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Biomedical subjects

J Desmond

Publications and source records attributed to J Desmond.

At least 19 recordsLinked to original sources
PubMed2002

Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients with rheumatoid arthritis: a prospective study incorporating HRCT scanning and pulmonary function tests.

OBJECTIVE: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. METHODS: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. RESULTS: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. CONCLUSION: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.

Administration, Oral↗
PubMed2002

Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis.

BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. OBJECTIVE: To identify clinical features that predict progressive FA in patients with RA. METHODS: An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly specific predictor of disease progression.

Aged↗
PubMed2001

Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests.

BACKGROUND: Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19-44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS: One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS: Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (TLCO), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS: HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.

Aged↗
PubMed2000

Methylation of transcription factor binding sites in the Epstein-Barr virus latent cycle promoter Wp coincides with promoter down-regulation during virus-induced B-cell transformation.

Two Epstein-Barr virus latent cycle promoters for nuclear antigen expression, Wp and Cp, are activated sequentially during virus-induced transformation of B cells to B lymphoblastoid cell lines (LCLs) in vitro. Previously published restriction enzyme studies have indicated hypomethylation of CpG dinucleotides in the Wp and Cp regions of the viral genome in established LCLs, whereas these same regions appeared to be hypermethylated in Burkitt's lymphoma cells, where Wp and Cp are inactive. Here, using the more sensitive technique of bisulfite genomic sequencing, we reexamined the situation in established LCLs with the typical pattern of dominant Cp usage; surprisingly, this showed substantial methylation in the 400-bp regulatory region upstream of the Wp start site. This was not an artifact of long-term in vitro passage, since, in cultures of recently infected B cells, we found progressive methylation of Wp (but not Cp) regulatory sequences occurring between 7 and 21 days postinfection, coincident with the period in which dominant nuclear antigen promoter usage switches from Wp to Cp. Furthermore, in the equivalent in vivo situation, i.e., in the circulating B cells of acute infectious mononucleosis patients undergoing primary EBV infection, we again frequently observed selective methylation of Wp but not Cp sequences. An effector role for methylation in Wp silencing was supported by methylation cassette assays of Wp reporter constructs and by bandshift assays, where the binding of two sets of transcription factors important for Wp activation in B cells, BSAP/Pax5 and CREB/ATF proteins, was shown to be blocked by methylation of their binding sites.

B-Lymphocytes↗
PubMed1996

Oral health week.

This article reports on the Oral Health Week held in December 1994 and focuses on an initiative by the BDA which organised dentists and volunteers from Age Concern in a project to look at oral health for the elderly. It examines the aims and the results of the week and draws some useful conclusions on improving the outcome if a project such as this were attempted again.

Aged↗
PubMed1996

Results of the 1995 readers' survey.

Following a survey of BDJ readers in 1992 the BDJ was redesigned and relaunched. In mid-1995 a follow-up survey was conducted. Its findings show big improvements in readers' assessment of the design, style and content of the journal.

Attitude of Health Personnel↗
PubMed1994

High resolution EEG: 124-channel recording, spatial deblurring and MRI integration methods.

This paper describes a method for increasing the spatial detail of the EEG and for integrating physiological data with anatomical models based on magnetic resonance images (MRIs). This method includes techniques to efficiently record EEG data from up to 124 channels, to measure 3-D electrode positions for alignment with MRI-derived head models, and to estimate potentials near the outer convexity of the cortex using a spatial deblurring technique which uses a realistic model of the structure of the head and which makes no assumptions about the number or type of generator sources. The validity of this approach has been initially tested by comparing estimated cortical potentials with those measured with subdural grid recordings from two neurosurgical patients. The method is illustrated with somatosensory steady-state evoked potential data recorded from 5 healthy subjects. Results suggest that deblurred 124-channel topographic maps, registered with a subject's MRI and rendered in 3 dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. The results also suggest that the potential for EEG as a functional neuroimaging modality has yet to be fully realized.

Adult↗
PubMed1994

Subdural grid recordings of distributed neocortical networks involved with somatosensory discrimination.

Previous studies suggest that evidence for the sub-second activation of distributed neural networks can be obtained by computing the covariance between segments of the scalp-recorded evoked potential. However, the cortical representation of such potentials is not known. Here we report a case study where the evoked potential covariance (EPC) measure was applied to data recorded from a 58-channel subdural grid implanted in an epilepsy patient. Recordings were made while the patient performed a task that required judging the somatosensory intensities of electrical stimuli and executing precise finger flexion responses in response to a subset of those stimuli. Post-stimulus EPC patterns involved covariances between somatosensory, motor, and temporal regions. Pre-stimulus EPC patterns involved these same regions, but only when it could be anticipated that the upcoming stimulus would likely require a response. The majority of the observed EPCs occurred with non-zero time-lags, and these EPCs often involved non-adjacent electrode pairs. Thus, the observed EPCs were unlikely to arise solely from volume conduction. Rather, they appeared to reflect the transient integration of activity across distinct cortical processing nodes.

Adult↗
PubMed1991

Seeing through the skull: advanced EEGs use MRIs to accurately measure cortical activity from the scalp.

There is a vast amount of untapped spatial information in scalp-recorded EEGs. Measuring this information requires use of many electrodes and application of spatial signal enhancing procedures to reduce blur distortion due to transmission through the skull and other tissues. Recordings with 124 electrodes are now routinely made, and spatial signal enhancing techniques have been developed. The most advanced of these techniques uses information from a subject's MRI to correct blur distortion, in effect providing a measure of the actual cortical potential distribution. Examples of these procedures are presented, including a validation from subdural recordings in an epileptic patient. Examples of equivalent dipole modeling of the somatosensory evoked potential are also presented in which two adjacent fingers are clearly separated. These results demonstrate that EEGs can provide images of superficial cortical electrical activity with spatial detail approaching that of O15 PET scans. Additionally, equivalent dipole modeling with EEGs appears to have the same degree of spatial resolution as that reported for MEGs. Considering that EEG technology costs ten to fifty times less than other brain imaging modalities, that it is completely harmless, and that recordings can be made in naturalistic settings for extended periods of time, a greater investment in advancing EEG technology seems very desirable.

Brain↗
PubMed1986

Reciprocal functional interaction of adjacent myocardial segments during regional ischemia: an intraventricular loading phenomenon affecting apparent regional contractile function in the intact heart.

The mechanism of the increase in function in myocardial segments adjacent to those subjected to regional ischemia is not known. To investigate the hypothesis that changes in regional loading are an important causative factor of this phenomenon, 17 dogs were instrumented with segmental shortening sonomicrometers in the left anterior descending and circumflex artery distributions, circumflex coronary flow probes and cuff occluders, as well as circumflex coronary pressure catheters. Additionally, the animals had aortic pressure catheters and ventricular pressure micromanometers. This animal model allowed modulation of regional inotropic state with regional ischemia or isoproterenol administration. With circumflex coronary bed ischemia, segmental shortening in the circumflex distribution decreased from 11.9 to 6.3% (p = 0.001) whereas left anterior descending regional shortening increased from 11.6 to 13.4% (p less than 0.001). These reciprocal changes occurred in the absence of changes in global afterload or heart rate. Systemic beta-receptor blockade did not change this response, suggesting that it was not reflex- or catecholamine-mediated. Infusing isoproterenol into the circumflex coronary artery resulted in an increase in circumflex regional shortening from 12.5 to 17.4% (p less than 0.02) whereas left anterior descending regional shortening decreased from 13.5 to 8.3% (p less than 0.001), again without change in heart rate or left ventricular or aortic pressure. These data suggest that reciprocal functional interaction between adjacent myocardial segments is a result of changes in regional afterload for the most part, with changes in local preload and timing of ejection also contributing to the observed effect.

Animals↗