Multiple human herpesvirus-8 infection

In Malawian patients with Kaposi sarcoma (KS) and their relatives, we investigated nucleotide-sequence variation in human herpesvirus-8 (HHV-8) subgenomic DNA, amplified from oral and blood samples by use of polymerase chain reaction. Twenty-four people had amplifiable HHV-8 DNA in >1 sample; 9 (38%) were seropositive for human immunodeficiency virus type 1, 21 (88%) were anti-HHV-8-seropositive, and 7 (29%) had KS. Sequence variation was sought in 3 loci of the HHV-8 genome: the internal repeat domain of open-reading frame (ORF) 73, the KS330 segment of ORF 26, and variable region 1 of ORF K1. Significant intraperson/intersample and intrasample sequence polymorphisms were observed in 14 people (60%). For 3 patients with KS, intraperson genotypic differences, arising from nucleotide sequence variations in ORFs 26 and K1, were found in blood and oral samples. For 2 other patients with KS and for 9 people without KS, intraperson genotypic and subgenotypic differences, originating predominantly from ORF K1, were found in oral samples; for the 2 patients with KS and for 4 individuals without KS, intrasample carriage of distinct ORF K1 sequences also were discernible. Our findings imply HHV-8 superinfection

Molecular markers relevant to myocardial injury following dental extraction in patients with or without coronary artery disease

Objectives The aim of this study was to characterize biological changes following dental extractions in patients with and without coronary artery disease (CAD). Materials and methods Forty-five patients (36 males and 9 females) referred for dental extraction underwent treatment and provided blood samples before, immediately after, and 24 h after the procedure. A broad array of biomarkers was employed to assess myocardial injury (highly sensitive troponin T, hs-TnT), bacterial burden (LPS endotoxin activity), and systemic inflammation (CRP, fibrinogen, IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α). Results Dental extraction in patients with and without CAD was associated with rises in hs-TnT (p = 0.013), hs-CRP (p < 0.001), fibrinogen (p = 0.005), endotoxin activity (p < 0.001), IFN-γ (p < 0.001), IL-6 (p < 0.001), IL-8 (p = 0.011), and IL-12 (p < 0.001) at 24 h compared with immediately post procedure. Changes in systemic inflammation and endotoxin activity were more evident in those with hs-TnT rise. Conclusions Simple dental extractions may cause mild increase in hs-TnT, indicating minor myocardial injury in both patients with and without CAD. Acute systemic inflammation and endotoxemia could represent a possible link between invasive dental treatment and increased risk of acute cardiovascular events. These findings indicate that invasive dental treatment (as simple as a single dental extraction) may impact negatively on clinical outcomes in dental patients, especially those with CAD

The Mouth and Lupus

The oral cavity is often referred to as a “mirror of the body” and can be the first site with clinical signs of a sometimes distant systemic disease. The oral manifestations of various systemic conditions may precede or follow closely the involvement of other parts of the body and, in some instances, can be the dominant feature that warrants a particular emphasis upon investigation and/or treatment. Oral disease can sometimes be having the greatest negative impact upon a patient with systemic illness. The presence of oral ulcers (including nasopharyngeal ulcers) is one of the 11 criteria defined by the American College of Rheumatology for the diagnosis of systemic lupus erythematosus (SLE). A thorough examination of the oral tissues can provide useful information to clinicians for an early diagnosis of SLE. Oral lesions would normally improve if lupus is adequately controlled and their reoccurrence is often an indicator of a new disease flare-up. A wide spectrum of oral signs and symptoms caused by lupus has been described and might be related not only to the disease itself, but also to concomitant secondary conditions or be the effect of different medications

Teaching periodontal pocket charting to dental students: a comparison of computer assisted learning and traditional tutorials

AIM: The aim of this study was to compare the effectiveness of a computer assisted learning (CAL) programme with that of traditional small group tutorials in teaching theoretical and practical aspects of periodontal pocket charting. METHOD: Sixty-one third year undergraduate dental students were randomized to either receive a tutorial or to work through the CAL programme. Students using the CAL programme completed questionnaires relating to previous computer experience and the ease of use of the programme. All students were assessed immediately after the intervention by means of a confidence log, a practical exercise and a further confidence log. They were assessed again three weeks later by means of a confidence log and a multiple-choice written test. RESULTS: There were very few significant differences between groups for any of the assessments used. However, subjective comments indicated that students occasionally felt disadvantaged if they had not received a tutorial. CONCLUSION: CAL and traditional teaching methods are equally effective in teaching periodontal pocket charting to undergraduate dental students

In vitro 3D tissue modelling: Insights into ameloblastoma pathogenesis

Ameloblastoma is a rare, benign oral tumour. Tumours develop within the jaw bone and are highly destructive and invasive, with cells migrating into the jaw and surrounding soft tissue. This is a little-understood disease which if left untreated causes dramatic bone destruction and maxillofacial disfigurement. Current treatment is radical surgery, often resulting in extensive loss of function and tissue. An ameloblastoma-derived cell line, AM-1, has been established [1]. Cells were isolated from a human tumour and immortalised by the addition of HPV-16 DNA. This study aims to (i) make a 3D in vitro ameloblastoma disease model, using plastic-compressed collagen gel [2] seeded with AM-1 cells, and (ii) use this bone construct to characterise tissue remodelling, cell growth and invasiveness

Human exercise-induced circulating progenitor cell mobilization is nitric oxide-dependent and is blunted in South Asian men

This article is available open access through the publisher’s website. Copyright @ 2010 American Heart Foundation.Objective— Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPC. We assessed CPC mobilization in response to exercise in Asian men and examined the role of NO in CPC mobilization per se. Methods and Results— In 15 healthy, white European men and 15 matched South Asian men, CPC mobilization was assessed during moderate-intensity exercise. Brachial artery flow-mediated vasodilatation was used to assess NO bioavailability. To determine the role of NO in CPC mobilization, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor l-NMMA, and norepinephrine.  Flow-mediated vasodilatation (5.8%±0.4% vs 7.9%±0.5%; P=0.002) and CPC mobilization (CD34+/KDR+ 53.2% vs 85.4%; P=0.001; CD133+/CD34+/KDR+ 48.4% vs 73.9%; P=0.05; and CD34+/CD45− 49.3% vs 78.4; P=0.006) was blunted in the South Asian group. CPC mobilization correlated with flow-mediated vasodilatation and l-NMMA significantly reduced exercise-induced CPC mobilization (CD34+/KDR+ −3.3% vs 68.4%; CD133+/CD34+/KDR+ 0.7% vs 71.4%; and CD34+/CD45− −30.5% vs 77.8%; all P<0.001). Conclusion— In humans, NO is critical for CPC mobilization in response to exercise. Reduced NO bioavailability may contribute to imbalance between vascular damage and repair mechanisms in South Asian men.British Heart Foundatio

Quantitative nanohistological investigation of scleroderma: An atomic force microscopy-based approach to disease characterization

Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen

Preliminary evaluation of the utility of optical coherence tomography in detecting structural changes during photobiomodulation treatment in patients with atrophic-erosive oral lichen planus

INTRODUCTION: Oral lichen planus (OLP) is a common oral inflammatory condition. Against symptomatic atrophic-erosive OLP, topical steroids, or photobiomodulation (PBM) are deployed. Optical coherence tomography (OCT) provides a real-time, non-invasive, tissue investigation. Aim of this study was to evaluate modifications of OCT pattern in patients with painful atrophic-erosive OLP, before and after treatment with PBM, comparing those results with patients treated with topical steroid. METHODS: Two groups of 20 OLP patients were evaluated. Group A underwent two daily application of 0.05% clobetasol propionate for 8 weeks; group B was treated with eight weekly PBM sessions using a 980/645 nm diode laser. OCT scans were performed before and after treatment, and six months after end of the proposed protocol. Changes of width of stratified epithelium (EP) and lamina propria (LP) were quantified. RESULTS: After 8-weeks, both groups experienced a significant increase of EP width (p  0.05). After six months, significant increase of EP width remained only in group B (p = 0.01), with no significant decrease of LP mean width in both groups (p > 0.05). CONCLUSIONS: Increase of EP and decrease of LP might be explained as consequence of clobetasol and PBM ability to promote epithelial healing, and to reduce interface inflammation. When investigated with OCT, clobetasol appears to provide more significant short-term structural changes, whereas PBM might guarantee long-term alterations

In-vivo usefulness of optical coherence tomography in atrophic-erosive oral lichen planus: Comparison between histopathological and ultrastructural findings

Oral lichen planus (OLP) is a common premalignant chronic inflammatory disorder. Optical Coherence Tomography (OCT) provides a real-time, non-invasive, and in-situ optical signature using light of varying wavelengths to examine tissue. Aim of the present study was to assess the possible role of OCT as diagnostic tool for atrophic-erosive OLP by examining OCT scans of healthy buccal mucosa, and comparing their ultrastructural features with those of a buccal mucosa affected by atrophic-erosive OLP, using their histopathological counterparts as the gold standard. Through grayscale (enface scan) and an application in which the vascularization of the tissue is visible (dynamic scan), it was possible to distinguish the healthy from the lichenoid pattern from 20 controls (12 M; 8 F; mean age: 41.32 years) and 20 patients with histologically confirmed atrophic-erosive OLP (7 M; 13 F; mean age: 64.27 years). In detail, mean width of stratified squamous epithelium (EP) and lamina propria (LP) were evaluated. Among controls, EP and LP showed a mean width of 300 (±50) and of 600 (±50) μm respectively; among cases, disruption of membrane basement prevented from any measurement. Furthermore, a differential pattern of EP and LP emerged between the two groups: a light-grayish, hypo-reflective, homogeneous area of EP recurring in controls turned into a hyper-reflective, non-homogeneous area among cases. Dynamic scan showed a differential profile of LP vascularization, varying from a hypo-reflective red area with small blood vessels in the control group, to a hypo/hyper-reflective area, completely overrun by a denser, wider blood flow amid OLP cases. Although histopathological examination remains the gold standard for OLP diagnosis, OCT could be a potentially helpful tool for the clinician and the pathologist, since it allows analysis of the vascularization of the sample without adversely affecting histological processing

A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma

Introduction Thymoma and thymic carcinoma (TC) are neoplastic diseases with reported chemosensitivity to a broad range of agents. However, because of the rarity of these diseases, few prospective trials have been conducted in patients with advanced thymic malignancies. We conducted a prospective phase II trial to evaluate the clinical activity of pemetrexed, a multitargeted antifolate agent, in previously treated patients with thymoma and TC. Methods A total of 27 previously treated patients (16 with thymoma and 11 with TC) with advanced, unresectable disease were treated with pemetrexed, 500 mg/m2, intravenously every 3 weeks for a maximum of six cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12, and steroid prophylaxis. Results The median number of cycles administered was 6 (range 1–6). Nine patients with a total of 14 events had grade 3 toxicities; no grade 4 toxicities were noted. In 26 fully evaluable patients, two complete and three partial responses (according to the Response Evaluation Criteria in Solid Tumors) were documented (all in patients with stage IVA thymoma, except for one partial response with stage IVA TC). A total of 14 patients completed the full six cycles of treatment, 7 patients progressed while undergoing therapy, 5 patients discontinued therapy because of intolerance, and 1 patient discontinued therapy because of progressive Morvan syndrome. The median progression-free survival time for all patients was 10.6 months (12.1 months for those with thymoma versus 2.9 months for those with TC). With 23 deaths at data cutoff, the median overall survival time was 28.7 months (46.4 months for those with thymoma versus 9.8 months for those with TC). Conclusions Pemetrexed is an active agent in this heavily pretreated population of patients with recurrent thymic malignancies, especially thymoma