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Biomedical subjects

M A Mendall

Publications and source records attributed to M A Mendall.

At least 37 records · Page 2Linked to original sources

Determinants of prescribing costs for ulcer-healing drugs and upper gastrointestinal endoscopy in general practice.

BACKGROUND: Prescriptions for ulcer-healing drugs (UHDs) and endoscopy costs represent major expenditures for dyspepsia in primary care. Healthcare expenditure for dyspepsia could be better understood if the factors contributing to the expenditure for dyspepsia could be identified. AIMS: To determine whether prescribing costs of UHDs and use of endoscopy in general practice were related to the characteristics of the practices or to the characteristics of the population it served DESIGN: Twenty-seven GP practices in south London were studied prospectively over 6 months. Prescribing costs for UHDs were obtained from PACT and data for endoscopies from hospital PAS systems. Demographic data on practice size, age and sex distribution were obtained from the district FHSA. The Jarman index, Townsend score and proportion of ethnic minorities in the practice population were determined from the Population Census Survey. RESULTS: Total expenditure on UHDs by the 27 practices was Pound Sterling 1 million per annum and endoscopy rate was 1.1% per annum. Expenditure on UHDs was negatively correlated with practice size (P = 0.006) and use of open access endoscopy (P < 0.005) and positively correlated with number of patients aged over 45 years (P = 0.007). Endoscopy use was positively correlated with proportion of ethnic minorities (P = 0.008) and negatively with male:female ratio (P = 0.049). CONCLUSIONS: Resource utilization on dyspepsia in general practice is determined by both practice and population characteristics.

Anti-Ulcer Agents↗

Screening dyspeptic patients for Helicobacter pylori prior to endoscopy: laboratory or near-patient testing?

BACKGROUND: It is unclear whether near-patient whole-blood diagnostic tests for Helicobacter pylori are of comparable accuracy to laboratory based ELISA for screening of dyspeptic patients prior to endoscopy. AIM: To compare two ELISA and two whole-blood tests in order to determine whether near-patient H. pylori diagnostic tests are an acceptable alternative to laboratory based ELISA tests for screening of dyspeptic patients prior to endoscopy. METHOD: One hundred and seven consecutive patients with dyspepsia (median age, 32 years; range, 16-45 years) were evaluated with Helico-G ELISA, Hmcap ELISA and Helisal whole-blood tests. A further 111 dyspeptic patients (median age, 51 years; range, 16-96 years) were evaluated with the Immunocard whole-blood test only. The 'gold standard' for infection was based on histology and the rapid urease test (CLO). RESULTS: Compared to the Helico-G test, both near-patient tests had a higher false negative rate (23-37% vs 5%, P< 0.003), and lower sensitivity and negative predictive value. The Immunocard had a higher specificity than did the Helisal (87% vs 63%, P=0.006); otherwise both near-patient whole-blood tests had similar performance. At a sensitivity of 95%, the Hmcap ELISA was more specific than the Helico-G ELISA (75% vs 67%) and had fewer false positives (25% vs 32%). The near-patient tests would wrongly classify up to 40% H. pylori positive dyspeptic patients and exclude them from endoscopy, compared to 5-6% for ELISA. CONCLUSIONS: Near-patient whole-blood H. pylori diagnostic tests are less accurate and thus not an acceptable alternative to laboratory based ELISA tests.

Adolescent↗

Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma.

OBJECTIVES: Chronic Helicobacter pylori infection has been associated with ischaemic heart disease although the mechanism by which it mediates this effect remains unclear. The objective was to determine whether it is also a risk factor for ischaemic cerebrovascular disease METHODS: A total of 238 patients and 119 controls were studied. Patients were characterised into stroke subtypes based on pathogenic mechanisms and carotid atheroma load was estimated using duplex ultrasound. H pylori seropositivity was determined on serum samples. RESULTS: H pylori seropositivity was more common in cases (58.8% v 44.5%, p=0.01). The odds ratio for cerebrovascular disease associated with seropositivity was 1.78 (95% confidence interval (95% CI) 1.14-2.77), and this remained significant after controlling for other risk factors including socioeconomic status (1.63 (95% CI 1.02-2.60). H pylori seropositivity was associated with large vessel disease (odds ratio 2.58 (95% CI 1.44-4.63), p=0.001) and lacunar stroke (odds ratio 2.21 (95% CI 1.12-4.38), p=0.02) but not stroke due to cardioembolism or unknown aetiology (odds ratio 1.16 (95% CI 0.66-2.02), p=0.5). Mean (SD) carotid stenosis was greater in patients seropositive for H pylori (37.3 (29.7) v 27.9 (26.2)%, p=0.01). There was no difference in the prevalence of seropositivity between patients with stroke and transient ischaemic attack (59.6% v 58.6%, p=0.9) CONCLUSION: Chronic H pylori infection is an independent risk factor for ischaemic cerebrovascular disease and may act, at least in part, by increasing atherosclerosis.

Aged↗

Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction.

BACKGROUND: The clinical significance of the association between elevated anti-Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients. METHODS AND RESULTS: We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or = 1/64 dilution. Patients with persisting seropositivity of > or = 1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5; P=.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (P=.02). CONCLUSIONS: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.

Administration, Oral↗

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

Aged↗

Transmission of Helicobacter pylori.

The epidemiology of Helicobacter pylori has been the attention of a great deal of study. The age and geographical distribution of infection is rapidly changing with improvements in living conditions, particularly in the childhood period. More than one mode and route of transmission is possible varying with local custom and practices. Infection may be acquired from environmental sources in certain parts of the developing world, but in most circumstances it is probably acquired interpersonally. Interpersonal transmission may be by either fecal-oral or oral-oral routes, depending on circumstances, but the former is likely to be the most important. The life-long chronic active gastritis associated with H pylori may have other consequences for health, such as growth in childhood and coronary heart disease.

Age Factors↗

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

OBJECTIVE: To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. DESIGN: Population based cross sectional study. SETTING: General practices in Merton, Sutton, and Wandsworth. SUBJECTS: A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. INTERVENTIONS: Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. MAIN OUTCOME MEASURES: Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. RESULTS: Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. CONCLUSION: The body's response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies.

Aged↗

Pathogenesis of gastric metaplasia of the human duodenum: role of Helicobacter pylori, gastric acid, and ulceration.

BACKGROUND & AIMS: The pathogenesis of gastric metaplasia (GM) in the duodenum is unclear. The aim of this investigation was to study the effect on the extent of GM of ulcer healing, Helicobacter pylori eradication, and acid suppression singly and in combination. The relationship between GM and gastroduodenal inflammation and H. pylori infection density was also studied. METHODS: Duodenal and gastric antral biopsy specimens were obtained from H. pylori-positive patients with duodenal ulcer and from H. pylori-positive nonulcer subjects. Biopsy procedures from patients with duodenal ulcer were repeated after 6 months of treatment. Nonulcer subjects were treated symptomatically and did not undergo re-endoscopy. RESULTS: Ulcer healing alone produced no change in GM or in gastroduodenal inflammation. H. pylori eradication produced a 42% reduction in GM and improvement in inflammation. Acid suppression produced a 43% reduction in GM but without a significant change in inflammation. A combination of H. pylori eradication and acid suppression produced an additive effect with a 66% reduction in GM. A positive relationship was detected between the extent of GM and antral H. pylori density, duodenitis score, and antral gastritis score. CONCLUSIONS: This study shows that the extent of duodenal GM is unrelated to the presence or absence of ulceration but is partly due to H. pylori and partly due to acid.

Adult↗

Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men.

OBJECTIVE: To determine whether Helicobacter pylori, a chronic bacterial infection often acquired in childhood, is associated with increased risk of coronary heart disease and stroke later in life. DESIGN: Nested case-control study. SETTING: Prospective study of cardiovascular disease in men aged 40-59 years at entry (1978-1980) in 24 British towns. SUBJECTS: 135 cases of myocardial infarction and 137 cases of stroke occurring before December 1991; 136 controls were identified, frequency matched to cases by town and age group. METHODS: Serum samples stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies. RESULTS: 95 of the myocardial infarction cases (70%) and 93 (68%) of the stroke cases were seropositive for H pylori compared with 78 (57%) of the controls (odds ratio for myocardial infarction 1.77, 95% confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke 1.57, 95% CI 0.95 to 2.60, P = 0.07). Helicobacter pylori infection was associated with manual social class, residence in Northern England or Scotland, cigarette smoking, higher systolic pressure and blood glucose, and a lower height-standardised forced expiratory volume in one second. Adjustment for these factors attenuated the relation between H pylori and myocardial infarction (odds ratio = 1.31, 95% CI 0.70 to 2.43, P = 0.40) and effectively abolished the relation with stroke (odds ratio = 0.96, 0.46 to 2.02, P = 0.92). The relation between helicobacter infection and fatal myocardial infarction was slightly stronger (odds ratio 2.41, 95% CI 1.13 to 5.12) but was also markedly attenuated after adjustment (1.56, 95% CI 0.68 to 3.61). CONCLUSION: In this prospective study the association between Helicobacter pylori infection and increased risk of myocardial infarction and stroke was substantially confounded by the relation between this infection, adult social class, and major cardiovascular risk factors.

Adult↗

Prospective screening of dyspeptic patients by Helicobacter pylori serology.

Helicobacter pylori infection is associated with 95% of duodenal ulcers and more than 80% of gastric ulcers. Several reports have indicated that screening for H pylori may avoid subsequent endoscopic examination. We screened 183 dyspeptic patients, aged under 45, by taking a history of sinister symptoms and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), together with serological testing for H pylori. Endoscopy was performed on 113 patients, of whom 90 (49%) were seropositive, 14 (8%) had sinister symptoms, and 9 (5%) had used NSAIDs regularly. In 34 (19%) patients we detected peptic ulceration. The remaining 70 (38%) patients who were H pylori seronegative, had no sinister symptoms, and had not taken NSAIDs (screen-negative), did not undergo endoscopy but were returned to their primary care physician for treatment of symptoms. At subsequent reassessment (of the non-endoscoped group), symptom severity (p = 0.002), interference with life events (p = 0.01), and medication (p = 0.0002) were all significantly lower in the 6 months after screening than in the 6 month period before screening. Only three screen-negative patients were re-referred after screening but their endoscopic findings were normal. Thus, 67 (36%) endoscopies were avoided. When the non-endoscoped screen-negative patients were compared with a cohort of endoscoped screen-negative patients, the groups did not differ in terms of symptom severity (odds ratio 1.12, 95% CI 0.53-2.35, p = 0.77) or interference with life events (0.82, 0.38-1.76, p-0.61). However, medication use was significantly less (0.37, 0.17-0.80, p = 0.01) in those who did not have an endoscopy. Our study indicates that colonisation screening based on H pylori serology, a history of sinister symptoms, or a history of NSAID use was worthwhile in dyspeptic patients. We avoided 37% of endoscopies and reduced drug usage without disadvantaging those not endoscoped.

Adult↗

Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors.

OBJECTIVE: To investigate the relation between seropositivity to chronic infections with Helicobacter pylori and Chlamydia pneumoniae and both coronary heart disease and cardiovascular risk factors. DESIGN: Cross sectional study of a population based random sample of men. Coronary heart disease was assessed by electrocardiography, Rose angina questionnaire, and a history of myocardial infarction; serum antibody levels to H pylori and C pneumoniae were measured, risk factor levels determined, and a questionnaire administered. SETTING: General practices in Merton, Sutton, and Wandsworth, south London. SUBJECTS: 388 white south London men aged 50-69. MAIN OUTCOME MEASURES: Evidence of coronary risk factors and infection with H pylori or C pneumoniae. RESULTS: 47 men (12.1%) had electrocardiographic evidence of ischaemia or infarction. 36 (76.6%) and 18 (38.3%) were seropositive for H pylori and C pneumoniae, respectively, compared with 155 (45.5%) and 62 (18.2%) men with normal electrocardiograms. Odds ratios for abnormal electrocardiograms were 3.82 (95% confidence interval 1.60 to 9.10) and 3.06 (1.33 to 7.01) in men seropositive for H pylori and C pneumoniae, respectively, after adjustment for a range of socioeconomic indicators and risk factors for coronary heart disease. Cardiovascular risk factors that were independently associated with seropositivity to H pylori included fibrinogen concentration and total leucocyte count. Seropositivity to C pneumoniae was independently associated with raised fibrinogen and malondialdehyde concentrations. CONCLUSIONS: Both H pylori and C pneumoniae infectins are associated with coronary heart disease. These relations are not explained by a wide range of confounding factors. Possible mechanisms include an increase in risk factor levels due to a low grade chronic inflammatory response.

Aged↗

Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease.

BACKGROUND: Two studies have suggested that seropositivity for Chlamydia pneumoniae (C. pneumoniae) is a risk factor for coronary heart disease (CHD) but the association remains tenuous. Further data is required in other populations to consolidate this observation. AIMS: Initially to determine descriptive risk factors for C. pneumoniae seropositivity in a general population sample and subsequently to examine the relation of seropositivity for this organism to CHD for the first time in a British population. SETTING: A single general practice health screening clinic and a cardiology clinic involving patients predominantly residing in south London and Surrey. SUBJECTS: 210 consecutive caucasian men (62%) and women (38%) aged 18-79 including 67 men aged 45-65. This latter group acting as controls were then also compared with 103 consecutive males aged 45-65 with angiographically confirmed coronary heart disease. METHODS: A questionnaire was administered by a research nurse and serum was analysed for IgG and IgA against C. pneumoniae and other Chlamydiae by a microimmunofluorescence test. Serum was said to be low positive at a specific IgG antibody titre of 16-32, and high positive if 64 or greater. RESULTS: Amongst the general practice health screening clinic population 14 subjects (7%) were excluded due to possible cross-reactivity with other Chlamydia species (predominantly C. trachomatis). Of the remaining 196 subjects, 13 (6%) had high positive C. pneumoniae IgG titres, 68 (35%) had low titres and 125 had no detectable antibody. After adjustment for sex, age, smoking history, social class and family size only one risk factor for high positive titres in this group was identified, which was the number of children currently living in the home (OR 2.29 (1.09-4.80), P = 0.03). No factors were significantly related to low titres. 22/100 (22%) cases with coronary heart disease and 3/64 (4.7%) of controls had high positive IgG titres for C. pneumoniae. Similarly 21% of cases and 9.4% of controls had positive C. pneumoniae specific IgA serology. 45% of cases and 44% of controls had low C. pneumoniae IgG titres. The association of CHD with a C. pneumoniae IgG titre of 64 or above was independent of all risk factors (OR 7.4 (1.7-33.1), P < 0.01). CONCLUSION: Serological evidence of C. pneumoniae infection is common amongst healthy British subjects. Smoking and social class are not important confounding variables in this study. Reinfection from contact with infected children in the home may be important in inducing higher titres in some subjects. These higher titres are more prevalent in subjects with coronary heart disease in the U.K. as reported in Finland and the U.S.A., and provide further evidence that C. pneumoniae may be important in the pathogenesis of this condition in these populations.

Adolescent↗