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Biomedical subjects

S Offenbacher

Publications and source records attributed to S Offenbacher.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acute-phase inflammatory response to periodontal disease in the US population.

Moderate elevation of serum C-reactive protein (CRP) is a risk factor for cardiovascular disease among apparently healthy individuals, although factors that create this inflammatory response in the absence of systemic illness have not been clarified. This study aimed to: (1) evaluate associations among periodontal disease, established risk factors for elevated CRP, and CRP levels within the US population; and (2) determine whether total tooth loss is associated with reduced CRP. Data were obtained from the third National Health and Nutrition Examination Survey. A random sample of the US population was interviewed in their homes and examined at mobile examination centers. CRP was quantified from peripheral blood samples and analyzed as a continuous variable and as the prevalence of elevated CRP (> or = 10 mg/L). Some 12,949 people aged 18+ years who had periodontal examinations and an additional 1,817 edentulous people aged 18+ years were included in the analysis. Dentate people with extensive periodontal disease (> 10% of sites with periodontal pockets 4+ mm) had an increase of approximately one-third in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people. Raised CRP levels among people with extensive periodontal disease persisted in multivariate analyses (P < 0.01), with established risk factors for elevated CRP (diabetes, arthritis, emphysema, smoking, and anti-inflammatory medications) and sociodemographic factors controlled for. However, CRP levels were similarly raised in edentulous people. Furthermore, the established risk factors for elevated CRP modified relationships between oral status and CRP levels. Periodontal disease and edentulism were associated with systemic inflammatory response in the US population, most notably among people who had no established risk factors for elevated CRP.

Acute-Phase Reaction↗
PubMed2000

The influence of sulfate-reducing bacteria colonization of 2 different bioresorbable barrier membranes for GTR. An 18-month case-controlled microbiologic and clinical study.

The purpose of the present microbiologic and case-controlled clinical study was to examine the colonization of 2 different resorbable barrier membranes by sulfate-reducing bacteria (SRB). The barrier membranes tested were Guidor matrix barrier and Resolut regenerative material. Ten patients exhibiting 3 Class II furcation defects and 7 intrabony defects were included in the study. The probing depth and the clinical attachment level at 4 surfaces per tooth were taken at the beginning of the study. Microbiologic samples were taken from the experimental sites and from the approximal sites of the adjacent teeth. Both types of resorbable membranes were positive for SRB colonization. The detection of SRB in 2 of 7 intrabony defects and in all defects with furcation involvement before the membrane placement indicated that these organisms are a common inhabitant of sites showing periodontal destruction and are associated with guided tissue regeneration (GTR). According to the clinical criteria for healing tendencies used in this study, the GTR procedures were less successful in the presence of SRB. There were no significant clinical effects of different resorbable membrane materials or membrane layout on attachment level changes for either the intrabony defect or furcation groups after 18 months. There were no statistical differences for sites that became exposed to SRB when compared to sites that remained unexposed after 18 months. The numeric significance of SRB in relation to the total microbial count needs to be determined to gain insight into the ecologic role of membrane resorption rates.

Absorbable Implants↗
PubMed2000

Periodontal medicine: emerging concepts in pregnancy outcomes.

The term periodontal medicine encompasses the study of the contribution of periodontal infections on several systemic conditions such as atherosclerosis, myocardial infarction, stroke, diabetes, and premature delivery. The early reports of a linkage between periodontitis and systemic conditions are gaining further support from additional epidemiological studies. The evidence continues to suggest that maternal periodontitis may bean important risk factor or risk indicator for pregnancies culminating in preterm low birth-weight deliveries. Potential mechanisms by which infectious challenge of periodontal origin and systemic inflammation may serve as a potential modifier of parturition are discussed. Furthermore, preliminary data are presented, supporting a hypothetical model in which periodontal pathogens disseminate systemically within the mother and gain access to the foetal compartment. Several aspects of this hypothetical model remain to be elucidated. Only the clarification of the mechanisms of pathogenesis of both periodontitis and premature deliveries will ultimately allow for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimise the deleterious effects of this chronic infectious and inflammatory condition on systemic conditions represents both an unprecedented challenge and opportunity to our profession.

Female↗
PubMed1999

The concept of "risk" and the emerging discipline of periodontal medicine.

Dental clinicians intuitively weigh patient risks for developing disease and use that information for making treatment decisions and recommendations. Periodontitis, for instance, is one oral disease with documented risk factors including smoking, specific plaque bacteria and diabetes mellitus. While this link between systemic disease and periodontitis was thought to be unidirectional, mounting evidence in the last decade suggests that the relationship may be bi-directional. Cross sectional and case control studies indicate that periodontitis may confer two and seven-fold elevations in risk for cardiovascular disease and premature low birth weight respectively. While these early studies indicate potential associations between oral and systemic health, they support the central hypothesis that periodontitis triggers both local and systemic host inflammatory responses. Consequently, a new discipline, periodontal medicine, has emerged in dentistry which seeks to further define these interrelationships through scientific inquiry. Ultimately, this new knowledge may prove useful in intervention strategies to reduce patient risks and prevent systemic disease outcomes. This manuscript clarifies the concept of risk, traces the emergence of periodontal medicine and serves as a resource for the oral health professional in assessing and utilizing the current evidence on periodontal-systemic disease connections.

Bacteria, Anaerobic↗
PubMed1999

Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.

BACKGROUND: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.

Autoimmunity↗
PubMed1999

Dental infections and atherosclerosis.

In most countries, coronary heart disease is one of the leading causes of morbidity and death. This report reviews the current evidence indicating that oral conditions (specifically periodontitis) may be a risk factor for atherosclerosis and its clinical manifestations and provides new preliminary data. This review is done in the context of the research indicating that inflammation plays a central role in atherogenesis and that there is a substantial systemic microbial and inflammatory burden associated with periodontal disease. Our review concentrates on 5 longitudinal studies that show oral conditions being associated with the onset of coronary heart disease while controlling for a variety of established coronary heart disease risk factors. In addition to published evidence, preliminary findings from our Dental Atherosclerosis Risk in Communities study also indicate that periodontal disease is associated with carotid intimal-medial wall thickness, a measure of subclinical atherosclerosis, adjusting for factors known to be associated with both conditions.

Arteriosclerosis↗
PubMed1999

Modulation of chronic enteric infection by distant oral infection.

This investigation determined the effects of a distant oral infection (Porphyromonas gingivalis) on a concurrent local enteric infection (Echerichia coli). A modified murine subcutaneous tissue chamber model was used. Subcutaneously implanted chambers with different microbial makeups were monitored for sloughing and their contents assayed for prostaglandin E2. Bilaterally implanted chamber experiments revealed that a distant "chronic" (immunization with heat-killed organism, followed by live challenge) P. gingivalis infection offered protection against a local chronic E. coli infection, as evidenced by delaying the time for 50% of the chambers to reject from day 19 to day 25 and a statistically significant prostaglandin E2 decrease from 529.4 +/- 176.6 ng/ml to 191.5 +/- 100.9 ng/ml (p < 0.01) (Mann-Whitney test). An acute (live challenge only) distant P. gingivalis infection or immunization with the heat-killed organism alone had no effect on "chronic" E. coli infection in this model. These data suggest that the presence of low-grade chronic oral infection may modify the responses to other infectious challenges.

Animals↗
PubMed1999

Etiologic models for incident periodontal attachment loss in older adults.

Etiologic factors for incident periodontal attachment loss (ALOSS) have not been conclusively identified. The purpose of this study was to develop etiologic models for ALOSS in older adults. Data on 697 older blacks and whites were obtained from 5 sequential examinations over 7 years in the Piedmont 65+ dental study, a complex random sample of older adults in North Carolina. Multivariable Poisson regression models were fit for average number of ALOSS events per person or site month at risk. In models for whites, molar sites, sites with adjacent caries, sites in persons who had: Porphyromonas gingivalis (P.g.) at least 2% of total microbial count (TMC), never had a dental checkup, more depression symptoms, fewer than 12 years of education, higher BANA score, or smoked, had significantly higher rates of ALOSS. In a separate model for blacks, interproximal and molar sites, sites in blacks who had: P.g. at least 2% of TMC, higher BANA score, never had a dental checkup, lower socioeconomic status (SES), or smoked, had significantly higher rates of ALOSS. These results confirm a multifactorial etiology for ALOSS in older adults and indicate that interventions aimed at infection, smoking, and preventive dental care utilization, may be most useful.

Black or African American↗
PubMed1999

Induction of prostaglandin release from macrophages by bacterial endotoxin.

This review summarizes the role of the monocytic responses to lipopolysaccharide as it relates to periodontal disease severity. Data are presented which illustrate that the levels of prostaglandin E2 (PGE2) secreted by systemic peripheral blood monocytes in culture, in the presence of bacterial endotoxins, are highly correlated with the levels observed in the gingival crevicular fluid. Furthermore, the different periodontal diagnostic categories have varying levels of monocytic and crevicular fluid PGE2, in juxtaposition with clinical disease severity. These data are consistent with the concept that there is close synchrony between the systemic responsiveness of peripheral blood monocytes with regard to prostanoid synthesis and the local levels of mediator present within the gingival crevice.

Adult↗
PubMed1999

Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis.

The early reports of a linkage between periodontitis and atherosclerosis have garnered further support by additional data generated by several investigative teams in many different countries. The evidence continues to suggest that periodontitis may be an important risk factor or risk indicator for cardiovascular pathology for some individuals. The term periodontitis-atherosclerosis syndrome (PAS) is proposed as a new diagnostic term to describe this condition in these individuals. Current evidence, albeit preliminary in nature, which describes a cluster of clinical signs and symptoms that are associated with this condition, is presented. It is clear that this syndrome will require considerable study and refinement before a definitive diagnosis and treatment plan can be formulated. Potential mechanisms by which systemic inflammation and infectious challenge of periodontal origin may serve as a potential modifier of cardiovascular disease are discussed in the context of a detailed working model of pathogenesis. This hypothetical model embraces many cellular and molecular components of atherogenesis and thromboembolic diseases from the perspective of periodontitis pathogenesis. Many aspects of the hypothetical model remain unproved; however, it is our opinion that only through the clarification of the mechanisms of pathogenesis can we ultimately construct a knowledge framework for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on the cardiovascular system represents an unprecedented challenge to our profession.

Arteriosclerosis↗
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

Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.

Arteriosclerosis↗
PubMed1999

Periodontitis and cytokine expression in CD14 deficient patients.

Patients with paroxysmal nocturnal haemoglobinuria (PNH) are deficient in monocytic CD14. The aim of this research was to determine the interrelationships among periodontal disease status, local levels, and monocytic secretion of inflammatory mediators in patients with PNH and matched controls. This study utilised a cross sectional, non-randomised design. PNH patients and matched controls (age, race, gender) were assessed for periodontal status, levels of PGE2 and IL-1beta within the gingival crevicular fluid (GCF), and levels released from lipopolysaccharide (LPS) stimulated peripheral blood monocytes in culture. Results indicate no statistical differences in extent and severity of periodontal disease or GCF mediator levels between the two groups. Monocyte responses to LPS demonstrated significant differences in PGE2 (P = 0.0009) and IL-1beta (P = 0.003) secretion with PNH monocytes secreting significantly less than controls. A significant positive association was found between the monocytic and GCF levels of PGE2 for all subjects (P = 0.003), PNH (P = 0.015), and control (P = 0.049) groups. This study demonstrated that GPI anchor deficient monocytes have reduced expression of inflammatory mediators in vitro.

Adult↗
PubMed1998

Inflammatory mediators of the terminal dentition in adult and early onset periodontitis.

Based upon the prosthodontic literature, subjects who are at the transition stage between natural dentition and edentulism are called "terminal dentition" (TD) cases. The aim of the present cross-sectional investigation was to characterize the local and systemic inflammatory responses in 2 groups of patients with terminal dentition periodontitis. Eight severe adult periodontitis terminal dentition (AP-TD) subjects and 8 early onset periodontitis terminal dentition (EOP-TD) subjects were entered into the study. Our purpose was to measure an extended battery of cytokines in the gingival crevicular fluid (GCF) and in lipopolysaccharide (LPS)-stimulated monocytic culture supernatants as well as gingival mononuclear cell messenger RNA (mRNA) transcripts determined from biopsy samples. Within the GCF there were 3 tiers (levels) of mediators based upon approximate 10-fold differences in concentration. The highest tier included prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2), the intermediate tier included tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN-gamma) and at the lowest concentration level were interleukin-4 (IL-4) and interleukin-6 (IL-6). Thus, the GCF analysis clearly indicated that in both AP-TD and EOP-TD groups the monocytic, i.e. IL-1 beta and PGE2 and Th1, i.e. IL-2 and IFN-gamma, inflammatory mediator levels quantitatively dominated over the Th2 mediators, i.e. IL-4 and IL-6. LPS-stimulated monocytic release of IL-1 beta, PGE2 and TNF alpha was significantly elevated in both AP-TD and EOP-TD groups compared to those of a control group of 21 subjects with moderate to advanced adult periodontitis. The cytokine mRNA expression of isolated gingival mononuclear cells showed that in both the AP-TD and the EOP-TD groups Th1 and Th2 cytokines were expressed, with low levels of IL-4 and IL-12. In conclusion, our data suggest that this cross-sectional TD periodontitis model may reflect progressive periodontal disease associated with tooth loss. Furthermore, although Th1 cytokine levels in the GCF dominate over the Th2 response, monocytic activation provides the main source of proinflammatory mediators. In addition, LPS-stimulated peripheral blood monocytes demonstrate an upregulated inflammatory mediator secretion in the terminal dentition.

Adult↗
PubMed1998

Pharmacokinetic and safety evaluations of ketoprofen gels in subjects with adult periodontitis.

This clinical trial used a randomized, partially double-blind, controlled parallel design to evaluate the pharmacokinetics and safety of the NSAID, ketoprofen (KTP), in gel formulations. Forty-two subjects, ages 35 to 57 years, with generalized, moderate to advanced adult periodontitis were recruited and randomized to one of 5 treatments over a 14 1/2-day treatment period: (1) 0.5% KTP gel; (2) 1.0% KTP gel; (3) 1.0% KTP alternate gel; (4) 2.0% KTP gel; and (5) 25 mg KTP capsule (positive control). Plasma samples were obtained on days 1 (pre-dosing, 0.5, 1, 2, 3, 6 hr), 8 (pre-dosing, 2 hr), 15 (pre-dosing, 2 hr), and 22 (7 days post-treatment). Plasma KTP concentrations were determined by means of high-performance liquid chromatography. Significant differences in mean area under the plasma concentration vs. time curve (AUC(0-infinity)) among the groups were detected (p < 0.001), with the 25 mg p.o. capsule exhibiting the largest value (5054 ng-hr/mL), the 2.0% gel exhibiting an intermediate value (2244 ng-hr/mL), the 1.0% gels exhibiting lower but comparable values (1516 for the alternate formulation vs. 1461 ng-hr/mL), and the 0.5% gel showing the lowest value (736 ng-hr/mL). Significant differences in dose- and weight-adjusted maximum plasma concentration (Cmax/dose/kg) were detected overall such that the 25 mg p.o. capsule demonstrated higher values as compared with the 4 gel formulations (p = 0.001). The 5 treatments exhibited similar mean times of maximum plasma concentration (tmax) values ranging from 0.6 to 1 hr. Systemic exposures relative to dose and body weight were lower for the gel formulations than for the capsule. The relative systemic bioavailability of the gels compared with peroral administration ranged from 54% to 69%.

Administration, Oral↗
PubMed1998

Periodontitis: a risk factor for coronary heart disease?

This paper evaluates the current information on the relationship between oral disease (specifically periodontitis) and atherosclerosis/coronary heart disease (CHD) to determine whether the information is sufficient to conclude that periodontitis is a risk factor for atherosclerosis/CHD. As background for this evaluation, the term "risk factor" is defined, and the 3 criteria used to establish exposures as risk factors are reviewed. In addition, epidemiologic criteria for defining an exposure as causal are presented. The available evidence then is evaluated according to the criteria for causality, which are extensions of the criteria for establishing a risk factor. This review is done in the context of the relationship between atherosclerosis/CHD and inflammation. A number of findings are briefly reviewed that link inflammation and atherosclerosis/CHD, such as: 1) prior flu-like symptoms were more common in cases of myocardial infarction than in concurrently sampled controls; 2) high levels of cytomegalovirus antibody titers were associated with elevated carotid intimal-medial wall thickness 18 years later; 3) prior infection with cytomegalovirus was a strong independent risk factor for restenosis after coronary atherectomy; 4) dental infections were more common in cases of cerebral infarction compared to community controls matched on age and sex; and 5) the gingival index was significantly correlated with fibrinogen and white cell counts in periodontal patients and controls, adjusted for age, smoking, and socioeconomic status. Three case-control studies and 5 longitudinal studies investigating the relationship between dental conditions and atherosclerosis/CHD are reviewed in terms of strength of associations, consistency of associations, specificity. of associations, time sequence between exposure and outcome, and degree of exposure and outcome. Related to the last criterion, new findings are presented which indicate that the extent of the periodontal infection, a measure reflecting microbial burden, also is related to onset of new CHD events. Our previously published model describing the potential biological mechanisms underlying the associations found is reviewed. This model places the associations into a context of an intrinsic or acquired hyperinflammatory monocyte trait that results in a more intense inflammatory response to lipopolysaccharide (LPS) challenges, such as periodontal infections. This hyperinflammatory response may promote atheroma formation and thromboembolic events. finally, new findings from ongoing animal studies are presented, indicating that high fat diets in atherosclerotic-susceptible mice induce greater inflammatory responses to Porphyromonas gingivalis challenges. We conclude that the available evidence does allow an interpretation of periodontitis being a risk factor for atherosclerosis/CHD. This conclusion, however. is made with some qualifications. While the associations found across a wide variety of subjects are remarkably consistent, for the most part they are represented by incidence odds ratios around 2.0. While this level of association would result in oral conditions contributing to a large number of CHD cases, it is possible that associations of this magnitude are due to bias in the study designs. In addition, some studies report that periodontitis is associated with all-cause mortality and low birth weight infants. These multiple associations detract from the credibility of periodontitis as a risk factor, as specificity of association is more often related to causality. However, all-cause mortality may largely be driven by mortality from cardiovascular events: and some exposures, such as smoking. are indeed risk factors for multiple conditions. On the other hand, current findings regarding the associations between oral conditions and atherosclerosis/CHD imply that the criteria for causality may be met in the not-too-distant future.

Animals↗