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PubMed1995

Renal transplantation in young children.

AIMS: To review the outcome of renal transplantation in small children treated with triple immunosuppression at a single Australian centre. METHODS: The medical records of all children under the age of five years undergoing renal transplantation from 1988 were reviewed. The duration of follow-up was 30 months (range 18-36). RESULTS: Six children received seven renal allografts (five living-related [LR] and two cadaveric [CD]). They had a median age of 3.75 years (range 1.5-4.9) and weight of 11.6 kg (9.1-14.5) at the time of transplantation. All patients received an immunosuppressive regime involving cyclosporin A, azathioprine and prednisolone. There were no deaths. The only graft lost was a CD graft (severe acute rejection within one week of transplantation). Hypertension occurred in all recipients and usually required more than one antihypertensive drug for treatment. Renal function measured by serum median creatinine concentration (range) was 0.05 mmol/L (0.03-0.11) at three months (n = 6) and 0.10 mmol/L (0.07-0.22) at 30 months (n = 4). Growth estimated from median (range) height standard deviation scores was -1.97 (-1.36-(-4.04)) at three months (n = 6) and -1.90 (-1.74-2.50) at 30 months (n = 4). No patient was entirely weaned from prednisolone. Cyclosporin A side effects included hirsutism (five patients), gingival hyperplasia (six patients) and nephrotoxicity (three patients). CONCLUSIONS: Satisfactory patient and graft survival can be accomplished in this recipient age group. The results compare with other international experience and accumulating Australian experience. Hypertension and poor skeletal growth were consistent observations. The long-term outcome of renal function using triple immunosuppression remains to be determined.

Azathioprine↗
PubMedDate not supplied

Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children.

The rate of onset of side effects was examined in 392 pediatric outpatients who received long-term monotherapy with phenobarbital (PB), primidone (PRM), phenytoin (PHT), carbamazepine (CBZ), or valproate (VPA) for epilepsy or febrile convulsions. The severity of side effects (based on need to alter treatment), the nature of each drug's most common side effects, and the doses and plasma levels of occurrence were recorded. Our results show that usually accepted therapeutic ranges are well tolerated. Indeed, although some form of side effect occurred in 50% of patients, treatment had to be changed in only 18% and the drug had to be stopped in only 7%. In decreasing order, the rates for side effects were PHT (71%) greater than PB (64%) greater than CBZ (43%) greater than VPA (43%) greater than PRM (29%). Serious side effects requiring withdrawal of treatment occurred at the following rates: PHT (10%) greater than VPA (8%) greater than PRM (8%) greater than PB (4%) greater than CBZ (3%). Among our patients, the best tolerated antiepileptic drug (AED) was CBZ, and the least tolerated was PHT. Behavioral disorders were most common with PB, neurologic disorders with PHT, digestive tract disorders with VPA, and gingival hyperplasia and hirsutism with PHT. Behavioral disorders involving excitement seen with PB and PRM occurred most commonly at low plasma levels. Behavioral disorders involving depression seen with PB and VPA, those involving excitement seen with PHT and VPA, and digestive disorders seen with VPA occurred particularly when plasma levels were high.

Adolescent↗
PubMed1992

Metabolism of antiepileptic medication: newborn to elderly.

Epilepsy affects individuals of all ages. Regimens of antiepileptic drugs (AEDs) and side-effect profiles differ for infants, children, adults, and the elderly. Thus, the epileptologist must be familiar with the specific changes of AED metabolism with age. In general, metabolic rates are fastest in children; therefore, AED half-lives are shortest in this group. Rates of AED elimination are slowest in neonates, infants, and children. Thus, children need larger dosages, on a mg/kg basis, than adults. The usual phenytoin (PHT) dosage in adults is 4-6 mg/kg per day, but children may need a dosage three to five times higher. On the other hand, the PHT dosages in the elderly may need to be 3-4 mg/kg per day to achieve therapeutic levels. Likewise, the half-life of carbamazepine (CBZ) is shortest in children and the elderly. Profiles of metabolites may also be age-specific, a difference of particular importance for valproate (VPA). The relative amount of VPA metabolized to 4-ene is more than twofold less in adults than in children, which may explain the different profile of hepatotoxicity seen by age. The elderly may be more vulnerable to adverse effects of AEDs. Many elderly have neurologic deficits that may render them more vulnerable to neurotoxic effects such as ataxia and cognitive disturbances. Also, low serum albumin concentrations, which result in decreased binding, may mask high serum AED concentrations. The hyponatremia associated with CBZ may be a particular concern in the elderly. Gingival hyperplasia, a concern in children, may not be a problem in the elderly.

Adolescent↗
PubMed1983

Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy.

Phenobarbital and phenytoin have good antiepileptic effect, but clinically significant untoward effects occur during their long-term use. Phenobarbital may cause hyperactivity, behavioral problems, sedation, and even dementia; these effects are dose related to some extent. Side effects of phenytoin include sedation, a cerebellar syndrome, phenytoin encephalopathy, psychosis, locomotor dysfunction, hyperkinesia, megaloblastic anemia, decreased serum folate level, decreased bone mineral content, liver disease, IgA deficiency, gingival hyperplasia, and a lupus-like hypersensitivity syndrome. Especially susceptible to the neurotoxic effects of phenytoin are epileptic children with severe brain damage who are on multiple drugs. In those children, balance disturbance may develop and be followed by gradual loss of locomotion. Among 131 mentally retarded epileptic patients, phenytoin intoxication occurred in 73 (56%), of whom 18 experienced persistent loss of locomotion. There is experimental evidence that the toxic action of phenytoin lies at the cellular level, predominantly in the cerebellum. Many experts avoid the long-term use of phenytoin because of its insidious and potentially dangerous side effects.

Abnormalities, Drug-Induced↗
PubMed2005

Cyclosporine in the treatment of myasthenia gravis.

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.

Adult↗
PubMed1984

Phenytoin induced gingival overgrowth in institutionalized epileptics.

In a cross-sectional, epidemiological study of phenytoin induced gingival overgrowth in 77 institutionalized persons with epilepsy, the severity of the gum lesions was quantified by means of a precise new technique. Lesion severity was then compared statistically to other clinical and laboratory parameters. Positive correlations were detected between overgrowth severity and gingival inflammation, probing depths, calculus accumulation, plaque score and the measurement gingival margin to mucogingival junction (GM-MGJ). No correlation was observed between lesion severity and patients age, daily drug dosage, plasma or saliva phenytoin level, or salivary concentration of the major phenytoin metabolite.

Adolescent↗
PubMed1986

The effect of a plaque control program on the development of phenytoin-induced gingival overgrowth. A 2-year longitudinal study.

The effect of a plaque control program on the development of phenytoin(PHT)-induced gingival overgrowth was studied in 16 epileptic children, 8-16 years of age during a 2-year longitudinal study. The parameters studied were: visible plaque index (VPI), gingival bleeding index (GBI), probing depth and gingival overgrowth. A preventive program was instituted before the start of the PHT-medication and included oral hygiene instruction and frequent professional tooth cleaning during the observation period. When gingival overgrowth was evaluated on the basis of probing depth, no patients on PHT therapy for 2 years developed pseudopockets (greater than or equal to 4 mm). During the 2-year observation period, there was a statistically significant increase (p less than 0.01) in the thickness of the marginal gingiva bucco-lingually in all patients. This gingival enlargement was already evident (p less than 0.01) after 1 month. The degree of gingival enlargement in this patient group did not increase significantly after the 1st year of PHT-medication and was not significantly correlated to the plasma concentration of PHT. The results of this study show that the development of PHT-induced gingival overgrowth could not be prevented by this specific plaque control program.

Adolescent↗
PubMed1992

Resolution of cyclosporin A (CsA)-induced gingival enlargement following reduction in CsA dosage.

Gingival enlargement due to the immunosuppressive drug, cyclosporin A (CsA), will resolve following discontinuation of drug therapy or extraction of adjacent teeth. This report presents a clinical observation on a patient in whom CsA-induced gingival enlargement failed to resolve with improved plaque control and scaling, but resolved quickly following reduction in the daily dosage of CsA. Despite less than optimal plaque control, the CsA-induced gingival enlargement did not recur on the reduced drug dosage over a 2-year observation period. This finding raises the possibility that reduction of CsA dosage below a certain critical level may lead to resolution of CsA-induced gingival enlargement.

Aged↗
PubMed1992

The incidence and severity of nifedipine-induced gingival overgrowth.

The gingival health of 19 patients with cardiovascular problems who were medicated with nifedipine was compared with a similar cohort treated with atenolol and a control group of healthy patients. In the nifedipine and atenolol groups, patients had been taking their respective medication for a minimum period of 6 months. Plaque scores were similar for all three groups. However, patients medicated with nifedipine had a significantly higher gingival index (P less than 0.005), gingival overgrowth scores (P less than 0.02) and probing sites greater than 3 mm (P less than 0.005) when compared with the atenolol and control groups. 4 patients in the nifedipine group experienced clinically significant gingival overgrowth which required surgical excision. Gingival changes in the nifedipine patients were not related to drug dosage or plaque scores. It is concluded that nifedipine therapy results in significant gingival changes, an effect which may be mediated by the drug's action on calcium transport.

Atenolol↗
PubMed1995

The pharmacokinetics of phenytoin in gingival crevicular fluid and plasma in relation to gingival overgrowth.

The aim of this study was to determine whether phenytoin (PHT) could be detected in gingival crevicular fluid (GCF), and to relate its concentration to both plasma level and degree of gingival overgrowth. 23 patients medicated with phenytoin for at least 6 months were clinically examined for signs of periodontal disease and gingival overgrowth. 12 patients out of these demonstrated clinically significant overgrowth and their plaque scores and gingival inflammation were greater than for the non-overgrowth group (p < 0.001). Phenytoin concentrations were determined by high performance liquid chromatography, and was detected in GCF. There was a significant correlation between the GCF and plasma phenytoin concentrations (p < 0.05), but it was not related to the extent of gingival overgrowth. Inflammation increased the GCF volume, but was not a determinant of GCF phenytoin concentration. It is concluded that effusion of phenytoin into GCF is regulated by the plasma levels of the drug, but its concentration in GCF is not related to the incidence of gingival overgrowth.

Adult↗
PubMed1996

Combined treatment approach to gingival overgrowth due to drug therapy.

A case of severe gingival overgrowth associated with combined drug therapy of cyclosporin A and nifedipine is reported. The frequently increased vascularity of the gingival tissues in such cases often causes problems with bleeding both during and after surgery. Acrylic suckdown splints have been used postoperatively to assist haemostasis; however, these can interfere with function and cause discomfort. This report describes a combined treatment approach using conventional gingivectomy and carbon dioxide laser for the removal of the hypertrophic soft tissue. The benefits of such combined treatment include reduced bleeding during surgery with consequent reduced operating time and rapid post-operative haemostasis, thus eliminating the need for a splint.

Blood Loss, Surgical↗
PubMed1996

The distribution of gingival overgrowth in organ transplant patients.

The distribution of gingival overgrowth was investigated in a cohort of organ transplant patients, who were medicated with cyclosporin or the combination of cyclosporin and a calcium channel blocking drug. Gingival overgrowth scores were significantly higher at buccal sites than lingual-palatally (p < 0.0001). There was no significant difference between upper and lower overgrowth scores (p = 0.88). The most severe overgrowth was seen in the canine region. Overgrowth between the central incisors was significantly less than in the canine region (p > or = 0.044) and was similar to that in the molar and premolar region. Although raised overgrowth scores were associated with increased levels of plaque and gingival inflammation, the distribution could not be explained by this observation.

Analysis of Variance↗
PubMed1996

Determinants of gingival overgrowth severity in organ transplant patients. An examination of the rôle of HLA phenotype.

The role of HLA phenotype as a risk factor for drug-induced gingival overgrowth was investigated in a cohort of 172 transplant recipients. Clinically significant overgrowth warranting surgical correction was observed in 72 patients (42%). Using stepwise regression modelling, 6 clinical parameters were identified as significant risk factors for the severity of gingival overgrowth. These were; age, sex, creatinine plasma level, duration of therapy, papilla bleeding index and concomitant medication with a calcium channel blocking drug. 3 HLA alleles were also identified as risk factors when adjusted for other clinically significant risk factors (HLA -DR2, A24, B37). However, when the p-values for the HLA variables were corrected to compensate for the use of multiple significance testing, only HLA-B37 remained statistically significant at the 5% level. Organ transplant patients are at risk of developing gingival overgrowth, with approximately 25% medicated with cyclosporin alone requiring corrective gingival surgery. This figure more than doubles in patients concomitantly medicated with a calcium blocking drug. The data at present available would suggest that the severity of gingival overgrowth is also significantly associated with the HLA-B37 phenotype.

Adolescent↗
PubMed1996

Histopathologic alterations of periodontium in cyclosporin-treated rats. Is the periodontium a target tissue for the drug?

Gingival dimensions and histopathologic alterations in periodontium were examined in rats continuously exposed to cyclosporin-A (CSA). 60 male Sprague-Dawley rats were divided into 2 groups. Rats in the test group daily received CSA in mineral oil by gastric feeding at a dosage of 30 mg/kg body weight for 6 weeks. Rats in the control group received mineral oil only. 10 rats from each group were sacrificed at 2-week intervals. Gingival dimensions were assessed from stone models obtained from the maxillary and mandibular incisal regions. Horizontal, sagittal and frontal tissue sections were obtained from these regions as well. Gingival dimensions in the mandibular and maxillary incisal regions were significantly increased in rats exposed to CSA. Light-microscopic observations revealed a granulation tissue formation at tooth-gingiva interface and an irregular bony surface on dental alveoli in experimental animals. Because both soft and hard tissue of periodontium in experimental rats being significantly effected by CSA compared to control animals, we hypothesized that the periodontium is a target tissue for CSA.

Alveolar Process↗
PubMed1996

Cyclosporin-A-induced gingival overgrowth in heart transplant patients. A cross-sectional study.

The incidence of gingival overgrowth secondary to the administration of cyclosporine A (CsA) is widely reported in renal transplant recipients, while there is no information about periodontal conditions in heart transplant patients. In the present cross-sectional investigation the relationship between clinical periodontal conditions and pharmacological profiles of CsA was determined in 39 patients (31 male and 8 female, aged 18-63 years, mean 45.6 +/- 15.2 years) who possessed their 6 upper and 6 lower anterior teeth. All patients had been on a CsA-based immunosoppression regimen for at least 6 months (6-101, mean 39.3 +/- 30.1). 2 periodontal parameters (recorded on the 12 anterior teeth only) relating to gingival overgrowth were considered: hyperplastic index and % of sites with probing depth > 3 mm. These parameters were always recorded by the same observer at first appointment and 2 months after an oral hygiene programme. Both non parametric statistical analysis (Kruskal-Wallis one-way analysis by rank, Wicoxon signed rank-test and Mann Whitney U-test) and parametric analysis (stepwise multiple regression analysis, one-sample and two-sample t-test) were used to investigate the relationship between the periodontal parameters (dependent variables) and a series of independent variables: age, sex, plaque index (PI), gingival index (GI), CsA dose, CsA blood level, duration of therapy (months since allograft). Results failed to demonstrate any significant correlation between gingival overgrowth and age, sex, CsA dose or CsA blood level, PI. A positive significant correlation was found between periodontal conditions and GI and a significant inverse correlation between periodontal conditions and duration of therapy, suggesting that the relation between CsA therapy and gingival overgrowth in heart-transplant patients could be time-related and the negative influence of the drug on the periodontal status could spontaneously decrease over time.

Adolescent↗
PubMed1996

The pathogenesis of drug-induced gingival overgrowth.

Gingival overgrowth is a well-documented unwanted effect, associated with phenytoin, cyclosporin, and the calcium channel blockers. The pathogenesis of drug-induced gingival overgrowth is uncertain, and there appears to be no unifying hypothesis that links together the 3 commonly implicated drugs. In this review, we consider a multifactorial model which expands on the interaction between drug and/or metabolite, with the gingival fibroblasts. Factors which impact upon this model include age, genetic predisposition, pharmacokinetic variables, plaque-induced inflammatory and immunological changes and activation of growth factors. Of these, genetic factors which give rise to fibroblast heterogeneity, gingival inflammation, and pharmacokinetic variables appear to be significant in the expression of gingival overgrowth. A more thorough understanding of the pathogenesis of this unwanted effect will hopefully elucidate appropriate mechanisms for its control.

Adult↗
PubMed1999

Unusual peripheral odontogenic tumors in the differential diagnosis of gingival swellings.

Differential diagnosis of gingival mass lesions includes several conditions and causes. Peripheral odontogenic tumors may mimic gingival swellings and, although rare, must be included in the differential diagnosis. The purpose of this article is to describe 3 different cases of peripheral odontogenic tumors and to discuss the differential diagnosis of gingival swelling. Histologic examination is mandatory when localized gingival swellings are surgically removed.

Adult↗