Systemische Krankheiten

 

A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage (i.e. Multiple organ dysfunction syndrome), diseases where multiple organ involvement is at presentation or in early stage are considered.

Addy, M. and P. Renton-Harper (1996). "Local and systemic chemotherapy in the management of periodontal disease: an opinion and review of the concept." J Oral Rehabil 23(4): 219-31.

ABSTRACT: Periodontal disease appears to arise from the interaction of pathogenic bacteria with a susceptible host. The main aims of disease management have been to establish a high standard of oral hygiene and to professionally and thoroughly debride the root surface Chemical agents could be considered for both aspects of management. Chemoprevention using supragingivally delivered agents such as chlorhexidine may be questioned for value in the pre-treatment hygiene phase but have well-established efficacy immediately preoperatively and during the post-operative weeks. Long-term maintenance use of chlorhexidine is problematic due to local side effects. Antiplaque toothpastes show modest benefits to gingivitis but are not proven to prevent recurrence of periodontitis. Chemotherapy may be directed at subgingival plaque, using antimicrobials, or at the host response using anti-inflammatory agents. Antimicrobials can be locally or systemically delivered. In most cases antimicrobial chemotherapy should be considered adjunctive to mechanical debridement. The advantages of local and systemic chemotherapy must be balanced against the disadvantages and potential side effects of agents. Antimicrobial chemotherapy offers little or no benefit to the treatment of most chronic adult periodontitis patients and should be reserved for the more rapid or refractory types of disease, and after the debridement phase. Despite the large number of studies there are insufficient comparative data to support any one local delivery system or systemic regimen as superior to another. Systemic versus local antimicrobials have not been compared to date. Host response modifying drugs such as non-steriodal anti-inflammatory drugs (NSAIDS) offer the potential to reduce breakdown and promote healing, including bone regeneration. However until more data are available, NSAIDs should not be used in the management of chronic periodontal diseases, there being no specific agent(s) or regimen established for use. Chemotherapy has an important place in the management of chronic periodontal diseases but routine use must be considered as an over prescription of these valuable agents.

Alexander, R. E. (2006). "Relationship between periodontal disease and systemic diseases." Tex Dent J123(2): 139; author reply 139.

Amar, S., N. Gokce, et al. (2003). "Periodontal disease is associated with brachial artery endothelial dysfunction and systemic inflammation." Arterioscler Thromb Vasc Biol 23(7): 1245-9.

ABSTRACT: OBJECTIVE: The purpose of this study was to determine whether periodontal disease is associated with endothelial dysfunction and systemic inflammation. Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown. METHODS AND RESULTS: We assessed flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery using vascular ultrasound in 26 subjects with advanced periodontal disease and 29 control subjects. The groups were matched for age and sex, and patients with hypercholesterolemia, diabetes mellitus, hypertension, and history of cigarette smoking were excluded. We also examined serum levels of C-reactive protein using an established high-sensitivity method. Subjects with advanced periodontal disease had lower flow-mediated dilation compared with control patients (7.8+/-4.6% versus 11.7+/-5.3%, P=0.005). Nitroglycerin-mediated dilation was equivalent in the two groups. Subjects with advanced periodontitis exhibited higher serum levels of high-sensitivity C-reactive protein compared with healthy controls patients (2.3+/-2.3 versus 1.0+/-1.0 mg/L, P=0.03). CONCLUSIONS: Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation, possibly placing them at increased risk for cardiovascular disease.

Bascones-Martinez, A. and M. Escribano-Bermejo (2005). "[Necrotizing periodontal disease: a manifestation of systemic disorders]." Med Clin (Barc) 125(18): 706-13.

ABSTRACT: Necrotizing periodontal disease (NPD) is an infection characterized by gingival necrosis presenting as "punched-out" papillae, with gingival bleeding, and pain. Prevotella intermedia and spirochetes have been associated with the gingival lesions. Predisposing factors may include emotional stress, immunosuppression, especially secondary to human immunodeficiency virus (HIV) infection, cigarette smoking, poor diet and pre-existing gingivitis. During the last few years, diagnosis of NPD has became more important not only because of its contribution to the appearance of clinical attachment loss and gingival sequelae, but also because it has been revealed as a marker for immune deterioration in HIV-seropositive patients.

Beck, J. D. and S. Offenbacher (2002). "Relationships among clinical measures of periodontal disease and their associations with systemic markers." Ann Periodontol 7(1): 79-89.

ABSTRACT: BACKGROUND: Recent investigations of the relationship between periodontitis and systemic disease require that periodontal disease also must be thought of as a disease process that is an exposure for a systemic disease or condition (outcome), rather than as the outcome itself. When viewing periodontal disease as an exposure, investigators must consider the clinical, microbiological, and inflammatory components of periodontitis that potentially convey risk for the systemic outcome of interest, which may or may not be the same as those associated with the assessments used to define tooth-based disease. Another important consideration is the temporal relationship between the exposure and the outcome of interest. METHODS: To explore which definitions of periodontal disease or clustering of clinical signs are important with regards to systemic exposure to inflammatory stress, we examined the relationship between clinical periodontal disease measures and 2 systemic inflammatory markers of increased risk for cardiovascular disease: serum soluble intercellular adhesion molecule (sICAM), which is a measure of vascular stress and serum C-reactive protein (CRP), which is a measure of hepatic acute-phase response. The Dental Arteriosclerosis Risk in Communities (ARIC) study, a cross-sectional study of the relationship between periodontal disease and cardiovascular disease, forms the basis for the examples used in this investigation. RESULTS: Our findings demonstrated that while attachment loss, probing depth, (PD) and bleeding on probing (BOP) are individually associated with sICAM and CRP, only BOP remains significant for sICAM when all 3 are in the model and, for CRP, only PD remains significant. Both of these clinical parameters were more robust in estimating the degree of systemic inflammation than traditional classifications of mild, moderate, and severe periodontitis or other measures of disease severity such as attachment loss. CONCLUSIONS: When selecting a definition of "systemic periodontitis" (periodontal disease that represents an exposure for a systemic condition), it is helpful to think of periodontal disease as a chronic oral infection with a number of clinical signs, rather than as the dento-centrically defined entity, periodontal disease. Thus, "systemic periodontitis" should be defined predicated upon those clinical signs that best represent the underlying mechanisms and temporal sequence that may affect that systemic outcome.

Beck, J. D. and S. Offenbacher (2005). "Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease." J Periodontol 76(11 Suppl): 2089-100.

ABSTRACT: There have been 42 published studies describing associations between oral conditions and cardiovascular diseases. In the absence of randomized controlled trials, the 16 longitudinal studies represent the highest level of evidence available. However, two databases produced eight of the 16 studies. There also is extensive variability in definitions of the oral exposure that include salivary flow, reported periodontal disease, number of teeth, oral organisms, antibodies to oral organisms, Total Dental Index, Community Periodontal Index of Treatment Needs, plaque scores, probing depth, attachment loss, and bone level. Variability also exists in the cardiovascular outcomes that include atherosclerosis measures and events, such as hospitalization for coronary heart disease (CHD), chronic CHD, fatal CHD, total stroke, ischemic stroke, and revascularization procedures. One of the criticisms of this research is that the exposure has not been represented by measures of infection. To begin to address this concern, we present new data showing that patterns of high and low levels of eight periodontal pathogens and antibody levels against those organisms are related to clinical periodontal disease as well as other characteristics of the individuals, such as age, race, gender, diabetic status, atherosclerosis, and CHD. As others before us, we conclude that the cumulative evidence presented above supports, but does not prove, a causal association between periodontal infection and atherosclerotic cardiovascular disease or its sequelae. A number of legitimate concerns have arisen about the nature of the relationship and, indeed, the appropriate definitions for periodontal disease when it is thought to be an exposure for systemic diseases. There is still much work needed to identify which aspects of the exposure are related to which aspects of the outcome. Principal component analyses illustrate the complexity of the interactions among risk factors, exposures, and outcomes. These analyses provide an initial clustering that describes and suggests the presence of specific syndromes.

Berglundh, T., B. Liljenberg, et al. (1998). "Local and systemic TCR V gene expression in advanced periodontal disease." J Clin Periodontol 25(2): 125-33.

ABSTRACT: The aim of the present investigation was to study the expression of specific alpha/beta T cell receptor (TCR) gene products in relation to some microbiological and immunological features of advanced destructive periodontitis. 21 individuals with advanced periodontal disease (diseased group) and 16 age- and sex-matched healthy subjects (healthy group) were recruited. Following a clinical examination of the diseased group, the 3 deepest interproximal sites in the upper and lower premolar- or molar segments (i.e., 12 sites in each individual) were selected for further analysis. Samples from the subgingival microbiota were obtained from the pocket of the selected sites and were prepared for a microbiological examination. The gingival tissue at one of the selected sites was also biopsied. Each excised soft tissue specimen was divided into 2 equal portions. One portion of the biopsy was prepared for histometric and morphometric analyses. The 2nd portion was snap frozen and prepared for immunohistochemical analysis. A sample of peripheral blood was obtained from each individual of the diseased and the healthy group and prepared for immunohistochemical analysis. The selected sites of the diseased group harbored varying numbers of microorganisms which have been associated with periodontal disease. The excised gingival tissue contained inflammatory lesions with substantial numbers of lymphocytes and plasma cells including T- and B-cells and a TCR V alpha/beta gene repertoire dominated by Vbeta 17. The TCR profile of the lesion, however, differed markedly from that of the circulating blood of the diseased subjects. While only minor differences were observed between the blood samples of the diseased and the healthy subjects regarding the TCR genes, CD5, HLA-DR and CD5+CD19 positive cells occurred in higher proportions in the blood samples of the subjects susceptible to periodontal disease than in healthy controls. It may be suggested that (i) TCR V alpha/Vbeta expression in peripheral blood samples of subjects with periodontal disease does not differ from that of healthy individuals, and (ii) the periodontitis lesion expresses a unique TCR repertoire in which the Vbeta 17 gene dominates.

Campbell, E. (2007). "It's more than the mouth: the effects of periodontal disease on systemic health." Dent Assist 76(3): 26-8, 30-1.

Celenligil-Nazliel, H., E. Kansu, et al. (1999). "Periodontal findings and systemic antibody responses to oral microorganisms in Behcet's disease." J Periodontol 70(12): 1449-56.

ABSTRACT: BACKGROUND: Behcet's disease is a multisystem disorder of unknown etiology, affecting predominantly the oral mucosa, skin, and eyes. Recurrent and painful episodes of oral ulcerations interfere with regular oral hygiene leading to rapid bacterial plaque accumulation. The aims of this study were to evaluate the periodontal status of patients with Behcet's disease and determine serum antibody responses to selected oral microorganisms, including major periodontopathogens in these patients. METHODS: Thirty-three patients with Behcet's disease and 15 healthy subjects were included in the study. Plaque, sulcular bleeding, periodontal index scores, probing depths, and total number of teeth were recorded. Serum IgG antibody levels to a panel of 13 oral microorganisms were determined. RESULTS: Significantly higher values for each of the clinical measures were observed in patients with Behcet's disease compared to healthy subjects (P <0.0001). Antibody levels to selected members of plaque, including Actinomyces viscosus, Streptococcus mutans, Streptococcus sanguis, Streptococcus oralis, Eikenella corrodens, Campylobacter rectus, and Prevotella intermedia were significantly lower in patients with Behcet's disease than in controls (P <0.001-0.05). In contrast, these patients exhibited significantly elevated antibody levels to Actinobacillus actinomycetemcomitans Y4 compared to controls (P <0.01). CONCLUSIONS: Our data indicate that the patients with Behcet's disease generally exhibit clinical findings of established periodontal disease. Decreased antibody responses to early colonizers of both supra- and subgingival plaque were observed along with the elevation in antibody levels to A. actinomycetemcomitans. These results suggest that the bacterial plaque ecology and/or immune responses to these microorganisms may be affected in Behcet's disease which could lead to changes in the expression of periodontal disease.

Chang, K. M., M. E. Ryan, et al. (1996). "Local and systemic factors in periodontal disease increase matrix-degrading enzyme activities in rat gingiva: effect of micocycline therapy." Res Commun Mol Pathol Pharmacol 91(3): 303-18.

ABSTRACT: We previously reported that both local and systemic factors relevant to the pathogenesis of periodontal disease can increase gingival collagenase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdown requires multiple enzyme interactions, the current study was carried out to determine the effects of bacterial endotoxin (LPS) (a local factor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) in the gingiva of rats. In addition, the effects of therapy with a semisynthetic tetracycline (minocycline) were investigated. Ten male, Sprague-Dawley rats were made diabetic by IV injection of streptozotocin. Four of the ten rats then received minocycline (10 mg/day) by oral gavage on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 microliters of E. coli LPS (10 mg/ml) by injection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with saline into the gingiva. At the end of the 3 week experimental period, gingival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased the four matrix-degrading enzyme activities in both gingiva and skin. In contrast, local LPS injection increased these enzyme activities in the gingiva alone. Systemic therapy with minocycline completely ameliorated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containing skin extract from diabetic rats also inhibited collagenase and gelatinase activities, but no inhibition was observed for elastase and beta-glucuronidase activities, indicating that the MMPs and other enzymes were inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.

Craig, R. G., P. Kotanko, et al. (2007). "Periodontal diseases--a modifiable source of systemic inflammation for the end-stage renal disease patient on haemodialysis therapy?" Nephrol Dial Transplant 22(2): 312-5.

Dietrich, T. and R. I. Garcia (2005). "Associations between periodontal disease and systemic disease: evaluating the strength of the evidence." J Periodontol 76(11 Suppl): 2175-84.

ABSTRACT: Much work has been published on the association between periodontal disease and systemic disease, including original reports, narrative reviews, systematic reviews, and meta-analyses. Based on the existent work, one can assign an evidence level and grade, using standard evidence-based criteria, to the data available in the four major categories of medical outcomes studied: cardiovascular/cerebrovascular, pregnancy, pulmonary, and diabetes. We discuss methodologic and conceptual problems in the study of oral-systemic associations, focusing as an example on the association between periodontal disease and cardiovascular/cerebrovascular disease. We argue that the hierarchical ranking of studies by levels of evidence may be misleading. In particular, while randomized controlled trials (RCTs) are needed to determine the efficacy of periodontal treatment to reduce the risk of cardiovascular events, they may be of limited value in determining the etiologic role of periodontal disease on coronary heart disease and stroke. We discuss limitations of RCTs as well as the limitations of currently available data from epidemiologic studies, including study design and confounding and misclassification errors. We conclude that well-designed observational studies into the associations between periodontal disease and systemic disease need to remain an integral component of future research efforts in order to fully understand such associations.

Dumitrescu, A. L. (2006). "Occurrence of self-reported systemic medical conditions in patients with periodontal disease." Rom J Intern Med 44(1): 35-48.

ABSTRACT: OBJECTIVES: The objective of this retrospective study was to investigate the occurrence of self-reported systemic disorders in patients referred to a specialist clinic for periodontal treatment and to determine if an association existed between general health and periodontal disease severity in this population. MATERIAL AND METHODS: The study design was a case-controlled, retrospective chart review. Patient charts (n=1044) were selected from the Department of Periodontology, Carol Davila University of Medicine and Pharmacy. These charts were examined to determine patient's self-reported systemic condition. In addition, the periodontal diagnosis was recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine the periodontal diagnosis. RESULTS: The most frequent disorders in patients with gingivitis were high blood pressure (35.85%), followed by coronary artery disease (15.741%), kidney and urinary tract disorders (15.71%) and allergic reactions (14.28%). 80% of patients with gingivitis had at least one of these disorders. The most frequent disorders in patients with periodontitis were high blood pressure (29.51%) followed by digestive disorders (18.92%), coronary artery disease (16.54%), kidney and urinary tract disorders (16.24%), endocrine disorders (10.58 %), rheumatoid arthritis/rheumatism (9.68%), Hepatitis A (9.38%), diabetes (8.79%) allergic reactions (8.79%), liver and gallbladder disorders (7.30%), sinusitis (6.55%), osteoporosis (5.51%) and respiratory disorders (5.36%). 81.96% of patients with periodontitis had at least one of these disorders. However, only rheumatoid arthritis was found to be more prevalent in periodontitis patients compared with gingivitis affected individuals (p<0.05). Multiple correlations were found between the independent variables. CONCLUSIONS: These findings support the results from previous investigators that a number of systemic conditions are closely associated with periodontal disease.

Fowler, E. B., L. G. Breault, et al. (2001). "Periodontal disease and its association with systemic disease." Mil Med 166(1): 85-9.

ABSTRACT: Periodontal diseases are oral disorders characterized by inflammation of the supporting tissues of the teeth. Usually, periodontitis is a progressively destructive loss of bone and periodontal ligament (loss of the attachment apparatus of the teeth). Periodontitis has documented risk factors, including but not limited to specific plaque bacteria, smoking, and diabetes mellitus. Initially, the link between systemic disease and periodontal diseases was thought to be unidirectional. Currently, there is increasing evidence that the relationship between these entities may be bidirectional. Recent case-control and cross-sectional studies indicate that periodontitis may confer a 7-fold increase in risk for preterm low birth weight infants and a 2-fold increase in risk for cardiovascular disease. These early reports indicate the potential association between systemic and oral health. Additionally, these studies support the central hypothesis that periodontal disease involves both a local and a systemic host inflammatory response. This knowledge of disease interrelationships may prove vital in intervention strategies to reduce patient risks and prevent systemic disease outcomes. Based on the current evidence of the periodontal-systemic disease connection, the purpose of this report is to help establish the groundwork for closer communication between physicians and periodontists in the military health care setting.

Garcia, R. I., M. M. Henshaw, et al. (2001). "Relationship between periodontal disease and systemic health." Periodontol 2000 25: 21-36.

Glurich, I., S. Grossi, et al. (2002). "Systemic inflammation in cardiovascular and periodontal disease: comparative study." Clin Diagn Lab Immunol 9(2): 425-32.

ABSTRACT: Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.

Graves, D. T., Y. Jiang, et al. (2000). "Periodontal disease: bacterial virulence factors, host response and impact on systemic health." Curr Opin Infect Dis 13(3): 227-232.

ABSTRACT: Teeth are coated with a biofilm that contains periodontal pathogens. Pathogens express virulence factors which enable them to invade and replicate within epithelial cells and to invade the underlying connective tissue. This stimulates production of prostaglandins and cytokines that induce tissue loss. In addition, these bacteria have the potential to modulate the course of systemic diseases such as atherosclerosis and to contribute to low birthweight and preterm labor.

Hamilton, J. (2005). "The link between periodontal disease and systemic diseases: state of the evidence 2005." J Calif Dent Assoc 33(1): 29-38.

Hills-Smith, H. and N. J. Schuman (1983). "Antibiotic therapy in pediatric dentistry. II. Treatment of oral infection and management of systemic disease." Pediatr Dent 5(1): 45-50.

Hyman, J. (2006). "The importance of assessing confounding and effect modification in research involving periodontal disease and systemic diseases." J Clin Periodontol 33(2): 102-3.

Jepsen, R. and G. A. Kuchel (2006). "Nutrition and inflammation: the missing link between periodontal disease and systemic health in the frail elderly?" J Clin Periodontol 33(5): 309-11.

Joag, S. V., I. Adany, et al. (1997). "Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS." J Virol 71(5): 4016-23.

ABSTRACT: Chimeric simian/human immunodeficiency virus (SHIV) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (HIV-1) on a background of simian immunodeficiency virus (SIV). We derived a SHIV that caused CD4+ cell loss and AIDS in pig-tailed macaques (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (SHIV(KU-1)) to inoculate macaques by the intravaginal route. Macaques developed high virus burdens and severe loss of CD4+ cells within 1 month, even when inoculated with only a single animal infectious dose of the virus by the intravaginal route. The infection was characterized by a burst of virus replication that peaked during the first week following intravenous inoculation and a week later in the intravaginally inoculated animals. Intravaginally inoculated animals died within 6 months, with CD4+ counts of <30/microl in peripheral blood, anemia, weight loss, and opportunistic infections (malaria, toxoplasmosis, cryptosporidiosis, and Pneumocystis carinii pneumonia). To evaluate the kinetics of virus spread, we inoculated macaques intravaginally and euthanized them after 2, 4, 7, and 15 days postinoculation. In situ hybridization and immunocytochemistry revealed cells expressing viral RNA and protein in the vagina, uterus, and pelvic and mesenteric lymph nodes in the macaque euthanized on day 2. By day 4, virus-infected cells had disseminated to the spleen and thymus, and by day 15, global elimination of CD4+ T cells was in full progress. Kinetics of viral replication and CD4+ loss were similar in an animal inoculated with pathogenic SHIV orally. This provides a sexual-transmission model of human AIDS that can be used to study the pathogenesis of mucosal infection and to evaluate the efficacy of vaccines and drugs directed against HIV-1.

John, V. and S. J. Kim (2002). "Periodontal disease and systemic disease. Clinical information for the practicing dentist." J Indiana Dent Assoc 81(2): 15-8.

ABSTRACT: The relationship between periodontal and systemic disease, previously called the "focal infection theory" or "focus of infection," has become an exciting area of clinical and laboratory research. Periodontal disease has been reported to influence diabetes mellitus, cardiovascular disease, osteoporosis, and respiratory disease. It also can influence the course and duration of pregnancy. This article reviews some of these associations and proposed mechanisms by which periodontal disease and systemic conditions influence each other. We also discuss clinical implications for our daily practice in dentistry.

Karaarslan, F., I. Coker, et al. (1998). "Disturbed systemic immune balance in periodontal disease." Autoimmunity 27(2): 123-4.

Kim, J. and S. Amar (2006). "Periodontal disease and systemic conditions: a bidirectional relationship." Odontology 94(1): 10-21.

ABSTRACT: For decades, physicians and dentists have paid close attention to their own respective fields, specializing in medicine pertaining to the body and the oral cavity, respectively. However, recent findings have strongly suggested that oral health may be indicative of systemic health. Currently, this gap between allopathic medicine and dental medicine is quickly closing, due to significant findings supporting the association between periodontal disease and systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. Significant effort has brought numerous advances in revealing the etiological and pathological links between this chronic inflammatory dental disease and these other conditions. Therefore, there is reason to hope that the strong evidence from these studies may guide researchers towards greatly improved treatment of periodontal infection that would also ameliorate these systemic illnesses. Hence, researchers must continue not only to uncover more information about the correlations between periodontal and systemic diseases but also to focus on positive associations that may result from treating periodontal disease as a means of ameliorating systemic diseases.

Kimura, I., J. Kuramoto, et al. (1990). "[A co-operative study on prophylactic effect of oral administration of high-dose amphotericin B syrup for systemic fungal infection in patients with hematological neoplasms. Chugoku-Shikoku Study Group of Mycosis with Hematologic Disease]." Gan To Kagaku Ryoho 17(5): 1027-32.

ABSTRACT: The prophylactic effect of the oral administration of high-dose amphotericin B syrup for the systemic fungal infection was studied in 36 patients with hematological neoplasms. Twenty nine patients received 2,400 mg/day of Amphotericin B syrup for during the remission induction therapy. One patient received 1,200 mg/day, 3 received 800 mg/day and 3 received 400 mg/day of Amphotericin B syrup. The prophylactic effect was recognized in 24 of 36 patients, 66.7%. As adverse effects gastrointestinal symptoms such as nausea and vomiting, hypochloremia and hypopotassemia associated with hypochloremia was observed in one patient, respectively, however, they were all controllable. The blood levels of Amphotericin B in patients received 2,400 mg/day was 0.092 +/- 0.055 micrograms/ml (n = 40) on 7th day and 0.110 +/- 0.046 micrograms/ml (n = 21) on 28th day, respectively. The administration of high-dose of Amphotericin B syrup is expected not only for the prophylaxis but also for the treatment of the systemic fungal infection.

Kinane, D. F., D. F. Lappin, et al. (1999). "Humoral immune responses in periodontal disease may have mucosal and systemic immune features." Clin Exp Immunol 115(3): 534-41.

ABSTRACT: 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.

Kinane, D. F. and G. J. Marshall (2001). "Periodontal manifestations of systemic disease." Aust Dent J46(1): 2-12.

ABSTRACT: Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.

Krall, E. A. (2001). "The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease." Ann Periodontol 6(1): 209-13.

ABSTRACT: Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

Lagervall, M., L. Jansson, et al. (2003). "Systemic disorders in patients with periodontal disease." J Clin Periodontol 30(4): 293-9.

ABSTRACT: BACKGROUND, AIMS: Over the past 10 years several studies have been published pointing towards a relationship between periodontal disease and various systemic disorders or diseases. The purpose of this retrospective study was to investigate the occurrence of self-reported systemic disorders in patients referred to a specialist clinic for periodontal treatment and to explore possible relationships between general health and periodontal disease severity in this population. MATERIAL AND METHODS: Data were collected from the dental records and the health questionnaires of 1006 subjects. Stepwise multiple linear regression analyses were adopted to calculate correlations between systemic disorders as independent variables and number of remaining teeth and the relative frequency of periodontal pockets of 5 mm or more, respectively, as the dependent variable. RESULTS: The number of remaining teeth was significantly and positively correlated to the presence of cardiovascular disease, diabetes and rheumatoid disease after adjustment for age, sex and smoking. The relative frequency of diseased sites, however, was not significantly correlated to any one of the investigated systemic health disorders. CONCLUSION: No significant associations between investigated systemic disorders and periodontal disease severity were found if the relative frequency of deep periodontal pockets was used as the clinical parameter for periodontal disease severity. However, cardiovascular disease, diabetes and rheumatoid disease were found to be significantly correlated to number of lost teeth, which may represent one aspect of periodontal health. This result held true in nonsmokers only.

Lamster, I. B. (2001). "Current concepts and future trends for periodontal disease and periodontal therapy, Part 1: Etiology, risk factors, natural history, and systemic implications." Dent Today 20(1): 50-5.

Lappin, D. F., A. M. McGregor, et al. (2003). "The systemic immune response is more prominent than the mucosal immune response in the pathogenesis of periodontal disease." J Clin Periodontol 30(9): 778-86.

ABSTRACT: BACKGROUND, AIM: The diseased periodontium appears to express features of a systemic and a mucosal immune response. Our aims were to determine differences in immunoglobulin expression between gingivitis and periodontitis lesions and to ascertain whether immune and inflammatory cells were recruited into the diseased periodontium by the mucosal addressin adhesion molecule (MAdCAM-1). METHODS: In situ hybridization and immunohistochemistry were used to detect the expression of chemokines, adhesion molecules and immunoglobulins in tissue sections of gingival and granulation tissues excised from periodontitis-affected sites and of healthy tissue and gingivitis-affected tissue excised during crown-lengthening procedures. RESULTS: Greater numbers of plasma cells were observed in periodontitis gingival/granulation tissue lesions compared with gingivitis lesions. While IgA1 were predominant in all lesions, IgA2 and J-chain expressing plasma cells were present in increased proportions in gingival tissues compared with granulation tissue. Intracellular adhesion molecule-1 (ICAM-1) was higher in periodontitis than in gingivitis and interleukin-8 mRNA was higher in lesions with a pronounced neutrophil infiltrate. Vascular cell adhesion molecule-1 (VCAM-1) localized to the deep connective tissue and indicated the presence of a systemic type of immune response in this region. Periodontal tissues (n=71 biopsies) did not appear to express MAdCAM-1, in positive control sections of small intestine where it was detected. CONCLUSION: Overall, the systemic-type immune response is predominant, and although the mucosal immune response is minor and limited to the superficial tissues it may have an important role in the host defense to periodontal pathogens.

Li, X., K. M. Kolltveit, et al. (2000). "Systemic diseases caused by oral infection." Clin Microbiol Rev 13(4): 547-58.

ABSTRACT: Recently, it has been recognized that oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as cardiovascular disease, bacterial pneumonia, diabetes mellitus, and low birth weight. The purpose of this review is to evaluate the current status of oral infections, especially periodontitis, as a causal factor for systemic diseases. Three mechanisms or pathways linking oral infections to secondary systemic effects have been proposed: (i) metastatic spread of infection from the oral cavity as a result of transient bacteremia, (ii) metastatic injury from the effects of circulating oral microbial toxins, and (iii) metastatic inflammation caused by immunological injury induced by oral microorganisms. Periodontitis as a major oral infection may affect the host's susceptibility to systemic disease in three ways: by shared risk factors; subgingival biofilms acting as reservoirs of gram-negative bacteria; and the periodontium acting as a reservoir of inflammatory mediators. Proposed evidence and mechanisms of the above odontogenic systemic diseases are given.

Mohammad, A. R., M. Brunsvold, et al. (1996). "The strength of association between systemic postmenopausal osteoporosis and periodontal disease." Int J Prosthodont 9(5): 479-83.

ABSTRACT: This cross-sectional study examined the strength of association between systemic osteoporosis and periodontal status in postmenopausal non-Hispanic white women. Twenty subjects with low bone density and a spine bone density of 0.753 +/- 0.039 dual-energy x-ray absorptiometry units (g/cm2) and 22 subjects with high bone density and a spine bone density of 1.032 +/- 0.028 dual-energy x-ray absorptiometry units (g/cm2) were randomly selected from a cohort of 565 women. Periodontal assessment included Plaque Index, Gingival Index, pocket depth, gingival recession, and periodontal attachment level. There were no significant differences in Plaque Index, Gingival Index, and probing depth in both groups; however, there were significant differences in gingival recession components of periodontal attachment level in both groups. This study suggests that systemic osteoporosis may contribute to periodontal attachment loss in the form of gingival recession.

Molloy, J., L. F. Wolff, et al. (2004). "The association of periodontal disease parameters with systemic medical conditions and tobacco use." J Clin Periodontol 31(8): 625-32.

ABSTRACT: OBJECTIVES: The objective of this study was to determine if an association existed between periodontal disease and various systemic medical conditions and tobacco use. MATERIAL AND METHODS: The study design was a case-controlled, retrospective chart review. Patient charts (n=2006) were selected from more than 13,000 active patients attending the University of Minnesota dental clinics. These charts were examined to determine patient's self-reported systemic condition and smoking history. In addition, the number of missing teeth and bone loss were recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine bone loss and number of missing teeth. Each examiner was blind to the findings of the other. RESULTS: After adjusting for age, sex, diabetes and smoking (yes/no) status, seven conditions were significantly (p=0.0003-0.04) related to bone loss or number of missing teeth (vascular disease, heart surgery, vascular surgery, heart attack, thyroid problems, arthritis, stomach ulcers). From these conditions, thyroid problems and arthritis had a negative association with bone loss. CONCLUSIONS: These findings support the results from previous investigators that a number of systemic conditions and smoking are closely associated with missing teeth or bone loss.

Montebugnoli, L., D. Servidio, et al. (2005). "Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease." J Clin Periodontol 32(2): 188-92.

ABSTRACT: OBJECTIVES: A relationship between poor oral health and coronary heart disease (CHD) and systemic inflammatory and haemostatic factors has been recently documented in an Italian population. The present study was performed to assess whether intensive dental care may produce a periodontal improvement along with a change in systemic inflammatory and haemostatic factors. MATERIAL AND METHODS: The study population consisted of 18 males aged 40-65 years with proven CHD and elevated values of systemic inflammatory and haemostatic factors. A detailed description of their oral status was given by using two different dental indices (clinical periodontal sum score and clinical and radiographic sum score). Blood samples were taken for measurement of the following systemic markers of inflammation [(C-reactive protein (CRP), leucocytes, fibrinogen)] and haemostatic factors [(von Willebrand factor, fibrin D-dimer and oxidized-low density lipoprotein (Ox-LDL)]. All parameters were determined in each subject at baseline, after 4 months as a control and 3 months after an intensive protocol of scaling and root planing. anova for repeated measures was used for the statistical analysis. RESULTS: No statistical difference was found between values at baseline and at the 4-month-control. All oral indexes showed a significant decrease (p< .01) 3 months after periodontal treatment. All systemic inflammatory indexes decreased but only the decrease in CRP reached statistical significance (p< .05). A significant decrease (p< .01) was also found as regards Ox-LDL among haemostatic factors. CONCLUSIONS: Preliminary results from the present study suggest an association between poor oral status and CHD, and provide evidence that the improvement of periodontal status may influence the systemic inflammatory and haemostatic situation.

Nualart Grollmus, Z. C., M. C. Morales Chavez, et al. (2007). "Periodontal disease associated to systemic genetic disorders." Med Oral Patol Oral Cir Bucal 12(3): E211-5.

ABSTRACT: A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefevre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefevre syndrome, where an established treatment protocol is available.

Offenbacher, S. (1999). "The link between periodontal disease and systemic health: a scientific update. Interview by Phillip Bonner." Dent Today 18(7): 88-9.

Otomo-Corgel, J. and R. L. Merin (2002). "Periodontal disease and systemic health--what you and your patients need to know." J Calif Dent Assoc 30(4): 307-11.

ABSTRACT: For many years, dentists have recognized the importance of dental health to general health. Recent research findings point to possible associations between chronic oral infections such as periodontitis and systemic health problems. This article will review the evidence for some of these associations and explore factors that may underlie oral-systemic disease connections.

Paquette, D. W. (2002). "The periodontal infection-systemic disease link: a review of the truth or myth." J Int Acad Periodontol 4(3): 101-9.

ABSTRACT: Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.

Persson, R. E., L. G. Hollender, et al. (2003). "Assessment of periodontal conditions and systemic disease in older subjects." J Clin Periodontol 30(3): 207-13.

ABSTRACT: BACKGROUND: An increased risk for periodontitis has been associated both with type-1 or insulin dependent diabetes (IDDM) and with type-2 or non-insulin dependent diabetes (NIDDM). AIMS: 1) To describe and analyze periodontal conditions in older low-income ethnic diverse subjects with or without a diagnosis of diabetes. 2) To assess to what extent diabetes mellitus is associated with periodontal status, and 3) how periodontitis ranks as a coexisting disease among other diseases in subjects with diabetes mellitus. MATERIAL AND METHODS: Radiographic signs of alveolar bone loss were studied in 1101 older subjects 60-75 years old (mean age 67.6, SD+/-4.7). The number of periodontal sites and the proportions of teeth with probing depth (PD) > or =5 mm, clinical attachment levels (CAL) > or =4 mm were studied in a subset of 701 of the subjects. RESULTS: IDDM was reported by 2.9% and NIDDM by 9.2% of the subjects. The number of remaining teeth did not differ by diabetic status. The number of sites with PD > or =5 mm and the proportion of PD with > or =5 mm was significantly smaller in the non-diabetic group (chi2=46.8, p<0.01, and chi2=171.1, p<0.001, respectively). Statistical analysis failed to demonstrate group differences for the number and proportions of sites with CAL > or =4 mm and for radiographic findings of alveolar bone loss. Combining all periodontal parameters revealed that the Mantel-Haenszel common odds of having IDDM/NIDDM and periodontitis was 1.8 : 1 (95% CI: 1.1-3.1, p<0.03). The common odds ratio estimate of an association between heart disease and diabetes was 3.6 : 1 (95% CI: 2.1-2.6, p<0.001). CONCLUSIONS: Probing depth differences between IDDM/NIDDM vs. non-diabetic subjects may reflect the presences of pseudo-pockets and not progressive periodontitis in many subjects with diabetes mellitus. Periodontitis is not a predominant coexisting disease in older subjects with diabetes mellitus.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. I. Focus on osteoporosis." J Clin Periodontol 29(9): 796-802.

ABSTRACT: BACKGROUND: Osteoporosis (OPOR) is a common chronic disease, especially in older women. Patients are often unaware of the condition until they experience bone fractures. Studies have suggested that OPOR and periodontitis are associated diseases and exaggerated by cytokine activity. Panoramic radiography (PMX) allows studies of mandibular cortical index (MCI), which is potentially diagnostic for OPOR. AIMS: i). To study the prevalence of self-reported history of OPOR in an older, ethnically diverse population, ii). to assess the agreement between PMX/MCI findings and self-reported OPOR, and iii). to assess the likelihood of having both a self-reported history of OPOR and a diagnosis of periodontitis. MATERIALS AND METHODS: PMX and medical history were obtained from 1084 subjects aged 60-75 (mean age 67.6, SD +/- 4.7). Of the films, 90.3% were useful for analysis. PMXs were studied using MCI. The PMXs were used to grade subjects as not having periodontitis or with one of three grades of periodontitis severity. RESULTS: A positive MCI was found in 38.9% of the subjects, in contrast to 8.2% self-reported OPOR. The intraclass correlation between MCI and self-reported OPOR was 0.20 (P < 0.01). The likelihood of an association between OPOR and MCI was 2.6 (95%CI: 1.6, 4.1, P < 0.001). Subjects with self-reported OPOR and a positive MCI had worse periodontal conditions (P < 0.01). The Mantel-Haentzel odds ratio for OPOR and periodontitis was 1.8 (95%CI: 1.2, 2.5, P < 0.001). CONCLUSIONS: The prevalence of positive MCI was high and consistent with epidemiological studies, but only partly consistent with a self-reported history of osteoporosis with a higher prevalence of positive MCI in Chinese women. Horizontal alveolar bone loss is associated with both positive self-reported OPOR and MCI.

Persson, R. E., L. G. Hollender, et al. (2002). "Assessment of periodontal conditions and systemic disease in older subjects. II. Focus on cardiovascular diseases." J Clin Periodontol 29(9): 803-10.

ABSTRACT: BACKGROUND: Panoramic radiographs (PMX)s may provide information about systemic health conditions. AIMS: i). To study clinical periodontal conditions and collect self-reported health status in a cohort of 1084 older subjects; ii). to study signs of alveolar bone loss and carotid calcification from panoramic radiographs obtained from these subjects; and iii). to study associations between study parameters. MATERIAL AND METHODS: PMXs from 1064 adults aged 60-75 (mean age 67.6, SD +/- 4.7) were studied. Signs of alveolar bone loss, vertical defects, and molar furcation radiolucencies defined periodontal status. Medical health histories were obtained via self-reports. Signs of carotid calcification were identified from panoramic radiographs. RESULTS: The PMX allowed assessment of 53% of the films (Seattle 64.5% and Vancouver 48.4%). A self-reported history of a stroke was reported by 8.1% of men in Seattle and 2.9% of men in Vancouver (P < 0.01). Heart attacks were reported by 12% of men in Seattle and 7.2% in Vancouver (N.S.). PMX evidence of periodontitis was found in 48.5% of the subjects, with carotid calcification in 18.6%. The intraclass correlation score for PMX findings of carotid calcification and stroke was 0.24 (95% CI: 0.10-0.35, P < 0.001). The odds ratio for PMX carotid calcification and periodontitis was 2.1 (95% CI: 1.3-3.2, P < 0.001), and for PMX carotid calcification and stroke 4.2 (95% CI: 1.9-9.1, P < 0.001). The associations disappeared when smoking was accounted for. A history of a heart attack was associated with stroke, gender, age, and PMX scores of alveolar bone loss. CONCLUSIONS: PMXs may provide valuable information about both oral conditions and signs of carotid calcification, data that are consistent with self-reported health conditions. Alveolar bone loss as assessed from PMXs is associated with cardiovascular diseases.

Pucher, J. J. and J. Otomo-Corgel (2002). "Periodontal disease and systemic health--diabetes." J Calif Dent Assoc 30(4): 312-6.

ABSTRACT: This article discusses the biologic basis of periodontal disease and diabetes mellitus. Following is a consideration of the possibility of a link between diabetes and periodontal disease. Mounting evidence suggests that there is, indeed, a connection between periodontal disease and diabetes.

Pussinen, P. J., K. Tuomisto, et al. (2007). "Endotoxemia, immune response to periodontal pathogens, and systemic inflammation associate with incident cardiovascular disease events." Arterioscler Thromb Vasc Biol 27(6): 1433-9.

ABSTRACT: OBJECTIVE: In periodontitis, overgrowth of gram-negative bacteria may cause endotoxemia and systemic inflammation leading to cardiovascular diseases (CVD). We investigated in a prospective study the associations of serum endotoxin, antibodies to periodontal pathogens, and inflammation markers with the risk of incident CVD. METHODS AND RESULTS: The FINRISK 1992 cohort of 6051 individuals was followed up for 10 years. We examined 185 incident CVD events and a control cohort of 320 individuals using a prospective case-cohort design. High antibody response to periodontal pathogens independently predicted incident CVD events with hazard ratios (HR, quartile 4 versus quartiles 1 to 3, 95% CI) of 1.87 (1.13 to 3.08). The subjects with a high antibody response and high CRP or interleukin (IL)-6 had multivariate-adjusted HRs of 3.01 (1.27 to 7.09) and 3.11 (1.42 to 6.83) compared with low-responders, respectively. The corresponding HRs for high endotoxin concentration were 1.82 (1.22 to 2.73, alone), 3.92 (1.99 to 7.74, with CRP), 3.54 (1.78 to 7.03, with IL-6), and 2.26 (1.13 to 4.52, with tumor necrosis factor (TNF)-alpha) after adjusting for age and gender. These associations were abolished after adjusting for serum lipids. High endotoxin/HDL ratio, however, had a multivariate-adjusted HR of 1.92 (1.19 to 3.08) for CVD events. CONCLUSIONS: Our results suggest that the exposure to periodontal pathogens or endotoxin induces systemic inflammation leading to increased risk for CVD.

Rivera-Hidalgo, F. (2001). "Systemic disease and periodontal disease." Tex Dent J 118(10): 944-53.

Roberts, G. L. (1951). "Oral infection in relation to systemic disease with special reference to the crowning of teeth." Med Press 226(25): 602-5.

Rose, L. F., B. J. Steinberg, et al. (2000). "The relationship between periodontal disease and systemic conditions." Compend Contin Educ Dent 21(10A): 870-7; quiz 878.

ABSTRACT: In this year's report of the United States Surgeon General on oral health in America, two major themes evolved: 1) oral health means much more than healthy teeth, and 2) oral health is integral to general health. This article describes how oral diseases, in particular periodontal diseases, are associated with other health problems, including cardiovascular disease, diabetes mellitus, complications of pregnancies, and osteoporosis.

Rudiger, S., G. Petersilka, et al. (1999). "Combined systemic and local antimicrobial therapy of periodontal disease in Papillon-Lefevre syndrome. A report of 4 cases." J Clin Periodontol 26(12): 847-54.

ABSTRACT: 4 patients, 2 pairs of siblings, suffering from Papillon-Lefevre syndrome were treated for periodontal disease. Following extraction of hopeless teeth, the children received scaling and adjunctive systemic antibiotics (metronidazole and amoxicillin for 7 to 10 days). In addition, they performed supragingival pulsated jet irrigation with 0.06% chlorhexidine digluconate 1 x daily. In 2 siblings, A. actinomycetemcomitans was suppressed subgingivally below detectable levels, pocket probing depths were reduced to 4 mm or less, and plaque and bleeding indices were low. No further disease progression was seen over a 3-year-period. Another female patient also showed clinical improvement and suppression of subgingival A. actinomycetemcomitans and B. forsythus up to the 9-month-follow-up, while her sister showed further attachment loss over the course of 4 years. The present case reports indicated that in some patients suffering from Papillon-Lefevre syndrome periodontal disease may be arrested by means of (i) oral hygiene instruction, (ii) extraction of severely diseased teeth, (iii) scaling, (iv) systemic antibiotics and (v) long-term antimicrobial irrigation.

Scannapieco, F. A. (1998). "Position paper of The American Academy of Periodontology: periodontal disease as a potential risk factor for systemic diseases." J Periodontol 69(7): 841-50.

ABSTRACT: This paper on periodontal disease as a potential risk factor for systemic diseases was prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology. It is intended to provide information regarding the role of periodontal disease in systemic diseases, including bacteremia, infective endocarditis, cardiovascular disease and atherosclerosis, prosthetic device infection, diabetes mellitus, respiratory diseases, and adverse pregnancy outcomes.

Scannapieco, F. A. (2004). "Periodontal inflammation: from gingivitis to systemic disease?" Compend Contin Educ Dent 25(7 Suppl 1): 16-25.

ABSTRACT: There has been a resurgence of interest in recent years in the systemic effects of oral infections such as periodontal diseases. The study of the various means by which periodontal infections and inflammation may influence a variety of systemic conditions is collectively referred to as periodontal medicine. The periodontium responds to tooth-borne biofilm (dental plaque) by the process of inflammation. Dental biofilms release a variety of biologically active products, such as bacterial lipopolysaccharides (endotoxins), chemotactic peptides, protein toxins, and organic acids. These molecules stimulate the host to produce a variety of responses, among them the production and release of potent agents known as cytokines. These include interleukin-1 beta, interleukin-8, prostaglandins, and tumor necrosis factor-alpha. There is a spectrum of periodontal response to these molecules, from mild gingivitis to severe destructive periodontitis. These and other host products and responses may influence a variety of important disease pathways, including atherosclerosis, mucosal inflammation, and premature parturition. The purpose of this article is to review the possible biological pathways by which periodontal diseases may influence these disease processes.

Seiler, J. S. and R. W. Herold (2005). "The use of systemic antibiotics in the treatment of aggressive periodontal disease." Gen Dent 53(2): 155-9; quiz 160, 145-6.

ABSTRACT: General dentists frequently encounter patients with aggressive periodontal disease and should be able to diagnose and manage this disease properly. Periodontal care in the absence of a comprehensive treatment plan and proper therapy can result in the rapid progression of the disease and, ultimately, tooth loss. It is important for the general dentist to diagnose, inform, and treat the periodontal patient accurately, using referral and nonsurgical, surgical, and antimicrobial/antibiotic therapy. This article provides a brief history of the classification of aggressive periodontal disease, describes the microorganisms associated with aggressive periodontal disease, discusses the selection and use of systemic antibiotics in therapy, and lists the various antibiotic regimens for treating aggressive periodontal disease.

Slots, J. and M. Ting (2002). "Systemic antibiotics in the treatment of periodontal disease." Periodontol 2000 28: 106-76.

Yamamoto, Y. (2001). "[Periodontal disease and systemic disease]." Clin Calcium 11(3): 315-8.

ABSTRACT: Periodontal diseases are now recognized as bacterial infections among the chronic diseases of humans. The influence of the oral environment on systemic health, especially the periodontium, has long been supported by scientific evidence. However, an evidence base for the influence of periodontal disease on vital organs such as heart, lung has only recently begun to be established. We are hopeful that this information will stimulate new collaborations between physicians and dentist and serve as basis for studies to help improve the total health.

Yeo, B. K., L. P. Lim, et al. (2005). "Periodontal disease -- the emergence of a risk for systemic conditions: pre-term low birth weight." Ann Acad Med Singapore 34(1): 111-6.

ABSTRACT: This paper addresses the problem of adverse pregnancy outcome in relation to periodontal disease. There is compelling evidence that a link exists between pre-term low birth weight (PLBW) and periodontitis. Although 25% to 50% of PLBW deliveries occur without any known aetiology, there is increasing evidence that infection may play a significant role in pre-term delivery. A model explaining the plausible relationship is proposed based upon the concept of infection leading to a cascade of inflammatory reactions associated with pre-term labour and periodontal disease. Current evidence has pointed to an interest in dental intervention studies to control periodontal disease as one of the potential strategies to reduce pre-term labour. This paper reviews the potential association between periodontal infection and adverse pregnancy outcomes.