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Biomedical subjects

M A Mendall

Publications and source records attributed to M A Mendall.

48 records · Page 3Linked to original sources

The effects of unsaturated fatty acids on Helicobacter pylori in vitro.

The effects of three unsaturated free fatty acids on Helicobacter pylori growth in vitro was determined. Growth of H. pylori in Brucella broth was inhibited in a dose-dependent manner by arachidonic, linoleic and oleic acids. The degree of inhibition at any one concentration was related to the degree of fatty acid unsaturation. Triolein, a triacylglycerol ester of oleic acid did not inhibit growth. Inhibition of H. pylori growth was associated with disruption of cell membranes. Incubation with 14C linoleic acid and 14C oleic acid showed incorporation of these fatty acids into H. pylori cell mass and phospholipids leading to alteration of the phospholipid composition of the organism. Incorporation was greater with linoleic than oleic acid and this was associated with a greater inhibition of growth. These findings indicate that H. pylori is sensitive to unsaturated free fatty acids through their incorporation into phospholipids and membrane destruction. This may have therapeutic implications.

Arachidonic Acids↗

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.

Adult↗

Serology for Helicobacter pylori compared with symptom questionnaires in screening before direct access endoscopy.

This prospective study aimed to compare serology for Helicobacter pylori with two, symptom questionnaires in screening patients before direct access endoscopy. Methods were compared in terms of the number of endoscopies saved and pathology missed in 315 patients referred to a gastroenterology unit by 65 local GPs. The serology used was based on an acid glycine extract of H pylori. One in-house questionnaire was based on the Glasgow dyspepsia (GLADYS) system and the other questionnaire was that reported by Holdstock et al. A cut off point of 6.3 U/ml for H pylori serology was selected for screening patients (97% sensitive and 75% specific). Serology was combined with a history of NSAID usage in determining who should have endoscopy. For the in-house questionnaire, a cut off score of more than 8 out of a possible maximum of 18 was chosen, after prior evaluation in 118 patients referred for direct access endoscopy (the sensitivity for detection of peptic ulcer was 88%, specificity 61%). A cut off score of more than 412 was used for the Holdstock questionnaire. In patients under 45 years, serology detected more peptic ulcers than the in-house questionnaire and the Holdstock questionnaire (27/28 v 24/28, NS and v 20/28, p < 0.05 respectively). The Holdstock questionnaire saved significantly more endoscopies than the other two methods (76/149 v 57/149 for the in-house questionnaire, p = 0.05 and 59/149 for serology, p = 0.05). In all age groups combined, serology was significantly better than the in-house and Holdstock questionnaires at detecting peptic ulcers and gastric cancer (61/63, 52/63, p<0.02, and 50/63, p<0.01 respectively). But serology saved significantly fewer endoscopies (89/315, 135/315, p<0.005, and 119/315, p<0.05 respectively). Serology was inferior to the Holdstock questionnaire at detecting severe oesophagitis. It is concluded that serology is the method of choice in screening before direct access upper gastrointestinal endoscopy in those under 45 years. It best combines a high sensitivity for peptic ulcer disease with a large reduction in unnecessary negative endoscopies.

Adolescent↗

Expression of trefoil peptides pS2 and human spasmolytic polypeptide in gastric metaplasia at the margin of duodenal ulcers.

Duodenal ulcers are associated with gastric metaplasia in the duodenum, both at the ulcer margin and at more distant sites in the duodenal bulb. pS2 and human spasmolytic polypeptide (hSP) are secretory peptides expressed in gastric epithelial cells and in gastric metaplasia. As these peptides may be important in ulcer healing, this study investigated the possibility that the expression of pS2 and hSP is increased in gastric metaplasia at the margin of duodenal ulcers. Duodenal bulb biopsy specimens from 12 duodenal ulcer patients were assessed. Sections were immunostained with monoclonal antibodies for pS2 and hSP. Cytoplasmic stain intensities were measured by an image analysis system and expressed as integrated optical density (IOD) units, In situ hybridisation for pS2 and hSP mRNA was carried out on parallel sections. Duodenal sections were also stained with diatase periodic acid Schiff/alcian blue to localise areas of gastric metaplasia. pS2 antigen staining in the duodenum was restricted to surface epithelial cells, and hSP to acinar and ductular components of Brunner's gland. mRNA localisation corresponded to immunostaining cells. In gastric metaplasia, pS2 expression was greater at the ulcer margin than away from the ulcer, as judged by the intensity of antibody staining (mean IOD units (SEM), 20.6 (3.3) v 9.5 (3.0); p < 0.001). There was a trend towards greater hSP staining at the ulcer margin but this did not achieve statistical significance. These findings support the putative role of pS2 and possible hSP in mucosal healing and providy further evidence for an autocrine 'ulcer-gastric metaplasia-repair' loop involving these trefoil peptides.

Brunner Glands↗

Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects.

The factors that determine which Helicobacter pylori infected subjects develop duodenal ulcer (DU) are unclear. This study tested the hypothesis that infection density and urease activity are higher in DU than non-DU subjects. Fifty five DU and 55 age and sex matched non-DU subjects were studied. Quantitative methods were used for measuring infection density (viable organism count) and urease activity (Berthelot reaction). DU subjects had a greater antral infection density (geometric mean of colony forming units/mg biopsy protein; 10.5 x 10(5) v 1.3 x 10(5), p < 0.001). They also had higher biopsy urease activity (geometric mean of NH3 nmol/min-1/mg protein-1; 103 v 25, p < 0.001). Urease activity per organism, however, was similar in the two groups showing that high antral urease activity in DU was a reflection of organism density. DU was not present in subjects with an antral infection density less than 10(5) colony forming units/mg protein. A correlation was present between H pylori viable counts and the severity and activity of gastritis. Both severity and activity of gastritis were greater in the antrum of DU compared with non-DU subjects but there was no difference in the body between the two groups. It is concluded that antral H pylori infection density is probably an important determinant of DU development, and that there is a baseline of infection density that is necessary for ulcer formation.

Adult↗

Helicobacter pylori infection in childhood: risk factors and effect on growth.

OBJECTIVE: To investigate the current prevalence of Helicobacter pylori infection in childhood, the risk factors for infection, and the effect of infection on growth in preadolescent schoolchildren. DESIGN: Population based sample of 7 year old schoolchildren followed up at age 11; data on risk factors for infection collected at age 7; presence of infection at age 11 determined by measurement of salivary IgG against H pylori by a newly developed enzyme linked immunosorbent assay (ELISA). Height was measured at 7 and 11 years of age. SUBJECTS: 554 schoolchildren from Edinburgh. RESULTS: 62 (11%) children had H pylori infection. Independent risk factors for infection were single parent families (adjusted odds ratio = 2.5; 95% confidence interval 1.1 to 5.7), the 10% most crowded homes (3.1; 1.3 to 7.2), and schools serving predominantly rented housing estates (2.5; 1.0 to 6.5). School catchment area was more important than parental social class or housing tenure. Growth in height between 7 and 11 was diminished in infected children by a mean of 1.1 cm (0.3 to 2.0 cm) over four years. This growth reduction was largely confined to girls (1.6 cm over four years), among whom it correlated with salivary IgG (P = 0.015). CONCLUSION: Data from salivary assay to investigate the epidemiology of H pylori suggest that factors relating to the type of community in which the child lives may now be as important for acquisition of this infection as features of the family home. The greater reduction of growth among infected girls raises the possibility that H pylori infection may delay or diminish the pubertal growth spurt.

Child↗

Salivary antibodies to Helicobacter pylori: screening dyspeptic patients before endoscopy.

Diagnostic tests on saliva have advantages compared with those on serum. In 119 consecutive dyspeptic patients referred for endoscopy we developed and validated an enzyme-linked immunosorbent assay to detect salivary immunoglobulins to Helicobacter pylori. Salivary IgG distinguished positive and negative cases (p < 0.0001), but salivary IgA did not. The optimum performance of salivary IgG (85%) was similar to that of serum IgG (90%) and better than that of salivary IgA. Using our assay and a history of regular use of non-steroidal anti-inflammatories in screening patients under 45 years, we detected all peptic ulcers while saving 39% of endoscopies.

Adolescent↗

Relation of Helicobacter pylori infection and coronary heart disease.

BACKGROUND: There is evidence suggesting that early life experience may influence adult risk of coronary heart disease (CHD). Chronic bacterial infections have been associated with CHD. OBJECTIVE: To determine whether Helicobacter pylori, a childhood acquired chronic bacterial infection, is associated with an increased risk of coronary heart disease in later life. DESIGN: Case-control study controlling for potential confounding variables with an opportunistically recruited control group. SUBJECTS: 111 consecutive cases with documented CHD were recruited from a cardiology clinic and 74 controls from a general practice health screening clinic. All were white men aged 45-65. METHODS: Serum was analysed for the presence of H pylori specific IgG antibodies by ELISA (98% sensitive and 94% specific for the presence of infection). RESULTS: 59% of the cases and 39% of the controls were seropositive for H pylori (odds ratio 2.28, chi 2 7.35, p = 0.007). After adjustment by multiple logistic regression for age, cardiovascular risk factors, and current social class, the effect of H pylori was little altered (odds ratio 2.15, p = 0.03). Further adjustment for various features of the childhood environment known to be risk factors for H pylori infection only slightly weakened the association (odds ratio 1.9). H pylori seropositivity was not related to the level of risk factors in the control population. CONCLUSION: In this pilot study the association of adult coronary heart disease with H pylori seropositivity suggests that the early childhood environment may be important in determining the risk of CHD in adult life. The association needs confirmation in other better designed studies. If H pylori itself is responsible for the association, then this is of great potential importance as the infection is treatable.

Aged↗

Childhood living conditions and Helicobacter pylori seropositivity in adult life.

Infection with Helicobacter pylori increases an individual's risk of peptic ulceration and gastric cancer. In the developed world, prevalence of infection rises with age and varies with social class. We used a cross-sectional study design to test the hypothesis that H pylori infection would be more closely associated with childhood living conditions than with current socioeconomic status. Prevalence of IgG antibodies against H pylori was determined with an enzyme-linked immunosorbent assay in 215 subjects (median age 46 years, range 18-82) attending a health-screening clinic in London. Seropositivity varied from 9% (age less than 30) to 67% (greater than or equal to 70). Subjects were asked about their living conditions at present and when they were aged 8 years. Absence of a fixed hot-water supply (p = 0.0005) and domestic crowding (p = 0.0005) in childhood were powerful independent risk factors for current infection with H pylori. Among current living conditions, only the number of children living in the household was independently associated with H pylori infection (p = 0.004). Most British adults infected with H pylori probably became infected by household contact in childhood.

Adult↗

Helicobacter pylori is an aetiological factor for ischaemic heart disease: the case in favour.

The evidence to date concerning the association between Helicobacter pylori infection and coronary heart disease is consistent with a modest increased risk. Research is currently being undertaken into factors which may modify this association. Probably, there is sufficient evidence given the ease of the proposed intervention to make it worthwhile to undertake a trial of eradication therapy.

Global Health↗