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A 4-year-old boy presented with his mother to genetics in the 1980s, with a family history (FH) of macrocephaly and intellectual disability (ID). He remained undiagnosed until his mother developed multiple cancers and was diagnosed with Cowden syndrome (CS) in 2017, a rare, multisystem cancer predisposition syndrome. CS was then confirmed in multiple family members. Clinical examination revealed potentially novel features; gingival enlargement, dental abnormalities and joint hyperextensibility. These features could contribute to revised PTEN hamartoma tumour syndrome, National Comprehensive Cancer Network, minor diagnostic criteria. The paediatric CS phenotype is still emerging and features expressed in this family during childhood could potentially aid paediatric diagnosis. This case reminds clinicians to seek genetic input for PTEN testing when macrocephaly is identified alongside, a personal or FH of ID, early-onset tumours (especially breast, bowel or thyroid) or multiple tumours. Thus detailed FH is pivotal to earlier CS diagnosis and improved patient outcomes.

Two brothers, completely asymptomatic until their first year of life, started to complain from gingival hypertrophy, progressive development of painful soft tissue masses on the fingers and toes, on the face and on the scalp. There were no neurological symptoms or mental delay for both brothers.

Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.

Background KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro‐intestinal, cardiovascular, and neurological manifestations. Methods Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well‐known clinical entities. Results In an 8‐year‐old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30‐week‐old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction. Conclusion The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth., KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro‐intestinal, cardiovascular, and neurological manifestations. The current report presents the first antenatal presentation of pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth. Furthermore, an additional vascular finding might have important implications on the clinical management of these patients.

First-line treatment of aplastic anemia(AA) and for AA patients ineligible for hematopoietic stem cell transplantation (HSCT) has consisted of antithymocyte globulin (ATG), the calcineurin inhibitor cyclosporine A (CsA), and more recently eltrombopag. However, at our institution, we have successfully substituted another calcineurin inhibitor, tacrolimus, as a part of immunosuppressive threatment (IST) for AA due to more favorable toxicity profile. Since there is limited data on the use of tacrolimus in aplastic anemia, we conducted a retrospective review of twenty patients treated with tacrolimus-based immunosuppressive therapy (IST) as a first- or second-line treatment. The overall response rate was comparable to that of patients treated with CsA (18 patients). However, there were no cutaneous side effects observed in patients receiving tacrolimus, a relatively common finding with CsA use. Our data suggest that tacrolimus-based IST is a potential option in AA and might have a more favorable toxicity profile compared to CsA.

An 18-year-old man presented to our hospital with muscular pain, diffuse petechiae, spontaneous thigh ecchymosis, edema and pain of the right knee, bilateral pretibial subcutaneous nodules, and gingival hypertrophy and hemorrhage. His history was positive for a mixed anxiety-depressive disorder and a restrictive diet caused by self-diagnosed food allergies. Skin lesions appeared like hyperkeratotic papules with coiled hairs and perifollicular hemorrhages. A diagnosis of scurvy was made upon demonstration of low serum levels of ascorbic acid. An allergy evaluation found cross-reactivity between pollens and food, related to the presence of panallergens. Moreover, we found that our patient was also affected by celiac disease. In conclusion, scurvy should be considered in the differential diagnosis of patients with petechiae and ecchymosis, especially when food restriction, malabsorption, or psychiatric disorders are present.

A 34-year-old man was admitted to hospital with progressive and severe lower limb pains, increasing wheelchair dependence and a spreading rash affecting the legs. Admission test results were normal including clotting screen and platelet count. Suggested diagnoses on a busy post-take ward round

Renal transplant is the renal replacement therapy of choice for all patients of chronic kidney disease. The aim of this study was to analyse the trends of medical complications in renal transplant recipients at our centre.it is a prospective cross sectional descriptive study. All the patients undergoing renal transplant at Armed Forces Institute of Urology from September 2013 to September 2015 were included in the study. The patients were followed prospectively till March 2016 and a complete data about their complications and lab investigations was maintained..This study included a total of 63 patients with a mean duration of follow-up of 14.05 months (SD±4.45). Infective complications as a group are the commonest complication occurring in over 50% of cases followed by haematological complications (17.5%), new onset diabetes after transplant (15.9%) and transplant dysfunction (14.3%) Cardiovascular complications were seen in only 4.8% cases but with high mortality. Gingival hypertrophy was seen in 4.8% cases.Medical complications are common after renal transplant especially in the early post-operative period. The only way forward is early recognition and aggressive treatment, as delays can cost losses in the form of kidney function, life and higher health care cost.

Made available in DSpace on 2018-12-11T17:28:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03-01. Added 1 bitstream(s) on 2021-07-15T15:04:01Z : No. of bitstreams: 1 S0365-05962016000200226.pdf: 299377 bytes, checksum: 1eb259ff0fc7a1d6773ff3b8470786a3 (MD5) Hyaline fibromatosis syndrome is the current name for clinical manifestations of diseases previously known as “infantile systemic hyalinosis” and “juvenile hyaline fibromatosis”. The authors report representative clinical cases of each one of the above subtypes with emphasis on cutaneous manifestations and difficulties for early diagnosis in this syndrome, essentially of multidisciplinary approach. Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp)

Hyaline fibromatosis syndrome (HFS) is the unifying term for infantile systemic hyalinosis and juvenile hyaline fibromatosis. HFS is a rare autosomal recessive disorder of the connective tissue caused by mutations in the gene for anthrax toxin receptor-2 (ANTXR2). It is characterized by abnormal growth of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. We reviewed the 84 published cases and their molecular findings, aiming to gain insight into the clinical features, prognostic factors, and phenotype-genotype correlations. Extreme pain at minimal handling in a newborn is the presentation pattern most frequently seen in grade 4 patients (life-limiting disease). Gingival hypertrophy and subcutaneous nodules are some of the disease hallmarks. Though painful joint stiffness and contractures are almost universal, weakness and hypotonia may also be present. Causes of death are intractable diarrhea, recurrent infections, and organ failure. Median age of death of grade 4 cases is 15.0 months (p25-p75: 9.5-24.0). This review provides evidence to reinforce the previous hypothesis that missense mutations in exons 1-12 and mutations leading to a premature stop codon lead to the severe form of the disease, while missense pathogenic variants in exons 13-17 lead to the mild form of the disease. Multidisciplinary team approach is recommended.

International audience; GATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder.

Tooth resorption (TR) is one of the most common dental diseases in cats. Determination of risk factors has not yet been fully assessed and, to the best knowledge of the authors, this disease has never been studied in Portuguese cats. The objective of this case-control study was to determine type and distribution of TR lesions, evaluate risk factors, and establish relationships between variables in this disease. The study included data from 71 cats admitted for general anesthesia for various reasons. The cats were randomly selected. The inclusion criteria were availability of clinical history and owner permission. Cats with known oral disease were not excluded from the study. All cats received ultrasonic scaling and polishing of the teeth, a thorough oral examination, and full-mouth radiographs. A strong statistical relation was found between age and TR. The age group of 10 to 15-years showed an increased risk of 6.56 times for TR occurrence compared with the group 0 to 4-years of age. Presence of gingivitis in all index levels was related to an increased risk for TR. No relation was found between age or gingivitis index and lesion type. Mandibular third premolar and molar teeth were most commonly affected by TR, especially for type 1 lesions. Canine teeth were statistically more likely to have type 2 lesions. The trend for the canine teeth to be more affected with type 2 lesions needs further verification.

Mucolipidosis II (MLII) is a severe systemic genetic disorder caused by defects in mannose 6-phosphate-dependent targeting of multiple lysosomal hydrolases and subsequent lysosomal accumulation of non-degraded material. MLII patients exhibit marked facial coarseness and gingival overgrowth soon after birth, accompanied with delayed tooth eruption and dental infections. To examine the pathomechanisms of early craniofacial and dental abnormalities, we analyzed mice with an MLII patient mutation that mimic the clinical and biochemical symptoms of MLII patients. The mouse data were compared with clinical and histological data of gingiva and teeth from MLII patients. Here, we report that progressive thickening and porosity of calvarial and mandibular bones, accompanied by elevated bone loss due to 2-fold higher number of osteoclasts cause the characteristic craniofacial phenotype in MLII. The analysis of postnatal tooth development by microcomputed tomography imaging and histology revealed normal dentin and enamel formation, and increased cementum thickness accompanied with accumulation of storage material in cementoblasts of MLII mice. Massive accumulation of storage material in subepithelial cells as well as disorganization of collagen fibrils led to gingival hypertrophy. Electron and immunofluorescence microscopy, together with (35)S-sulfate incorporation experiments revealed the accumulation of non-degraded material, non-esterified cholesterol and glycosaminoglycans in gingival fibroblasts, which was accompanied by missorting of various lysosomal proteins (α-fucosidase 1, cathepsin L and Z, Npc2, α-l-iduronidase). Our study shows that MLII mice closely mimic the craniofacial and dental phenotype of MLII patients and reveals the critical role of mannose 6-phosphate-dependent targeting of lysosomal proteins for alveolar bone, cementum and gingiva homeostasis.

OBJECTIVE: To identify the risk factors for periodontal changes in adult patients during orthodontic treatment by evaluating the periodontal status of banded second molars using the gingival index (GI). MATERIAL AND METHODS: The sample consisted of 100 adult patients divided into two groups: the Orthodontics group, undergoing corrective treatment with fixed appliances and bands cemented to the four second molars, and the Control group, with no prior history of orthodontic treatment, age and sex matched. Group GI values were compared using the Wilcoxon test. Additionally, a multivariate logistic regression was performed to study the risk factors for increases in the GI. RESULTS: Individuals in the Orthodontics group showed a significantly higher GI than those in the Control group. Logistic regression revealed that among the risk factors found to increase GI, the following proved significant (in order of importance): plaque index, subgingival encroachment of the cervical margins of bands, probing depth, and length of orthodontic treatment. CONCLUSIONS: Banded second molars of adult patients during orthodontic treatment showed more clinical signs of gingival inflammation than those of untreated individuals. Moreover, major risk factors identified included the presence of plaque and the presence of subgingival band margins.

We studied morphological changes at the maxillary first molar in a model rat for type 2 spontaneous diabetes mellitus (DM), the Goto-Kazizaki (GK) rat, vs. the normal 8-week-old Wistar rat. Serial frontal sections of the gingiva of the maxilla with the bone were prepared from the rats. Image analyses, performed on light micrographs of the hematoxylin-eosin stained specimens, allowed comparison of the thickness of the keratinized, granular, prickle, and basal layers. In addition, the cell population of the granular and prickle layers and the cross-sectional area of the connective tissue beneath the mucosal epithelium were examined. The thickness of the capillary of the maxillary first molar was determined by image analysis of scanning electron micrographs of microvascular corrosion cast specimens. We found that the thickness of the keratinized, granular, and prickle layers was significantly higher in the DM vs. normal group, as were the cell population of the granular and prickle layers. In contrast, the cross-sectional area of the connective tissue beneath the mucosal epithelium, and the thickness of the capillary were significantly lower in the DM vs. normal sections. Therefore, we consider that the DM-associated hyperglycemia causes hypertrophy of the mucosal epithelium, atrophy of the connective tissue beneath the mucosal epithelium, and micro-angiopathy of the capillary of the palatal gingiva of the maxillary first molar in the GK rat.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal-recessive hereditary disease, characterized by gingival hypertrophy, flexion contractures of joints, bone lesions, hyaline deposition in the extracellular spaces of the dermis and soft tissues, stunted growth, and skin lesions such as multiple nodules, tumors and pink, pearly papules. No case of JHF with a mandibular bone involvement, exists in the literature. Bone involvement in JHF is an uncommon finding and distinct solitary lesions in the calvarial bones has been reported by some authors. A 21-year-old male patient was referred to Diyarbakir Military Hospital, Department of Dental Service. Clinical findings were consistent with a solid alveolar mass in the right mandibular premolar-molar region and displaced right mandibular molar teeth. Orthopantomographic examination showed impaction of all lower right molars in a mixed radioopaque/radiolucent area. Microscopically, increased nodular connective tissue was seen under the lobulated mucosal surfaces of the resected area. The case presented here had a localized fibrous proliferation that infiltrated bone trabeculae and caused displacement of teeth. Juvenile hyaline fibromatosis should be considered in the differential diagnosis with the other intraosseous radiolucent-patchy opaque lesions of jaw bones. Based on the clinical and histopathological findings, a diagnosis of JHF was made.

Between 1978 and 1980, 45 cases of acute monoblastic leukaemia have been diagnosed, treated and followed in our institute. Morphological diagnosis was performed according to the French-American-British classification. Tumoral syndrome (particularly extra-medullary) and hyperleucocytosis were the most striking findings at the time of diagnosis. Cytogenetic analysis performed in 31 cases before treatment has showed that abnormality of the long arm of chromosome 11 seemed to be more frequently associated with the poorly differentiated cytological subtype M5 (a). Intensive chemotherapy with zorubicin and cytosine arabinoside led to complete remission in 75% of the cases. Central nervous system prophylaxis appeared definitively useful in preventing meningeal relapse. Despite a prolongation of the median duration of complete remission which now reaches 12 months, the prognostic is still poor.

Purpose: The location of the gingival zenith in a medial-lateral position relative to the vertical tooth axis of the maxillary anterior teeth remains to be clearly defined. In addition, the apex of the free gingival margin of the lateral incisor teeth relative to the gingival zeniths of the adjacent proximal teeth remains undetermined. Therefore, this investigation evaluated two clinical parameters: (1) the gingival zenith position (GZP) from the vertical bisected midline (VBM) along the long axis of each individual maxillary anterior tooth; and (2) the gingival zenith level (GZL) of the lateral incisors in an apical-coronal direction relative to the gingival line joining the tangents of the GZP of the adjacent central incisor and canine teeth under healthy conditions. Materials and Methods: A total of 240 sites in 20 healthy patients (13 females, 7 males) with an average age of 27.7 years were evaluated. The inclusion patient criteria were absence of periodontal disease, gingival recession, or gingival hypertrophy as well as teeth without loss of interdental papillae, spacing, crowding, existing restorations, and incisal attrition. GZP dimensions were measured with calibrated digital calipers for each individual tooth and within each tooth group in a medial-lateral direction from the VBM. GZLs were measured in an apical-coronal direction from a tangent line drawn on the diagnostic casts from the GZPs of the adjacent teeth. Results: This study demonstrated that all central incisors displayed a distal GZP from the VBM, with a mean average of 1 mm. Lateral incisors showed a deviation of the gingival zenith by a mean of 0.4 mm. In 97.5% of the canine population, the GZP was centralized along the long axis of the canine. The mean distance of the contour of the gingival margin in an apical-coronal direction of the lateral incisors (GZL) relative to gingival line joining the tangent of the adjacent central and canine GZPs was approximately 1 mm. Conclusion: This investigation revealed a GZP mean value of 1 mm distal from the VBM for the central incisor tooth group. The lateral incisors showed a mean average of 0.4 mm. Thecanine tooth group demonstrated almost no deviations of the GZP from the VBM. The GZL of the lateral incisors relative to the adjacent central incisor and canine teeth were more coronal by approximately 1 mm. These data could be used as reference points during esthetic anterior oral rehabilitation. CLINICAL SIGNIFICANCE The information presented in this article can be clinically applied to reestablish the proper intratooth GZPs of the maxillary anterior teeth during periodontal crown lengthening or root coverage procedures. In addition, the intra-arch gingival level of the lateral incisor gingival zenith relative to the adjacent central and canine teeth can be appropriately established.

An immunoperoxidase technique was used to compare the number of CD1a+ and factor XIIIa+ dendritic cells (DCs), and CD68+ Macrophages (M) in 30 gingival samples from subjects with clinically healthy periodontitium (HP) and 10 samples from subjects with drug-induced gingival enlargement (DIGE). Fewer CD1a+ and factor XIIIa+ DCs were found in areas with inflammatory infiltration (II) of the lamina propria (LP) in the group with immunosuppressed DIGE (IDIGE) compared to the group with HP. In the sulcular and junctional/pocket epithelia, the number of CD1a+ DCs was decreased in the group with IDIGE (p < 0.05). There was a tendency toward a reduced number of CD1a+ DCs and CD68+ M in areas without inflammatory infiltrate of the LP in the group with IDIGE. The alterations in the number of antigen-presenting cells (APCs) may be the reason for the decreased periodontal inflammation and breakdown clinically observed in subjects who are immunosuppressed.

The Central Institute for Stomatology and Maxillo-facial Surgery in Moscow is one the main centers for the treatment of pediatric head and neck tumors in the territory of the former Soviet Union. A series of 33 patients presenting with cherubism (24 children and 9 of their parents) is presented. The authors discuss the atypical clinical presentations, the relevant associated anomalies and the different treatment strategies. They report the first case of cherubism associated with gingival hypertrophy without neurological signs.

AIM: To compare undisturbed plaque formation on teeth bonded with different types of orthodontic brackets with non-bonded control teeth, via a de novo plaque growth experiment over a 7-day period. MATERIAL AND METHODS: A randomized controlled trial with split-mouth design was set up enroling 16 dental students. Within each subject sites with Speed(S) and GAC(G), brackets and control sites were followed. Clinical periodontal parameters were recorded at baseline, on days 3 and 7. Microbiological samples were taken from the brackets and the teeth on days 3 and 7. RESULTS: Both anaerobe and aerobe colony-forming units (CFU) were significantly higher in S-sites than in G-sites (p=0.0002, p=0.02). The shift from aerobic to anaerobic species was observed earlier in S-sites than in G-sites. The aerobe/anaerobe CFU ratio was significantly lower in S-sites than in G-sites (p=0.01). On day 3, the crevicular fluid flow was significantly higher in S-sites than in control sites (p=0.01). On day 7, S-sites and G-sites showed a significantly higher crevicular flow than control sites (both p

Gum hypertrophy is a well-known and important adverse effect of phenytoin therapy in a neurosurgical patient. We present an interesting case of a 21-year-old man who, following head injury after a road traffic accident, developed status epilepticus diagnosed with gum hypertrophy in the jaws, with ongoing antiepileptics. He was managed conservatively as per hospital protocol.

Mucolipidosis type II (ML II, OMIM 252,500) is an autosomal recessive disorder clinically characterized by facial dysmorphia similar to Hurler syndrome and pronounced gingival hypertrophy. The disorder is caused by a defect in targeting acid hydrolases on the surface of lysosomes, which impede their entry and lead to accumulation of undigested substrates in lysosomes. The onset of the symptoms is usually in infancy, beginning in the 6th month of life. Early onset, at birth or even in utero, is a sign of severity and involves the specific dysmorphia as well as skeletal dysplasia related to hyperparathyroidism. We report on a severe neonatal form of this disorder revealed by respiratory distress with severe chest deformity. The dysmorphic syndrome, combining coarse features, pronounced gingival hypertrophy, with diffuse bone demineralization and secondary hyperparathyroidism associating significant elevation of parathyroid hormone and alkaline phosphatase with normal levels of vitamin D and calcium were characteristics of mucolipidosis type II. Recognizing this specific association of anomalies helps eliminate the differential diagnosis and establish appropriate diagnosis and care.

The authors present their own experience regarding the detection of hemopathies based upon the alterations of oral and tongue mucosae. The blood test confirmed the suspicion of hemopathy.

Lymphoblastic lymphoma-leukemia (LBLL) most commonly presents with mediastinal masses (50-75%), while pleural and pericardial effusion may also be present. Lymphadenopathy usually in the neck, axilla or supraclavicular regions, is considered as another typical presentation of the disease. This is a case report of a six-year-old boy with unusual huge enlargement of maxilla, mandible and soft palate as well as gingival hypertrophy which led to secondary respiratory and feeding difficulties. Morphologic and flowcytometric evaluation of bone marrow aspiration showed that it was a T cell type acute leukemia which may be due to dissemination of a lymphoblastic lymphoma and considered as a case of lymphoma-leukemia. After appropriate treatment, the symptoms of the patient relieved significantly and he is in complete remission for about one year.

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3-15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C(IN)). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m(2) twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9+/-4.8 to 119.9+/-5.9 mL/1.73 m(2) per min (P0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26-2.94] mg/kg/d pre-MMF to 0.29 [0-1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.

The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects.In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake.Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P0.01), although CsA doses and concentrations were not different between these two groups.We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.

We evaluated the frequency and prognostic significance of extramedullary infiltrates (EMI) at presentation of acute myeloid leukemia (AML) in adult patients. Of 331 cases with de novo AML, 101(30.5%) had extramedullary infiltrates at diagnosis. The extramedullary manifestations included: lymphadenopathy, splenomegaly, hepatomegaly, gingival hypertrophy, skin infiltrates and involvement of central nervous system (CNS). Patients with EMI had a high initial WBC count and a high proportion of M4/M5 morphological variants. The complete remission rate (CR) with induction chemotherapy was lower in patients with EMI (P=0.0077) and their overall survival was also inferior (P=0.0017). Flow cytometric evaluation of the surface antigens expressed by the leukemic blasts for CD34, TdT, HLADR, CD7, CD19 and CD56 found that only CD56 expression was associated with EMI. The association of CD56 expression with lymphadenopathy was statistically significant (P=0.035). Abnormal karyotypes were found in 50.6% of patients with EMI and 49.7% of patients without EMI. Only 11q23 abnormalities were associated with specific sites of EMI; lymphadenopathy (P=0.0111) and gingival hypertrophy (P=0.0016). Our study of adult AML patients demonstrates that EMI at diagnosis is associated with CD56 expression by leukemic blasts, 11q23 karyotypic abnormalities, low complete remission rate and poor overall survival.

BACKGROUND: Infantile systemic hyalinosis is a rare genetic disorder which involves accumulation of hyaline in the skin, bones, mucous membranes, and occasionally, also in internal organs. The major manifestations include painful articular contractures, cutaneous lesions (hyperpig-mentation, subcutaneous nodules), malnutrition resulting from diarrhoea, gingival, labial and buccal hypertrophy. CASE REPORT: The phenotype characteristics of infantile systemic hyalinosis (ISH) in a two year old boy were present. The characteristics of flattered occiput, limited limb movements and articular abnormalities of elbows and knees. Dental findings showed excessive gingival hypertrophy completely covering maxilary and mandibular teeth treatment. The gingival hypertrophy was surgically treated by gingivectomy under general anaesthesia. FOLLOW-UP: The patient showed a full constellation of clinical manifestations of the disease. Despite the surgical intervention no improvement in oral hygiene was observed. CONCLUSIONS: Surgical treatment of the gingival hypertrophy was the treatment of choice.

Human multipotent mesenchymal stromal cells (hMSCs) produce tumor necrosis factor (TNF)-α-stimulated protein 6 (TSG-6). TSG-6 modulates proinflammatory cytokine cascades and enhances tissue repair. This study tests the effects of recombinant human TSG-6 (rhTSG-6) on gingival wound healing within the first 2 days post-surgery.After gingival resection in 120 Sprague-Dawley rats, 2 µg rhTSG-6 in 5-µL phosphate-buffered saline (PBS) or the same volume of only PBS solution was injected into gingival tissue approximating the surgical wound. Control animals did not receive injections. Tissue biopsies and blood were collected at 1 to 2, 6 to 8, 24, and 48 hours post-surgery (n = 10 per group). Specimens were analyzed via histologic analysis and enzyme-linked immunosorbent assay (ELISA) for quantification and comparison of inflammatory markers interleukin (IL)-1β, IL-6, TNF-α, and myeloperoxidase (MPO). Wound photographs were taken for a double-masked clinical assessment at each time period. Weights were recorded for all animals pre- and post-surgery.Animals injected with rhTSG-6 had significantly less severe clinical inflammation at 6 to 8 (P = 0.01228), 24 (P = 0.01675), and 48 (P = 0.0186) hours. Sham and control animals had more weight loss at 24 and 48 hours. Sham and control animals had more pronounced cellular infiltrate. rhTSG-6-treated animals had significantly less MPO (P = 0.027) at 24 hours and IL-1β (P = 0.027) at 24 and 48 hours. IL-6 showed a marginal significant difference at 6 to 8 hours, but there was no significant difference for TNF-α.rhTSG-6 reduced postoperative gingival inflammation by reducing levels of proinflammatory cytokines and cellular infiltrate and may offer significant promise as an anti-inflammatory agent for gingival surgery.

In the present immunohistochemical study, the expression of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 in the gingival tissues of renal transplant patients treated with cyclosporin A was assessed. Gingival overgrowth (GO) frequently occurs in transplant patients receiving immunosuppressive drugs such as cyclosporine and this gingival inflammation might play an important role in the pathogenesis of drug-induced GO.Twenty-eight human gingival biopsies were taken from healthy patients with chronic periodontitis (N.=14 control group), and from renal transplant recipients treated with cyclosporin A (N.=14 test group). The retrieved specimens were immunohistochemically processed and stained for vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67.The levels of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 were found to be significantly different among groups (P0.001), with patients treated with cyclosporin A showing higher levels of all the analyzed markers compared to control group.In summary, the data from this pilot study suggests that the investigated factors have a role in the inflammation processes associated to immunosuppressive therapy. However, further studies with a larger sample population need to be conducted for an exhaustive knowledge of the mechanisms leading to GO.

One hundred percent of adult patients with chronic renal failure (CRF) develop cutaneous findings as a result of uremia or due to therapeutic interventions. To date, pediatric incidence studies have been limited to Caucasian children. However, recent reports have indicated that more African American patients progress to end-stage renal disease (ESRD). This is the first study to assess the prevalence of renal failure-related skin disease in children of color, including African American and Hispanic patients. Thirty children were evaluated by history and physical examination, with assignment to one of three treatment categories: transplanted (n = 10), dialyzed (n = 16), or medically managed (n = 4). Skin findings were divided into uremic, drug-related, or infectious disease types. The incidence of skin disease was 100%. Xerosis was the single most common finding, often accompanied by pruritus. Cushinoid features were common despite the addition of steroid-sparing agents. Cyclosporin A-treated African American children had a high incidence of gingival hypertrophy (72%) and an even higher incidence of hypertrichosis (100%). Acral warts and nevi were common findings, the latter correlating with the length of immunosuppression. There is a high incidence of cosmetically disfiguring side effects (Cushinoid facies, hypertrichosis, and gingival hypertrophy) in children within all treatment categories, primarily related to drug treatment. Further study is required to determine the long-term sequelae, including psychological disturbances, of cutaneous disease in children of color with CRF.

The juvenile hyaline fibromatosis (JHF) is a rare tumorous autosomal recessive disease of the connective tissue. The etiopathogenesis of the disease is unknown. Typical diagnostic criteria are multiple hyaline subcutaneous fibroma, filamentous tumors of the skin, gingival hypertrophy, muscle contractures of the extremities and multiple osteolytic bone destructions. Involvement of visceral organs is not described. Mental development and life expectancy are normal. Until today, no causal treatment of the JHF exists. Surgical excision of the dermal tumors is indicated for functional and aesthetic improvement. Complete excision should be executed in the early phase of their development. This has shown the best functional and aesthetic results, especially in facial areas. The progress of the disease is individual. Due to frequent recurrencies, repeated resections and revisions may be necessary. Interdisciplinal counseling and therapy, particularly physiotherapy, may partially improve the state of function.

Gingival enlargement is a common form of periodontal tissue reaction to several irritating factors. The most common form is the drug related gingival hyperplasia--nevertheless the heredity gingival fibromatosis and hematological cases can also occur and might impose a challenge to periodontists. After a short literature summary three Case reports are presented. The first case is a drug related gingival overgrowth in a young kidney transplant women who took Cyclosporin-A. The excessive mass of fibrotic tissue was removed by a series of internal beveled incision and the oral and buccal gingival flaps were united with sutures. The healing was uneventful and during the follow up patient's compliance and oral hygiene was superb. The second case is a very severe antihypertensive drug related gingival overgrowth in a 62 years old man interfering with the closure of his lip and corrected with a combination of conventional gingivectomy and internal reverse beveled incision both and Ca-channel blockers. The third case is a 42 years old woman with chronic idiopathic hemolytic anemia who presented a sudden onset acute excessive generalized gingival enlargement accompanied with severe pain and fever. At admission she was suspect for leukemia. After obtaining biopsy samples and having negative histology the soft tissue mass was removed under general anesthesia with conventional gingivectomy technique, but after a couple of days the severe pain and gingival swelling recurred. With administering systemic corticosteroid therapy (32 mg Medrol), the gingiva healed in five days and the one year follow-up showed a stable hematological and periodontal status. Today the more conservative internal beveled incision is preferred over the conventional gingivectomy in the most cases because it provides a more predictable healing and better esthetics. The recurrence of the drug related gingival hyperplasia can be anticipated by meticulous postoperative individual oral hygiene and regular supportive therapy.The combined conservative and surgical therapy leads to predictable postoperative result even in very severe systematically motivated gingival enlargements, nevertheless the successful patients management needs good cooperation with medical doctors and with the patients themselves.

The aim of the present study was to highlight the relationship between the level of oral hygiene and the context in which the patient receives dental treatment, demonstrating that home service is essential and effective to decrease the incidence of periodontal diseases.The study was initially conducted on a heterogeneous sample of patients including 48 individuals with psycho-motor deficits. The study included 28 males (58.3%) and 20 females (41.7%) aged between 18 and 50 years, coming from two different sites ("Fa.Di.Vi… e oltre" and "Dentistry Unit, Istituto G. Gaslini" in Genoa). The patients were evaluated during the period 2008-2009. After this first pilot study, a clinical trial was conducted within the educational center "Il Granello", with the participation of 20 patients with disabilities.This study demonstrates that home assistance is essential and effective to decrease the incidence of those periodontal diseases induced by bacterial dental plaque accumulation, and associated with aggravating factors like the repeated use of drugs, such as benzodiazepines, phenylhydantoin, and cyclosporin A, that cause gingival hypertrophia.This study was proposed to demonstrate that the availability of a dental service within institutions could improve not only the dental-periodontal conditions of the participants, but also decrease the admission of these subjects to hospitals, contributing to the reduction of public expenditure by the Health Care System.

The aim of this study is to evaluate gingival collagen for the effect of treatment with the Erbium:YAG Kesler handpiece. The handpiece is designed for gingival resurfacing in cases of hypertrophic gingiva and gingival pigmentation.Lasers represent recent technological advances that afford new options for the treatment of periodontal diseases. However, lasers used for esthetic gingival soft tissue resurfacing require careful histopathological evaluation of the effects on tissue. In particular, it is important to determine the effect of laser irradiation on connective tissue, especially the collagen fibers. To date, no stage-wise clinical or histological studies have been performed addressing this issue.Ten patients underwent irradiation with the following parameters: energy per pulse, 500 mJ; repetition rate, 10 pps; spot size, 3 mm. Gingival biopsy specimens were derived from 6 patients with hypertrophic gingiva and 4 with gingival pigmentation. The patients were examined before laser treatment and at 7 and 14 days after laser treatment. The tissues were fixed in tymph node revealing solution (LNRS), embedded in paraffin, sectioned at 5 microm, and stained with hematoxylineosin. The status of collagen in the treatment site was examined under polarized light after picrosirius red (PSR) staining. PSR is a collagen stain that differentiates collagen fiber density or size by means of a spectrum of color changes under polarized light. The major colors are red, orange, yellow, and green.We found a significant difference in the properties of collagen fibers at the first week and at 14 days post-treatment. In the normal gingiva, the predominant polarization colors were in the red-orange range, signifying tightly packed, mature collagen. During the first postoperative week, collagen fibers exhibited polarization colors in the green to green-yellow range, implying loosely packed collagen fibers. After 2 weeks, collagen fibers reacquired their preoperative PSR characteristics.We conclude that sequential series of changes accompany photothermal treatment of the gingiva. The occurrence of this sequence in all successful outcome cases may suggest the importance of these temporally sequenced changes in collagen during gum healing. In any event, the status of PSR staining of gum collagen provides a useful adjunct in the assessment of gingival health.

Juvenile hyaline fibromatosis is a rare autosomal recessive disease of the connective tissue. We present the case of a 6-year-old normal mental developed boy with confluent pearly papules behind the ears and in the paranasal folds, firm nodules of the scalp, the back and metaphalangs, and severe gingival hypertrophy.

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.

Infantile systemic hyalinosis is an autosomal recessive disease characterized by severe progressive flexion contractures, multiple recurring subcutaneous tumours, and gingival hypertrophy. It is caused by mutations in the gene encoding capillary morphogenesis protein-2 (CMG2). Here we report a Saudi infant with infantile systemic hyalinosis who presented with intractable diarrhea, and we review the literature emphasizing recent developments in the molecular genetics of this disease.

Mowat-Wilson syndrome is a genetic disease characterized by typical facial features, Hirschsprung disease and multiple congenital abnormalities. MWS is a single gene disorder. One of the most specific clinical signs in MWS is the distinctive face. We report a two-year-old boy with multiple congenital anomalies. He had peripupillary atrophy and gingival hypertrophy different from the literature. The patient was also diagnosed with his clinical findings. These features may be important in Mowat-Wilson syndrome and clinicians should keep these findings in mind.

A 5-year-old male child, diagnosed as having initial steroid-resistant nephrotic syndrome, was administered oral cyclosporine (5 mg/kg/day) along with alternate-day prednisolone. He developed severe lip and gingival hypertrophy, had difficulty in lip closure and his gingiva was visible through the lips at rest (Fig. 1). As the child attained only partial remission after 12 weeks of cyclosporine therapy, his medication was changed to tacrolimus. The lip hypertrophy decreased within 10 weeks of tacrolimus therapy, he was able to close his lips as the gingival hypertrophy also decreased and he achieved complete remission (Fig. 2). Gingival hypertrophy is a well-known side-effect of cyclosporine therapy; however, lip hypertrophy is a rarely noted side-effect [1]. Histopathological examination of the hypertrophied lip showed inflammatory papillary hyperplasia with focal ulceration and plasma cell infiltration. It has been reported that cyclosporine affects signaling molecules in fibroblasts differently from other cell types, and an increase in AP-1 transcription factor activity may affect the expression of fibrogenic molecules in gingiva and promote gingival overgrowth [2]. Tacrolimus has lesser incidence and severity of hirsutism, gingivitis, and gingival hyperplasia as compared to cyclosporine [3]. Azithromycin can also reduce cyclosporine-induced lip and gingival hypertrophy [4]. In rare cases surgical reduction may be required. Clinicians using cyclosporine should be aware of lip hypertrophy and its management.

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.

To compare the current (t1) periodontal status of post-liver transplantation patients to their status 10 years earlier (t0).Seventeen patients 45 to 71 years of age who were evaluated approximately 10 years previously were enrolled in the study. All subjects had undergone a liver transplantation 1 to 10 years prior to the initial examination (t0). Clinical and radiographic parameters were recorded for the Ramfjord Index teeth and compared between t0 and t1, including Plaque Index (PI), Gingival Index (GI), probing depth (PD), clinical attachment level (CAL), and gingival overgrowth (GO). Bone loss was measured on digitized images of panoramic radiographs.Mean PI, GI, CAL, and GO were slightly lower at t1 than at t0; however, these differences were not statistically significant (P.05, Student t test for paired observations). The mean PD was reduced at t1 (2.43 ± 0.18 mm) compared with t0 (3.35 ± 0.22 mm), which was statistically significant (P = .001, Student t test for paired observations). To the contrary, the mean radiographic bone loss at t1 was higher than at t0 (5.61 vs 4.48 mm, respectively), which was also statistically significant (P = .017). Tooth loss was observed in some of these patients, ranging from 0 to 4 during the 10 years of follow-up, which amounted to an annual rate of 0.24 teeth per patient.Post-liver transplantation patients maintained stable clinical periodontal parameters during a 10-year period; however, some radiographic bone loss occurred during this time.

Primary extra-nodal non-Hodgkin's lymphomas (NHL) constitute 25-40% of NHL but less than 1% arises in oral cavity. Here in 53-year-old man with stage IE gingival diffuse large B cell lymphoma who was treated successfully with chemotherapy and radiotherapy was presented.