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Biomedical subjects

M Plummer

Publications and source records attributed to M Plummer.

At least 19 recordsLinked to original sources

A case-control study of gastric cancer in Venezuela.

A case-control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high-risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio-economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal-structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non-drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela.

Adult↗

Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa.

OBJECTIVE: Helicobacter pylori infection causes gastric diseases, but the responsible mechanisms are not completely understood. They can involve DNA and tissue damage induced by reactive oxygen and nitrogen species. Our aim is to investigate the effects of bacterial eradication on oxidative stress by measuring changes of relevant markers. METHODS: Antral biopsies were obtained from 34 patients with chronic atrophic gastritis and peptic ulcer disease before and after bacterial eradication. The expression of inducible nitric oxide synthase (iNOS) and levels of nitrotyrosine (NTYR) and 8-hydroxy-2'-deoxyguanosine were assessed immunohistochemically as markers of nitric oxide (NO) production and of damage to proteins and DNA, respectively. RESULTS: Before treatment, the percentages of patients with staining were: 56 for iNOS in inflammatory cells, 79 and 61 for NTYR and 8-hydroxy-2'-deoxyguanosine in foveolar cells, respectively, and 82 for 8-hydroxy-2'-deoxyguanosine in lymphoid follicles. NTYR staining was associated with the intensity of inflammation (p = 0.04) and gastritis activity (p = 0.07). The prevalence of 8-hydroxy-2'-deoxyguanosine tended to be associated with that of NTYR. After successful H. pylori eradication, the prevalence of iNOS and NTYR (in mild gastritis) staining decreased (p < 0.001 and p < 0.06, respectively). 8-Hydroxy-2'-deoxyguanosine staining disappeared in 24% of cases but appeared in 18% of previously negative cases despite eradication. CONCLUSION: Targets of oxidative stress associated with H. pylori infection are inflammatory and deep foveolar cells and lymphoid follicles. This is the first report of 8-hydroxy-2'-deoxyguanosine localization in gastric mucosa. Oxidative stress is reduced by bacterial eradication in the first stages of mild gastritis. Moderate-severe gastritis may be a step that is reversible for iNOS, but partly irreversible for NTYR and 8-hydroxy-2'-deoxyguanosine.

8-Hydroxy-2'-Deoxyguanosine↗

Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica.

BACKGROUND: Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. METHODS: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. RESULTS: Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500). CONCLUSIONS: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

Adult↗

Lewis antigen alterations in a population at high risk of stomach cancer.

Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of progression in precursor lesions of gastric cancer. Additionally, Lewis antigen and secretor phenotype have been related to Helicobacter pylori infection and gastric epithelial damage. The two objectives of this study were to correlate Lewis antigen alterations with histochemical changes and to explore the relationship between Lewis and secretor phenotypes and gastric epithelial damage related to H. pylori infection. The study subjects were selected from a chemoprevention trial in Tachira State, Venezuela, an area with a high risk of gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype individuals was closely related to the severity of the histological lesions, especially to dysplasia and type III intestinal metaplasia lesions. A weak relationship was observed between nonsecretor individuals and more advanced lesions of IM, but this association was not statistically significant. There was no relationship between secretor phenotype and H. pylori status, atrophy, regenerative activity, erosion, or ulcer.

Adult↗

Helicobacter pylori and stomach cancer: a case-control study in Venezuela.

The role of Helicobacter pylori infection in gastric cancer was evaluated in a high-risk population in Venezuela using serological assays in a study of 302 cases and 483 neighborhood controls. To investigate the claim that assays for H. pylori should use antigens derived from local strains, four different assays derived from Venezuelan and European strains were used. Prevalence of IgG H. pylori antibodies in controls was very high, with estimates between 72 and 92%. Prevalence was similar in cases and controls. However, cases had lower antibody titers. This effect was observed only in subjects with low pepsinogen (PG) levels PGI/PGII <3.0), which suggested that extensive atrophy in cases causes a loss of H. pylori infection, with a consequent reduction in antibody titer. In addition, advanced cases (stage II or higher) had lower antibody titers than less advanced cases, which indicated that the lower antibody titers in cases may be attributable partially to a diminished immune response. All of the four assays for anti-H. pylori antibodies gave similar results. No evidence was found for the superiority of the assay based on Venezuelan strains. These results are consistent with other case-control studies in high-risk populations and highlight the difficulties of investigating H. pylori infection in retrospective studies.

Adult↗

Histological diagnosis of precancerous lesions of the stomach: a reliability study.

BACKGROUND: Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. METHODS: A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. RESULTS: When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. CONCLUSIONS: These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.

Adult↗

Determinants of plasma anti-oxidant vitamin levels in a population at high risk for stomach cancer.

Our objective was to identify the determinants of plasma levels of anti-oxidant vitamins which have been linked with decreased risk of cancer and other chronic diseases. Correlation analyses were performed between baseline plasma levels of ascorbic acid, alpha- and beta-carotenes, cryptoxanthin, lycopene and alpha- and gamma-tocopherols and baseline information on dietary and other demographic and life-style factors among 1,364 subjects 35-69 years of age, who are participants in a chemoprevention trial on pre-cancerous lesions of the stomach in Venezuela. Males had lower levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin and higher levels of alpha-tocopherol than females. This finding was confirmed in non-smokers and non-drinkers. In females, but not in males, age was positively associated with levels of ascorbic acid, cryptoxanthin, alpha- and beta-carotene and gamma-tocopherol. Male tobacco users had lower plasma levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin than nonusers, and regular alcohol drinkers had a decreased plasma levels of beta-carotene compared with non-drinkers. Female tobacco users had lower levels of ascorbic acid and cryptoxanthin than non-users, and regular alcohol drinkers had lower levels of ascorbic acid and lycopene than non-drinkers. Frequencies of consumption of fresh fruits, fruit juice, raw vegetables and plantains showed weak positive associations with plasma levels of several vitamins studied in both sexes. Sex, age in females, tobacco and alcohol use and dietary consumption affected plasma anti-oxidant vitamin levels in this population significantly. These factors may influence the effect of anti-oxidant treatment in intervention trials.

Adult↗

Community health for Rwandan refugees.

Health education and disease prevention programs are essential elements in every health care system. We normally envision community health programs in urban and rural settings across Canada. However, health education and disease prevention have also become a fundamental part of the health care system for refugee communities around the world.

Adult↗

Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease.

There are approximately 20,000 excess deaths from cardiovascular disease each winter in England and Wales. The reasons for the excess have not been fully elucidated. For one year, we studied 96 men and women aged 65-74 living in their own homes in order to examine seasonal variation in plasma fibrinogen and factor VII clotting activity (FVIIc), and to investigate relationships with infection and other cardiovascular-disease risk factors. Both fibrinogen and FVIIc plasma values were greater in winter with estimated winter-summer differences (confidence intervals) of 0.13 (0.05-0.20) g/L for fibrinogen and 4.2 (1.2-7.1)% of standard for FVIIc. These differences could account for 15% and 9% increases in ischaemic heart disease risk in winter respectively. After adjustment for confounding by season, fibrinogen was strongly related to neutrophil count (p < 0.0001), C-reactive protein (p < 0.0001), alpha 1-antichymotrypsin (p < 0.0001), and self-reported cough (p < 0.0001) and coryza (p = 0.0004), but not to ambient temperature. Therefore, we suggest that seasonal variation in fibrinogen might be induced by winter respiratory infections via activation of the acute phase response. Seasonal variations in the cardiovascular risk factors fibrinogen and FVIIc provide further possible explanations for the marked seasonal variation in death from ischaemic heart disease and stroke in the elderly.

Acute-Phase Proteins↗

Adjustment for bias due to errors in exposure assessments in multicenter cohort studies on diet and cancer: a calibration approach.

An advantage of multicenter cohort studies on diet and cancer is that these may include populations over a wide range of dietary exposure. With some simplifying assumptions, the information from such multicenter studies may be divided into 1) estimated relationships within each of the separate cohorts, between individual-level measurements of dietary exposure and disease outcome, and 2) an estimated between-cohort relationship, between the mean intake measurements and mean incidence rates. Errors in the dietary exposure measurements may lead to different amounts of bias in each of these estimated relationships, in particular when dietary questionnaire methods cannot easily be standardized. A calibration approach can be used to adjust for such differences in bias. This will improve the relative weighting of within- and between-cohort components of evidence for a diet-disease association.

Cohort Studies↗

Calibration in multi-centre cohort studies.

BACKGROUND: This paper is concerned with overcoming problems caused by measurement error in multi-centre studies of diet and disease. Measurement error causes differential bias, so the information on the diet-disease relationship from different cohorts is not directly comparable. Hence this information needs to be calibrated before the data are combined in an eventual meta-analysis. We consider the design of calibration substudies. We distinguish two forms of information from a multi-centre cohort study. The first is subject-level information, which comes from the variation of disease rate within cohorts. The second is cohort-level information, which comes from the variation of disease rate between cohorts. The requirements of the calibration study are different for these two forms of information. METHODS: Calibration is carried out by remeasuring diet in a subsample of each cohort using a standardized reference method. This reference measurement should yield unbiased estimates of habitual intake. RESULTS: Using a criterion of efficiency, relative to a perfectly calibrated study, we show that the sample size should be a multiple of the expected number of cases in each cohort. To control for confounding, each cohort should be stratified and the ratio of sample size to number of cases should be constant within strata. CONCLUSIONS: Since the required sample size is related not to the size of the cohort, but to the eventual number of cases of disease, calibration samples need not be prohibitively large. They should, however, be concentrated on those parts of the cohort, such as older age groups, which will yield most cases.

Bias↗

Measurement error in dietary assessment: an investigation using covariance structure models. Part I.

Repeated measures of diet are analysed in an attempt to discover the measurement error properties of various dietary assessment methods. It is customary in such studies to assume that one reference measurement is 'valid' (without error) but this assumption is not tenable. An alternative approach, widely used in social science, is to model the covariance matrix of the repeated measures. We apply this methodology to assessments of nitrogen intake, which is essentially equivalent to protein intake.

Bias↗

Measurement error in dietary assessment: an investigation using covariance structure models. Part II.

In Part I we presented a covariance structure model for analysing measurement error in the assessment of nitrogen intake. In this paper we include data on urine nitrogen excretion which allows a critical assessment of the model proposed. Inclusion of urine nitrogen data produces more pessimistic estimates of the quality of dietary intake measurements and shows that previous assumptions about independence of measurement error were wrong. This underscores the need for well founded assumptions in the analysis of measurement error.

Bayes Theorem↗

An outbreak of Salmonella mikawasima associated with doner kebabs.

During October 1992 an increase in the number of isolates of Salmonella mikawasima, a rare serotype, was noted including a cluster of nine cases in the South West Thames region. A case control study was conducted and univariate analysis showed a statistical association between illness and eating at take-away A for cases compared with household controls (P = 0.003) and with neighbourhood controls (P = 0.0245). Cases were also more likely to have eaten kebabs than were controls or average take-away A customers, implicating doner kebabs as the most likely vehicle of infection. Plasmid profile analysis of the nine cases' isolates showed them to be indistinguishable and to be characterized by a single plasmid of approximately 60 MDa. The original source of the Salmonella mikawasima contamination was not determined, but food preparation practices for kebabs at take-away A were insufficient to protect against illness if contaminated. This outbreak was only recognized because of the unusual serotype, but could be an indication of a more widespread problem with doner kebabs.

Adolescent↗

Seasonal variation of serum lipids in an elderly population.

We investigated seasonal variation in serum lipids in 96 volunteers aged 65-74 years who were studied at 2-monthly intervals for one year. Periodic regression analysis revealed highly significant seasonal variation in serum total cholesterol and high-density lipoprotein (HDL) cholesterol. Peak levels for both occurred in winter with corresponding summer troughs. The seasonal difference for total cholesterol was 0.32 mmol/l (95% CI 0.23-0.41, p < 0.0001) and that for HDL cholesterol 0.16 mmol/l (95% CI 0.12-0.19, p < 0.0001). Low-density lipoprotein (LDL) cholesterol was highest in winter in men only (seasonal difference 0.27 mmol/l, 95% CI 0.15-0.39, p < 0.0001), and triglycerides were significantly greater in late winter for women only (seasonal difference 0.22 mmol/l, 95% CI 0.09-0.35, p = 0.002). The timing of seasonal variation in total cholesterol and triglycerides would be consistent with a role in the seasonal variation in vascular deaths, but our finding of a relatively high HDL: total cholesterol ratio in winter makes this less likely.

Aged↗

Seasonal variation of blood pressure and its relationship to ambient temperature in an elderly population.

OBJECTIVE: To measure the magnitude and timing of seasonal variation of blood pressure and related factors in the elderly living in the community, and to assess their potential impact on cardiovascular risk. DESIGN: Prospective study; from January 1991 to February 1992 blood pressure and other variables were measured at 2-monthly intervals in each subject in their own homes. SUBJECTS: Ninety-six men and women, age range 65-74 years, recruited from a single group general practice in Cambridge. MAIN OUTCOME MEASURES: Seasonal variation of blood pressure, seasonal variation of prevalence of hypertension, seasonal variation of ambient temperature and body mass index. RESULTS: Both systolic (SBP) and diastolic blood pressure (DBP) were greatest during the winter across the whole distribution of blood pressure. There was a fourfold increase in the proportion of subjects with blood pressures > 160/90 mmHg in winter compared with in summer. Regression analysis revealed highly significant seasonal differences in both SBP and DBP. After adjustment for confounding seasonal effects, a 1 degree C decrease in living-room temperature was associated with rises of 1.3 mmHg in SBP and 0.6 mmHg in DBP. CONCLUSIONS: Seasonal variation of blood pressure is heightened in older adults and may partly explain the greater cardiovascular disease mortality of elderly subjects during the winter. The blood pressures of elderly people may be inversely related to the ambient temperature. The public health implications of these findings deserve further investigation.

Aged↗

Carinal forceps biopsy via the fiberoptic bronchoscope in the routine staging of lung cancer.

Main carinal biopsy was carried out in 58 consecutive patients with endobronchial (endoscopically visible) bronchogenic carcinoma. Overall, the results of the biopsy were positive in 8 of 58 patients (13.8%). The biopsy results were positive in 6 of 15 (40%) patients whose carina appeared abnormal as compared with 2 of 43 (4.7%) whose carina appeared normal (P = .0025). In those patients with subtle carinal abnormalities (carinal widening or erythema) but without gross tumor involvement, the biopsy findings were positive in 5 of 14 (36%). Unlike in previous studies, a significant percentage of positive carinal biopsy findings was associated with left upper lobe lesions. There were no complications associated with the procedure. Although the yield on blind carinal biopsies (visually normal carina) with the flexible fiberoptic bronchoscope is lower than that previously reported with the rigid bronchoscope, it remains a low-risk procedure that can spare a number of patients the morbidity and expense of more invasive surgical staging when applied as a routine part of diagnostic bronchoscopy in patients with endoscopically visible bronchogenic carcinoma.

Bronchoscopy↗