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Biomedical subjects

K S Kornman

Publications and source records attributed to K S Kornman.

At least 19 recordsLinked to original sources
PubMed2000

Effect of interleukin-1 gene polymorphisms on gingival inflammation assessed by bleeding on probing in a periodontal maintenance population.

Bleeding on probing (BOP) is the most significant clinical parameter for the assessment of periodontal inflammation. The aim of this prospective longitudinal trial was to study the association between allelic variants of the IL-1 gene complex and gingival inflammation. Three hundred and twenty-three randomly selected periodontal maintenance patients (64.4% females) received a periodontal examination that included probing depth measurements and BOP at each of 4 supportive periodontal therapy (SPT) appointments. A blood sample taken from each subject was analysed for the presence of specific allotypes of the IL-1 gene complex. Two polymorphisms located at +4845 bp in the IL-1 alpha region and at +3954 bp in the IL-1 beta region were evaluated by a polymerase chain reaction method; 35.3% of the examined subjects were positive for specific combinations of allotypes of the IL-1 gene complex previously associated with an increased risk for severe periodontitis. The population consisted of 90 current smokers and 94 former smokers. An analysis of the association between the IL-1 genotype and BOP in the whole population (including smokers) did not reach statistical significance because of the overriding effect of smoking. A subset analysis of the 139 never smokers indicated that genotype positive patients had a significantly elevated chance of presenting an increase in the BOP% over a 4-appointment recall period (p = 0.03) after correcting for oral hygiene. In fact, patients who were genotype-negative had a 50% smaller chance of showing increases in BOP% during SPT. A further analysis explored the relationship between the genotype and the level of BOP% at the most recent recall visit. A generalized linear model showed a statistically significant effect of the genotype status after correcting for plaque accumulation and prevalence of residual pockets (> or = 5 mm). Genotype-negative subjects had significantly lower BOP% (p = 0.0097). It is concluded that the increased BOP prevalence and incidence observed in IL-1 genotype-positive subjects indicates that some individuals have a genetically determined hyper-inflammatory response that is expressed in the clinical response of the periodontal tissues.

Adult↗
PubMed2000

Interleukin-1 genetic association with periodontitis in clinical practice.

BACKGROUND: Periodontitis is a bacterial disease modified by multiple risk factors. The pro-inflammatory cytokine interleukin- (IL-1) is a key regulator of the host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. It has been reported that variations in the IL-1 gene cluster on chromosome 2 are associated with increased susceptibility to severe adult periodontitis. METHODS: The present study evaluated the association between a composite IL-1 genotype, including allele 2 at each of two loci (IL-1A +4845 plus IL- B +3954), and a broad spectrum of periodontally healthy to diseased patients in a population that is typically encountered in a dental practice setting. Ninety patients, non-smokers or former smokers with less than 10 pack-year (pk/yr) history, were recruited from a private dental practice. The major outcome variable was bone loss determined by computerized linear measurements of radiographs. Genotypes were analyzed from finger-stick blood samples using previously reported methods. RESULTS: Multivariate logistic regression models demonstrated that patient age, former smoking history, and the IL-1 genotype were significantly associated with severity of adult periodontitis. For non-smokers or former light smokers (<5 pk/yr), IL-1 genotype positives were at increased odds ratio of having moderate to severe periodontal disease of 3.75 (95% CI: 1.04-13.50) to 5.27 (95% CI: 1.23-22.70), depending on ethnicity, compared to IL-1 genotype negatives. Former moderate smokers (>5 pk/yr and <10 pk/yr) who were IL-1 genotype negative were at increased odds ratio of having moderate to severe periodontal disease of 7.43 (95% CI: 1.20-46.20) compared to non-smokers or former light smokers who were IL-1 genotype negative. In addition, past smoking history was also a significant effect modifier as demonstrated by the statistically significant interaction between past smoking history status and IL-1 genotype status. CONCLUSIONS: This study demonstrates that the composite IL-1 genotype is significantly associated with the severity of adult periodontitis. It also confirmed that both IL-1 genotyping and smoking history provide objective risk factors for periodontal disease in a private practice environment.

Adult↗
PubMed2000

Genetic polymorphisms of the IL-1alpha and IL-1beta genes in African-American LJP patients and an African-American control population.

BACKGROUND: A functional polymorphism of the interleukin-1 beta (IL-1beta) gene has been proposed to be a risk factor for periodontitis. In adult forms of periodontitis, non-smokers of northern European heritage carrying the "2" allele of the IL-1alpha-889 and the IL-1beta +3953 RFLPs in either the heterozygous or the homozygous state at both loci were observed to have a greater risk for developing severe periodontitis. Studies of early-onset periodontitis (EOP) found that allele "1" of both IL-1alpha-889 and IL-1beta +3953 was transmitted more frequently with the EOP phenotype. The purpose of the present study was to determine the prevalence of the IL-1alpha and IL-1beta genotype polymorphisms in an African-American (AA) control population and in 37 African-Americans with localized juvenile periodontitis (LJP). METHODS: The IL-1alpha +4845 and IL-1beta +3953 loci were genotyped by PCR amplification, followed by restriction enzyme digestion and gel electrophoresis. The IL-1alpha +4845 locus, in linkage disequilibrium (>99%) with IL-1alpha-889, was genotyped because it is technically easier. Data were analyzed using r x c contingency tables. RESULTS: The IL-1beta +3953 allele "1" was carried by >99% of the AA control population and by 100% of the AA LJP group, with most individuals being homozygous 1,1. The prevalence of the composite genotype with at least one allele "2" at each of the IL-1beta +3953 and IL-1alpha +4845 loci was 14% (AA control group) and 8% (AA LJP group). CONCLUSIONS: Given the high frequency of the IL-1beta allele "1" in the African-American population, it would appear that knowledge of this +3953 polymorphism would provide little diagnostic or predictive information for LJP.

Adult↗
PubMed1999

Host modulation as a therapeutic strategy in the treatment of periodontal disease.

Specific microorganisms initiate the immunoinflammatory processes that destroy tissue in periodontitis. Recent work has demonstrated, in addition to bacterial control, that modulation of the host immunoinflammatory response is also capable of controlling periodontitis. Matrix metalloproteinases (MMPs) destroy collagen and other matrix components, and the osteoclastic bone remodeling determines the periodontal bone response to a bacterial challenge. Other components of the biology, including cytokines and prostanoids, regulate MMPs and bone remodeling and are also involved in regulating the production of defensive elements, such as antibody. Agents directed at blocking MMPs or osteoclastic activity are effective in reducing periodontitis. Agents that inhibit prostaglandin E2 and selective blockage of specific cytokines have also been effective. Improved knowledge of bacterium-host interactions and of the processes leading to tissue destruction will help to identify targets for host modulation to reduce periodontitis in selected situations.

Alveolar Bone Loss↗
PubMed1999

Interleukin-1 genotypes and the association between periodontitis and cardiovascular disease.

An epidemiological association between periodontitis and cardiovascular disease has been reported in multiple studies. Various mechanisms have been proposed as potential explanations for this association, including a common factor that predisposes certain individuals to a hyper-responsive inflammatory response. Variations in the genes that regulate the interleukin-1 (IL-1) response have been associated with both periodontal disease and cardiovascular disease. New data indicate that one pattern of IL-1 genetic polymorphisms, characterized by the IL-1A (+4845) and IL-1B (+3954) markers, is associated with periodontitis but not certain measures of atherosclerosis. Another IL-1 genetic pattern, characterized by the IL-1B (-511) and IL-1RN (+2018) markers, is associated with atherosclerotic plaque formation, as measured by angiography and arterial wall thickness, but not periodontitis. These two patterns also have different functional implications relative to IL-1 biological activity. Studies of IL-1 gene polymorphisms, atherosclerotic plaque instability and cardiovascular clinical events are in progress. Hypothetical models are presented to explain how IL-1 genetic factors may be involved in cardiovascular disease.

Angiography↗
PubMed1999

The influence of interleukin gene polymorphism on expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissue and gingival crevicular fluid.

BACKGROUND: A specific composite genotype of the polymorphic interleukin-1 (IL-1) gene cluster has recently been associated with severe periodontitis. One polymorphism of the composite periodontitis-associated genotype (PAG) has been functionally linked with expression of high levels of IL-1. The purpose of this study was to test whether gingival crevicular fluid (GCF) levels of IL-1beta and tumor necrosis factor-alpha (TNFalpha), and gingival tissue levels of IL-1alpha, IL-1beta, and TNFalpha correlate with PAG, and to examine the effect of conservative periodontal therapy on these levels. METHODS: Twenty-two adults with moderate to advanced periodontal disease were enrolled. Polymerase chain reaction amplification and restriction enzymes were used to identify specific polymorphisms from peripheral blood samples. GCF samples were collected at baseline and 3 weeks following conservative treatment and analyzed by ELISA for IL-1beta and TNFalpha. An interproximal gingival biopsy was collected at baseline and follow-up and analyzed for IL-1alpha, IL-1beta, and TNFalpha by ELISA. RESULTS: The genotyping identified 7 as PAG(+) and 15 as PAG(-). The 2 groups were comparable in terms of existing periodontitis and age. In shallow sites (<4 mm), total IL-1beta in GCF was 2.5 times higher for PAG(+) patients prior to treatment (P=0.03), and 2.2 times higher after treatment (P=0.04), while differences were less apparent in deeper sites. Following treatment, a reduction in IL-1beta concentration in GCF was seen for PAG(-) but not for PAG(+) patients. While not statistically significant, a trend was observed in mean tissue levels of IL-1beta which were 3.6 times higher in PAG(+) versus PAG(-) patients (P=0.09). CONCLUSIONS: These data suggest that PAG(+) patients may demonstrate phenotypic differences as indicated by elevated levels of IL-1beta in GCF.

Adult↗
PubMed1998

Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis.

Periodontitis is a collection of chronic inflammatory diseases that are caused by specific bacteria. The bacteria activate inflammatory mechanisms in the periodontal tissues that destroy collagen and bone that support the teeth. Although bacteria are essential for the initiation of periodontitis, the quantity and types of bacteria have not been sufficient to explain the differences in disease severity. In recent years, it has become evident that for many common chronic diseases, there are modifying factors that do not cause the disease but rather amplify some disease mechanisms to make the clinical condition more severe. There are now data to suggest that a few factors which amplify the inflammatory process make people susceptible to an increased severity of periodontitis. Studies of untreated disease in Sri Lanka identified 3 patterns of disease progression. Studies in twins suggested that part of the clinical characteristics of periodontitis may be explained by genetic factors, but previous attempts to identify genetic markers for periodontitis have been unsuccessful Some genetic variations (polymorphisms) are commonly found in our population and represent a mechanism by which individuals may exhibit variations within the range of what is considered biologically normal. Since certain cytokines are key regulators of the inflammatory response and are important in periodontitis, we investigated the relationship between genetic variations associated with cytokine production and periodontitis severity. There are several polymorphisms in the cluster of genes that influence IL-1 biological activity. In recent clinical trials, two of these polymorphisms, when found together, have been associated with a significant increase in the risk for severe generalized periodontitis. Genetic association with periodontitis was evident only when smokers were excluded from the analysis, confirming the importance of smoking, and suggesting that both smoking and the IL- I genotype are independent factors in severe periodontitis. It is notable that 1 polymorphism associated with severe periodontitis in our study is also known to correlate with a 2- to 4-fold increase in IL-1 beta production. These findings are consistent with the current model of how genetic factors influence common chronic diseases. If we apply this model to periodontitis, it would involve the following: 1) a disease-initiating factor that would undoubtedly be specific bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans. and Bacteroides forsythus: and 2) modifiers of disease mechanisms that account for the clinical severity, including smoking, the IL-I genotype, certain systemic diseases, and psychosocial stress. The association of the IL-I genotype with severe periodontitis is consistent with several lines of periodontal research. Several studies have suggested there is a substantial genetic influence in periodontal disease. Although specific genetic markers have been identified in the uncommon juvenile forms of periodontitis, previous studies of specific genetic markers in adults with periodontitis have not been encouraging. Many investigators have, however, demonstrated a role for IL-1 in the initiation and progression of periodontitis. For example, IL-1 activates the degradation of the extracellular matrix and bone of the periodontal tissues, and elevated tissue or gingival fluid levels of IL-1 beta have been repeatedly associated with periodontitis. In addition, IL-1 is a strong enhancer of tissue levels of PGE2 and TNF-alpha. The association of severe periodontitis with smoking and the IL-1 genotype suggest a role for these factors in the pathogenesis of periodontitis. The finding that host modifying factors are associated with severe periodontitis suggest a biological mechanism by which some individuals, if challenged by bacterial accumulations, may have a more vigorous immunoinflammatory response, leading to more severe clinical disease. (ABSTRACT

Adult↗
PubMed1997

The interleukin-1 genotype as a severity factor in adult periodontal disease.

Although specific bacteria, dental plaque, and age are associated with periodontal disease, there are currently no reliable predictors of periodontitis severity. Studies in twins have suggested a genetic contribution to the pathogenesis of periodontitis, but previous attempts to identify genetic markers have been unsuccessful. The pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are key regulators of the host responses to microbial infection. IL-1 is also a major modulator of extracellular matrix catabolism and bone resorption. We report a specific genotype of the polymorphic IL-1 gene cluster that was associated with severity of periodontitis in non-smokers, and distinguished individuals with severe periodontitis from those with mild disease (odds ratio 18.9 for ages 40-60 years). Functionally, the specific periodontitis-associated IL-1 genotype comprises a variant in the IL-1B gene that is associated with high levels of IL-1 production. In smokers severe disease was not correlated with genotype. In this study, 86.0% of the severe periodontitis patients were accounted for by either smoking or the IL-1 genotype. This study demonstrates that specific genetic markers, that have been associated with increased IL-1 production, are a strong indicator of susceptibility to severe periodontitis in adults.

Adult↗
PubMed1996

Refractory periodontitis: critical questions in clinical management.

Refractory periodontitis appears to be a patient phenomenon with a clinical pattern that may be the result of different influences including genetic factors and exogenous factors that alter the host response to the bacterial challenge. Different patients may have different mechanisms involved in their disease and therefore may show different response patterns following therapy. Although localized non-responsive sites in otherwise responsive patients should not be considered refractory periodontitis, such sites do present substantial therapeutic problems. Initial evidence suggests that local delivery tetracycline provides significant advantages in the management of such sites. Although refractory periodontitis cases appear to be primarily the result of host alterations, the most predictable approach to therapy at present involves systemic antibiotics in conjunction with local therapy. The goal of antibiotic therapy should be to eliminate from detection the target bacteria that were present prior to therapy. Good plaque control, regular professional maintenance therapy, regular microbial monitoring, and control of risk factors are important aspects of the long term maintenance of these cases.

Anti-Bacterial Agents↗
PubMed1995

Adjunctive supragingival irrigation with acetylsalicylic acid in periodontal supportive therapy.

To assess the clinical efficacy of adjunctive supragingival irrigation with buffered 0.3% acetylsalicylic acid (ASA), 60 patients with periodontitis receiving supportive periodontal therapy were randomly assigned to 1 of 3 home regimens: (1) 1x daily adjunctive supragingival irrigation with 300 ml water immediately followed by 200 ml of buffered 0.3% ASA; (2) 1x daily adjunctive supragingival irrigation with 500 ml water; or (3) normal oral hygiene alone. Clinical parameters were assessed at baseline and 6 months. Irrigator use was measured by timers built into the irrigator units. Results at 6 months showed that both supragingival irrigation with buffered 0.3% ASA and supragingival irrigation with water significantly reduced gingival index scores (median 0.1 and 0.35, respectively) and pocket probing depths (both median 0.26 mm) compared to the control group. In addition, irrigation with water resulted in a significant reduction in bleeding on probing (median 0.13), whereas irrigation with buffered 0.3% ASA had no significant effect on bleeding on probing compared to the control group. The clinical efficacy of irrigation with either ASA or water was found to be positively correlated to initial disease severity and irrigator use. Thus, frequent supragingival irrigation with either 0.3% ASA or water in addition to regular oral hygiene appears to be a beneficial adjunct to periodontal supportive therapy in patients with moderate to severe signs of periodontitis. However, the use of buffered 0.3% ASA as an irrigant does not seem to enhance the clinical efficacy of supragingival irrigation on periodontal health.

Adult↗
PubMed1994

Early-onset periodontitis in Hispanic-American adolescents associated with A. actinomycetemcomitans.

This study examines the frequency of oral disease in an adolescent population, and assesses the relationship to Actinobacillus actinomycetemcomitans. A total of 470 eighth grade students from San Antonio, Texas, were examined clinically for number of teeth, frequency of gingival inflammation, frequency of sites with BOP, and frequency of sites with 3-5 mm pockets, and pockets > 5 mm. The population ranged in age from 12 to 17 yr and was 93% Hispanic. Heavy accumulations of plaque and calculus were frequently observed and were associated with gingival inflammation, as 95.6% of the students exhibited bleeding on probing, and 99.6% of the students presented with at least on quadrant of inflammation upon visual examination. Significantly, 25.7% of the students exhibited early-onset periodontitis (EOP) with 1.7% diagnosed as LJP. Many students exhibited substantial levels of plaque and calculus, but no clinical evidence of loss of attachment. Subjects with periodontitis (EOP or LJP) presented with elevated systemic IgG antibody to A. actinomycetemcomitans serotype b and subgingival plaque samples positive for the microorganism. These results describe the prevalence of EOP/LJP in an adolescent Hispanic population from South Texas. The findings support that A. actinomycetemcomitans may represent a pathogen in periodontitis and while oral health care may be poor, contact with the microorganism appears to be required to initiate disease in this population.

Adolescent↗
PubMed1994

Histomorphometrical analysis of the effects of the bisphosphonate alendronate on bone loss caused by experimental periodontitis in monkeys.

This study tested the efficacy of alendronate, a bisphosphate, in reducing alveolar bone loss caused by experimental periodontitis in cynomolgus monkeys. Periodontitis was initiated in adult monkeys by ligating mandibular molar teeth at the cementoenamel junction (CEJ) and subsequently inoculating the ligature with Porphyromonas (Bacteroides) gingivalis. Contralateral, homologous non-ligated teeth served as controls. Animals received, intravenously, either saline (placebo) or alendronate at 0.05 or 0.25 mg/kg every 2 weeks for 16 weeks. After the animals were sacrificed, coronal sections through mandibular molars were subjected to histomorphometrical analysis. No overt side-effects were observed in any of the animals participating in this study. In placebo-treated animals, ligation and inoculation resulted in significant bone loss both at the CEJ and at the furcation. Alendronate at 0.05 mg/kg significantly reduced bone loss associated with the experimental periodontitis at both sites. In contrast, the dose of 0.25 mg/kg was ineffective in attenuating alveolar bone loss in the furcation area and only slightly effective in preventing it at the CEJ area. The results of the histomorphometric analysis correlate closely with those of the radiographic analysis of the same experiment. These data indicate that alendronate could reduce the loss of alveolar support associated with periodontitis and suggest that bisphosphonates, by virtue of their significant inhibitory action on osteoclasts, may become a treatment modality in the battle against alveolar bone destruction during periodontal disease.

Alendronate↗