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Biomedical subjects

Malcolm Campbell

Publications and source records attributed to Malcolm Campbell.

16 recordsLinked to original sources
PubMed2006

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity.

OBJECTIVE: This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. METHODS: Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. RESULTS: Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 microg/ml) nor native LDL (100 microg/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 microM), and MnTBAP (a free radical scavenger, 50 microM). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2- levels were determined in IMA versus CA VSMC. CONCLUSIONS: Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2006

Palliative care in primary care: a study to determine whether patients and professionals agree on symptoms.

BACKGROUND: Difficulties in managing symptoms of palliative care patients at home have been identified, yet there has been no investigation of agreement on symptom assessment in primary care. Lack of agreement between patients' and primary care professionals' symptom assessments may be contributing to difficulties in symptom control. AIM: To investigate agreement on symptom assessments between patients at home and GPs and district nurses. DESIGN OF STUDY: Prospective, self-completed, structured symptom assessments. SETTING: Routine contacts with adult palliative care patients estimated to be in their last year of life. METHOD: Patient and professional symptom assessments were obtained using CAMPAS-R, a comprehensive and reliable measure validated for palliative care in the community. Prevalence of reported symptoms was calculated in patient-professional pairs. Intraclass correlation techniques (ICCs) and percentage agreement were used to determine how well symptom assessments of patients and professionals agreed. RESULTS: Anxiety and depression were significantly more likely to be reported by professionals, and GPs over-identified nausea, vomiting and constipation. Professionals assessed emotional symptoms as more severe than patients. Agreement on scoring of physical symptoms was better, although this was at least partially due to agreement on absence of symptoms. Unlike previous reports, pain scores recorded by doctors in this study, were not significantly different from patients. CONCLUSION: This quick and easy to complete assessment tool, CAMPAS-R, has potential for monitoring quality of palliative care symptom control at home.

Adult↗
PubMed2005

Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease.

Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.

Adrenal Cortex Hormones↗
PubMed2005

Nursing attitudes towards acute mental health care: development of a measurement tool.

AIM: This paper reports the development, piloting and validation of a tool to measure attitudes for use with nursing staff working in acute mental health care units. BACKGROUND: The quality of care provided for service users in acute mental health care has come under both scrutiny and severe criticism. The attitudes of staff working in these environments have been cited as a contributory factor in poor care. No measure of attitudes specific to acute mental health has been reported. METHODS: A 64-question measure was constructed and distributed to a sample of qualified and unqualified nurses drawn from seven mental health care units in the North of England. Exploratory factor analysis and a number of other statistical tests were performed to validate the questionnaire. RESULTS: Preliminary analysis reduced the original 64 questions to 37. Five components were retained, accounting for 42% of the variance, and the five rotated factors were identified. The resultant 'Attitudes Towards Acute Mental Health Scale' (ATAMHS) achieved good internal reliability, with a Cronbach's alpha of 0.72. CONCLUSION: The construction and validation of the ATAMHS measure will enable improved understanding of the attitudes of nursing staff working in acute mental health care settings to occur. This measure is available for use in a clinical area of nursing in which attitude change is of fundamental importance for future development of care.

Acute Disease↗
PubMed2004

The COPD criteria.

Explore the source record for details and available documents.

Journal Article↗
PubMed2004

Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CbetaII.

Hyperglycemia increases expression of platelet-derived growth factor (PDGF)-beta receptor and potentiates chemotaxis to PDGF-BB in human aortic vascular smooth muscle cells (VSMCs) via PI3K and ERK/MAPK signaling pathways. The purpose of this study was to determine whether increased activation of protein kinase C (PKC) isoforms had a modulatory effect on the PI3K and ERK/MAPK pathways, control of cell adhesiveness, and movement. All known PKC isoforms were assessed but only PKCalpha and PKCbetaII levels were increased in 25 mmol/L glucose. However, only PKCbetaII inhibition affected (decreased) PI3K pathway and MAPK pathway activities and inhibited PDGF-beta receptor upregulation in raised glucose, and specific MAPK inhibition was required to completely block the effect of glucose. In raised glucose conditions, activity of the ERK/MAPK pathway, PI3K pathway, and PKCbetaII were all sensitive to aldose reductase inhibition. Chemotaxis to PDGF-BB (360 pmol/L), absent in 5 mmol/L glucose, was present in raised glucose and could be blocked by PKCbetaII inhibition. Formation of lamellipodia was dependent on PI3K activation and filopodia on MAPK activation; both lamellipodia and filopodia were eliminated when PKCbetaII was inhibited. FAK phosphorylation and cell adhesion were reduced by PI3K inhibition, and although MAPK inhibition prevented chemotaxis, it did not affect FAK phosphorylation or cell adhesiveness. In conclusion, chemotaxis to PDGF-BB in 25 mmol/L glucose is PKCbetaII-dependent and requires activation of both the PI3K and MAPK pathways. Changes in cell adhesion and migration speed are mediated mainly through the PI3K pathway.

Aorta↗
PubMed2004

Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways.

Atheroma formation involves the movement of vascular smooth muscle cells (VSMC) into the subendothelial space. The aim of this study was to determine the involvement of PI3K and MAPK pathways and the importance of cross-talk between these pathways, in glucose-potentiated VSMC chemotaxis to serum factors. VSMC chemotaxis occurred in a serum gradient in 25 mmol/L glucose (but not in 5 mmol/L glucose) in association with increased phosphorylation (activation) of Akt and ERK1/2 in PI3K and MAPK pathways, respectively. Inhibitors of these pathways blocked chemotaxis, as did an mTOR inhibitor. VSMC expressed all class IA PI3K isoforms, but microinjection experiments demonstrated that only the p110beta isoform was involved in chemotaxis. ERK1/2 phosphorylation was reduced not only by MAPK pathway inhibitors but also by PI3K and mTOR inhibitors; when PI3K was inhibited, ERK phosphorylation could be induced by microinjected activated Akt, indicating important cross-talk between the PI3K and ERK1/2 pathways. Glucose-potentiated phosphorylation of molecules in the p38 and JNK MAPK pathways inhibited these pathways but did not affect chemotaxis. The statin, mevinolin, blocked chemotaxis through its effects on the MAPK pathway. Mevinolin-inhibited chemotaxis was restored by farnesylpyrophosphate but not by geranylgeranylpyrophosphate; in the absence of mevinolin, inhibition of farnesyltransferase reduced ERK phosphorylation and blocked chemotaxis, indicating a role for the Ras family of GTPases (MAPK pathway) under these conditions. In conclusion, glucose sensitizes VSMC to serum, inducing chemotaxis via pathways involving p110beta-PI3K, Akt, mTOR, and ERK1/2 MAPK. Cross-talk between the PI3K and MAPK pathways is necessary for VSMC chemotaxis under these conditions.

Alkyl and Aryl Transferases↗
PubMed2004

Eformoterol Turbohaler compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids.

The aim of the study was to compare the efficacy of the inhaled long-acting beta2-agonists eformoterol and salmeterol when added to existing inhaled corticosteroid (ICS) therapy in symptomatic asthmatic children. This randomized, 12-week, parallel-group study, performed in a primary care setting, included 156 children and adolescents (aged 6-17 years) with moderate persistent asthma. Patients were randomized to open-label eformoterol (Oxis) Turbohaler 9 microg (delivered dose) or salmeterol Accuhaler 50 microg, both b.i.d, added to current ICS. Assessments included: changes in daytime reliever beta2-agonist therapy (primary variable), total 24-h reliever use, lung function, clinic and diary symptom scores, patient and carer health-related quality of life (HRQL) and adverse events. Daytime reliever use decreased significantly (p < 0.001) from baseline by 65% and 52%, respectively in the eformoterol and salmeterol treatment groups. Compared with salmeterol, eformoterol produced a greater decrease in daytime (-0.46 inhalations/day; p = 0.081) and 24-h (-0.70 inhalations/day; p = 0.043) reliever use. The percentage of patients who did not require any reliever medication during the study was significantly higher in the eformoterol group (p < 0.05 vs. salmeterol at weeks 8 and 12). Clinic and diary card peak expiratory flow and symptom measures all improved from baseline in both treatment arms. There was a significantly greater effect in favour of eformoterol for the reduction in clinic-assessed overall night-time symptoms (p < 0.05 vs. salmeterol). Clinically relevant improvements in patient-assessed HRQL occurred during treatment with eformoterol and salmeterol, but carer-assessed HRQL was improved to a clinically relevant extent, only with eformoterol. Both treatments were well tolerated. In children and adolescents with moderate persistent asthma, add-on therapy with eformoterol was well tolerated and at least as effective as salmeterol.

Administration, Inhalation↗
PubMed2003

Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis.

The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevated D-glucose induced an increase in the PDGFbeta receptor that was inhibited by phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway inhibitors. Exposure to 25 mmol/l D-glucose (HG) induced increased phosphorylation of protein kinase B (PKB) and extracellular-regulated kinase (ERK). All HG chemotaxis assays (with either 10 days' preincubation in HG or no preincubation) in a FCS or PDGF-BB gradient showed positive chemotaxis, whereas those in 5 mmol/l D-glucose did not. Assays were also run with concentrations ranging from 5 to 25 mmol/l D-glucose. Chemotaxis was induced at concentrations > or =9 mmol/l D-glucose. An anti-PDGFbeta receptor antibody inhibited glucose-potentiated VSMC chemotaxis, as did the inhibitors for the PI3K and MAPK pathways. This study has shown that small increases in D-glucose concentration, for a short period, increase VSMC expression of the PDGFbeta receptor and VSMC sensitivity to chemotactic factors in serum, leading to altered migratory behavior in vitro. It is probable that similar processes occur in vivo with glucose-enhanced chemotaxis of VSMCs, operating through PDGFbeta receptor-operated pathways, contributing to the accelerated formation of atheroma in diabetes.

Androstadienes↗