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Biomedical subjects

D F Kinane

Publications and source records attributed to D F Kinane.

At least 55 records · Page 3Linked to original sources
PubMed2000

Aetiology and pathogenesis of periodontal disease.

Gingivitis is modified by several factors including smoking, ion channel blocking drugs and hormonal changes such as those seen in puberty or pregnancy. Periodontitis is also initiated by microbial plaque which follows on from gingivitis, but occurs in only 10 to 15% of the population and is influenced by the individual's immune and inflammatory response. Studies on the humoral and cellular immune response in periodontal disease indicate that: a) homing of relevant immune cells takes place within the periodontium; b) plasma cells are among the most active secretory cells in the gingiva; c) that immunoglobulin subclasses are similar between blood and the gingival pocket fluid for IgG but not for IgA; and that d) an individual's ability to mount a specific antibody response to periodontopathogenic organisms may indicate their susceptibility to the disease and their likely response to treatment. Recent reviews of the pathology of periodontal disease suggest that a histopathological established lesion with plasma cell predominance is likely to undergo periodontal bone loss. Furthermore, susceptibility to periodontitis may be related to whether plasma cells predominate in the tissues of an individual or a site as result of the microbial challenge of dental plaque. A tendency for an individual or site to form an extensive plasma cell infiltrate may indicate an inability to defend against periodontal bacteria and thus a predisposition to periodontitis. The various susceptibility factors such as smoking, medical condition, genetics, plaque control and local factors may all interact to influence the host response and specifically the immune response.

Alveolar Bone Loss↗
PubMed2000

Susceptibility and risk factors in periodontal disease.

Epidemiological studies demonstrate a high prevalence of advanced destruction but also that relatively few individuals in each age group account for most of the advanced periodontal disease. The available data suggest that three quarters of advanced periodontal disease could be prevented by targeting an effective preventive strategy on the 28% of individuals especially at risk. Questions remain regarding: 1) whether an acceptable cost-effective preventive strategy can be devised; and 2) whether it is possible to establish a simple method of identifying the 'at risk' group. The various risk factors are numerous and include systemic diseases, smoking, drug therapy, hormonal disturbances and genetic factors as well as the more mundane factors such as plaque control and socio-economic and education and attitude factors. Aside from these factors, many patients present with periodontal disease and have no discernible predisposition other than possibly genetic, for which we can not currently test, and for the vast majority of patients there would appear to be no other alternative to periodic thorough examination for all patients, early treatment of all periodontal lesions and appropriate dental health education.

Adult↗
PubMed2000

Local antimicrobial therapies in periodontal disease.

Periodontal therapy has the primary aim of halting periodontal disease progression. Clinical trials over the years have indicated that meticulous scaling and root planing in conjunction with a patient's proper plaque control can arrest periodontitis, but this therapy is not always completely effective and thus adjunctive therapies need to be considered. Local delivery of antibacterial agents into periodontal pockets has been extensively developed and investigated since the late 1970s and many systems have been designed to maintain high levels of antimicrobial agents in the crevicular fluid with minimal systemic uptake. More recently subgingival antimicrobial delivery systems have become available to the practising periodontist for clinical use. These systems, employ different antimicrobial agents but also different delivery systems which influence the concentration of available drug over time. The dental profession is confused by the wide variety of available slow release subgingival antimicrobial devices on the market and clearly comparative independent assessment of these therapies is needed. This review will summarise the findings of a comparative study on three commonly available periodontal local delivery antimicrobial systems on sites with previously unsuccessful mechanical therapy. The slow release devices studied adjunctively with root planing were: Actisite, Dentomycin and Elyzol, compared to root planing alone. Substantivity of an antimicrobial system is the ability of the system to maintain an effective concentration of drug over time which may be the most significant difference between the three delivery systems rather than the type of antimicrobial drug used. Although all three locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regime of scaling and root planing plus tetracycline fibre placement gave the greatest reduction in probing pocket depth over the six months after treatment.

Administration, Topical↗
PubMed1999

Scientific basis of a matrix metalloproteinase-8 specific chair-side test for monitoring periodontal and peri-implant health and disease.

Matrix metalloproteinases (MMPs), especially collagenase-2 (MMP-8), are key mediators of irreversible tissue destruction associated with periodontitis and peri-implantitis. MMP-8 is known to exist in elevated amounts and in active form in the gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF) from progressing periodontitis and peri-implantitis lesions and sites, respectively. (Sorsa et al. Ann. N.Y. Acad. Sci. 737: 112-131 [1994]; Teronen et al. J. Dent. Res. 76: 1529-1537 [1997]). We have developed monoclonal antibodies to MMP-8 (Hanemaaijer et al. J. Biol. Chem. 272: 31504-31509 [1997]) that can be used in a chair-side dipstick test to monitor the course and treatment of periodontitis and peri-implantitis. Monoclonal and polyclonal antibody tests for MMP-8 coincided with the classical functional collagenase activity test from GCF and PISF (Sorsa et al. J. Periodont. Res. 22: 386-393 [1988]) in periodontal and peri-implant health and disease. In future a chair-side functional and/or immunological MMP-test can be useful to diagnose and monitor periodontal and peri-implant disease and health.

Antibodies↗
PubMed1999

No association with HLA-DQB1 in European Caucasians with early-onset periodontitis.

Periodontitis is a chronic inflammatory disease of the supporting tissues of the teeth that may ultimately result in tooth loss. The human leukocyte antigen (HLA) complex plays an important role in immune responsiveness and may be involved in antigen recognition of periodontal pathogens. A recent report of a Japanese population found an association between an atypical BamHI site in the HLA-DQB1 gene and a severe form of early-onset periodontitis (EOP). The aim of the present study was to test for the existence of the site in a European Caucasian EOP population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No statistically significant differences were found between the patients and controls with regard to the presence of the BamHI site. It was concluded that this lack of association could reflect racial genetic variation in HLA allelic frequencies.

Alleles↗
PubMed1999

Relative proportions of mononuclear cell types in periodontal lesions analyzed by immunohistochemistry.

In this study, we investigated the relative proportions of infiltrating mononuclear inflammatory cells in sections of granulation tissue from periodontitis lesions in both adult periodontitis (AP) and early onset periodontitis (EOP) patients. We utilised a set of cluster of differentiation (CD) antigen-specific monoclonal antibodies to detect different cell types within the tissues. These included anti-CD 20 (B cells), anti-CD 3 (pan T cells) and anti-CD 45RO (memory T cells), anti-CD 4 (helper T cells) anti-CD 8 (suppressor T cells) and anti-CD 68 (monocyte/macrophage). Biopsies of granulation tissue were obtained from 9 patients with adult periodontitis (AP), from 10 patients with early onset periodontitis (EOP) and for comparative purposes, biopsies of gingival tissue from 4 patients with AP. A significantly greater number of T cells (p < 0.05) were observed in EOP and gingival sections than in AP sections. In addition, a greater number of B cells were observed in the granulation tissues than in the gingiva (p < 0.05). The relative numbers of B cells (CD 20). T cells (CD 3) and macrophages (CD 68) were expressed as a percentage of their combined total for each of the patient groups and indicated that the proportion of B lymphocytes was greater in AP sections than in EOP or gingival sections (p < 0.02). The proportion of T cells was lower in the AP periodontitis sections than in the EOP periodontitis sections (p < 0.05). There were no significant differences in the proportion of macrophages between the 3 categories of tissue specimens. The relative ratios of B cells (CD 20) to T cells (CD 3) and B cells (CD 20) to memory T cells (CD 45RO) and macrophages (CD 68) to T cells (CD 3) and memory T cells (CD 45RO) were analyzed and indicated that there was a significant increase in the B to T cell ratio in AP sections compared to EOP and gingival sections (p < 0.02). There was also a significant increase in the macrophage to T cell ratio in AP sections as indicated by CD 68 to CD 3 ratios (p < 0.05). There were no differences regarding the relative proportions of memory T cells or in the ratios of CD 4+ to CD 8+ T cells in the different disease categories. In conclusion, these differences in the relative proportions of B cells, T cells and macrophages may reflect a difference in the immunopathology of AP and EOP.

Adult↗
PubMed1999

Differences in the inflammatory response in young and old human subjects during the course of experimental gingivitis.

The aim of the present experiment was to study changes in (i) the composition of the inflammatory cell infiltrates and (ii) levels of alpha 2-macroglobulin, lactoferrin and IgG subclasses in gingival crevicular fluid in young and old individuals during 3 weeks of plaque formation. To establish healthy gingival conditions, all subjects received professional tooth cleaning during a 4 week pre-experimental period. The experimental sites included the mesio-palatal, palatal, and disto-palatal surfaces of all teeth present in the 15...25 tooth region. At baseline (day 0) assessments of plaque and gingivitis, microbial sampling and gingival fluid assessment were performed and one gingival biopsy harvested from each subject. Following the baseline examination, the participants abolished mechanical tooth cleaning measures in the palatal and approximal surfaces of 15...25. The clinical examination and the gingival fluid measurement were repeated on days 7, 14 and 21 of no oral hygiene. The microbiological sampling and the biopsy procedure were repeated on days 7 and 21. The gingival crevicular fluid samples harvested from the old individuals had higher levels of alpha 2-macroglobulin and IgG3 compared to young subjects. The immunohistochemical analyses of the biopsies demonstrated that the gingival lesion representing the old individuals harbored a higher proportion of B-cells and a lower density of PMN cells compared to the infiltrate in the young group of subjects. It is suggested that differences exist in the inflammatory response to de novo plaque formation in young and old individuals.

Adult↗
PubMed1999

Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry.

In this study, we investigated the synthetic and proliferative activity of infiltrating mononuclear cells in sections of granulation tissue from periodontitis lesions in both adult periodontitis (AP) and early onset periodontitis (EOP) patients. We also investigated the role of apoptosis in the remodelling of the inflamed tissue. We utilised a Ki-67 antigen specific antibody and a histone messenger RNA (mRNA) probe to detect cells undergoing cell division in the sections. Oligonucleotide probes for 28S ribosomal RNA and for the detection of poly A mRNA were utilised to detect cells with synthetic capacity. Apoptosis was determined using terminal transferase labelling of fragmented DNA with Biotin labelled dUTP. Biopsies of granulation tissue were obtained from 9 AP patients, from 10 EOP patients and for comparative purposes, biopsies of gingival tissue from 4 patients with AP. There were no differences regarding the relative proportions of cells with synthetic capacity or in the numbers of dividing cells in the periodontitis tissue sections. However, we observed an increase in the number of dividing cells in the AP granulation tissues compared to the AP gingival sections and that these cells were predominantly fibroblast like in appearance. Apoptotic cells consisted mainly of connective tissue cells; mainly fibroblasts with few if any leukocytes being apoptotic other than polymorphonuclear leukocytes. Only a few cyto-phagocytic macrophages were ever observed in the gingival and granulation tissues. We conclude that the turnover of infiltrating leukocytes in inflamed periodontal tissue is low, that they probably arrive at this site by recruitment from distant lymph nodes, and that neither cell division nor programmed cell death significantly alter the numbers of inflammatory cells. On the other hand, fibroblast apoptosis and cell division occur within the periodontium as these are typical processes in the normal turnover and remodelling of these tissues.

Adult↗
PubMed1999

GCF levels of MMP-3 and MMP-8 following placement of bioresorbable membranes.

Matrix metalloproteinases (MMPs) are responsible for remodeling and degrading extracellular matrix and basement membrane components. MMP-3 and -8 levels were assessed in this study during the early healing phase following a guided tissue regeneration (GTR) procedure. 32 patients, having 2 or 3 walled intrabony defects of PD > or =6 mm, were stratified into 2 groups on the basis of age, sex, smoking status and disease severity. All intrabony defects were treated using the resorbable Guidor membrane but only 1 group of patients was given a pre-operative dosage of antibiotic (3 g amoxycillin). GCF samples for the quantification of MMP-3 and -8 levels were obtained from the intrabony site where a membrane was placed (membrane site), from the non-adjacent site on the adjacent tooth which was involved in the surgical flap (surgical control site), and from a healthy site (healthy) on the contralateral side. The GCF samples taken at baseline, 1 week, 4 weeks and 3 months after surgery were analyzed using an enzyme linked immunoabsorbent essay (ELISA) for MMP-3 and using a time-resolved immunofluorescence assay (IFMA) for MMP-8. MMP-3 was detected in a very low % of sites at baseline while relatively high levels of MMP-8 were detected at all 3 types of sites at baseline. MMP-8 levels increased for all sites at week 1, and this was statistically significant for the membrane site, but at week 4, the levels decreased for both the membrane and the surgical sites. There was no statistically significant difference between the levels of MMP-3 and -8 in the antibiotic and non-antibiotic group. Collagen remodelling occurs during the early wound healing period following surgical and regenerative procedures. The levels of MMP-3 and -8 in GCF appear to reflect these processes. Interestingly, the presence of the membranes appeared to increase the levels of MMP-3 and -8 and may relate to the resorption of the resorbable membrane by host systems.

Absorbable Implants↗
PubMed1999

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↗
PubMed1999

Analysis of genetic polymorphisms at the interleukin-10 and tumour necrosis factor loci in early-onset periodontitis.

Early onset periodontitis (EOP) is considered to have a substantial genetic basis, although the gene or genes involved have not been elucidated. The aim of the present study was to investigate possible links between generalized EOP (GEOP) and genes regulating expression of the cytokines tumour necrosis factor (TNF) and interleukin-10 (IL-10). Microsatellite marker DNA sequences corresponding to phenotypic variations in cytokine response were analysed. Genotypic variations in cytokine response have been shown in vitro for TNF and IL-10, and specific alleles are implicated in diseases such as systemic lupus erythmatosus (SLE) and rheumatoid arthritis (RA). Two microsatellites at the IL-10 locus, IL10.R and IL10.G, and 1 microsatellite at the TNF locus, TNFa, were typed for 77 GEOP patients in the West of Scotland. Due to the highly polymorphic nature of the microsatellite loci, a statistical comparison with ethnically matched healthy controls (TNFa, n = 91, IL10.R, n = 94, IL10.G, n = 102) was conducted using a Monte Carlo simulation for each marker. No significant differences were observed for any of the 3 markers, although there were possible indications of trends similar to those observed in SLE for the IL10.G marker. In conclusion, no links were found between GEOP and microsatellites at TNFa, IL10.R or IL10.G loci.

Adult↗
PubMed1999

Periodontitis modified by systemic factors.

Microbial dental plaque is the initiator of periodontal disease but whether it affects a particular subject, what form the disease takes, and how it progresses, are all dependent on the host defenses to this challenge. Systemic factors modify all forms periodontitis principally through their effects on the normal immune and inflammatory defenses. Some good examples of this effect exist such as when there is a reduction in number or function of polymorphonuclear leukocytes (PMNs) that may result in an increased rate and severity of periodontal destruction. Many other systemic factors are much less clear cut and are difficult to causally link to periodontitis. In many cases the literature is insufficient to make definite statements on links between systemic factors and periodontitis. It is also at times difficult to be precise regarding the causative agent in systemic exposures such as smoking and even prescribed drug therapy. The possible role of systemic diseases and systemic exposures in initiating or modifying the progress of periodontal disease is clearly a complex issue. It is however generally agreed that several conditions may give rise to an increased prevalence, incidence, or severity of gingivitis and periodontitis. The categorization of the systemic modifying factors causing periodontitis and the evidence to support the role of these factors are the focus of this review. An attempt has been made to consider the conditions under broad headings, but it will be clear that many conditions fall within more than one category and that for several conditions only case reports exist whereas in other areas an extensive literature is present.

Diabetes Complications↗
PubMed1999

A six-month comparison of three periodontal local antimicrobial therapies in persistent periodontal pockets.

BACKGROUND: Currently, several local antimicrobial delivery systems are available to periodontists. The aim of this 6-month follow-up parallel study was to evaluate the efficacy of three commercially available local delivery systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions. METHODS: Seventy-nine patients with 4 pockets > or = 5 mm and bleeding on probing and/or suppuration were randomized into 4 treatment groups which included: scaling and root planing alone (S) (20 patients), or in conjunction with the application of 25% tetracycline fibers (S+Tet) (19 patients), or 2% minocycline gel (S+Min) (21 patients), or 25% metronidazole gel (S+Met) (19 patients). Clinical measurements were taken at baseline, 6 weeks, 3 months, and 6 months after antimicrobial application. Treatments were applied using the distributors' recommended protocols. RESULTS: All 4 therapies resulted in significant improvements from baseline in probing depth, attachment level, bleeding on probing, and the Modified Gingival Index (MGI) scores. The improvements in clinical parameters were greater in all 3 adjunctive treatment groups than scaling and root planing alone. The mean probing depth reductions at 6 months were: scaling + tetracycline = 1.38 mm; scaling + metronidazole = 0.93 mm; scaling + minocycline = 1.10 mm; and scaling alone = 0.71 mm. The probing depth reduction at all time points was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group (P<0.01). There was also a significant improvement for scaling plus tetracycline fiber application over scaling and metronidazole at both 6 weeks and 3 months, although this did not remain significant at the 6-month visit. While the frequency of sites with suppuration was markedly reduced following all antimicrobial treatments, the most effective reductions were seen in the scaling plus tetracycline fiber group, followed by the minocycline group. CONCLUSIONS: Although all 3 locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regimen of scaling and root planing plus tetracycline fiber placement gave the greatest reduction in probing depth over the 6 months after treatment.

Adult↗
PubMed1998

Relative distribution of plasma cells expressing immunoglobulin G subclass mRNA in human dental periapical lesions using in situ hybridization.

Immunoglobulin G (IgG)-producing plasma cells are the predominant immunoglobulin secreting plasma cells in human dental periapical lesions, compared with immunoglobulin A- and immunoglobulin M-producing plasma cells. In this study, the cells expressing mRNA, that encoded the distinct IgG subclasses, were detected using an in situ hybridization technique in 25 periapical lesions. These lesions consisted of 14 periapical granulomas and 11 radicular cysts. Four oligonucleotide probes were chemically synthesized from IgG subclass-specific hinge region genes to ensure specificity of the probes. Plasma cells expressing mRNA, which coded for the IgG subclasses, were detected in formalin-fixed/paraffin wax-embedded sections. Background staining was negligible in all of the sections tested. The in situ hybridization method used in this study was both specific and sensitive for the detection of mRNA encoding each of the four distinct IgG subclasses, whereas the cells retained good morphology. The relative proportions of plasma cells expressing each of the IgG subclass-specific mRNAs in both granulomas and cysts were as follows: IgG1 (57.4 and 55.5%); IgG2 (34.1 and 34.6%); IgG3 (4.0 and 4.3%); and IgG4 (4.0 and 5.5%). There were no significant differences between the percentages of plasma cells expressing each of the IgG subclass mRNAs between the two types of lesions. IgG1 producing plasma cells comprised the highest proportion of IgG-producing plasma cells in both types of periapical lesion. IgG2-producing plasma cells were next in abundance, followed by plasma cells for either IgG3 or IgG4, which were in roughly equivalent numbers.

Adult↗
PubMed1998

Periodontal diseases' contributions to cardiovascular disease: an overview of potential mechanisms.

Periodontitis and atherosclerosis have complex etiologies, genetic and gender predispositions, and potentially share many risk factors-the most significant of which may be smoking status. These diseases also have many pathogenic mechanisms in common. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The severity and chronicity of periodontal disease provides a rich source of subgingival microbial and host response products and effects over a long time period. The objective of this review is to consider the mechanisms whereby diseases such as periodontitis, which is chronic and Inflammatory In nature and initiated by microbial plaque, can predispose to atherosclerosis. In common with periodontal disease. the pathogenesis of atherosclerosis is not completely understood and both diseases are currently under Intensive investigation. Two main processes in particular are worthy of consideration and may provide the link between these 2 diseases, namely the lipopolysaccharide-related responses and the hyperresponsive monocyte phenomenon. Insufficient experimental evidence exists, however, to further support these hypotheses at present and clearly more research is needed on both of these processes and the interrelationships between both diseases.

Arteriosclerosis↗
PubMed1997

Factors influencing the diagnosis and management of periodontal disease by general dental practitioners.

OBJECTIVE: To identify factors influencing the diagnosis and management of periodontal disease by general dental practitioners. DESIGN: The study was conducted in two stages. 1. Analysis of returns to the Scottish Dental Practice Board. 2. Data collection via a postal questionnaire distributed to 500 general dental practitioners (27% of Scottish practitioners). RESULTS: 374 (75%) questionnaires were completed and returned. Analysis revealed the majority of treatment provided was in the form of simple scale and polishes, with multi-visit periodontal therapy comprising less than 0.2% of all non-surgical periodontal treatment. While the majority of respondents were confident in their ability to diagnose periodontal disease, only 40% were confident in treating it. Patient related factors were seen as the major hindrance to disease management, although time factors and the low level of fees were viewed by at least one half of respondents as major constraints. CONCLUSIONS: Greater efforts are required to motivate and inform patients of the necessity for and benefits of periodontal treatment, as is emphasis on appropriate treatment of early to moderate forms of disease. There is also a need for the development of appropriate, evidence-based clinical guidelines and fiscal arrangements to facilitate such provision.

Adolescent↗