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[An increase in gingival volume induced by drugs (phenytoin, cyclosporine and calcium antagonists). A review of the literature].

The aim of this review is to evaluate the side effects of some drug therapies on the gingival tissue in certain susceptible individuals. Phenytoin, cyclosporine-A and a variety of calcium channel blockers have been shown to produce gingival overgrowth. In this paper the pharmacodynamics and pharmacokinetics of these drugs, the pathogenesis, the clinical aspect of the enlargement and its treatment are examined. Several of the reviewed theories on pathogenesis are well documented in the literature, while others are controversial and less described. The old term gingival hyperplasia is not exact because histologically an increase in the number of fibroblasts has not been demonstrated, but an increase has been found out in the amount of collagen fibers and noncollagenous proteins in the connective tissue. The clinical findings have the same characteristics both in location and growth pattern while prevention is primarily directed at the removal of local irritant factors. The prevalence and severity of gingival enlargement increase in heart transplant patients who are often medicated with cyclosporin and channel blockers.

Anticonvulsants↗

The relationship of initial clinical parameters to the long-term response in 112 cases of periodontal disease.

The purpose of the present study was to determine whether any of the clinical parameters recorded during an initial periodontal examination would relate to the course of periodontal cases maintained for long periods of time. Based on available documentation, cases which had a downhill course were assembled from a population previously studied. In addition, long-term cases currently under maintenance care were drawn from our private practice. On average, the patients had been under care for 23 years. The study population was heavily weighted toward downhill cases to better compare these cases with those usually found in periodontal practice. Positive statistical correlations were found between the amount of subgingival calculus and the degree of gingival inflammation at initial examination. Disease severity initially was positively correlated to long-term course of disease. The amount of subgingival calculus did not relate to the long-term result. There was a strong correlation between inflammatory gingival hyperplasia initially and good long-term maintenance. The results suggest that, in combination, initial characteristics of periodontal cases coupled with long-term results of treatment may aid in further subclassifying the periodontal diseases.

Adult↗

[Gingival hypertrophy due to cyclosporine. A clinico-statistical study in 82 patients].

Eighty-two patients were observed at the Dental Department at Parma University. Seventy-six of them had renal transplant and 6 liver transplant. They were in immunosuppressive therapy with cyclosporina, 42 of them were also in calcium antagonist therapy. Gingival hypertrophy was observed in 52 subjects (63.4%) 25 (30%) patients underwent surgical operation, 6 of them (24%) showed a relapse about 3 months after the first operation. Clinical data were measured in accordance with 5 indicators: the level of oral hygiene, cyclosporinemia, contemporaneous use of calcium antagonist, the duration of therapy and the DMF index. By the results obtained, it's possible to suppose that the gravity of the disease is related to the contemporaneous use of calcioantagonist, but it wasn't highly significant (p < 0.05). The degree of oral hygiene was decidedly in relation to the most severe forms of gingival hyperplasia (grade 2-3), (p < 0.001). No relation was found for the duration of therapy, distribution of the DMF index and the level of drugs in the blood.

Adolescent↗

Hereditary gingival fibromatosis: a systematic review.

Generalized gingival enlargement can be caused by a variety of etiological factors. It can be inherited (hereditary gingival fibromatosis [HGF]); associated with other diseases characterizing a syndrome; or induced as a side effect of systemic drugs, such as phenytoin, cyclosporin, or nifedipine. HGF, previously known as elephantiasis gingivae, hereditary gingival hyperplasia, and hypertrophic gingiva, is a genetic disorder characterized by a progressive enlargement of the gingiva. This review will focus on diagnosis, treatment, and control of HGF. The pattern of inheritance, the histopathologic characteristics, and the known biologic and genetic features associated with HGF are also emphasized.

Fibroblasts↗

Juvenile hyaline fibromatosis: two new patients and review of the literature.

We report on a sister and a brother (born to normal consanguineous parents) with joint contractures and osteolytic lesions of bones. The sister had also gingival hyperplasia and skin lesions consisting of multiple tumors of the face, nose, palate, ears, and neck. Histologic examination showed findings of juvenile hyaline fibromatosis. The literature is reviewed, and 15 cases already reported are summarized.

Child, Preschool↗

Vitamins for epilepsy.

BACKGROUND: Vitamins have been reported to be effective in controlling certain types of seizures and to prevent some of the harmful effects of antiepileptic drugs (AEDs). In this review we will summarize evidence from randomized controlled trials. OBJECTIVES: To assess if vitamins improve seizure control, reduce adverse effects of AEDs or improve the quality of life in people with epilepsy. SEARCH STRATEGY: We searched MEDLINE from 1966 to 2004, the Cochrane Epilepsy Group trials register (December 2004), CENTRAL (the Cochrane Controlled Trials Register) (TheCochraneLibrary Issue 4, 2004), and cross-references from identified studies. SELECTION CRITERIA: Randomized or quasi-randomized studies investigating the effects of one or more vitamins given alone or in addition to AEDs to people of any age with any type of epilepsy. DATA COLLECTION AND ANALYSIS: Both reviewers assessed the trials for inclusion and extracted the data. Outcomes assessed included seizure frequency, gingival hyperplasia, neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase, hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes. Primary analyses were by intention to treat. MAIN RESULTS: Fifteen studies met our inclusion criteria and were of poor methodological quality. None described randomization methods and most enrolled small numbers of participants. Nine studies (331 participants) investigated folic acid. Two studies (75 participants) found no effect for the outcome 50% or greater reduction in seizure frequency (OR 0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival health, intelligence, behavior, mental health or personality, or measures of red blood volume and hemoglobin content. Folic acid was not associated with any consistent changes in serum phenytoin or phenobarbitone levels or improvement in the mean motor conduction velocities of peripheral nerves. One small study (72 participants) found that thiamine improves neuropsychological functions related to psychomotor speed, visuospatial abilities, selective attention and verbal abstracting ability. One study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p < 0.00001). The studies found no significant effects on serum calcium, alkaline phosphatase or general well-being. One small study (24 participants) found a significant decrease in seizure frequency in those treated with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to 130.92). AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions.

Anticonvulsants↗

[The CO2 laser in stomatology. Part 2].

The second part of this review presents and discusses evidence in the recent literature for the application of the CO2 laser for the therapy of stomatologic lesions. Clinical outcomes and complications for the use of the CO2 laser are presented for the following stomatological conditions: leukoplakia, lichen planus, benign soft-tissue and salivary gland tumors, reactive soft tissue changes (i.e., fibroepithelial polyps), recurrent aphthous stomatitis, drug-induced gingival hyperplasia, mucous extravasation and mucous retention cysts, herpes simplex virus-induced lesions, maxillary midline frenum, and ankyloglossia (tongue-tie). This review outlines indications in which the CO2 laser is the treatment method of choice and in which situations the laser has still to be applied with caution.

Carbon Dioxide↗

Hereditary gingival fibromatosis with a recessive mode of inheritance. Case reports.

Hereditary gingival fibromatosis is characterized by varying degrees of attached gingival hyperplasia and may in rare cases present as a feature of a generalized syndrome. It is usually inherited as an autosomal dominant condition though recessive forms are described. The dental and genetic features of an affected brother and sister with a probably unique autosomal recessive hereditary fibromatosis syndrome are presented.

Adolescent↗

Calcium antagonists and deep gingival pockets in the population-based SHIP study.

AIM: Gingival overgrowth is a common undesired side-effect in patients taking calcium channel blockers. Different reports have suggested that the drug-induced gingival hyperplasia may aggravate inflammatory periodontal disease. However, representative epidemiological data are lacking. We investigated the association between the intake of calcium antagonists and periodontitis in a population-based analysis including the most important risk factors of periodontitis. METHODS: In a cross-sectional epidemiological investigation involving 4290 subjects aged 20-80 years, we recorded periodontal risk factors and identified participants using calcium antagonists. Periodontal parameters, attachment loss, probing depth and number of teeth were assessed. In a subgroup analysis with matched pairs, 456 subjects using calcium antagonists and 456 without were compared for periodontal status. RESULTS: Subjects treated with calcium antagonistic drugs had significantly deeper gingival pockets than their drug-free counterparts. This was observed in the total population of 4290 and confirmed by logistic regression analyses (P < 0.001) controlled for the known risk factors of periodontitis (age, sex, smoking, education). In the matched-pair analysis only the probing depth was increased: extent probing depth > or = 4 mm median 23.5 vs. 17.0% (P < 0.001); mean probing depth 3.0 +/- 0.8 vs. 2.7 +/- 0.9 mm (P < 0.001). No differences were found in extent and severity of clinical attachment loss and in the number of teeth. The risk of gingival overgrowth was aggravated in smokers. CONCLUSION: In the general population, treatment with calcium antagonists leads to gingival overgrowth without an aggravation of periodontal disease. Interaction with smoking indicates the multifactorial background of the undesired effect of calcium antagonists.

Adult↗

Insulin-dependent diabetes mellitus and oral soft tissue pathologies. I. Prevalence and characteristics of non-candidal lesions.

OBJECTIVE: A large epidemiologic study on oral health has found that several oral soft tissue lesions were more prevalent in subjects with insulin-dependent diabetes mellitus than in control subjects without diabetes. Our objective in part I of this article is to characterize those lesions not associated with Candida. STUDY DESIGN: This cross-sectional study determined the prevalence and characteristics of oral soft tissue diseases identified during a comprehensive oral evaluation of 405 adult subjects with diabetes and 268 control subjects without diabetes. RESULTS: Twenty specific oral soft tissue lesions were identified. Nearly twice as many subjects with diabetes as subjects without diabetes were found to have one or more oral soft tissue lesions (44.7% vs 25.0%; P <.0001). Subjects with diabetes also had significantly higher prevalence rates for 7 lesions, 3 of which were non-candidal: fissured tongue, irritation fibroma, and traumatic ulcers. (Four lesions generally associated with Candida infection-median rhomboid glossitis, denture stomatitis, generalized atrophy of the tongue papillae, and angular cheilitis-will be described in part II of this article.) There were no differences found between the subjects with diabetes and the control subjects for lichen planus, gingival hyperplasia, or salivary gland disease. CONCLUSIONS: Oral soft tissue lesions were seen more frequently in subjects with insulin-dependent diabetes than in the control subjects. Characterization of 3 non-candidal lesions suggests that they are associated with trauma, delayed healing, or both.

Adult↗

[Oral health and treatment needs of 12-13 year-old epileptic schoolchildren in two special schools in the West Cape].

The aim of this study was to determine the oral health status and treatment needs of 12-13 year old epileptic children at the Jan Kriel and Bet-El schools for neurologically handicapped children. This information will be used as a guideline to aid the planning and evaluation of oral health programs at both institutions. A total of 25 White and 25 Coloured epileptic schoolchildren were respectively examined at Jan Kriel and Bet-El. The variables examined were the status and treatment needs for both caries and periodontal lesions, phenytoin-induced gingival hyperplasia and fractures of anterior teeth. The measurement of the variables were based on the criteria of the World Health Organization. The mean DMFT at Bet-El was 4,8 in comparison with 2,0 at Jan Kriel. No children at Bet-El were caries free, whilst 32 per cent of the children at Jan Kriel were caries free. Sixty four per cent of the children at Jan Kriel needed no treatment for caries in comparison with the 8 per cent at Bet-El. Caries treatment needs consisted mainly of 1- and 2-surface restorations at both institutions. Only 8 per cent of the children examined at Bet-El were periodontally sound in comparison to the 32 per cent of the children at Jan Kriel. A high prevalence of gingival bleeding on probing was observed at both institutions. A need for oral hygiene instructions existed at both institutions. More than 50 per cent of the children at Bet-El needed scaling and polishing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hypertrichosis lanuginosa in a mother and son.

Hypertrichosis lanuginosa (without gingival hyperplasia) is described in a mother and son; the latter also had photophobia, infantile genitalia, growth retardation, hypotension, low IQ and dental abnormalities (hyperdontia, permanence of deciduous and delayed eruption of permanent teeth). Both have normal dermatoglyphics. Some clinical findings are discussed. The presence of this syndrome in a mother and son supports an autosomal mode of inheritance (with variable expressivity). Hypertrichosis lanuginosa is a pure monomultidysplasia and may be classified with the tricho-odontic sub-group of the ectodermal dysplasias.

Abnormalities, Multiple↗

Hereditary gingival fibromatosis: aggressive 2-stage surgical resection in lieu of traditional therapy.

INTRODUCTION: Hereditary gingival fibromatosis (HGF) is a rare condition characterized by progressive enlargement of the gingiva. Most cases follow autosomal dominant genetics, with a reported incidence of 1 in 750,000. In addition to cosmetic concerns, the compromised oral cavity may cause difficulty with eating, speech, hygiene, and oral competence. In addition, social consequences can be dramatic, forcing patients to lead isolated, reclusive lives. Traditional therapy uses serial gingival resections ("quadrantectomies") with primary closure. However, this method is associated with frequent recurrence and additional resections. We report on a family of 12 siblings, 8 of whom, including monozygotic twins, are affected with HGF. We describe corrective surgery for 3 siblings, as well as their long-term follow-up. METHODS: Three sisters suffered from severe maxillary and mandibular gingival hyperplasia. All complained similarly of weight loss, difficulty with articulation, and social isolation. Physical examination revealed massive overgrowth of both maxillary and mandibular gingiva, as well as multiple ectopic teeth. Following diagnostic biopsy, all 3 patients underwent staged resections. The first stage involved resection of the maxillary component, followed by a planned second-stage resection of the mandibular component. All resections included gingivectomies, odontectomies, and alveolar ridge ostectomies. The oral cavity was allowed to heal by secondary intention. RESULTS: All 3 patients were female, and ages ranged from 34-48 years (mean: 43). Follow-up on the 3 patients ranged from 3-18 months (mean: 11 months). There has been no evidence of recurrence to date. The gingiva remucosalized uneventfully within several weeks, and all patients are tolerating solid food. All patients report dramatically improved speech, oral hygiene, and self-confidence. CONCLUSIONS: In an effort to address the high recurrence rate, we describe our aggressive surgical approach, including resection of the hypertrophied gingiva and alveolar processes. Two-staged gingival resection, as opposed to the more traditional 4-stage quadrantectomy approach, has resulted in no recurrence to date, suggesting an improved outcome over the traditional techniques.

Adult↗

Simultaneous assay of adenosine deaminase and purine nucleoside phosphorylase activity as possible biochemical means to detect non-Hodgkin lymphomas of the oral cavity.

BACKGROUND AND METHODS: This study proposes the usefulness of simultaneous assay of adenosine deaminase (enzyme code [EC] 3.5.4.4; ADA) and purine nucleoside phosphorylase (EC 2.4.2.1; PNP) activities in a biopsy specimen as a biochemical test adjunctive to the histologic diagnosis of oral non-Hodgkin lymphomas (NHL). RESULTS: NHL tissues showed an ADA activity of more than 1428 nmol/h/mg of protein, and more than 3451 nmol/h/mg of protein was the sum of ADA and PNP activity. In contrast to this finding, all the 106 lesional tissues affected by various carcinomas, various benign tumors, various cysts, ameloblastomas, osteosarcomas, gingival hyperplasia, and inflammation showed an ADA activity of less than 1000 nmol/h/mg of protein, except for 2. The sum of ADA and PNP activity was less than 2249 nmol/h/mg of protein in these diseases, except for squamous carcinoma. Different control tissues of the oral cavity showed less than 766 nmol/h/mg of protein in ADA activity, and the highest sum of ADA and PNP activity in these was only 1384 nmol/h/mg of protein. CONCLUSIONS: These findings suggest that a strong suspicion of oral NHL is justified when the sum of ADA and PNP activity in a biopsy specimen exceeds 3000 nmol/h/mg of protein and ADA activity is greater than 1000 nmol/h/mg of protein.

Adenosine Deaminase↗

Factor XIIIa-containing cells and fibrosis in oral and maxillofacial lesions: an immunohistochemical study.

The distribution of subunit A of blood coagulation factor XIII (FXIIIa) was investigated by the avidin-biotin-peroxidase complex (ABC) method in various oral and maxillofacial tissues. These tissues were from normal tongue, gingiva, lip, and submandibular gland, and from Dilantin gingival hyperplasia (one case), pyogenic granuloma (three cases), peripheral fibroma (four cases), squamous cell carcinoma (seven cases), chronic sclerosing submandibular adenitis (two cases), and fibrous dysplasia of the mandibular bone (one case). The distribution of collagenous components was examined in the same tissues by means of the Sirius red F3BA method. By means of the ABC method, FXIIIa was detected in the cytoplasm of certain connective tissue cells in each of the tissues examined. These FXIIIa-containing cells were sparse in the normal tissues but evidently abundant in the fibrous connective tissue of inflammatory and neoplastic lesions. In the present study, the close relationship between the distribution of FXIIIa-containing cells and that of collagenous components is demonstrated. The role that FXIIIa-containing cells play in the process of fibrosis is discussed.

Collagen↗

Juvenile hyaline fibromatosis: ultrastructural study.

Juvenile hyaline fibromatosis is a multisystemic disorder characterized by a triad of cephalic fibrous outgrowths, gingival hyperplasia, and flexion contractures. The aim of this study was to find new ultrastructural features that could be useful for differentiating this entity from other types of fibromatosis. Mucosal lesions processed for light and electron microscopy by routine techniques showed hyperactive-appearing spindle-shaped fibroblasts and dysplastic mesenchymal cells. Dilated rough endoplasmic reticulum, prominent Golgi complexes, and multivesicular bodies as well as single membrane vesicles filled with fibrillogranular material were seen within the cytoplasm of dysplastic mesenchymal cells. Many fibrillogranular vesicles contained smaller vesicles. There were also invaginations of the cell membrane that contained fibrillogranular material similar to that seen in the single membrane vesicles, suggesting engulfment of an extracellular substance. The stroma contained both normal and serrated collagen fibrils, microfibrils, and two types of fibrillogranular material, one of them with a characteristic banding pattern. Our clinical and histopathologic findings resemble those previously described in cases of infantile systemic hyalinosis and juvenile hyaline fibromatosis. So many features of these two conditions overlap that it is difficult not to consider them as parts of a spectrum of the same disorder.

Fibroma↗

The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: longitudinal analysis of a population-based registry.

OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.

Adult↗

Cyclosporin A for the treatment of aplastic anemia refractory to antithymocyte globulin.

Antithymocyte globulin (ATG) is an established form of therapy for severe aplastic anemia (SAA). However, in patients who do not respond to this treatment and who are not candidates for bone marrow transplantation few successful therapeutic alternatives exist. We report two such patients who have shown a therapeutic response to Cyclosporin A (CSA) (Sandimmune, Sandoz). Case 1, a 15 year old male, and Case 2, a 34 year old female, were diagnosed as having SAA in September 1984 and May 1984 respectively. Treatment with high dose Methylprednisolone (MPN) and ATG in Case 1 and MPN, ATG and Oxymetholone in Case 2 for ten days was ineffective in both cases. Case 1 developed anaphylaxis with both repeat ATG and ALG (antilymphoblast globulin), and Case 2 failed to respond to repeat ATG. Both required frequent packed cells and platelet transfusions. At five and six months respectively following completion of ATG therapy, CSA was started at 10 mg/kg/day in divided doses orally. Renal and liver functions and CSA blood levels were followed. Within six weeks both patients exhibited a hematologic response and were no longer transfusion dependent. On maintenance therapy of 4 mg/kg/day (Case 1) and four months after discontinuing CSA (Case 2) the hematologic values are as follows: hemoglobin 160 and 130 g/L, absolute granulocyte count 3100 and 1640 X 10(9)/L, and platelets 132 and 84 X 10(9)/L respectively. Side effects included hypertrichosis, gingival hyperplasia and mild reversible nephrotoxicity. CSA appears to represent an effective form of therapy for patients with SAA refractory to ATG.

Adolescent↗