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D O'Halloran

Publications and source records attributed to D O'Halloran.

14 recordsLinked to original sources
PubMed2004

Alcohol intake and insulin resistance. A cross-sectional study.

BACKGROUND AND AIM: The development of insulin resistance is a critical step in the pathogenesis of type 2 diabetes. The effect of alcohol intake on insulin sensitivity/resistance is not well defined. The aim of this study was to examine the association between alcohol intake and insulin resistance in a sample of middle-aged men and women with data on a wide range of potential confounding factors, including diet. METHODS: We performed a cross sectional study involving a group of 1018 men and women, sampled from 17 general practice lists in the South of Ireland, with a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and a food frequency questionnaire and provided fasting blood samples for analysis of glucose and insulin. Insulin resistance was estimated on the basis of fasting glucose and insulin, using the glucose homeostasis model (HOMA scores). Insulin resistance was defined as the upper quartile of the HOMA scores. RESULTS: We found evidence of a U-shaped relationship between alcohol intake and insulin resistance fitted as a continuous variable (HOMA scores) with lowest levels in light drinkers (between 0.5 to 0.99 units per day) relative to the other drinking categories. However no significant association between alcohol intake and HOMA score was observed in fully adjusted analyses, including adjustment for dietary saturated fat and fruit and vegetables intake. In logistic regression analysis with insulin resistance (categorical) as the dependent variable, we observed that ex-drinkers were at higher risk of insulin resistance compared to occasional drinkers independently of age, sex, BMI and waist circumference, (OR=2.4, 95% CI, 1.1-5.7, p=0.04). On further adjustment for potential confounders including diet this association was also attenuated and was non-significant. CONCLUSIONS: The reported effects of alcohol intake on insulin resistance may be confounded by other aspects of lifestyle, especially diet.

Alcohol Drinking↗
PubMed2004

Rationalising the design of polymeric thermoresponsive biomaterials.

We investigated the cell adhesion and growth of a series of thermoresponsive copolymers of N-isopropylacrylamide (NIPA) and N-tert-butylacrylamide (NtBA) above their lower critical solubility temperatures (LCST). It was found that cell adhesion and growth on the solvent cast films improved with increasing the NtBA content in the copolymers. The improvement was dependent on cell line. The surfaces of copolymers were analysed by atomic force microscopy. The topography of polymer films was not dependent on composition. The differences in the cell attachment and growth were attributed to the variation of surface energy with composition. The surface energy of copolymers decreased with the increase in the NtBA content. We conclude that poly(N-isopropylacrylamide) (poly(NIPA)) is a relatively poor substrate for cell growth and proliferation. However, its ability to support cell growth can be significantly improved by suitable modification.

Acrylamides↗
PubMed2000

Evaluation of standard haemodynamic tests of autonomic function and HbA1c as predictors of delayed gastric emptying in patients with type 1 diabetes mellitus.

We examined the relation between chronic glycaemic control (using glycosylated haemoglobin), haemodynamic autonomic function and rate of gastric emptying in 16 patients with type 1 diabetes mellitus. Gastric emptying was measured using a paracetamol absorption technique. Parameters of gastric emptying include area under the plasma paracetamol concentration time curve. Patients were classified as diabetic autonomic neuropathy positive or negative using five standardized haemodynamic reflex tests. Area under the plasma paracetamol concentration time curve in the neuropathy positive (10.36 (4.5) mmol.-1. min) and negative (9.84 (3.0) mmol.-1. min) groups were similar (.P.=0.42) using unpaired Student's.t. -tests. Glycosylated haemoglobin concentration and area under the plasma paracetamol concentration time curve (.n.=16) demonstrated a Pearson's correlation co-efficient of 0.24. Neither tests of haemodynamic autonomic function, nor concentration of glycosylated haemoglobin, are predictive of diabetic gastroparesis.

Absorption↗
PubMed2000

Circulating insulin-like growth factor II and colorectal adenomas.

Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55-64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.

Adenoma↗
PubMed1996

Clinical studies of multiple endocrine neoplasia type 1 (MEN1)

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.

Adolescent↗
PubMed1995

11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.

A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1989

Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal peptide, substance P, and neurotensin.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.

Animals↗
PubMed1988

Investigation of aminoglycoside nephrotoxicity in cystic fibrosis patients.

Cystic fibrosis patients are a special risk group for nephrotoxic effects of amino-glycosides (AG). The traditional methods of assessing renal damage are very insensitive, and toxicity is not detected until serious functional damage is evident. The aims of the present study were to monitor early markers of nephrotoxicity in cystic fibrosis patients treated with gentamicin. Urinary excretion of beta-N-acetylglucosaminase (beta-NAG, a lysosomal enzyme) and low molecular weight proteins as identified on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were prospectively studied in cystic fibrosis outpatients and inpatients. Urinary excretions of beta-NAG and low molecular weight proteins were normal in cystic fibrosis patients not being treated with gentamicin. All patients being treated with intravenous gentamicin (average dose, 2.5 g over 9 days) showed markedly elevated urinary excretion of beta-NAG. SDS-PAGE of serial urine samples from CF patients during intravenous AG therapy showed increasing excretion of low molecular weight proteins. Protein excretion profiles from control subjects showed no change over equivalent time periods. CF patients receiving nebulized AG did not show altered protein excretion. beta-NAG excretion patterns were similar to changes detected in the SDS-PAGE system. No gross nephrotoxicity developed in these patients. Blood urea nitrogen, plasma creatinine, and plasma magnesium concentrations remained within normal limits. The pattern of protein excretion on SDS-PAGE was consistent with renal tubular rather than glomerular damage. The SDS-PAGE system provides an additional means of monitoring early subclinical nephrotoxicity of AG in CF patients.

Acetylglucosaminidase↗
PubMedDate not supplied

Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications.

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.

Acromegaly↗
PubMedDate not supplied

Established cardiovascular disease and CVD risk factors in a primary care population of middle-aged Irish men and women.

Contemporary Irish data on the prevalence of major cardiovascular disease (CVD) risk factors are sparse. The primary aims of this study were (1) to estimate the prevalence of major cardiovascular disease risk factors, including Type 2 Diabetes Mellitus, in the general population of men and women between the ages of 50 and 69 years; and (2) to estimate the proportion of individuals in this age group at high absolute risk of cardiovascular disease events on the basis of pre-existing cardiovascular disease or as defined by the Framingham equation. Participants were drawn from the practice lists of 17 general practices in Cork and Kerry using stratified random sampling. A total of 1018 people attended for screening (490 men, 48%) from 1473 who were invited, a response rate of 69.1%. Cardiovascular disease risk factors and glucose intolerance are common in the population of men and women aged between 50 and 69 years. Almost half the participants were overweight and a further quarter met current international criteria for obesity, one of the highest recorded prevalence rates for obesity in a European population sample. Forty per cent of the population reported minimal levels of physical activity and 19% were current cigarette smokers. Approximately half the sample had blood pressure readings consistent with international criteria for the diagnosis of hypertension, but only 38% of these individuals were known to be hypertensive. Eighty per cent of the population sample had a cholesterol concentration in excess of 5 mmol/l. Almost 4% of the population had Type 2 Diabetes Mellitus, of whom 30% were previously undiagnosed. A total of 137 participants (13.5%) had a history or ECG findings consistent with established cardiovascular disease. Of the remaining 881 individuals in the primary prevention population, a total of 20 high-risk individuals (19 male) had a risk of a coronary heart disease event > or = 30% over ten years according to the Framingham risk equation, giving an overall population prevalence of 2.0% (95% CI 1.3 - 3.0). At a risk level > or = 20% over ten years, an additional 91 individuals (8.9%) were identified. Thus a total of 24.4% of the population were at risk either through pre-existing CVD (13.5%) or an estimated 10-year risk exceeding 20% according to the Framingham risk equation (10.9%). Thus a substantial proportion of middle-aged men are at high risk of CVD. The findings emphasise the scale of the CVD epidemic in Ireland and the need for ongoing monitoring of risk factors at the population level and the need to develop preventive strategies at both the clinical and societal level.

Aged↗
PubMedDate not supplied

Prevalence and lifestyle determinants of the metabolic syndrome.

Participants with the metabolic syndrome are at risk of developing type 2 diabetes and coronary heart disease. The aim of this study was to determine the role of lifestyle risk factors in the development of the metabolic syndrome with particular reference to physical activity, smoking and alcohol consumption. We performed a cross sectional study of the prevalence of CVD risk factors and glucose intolerance, including type 2 diabetes involving a group of 1473 men and women were sampled from 17 general practice lists in the South of Ireland. A total of 1018 attended for screening, giving a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and provided fasting blood samples for analysis of glucose, insulin and lipids. The metabolic syndrome was defined according to the current WHO criteria. The prevalence of the metabolic syndrome was 21.0% (95% C.I. 18.7% to 24.1%). In multivariate analyses with the metabolic syndrome as the dependent variable we observed a significant, independent inverse association with physical activity level (OR = 0.60; 95% CI, 0.39-0.90 for medium and OR = 0.51; 95% CI, 0.28-0.93) for high level of activity relative to the low level of activity group). Ex-drinkers had a higher prevalence of the syndrome in multivariate analysis relative to occasional drinkers, (OR = 2.38; 95% CI, 1.08-5.26). Prevalence of the metabolic syndrome was not significantly associated with current alcohol consumption or with smoking status. These data highlight the importance of physical inactivity in the aetiology of the metabolic syndrome.

Aged↗
PubMedDate not supplied

Gastric electrical stimulation: a report of two cases.

Gastroparesis refractory to prokinetic agents poses a major challenge to the physician and patient, alike. In the past 5 years, electrical methods to treat gastroparesis have emerged from animal and human experiments to a potentially valuable tool in clinical gastroenterology. One of these methods, known as gastric electrical stimulation (GES), is being increasingly used in specialized centres worldwide, but had never been tried in Ireland. We describe here our experience with the first two implantations of gastric neurostimulators performed in Ireland and the outcome with these 2 patients. Our results at 6 months show reduction in symptoms and improvement in quality of life, which is encouraging and should prompt further evaluation of GES for patients with gastroparesis refractory to medical therapy.

Adult↗