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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 91 records · Page 5Linked to original sources
PubMed2002

Primary care based clinics for asthma.

BACKGROUND: Primary care clinics for asthma have been encouraged and are becoming widespread in some countries, particularly in the UK. OBJECTIVES: To determine the effectiveness of organised asthma care via primary care based asthma clinics. SEARCH STRATEGY: A search of the Cochrane Airways Group register and Cochrane Controlled Trials Register using the following search strategy: clinic* OR general pract* OR family pract* or primary care. Separate and additional searches were also conducted using MEDLINE, CINAHL and EMBASE databases. SELECTION CRITERIA: Trials had to be performed in primary care and be restricted to patients with asthma. Care could be delivered by doctor or nurse. Two reviewers independently ascertained the relevance of trials from titles and abstracts obtained from the searches. Relevant full text articles were retrieved with two reviewers assessing each study for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently conducted all data abstraction and analysis and all disagreements were resolved by discussion. For the dichotomous variables, odds ratio (OR) or relative risks (RR) with 95% Confidence Interval (95%CI) were calculated for individual outcomes. MAIN RESULTS: Only one trial met the criteria for inclusion in the review. This trial provided 11 outcome measures of which two showed a significant effect of the intervention. More patients in the intervention group had peak flow meters (RR 1.30; 95%CI 1.05,1.61) and fewer patients in the intervention group were likely to wake up at nights due to their asthma (RR 0.30; 95%CI 0.16, 0.81). REVIEWER'S CONCLUSIONS: There is limited evidence of benefit for primary care based asthma clinics, but firm conclusions cannot be formed until more good quality trials have been carried out.

Asthma↗
PubMed2002

Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss. OBJECTIVES: To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies. SELECTION CRITERIA: Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors. MAIN RESULTS: Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used. REVIEWER'S CONCLUSIONS: In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.

Administration, Inhalation↗
PubMed2002

Non-myeloablative stem cell transplantation for congenital immunodeficiencies.

Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital immunodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality. We have therefore used a low-intensity conditioning regime for transplantation in this group of immunodeficiency patients. Twenty-one patients with a variety of different immunodeficiencies were treated using the following conditioning regimes: (1) fludarabine/melphalan/ATG or Campath 1H (n=16), (2) fludarabine/cyclophosphamide/Campath 1H (n=1), (3) TBI/CyA/MMF (n=1), (4) fludarabine/melphalan/busulphan/ATG (n=3). In 13 cases matched (n=9) and 1 Ag mismatched (n=4) unrelated donors were used and in eight cases transplants from matched siblings (n=4), 1 Ag mismatched sibling (n=1), matched parent (n=1) and haploidentical parents (n=3) were performed. At a median follow-up of 13 months, 19 of 21 (90%) patients were still alive following the transplant procedure. Despite a T cell replete graft and the use of unrelated donor grafts in the majority of patients studied there was no evidence of significant organ disease. Immune reconstitution in terms of CD3+ and CD4+ T cell recovery and function was equivalent in comparison with a historical cohort. We believe that this low-intensity approach has significant implications for transplantation of individuals with immunodeficiency states with established organ disease.

Adolescent↗
PubMed2002

Ectopic expression of the GABA(A) receptor alpha6 subunit in hippocampal pyramidal neurons produces extrasynaptic receptors and an increased tonic inhibition.

We generated transgenic (Thy1alpha6) mice in which the GABA(A) receptor alpha6 subunit, whose expression is usually confined to granule cells of cerebellum and cochlear nuclei, is ectopically expressed under the control of the pan-neuronal Thy-1.2 promoter. Strong Thy1alpha6 subunit expression occurs, for example, in deep cerebellar nuclei, layer V iscocortical and hippocampal pyramidal cells and dentate granule cells. Ligand binding and protein biochemistry show that most forebrain alpha6 subunits assemble as alpha6betagamma2-type receptors, and some as alpha1alpha6betagamma2 and alpha3alpha6betagamma2 receptors. Electron microscopic immunogold labeling shows that most Thy1-derived alpha6 immunoreactivity is in the extrasynaptic plasma membrane of dendrites and spines in both layer V isocortical and CA1pyramidal cells. Synaptic immunolabeling is rare. Consistent with the alpha6 subunits' extrasynaptic localization, Thy1alpha6 CA1 pyramidal neurons have a five-fold increased tonic GABA(A) receptor-mediated current compared with wild-type cells; however, the spontaneous IPSC frequency and the mIPSC amplitude in Thy1alpha6 mice decrease 37 and 30%, respectively compared with wild-type. Our results strengthen the idea that GABA(A) receptors containing alpha6 subunits can function as extrasynaptic receptors responsible for tonic inhibition and further suggest that a homeostatic mechanism might operate, whereby increased tonic inhibition causes a compensatory decrease in synaptic GABA(A) receptor responses.

Action Potentials↗
PubMed2002

Successful treatment of post-transplant lymphoproliferative disorder in autologous blood stem cell transplant recipients.

We report three cases of post-transplant lymphoproliferative disorder (PTLD) in the context of autologous stem cell transplantation (ASCT) for multiple myeloma (MM) and non-Hodgkin's lymphoma. The first two cases received ASCT for MM, one with a CD34-selected autograft and the other with an unmanipulated autograft. Both these cases of PTLD achieved a complete response following treatment with IVIG, gancyclovir, solumedrol and interferon (IFN). The third case received ASCT with an unmanipulated autograft for relapsed angioimmunoblastic lymphoma. He also achieved a complete response but only after rituximab was added to IVIG, gancyclovir, solumedrol and IFN. None of these patients experienced a relapse of their PTLD with follow-up ranging from 1.5 to 5 years. These cases highlight the importance of considering PTLD in the differential diagnosis of lymphadenopathy and fever post ASCT. They also demonstrate the possibility of durable complete remission of post-ASCT PTLD following antiviral and immune modulating therapy.

Adult↗
PubMed2002

A randomised, double-blind, double-dummy comparison of the efficacy and tolerability of lercanidipine tablets and losartan tablets in patients with mild to moderate essential hypertension.

A double-blind, double-dummy, randomised, multicentre study to compare the efficacy and tolerability of lercanidipine with losartan. Patients with mild to moderate hypertension (supine diastolic blood pressure (DBP) 95-115 mm Hg) were enrolled and underwent a placebo run-in period of 14-30 days before random allocation to lercanidipine tablets 10 mg once-daily (n = 234) or losartan tablets 50 mg once-daily (n = 231) during the assessment period (approximately 16 weeks). Titration to lercanidipine 20 mg once-daily (two 10 mg tablets) or losartan 100 mg once-daily (two 50 mg tablets) was allowed after 8 weeks, if necessary. At the end of the study, 71% of patients who received lercanidipine tablets had achieved normalised DBP (ie, < or =90 mm Hg) and 81% had responded to treatment (ie, DBP < or =90 mm Hg or a decrease in DBP > or =10 mm Hg). The corresponding numbers in the losartan tablets group were 65% and 78%, respectively. In those patients who required dose titration, there was evidence of a greater response with lercanidipine tablets than with losartan tablets. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. In conclusion, the antihypertensive effects of lercanidipine tablets were comparable with those of losartan tablets; both treatments gave a high response rate for an antihypertensive monotherapy and were very well tolerated.

Adolescent↗
PubMed2002

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Adult↗
PubMed2002

Clinicopathological significance of the 'keloid-like' collagen and myxoid stroma in advanced rectal cancer.

AIM: To establish the histological categorization of fibrotic stroma which reflects the biological behaviour of advanced rectal cancer. METHODS AND RESULTS: Six hundred and twenty-seven surgically resected cases of advanced rectal carcinoma were examined. We histologically categorized fibrotic stroma in the invasive frontal region into three groups: type A, multiple fine and mature fibres were stratified into layers; type B, broad bands of eosinophilic hyalinized collagen ('keloid-like' collagen) were intermingled; type C, myxoid stroma. Type A stroma was observed in 63% of patients, type B stroma in 25%, type C stroma in 12%. The incidence of type A stroma decreased in accordance with Dukes stage (98% in Dukes A; 73% in B; 41% in C1; 29% in C2) and conversely, there was an increase of C type (0% in Dukes A; 4% in B; 20% in C1; 54% in C2). Stroma type had a significant correlation with long-term survival (80% of 5-year survival in type A stroma; 54% in type B; 26% in type C). Based on multivariate analysis, it was found that the stromal pattern had independent prognostic value, together with nodal involvement, growth pattern, and lymphocyte infiltration. CONCLUSIONS: Tumour fibrotic stroma may play an important role as a regulator of neoplastic behaviour. Pathological categorization of the fibrotic stroma is helpful for predicting the prognostic outcome of patients with rectal carcinoma.

Adult↗
PubMed2002

Assertive community treatment: development of the team, selection of clients, and impact on length of hospital stay.

Mental health services have been criticized for the lack of focus and response to people suffering from a serious mental illness (SMI). Assertive community treatment (ACT) offers the potential for greater partnership working between the user and provider of mental health services. The author describes one approach in developing ACT in the UK. Four criteria were developed to identify the most appropriate service users for ACT: those with SMI, illness instability, illness disability and risk to self or others. Fifty-five clients were identified using these criteria and tracked for their length of hospital stay and frequency of admission 2 years before acceptance to an ACT team and for 12 months after. Duration of hospital stay was unchanged although both the frequency and total numbers of bed days were reduced.

Adult↗
PubMed2002

Small-group work and assessment in a PBL curriculum: a qualitative and quantitative evaluation of student perceptions of the process of working in small groups and its assessment.

The problem based learning (PBL) curriculum at Manchester emphasizes small-group work. This is supported through group assessment where students assess key aspects of their group's function. In the study described here the authors evaluated students' perceptions of both PBL group work and what a group assessment needs to assess. They aimed to produce a description of the cognitive and motivational influences on group process and unpack the ways they contribute to a successful PBL group so that the kinds of skills an effective assessment should assess could be identified. Focus groups and a questionnaire were used to generate the data. The focus group results indicate that students support PBL group work as a method of learning, and that those groups that work cooperatively are perceived as facilitating the most motivating learning environment. The students supported the assessment being summative and felt that it could be simplified to measure: behavioural skills contributing to maximizing motivation of the group process; and cognitive skills relating to the content of the group discussion. The questionnaire results also supported the use of a summative assessment of small-group work that evaluates the domains of group process and the content of the group discussion.

Adult↗
PubMed2002

Analysis of toxin profiles in three different fish species causing ciguatera fish poisoning in Guadeloupe, French West Indies.

A grey snapper (Lutjanus griseus), a grouper (Serranidae) and a black jack (Caranx lugubris) were implicated in three different ciguatera poisonings in Guadeloupe, French West Indies. A mouse bioassay indicated toxicity for each specimens: 0.5-1, > or = 1 and > 1 MUg g(-1), respectively. After purification by gel filtration chromatography, the samples were analysed by high-performance liquid chromatography coupled to mass spectrometry (LC-MS). The toxin profiles differ from one fish to another. C-CTX-1 was detected at 0.24, 0.90 and 13.8 ng g(-1) flesh in the snapper, grouper and jack, respectively. It contributed only to part of the whole toxicity determined by the mouse bioassay. Other toxins identified were C-CTX-2 (a C-CTX-1 epimer), three additional isomers of C-CTX-1 or-2, and five ciguatoxin congeners (C-CTX-1127, C-CTX-1143 and its isomer C-CTX-1143a, and C-CTX-1157 and its isomer C-CTX-1157b). Putative hydroxy-polyether-like compounds were also detected in the flesh of the grouper with [M+ + H]+ ions at m/z 851.51, 857.50, 875.51, 875.49 and 895.54 Da. Some of these compounds have the same mass range as some known dinoflagellate toxins. In conclusion, this study confirms the usefulness of LC-MS analysis to determine the ciguatoxins levels and the toxin profile in fish flesh hazardous to humans.

Adult↗
PubMed2002

Colistin stimulates the activity of neutrophil elastase and Pseudomonas aeruginosa elastase.

Nonantimicrobial effects of antibiotics may contribute to their activity in the treatment of infective airway disease. The aim of this study was to identify antibiotics used for the treatment of infection in cystic fibrosis that may alter the activity of human neutrophil elastase (HNE) and Pseudomonas aeruginosa elastase (PE). The effect of antibiotics on the activity of purified HNE and PE, and HNE in sputum was assessed using colourimetric and fluorescent substrate assays by kinetic measurements, and by examining the interaction of HNE with inhibitors. Ceftazidime, tobramycin, and gentamycin slightly inhibited purified HNE activity whereas erythromycin and colistin significantly stimulated purified HNE and PE (395 and 557%, respectively). However, only colistin increased HNE activity in sputum (+102%) and was therefore studied in more detail. This increase in activity was not due an interference with the specific inhibition of HNE by alpha1-antitrypsin but colistin was found to reverse the inhibitory effects of small molecular weight molecules like heparin. Colistin increases the activity of human neutrophil elastase and Pseudomonas aeruginosa elastase, two proteases that contribute to the pathogenesis of cystic fibrosis airway disease.

Adolescent↗
PubMed2002

Neutrophil survival is prolonged in the airways of healthy infants and infants with RSV bronchiolitis.

Large numbers of neutrophils in the airway of infants infected by respiratory syncytial virus (RSV) are recruited by chemokines, such as interleukin-8, and specific inflammatory molecules can delay apoptosis increasing their longevity. The aim of this study was to investigate whether airway secretions in RSV bronchiolitis contain factors that influence neutrophil apoptosis. Nasal lavage fluid (NLF) was obtained from 24 infants with RSV bronchiolitis (31 infant controls and 12 adults). Neutrophils isolated from healthy adult volunteers were incubated with the NLF in Dulbecco modified Eagle medium (DMEM) for 24 h, and apoptosis and necrosis were quantified using Hoechst 33342 and propidium iodide viability dyes. The presence of putative factors that delay neutrophil apoptosis was investigated using inhibitors to leukotriene-B4, lipopolysaccharide and the IL-8 receptor CXCR2, and blocking antibodies to granulocyte-monocyte colony-stimulating factor. Characterisation of NLF involved tests of thermal instability, proteolysis, deoxyribonuclease digestion and molecular filtration. NLF from infants with RSV bronchiolitis and controls significantly delayed neutrophil apoptosis, whereas NLF from healthy adults did not. None of these inhibitor molecules blocked this delay in apoptosis but activity was heat liable and >3 kDa. The study showed that nasal lavage fluid from infants significantly delays neutrophil apoptosis. The speculation is that the prolonged survival of neutrophils in the infant airway contributes to the characteristic accumulation of neutrophils in the airways of infants with respiratory infections.

Adult↗
PubMed2002

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Adult↗
PubMed2001

Effective communication in health care: exploring the skills of the teachers.

Following the growing commitment to teach communication skills in health care, a project was designed to identify a group of Health Professionals with a responsibility for teaching communication skills in Health Care. This group would have their communication skills assessed, using positive feedback, and attend workshops to improve both their communication and teaching skills. Four key tutors were recruited to the study and were each asked to identify a further three tutors, in their own geographical area, to form a "cell". This sample of 16 tutors remained constant throughout the study. Skills were monitored by the assessment of audio-taped interviews, one made prior to the first workshop and two others at agreed intervals. Written feedback was given on the first interview, plus the option of verbal feedback on a skills study day. Written feedback was given on subsequent interviews. Changes in skills were monitored and baseline skills compared to previous skills training. The results show, with two exceptions, that there appears to be a link between baseline skills and previous training in communication skills. For three "cells", there are gains in overall scores from first to third interview, but for the fourth "cell", which had high baseline scores, there was only minimal change. The work suggests, that for those who teach Communication in Health Care, training is a pre-requisite. Further work is required in this area.

Clinical Competence↗