. pylori infection in a developed country. SUBJECTS AND SETTING: Overall 4742 subjects, aged 12-64, from Northern Ireland were randomly selected. METHODS: Helicobacter pylori specific IgG antibodies were measured by enzyme linked immunosorbent assay, using an acid-glycine extract antigen, in stored serum from subjects who had participated in three linked population-based surveys of cardiovascular risk factors performed in 1986 and 1987. RESULTS: The overall prevalence of H. pylori infection was 50.5%. Prevalence increased with age from 23.4% in 12-14 year olds to 72.7% in 60-64 year olds: chi 2 for trend 518, P < 10(-4). In subjects aged > or = 25, infection was more common in males (60.9%) than females (55.2%): chi 2 = 9.53, P < 0.01. This relation remained significant after adjusting for age, and measures of socioeconomic class: odds ratio (OR) for infection, male versus female was 1.19 (95% confidence interval [CI]: 1.02-1.40). Infection was associated with social class: the adjusted OR of infection in subjects from manual social classes relative to those from non-manual classes was 1.7 (95% CI: 1.47-1.98). Infection was significantly more common in current smokers and ex-smokers than in subjects who had never smoked: adjusted OR for infection, ex-smokers versus never smoked was 1.22 (95% CI: 1.01-1.49); for smokers of > or = 20/day versus never smoked OR = 1.33 (95% CI: 1.05-1.67). Infection was not associated with height in adult males but mean height in infected women was lower than in uninfected women after adjusting for age and socioeconomic status: difference in mean height (SE), -0.85 cm (0.32), P < 0.01. There was no demonstrable relationship between H. pylori infection and current alcohol intake. CONCLUSIONS: This study demonstrated a high prevalence of infection in a population from a developed country. Previously reported associations between H. pylori infection, age, sex, social class, and reduced height in females were confirmed and smoking was identified as a possible risk factor for H. pylori infection.

Adolescent↗

PubMed1997

Differential stimulation of interleukin-12 (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa.

The objective of these experiments was to examine the ability of Helicobacter pylori to stimulate interleukin-10 (IL-10) or IL-12 and select for either Th1 or Th2 cells. Gastric biopsy specimens were collected from patients who were categorized with respect to the presence of H. pylori and gastric disease as well as their age, gender, medications, and other factors. As Th1 and Th2 cells are selected by IL-12 and IL-10, respectively, biopsy specimens were screened for mRNA and protein for these cytokines. Although mRNA for IL-12 and IL-10 was detected in biopsy specimens obtained from both infected and uninfected patients, IL-12 protein predominated. Levels of IL-10 and IL-12 in gastric tissue did not change in response to infection. Moreover, gamma interferon (IFN-gamma)-producing T cells were found in both the infected and the uninfected gastric mucosa. Stimulation of peripheral blood leukocytes from either infected or uninfected donors with various concentrations of live or killed H. pylori induced immunoreactive IL-12 and IL-10. After stimulation with live H. pylori, IL-12 levels increased more than 30-fold, whereas IL-10 levels increased only 2- to 5-fold, compared to cells stimulated with medium alone. Interestingly, killed H. pylori induced significantly more IL-10 (P < 0.05) than live H. pylori, while recombinant urease only induced IL-10. These results demonstrate that live H. pylori selectively stimulates the induction of IL-12 and Th1 cells that produce IFN-gamma, whereas preparations used in oral vaccines induce more IL-10 and may favor Th2 cell responses.

Adult↗

PubMed1997

Community-acquired lower respiratory tract infection: implementation of an antibiotic protocol.

Enthusiastic formulation of clinical guidelines continues to increase but although theoretical difficulties in guideline implementation have been recognised, little attention has been paid to their effectiveness in everyday clinical practice. The introduction of a protocol for empirical treatment of lower respiratory tract infection (PETRI) to an acute medical take-in unit in Belfast is described. Early involvement of all relevant staff, preparation of user-friendly flow charts, and imaginative publicity, resulted in an initial implementation rate of 75%. The role of implementation as a significant rate-limiting step in the audit cycle is emphasised.

Anti-Bacterial Agents↗

PubMed1996

Helicobacter pylori infection in children: relation with current household living conditions.

BACKGROUND: Studies demonstrating that deprived household living conditions during childhood are risk factors for acquisition of Helicobacter pylori infection have been performed mainly in adults, who probably acquired the infection several decades ago. This study investigates whether deprived household living conditions remain important risk factors for infection in subjects (children) with recently acquired infection. AIMS: To examine the relation between current household living conditions and acquisition of H pylori infection in childhood. SUBJECTS/SETTING: Opportunistically recruited group of 367 children, aged 3 to 15 years, undergoing routine non-gastrointestinal day surgery. METHODS: Anti-H pylori IgG antibodies measured by a commercial enzyme linked immunosorbent assay validated for use in children. Postal questionnaire collecting sociodemographic data and data on household living conditions. RESULTS: Infection was associated with social class and overcrowding in the household. After adjustment for age, social class, and household density, a positive association remained between infection with H pylori and bed-sharing between children and parents on one or two nights per week, odds ratio for infection (95% CI), 2.29 (1.21, 4.32) or more frequently, odds ratio for infection (95% CI), 2.95 (1.35, 6.45). CONCLUSIONS: The continuing importance of household living conditions in the acquisition of H pylori infection is confirmed and household crowding and sharing a bed with a parent are identified as risk factors for infection.

Adolescent↗

PubMed1996

Randomised controlled trial of ranitidine versus omeprazole in combination with antibiotics for eradication of Helicobacter pylori.

This study compared high dose ranitidine versus low dose omeprazole with antibiotics for the eradication of H pylori. 80 patients (mean age 48 years, range 18-75) who had H pylori infection were randomised in an investigator-blind manner to either a two-week regime of omeprazole 20 mg daily, amoxycillin 500 mg tid and metronidazole 400 mg tid (OAM), or ranitidine 600 mg bd, amoxycillin 500 mg tid and metronidazole 400 mg tid (RAM), or omeprazole 20 mg daily and clarithromycin 500 mg tid (OC), or omeprazole 20 mg daily and placebo (OP). H pylori was eradicated in 6 of 19 patients in the OAM group (32%); 8 of 18 in the RAM group (44%), 4 of 15 in the OC group (27%); none of 18 in the OP group (0%). [< P0.005 for OAM, RAM, OC vs OP; P = N.S. between OAM, RAM, OC]. Overall metronidazole resistance was unexpectedly high at 58%. Eradication rates in metronidazole sensitive patients were 71% (5/7) and 100% (3/3) for OAM and RAM respectively. In conclusion, H pylori eradication rates using high dose ranitidine plus amoxycillin and metronidazole may be similar to that of low dose omeprazole in combination with the same antibiotics for omeprazole with clarithromycin. Overall eradication rates were low due to a high incidence of metronidazole resistance but were higher in metronidazole-sensitive patients. Even high dose ranitidine with two antibiotics achieves a relatively low eradication rate. These metronidazole-based regimens cannot be recommended in areas with a high incidence of metronidazole resistance.

Adolescent↗