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1.
Acute Med ; 17(1): 10-17, 2018.
Article in English | MEDLINE | ID: mdl-29589600

ABSTRACT

Physical inactivity causes morbidity, mortality and healthcare expenditure. A minority of people undertake sufficient physical activity to meet the DoH recommendations. NICE has determined that brief advice in primary care is costeffective in increasing physical activity levels but there is no current recommendation for secondary care. Acute medical admissions represent "teachable moments" where patients might be receptive to advice. Qualitative methodology was used to determine the perspectives of acute medical in-patients on their willingness to receive physical activity advice and on its format and delivery. Most participants thought physical activity should be discussed by health care professionals if it related to the reason they were admitted to hospital but wanted individually-tailored advice on overcoming their specific barriers to physical activity.


Subject(s)
Exercise , Health Personnel , Patient Admission , Adult , Emergencies , Female , Health Knowledge, Attitudes, Practice , Health Promotion/methods , Humans , Male , Qualitative Research
2.
Acute Med ; 16(3): 104-106, 2017.
Article in English | MEDLINE | ID: mdl-29072867

ABSTRACT

The Society for Acute Medicine's Benchmarking Audit (SAMBA) was undertaken for the 5th time in June 2016. For the first time, data on telephone triage calls prior to admission to Acute Medical Units were collected: 1238 patients were referred from Emergency Departments, 925 from General Practitioners (GPs), 52 from clinics and 147 from other sources. Calls from Emergency Departments rarely resulted in admission avoidance. Calls from Primary Care resulted in avoidance of an admission in 115 (12%) patients; the percentage of avoided admissions was highest if the call was taken by a Consultant. Consultant triage might result in admission avoidance but the impact of local context on the effectiveness is not clear.

3.
BMC Health Serv Res ; 17(1): 624, 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28870188

ABSTRACT

BACKGROUND: Hospital discharge summaries are a key communication tool ensuring continuity of care between primary and secondary care. Incomplete or untimely communication of information increases risk of hospital readmission and associated complications. The aim of this study was to evaluate whether the introduction of a new electronic discharge system (NewEDS) was associated with improvements in the completeness and timeliness of discharge information, in Nottingham University Hospitals NHS Trust, England. METHODS: A before and after longitudinal study design was used. Data were collected using the gold standard auditing tool from the Royal College of Physicians (RCP). This tool contains a checklist of 57 items grouped into seven categories, 28 of which are classified as mandatory by RCP. Percentage completeness (out of the 28 mandatory items) was considered to be the primary outcome measure. Data from 773 patients discharged directly from the acute medical unit over eight-week long time periods (four before and four after the change to the NewEDS) from August 2010 to May 2012 were extracted and evaluated. Results were summarised by effect size on completeness before and after changeover to NewEDS respectively. The primary outcome variable was represented with percentage of completeness score and a non-parametric technique was used to compare pre-NewEDS and post-NewEDS scores. RESULTS: The changeover to the NewEDS resulted in an increased completeness of discharge summaries from 60.7% to 75.0% (p < 0.001) and the proportion of summaries created under 24 h from discharge increased significantly from 78.0% to 93.0% (p < 0.001). Furthermore, five of the seven grouped checklist categories also showed significant improvements in levels of completeness (p < 0.001), although there were reduced levels of completeness for three items (p < 0.001). CONCLUSION: The introduction of a NewEDS was associated with a significant improvement in the completeness and timeliness of hospital discharge communication.


Subject(s)
Communication , Efficiency, Organizational/standards , Electronic Data Processing , Hospital Information Systems , Patient Discharge , Electronic Data Processing/standards , Electronic Data Processing/trends , Electronic Health Records , England , Hospital Information Systems/standards , Hospital Information Systems/trends , Humans , Longitudinal Studies , Patient Discharge/standards , Patient Discharge/trends , Quality Improvement , Retrospective Studies
5.
Lancet ; 386(9989): 137-44, 2015 Jul 11.
Article in English | MEDLINE | ID: mdl-25956718

ABSTRACT

BACKGROUND: Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. METHODS: In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. FINDINGS: Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7-21; p=0·005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference -2·0 [95% CI -12·0 to 7·0]; p=0·50). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference -12% [95% CI -35 to 11]; p=0·23), with fewer RBC units transfused (mean 1·2 [SD 2·1] vs 1·9 [2·8]; difference -0·7 [-1·6 to 0·3]; p=0·12), although these differences were not significant. We noted no significant difference in clinical outcomes. INTERPRETATION: A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding. FUNDING: NHS Blood and Transplant Research and Development.


Subject(s)
Erythrocyte Transfusion/methods , Gastrointestinal Hemorrhage/therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Gastrointestinal Hemorrhage/blood , Guideline Adherence , Hemoglobins/metabolism , Humans , Male , Middle Aged , Patient Selection , Research Design , Selection Bias
6.
Clin Med (Lond) ; 15(1): 15-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25650192

ABSTRACT

The performance of acute medical units (AMUs) against published quality indicators is variable. We aimed to identify the impact of case-mix and unit resources on timely assessment and discharge of patients admitted to 43 AMUs on a single day in June 2013, as part of the Society for Acute Medicine's benchmarking audit 2013. Performance against quality indicators was at its worst in the early evening hours. Units admitting fewer than 40 patients performed better. Patients who were more frail, as measured by the Clinical Frailty Scale, were also more likely to have significant physiological abnormalities and a higher risk of death, as measured by the National Early Warning Score. Our analysis suggests that resource allocation at the front door is related to quality indicators. Teams will need strengthening in the evening hours and if looking after higher numbers of frail patients.


Subject(s)
Benchmarking , Emergency Service, Hospital/statistics & numerical data , Emergency Service, Hospital/standards , Health Status Indicators , Hospitalization/statistics & numerical data , Quality Indicators, Health Care/statistics & numerical data , Aged , Aged, 80 and over , Female , Frail Elderly , Humans , Male , Medical Audit , Middle Aged , Triage
7.
Acute Med ; 14(3): 99-103, 2015.
Article in English | MEDLINE | ID: mdl-26767198

ABSTRACT

BACKGROUND: The Society for Acute Medicine's Benchmarking Audit (SAMBA) serves as a tool for Acute Medical Units to compare and improve their quality of care. AIM: To audit the performance of Acute Medical Units against clinical quality indicators, standards by the Royal College of Physicians and Specialist Societies relevant to the practice of Acute Medicine. METHODS: An online survey of unit profiles and staffing levels on the audit day was followed by a 24-hour data collection on Thursday the 19th of June 2014 for all patients seen by the local Acute Medicine teams as part of the general medical take. Patients were followed-up for 72 hours. We reviewed the impact of staffing levels on performance indicators. RESULTS: 66 Acute Medical Units admitted 2333 patients during the 24-hour period. Compliance with the quality standards of SAM was as follows: 84% of patients had an early warning score recorded within 30 minutes of admission, 81% of patients had been seen by a competent decision maker within four hours and 73% of patients were seen by a consultant physician within the appropriate period of time. Only 56% of patients received a standard of care compatible with all three quality standards. We found no relation between unit characteristics, staffing and performance indicator. CONCLUSION: There remains a gap between the standard described by the quality indicators and the performance of Acute Medical Units during a one-day audit.

8.
Transfus Med Rev ; 27(3): 146-53, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23706959

ABSTRACT

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is <8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is <10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial.


Subject(s)
Blood Transfusion/methods , Gastrointestinal Hemorrhage/therapy , Practice Guidelines as Topic , Research Design , Hospitalization , Humans , Quality of Life , United Kingdom
10.
Prim Care Respir J ; 19(1): 21-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20157684

ABSTRACT

INTRODUCTION: The identification and management of adults presenting with pneumonia is a major challenge for primary care health professionals. This paper summarises the key recommendations of the British Thoracic Society (BTS) Guidelines for the management of Community Acquired Pneumonia (CAP) in adults. METHOD: Systematic electronic database searches were conducted in order to identify potentially relevant studies that might inform guideline recommendations. Generic study appraisal checklists and an evidence grading from A+ to D were used to indicate the strength of the evidence upon which recommendations were made. CONCLUSIONS: This paper provides definitions, key messages, and recommendations for handling the uncertainty surrounding the clinical diagnosis, assessing severity, management, and follow-up of patients with CAP in the community setting. Diagnosis and decision on hospital referral in primary care is based on clinical judgement and the CRB-65 score. Unlike some other respiratory infections (e.g. acute bronchitis) an antibiotic is always indicated when a clinical diagnosis of pneumonia is made. Timing of initial review will be determined by disease severity. When there is a delay in symptom or radiographic resolution beyond six weeks, the main concern is whether the CAP was a complication of an underlying condition such as lung cancer.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/drug therapy , Community-Acquired Infections/prevention & control , Humans , Patient Education as Topic , Physicians, Family , Pneumonia, Bacterial/prevention & control , Primary Health Care , Risk Factors , Severity of Illness Index , Societies, Medical , United Kingdom
11.
Br J Clin Pharmacol ; 68(2): 260-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19694747

ABSTRACT

AIMS: The primary aim of this paper is to provide comprehensive contemporaneous data on the demographics, patterns of presentation and management of all episodes of deliberate self-poisoning presenting to a large regional teaching hospital over a 12 month period. METHODS: We undertook detailed, retrospective analyses using information from electronic patient records and local patient-tracking, pathology and administrative databases. Statistical analyses were performed using Chi-squared tests, anova and two-tailed t-tests (Graphpad Prism). RESULTS: One thousand five hundred and ninety-eight episodes of deliberate self-poisoning presented over the year. Demographic data and information on the month, day and time of admission are provided. 70.7% presented to the emergency department (ED) within 4 h of ingestion. 76.3% of patients had only one episode in an extended 29 month follow-up period. A mean of 1.72 drugs were taken per episode with just over half of all episodes involving a single drug only. Paracetamol and ibuprofen were the two most commonly ingested drugs involved in 42.5% and 17.3% of all overdoses respectively. 56.3% of patients taking paracetamol reported ingesting over 8 g (one over the counter packet). Detailed mapping of the patients' pathway through the hospital allowed an estimation of the hospital cost of caring for this patient group at pound 1.6 million pounds per year. CONCLUSIONS: We present comprehensive and contemporary data on presentations to hospital resulting from deliberate self-poisoning. We include demographic information, presentation patterns, drugs used, a detailed analysis of episodes involving paracetamol and an estimate of the financial burden to hospitals of overdose presentations.


Subject(s)
Acetaminophen/poisoning , Drug Overdose/epidemiology , Self-Injurious Behavior/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Drug Overdose/economics , Emergency Service, Hospital/economics , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Self-Injurious Behavior/economics , United Kingdom/epidemiology , Young Adult
12.
Am J Respir Crit Care Med ; 178(12): 1257-61, 2008 Dec 15.
Article in English | MEDLINE | ID: mdl-18755924

ABSTRACT

RATIONALE: Previous studies have suggested that people with idiopathic pulmonary fibrosis (IPF) may be at increased risk of vascular disease. OBJECTIVES: To quantify the risk of cardiovascular disease before and after a diagnosis of IPF. METHODS: We used computerized primary care data from the Health Improvement Network to quantify the relative risk of having a cardiovascular event (acute coronary syndrome, angina, atrial fibrillation, deep-vein thrombosis, and cerebrovascular accident) either before or after having a diagnosis of IPF in comparison to age, sex, and community-matched general population control subjects. MEASUREMENTS AND MAIN RESULTS: Our study included 920 incident case subjects of IPF (mean age at diagnosis, 71 yr; 62% male) and 3,593 matched control subjects. There was an increased risk of acute coronary syndrome (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.15-2.03), angina (OR, 1.84; 95% CI, 1.48-2.29) and deep-vein thrombosis (OR, 1.98; 95% CI, 1.13-3.48) in the period before the diagnosis of IPF. During the follow-up period, there was a marked increased risk of acute coronary syndrome (rate ratio [RR], 3.14; 95%CI, 2.02-4.87) and deep-vein thrombosis (RR, 3.39; 95% CI, 1.57-7.28). None of these estimates were confounded by smoking habit or modified by age or sex. CONCLUSIONS: People with IPF have an increased risk of vascular disease in comparison with the general population. This effect is most marked for acute coronary syndrome and deep-vein thrombosis after the diagnosis of IPF has been made.


Subject(s)
Idiopathic Pulmonary Fibrosis/complications , Population Surveillance , Vascular Diseases/etiology , Aged , Confidence Intervals , Female , Follow-Up Studies , Humans , Idiopathic Pulmonary Fibrosis/epidemiology , Incidence , Male , Odds Ratio , Retrospective Studies , Risk Assessment/methods , Risk Factors , Survival Rate , United Kingdom/epidemiology , Vascular Diseases/epidemiology
13.
Am J Respir Cell Mol Biol ; 38(1): 1-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17673687

ABSTRACT

Relaxation of airway smooth muscle is dependent predominantly upon elevation of cell cAMP content. Although the processes involved in elevation of cell cAMP content are reasonably well established, the mechanisms governing subsequent control of cAMP turnover are less clear. Breakdown of cAMP is solely regulated by phosphodiesterase (PDE) isoenzymes. We have previously reported that PDE4 family members are likely to be important in this process, and that expression of PDE4D variants is actively regulated at the transcriptional level. Here, we demonstrate a key role for PDE4D5 in the control of beta(2)-adrenoceptor (beta(2)AR)-stimulated cAMP activity in human airway smooth muscle cells using splice variant-specific small interfering RNA knockdown. Furthermore, we show, using an Epac (exchange protein directly activated by cAMP)-based, cAMP-sensitive fluorescent probe, that these intracellular cAMP gradients are controlled both temporally and dynamically by PDE4D5. Elevation of cAMP within the cytoplasm after beta(2)AR stimulation is rapid and shows no distinct spatial compartmentalization in these cells. These data suggest that PDE4D5, despite being a minor component of the tissue PDE pool, is the key physiological regulator of beta(2)AR-induced cAMP turnover within human airway smooth muscle.


Subject(s)
Cyclic AMP/metabolism , Muscle Relaxation/physiology , Myocytes, Smooth Muscle/enzymology , Phosphoric Diester Hydrolases/metabolism , Receptors, Adrenergic, beta-2/biosynthesis , Trachea/enzymology , Cells, Cultured , Cyclic AMP/genetics , Cyclic Nucleotide Phosphodiesterases, Type 3 , Cyclic Nucleotide Phosphodiesterases, Type 4 , Gene Expression , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Myocytes, Smooth Muscle/cytology , Phosphoric Diester Hydrolases/genetics , RNA, Small Interfering/genetics , Receptors, Adrenergic, beta-2/genetics , Trachea/cytology , Transcription, Genetic/physiology
14.
Respir Med ; 101(12): 2534-40, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17870458

ABSTRACT

BACKGROUND: The aim of this study was to use a longitudinal computerised health care dataset (The Health Improvement Network) to provide information on the overall incidence of cancer, and on the incidence of organ-specific cancers, in people with idiopathic pulmonary fibrosis (IPF) and sarcoidosis in comparison to the general population. METHODS: Incident cases of IPF and sarcoidosis were identified with up to four controls matched by age, gender and general practice. Cancer incidence rates were compared between cohorts using Cox regression and adjusting for age, gender and smoking habit. RESULTS: One thousand and sixty-four incident cases of IPF (mean age at diagnosis 71.5 years; 62.4% male) were identified. Overall, the incidence of cancer was increased in people with IPF compared to the general population (rate ratio 1.51; 95% CI 1.20-1.90), but this was largely due to a marked increase in the incidence of lung cancer (rate ratio 4.96; 95% CI 3.00-8.18). One thousand one hundred and fifty-three incident cases of sarcoidosis (mean age at diagnosis 47.0 years; 47.2% male) were identified. There was an overall increased incidence of cancer in sarcoidosis (rate ratio 1.65; 95% CI 1.22-2.24) and this was largely explained by an increase in the incidence of skin cancers (rate ratio 1.86; 95% CI 1.11-3.11). CONCLUSIONS: This study provides further evidence of a marked increase in the incidence of lung cancer in people with IPF, but we found no increase in the risk of other cancers. People with sarcoidosis did have an increase risk of skin cancers, but not cancers at other sites.


Subject(s)
Neoplasms/epidemiology , Pulmonary Fibrosis/epidemiology , Sarcoidosis, Pulmonary/epidemiology , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Female , Health Surveys , Humans , Incidence , Longitudinal Studies , Lung Neoplasms/complications , Lung Neoplasms/epidemiology , Male , Middle Aged , Neoplasms/complications , Primary Health Care/statistics & numerical data , Proportional Hazards Models , Pulmonary Fibrosis/complications , Sarcoidosis, Pulmonary/complications , Sex Factors , Skin Neoplasms/complications , Skin Neoplasms/epidemiology , Smoking/epidemiology , United Kingdom/epidemiology
15.
Respir Med ; 101(3): 670-5, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16928442

ABSTRACT

BACKGROUND: Trans-bronchial needle aspiration (TBNA) is a simple, safe technique that can be performed without additional resources in any centre with a bronchoscopy service. It provides rapid diagnostic information in malignant and benign conditions and staging information in non-small cell lung cancer (NSCLC) and may avoid the delays, risks, in-patient stay and financial implications associated with surgical exploration of the mediastinum. Despite this, centres have been slow to adopt the technique. This may be due to the lack of clarity about the clinical success of TBNA in everyday clinical practice and the absence of a single valid measurement of clinical utility for TBNA against which to audit. METHODS: We undertook a retrospective analysis of all TBNA carried out at Nottingham City Hospital since the service began. "Success" was carefully and strictly defined. The influences of various factors on the likelihood of a successful outcome were analysed. RESULTS: Fifty percent (71/142) of patients undergoing TBNA received an exact histological diagnosis whilst in 72% (97/134) of patients in whom a final diagnosis was made, TBNA results correctly predicted malignant versus benign conditions. We defined the former, more stringent, outcome measure as "success--exact". This outcome was not significantly affected by patient age or gender, lesion size or position, experience of the bronchoscopist or number of aspiration attempts. Final diagnosis strongly influenced "success--exact" with NSCLC 6.5 times and small cell lung cancer 28.5 times more likely to yield a diagnostic sample than benign conditions. CONCLUSIONS: TBNA should be used as a standard first line invasive investigation for diagnosis of mediastinal lymphadenopathy or submucosal endobronchial disease. The stringent outcome defined in this study as "success--exact" is simple for clinicians and patients to understand and would be a useful definition to standardise audit and future research.


Subject(s)
Biopsy, Needle/methods , Bronchoscopy/methods , Lung Diseases/diagnosis , Lung/pathology , Age Factors , Aged , Female , Humans , Lung Diseases/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Sex Factors
16.
J Biol Chem ; 277(39): 35980-9, 2002 Sep 27.
Article in English | MEDLINE | ID: mdl-12121997

ABSTRACT

Phosphodiesterase 4D (PDE4D), part of the complex cAMP-specific PDE4 family, plays a pivotal role in the regulation of airway smooth muscle relaxation by catalyzing the hydolysis of cAMP. Its gene on chromosome 5q12 encodes 5 splice variants, which show tissue-dependent expression and regulation. The genomic arrangement of PDE4D was determined using in silico methods, and a putative promoter of one of the protein kinase A-activated, long isoforms, PDE4D5 was identified. Promoter-luciferase constructs, transiently transfected into a beta(2) adrenoreceptor-expressing CHO-K1 cell line, were used to demonstrate that the PDE4D5 promoter up-regulated reporter gene expression in response to increased cell cAMP. Site-directed mutagenesis of the cAMP-response element (CRE) at position -201 identified this as the principal component of the mechanism underlying this cAMP responsiveness. In the second part of this study, cAMP-dependent induction of PDE4D5 transcript in primary cultured human airway smooth muscle cells (hASMs) was demonstrated using both qualitative reverse-transcriptase PCR and quantitative real-time PCR. Isolated PDE4D5 isoenzyme activity, measured after selective immunoprecipitation from hASMs, confirmed that this increase in expression led to an up-regulation of functional activity. We present evidence for cAMP-driven PDE4D5 up-regulation in hASMs and suggest a CRE-containing, isoform-specific promoter as the primary mechanism.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Cyclic AMP/metabolism , Muscle, Smooth/cytology , Phosphoric Diester Hydrolases/biosynthesis , Phosphoric Diester Hydrolases/chemistry , Trachea/cytology , Up-Regulation , 8-Bromo Cyclic Adenosine Monophosphate/metabolism , Alternative Splicing , Animals , Base Sequence , CHO Cells , Chromosomes, Human, Pair 5 , Cricetinae , Culture Media, Serum-Free/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 3 , Cyclic Nucleotide Phosphodiesterases, Type 4 , Down-Regulation , Genes, Reporter , Humans , Kinetics , Luciferases/metabolism , Models, Genetic , Molecular Sequence Data , Mutagenesis, Site-Directed , Precipitin Tests , Promoter Regions, Genetic , Protein Isoforms , Protein Structure, Tertiary , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic , Transfection
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