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Biomedical subjects

A Buckley

Publications and source records attributed to A Buckley.

At least 19 recordsLinked to original sources

Posttransplant lymphoproliferative disorder: a pictorial review.

Posttransplant lymphoproliferative disorder (PTLD) is a serious and potentially fatal complication after solid organ and haemopoietic stem cell transplantation. The frequency of PTLD varies with the type of organ transplant but overall it affects 2-10% of all solid organ transplant recipients. Most cases develop within 1 year after the transplant, although occasional cases present 5-10 years later. Posttransplant lymphoproliferative disorder is clinically and pathologically heterogeneous - the majority are of the non-Hodgkin's lymphoma type, whereas Hodgkin's lymphoma arising after transplantation is rare. We have retrospectively reviewed patients with a histological diagnosis of PTLD after a solid organ transplant. We present the imaging features and a clinical review of this condition. Early diagnosis of PTLD may alter the management and outcome of the disease. The radiologist can play a vital role in establishing the diagnosis by imaging features supplemented with percutaneous biopsy and also in monitoring the disease response to treatment.

Humans↗

Proxy completion of EQ-5D in patients with dementia.

There are measurement difficulties associated with the assessment of health-related quality of life (HRQL) in older people with dementia. The use of proxies is a commonly employed approach to overcome such problems. The research reported in this paper sought to identify, specifically for the EuroQol EQ-5D HRQL instrument, whether construct validity is greater for 'family caregivers' or 'clinicians' as two alternative sources of proxy information for patients with a diagnosis of dementia. This involved the exploration of the strength of the associations between clinical measures of illness severity and EQ-5D data. The data appear to reveal a pattern suggesting that the viewpoint of the proxy (i.e., clinician or family caregiver) is important. The findings suggest that the data provided by clinicians (when compared to data from carers) had higher construct validity for the more observable dimensions of the EQ-5D instrument (i.e., 'mobility' and 'self-care'). Conversely, the data from family carers had higher construct validity for the less observable dimensions (i.e., 'usual activities' and 'anxiety/depression'). Previous research on proxy provision of HRQL data has tended to focus on trying to identify a single proxy. The results of this study suggest that using carefully matched sets of measures and assessment perspectives may produce more valid EQ-5D health state descriptions.

Activities of Daily Living↗

Characteristics of US adults with the metabolic syndrome and therapeutic implications.

BACKGROUND: The third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program defines clinical criteria for diagnosis of the metabolic syndrome, which increases cardiovascular risk and is a target for therapy. AIM: We analysed the third National Health and Nutrition Examination Survey (NHANES III; 1988-94) to determine how many US adults meet these criteria and are recommended for lipid-modifying drug therapy by ATP III. METHODS: NHANES III data were used to estimate the number of individuals with the metabolic syndrome and the number recommended for treatment by ATP III, based on 1990 census data. RESULTS: An estimated 36.3 million (23%) US adults have the metabolic syndrome. Of these, 84% met the criterion for obesity, 76% for blood pressure, 75% for HDL-C, 74% for triglycerides and 41% for glucose. Most (54%) are in the higher risk categories of ATP III, yet only 39% overall are recommended for drug therapy by ATP III cutpoints; of these, most will achieve LDL-C targets with reductions of 35-40%. Of the 15.3 million individuals with the metabolic syndrome and triglycerides > or = 2.26 mmol/l (200 mg/dl), non-HDL-C is above ATP III recommendations in 11.6 million. CONCLUSIONS: Of the large number of Americans with the metabolic syndrome, ATP III recommends drug therapy for only a minority, because LDL-C typically is not substantially elevated. Instead, high triglycerides and low HDL-C are more common; clinical trial data are needed to determine whether optimal therapy should focus on reductions in LDL-C or on comprehensive improvements to the lipid profile.

Adult↗

Understanding of informed consent by demented individuals.

BACKGROUND: The informed consent process is central to the conduct of research but may be difficult for cognitively impaired participants to understand. The authors developed a brief test addressing the elements of informed consent for a specific minimum-risk nontreatment research protocol. OBJECTIVE: To evaluate and document understanding of informed consent by elderly research participants across a range of dementia severity. METHODS: The elements of informed consent regarding participation in a longitudinal study of healthy aging and dementia were reviewed with both demented (n = 250) and nondemented (n = 165) participants who then completed a short test requiring yes-no responses to assess understanding of these elements. Demented participants had very mild, mild, or moderate dementia as staged by the Clinical Dementia Rating. RESULTS: After adjusting for education, performance on the test varied with dementia severity in mean differences and by correlation. All nondemented and very mildly demented participants and 92% of mildly demented participants provided correct answers for at least 8 of 10 true-false items, whereas only 67% of the moderately demented participants achieved this level of accuracy. CONCLUSIONS: Demented individuals, very mild and mild, understood informed consent information for this nontreatment research study. Understanding notably declined in the moderate stage of dementia. Brief tests may be useful as one method to assess understanding of the consent process for specific studies.

Aged↗

Experimental studies of sewer exfiltration.

The effects of joint openings and in-pipe sediment on exfiltration losses in an experimental sewer are reported and the influence of flow and head on loss rates are also evaluated. Exfiltration rates tend to be exponential with changes in head for clean-water tests but exhibit power functions when the pipe is subject to sedimentation. In-pipe sediment leads to an effective sealing of joints especially if the invert deposits are both organic in nature and contain saturated adhesive material such as shredded toilet tissue. Simple tracer techniques are described to quantify exfiltration losses and the potential effects of tracer adsorption by pipe solids are evaluated.

Adsorption↗

The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation.

BACKGROUND: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. OBJECTIVES: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). METHODS: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques. RESULTS: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). CONCLUSIONS: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.

Aged↗

Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation.

AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.

Apoptosis↗

Preliminary report: skeletal muscle cell lipid and oxygen supply.

In a group of 12 normal-weight, normotensive, nondiabetic adult females, the intramyocellular lipid (IMCL) to creatine ratio of the soleus muscle was determined using localized (1)H-magnetic resonance spectroscopy ((1)H-MRS) and related to skeletal muscle blood (and oxygen) supply (as assessed by near infrared spectroscopy [NIRS] of the forearm). A significant positive association was found between IMCL content and reoxygenation rate of forearm muscle hemoglobin (Hb) after 1 minute of ischemic exercise (r = .70, P = .01). The relative efficiency of skeletal muscle oxygen supply may be a determining factor of IMCL content in skeletal muscle.

Adult↗

Does the presence of hibernating myocardium in patients with impaired left ventricular contraction affect QT dispersion?

BACKGROUND: Hibernating myocardium is associated with increased cardiovascular events. Increased QT dispersion on the surface electrocardiogram is a marker for serious ventricular arrhythmias. In this study, we determine whether hibernating myocardium is associated with increased QT dispersion in patients with coronary artery disease and impaired left ventricular contraction. METHODS: Positron emission tomography with (13)N-ammonia and (18)F-fluorodeoxyglucose determined the presence of metabolic-perfusion mismatch defect. QT dispersion was measured by means of a digitizing tablet with validated software. QT intervals were measured on two separate occasions by two investigators blinded to the result of the positron emission tomography scans. RESULTS: Forty-two patients with impaired left ventricular contraction were studied. They were divided into two groups: group A was made up of patients with mismatch defects (n = 26) and group B was made up of patients with no mismatch defects (n = 16). The mean (SD) QT dispersion measurements were 61.7 +/- 29.8 ms and 70 +/- 24.6 ms for groups A and B, respectively (not significant). When the patients were divided according to the dominant viability status of the impaired myocardial segment, a similar result was found. The patients whose impaired myocardium was dominantly hibernating (n = 19) had a mean QT dispersion of 66.4 +/- 31.9 ms compared with 63.6 +/- 24.8 ms in the patients whose impaired myocardium was mainly scarred (not significant). CONCLUSIONS: QT dispersion is not affected by the presence of hibernating myocardium and is therefore not clinically useful in identifying patients with this phenomenon. This is in contrast with recent reports by other groups and calls for further investigation of this dichotomy.

Ammonia↗

EQ-5D in patients with dementia: an investigation of inter-rater agreement.

BACKGROUND: There are difficulties in obtaining health-related quality of life (HRQL) data from patients with dementia due to variation in their cognitive ability, degree of insight and capacity to make judgments. The use of proxies is one solution. OBJECTIVES: To examine the inter-rater agreement of patient and proxy completion of the EuroQol EQ-5D instrument (EQ-5D). RESEARCH DESIGN: The EQ-5D instrument was completed separately by patients, their caregivers and a physician. Assessment of inter-rater agreement involved comparison of self-completed (patient) and proxy-completed (caregiver and physician) responses for each dimension of EQ-5D, using a weighted kappa score. Three key hypotheses were tested. (1) Interrater agreement would be stronger between patient and caregiver than between patient and physician. (2) Interrater agreement would be stronger on the 'observable' and objective dimensions of EQ-5D. (3) Interrater agreement between patient and proxies would be stronger for patients with earlier dementia. SUBJECTS: The sample comprised 64 patients with a range of dementia severity. MEASURES: The EQ-5D health state classification system and visual analogue scale were used to assess HRQL. Global severity of dementia was determined using the Clinical Dementia Rating Scale. RESULTS: The principal finding of this study was that responses to EQ-5D questions were highly variable across the three raters such that none of the three hypotheses were strongly supported. CONCLUSIONS: The data provide some support for the use of EQ-5D when interviewer administered. However, there are serious concerns regarding the validity of patient self-rated HRQL data obtained in this study and uncertainty exists regarding who the appropriate proxy should be, as different groups of proxies provide different results. It was not clear whether caregivers or physicians represent better proxies. Further research should focus on the comparison of caregivers and physicians as proxies.

Activities of Daily Living↗

Lactogenic immunity following vaccination of cattle with bovine coronavirus.

In order to investigate the ability of an oil adjuvanted vaccine containing bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant cows and heifers were vaccinated and specific virus neutralising antibody levels determined in serum, colostrum and milk. Pre-existing antibody titres (as a result of natural infection) in the serum of these animals were found to be significantly increased as a result of a single shot vaccination carried out between 2 and 12 weeks before calving. This was reflected in a similar increase in the titre and duration of specific antibody in milk and colostrum that was passed on to the calves. The overall response observed was highly dependent on an adequate antigen payload being incorporated within the single dose vaccine. No abnormal local or systemic reactions were observed as a result of vaccination. It is hoped that this approach will lead to the production of a superior commercial vaccine for the protection of neonatal calves against enteric coronavirus infection.

Animals↗

Humoral immune responses in periodontal disease may have mucosal and systemic immune features.

The humoral immune response, especially IgG and IgA, is considered to be protective in the pathogenesis of periodontal disease, but the precise mechanisms are still unknown. Immunoglobulins arriving at the periodontal lesion are from both systemic and local tissue sources. In order to understand better the local immunoglobulin production, we examined biopsy tissue from periodontitis lesions for the expression of IgM, IgG, IgA, IgE and in addition the IgG and IgA subclasses and J-chain by in situ hybridization. Tissues examined were superficial inflamed gingiva and the deeper granulation tissue from periodontal sites. These data confirm that IgM, and IgG and IgA subclass proteins and J-chain can be locally produced in the periodontitis tissues. IgG1 mRNA-expressing cells were predominant in the granulation tissues and in the gingiva, constituting approx. 65% of the total IgG-expressing plasma cells. There was a significantly increased proportion of IgA-expressing plasma cells in the gingiva compared with the granulation tissue (P < 0.01). Most of the IgA-expressing plasma cells were IgA1, but a greater proportion expressed IgA2 mRNA and J-chain mRNA in the gingival tissues (30.5% and 7.5%, respectively) than in the periodontal granulation tissues (19% and 0-4%, respectively). The J-chain or dimeric IgA2-expressing plasma cells were located adjacent to the epithelial cells, suggesting that this tissue demonstrates features consistent with a mucosal immune response. Furthermore, we were able to detect the secretory component in gingival and junctional epithelial cells, demonstrating that the periodontal epithelium shares features with mucosal epithelium. In contrast, deeper tissues had more plasma cells that expressed IgM, and less expressing IgA, a response which appears more akin to the systemic immune response. In conclusion, this study suggests that immune mechanisms involved in the pathogenesis of periodontitis may involve features of both the mucosal and systemic immune systems, dependent on tissue location.

Adult↗

Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm.

BACKGROUND: Some previous reports have indicated beneficial cardiac effects of nasal continuous positive airway pressure (NCPAP) in patients with severe congestive heart failure (CHF), but others have reported deleterious cardiac effects, particularly among patients in atrial fibrillation (AF). The aim of this study was to determine if differences in cardiac rhythm influence the acute cardiac response to NCPAP. METHODS: Eleven consecutive patients with CHF were recruited, six in atrial fibrillation (AF) and five with sinus rhythm (SR). Cardiac index was measured during awake NCPAP application by the thermodilution technique during cardiac catheterisation. NCPAP was applied in a randomised sequence at pressures of 0, 5, and 10 cm H2O with three 30 minute applications separated by 20 minute recovery periods without NCPAP. RESULTS: Significant differences were found between the AF and SR groups for cardiac index responses to NCPAP (p = 0.004, ANOVA) with a fall in cardiac index in the AF group (p = 0.02) and a trend towards an increase in the SR group (p = 0.10). Similar differences were seen between the groups in stroke volume index responses but not in heart rate responses. Changes in systemic vascular resistance were also significantly different between the two groups (p < 0.005, ANOVA), rising in the AF group but falling in the SR group. CONCLUSIONS: These data indicate an important effect of underlying cardiac rhythm on the awake haemodynamic effects of NCPAP in patients with CHF.

Aged↗