Search PubMed⌕ Search

Biomedical subjects

M Nicolaou

Publications and source records attributed to M Nicolaou.

16 recordsLinked to original sources

Early outcomes in the elderly: a meta-analysis of 4921 patients undergoing coronary artery bypass grafting--comparison between off-pump and on-pump techniques.

OBJECTIVE: To assess early outcomes in the elderly population undergoing coronary revascularisation with and without cardiopulmonary bypass (CPB). METHODS: Meta-analysis of all retrospective, non-randomised studies comparing off-pump coronary artery bypass (OPCAB) versus CPB techniques in the elderly (> 70 years) between 1999 and 2005. Age-related early outcomes of interest were death, stroke, atrial fibrillation (AF), renal failure and length of stay in hospital. The random effects model was used. Sensitivity and heterogeneity were analysed. RESULTS: Analysis of 14 non-randomised studies comprising 4921 patients (OPCAB, 1533 (31.1%) and CPB, 3388 (68.9%)) showed a significantly lower incidence of death in the OPCAB group (odds ratio (OR) 0.48, 95% CI 0.28 to 0.84). This effect was greater in OPCAB octogenarians (OR 0.26, 95% CI 0.12 to 0.57). The pattern of incidence of stroke among the OPCAB octogenarians (OR 0.19, 95% CI 0.07 to 0.56) was similar. The incidence of AF was lower in the OPCAB group (OR 0.77, 95% CI 0.61 to 0.97). The incidence of renal failure did not differ. Length of hospital stay was shorter in the OPCAB group, although with significant heterogeneity. CONCLUSIONS: OPCAB may be associated with lower incidence of death, stroke and AF in the elderly, which may result in shorter length of hospital stay. A large randomised trial would confirm whether the elderly would benefit more from OPCAB surgery.

Aged↗

Comparison of laparoscopic and open ileocecal resection for Crohn's disease: a metaanalysis.

BACKGROUND: The role of laparoscopic surgery for patients with ileocecal Crohn's disease is a contentious issue. This metaanalysis aimed to compare open resection with laparoscopically assisted resection for ileocecal Crohn's disease. METHODS: A literature search of the Medline, Ovid, Embase, and Cochrane databases was performed to identify comparative studies reporting outcomes for both laparoscopic and open ileocecal resection. Metaanalytical techniques were applied to identify differences in outcomes between the two groups. Sensitivity analysis was undertaken to evaluate the heterogeneity of the study. RESULTS: Of 20 studies identified by literature review, 15 satisfied the criteria for inclusion in the study. These included outcomes for 783 patients, 338 (43.2%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 6.8%. The operative time was significantly longer in the laparoscopic group, by 29.6 min (p = 0.002), although the blood loss and complications in the two groups were similar. In terms of postoperative recovery, the laparoscopic patients had a significantly shorter time for recovery of their enteric function and a shorter hospital stay, by 2.7 days (p < 0.001). CONCLUSIONS: For selected patients with noncomplicated ileocecal Crohn's disease, laparoscopic resection offered substantial advantages in terms of more rapid resolution of postoperative ileus and shortened hospital stay. There was no increase in complications, as compared with open surgery. The contraindications to laparoscopic approaches for Crohn's disease remain undefined.

Crohn Disease↗

Acculturation and education level in relation to quality of the diet: a study of Surinamese South Asian and Afro-Caribbean residents of the Netherlands.

BACKGROUND: To consider the changes in overall diet quality following migration we examined the associations of acculturation variables and education level with diet in Surinamese South Asian and Surinamese Afro-Caribbean origin on the one hand, and ethnic Dutch residents of the Netherlands on the other. Surinam is a former Dutch colony in South America. METHODS: We randomly selected men and women aged 35-60 years: ethnic Dutch, n = 552; South Asian, n = 306; Afro-Caribbean, n = 660. Intakes of fruit, vegetables, red meat, fish, vegetable oils, breakfast and salt were measured using a short questionnaire that formed the basis for a 'diet quality indicator' score. Highest education was measured and acculturation of the Surinamese groups was assessed by age at migration, number of resident years and a scale measure of social contacts with ethnic Dutch. RESULTS: Compared with ethnic Dutch, both Surinamese groups scored higher on overall diet quality (P < or = 0.001) but some aspects of diet (breakfast and salt use) were less prudent. Education was positively associated with diet quality in ethnic Dutch (P < or = 0.01), but not consistently so in Surinamese. Associations with social contact with ethnic Dutch varied for different quality aspects of the diet. Residence duration (mean = 22 years) and age at migration (mean = 21 years) were not associated with diet. CONCLUSIONS: A greater degree of acculturation does not necessarily lead to a less healthful diet in migrants. In addition, the association of education level with diet may differ for migrant groups. The diet of migrants differ from host populations, suggesting that migrant groups should be considered in the development of nutrition health promotion activities.

Acculturation↗

Spontaneous rupture of a true uterine artery aneurysm: a cause of retroperitoneal haematoma.

We report the first case of spontaneous rupture of a true uterine artery aneurysm in a 69-year-old woman presenting with severe abdominal pain, a left iliac fossa mass, anaemia and a retroperitoneal haematoma on CT scanning. In this patient, the aneurysm was successfully embolised using microcoils. The different imaging modalities used for diagnosis and the treatment options are discussed.

Abdominal Pain↗

Successful use of Botulinum toxin-A for the treatment of neck and anterior chest wall flushing.

Neck and anterior chest wall flushing can be a social handicap to the sufferer and current treatment options are often unsatisfactory. We report the case of a 48-year-old woman with severe flushing of the anterior neck and anterior chest wall which resolved after three treatments of intracutaneous botulinum toxin A injections. We believe that this treatment method for skin flushing is simple, effective and free of significant side effects at these sites. Further studies are needed to evaluate the duration of the therapeutic effect.

Botulinum Toxins, Type A↗

Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential contribution to the gene activity and risk for AD.

We have analyzed the 5'-upstream promoter region of the presenilin 2 gene (PSEN2) for regulatory elements and examined Alzheimer disease (AD) patients and non-demented individuals for polymorphisms in the 5' upstream promoter region of the PSEN2 gene. Direct sequencing analysis detected a common single adenine (A) nucleotide deletion polymorphism in the upstream promoter region of the PSEN2 gene. Examination of cohorts of AD patients and age-matched control individuals revealed no statistically significant differences in the frequency of this polymorphism when compared with the total sample of AD patients and control individuals. However, subgroup and regression analysis suggested that the relatively rare -A/-A genotype increases risk of AD among subjects lacking apolipoprotein E (APOE) epsilon4 and among persons ages 65 years and younger. DNA sequence and DNA-protein binding analysis demonstrated that this mutation negates binding with putative repressor transcription factor (TF), interferon regulatory factor 2 (IRF2), in nuclear extracts prepared from the aged human brain neocortex. However this mutation creates a potential regulatory element, C/EBPbeta, that is responsive to pro-inflammatory (PI) induction. The expression activity assay with luciferase reporter gene into normal human neural progenitor cells in primary culture shows that the mutant PSEN2 regulatory region exhibits a 1.8-fold higher level of basal expression and is sensitive to IL-1beta and Abeta42, but that it is synergistically induced 3.2-fold over the wild-type PSEN2 by [IL-1beta+Abeta42]. These results suggest that under Pl and oxygen stress conditions relatively minor variations in PSEN2 promoter DNA sequence structure can enhance PSEN2 gene expression and that consequently these may play a role in the induction and/or proliferation of a Pl response in AD brain.

5' Untranslated Regions↗

Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease.

Amyloid beta-peptide (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD). The gene encoding the beta-site APP cleaving enzyme (BACE), one of two enzymes that sequentially cleave the beta-amyloid precursor protein to generate Abeta, has recently been cloned. We tested the hypothesis that BACE might be genetically associated with AD by linkage analysis (56 pedigrees), by direct nucleotide sequencing of the entire open reading frame (20 subjects with familial AD, and 10 subjects with sporadic AD) and by allelic association analysis (155 AD cases and 173 non-demented controls). Our results revealed no evidence for either genetic linkage or allelic association between BACE and AD, and no coding sequence mutations were detected in the open reading frame of the BACE gene. These data suggest that while BACE protein plays an important role in the pathogenesis of AD, and may be a robust therapeutic target, it is unlikely to be a major AD susceptibility locus.

Aged↗

Genetic predisposition to stroke in relatives of hypertensives.

BACKGROUND AND PURPOSE: The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. METHODS: Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex. RESULTS: The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9. 7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0). CONCLUSIONS: Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.

Aged↗

Power of concordant versus discordant sib pairs at different penetrance levels.

Knowing the answers, we used the GAW11 data set to compare the power and efficiency of discordant versus concordant affected sib pairs for qualitative traits at different levels of penetrance. Samples of 200 concordant sib pairs outperformed discordant sib pairs for low penetrance (40%) and 70% penetrance models while at 90% penetrance they performed equally well. Increasing the sample size of discordant sib pairs to twice that of concordant pairs was not enough to reach the power of concordant sib pairs at the 40% and 70% penetrance models. For low penetrance using a combination of concordant and discordant sib pairs resulted in higher power than using discordant sib pairs alone. At 90% penetrance, the power of concordant and discordant sib pairs was similar in the region close to the gene while concordant sib pairs performed better at locations further from the gene.

Genetic Linkage↗

Stratification techniques to explore genotype environment interactions.

Linkage analysis was performed on the GAW11 Problem 2 data set using stratification to explore the effects of the environmental risk factors and the differences between mild and severe phenotypes. Analysis of the four study populations stratified by the two risk factors identified regions on chromosomes 3 and 5 with significant evidence for linkage. Other loci were sought by removing families consistent with linkage to the chromosome 3 locus. Our studies identified a locus on chromosome 3 (markers 43-46) associated with the mild phenotype in the presence of risk factor 1 and with the severe phenotype independent of risk factor 1. This suggests that distinct allelic variants at the chromosome 3 locus may cause different forms of disease. The locus identified on chromosome 5 (markers 36-39) was linked to the severe phenotype, but exposure to factor 1 or 2 may have a protective effect. The regions on chromosomes 3 and 5 appeared to have independent roles in disease etiology. Evidence for two loci on chromosome 1 linked to the mild form was found. The methods successfully identified linkages and interaction consistent with the generating model.

Environment↗

Identification of a polymorphic glutamic acid stretch in the alpha2B-adrenergic receptor and lack of linkage with essential hypertension.

Essential hypertension, a clinically significant elevation in blood pressure with no recognizable cause, is believed to be attributable to the collective effect of genetic predisposing factors in combination with specific environmental factors, such as diet and stress. Of the genetic causes, genes coding for proteins involved in blood pressure regulation, such as the alpha- and beta-adrenergic receptors, are obvious candidates. The alpha2-adrenergic receptor plays a key role in the sympathetic nervous system by mediating the effects of epinephrine and norepinephrine. To evaluate the potential role between the alpha2B receptor and essential hypertension, we scanned the alpha2B-receptor gene for genetic variation in 108 affected sibling pairs. The screening revealed two major forms of the receptor. They differ by the presence of either 9 or 12 glutamic acid residues in the acidic domain of the third cytoplasmic loop of the protein. Investigation of the pattern of this variation in hypertensive sibling pairs suggests that the alpha2B receptor locus does not contribute substantially to genetic susceptibility for essential hypertension.

Alleles↗

Evidence for linkage between essential hypertension and a putative locus on human chromosome 17.

Several clinical and animal studies indicate that essential hypertension is inherited as a multifactorial trait with a significant genetic and environmental component. In the stroke-prone spontaneously hypertensive rat model, investigators have found evidence for linkage to blood pressure regulatory genes (quantitative trait loci) on rat chromosomes 2, 10, and X. In 1 human study of French and UK sib pairs, evidence for linkage has been reported to human chromosome 17q, the syntenic region of the rat chromosome 10 quantitative trait loci (QTL). Our study confirms this linkage (P=0.0005) and refines the location of the blood pressure QTL.

Aged↗

Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q.

Familial orthostatic hypotensive disorder is characterized by light-headedness on standing, which may worsen to syncope, palpitations, and blue-purple ankle discoloration, and is accompanied by a marked decrease in systolic blood pressure, an increase in diastolic pressure, and tachycardia, all of which resolve when supine. We ascertained three families in which this disorder is inherited as an autosomal dominant trait with reduced penetrance. A genomewide scan was conducted in the two largest families, and three regions with multipoint LOD scores >1.5 were identified. Follow-up of these regions with additional markers in all three families yielded significant evidence of linkage at chromosome 18q. A maximum multipoint LOD score of 3.21 in the three families was observed at D18S1367, although the smallest family had negative LOD scores in the entire region. There was significant evidence of linkage in the presence of heterogeneity at 18q, with a maximum LOD score of 3.92 at D18S1367 in the two linked families. Identification of the gene responsible for orthostatic hypotensive disorder in these families may advance understanding of the general regulatory pathways involved in the continuum, from hypotension to hypertension, of blood pressure.

Blood Pressure↗

The influence of the hypertensive patient's education in compliance with their medication.

The purpose of this study was to examine the relationships between patient's education in compliance with their medical regimen and the external variables: (1) "years of schooling," (2) duration of treatment, and (3) compliance with the medical regimen. The hypothesis tested in this study was as follows: "Hypertensive individuals who are educated about the importance of their medication and about the consequences of not taking the prescribed dosage will show better compliance with their prescribed drug regimen than those who are not thus educated." The sample of the study consisted of 40 hypertensive patients. A "posttest-only" control group design was used in this study. The hypothesis of the study was tested by using the Mann-Whitney U test. For the relationship between the external variables (years of schooling, duration of treatment, and compliance with the medical regimen), the Spearman test was used. The findings of the study revealed a statistically significant difference between compliance levels in the experimental group and in the control group (U = 130, p < 0.05), a positive correlation between "years of schooling" and compliance (rs = 0.33, p = 0.04), and a negative correlation between duration of treatment and compliance (rs = -0.45, p = 0.005). The findings support the hypothesis of the study.

Aged↗