bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Biologic Response Modifiers in Human Clinical Trials
Authors: Graves Dana T.
Published: October 2010

To optimize regeneration of the periodontium, new cementum, periodontal ligament, and bone must be formed. Conventional periodontal surgery decreases the likelihood of continued progressive periodontal disease however, it does not lead to significant periodontal regeneration. In vitro studies have identified a class of biologic response modifiers loosely referred to as growth factors, which stimulate the cellular events of tissue regeneration. The most promising are mitogenic and differentiation factors. Based on promising results from animal studies, the application of growth factors to predictably stimulate periodontal regeneration is entering human clinical trials. This manuscript deals with several important considerations in testing biologic response modifiers in humans. Suggestions are made regarding the following parameters: 1) selection of the unit of measurement; 2) patient and lesion selection; 3) identification of controls; 4) selection of outcome parameters; 5) statistical approach; and 6) considerations in treatment regimens.
The Food and Drug Administration and the Regulation of Clinical Trials for Endosseous Implants
Authors: Scott Pamela D. , Runner Susan
Published: October 2010

The Office of Device Evaluation (ODE), within the Center for Devices and Radiological Health of the Food and Drug Administration is the primary component responsible for the premarket review of medical devices. Dental devices are reviewed by the Dental Devices Branch within ODE. Premarket submissions to FDA for dental endosseous implants should include complete characterization of the device and often may necessitate the inclusion of mechanical and other bench testing and clinical data. FDA guidance documents are available which outline the information that should be included in the submissions. The guidance document for premarket approval submissions for dental endosseous implants also provides guidance on clinical trials for dental implants. This guidance document addresses such issues as the number of patients and study sites, length of followup, post‐implant assessment, and pooling of data. The review of dental endosseous implants involves many challenging issues, including success/failure criteria, new designs and new indicated uses. The Dental Branch continues to gather information to address these issues. Ann Periodontol 1997; 2:284– 290.
Outcomes and Their Measurement in Clinical Trials of Endosseous Oral Implants
Authors: van Steenberghe D.
Published: October 2010

The clinical suitability of an oral implant system should be substantiated by wellplanned clinical trials that meet the expectations of both the patient and the clinician; i.e., to offer anchorage to a dental prosthesis for one or more decades. The literature often reports on the survival rather than on the success rate, and for the latter a large variety of more or less stringent criteria have been proposed. Although the use of cumulative percentages to assess survival or success on consecutive patients, the so‐called Kaplan‐Meier statistics, is essential, many publications only report on absolute percentages, thus giving much too optimistic results. Indeed, the large number of recently inserted implants tend to dilute the small fraction that has gone through the maximum observation period. Multi‐center studies on consecutive patients who are not selected on the basis of bone quality and. volume should be recommended. Otherwise the labeling of the implant should clearly mention which groups; e.g., smokers or patients with limited bone volume are not part of the validated target group. The final outcome measurement would be that an endosseous implant is no longer able to carry out its purpose: to anchor or support successfully a functional dental prosthesis. Like many other clinical evaluations, surrogate parameters have been sought to assess interim success rates. The stability of the marginal bone level is one parameter proposed by many, although bone loss as such is not synonymous with failure. Several implant systems with a roughened surface (plasma sprayed or coated) suffer from progressive marginal bone loss and consequently ongoing loss of implants even after 5 or more years. Those implant systems should be evaluated with cumulative success rates over a period of 10 years. Only those that demonstrated a clustering of both bone and implant loss during the first 1 or 2 years after insertion and subsequently a levelling off for those two parameters—a so‐called plateau pattern, should be allowed to draw conclusions after 5 years. Since radiographs reveal only the approximal areas, measurement of the attachment level by means of probing towards a reference point on the abutment should also be performed annually. Intra‐oral radiographs can only reveal absence of radiolucency at the bone‐implant interface, but do not prove osseointegration. The use of an electronic device offers objective results and reveals even subclinical mobilities of endosseous implants. One can conclude that there is an urgent need for a consensus between health authorities, third parties, and the scientific community to define a set of universally‐acceptable success criteria, to impose the use of cumulative success rates, and to ask for observation periods of 10 years for implants that do not demonstrate stable results after one or two years. Ann Periodontol 1997;2:291–298.
Clinical Trials on Implants in Regenerated Bone
Authors: Buser Daniel A. , Tonetti Maurizo
Published: October 2010

The lack of a sufficient volume of healthy jaw bone was the most important local contraindication for the placement of dental implants in the 1980s. Thus, several attempts have been made in the past 10 years to develop new surgical methods for the reconstruction of lost jaw bone in potential implant patients. At present, methods such as guided bone regeneration utilizing barrier membranes or sinus lift procedures are widely used in dental offices. There are, however, some concerns about the efficacy and predictability of these procedures. There is a need to determine how new bone regenerative procedures should be properly evaluated. The goal of the present paper is to establish some guidelines for clinical trials on implants in regenerated bone. It is proposed that such trials should be conducted in two main phases according to predetermined endpoints. The first main phase evaluates the new bone regenerative procedure. This almost always requires an initial development period including step‐by‐step modifications to identify essential surgical factors for the achievement of successful treatment outcomes. At the end, the surgical protocol will be established in detail. This is followed by the validation period to evaluate efficacy and predictability of this surgical protocol in a clinical study with consecutively treated patients. After successful bone regeneration has been properly documented, the second main phase evaluates the implants inserted in regenerated hone in a prospective clinical study utilizing the same protocol as for implants in pristine, non‐regenerated bone. This documentation allows the evaluation of tissue integration of these implants and their 5‐year success rates. Ann Periodontol 1997;2:329– 342.
Clinical Trials on Therapies for Peri‐Implant Infections
Authors: Lang Nikiaus P. , Mombelli Andrea , Tonetti Maurizio S. , Brägger Urs , Hämmerle Christoph H.F.
Published: October 2010

Peri‐implant infections are pathological conditions which are normally localized in the soft tissues surrounding an oral implant. They may range from a rather localized mucositis lesion reflecting the host response to a bacterial challenge to a more advanced lesion “termed peri‐implantitis” when previously osseointegrated oral implants have been partially disintegrated; i.e. have lost alveolar bone around the implant. Usually these lesions start as a result of plaque accumulation and show similar progression as observed around teeth. Muscositis seems to be a prerequisite for the following peri‐implantitis. However, the factors involving the transition to a more advanced lesion are still not known. Logically, the therapy for peri‐implant infection has to be related to antibacterial treatment prior to the attempt to surgically regenerate peri‐implant alveolar bone lost as a result of the infection. In order to diagnose these lesions at an early stage frequent assessments of clinical parameters are needed during maintenance therapy. The anti‐infective treatment may intercept the development of the lesion. Following mechanical debridement of plaque deposits the application of efficacious antiseptics (Chlorhexidine) is a necessity. Following this, antibiotics may cumulatively be applied to control the infection. Only a few longitudinal studies have documented the efficacy of such treatment regimens, and controls have generally not been available for ethical reasons. In regenerating the lost jaw bone only case reports are available today. Controlled animal studies will have to be performed to document the possibility of re‐osseointegration and the factors influencing predictability. Ann Periodontol 1997;2:343–356.
Design Principles nand Statistical Considerations in Periodontal Clinical Trials
Authors: Koch Gary G. , Paquette David W.
Published: October 2010

Although clinical trials are a small subset of conducted biomedical research, they have become powerful investigational tools for the evaluation and approval of new treatments by clinician groups and regulatory agencies like the US Food and Drug Administration. To impact the delivery of care, trials in general must meet three criteria: clarity, comparability, and generalizability. Accordingly, trials can offer meaningful data if they have procedures which are well defined and subjects who represent a reasonably homogeneous population. The evaluation of Periodontptis interventions presents several challenges due to the disease's heterogeneity and its irregular, episodic pattern; nevertheless, the intent of these novel interventions is to prevent, diagnose, inhibit, or reverse periodontal disease progression. Careful consideration of the trial's objectives should dictate clinical endpoints (primary and surrogate), comparison groups (placebo, standard therapy, test therapy), and equivalence versus superiority as the basis for conclusions. Several design elements such as control population specification, randomization, masking, sample size calculation, and standardization of procedures for patient care and assessment can decrease potential bias and variability. In both parallel and paired (split‐mouth) design trials, multiplicities of endpoints, treatments, and subgroups require strategies which address the broader scope of chance findings without excessive loss of study power. Also, the longitudinal assessment of multiple periodontal sites within patients produces correlated data structures for which analytic methods need to account for the appropriate sampling unit. With these design and analytic elements, clinical trials can provide important evidence to investigators, patients, and governmental agencies for the introduction of novel interventions in periodontal practice. Ann Periodontol 1997;2:42–63.
Subject Recruitment, Retention, and Compliance in Clinical Trials in Periodontics
Authors: Milgrom Peter M. , Hujoel Philippe P. , Weinstein Philip , Holborow Douglas W.
Published: October 2010

Recruitment of subjects in randomized controlled trials is the process of screening and enrolling a predetermined number of subjects within a planned time. Differences between projected and actual recruitment rates are common and, when large, form a serious threat to the successful completion of the trial. Recruitment can be enhanced by 1) use of different, concurrent recruitment methods; 2) avoiding underestimations of the costs and time intensity of subject recruitment; and 3) regular monitoring of the efficiency of the recruitment effort. The recruitment process can be complicated by legal requirements of proper representation of sex and race characteristics or by stringent entry criteria. Complex designs (e.g., trials with a pre‐randomization placebo run‐in, split‐mouth designs) have not yet shown to be cost‐effective and may endanger recruitment success. Enhancing both subject retention and protocol compliance requires careful planning, attention to product design and staff training. The impact on trial findings is discussed. Ann Periodontol 1997;2:64–74.
Phagocytic Function of Salivary PMN After Smoking or Secondary Smoking
Authors: Numabe Yukihiro , Ogawa Tomohisa , Kamoi Hisahiro , Kiyonobu Kohichi , Sato Soh , Kamoi Kyuichi , Deguchi Shinji
Published: October 2010

Alterations in polymorphonuclear leukocyte (PMN) functions, such as phagocytosis, Chemotaxis, and oxidative burst, play a pivotal role in periodontal pathogenesis. In addition, previous studies have demonstrated a strong relationship between smoking and periodontal disease. In the present study, the effect of cigarette smoking or passive smoking (secondary smoking) on the phagocytic function of salivary PMN (SPMN) was investigated. Twenty volunteers with clinically healthy gingiva (10 smokers, 10 non‐smokers) participated in this study. In a small room, the smokers and passive smokers (non‐smokers) were instructed to smoke and breathe, respectively, in an identical, specific way for about 4 minutes. SPMN was isolated immediately before and after smoking or passive smoking. PMN was then incubated with fluoresbrite beads for 45 minutes at 37°C and the phagocytic status estimated by using a flow cytometer. Cell viability was determined by trypan blue exclusion (smokers before smoking: 88.3%; smokers after smoking: 89.6%; non‐smokers before passive smoking: 89.0%; non‐smokers after passive smoking: 89.4%). In both smokers and passive smokers, the proportion of phagocytic cells increased between before and after smoking (smokers before: 33.2%; after: 42.1%; passive smokers before: 36.2%; after: 44.1%). Both increases were statistically significant (P < 0.01). These results demonstrate that the phagocytic activity of SPMN intensifies after smoking and passive smoking. They also suggest that certain substances in cigarette smoke, perhaps nicotine, overstimulate the host response in the oral cavity. Ann Periodontol 1998;3:102–107.
The Pathobiology of Periodontal Diseases May Affect Systemic Diseases: Inversion of a Paradigm
Authors: Page Roy C.
Published: October 2010

A new paradigm for the pathobiology of periodontitis is presented, and the manner in which periodontitis may relate to susceptibility for certain systemic diseases such as cardiovascular disease and preterm labor is described. Periodontitis is caused by a small group of Gram‐negative bacteria present on the tooth root surfaces as biofilms. Lipopolysaccharide (LPS) and other substances gain access to the gingival tissues, initiate and perpetuate immunoinflammation, resulting in production of high levels of proinflammatory cytokines. These induce production of matrix metalloproteinases which destroy the connective tissues of the gingiva and periodontal ligament, and prostaglandins which mediate alveolar bone destruction. Periodontitis may enhance susceptibility to systemic diseases in several ways. LPS and viable Gram‐negative bacteria from the biofilms and proinflammatory cytokines from the inflamed periodontal tissues may enter the circulation in pathogenic quantities. In addition, periodontitis and certain systemic diseases, such as cardiovascular disease, share risk factors including tobacco smoking, male gender, race/ethnicity, stress, and aging. Ann Periodontol 1998;3:108–120.
Etiopathogenesis of Cardiovascular Disease: Hemostasis, Thrombosis, and Vascular Medicine
Authors: Lowe Gordon D.O.
Published: October 2010

The role of hemostatic variables (which promote hemostatic plugs and thrombi) and rheological variables (which affect blood flow) in the pathogenesis of vascular diseases (ischemic heart disease, stroke, and peripheral arterial disease) is reviewed, with emphasis on epidemiological studies. Rheological variables are consistently associated with both prevalent and incident cardiovascular disease. These associations are only partly explained by conventional risk factors. The predictive value of plasma viscosity for cardiovascular events is partly explained by fibrinogen, and partly by lipoproteins. The associations of whole blood viscosity with cardiovascular disease are partly explained by plasma viscosity and partly by hematocrit. White cell count, but not platelet count, predicts ischemic heart disease events. Cigarette smokers have higher levels of rheological variables than non‐smokers; these increases are partly or wholly reversible in ex‐smokers. Lipoprotein reduction by pravastatin lowers plasma and whole‐blood viscosity, which may be one mechanism through which lipid lowering produces an early reduction in cardiovascular events. Data from the Edinburgh Artery Study suggest that viscosity is related both to the extent of atherosclerosis, and to ischemia in the presence of a given degree of atherosclerotic stenoses. Among hemostatic variables, fibrinogen, factor VIII: vWF complex, tPA antigen, and fibrin D‐dimer are associated with both prevalent and incident cardiovascular disease. Again, these associations are only partly explained by conventional risk factors. They suggest that endothelial disturbance and increased fibrin turnover may play roles in cardiovascular disease. Hemostatic and rheological variables are therefore associated with both prevalent and incident cardiovascular disease, and may be mechanisms through which risk factors such as smoking, hyperlipidemia and infections (including oral infections) may promote vascular events. Ann Periodontol 1998;3:121–126.
Enhanced Interaction of Advanced Glycation End Products With Their Cellular Receptor RAGE: Implications for the Pathogenesis of Accelerated Periodontal Disease in Diabetes
Authors: Lalla Evanthia , Lamster Ira B. , Schmidt Ann Marie
Published: October 2010

The prevalence and severity of periodontal disease is increased in patients with both insulin‐deficient and insulin‐resistant forms of diabetes. While a number of underlying factors likely contribute to enhanced periodontal inflammation and alveolar bone loss in diabetes, a common characteristic of these disorders, regardless of etiology, is the presence of hyperglycemia. A critical consequence of hyperglycemia is non‐enzymatic glycation and oxidation of proteins and lipids. After a series of reversible reactions which lead to the generation of Schiff bases/Amadori products, a further series of complex molecular rearrangements ensues which results in the formation of the irreversible advanced glycation end products, or AGEs. AGEs accumulate during the process of normal aging in the plasma and tissues, but to an accelerated degree in patients with diabetes. A central means by which AGEs are believed to impart their pathogenic effects is via interaction with specific cellular receptors; the best‐characterized of these is receptor for AGE, or RAGE. RAGE, a member of the immunoglobulin superfamily of cell surface molecules, is present in increased levels on target cells in diabetes, such as endothelial cells and monocytes. One consequence of AGE‐RAGE interaction is the generation of enhanced cellular oxidant stress, a means by which cell signaling pathways may be activated, thereby resulting in altered cellular phenotype and cellular dysfunction. In this report, we will review our studies to date on AGEs and RAGE and consider the implications of their enhanced interaction in the pathogenesis of accelerated periodontal disease in diabetes. Ann Periodontol 1998;3:13–19.
Periodontal Diseases' Contributions to Cardiovascular Disease: An Overview of Potential Mechanisms
Authors: Kinane D.F.
Published: October 2010

Periodontitis and atherosclerosis have complex etiologies, genetic and gender predispositions, and potentially share many risk factors—the most significant of which may be smoking status. These diseases also have many pathogenic mechanisms in common. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The severity and chronicity of periodontal disease provides a rich source of subgingival microbial and host response products and effects over a long time period. The objective of this review is to consider the mechanisms whereby diseases such as periodontitis, which is chronic and inflammatory in nature and initiated by microbial plaque, can predispose to atherosclerosis. In common with periodontal disease, the pathogenesis of atherosclerosis is not completely understood and both diseases are currently under intensive investigation. Two main processes in particular are worthy of consideration and may provide the link between these 2 diseases, namely the lipopolysaccharide‐related responses and the hyperresponsive monocyte phenomenon. Insufficient experimental evidence exists, however, to further support these hypotheses at present and clearly more research is needed on both of these processes and the interrelationships between both diseases. Ann Periodontol 1998;3:142–150.
A New Causal Model of Dental Diseases Associated With Endocarditis
Authors: Drangsholt Mark T.
Published: October 2010

Infective endocarditis (IE) is a serious disease that is associated with dental diseases and treatment. The objective of this study was to summarize the epidemiological information about IE and reevaluate previous causal models in light of this evidence. The world biomedical literature was searched from 1930 to 1996 for descriptive and analytic epidemiological studies of IE. Multiple searching strategies were performed on 9 databases, including MEDLINE, CATLINE, and WORLDCAT. Results show that: 1) the incidence of IE varies between 0.70 to 6.8 per 100,000 person‐years; 2) the incidence of IE increases 20‐fold with advancing age; 3) over 50% of all IE cases are not associated with either an obvious procedural or infectious event 3 months prior to developing symptoms; 4) about 8% of all IE cases are associated with periodontal or dental disease without a dental procedure; 5) the time from the diagnosis of heart valve deformities to the development of IE approaches 20 years; 6) the median time from identifiable procedures to the onset of IE symptoms is about 2 to 4 weeks; 7) the risk of IE after a dental procedure is probably in the range of 1 per 3,000 to 5,000 procedures; and 8) over 80% of all IE cases are acquired in the community, and the bacteria are part of the host's endogenous flora. The synthesis of these data demonstrates that IE is a disorder with the epidemiological picture of a chronic disease such as cancer, instead of an acute infectious disease, with a long latent period and possibly several definable intermediates or stages. A new causal model is proposed that includes early bacteremias that may “prime” the endothelial surface of the heart valves over many years, and a late bacteremia over days to weeks that allows adherence and colonization of the valve, resulting in the characteristic fulminant infection. Ann Periodontol 1998;3:184–196.
The Oral Health Status of Individuals on Renal Dialysis
Authors: Naugle Kimberley , Darby Michele L. , Bauman Deborah B. , Lineberger L. Truett , Powers Ralph
Published: October 2010

The primary purpose of this investigation was to determine the oral health status of individuals undergoing renal dialysis in southeastern Virginia. A sample was identified for this cross‐sectional study via a local health maintenance organization. Three subgroups of the population were studied: 1) those who have been on renal dialysis for less than a year; 2) those on renal dialysis for 1 to 3 years; and 3) those on renal dialysis for longer than 3 years. Three dental indices—the Peribdontal Disease Index; the Decayed, Missing, Filled Index; and the Simplified Oral Hygiene Index—were used to identify periodontal disease, dental caries activity, and oral hygiene status. Data were compiled and analyzed by using the parametric test, 1 ‐way analysis of variance. Results suggested that 100% (n = 45) of the individuals undergoing renal dialysis presented with some form of periodontal disease ([unk] = 3.15, SD = 1.41). The majority (64%) of the sample displayed either severe gingivitis (28%) or early periodontitis (36%). Sixty‐four percent of the sample displayed a high DMF Index ([unk] = 11.77, SD = 7.55), while 98% of the sample accumulated calculus. Oral debris was present in 100% of the sample, resulting in a high Simplified Oral Hygiene Index score ([unk] = 3.24, SD = 1.26), suggesting an increased need for oral care instruction. Findings led to the conclusion that the renal dialysis population in southeastern Virginia, regardless of length of time on dialysis, is in need of comprehensive professional oral care and self‐care instruction. Oral disease was present and is a source of active infection in these medically compromised individuals and, as such, has dire implications for morbidity and mortality. Ann Periodontol 1998;3:197–205.
Periodontal Disease as a Complication of Diabetes Mellitus
Authors: Nishimura Fusanori , Takahashi Keiso , Kurihara Mikinao , Takashiba Shogo , Murayama Yoji
Published: October 2010

Based on our clinical observations that patients with insulin‐dependent diabetes mellitus (IDDM) are subject to periodontal disease, we developed the hypothesis that hyper‐ or hypoglycemia might contribute to the pathogenesis of diabetic periodontitis. In this article, experimental facts that substantiate this hypothesis are presented on the basis of our studies and then discussed. Hyperglycemia progressively glycates body proteins, forming advanced glycation end products (AGE), which stimulate phagocytes to release inflammatory cytokines such as TNF‐α and IL‐6. In this context, to understand the effects of hyperglycemic episodes on periodontal health, 24 adolescent IDDM patients were examined for their periodontal status, and 3 of them were found to have periodontitis. Laboratory analyses on these 3 patients revealed that 2 had elevated serum TNF‐α levels. These results may partly support the current hypothesis of a mechanism of diabetic complications in which abnormal cytokine levels induced by AGE could exacerbate inflammatory responses. In IDDM patients, the diabetes is often accompanied not only by hyperglycemic episodes but also by iatrogenic hypoglycemia. Periodontal ligament cells (PDL) cultured under hyperglycemic conditions were impaired in such biological functions as adhesion and motility, while cells cultured under hypoglycemic conditions (10 mg/dL) gradually dissociated from their anchor and underwent cell death. These phenomena correlated well with the expression profile of fibronectin receptor. Interestingly, these changes due to the different glucose levels were observed more intensively in PDL than in other fibroblastic cells, suggesting that the biological functions of PDL are easily led to impairment by variation or rapid fluctuation of glucose levels. These observations suggest that hyperglycemia could indirectly exacerbate inflammatory tissue destruction through the body's scavenger system against AGE, and that both hyper‐ and hypoglycemia might directly impair the biological functions of periodontal connective tissues through cell‐matrix interactions. Ann Periodontol 1998;3:20–29.
Poor Periodontal Health of the Pregnant Woman as a Risk Factor for Low Birth Weight
Authors: Dasanayake Ananda P.
Published: October 2010

In both developed and developing countries, low birth weight (LBW) has a tremendous impact on both the health care system and the individual families affected. This warrants the continuous search for risk factors for LBW that are amenable to prevention. Can poor oral health of the pregnant woman be one such factor? In a 1:1 matched casecontrol study (N = 55 pairs), we evaluated the hypothesis that poor oral health of the pregnant woman is a risk factor for LBW. The effect of periodontal and dental caries status of the woman at the time of delivery on the birth weight of the infant was evaluated by using conditional logistic regression analyses, while controlling for known risk factors for LBW. Mothers of LBW infants were shorter, less educated, married to men of lower occupational class, had less healthy areas of gingiva and more areas with bleeding and calculus, and gained less weight during the pregnancy. Conditional logistic regression analyses indicated that mothers with more healthy areas of gingiva (OR = 0.3, 95% CI = 0.12 – 0.72) and those who were taller (OR = 0.86, 95% CI = 0.75 – 0.98) had a lower risk of giving birth to an LBW infant. Risk of LBW was higher in mothers who had no or late prenatal care (OR = 3.9, 95% CI = 1.24 – 12.2). We conclude that poor periodontal health of the mother is a potential independent risk factor for LBW. Ann Periodontol 1998;3:206–212.
Preterm Birth: Associations With Genital and Possibly Oral Microflora
Authors: Hill Gale B.
Published: October 2010

Opportunistic pathogenic microbes are indigenous to the female lower genital tract and etiologic in many types of pelvic infections and, apparently, a portion of preterm birth (PTB) cases. Bacterial vaginosis (BV) is a clinical syndrome based on an altered genital microflora in which Gardnerella vaginalis; anaerobic species primarily among Prevotella, Porphyromonas, Bacteroides, Peptostreptococcus, and Mobiluncus; Mycoplasma hominis; and Ureaplasma urealyticum become predominant in vaginal secretions. This BV complex of microbes, compared to a normal vaginal microflora dominated by facultative lactobacilli, is associated with significantly increased risks for preterm labor, preterm premature rupture of membranes, PTB, and other perinatal infectious complications. Pathogenetic mechanisms include an ascending route of infection and/or inflammatory process due to microbial products and maternal and/or fetal response(s) with production of prostaglandins and cytokines. In the presence of periodontal disease, oral opportunistic pathogens and/or their inflammatory products also may have a role in prematurity via a hematogenous route. Fusobacterium nucleatum, a common oral species, is the most frequently isolated species from amniotic fluid cultures among women with preterm labor and intact membranes. Also, the species and subspecies of fusobacteria identified from amniotic fluid most closely match those reported from healthy and diseased subgingival sites, namely F. nucleatum subspecies vincentii and F. nucleatum subspecies nucleatum, compared to strains identified from the lower genital tract. Although these fusobacteria also could be acquired through cunnilingus from a partner, new data associating maternal periodontal disease with preterm low birth weight taken with the isolation of F. nucleatum, Capnocytophaga, and other oral species from amniotic fluid support further study of a possible additional route, oral‐hematogenous, to PTB. Ann Periodontol 1998;3:222–232.
The Association Between Alveolar Bone Loss and Pulmonary Function: The VA Dental Longitudinal Study
Authors: Hayes Catherine , Sparrow David , Cohen Michel , Vokonas Pantel S. , Garcia Raul I.
Published: October 2010

The effect of oral conditions on medical outcomes is not well understood. The purpose of this epidemiological investigation was to examine whether the risk for chronic obstructive pulmonary disease (COPD) is enhanced among individuals with a history of periodontal disease as assessed by radiographic alveolar bone loss (ABL). Subjects were selected from the VA Dental Longitudinal Study, a long‐term study of aging and health in male veterans who were medically healthy at baseline. Subjects are not VA patients. Those subjects with a forced expiratory volume in 1 second (FEV1) less than 65% of predicted volume were categorized as having COPD. ABL was assessed by using full‐mouth series periapical films measured by a Schei ruler. Bone loss at each interproximal site was measured in 20% increments, and the mean whole‐mouth bone loss score was calculated. Logistic regression analysis was used to determine the independent contribution of bone loss measurement at baseline to the subsequent risk of developing COPD over a 25‐year follow‐up period. Covariates included measures of smoking, height, age, education, and alcohol consumption. Of the 1,118 medically healthy dentate men at baseline, 261 subsequently developed COPD. We found that ABL status at baseline was an independent risk factor for COPD, with subjects in the worst population quintile of bone loss (mean ABL > 20% per site) found to be at significantly higher risk (OR = 1.8; 95% CI = 1.3, 2.5). The results of this analysis indicate that increased ABL is associated with an increased risk for COPD. Ann Periodontol 1998;3:257–261.
Implications of Oral Infections on Systemic Diseases in the Institutionalized Elderly With a Special Focus on Pneumonia
Authors: Limeback Hardy
Published: October 2010

Systemic infection in the elderly patient living in a chronic care setting presents a significant burden to the health care system. The extent to which oral organisms cause systemic infections through hematogenous dissemination in the institutionalized elderly is still unknown. A more likely and common route of systemic infection by oral microorganisms is through aspiration of oropharyngeal fluids containing oral pathogenic microorganisms, which colonize the lower respiratory tract and cause pneumonia. Respiratory pathogens emerge in the dental plaque of elderly patients with very poor oral hygiene and severe periodontal disease. In the chronic care setting, aspiration of oropharyngeal fluids contaminated with these bacteria occurs in patients with diminished host defenses, resulting in bacterial pneumonia. This is also a problem in intensive care units in the hospital setting. In one study, pre‐rinsing with a 0.12% chlorhexidine gluconate mouthwash significantly lowered the mortality rate from postsurgical pneumonia in patients undergoing open heart surgery. Selective digestive decontamination, a technique involving the topical application of antimicrobials to reduce the risk of colonization of the respiratory tract, has been used to reduce the incidence of nosocomial pneumonia in the acute care setting of hospitals. This technique has not been employed in the nursing home setting. Whether improving oral hygiene would also lower the risk in either of these settings has not been studied. A number of obstacles must be overcome in designing studies to investigate the relationship between oral infections and lung infections in the institutionalized elderly. Ethical issues must be addressed, and full collaboration of the medical team is required. Future studies should establish whether reducing the risk for pneumonia in the institutionalized elderly is possible through improved oral health. Ann Periodontol 1998;3:262–275.
Helicobacter pylori: The Mouth, Stomach, and Gut Axis
Authors: Oshowo A. , Gillam D. , Botha A. , Tunio M. , Holton J. , Boulos P. , Hobsley M.
Published: October 2010

The aim of this study was to identify the natural reservoir and route of transmission of Helicobacter pylori infection. Two hundred eight (208) dyspeptic patients (114 males, 94 females; peak age of cohort, 50–59.9 years) were recruited. Specimens were collected from saliva, supra‐ and subgingival dental plaque, tongue scrapings, and oropharyngeal swabs. At subsequent endoscopy, gastric antral biopsy was performed for the rapid urease test (RUT), microbiological culture, and, in some patients, histology. Gastric juice samples were aspirated, and in 50 patients duodenal aspirate was collected. Polymerase chain reaction (PCR) with primers targeted to the 16S rRNA sequence of H. pylori was also employed for each of the specimens. In those patients where H. pylori was detected from multiple sites (dental plaque, gastric juice, gastric biopsy, and duodenal aspirate), restriction endonuclease digestion with Hae III was performed to determine if they were epidemiologically linked. The results indicated that 15/208 patients (7%) tested positively for H. pylori by PCR in dental plaque; only 2 samples were positive by culture. In none of the other oral sites sampled was H. pylori detected by any test used in the study. Gastric juice and gastric biopsy specimens from 36/208 patients (17%) and 114/208 patients (55%), respectively, were positive by PCR. Duodenal aspirate from 6/50 patients (12%) also tested positively by PCR. All specimens tested by restriction endonuclease digestion with Hae III (15/15 patients) were positive in both antrat biopsy and gastric juice specimens, as well as 5 specimens from the duodenal aspirate. Four of the dental plaque strains had restriction patterns similar to those of the stomach and duodenal sites, providing evidence that these sites were infected with the same strain of H. pylori. In conclusion, the results suggest that H. pylori selects the gastric mucosa as its preferred site. The detection in dental plaque could indicate that the oral cavity may act as a reservoir or sanctuary for the organism. Whether H. pylori is a resident or transient oral microorganism is still unclear, although it is more likely to be transient in nature. Ann Periodontol 1998;3:276–280.
Models to Evaluate the Role of Stress in Periodontal Disease
Authors: Genco Robert J. , Ho Alex W. , Kopman Jeffrey , Grossi Sara G. , Dunford Robert G. , Tedesco Lisa A.
Published: October 2010

We evaluated the association of stress, distress, and coping behaviors with periodontal disease in 1,426 subjects, aged 25 to 74, in Erie County, NY. Demographic characteristics, medical and dental history, and tobacco and alcohol consumption, as well as clinical assessments of supragingival plaque, subgingival flora, gingival bleeding, calculus, probing depth, clinical attachment level (CAL), and radiographic alveolar bone loss (ABL) were obtained for each subject. Subjects also completed a set of 5 psychosocial instruments that measured life events, daily strains, hassles and uplifts, distress, and coping behaviors. Internal consistencies of all subscales on the instruments were high, with Cronbach's alpha ranging from 0.88 to 0.99. Logistic regression indicated that financial strain was significantly associated with greater attachment and alveolar bone loss (OR 1.70; 95% CI, 1.09–2.65; and 1.68; 95% CI, 1.20–2.37, respectively) after adjusting for age, gender, and smoking. When those with financial strain were stratified with respect to coping behaviors, it was found that those who exhibited high emotion‐focused coping (inadequate coping) had an even higher risk of having more severe attachment loss (OR 2.24; 95% CI, 1.15–4.38) and alveolar bone loss (OR 1.91; 95% CI, 1.15–3.17) than those with low levels of financial strain within the same coping group, after adjustment for age, gender, and cigarette smoking. After further adjusting for number of visits to the dentist, those with financial strain who were high emotion‐focused copers still had higher levels of periodontal disease based on CAL (OR 2.12; 95% CI, 1.07–4.18). In contrast, subjects with high levels of financial strain who reported high levels of problem‐based coping (good coping) had no more periodontal disease than those with low levels of financial strain. Salivary cortisol levels were higher in a test group exhibiting severe periodontitis, a high level of financial strain, and high emotion‐focused coping, as compared to a control group consisting of those with little or no periodontal disease, low financial strain, and low levels of emotion‐focused coping (11.04 ± 4.4 vs. 8.6 ± 4.1 nmol/L salivary cortisol, respectively). These findings suggest that psychosocial measures of stress associated with financial strain are significant risk indicators for periodontal disease in adults. Further prospective studies are needed to help establish the time course of stress, distress, and inadequate coping on the onset and progression of periodontal disease, as well as to evaluate the mechanisms by which stress exerts its effects on periodontal infections. Ann Periodontol 1998;3:288–302.
Glycemic Control and Alveolar Bone Loss Progression in Type 2 Diabetes
Authors: Taylor George W. , Burt Brian A. , Becker Mark P. , Genco Robert J. , Shlossman Marc
Published: October 2010

This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) ≥ 9%; the BC group had HbA1 < 9%. Data from the longitudinal study of the oral health of residents of the Gila River Indian Community were analyzed. Of the 359 subjects, aged 15 to 57 with less than 25% radiographic bone loss at baseline, 338 did not have type 2 DM, 14 were BC, and 7 were PC. Panoramic radiographs were used to assess interproximal bone level. Bone scores (scale 0–4) corresponding to bone loss of 0%, 1% to 24%, 25% to 49%, 50% to 74%, or ≥ 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow‐up, the outcome, was specified on a 4‐category ordinal scale as no change, or a 1‐, 2‐, 3‐, or 4‐category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow‐up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups. Ann Periodontol 1998;3:30–39.
Lifestyle and Periodontal Health Status of Japanese Factory Workers
Authors: Shizukuishi Satoshi , Hayashi Naoji , Tamagawa Hiroo , Hanioka Takashi , Maruyama Soichiro , Takeshita Tatsuya , Morimoto Kanehisa
Published: October 2010

The present study investigated the association of lifestyles to periodontal health status of workers in a manufacturing company in Japan. In an annual health checkup, periodontal health status was assessed by using the Community Periodontal Index (CPI) criteria and analyzed by modified Miller's CPI score. Lifestyle information was also obtained by a self‐administered questionnaire. Bivariate and multivariate analyses were used to examine the relationship between lifestyle, and oral health care variables and 2 indicators of periodontal health status. These were the modified Miller's CPI score and the probability of subjects in the upper 25th percentile of CPI distribution as an indicator of poor periodontal health. The modified Miller's CPI score was found to increase with age, but to vary according to the workers' lifestyles. In bivariate analyses, significant variables were age, smoking, alcohol consumption, toothbrushing frequency, toothbrushing method, and use of interdental cleaners. In multivariate analyses, age, smoking, and use of interdental cleaners had significantly independent effects. Amount of smoking or alcohol consumption was associated with periodontal health status. Excessive use of alcohol may contribute to the development of periodontal disease, although further investigations are required to confirm this finding. The data from this study indicate that lifestyles which include smoking and insufficient oral health care have an independent association with periodontal disease. Ann Periodontol 1998;3:303–311.
Osteoporosis: A Possible Modifying Factor in Oral Bone Loss
Authors: Jeffcoat M.K.
Published: October 2010

There has been increasing interest in the interrelationship between systemic osteoporosis, oral bone loss, tooth loss, and risk factors for these conditions. Because the severity of alveolar bone loss increases with age, it has long been hypothesized that it may, in part, be related to systemic conditions that also predispose the patient to osteoporosis/osteopenia. The purpose of this paper is to review the risk factors for osteoporosis and periodontitis, as well as the evidence that loss of oral bone mineral may be related to systemic osteopenia. There is also evidence that therapies designed to influence systemic bone mineral density, such as hormone replacement and bisphosphonate therapy, may be associated with less tooth loss and a slower loss of alveolar bone, respectively. Ann Periodontol 1998;3:312–321.
Bone Mineral Density in Periodontally Healthy and Edentulous Postmenopausal Women
Authors: Bando Kaoru , Nitta Hiroshi , Matsubara Masaaki , Ishikawa Isao
Published: October 2010

Osteoporosis is the most common metabolic disease among postmenopausal women. Reduced masticatory function caused by tooth loss may be a contributing risk factor of osteoporosis. The present study examined the effect of dentate state on skeletal bone mineral density (BMD) in postmenopausal women. Fourteen periodontally healthy dentate subjects (group H; mean age: 64.0 ± 5.5 years) and 12 edentulous subjects (group E; mean age: 67.1 ± 2.9 years) were randomly selected from the clinics of the departments of Periodontology and Gerodontology, respectively. Informed consent was obtained from all participants. BMD of the lumbar spine (L2‐L4) was measured by dual energy x‐ray absorptiometry. In addition, occlusal force was measured in 11 group H subjects and 8 group E subjects by using an occlusal diagnostic system. Risk factors associated with osteoporosis including age, calcium intake, physical activity, and cigarette smoking and causes of tooth loss were assessed by interview and questionnaire sent to all participants. The BMD of group H was 1.07 ± 0.21 g/cm2 and that of group E was 0.89 ± 0.17 g/cm2, which was significantly different (P < 0.05). The occlusal force of group H and E patients was 312.4 ± 148 N and 56.3 ± 36 N, respectively, which was significantly different (P < 0.05). Risk factors such as calcium intake, physical activity, and smoking did not differ significantly between the 2 groups. Thus, the periodontally healthy dentate women, who showed about 6 times higher occlusal force than edentulous women, maintained significantly higher BMD of the lumbar spine than edentulous women. Our results suggest that sufficient masticatory function with periodontally healthy dentition may inhibit or delay the progress of osteoporotic change in skeletal bone or that edentulous women may be more susceptible to osteoporosis. Ann Periodontol 1998;3:322–326.