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Biomedical subjects

A Gallagher

Publications and source records attributed to A Gallagher.

At least 19 recordsLinked to original sources
PubMed2006

The effect of the optimal use of rapid-acting insulin analogues on insulin secretion in Type 2 diabetes.

The abnormal glucose tolerance of Type 2 diabetes is characterized by post-prandial hyperglycaemia. We aimed to examine whether the restoration of a more physiological insulin profile using rapid-acting insulin analogues might, through effects on glucose toxicity, improve endogenous insulin secretion rate (ISR) and secondly improve markers of vascular risk. Eighteen people with insulin-treated Type 2 diabetes were recruited into a single centre, cross-over, open-labeled study. The order of pre-meal unmodified human insulin or insulin aspart was randomized: treatment periods lasted at least 8-12 weeks after which ISR was assessed by stepped low-dose glucose infusion and fasting markers of vascular risk measured. Glucose control was good (HbA(1c) 6.94+/-0.12 (+/-S.E.)% versus 7.07+/-0.13%, NS) with insulin aspart and human insulin. Mean post-prandial self-monitored blood glucose concentration was also good particularly with insulin aspart (7.5+/-0.41 mmol/l versus 8.19+/-0.34 mmol/l) but the difference did not reach statistical significance. Over 160 min ISR did not differ between insulin aspart and human insulin and there was also no change in various markers of vascular risk. In conclusion a meal-time+basal insulin regimen gave close to normal post-prandial blood glucose control with both the insulin aspart and human insulin regimens, such that no difference in ISR or markers of vascular risk could be demonstrated.

Aged↗
PubMed2006

Equipment standards for interventional cardiology.

Interventional radiology has seen rapid growth in cardiology and represents an alternative to hazardous surgery. Recently there has been a substantial growth in the number of procedures being performed and interventional cardiology (IC) procedures are the most common interventional procedures in Europe. Advances in imaging technology have facilitated the development of increasingly complex radiological IC equipment. Currently, the technology is developing at a rate ahead of supporting research, equipment standards and a regulatory framework. International standards play a key role in the design, manufacture and performance of radiological IC equipment. A survey of 12 IC systems (15 imaging chains) was conducted in Irish hospitals. The aim of the study was to assess the imbalance between rapidly advancing technology and existing standards and to propose recommendations for new IC equipment standards. The results demonstrate the need for definitive equipment requirements and standardisation in the design, manufacture, acceptance and maintenance of IC equipment.

Cardiology↗
PubMed2006

Molecular methods for virus discovery.

The potential use of novel cell substrates from diverse animal species raises concerns about the transmission of hitherto unknown viral agents. Viruses that do not cause a cytopathic effect in cell culture may escape detection by conventional methods and molecular methods may therefore prove useful for screening for hitherto unknown viruses. This review describes currently used molecular methods for virus discovery, including degenerate PCR assays, representational difference analysis and rolling circle amplification, and summarises the advantages and disadvantages of each technique.

Amino Acid Sequence↗
PubMed2005

The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes.

A variety of abnormalities of metabolic, haemostatic and endothelial markers are associated with Type 2 diabetes. Evidence suggests that poor post-prandial blood glucose control may contribute to vascular risk. We aimed to examine whether the restoration of a more physiological insulin profile post-prandially would improve these abnormalities. Twenty-one patients with insulin-treated Type 2 diabetes were recruited into a single centre, crossover, double-blind study. Patients were randomized to unmodified human insulin or insulin aspart before main meals for 6-week study periods, both together with NPH insulin. At the end of each study period, pre-breakfast levels of markers of vascular risk were assessed and a test meal performed. There was no significant difference in HbA(1c) (7.04 +/- 0.13% (+/-S.E.) versus 7.15 +/- 0.11%, P = 0.060) with insulin aspart compared to human insulin at the end of each study period. The mean post-prandial blood glucose concentration at 90 min from self-monitored results was lower with insulin aspart than with human insulin (7.9 +/- 0.4 mmol/l versus 9.3 +/- 0.4 mmol/l, P = 0.011) as was study day post-prandial blood glucose at 90 min (8.4 +/- 0.5 mmol/l versus 9.2 +/- 0.6 mmol/l, P = 0.046). No significant differences were found in fasting lipid profile, apolipoproteins, fibrinogen, plasminogen activator inhibitor-1, E-selectin, or homocysteine between the two study periods. Insulin aspart resulted in improved post-prandial glycaemic control when compared to human insulin in Type 2 diabetic patients, but this was not associated with changes in markers of vascular risk.

Aged↗
PubMed2002

Associations between physical fitness and activity patterns during adolescence and cardiovascular risk factors in young adulthood: the Northern Ireland Young Hearts Project.

The aim of the present study was to examine relationships between cardiovascular disease (CVD) risk factor status in young adulthood (mean age = 22.5 yrs) and antecedent physical fitness and physical activity at ages 12 and 15 years. The data were obtained from the Young Hearts Project, a longitudinal observational study of CVD risk factors in a representative sample of young people from Northern Ireland. Physical fitness was measured by the 20-metre endurance shuttle run, and physical activity and sports participation by a self-report recall questionnaire. CVD risk factors examined included serum total cholesterol (TC) and HDL cholesterol concentrations, the TC:HDL ratio, systolic and diastolic blood pressure and body fatness (sum of four skinfolds). Linear regression analyses showed modest relationships between physical fitness in adolescence and both TC:HDL ratio and body fatness in young adulthood. No such relationships were apparent for adolescent physical activity. The promotion of physical fitness during adolescence may reduce exposure to other risk factors lasting into early adulthood.

Adolescent↗
PubMed2002

Attenuation of the virulence of Porphyromonas gingivalis by using a specific synthetic Kgp protease inhibitor.

The Arg- and Lys-gingipains of Porphyromonas gingivalis are important virulence determinants in periodontal disease and may correspond to targets for immune- or drug-based treatment strategies. In this investigation we aimed to determine which of these enzymes represents the most promising molecular target for protease inhibitor-based therapy and to examine the effectiveness of the resultant compound in a murine virulence assay. Isogenic mutants with mutations in rgpA and rgpB (encoding Arg-gingipains) and in kgp (encoding Lys-gingipain) and a double mutant with mutations in rgpA and rgpB were prepared by using P. gingivalis W50. The virulence of these mutants indicated that Kgp is a promising drug target. Combinatorial chemistry was used to define the optimal substrate of Kgp, and from this information a specific slowly reversible inhibitor with a nanomolar K(i) was designed and synthesized. Growth of P. gingivalis W50 in the presence of this compound resembled the phenotype of the kgp isogenic mutant; in both instances bacterial colonies failed to form pigment on blood agar, and only poor growth was obtained in a defined medium containing albumin as the sole protein source. Furthermore, pretreatment of the wild-type organism with the Kgp inhibitor led to a significant reduction in virulence in the murine assay. These data emphasize the conclusion that Kgp is an important factor for both nutrition and virulence of P. gingivalis and that inhibitors of this enzyme may have therapeutic potential for the control of P. gingivalis infections. Protease inhibitors may be a potentially novel class of antimicrobial agents with relevance to the control of other bacterial pathogens.

Adhesins, Bacterial↗
PubMed2002

Cerebral venous thrombosis during diabetic ketoacidosis.

Neurological deterioration during an episode of diabetic ketoacidosis is usually assumed to be caused by cerebral oedema. We present a case of cerebral venous sinus thrombosis presenting in a similar manner, also associated with severe iron deficiency anaemia. Computed tomography scanning provided the correct diagnosis and allowed institution of anticoagulation with improvement in neurological outcome. Neuroimaging should always be performed in suspected cerebral oedema associated with diabetic ketoacidosis in order to exclude other pathologies.

Anticoagulants↗
PubMed2002

Undignifying institutions.

Declarations of the importance of dignity in health care are commonplace in codes of practice and other mission statements, yet these documents never clarify dignity's meaning. Their vague aspirations are compared to comments from staff and patients about opportunities for and barriers against the promotion of dignity in elderly care institutions. These suggest that while nurses and health care assistants have an intuitive understanding of dignity, they either do not or cannot always bring it about in practice. Thus, despite stated intentions to promote dignity, it appears that the circumstances of at least some elderly care institutions cause patients to experience avoidable indignities. Such institutions are "undignifying institutions" because they fail to acknowledge dignity's basic components, focus excessively on quantifiable priorities, and have insufficient resources available to assure consistently dignifying care. As a partial solution, we argue that health workers should be taught to understand and specify the components of dignity, which will better prepare them to challenge undignifying practices and to recognise opportunities for dignity promotion.

Aged↗
PubMed2001

Signals that initiate somatic hypermutation of B cells in vitro.

Somatic hypermutation is initiated as B lymphocytes proliferate in germinal centers. The signals that switch on the mutation process are unknown. We have derived an in vitro system to define signals that will initiate mutation in normal, naive splenic B cells. We find that three signals are required to allow detection of somatic mutation in vitro; these are anti-Ig, anti-CD40, and anti-CD38. If any one of these is omitted, mutation remains off. We show that CD40 is obligatory in vivo, as CD40 knockout mice exhibit no Ag-driven mutation. In contrast, CD38 is not, as CD38 knockout mice mutate normally. We believe that, in vitro, CD38, in combination with other stimuli, drives extensive cell division, allowing the detection of mutated sequences. However, in germinal centers in vivo, proliferative activity is instigated by a different molecule. This is the first demonstration of the initiation of hypermutation in vitro with normal splenic B cells using defined stimuli.

ADP-ribosyl Cyclase↗
PubMed2001

Screening for herpesvirus genomes in common acute lymphoblastic leukemia.

There is epidemiological evidence that infection may play a role in the etiology of childhood leukemia in particular common B cell precursor acute lymphoblastic leukemia. A panel of 20 leukemic samples (panel 1) was examined for the presence of four lymphotropic herpesviruses using conventional molecular techniques. A second independent panel of 27 leukemic samples (panel 2), along with 28 control peripheral blood samples from children with other forms of cancer, was tested for the presence of the same four viruses using sensitive real-time quantitative PCR. While herpesvirus genomes were detected, they were present at very low levels; detection rates and levels were similar in the leukemic and control panels. In addition we surveyed 18 leukemic samples (five from panel 1, six from panel 2 and a further seven samples not previously analyzed) using a degenerate PCR assay capable of detecting the genomes of known herpesviruses plus putative new members of the family. No novel herpesvirus genomes were detected suggesting that a herpesvirus is unlikely to be etiologically involved as a transforming agent in common acute lymphoblastic leukemia.

Adolescent↗
PubMed2001

Sequence analysis of feline caliciviruses isolated from the oral cavity of clinically normal domestic cats (Felis catus) in Florida.

Four isolates (7.3 per cent) of feline calicivirus (FCV), from oropharyngeal swabs taken from 55 unvaccinated apparently healthy cats, were identified by electron microscopy and reverse transcription-polymerase chain reaction (RT-PCR). A 671-bp fragment, comprising part of region B, all of regions C, D, and E and part of region F of the FCV capsid protein gene, was amplified from each isolate by RT-PCR and cloned for sequence analysis. Amino acid sequence comparison of these regions revealed significant sequence divergence from the F9 vaccine strain within regions C, E, and F. The hypervariable region E of the four Florida isolates and the NADC isolate contained three fewer amino acids than the commonly used F9 vaccine strain. This work provides support to the idea that currently circulating FCV strains may differ substantially from presently used vaccine strains.

Amino Acid Sequence↗
PubMed2001

The UK Human Rights Act 1998: implications for nurses.

In this article we consider some of the implications of the UK Human Rights Act 1998 for nurses in practice. The Act has implications for all aspects of social life in Britain, particularly for health care. We provide an introduction to the discourse of rights in health care and discuss some aspects of four articles from the Act. The reciprocal relationship between rights and obligations prompted us to consider also the relationship between guidelines in the United Kingdom Central Council's Code of professional conduct and the requirements of the Human Rights Act 1998. We conclude with the recommendation that the new legislation should be welcomed for its potential to support good practice and to urge critical and reflective practice rather than as yet another burdensome bureaucratic imposition.

Codes of Ethics↗
PubMed2001

Field enhancement in apertureless near-field scanning optical microscopy.

The near field of an apertureless near-field scanning optical microscopy probe is investigated with a multiple-multipole technique to obtain optical fields in the vicinity of a silicon probe tip and a glass substrate. The results demonstrate that electric field enhancements of >15 relative to the incident fields can be achieved near a silicon tip, implying intensity enhancements of several orders of magnitude. This enhancement arises both from the antenna effect of the elongated probe and from a proximity effect when the probe is near the substrate surface and its image dipoles play a role.

Journal Article↗
PubMed2000

Role of cAMP-dependent protein kinase (PKA) in opioid agonist-induced mu-opioid receptor downregulation and tolerance in mice.

Studies suggest that acute and chronic opioids can regulate the cAMP-dependent protein kinase (PKA) signaling pathway and that changes in this pathway may be involved in opioid tolerance. In the present study, we examined the role of cAMP-PKA on mu-opioid receptor downregulation and tolerance in mice. Mice were injected intracerebroventricular (i.c.v.) and intrathecal (i.t.) once a day with an antisense oligodeoxynucleotide directed at the mRNA for the alpha catalytic subunit of mouse PKA. Controls were treated with saline or a mismatch oligodeoxynucleotide. On day 2 of treatment, mice were implanted s.c. with a 25-mg morphine pellet and an osmotic minipump infusing morphine (40 mg/kg/day) for 3 days. Other mice were implanted with an osmotic minipump infusing etorphine (125, 250 microg/kg/day) for 2 days. Control mice were implanted s.c. with inert placebo pellets. At the end of treatment, pumps and pellets were removed and mice tested for morphine or etorphine analgesia. Other mice were sacrificed and mu-opioid receptor binding assays conducted in whole brain. Both infusion doses of etorphine produced significant tolerance (ED(50) shift = 3.6 and 6.3-fold). The higher etorphine infusion produced downregulation of mu-receptor density ( approximately 30%) while the lower infusion dose of etorphine did not. Morphine treatment also produced significant tolerance in mice (ED(50) shift = 4.5-fold), but no receptor downregulation. Antisense to PKA partially blocked tolerance induced by the higher dose of etorphine, but had no effect on receptor downregulation. On the other hand, antisense to PKA completely blocked tolerance induced by morphine and the lower infusion dose of etorphine. The mismatch oligodeoxynucleotide had no effect on any measure. These results suggest that PKA has a limited role in opioid agonist-induced receptor downregulation. However, the partial block of tolerance for the high infusion dose of etorphine and the complete block of tolerance for morphine and the low infusion dose of etorphine suggests that PKA may play a critical role in tolerance that is "receptor-regulation-independent."

Analgesics, Opioid↗
PubMed2000

Analysis of post-translational modification of mycobacterial proteins using a cassette expression system.

A recombinant expression system was developed to analyse sequence determinants involved in O-glycosylation of proteins in mycobacteria. By expressing peptide sequences corresponding to known glycosylation sites within a chimeric lipoprotein construct, amino acids flanking modified threonine residues were found to have an important influence on glycosylation. The expression system was used to screen mycobacterial sequences selected using a neural network (NetOglyc) trained on eukaryotic O-glycoproteins. Evidence of glycosylation was obtained for eight of 11 proteins tested. The results suggest that sites involved in O-glycosylation of mycobacterial and eukaryotic proteins share similar structural features.

Alkaline Phosphatase↗