Expression of fibronectin-binding integrins in gingival epithelium in drug-induced gingival overgrowth.

BACKGROUND AND OBJECTIVE: Gingival overgrowth is a side-effect of nifedipine and cyclosporin medications. Integrins are transmembrane glycoproteins that mediate cell adhesion, regulate cell proliferation and participate in the regulation of tissue fibrosis. The aim of this study was to investigate whether expression of epithelial cell integrins is linked to the development of drug-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival biopsies of patients taking nifedipine, cyclosporin, or a combination of both medications, were used. Expression of the alpha5beta1, alphavbeta1 and alphavbeta6 integrins, and of cellular extra domain A of fibronectin, was localized in frozen sections using immunohistochemistry. RESULTS: The activated conformation of the beta1, alpha5beta1 and alphavbeta6 integrins were more frequently expressed in distinct locations in the oral epithelium in the combined drug group. Cellular extra domain A of fibronectin, a ligand for both alpha5beta1 and alphavbeta6 integrins, was expressed within the connective tissue of all groups. It was also expressed around the basal keratinocytes of the control, nifedipine and cyclosporin-induced gingival overgrowth groups, but not in the combined medication group. No relationship between the presence of inflammation and integrin expression was found. CONCLUSION: The results indicate that expression of certain integrins is up-regulated in the epithelium of drug-induced gingival overgrowth where they could participate in controlling the formation of elongated rete ridges and tissue fibrosis.

MMP-3 and -8 expression is found in the condylar surface of temporomandibular joints with internal derangement.

BACKGROUND: Internal derangement is one of the most common disorder of the temporomandibular joint (TMJ). The aim of this study was to investigate the associations of matrix metalloproteinase (MMP)-3 and -8 expression in articular condylar surface with different stages of TMJ internal derangement according to Wilkes (Minn Med, 1978; 61: 645-52) and osteoarthrosis (OA) according to Dijkgraaf et al. (J Oral Maxillofac Surg, 1995; 53: 1182-92). METHODS: The study was based on 54 condylar specimens obtained during TMJ surgery. Immunohistochemistry using antibodies specific to MMP-3 and -8, represented in cartilage destruction, was carried out. RESULTS: In all tissue specimens, MMP-3 expression was intense in the surface layer but showed less intensive staining in the deeper layers. Some MMP-8 expression was also seen. The severity of TMJ internal derangement, however, did not seem to have a statistically significant correlation (P<0.05) with the expression of these enzymes. CONCLUSION: The study confirms that distinct expression of MMP-3 and -8 is found in the condylar surface of TMJs with internal derangement.

Matrix metalloproteinases in mild and severe temporomandibular joint internal derangement synovial fluid.

OBJECTIVES: The first objective of this study was to verify the presence of and identify the molecular forms of matrix metalloproteinases (MMPs), including collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), in the synovial fluid (SF) of mild and severe temporomandibular joint internal derangement (TMJ-ID). Another objective was to evaluate whether the SF MMPs are potential diagnostic markers that reflect the stage of intra-articular inflammation in the TMJ. STUDY DESIGN: The subjects were 44 patients with mild (n = 16) or severe (n = 28) TMJ-ID; they were classified on the basis of subjective symptoms, clinical and radiographic findings, and surgical observations. The patients were surgically treated, and SF samples were collected immediately before the operation. The collagenase activity of SF samples was analyzed by means of a type I collagen degradation assay. The levels and molecular forms of the SF MMPs as well as the tissue inhibitors of MMPs (TIMP-1 and TIMP-2) were analyzed with Western immunoblotting and gelatin zymography. RESULTS: The SF of both the mild and the severe TMJ-ID patients exhibited free collagenase activity and activity capable of further degrading the (3/4)(alphaA) fragments. Ninety-two-kilodalton proMMP-9 and its 121-kD complex form, as well as 72-kD proMMP-2 were significantly increased in the mild TMJ-ID group (P <.05 in all cases). Both 70- to 80-kD neutrophil type and 45- to 55-kD mesenchymal cell-type MMP-8 (corresponding to the latent and active forms) were observed in mild and severe TMJ-ID SF, but they predominated in mild TMJ-ID. Both MMP-1 and MMP-13 were observed in both groups, and in mild TMJ-ID SF the low-molecular weight forms of MMP-1 indicated activation of the enzyme. CONCLUSIONS: The degradation of type I collagen in the TMJ is evidently due to the collective action of many collagenolytic MMPs present in the SF of patients with mild and severe TMJ-ID. The elevated levels of MMP-2, MMP-9, and MMP-8 in the SF of patients with mild TMJ-ID eventually reflect the active phase of TMJ destruction. These observations may have considerable diagnostic and therapeutic significance in the management of TMJ disorders.

Macrophages and lymphocyte subpopulations in nifedipine- and cyclosporin A-associated human gingival overgrowth.

BACKGROUND: Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both drugs have immunomodulating effects. It has been suggested that altered immune response is associated with drug-induced gingival overgrowth. In this study, we evaluated whether there were differences in macrophages and lymphocyte subpopulations in human nifedipine- and CsA-associated gingival overgrowth as compared with those in normal gingiva. METHODS: Biopsy samples of overgrown gingiva were obtained from 9 nifedipine-treated cardiac outpatients, 13 CsA-treated renal transplant recipients including 9 patients who were also receiving nifedipine, and 30 healthy control individuals undergoing dental treatment. Serial 5 microm thick cryostat sections were stained with mAbs for CD20 (B-pan), CD68 (macrophages), CD4 (T-helper/inducer), and CD8 (T-cytotoxic/suppressor) using an avidin-biotin-horseradish peroxidase complex method. Numbers of mAb-labeled and all nucleated cells were determined in 3 areas: the connective tissue beneath the sulcular epithelium, the middle connective tissue, and the connective tissue beneath the oral epithelium. Distributions of each type of cell were expressed as percentages of mAb-labeled cells in relation to total number of nucleated cells in a counting zone. Significances of differences between groups were tested by means of the Kruskal-Wallis test, and between pairs of results by means of the Mann-Whitney U-test. RESULTS: The proportion of CD8-labeled cells was significantly higher in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P = 0.014). In both medicated groups, the proportions of CD68-labeled cells were higher in all counting zones than in the controls, but statistically significantly only in the nifedipine group in the connective tissue beneath the oral epithelium (P = 0.008). No intergroup differences were found with respect to CD4- and CD20-labeled cells. The CD4/CD8 ratio was significantly lower in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P= 0.013). CONCLUSION: The results support the idea that immune response may be altered in drug-induced gingival overgrowth.

Mitotic activity of keratinocytes in nifedipine- and immunosuppressive medication-induced gingival overgrowth.

BACKGROUND: The purpose of the study was to compare mitotic activity in the basal cell layer of normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth. METHODS: Gingival samples were collected from 19 generally healthy individuals, 12 nifedipine-medicated cardiac patients, and 22 immunosuppression-medicated (azathioprine, prednisolone, and cyclosporin A) organ transplant recipients. The transplant recipients were divided into those not taking nifedipine and those taking nifedipine. Cryostat sections were stained with monoclonal antibody for Ki-67, using an avidin-biotin-enzyme complex method. The mitotic activities of epithelial cells were determined as percentages of Ki-67 labeled cells in relation to total numbers of epithelial cells in the basal layer of oral, oral sulcular, and sulcular epithelium. RESULTS: Mitotic activities were significantly higher in all 3 medication groups in the oral epithelium (P < or =0.003), and in the immunosuppression group in the sulcular epithelium (P= 0.032) than in the controls. In the oral sulcular epithelium, mitotic activity was fairly similar in all medication groups. In the nifedipine group a significant negative correlation was found between duration of nifedipine medication and the percentage of Ki-67 labeled cells in the oral epithelium (P= 0.025). CONCLUSIONS: The results suggest that the increased epithelial thickness observed in nifedipine- and cyclosporin A-induced gingival overgrowth is associated with increased mitotic activity, especially in the oral epithelium.

The effect of surgical treatment of the temporomandibular joint: a survey of 70 patients.

Most patients with temporomandibular disorders (TMD) can be successfully treated by conservative methods, but approximately 10-20 percent have persistent symptoms. The aim of this study was to evaluate the signs and symptoms of TMD in patients treated with open surgery of the TMJ. Seventy-two patients (13 men, 59 women, mean age 37 years, range 14-68 years) were evaluated during an eight-year period. Altogether 45 right TMJs and 39 left TMJs were treated, including both TMJs during the same operation in eight of the cases. The patients were evaluated at follow-up in 1997. The degree of TMD at follow-up was assessed using the anamnestic and clinical dysfunction Helkimo indices. Most of the patients reported at the follow-up that they were subjectively satisfied with the surgical treatment. The main clinical findings in the post surgical patients at follow-up were TMJ sounds and deviation of the mandible during opening. The tenderness in the masticatory muscles and TMJs on palpation was reduced significantly and the ranges of mandibular movement were improved for all the patients. The mean anamnestic and clinical indices decreased with a statistical significance from the shortest follow-up group (Group I) to the longest on group (Group IV) (p = 0.000). The conclusion of this study was that after open surgical treatment of the TMJ, the patients have significantly better functioning of the masticatory system and reduced signs and symptoms of TMD in the long term.

Density of CD1a-labeled Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth.

BACKGROUND: The purpose of this study was to compare the distribution of Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth by means of an immunohistochemical study. METHODS: Gingival samples were collected from 11 nifedipine-medicated cardiac patients, 22 triple-medicated (azathioprine, prednisolone, and cyclosporin A) renal transplant recipients, and 28 generally healthy individuals. Patients were grouped into the immunosuppression group, the combined immunosuppression and nifedipine group, the nifedipine group, and the generally healthy control group. Five microm-thick cryostat sections were stained with monoclonal antibody (mAb) for CD1a using an avidin-biotin-enzyme complex (ABC) method. Numbers of CD1a-labeled cells/mm2 were determined in 6 areas: oral epithelium, oral sulcular epithelium, sulcular epithelium, middle connective tissue, connective tissue beneath the oral epithelium, and connective tissue beneath the sulcular epithelium. Significances of differences between the groups were tested by means of the Kruskall-Wallis test, and significances of differences between pairs of results by the Mann-Whitney U-test and the t test. RESULTS: Numbers of CD1a-labeled cells were significantly lower in the medicated groups than in controls in all 3 epithelial areas (P <0.0001) and in the connective tissue beneath the sulcular epithelium (P <0.0021). There were significantly fewer CD1a-labeled cells in the sulcular epithelium in the nifedipine group than in the other medication groups. CONCLUSIONS: The reduced numbers of CD1a-labeled cells found in nifedipine-induced gingival overgrowth were similar to the reduced numbers of CD1a-labeled cells in gingival overgrowth associated with immunosuppressive medication.

Changes in electrical activity of masseter and temporal muscles after temporomandibular joint surgery. A one-year follow up.

The functioning of the masseter and anterior temporal muscles was recorded by electromyography (EMG) in 15 patients with disc interference of the temporomandibular joints, before surgery and three months, six months and one year afterwards. EMG recordings were made during maximal bite in intercuspal position and while chewing. The mean electrical activity in the masseter and anterior temporal muscles, both on the operated and nonoperated sides, decreased markedly three months after surgery, especially during maximal bite in intercuspal position, but increased to above the preoperative values at the one-year recording in both functions. Statistically, significantly lower activities were seen on the operated side in patients with anterior dislocation of the disc without reduction, as compared to patients with reduction of the disc. The EMG activities of the masseter muscles on the nonoperated side were significantly lower in women and in older patients, as well as in patients with a longer duration of symptoms than in men and younger patients.

Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior in human cell cultures.

Nickel-titanium alloy (Nitinol) is a metallic biomaterial that has a unique thermal shape memory, superelasticity, and high damping properties. Nitinol is potentially very useful in orthopedic surgery, for example. At present, there are not enough confirmative biocompatibility data available on Nitinol. The aim of our study was to clarify the primary cytotoxicity and corrosion rate of Nitinol in human cell cultures. Comparisons were made with stainless steel (Stst), titanium (Ti), composite material (C), and control cultures with no test discs. Human osteoblasts (OB) and fibroblasts (FB) were incubated for 10 days with test discs of equal size, 6 x 7 mm. The cultures were photographed and the cells counted. Samples from culture media were collected on days 2, 4, 6, and 8, and the analysis of metals in the media was done using flameless atomic absorption spectrophotometry. The proliferation of FB was 108% (Nitinol), 134% (Ti) (p < 0.02), 107% (Stst), and 48% (C)(p < 0.0001) compared to the control cultures. The proliferation of OB was 101% (Nitinol), 100% (Ti), 105% (Stst), and 54% (C) (p < 0.025) compared to the controls. Initially, Nitinol released more nickel (129-87 micrograms/L) into the cell culture media than Stst (7 micrograms/L), but after 2 days the concentrations were about equal (23-5 micrograms/L versus 11-1 micrograms/L). The titanium concentrations from both Nitinol and Ti samples were all < 20 micrograms/L. We conclude that Nitinol has good in vitro biocompatibility with human osteoblasts and fibroblasts. Despite the higher initial nickel dissolution, Nitinol induced no toxic effects, decrease in cell proliferation, or inhibition on the growth of cells in contact with the metal surface.

Clinical and computed tomographic findings in costochondral grafts replacing the mandibular condyle.

PURPOSE: The aim of this study was to evaluate by computed tomography (CT) and clinically the structure and function of costochondral grafts (CCG) used to replace the mandibular condyles. MATERIAL AND METHODS: CT and clinical examination were performed in 11 patients with CCGs (9 female, 2 male; mean age at surgery, 25 years; range, 9 to 44 years) approximately 4.5 years after surgery (range, 5 months to 10.5 years). One mandibular condyle was replaced in six patients and two in five patients. RESULTS: Facial asymmetry was observed in two cases and palpation tenderness of the TMJs or clicking and crepitation were found in 10 of 16 operated TMJs. In three cases coronal CT scans showed the graft to be situated laterally in the mandibular fossa, and lateral overgrowth of the graft was seen in three cases. In two cases, coronal CT slices showed that a new fossa had developed. In most cases translatory movement of the graft was minimal. The graft was either partially or almost completely mineralized, especially in cases with longer follow-up. CONCLUSIONS: Most of the patients in this study seemed to have benefitted from replacement of the deformed mandibular condyle with a CCG as estimated by improved range of mandibular movements and decreased symptoms. There were some problems related to unpredictable growth and location of the graft, as well as restricted movement of the replaced condyle. In the future, care should be taken to ensure proper postoperative functional therapy and to examine the role of cartilage thickness on future growth in young patients.

The importance of regular dental treatment in patients with cyclic neutropenia. Follow-up of 2 cases.

Data on two patients with cyclic neutropenia are presented. They demonstrate that regular tooth care and professional dental treatment can prevent progressive periodontal breakdown but that neglecting oral hygiene soon leads to periodontal pathology. Regular, monthly professional removal of dental plaque and calculus, and rinsing with 0.2% chlorhexidine gluconate during neutropenia help maintain periodontal attachment level. The caries susceptibility and the apical periodontitis in the intact anterior tooth of the female patient indicate the possibility of cyclic neutropenia playing a role in caries and pulpal pathology.

Surgical treatment of condylar process fractures using axial anchor screw fixation: a preliminary follow-up study.

PURPOSE: The aim of this study was to evaluate use of the axial anchor screw system in the treatment of condylar process fractures. PATIENTS AND METHODS: Seven adult patients with displaced condylar process fractures were treated using axial anchor screw fixation. Indications for surgery were severe dislocation of the condyle and occlusal changes. Clinical and radiologic examinations were performed 6 weeks, 6 months, and approximately 2 years postoperatively (range, 18 to 30 months). Clinical factors recorded were occlusion, range of mandibular movement, and findings on palpation of the temporomandibular joints. Ramus height and angulation between the mandibular ramus and the dislocated condyle were measured and compared with the contralateral side preoperatively and at the last follow-up. RESULTS: The postoperative course was uneventful in most patients. All were free of pain, and the occlusion and facial symmetry were normal. Radiographs generally showed excellent fracture reduction. Translation of the condyles on mouth opening was symmetrical. No signs of resorption or osteoarthrosis were evident in most cases. However, some patients had complications. These involved unsatisfactory reduction in one patient causing osteolysis at the fracture line. In another patient bone over the screw fractured and the condyle and the screw tilted in a medial direction. CONCLUSION: Treatment of condylar process fractures using the axial anchor screw system is ideal in certain cases. The complications and difficulties seen may be avoidable by appropriate patient selection and techniques.

Clinical, magnetic-resonance imaging and surgical findings in patients with temporomandibular joint disorder--a survey of 47 patients.

The purpose of this study was to evaluate and correlate the clinical, magnetic-resonance imaging (MRI), and surgical findings in 47 patients with temporo-mandibular joint (TMJ) disorders. 51 TMJs (24 right, 27 left) were operated on, because 4 patients underwent treatment of both TMJs. The best correlation between MRI and surgical findings was noted in connection with position of the disk. This was surgically confirmed altogether in 88% of cases (45/51). The clinical diagnosis was confirmed by surgical findings in 75% of cases of anterior dislocation of the disk with reduction and 89% of cases of anterior dislocation of the disk without reduction. Bone changes noted by MRI were confirmed by surgery in 71% of cases. MRI was excellent especially relating to disk position and changes in disk morphology. The results show also that there are findings using MRI, e.g. of joint effusion, which cannot be confirmed during surgery.

Development of the neurocranium after transsutural fixing by new, resorbable poly-L-lactide miniplates. A comparison to fixing with the common titanium miniplates.

The right coronal sutures of twelve (12) newborn rabbits were fixed with commercially available, self-reinforced poly-L-lactide miniplates, with eight (8) rabbits sham treated with titanium miniplate fixation as reference experiments, in order to demonstrate the possible effects on skull growth. After six (6) months follow-up, both types of plate were detected to have caused a similar asymmetry in the neurocranium. Therefore, in our opinion, fixing across growing sutures, even with the new biodegradable devices, should be avoided.

Effect of periodontal treatment on gingival overgrowth among cyclosporine A-treated renal transplant recipients.

No data exist on any association between combined cyclosporine A (Cy A) and dihydropyridine (DHP) medication and the effect of periodontal treatment on the occurrence of gingival overgrowth (GO) among renal transplant recipients. Clinical data on 27 renal transplant recipients treated with Cy A are presented here, including determinations of serum creatinine, whole blood Cy A concentration, existence of DHP treatment, and periodontal status. GO was classified into four categories according to the clinical changes: score 0 = no GO; score 1 = mild GO; score 2 = moderate GO; and score 3 = severe GO. All participants received hygiene phase periodontal treatment and gingivectomies were performed on 10 who originally had score 2 or 3 GO and pocketing. Fourteen (14) of the recipients had no overgrown gingiva or less than at the initial examination, and none of them had GO score 2 or 3 at the time of re-examination (group A). Thirteen (13) participants had more overgrown gingiva than initially or developed score 2 GO after gingivectomies (group B). Group B included significantly more DHP-medicated recipients than group A (6/13 and 1/14 respectively; P < 0.03). The concomitant administration of Cy A and DHP resulted in a significantly increased percentage of score 2 overgrown gingival units as compared with Cy A alone (P < 0.03). It is concluded that combined treatment with Cy A and DHP is a significant risk factor for progression or recurrence of GO after periodontal treatment among susceptible patients.

Gingival overgrowth among renal transplant recipients and uraemic patients.

No detailed data exist on an association between combined cyclosporin (CsA) and dihydropyridine (DHP) medication and gingival overgrowth among renal patients. Thirty-five renal transplant recipients treated with CsA and 28 uraemic patients participated in this research. Fourteen of the recipients and 14 of the uraemic patients were receiving DHP. The examination included determination of the duration of the CsA and DHP treatment protocols, the mean daily oral dose of DHP, and periodontal status. Gingival overgrowth was classified into four categories according to the clinical changes: score 0 = no gingival overgrowth, score 1 = mild gingival overgrowth, score 2 = moderate gingival overgrowth, and score 3 = severe gingival overgrowth. The prevalence of clinically obvious gingival overgrowth (scores 2 and 3) was 35% in those treated with CsA and DHP, 24% with CsA and 21% with DHP. The concomitant administration of CsA and DHP resulted in a significantly increased percentage of scores 2 and 3 overgrown gingival units as compared with DHP alone (P < 0.05). Gingival overgrowth (scores 1, 2, 3) did not correlate with either the daily oral dose of DHP or the duration of DHP treatment. Combined treatment with CsA and DHP did not significantly increase the prevalence of gingival overgrowth, but it did increase the severity of it among susceptible patients.

Failures in the osseointegration of endosseous implants.

A total of 68 patients, 26 men and 42 women, aged 21 to 86 years, were treated with 204 endosseous implants (TPS, ITI, Bonefit, or Biolox) from 1985 to 1990. They were examined at their latest recall visit approximately 22.5 months after surgery, the range varying greatly between the implant systems used (from 4 to 60 months). Fourteen implants were lost during the observation period because of failures in osseointegration. There were no statistically significant differences in success rates between the implant systems during the observation period. The Periotest values, however, differed between the Bonefit and ITI implants in maxillae (P < .001) and mandibles (P < .01), and between successful and failed TPS implants (P < .001, unpaired t test). In four of the failures, all ITI implants, the prosthetic restorations (fixed dentures and single crowns) had been lost. All other failures were treated by using the previous complete denture. Possible causes of failure included advanced age and poor general health of the patient, complications in the surgical procedures, and compromised oral hygiene.

Gingival overgrowth among renal transplant recipients related to immunosuppressive medication and possible local background factors.

The aim of this study was to determine the occurrence of gingival overgrowth (GO) among renal transplant recipients and to analyze possible background factors causing GO among cyclosporine-treated (CsA) patients as compared with others receiving azathioprine (Aza). A total of 32 recipients, 22 treated with CsA and 10 with Aza (ages 22 to 68 years) participated. The examination included determination of renal function, whole blood CsA concentration, and periodontal status. The tooth surface data were analyzed in terms of the given background variables for GO in the whole patient sample by logistic regression analysis. The occurrence of GO was significantly higher in the CsA group as compared with the Aza group (P less than 0.03). The CsA responders had significantly more gingival units overgrown as compared with the Aza responders (P less than 0.005). There were no differences in age, sex, whole blood concentration of CsA, or duration of CsA medication between the responders and non-responders. Expressed as individual means, the gingival inflammation scores were significantly higher among the CsA responders than among the CsA non-responders (P less than 0.005). Analysis of the surface data showed that CsA had an independent major effect on GO. Furthermore, simultaneous gingival bleeding increased the risk of overgrowth (odds ratio = 2). The results show that CsA medication is a significant factor for GO and the risk of the occurrence of GO is further increased by simultaneous gingival inflammation.