Search PubMed⌕ Search

Biomedical subjects

I Fraser

Publications and source records attributed to I Fraser.

At least 19 recordsLinked to original sources

Systemic sensitivity to corticosteroids in smokers with asthma.

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.

Adult↗

The role of stable isotopes in human identification: a longitudinal study into the variability of isotopic signals in human hair and nails.

Recent natural catastrophes with large-scale loss of life have demonstrated the need for a new technique to provide information for disaster victim identification when DNA methods fail to yield the identification of an individual, or in other situations where authorities need to determine the recent geographical life history of people. The latter may be in relation to the identification of individuals detained on suspicion of terrorism or in relation to people-trafficking or smuggling. One proposed solution is the use of stable isotope profiling (SIP) using isotope ratio mass spectrometry (IRMS). Exploiting the link between the isotopic signal of dietary components and the isotopic composition of body tissue, the aim of this study was to refine a non-invasive method of analysing human material such as scalp hair and fingernails using SIP and to assess the degree of natural variability in these profiles. Scalp hair and fingernail samples were collected from British and non-British volunteers at Queen's University Belfast every 2 weeks for a minimum of 8 months. Samples were analysed using IRMS to determine their isotopic composition for 13C, 15N, 2H and 18O. The results of this longitudinal study yielded information on the natural variability of the isotopic composition of these tissues. The data demonstrate the relatively low degree of natural variation in the 13C/15N isotopic abundance of scalp hair and fingernails whilst greater variations were recorded in the hydrogen and oxygen values of the same samples. The 15N and 18O values of nail are noticeably more variable than that of scalp hair from the same subject. A hypothesis explaining this trend is put forward based on the faster rate of formation of hair than of nails. This means that there is less time for the compounds forming hair to be affected by biochemical processes that could alter their isotopic signature.

Biomarkers↗

Serum and sputum neurotrophin levels in chronic persistent cough.

BACKGROUND: Neurotrophins (NTs) are a family of growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin3 (NT-3) that are involved in inflammation. Serum and induced sputum NT levels are increased in asthma and in cough because of idiopathic pulmonary fibrosis, respectively. Neurogenic inflammation is implicated in the pathogenesis of chronic cough in individuals with normal chest radiography, but the role of NTs in this condition is unknown. OBJECTIVE: To assess if NT levels are elevated in the serum and airways in subjects with chronic persistent cough. METHODS: Eighty-one subjects with chronic cough persistent for over 1 year; with normal chest radiography and spirometry were included. Thirty healthy subjects were controls. Serum NGF, BDNF and NT-3 were measured by enzyme immunoassay. In a subset, NGF was measured in induced sputum. Sputum cell counts and allergen-specific serum IgE were measured and all patients received specific sequential treatment trials to achieve a final diagnosis for the cough. RESULTS: There was no significant difference either in the levels of serum or sputum NTs in chronic cough subjects compared with controls or between the most common causes of cough: post-nasal drip syndrome, gastro-oesophageal reflux disease, asthma and bronchiectasis. The median (inter-quartile range) for sputum NGF (pg/mL) was 516 (296-772) in healthy controls and 580 (312-880) in subjects with chronic cough (P=0.284). There was no correlation between NT levels and sputum cell counts. Sputum NGF levels correlated with duration of cough (r=0.34, P=0.002). CONCLUSION: NTs are not elevated in induced sputum or serum of subjects with chronic persistent cough. This implies that NTs do not have a central role in perpetuating airway inflammation in chronic persistent cough.

Adult↗

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

Animals↗

Effect of aging on pheromone emission from a commercial beet armyworm (Lepidoptera: Noctuidae) lure and trap efficiency.

The effect of aging on a commercial pheromone-based lure for attractiveness to male adult beet armyworms, Spodoptera exigua (Hübner), was assessed in terms of trapping efficiency and volatile emissions of two key components: (Z,E)-9,12-tetradecadienyl acetate and (Z)-9-tetradecen-1-ol. In field assays conducted in the Lower Rio Grande Valley, Texas, for 9 wk (June-August 2000) and for 8 wk (March-May) in Tamaulipas, Mexico, 0-1-wk-old lures collected greater than four-fold more male beet armyworm adults than lures that had been aged for 3-4 wk. Using solid phase microextraction and gas chromatographic analysis of the volatiles, mean (Z,E)-9,12-tetradecadienyl acetate emission declined by 32% after 5 wk of aging in a ventilated environmental chamber at 29.4 degrees C, 3.5% RH, to simulate subtropical summers. Mean (Z)-9-tetradecen-1-ol emission was reduced by 62% after 4 wk of aging. Under the tropical and subtropical conditions of this study, the capacity of the lure to attract moths into the trap declined after aging for 3 wk. The blend ratio (Z,E) -9,12-tetradecadienyl acetate: (Z)-9-tetradecen-1-ol declined 29% when the lure was aged for 5 wk. This study will assist in the development of a standard trapping system for assessing adult beet armyworm populations in the tropical and subtropical conditions to which the species is endemic.

Animals↗

Molecular epidemiology of two fowl cholera outbreaks on a free-range chicken layer farm.

Two outbreaks of fowl cholera on a multiage free-range egg farm were investigated. The outbreaks occurred in 1994 and 2002. A total of 22 strains of Pasteurella multocida were available for study, 11 from the 1994 outbreak and 11 from the 2002 outbreak. Lesions typical of acute fowl cholera were seen in the 1994 outbreak, whereas both acute and chronic fowl cholera occurred in the 2002 outbreak. The isolates were examined in an extended phenotypic typing methodology, by a P. multocida-specific polymerase chain reaction (PCR), by the Heddleston somatic serotyping scheme, and by restriction endonuclease analysis (REA) typing using the enzyme HpaII. All 22 strains had the same phenotypic properties, all were confirmed as P. multocida by PCR, all were Heddleston serovar 4, and all had the same REA pattern. The results indicate that these 2 outbreaks were caused by the same clone of P. multocida--despite the 8-year time period between the outbreaks.

Animal Husbandry↗

Factors affecting the extent of dermal absorption of solvent vapours: a human volunteer study.

OBJECTIVES: We have previously reported that solvent vapours can be absorbed through the skin and that the extent varies markedly and depends on the chemical. For some chemicals, the extent of absorption is significant, e.g. for 1-methoxy-2-propanol dermal absorption accounts for up to 14% of the total absorbed dose after 8 h exposure at the OES. We have conducted a second study using 2-butoxyethanol to investigate the influence of temperature, humidity and clothing on the dermal absorption of vapours. As for the first study, the extent of dermal absorption was determined by biological monitoring to measure the resultant body burden of the chemical. METHODS: Four volunteers were exposed on nine occasions. For eight of these exposures they wore air-fed half-masks to supply clean air for the inhalation route. The 'baseline' conditions (one 'whole body' and one 'skin only' exposure) were 25 degrees C, 40% relative humidity with volunteers wearing shorts and T-shirt. For each subsequent exposure, a single parameter was changed: humidity (60%, 65%), temperature (20 degrees C, 30 degrees C) or clothing (minimal and overalls). Finally, a 'industrial scenario' was conducted where volunteers wore overalls over their shorts and T-shirts and environmental conditions reflected high temperature and high humidity (30 degrees C, 60%), such as might be encountered in a tank-cleaning operation or similar. RESULTS: Results show that 'baseline' dermal absorption of 2-butoxyethanol vapour was, on average, 11% of the total absorbed dose. Higher temperature (30 degrees C, mean 14%, P = 0.03) and greater humidity (65% RH, mean 13%, P = 0.1) increased dermal absorption. The wearing of whole-body overalls did not attenuate absorption (mean 10%). By combining several factors together in the 'industrial scenario', dermal absorption of vapours was significantly increased with a mean of 39% of the total absorbed dose. CONCLUSIONS: The work has shown that dermal absorption of vapours can be significant and that environmental conditions may affect the absorption. Some types of protective clothing may not be suitable to reduce absorption. The possibility of dermal absorption of vapours should be considered particularly for workers in high vapour concentration conditions where control of exposure relies on respiratory protection.

Adult↗

Telomerase expression of malignant epithelial cells correlates with Dukes' stage in colorectal cancer.

BACKGROUND: The ribonucleoprotein telomerase has been proposed as a potential prognostic marker for malignancy. Whether telomerase activity of clinical specimens correlates with other clinico-pathological variables, however, remains controversial. This is at least in part due to the varying contribution that nonmalignant cells will make to the net activity when extracts are assayed for telomerase activity. We therefore designed experiments to assay telomerase activity of isolated malignant cells of primary colorectal cancers. METHODS: Thirty colorectal cancer and 20 corresponding specimen taken from macroscopically normal regions of the colon were mechanically disaggregated and digested with collagenase, DNase and hyaluronidase. The epithelial cell population was separated using Ber-EP4 pan-epithelial antibody and Magnetic Activated Cell Sorting technique. Haematoxylin and eosin staining was used to assess the proportion of recovered epithelial cells which were malignant. Telomerase activity was assayed by the Telomeric Repeat Amplification Protocol, which was quantified by PhosphorImager with Image Quant software. RESULTS: Epithelial cells of three of 20 normal mucosa specimens were telomerase positive with weak activity (mean 3.7 TPGs, Total Product Generated, range 1.4-5.1TPGs). In the cancer group the vast majority (>95%) of the epithelial cells recovered were malignant by cytological criteria. Epithelial cells were telomerase positive in all the cancers, with a wide range of telomerase activity values (mean 22.7 TPGs, range 0.19-308 TPGs). Telomerase activity correlated with Dukes' stage (r = 0.52, P=0.004, Spearman's rank). CONCLUSIONS: Pathological stage correlates with telomerase activity of the malignant cell population of the primary tumour in colorectal cancer. This suggests that telomerase activity increases during the progression of a cancer and may have implications for the design of anticancer (antitelomerase) agents.

Journal Article↗

The secret (GTN) of successful ERCP cannulation: a prospective randomised controlled study.

BACKGROUND: A key step for success at endoscopic retrograde cholangio-pancreatography (ERCP) is cannulation of the sphincter of Oddi. This prospective randomised controlled study was conducted to assess the effect of glyceryl trinitrate (GTN) on ease of cannulation. METHOD: Two hundred and fifty four patients undergoing ERCP were randomised into two groups, 126 controls and 128 pre-treated with GTN. RESULT: There were 29 cannulation failures in the whole group (overall failure rate of 11.4%). Failure was significantly less common in the GTN group, 7.03% (9/128) as compared with 15.8% (20/126) in the control group (p=0.0002). Deep cannulation was desired but not achieved in 45/200 patients (22.5%) Of these, 18.4% (19/103) were in the GTN group versus 26.8% (26/97) in the control group. This pattern of difference applied to both trained and trainee endoscopists. No significant side effects of GTN were noticed. CONCLUSION: GTN appears to be safe and effective in improving ERCP success rate. We recommend its routine use.

Aged↗

Butadiene--progress under the European Union Existing Substances Regulation.

A draft risk assessment report (RAR) for 1,3-butadiene has been produced by the UK under the European Union's Existing Substances Regulation (ESR). In line with the requirements of ESR, the RAR presents an evaluation of the hazards and risks of butadiene to human health (for workers, consumers and the general public) and to the environment. If as a result of the risk assessment, concerns for human health and/or the environment are identified, proposals for measures to reduce those risks may be developed. In relation to the human health elements of the ESR RAR for butadiene, the risk assessment involves a comparison of health effects against exposures in the three population sectors. The position arrived at on risk is described in qualitative rather than quantitative terms. For butadiene, the conclusion reached for the human health hazard assessment has been influenced significantly by both the animal and human data available. Species differences in toxicity, in particular with regard to mutagenicity and carcinogenicity, are considered along with the mechanistic arguments for these differences and their relevance for human health. The information presented in the RAR has been extensively discussed within the EU and a generally agreed position has been reached, with respect to human health hazard and risk. It is concluded that whilst the risks to human health at current exposure levels in the workplace, for consumers and following exposure via the environment are uncertain, there are concerns for human health effects for all three populations. Thus, there is a need to limit the risks. The next stage in the ESR process will be to consider what, if any, additional risk reduction measures may be required, taking into account existing control measures.

Butadienes↗

A prospective randomised multicentre trial comparing 10 Fr Teflon Tannenbaum stents with 10 Fr polyethylene Cotton-Leung stents in patients with malignant common duct strictures.

BACKGROUND: Stent blockage is a multifactorial process in which stent design and materials, bacteria, proteins, and bile viscosity play a role. AIMS: To compare the patency of the 10 Fr Teflon Tannenbaum (TT) stent to that of the 10 Fr Cotton-Leung (CL) polyethylene stent with sideholes, in patients with malignant obstructive jaundice. METHODS: Patients were recruited to this prospective multicentre randomised study if they had a newly diagnosed malignant bile duct stricture below the hilum of the liver suitable for stenting with a 10 Fr stent. Data were collected and monitored by a professional monitoring company. Primary patency was the interval between stent placement and first exchange or death without recurrent jaundice. RESULTS: 134 consecutive patients were recruited between November 1994 and June 1997; 65 were randomised to the TT stent and 69 to the CL stent. Median patency and 95% confidence intervals were 181 (59, 303) days for the TT stent and 133 (92, 174) days for the CL stent, with no significant difference between the two stents (p=0.49). Median survival and 95% confidence intervals were 115 (71, 159) days for the TT stent and 151 (112, 190) days for the CL stent, with no significant difference between the two stents (p=0.765). CONCLUSION: Neither Teflon as a stent material nor the Tannenbaum design prolong the patency of plastic stents.

Adult↗

Can cultural competency reduce racial and ethnic health disparities? A review and conceptual model.

This article develops a conceptual model of cultural competency's potential to reduce racial and ethnic health disparities, using the cultural competency and disparities literature to lay the foundation for the model and inform assessments of its validity. The authors identify nine major cultural competency techniques: interpreter services, recruitment and retention policies, training, coordinating with traditional healers, use of community health workers, culturally competent health promotion, including family/community members, immersion into another culture, and administrative and organizational accommodations. The conceptual model shows how these techniques could theoretically improve the ability of health systems and their clinicians to deliver appropriate services to diverse populations, thereby improving outcomes and reducing disparities. The authors conclude that while there is substantial research evidence to suggest that cultural competency should in fact work, health systems have little evidence about which cultural competency techniques are effective and less evidence on when and how to implement them properly.

Acculturation↗

Employers: quality takers or quality makers?

This article provides a synthesis of past research to help understand the extent to which employers are using their considerable market power to drive health care quality. Are employers quality takers or quality makers? The literature provides some clues about aspects of quality employers are attempting to influence, strategies they are pursuing to influence quality, and their impact. Some employers are interested in some indicators of quality and are incorporating them in a variety of different purchasing strategies. The indicators most frequently used by employers, however, probably are not the ones that clinical experts and policy makers would select as most reflective of clinical quality. It appears that employers as a group are becoming more informed quality takers but are not yet quality makers--with the exception of a few well-resourced outliers. Recent events provide mixed signals about whether the future employer role in influencing quality will diminish, stall, or flourish.

Commerce↗

Wrestling with typology: penetrating the "black box" of managed care by focusing on health care system characteristics.

The health care system has undergone a fundamental transformation undermining the usefulness of the typology of the health maintenance organization, the independent practice association, the preferred provider organization, and so forth. The authors present a new approach to studying the health care system. In matrix form, they have identified a set of organizational and delivery characteristics with the potential to influence outcomes of interest, such as access to services, quality, health status and functioning, and cost. The matrix groups the characteristics by domain--financial features, structure, care delivery and management policies, and products--and by key roles in the health care system--sponsor, plan, provider intermediary organization, and direct services provider. The matrix is a tool for researchers, administrators, clinicians, data collectors, regulators, and other policy makers. It suggests a new set of players to be studied, emphasizes the relationships among the players, and provides a checklist of independent, control, and interactive variables to be included in analyses.

Data Collection↗