Osseointegration: biological events in relation to characteristics of the implant surface.

Osseointegration of titanium implants is a complex biological process involving interactions between immuno-inflammatory responses, angiogenesis and osteogenesis, all of which are influenced by the physical and chemical characteristics of the implant surface. An implant surface with moderately rough topography and high surface energy influences cellular activities, enhancing peri-implant bone wound healing. Primary mechanical stability of the implant is essential for osseointegration. In this article we review some of the more important biological events of peri-implant bone wound healing in the process of osseointegration, and discuss how the biophysical properties of implant surfaces influence cellular responses.

Race/ethnicity in biomedical research and clinical practice.

There is ongoing debate as to whether persons of different racial/ethnic groups are biologically significantly different, and, if such differences exist, whether they are relevant in relation to disease susceptibility and to treatment outcomes. There is also debate about the benefits of using race/ethnicity as a factor in clinical decision making, and as a variable in biomedical or public health research, because of the emotional sensitivities attached to race/ethnic categorisation. Such categorisation may also divert attention from underlying issues such as socioeconomic status and lack of access to modern health care. In this short article we will discuss these controversies, and will emphasize the importance of responsible and sensitive use of race/ethnicity as a variable in biomedical research and in clinical practice.

Alcohol and oral squamous cell carcinoma.

Alcohol is a risk factor for oral squamous cell carcinoma. It enhances the permeability of the oral epithelium, acts as a solvent for tobacco carcinogens, induces basal-cell proliferation, and generates free radicals and acetaldehyde, which have the capacity to cause DNA damage. Alcohol-associated malnutrition and immune suppression may further promote carcinogenesis. However, acetaldehyde, the first metabolite of ethanol, is the critical agent by which prolonged and excessive consumption of alcoholic beverages increases the risk of oral squamous cell carcinoma. Alcohol also acts synergistically with the products of tobacco combustion in the pathogenesis of oral squamous cell carcinoma.

Peri-implant mucositis and peri-implantitis: clinical and histopathological characteristics and treatment.

Osseointegrated dental implants are used routinely in dentistry in the confidence of predictable success. However, if the implant surfaces become colonised by pathogenic bacteria, the plaque-induced inflammation around the implants may cause peri-implant tissue destruction. Peri-implant mucositis is a reversible, plaque-induced inflammatory lesion confined to the peri-implant soft tissue unit and clinically is characterised by redness, swelling and bleeding on gentle probing. Peri-implantitis is an extension of peri-implant mucositis to involve the bone supporting the implant: it is characterised by loss of osseointegration of the coronal part of the implant, by increased probing depth and by bleeding and/or suppuration on probing. Established peri-implantitis does not respond predictably to treatment. The best management of plaque-induced peri-implant inflammatory diseases is prevention. Regular personal and professional cleaning of the implant is mandatory to minimise bacterial load. Despite our best efforts, plaque-induced peri-implant inflammatory diseases will occur frequently, and as these diseases respond best to early treatment, early detection of peri-implant mucositis by regular assessment will permit timely treatment. Peri-implant mucositis is readily treated non-surgically. Peri-implantitis is more difficult to treat largely because of the problem of decontamination of the roughened, threaded surfaces of exposed implants. As a rule, surgical treatment will be necessary, and even then success is not assured.

Peri-implant mucositis and peri-implantitis: bacterial infection.

Osseointegrated dental implants have a ong-term success rate of over 90%, but may be threatened by peri-implant mucostis and peri-implantitis, bacteria biofilm-induced inflammatory conditions. While peri-implant mucositis is a reversible inflammatory condition confined to the peri-implant soft-tissue unit, peri-implantitis is characterised by progressive inflammatory destruction of the crest of the alveolar bone supporting the implant, by increased peri-implant probing depths, and by bleeding and/or suppuration on probing. Effective treatment of peri-implant mucositis will prevent the development of peri-implantitis. Plaque accumulation on the implant/abutment surface juxtaposed to the junctional epithelium and to the connective tissue zone of the peri-implant soft-tissue unit induces the development of peri-implant mucositis which can subsequently progress to peri-implantitis. The aim of this paper is to review some aspects of bacterial infection of the tissue supporting dental implants, and to explore how to maintain the healthy peri-implant soft-tissue unit.

The peri-implant soft tissue unit: a literature review.

Restoration of the integrity of the dentition with endosseous implants is a treatment option made available to patients not only by specialists but increasingly also by non-specialist dental practitioners. Properly done implants at well-selected sites in suitable persons remain functionally and biologically sound for many years. An important factor n determining the success of implants s the integrity of the peri-implant soft tissue unit. Therefore, the implant placement protocol and the restorative protocol should be designed to favour the formation and maintenance of the peri-implant soft tissue unit. The purpose of this short review is to refresh the reader's knowledge of some important factors with regard to establishing and maintaining the integrity of the peri-implant soft tissue.

HPV-associated oral warts.

Human papillomavirus (HPV) is strictly epitheliotropic, infecting stratified squamous cutaneous and mucosal epithelial cells. Oral HPV infection may be subclinical or putatively associated with benign or malignant oral neoplasms. The benign HPV-associated oral lesions, focal epithelial hyperplasia (Heck disease), oral squamous cell papilloma, oral verruca vulgaris (common wart) and oral condyloma acuminatum, are collectively referred to as oral warts. Oral warts are usually asymptomatic, may be persistent or uncommonly, may regress spontaneously. HPV-associated oral warts have a prevalence of 0.5% in the general population, occur in up to 5% of HIV-seropositive subjects, and in up to 23% of HIV-seropositive subjects on highly active antiretroviral therapy. This paper is a clinico-pathological review of HPV-associated oral warts.

Lupus erythematosus: a short account.

Lupus erythematosus is a chronic autoimmune inflammatory disease with diverse clinical manifestations including arthritis, skin disorders and kidney disease. Pathologically it is characterised by complex interactions between multiple genetic, epigenetic and extraneous factors; and serologically by the presence of a variety of antibodies which are reactive to intracellular molecular constituents. Impaired clearance of apoptotic cells and of immune complexes, loss of immune tolerance to self-antigens and dysregulation of the cytokine network act synergistically with extraneous factors such as ultraviolet radiation, viruses and certain drugs to induce and sustain lupus erythematosus.

Discoid lupus erythematosus as it relates to cutaneous squamous cell carcinoma and to photosensitivity.

Lupus erythematosus is a chronic inflammatory autoimmune disease with diverse clinical manifestations ranging from an indolent chronic cutaneous form to a severe potentially life-threatening disease, systemic lupus erythematosus. Discoid lupus erythematosus is a subphenotype of chronic cutaneous lupus erythematosus, characterised by scaly disk-shaped plaques which may be localised or widespread, occurring predominantly on sun-exposed skin and which may rarely progress to squamous cell carcinoma. The pathogenesis of discoid LE comprises complex interactions between multiple susceptibility genes involved in immune responses and clearance of apoptotic cells on the one hand, and environmental factors on the other. Herein, we discuss some aspects of the pathogenesis of discoid lupus erythematosus in relation to ultraviolet radiation and malignant transformation.

Syphilis in the context of HIV infection.

Both HIV infection and syphilis are sexually transmitted diseases, share the same risk factors for acquisition and often occur concurrently. Syphilis may promote HIV acquisition and transmission and HIV infection may alter the course and response of syphilis to treatment. Oral lesions may occur at any symptomatic stage during the course of a syphilitic infection, usually presenting as any one of a number of distinct clinical forms, but not infrequently with a variety of nonspecific clinical features, or clinical features mimicking other disease entities. In South Africa where HIV infection is epidemic, syphilis is prevalent. It is the purpose of this paper to review the interrelationship between syphilis and HIV infection, and the oral manifestations of syphilis.

Oral cancer-associated paraneoplastic syndromes.

Paraneoplastic syndromes are cancer-associated endocrinological, haematological, dermatological or neurological disorders, which are directly related neither to the physical effects of the tumour mass, nor to invasion by the primary tumour, nor to metastasis of the tumour; nor are they associated either with the side-effects of anticancer treatment or with any of the complications of cancer. These syndromes are brought about by the ectopic production of biological mediators by the malignant tumour cells, or by immunological responses to the malignancy. Certain cancers are typically associated with specific paraneoplastic disorders. Though uncommonly, oral carcinomata have reportedly been associated with paraneoplastic pemphigus, humoral hypercalcaemia of malignancy, syndrome of inappropriate antidiuretic hormone, and paraneoplastic leukocytosis syndrome.

Chemotherapy- and radiotherapy-induced oral mucositis: pathobiology, epidemiology and management.

Oral mucositis is a debilitating complication of anticancer treatment, characterised by erythematous, atrophic, erosive or ulcerative lesions. Oral mucositis is almost always painful, affects eating, sleeping, and speech and affects the physiological and social well-being of the patient. The pathophysiology of the condition is not well understood. Guidelines to the treatment of oral mucositis are often contradictory so that there is no evidence based standard treatment protocol. Therefore the treatment is empiric. This paper offers a brief review of current knowledge of the pathophysiology and treatment of oral mucositis.

A short account of cancer--specifically in relation to squamous cell carcinoma.

Cancer is the outcome of a complex multifactorial process of cytogenetic and epigenetic changes that affect cell cycle progression, apoptosis, DNA repair mechanisms and cell differentiation. Cancer cells have the capacity to evade the immune system, to invade tissues and to metastasize. Cancer is treated by surgery, chemotherapy and radiotherapy, each as single treatment modalities or more often in combination. Failure of treatment to cure a patient of cancer may be owing to the fact that radiotherapy and chemotherapy can eradicate transit-amplifying cells which are characterized by uncontrolled proliferation and prolonged survival; but cannot eradicate all cancer stem cells that divide slowly, have a relatively unlimited self-renewal capacity and express anti-apoptotic genes; and also owing to the fact that surgery cannot always eliminate occult fields of pre-cancerization.

HPV modulation of host immune responses.

Host immune responses to HPV are generally low-level because the virus, being confined to basal epithelial cells is shielded from the circulating immune cells during initial stages of infection. In this location there is only a limited expression of viral proteins. Other factors contributing to the low level of host immunity are that HPV infection is non-lytic (does not cause death of the infected cell); that a functionally active immune response is generated only at later stages of HPV infection, in post-mitotic suprabasal keratinocytes where all viral genes are expressed; and that only in suprabasal keratinocytes has the HPV DNA been sufficiently amplified to be detected by the host immune-surveillance cells. In addition to the natural low-level immune responses towards HPV, HPV also employs several mechanisms to down-regulate innate and cell-mediated immunity, thus facilitating host immune evasion and persistent infection. The environment, lifestyle, the genetic make-up of the host, and the viral genomic characteristics can also influence the persistence of HPV infection, and consequential diseases. Persistent infection with high-risk HPV is associated with increased risk of developing HPV-mediated premalignancy and malignancy. It is not clear if the natural humoral immune response as opposed to vaccination is effective in eliminating primary HPV infection or in preventing progression of infection; but after initial infection, the host develops HPV-specific T cell immune responses that appear to be capable of clearing established infection, of protecting against progression of early HPV-associated intraepithelial neoplastic lesions to squamous cell carcinoma, and of preventing reinfection.

Focal epithelial hyperplasia (Heck disease) related to highly active antiretroviral therapy in an HIV-seropositive child. A report of a case, and a review of the literature.

Focal epithelial hyperplasia is increasingly frequently observed in rural South African communities. HIV-seropositive subjects have a higher prevalence of oral human papillomavirus (HPV) infections than immunocompetent subjects; and paradoxically, the introduction of highly active antiretroviral therapy for treatment of HIV-seropositive subjects is associated with increased frequency of focal epithelial hyperplasia. We describe a case of focal epithelial hyperplasia in an HIV-seropositive child receiving highly active antiretroviral therapy, who was successfully treated by using diode laser ablation.

The pathobiology and mechanisms of infection of HPV.

There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.

HIV-associated Kaposi sarcoma in African children.

HIV-associated Kaposi sarcoma (HIV-KS) is common in African countries where HIV infection is pandemic and anti-retroviral medication is not readily available. Human herpesvirus-8 (HHV-8), which is the essential, but not the sole aetiological factor in KS, is endemic in sub-Saharan Africa and is substantially more prevalent in HIV-seropositive than in HIV-seronegative subjects. In children in sub-Saharan Africa, KS, whether it be HIV-KS or African endemic KS is much more prevalent than any other epidemiological forms of KS. In addition, in sub-Saharan children oral KS is common, and the life-expectancy of HIV-seropositive children with KS is short. Since generalized systemic KS is frequently associated with oral HIV-KS, it is advisable to introduce systemic cytotoxic chemotherapy early in the course of oral HIV-KS. Although the introduction of highly active antiretroviral therapy (HAART) brought about a decline in the incidence of HIV-KS worldwide, HIV-KS remains a significant problem in sub-Saharan Africa where the prevalence of HHV-8 infection is high and access to HAART is limited.

Primary Oral Tuberculosis as an Indicator of HIV Infection.

We present a case of primary oral tuberculosis that led to the diagnosis of HIV infection. Our patient had clinically nonspecific ulcers on the labial mucosa and on the ventral surface of the tongue which were diagnosed as being tuberculous only on histological examination. This raised the suspicion of HIV infection that was subsequently confirmed by blood tests. The oral lesions resolved after 4 weeks of antituberculosis treatment. Some aspects of the pathogenesis of HIV-tuberculosis coinfection are discussed.

Tuberculosis part 3: HIV-tuberculosis co-infection.

Tuberculosis is the most common opportunistic infection in HIV-seropositive persons. Tuberculosis may occur at any stage of HIV disease but the prevalence of TB increases with the progressive diminution of CD4+ T cell numbers. There is a synergistic relationship between tuberculosis and HIV infection as each accelerates the progression of the other.