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Biomedical subjects

S Edwards

Publications and source records attributed to S Edwards.

At least 55 records · Page 3Linked to original sources

[Comparison of the emergency medical services systems of Birmingham and Bonn: process efficacy and cost effectiveness].

OBJECTIVE: Due to rising health care costs there is a need to verify that the treatment by Emergency Medical Services (EMS) systems is efficient and cost effective. The integration of emergency physicians is inherent part of out-of-hospital emergency care and regulated by law in Germany but not in England and the United States of America. Aim of this study therefore was to conduct a cost performance analysis by evaluating the underlying structure, the costs incurred and the achieved performance in two EMS systems with paramedics or emergency physicians on scene. METHODS: The study was carried out in West-Birmingham, a part of the West-Midlands-Ambulance-Service (WMAS), and the EMS of Bonn. Pre defined questionnaires, EMS protocols, calculations of purchasing power parity and recent publications concerning out-of-hospital resuscitation (CPR) were used to evaluate the operating costs, to describe the structure and to measure the quality of performance. Significance was assumed at p < 0.01 for CHI(2)- or t-test, respectively. RESULTS: Birmingham used state of the art technology for dispatch and logistics whereas Bonn trusted in high qualified personnel. In the 1st quarter 1997 the Mainz-Emergency-Evaluation Score could be achieved before (MEES A) and after preclinical treatment (MEES B) in 3502 and 3422 patients in Birmingham and Bonn, respectively. In Birmingham 7.5 % and in Bonn 17 % of all patients could be improved by the EMS treatment, respectively (p < 0.01). Looking at severely ill patients (MEES A < 22) the EMS in West-Birmingham achieved an improvement in 27.9 % of these patients with an averaged change in MEES of 0.9 +/- 1.7 points in all of them. In contrast the Bonn EMS improved the status in 47.8 % of these patients and MEES A could be improved considerably by 2.3 +/- 3.4 points (p < 0.01). Pharmacological treatment was less frequently used in Birmingham than in Bonn (12.9 % vs. 32.4 %, respectively; p < 0.01). At equal incidences of CPR attempts discharge rate after CPR was only 4 % in WMAS compared to 14.7 % in Bonn-North (p < 0.01). Per inhabitant and year total costs amounted to 10.43 euro for the EMS system in Birmingham, which is 42 % less than in Bonn. Unit hour utilisation reached 0.6 in Birmingham and only 0.33 in Bonn. In severely ill patients the improvement of MEES A by 0.1 points cost per inhabitant and year 1.16 euro in Birmingham and only 0.65 euro in Bonn. The survival of one patient after CPR was calculated to 0.7 euro in Birmingham and 0.17 euro in Bonn. CONCLUSIONS: The provider of the EMS in West-Birmingham--WMAS--organised a reliable system with high efficiency concerning unit hour utilisation and response time reliability. In the EMS of Bonn, in contrast, the complex therapy by the emergency physicians improved MEES considerably and increased probability of survival after CPR at a higher level of efficiency. Further investigations however are necessary to evaluate the presented parameter of efficiency.

Allied Health Personnel↗

Lactic acidosis in HIV infected patients: a systematic review of published cases.

OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.

Acidosis, Lactic↗

Bacterial community dynamics across a floristic gradient in a temperate upland grassland ecosystem.

Alterations in soil bacterial communities across a transect between a semi natural upland grassland and an agriculturally improved enclosure were assessed using culture-based methods and a nucleic-acid-based method, terminal restriction fragment length polymorphism (TRFLP). While plant diversity decreased across the transect towards the improved area, numbers of 16S rDNA terminal restriction fragments increased, indicating an increase in numbers of bacterial ribotypes. Bacterial numbers, microbial activity, and potential functional diversity also followed a similar trend, increasing with decreasing plant diversity. Alterations in bacterial community structure were coincident with changes in soil physicochemical properties which also changed across the transect. Increases in soil pH, nitrate, phosphorus, potassium, and calcium occurred toward the improved grassland, while organic matter and ammonium declined. The inverse relationship between floristic diversity and bacterial ribotype numbers suggests that soil physicochemical factors may be as influential in determining bacterial diversity in soils of upland grassland communities as floristic diversity.

Bacteria↗

Contamination of environmental surfaces by genital human papillomaviruses.

OBJECTIVE: To investigate contamination of environmental surfaces with human papillomaviruses (HPV) DNA in two genitourinary medicine (GUM) clinics and in an on-site staff leisure and fitness centre. METHODS: Samples were collected from the treatment rooms and patients' toilets of two GUM clinics situated at two hospital sites and from the toilets of the staff leisure and fitness centre on one of the sites. Samples were tested for the presence of HPV DNA by nested polymerase chain reaction (PCR), and HPV amplicons were typed by reverse line hybridisation using HPV type specific oligonucleotide probes complementary to 35 HPV types. All samples were also tested for beta globin DNA by PCR in order to assess their quality. RESULTS: HPV DNA was found to be present at more than 50% of the sites sampled in one of the GUM clinics, but was absent in the second, and also from the staff leisure and fitness centre. All HPV DNA detected was found to be cell associated. The most commonly found HPV types were 6, 11, and 16, respectively. HPV infected cells were found to be localised mainly to surfaces used predominantly by medical staff. CONCLUSIONS: This study has identified contamination of the environment of a GUM clinic. Possible sources for the contamination of the clinic toilets were from genital sites via hands to the environment. Within the treatment rooms the most likely route of HPV DNA contamination of the environment was via the doctor's gloved hands.

Ambulatory Care Facilities↗

News from the frontline: sexually transmitted infections in teenagers attending a genitourinary clinic in south east London.

OBJECTIVES: To define the incidence and characterise the clinical presentation of sexually transmitted infections (STI) in people aged <or=16 years old attending a genitourinary clinic in south east London. METHODS: Cross sectional analysis of clients aged <or=16 years attending one genitourinary clinic. A subgroup was identified for priority treatment. Data collected included age, reason for presentation, diagnosis, contraceptive use, and adherence to therapy. Diagnoses were compared to the KC60 codes for female attendances of all ages. RESULTS: 144 females and 18 males with a mean age of 15.4 years attended, of whom 49% were symptomatic. Compared to other attenders, clients aged <or=16 years were significantly more likely to have an STI (64% versus 22%, p <0.00000001); 27 were pregnant (of whom 96% requested a termination of pregnancy); 47% did not return for follow up; and 12% did not adhere to treatment plan. Those diagnosed with an STI were significantly less likely to reattend (p<0.001). CONCLUSIONS: There is a high rate of STIs in 16 year olds compared to national figures and to general clinic attenders. Poor contraception is often overlooked within the genitourinary medicine clinic. Young attenders frequently fail to reattend for follow up. Priority treatment did not affect outcome. Further strategies are needed to identify ways to improve young people's access to genitourinary medicine clinics.

Adolescent↗

Controlled trial of three weeks nicotine replacement treatment in hospital patients also given advice and support.

BACKGROUND: Smoking is a major public health issue, estimated as causing 120 000 deaths in the UK per year. Smoking cessation is an important aspect of the treatment of many diseases. Nicotine replacement therapy (NRT) has been shown to increase cessation rates among healthy volunteers and in general practice, but it is not clear whether it has an effect in hospital patients. METHODS: Patients referred by their hospital doctor to the smoking cessation counsellor and who agreed to participate in the study were randomised to receive either NRT given as a nicotine patch daily and a nicotine inhalator on an as needed basis plus advice and support (AS+NRT), or to receive just advice and support (AS). Claims of smoking cessation were validated at 1 week, 3 months, 6 months, and 1 year by carbon monoxide (CO) breath testing. RESULTS: A total of 245 patients were randomised, 136 AS+NRT and 109 AS. There were no significant demographic differences between the two groups at baseline. At 1 year 35 (14%) had sustained cessation confirmed by a CO breath test, 20/136 (15%) AS+NRT and 15/109 (14%) AS, p=0.857. One hundred and ten patients gave up smoking for at least 1 week, 54% AS+NRT and 33% AS (p<0.001). By 6 months there was no significant difference between the two groups (22/136 (16%) AS+NRT and 15/109 (14%) AS). CONCLUSION: In hospital patients NRT, given as regular daily patches plus an inhalator to be used as needed, did not add to the smoking cessation rate achieved at 1 year by regular advice and support, despite significantly increasing the cessation rate at 1 week.

Administration, Cutaneous↗

Lifestyle factors and Ki-ras mutations in colon cancer tumors.

Heterogeneity in colon tumors implies that environmental, lifestyle, or genetic factors influence the type of mutations seen in tumors. In this study we evaluate the association between previously identified risk factors for colon cancer and Kirsten-ras (Ki-ras) mutations in tumors. The presence of Ki-ras mutations in codons 12 and 13 were determined in a population-based case-control study of colon cancer. Participants were between 30 and 79 years of age at time of diagnosis and include both men and women. Questionnaire data were used to obtain information on lifestyle factors. Valid study data and Ki-ras mutational status were available from 1428 cases of colon cancer, data from 2410 controls were available for comparative purposes. Participants with Ki-ras mutations were more likely to have proximal rather than distal tumors. Cigarette smoking, use of aspirin and/or NSAIDs, use of vitamin/mineral supplements, and consumption of caffeine were associated with both Ki-ras+ and Ki-ras- tumors; the associations were not confounded by dietary intake or other lifestyle factors. Among men, but not among women, those with low levels of physical activity were more likely to have a tumor with a Ki-ras mutation than one without a Ki-ras mutation. However, among women, those with a larger BMI were more likely to have a Ki-ras mutation in their tumor. Given the limited information available on what causes Ki-ras mutations, the information generated from this study indicates that these factors previously associated with colon cancer work through other disease pathways.

Adult↗

Incidence, location, pathology, and significance of pulmonary homograft stenosis after the Ross operation.

BACKGROUND: The Ross operation has several theoretical advantages. However, concern exists regarding evolving pathology in the pulmonary homograft. METHODS AND RESULTS: Consecutive patients (n=144; mean age 31 years, range 2 months to 64 years) undergoing the Ross operation were studied between 1993 and 2000. Echocardiographic examination of the pulmonary homograft was performed immediately after surgery, then at yearly intervals for a mean interval of 48 months. Fifteen patients (mean age 37 years) in whom echocardiography revealed peak pulmonary gradients >/=30 mm Hg (mean 46+/-18 mm Hg) underwent MRI with velocity mapping in a Picker 1.5-T magnet. No patient had more than mild pulmonary regurgitation. Four patients required reoperation for rapidly progressive pulmonary homograft stenosis; in all 4, there was macroscopic and microscopic evidence of a pronounced chronic adventitial reaction, with perivascular infiltration producing extrinsic compression. Freedom from any pulmonary homograft stenosis at 7-year follow-up was 79.7%, with instantaneous hazard falling to zero after 4 years. Freedom from reoperation at 7 years was 96.7%. In those studied with MRI, there was evidence of narrowing of the whole homograft or distal suture line in 14 of 15 patients, with obvious excess surrounding tissue in 11. Mean minimum diameter and peak velocity by MRI were 11+/-2 mm and 3.2+/-0.7 m/s, respectively. Multivariate analysis of patient-, surgery-, and homograft-related variables did not reveal any significant risk factors for development of neopulmonary stenosis. CONCLUSIONS: Pulmonary homograft stenosis after the Ross operation is clinically important and appears to represent an early postoperative inflammatory reaction to the pulmonary homograft that leads to extrinsic compression and/or shrinkage.

Adult↗

CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers.

Variation in the penetrance estimates for BRCA1 and BRCA2 mutations carriers suggests that other genetic polymorphisms may modify the cancer risk in carriers. A previous study has suggested that BRCA1 carriers with longer lengths of the CAG repeat in the androgen receptor (AR) gene are at increased risk of breast cancer (BC). We genotyped 188 BRCA1/2 carriers (122 affected and 66 unaffected with breast cancer), 158 of them of Ashkenazi origin, 166 BC cases without BRCA1/2 mutations and 156 Ashkenazi control individuals aged over 56 for the AR CAG and GGC repeats. In carriers, risk analyses were conducted using a variant of the log-rank test, assuming two sets of risk estimates in carriers: penetrance estimates based on the Breast Cancer Linkage Consortium (BCLC) studies of multiple case families, and lower estimates as suggested by population-based studies. We found no association of the CAG and GGC repeats with BC risk in either BRCA1/2 carriers or in the general population. Assuming BRCA1/2 penetrance estimates appropriate to the Ashkenazi population, the estimated RR per repeat adjusted for ethnic group (Ashkenazi and non-Ashkenazi) was 1.05 (95%CI 0.97-1.17) for BC and 1.00 (95%CI 0.83-1.20) for ovarian cancer (OC) for CAG repeats and 0.96 (95%CI 0.80-1.15) and 0.90 (95%CI 0.60-1.22) respectively for GGC repeats. The corresponding RR estimates for the unselected case-control series were 1.00 (95%CI 0.91-1.10) for the CAG and 1.05 (95%CI 0.90-1.22) for the GGC repeats. The estimated relative risk of BC in carriers associated with > or =28 CAG repeats was 1.08 (95%CI 0.45-2.61). Furthermore, no significant association was found if attention was restricted to the Ashkenazi carriers, or only to BRCA1 or BRCA2 carriers. We conclude that, in contrast to previous observations, if there is any effect of the AR repeat length on BRCA1 penetrance, it is likely to be weak.

Adult↗

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity.

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.

Adrenal Cortex↗

Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci.

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

Chromosome Mapping↗

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

Algorithms↗

Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer.

There are sex differences in the occurrence of microsatellite instability (MSI) in colon tumors. Taken together with the epidemiological evidence that hormone replacement therapy (HRT) and, less consistently, parity, are inversely associated with colon cancer, it has been hypothesized that estrogens are associated with MSI. The purpose of this study was to evaluate sex-specific differences in the prevalence of MSI in colon tumors and to determine whether reproductive history and hormonal exposures are associated with MSI. Using data from a population-based case-control study of 1836 cases with MSI data and 2410 population-based controls, we evaluated sex, reproductive factors, and hormone exposure in relation to the presence or absence of MSI in tumors. MSI was evaluated by a panel of 10 tetranucleotide repeats, the noncoding mononucleotide repeat BAT-26, and the coding mononucleotide repeat in transforming growth factor beta receptor type II (TGFbetaRII). Exposure data on reproduction, hormone use, obesity, and physical activity were obtained from an interviewer-administered questionnaire. Women were less likely then men to have MSI+ tumors at a young age and more likely to have unstable tumors at an older age; we observed a significant interaction (P < 0.01) between age, sex, and MSI. Evaluation of reproductive factors showed that women who had ever been pregnant had half the risk of MSI+ tumors compared with women who had never been pregnant. In complementary fashion, total ovulatory months were associated with an increased risk of MSI+ tumors [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-4.0 comparing MSI+ versus MSI- tumors]. Age at first and last pregnancy did not influence the association. The observed associations were strongest among women <60 years of age at the time of diagnosis. Having used oral contraceptives was associated with a lower risk of MSI+ tumors (OR, 0.7; 95% CI, 0.4-1.2); recent users of HRT were at a reduced risk of MSI+ tumors (OR, 0.8; 95% CI, 0.5-1.4); and women who were former HRT users were at an increased risk of MSI+ tumors (OR, 1.8; 95% CI, 1.1-3.0). Obesity and lack of physical activity were associated with an elevated risk of both MSI+ (OR, 1.7; 95% CI, 0.7-3.3) and MSI- (OR, 2.2; 95% CI, 1.7-3.) tumors in men, but only with MSI- (OR, 1.5; 95% CI, 1.1-2.2) tumors in women. The excess of MSI+ tumors in women is explained by the excess of MSI+ tumors at older ages. Our data suggest that estrogen exposure in women protects against MSI, whereas the lack of estrogen in older women increases risk of instability. HRT in these older women may, again, reduce the risk of unstable tumors. A model for the way in which estrogens (endogenous, exogenous, and obesity-associated) modify the risk of MSI+ tumors is proposed.

Adipose Tissue↗