Search PubMed⌕ Search

Biomedical subjects

S A Lewis

Publications and source records attributed to S A Lewis.

At least 19 recordsLinked to original sources

Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.

BACKGROUND: In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. METHODS: Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. RESULTS: 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. CONCLUSIONS: A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.

Adult↗

Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease.

BACKGROUND: Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown. METHODS: The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire. RESULTS: After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls. CONCLUSION: There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.

Airway Obstruction↗

Relationship between FEV1 reduction and respiratory symptoms in the general population.

Obstructive airways diseases typically present with dyspnoea, cough and wheeze, and are defined by a reduced forced expiratory volume in one second (FEV1/forced vital capacity (FVC) ratio. Traditionally, however, the severity of chronic obstructive pulmonary disease is graded by the FEV1 % predicted rather than the FEV1/FVC ratio, whilst other potentially valid measures of FEV1 impairment, such as the absolute difference of FEV1 from predicted or the absolute level of FEV1, tend not to be used. The authors have therefore explored the relationship between these different measures of FEV1 impairment and chronic respiratory symptoms in a general population sample. FEV1 and FVC were measured and questionnaire data were obtained on cough, wheeze, shortness of breath and general self-reported breathing trouble in a cross-sectional survey of 2,633 adults aged 18-70 yrs from a district of Nottingham, UK. Odds ratios for each symptom were calculated for declining levels of absolute FEV1, FEV1 % pred, absolute difference of FEV1 from predicted, and FEV1/FVC ratio. They were plotted to display the shape and strength of these relationships before and after adjustment for each other measure. The odds of symptoms increased with declining levels of all FEV1 measures, particularly for wheeze and general breathing trouble. Although this study was not sufficiently powerful to detect significant differences between measures, these relationships were consistently strongest, before and after adjustment, for FEV1 % pred, particularly below a threshold of approximately 75%. The authors conclude that forced expiratory volume in one second % predicted appears to be the measure of airflow impairment most closely associated with chronic respiratory symptoms in the general population.

Adolescent↗

Living near a main road and the risk of wheezing illness in children.

The effect of road vehicle traffic pollution on asthma is still not clearly understood. However, any effect is likely to be most marked among those who live within 150 m of a main road, because this is the distance within which concentrations of primary vehicle traffic pollutants are raised above ambient background levels. We have investigated the relation between proximity of the family home to the nearest main road, estimated objectively using geographical information system software, and the risk of wheeze in the past year in a case-control sample of 6,147 primary schoolchildren (age 4 to 11 yr) and a random cross-sectional sample of 3,709 secondary schoolchildren (age 11 to 16 yr) in Nottingham, United Kingdom. Among children living within 150 m of a main road, the risk of wheeze increased with increasing proximity by an odds ratio (OR) of 1.08 (95% confidence interval [CI] 1.00 to 1.16) per 30-m increment in primary schoolchildren, and 1.16 (1.02 to 1.32) in secondary schoolchildren. Most of the increased risk was localized to within 90 m of the roadside. Among primary schoolchildren, effects were stronger in girls than boys (p(interaction) = 0.02). Living within approximately 90 m of a main road is associated with a proximity-related increase in the risk of wheezing illness in children.

Case-Control Studies↗

Increased risk of allergy associated with the use of kerosene fuel in the home.

Allergic diseases are becoming increasingly prevalent in developing countries, consistent with an environmental etiology associated with affluence or urbanization. We have tested the hypothesis that the risk of allergy is increased by the use of non-biomass fuels (kerosene, gas or electricity) in the home, using data from a survey of the urban population of Jimma, Ethiopia. Questionnaire data on allergic symptoms, domestic fuel use and lifestyle factors were collected from 9844 adults and children, and allergen skin sensitization measured in a subsample of 2372. Use of any non-biomass fuel was reported by 959 individuals (10%), usually in combination with biomass fuel, and was significantly associated with an increased risk of allergic sensitization (age, sex and socio-economic status adjusted odds ratio (95% confidence interval) = 1.78 [1.06 to 2.97]) and wheeze (1.56 [1.07 to 2.26]), rhinitis (2.06 [1.46 to 2.91]) and eczema (2.82 [1.61 to 4.96]) relative to use of biomass fuel only. These effects were predominantly due to kerosene, which was significantly related to all outcomes, and gas, which was strongly related to allergic sensitization. Our findings suggest that domestic combustion of refined fossil fuels increases the risk of allergic sensitization and symptoms, and may have contributed to the increasing prevalence of allergic disease.

Adolescent↗

Measurement of CP-violating asymmetries in B0 decays to CP eigenstates.

We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23x10(6) Upsilon(4S)-->BbarB decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events in which one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay time distributions in such events. The result is sin2beta = 0.34+/-0.20 (stat)+/-0.05 (syst).

Journal Article↗

Association of specific allergen sensitization with socioeconomic factors and allergic disease in a population of Boston women.

BACKGROUND: Socioeconomic differences in allergic disease prevalence have been reported; asthma has been associated with poverty in the United States and hay fever and eczema with relative affluence elsewhere. It is not yet established to what degree such differences in disease prevalence reflect patterns of sensitization and specific allergen sensitivities. OBJECTIVE: We analyzed specific and total IgE measurements in a sample of 458 women, enriched for allergic disease, from the metropolitan Boston area to establish the relation of allergen sensitization to markers of socioeconomic status (SES) and to the prevalence and socioeconomic pattern of allergic disease in this community. METHODS: Total and specific IgE antibodies were measured with the UNICAP System; self-reported allergic disease, household income, education, and race-ethnicity were ascertained with a questionnaire; and a further marker of poverty (percentage living below the poverty level) in the women's area of residence was established on the basis of zip codes. Analysis was performed with SAS statistical software. RESULTS: Markers of low SES were univariately associated with increases in total IgE, number of allergen sensitizations, and levels of specific IgE. Socioeconomic differences in sensitization to cockroach (35% vs 6% in the highest and lowest poverty areas), animal (44% vs 26%), and ragweed (49% vs 23%) allergens were most marked. Sensitization primarily to indoor inhalant allergens (not ragweed or ryegrass) were associated with an increased risk of asthma, even after adjustment for SES. CONCLUSION: We have demonstrated a socioeconomic gradient in sensitization that concords with increased rates of asthma in less affluent communities in this population.

Adolescent↗

Siblings, multiple births, and the incidence of allergic disease: a birth cohort study using the West Midlands general practice research database.

BACKGROUND: The presence of older siblings reduces the risk of developing hay fever, eczema and atopy, but findings for asthma have been inconsistent. Whether twins have a reduced risk of allergic disease is also unclear. We have investigated these questions in a birth cohort analysis of the West Midlands General Practice Research Database (GPRD). METHODS: Our birth cohort included 29,238 children. The incidence of allergic disease was examined according to the number of siblings, multiple births, and parental allergic disease and smoking habit using Cox regression. RESULTS: There was a dose related decrease in the incidence of eczema and hay fever with increasing number of older siblings (hazard ratio for children with three or more older siblings compared with none 0.70 (95% CI 0.64 to 0.76) for eczema and 0.67 (95% CI 0.52 to 0.86) for hay fever). In contrast, the presence of older siblings increased the incidence of asthma (HR 1.17, 95% CI 1.06 to 1.29), although this effect was strongly dependent on age of diagnosis. For children diagnosed over the age of 2 years the presence of older siblings was protective (HR 0.66, 95% CI 0.52 to 0.82), while below this age the reverse was true (HR 1.38, 95% CI 1.24 to 1.54). Members of a multiple birth had a reduced incidence of all three allergic diseases. Birth order and multiple birth effects were independent of sex, maternal age, consulting behaviour, and parental allergy and smoking habit. CONCLUSIONS: The presence of older siblings and being a member of a multiple birth appears to protect against the development of eczema, hay fever, and asthma diagnosed after the age of 2. In contrast, the presence of older siblings increases the incidence of early asthma.

Adolescent↗

Adverse effects of oral corticosteroids in relation to dose in patients with lung disease.

BACKGROUND: The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group. METHODS: Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression. RESULTS: A total of 367 patients (> or = 50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising. CONCLUSIONS: By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.

Administration, Oral↗

Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies.

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community. Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression. Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20 provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.

Adult↗

The relation between peripheral blood leukocyte counts and respiratory symptoms, atopy, lung function, and airway responsiveness in adults.

STUDY OBJECTIVES: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults. DESIGN: A cross-sectional general population study. SETTING: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic regression to adjust for potential confounders, including age, sex, and smoking history. RESULTS: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease. CONCLUSIONS: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and monocytes may play a distinct role in the pathogenesis of allergic and nonallergic respiratory disease.

Adolescent↗

Tactile illusion perception in patients with central pain.

OBJECTIVE: To evaluate lemniscal pathways in patients with central pain (CP) by use of a novel tactile illusion (TI)-producing technique. PATIENTS AND METHODS: Somatosensory (SS) and TI testing was performed on the unaffected and affected wrists of 27 patients with unilateral central nervous system injury and unilateral CP. Data on TI testing-naive control subjects were used to adjust for a learning effect. RESULTS: Testing in CP patients with cervical and brainstem injuries revealed predominantly unchanged or decreased SS perception on the affected side compared with the unaffected side. The majority of cervical- and brainstem-injured subjects with CP had improved TI performance on the affected side compared with the unaffected side. All the thalamic-injured and most of the suprathalamic-injured CP patients had altered SS testing with either decreased or increased SS perception noted. In these same CP patients the majority had reduced TI perception on the affected side compared with the unaffected side. Unexpectedly, perseveration of numbers was noted in patients with Dejerine-Roussy syndrome, and expanded TI testing was performed to better define this observation. CONCLUSION: Cervical spinal cord-injured CP patients may have improved TI perception, whereas the majority of patients with supraspinal injuries and CP have reduced SS and TI perception. A unique sensory phenomenon of TI perseveration was observed in some patients with Dejerine-Roussy syndrome.

Adult↗

Processes involved in the development of latent fingerprints using the cyanoacrylate fuming method.

Chemical processes involved in the development of latent fingerprints using the cyanoacrylate fuming method have been studied. Two major types of latent prints have been investigated-clean and oily prints. Scanning electron microscopy (SEM) has been used as a tool for determining the morphology of the polymer developed separately on clean and oily prints after cyanoacrylate fuming. A correlation between the chemical composition of an aged latent fingerprint, prior to development, and the quality of a developed fingerprint has been observed in the morphology. The moisture in the print prior to fuming has been found to be more important than the moisture in the air during fuming for the development of a useful latent print. In addition, the amount of time required to develop a high quality latent print has been found to be within 2 min. The cyanoacrylate polymerization process is extremely rapid. When heat is used to accelerate the fuming process, typically a period of 2 min is required to develop the print. The optimum development time depends upon the concentration of cyanoacrylate vapors within the enclosure.

Cyanoacrylates↗

ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of tubulin-folding cofactor D with native tubulin.

The ADP ribosylation factor-like proteins (Arls) are a family of small monomeric G proteins of unknown function. Here, we show that Arl2 interacts with the tubulin-specific chaperone protein known as cofactor D. Cofactors C, D, and E assemble the alpha/beta- tubulin heterodimer and also interact with native tubulin, stimulating it to hydrolyze GTP and thus acting together as a beta-tubulin GTPase activating protein (GAP). We find that Arl2 downregulates the tubulin GAP activity of C, D, and E, and inhibits the binding of D to native tubulin in vitro. We also find that overexpression of cofactors D or E in cultured cells results in the destruction of the tubulin heterodimer and of microtubules. Arl2 specifically prevents destruction of tubulin and microtubules by cofactor D, but not by cofactor E. We generated mutant forms of Arl2 based on the known properties of classical Ras-family mutations. Experiments using these altered forms of Arl2 in vitro and in vivo demonstrate that it is GDP-bound Arl2 that interacts with cofactor D, thereby averting tubulin and microtubule destruction. These data establish a role for Arl2 in modulating the interaction of tubulin-folding cofactors with native tubulin in vivo.

Fungal Proteins↗

Inhaled corticosteroid use and bone-mineral density in patients with asthma.

BACKGROUND: Inhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years. METHODS: We studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20-40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis. FINDINGS: Median duration of inhaled corticosteroid treatment was 6 years (range 0.5-24), and median cumulative dose was 876 mg (87-4380). There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2-L4), femoral neck, Ward's triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0.16 SD (95% CI 0.04-0.28). Similar decreases were found at the femoral neck, Ward's triangle, and trochanter. Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations. INTERPRETATION: This study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.

Absorptiometry, Photon↗