PubMed Health⌕ Search

Biomedical subjects

A Kennedy

Publications and source records attributed to A Kennedy.

At least 19 recordsLinked to original sources
PubMed2006

Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study.

OBJECTIVE: To investigate the association between brain amyloid load in Alzheimer disease (AD) measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition. METHODS: Nineteen subjects with AD and 14 controls had [11C]PIB-PET and underwent a battery of psychometric tests. Twelve of those subjects with AD and eight controls had [18F]FDG-PET. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping. [11C]PIB binding and rCMRGlc were correlated with scores on psychometric tests. RESULTS: AD subjects showed twofold increases in mean [11C]PIB binding in cingulate, frontal, temporal, parietal, and occipital cortical areas. Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. Two patients fulfilling the clinical criteria for AD had normal [11C]PIB at baseline. Over 20 months this remained normal in one but increased in the cingulate of the other. Mean levels of temporal and parietal rCMRGlc were reduced by 20% in AD and these correlated with mini mental scores, immediate recall, and recognition memory test for words. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal and parietal cortices. CONCLUSION: [11C]PIB-PET detected an increased amyloid plaque load in 89% of patients with clinically probable Alzheimer disease (AD). The high frontal amyloid load detected by [11C]PIB-PET in AD in the face of spared glucose metabolism is of interest and suggests that amyloid plaque formation may not be directly responsible for neuronal dysfunction in this disorder.

Aged↗
PubMed2006

Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts.

This study demonstrates, through a combination of stringent screening methods and thorough validation, that it is possible to identify transmembrane proteins preferentially expressed in primary breast tumour cells. mRNA was extracted from tumour cells isolated from invasive breast cancers and it was then subtracted against normal breast tissue mRNA prior to the generation of a signal sequence-trap library. Screening of the library identified 31 positive clones encoding 12 cell-surface and 12 secreted proteins. The expression of a subset of transmembrane genes was then interrogated using a high-throughput method (tissue microarray) coupled with cutting-edge in situ techniques in a large cohort of patients who had undergone uniform adjuvant chemotherapy. Expression of CD98 heavy chain (CD98HC) and low-level expression of the insulin-like growth factor 2 receptor/mannose-6-phosphate receptor (IGF2R/M6PR) correlated with poor patient prognosis in the whole cohort. Expression of bradykinin receptor B1 (BDKRB1) and testis enhanced gene transcript (TEGT) correlated with good prognosis in woman with oestrogen receptor (ER)-negative breast tumours. These results indicate that this combined approach of isolating primary tumour cells, generating a library to specifically isolate signal-sequence-containing transcripts, and in situ hybridization on tissue microarrays successfully identified novel prognostic markers (BDKRB1, CD98hc, and TEGT) and potential transmembrane therapeutic targets (CD98hc) in breast cancer.

Apoptosis Regulatory Proteins↗
PubMed2005

A randomised controlled trial of self-help interventions in patients with a primary care diagnosis of irritable bowel syndrome.

INTRODUCTION: Functional abdominal symptoms are very common and account for nearly two million primary care consultations in Britain every year and produce significant morbidity. The aims of this study were to evaluate the impact of two self-help interventions on consultation rates and symptom severity in patients with a primary care diagnosis of irritable bowel syndrome. METHODS: A total of 420 patients from 54 primary care centres were randomised either to receive self-help information in the form of a guidebook or the guidebook plus a "self-help" group meeting or to be in a control group receiving neither intervention. Data were collected using questionnaires and primary care records. RESULTS: At one year, patients in the guidebook group had a 60% reduction in primary care consultations (p < 0.001) and a reduction in perceived symptom severity (p < 0.001) compared with controls. Allocation to the self-help group conferred no additional benefit. Actual symptom scores did not change significantly in any group. Costs per patient were reduced by Pounds 73 (confidence interval Pounds 43, Pounds 103) or 40% per year. CONCLUSION: Introduction of a self-help guidebook results in a reduction in primary care consultations, a perceived reduction in symptoms, and significant health service savings. This suggests that patients attending their primary care physician with functional abdominal symptoms should be offered self-help information as part of their management.

Adult↗
PubMed2005

Mucosal bacteria in ulcerative colitis.

Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease of unknown aetiology, although bacterial species belonging to the normal colonic microbiota are known to be involved in its initiation and maintenance. Several organisms have been linked to the disease; however, mucosa-associated bacteria are more likely to be involved than their luminal counterparts, due to their close proximity to the host epithelium. Comparative bacteriological analyses were done on rectal biopsies to investigate differences in mucosal bacteria in patients with UC and healthy controls. Complex bacterial communities were found in both groups, with significant reductions in bifidobacterial numbers in UC, which suggested that they might have a protective role in the disease. Accordingly, a therapy for treating UC was designed, with the aim of modifying the mucosal microbiota to increase bifidobacterial colonisation and reduce inflammation. Ranges of mucosal and faecal bifidobacteria were tested for their substrate preferences and their abilities to survive under a variety of environmental conditions. A synbiotic comprising a probiotic (Bifidobacterium longum) isolated from healthy rectal mucosa combined with a prebiotic (oligofructose-enriched inulin - Synergy 1) was developed. The treatment was used in a randomised controlled trial involving eighteen patients with active UC, for a period of 1 month. Rectal biopsies were collected at the beginning and end of the study. Bacteriological analysis and transcription levels of epithelium-related immune markers were assessed. Results demonstrated that short-term synbiotic treatment resulted in increased bifidobacterial colonisation of the rectal mucosa and induced significant reductions in the expression of molecules that control inflammation in active UC.

Adult↗
PubMed2005

Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state. METHODS: A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured. RESULTS: Sigmoidoscopy scores (scale 0-6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p=0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p=0.016, 0.038, and 0.008, respectively). Tumour necrosis factor alpha and interleukin 1alpha, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p=0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue. CONCLUSIONS: Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.

Adult↗
PubMed2005

The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease.

OBJECTIVE: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. METHODS: Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function. RESULTS: The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups. CONCLUSION: This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease.

Adult↗
PubMed2005

ECT in depression.

Explore the source record for details and available documents.

Major Depressive Disorder↗
PubMed2004

New HLA-B alleles detected by polymerase chain reaction-sequence-specific oligonucleotide typing: HLA-B*0725, B*0728, and B*3808.

Three novel alleles, human leukocyte antigen (HLA)-B*0725, B*0728, and B*3808, were discovered during routine genotyping of samples for the Australian Bone Marrow Donor Registry and Australian Cord Blood Bank. The new alleles contain amino acid changes in the antigen-binding site of the expressed HLA protein, which may alter the antigen-binding properties of the functional protein.

Base Sequence↗
PubMed2004

Detection of a novel HLA-A allele by polymerase chain reaction-sequence-specific oligonucleotide typing: HLA-A*0252.

Anew human leukocyte antigen (HLA) class I allele, HLA-A*0252, has been found during routine typing of samples for the Australian Bone Marrow Donor Registry. A*0252 differs from A*020101 at four codon positions, with all the new polymorphisms resulting in an amino acid change. The amino acids involved are located in the antigen-binding region of the HLA protein.

Base Sequence↗
PubMed2004

Identification of new HLA-C alleles by polymerase chain reaction-sequence specific oligonucleotide typing: Cw*0314 and Cw*1511*.

In this article, we report two new human leukocyte antigen-C (HLA-C) alleles, HLA-Cw*0314 and Cw*1511, which were identified during routine tissue typing of donors for the Australian Bone Marrow Donor Registry and Australian Cord Blood Bank. HLA-Cw*0314 shows six codon changes in exon 3 compared to Cw*030401 and shares some sequence homology with Cw*07 alleles. Cw*1511 has two nucleotide changes compared with Cw*150201 in exon 2, both resulting in amino acid changes in the protein sequence.

Alleles↗
PubMed2004

Identification of two novel HLA class II alleles, DQB1*0311 and DQB1*0620.

Two novel HLA class II alleles have been identified in routine typing of a kidney transplant patient and a cord blood unit from the Australian Cord Blood Bank in Sydney. Sequence analysis of exon 2 of the DQB1 genes revealed the novel polymorphism. A substitution of A to C at nucleotide position 136 has been identified for the DQB1*0311 allele when compared to the closest-matched allele, DQB1*030201. An identical substitution has also been identified for the DQB1*0620 allele when compared to the closest-matched allele, DQB1*0602. The substitution results in an amino acid change from methionine to leucine at position 46 implicating different specificity and affinity of antigen binding.

Alleles↗
PubMed2004

Iron status and haematological changes in adolescent female inpatients with anorexia nervosa.

OBJECTIVES: (i) To investigate the incidence of iron deficiency (both latent iron deficiency and iron deficiency anaemia) in post menarchal female adolescent patients hospitalized with anorexia nervosa. (ii) To observe changes in iron status during refeeding. METHODS: During the study period all post menarchal female patients admitted to the adolescent unit with anorexia nervosa were invited to participate. Ferritin, serum iron, transferrin and transferrin saturation were measured on admission and discharge. Haemoglobin, haematocrit, weight, and body mass index were monitored weekly. RESULTS: All 12 eligible patients participated in the study. Four patients had elevated ferritin levels on admission. Ten of the 12 showed a statistically significant fall in serum ferritin at time of discharge compared with admission (P = 0.004). One of 12 patients had a low serum iron at presentation. All 12 had normal serum iron levels at discharge. Nine of the 12 subjects had a higher serum iron at discharge which was statistically significant (P = 0.046). There was no significant change in haemoglobin levels when comparing admission and discharge levels. Nine of the 12 patients however, transiently developed anaemia, at some stage during treatment. CONCLUSIONS: Iron deficiency is uncommon at both presentation and after nutritional rehabilitation in post menarchal adolescent females with anorexia nervosa. This is most likely due to increased iron storage secondary to the contraction of the circulating blood volume and reduced iron losses from (secondary) amenorrhoea. The fall in ferritin observed during treatment is due to haemopoiesis necessary to fill the increased blood volume associated with weight gain. This also results in normalization of the haemoglobin and haematocrit.

Adolescent↗
PubMed2004

Patients' experiences of an open access follow up arrangement in managing inflammatory bowel disease.

BACKGROUND: Improving access is a key policy issue in improving quality of care and extending patient choice and participation. People's experience of changing from fixed outpatient appointments to more flexible direct access arrangements for chronic disease has been underexplored. OBJECTIVES: To examine patients' views on using an open system of access compared with fixed outpatient appointments as part of a guided self-management intervention for inflammatory bowel disease (IBD). DESIGN: Embedded qualitative study undertaken alongside a randomised controlled trial. Semi-structured interviews were undertaken to obtain an in depth understanding of patients' experience of the change in access arrangements. PARTICIPANTS: A purposive sample (n = 30) was drawn from the intervention group (n = 700) according to a range of responses to the trial baseline and follow up quantitative measures. RESULTS: 28 interviews were included in the analysis. Compared with the previous system of fixed appointments, preference for the new open access system was based on enhanced personal control in contacting services and the view that it fitted better with everyday routine management and the requirement for urgent medical contact when symptoms fail to respond to medication. Preference for retaining fixed appointments was based on a sense of security from gaining access which did not require the individual to initiate the request for medical help. CONCLUSIONS: Open access may fit better with patients' self-management of their condition and everyday routines, roles and responsibilities. Ensuring that outpatient organisational arrangements and personnel are responsive to patient initiated requests for appointments is likely to impact on the acceptability of this type of access arrangement. Some people may continue to prefer the fixed appointment system which should be retained if patient choice is to be respected.

Adaptation, Psychological↗
PubMed2003

Parental perceptions surrounding risks and benefits of immunization.

In recent years, parental concerns about vaccine safety have increased as the threat of disease has decreased. A national survey showed that, in general, parents agree that vaccines benefit their children and that their children may be at risk for contracting a disease if unvaccinated. When asked about understanding the benefits and risks of vaccines, most parents (57%) found numbers and statistics most helpful. A substantial minority (17%) of parents were somewhat or not confident in vaccine safety. Parents less confident in vaccine safety agreed less with the statement that they usually followed the advice of their child's doctor. Incomes and education levels affected responses. This positive relationship between confidence in vaccine safety and reliance on doctors for advice may indicate the need for healthcare providers to identify opportunities to (1) solicit questions about vaccine safety, (2) address vaccine safety-related questions in a way meaningful to parents, and (3) strengthen doctor-patient relationships. A parent communication tool is proposed.

Attitude to Health↗
PubMed2003

Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure.

OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a beta3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 microg/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54% increase in daily food intake and a 12% increase in body weight. An 8% decrease in VO(2) measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.

Adipose Tissue, Brown↗
PubMed2003

A randomised controlled trial to assess the impact of a package comprising a patient-orientated, evidence-based self-help guidebook and patient-centred consultations on disease management and satisfaction in inflammatory bowel disease.

OBJECTIVES: To determine if a whole systems approach to self-management improves clinical outcomes and leads to cost-effective use of NHS services. DESIGN: Nineteen hospitals were randomised to 10 control sites and nine intervention sites. Consultants from intervention sites received training in patient-centred care before recruitment and introduced the intervention to eligible patients. Patients at the control sites were recruited and went on to have an ordinary consultation. Qualitative interviews were undertaken to obtain an in-depth understanding of patients' and consultants' experience of the intervention. SETTING: Follow-up outpatient clinics at 19 hospitals in the north-west of England. PARTICIPANTS: Seven hundred patients (297 at intervention sites and 403 at control sites) with established ulcerative colitis or Crohn's disease, aged 16 years and over, and able to write in English. INTERVENTIONS: Consultants were trained to provide a patient-centred approach to care. Guidebooks on ulcerative colitis and Crohn's disease were developed with patients prior to the study. Patients prepared a written self-management plan and self-referred to services based on a self-evaluation of their need for advice. MAIN OUTCOME MEASURES: Rates of hospital outpatient consultation, quality of life (QoL) and acceptability to patients. Health service resource use and assessed cost effectiveness using the EQ-5D. RESULTS: After 1 year, the intervention resulted in fewer hospital visits, without change in the number of primary care visits. Patients felt more able to cope with their condition. The intervention produced no reduction in QoL and did not raise anxiety. The intervention group reported fewer symptom relapses; 74% of patients in the intervention group indicated a preference to continue the system. Qualitative results showed the guidebook was effective but organisational limitations constrained patient-centred aspects of the intervention for some. Cost-effectiveness analyses favoured self-management over standard care. CONCLUSIONS: Further use of this method in chronic disease management seems likely to improve overall patient satisfaction and reduce health expenditure without evidence of adverse effect on disease control. Further attention needs to be given to self-referral and access arrangements and a re-distribution of control to patients through increased adherence to patient-centred norms on the part of consultants. Future research is recommended to evaluate the operating systems within secondary and primary care that would allow self-managers to self-refer and to keep them informed of new treatments, also to explore models for training health professionals in self-care methods, to study long-term effects of self-management in chronic disease and to transfer this approach to other chronic conditions.

Adolescent↗