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Biomedical subjects

P Holmstrup

Publications and source records attributed to P Holmstrup.

At least 19 recordsLinked to original sources

Comparison of ready-to-use EMDOGAIN-gel and EMDOGAIN in patients with chronic adult periodontitis.

OBJECTIVES: The aim of this multicenter trial was to compare the clinical and radiographical outcome of a ready-to-use Emdogain-gel (test) with the marketed Emdogain (control). METHODS: Subjects with bilateral infrabony defects > or =4 mm deep and > or =2 mm wide according to radiographs were selected. 88 subjects with probing pocket depth (PPD) > or =6 mm > or =1 month after supervised oral hygiene and scaling participated. At baseline plaque index, bleeding on probing, PPD and probing attachment level were recorded and reproducible radiographs for computer-based bone level measurements were taken. In each subject, 1 tooth was randomly treated with the test and 1 tooth with the control gel. Examinations were repeated 8 and 16 months post-operatively. RESULTS: After 16 months, the mean test PPD was 4.1 mm and the mean control PPD 4.2 mm. The mean gain of attachment was 2.7 mm for test and 2.9 mm for the control sites, and the radiographic measurements demonstrated a mean gain of 1 mm for both test and control sites. CONCLUSION: This series of cases demonstrated a statistically significant reduction of pocket depths and gain of attachment and bone after 8 and 16 months with no difference between the 2 preparations.

Adult↗

Occupational exposure to airborne proteolytic enzymes and lifestyle risk factors for dental erosion--a cross-sectional study.

This study examined the hypothesis that occupational exposure to airborne proteolytic enzymes is associated with dental erosions on the facial surfaces of exposed teeth. Individuals (n = 425) working at a pharmaceutical and biotechnological enterprise (Novozymes A/S) were examined; their mean age was 35 years (range = 18-67 years) and 143 (34%) were women. Two hundred and two of these individuals were newly employed by the company. Occupational exposure was assessed from questionnaire and workplace information. For practical analytical purposes, individuals were categorized as either previously exposed to proteolytic enzymes or not. Information on relevant lifestyle factors and medical history was obtained from a questionnaire. The main effect measure was facial erosion, but lingual erosion indices and the presence of Class V restorations were also considered. The validity of these measures was shown to be very high. Adjusted for potential confounders, there was no association between history of occupational exposure to proteolytic enzymes and prevalent facial or lingual erosion. With respect to prevalence of Class V restorations, the association was significant. The present study did not support directly our primary hypothesis that occupational exposure to airborne proteolytic enzymes is associated with dental erosions on the facial surfaces of exposed teeth. However, the results indicate that exposure to proteolytic enzymes may lead to pronounced tooth substance loss, demanding treatment.

Adolescent↗

A clinical index for evaluating and monitoring dental erosion.

This study describes a new fine-scaled system for classifying initial and advanced dental erosions. The system includes the use of study casts of the teeth in an epoxy resin with an accurate surface reproduction. The severity of erosion on each tooth surface is scored according to six grades of severity. In addition, the presence of a Class V restoration and dental erosion on the same surface increases the erosion score, as it is assumed that the need for restorative treatment can be caused by the erosion. A high inter-examiner agreement was found when the present scoring system was used by two examiners on the same sample. With this prerequisite it is proposed that an index value for facial, oral, incisal/occlusal and cervical surfaces is calculated as the mean value of scores for the respective surfaces. The index values represent the severity of tooth substance loss in various locations of the oral cavity and are furthermore suitable for data analysis. The system is thereby well-suited for determining etiologic factors and monitoring the progression of erosion over time.

Disease Progression↗

Expression of VLA-integrins and their related basement membrane ligands in gingiva from patients of various periodontitis categories.

Periodontitis is characterized by destruction of dento-gingival fibers and apical migration of the junctional epithelium. Tissue destruction may be associated with altered interactions between epithelium and connective tissue mediated by integrins localized in the basement membrane zone. We examined the expression of alpha2beta1, alpha3beta1, alpha4/alpha5/beta1, alpha6beta4 and their related extracellular matrix (ECM) ligands: laminin-1, laminin-5, and collagen type IV in untreated periodontitis sites of various categories. The expression and location of ECM proteins along the basement membrane were found to be similar between clinically healthy and periodontitis affected tissues. However, ECM proteins were more diffusely distributed in connective tissue (CT) of periodontitis tissues as streak-like/ fibrillar/granular stainings, particularly beneath the pocket epithelium (PE) and around the blood vessels. This may reflect an increase in inflammatory cell migration. The more widespread distribution of integrins alpha2beta1, alpha3beta1 in PE of periodontitis specimens may be related to disease activity and increased rate of keratinocyte proliferation and migration. Moreover, the weaker expression of alpha6beta4 in junctional epithelium (JE) of periodontitis affected tissues may be related to the epithelial detachment from the tooth surface. Clarification of expressions of integrins and their ligands in relation to known clinical disease susceptibility factors may provide information on the onset and progression mechanisms of periodontal disease destruction.

Adolescent↗

Non-plaque-induced gingival lesions.

The origin of gingival inflammation is occasionally different from that of routine plaque-associated gingivitis, and such non-plaque-associated types of gingivitis often present characteristic clinical features. Examples of such forms of gingivitis are specific bacterial, viral, and fungal infections. Specific bacterial infections of gingiva may be due to Neisseria gonorrhea, Treponema pallidum, streptococci, and other organisms. The most important viral infections of gingiva are herpes simplex virus type 1 and 2 and varicella-zoster virus. Fungal infections may be caused by several fungi, the most important of these being Candida species including C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. guillermondii. Gingival histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum and, as for the other specific infections of gingiva, a confirmed diagnosis may require histopathologic examination and/or culture. Atypical gingivitis may also occur as gingival manifestations of dermatological diseases, the most relevant of these being lichen planus, pemphigoid, pemphigus vulgaris, erythema multiforme, and lupus erythematosus. Non-plaque induced gingival inflammation can be caused by allergic reactions to dental restorative materials, toothpastes, mouthwashes, and foods. In addition, gingival inflammation may result from toxic reactions, foreign body reactions, or mechanical and thermal trauma.

Communicable Diseases↗

Dissolution of type I collagen fibrils by gingival fibroblasts isolated from patients of various periodontitis categories.

The classification of periodontitis in various disease categories, including juvenile periodontitis, rapidly progressive adult periodontitis and slowly progressive adult periodontitis is based mainly on differences in disease progression and age group susceptibility. Because dissolution of collagen fibers is an integral part of periodontal attachment loss, we investigated whether the clinical differences among these periodontitis/control groups are reflected in the collagen-degrading activity of gingival fibroblasts isolated from affected tissues. All fibroblast strains isolated from the 4 groups (n = 48) displayed cell-associated collagenolytic activity when seeded in contact with a reconstituted film of type I collagen fibrils. Cells from the control group (n = 14) dissolved the collagen fibril film twice as fast as those from each of the 3 disease groups (juvenile periodontitis (n = 13), rapidly progressive adult periodontitis (n = 7), and slowly progressive adult periodontitis (n = 14)). Both interleukin-1 beta and phorbolester accelerated the rate of dissolution 2-4-fold, but even after cytokine or phorbolester stimulation control cells were still considerably more effective in dissolving the collagen fibrils than cells from the disease groups. The observation made in this study, that dissolution of collagen fibrils by gingival fibroblasts from periodontally diseased individuals is significantly slower than by cells from healthy control subjects, challenges disease paradigms based on a direct relationship between collagenolytic potential and disease activity.

Adolescent↗

Update on oral lichen planus: etiopathogenesis and management.

Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways, an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other disorders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as with liver disease, have emerged. The management of lichen planus is still not totally satisfactory, and there is as yet no definitive treatment, but there have been advances in the control of the condition. There is no curative treatment available; immunomodulation, however, can control the condition. Based on the observed increased risk of malignant development, OLP patients should be offered regular follow-up examination from two to four times annually and asked to report any changes in their lesions and/or symptoms. Follow-up may be particularly important in patients with atrophic/ulcerative/erosive affections of the tongue, the gingiva, or the buccal mucosa. Much more research is required into the genetic and environmental aspects of lichen planus, into the premalignant potential, and into the possible associations with chronic liver, and other disorders. More clinical studies are required into the possible efficacy of immunomodulatory drugs such as pentoxifylline and thalidomide.

Adjuvants, Immunologic↗

Placebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings.

Treatment of patients who attribute their environmental illness to mercury from amalgam fillings is largely experimental. On the Symptom Check List, overall distress, and somatization, obsessive-compulsive, depression, and anxiety symptom dimensions, were increased in 50 consecutive patients examined, and Eysenck Personality Questionnaire scores suggested less extroversion and increased degree of emotional liability. Succimer (meso-2, 3-dimercaptosuccinic acid) was given at a daily dose of 30 mg/kg for five days in a double-blind, randomized placebo-controlled trial. Urinary excretion of mercury and lead was considerably increased in the patients who received the chelator. Immediately after the treatment and 5 to 6 weeks later, most distress dimensions had improved considerably, but there was no difference between the succimer and placebo groups. These findings suggest that some patients with environmental illness may substantially benefit from placebo.

Adult↗

Factors affecting IL-1-mediated collagen metabolism by fibroblasts and the pathogenesis of periodontal disease: a review of the literature.

Fibroblasts have been studied extensively for their contribution to connective tissue destruction in diseases where the metabolism of extracellular matrix components plays an essential part in their pathogenesis. A considerable dissolution, especially of collagen fibrils, is a well-known characteristic of the periodontal ligament and the gingival connective tissue in microbial-induced periodontal disease. Fibroblasts, responsible for the assembly of the extracellular matrix, are capable of responding directly to oral microbial challenges or indirectly, following activation of the host immune response, and can alter the composition of connective tissue in several ways: synthesis of inflammatory mediators, their receptors and antagonists; fibroblast proliferation; collagen synthesis; phagocytosis of collagen fibrils; and synthesis of proteolytic enzymes, including matrix metalloproteinases and their corresponding inhibitors. The contributions of these cellular fibroblastic properties to the pathogenesis of periodontal disease are reviewed in the context of the cytokine, interleukin-1, as the inflammatory regulator.

Bacterial Physiological Phenomena↗

Human papillomavirus in oral premalignant lesions.

The aetiology of oral premalignant lesions is generally accepted to be multifactorial. Tobacco and alcohol are established as important cofactors in malignant development in the oral cavity, but in addition microorganisms, such as human papillomavirus (HPV), have gained much interest over the past decade. For many years, HPV has been accepted as an important cofactor in the development of cervical cancer, originating from a mucous membrane with similarities to the oral mucosa. 49 patients with oral premalignant lesions and 20 control patients with normal oral mucosa and no history of HPV infection were examined for the presence of HPV by immune histochemical staining using the peroxidase anti-peroxidase technique (PAP), DNA-DNA in situ hybridisation (ISH), and polymerase chain reaction (PCR) analysed by Southern blot hybridisation with an HPV 16 specific probe. The investigations revealed that HPV was found in 62.5% of the verrucous leucoplakias, 50.0% of the erythroplakias, 45.5% of the homogeneous leucoplakias, 33.3% of erythroleucoplakias and in 12.5% of the nodular leucoplakias. An overall HPV detection rate in the examined premalignant lesions was 40.8% and no patients in the control sample were positive. Concerning oral cancer development, it seems likely that HPV may be a cofactor, as 100% of patients who developed oral cancers within 4-12 years were all positive for HPV, one being positive for HPV 16.

Adult↗

Microbiology of ligature-induced marginal inflammation around osseointegrated implants and ankylosed teeth in cynomolgus monkeys (Macaca fascicularis).

The microbiota associated with ligature-induced marginal inflammation around osseointegrated dental implants, ankylosed teeth, and normal control teeth was investigated in 8 cynomolgus monkeys (Macaca fascicularis). Submucosal/subgingival plaque was sampled with paper points on the day of literature placement and after 7 weeks. The samples were evaluated by phase-contrast microscopy and by cultivation on enriched non-selective and various solid media. The submucosal/subgingival flora was changed 7 weeks after ligation. The total number of cultivable bacteria and the proportions of motile rods, anaerobic Gram-negative rods, black-pigmented rods, Porphyromonas gingivalis, and Prevotella intermedia increased significantly around implants, ankylosed teeth, and normal control teeth. Except for a significantly higher proportion of anaerobic Gram-positive cocci around implants compared to ankylosed teeth and normal control teeth at the end of the study, no significant microbiological differences were observed between implants, ankylosed teeth, and normal control teeth neither at baseline nor at the end of the study. Consequently, the microbiota associated with marginal inflammation around implants, ankylosed teeth, and normal control teeth appears to be rather similar in cynomolgus monkeys.

Animals↗

Bacterial-stimulated cytokine production of peripheral mononuclear cells from patients of various periodontitis categories.

Periodontitis is a general term for disease categories, including juvenile periodontitis (JP), rapidly progressive periodontitis (RPP), and adult periodontitis (AP), which may or may not share a common etiology and pathogenesis. These disease categories are characterized by differences in progression of tissue destruction and differences in age group susceptibility, but not, to our knowledge, by differences in cytokine responses of inflammatory cells. The present study examined blood cell counts and interindividual variation in the ability of PBMC of patients in three different categories of periodontitis to produce cytokines after stimulation with different oral bacterial species in vitro. The AP group had a significantly lower production of IL-1ra when stimulated with Porphyromonas gingivalis (P.g.) and Actinobacillus actinomycetemcomitans (A.a.) (P < 0.05). Streptococcus sanguis (S.s.), which is associated with normal periodontal conditions, induced extremely high levels of IL-1 alpha and TNF alpha production in all groups. The RPP group had a significantly higher number of monocytes (MC) than the AP group (P < 0.05). Additionally, JP patients had a significantly higher concentration of polymorphonuclear granulocytes compared to juvenile controls (P < 0.05). In conclusion, IL-1 alpha, TNF alpha, or IL-6 production by peripheral blood MC after in vitro stimulation with oral bacterial type stains may not distinguish different categories of periodontitis. The results support the hypothesis that the cytokine IL-1ra is produced in different concentrations in the two groups: RPP and AP. Furthermore, elevated MC concentration in the RPP group compared to the AP group may be an important pathogenic feature in RPP.

Adolescent↗

Periodontal diseases in HIV-infected patients.

Periodontal diseases may be the first clinical sign of human immunodeficiency virus (HIV)-infection. Since the immunosuppression and subsequent susceptibility may alter the responses of the oral tissues as well as the microflora, both periodontal treatment and result of therapy may be modified. The periodontal diseases in HIV-seropositive patients include common as well as less conventional forms of gingivitis and periodontitis, and bacterial, mycotic and viral infections are seen. Neoplasias may also involve the periodontium; most common are Kaposi's sarcoma and non-Hodgkin's lymphoma. Recent studies of unselected groups of patients indicate that periodontal health in at least some groups of HIV-seropositive patients is better than previously reported.

Gingival Neoplasms↗

Identification of Candida albicans types related to healthy and pathological oral mucosa.

This study comprised 100 healthy dentate adults and 53 patients with either chronic erythematous oral candidosis or oral leukoplakic lesions. The presence of yeasts was determined by microscopical examination of PAS-stained smears and by culture. Biopsy material was obtained from all lesions. The isolated yeasts were identified to species level. Strain phenotypes of 147 Candida albicans isolates were determined on the basis of the ODDS & ABBOTT procedure (25, 26). Yeasts were found in the mouth of healthy dentate individuals both by culture and by smears. The identification of hyphae in healthy mucosa indicates that the presence of these structures is not an unequivocal sign of candidal infection. The results support the view that tobacco smoking may be a predisposing factor for candidal infection. Also, the results have shown an association between the occurrence of yeasts and the type of leukoplakic lesions. Finally, the strain differentiation has indicated an oral mycoflora in patients with candidal lesions disappearing after antimycotic treatment which was more homogeneous in composition than in patients with irreversible lesions; furthermore, certain strains may possess properties which may be important in the development of pathological conditions and premalignant changes.

Adult↗

Keratin staining pattern in clinically normal and diseased oral mucosa of lichen planus patients.

The keratin pattern in oral epithelia is related to the type of terminal differentiation observed morphologically (keratinization/nonkeratinization) and to the presence or absence of epithelial dysplasia. Furthermore, it has been suggested recently that inflammatory phenomena influence the keratin expression in human gingiva. The aim of the present study was to describe the keratin pattern in oral lichen planus (OLP) lesions, which are well known to be characterized by hyperkeratinization and severe inflammatory changes, in order to elucidate the role of inflammation in keratin expression of oral epithelia. Tissue sections were stained with antikeratin antibodies directed to groups of keratins (AE1 and AE2) and to single keratin proteins (Nos. 5, 8, 13, and 19). The keratin pattern in OLP lesions differed in some respects from that of leukoplakias and frictional keratoses as characterized in previous studies. No consistent patterns for use in a diagnostic context were found. However, the changes in OLP lesions did not mimic those previously described in inflamed gingival specimens and in oral epithelial dysplasias. Thus, the results encourage further studies on the potential diagnostic use of keratin expression in premalignant oral lesions. Furthermore, the study suggests that the inflammatory reaction seen in OLP lesions does not influence keratin expression in a way comparable with the suggested influence of inflammation in gingival specimens.

Antibodies, Monoclonal↗

A comparison of the effect of epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor on rat periodontal ligament fibroblast-like cells' DNA synthesis and morphology.

An enhanced formation of bone, dentin, and collagen fibers in periodontal wounds after application of polypeptide growth factors has recently been reported. However, the complex environment in vivo makes it impossible to determine the specific effects of growth factors on various cells involved in the wound-healing process. We have therefore investigated the mitogenic and morphogenic effects of recombinant epidermal growth factor (rEGF), natural platelet-derived growth factor (nPDGF), and natural fibroblast growth factor (nFGF) on periodontal ligament fibroblast-like cells. A cell line was established from rat PDL tissue. The cell line was characterized according to morphology, growth pattern, cytoskeletal proteins, and growth kinetics. The mitogenic effect of growth factors was assessed by incorporation of [3H]thymidine in the cellular DNA for 4 hours. Differences between groups of observations were assessed by the Student t-test. The morphogenic effects of growth factors were described with respect to growth pattern, cell orientation, and cell and nucleus form after a random photographic recording. The fibroblast-like cell type and the non-transformed phenotype of the cell line have been identified by the presence of parameters considered to be characteristic of a normal fibroblast-like cell line. The morphogenic analysis of both experimental and control cultures showed a monolayer of adherent cells with spindle or stellate morphology, a random alignment and round or elongated nuclei. Incorporation of [3H]-thymidine was increased in a dose-dependent manner by all growth factors. Maximal effect on the DNA synthesis was: rEGF, 131%; nPDGF, 274%; and nFGF, 182%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ligature-induced marginal inflammation around osseointegrated implants and ankylosed teeth.

The purpose of the investigation was to gain more understanding of marginal inflammatory reactions around osseointegrated implants. The significance of the lacking periodontal ligament of implants was examined in the initial breakdown phase of supporting tissues by comparing clinical and radiographic manifestations of ligature-induced marginal inflammation related to osseointegrated implants with those around ankylosed and normal control teeth in 8 cynomolgus monkeys (Macaca fascicularis). Bilateral extraction of the first and second mandibular molars was carried out initially, and 12 weeks later 2 implants were placed in each side. Ankylosis of the second maxillary molars was established by extracting and replanting the teeth after a drying period. When ankylosis and osseointegration were established, ligature-induced marginal inflammation was induced in the right or left side at random around implants, ankylosed teeth and normal control teeth (second maxillary premolar) for 7 weeks. Although the clinical manifestations as expressed by plaque score, gingival score, probing depth and attachment loss were quite similar, the radiographic features differed. Significant loss of bone height was limited to implants and ankylosed teeth and did not occur in relation to normal control teeth. Furthermore, the bone loss around implants was significantly greater than the loss around ankylosed teeth. Bone loss was limited to implants and ankylosed teeth; the study therefore suggests that the presence of marginal inflammation around implants and ankylosed teeth may have more serious implications than does marginal inflammation around teeth with a periodontal ligament. However, variations in microbiota and susceptibility of different jaw positions to periodontal breakdown may influence the results of this study.

Alveolar Bone Loss↗