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Biomedical subjects

A J Cameron

Publications and source records attributed to A J Cameron.

At least 19 recordsLinked to original sources

Is grand multiparity associated with an increased risk of dysglycaemia?

AIMS/HYPOTHESIS: We sought to determine the risk of diabetes and IGT/IFG with grand multiparity. SUBJECTS, MATERIALS AND METHODS: Women, aged > or =25 years, from the Australian Diabetes, Obesity and Lifestyle Study and the Crossroads Undiagnosed Disease Study (a rural study in Victoria, Australia), participated in a household census (response 67 and 70%, respectively), subsequently attending a biomedical examination that included an oral glucose tolerance test (58% [6198] and 69% [819]). RESULTS: After adjusting for age, obesity and socio-economic status, diabetes, but not IGT/IFG, was less common among women with a parity of 1 to 2 (odds ratio [OR]=0.64 [0.48-0.84]) and 3 to 4 (OR=0.72 [0.53-0.96]) than in grand multiparous women. This relationship was unrelated to past hysterectomy, use of the oral contraceptive pill or menopausal status. CONCLUSIONS/INTERPRETATION: Grand multiparity is associated with an increased risk of diabetes but not of IGT/IFG. We postulate that parity accelerates transition from IGT/IFG to diabetes, more than it does transition from normal glucose tolerance to IGT/IFG.

Adult↗

Associations of TV viewing and physical activity with the metabolic syndrome in Australian adults.

AIMS/HYPOTHESIS: We analysed a sample of Australian adults to determine the strength of associations of TV viewing and participation in physical activity with the metabolic syndrome. METHODS: This population-based cross-sectional study included 6,241 adults aged > or =35 years who were free from diagnosed diabetes mellitus and self-reported ischaemic disease and were not taking lipid-lowering or antihypertensive drugs. The metabolic syndrome was defined according to the 1999 World Health Organization criteria. Participants self-reported TV viewing time and physical activity time for the previous week. RESULTS: The adjusted odds ratio of having the metabolic syndrome was 2.07 (95% CI 1.49-2.88) in women and 1.48 (95% CI 0.95-2.31) in men who watched TV for >14 h per week compared with those who watched < or =7.0 h per week. Compared with those who were less active (<2.5 h per week), the odds ratio for the metabolic syndrome was 0.72 (95% CI 0.58-0.90) in men and 0.53 (95% CI 0.38-0.74) in women who were active (> or =2.5 h per week). Longer TV viewing (>14 h per week) was associated with an increased risk of insulin resistance, obesity and dyslipidaemia in both men and women. A total physical activity time of > or =2.5 h per week was associated with a reduced prevalence of both insulin resistance and dyslipidaemia in both sexes and reduced prevalence of both obesity and hypertension in women. CONCLUSIONS/INTERPRETATION: Increased TV viewing time was associated with an increased prevalence of the metabolic syndrome, while physical activity was associated with a reduced prevalence. Population strategies addressing the metabolic syndrome should focus on reducing sedentary behaviours such as TV viewing, as well as increasing physical activity.

Australia↗

Relationship between body mass index, diet, exercise and gastro-oesophageal reflux symptoms in a community.

BACKGROUND: Body mass index (BMI) is a risk factor for gastro-oesophageal reflux but may simply be explained by diet and lifestyle. AIM: We aimed to determine the contribution of BMI, diet and exercise to GER. METHODS: Community subjects (n = 211, mean age = 36 years, 43% males) completed validated questionnaires on gastro-oesophageal reflux, energy expenditure (Harvard Alumni Activity Survey), dietary intake (Harvard Food Frequency Questionnaire) and measures of personality and life event stress. Diet, exercise, BMI and other potential risk factors for reflux were analysed using logistic regression analyses. RESULTS: The overall mean (+/- s.d.) BMI was 26.6 (+/- 5.7); 79 (37%) reported infrequent (< weekly) reflux and 16 (8%) reported frequent (> or = weekly) reflux. The median caloric intake was 2097 cal/day and the median daily energy expenditure was 1753 cal/day. Among those with BMI > 25, 10% reported frequent reflux compared to 4% of those with BMI < or = 25. In a model which included age, sex and Symptom Checklist-90 somatisation T-score, BMI was associated with reflux (OR per 5 units = 1.9, 95% CI: 1.2, 3.0). In models which included diet and exercise variables, BMI but not diet or exercise was associated with reflux. CONCLUSION: BMI may be associated with symptomatic gastro-oesophageal reflux independent of diet and exercise.

Adult↗

Strain differences in three measures of ethanol intoxication in mice: the screen, dowel and grip strength tests.

Mice from 8 to 21 inbred strains were tested for sensitivity to ethanol intoxication using a range of doses and three different measures: the screen test, the dowel test and a test of grip strength. Strains differed under nearly all conditions. For the dowel test, two dowel widths were employed, and mice were tested immediately or 30 min after ethanol. For the dowel and screen tests, low doses failed to affect some strains, and the highest doses failed to discriminate among mice, maximally affecting nearly all. For grip strength, a single ethanol dose was used, and mice of all strains were affected. Pharmacokinetic differences among strains were significant, but these could not account for strain differences in intoxication. For doses and test conditions in the middle range, there were only modest correlations among strain means within a test. In addition, genotypic correlations across tests were modest to quite low. These results suggest that different specific versions of a test reflect the influence of different genes, and that genetic influences on different tests were also distinct.

Alcoholic Intoxication↗

Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter?

OBJECTIVE: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius. RESEARCH DESIGN AND METHODS: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n=4036). Other cardiovascular risk factors were assessed among those without known diabetes. RESULTS: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2-6.0) vs. 2.9% (2.3-3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9-10.2) vs. 13.9% (12.6-15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides. CONCLUSION: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.

Adult↗

Waist circumference, waist-hip ratio and body mass index and their correlation with cardiovascular disease risk factors in Australian adults.

OBJECTIVES: To compare body mass index (BMI), waist circumference and waist-hip ratio (WHR) as indices of obesity and assess the respective associations with type 2 diabetes, hypertension and dyslipidaemia. DESIGN AND SETTING: A national sample of 11 247 Australians aged > or =25 years was examined in 2000 in a cross-sectional survey. MAIN OUTCOME MEASURES: The examination included a fasting blood sample, standard 2-h 75-g oral glucose tolerance test, blood pressure measurements and questionnaires to assess treatment for dyslipidaemia and hypertension. BMI, waist circumference and WHR were measured to assess overweight and obesity. RESULTS: The prevalence of obesity amongst Australian adults defined by BMI, waist circumference and WHR was 20.8, 30.5 and 15.8% respectively. The unadjusted odds ratio for the fourth vs. first quartile of each obesity measurement showed that WHR had the strongest relationship with type 2 diabetes, dyslipidaemia (women only) and hypertension. Following adjustment for age, however, there was little difference between the three measures of obesity, with the possible exceptions of hypertension in women, where BMI had a stronger association, and dyslipidaemia in women and type 2 diabetes in men, where WHR was marginally superior. CONCLUSIONS: Waist circumference, BMI and WHR identified different proportions of the population, as measured by both prevalence of obesity and cardiovascular disease (CVD) risk factors. Whilst WHR had the strongest correlations with CVD risk factors before adjustment for age, the three obesity measures performed similarly after adjustment for age. Given the difficulty of using age-adjusted associations in the clinical setting, these results suggest that given appropriate cut-off points, WHR is the most useful measure of obesity to use to identify individuals with CVD risk factors.

Adult↗

Differential recruitment of accessory molecules by FcgammaRI during monocyte differentiation.

Aggregation of the human high-affinity receptor for immunoglobulin G, FcgammaRI, results in initiation of intracellular signaling cascades. However, as the receptor contains no known signaling motif, it is required to recruit an accessory molecule. The gamma chain has been proposed to fulfil this role. Here, we show that in U937 cells differentiated to a more macrophage-like phenotype with dibutyryl cAMP, FcgammaRI no longer signals through the gamma chain but rather uses FcgammaRIIa to initiate tyrosine phosphorylation. Expression of the gamma chain is, however, increased in the dbcAMP-induced cells, but here the gamma chain specifically associates with the IgA receptor, FcalphaRI. Recruitment of the gamma chain either by FcgammaRI in cytokine-primed cells or by FcalphaRI in dbcAMP-induced cells couples ligand binding to the activation of phosphatidyl choline-specific phospholipase D.

Antigen-Antibody Complex↗

Secular trends in the epidemiology and outcome of Barrett's oesophagus in Olmsted County, Minnesota.

BACKGROUND: The incidence of oesophageal adenocarcinoma has increased greatly. Barrett's oesophagus is a known risk factor. AIMS: To identify changes in the incidence, prevalence, and outcome of Barrett's oesophagus in a defined population. SUBJECTS: Residents of Olmsted County, Minnesota, with clinically diagnosed Barrett's oesophagus, or oesophageal or oesophagogastric junction adenocarcinoma. METHODS: Cases were identified using the Rochester Epidemiology Project medical records linkage system. Records were reviewed with follow up to 1 January 1998. RESULTS: The incidence of clinically diagnosed Barrett's oesophagus (>3 cm) increased 28-fold from 0.37/100 000 person years in 1965-69 to 10.5/100 000 in 1995-97. Of note, gastroscopic examinations increased 22-fold in this same time period. The prevalence of diagnosed Barrett's oesophagus increased from 22.6 (95% confidence interval (CI) 11.7-33.6) per 100 000 in 1987 to 82.6/100 000 in 1998. The prevalence of short segment Barrett's oesophagus (<3 cm) in 1998 was 33.4/ 100 000. Patients with Barrett's oesophagus had shorter than expected survival but only one patient with Barrett's oesophagus died from adenocarcinoma. Only four of 64 adenocarcinomas occurred in patients with previously known Barrett's oesophagus. CONCLUSIONS: The incidence and prevalence of clinically diagnosed Barrett's oesophagus have increased in parallel with the increased use of endoscopy. We infer that the true population prevalence of Barrett's oesophagus has not changed greatly, although the incidence of oesophageal adenocarcinoma increased 10-fold. Many adenocarcinomas occurred in patients without a previous diagnosis of Barrett's oesophagus, suggesting that many people with this condition remain undiagnosed in the community.

Adenocarcinoma↗

The history of Barrett esophagus.

The term Barrett esophagus has become well established in the medical literature to indicate columnar metaplasia of the distal esophagus associated with chronic gastroesophageal reflux disease. However, the historical events that led to the use of this term have become obscured. Here, the historical aspects of Barrett esophagus are reviewed, providing insight not only to this condition but also to the evolution of medical thought in general.

Barrett Esophagus↗

Videoendoscopic diagnosis of esophageal motility disorders.

BACKGROUND: Esophageal motility disorders are usually diagnosed by manometry. We evaluated videoendoscopy as a diagnostic test. METHODS: In this study, 20 patients with achalasia, 13 with scleroderma, and 33 control subjects had a standard endoscopic examination followed by protocol videotaping of swallows to observe contractions in the esophagus and in the lower esophageal sphincter. Tapes were later reviewed by 2 blinded observers who recorded their motility findings and diagnoses. RESULTS: In the mid esophagus at 25 cm, lumen-occluding peristaltic contractions were identified in 26 of 33 control subjects versus 1 of 20 achalasia (p < 0.001) and 3 of 13 scleroderma patients (p < 0.005). As viewed in the lower esophagus, the lower esophageal sphincter opened normally in 31 of 33 control subjects versus 1 of 20 achalasia (p < 0.001). In scleroderma, the sphincter never closed in 12 of 13 patients (p < 0. 001 versus control subjects). A diagnostic sequence of sphincter opening followed by contraction in the esophageal body and subsequent sphincter closing was seen in 33 of 33 control subjects, 2 of 20 achalasia, and 1 of 13 scleroderma patients (both, p < 0. 001). The observers made the correct diagnosis in 96% of cases. CONCLUSIONS: Achalasia and esophageal scleroderma can be identified by endoscopic observation of motility. This procedure may represent an adjunctive diagnostic test to manometry.

Endoscopy, Digestive System↗

The human high-affinity immunoglobulin G receptor activates SH2-containing inositol phosphatase (SHIP).

On cytokine-primed U937 cells, aggregation of the human high-affinity immunoglobulin receptor, FcgammaRI, initiates signal transduction cascades which lead to the release of calcium from intracellular stores and no significant calcium influx. In these cells, aggregation of FcgammaRI results in no significant increase in inositol trisphosphate production, but rather phospholipase D is activated. Here we show that, in interferon-gamma (IFN-gamma)-primed cells, the SH2 containing inositol 5' phosphatase, SHIP, is constitutively associated with the membrane fraction. Following aggregation of FcgammaRI, SHIP is rapidly and transiently tyrosine phosphorylated and becomes associated with the adapter molecule Shc. Shc also becomes tyrosine phosphorylated and translocates from the cytoplasm to the membrane fraction concomitant with the association between Shc and SHIP. Further, SHIP and Shc appear to be recruited to membrane-associated immune complexes following FcgammaRI aggregation. As no immunoreceptor inhibitory motif has been demonstrated to associate with FcgammaRI, these data suggest that SHIP may be recruited to the receptor through an SH2 domain interaction with Shc.

Adaptor Proteins, Signal Transducing↗

Esophageal lichen planus: the Mayo Clinic experience.

Lichen planus (LP) is an inflammatory papulosquamous disease which may affect the squamous epithelium of the esophagus. We reviewed six patients with esophageal lichen planus (ELP) seen at Mayo Clinic Rochester between 1984 and 1998. The presenting symptoms were dysphagia (in all six patients) and odynophagia (two patients). Cervical esophageal strictures were seen in four patients; average number of esophageal dilatations required was 15 (range, 10-18). Esophageal biopsies demonstrated the classical histologic findings of ELP in two patients, and a lymphocytic infiltrate in the other four. Concomitant lichen planus (LP) was seen at other sites in five patients: all five had oral LP preceeded by ELP symptoms in all five; three had genital LP preceeded by ELP symptoms in all three; two had dermal LP, preceeded by ELP symptoms in one. Proton pump inhibitors were tried unsuccessfully in all patients. Four patients were started on systemic steroid medication; three had resolution of symptoms within 1 month.

Adult↗

Barrett's esophagus: prevalence and size of hiatal hernia.

OBJECTIVE: Barrett's esophagus is caused by gastroesophageal reflux and predisposes to adenocarcinoma. Hiatal hernia may cause reflux. The prevalence and size of hernias in patients with Barrett's esophagus was investigated. METHODS: Axial hernia length and the width of the diaphragmatic hiatus were measured prospectively at endoscopy. RESULTS: A 2-cm or longer hernia was found in 96% of 46 patients with Barrett's esophagus, in 42% of 103 controls (p < 0.001), and in 72% of 18 patients with short segment Barrett's esophagus (p < 0.05 vs controls). A hernia was found in 71% of 31 controls with esophagitis and in 29% of 72 controls without esophagitis (p < 0.001). Of 54 controls with neither esophagitis or reflux symptoms, 20% had a hernia. Mean hernia length was 3.95 cm in Barrett's esophagus, and 2.81 cm in controls (p < 0.005). Mean hiatus width was 3.52 cm in patients with Barrett's esophagus and hernia, and 2.24 cm in controls with hernia. Hernia length was similar in patients with and without esophagitis, and in short segment Barrett's esophagus. CONCLUSIONS: Most patients with Barrett's esophagus have hiatal hernia; their hernias are longer and the hiatal openings wider than in controls with or without esophagitis. Hiatal hernia likely contributes to the development of Barrett's esophagus.

Adult↗

A molecular switch changes the signalling pathway used by the Fc gamma RI antibody receptor to mobilise calcium.

BACKGROUND: Leukocytes express Fc gamma receptors, which are specific for the constant region of immunoglobulin G. Aggregation of these receptors activates a repertoire of responses that can lead to targeted cell killing by antibody-directed cellular cytotoxicity. The nature of the myeloid response to Fc gamma receptor aggregation is highly variable and depends on the maturation state of the cell, but little is known about the signalling mechanisms underlying this variability. RESULTS: We show here that differentiation of a monocytic cell line, U937, to a more macrophage phenotype resulted in an absolute and fundamental switch in the nature of the phospholipid signalling pathway recruited following Fc gamma receptor aggregation. In cytokine-primed monocytes, aggregation of the high-affinity receptor Fc gamma RI resulted in the activation of phospholipase D and sphingosine kinase, which in turn led to the transient release of stored calcium; these effects were mediated by the gamma chain, an Fc gamma RI accessory protein. In contrast, in cells differentiated to a more macrophage type, aggregation of Fc gamma RI resulted in the Fc gamma RIIa-mediated activation of phospholipase C, and the resulting calcium response was prolonged as calcium entry was stimulated. CONCLUSIONS: The switch in Fc gamma RI signalling pathways upon monocyte differentiation is mediated by a switch in the accessory molecule recruited by Fc gamma RI, which lacks its own intrinsic signal transduction motif. As many immune receptors have separate polypeptide chains for ligand binding and signal transduction (allowing a similar switch in signalling pathways), the mechanism described here is likely to be widely used.

Bucladesine↗