(C3) The oral epithelial cell and first encounters with HIV-1.

Adv Dent Res. 2006;19(1):158-66

Authors: Herzberg MC, Weinberg A, Wahl SM

The oral epithelium is the site of first exposure of HIV-1 to host tissues during oral sex with an infected partner or through breast-feeding by an infected mother. Although the oral epithelium is distinguishable by its apparent resistance, the mucosal surfaces represent a primary target of HIV-1. After oral exposure and swallowing, infection is detected prominently in the gastrointestinal tract, which becomes depleted of CD4+ T-cells. The oral cavity and palatine tonsils appear to resist infection and transfer to susceptible lymphoid cells in the lamina propria by local anti-HIV-1 mechanisms. In some cases, expression of these antiviral mechanisms increases after exposure to HIV-1. During primary exposure and before seroconversion, based on limited in vitro and primate data, a window of opportunity for capture of HIV-1 by the oral epithelium may exist. After seroconversion, the risk of infectious HIV-1 appearing in saliva is negligible. This report considers evidence that oral epithelium has the potential both to enable and to resist infection by HIV-1.

PMID: 16672567 [PubMed - indexed for MEDLINE]

(C2) Saliva, breast milk, and mucosal fluids in HIV transmission.

Adv Dent Res. 2006;19(1):152-7

Authors: Page-Shafer K, Sweet S, Kassaye S, Ssali C

The oral environment has received various amounts of attention in association with HIV infection and pathogenesis. Since HIV infection occurs through mucosal tissue, oral factors-including tissue, fluids, and compartments-are of interest in furthering our understanding of the diagnosis, infectivity, transmission, and pathogenesis of disease. This report reviews: (1) HIV testing and diagnoses with oral fluids; (2) post-natal acquisition of HIV in association with breast-feeding from HIV-positive mothers; and (3) oral sex and HIV transmission. In the first, we examine how oral fluids are used to detect HIV infection and review current consensus on the role of salivary molecules as markers for immunosuppression. Second, lactation-associated HIV acquisition is reviewed, with special consideration of emerging issues associated with the impact of anti-retroviral therapies. Last, we consider current data on the risk of HIV infection in association with oral sex. Investigation of these diverse topics has a common goal: understanding how HIV presents in the oral environment, with an aim to rapid and accessible HIV diagnosis, and improved prevention and treatment of infection.

PMID: 16672566 [PubMed - indexed for MEDLINE]

(B3) Markers of immunodeficiency and mechanisms of HAART therapy on oral lesions.

Adv Dent Res. 2006;19(1):146-51

Authors: Flint SR, Tappuni A, Leigh J, Schmidt-Westhausen AM, MacPhail L

Highly active anti-retroviral therapy (HAART) has revolutionized the treatment and prognosis of HIV disease and AIDS in those who can take advantage of the treatment. There are currently 20 different anti-retroviral drugs in 4 different classes that are used in specific combinations. Suppression of HIV replication and immune reconstitution are goals of therapy. Since the prevalence of some easily detectable oral manifestations of HIV/AIDS (OMHIV/AIDS) decreases with HAART, it has been suggested that they might be clinically useful surrogate markers of HAART efficacy and immune status. This might be particularly useful if their recurrence presaged or accompanied HAART failure. To date, there has been little work in this area, but its potential value to the clinical management of HIV/AIDS is apparent, especially if frequent measures of viral load and CD4 cell counts are not readily available. However, the usefulness of OMHIV/AIDS as signals for HAART failure is complicated by three phenomena: the immune reconstitution syndrome, the similarity of some adverse reactions of HAART to OMHIV/AIDS, and the direct inhibitory effect of HAART medications on some OMHIV/AIDS (e.g., inhibition of oral candidosis by protease inhibitors). This workshop considered the current evidence and proposed pertinent research questions.

PMID: 16672565 [PubMed - indexed for MEDLINE]

(B2) Periodontal diseases and other bacterial infections.

Adv Dent Res. 2006;19(1):139-45

Authors: Umadevi M, Adeyemi O, Patel M, Reichart PA, Robinson PG

The workshop addressed the following questions with respect to periodontal diseases and bacterial infections seen in HIV infection: (1) What is linear gingival erythema? Is it prevalent only in HIV disease? A crude Delphi technique was used to ascertain whether LGE existed, but a consensus could not be reached. It was agreed that a diagnosis of LGE should be considered only if the lesion persists after removal of plaque in the initial visit. (2) Do periodontal pockets contribute to viremia in HIV infection? At present, the data are not available to answer this question. (3) Do anti-viral drugs reach the sulcular fluid in significant concentrations? No one at the workshop was aware of data that could answer this question. (4) Does concurrent tuberculosis infection modify the oral manifestations of HIV infection? Though analysis of data from the developing countries does suggest an association between tuberculosis and oral candidiasis, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary, for any conclusions to be derived. (5) What pathogens are involved in periodontal diseases in HIV infection? Periodontal disease may be initiated by conventional periodontal pathogens. But the progression and tissue destruction depend upon the presence of typical and atypical micro-organisms, including viruses, their by-products, increased secretion of potentially destructive inflammatory mediators, and overwhelming host response. (6) How can we diagnose the diseases seen in HIV infection? The answer can be obtained only with data from controlled and blinded studies. It is necessary to design collaborative multi-center longitudinal studies. The results obtained from such large sample sizes can contribute eventually to interpretation of the outcome.

PMID: 16672564 [PubMed - indexed for MEDLINE]

(B1) Candida and mycotic infections.

Adv Dent Res. 2006;19(1):130-8

Authors: Coogan MM, Fidel PL, Komesu MC, Maeda N, Samaranayake LP

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.

PMID: 16672563 [PubMed - indexed for MEDLINE]

(A3) HIV Phenotypes, oral lesions, and management of HIV-related disease.

Adv Dent Res. 2006;19(1):122-9

Authors: Blignaut E, Patton LL, Nittayananta W, Ramirez-Amador V, Ranganathan K, Chattopadhyay A

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

PMID: 16672562 [PubMed - indexed for MEDLINE]

(A2) Oral health and general health.

Adv Dent Res. 2006;19(1):118-21

Authors: Johnson NW, Glick M, Mbuguye TN

The interactions between oral and systemic health are bi-directional and complex, involving many pathways. Regarding health as not merely the absence of disease, but as a state of total well-being, these interactions profoundly influence the progress of many diseases, and the quality of life and economic performance of HIV-infected individuals and populations. The evidence base for specific interactions is currently weak, partly because few good-quality studies have been published, partly because of the naïveté of the instruments currently available for recording these interactions and their inherent complexity. Recording quality of life should be a fundamental aspect of all future studies. The most significant conclusion of this Workshop is the need for all involved in oral health research and oral health care to be seen as, and to act as, essential partners in comprehensive care for whole patients and communities.

PMID: 16672561 [PubMed - indexed for MEDLINE]

(A1) Identification of oral health care needs in children and adults, management of oral diseases.

Adv Dent Res. 2006;19(1):106-17

Authors: Hodgson TA, Naidoo S, Chidzonga M, Ramos-Gomez F, Shiboski C

The workshop considered five questions reviewing the identification of international oral health care needs of children and adults, and the management of oral diseases in resource-poor countries: (1) What is the role of the dental profession in the management of the HIV-infected individual? (2) Identifying health care needs-What are the epidemiology and disparities of HIV-associated oral lesions in children from different continents? (3) How effective is HIV treatment in controlling oral diseases? (4) Could we develop basic inexpensive oral and dental care protocols for economically deprived HIV-infected patients? and (5) What is the best method of arranging resources to meet the oral health care needs of people with HIV disease? The consensus of the workshop participants was that there is a need to re-target research efforts to non-established market economy countries and prioritize research in these regions to children with HIV disease. It will be important to assess commonalities and variations in oral health needs across geographical and cultural boundaries, and research efforts should be centralized in resource-poor countries to support multi-center longitudinal standardized studies. It is essential that oral health research be integrated into other health care research programs, to make these research priorities and public health initiatives feasible.

PMID: 16672560 [PubMed - indexed for MEDLINE]

Biology of HPV in HIV infection.

Adv Dent Res. 2006;19(1):99-105

Authors: Palefsky J

HIV-positive men and women are at increased risk of anogenital and oral HPV infection. The risks for HPV-associated high-grade intra-epithelial neoplasia (IN) and cancer are also increased. The prevalence of oral, anal, and cervical HPV infection in HIV-positive individuals compared with HIV-negative individuals increases with progressively lower CD4+ levels, as does incident high-grade IN. In contrast to IN, development of cancer is not related to lower CD4+ level. With increasing grades of IN and cancer, the proportion of tissues with copy-number abnormalities (CNA) increases, with one of the most common genetic changes being amplification of chromosome 3q. The presence of CNA is associated with the integration of HPV DNA into the host genome, with loss of HPV E2 and/or E2 rearrangement. This suggests a link between CNA and increased HPV-induced chromosomal instability mediated through de-repressed E6 and E7 expression consequent to loss of functional E2 protein. In addition, epigenetic changes occur with increasing frequency in high-grade IN and cancer, such as hypermethylation leading to down-regulation of potential tumor suppressor genes. Analysis of these data together suggests that immune suppression plays a more prominent role in the earlier stages of HPV-associated disease, up to and including incident high-grade IN. Persistent high-grade IN and development of cancer may be more strongly related to the cumulative effect of HPV-associated genetic instability and the resulting host genetic changes. There are few data to suggest a direct role for HIV in the pathogenesis of HPV-associated neoplasia, but HIV-associated attenuation of HPV-specific immune responses may allow for persistence of high-grade IN and sufficient time for accumulation of genetic changes that are important in progression to cancer.

PMID: 16672559 [PubMed - indexed for MEDLINE]

Cytomegalovirus co-infection in AIDS-associated oral Kaposi's sarcoma.

Adv Dent Res. 2006;19(1):96-8

Authors: Meer S, Altini M

The increasing appearance of AIDS-associated oral Kaposi's sarcoma (KS) in South Africa may be ascribed to the later start of the HIV epidemic, more patients reaching stages III and IV, and the inaccessibility of most patients to anti-retroviral therapy. The objective of this study was to demonstrate cytomegalovirus (CMV) co-infection in oral KS and to consider its possible significance. We reviewed 20 cases of oral KS in known HIV-positive patients without active CMV disease. HHV8 PCR and CMV immunohistochemistry were performed. HHV8 DNA was present in all cases. CMV inclusions were detected in five cases. The significance of CMV co-infection in oral KS is unclear. The inclusions suggest active infection, although there is no evidence to support CMV in the pathogenesis of KS. Nonetheless, it is vital that physicians be alerted to active CMV infection, so that timely intervention and careful observation can be instituted, ensuring early diagnosis and treatment.

PMID: 16672558 [PubMed - indexed for MEDLINE]

Oral EBV and KSHV infection in HIV.

Adv Dent Res. 2006;19(1):91-5

Authors: Webster-Cyriaque J, Duus K, Cooper C, Duncan M

The gamma herpesviruses, Kaposi's-sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are tightly associated with the development of AIDS-associated oral disease and malignancy during immune suppression. The objective of this investigation was to characterize oral infection and pathogenesis in healthy and immune-suppressed individuals. To characterize oral EBV and KSHV infection, we examined throat washings and oral epithelial cells from HIV-positive and HIV-negative individuals. Quantitative/real-time polymerase-chain-reaction (PCR) assays, transmission electronmicroscopy, immunostaining, and sequence analysis were used to identify viral infection. Virus was isolated from throat-wash samples and was used to infect epithelial and lymphoid cell lines. We detected EBV and KSHV in the oral cavity in healthy and immune-suppressed individuals. Viral strain analysis of KSHV K1 in multiple clones from the oral cavities of healthy persons and immunosuppressed patients detected several strains previously detected in KS lesions, with minor strain variation within individuals. Immunoelectron microscopy for multiple viral antigens detected consistent expression of viral proteins and oral epithelial specimens. In oral epithelial cells infected with wild-type KSHV in vitro, the K8.1 glycoprotein associated with lytic KSHV infection was detected in both primary and telomerase immortalized oral epithelial cultures by 24 hours post-infection. Virions were detected, subsequent to infection, by scanning electron microscopy. Oral epithelial cells were also infected in vitro with wild-type EBV originating from throat washes. Analysis of these data suggests that, like EBV, KSHV infection is present in the oropharynx of healthy individuals, is transmissible in vitro, and may be transmitted by saliva.

PMID: 16672557 [PubMed - indexed for MEDLINE]

Conceptual emergence of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) as an oral herpesvirus.

Adv Dent Res. 2006;19(1):85-90

Authors: Teo CG

Recognition of the various clinico-epidemiologic forms of Kaposi's sarcoma, a disease putatively caused by an infectious agent, did not provide ready clues as to how that agent might be transmitted, although fecal and sexual routes were implicated. Application of serologic and genome-detection assays, and cell-culture studies following the identification of human herpesvirus 8 as the causative agent now implicate that virus as one that is orally shed. While oral transmission of the virus might account for the viral endemicity in Africa and Mediterranean countries, why it is particularly prevalent among male homosexuals in the West remains more difficult to explain. Such explanation may be sought from behavioral studies into the role saliva plays in sexual interactions.

PMID: 16672556 [PubMed - indexed for MEDLINE]

Candida-host interactions in HIV disease: relationships in oropharyngeal candidiasis.

Adv Dent Res. 2006;19(1):80-4

Authors: Fidel PL

Oropharyngeal candidiasis (OPC) caused by the commensal organism, Candida albicans, is the most common oral infection in HIV disease. Although cell-mediated immunity (CMI) by Th1-type CD4+ T-cells is considered the predominant host defense mechanism against OPC, other systemic or local immune mechanisms are critical when blood CD4+ T-cells are reduced below a protective threshold. For example, the Th cytokine profile in saliva may influence resistance or susceptibility to OPC. In OPC lesions, CD8+ T-cells become accumulated at the lamina propria-epithelium interface, suggesting some role for CD8+ T-cells against OPC. However, the absence of CD8+ T-cells close to Candida at the outer epithelium indicates that susceptibility to OPC involves a dysfunction in the CD8+ T-cells or in the micro-environment. Further evaluation of the buccal mucosa lesion showed that CD8 T-cell-associated cytokine and chemokine mRNA is increased compared with buccal mucosa from lesion-negative matched controls. The majority of CD8+ T-cells present possess the alphabeta T-cell receptor and several homing receptors (i.e., 4beta7, 4beta1, ebeta7). While several adhesion molecules are similar in OPC+ vs. OPC- persons, E-cadherin is reduced in the tissue of OPC+ persons. These results support evidence for a role for CD8+ T-cells against OPC, but suggest that a putative dysfunction in mucosal T-cell trafficking may be associated with susceptibility to infection. Similar levels of Candida-specific antibodies in persons with and without OPC confirmed a limited role for humoral immunity. Finally, oral epithelial cells inhibit the growth of Candida in vitro in a static rather than a cidal manner. Clinically, oral epithelial cell anti-Candida activity is reduced in HIV+ persons with OPC, compared with controls. The mechanism of action includes a strict requirement for cell contact by an acid-labile moiety on intact, but not necessarily live, epithelial cells, with no role for soluble factors. Taken together, host defense against OPC involves several levels of activity. The status and efficiency of local host defenses when blood CD4+ T-cells are not available appear to play a role in protection against or susceptibility to OPC.

PMID: 16672555 [PubMed - indexed for MEDLINE]

Implications of HIV disease for oral health services.

Adv Dent Res. 2006;19(1):73-9

Authors: Robinson PG

This paper, by means of a quality framework, reviews health services research in relation to people with HIV infection. The relevance of oral health care services to people's needs is considered in terms of the goal of health services to reduce the burden of disease on the everyday life of the population. Dental services may therefore have a role in primary prevention in the HIV epidemic, passing on information about HIV and promoting health through the early diagnosis and treatment of oral disease. Effectiveness research of oral health care in HIV assesses the usefulness of oral diagnosis, whether care is safe, and whether treatment is clinically effective. Few data are available on the efficiency of services. People with HIV still have problems accessing dental care, due to the volume of care available in relation to their need and acceptability of care. Access problems in the US are compounded by social inequality. Health services research data are particularly sparse in resource-poor countries, and there is a need to translate the available information into treatment guidelines appropriate to these settings. The research community and funding agencies should place greater emphasis on the quality of oral health services for people with HIV.

PMID: 16672554 [PubMed - indexed for MEDLINE]

Skin lesions: mirror images of oral lesion infections.

Adv Dent Res. 2006;19(1):69-72

Authors: Phanuphak N

Skin lesions can be the presenting signs for HIV disease and are among the most prevalent manifestations throughout the course of HIV disease. Correlation of skin diseases and HIV disease staging has long been recognized and used to guide medical management in resource-limited settings. The purpose of this paper is to give a review of common skin infections presented in HIV-infected patients. Common skin infections presenting in HIV-infected patients include viral, fungal, mycobacterial, and bacterial infections, along with skin infestation. Key diagnostic points correlate with certain HIV disease staging for many skin diseases. These can help facilitate appropriate diagnosis and referral by health care personnel when treating HIV-infected patients who have skin lesions. Knowledge of common skin manifestations found in HIV-infected patients is essential for all health care personnel who work in the HIV field. Most skin infections presenting in HIV-infected patients can be treated effectively if the correct diagnosis and appropriate referral are made promptly.

PMID: 16672553 [PubMed - indexed for MEDLINE]

Oral lesions in HIV infection in developing countries: an overview.

Adv Dent Res. 2006;19(1):63-8

Authors: Ranganathan K, Hemalatha R

HIV infection is a major global health problem affecting developing and developed countries alike. Oral lesions that are associated with this disease are important, since they affect the quality of life of the patient and are useful markers of disease progression and immunosuppression. Oral lesions in HIV infection have been well-documented in developed countries, but there are fewer reports on oral lesions from developing countries. Oral candidiasis is the most common opportunistic infection seen in all continents. Kaposi's sarcoma has been reported only from Africa and Latin America, while histoplasmosis and penicilliosis were reported in patients with advanced disease from Thailand. HIV-associated salivary gland disease has a high prevalence in Africa and Latin America, especially in the pediatric group. It is clear that there are considerable regional variations in the oral manifestations of HIV infection, depending both on the populations studied and on the clinical expertise available, among other factors. Well-designed and -documented studies are necessary for the correct assessment of the nature and magnitude of the problem in developing countries, if oral health measures are to be effectively formulated for the HIV-infected.

PMID: 16672552 [PubMed - indexed for MEDLINE]

Oral lesions of HIV disease and HAART in industrialized countries.

Adv Dent Res. 2006;19(1):57-62

Authors: Hodgson TA, Greenspan D, Greenspan JS

The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.

PMID: 16672551 [PubMed - indexed for MEDLINE]

Differential mucosal susceptibility in HIV-1 transmission and infection.

Adv Dent Res. 2006;19(1):52-6

Authors: Moutsopoulos NM, Greenwell-Wild T, Wahl SM

HIV infection occurs primarily through mucosal surfaces, indicating that protection at mucosal sites may be crucial in prevention and treatment. The host innate and adaptive immune elements provide a level of protection, which differs between mucosal compartments, and appears to be most successful in the oral environment, where transmission is rare. In addition to the distinct oral mucosal architecture and cellular constituents, oral fluids, unlike other mucosal secretions, are rarely a vehicle for HIV infection. Multiple soluble factors may contribute to this antiviral activity, including neutralizing antibodies, secretory leukocyte protease inhibitor (SLPI), antiviral peptides such as defensins and cystatins, glycoproteins including thrombospondin and lactoferrin, and complement components. Understanding the antiviral activities of these and other potential resistance factors is becoming increasingly important in attempts to design treatments in the era of HAART resistance. In this regard, the mechanism of anti-HIV action of SLPI has recently been further elucidated by the discovery of its binding protein/receptor, which plays a key role in the infection of macrophages and may consequently be a novel therapeutic target. Continued elucidation of the unique features of mucosal HIV immunology is essential for understanding HIV pathogenesis and for developing effective vaccines and therapeutics.

PMID: 16672550 [PubMed - indexed for MEDLINE]

Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of resistance or susceptibility to HIV infection?

Adv Dent Res. 2006;19(1):49-51

Authors: Cutler CW, Jotwani R

The basic premise of whether transmission of HIV-1 through the oral mucosa actually occurs, and through what route, is a topic of intense interest. Our work has focused on HIV-1 receptors/co-receptors and alpha-defensin-1 in situ in human gingiva. Regardless of HIV-1 infection, the role that C-type lectin receptors might play in periodontal pathogenesis is of great interest. We have shown that the gingival lamina propria, when inflamed, becomes increasingly infiltrated with DC-SIGN+MR+ dermal dendritic cells (DDCs), while the inflamed epithelium shows a decrease in Langerin+ Langerhans cells (LCs). Moreover, DDCs and LCs contribute to the mature CD83+ DC pool in situ, and form immune conjugates with CD4+ T-cells in the lamina propria (Jotwani and Cutler, 2003). This raises the intriguing possibility that oral mucosal DCs may be involved in HIV-1 transfer to T-cells in situ. However, this possibility is tendered by the challenges faced by the virus in gaining access to oral mucosal immune cells, including their ability to survive the salivary defenses, cross the mucosal barrier, resist inactivation by alpha-defensins, and overcome the paucity of co-receptor CCR5 in (healthy) oral mucosa (i.e., required for productive infection [Jotwani et al., 2004]). To date, there is little evidence of direct infection by HIV-1 of oral mucosal DCs/T cells and other cells in situ. Abbreviations used in this paper: CP, chronic periodontitis; CCR5, chemokine receptor 5; CXCR4, C-X-C receptor 4; DCs, dendritic cells; DC-SIGN, DC-specific ICAM-3 grabbing non-integrin; DDC, dermal dendritic cells; LCs, Langerhans cells; LP, lamina propria; MR, mannose receptor.

PMID: 16672549 [PubMed - indexed for MEDLINE]

Role of human beta-defensins in HIV infection.

Adv Dent Res. 2006;19(1):42-8

Authors: Weinberg A, Quiñones-Mateu ME, Lederman MM

Mechanisms of resistance to HIV-1 infection in the human oral cavity are incompletely understood. While salivary components have been implicated in protection, there is growing evidence that human beta-defensins (hBDs), originating in oral epithelial cells, may be playing an important role in the prevention of HIV infection. New antiviral, chemotactic, and immunosurveillance properties are being attributed to hBDs, which are small cationic antimicrobial innate response molecules expressed in mucosal epithelium. Inducible hBDs are always expressed in normal oral epithelium, a property not shared by other mucosal barriers. Data reviewed in this paper demonstrate that: (1) HIV-1 X4 and R5 phenotypes induce hBD-2 and -3 mRNA in normal human oral epithelial cells; (2) hBD-2 and -3 inhibit HIV-1 infection by both viral strains, with greater activity against X4 viruses; and (3) this inhibition is due to a direct interaction with virions and through modulation of the CXCR4 co-receptor. These properties may be exploited as strategies for mucosal protection against HIV-1 transmission.

PMID: 16672548 [PubMed - indexed for MEDLINE]

Dendritic cells and HIV infection: activating dendritic cells to boost immunity.

Adv Dent Res. 2006;19(1):36-41

Authors: Teleshova N, Kenney J, Robbiani M

Dendritic cells (DCs) are white blood cells that coordinate innate and adaptive immunity. They are distributed within epithelia and mucosal-associated lymphoid tissues, positioned to entrap incoming pathogens or vaccines. Human immunodeficiency virus (HIV) and the non-human primate equivalent (SIV) exploit DCs to amplify infection, underscoring the need to harness strategies that promote presentation of virus by DCs to stimulate potent anti-viral immunity instead of virus transmission. Two main subsets of DCs need to be considered: myeloid (MDC) and plasmacytoid (PDC) subsets. Using the SIV-macaque system to advance oral vaccine research, we examined macaque PDC and MDC biology, identifying ways to activate DCs and boost antiviral immunity. Immunostimulatory oligodeoxyribonucleotides (ISS-ODNs) stimulated PDC/MDC mixtures to up-regulate co-stimulatory molecule expression and to secrete both IFN-alpha and IL-12. Additionally, ISS-ODNs augmented SIV-specific IFN-gamma responses induced by virus-bearing DCs. ISS-ODN-driven DC activation is being pursued to improve oral/nasopharyngeal mucosal vaccines and therapies against HIV.

PMID: 16672547 [PubMed - indexed for MEDLINE]

The effects of HIV infection on oral mucosal immunity.

Adv Dent Res. 2006;19(1):29-35

Authors: Challacombe SJ, Naglik JR

Oral mucosal infections, especially candidiasis, are a feature of HIV disease, suggesting that compromised mucosal immunity within the oral cavity is a consequence of the viral infection. However, how this mucosal immunity is compromised and at what stage of HIV infection this occurs are unclear. Better understanding of the protection of the oral cavity against infection has allowed us to gain some insight into the local consequences of HIV infection. From a humoral perpective, IgA2 subclasses are reduced in HIV infection in saliva, and total secretory IgA levels are reduced in later disease. Similarly, mucosal antibody responses appear near normal in early HIV infection but reduced in AIDS. There is now convincing evidence that salivary IgA can be neutralizing to HIV 1 and HIV 2, as well as block epithelial transmigration. Oral cellular immunity is also affected by HIV infection. Transmission of HIV from one oral cell type to another appears to be confirmed by work showing that HIV can bind to or infect epithelial cells, Langerhans cells, and other mucosal cells. CXCR4 tropic (via GalCer and CXCR4) and dual tropic HIV strains have been shown to be able to infect normal human oral keratinocytes (NHOKs), and infectious HIV virions can also be conveyed from NHOKs to activated peripheral blood lymphocytes, suggesting a potential role of oral epithelial cells in the transmission of HIV infection. There is evidence of up-regulation of various receptors, including HIV receptors, on the surface of oral epithelium, and the epithelium may become more permeable. HIV may exploit this antigen uptake mechanism to cross epithelial barriers during co-infection with damage-inducing pathogens such as Candida. Immune responsiveness to many of the co-pathogens associated with HIV has been demonstrated to depend on a family of innate recognition molecules, known as Toll-like receptors (TLR), and recognition of a single pathogen can involve activation of multiple TLRs. Consequently, TLR-pathogen interactions could play an indirect but major role in regulating HIV-associated disease in the oral cavity. Thus, HIV infection appears to have both direct and indirect effects on oral mucosal immunity, affecting both cellular and humoral immunity as well as both specific and innate immunity.

PMID: 16672546 [PubMed - indexed for MEDLINE]

Innate and adaptive mucosal immunity in protection against HIV infection.

Adv Dent Res. 2006;19(1):21-8

Authors: Bergmeier LA, Lehner T

The appalling toll on the populations of developing countries as a result of the HIV epidemic shows no signs of abatement. While costly drug therapies are effective in developed nations, the sheer scale of the epidemic elsewhere makes the need for a vaccine an ever more urgent goal. The prevalent DNA prime-viral boost strategy aims to elicit cytotoxic lymphocytes (CTL) against HIV, but this approach is undermined by the rapid mutation of HIV, which thereby escapes CTL control. Alloimmunity has been found to be protective in vertical transmission from infected mothers to their babies, in alloimmunization of women with their partners' mononuclear cells, and in monkeys immunized with SIV grown in human T-cells. Vaginal mucosal immunization, as a result of unprotected sex with a regular partner, induced in vitro protection against HIV infection, and this was confirmed in macaques. The second type of natural protection is found in persons with the homozygous 32 CCR5 mutation, a 32-base-pair deletion of the CCR5 gene, which results in a lack of cell-surface expression of CCR5, which is associated with an increase in CC chemokines and the development of CCR5 antibodies. These two 'experiments of nature' have been used to develop vaccine strategies--first, in vaginal immunization of macaques with CCR5 peptides, in addition to HIV envelope (env) and SIV core (gag) antigens, all of which were linked to the 70-kD heat-shock protein (HSP70); and second, in mucosal allo-immunization of macaques, which also gave rise to in vitro protection from infection. Immunization with this vaccine elicited serum and vaginal IgG and IgA antibodies, IFNgamma- and IL-12-producing cells, and increased concentrations of CCL-3 and CCL-4. Vaginal challenge with a simian immunodeficiency virus engineered to carry a human envelope protein (SHIV 89.6) showed significant clearance of SHIV in the immunized macaques. This platform strategy will now be developed to activate the co-stimulatory pathways with the aim of enhancing the primary allogeneic and CCR5-directed responses which are involved in natural protection against HIV infection.

PMID: 16672545 [PubMed - indexed for MEDLINE]

Policy for prevention of oral manifestations in HIV/AIDS: the approach of the WHO Global Oral Health Program.

Adv Dent Res. 2006;19(1):17-20

Authors: Petersen PE

The HIV/AIDS pandemic has become a human and social disaster, particularly affecting the developing countries of Africa, Southeast Asia, and Latin America. By the end of 2004, about 40 million people were estimated to be infected by HIV globally. The health sectors in many affected countries are facing severe shortages of human and financial resources, and are struggling to cope with the growing impact of HIV/AIDS. In most developed countries, the availability of antiretroviral treatment has resulted in a dramatic reduction in HIV/AIDS-related mortality and morbidity. In contrast, in the developing countries, there is little access to treatment, and access to HIV-prevention services is poor. The '3 by 5' initiative was launched by the WHO and UNAIDS in 2003 with the aim of providing antiretrovirals to three million people in developing countries by the year 2005. HIV infection has a significant negative impact on oral health, with approximately 40-50% of HIV-positive persons developing oral fungal, bacterial, or viral infections early in the course of the disease. Oral health services and professionals can contribute effectively to the control of HIV/AIDS through health education and health promotion, patient care, effective infection control, and surveillance. The WHO Global Oral Health Program has strengthened its work for prevention of HIV/AIDS-related oral disease. The WHO co-sponsored conference, Oral Health and Disease in AIDS, held in Phuket, Thailand (2004), issued a declaration calling for action by national and international health authorities. The aim is to strengthen oral health promotion and the care of HIV-infected persons, and to encourage research on the impact that HIV/AIDS, public health initiatives, and surveillance have on oral health.

PMID: 16672544 [PubMed - indexed for MEDLINE]

HIV pathogenesis: knowledge gained after two decades of research.

Adv Dent Res. 2006;19(1):10-6

Authors: Levy JA

Great progress has been made in our understanding of HIV since its initial discovery about 20 years ago. The ability of HIV to infect CD4+ lymphocytes and a wide variety of other cells in the body is appreciated, as is its role in immunologic, gastrointestinal, and brain disorders. HIV enters cells via the CD4 molecule, chemokine co-receptors (CXCR4, CCR5), and other cell-surface proteins. Several accessory virus-associated genes (e.g., Rev, Tat, Nef) have uncovered unique pathways that can also be observed in normal cells. Recently, the discovery of natural cellular resistant factors (APOBEC3G and TRIM5a) has provided avenues for novel antiviral therapies. Studies of long-term survivors have given insight into immune responses that control HIV and can prevent infection. Neutralizing antibodies and CD8+ cell cytotoxic responses, as well as plasmacytoid dendritic cells and CD8+ cell non-cytotoxic antiviral responses, are adaptive and innate immune activities mediating this anti-HIV effect. HIV vaccine studies have indicated that conventional approaches do not work against this integrated intracellular parasite. While much has been learned about HIV, more details are needed about its infection cycle and its pathologic effects in the body. The past 20 years have yielded important information on HIV/AIDS that should lead to effective anti-HIV therapies and a vaccine.

PMID: 16672543 [PubMed - indexed for MEDLINE]

Overview and research agenda arising from the 5th World Workshop on Oral Health and Disease in AIDS.

Adv Dent Res. 2006;19(1):5-9

Authors: Challacombe S, Coogan M, Williams D, Greenspan J

PMID: 16672542 [PubMed - indexed for MEDLINE]

The Phuket Declaration.

Adv Dent Res. 2006;19(1):4

Authors:

PMID: 16672541 [PubMed - indexed for MEDLINE]

The Data Stations Project of the Dutch Dental Association.

Adv Dent Res. 2005 Dec;18(3):50-2

Authors: Bruers JJ, Zeegers GL

Within the framework of the research project Data Stations, the Dutch Dental Association (NMT) periodically collects data about the care dentists render to patients, about the way in which they run their practices, and about views and/or wishes of dentists with regard to (current) issues within the dental profession. This paper focuses on the motives underlying the decision of the NMT to undertake the Data Stations Project, and on the way this project is organized. Particular attention will be given to the types of data and the kinds of information this project produces.

PMID: 16385013 [PubMed - indexed for MEDLINE]

Evaluating restorative materials and procedures in dental practice.

Adv Dent Res. 2005 Dec;18(3):46-9

Authors: Burke FJ

A wide variety of research methods are appropriate to general dental practice, including clinical trials of materials, assessment of materials and techniques, treatment trends, and assessment of behavior and attitudes, of dentists as well as patients. This paper will describe the use of practice-based networks to evaluate the effectiveness of materials and techniques in dental practice. Several practice-based research groups are presently in operation in the UK and the USA, generally carrying out evaluations of the handling of materials, but with increasing emphasis on the clinical evaluation of restorations. Use of the Dental Practice Board (of England and Wales) database has proved to be a fruitful source of data on the long-term outcome of restorations. Dental practice can provide the large pool of patients available for research. To utilize this pool of patients, dental practitioners and their support staff require training in collecting data.

PMID: 16385012 [PubMed - indexed for MEDLINE]

Use of dental service data to inform research and policy.

Adv Dent Res. 2005 Dec;18(3):42-5

Authors: Whelton H, O'Mullane D, Burke FM, Woods N, Cronin M

Data collected routinely in dental care delivery systems could be used to inform research and policy. Projects in which data were collected with the help of general dental practitioners are outlined. In an EU-funded project, six partners collaborated to develop a methodology designed to establish links between characteristics of a health care system and health outcome, and to determine the characteristics of oral health care systems which promote oral health and those which are detrimental to oral health. The results indicated that the data collected in the different systems investigated varied enormously, and they could not be easily adapted to help in developing policy. A theoretical model was developed in which the production of oral health care was considered separately from the production of oral health. In the second example, the longevity of the restorations in a dental care delivery system in Ireland was investigated by routine service data.

PMID: 16385011 [PubMed - indexed for MEDLINE]

Experience of clinical trials in general dental practice.

Adv Dent Res. 2005 Dec;18(3):39-41

Authors: Clarkson J

There is considerable debate about the feasibility and appropriateness of research in dental primary care, particularly the conduct of clinical trials compared with other research designs. While an evidence-based approach to clinical practice is advocated to improve patient care, research relevant to primary care is sparse, with a gap between research findings and clinical practice. Conducting research in a primary care setting is important, while recruitment and retention methods are crucial for generalizability of the results. Systematic reviews show that high-quality trials provide more reliable outcomes, due to methods such as concealment of allocation to groups, blinding, and particularly outcome assessment and loss to follow-up. Our experience of clinical trials in general dental practice has given insight into the design and conduct that ensure feasibility and generalizability. However, only with adequate funding, good infrastructure, and networks can research be conducted in dental primary care.

PMID: 16385010 [PubMed - indexed for MEDLINE]

Oral research in primary care.

Adv Dent Res. 2005 Dec;18(3):37-8

Authors: Burke FM, O'Mullane D

PMID: 16385009 [PubMed - indexed for MEDLINE]

The Oral Fluid MEMS/NEMS Chip (OFMNC): diagnostic and translational applications.

Adv Dent Res. 2005 Jun;18(1):3-5

Authors: Li Y, Denny P, Ho CM, Montemagno C, Shi W, Qi F, Wu B, Wolinsky L, Wong DT

The ability to monitor health status, disease onset and progression, and treatment outcome through non-invasive means is a most desirable goal in health-care promotion and delivery. There are three prerequisites for this goal to be realized: specific biomarkers associated with a health or disease state, a non-invasive approach to detect and monitor the biomarkers, and the technologies to discriminate between and among the biomarkers. We present a roadmap to achieve these goals using oral fluids as the diagnostic medium to scrutinize the health and/or disease status of individuals. This is an ideal opportunity to bridge state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral fluid for diagnostic applications. As the "mirror of body", oral fluid is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous.

PMID: 16000263 [PubMed - indexed for MEDLINE]

The use of soluble, salivary c-erbB-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study.

Adv Dent Res. 2005 Jun;18(1):17-24

Authors: Streckfus C, Bigler L

A surge of new technological developments, coupled with the limitations of existing disease-detection methodologies, is propelling the field of medical diagnostics forward at unprecedented rates. Advancements in proteomics and nanotechnology are paving the way for diagnostic tests that will be capable of rapid multi-analyte detection in both laboratory and non-laboratory settings. Technological advancements have also benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium that can be collected simply and non-invasively. Salivary biomarkers have been identified that may provide diagnostic information about a variety of cancers and other diseases. In particular, proof-of-principle has been demonstrated for salivary c-erbB-2, whose elevation has been shown to correlate strongly with breast malignancy in women. The purpose of this manuscript is to review the past literature and present the current research focused on the use of saliva as a diagnostic medium for the detection of malignancies that are remote from the oral cavity.

PMID: 15998939 [PubMed - indexed for MEDLINE]

Point detection of pathogens in oral samples.

Adv Dent Res. 2005 Jun;18(1):12-6

Authors: Malamud D, Bau H, Niedbala S, Corstjens P

PMID: 15998938 [PubMed - indexed for MEDLINE]

DNA microarrays as salivary diagnostic tools for characterizing the oral cavity's microbial community.

Adv Dent Res. 2005 Jun;18(1):6-11

Authors: Smoot LM, Smoot JC, Smidt H, Noble PA, Könneke M, McMurry ZA, Stahl DA

PMID: 15998937 [PubMed - indexed for MEDLINE]

Retrieval and classification of dental research articles.

Adv Dent Res. 2003 Dec;17:115-20

Authors: Bartling WC, Schleyer TK, Visweswaran S

Successful retrieval of a corpus of literature on a broad topic can be difficult. This study demonstrates a method to retrieve the dental and craniofacial research literature. We explored MeSH manually for dental or craniofacial indexing terms. MEDLINE was searched using these terms, and a random sample of references was extracted from the resulting set. Sixteen dental research experts categorized these articles, reading only the title and abstract, as either: (1) dental research, (2) dental non-research, (3) non-dental, or (4) not sure. Identify Patient Sets (IPS), a probabilistic text classifier, created models, based on the presence or absence of words or UMLS phrases, that distinguished dental research articles from all others. These models were applied to a test set with different inputs for each article: (1) title and abstract only, (2) MeSH terms only, or (3) both. By title and abstract only, IPS correctly classified 64% of all dental research articles present in the test set. The percentage of correctly classified dental research articles in this retrieved set was 71%. MeSH term inclusion decreased performance. Computer programs that use text input to categorize articles may aid in retrieval of a broad corpus of literature better than indexing terms or key words alone.

PMID: 15126221 [PubMed - indexed for MEDLINE]

Dental data mining: potential pitfalls and practical issues.

Adv Dent Res. 2003 Dec;17:109-14

Authors: Gansky SA

Knowledge Discovery and Data Mining (KDD) have become popular buzzwords. But what exactly is data mining? What are its strengths and limitations? Classic regression, artificial neural network (ANN), and classification and regression tree (CART) models are common KDD tools. Some recent reports (e.g., Kattan et al., 1998) show that ANN and CART models can perform better than classic regression models: CART models excel at covariate interactions, while ANN models excel at nonlinear covariates. Model prediction performance is examined with the use of validation procedures and evaluating concordance, sensitivity, specificity, and likelihood ratio. To aid interpretation, various plots of predicted probabilities are utilized, such as lift charts, receiver operating characteristic curves, and cumulative captured-response plots. A dental caries study is used as an illustrative example. This paper compares the performance of logistic regression with KDD methods of CART and ANN in analyzing data from the Rochester caries study. With careful analysis, such as validation with sufficient sample size and the use of proper competitors, problems of naïve KDD analyses (Schwarzer et al., 2000) can be carefully avoided.

PMID: 15126220 [PubMed - indexed for MEDLINE]

Bayesian machine learning and its potential applications to the genomic study of oral oncology.

Adv Dent Res. 2003 Dec;17:104-8

Authors: Sebastiani P, Yu YH, Ramoni MF

With the completion of the Human Genome Project and the growing computational challenges presented by the large amount of genomic data available today, machine learning is becoming an integral part of biomedical research and plays a major role in the emerging fields of bioinformatics and computational biology. This situation offers unparalleled opportunities and unprecedented challenges to machine learning research in general and to Bayesian learning methods in particular. This paper outlines some of the opportunities and the challenges of this endeavor, it describes where the efforts of "cracking the code of life" can most benefit from a Bayesian approach, and it identifies some potential applications of Bayesian machine learning methods to the genomic analysis of squamous cell carcinomas of the head and neck.

PMID: 15126219 [PubMed - indexed for MEDLINE]

Comparative genomics and structure prediction of dental matrix proteins.

Adv Dent Res. 2003 Dec;17:100-3

Authors: Krishnaraju RK, Hart TC, Schleyer TK

Non-collagenous matrix proteins secreted by the ameloblasts (amelogenin) and odontoblasts (osteocalcin) play important roles in the mineralization of enamel and dentin. In this study, comparative genomics approaches were used to identify the functional domains and model the three-dimensional structure of amelogenin and osteocalcin, respectively. Multiple sequence analysis of amelogenin in different species showed a high degree of sequence conservation at the nucleotide and protein levels. At the protein level, motifs (a sequence pattern that occurs repeatedly in a group of related proteins or genes), conserved domains, secondary structural characteristics, and functional sites of amelogenin from lower phyla were similar to those of the higher-level mammals, reflecting the high degree of sequence conservation during vertebrate evolution. Osteocalcin, produced by both odontoblasts and osetoblasts, also showed sequence similarity between species. Three-dimensional structure predictions developed by modeling of conserved domains of osteocalcin supported a role for glutamic acid residues in the calcium mineralization process.

PMID: 15126218 [PubMed - indexed for MEDLINE]

Genetic and molecular characterization of a dental pathogen using genome-wide approaches.

Adv Dent Res. 2003 Dec;17:95-9

Authors: Actis LA, Rhodes ER, Tomaras AP

Actinobacillus actinomycetemcomitans causes periodontitis, a costly chronic infection that affects a large number of patients. The pathogenesis of this dental infection is a multifactorial process that results in a serious degenerative disease of the periodontium. Although significant progress has been achieved after the identification of this Gram-negative bacterium as the etiological agent of this infection, much remains to be done to understand in detail the bacterial factors and host-pathogen interactions involved in the pathogenesis of this disease. Classic research approaches have resulted in the identification of important virulence factors and cellular processes, although they have provided a rather narrow picture of some of the steps of this complex process. In contrast, a much wider picture could be obtained with the application of tools such as bioinformatics and genomics. These tools will provide global information regarding the differential expression of genes encoding factors and processes that lead to the pathogenesis of this disease. Furthermore, comparative genomics has the potential of helping us to understand the emergence and evolution of this human pathogen. This genome-wide approach should provide a more complete picture of the pathogenesis process of this disease, and will facilitate the development of efficient diagnostic, preventive, and therapeutic measures for this disease.

PMID: 15126217 [PubMed - indexed for MEDLINE]

Overview of bioinformatics and its application to oral genomics.

Adv Dent Res. 2003 Dec;17:89-94

Authors: Kuo WP

The "informatics revolution" in both bioinformatics and dental informatics will eventually change the way we practice dentistry. This convergence will play a pivotal role in creating a bridge of opportunity by integrating scientific and clinical specialties to promote the advances in treatment, risk assessment, diagnosis, therapeutics, and oral health-care outcome. Bioinformatics has been an emerging field in the biomedical research community and has been gaining momentum in dental medicine. This area has created a steady stream of large and complex genomic data, which has transformed the way a clinical or basic science researcher approaches genomic research. This application to dental medicine, termed "oral genomics", can aid in the molecular understanding of the genes and proteins, their interactions, pathways, and networks that are responsible for the development and progression of oral diseases and disorders. As the result of the Human Genome Project, new advances have prompted high-throughput technologies, such as DNA microarrays, which have become accepted tools in the biomedical research community. This manuscript reviews the two most commonly used microarray technologies, basic microarray data analysis, and the results from several ongoing oral cancer genomic studies.

PMID: 15126216 [PubMed - indexed for MEDLINE]

Using information technology and community-based research to improve the dental health-care system.

Adv Dent Res. 2003 Dec;17:86-8

Authors: Atchison KA

It is commonly acknowledged that the United States' health-care system produces some of the finest care in the world for some people but fails to meet the needs of others. The Institute of Medicine (IOM) issued six aims for a redesigned health-care system, that it be: safe, effective, patient-centered, timely, efficient, and equitable. The purpose of this paper is to use an ongoing community-based study to illustrate current problems in the provision of oral health services that could be addressed through information technology. Appropriate use of information technology can assist dental schools and clinics in community-based clinical outcomes research needed to assemble the evidence base for improving oral health care. This conference serves as an important steppingstone to establish a means for information technology to improve the community's oral health.

PMID: 15126215 [PubMed - indexed for MEDLINE]

Health services research.

Adv Dent Res. 2003 Dec;17:82-5

Authors: Bailit HL

The major barriers to the collection of primary population-based dental services data are: (1) Dentists do not use standard record systems; (2) few dentists use electronic records; and (3) it is costly to abstract paper dental records. The value of secondary data from paid insurance claims is limited, because dentists code only services delivered and not diagnoses, and it is difficult to obtain and merge claims from multiple insurance carriers. In a national demonstration project on the impact of community-based dental education programs on the care provided to underserved populations, we have developed a simplified dental visit encounter system. Senior students and residents from 15 dental schools (approximately 200 to 300 community delivery sites) will use computers or scannable paper forms to collect basic patient demographic and service data on several hundred thousand patient visits. Within the next 10 years, more dentists will use electronic records. To be of value to researchers, these data need to be collected according to a standardized record format and to be available regionally from public or private insurers.

PMID: 15126214 [PubMed - indexed for MEDLINE]

The role of information technology and informatics research in the dentist-patient relationship.

Adv Dent Res. 2003 Dec;17:77-81

Authors: Kirshner M

A high-value doctor-patient relationship is based on a set of parameters which include the interpersonal relationship between the patient and the doctor. Based on the Primary Care Assessment Survey model, measures of the interpersonal relationship are associated with communication, interpersonal care, contextual knowledge of the patient, and trust. Despite the proven value of the doctor-patient relationship, current trends indicate that the quality of these relationships is on the decline. The advent of communication and information technologies has greatly affected the way in which health care is delivered and the relationship between doctors and patients. The convergence of communication and information technology with biomedical informatics offers an opportunity to affect the character of the doctor-patient relationship positively. This paper examines the intersection of the key features of the doctor-patient relationship and a variety of Internet-based, clinical, and administrative applications used in dental practice. This paper discusses the role of dental informatics research vis-à-vis the doctor-patient relationship and explores how it may inform the next generation of information technologies used in dental practice.

PMID: 15126213 [PubMed - indexed for MEDLINE]

AIDA: web agents in dental treatment planning.

Adv Dent Res. 2003 Dec;17:74-6

Authors: Finkeissen E, Stamm I, Müssig M, Streicher J, Koke U, Helmstetter C, Hassfeld S, Wetter T

The objective of the AIDA project (Artificial Intelligent Dental Agents, http://aida.uni-hd.de) is the analysis of dental decision-making, the design of a computer-based decision support system, as well as the testing of the decision structure in interactions with dental experts, practicing dentists, and patients. The planning of the solution alternatives for an individual patient is based on a top-down structure for dental decision-making, aiming at a standardization of the argumentation. From a theoretical point of view, decision support can be provided only for anticipated decisions (planning). Moreover, only parts of these anticipated decisions can be supported. Accordingly, a separation of these partial aspects has to take place before one is able to build decision support systems. For prosthetic dentistry, clinicians have been shown how to use individual patient findings to sketch the possible treatment alternatives and later derive guidelines for the treatment. The planning module for fixed prostheses has already been integrated into a software agent. Planning modules for other types of prostheses are currently specified, implemented, and verified.

PMID: 15126212 [PubMed - indexed for MEDLINE]

Decision support at the point of care: challenges in knowledge representation, management, and patient-specific access.

Adv Dent Res. 2003 Dec;17:69-73

Authors: Greenes RA

Many applications in a clinical information system can benefit from the incorporation of medical knowledge to provide patient-specific, point-of-care decision support. These include computer-based provider order entry, referral, clinical result interpretation, consultation, adverse event monitoring, scheduling, shared patient-doctor decision-making, and generation of alerts and reminders, among others. To be executable, knowledge must be represented in the form of rules, constraints, calculations, guidelines, and other logical/algorithmic formats. The main difficulty is that the integration of such knowledge into clinical applications, when it occurs, tends to be very system- and application-specific, often encoded in a programming language, or even in the formating specifications of a user interaction display. Also, the data references and services invoked are highly dependent on the system/platform and electronic medical record implementation. This makes it difficult and time-consuming to encode authoritative evidence-based knowledge, severely limits the ability to disseminate and share successes, and hampers efforts to review and update the logic as medical knowledge changes. Solutions to this problem involve the development of standards-based representations for medical knowledge, and tools for authoring/editing, dissemination, adaptation to local environments, and execution. Numerous approaches are being pursued, all of which will be described in this presentation.

PMID: 15126211 [PubMed - indexed for MEDLINE]

Designing clinically useful systems: examples from medicine and dentistry.

Adv Dent Res. 2003 Dec;17:65-8

Authors: Koch S

Despite promising results in medical informatics research and the development of a large number of different systems, few systems get beyond a prototype state and are really used in practice. Among other factors, the lack of explicit user focus is one main reason. The research projects presented in this paper follow a user-centered system development approach based on extensive work analyses in interdisciplinary working groups, taking into account human cognitive performance. Different medical and health-care specialists, together with researchers in human-computer interaction and medical informatics, specify future clinical work scenarios. Special focus is put on analysis and design of the information and communication flow and on exploration of intuitive visualization and interaction techniques for clinical information. Adequate choice of the technical access device is made depending on the user's work situation. It is the purpose of this paper to apply this method in two different research projects and thereby to show its potential for designing clinically useful systems that do support and not hamper clinical work. These research projects cover IT support for chairside work in dentistry (http://www.dis.uu.se/mdi/research/projects/orquest) and ICT support for home health care of elderly citizens (http://www.medsci.uu.se/mie/project/closecare).

PMID: 15126210 [PubMed - indexed for MEDLINE]

Computational models of oral and craniofacial development, growth, and repair.

Adv Dent Res. 2003 Dec;17:61-4

Authors: Hammond P, Hutton T, Maheswaran S, Modgil S

This paper illustrates how biological and clinical problems stimulate research in biomedical informatics and how such research contributes to their solution. The computational models described use techniques from Logic Programming, Machine Learning, Computer Vision, and Biomathematics. They address problems in the development, growth, and repair of oral and craniofacial tissues arising in cell biology, clinical genetics, and dentistry. At the micro-level, the dynamic interaction of cells in the oral epithelium is modeled. At the macro-level, models are constructed of either the craniofacial shape of an individual or the craniofacial shape differences within and between healthy and congenitally abnormal populations. In between, in terms of scale, there are models of normal dentition and the use of computerized expert knowledge to guide the design of dental prostheses used to restore function in partially edentulous patients.

PMID: 15126209 [PubMed - indexed for MEDLINE]

Spectrophotometric analysis of all-ceramic materials and their interaction with luting agents and different backgrounds.

Adv Dent Res. 2003 Dec;17:55-60

Authors: Barath VS, Faber FJ, Westland S, Niedermeier W

In this study, two All-Ceramic (AC) materials--Empress 2 (EMP) (Ivoclar Vivadent AG, Schaan, Liechtenstein) and In-Ceram ALUMINA (ICA) (Vita Zahnfabrik, Bad S&#xE4;ckingen, Germany)--were analyzed, along with the effects of 3 luting agents-viz. Zinc Phosphate cement (ZNPO, PhospaCEM PL, Ivoclar Vivadent AG, Schaan, Liechtenstein), Glass Ionomer Cement (GIC, Ketac-Cem Radiopaque, ESPE Dental AG, Seefeld, Germany), and Compolute (COMP, ESPE Dental AG, Seefeld, Germany)--on the final color, using the CIELab system. Color differences (DeltaL, Deltaa, Deltab, and DeltaE) were calculated for samples with luting agents and for samples without luting agents with standard white and black backgrounds, with the use of a spectrophotometer, Luci 100 (Dr. Lange, Berlin, Germany). One-way ANOVA for DeltaL, Deltaa, Deltab, and DeltaE within both the AC systems, with and without luting agents, showed significant contributions of the background (p < 0.05). EMP was seen to be more translucent than ICA. Darker ceramics showed less color variation. Luting agents altered the final color of the restoration. ZNPO was least translucent, followed by GIC and COMP. Marginal increases in thicknesses of ICA samples (0.4 mm) do not show a statistically significant color difference. No method exists to predict the outcome of an AC restoration based on consideration of the luting agent and the background color.

PMID: 15126208 [PubMed - indexed for MEDLINE]