Genital ulcers as diagnostic clue for acute myeloid leukaemia.

Acute myeloid leukaemia is a myeloid neoplasm with an extremely varying clinical appearance. Skin lesions are common for specific subtypes of acute myeloid leukaemia but are often misinterpreted. Here, we present a case of acute myeloid leukaemia in a young woman exhibiting genital ulcerations and gingival erosions.

Inflammatory environment induces gingival tissue-specific mesenchymal stem cells to differentiate towards a pro-fibrotic phenotype.

BACKGROUND INFORMATION: Human gingival tissues are prone to hyperplasia under inflammatory stimuli. We have identified gingival tissue-specific mesenchymal stem cells (GMSCs) and found their functional change being correlated with drug-induced gingival hyperplasia. However, whether these cells exhibit characteristics of pro-fibrotic phenotype under inflammatory condition remains unknown. RESULTS: GMSCs isolated from human normal gingival tissues (N-GMSC) and inflammatory gingival tissues (I-GMSC) were cultured in vitro, representative cytokines were added to simulate the in vivo inflammatory environment. Under the influence of the inflammatory cytokines, GMSCs exhibited higher rate of proliferation than those under normal condition, while their potential for osteogenic and adipogenic differentiation was suppressed. The expression of matrix metalloproteinases (MMP)-1, MMP-2, IL-1, IL-6, TNF-α and type 1 collagen was significantly higher in I-GMSCs than in N-GMSCs. Furthermore, compared with dental pulp stem cells, GMSCs showed different pattern of gene expression and extracellular matrix formation in inflammatory environment. CONCLUSIONS: Inflammatory microenvironment induces GMSCs to differentiate towards a pro-fibrotic phenotype, which could underlie the hyperplastic appearance of inflammatory gingiva.

The role of pathophysiological explanations in clinical case representations of dental students and experts.

INTRODUCTION: Teaching of biomedical knowledge lays the foundations for the understanding and treatment of diseases. However, the representation of pathophysiological explanations in the management of clinical cases differs for various levels of medical expertise and different theories have been proposed to explain this phenomenon. The present study investigated for the first time how biomedical knowledge is used in clinical reasoning in dental medicine. MATERIALS AND METHODS: In an experimental study 20 experts in the field of Periodontology and 61 students of different levels of training produced written pathophysiological explanations after having studied three different clinical cases. By comparing the written protocols to a visualised expert-made 'canonical' explanation the concepts used in the pathophysiological explanation were counted and classified as well as the links between concepts. RESULTS: The statistical analysis by MANOVA showed significant differences between third- and fourth-year students, students of intermediate expertise level (fifth-year) and experts for various parameters qualifying concepts or links of the written pathophysiological explanations. The participants of intermediate expertise level produced a high rate of concepts and links; however, characteristic findings for knowledge encapsulation in the different levels of expertise were not evident. The analysis showed that the design of the clinical cases and of the canonical explanations significantly influenced the outcomes. CONCLUSION: The present study demonstrated the pathophysiological representations of clinical cases in dental students and experts to be different from other medical disciplines. It could be assumed that this observation is based on different contents for teaching of practical skills and diagnostic procedures in dental compared with medical education.

A painful gum.

CASE STUDY: This middle aged Malaysian man presented complaining of painful gums for a few months. He is known to have had epilepsy since childhood.

On the relation of nitric oxide to nifedipine-induced gingival hyperplasia and impaired submandibular glands function in rats in vivo.

Calcium-channel blockers such as nifedipine could be associated with gingival overgrowth. The aim of this study was to examine the role of nitric oxide (NO) on nifedipine-induced gingival hyperplasia along with submandibular secretory function in rats. Animals in divided groups received nifedipine (250 mg/kg diet) alone and in combination with L-arginine (2.25% w/v) or N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.7% w/v) in drinking water for 20 days. Controls received only tap water. Pure submandibular saliva was collected intraorally by micropolyethylene cannula and the mandibular gingiva was examined by means of dissecting microscope for signs of redness, thickness, inflammation and exuda. Twenty-day nifedipine treatment induced gingival hyperplasia accompanied with reduced salivary flow rate and concentrations of total protein, epidermal growth factor (EGF) and calcium in comparison with controls. Co-treatment of animals with nifedipine and L-arginine protected from gingival hyperplasia and retained flow rate, and concentrations of total protein, EGF and calcium in normal levels. Co-treatment of animals with nifedipine and L-NAME potentiated nifedipine-induced gingival hyperplasia and reductions in flow rate and concentrations of total protein, EGF, and calcium. It is concluded that nifedipine-induced gingival hyperplasia is associated with salivary dysfunction. Activation of cGMP-dependent positive signal-transduction mechanisms in salivary glands might be the mechanism for protective effects of NO against nifedipine-induced gingival hyperplasia.

Phenytoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin do not alter the effects of bacterial and amplified plaque extracts on cultures of fibroblasts from normal and overgrown gingivae.

Local irritation of gingival tissue by plaque is among the factors which affect development of gingival overgrowth in patients undergoing chronic phenytoin (PHT) therapy. Variability in the cytotoxicity of plaque components or of plaque substances plus PHT and/or its metabolites toward gingival fibroblasts may relate to whether gingival overgrowth forms in a particular patient. Fibroblasts from healthy and overgrown gingivae were incubated with (a) PHT and its major human metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), (b) microbial and "amplified" plaque extracts, and (c) microbial and "amplified" plaque extracts plus PHT and HPPH. Cell numbers and cell-associated protein were determined for each incubation preparation. A wide range in cytotoxic response to a particular microbial or plaque extract occurred among cell strains. Plaque extracts from different subjects had variable cytotoxicity toward a cell strain. The differences among fibroblast strains in response to an extract and the variability in cytotoxicity of different plaque extracts toward a cell strain were not related to their source from normal or overgrown gingivae. Cell numbers and cell-associated protein were similar for incubation mixtures containing extracts with and without PHT and HPPH. These data do not show differences among cytotoxicity levels of plaque extracts, the response of particular gingival fibroblast strains to plaque components, or interaction between drugs and certain plaque samples which explain development of gingival overgrowth in some subjects receiving chronic PHT therapy.

Heparan sulfate interacting protein (HIP/L29) negatively regulates growth responses to basic fibroblast growth factor in gingival fibroblasts.

Basic fibroblast growth factor (bFGF) modulates gingival growth, and its release from heparan sulfate (HS) in the extracellular matrix (ECM) governs local tissue bioavailability. We identified a heparin/HS interacting protein (HIP/L29) that recognizes specific HS sequences. We hypothesize that HIP/L29, by modulating the interactions of bFGF with HS chains on proteoglycans, could regulate bFGF bioavailability. To investigate interactions between bFGF and HIP/L29, we isolated and cultured fibroblasts from normal gingiva and overgrown gingiva from patients on cyclosporine (CSA). bFGF significantly stimulated gingival fibroblast proliferation with or without heparin. Recombinant human HIP/L29 dramatically decreased bFGF-induced proliferation, but did not alter responses to insulin-like growth factor-1 (IGF-1). Analysis of mitogen-activated protein kinase (MAPK) phosphorylation patterns showed that bFGF stimulation of p44 (Erk-1), but not p42 (Erk-2), also was inhibited by HIP/L29 in a dose-dependent manner. Together, these results support our hypothesis that HIP/L29 modulates the bioavailability and action of bFGF.

Management of arthrogryposis multiplex congenita. A case report.

Arthrogryposis multiplex congenita is a rare disorder of skeletal muscle development which is characterized by deforming contractures of the joints, but seldom affects the temporomandibular joint. This report reviews the condition and reports the findings and periodontal management of a patient referred with arthrogryposis multiplex congenita which required treatment for severe dilantin gingival hyperplasia.

Age dependency of cyclosporin A-induced gingival overgrowth in rats.

Effects of age on cyclosporin A- (CsA) induced gingival overgrowth were investigated in Fischer rats. Rats 15, 30, 45, and 60 days old were fed a diet containing cyclosporin A (120-200 micrograms/g) for 40 days. Gingival overgrowth was estimated by measuring the gingival sulcus depth with a thin color slide probe under a stereoscopic dissecting microscope. The youngest group (15 days old) of rats developed the most significant gingival overgrowth (buccal sulcus depth of mandibular first molar, CsA-treated rat/untreated rat: 875 +/- 78/275 +/- 25 micron, mean +/- SD, P < 0.001), followed by those in which CsA treatment was initiated at age 30 days (505 +/- 29/267 +/- 56, P < 0.001) and 45 days (400 +/- 45/267 +/- 25, P < 0.001). Significant gingival overgrowth was not induced in rats when CsA treatment had been started at age 60 days (310 +/- 38/292 +/- 18). Average body weight gain of CsA-treated rats during this experiment period was not different from untreated rats of the same age group. These results suggest that CsA-induced gingival overgrowth in rats is age dependent.

Localized juvenile spongiotic gingival hyperplasia: a report of 3 cases.

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a recently described benign condition that affects the gingiva of children and young adults. Clinically distinctive, LJSGH presents as a localized area of erythema on the attached gingiva, with a subtly papillary surface architecture. The lesions are generally biopsied because of the lack of resolution with conservative oral hygiene therapeutic measures and esthetic concerns. The histopathology has a characteristic appearance of subtle papillary epithelial hyperplasia, acute inflammation, and numerous engorged capillary vascular spaces in the lamina propria, although clinical correlation is necessary to make the diagnosis. The purposes of this paper were to: introduce localized juvenile spongiotic gingival hyperplasia to the pediatric dental community; document its clinical and histologic features and treatment and the follow-up of three cases; and discuss the most common clinical differential diagnoses.

Potentiation of fibroblast spreading by extracellular matrix from fibroblasts derived from phenytoin-induced gingival overgrowth.

Cell attachment and spreading appear when a cell, on contact with an appropriate substratum, adheres and changes its shape and accommodates to the substratum. The transition from a non-spreading to a spreading state is a prerequisite for growth. Cell-free extracellular matrix (ECM) was produced by fibroblast-like cells from normal gingiva (N-ECM) and phenytoin-induced gingival overgrowth (PHT-ECM). The effect of the ECM on cell attachment and spreading of human gingival fibroblasts was studied in the presence of 2% serum. Within 30 min after seeding 40% of the normal fibroblast cells showed an advanced flattening on PHT-ECM-prepared dishes, compared with 10% on normal ECM-prepared dishes and 5% on uncoated plastic dishes. The results indicate that cells derived from PHT-induced gingival overgrowth produce an ECM with special properties, which could regulate cell functions such as cell attachment and spreading.

[Biochemical characterization of phenytoin-induced hyperplastic human gingival fibroblasts. Non-collagenous proteins biosynthesis].

Phenytoin (PHT), administered as an anticonvulsant, has a side effect gingiva overgrowth in approximately 50% of patients. The present study was attempted to explore the biochemical mechanism on non-collagenous protein biosynthesis as affected by PHT. Responder cells (RES A3, RES C2) of a patient with gingival overgrowth were obtained by the method of Kawase et al. Normal human gingival fibroblasts (Gin-1), purchased from ATCC, were also used. All cells were inoculated at 1 x 10(4) cells/cm2 (12 multi-well plate or 60 mm tissue culture dish), and then cultured for 4, 8 and 12 days with or without PHT (5 micrograms/ml). Prior to harvesting at the indicated times, cells were incubated with 14C-amino acids (1.25 microCi/ml) for 24 hours. The 14C-labeled proteins were isolated from the cell layers including extracellular matrix, following Kurkinen et al. with a minor change. Each 14C-labeled fraction was dissolved in 3 ml of Aquasol-2 and the radioactivity by a liquid scintillation counter. The DNA content of cell layers affected by PHT was increased on Gin-1, RES A3 and RES C2 at the post-confluence, resulting also in an increase in cell number. Two morphologically different phenotypes of responder cells were observed, differing in nuclear and cell sizes. At 12 days culture, RES A3, were stimulated by PHT, showed increased synthesis of both total extractable proteins (EP) and binding proteins (BP) labeled with 14C-amino acids. Therefore, at least two distinct phenotypic responder cells are present in the PHT-induced overgrowth gingiva, alter the synthesis of non-collagenous proteins.

Clinical and pharmacologic correlations in cyclosporine-induced gingival hyperplasia.

Cyclosporine-induced gingival hyperplasia was investigated in a clinical study of 100 patients over a period of 2 1/2 years. Seventy percent of the patients exhibited at least mild gingival hyperplasia. For doses within the therapeutic range, no direct correlation was found between the oral dose or the serum trough concentration of cyclosporine and the severity of gingival hyperplasia. The presence of dental plaque was found to be related to the presence of gingival hyperplasia, but only a weak correlation existed between the abundance of plaque and the severity of gingival hyperplasia. Children and especially adolescents had a greater risk of developing cyclosporine-induced gingival hyperplasia than adults had. In 21 patients followed for 1 to 18 months after cessation of cyclosporine therapy, induced gingival hyperplasia was found to be clinically reversible.

[Clinical study of gingival hyperplasia in epilepsy patient].

Diphenylhydantoin, which was first introduced in clinic by Meritt and Putnam in 1938, has been in wide use for the treatment of epilepsy because of its excellent antispasmodic action. On the other hand, Diphenylhydantoin induced gingival hyperplasia has been examined by many authors in the dental field since gingival hyperplasia was reported by Kimball as its side effect. Recently, we had an opportunity for performing gingivectomy on hypertrophic gingivitis in an epileptic with mental retardation and visual disturbance, on Phenytoin (5,5-Diphenylhydantoin) medication. Some information obtained is reported, together with its therapeutic course.

[Mastocytes and the oral cavity. Anatomy and function]. / Mastocytes et cavité buccale. Anatomie et fonction.

One hundred and three teeth with chronic pulpitis, twelve chronic periapical lesions and eleven oral various soft tissue biopsies were used to discuss the presence, the anatomy and function of mast cells. The mast cell induces veinules dilatation during the early phase of inflammation by histamine release, collagen lysis, bone resorption and epithelium proliferation. It can be observed in every chronic lesion and plays a part in both humoral and cellular immunological phenomenons. A more accurate knowledge of its biochemical actions could help in understanding the mechanism of pain in certain clinical dental crisis.