Case report of atypical osteonecrosis of the jaws: a clinical dilemma.

Osteonecrosis of the jaws is defined as exposed jawbone that persists for more than eight weeks. Treatment may be challenging and can adversely affect the patient's quality of life. We present a male patient who was referred to our department with areas of extensive osteonecrosis in the maxilla and mandible. He had no history of antiresorptive, antiangiogenic treatments, or radiotherapy to the head and neck. He had a history of renal transplantation, diabetes, glucocorticoids, and periodontal disease. This case highlights multiple aetiological factors that can contribute to osteonecrosis and the diagnostic dilemma that they may cause.

Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations.

AIM: To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. METHODS: The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. RESULTS: None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. CONCLUSION: Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Dental implants and squamous cell carcinoma in the at risk patient--report of three cases.

Osseointegrated dental implants are increasingly used in the rehabilitation of the dental patient. They have a particular role in dental rehabilitation following treatment for oral cancer. Data is presented that suggests that, in the at risk patient, squamous cell carcinoma may develop in association with dental implants.

Infection of stationary human brain aggregates with HIV-1 SF162 and IIIB results in transient neuronal damage and neurotoxicity.

The cellular basis of HIV associated dementia has been correlated with microglial activation and neuronal dysfunction in symptomatic HIV-1 disease. As a cellular model of HIV-1 infection of brain tissue in vitro, we established a stationary human brain aggregate (SHBA) system to compare infection of HIV-1 SF162 (R5 virus) to that of IIIB (X4 virus). Aggregates were analysed by immunohistochemistry, morphometry, flow cytometry and p24 ELISA. SHBAs had a 1 mm(3) size with a mixed cellular composition of 36% neurones, 27% astrocytes, 2% macrophages/microglia and 14% oligodendrocytes. Infection of SHBA's with the R5 HIV-1 SF162 virus led to the expression of HIV-1 p24 antigen in 6% of cells. Infection with this R5 using virus culminated in transient neuronal damage and a decrease in mitotically active progenitor cells within aggregates. Infection with X4 using HIV-1 IIIB was associated with astrocytosis and neurotoxicity. We propose that: (1) the pattern of cellular damage elicited by HIV-1 infection of brain tissue in vitro depends on virus subtype as determined by its preferential use of R5 or X4 chemokine receptors for entry into cells; (2) SHBAs are a reliable and readily established model of the cellular complexity of human brain tissue in vitro.

Oral manifestations of an HIV positive cohort in the era of highly active anti-retroviral therapy (HAART) in South London.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is associated with oral manifestations of diagnostic and prognostic importance. With the advent of Highly Active Anti-retroviral Therapy (HAART) there is anecdotal evidence to suggest that the prevalence of oral lesions has declined. The number of prevalence studies, carried out in the era of HAART is, however, meagre. Our aim was to study the prevalence of the oral manifestations of HIV in a population, predominantly on HAART, attending a Genito-Urinary Medicine Centre in South London. METHODS: This cross sectional study included 203 adult volunteers, comprising 76% males and 24% females. One third of the subjects were from the predominantly African or Afro- Caribbean ethnic minority groups resident in London. The relationship between the prevalence of oral lesions and demographic variables, therapeutic regimes, viral load and CD4 counts were evaluated. RESULTS: One hundred (49%) of the patients had no detectable oral lesions. Oral lesions detected most frequently included oral hairy leukoplakia (9.9%), HIV associated periodontal diseases (9.9%) and oral candidiasis (4.9%). Three subjects had multiple papillomatous growths. Most cases (n = 17/20) of oral hairy leukoplakia were in individuals with a detectable (> 400 copies/ml) plasma RNA viral load. The majority (n = 8/10) of our patients with oral candidiasis had a plasma RNA viral load > 10,000 copies/ml and half (n = 5/10) had a CD4 count < 200 cells/mm3. Logistic regression analysis suggested that the presence of an oral lesion was not associated with any demographic features except for periodontal diseases which were associated with tobacco smoking (P = 0.023). CONCLUSIONS: The prevalence of so called 'strongly associated' oral lesions of HIV is low in this South London HIV-infected population on HAART, and the relative frequency is different from that cited in the literature from the pre-HAART era. The oral lesions detected were found mostly in people with low CD4 counts and high HIV-1 RNA viral loads, suggesting they were very immunocompromised, not on, or declining therapy, or that their therapy was failing.

Evidence for a post-entry barrier to R5 HIV-1 infection of CD4 memory T cells.

BACKGROUND: HIV-1 strains R5 and X4 can infect CD4 memory T cells in vivo. Anti-CD3/28 stimulation induces beta-chemokines and CCR5 down-regulation and renders these cells resistant to R5 HIV-1 infection. Here we describe an additional cellular mechanism that blocks productive R5 HIV-1 infection of CD4 memory T cells. METHODS: Blood-derived CD4 memory T cells and CD4 T-cell clones were infected with primary R5 and X4 HIV-1 strains. Virus replication was correlated with CCR5 expression and beta-chemokine production. Virus entry and infectivity were measured by PCR for early and late products of HIV reverse transcription respectively. RESULTS: R5 strains were up to 1000-fold less infectious than X4 viruses for CD4 memory T cells. This resistance was independent of CCR5 levels and of the Delta-32 mutation and the CCR2-V64I/CCR5-59653T linked mutations. Blocking endogenous beta-chemokines relieved minimally this restriction. At the single cell level, CD4 memory cells were either permissive or non-permissive for R5 HIV-1 infection. R5 HIV titre was up to 10-fold lower than X4 virus titre even in a permissive clone. However, R5 viruses replicated as efficiently as X4 viruses in the permissive clone when neutralizing anti-beta chemokine antibodies were added. Non-permissive cells blocked a post-entry step of the virus life-cycle and expressed early but not late HIV transcripts. Neutralizing anti-beta chemokine antibodies promoted R5 virus replication marginally in the non-permissive clone. CONCLUSION: Some blood memory CD4 T cells retard R5 HIV-1 replication via endogenous beta-chemokines whereas others block productive R5 HIV-1 infection by an additional mechanism that interferes with a post-entry step of the virus life cycle. These natural barriers might contribute to lower pathogenicity of R5 HIV-1 strains for CD4 memory T cells than X4 viruses that emerge late in disease.

Prevalence and incidence of oral lesions--the changing scene.

A range of oral mucosal and periodontal lesions is associated with HIV infection and HIV disease progression. These are often symptomatic and require treatment in themselves, and also have a diagnostic and prognostic role in the management of the underlying HIV disease. These lesions have been broadly divided into: (a) those strongly associated with HIV such as oral candidoses, oral hairy leukoplakia and Kaposi's sarcoma; (b) those less strongly associated such as swellings of the major salivary glands; and (c) those least commonly associated such as recurrent aphthous ulcers. Overall the prevalence and severity of these lesions inversely correlate with the level of immunosuppression. With the passage of time, there has been improved understanding of the disease pathogenesis resulting in the development of new drugs to combat this infection. Medication has changed from monotherapy to current triple combination therapy (Highly Active Anti-Retroviral Therapy). This review looks at the impact of changing therapy on the prevalence of the various oral lesions associated with HIV. It finds a decrease in the prevalence of the oral lesions in the era of combination therapy as compared to earlier periods. It also shows a change in the types of lesions which predominate with those previously placed amongst the strongly associated lesions no longer being predominant in the era of combination therapy where such treatment is available.

CD7 expression distinguishes subsets of CD4(+) T cells with distinct functional properties and ability to support replication of HIV-1.

Enrichment of a subset of CD4(+)CD45R0(+)CD7(-) T cells has been observed in HIV-infected individuals. We have investigated the ability of CD7(+) and CD7(-) T cells to support replication of HIV and show that virus replicates preferentially in CD7(+) cells. Several possible mechanisms that may underlie such differences in susceptibility to HIV were studied. Our data demonstrate that mitogen stimulation induces poor expression of CD25 and IL-2 in CD7(-) compared with CD7(+) cells. We also show that uninfected CD7(-) cells are more resistant to mitogen-induced apoptosis than CD7(+) cells. Our data support the view that the CD7(-) subset is inherently resistant to HIV replication and that this is due in part to reduced CD25 expression and IL-2 production.