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S A Evans

Publications and source records attributed to S A Evans.

At least 19 recordsLinked to original sources

Systemic cytokine levels in community-acquired pneumonia and their association with disease severity.

Pro-inflammatory and anti-inflammatory cytokines are important mediators in the host response to infection. In contrast to the pro-inflammatory cytokines little is known about anti-inflammatory cytokines in community-acquired pneumonia (CAP) and their relation to disease severity. Circulating levels of three pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha) and two anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist (IL-1ra)) were measured using an enzyme immunoassay on admission, day 3 and day 5 in 24 patients with CAP. The modified British Thoracic Society (BTS) prognostic rule and Acute Physiology and Chronic Health Evaluation (APACHE) II score were used to assess disease severity. IL-6, TNF-alpha, IL-10 and IL-1ra concentrations were detected in most patients on admission and decreased significantly on day 3 and day 5 in all survivors. A significant difference between the BTS high-risk and low-risk groups was only found for IL-6 (median (range) 477 pg x mL(-1) (7.6-1402 pg x mL(-1)) versus 81.6 pg x mL(-1) (0-943 pg x mL(-1)); p<0.05). IL-6 also correlated with the APACHE II scores on admission. Concentrations of anti-inflammatory cytokines were elevated on admission in community-acquired pneumonia but they did not correlate with disease severity scores.

APACHE↗

Novel posttranslational activation of the LYS2-encoded alpha-aminoadipate reductase for biosynthesis of lysine and site-directed mutational analysis of conserved amino acid residues in the activation domain of Candida albicans.

The alpha-aminoadipate pathway for lysine biosynthesis is present only in fungi. The alpha-aminoadipate reductase (AAR) of this pathway catalyzes the conversion of alpha-aminoadipic acid to alpha-aminoadipic-delta-semialdehyde by a complex mechanism involving two gene products, Lys2p and Lys5p. The LYS2 and LYS5 genes encode, respectively, a 155-kDa inactive AAR and a 30-kDa phosphopantetheinyl transferase (PPTase) which transfers a phosphopantetheinyl group from coenzyme A (CoA) to Lys2p for the activation of Lys2p and AAR activity. In the present investigation, we have confirmed the posttranslational activation of the 150-kDa Lys2p of Candida albicans, a pathogenic yeast, in the presence of CoA and C. albicans lys2 mutant (CLD2) extract as a source of PPTase (Lys5p). The recombinant Lys2p or CLD2 mutant extract exhibited no AAR activity with or without CoA. However, the recombinant 150-kDa Lys2p, when incubated with CLD2 extract and CoA, exhibited significant AAR activity compared to that of wild-type C. albicans CAI4 extract. The PPTase in the CLD2 extract was required only for the activation of Lys2p and not for AAR reaction. Site-directed mutational analysis of G882 and S884 of the Lys2p activation domain (LGGHSI) revealed no AAR activity, indicating that these two amino acids are essential for the activation. Replacement of other amino acid residues in the domain resulted in partial or full AAR activity. These results demonstrate the posttranslational activation and the requirement of specific amino acid residues in the activation domain of the AAR of C. albicans.

Aldehyde Oxidoreductases↗

Banning the "A word": where's the evidence?

BACKGROUND: It is argued that use of the term "accident" has a negative effect on prevention efforts as the term implies that such events are due to chance. AIM: To test the hypothesis that use of "injury" in place of "accident" can influence professional attitudes towards "accident/injury" prevention. SETTING: Leeds Health Authority area serving the population (n=740,000) of the city of Leeds in the Yorkshire region of England. METHOD: A randomised comparative study. Altogether 183 health visiting staff in the Leeds area were randomised (by place of work) to one of two groups. Each group received a similar postal questionnaire assessing attitudes relating to accident/injury prevention. One group received a questionnaire using only accident terminology while the other used injury terminology throughout. RESULTS: Fifty responses in the accident group were received and 39 in the injury group. Analysis by Mann-Whitney U tests showed little difference in group responses. The only significant finding was that respondents in the "accident" group were more likely to rank "accident prevention" of higher importance relative to respondents in the "injury" group (median 2, 25%-75% quartiles 1.8-4.0 compared with median 4, 25%-75% quartiles 2.0-5.0, p=0.04). However, this may have been a chance finding due to the multiple comparisons made. CONCLUSIONS: This study has shown little difference in health visitor responses when "accident" is replaced with "injury". It is possible that the effect of changing terminology is more nebulous--influencing society at large. However, it would be as well to recognise the lack of evidence and clarity relating to the terminology debate. Otherwise, there is a danger that the "injury" believers may become alienated from the "accident" diehards.

Accident Prevention↗

A final lesson.

Explore the source record for details and available documents.

Attitude to Death↗

Monocytes are a rheologically heterogeneous population of cells.

The effect of increased adhesiveness and decreased deformability of leukocytes following activation can have a profound effect on flow through the microcirculation. Measurement of leukocyte deformability is therefore an important tool in the study of the pathology of vascular diseases. Although much work has been done on the rheological properties of lymphocytes and granulocytes, there is little information available on the larger mononuclear cells, the monocytes. To investigate monocyte rheology, attempts were made to purify monocytes by a variety of methods. Purified monocytes were then filtered through 5 microm polycarbonate filters, with flow profiles (change in volume with time) recorded over 300 seconds. The profiles were analysed by least squares fitting to an appropriate mathematical model. Analysis of filtration data demonstrated 3 distinct sub-populations of monocytes with differing rheological properties. Other workers have characterised monocytes into defined subsets on the basis of their size, phagocytic ability or expression of cell surface markers. The definition of monocytes into defined rheological subsets is a new and useful addition to these studies.

Cell Separation↗

Examination of a rheological profile for blood using micropore filters.

Various techniques have been used to assess the flow properties of blood and blood cells in a range of clinical situations. Filtration through microfilters offers a single technique for measuring the flow properties of all cellular components of blood in one experiment but depends on an assumed ability to recognize cells that make up <10% of leucocytes. The remaining leucocytes, labelled fast leucocytes, were previously presumed to be lymphocytes and granulocytes. This study confirmed the identities of these fast leucocytes as those of lymphocytes and granulocytes in undiluted blood. The transit time for lymphocytes (1.2 s) and granulocytes (1.6 s) is close to that recorded for fast leucocytes (1.7 s). The resistance of each type of blood cell to flow through 5 microm filters was defined in this study as the product of the concentration of that cell in blood and its transit time through a pore in the filter. The total resistance to flow of healthy blood through the filter is 4.46 x 10(7) s/ml and is attributed to plasma (2.7%), red cells (25.9%), fast leucocytes (25.3%) and slow leucocytes (46.1%). In a cohort of 21 men with peripheral arterial disease the total resistance was increased to 7.82 x 10(7) s/ml and attributed to plasma (1.5%), red cells (14.5%), fast leucocytes (21.0%) and slow leucocytes (63.00%). This analysis therefore provides a single test for assessing the flow properties of all the cellular components of blood and plasma.

Blood Viscosity↗

Utilising a defective IBV RNA for heterologous gene expression with potential prophylactic application.

Based on the natural ability of coronaviruses to undergo homologous RNA recombination, we are working to produce infectious bronchitis virus (IBV) recombinants using RNA generated from recombinant fowlpox viruses (FPV). The aim is to replace the spike (S) gene of an existing IBV vaccine strain with the S gene of a heterologous strain. CD-61 is an IBV defective RNA (D-RNA) derived from a naturally occurring IBV D-RNA (CD-91). CD-61 D-RNA is being investigated as an RNA vector for the expression of heterologous genes. T7-derived RNA transcripts of CD-61 can be replicated and passaged in the presence of helper virus, following electroporation into IBV-infected cells. CD-61 cDNA was modified by the addition of the hepatitis delta virus ribozyme plus T7 terminator downstream of the 3'UTR. This allowed the synthesis of discreet RNA transcripts. The complete cassette was cloned into an FPV transfer vector (pEFL10) for generating recombinant fowlpox viruses. FPV/CD-61 recombinants will be assessed for D-RNA production in IBV-infected cells. The luciferase reporter gene sequence has been inserted into the modified CD-61, under the control of the IBV transcription associated sequence (TAS) from gene 5. Luciferase has been successfully expressed from CD-61 in helper virus-infected cells.

Animals↗

Leucocyte filterability: comparing diluted with undiluted blood.

Red blood cells and about 95% of white blood cells have an immediate and constant effect on the flow of undiluted or diluted blood through 5 microm filters. The remaining 5% of all leucocytes exert an increasing influence on flow such that the rate of flow of diluted and undiluted blood through these filters is continually declining over a period of 150 s. Analysis of this declining flow rate enables these cells to be counted and their rheological properties to be deduced. Approximately 50% of these slow leucocytes pass through the filters with a transit time of about 30 s and the remaining cells act as pore blockers for 150 s. The numbers and flow properties of slow leucocytes was approximately the same in blood from young women (25 years) and older men (65 years). However, the number of slow leucocytes was increased in a group of men (65 years) suffering from peripheral arterial occlusive disease. Dilution of the blood with phosphate-buffered saline increased the numbers of slow leucocytes in both of the older, but not the younger, group of volunteers. This effect was particularly noticeable in the patient group. It is recommended that filtration studies of the rheological profile of leucocytes can, and must, be performed with undiluted blood. The properties after dilution may sometimes, but not invariably, reflect changes ex vivo as well as inherent differences in the cells themselves.

Adult↗

Methods for studying leukocyte filterability in undiluted blood from intermittent claudicants.

Leukocytes are characterised from their influence on the filterability of undiluted blood from patients with PAOD (intermittent claudicants - Fontaine Stage II) and a group of sex and age-matched controls. Undiluted blood was filtered through 5 microm Nuclepore (Hemafil) filters for 300 s, at 711 Pa and room temperature, using a custom-made constant pressure filtrometer. Four populations of leukocytes are identified in both groups. In the control group, 94.4% of the leukocytes are identified as fast leukocytes with a transit time of 1.8 s. The remaining white cells are recognised as slow flowing leukocytes and subdivided into three further sub-populations. The first of these (SL1; 2.8% of total leukocyte count) is characterised by a transit time of 31.7 s, a second population (SL2; 1.5% of total leukocyte count) by a transit time of 145.8 s while the remaining cells are identified as pore blockers (PB) under these conditions. A similar rheological classification is valid in the patients but the sum of the three minor populations is elevated compared to controls (p = 0.001) although there is no overall leukocytosis. The only significant difference in flow properties of any blood cells, between the two groups of volunteers, is seen in the major population of leukocytes with an elevated transit time of 2.4 s. Stepwise regression analysis identifies the concentration of fast leukocytes, SL2 and PB as the major variables affecting blood flow through the filter. It is argued that the higher concentration of SL2 and PB probably reflect the increased sensitivity of neutrophils to physical stimuli.

Aged↗

Socioeconomic status and the prevention of child home injuries: a survey of parents of preschool children.

OBJECTIVES: To examine the effect of socioeconomic status on the attitudes parents of preschool children towards child home safety issues and practice of home safety measures. SETTING: A community based study in the Lanarkshire Health Board area, a mixed urban-rural setting in central Scotland. METHODS: A postal survey of two random samples of parents of preschool children (aged 3 years). One sample (A) involved parents living in more affluent areas and the other (B) parents living in less affluent areas. RESULTS: In general, parents in both groups showed similar attitudes towards home safety. The only significant differences to emerge were over parental perceptions of the safety of the neighbourhood in which they lived and over the availability of money to keep their child safe (group B > group A, p < 0.0042). Parents from group B also tended to report similar or safer levels of home safety behaviour to parents from group A. CONCLUSIONS: The findings do not suggest that differences in the injury experience of children from more and less affluent backgrounds are due to differences in parental attitude, knowledge, or practice of home safety measures. Thus, the study does not support the selective targeting of families from less affluent areas with educational interventions. Instead, the findings do support the use of a multi-method approach to home safety, where educational approaches are complemented by environmental modification.

Accidents, Home↗

Correlation between 99Tcm-HMPAO-SPECT brain image and a history of decompression illness or extent of diving experience in commercial divers.

OBJECTIVES: To explore the use of 99technetiumm-hexamethyl propylene amine oxime single photon computed tomography (HMPAO-SPECT) of the brain as a means of detecting nervous tissue damage in divers and to determine if there is any correlation between brain image and a diver's history of diving or decompression illness (DCI). METHODS: 28 commercial divers with a history of DCI, 26 divers with no history of DCI, and 19 non-diving controls were examined with brain HMPAO-SPECT. Results were classified by observer assessment as normal (I) or as a pattern variants (II-V). The brain images of a subgroup of these divers (n = 44) and the controls (n = 17) were further analysed with a first order texture analysis technique based on a grey level histogram. RESULTS: 15 of 54 commercial divers (28%) were visually assessed as having HMPAO-SPECT images outside normal limits compared with 15.8% in appropriately identified non-diver control subjects. 18% of divers with a history of DCI were classified as having a pattern different from the normal image compared with 38% with no history of DCI. No association was established between the presence of a pattern variant from the normal image and history of DCI, diving, or other previous possible neurological insult. On texture analysis of the brain images, divers had a significantly lower mean grey level (MGL) than non-divers. Divers with a history of DCI (n = 22) had a significantly lower MGL when compared with divers with no history of DCI (n = 22). Divers with > 14 years professional diving or > 100 decompression days a year had a significantly lower MGL value. CONCLUSIONS: Observer assessment of HMPAO-SPECT brain images can lead to disparity in results. Texture analysis of the brain images supplies both an objective and consistent method of measurement. A significant correlation was found between a low measure of MGL and a history of DCI. There was also an indication that diving itself had an effect on texture measurement, implying that it had caused subclinical nervous tissue damage.

Adult↗

Effect of inflammation on the proliferation of human gingival epithelial cells in vitro.

The adaptive or pathologic responses of epithelial cells to inflammation are poorly characterized. The purpose of this study was to determine if epithelial cells cultured from clinically healthy and inflamed human gingival tissues express differences in proliferation rate and viability. Briefly, the inflammation status of individual donor sites from 101 patients was visually assessed at the time of periodontal surgery and categorized as either non-to-slightly inflamed, moderately inflamed, or severely inflamed. Discarded gingival tissues were then processed to obtain primary cell cultures, for which proliferation rates were determined by calculating the ratio of mean population doublings to the number of days required for cultures to become confluent. In general, the cells in the minimally inflamed group exhibited characteristics different than cells in the moderately and severely inflamed groups. Specifically, the cells obtained from clinical sites which exhibited no-to-slight inflammation had a significantly higher mean proliferation rate than cells in either the moderate inflammation group or the severe inflammation group. Based on trypan blue exclusion, the cells obtained from clinical sites which exhibited no-to-slight inflammation also were more viable than cells obtained from sites with moderate inflammation or severe inflammation. Microscopic evaluation showed morphological changes associated with increased inflammation. Cell cycle analysis by fluorescent-activated cell sorting (FACS) revealed a directly proportional relationship between the degree of inflammation and apoptosis, and a strong inversely proportional trend between the degree of inflammation and the numbers of cells undergoing mitosis. Taken together, these data suggest that epithelial cell proliferation and viability are inversely associated with the degree of gingival inflammation, once a putative "adaptive threshold" is exceeded. Elucidation of the underlying mechanisms will likely lead to improvements in clinical diagnosis and treatment.

Adult↗

Breathlessness and exercise capacity in heart failure: the role of bronchial obstruction and responsiveness.

The cause of the breathlessness and reduced exercise capacity that occur in patients with chronic heart failure remains obscure. We examined the hypothesis that airway obstruction and bronchial hyper-responsiveness, which are recognised features of chronic heart failure, might contribute to the breathlessness and reduced exercise capacity in this condition. We studied 37 patients (7 female) with chronic heart failure, of mean age 61 years. Each patient underwent: (i) lung function testing with spirometry and expiratory flow volume loops. (ii) Measurement of bronchial responsiveness to methacholine. (iii) Symptom-limited treadmill exercise capacity using both incremental and fixed workload protocols, with measurement of Borg scores for breathlessness. Lung function was not significantly related to either exercise time, or Borg symptom scores in either exercise protocol. Bronchial hyper-responsiveness to methacholine was demonstrated in 12 patients. Exercise time did not correlate with the degree of bronchial hyper-responsiveness in these 12 patients. Group mean exercise time and Borg scores were not significantly different in these 12 patients when compared to the 25 patients in whom bronchial hyper-responsiveness was not found. We conclude that airway obstruction and bronchial hyper-responsiveness are not likely to be important determinants of reduced exercise capacity and breathlessness in chronic heart failure.

Airway Obstruction↗

Leucocyte filterability: comparing diluted blood with purified cell suspensions.

Current rheological trends in filtration studies involve purification of cell subpopulations in order to study near-homogenous populations of cells, and this means that time-consuming and possibly cell-damaging procedures are used. Filtration of diluted blood offers the possibility of determining the properties of subpopulations of cells with minimal cell manipulation. The filtration properties of granulocytes and lymphocytes result in their being detected as one kinetic population, and therefore a combined granulocyte/lymphocyte pore transit time is calculated. There was no significant change seen in the combined granulocyte/lymphocyte transit time over the normal range of differential count. Filtration of diluted blood is a more reproducible way of measuring granulocyte and lymphocyte filterability, because purification of these cells gives rise to more scatter and larger ranges in the measured pore transit time, and significant day-to-day variation. A combined granulocyte/lymphocyte transit time is therefore an acceptable and reproducible way of assessing leucocyte rheology in diluted blood, when the differential count lies within the normal range. If changes in the granulocyte/lymphocyte transit time are detected, then cell purification may yield additional information on the subpopulations. Therefore, particularly in pathological samples, a combination of these approaches will yield more information than either test alone.

Filtration↗

Effect of workbout duration on the physical working capacity at fatigue threshold (PWCFT) test.

The purpose of this study was twofold: (1) to determine the effect of increasing the duration of the workbout at each power output during the physical working capacity at fatigue threshold (PWCFT) test from 2 to 3 or 4 min, and (2) to examine the time to exhaustion during continuous workbouts at the PWCFT. Twelve adult males (means +/- SD = 22.4 +/- 3.0 years) volunteered to perform three PWCFT tests using workbout durations of 2, 3, and 4 min. Following the determination of the PWCFT values, nine of the subjects performed continuous workbouts at PWCFT2 and PWCFT4 for as long as possible. The mean PWCFT value using 4-min workbouts (PWCFT4 = 168.8 +/- 45.1 W) was significantly less (p < 0.05, 19.1%) than that using 2-min workbouts (PWCFT2 = 208.9 +/- 59.0 W). However, only two subjects were able to complete 60 min at PWCFT4 and none of the subjects were able to complete 60 min at PWCFT2. Therefore, although increasing the duration of the workbout at each power output resulted in a lower PWCFT4, these findings do not support a recommendation for a change in the PWCFT test protocol.

Adult↗

Pulmonary Mycobacterium kansasii infection: comparison of radiological appearances with pulmonary tuberculosis.

BACKGROUND: A study was undertaken to determine if there are differences in the radiological appearances at presentation between pulmonary infections caused by Mycobacterium kansasii and Mycobacterium tuberculosis. Correct recognition of the organism has important implications with regard to initial therapy and contact tracing. METHODS: The initial chest radiographs of 28 patients with pulmonary M kansasii infection were compared with those of 56 age, sex, and race matched patients with M tuberculosis infection. All patients in both groups were culture positive and none was known to be HIV positive. The radiographs were analysed independently by two radiologists who were unaware of the causative organism. RESULTS: Radiographic abnormalities in patients with M kansasii infection were more frequently unilateral and right side predominant, while those with tuberculosis more frequently involved a lower lobe. Air space shadowing involving more than one bronchopulmonary segment and pleural effusions were seen less frequently in M kansasii infection (four of 28 (14%) versus 30 of 56 (54%) and none of 28 versus 15 of 56 (27%)). Cavitation (21 of 28 (75%) versus 34 of 56 (61%) was seen to a similar extent in patients with M kansasii infection and in those with tuberculosis. Cavities tended to be smaller in patients with M kansasii infection (p < 0.01). CONCLUSIONS: Differences are seen in the radiographic appearances of pulmonary infection caused by M kansasii and M tuberculosis. These differences are not sufficient to allow a positive diagnosis on the basis of radiographic findings alone, but the presence of a pleural effusion or lower lobe involvement makes M kansasii infection very unlikely.

Diagnosis, Differential↗

Pulmonary Mycobacterium kansasii infection: comparison of the clinical features, treatment and outcome with pulmonary tuberculosis.

BACKGROUND: In the United Kingdom Mycobacterium kansasii is the most common pulmonary non-tuberculous mycobacteria to cause disease in the non-HIV positive population. METHODS: The clinical features, treatment, and outcome of 47 patients (13 women) of mean (SD) age 58 (17) years with culture positive pulmonary M kansasii infection were compared with those of 87 patients (23 women) of mean (SD) age 57 (16) years with culture positive pulmonary M tuberculosis infection by review of their clinical and laboratory records. Each patient with M kansasii infection was matched for age, sex, race and, where possible, year of diagnosis with two patients with M tuberculosis infection. RESULTS: All those with M kansasii infection were of white race. Haemoptysis was more common in patients infected with M kansasii but they were less likely to present as a result of an incidental chest radiograph or symptoms other than those due to mycobacterial infection. Patients with M kansasii were also less likely to have a history of diabetes, but the frequency of previous chest disease and tuberculosis was similar. An alcohol intake of > 14 units/week was less frequent in those with M kansasii, but there were no significant differences in drug history, past and present smoking habit, occupational exposures, social class, or marital status. Patients with M kansasii received a longer total course of antimycobacterial therapy and, in particular, extended treatment with ethambutol and rifampicin was given. There was no significant difference in outcome between pulmonary M kansasii or M tuberculosis infection. CONCLUSIONS: There are group differences between the clinical features of the two infections but, with the possible exception of diabetes and alcohol intake, these features are unlikely to be diagnostically helpful. Treatment of M kansasii infection with ethambutol, isoniazid, and rifampicin in these patients was as effective as standard regimens given to patients infected with M tuberculosis.

Adult↗