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Biomedical subjects

C M Roberts

Publications and source records attributed to C M Roberts.

At least 19 recordsLinked to original sources

MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes.

The metalloprotease disintegrin cysteine-rich (MDC) proteins are a recently identified family of transmembrane proteins that function in proteolytic processing of cell surface molecules and in cell adhesion. Since lymphocytes must interact with a constantly changing environment, we hypothesized that lymphocytes would express unique MDC proteins. To identify MDC proteins expressed in human lymph node, a polymerase chain reaction-based strategy combined with degenerate oligonucleotide primers was employed. We report here the identification of MDC-L (ADAM 23), a novel member of the MDC protein family. The results obtained from cDNA cloning and Northern blot analysis of mRNA isolated from various lymphoid tissues indicate that a 2.8-kilobase mRNA encoding a transmembrane form, MDC-Lm, and a 2.2-kilobase mRNA encoding a secreted form, MDC-Ls, are expressed in a tissue-specific manner. MDC-L mRNA was shown to be predominantly expressed in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix, and trachea. Furthermore, immunohistochemical staining with an anti-MDC-L antibody demonstrated that cells with typical lymphocyte morphology are responsible for expression of the MDC-L antigen in these lymphoid tissues. MDC-Lm was found to be expressed on the surface of human peripheral blood lymphocytes and transformed B- and T-lymphocyte cell lines as an 87-kDa protein. Thus, we have identified a novel lymphocyte-expressed MDC protein family member.

ADAM Proteins

Clinical value and cost of a respiratory sleep-related breathing disorders screening service for snorers referred to a District General Hospital ENT department.

Sleep-related breathing disorders and snoring often co-exist in the community. We hypothesized that a significant proportion of patients referred from primary care to ENT surgeons for management of snoring might have significant sleep-related breathing disorders requiring medical management. The Respiratory Medicine Department at Whipps Cross Hospital, London, U.K. screened all such referrals using sleep questionnaires, overnight oximetry and diagnostic sleep studies where necessary as recommended by the Royal College of Physicians of London. Over 38 months, 115 patients were screened, of whom 43 (38%) had clinically significant sleep-disordered breathing. One-third were established on nasal continuous positive airway pressure ventilation and the remainder were mainly offered conservative treatment. The cost of the screening service is estimated at 14,000 Pounds for the initial year. The savings to the ENT service and the possible long-term benefits to the patients identified as having sleep-disordered breathing balance this. We conclude that screening all referred snorers for sleep-disordered breathing using a simple protocol identifies a significant number requiring medical management at a relatively low cost to the service provider.

Ambulatory Care

Rare diseases.

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Humans

Screening patients in general practice with COPD for long-term domiciliary oxygen requirement using pulse oximetry.

Epidemiological data suggest long-term oxygen therapy (LTOT) delivered by oxygen concentrators in patients with severe hypoxic chronic obstructive pulmonary disease (COPD) is under-prescribed by General Practitioners (GPs) in England and Wales. One reason for this may be the unavailability to GPs of a measure of arterial oxygenation needed to fulfil the defined prescription criteria. Provision of a non-invasive measure of oxygenation may improve detection of hypoxic subjects and increase appropriate prescribing. This study aimed to evaluate pulse oximetry in a general practice setting and to screen for severe undetected hypoxaemia fulfilling the LTOT prescription criteria in patients with COPD. All COPD patients attending surgery in two practices were screened with oximeters for hypoxaemia. Those with an oxygen saturation of < or = 92% were referred to hospital for formal arterial blood gas analysis and an oxygen concentrator assessment. GPs were asked to evaluate their experience in the ease of use and application of oximetry. The number of patients receiving oxygen by concentrator before the study was compared with the national rate and the number after the study with the estimated need suggested by epidemiological studies. Over a 12-month period a total of 114 patients were screened in the two practices with a combined list size of 15,742. Thirteen patients had saturations of < or = 92%. Two refused and 11 underwent formal arterial gas analysis. Three had PaO2 < 7.3 kPa and new prescriptions for oxygen concentrators were made in these previously unsuspected severely hypoxaemic subjects as a result. One other hypoxaemic subject was referred and found to have another treatable medical condition. The initial prevalence of concentrator prescription (0.013% CI 0.003, 0.047) was similar to the national rate (0.024%) and the prevalence observed after screening (0.031%, CI 0.013, 0.073) fell within the lower suggested prescription need of previous epidemiological data (0.02-0.10%). All practitioners found the oximeters simple to use and helpful in assisting with assessment of the severity of their patient's condition. Oximetry provides a readily usable non-invasive method of screening and when applied to all COPD patients seen in general practice can reveal those fulfilling the criteria for long term oxygen who would otherwise not be identified as needing this treatment.

Aged

The value of forced expiratory volume in 1 s in screening subjects with stable COPD for PaO2 < 7.3 kPa qualifying for long-term oxygen therapy.

Guidelines on the management of chronic obstructive pulmonary disease (COPD) issued by the European Respiratory Society (ERS), British Thoracic Society (BTS), American Thoracic Society (ATS), and Department of Health for England and Wales (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below which arterial blood gas analysis should be performed to determine the presence of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement. This study aimed to determine the value of FEV1 at these different levels in screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable COPD. Comparative measures were taken against other lung function tests of volume and diffusing capacity. A retrospective analysis of paired lung function and arterial oxygen measurements in 491 subjects was made. The positive and negative predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS), FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between lung function variables and PaO2 was established. Logistic regression analysis was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using FEV1 to screen for LTOT requirement produced a high negative predictive value at all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1 < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%, FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40), FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships. Logistic regression also placed FEV1 % pred and TLCO % pred as the best predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1 may be used to exclude subjects from further investigation for LTOT and prevent unnecessary arterial sampling.

Adult

A summary of fraud and abuse issues affecting clinical research programs.

In an environment where the health care industry is under unprecedented scrutiny, it is important for all of those involved in the delivery of patient care and clinical research to be aware of and adhere to government grant requirements and billing practices. Fraud and abuse violations, no matter how minor they may seem, can result in substantial consequences for the grantee institutions and the investigators themselves.

Academic Medical Centers

Comparison of the efficacy of a demand oxygen delivery system with continuous low flow oxygen in subjects with stable COPD and severe oxygen desaturation on walking.

BACKGROUND: Provision of ambulatory oxygen using an intermittent pulsed flow regulated by a demand oxygen delivery system (DODS) greatly increases the limited supply time of standard portable gaseous cylinders. The efficacy of such a system has not previously been studied during submaximal exercise in subjects with severe chronic obstructive pulmonary disease (COPD) in whom desaturation is likely to be great and where usage is often most appropriate. METHODS: Fifteen subjects with severe COPD and oxygen desaturation underwent six minute walk tests performed in random order to compare the efficacy of a demand oxygen delivery system (DODS) with continuous flow oxygen. Walk distance, breathlessness, oxygen saturation, resting time, and recovery time (objective and subjective) were recorded and compared for each walk. RESULTS: Breathing continuous oxygen compared with baseline air breathing improved mean walk distance (295 m versus 271 m) and recovery time (47 seconds versus 112 seconds), whilst the lowest recorded saturation (81% versus 74%) and time desaturated below 90% (201 seconds versus 299 seconds) were reduced. When the DODS was compared with air breathing only the walk distance changed (283 m versus 271 m). A comparison of the DODS with continuous oxygen breathing showed the DODS to be less effective at oxygenating subjects with inferior lowest saturation (78% versus 81%), time spent below 90% (284 seconds versus 201 seconds), time to objective recovery (83 seconds versus 47 seconds), and walk distance (283 m versus 295 m). CONCLUSIONS: Neither of the delivery systems was able to prevent desaturation in these subjects. The use of continuous flow oxygen, however, was accompanied by improvements in oxygenation, walk distance, and recovery time compared with air breathing. The DODS produced only a small increase in walk distance without elevation of oxygen saturation, but was inferior to continuous flow oxygen in most of the measured variables when compared directly.

Administration, Inhalation

Concept mapping: an effective instructional strategy for diet therapy.

Concept mapping is an instructional strategy that requires learners to identify, graphically display, and link key concepts in instructional reading material. Although proven effective in numerous disciplines as a means to promote critical thinking and self-directed learning, concept mapping has not been tested in diet therapy. The objective of this study was to implement concept mapping as a small-group, cooperative learning strategy in an upper-division diet therapy course and to evaluate student attitudes about the effect of concept mapping on knowledge, self-directed learning, problem-solving, and collaborative skills. Students in the first semester (n = 27) initially learned course material by lecture (4 weeks) followed by an integrated mapping/lecture format (12 weeks); the second semester (n = 25) used an integrated mapping lecture format for the full 16 weeks. At the end of both semesters, students completed a 10-item original survey questionnaire. Responses for first (n = 25) and second (n = 21) semesters were analyzed independently. Results indicated that a majority of students thought participation in concept mapping enhanced knowledge of diet therapy principles (n = 19 of 25; 18 of 21), self-directed learning (n = 14 of 25; 18 of 21), critical thinking (n = 21 of 25; 14 of 21), problem-solving (n = 22 of 25; 16 of 21), and collaboration (n = 24 of 25; 20 of 21) skills. When noncooperation of teammates was a factor, concept mapping was viewed as more frustrating and time consuming than lecture. This study demonstrated concept mapping as an effective learning strategy for diet therapy; it improves students' ability to engage in self-directed learning, critical thinking, collaboration, and creative problem solving. Results suggest that concept mapping is most effective when accompanied with comprehensive training, coordinated lectures, instructor guidance, and long-term practice.

Concept Formation

Arterialised earlobe blood gas analysis: an underused technique.

BACKGROUND: Techniques for sampling arterialised capillary blood from the finger pulp and the earlobe were first described over two decades ago but, although close agreement between arterial values and earlobe samples has been demonstrated in normal subjects, this technique is not in common usage. METHODS: Forty patients with chronic lung disease and a wide range of arterial blood gas values were studied. Simultaneous earlobe and arterial samples were drawn with the patient at rest and analysed in the same blood gas analyser. The respiratory function laboratory staff in 50 UK hospitals with a respiratory department were telephoned and asked whether the technique was used in their hospital and the reasons, if known, for not adopting it. RESULTS: Earlobe and arterial blood gas tensions agreed closely over a wide range of values of arterial pH, PCO2 (mean difference 0.21, 95% confidence intervals -0.24 to +0.67 kPa) and PO2 (mean difference -0.17, 95% confidence intervals -1.09 to +0.75 kPa), especially at arterial PO2 values lower than 8 kPa. Of 50 UK centres surveyed 18% used the arterialised earlobe technique and 4% had plans to introduce it. Reasons for not using it were lack of knowledge in 64%, no blood gas analyser in 6%, the technique was considered inaccurate in 4%, and insufficient staff in 4%. CONCLUSIONS: Although earlobe blood gas analysis is sufficiently accurate to be reliably substituted for arterial sampling in routine clinical practice, most centres in the UK do not use the technique. The main reasons for this appear to be lack of knowledge of its existence and uncertainty over its accuracy.

Blood Gas Analysis

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus.

BACKGROUND AND DESIGN: Seventeen patients with subacute cutaneous lupus erythematosus (SCLE) were compared with 15 patients with discoid lupus erythematosus (DLE) to evaluate the relationship of 60- and 52-kd Ro/SSA autoantibodies to the clinical diagnosis and to evaluate assays for anti-Ro/SSA. RESULTS: All serum samples from patients with SCLE had precipitating anti-Ro/SSA antibodies in immunodiffusion, and all had high titer anti-60-kd Ro/SSA in enzyme-linked immunosorbent assay. Immunoblotting was inadequately sensitive for detecting anti-60-kd Ro/SSA. Fifteen patients with SCLE had anti-52-kd Ro/SSA (11 high titer, four low titer). Only one of the 15 patients with DLE had precipitating, high-titer anti-Ro/SSA. Nine other patients with DLE had low-titer anti-60-kd Ro/SSA, and four had low-titer anti-52-kd Ro-SSA. Low-titer anti-Ro/SSA did not confer an increased risk for photosensitivity in the DLE group. CONCLUSIONS: High-titer, precipitating antibodies to Ro/SSA are typical of SCLE and unusual in DLE. Low-titer, nonprecipitating antibodies to Ro/SSA are common in DLE and could be an indication of pathogenic factors shared with SCLE. However, low titers of anti-Ro/SSA do not confer a significant risk for SCLE skin lesions. For the purpose of clinical evaluation of skin disease, immunodiffusion assays for anti-Ro/SSA are cost-effective and informative.

Autoantigens

Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction.

OBJECTIVE: To determine if unilateral thoracic irradiation results in a lymphoid alveolitis in both irradiated and unirradiated lung fields. DESIGN: A prospective, nonrandomized study. PATIENTS: Women receiving postoperative radiotherapy for carcinoma of the breast were evaluated both before and 4 to 6 weeks after radiotherapy. Findings after radiotherapy in 15 asymptomatic patients were compared with findings in a group of patients with clinical radiation pneumonitis. MEASUREMENTS: History, physical examination, chest radiograph, quantitative gallium lung scanning, respiratory function tests, bronchoalveolar lavage, and lavage lymphocyte subset analysis. RESULTS: After irradiation, lavage lymphocytes increased significantly (34.5% versus 46.8%; P = 0.01) in the 17 patients studied prospectively. There was an associated reduction in vital capacity (102.5% versus 95.5%; P = 0.04). Comparison of results in patients before treatment, after treatment without clinical pneumonitis, and after treatment with clinical pneumonitis showed a dramatic increase in total lymphocytes after irradiation (6.3 versus 9.4 versus 35.2 million, respectively; P = 0.005), particularly in those with clinical pneumonitis. Only in those with clinical pneumonitis was this accompanied by an increase in the gallium index (3.7 versus 3.4 versus 9.0, respectively; P < 0.001). Vital capacity was also progressively reduced (102.5% versus 96.9% versus 76.7%, respectively; P = 0.04), as was diffusing capacity (98.6% versus 91.4% versus 72.6%, respectively; P = 0.003). No statistical differences existed between irradiated and unirradiated sides of the chest in either lavage or gallium lung scan studies. CONCLUSION: In most patients, a lymphocytic alveolitis develops in both lung fields after strictly unilateral thoracic irradiation; this is more pronounced in patients developing clinical pneumonitis. These findings suggest that radiotherapy may cause a generalized lymphocyte-mediated hypersensitivity reaction.

Adult

Training opinion leaders to promote safer sex.

Training opinion leaders in a men's residence hall in a brief program focused on communication and life skills is an effective way to stimulate peer discussions on HIV prevention and risk reduction and appears likely to have positive influences on behavioral change or intention. The program at the University of Wisconsin-Madison was extremely cost-effective and generated more than 350 conversations in a single residence hall in 1 month. This limited intervention revealed several key indicators of risk reduction. We believe that larger, more refined programs over a longer period will produce sustained prevention benefits and changes in the peer norms that so strongly influence behavior.

Curriculum

Effect of arterial oxygen desaturation on six minute walk distance, perceived effort, and perceived breathlessness in patients with airflow limitation.

BACKGROUND: The effect of exercise induced hypoxaemia in determining submaximal exercise capacity, perceived breathlessness, and perceived exertion is not known. The purpose of this study was to investigate the relation of these variables to the results of lung function tests and the degree of hypoxaemia during submaximal exercise in patients with airflow limitation. METHODS: Forty two patients with chronic obstructive airways disease and 28 patients with chronic severe asthma were studied. Spirometry was performed and gas transfer (TLCO) and lung volumes were measured. Submaximal exercise capacity was assessed with a standardised six minute walk test. Arterial oxygen desaturation during the walk test was monitored by a portable pulse oximeter. Patients rated their perceived degree of respiratory impairment on a Medical Research Council (MRC) breathlessness scale before the walk. Perceived breathlessness was measured by means of a linear visual analogue scale and exertion on the Borg scale after the walk. RESULTS: The six minute walk distance was strongly correlated (r value) with TLCO (0.68), peak expiratory flow (PEF: 0.55), forced expiratory volume in one second (FEV1: 0.53), transfer coefficient KCO: 0.49), age (-0.49), and forced vital capacity (FVC: 0.48) but not with oxygen desaturation during the walk. Walk distance was also correlated with the breathlessness rating on the MRC scale (-0.52), but less strongly with perceived breathlessness (-0.35) and perceived exertion (-0.30). The prediction equation for the six minute walk distance in metres (6MD) generated by multiple regression analysis was 6MD = 387 + 29.7 (TLCO) -3.1 (age) + 0.35 (PEF 1/min), which accounted for 50% of the total variance in walk distance. The mean level of saturation during the walk correlated most significantly with TLCO (0.55), FEV1/FVC (0.54), and PEF (0.48), but not with walk distance or with the rating on any of the analogue scales. The prediction equation produced by multiple regression analysis for the mean level of saturation during the walk was MEANSAT(%) = 1.3(TLCO) + 1.5 (base-line saturation) - 0.01 (6MD) - 54. CONCLUSIONS: Oxygen desaturation during the six minute walk is not related to walk distance, nor does it determine the degree of perceived exertion or perceived breathlessness in patients with airflow limitation. Patients who consider themselves the most disabled by breathlessness have the shortest six minute walk distance but do not necessarily have appreciable desaturation.

Asthma

Collateral ventilation and gas exchange during airway occlusion in the normal human lung.

The effectiveness of collateral ventilation in maintaining alveolar gas tensions in obstructed lung segments was investigated using fiberoptic bronchoscopy to place an occluding catheter-tip balloon in selected lobar and segmental bronchi in supine normal human subjects. Gas tensions from beyond the occlusion were measured with a respiratory mass spectrometer. Collateral ventilation is known to be minimal between lobes; therefore, values measured in obstructed lobes provide a control. No significant difference was found between the partial pressures of oxygen or carbon dioxide measured in obstructed lobes and in obstructed segments. In both cases respiratory gas tensions approached reported values for mixed venous levels. The time taken to attain a steady state of gas composition in the obstructed lung was rapid (approximately 50 s), and it was no different for lobes and segments. In addition, collateral ventilation was assessed by measuring the amount of helium reaching occluded lobes and segments when subjects breathed a mixture of 21% oxygen and 79% helium. The rate of rise in helium concentration was less than 1%/min in both lobes and segments, a figure that may be explained by delivery of helium in recirculated blood rather than by collateral ventilation. We conclude that intersegmental collateral ventilation has a negligible role in the maintenance of alveolar gas tensions in supine normal humans during tidal breathing.

Adult

Changes in epithelial lining fluid albumin associated with smoking and interstitial lung disease.

Albumin is an important plasma protein which is useful in the assessment of in vivo membrane permeability in the lung. In subjects with interstitial lung disease (ILD) the relationship between albumin recovered from bronchoalveolar lavage (BAL) and other markers of inflammatory activity may provide useful information of the pathogenesis of the disease process. Unfortunately, its measurement is hampered by the variable dilution in BAL fluid. In this study, urea was used as a marker of epithelial lining fluid (ELF) dilution allowing the calculation of an apparent epithelial lining fluid volume and adjusted albumin content. We examined the relationship between ELF albumin content and BAL cell counts, immunoglobulin content, respiratory function tests and gallium lung scans in both smokers and nonsmokers with and without interstitial lung disease. Forty seven subjects with connective tissue disease and interstitial lung disease and 51 subjects with either connective tissue disease but no pulmonary involvement or non pulmonary malignancy (18 current smokers) underwent BAL, gallium lung scans and respiratory function tests. The subjects with ILD were further subdivided into those with active ILD or bronchiolitis using cluster analysis. In smokers without ILD an increased ELF volume and a decrease in ELF albumin were found. Increased ELF albumin was related to increased age. In subjects with ILD, increased albumin was strongly correlated with increased BAL lymphocyte absolute and differential counts, which overwhelmed any age or smoking effect. These findings suggest a possible causal relationship between lung vascular permeability and lymphocyte numbers in subjects with interstitial lung disease and reinforce the need to consider smoking and age as confounding factors in BAL analysis.

Biomarkers