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Biomedical subjects

L J Walsh

Publications and source records attributed to L J Walsh.

At least 19 recordsLinked to original sources

Prostaglandin E2 enhances alveolar bone formation in the rat mandible.

Prostaglandin E2 (PGE2) induces bone formation in stress-bearing bones. The mandible, a stress-bearing bone, is loaded daily during mastication. The aim of this study was to determine if PGE2 delivered locally to the mandible over 20 days enhances alveolar bone deposition. In 18 Lewis rats, controlled-release pellets containing PGE2 were implanted on the buccal aspect on the left-hand side of the mandible, mesial to the root of the first molar. Controlled-release pellets locally delivered 0.1, 0.05, or 0.025 mg/day of PGE2. The right side of the mandible was used as a matched control for each animal. Six sham-treated animals were implanted with a placebo pellet. On days 7 and 19, animals were injected with the bone markers tetracycline and calcein, respectively. On day 21, animals were sacrificed and undecalcified tissues obtained for morphometrical analysis. Morphometrical measurements were analyzed by paired t test to determine differences between the matched samples and one-way ANOVA to compare the different treatment groups. A significant increase in alveolar bone area was observed in mandibles treated with 0.1 and 0.05 mg/day when compared with matched controls and the placebo group. This was accompanied by a significant increase in alveolar bone height and width. The proportions of double-labeled surface (dLS), the mineral apposition rate (MAR), and bone formation rate (BFR) were significantly increased in mandibles treated with the two higher doses of PGE2. The proportion of resorptive surface (RS) was significantly reduced in these two groups. It is concluded that PGE2 induces alveolar bone formation in the mandible when locally delivered at a dose of 0.1 or 0.05 mg/day for 20 days.

Animals↗

Immunoglobulins in saliva of preterm and full-term infants.

The aim of this longitudinal study was to determine salivary levels of total IgA, IgG and IgM in 84 preterm and 214 full-term infants, from birth to 18 months of age. Unstimulated whole saliva was collected from each infant at birth, and subsequently at 3-monthly intervals. Immunoglobulin levels were estimated using an ELISA technique. At birth, IgA was detected in 147/214 (69%) full-term infants but only 47/84 (56%) preterm infants (P < 0.01). In the case of IgG, 61% of full-term and 56% of preterm infants showed detectable levels, whereas IgM was found in 71% and 73%, respectively. Levels of IgA and IgG rose from birth to 18 months, whereas IgM levels did not change significantly. Increases in salivary levels of IgA were associated with introduction of solid foods (P < 0.001), as well as tooth eruption (P < 0.001). Our results indicate that the majority of full-term and preterm infants are orally immunocompetent at birth.

Chi-Square Distribution↗

The current status of laser applications in dentistry.

A range of lasers is now available for use in dentistry. This paper summarizes key current and emerging applications for lasers in clinical practice. A major diagnostic application of low power lasers is the detection of caries, using fluorescence elicited from hydroxyapatite or from bacterial by-products. Laser fluorescence is an effective method for detecting and quantifying incipient occlusal and cervical carious lesions, and with further refinement could be used in the same manner for proximal lesions. Photoactivated dye techniques have been developed which use low power lasers to elicit a photochemical reaction. Photoactivated dye techniques can be used to disinfect root canals, periodontal pockets, cavity preparations and sites of peri-implantitis. Using similar principles, more powerful lasers can be used for photodynamic therapy in the treatment of malignancies of the oral mucosa. Laser-driven photochemical reactions can also be used for tooth whitening. In combination with fluoride, laser irradiation can improve the resistance of tooth structure to demineralization, and this application is of particular benefit for susceptible sites in high caries risk patients. Laser technology for caries removal, cavity preparation and soft tissue surgery is at a high state of refinement, having had several decades of development up to the present time. Used in conjunction with or as a replacement for traditional methods, it is expected that specific laser technologies will become an essential component of contemporary dental practice over the next decade.

Dental Care↗

A longitudinal study of Streptococcus mutans colonization in infants after tooth eruption.

We previously reported that, before tooth eruption, over one-half of infants aged 6 mos were already infected with Streptococcus mutans. The aim of this investigation was to determine the colonization of S. mutans after tooth eruption in the same cohort of 111 infants (35 pre-term, 76 full-term). Our results showed that S. mutans colonization increased with increasing age, so that by 24 mos of age, 84% harbored the bacteria (p < 0.01). The mean and median ages of S. mutans colonization in dentate infants were 15.7 mos and 16.0 mos, respectively. Factors associated with S. mutans colonization were sweetened fluids taken to bed (p < 0.01), frequent sugar exposure (p < 0.03) and snacking (p < 0.03), sharing of foods with adults (p < 0.03), and maternal S. mutans levels of > 10(5) CFU/mL (p < 0.02). In contrast, non-colonization of S. mutans was associated with toothbrushing (p < 0.03) and multiple courses of antibiotics (p < 0.001). Analysis of our data establishes the timing of S. mutans colonization in children from birth to 24 mos of age.

Age Factors↗

Expression of RANTES and CCR1 in oral lichen planus and association with mast cell migration.

BACKGROUND: T lymphocytes and mast cells infiltrate the lamina propria in oral lichen planus (OLP). Chemokines and their receptors are involved in T cell and mast cell migration and accumulation during the inflammatory process. METHODS: In the present study, we investigated the role of RANTES and its receptors in OLP using immunohistochemistry, RT-PCR and an in vitro chemotaxis assay. RESULTS: RANTES and CCR1 were expressed on T cells and mast cells in OLP, while OLP lesional T cell supernatants stimulated CCR1 mRNA expression in a human leukemia mast cell line (HMC-1). TNF-alpha stimulated CCR1, CCR4 and CCR5 mRNA expression in the same cell line. OLP lesional T cell supernatants stimulated HMC-1 migration, which was partly inhibited by anti-RANTES antibody. CONCLUSIONS: The present study shows, for the first time, the distribution of RANTES and CCR1 in OLP. It is hypothesized that RANTES and CCR1 may play important roles in mast cell trafficking and related events in OLP.

Cell Line↗

Mast cell/T cell interactions in oral lichen planus.

Lichen planus is a disorder characterized by lesions of the skin and oral mucous membranes. Although many patients have involvement of both skin and oral mucosa at some stage during the progress of the disease, a larger group has oral involvement alone. It has been reported that oral lichen planus (OLP) affects one to two percent of the general population and has the potential for malignant transformation in some cases (1, 2). Like many chronic inflammatory skin diseases, it often persists for many years. Numerous disorders may be associated with OLP such as graft-vs.-host disease and Hepatitis C virus infection (3), however, it is unclear how such diverse influences elicit the disease and indeed whether they are identical to idiopathic OLP. Available evidence supports the view that OLP is a cell-mediated immunological response to an induced antigenic change in the mucosa (4-6). Studies of the immunopathogenesis of OLP aim to provide specific novel treatments as well as contributing to our understanding of other cell-mediated inflammatory diseases. In this paper, the interactions between mast cells and T cells are explored from the standpoint of immune regulation. From these data, a unifying hypothesis for the immunopathogenesis of OLP is then developed and presented.

Antigens↗

Pulpal heat changes with newly developed resin photopolymerisation systems.

Composite resin is a widely-used direct tooth coloured restorative material. Photoactivation of the polymerisation reaction can be achieved by visible blue light from a range of light sources, including halogen lamps, metal halide lamps, plasma arc lamps, and Light Emitting Diode (LED) lights. Concerns have been raised that curing lights may induce a temperature rise that could be detrimental to the vitality of the dental pulp during the act of photoactivation. The present study examined heat changes associated with standardised class V restorations on the buccal surface of extracted premolar teeth, using a curing time of 40 seconds. The independent effects of type of light source, resin shade, and remaining tooth thickness were assessed using a matrix experimental design. When a conventional halogen lamp, a metal halide lamp and two different LED lights were compared, it was found that both LED lamps elicited minimal thermal changes at the level of the dental pulp, whereas the halogen lamp induced greater changes, and the metal halide lamp caused the greatest thermal insult of all the light sources. These thermal changes were influenced by resin shade, with different patterns for LED versus halogen or halide sources. Thermal stress reduced as the remaining thickness of tooth structure between the pulp and the cavity floor increased. From these results, it is concluded that LED lights produce the least thermal insult during photopolymerisation of composite resins.

Acid Etching, Dental↗

Comparison of five selective media for the growth and enumeration of Streptococcus mutans.

BACKGROUND: Although a few growth media are available for selective isolation of the cariogenic bacteria, Streptococcus mutans (S. mutans), it is still unclear as to which is the most efficacious. This study compared the selectivity and sensitivity of five different media for growing a laboratory strain of S. mutans (NCTC 10449), and for enumerating S. mutans from teeth of a group of young children, aged 2-10 years. METHODS: The media tested in this study were mitis salivarius with bacitracin (MSB), mitis salivariuskanamycin-bacitracin (MSKB), glucose-sucrose-tellurite-bacitracin (GSTB), trypticase soy-sucrose-bacitracin (TYS20B) and tryptone-yeast-cysteine-sucrose-bacitracin (TYCSB) agars. These were prepared according to the respective manufacturer's instructions. RESULTS: The results showed that at concentrations of bacteria 1 x 10(3) to 1 x 10(10)/mL, the recovery of the laboratory S. mutans strain was highest in TYCSB agar, followed by in descending order by TYS20B, MSB, GSTB, and MSKB (p<0.01). Similar results were obtained using dental plaque samples collected from swabs of the teeth of a group of children. In the clinical samples, TYCSB again showed the highest recovery rates of S. mutans compared to the other four media. Results were reproduced at dilutions of the samples at 1:20 x 10(6) to 1:2 x 10(6), and S. mutans concentrations of 1.6 to 7.7 Log 10 CFU/mL. In addition, there were highest ratios of mutans to non-mutans bacteria in TYCSB compared to the other media, suggesting high selectivity of this media for mutans species. CONCLUSION: The results of our study suggest that TYCSB is the most sensitive and selective media for culture of S. mutans for laboratory and clinical studies.

Agar↗

The pathogenesis of oral lichen planus.

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown.

Animals↗

Matrix metalloproteinases and their inhibitors in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is characterized by a sub-epithelial lymphocytic infiltrate, basement membrane (BM) disruption, intra-epithelial T-cell migration and apoptosis of basal keratinocytes. BM damage and T-cell migration in OLP may be mediated by matrix metalloproteinases (MMPs). METHODS: We examined the distribution, activation and cellular sources of MMPs and their inhibitors (TIMPs) in OLP using immunohistochemistry, ELISA, RT-PCR and zymography. RESULTS: MMP-2 and -3 were present in the epithelium while MMP-9 was associated with the inflammatory infiltrate. MMP-9 and TIMP-1 secretion by OLP lesional T cells was greater than OLP patient (p < 0.01) and healthy control subject (p < 0.001) peripheral blood T cells. MMP-9 and TIMP-1 mRNA levels were greater in OLP lesional T cells compared with healthy control subject peripheral blood T cells p < 0.01). Tumor necrosis factor (TNF)-alpha upregulated OLP lesional T-cell MMP-9 (not TIMP-1) mRNA and secretion (p < 0.05). The in vitro activation rate of MMP-9 from OLP lesional T cells was greater than that from OLP peripheral blood T cells (p < 0.05). CONCLUSION: T-cell-derived MMP-9 may be involved in the pathogenesis of OLP. Relative over-expression of MMP-9 (compared with TIMP-1) may cause BM disruption and facilitate intra-epithelial T-cell migration in OLP.

Adult↗

A fluorometric microassay for histamine release from human gingival mast cells.

Mast cells are important effector cells of the immune system. We describe a rapid and inexpensive microassay to determine histamine release from human gingival mast cells. The assay is based on the coupling of histamine with o-phthalaldehyde (OPT) at a highly alkaline pH to form a fluorescent product. Using this assay with a sample volume of 10 microl/well in a 384 black well microplate, the histamine detection limit was 0.031 microg/ml. The human mast cell line (HMC-1) and fresh mast cells isolated from human gingival tissue (n = 10) were stimulated with substance P, anti-IgE or calcium ionophore A23187. Calcium ionophore significantly increased histamine release from HMC-1 cells and gingival mast cells (p < 0.05). This microassay will facilitate the study of mast cell histamine release in diseased oral mucosa.

Cells, Cultured↗

Adverse effects of oral corticosteroids in relation to dose in patients with lung disease.

BACKGROUND: The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients. In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group. METHODS: Data on oral corticosteroid use, lifestyle, fractures, and other possible adverse effects were collected by questionnaire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma, chronic obstructive pulmonary disease, or alveolitis and age and sex matched control subjects. Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression. RESULTS: A total of 367 patients (> or = 50 years, 48% female) and 734 control subjects completed the questionnaire. The cumulative incidence of fractures since the time of diagnosis was 23% for patients taking oral corticosteroids and 15% in the control group (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3 to 2.6). Patients were more likely to have had a fracture of the vertebrae (OR 10; 95% CI 2.9 to 34), hip (OR 6; 95% CI 1.2 to 30), and ribs or sternum (OR 3.2, 95% CI 1.6 to 6.6) than control subjects. They also reported a significant increase in cataracts, use of antacids, muscle weakness, back pain, bruising, oral candidiasis, and having fewer teeth. The effects of oral corticosteroids were dose related: the odds ratio for patients in the highest compared with the lowest cumulative dose quartile (median prednisolone dose 61 g versus 5 g) ranged from 2 for all fractures to 9 for vertebral fractures and bruising. CONCLUSIONS: By quantifying the morbidity associated with the use of oral corticosteroids, this study should help to rationalise their long term use.

Administration, Oral↗

Association of Streptococcus mutans infection and oral developmental nodules in pre-dentate infants.

Since dental caries may present soon after tooth eruption, we hypothesized that colonization of Streptococcus mutans can occur in the predentate stages. In this study, we examined S. mutans colonization and its association with oral developmental nodules (Bohn's nodules) in 60 pre-term and 128 full-term, three-month-old infants. Overall, S. mutans was cultured from 30% (56/188) of the infants, and oral developmental nodules were noted in 55% (103/188). Compared with the pre-term, full-term infants showed a higher prevalence of S. mutans (34% vs. 20%, p < 0.02) as well as developmental nodules (61% vs. 42%, p < 0.05). In both groups, S. mutans was positively associated with numbers of developmental nodules in a dose-response relationship (p < 0.001), and with maternal salivary levels of the bacteria (p = 0.03). The permanence of S. mutans infection was confirmed by repeat saliva sampling at 6 months of age. Our results thus showed that many infants have already acquired S. mutans at 3 months of age, prior to tooth eruption.

Alveolar Process↗

Oral colonization of Streptococcus mutans in six-month-old predentate infants.

We hypothesize that S. mutans colonization occurs more frequently in pre-term children due to their relative immaturity. In this study of 172 predentate, six-month-old infants, we found that 50% of pre-term and 60% of full-term children harbored S. mutans. The colonization was confirmed by repeat sampling. Although there were minor differences, factors associated with S. mutans infection in pre-term and full-term infants were generally similar. In both groups, increased frequency of sugar was ranked the most important factor (p < 0.001), followed by breast-feeding (p < 0.001), and habits which allowed saliva transfer from mother to infant (p < 0.01). By contrast, non-colonization of S. mutans was associated with multiple courses of antibiotics (p < 0.001). Compared with pre-term children, there were higher percentages of full-term who had night feedings and consumed sugar during sleep times. Mothers with infected infants had S. mutans levels > 5 x 10(5) CFU/mL saliva (p < 0.001), poorer oral hygiene, more periodontal disease, and lower socio-economic status (p < 0.02) and snacked frequently (p < 0.001), compared with mothers with non-infected infants.

Anti-Bacterial Agents↗

Mast cell degranulation and the role of T cell RANTES in oral lichen planus.

OBJECTIVES: The present study investigated mast cell degranulation in oral lichen planus (OLP) and the effect of OLP lesional T cell supernatants on mast cell degranulation. MATERIALS AND METHODS: Immunohistochemistry was used to identify mast cell degranulation in both OLP (n = 22) and normal control (n = 14) tissues. OLP lesional T cell lines (n = 5) and HMC-1 (a human leukemia mast cell line) were used to examine the effects of OLP T cell supernatants on mast cell degranulation in vitro. RESULTS: Approximately 60% of mast cells were degranulated in OLP. OLP lesional T cells expressed mRNA for RANTES, and TNF-alpha stimulation upregulated OLP lesional T cell RANTES secretion. OLP lesional T cell supernatants induced degranulation of HMC-1 with release of TNF-alpha and histamine. Human recombinant RANTES similarly induced mast cell degranulation. Anti-RANTES antibody blocked OLP lesional T cell supernatant-induced mast cell degranulation. CONCLUSIONS: This study is the first to show that OLP lesional T cells produce and secrete RANTES which triggers human mast cell degranulation. Degranulating mast cells release TNF-alpha which upregulates OLP lesional T cell RANTES secretion. Such a cyclical mechanism may underlie disease chronicity and future therapies may include blocking RANTES or TNF-alpha activity in OLP.

Antibodies↗

Dental education in Queensland I: the 1-3-1 model.

Dental education worldwide is under great pressure. This pressure is being driven not only by changing patterns of oral disease but also by economic factors both inside and outside universities. Technological advances and changing educational philosophies across the board also impact significantly on what we do and how we do it. This article outlines how the School of Dentistry at The University of Queensland is responding to these pressures within the context of local political, educational and economic realities. The so-called 1-3-1 model that has been adopted involves one year of basic science, three years of applied dental science and one year of extramural clinical practice. This model represents a partnership with the Queensland Department of Health and will: Involve dental education and the Dental School in the provision of health care to the community. Place the Dental School in a position to influence the delivery and quality of oral health care in the population and to assume some of the responsibility for it. Provide a wide range of clinical and community experiences for students prior to graduation. Allow the adoption of modern teaching methods such as Problem Based Learning (PBL) in Years II-IV with all the additional benefits e.g. communication skills. Provide an extended clinical period for the acquisition and development of clinical and technical skills prior to graduation. Be cost-effective both to the university and the health service. Allow for outside input without compromising the knowledge and research base. It is recognised that while the 1-3-1 model may meet the demands of a large, decentralised state such as Queensland, it may not be suitable for all institutions. In this context diversity in approach is one of the strengths of dental education, nationally and internationally.

Clinical Competence↗

Dental education in Queensland: II. Principles of curriculum design.

A modern dental curriculum must produce graduates who are competent to practise in a variety of settings immediately upon graduation; cognisant of community needs and the social milieu in which they serve their patients' health needs; able to anticipate and cope with changes following graduation; committed to self-improvement, willing to change to reflect best clinical practice; and equipped with skills for self-assessment and lifelong learning. This requires the appropriate balance of emphasis on educational content and educational process. This paper outlines the design considerations underlying the new BDSc curriculum at the University of Queensland. This curriculum uses an integrated rather than subject-based approach, with student-centred modes of learning as the principal learning style. Active learning strategies develop critical thinking and clinical problem-solving skills. Learning occurs in the context of a clinical situation (either overt or implied). Year 2 provides the major scientific foundations, and later years build upon this base, particularly through problem-based learning. Senior clinical staff involved in teaching in earlier parts of the course, help provide an overt clinical context to learning activities. The integrated curriculum model provides clinically relevant education in basic sciences and scientifically based education in clinical care. The curriculum has a focus on outcomes and on preparation for general practice. Importantly, it has an open and transparent structure, and each component is linked explicitly with the competencies expected of the new dental graduate.

Clinical Competence↗

Inhaled corticosteroid use and bone-mineral density in patients with asthma.

BACKGROUND: Inhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years. METHODS: We studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20-40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis. FINDINGS: Median duration of inhaled corticosteroid treatment was 6 years (range 0.5-24), and median cumulative dose was 876 mg (87-4380). There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2-L4), femoral neck, Ward's triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0.16 SD (95% CI 0.04-0.28). Similar decreases were found at the femoral neck, Ward's triangle, and trochanter. Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations. INTERPRETATION: This study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.

Absorptiometry, Photon↗