John T. Grbic

B-endorphin modulates human immune activity via non-opiate receptor mechanisms

Here we report that Beta-endorphin is a potent and efficacious suppressor of phytohemagglutinin induced T-lymphocyte blastogenesis when human leukocytes are exposed early in the course of mitogenic activation. This suppression becomes more difficult to observe, however, if blastogenesis is established by prior exposure to mitogen. Suppression by Beta-endorphin is not blocked by pretreatment with the opiate antagonist naloxone. These results, therefore, suggest that neuroendocrine modulation of human immune expression may be a peripheral physiological function of Beta-endorphin which is mediated by mechanisms distinct from traditional opiate receptors.

Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Pagets disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.

Oral manifestations of HIV infection in homosexual men and intravenous drug users: Study design and relationship of epidemiologic clinical, and immunologic parameters to oral lesions☆

This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users. Both seropositive and seronegative persons were studied. A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions. The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience. The prevalence and type of oral lesions differed in the two seropositive groups. In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected. We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men. For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment. In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users. This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users. Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

Development of a risk profile for periodontal disease: microbial and host response factors.

Advances in our understanding of the relationship between the microbial challenge and the host response in periodontal disease have led to the search for pathogenesisbased risk indicators or risk factors for disease progression. This evaluation is based on analysis of non-invasive or minimally invasive samples that allow measurement of the subgingival plaque microflora or the host response in gingival crevicular fluid (GCF), serum, or saliva. Studies conducted by us have indicated that in GCF, persistently elevated levels of β-glucuronidase (βG, a marker for primary granule release from polymorphonuclear leukocytes) are associated with clinical attachment loss in patients with periodontitis. This finding has been confirmed in a multicenter trial. We have also observed that a statistically significant positive correlation exists between βG in GCF and measures of the subgingival microbial challenge, but the correlation was less than 0.5, suggesting variations in the host response to the challenge. Furthermore, βG levels in GCF were inversely correlated with the IgG serum antibody titer to a panel of periodontal pathogens, suggesting the essentially protective function of the systemic humoral response in periodontal disease. Data in the literature support this concept. In addition, recent studies of the relationship of antibody isotypes in GCF to progression of clinical attachment loss have suggested that IgA in GCF has a protective function. This may relate to the lack of complement activation by IgA. Alternately, the development of IgA antigen-specific responses are T-cell dependent, and reductions in local levels of IgA may indicate a decrease in T-helper cell function. These data have allowed development of strategies for identifying individual risk profiles for patients with periodontal disease based on the host response to the microbial challenge. With identification of these risk indicators/risk factors for active periodontal disease, the next challenge is to provide clinicians with access to the tests and analyses that are required for this approach to periodontal diagnosis. Improved patient management should result from the incorporation of these tests into clinical practice. J Periodontol 1994;65:511-520.

Interleukin-1β and β-Glucuronidase in gingival crevicular fluid from molars during rapid palatal expansion

Abstract This study examined whether the inflammatory mediators interleukin (IL-1β) and β-glucuronidase (βG) are present in the gingival crevicular fluid (GCF) of children undergoing rapid palatal expansion and whether their levels vary upon activation of the appliance and movement of the maxillary first molars. Nine adolescent patients who needed palatal expansion were studied. Each patient received a periodontal prophylaxis and instruction in proper home care, including rinsing with chlorhexidine. Four weeks later, a modified Hyrax appliance was inserted. The jackscrew was activated twice daily until the appropriate expansion was achieved. GCF samples were collected at 2 pretreatment observation periods and 9 observation periods after placement of the appliance. Samples were collected with filter paper strips and analyzed by means of ELISA and time-dependent fluorometry for IL-1β and βG, respectively. The values recorded at the observation period 2 weeks after the periodontal prophylaxis were used as baseline. Paired t tests were used to compare mediator levels at this baseline to the levels obtained at each of the subsequent observations. The results indicate that (1) βG and IL-1β are present in GCF of young, healthy individuals, (2) their levels decrease following a strict regimen of plaque control, (3) orthodontic/orthopedic forces evoke changes in the levels of the inflammatory mediators IL-1β and βG in the periodontal tissues that can be detected in GCF. The results of this study support the hypothesis that mechanical stimulus causes an inflammatory reaction within the periodontal tissues, which in turn may trigger the biological processes associated with bone remodeling. (Am J Orthod Dentofacial Orthop 1998; 114: 686-96)

Current Status of Tests for Periodontal Disease

The methods applied to the diagnosis of periodontal disease are changing. Historically, static clinical and radiographic parameters have formed the basis of the periodontal evaluation. As the limitations of these traditional procedures became clear, several new techniques have been proposed as diagnostic tests for periodontal disease. These tests are based on improved understanding of the pathogenesis of periodontal disease, and can be considered in three categories: assessment of physical changes in the periodontium, the bacterial infection, and the host response to the infection. Several technical questions must be addressed before these tests can be widely utilized. These specific concerns include such matters as the information available from the tests (e.g., Does the test provide a measure of disease severity or identify the site, region, or patient experiencing active disease?), the most appropriate test configurations, the statistical analysis of data from trials examining the accuracy of the tests, and selection of patients who would benefit from these procedures. Last, several important practical issues must be examined before these tests can be expected to gain widespread acceptance. These include familiarization of dental practitioners with the use of diagnostic tests and the medical laboratory, the role of regulatory agencies in determining the claims made by these tests, and the medical/dental insurance benefits provided for these services.

Comparison of levels of inflammatory mediators IL-1β and βG in gingival crevicular fluid from molars, premolars, and incisors during rapid palatal expansion

INTRODUCTION Previously, we reported fluctuation of the levels of the inflammatory mediators interleukin-1beta (IotaL-1beta) and beta-glucuronidase (betaG) in gingival crevicular fluid (GCF) from the maxillary first molars in adolescents undergoing rapid palatal expansion. In this study, we compared the responses of IL-1beta and betaG in the GCF of the maxillary first molars, first premolars, and central incisors during palatal expansion at the same patients. METHODS Nine patients requiring palatal expansion were selected at the postdoctoral orthodontic clinic at Columbia University College of Dental Medicine. Each patient received periodontal prophylaxis and instructions in proper home care including rinsing with chlorhexidine. Four weeks after periodontal prophylaxis, a modified hyrax appliance was placed. The jackscrew was activated twice daily until the appropriate expansion was achieved. GCF samples were collected before and after periodontal prophylaxis and during passive wearing of the appliance, active orthodontic treatment, and retention. Fluid samples were collected with filter paper strips and analyzed by ELISA and time-dependent fluorometry for IL-1beta and betaG, respectively. The values recorded after periodontal prophylaxis were used as the baseline. Paired t tests were used to compare mediator levels at baseline with the levels obtained at each subsequent observation. RESULTS The results validate that IL-1beta and betaG are present in the GCF of adolescents, and, although their level decreases after a strict regimen of plaque control, it increases during orthodontic or orthopedic movement. Moreover, this study demonstrates that both heavy and light forces evoke increased levels of IL-1beta and betaG, stronger forces cause higher levels of inflammatory mediators, and both IL-1beta and betaG respond to direct and indirect application of mechanical force to teeth. CONCLUSIONS This investigation corroborates previous findings that an inflammatory process occurs during application of mechanical force to teeth. Although this inflammation is considered relatively aseptic, additional inflammation, such as that induced by plaque accumulation, must be avoided during orthodontic or orthopedic treatment.

Analysis of Multiple 2x2 Tables with Site-specific Periodontal Data

Periodontal data typically consist of observations made at multiple sites within each patient. Observations within a patient tend to be positively correlated; hence, standard statistical techniques that assume independence are invalid. Regression techniques for correlated data have been proposed; communicating results from these models, however, is difficult, due to their inherent complexity. Simpler statistical approaches have also been proposed, but many of these methods can be applied only when covariates are specific to the subject, and do not vary from site to site within a subject. In this paper, we present two methods for the analysis of multiple 2x2 tables containing site-specific periodontal data. The methods presented are modifications of the well-known Mantel-Haenszel methods. We illustrate these methods using a subset of data from a clinical trial examining the effects of scaling and root planing on levels of interleukin-1β.

Usefulness of Self-Reported Periodontal Disease to Identify Individuals With Elevated Inflammatory Markers at Risk of Cardiovascular Disease

Periodontal disease has been associated with cardiovascular disease (CVD), and inflammation may represent a common pathophysiology. Oral health screening in the context of CVD risk assessment represents a potential opportunity to identify individuals at risk for CVD. The purposes of this study were to determine if self-reported oral health status is independently associated with inflammatory markers and if oral health assessment as part of CVD risk screening can identify at-risk individuals without traditional CVD risk factors. A baseline analysis was conducted among participants in the National Heart, Lung, and Blood Institutes Family Intervention Trial for Heart Health (FIT Heart; n = 421, mean age 48 +/- 13.5 years, 36% nonwhite) without CVD or diabetes who underwent standardized assessment of oral health, lifestyle, CVD risk factors, and the inflammatory markers high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2). Statistical associations between oral health, risk factors, and inflammatory markers were assessed, and logistic regression was used to adjust for effects of lifestyle and potential confounders. Periodontal disease was independently associated with being in the top quartile of lipoprotein-associated phospholipase A(2) compared with the lower 3 quartiles (odds ratio 1.9, 95% confidence interval 1.1 to 3.2) after adjustment for lifestyle and risk factors. Histories of periodontal disease were reported by 24% of non-overweight, non-hypertensive, non-hypercholesterolemic participants, and of these participants, 37% had elevated high-sensitivity C-reactive protein (> or =3 mg/L) or lipoprotein-associated phospholipase A(2) (> or =215 ng/ml) levels. In conclusion, self-reported periodontal disease is independently associated with inflammation and common in individuals without traditional CVD risk factors.

Impact of osteonecrosis of the jaw on osteoporosis management: executive summary of an ESCEO and Foundation for Research on Osteoporosis and other Bone Diseases Working Group Meeting

The first reports of osteonecrosis of the jaw in patients taking bisphosphonates to reduce excessive bone resorption were published in 2003. Subsequent reports raised concern and resulted in manufacturers writing letters of caution to physicians and dentists. Recommendations were issued by the US FDA, and the European Agency for the Evaluation of Medicinal Products requested that pharmaceutical companies update their product information and package leaflets. The European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the Foundation for Research on Osteoporosis and other Bone Diseases Working Group Meeting was convened on 14 December 2006 in Geneva, Switzerland, to review the available data and published guidelines on this rare but serious condition. The purpose of the meeting was to assess the impact of osteonecrosis of the jaw on the management of osteoporosis. The discussion focused on the current definition of osteonecrosis of the jaw, its epidemiology and pathophysiolo...