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Biomedical subjects

S Lewis

Publications and source records attributed to S Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2004

Overexpression of cyclooxygenase-2 in non-small cell lung cancer.

Evidence is accumulating to suggest that the inducible isoenzyme of cyclooxygenase (COX)-2 is up-regulated in human cancers and epidemiological studies indicate that COX inhibitors may have a protective effect on the development of lung cancer. We used immunohistochemistry and Western blotting to investigate COX expression in lung tumour specimens and three lung cancer cell lines. Sixty-five archival lung tissue samples, including 46 squamous cell and 6 adenocarcinoma lung resections, and 13 small cell lung cancer (SCLC) biopsies were studied. Dense and intense cytoplasmic COX-2 staining was found in all 52 resections from non-small cell lung cancer (NSCLC). The staining was diffuse and much stronger than adjacent respiratory epithelium. COX-2 staining was relatively weak in the majority of the SCLC samples. The bronchial and bronchiolar epithelium in the surrounding normal lung structures showed uniform COX immunoreactivity with apical concentration of the stain. There was no increase in COX-1 staining in any tumour type. Western blot analysis of the cancer lines revealed significantly higher expression of COX-1 in CORL23 line and COX-2 in two NSCLC cell lines (MOR/P; A549) compared with the expression of COX-1 and COX-2 in cultured normal bronchial epithelial cells. Our findings demonstrated COX-2 overexpression in NSCLC.

Adenocarcinoma↗
PubMed2004

Major complications after percutaneous nephrostomy-lessons from a department audit.

AIM: To audit the performance of our percutaneous nephrostomy service by comparing the major complication rate with the standards recommended by the Society of Cardiovascular and Interventional Radiology and the American College of Radiology: major haemorrhage in <4%, and septic shock in <4%. Secondary aims were to identify common sources of errors for quality improvement measures. METHODS: Major complications sustained between January 1997-December 2002 were identified. All cases had been carried out by the interventional radiology service of a large teaching hospital with the assistance of a nurse and radiographer, under fluoroscopic and ultrasound guidance using a Seldinger technique. Existing department protocols specified pre-procedure antibiotics for suspected infected cases and normal coagulation studies. From records and review of case notes pertinent clinical/procedural details and eventual outcome were assessed. The following were particularly noted: adherence to protocols, clinical status at time of procedure, delay in referral, complication sustained, signs of infection or coagulopathy, timing of procedure (in versus out of hours), level of operator and technical faults. RESULTS: Ten of 318 (3.1%) cases sustained a major complication: five had sepsis alone, two haemorrhage (one with sepsis as well) and three patients had a major pelvic injury (one with sepsis as well). Thus the major sepsis and haemorrhage rates were 2.2 and 0.6%, and were within the recommended threshold limits but proportionately more complications occurred out of hours: six of 105 (5.7%) versus four of 312 (1.8%; p=0.087). Sepsis was the most serious complication and may have contributed to the death of two patients. On individual case analysis, failed instrumentation with delay to definitive renal drainage was a common factor with sepsis; but the following were contributory factors in one or more cases: omitted antibiotics (in three of 10; two became septic), technical factors in four cases [medial renal puncture (n=1), damage due to fascial dilator (n=1) or peelaway sheath (n=2)] and delay in diagnosis/therapy (of 1-8 days, in six of 10 cases of whom four out of six became septic). One pelvic injury required surgical correction (contributory factor-faulty use of peelaway sheath). Patients with haemorrhage settled with prolonged tube drainage alone. CONCLUSION: An adequately staffed percutaneous nephrostomy service can perform within published clinical standards. Best practice factors identified were: attention to agreed protocols and algorithms, pre-procedure antibiotics, careful renal puncture and care with use of dilators/peelaway sheaths, but the paramount finding was that sepsis was the most serious complication, contributing to death (two of 10 in this study) or a significant increase in the level of care required. The risk is greatest after failed instrumentation (retrograde ureteral stent or percutaneous nephrostomy insertion) and particularly if there is a further delay before establishment of renal drainage. A close working relationship between interventional radiologists and urologists is crucial.

Adult↗
PubMed2004

The role of the clinical nurse specialist in epilepsy. A national survey.

PURPOSE: To review and describe the key roles of the UK clinical nurse specialist in epilepsy (CNSE), and to identify the specialist nurses' contribution to care through an exploration of CNSE's perceptions of their roles. METHOD: Using the Delphi technique [Applied Project Design and Analysis, 3rd ed., Churchill Livingstone, London, 2000, p. 243] a national survey of all known UK CNSEs was completed. One hundred and thirty questionnaires identifying nine key hypotheses central to the role of the CNSE were distributed and 76 valid questionnaires returned. RESULTS: The response rate was 63% and was geographically representative of the UK population of CNSEs. CNSEs were employed in a range of hospital and community settings with differing patient groups. Seventy-two percent of respondents held higher academic nursing qualifications but only 36% had previous epilepsy or neurology experience. Thirty percent of respondents had been employed in the role of CNSE for more than 5 years and 84% were employed as a G or H grade nurse. Only 39% of CNSEs held nurse-led clinics and of those 32% were responsible for all decisions made during their clinic. Furthermore, 40% of CNSEs saw new patients who had not previously been reviewed by one of the medical team. The level of responsibility for drug management was mainly at a monitoring and advisory level but a small number of CNSEs held much greater responsibility. The responses to the nine hypotheses were compared using cross tabulations. CONCLUSION: The findings of the study and the review of the CNSE in the UK revealed that the key roles of the CNSE were difficult to define. Yet, the respondents identified that there were common core features central to their contribution to care as specialist nurses.

Delphi Technique↗
PubMed2004

Good practices that address continuity during transition from child to adult care: synthesis of the evidence.

BACKGROUND: Effective transition to adult services is required by an increasing number of children with ongoing needs. AIM: To identify practices that promote continuity at transition between child and adult services. METHODS: Systematic examination of the evidence from two search strategies yielding 5319 items. RESULTS: Only three of the 126 appraised items had strong external validity. A large range of different practices, which focused on the service, the young person and the family, were identified. Practices within the service addressed structural, process and outcome components. CONCLUSION: Four transition models are proposed for testing.

Adolescent↗
PubMed2004

Management of a snake bite in the field.

We present a case of an 18-year-old British soldier who was bitten by an unidentified snake whilst stationed on the Iran/Iraq border. He was evacuated to the closest Role 2+ medical facility. Within 2 days he had developed bruising and a haematoma at the bite site. An improvised measure of clotting status, the bleeding time, was employed, showing that his blood was severely anticoagulated. He was transferred to the Field Hospital where coagulation screen revealed a DIC picture. He required 5 units of cryoprecipitate and 2 doses of antivenom. This case report demonstrates the need for prompt evacuation to a Role 3 facility in such cases, whether symptomatic or not.

Adolescent↗
PubMed2004

Time course of action of two inhaled corticosteroids, fluticasone propionate and budesonide.

BACKGROUND: It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP). METHODS: Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action. RESULTS: There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments. CONCLUSION: PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.

Administration, Inhalation↗
PubMed2004

Amino acids and asthma: a case-control study.

Amino acids contribute to various anti-oxidant and immunological activities relevant to asthma pathogenesis, raising the possibility that differences in amino acids may be involved in asthma aetiology. The authors hypothesised that cystine reduces the risk of asthma via glutathione metabolism. Methionine, glutamine, glutamic acid and glycine may have potential protective effects, whilst arginine, phenylalanine and tryptophan may have adverse effects in asthma. Fasting plasma levels of amino acids were compared in a case-control study. A total of 89 adults, aged 18-65 yrs, with asthma controlled by inhaled corticosteroids, were recruited from a volunteer database and local primary care registers, and compared with 89 controls individually matched for age, sex and primary care centre. Contrary to the primary hypothesis, cases had higher fasting plasma cystine levels than controls, and there was no difference between cases and controls in any of the other amino acids tested, with the exception of plasma glycine, which was associated with a strongly reduced risk of asthma (odds ratio for the highest tertile compared to lowest 0.30 (95% confidence interval (0.11-0.82)). This study negates the hypothesis that higher fasting plasma cystine levels have a protective effect on the risk of asthma, although the inverse correlation with plasma glycine deserves further investigation.

Adolescent↗
PubMed2004

What is the best imaging strategy for acute stroke?

OBJECTIVES: To determine the cost-effectiveness of computed tomographic (CT) scanning after acute stroke. To assess the contribution of brain imaging to the diagnosis and management of stroke, and to estimate the costs, benefits and risks of different imaging strategies in order to provide data to inform national and local policy on the use of brain imaging in stroke. DESIGN: A decision-analysis model was developed to represent the pathway of care in acute stroke using 'scan all patients within 48 hours' as the comparator against which to cost 12 alternative scan strategies. SETTING: Hospitals in Scotland. PARTICIPANTS: Subjects were patients admitted to hospital with a first stroke and those managed as outpatients. INTERVENTIONS: The effect on functional outcome after ischaemic or haemorrhagic stroke, tumours or infections, of correctly administered antithrombotic or other treatment; of time to scan and stroke severity on diagnosis by CT or MRI; on management, including length of stay, functional outcome, and quality-adjusted life years (QALYs), of the diagnostic information provided by CT scanning; the cost-effectiveness (cost versus QALYs) of different strategies for use of CT after acute stroke. MAIN OUTCOME MEASURES: Death and functional outcome at long-term follow-up; accuracy of CT and MRI; cost of CT scanning by time of day and week; effect of CT diagnosis on change in health outcome, length of stay in hospital and QALYs; cost-effectiveness of various scanning strategies. RESULTS: CT is very sensitive and specific for haemorrhage within the first 8 days of stroke only. Suboptimal scanning used in epidemiology studies suggests that the frequency of primary intracerebral haemorrhage (PICH) has been underestimated. Aspirin increases the risk of PICH. There were no reliable data on functional outcome or on the effect of antithrombotic treatment given long term after PICH. In 60% of patients with recurrent stroke after PICH, the cause is another PICH and mortality is high among PICH patients. A specific MR sequence (gradient echo) is required to identify prior PICH reliably. CT scanners were distributed unevenly in Scotland, 65% provided CT scanning within 48 hours of stroke, and 100% within 7 days for hospital-admitted patients, but access out of hours was very variable, and for outpatients was poor. The average cost of a CT brain scan for stroke was pounds 30.23 to pounds 89.56 in normal working hours and pounds 55.05 to pounds 173.46 out of hours. Average length of stay was greatest for severe strokes and those who survived in a dependent state. For a cohort of 1000 patients aged 70-74 years, the policy 'scan all strokes within 48 hours', cost pounds 10,279,728 and achieved 1982.3 QALYS. The most cost-effective strategy was 'scan all immediately' (pounds 9,993,676 and 1982.4 QALYS). The least cost-effective was to 'scan patients on anticoagulants, in a life-threatening condition immediately and the rest within 14 days'. CONCLUSIONS: In general, strategies in which most patients were scanned immediately cost least and achieved the most QALYs, as the cost of providing CT (even out of hours) was less than the cost of inpatient care. Increasing independent survival by even a small proportion through early use of aspirin in the majority with ischaemic stroke, avoiding aspirin in those with haemorrhagic stroke, and appropriate early management of those who have not had a stroke, reduced costs and increased QALYs.

Aged↗
PubMed2003

The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement.

N-Butyldeoxynojirimycin (NB-DNJ, miglustat 'Zavesca') is an orally active iminosugar which inhibits the biosynthesis of macromolecular substrates that accumulate pathologically in glycosphingolipidoses. Clinical trials of NB-DNJ in patients with Gaucher's disease demonstrate the therapeutic potential of such substrate inhibitors in the glycolipid storage disorders. However, macrophage-targetted enzyme replacement using intravenous mannose-terminated human glucocerebrosidase (imiglucerase, Cerezyme) is highly effective in ameliorating many of the manifestations of Gaucher's disease and is a treatment in widespread use. Given that imiglucerase and miglustat are now both licensed for the treatment of Gaucher's disease, there is a need to review their therapeutic status. Here the treatment of type 1 (non-neuronopathic) Gaucher disease is evaluated with particular reference to the emerging role of oral N-butyldeoxynojirimycin (miglustat) as a substrate-reducing agent. This position statement represents the consensus viewpoint of an independent international advisory council to the European Working Group on Gaucher Disease.

Clinical Trials as Topic↗
PubMed2003

Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis.

AIMS: To test the hypothesis that cyclooxygenase (COX)-1 or COX-2 expression is defective in lungs in idiopathic pulmonary fibrosis (IPF) and to characterize the cellular distribution. IPF is a progressive inflammatory lung disorder with an adverse prognosis. Previous work has shown that prostaglandin E2 (PGE2) regulates collagen deposition and fibroblast proliferation and a defect in COX regulation may contribute to the fibrosis that occurs in IPF. METHODS: Immunohistochemistry was utilized to determine COX immunoreactivity in lung sections from 25 IPF, six sarcoidosis and 14 control subjects. RESULTS: COX-1 and COX-2 expression in bronchiolar epithelial cells was significantly lower in IPF and sarcoidosis than in controls. No significant difference was found in COX-2 expression between macrophages in IPF and control sections, but COX-2 was reduced in macrophages in sarcoidosis compared with controls. CONCLUSIONS: These studies confirm COX-2 loss in bronchial epithelial cells but not macrophages in IPF, and show for the first time reduced constitutive COX-1 expression in epithelial cells and macrophages. Similar abnormalities were observed in sarcoidosis.

Adult↗
PubMed2003

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England.

OBJECTIVE: To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK. METHODS: The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45-76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants' serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour. RESULTS: The seroprevalence of undetected coeliac disease in this general population sample aged 45-76 was 1.2% (95% confidence interval (CI) 0.9-1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being "good or excellent" (odds ratio (OR) 1.76 (95% CI 0.90-3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14-0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3-7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5-8.2)) compared with EMA negative participants. CONCLUSIONS: Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45-76 years, a value similar to several other countries. Those affected report "better health" but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.

Age Distribution↗