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Biomedical subjects

K D O'Brien

Publications and source records attributed to K D O'Brien.

At least 37 records · Page 2Linked to original sources

Perceptions of the risks and benefits of orthodontic treatment.

Recent National Health Service changes have brought about a greater involvement of the consumers of medical and dental care in decision making regarding their treatment. The aim of this study was to investigate the level of awareness of the risks and benefits of orthodontic treatment among potential consumers and their referring dentists. Parents of patients referred for orthodontic treatment were issued with a questionnaire about the risks and benefits of treatment and the reason the child had been referred. Study models were also made of the child's teeth. The patients' dentists were issued with a similar questionnaire. The results revealed that most of the parents were aware of the benefits of treatment in general and the reason that their own child required it. This awareness was greater where the orthodontic need on aesthetic grounds was greater. There was less awareness of the risks of treatment though again this was greater among those with a greater need for treatment. When the perceptions of the dentists were evaluated, they were more aware of the risks but were not communicating this to the parents. Since for some patients the risks of treatment may outweigh the benefits, it would be helpful if dentists could provide this information for patients before referral.

Adolescent↗

Osteopontin is expressed in human aortic valvular lesions.

BACKGROUND: Nonrheumatic stenosis of trileaflet aortic valves, in which calcification is a prominent feature, has been termed a "degenerative" condition, but it has been demonstrated recently that chronic inflammation is a characteristic feature of the developing lesion of aortic stenosis. This observation raised the possibility that calcification in the aortic valve might be actively regulated. Thus, the present study investigated whether osteopontin, a protein implicated in the regulation of both normal and dystrophic calcification, could be detected in lesions of valvular aortic stenosis. METHODS AND RESULTS: Morphological and immunohistochemical studies were performed on 14 human aortic valves, representing a range of pathology from normal to clinically stenotic. The extent of calcification and macrophage accumulation and their relation to the presence of osteopontin protein were characterized. Highly statistically significant associations were found between the degree of osteopontin expression and the degrees of both calcification and macrophage accumulation in early through late lesions of aortic stenosis. Further, in situ hybridization localized osteopontin mRNA to a subset of lesion macrophages. CONCLUSIONS: These results suggest that, rather than representing a degenerative and unmodifiable process, calcification in aortic stenosis may be, in part, an actively regulated process with the potential for control either through modification of inflammation or synthesis of proteins such as osteopontin, which may modulate calcification in this tissue.

Aortic Valve↗

Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis.

BACKGROUND: In human atherosclerosis, most clinical events occur when plaque integrity is compromised and hemorrhage and thrombosis result. One mechanism for this might be the release by plaque cells of matrix-degrading proteases, such as interstitial collagenase (matrix metalloproteinase-1, MMP-1), which degrades two major plaque structural proteins, types I and III collagen. This study was undertaken to determine whether MMP-1 is expressed in human atherosclerotic plaques. METHODS AND RESULTS: To determine the cellular source and location of MMP-1 in human carotid atherosclerotic lesions, in situ hybridization and immunohistochemistry were performed on 20 endarterectomy specimens. Six nonatherosclerotic carotid arteries also were studied. Intense MMP-1 expression (mRNA and protein) was detected in a subset of plaque macrophages located at the borders of the lipid cores adjacent to fibrous caps and shoulder regions. Subsets of plaque smooth muscle cells and endothelial cells also expressed MMP-1. There was a strong correlation between the percentage of the lipid core occupied by hemorrhage and the percentage of the lipid core perimeter positive for MMP-1 (r = .823, P = .0001). MMP-1 was not detected in any cell type in nonatherosclerotic carotid arteries. CONCLUSIONS: This study demonstrates that MMP-1 is expressed by several cell types in human carotid atherosclerosis and that there is a correlation between the expression of the protease and histopathological evidence of plaque instability. Since MMP-1 may degrade the major structural collagens of the plaque, expression of the protease by macrophages in regions critical to plaque integrity could contribute to plaque expansion, rupture, and hemorrhage.

Aged↗

The relationship between the index of orthodontic treatment need and consensus opinion of a panel of 74 dentists.

This study looked at the aesthetic and dental health components of the index of orthodontic treatment need in relation to peer assessment of dental health and aesthetic need (panel of 74 dentists). The dental health component had a Spearmans correlation coefficient of +0.64 and the aesthetic component +0.86 when compared with the mean subjective opinion of 74 dentists. It has been proposed to have three categories for both the dental health and aesthetic components in accordance with consensus opinion. The panel of 74 examiners were more likely to regard aesthetics as a greater need for treatment than dental health.

Attitude of Health Personnel↗

The effectiveness of Class II, division 1 treatment.

The aim of this retrospective study was to evaluate the effectiveness of orthodontic treatment in terms of two outcome variables, namely, the percentage change in a valid and reliable occlusal index, the Peer Assessment Rating (PAR) score, and the duration of treatment. Data were collected from the records of 250 patients with Class II, Division 1 malocclusions who were treated in the Orthodontic Department of the University of Pittsburgh between 1977 and 1989. The relationships between the outcome and the treatment variables were analyzed with multiple regression techniques. Those variables significantly associated with the duration of treatment (p < 0.01) were (1) the pretreatment PAR score, (2) the number of treatment stages, (3) the percentage of appointments attended, (4) the number of appliance repairs, and (5) whether the patient was treated with or without extractions. The only variable that influenced the percentage change in PAR was the pretreatment PAR score (p < 0.01).

Adolescent↗

The use of occlusal indices: a European perspective.

Although occlusal indices are used in connection with public health orthodontic programs in some states, their adoption in everyday practice in the United States is extremely limited. On the other hand, indices are used extensively in Northern Europe, especially in determining access to public health orthodontics or the level of third party copayment. This article describes the development and validation of two new indices, IOTN (an index of treatment need) and PAR (an index of treatment outcome). Their application in a series of studies has led us to conclude that occlusal indices have a role in resource allocation and planning, promoting treatment standards, identifying prospective patients, and informed consent.

Europe↗

Calibration of dentists in the use of occlusal indices.

Dentists' opinions as to both need for and outcome of orthodontic treatment show wide variation. Within the profession there is an opportunity to reduce subjective bias and standardise criteria by the use of occlusal indices. The results of this study demonstrate that a group of dentists can easily be trained to record the Aesthetic and Dental Health Components of the Index of Orthodontic Treatment Need and the PAR index to a satisfactory level.

Bias↗

The biology of the artery wall in atherogenesis.

A great deal of progress has been made in the past few years in our understanding of the processes involved in atherogenesis and in mechanisms by which commonly accepted risk factors may affect these processes. These insights have allowed us to understand how various interventions may retard atherogenesis and decrease clinical events by improving plaque stability. The identification of new risk factors, such as lipoprotein(a), and of particular molecules that can be identified in atherosclerotic tissue, such as adhesion molecules, growth factors, cytokines, and proteins that regulate cholesterol uptake and removal, have identified several potential new targets for therapeutic intervention. Advances in molecular biologic techniques, including transgenic techniques, have markedly increased the types of potential interventions available. A major challenge for the future will be to determine which among this plethora of therapeutic possibilities holds the most promise for decreasing the morbidity and mortality associated with this disease.

Animals↗

Lipoprotein lipase is produced by cardiac myocytes rather than interstitial cells in human myocardium.

Lipoprotein lipase (LPL) may play an important role in myocardial metabolism by releasing free fatty acids from triglycerides for oxidation by myocytes. However, studies in species other than humans have differed in their conclusions as to whether LPL is produced by cardiac myocytes or interstitial cells. The location and source of LPL in human myocardium were determined on formalin-fixed samples from 25 cardiomyopathy patients and seven control patients. LPL protein was detected immunohistochemically on cardiac myocytes, adipocytes, and endothelial cells, as well as on interstitial cells consisting of both vascular pericytes and smooth muscle cells. In all 32 patients, in situ hybridization localized LPL mRNA to cardiac myocytes and adipocytes, but LPL mRNA was not detected in interstitial cells. Quantitative in situ hybridization failed to reveal correlations between LPL mRNA levels and New York Heart Association functional class, left ventricular ejection fraction, or beta-adrenergic agonist therapy. Also, quantitative in situ hybridization demonstrated apparently linear loss of detectable myocardial mRNA after onset of ischemia, with a disappearance half-time of approximately 26 hours. In summary, LPL is produced primarily by cardiac myocytes rather than by interstitial cells in human myocardium. Furthermore, LPL protein is present on cells with and without detectable LPL mRNA, suggesting that LPL is translocated from sites of synthesis to sites of utilization.

Adipocytes↗

Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies.

BACKGROUND: Nonrheumatic stenosis of trileaflet aortic valves, often termed senile or calcific valvular aortic stenosis, is considered a "degenerative" process, but little is known about the cellular or molecular factors that mediate its development. METHODS AND RESULTS: To characterize the developing aortic valvular lesion, we performed histological and immunohistochemical studies on Formalin-fixed and methanol-Carnoy's-fixed paraffin-embedded aortic valve leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82 years) with normal leaflets (n = 6), mild macroscopic leaflet thickening (n = 15), or clinical aortic stenosis (n = 6). Focal areas of thickening ("early lesions") were characterized by (1) subendothelial thickening on the aortic side of the leaflet, between the basement membrane (PAS-positive) and elastic lamina (Verhoeff-van Gieson), (2) the presence of large amounts of intracellular and extracellular neutral lipids (oil red O) and fine, stippled mineralization (von Kossa), and (3) disruption of the basement membrane overlying the lesion. Regions of the fibrosa adjacent to these lesions were characterized by thickening and by protein, lipid, and calcium accumulation. Control valves showed none of these abnormalities. Immunohistochemical studies were performed using monoclonal antibodies directed against macrophages (anti-CD68 or HAM-56), and contractile proteins of smooth muscle cells or myofibroblasts (anti-alpha-actin and HHF-35) or rabbit polyclonal antiserum against T lymphocytes (anti-CD3). In normal valves, scattered macrophages were present in the fibrosa and ventricularis, and occasional muscle actin-positive cells were detected in the proximal portion of the ventricularis near the leaflet base, but no T lymphocytes were found. In contrast, early lesions were characterized by the presence of an inflammatory infiltrate composed of non-foam cell and foam cell macrophages, occasional T cells, and rare alpha-actin-positive cells. In stenotic aortic valves, a similar but more advanced lesion was seen. CONCLUSIONS: The early lesion of "degenerative" aortic stenosis is an active inflammatory process with some similarities (lipid deposition, macrophage and T-cell infiltration, and basement membrane disruption) and some dissimilarities (presence of prominent mineralization and small numbers of smooth muscle cells) to atherosclerosis.

Aged↗

Dentists variation in the determination of orthodontic treatment need.

The criteria that dentists use to judge the need for orthodontic treatment are not clear. This study investigates variation in dentists' perception of orthodontic treatment need. Seventy-four dentists were asked to assess 320 dental casts in relation to aesthetic and dental health need. The results of this investigation revealed that the panel was divided as what constituted a need for orthodontic treatment on dental health grounds. It is suggested that one method of achieving a more uniform evaluation of orthodontic treatment need is the use of an occlusal index. Until an occlusal index is accepted and used by the profession, the distortion of need and demand for orthodontic treatment by dentists' unequal perceptions will continue.

Attitude of Health Personnel↗

Apolipoprotein E localization in human coronary atherosclerotic plaques by in situ hybridization and immunohistochemistry and comparison with lipoprotein lipase.

Apolipoprotein E (apo E) mediates both lipid accumulation by and removal from cells and may be secreted by both macrophages and smooth muscle cells in vitro, but its cellular source in atherosclerotic plaques is not known. Lipoprotein lipase (LPL) also enhances cell lipid accumulation and is synthesized by macrophage foam cells in atherosclerotic plaques. To determine the cellular source of apo E in human coronary atherosclerotic lesions and its relationship to LPL synthesis, in situ hybridization and immunohistochemistry were performed on 12 atherosclerotic plaques and six nondiseased coronary artery segments from 10 cardiac transplant recipients. Apo E messenger RNA was localized to both non-foam cell and foam cell macrophages in plaques, but not to other cell types, and was not detected in nonatherosclerotic arteries. Half of the regions with non-foam cell macrophages expressed neither apo E nor LPL messenger RNA, whereas 86% of macrophage foam cell-containing regions contained both messenger RNAs. Polyclonal antisera raised against human apo E localized apo E protein to the surface of macrophages and surrounding matrix in plaques but not in control coronary segments. An LPL-specific monoclonal antibody demonstrated that, similar to apo E, LPL protein on foam cell and non-foam cell macrophages was detected in atherosclerotic lesions, but LPL was also localized to intimal muscle smooth muscle cells and was not distributed as widely in association with matrix as was apo E. The expression of both apo E and LPL in atherosclerotic lesions but not in normal intima suggest that these molecules play a role in lipid metabolism in atherosclerosis.

Apolipoproteins E↗

Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis.

Endothelial attachment is the initial step in leukocyte recruitment into developing atherosclerotic lesions. To determine whether vascular cell adhesion molecule-1 (VCAM-1) expression may play a role in inflammatory cell recruitment into human atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recombinant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients. Immunophenotyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells. To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed. All atherosclerotic plaques contained some VCAM-1, compared to 45% of control segments. VCAM-1 was found infrequently on endothelial cells at the arterial lumen din both plaques (21%) and in control segments (27%), but was prevalent in areas of neovascularization and inflammatory infiltrate in the base of plaques. Double immunostaining and in situ hybridization confirmed that most VCAM-1 was expressed by subsets of plaque smooth muscle cells and macrophages. The results document the presence of VCAM-1 in human atherosclerosis, demonstrate VCAM-1 expression by human smooth muscle cells in vivo, and suggest that intimal neovasculature may be an important site of inflammatory cell recruitment into advanced coronary lesions.

Animals↗

The use of occlusal indices in assessing the provision of orthodontic treatment by the hospital orthodontic service of England and Wales.

This retrospective study was carried out to assess the need for orthodontic treatment and the standard of treatment provided by a sample of 17 hospital-based orthodontic departments. A total of 1630 sets of patients records were collected and analysed for orthodontic treatment need and standard of treatment with the Index of Orthodontic Treatment Need and the PAR index, respectively. The data were analysed with a variant of analysis of covariance using linear modelling techniques. In general terms it appeared that the hospital service provided treatment of a high standard, in terms of dento-occlusal change, to a caseload of patients that were in need of treatment. The effectiveness of treatment provision was influenced by the grade of operator, the choice of treatment methods and by the departmental attitudes and aspirations.

Appointments and Schedules↗

Process analysis of treatment provided by the hospital orthodontic service.

This investigation evaluates the influence of several process variables upon the number of attendances required to complete orthodontic treatment provided by the hospital service of England and Wales. The hospital records and study casts of 1630 patients were collected from 17 District General Hospital Departments. The study casts were analysed with the Peer Assessment Rating. The following information was collected from the hospital records; the patients' sex, the number of attendances required to complete treatment, the type of treatment provided and the operator. The data were analysed with multiple regression techniques. It appeared that the number of attendances was influenced by the pretreatment malocclusion severity, the type of treatment, the experience of the operator and the department from which the treatment was delivered.

Dental Records↗

The development of the PAR Index (Peer Assessment Rating): reliability and validity.

The PAR Index has been developed to provide a single summary score for all the occlusal anomalies which may be found in a malocclusion. The score provides an estimate of how far a case deviates from normal alignment and occlusion. The difference in scores between the pre- and post-treatment cases reflects the degree of improvement and, therefore, the success of treatment. Excellent reliability was exhibited within and between examiners (Intraclass Correlation Coefficient, R greater than 0.91). The components of the PAR Index have been weighted to reflect current British orthodontic opinion and is flexible in that the weightings could be changed to reflect future standards and standards currently being achieved in other countries. The PAR Index offers uniformity and standardization in assessing the outcome of orthodontic treatment.

Bicuspid↗