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Biomedical subjects

K D O'Brien

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

At least 55 records · Page 3Linked to original sources

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↗

Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.

Lipoprotein lipase (LPL), hydrolyzes the core triglycerides of lipoproteins, thereby playing a role in their maturation. LPL may be important in the metabolic pathways that lead to atherosclerosis, since it is secreted in vitro by both of the predominant cell types of the atherosclerotic plaque, i.e., macrophages and smooth muscle cells. Because of uncertainty concerning the primary cellular source of LPL in atherosclerotic lesions, in situ hybridization assays for LPL mRNA were performed on 12 coronary arteries obtained from six cardiac allograft recipients. Macrophages and smooth muscle cells were identified on adjacent sections with cell-specific antibodies and foam cells were identified morphologically. LPL protein was localized using a polyclonal antibody. LPL mRNA was produced by a proportion of plaque macrophages, particularly macrophage-derived foam cells, but was not detected in association with any intimal or medial smooth muscle cells. These findings were confirmed by combined immunocytochemistry and in situ hybridization on the same tissue sections. LPL protein was detected in association with macrophage-derived foam cells, endothelial cells, adventitial adipocytes, and medial smooth muscle cells, and, to a lesser extent, in intimal smooth muscle cells and media underlying well-developed plaque. These results indicate that macrophage-derived foam cells are the primary source of LPL in atherosclerotic plaques and are consistent with a role for LPL in the pathogenesis of atherosclerosis.

Arteriosclerosis↗

An analysis of the effects of place of childhood, undergraduate and postgraduate education upon the regional distribution of specialist orthodontic practitioners.

In 1989, a survey of specialist orthodontic practitioners was carried out. Questionnaires were sent to all members of the British Association of Orthodontists who were engaged in full-time specialist practice. This yielded a response rate of 72%. One part of the questionnaire was directed towards details concerned with the practitioner's place of childhood, undergraduate and postgraduate education. The regions in the UK were grouped into two large areas of the 'north' and the 'south'. It was evident that most of the practitioners had received their orthodontic training in the 'south' of England and were employed within the same region. Detailed data analysis was carried out using the Mantel-Haenszel chi-squared test. This revealed that there was a strong association between the place of postgraduate orthodontic training and place of employment of the specialist practitioner (chi 2 = 48.6, P less than 0.00001). The data suggest that one method of reducing the present unequal distribution of the specialist orthodontic practitioner would be to increase the number of postgraduate training places in those regions with low levels of orthodontic manpower.

Adult↗

Quality control in orthodontics: indices of treatment need and treatment standards.

Two reliable and valid occlusal indices have been developed to assess treatment need (Index of Treatment Need, IOTN) and the standard of treatment (The PAR Index, Peer Assessment Rating). The IOTN assesses both dental aesthetics and dental health need. The PAR index provides a single summary score for the overall alignment and occlusion. The difference between the pre- and post-treatment scores reflects the degree of improvement and the success of orthodontic intervention and active treatment. Several practical uses of the indices are described: the estimation of treatment need in an unselected and a referred population and the assessment of the standard of treatment in the Hospital and General Dental Services. It has been suggested that the use of the occlusal indices would offer several advantages: (1) uniformity in prescribing patterns, (2) safeguards for the patient, (3) patient counselling and (4) monitoring and promoting standards.

Discriminant Analysis↗

Quality control in orthodontics: factors influencing the receipt of orthodontic treatment.

The factors which influence the uptake of orthodontic treatment are reviewed with respect to the features and aspirations of the consumers (patients and parents) and the providers (dentists, orthodontists and health system). It appears that the assessment of orthodontic treatment need is influenced by many variables relating to opportunity and demand for treatment; this results in a marked lack of uniformity in treatment uptake.

Adolescent↗

Quality control in orthodontics: risk/benefit considerations.

The literature concerning risk/benefit appraisal for orthodontic treatment is reviewed with respect to factors which influence dental health, social psychological well-being and the harmful effects of orthodontic treatment. There is little evidence to suggest that the absence of malocclusion is associated with a measurably higher self-esteem and life fulfillment, or with major advantages for dental health, except for a limited number of traits. With regard to treatment, small risks of iatrogenic harm exist, while the effects of partial or total failure of treatment, and the lack of long-term stability of results should not be underestimated.

Adolescent↗

Light cured direct bonding--is it necessary to use a primer?

A study was undertaken to assess the influence of a low viscosity unfilled 'primer' resin upon the shear bond strength of a bracket adhesive combination to etched enamel and at the separate interfaces of the bonding system, namely the bracket/adhesive and the enamel/adhesive interfaces. No significant differences were detected between the bond strengths when an unfilled resin phase was utilized (P greater than 0.05).

Acid Etching, Dental↗

The specialist orthodontic practitioner. The 1989 survey.

In 1989, a survey of specialist orthodontic practitioners was carried out, with the cooperation of the British Association of Orthodontists. Questionnaires were sent to all BAO members in full-time specialist orthodontic practice; a 72% response was achieved. The results revealed that the specialist orthodontic practitioner service was well equipped and adequately qualified to accept a role as providers of the majority of UK orthodontic treatment. When new patient treatments were analysed, it was found that fixed appliance treatment was proposed for 60% of patients. However, the majority of the respondents felt that the system of remuneration in the GDS encouraged quantity as opposed to quality of treatment.

Adult↗

A clinical trial of an indirect bonding technique with a visible light-cured adhesive.

A trial was carried out to evaluate the clinical performance of a visible light-cured adhesive when used with a foil mesh base in an indirect bonding technique. Thirty-seven patients entered the trial, and a total of 407 brackets were placed. The incidence and site of bond failure were recorded. The overall failure rate was 6.5%. There were no significant differences detected between the failure rates for either the upper or the lower arches or for the anterior and the posterior segments of the arches (p less than 0.01).

Acrylates↗