Search PubMed⌕ Search

Biomedical subjects

B McGuinness

Publications and source records attributed to B McGuinness.

10 recordsLinked to original sources
PubMed2006

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease.

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure). Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

Alzheimer Disease↗
PubMed2006

Spontaneous coeliac artery dissection.

A patient with spontaneous coeliac artery dissection that presented as upper abdominal pain is reported. This was diagnosed on contrast-enhanced multislice helical CT. The patient was treated conservatively and follow-up CT showed mild aneurysmal change of the splenic artery and a small splenic infarct. Isolated dissection of the visceral arteries (and, in particular, the coeliac artery) is extremely rare. With such limited evidence, decisions over best management are difficult, but depend on initial severity and progression at follow up.

Aortic Dissection↗
PubMed1996

Affinity-based screening of combinatorial libraries using automated, serial-column chromatography.

We have developed an automated serial chromatographic technique for screening a library of compounds based upon their relative affinity for a target molecule. A "target" column containing the immobilized target molecule is set in tandem with a reversed-phase column. A combinatorial peptide library is injected onto the target column. The target-bound peptides are eluted from the first column and transferred automatically to the reversed-phase column. The target-specific peptide peaks from the reversed-phase column are identified and sequenced. Using a monoclonal antibody (3E-7) against beta-endorphin as a target, we selected a single peptide with sequence YGGFL from approximately 5800 peptides present in a combinatorial library. We demonstrated the applicability of the technology towards selection of peptides with predetermined affinity for bacterial lipopolysaccharide (LPS, endotoxin). We expect that this technology will have broad applications for high throughout screening of chemical libraries or natural product extracts.

Amino Acid Sequence↗
PubMed1990

Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.

Amino Acid Sequence↗
PubMed1978

Psychoneurotic profiles in the adult population.

Self-reported psychoneurotic characteristics and aspects of affective status have been examined within the adult population of a market town and the surrounding rural community using a standardized instrument. Features of anxiety in particular are more common amongst females than males, peaking in the third, fourth (phobic avoidance behaviour being also especially evident at this time) and fifth decades of life. Many of the characteristics are also importantly related to age in both sexes and to social class. Some are widespread within the population and probably reflect more enduring personality traits. Others are less common, more age specific (e.g. early adult life, middle age, the menopause in females; the involutional period in males) and are probably more often construed by the individuals concerned and by others as 'illness'. The similarity of the relevant segment of the present profiles to those previously obtained from a suburban population aged 40-65 years is noteworthy. The most likely interpretation is that the measuring instrument is reliable and that the reporting behaviour of psychoneurotic and effective characteristics and morbidity is identical in both populations.

Adolescent↗
PubMed1975

Isocaloric diet changes and electroencephalographic sleep.

Electroencephalographic (E.E.G.) sleep changes were studied in eight young healthy male subjects who were given a normal balanced diet or a high-carbohydrate/low-fat or low-carbohydrate/high-fat isocaloric diet, according to an experimental design. Significantly less slow-wave sleep (S.W.S.) was found after consuming a high-carbohydrate/low-fat diet than after consuming a normal balanced diet or a low-carbohydrate/high-fat diet. The latter two diets did not differ in terms of the amounts of S.W.S. Both high-carbohydrate/low-fat and low-carbohydrate/high-fat isocaloric diets, especially the former, were associated with significantly more rapid-eye-movement (R.E.M.) sleep than was the normal balanced diet. These findings emphasise the importance of daily diet for the following night's sleep.

Diet↗
PubMedDate not supplied

Peptides as affinity surfaces for protein purification.

The tetrapeptide GPRP was previously shown to be an effective affinity ligand for fibrinogen when immobilized to Fractogel (Kuyas et al., 1990). The authors synthesized the GPRP peptide directly onto an aminefunctionalized POROS chromatographic resin to demonstrate the effectiveness of this approach for generating perfusive affinity media. Fibrinogen from plasma bound to an NH2-GPRP-POROS column under 50 mM phosphate buffer, 0.15 M NaCl, pH 7 at 15 ml/min flow rate. The bound fibrinogen showed weak clotting activity when eluted with 20 mM acetate buffer, pH 4. The peptide column did not bind denatured fibrinogen. The dynamic binding capacity of the column by frontal analysis was 10.2 mg/ml column volume. The total analysis time was under 5 min. Similarly, the CAQCHTVEK peptide of cytochrome c with heme group covalently attached to the SH groups of the two cysteines is known to bind to albumins (Adams et al., 1989). A simplified peptide analogue, GAQGHTVEK, was synthesized directlyon POROS resin. Under 20 mM MES, pH 6, albumin from human serum bound specifically to this peptide column and eluted with a salt gradient at 0.2 M NaCl, 20 mM MES (2-[N-Morpholino]ethane sulfonic acid), pH 6. The dynamic binding capacity of human serum albumin by frontal analysis was 19 mg/ml column volume. Thus, this column can purify albumin from human serum under non-denaturing conditions.

Chromatography, Affinity↗