Transbronchial biopsy as a tool to evaluate small-airways disease in asthma. Cons.
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Biomedical subjects
Publications and source records attributed to A James.
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One of the commonest indications for PEG is nutritional support in dysphagia. We investigated the current practice of PEG insertion in South Wales (UK). A postal questionnaire was sent to hospital consultants with responsibility for acute medical/geriatric intake in the South Wales area. Eighty-eight of 114 (78.5%) responded. In 69 of 107 (65%) responses (Radiologists and Geriatricians also performed PEG in some hospitals) Gastroenterologists performed the insertion of PEG. Seventy-one (87%) always involved speech therapists before PEG insertion. Forty-five (55%) and 47 (57%) always involved dieticians and nurses, respectively. Eighty (92%) involved carers before PEG. Sixty-three (76%) used nasogastric feed for nutritional support before PEG. Thirty-six of 80 (45%) responses would wait more than 2 weeks before inserting PEG (range less than 7 days to more than 6 weeks). Five (6.5%) preferred long-term nasogastric feed to PEG. Twenty-five (30%) had definite knowledge of a PEG clinic in their hospital and 38 of 77 (49%) who responded to this question said there was no routine follow-up or were not aware about follow up of PEG patients. There is wide variation in the timing of PEG insertion and involvement of paramedical staff. More research needs to be undertaken to provide evidence so guidelines can be developed in this area. Follow up of patients with PEG is poor but current evidence suggests follow up of these patients may be worth while as some patients with dysphagic stroke can regain their swallow late.
UNLABELLED: The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any METHOD: Neither did any marker of airway inflammation relate to recent symptoms, unlike PC20, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s (FEV1) and both NO and sputum ECP (r=-0.46, p=<0.001; r=-0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV1 (PC20) (r=-0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.
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The region of human chromosome 6 containing the MHC has been identified as influencing asthma and atopy (allergy) by several genome-wide searches. The MHC contains many genes with potential effects on innate and specific immunity. As a first step in dissecting MHC influences on asthma and its underlying quantitative phenotypes, we have examined the HLA-DRB1 locus in a population sample consisting of 1004 individuals from 230 families from the rural Australian town of Busselton. The locus was strongly associated with the (log(e)) total serum IgE concentration, accounting for 4.0% of the sigma(2) (variance) in that trait (multi-allelic test, P=0.00001). The locus also influenced specific IgE titres to common allergens (multi-allelic tests, 2.8% sigma(2) for the house dust mite allergen Der p I, P=0.0013; 3.0% of sigma(2) for Der p II, P=0.0007; and 2.1% of sigma(2) for the cat allergen Fel d I, P=0.014). No associations were found to the categorical phenotype of asthma, or to the quantitative traits of peripheral blood eosinophil counts and bronchial hyper-responsiveness. Transmission disequilibrium tests excluded genetic admixture as a cause of false-positive findings. The results indicate that HLA-DRB1 alleles modulate the total serum IgE concentration and IgE responses to allergens, but do not account for the previous observations of linkage of asthma to the MHC.
The recent move to revitalize social democracy in the UK under the New Labour government, explored by Giddens as 'the Third Way', embraces many of Etzioni's ideas on communitarianism. The principles that emerge from these political philosophies, such as the involvement of local communities in policy consultations and implementation, have largely been welcomed as a reflection of the aim of revitalizing civic society in the context of a range of social policies. It is argued, however, that for children, contrary to this general trend, many of these policies represent attempts to increase the social control of children. Their effect has been to restrict children's agency and their rights, rather than to increase their participation as citizens, and thus,in spite of the requirements of the UN Convention on the Rights of the Child, children continue to be marginalized.
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BACKGROUND: Children with difficult asthma experience frequent symptoms despite treatment with high dose inhaled steroids. Persistent symptoms may result from persistent airway inflammation which can be monitored by measuring exhaled nitric oxide (NO). This study aimed to assess the role of airway inflammation, using NO as a surrogate, in children with difficult asthma and to investigate the response to oral prednisolone. METHODS: NO was measured in 23 children (mean age 11.7 years) with difficult asthma, before and after 2 weeks of treatment with oral prednisolone. The clinical response was assessed by spirometric tests, peak flow, bronchodilator use, and symptoms. Adherence to treatment was assessed by measuring serum prednisolone and cortisol concentrations. NO was measured in 55 healthy children to establish a normal range. RESULTS: NO concentrations were higher in asthmatic patients than in controls (geometric mean 11.2 v 5.3 ppb, p<0.01). Using grouped data, the concentration of NO fell following prednisolone (11.2 v 7.5 ppb, p<0.01) accompanied by an improvement in morning peak flow (p<0.05). The baseline NO concentration was raised (>12.5 ppb) in nine asthmatic patients and remained high after prednisolone in five. Thirteen had normal levels of NO (<12.5 ppb) before and after prednisolone. Thirteen asthmatic patients remained symptomatic following prednisolone; NO levels were raised on both occasions in five of these and were normal in seven. CONCLUSIONS: As a group, the asthmatic subjects demonstrated evidence of airway inflammation which responded to prednisolone. At least two subgroups of patients were identified: one with persistently raised NO levels despite treatment with oral prednisolone indicating ongoing steroid insensitive inflammation, and another with normal levels of NO. Both subgroups included patients with persistent symptoms, which suggests that different patterns of difficult asthma in children exist.
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A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.
(E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic vinylic substitution (S(N)V) with mercaptans, including thiouracile, to give the corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2-(methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding thioether by reaction with methyl iodide in diethyl ether, underwent isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO with an activation energy of 14 kcalmol(-1). At pH 7, the (E)-1-methyl-4-[2-(methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was a second-order reaction (k = 4,100 M(-1)s(-1) at 30 degrees C) and gave the corresponding substitution product with an intense long wavelength absorption band (lambdamax=360 nm, epsilon = 27,500 M(-1)cm(-1)). The modification of different enzymes of known structure with 19 showed the high selectivity of this reagent towards thiol groups and its usefulness in the quantitative determination of free thiol groups in proteins.
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OBJECTIVE: To examine the association of social desirability (SD) responding ("defensiveness") and cortisol levels. METHODS: Marlowe-Crowne SD scores and morning salivary cortisol were measured in firefighters. RESULTS: SD scores were associated with higher cortisol levels (r=.28) in 60 firefighters under age 45, but not in 25 older firefighters (or the combined sample). CONCLUSION: The results are consistent not only with SD scores being an indicator of coarctation of experience as a coping mechanism, but also (at least for younger persons) perhaps a risk factor for the psychobiological dysfunctions associated with chronic elevations of cortisol.
Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Antibodies to the adhesion molecules CD44, E-cadherin, ICAM- 1, and integrin chains alpha2, alpha3, alpha4, alpha5, alpha6, alpha v, beta1, beta3 and beta7 failed to inhibit breast cancer cell migration through bone marrow fibroblasts. Inhibitors of matrix metalloproteases, 1, 10-phenanthroline, Ro-9790, TIMP-1 and TIMP-2 were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts. Modulation of MMP production by cell-cell contact or soluble factors suggests a mechanism by which breast cancer cells can enhance their ability to invade the bone marrow microenvironment.
Smooth muscle is present and probably functional in the airways in utero and increases in absolute area during growth with little further change during adulthood. It encircles the entire airway below the level of the main bronchus, in a roughly circular orientation, except at high lung volumes. It occupies relatively more of the airway wall in the peripheral airways, reaching a maximum in the membranous bronchioles. Measurement of smooth muscle area in the airway wall is confounded by clinical classification of cases, methods of tissue retrieval and preparation, staining and orientation of sections, magnification, image analysis and statistical methods of comparison between groups. Airway smooth muscle area is pathologically increased in inflammatory conditions of the airways such as chronic obstructive pulmonary disease, in relation to airways obstruction, and asthma, in relation to severity and airway size (between 25 and 250% compared with control cases). It is increased in sudden infant death syndrome, but there are few studies in other conditions such as bronchiectasis. In asthma, smooth muscle must shorten (not necessarily to an abnormal degree) for the structural abnormalities of the airway to manifest as excessive airway narrowing. Not surprisingly there is renewed interest in the relationships between the mechanical and contractile properties of smooth muscle, parenchymal properties and lung volume and how these interact to determine smooth muscle length. The relative importance of smooth muscle area and mechanical properties, altered airway structure and airway inflammation in disease are yet to be determined.
An adaptive psychophysical procedure was used to estimate the vibration detection threshold at seven spatially matched sites on the two sides of the face and at one scalp site. Repeated measurements over six testing sessions were made for stimuli vibrating at 1, 10 and 100 Hz for each of 21 neurologically healthy, young adult females. Approximately 14 stimulus trials were required to obtain each estimate of the threshold amplitude. Thresholds varied as a function of frequency (p < 0.0001), side (p < 0.001) and site (p < 0.0001). Compared to stimulation at 100 Hz at which the estimates were lowest, thresholds were 3.1 times greater at 10 Hz and 5.4 times greater at 1 Hz. Thresholds were lowest on the vermilion and highest on the cheek and chin. The preauricular skin and scalp exhibited an intermediate level of sensitivity. Whereas thresholds were comparable on the two sides of the face for stimulation at 1 Hz, they averaged 1.33 times greater on the right side for stimulation at 10 and 100Hz. Moreover, thresholds obtained during the last two sessions were 16% higher than those obtained during the first two sessions (p < 0.02), suggesting that subjects on average became more conservative in reporting the presence of the stimulus. The sensitivity in discriminating differences in tactile function favors use of the rapidly administered testing procedure in a clinical setting.
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