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Massimo Petruzzi
Ruolo
Professore Associato
Organizzazione
Università degli Studi di Bari Aldo Moro
Dipartimento
DIPARTIMENTO INTERDISCIPLINARE DI MEDICINA (DIM)
Area Scientifica
AREA 06 - Scienze mediche
Settore Scientifico Disciplinare
MED/28 - Malattie Odontostomatologiche
Settore ERC 1° livello
Non Disponibile
Settore ERC 2° livello
Non Disponibile
Settore ERC 3° livello
Non Disponibile
Burning mouth syndrome (BMS) is characterised by the presence of a burning sensation in the oral mucosa in the absence of any clinically apparent mucosal sign. It occurs more commonly in older women and often affects the tongue tip and lateral borders, lips, and hard and soft palates. Besides the burning sensation, patients with BMS may complain of unremitting oral mucosal pain, dysgeusia, and xerostomia. The exact pathophysiology of primary BMS remains unknown. A major challenge for the clinician is the treatment of BMS: identifying possible causative factors is the first step, but BMS is often idiopathic. Drug therapy, in addition to behavioural therapy and psychotherapy, may help to eliminate the symptoms. Considering the growing incidence of BMS in older people, further research is required to determine the true efficacy of current management strategies for patients with this disorder.
Previous studies have demonstrated that patients affected by Oral Lichen Plauns (OLP) show lower levels of salivary fibronectin when compared with normal control group. Similarly, tissutal fibronectin expression is lost in epidermal basal layer and papillary dermis of OLP patients. To date, no data exist about the potential role of Plasma Fibronectin(PFn) in OLP pathogenesis, diagnosis and treatment. Objectives of the present study are: a) to determine the PFn levels in OLP patients b) to evaluate a possible association between OLP clinical form and PFn levels c) to determine the PFn levels in relation to OLP signs and symptoms treatment. Twenty consecutive patients affected by OLP were enrolled. All patients were treated for eight weeks with topical clobetasol 0.05%. OLP signs and symptoms were scored before and after treatment. PFn level was determined by a nephelometric system. OLP signs and symptoms significantly improved after treatment. The mean levels of PFn were 31.84mg/dL at the beginning and 26.76mg/dL at the end of the study. The difference was not statistically significant (p=0.60). PFn in OLP patients remains in normal value range. OLP clinical form does not influence the PFn levels. Amelioration of symptoms and signs of atrophic-erosive and reticular OLP are induced by clobetasol treatment and the PFn seems not to interfere in the healing processes induced by topical corticosteroid. In contrast to what is observed in traumatic or diabetic wound healing, levels of PFn do not promote OLP lesions healing. PFn is not to be considered as a marker of OLP disease activity and its role in OLP pathogenesis remains still unclear.
The apical portion of the implant osteotomy receives less irrigation and cooling during surgical preparation. High bone temperatures, above the critical 10°C threshold, may impair osseointegration, particularly, around dense cortical bone. The aim of this study is to evaluate the apical cortical plate temperature increase with two different devices and pressure loads in a porcine rib ex-vivo model.
The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P=0.002), duration of mucositis (P=0.003) and the average grade of mucositis (P=0.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.
The clinical management of OLP represents a considerable challenge for the oral physician. The aim of this review is to assess the main intervention used in the management of OLP and the efficacy of every type of treatment.
Objective: The aim of this prospective controlled study is the comparison between long-term children survived leukaemia and a control group in terms of the decayed, missing or filled permanent teeth (DMFT) and dental anomalies. Study design: Fifty-two long term children survived leukaemia, aged from 8 to 15 years (27 females, 25 males; mean age 11.5 years) were evaluated for the possible effects of the anti-leukaemic therapy on dental development and compared to a control group of 52 healthy children (27 females, 25 males, mean age 11 years). All long-term children who survived were at least 24 months in continuous complete remission. The study of the dental status with a routine oral examination and panoramic radiographs was performed. The DMFT (recorded according to the WHO criteria) and dental anomalies were registered and evaluated. Results: The results of this study evidence that long-term children survived leukaemia, in comparison with the control group, have an higher risk to develop dental caries and show a greater severity of dental anomalies including V-shaped roots, dental agenesis, microdontia, enamel dysplasias. Conclusions: Paediatric patients with haemathological diseases require a special attentions in dental care in addition to the antineoplastic treatment. Therefore, oral hygiene and oral health can be maintained thanks to a close cooperation between the paediatric oncohaematologists, pediatrics dental surgeons and dental hygienists.
Upper incisors are the most frequently involved teeth in traumatic dental injuries. Soft tissues (lips and/or oral mucosa) adjacent to incisal edge can receive direct and/or indirect traumas. Laceration of the lower lip is a not rare eventuality and teeth fragments could be embedded in labial soft tissue. The reattachment of these fragments, if possible, is the elective treatment choice, thanks to the modern adhesive and restorative techniques. The authors present a case of a white Caucasian 10-year-old child, who attended the dental clinic for the treatment of both upper central incisors’ crown fractures. The fragment of the left incisor was retrieved embedded in the lower lip. It was successfully surgically removed and reattached using a composite adhesive technique. A careful clinical and radiographic examination with the surgical removal of tooth fragments could prevent undesirable foreign body reaction, infection and scarring. The authors also reviewed the most relevant literature concerning tooth fragment reattachment after removal from oral soft tissues.
BACKGROUND: Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. STUDY DESIGN: Prospective multinational cohort. SETTING & PARTICIPANTS: 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). PREDICTORS: Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. OUTCOMES: All-cause and cardiovascular mortality at 12 months after dental assessment. MEASUREMENTS: Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. LIMITATIONS: Convenience sample of clinics. CONCLUSIONS: In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival.
To compare the results of psychometric tests in patients with BMS and controls, participants were tested for depression, anxiety, fatigue and distress. Patients with BMS had noticeably higher scores for depression, fatigue and distress, compared to controls. Depression and distress were significantly correlated with the burning symptom. Moreover, distress and burning symptoms proved to be interdependent. Depression seems to play a specific role in BMS. Burning symptoms affect quality of life of patients and they could be a predictor of distress.
Using proteome databases and exploiting the concept that a rare sequence is a potential epitope, epitopic sequences derived from Porphyromonas gingivalis fimA type I protein were examined for pentapeptide sequence similarity score to the human proteome. We obtained data showing that most of the linear bacterial determinants are (or are formed by) peptide fragment(s) absent (or rarely found) in the human proteins. These results seem to confirm the hypothesis that low-sequence similarity may contribute to shape the epitope repertoire and provides a potential tool for designing new immunotherapeutic approaches to apply in Porphyromonas gingivalis infected periodontitis
Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre-MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders.
The objective was to compare toluidine blue (TB) and autofluorescence (AF) for the detection of oral dysplasia and squamous cell carcinoma (OSCC) in clinically suspicious lesions according to conventional examination. Fifty-six clinically suspicious lesions were subjected to AF and TB examination. Data were compared using two different scenarios: in the first, mild dysplasia was considered as positive, while in the second, it was considered as negative. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), accuracy, and concordance were calculated. AF sensitivity and specificity were 70.0 and 57.7%, respectively, while TB showed a sensitivity of 80% and a specificity of 61.5%. The sensitivity increased in the second scenario in both AF (76.5%) and TB (88.2%). The specificity decreased in AF and TB, showing the same value (51.3%). PPV was higher in TB than in AF (70.6 versus 65.6%) and similarly for NPV (72.7 versus 62.5%). In the second scenario, TB PPV was 44.1% and NPV was 90.9%; AF PPV was 40.6% and NPV was 83.3%. TB showed greater accuracy than AF in the first scenario (62.5 versus 58.9%). AF and TB are both sensitive but not specific in OSCC and dysplasia diagnosis.
Objectives. Mucous Membrane Pemphigoid (MMP) is the clinical phenotype of a group of rare autoimmune blistering diseases characterized by autoantibodies directed against different structural proteins in epithelial basement membranes. Diagnoses of MMP is routinely verified by direct immunofluorescence (DIF) of oral mucosa biopsy tissue. ELISA detection of autoantibodies in serum is now employed for the diagnosis of pemphigoid and for monitoring the disease activity. The aim of this study was to evaluate ELISA sensitivity, specificity, PPV, NPV in oral MMP patients. Methods. Patients with oral lesions compatible with MMP, were enrolled. Two different specimens were obtained during the surgical biopsy: one for the histopathological assessment and the other for the DIF. ELISA plates, precoated with recombinant ectodomains of the epitope NC16a of the BP180 antigen and carboxy-terminal domains of BP230 antigen were used. All ELISAs were performed according to the manufacturer’s instructions. Values greater than 8,7 U/ml were considered positive. Histopathological and DIF results were considered as the gold standard. Global validation of the test results was established by calculating the sensitivity, specificity and both the positive and negative predictive values. Results. Sixty-four patients were enrolled (M:F=1:4). Ages ranged from 40 to 82 years (mean 61 years). There were 30 patients with MMP, 16 patients with OLP, 14 affected by PV, 3 lichenoid dysplasia and 1 erythema multiforme. ELISA sensitivity and specificity was respectively 47 and 79%. PPV percentage was 67% while NPV was 63%. Conclusions. In suspected oral MPP, both ELISA tests and histopathological + DIF have to be performed because of ELISA low sensitivity. Although BP180 and BP230 are the major target antigens in patients with MMP limited to the oral cavity, they are not the only. This aspect may explain the low sensitivity rate of ELISA in oral MMP when used as the sole diagnostic support.
This preliminary study aims to establish the Virtual Chromoendoscopic Magnification (VCM) feasibility to visualize and distinguish the Intraepithelial Papillary Capillary Loops (IPCL) patterns of benign oral pathologies from malignant ones. Thirty-one consecutive subjects affected by oral lesions/pathologies underwent white light examination and VCM imaging by the Narrow Band Imaging System (Olympus Medical Systems Corp., Tokyo, Japan). A class system of four IPCL types corresponding to progressive vessel disarray was adopted. IPCL type IV were considered criterion of malignancy. A histopathological exam completed the diagnosis: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. IPCL patterns of benign oral entities ranged from types I to III. IPCL type IV was associated with malignancy in 4 out of 6 cases. Sensitivity, specificity, PPV, and NPV were 100%, 93%, 67% and 100%, respectively. This study preliminarily describes IPCL patterns of different oral mucosal diseases and confirms the association between IPCL IV and oral cancer.
Diffuse-type giant cell tumour (DTGCT) is a benign but destructive proliferative disorder of the synovium of joint capsules, tendons and bursae. Lesions originating from the articular synovium may grow intra-articularly or expand widely extra-articularly. Rare cases may develop only in peri-articular tissues. Temporomandibular joint (TMJ) involvement is exceptional and only two cases of purely extra-articular TMJ-DTGCT have been reported. The authors report an additional case of extra-articular TMJ-DTGCT. The clinical features, histopathological characteristics, imaging modalities and diagnostic methods for DTGCT are discussed together with a literature review based on the clinical aspects of TMJ involvement.
Implant rehabilitation in oral lichen planus (OLP) is a major challenge for clinicians and patients. There is limited scientific evidence, primarily case reports and small case series. We conducted a literature review of data on the effectiveness and safety of implant rehabilitation in OLP patients. MATERIAL AND METHODS: We searched MEDLINE, Embase and Cochrane databases for articles on implant placement in OLP patients (searches from 1980 to 2011). RESULTS: Eight studies (41 OLP patients rehabilitated with 135 implants) met the inclusion criteria. Survival rate of implants was 94.8% over a mean follow-up of 56.5 months. CONCLUSIONS: There is very limited evidence on the safety and benefits of implant placement in OLP patients. Implant loss appears not to be directly related to OLP, but linked to factors such as parafunctions, poor bone quality and marginal mandibular resection. The benefits and harms of using implants in people with OLP require thorough evaluation in properly designed randomised, controlled studies. CLINICAL RELEVANCE: OLP is not an absolute contraindication for implant insertion and there is no increased risk of failure. Implants should be positioned only if mucosal signs and symptoms are in the remission phase. A careful oral hygiene and frequent follow-up are the main recommendations in OLP patients rehabilitated with implants.
To compare the performance, by scanning electron microscopic analysis, of the interface between tooth and four commercial restorative composite resins in Class I cavities following exposure to acidified artificial solution, pH 4.5, with a background electrolyte composition similar to saliva, 600 teeth were divided into 4 groups. The first group was treated with microfilled light-cured Heliomolar; the second group with Durafill; the third group with the microfilled self-cured Isomolar; and the fourth group was treated using the hybrid self-cured Miradapt. All teeth of each group were randomly divided into two sub-groups: A) a control group that was immersed in artificial saliva (pH 7); B) a study group that was immersed in artificial saliva acidified with phosphoric acid (pH 4.5) in order to obtain artificial caries. The samples were examined by scanning electron microscopy. Data were analyzed using Pearsons Chi-squared test (χ2) with R statistical software. The statistical analyses demonstrated significant differences in the two sub-groups A and B when considered for the light-cured composites whereas no difference was monitored for self-cured composites. Statistical analysis (p minore di 0.001) also demonstrated that the type of composite strongly influenced the infiltration grade. Our results demonstrate that incremental layering techniques might improve the marginal adaptation for light-cured composites, while self-cured show a marked polymerization contraction which can cause marginal breakdown.
Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.
Oral mucosal diseases in the clinical practice Oral mucosal evaluation is crucial in the routine dental visits. The identification of lesions (of different etiopathogenetic origin) is fundamental to initiate a proper diagnostic pathway and to perform a correct and early treatment (pharmacological and/or surgical). The diagnostic delay has medico-legal implications for the dentist and influences the clinical outcomes for the patient, including his quality of life. This article aims to discuss the main clinical aspects of oral mucosal diseases and their correlations with systemic health. Moreover, treatment strategies are provided according to the evidence based dentistry. Numerous clinical pictures are provided as support to the text.
Stem cells play a role in many mucosal disorders characterised by abnormal proliferation and differentiation of keratinocytes, such as oral lichen planus (OLP). In OLP there were changes in stem cell markers as component of integrin complexes α6 and β1 integrin increased along with increase of melanoma-associated chondroitin sulphate proteoglycan (MCSP) and decreased of notch1 (N1) and keratin 15 (K15). Stem cell marker expression may be altered by pathological signalling in these lesions. Cadherins are transmembrane receptors that provide cell-cell contact and communication function through calcium-dependent homophilic and heterophilic interactions. In actively diseased areas of OLP lesions, basal keratinocytes downregulate CD40 and were focally E-cadherin-negative, in contrast to non-diseased areas and normal oral mucosa. This loss of E-cadherin expression may contribute to epithelial basal cell destruction and T-cell migration into the epithelial compartment in OLP. In addition, Growth factor pathways as a role in OLP and has been analyzed in this review.
Candida albicans is a typical commensal microorganism of the oral cavity that can become virulent in certain conditions and cause denture stomatitis (DS). Many conditions can predispose for DS, including local and systemic alterations. The therapeutical approach to DS is various and both topical and systemic alternatives can be considered. Azoles molecules are the most common used, both topically and systemically, but in recent years various alternatives have been proposed. This review aims to examine the scientific literature to evaluate the effectiveness of conventional therapies and the potential of the new ones.
Oral mucous membrane pemphigoid (OMMP) is a rare inflammatory autoimmune mucocutaneous disorder. Oral mucosa is affected in 90% of cases. Its development is chronic, with a possible involvement of ocular, laryngeal and genital mucosa. Spontaneous remission is rare. Although the etiology of OMMP is still unclear, there is evidence that it is a complex autoimmune disease mediated by autoantibodies directed against different components of the basement membrane zone. Cellular immunity is also involved in the pathogenesis. Atrophic and erosive lesions are the sequelae of the rupture of the subepithelial blisters. The treatment is usually aimed at relieving pain and may include corticosteroids and immunosuppressive agents. However, the use of these drugs may be inefficacious. Oral hygiene and follow-up are mandatory for patients affected by OMMP. It is important to increase awareness of oral lesions in autoimmune blistering/erosive dermatologic conditions.
The enamel defects (EDs) may present with a variety of clinical manifestations with increasing severity from the sole appearance of pale discoloration to remarkable structural alterations. EDs are responsible for higher caries receptivity. In vivo reflectance confocal microscopy (RCM) allows to image in vivo at microscopic resolution of the dental surface, thus avoiding the tooth extraction and the sample preparation because of its ability to optically scan living tissues along their depth. Aim of this study is the in vivo assessment at microscopic resolution of dental surfaces affected by EDs without resorting to invasive methods such as teeth extractions, to define histological findings occurring in chromatic and/or structural EDs. For the purpose, 15 children, referring at the Dental Clinic of the Second University of Naples, affected by several degrees of EDs, were enrolled and underwent in vivo RCM imaging to microscopically define the ED confocal features using a commercially available hand-held reflectance confocal microscope with neither injuries nor discomfort. Totally, 29 teeth were imaged. Results demonstrated images good in quality and the capability to detect EDs such as unevenness, grooves, and lack of mineralization according to their clinical degree of disarray. The present in vivo microscopic study on EDs allowed to highlight structural changes in dental enamel at microscopic resolution in real-time and in a non-invasive way, with no need for extraction or processing the samples. Further experiments could define the responsiveness to remineralizing procedures as therapeutic treatments.
BACKGROUND: People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated.Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required.Methods/design: The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022. DISCUSSION: This large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease.
Background: The presence of atrophic-erosive lesions among gingival tissues makes oral hygiene procedures difficult for several reasons. Plaque control and rigorous oral hygiene are a fundamental requisite for the treatment of any oromucosal disease. Case report: A patient suffering from a mixed atrophicerosive form of oral lichen planus (OLP), with serious gingival involvement, was also treated with the topical application of clobetasol propionate 0.05% using gingival trays. The highest hygiene standards of both patient and trays were of fundamental importance. Discussion: The management of the patient suffering from gingival atrophic-erosive OLP requires the synergic treatment of both dentist and dental hygienist, whose contribution supports the corticosteroid and ⁄ or immunosuppressive treatment.
Oral lichen Planus (OLP) is a chronic inflammatory disease involving skin and mucous membranes. Its etiology is still uncertain whilst an autoimmune mechanism is known to be implicated. OLP is commonly considered a geriatric disease and gender differences in prevalence are clear, whereby females are generally more frequently affected than males more often during the 5th and 6th decades of life. Lesions are symmetrical and bilateral and the buccal mucosa is frequently involved. The risk of malignant transformation is extremely low. This study aims to describe both the clinical characteristics and the prevalence of OLP among a group of patients from Southern Italy. The results of the present study were compared to analogous retrospective studies.
The incidence of chronic renal failure (CRF) is approximately 200 cases per million people in different Western countries. Recent data indicate that the incidences of these pathologies are increasing. Ninety percent of patients with CRF report oral signs and symptoms that affect both the bone and soft tissues. A broad range of lesions may be observed in chronic uratemia patients, including the following: gingival hyperplasia, enamel hypoplasia, petechiae, gingival bleeding, and others lesions. These patients require various types of treatment ranging from dietary and lifestyle changes to dialysis and kidney transplantation. CRF often leads to multiple oral manifestations that are difficult for dentists to manage. The present study examined the characteristics of this disease, the existing therapeutic options and the relevant considerations for dental professionals.
Orofaciodigital syndrome (OFD) is a group of hereditary disorders identified by malformations of the mouth (oris), face (facies), hands and feet (digitus=finger and toe). Although there are several different types reported in the literature, there is a great overlap in their clinical presentation. The full spectrum of all disorders due to OFD is not yet fully understood, since each patient shows variations in the expression of the syndrome. In the oral cavity, teeth are often affected by various alterations, such as dental caries, abnormal teeth, enamel hypoplasia, supernumerary teeth and dental agenesis. Treatment of a syndromic patient with a complex picture showing conditions such as palatine fissures and a severe hypodontia involves a multidisciplinary approach and a careful periodical follow-up.
Lymphatic Malformation (LM) according to ISSVA Classification, is a rare benign disorder with unknown aetiology. LM may grow slowly over years or develop rapidly over the course of days becoming a bulky lump, infected or bleeding. We propose our three steps Diode Laser protocol for LM management, based on its persistent vascular blood component. 1. Histological and cytological examination, to evaluate the vascular blood component (10-40%), shows mature lymphocytes with red blood cells and endothelial cells. 2. Diode Laser Photocoagulation (DLP) in pulsed mode (on 100ms / off 400ms) at 10W and 800nm with a 300μm fibre kept 2-3mm from the tissues, to reduce the lesion. 3. Diode Laser surgical excision in pulsed mode (on 50ms / off 200ms) at 8W and 800nm with a 300 μm fibre in close contact with tissues, and histological intraoperative margins control on frozen sections. Even if it has inconstant results (lesions decreasing rate is 10% to 40% proportionally to vascular blood component), DLP simplifies the last and the most important step. Use of Diode Laser also in surgical excision reduces intra and postoperatory complications.
Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting.
The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases.
BACKGROUND: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. METHODS: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. CONCLUSION: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.
INTRODUCTION: PHACES is an acronym which refers to a syndrome charachterized by Posterior cranial fossa malformation, Hemangiomas of the head, Arterial abnormalities, Cardiac abnormalities, Eye abnormalities, Sternal clefting. The syndrome shows a female to male predilection of 9:1. There is no definitive evidence of a familial tendency although an X chromosome linked dominant single gene etiology has been suggested with lethality in males. The diagnosis of PHACES syndrome requires the presence of a segmental hemangioma >5 cm in diameter of the head plus 1 major criterion or 2 minor criteria. There are many treatment options, one of the mainstay therapies is laser photocoagulation. The aim of this work is to show the differential diode laser treatment of intraoral hemangiomas (IH) and perioral hemangiomas (PH) in patients with PHACES syndrome. METHODS: We report the cases of 4 patients (age median 21 years) affected by the syndrome, showing 26 IH and 15 PH. Diagnostic protocol consist on: appropriate clinical exam (highlighting prominent reddish purple plaque-like lesions on lips, tongue, cheek, palate, mouth floor), echocardiogram, ophtalmologic and endocrinologic exams, MRI of the head and MRA of head and neck. Patients were treated with multiple laser sessions. A different approach depending on the site of the lesions was used: repeated diode laser impulses in pulsed mode at the power of 14-20W and the wavelength of 800 nm for IH and lower power for PH, preceded by treated site cooling to avoid the tissue damage. RESULTS and CONCLUSIONS: IH totally healed after 1 or 2 sessions. In each session only a limited area of the PH was treated, obtaining a progressive improvement of the lesions. Both in IH and PH slight post-operatory pain, bleeding and edema was proved, with a low incidence of complications such as ulceration and super-infection. Diode laser has been proved to be very effective as non-invasive treatment for IH and PH in PHACES syndrome patients.
BACKGROUND: Oral disease may be increased in people with chronic kidney disease (CKD) and, due to associations with inflammation and malnutrition, represents a potential modifiable risk factor for cardiovascular disease and mortality. We summarized the prevalence of oral disease in adults with CKD and explored any association between oral disease and mortality. METHODS: We used systematic review of observational studies evaluating oral health in adults with CKD identified in MEDLINE (through September 2012) without language restriction. We summarized prevalence and associations with all-cause and cardiovascular mortality using random-effects meta-analysis. We explored for sources of heterogeneity between studies using meta-regression. RESULTS: Eighty-eight studies in 125 populations comprising 11 340 adults were eligible. Edentulism affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence interval (CI), 16.4-25.6]}. Periodontitis was more common in CKD Stage 5D [56.8% (CI, 39.3-72.8)] than less severe CKD [31.6% (CI, 19.0-47.6)], although data linking periodontitis with premature death were scant. One-quarter of patients with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2-51.1)] and a minority used dental floss [11.4% (CI, 6.2-19.8)]; oral pain was reported by one-sixth [18.7% (CI, 8.8-35.4)], while half of patients experienced a dry mouth [48.4% (CI, 37.5-59.5)]. Data for kidney transplant recipients and CKD Stages 1-5 were limited. CONCLUSIONS: Oral disease is common in adults with CKD, potentially reflects low use of preventative dental services, and may be an important determinant of health in this clinical setting.
TThis study aimed at assessing whether proanthocyanidin, a collagen cross-linker, affects the adhesion strength of resin composites on the dentine surface. Freshly extracted, caries-free, human molars (N=55) were embedded in transparent resin and bisected. The halves were then assigned to either a treated or a non-treated group, where the treatment consisted of a 10 min incubation in a 6.5% proanthocyanidin solution in PBS. A resin composite cylinder was polymerized perpendicularly to the dentinal surfaces and shear tests were made, using an Instron-like machine. The fracture surfaces were characterized by optical (Picro-Sirius Red stain) and electron microscopy (FESEM EDX analysis). Mean bond strength values were 10.73 MPa (SD 3.70) for the treated group and 8.69 MPa (SD 3.20) for the non-treated group (p less than 0.05 Students t-test). No constant fracture patterns could be found within the two groups. Proanthocyanidin treatment may improve the adhesion properties of the dentine-bonding interface.
The aim of this study was to evaluate the prevalence of psychiatric symptoms in patients with oral lichen planus (OLP) compared to a control group. Eleven patients (mean age 65.2 years-old), with diagnosis of OLP and 13 controls (mean age 64.8 years-old) underwent a psychiatric evaluation with five psychometric scales: Visual Analogue Scale (VAS), Hamilton Rating Scale for Depression (HAM-D), State-Trait Anxiety Inventory (STAI 1-2), Distress Thermometer (DT) and Brief Fatigue Inventory (BFI). Seventy-three % of OLP group presented a VAS score of mild type; 9% had depressive symptoms; 100% of the sample had a score above the cut-off for state and trait anxiety; 45% presented Distress (36% moderate type). However, no statistical difference was found in comparison with the control group. In this study, there was no difference in these parameters between the OLP group and the control group. Perhaps, a larger cohort of patients could give different results.
INTRODUCTION: Pyogenic granuloma (PG) is a relatively common benign mucocutaneous lesion. The term is a misnomer as the lesion does not contain pus nor it is granulomatous. Etiology of the lesions is unknown, but predisposing factors that have been reported include pregnancy, trauma, vascular malformation and chronic inflammation. PG are usually solitary lesions. The most common intraoral site is marginal gingiva, but lesions have been reported on palate, buccal mucosa, tongue, and lips. Extraoral sites commonly involve the skin of face, neck, upper and lower extremities, and mucous membrane of nose and eyelids. In this report, we seek to highlight the therapeutic advantages achieved with diode laser in intraoral PG treatment compared with surgical excision. MATERIAL AND METHODS: We report the cases of 85 patients presenting intraoral dull red, sessile, or pedunculated smooth surfaced nodule that may easily bleed, crust, or ulcerate. 62 were treated with surgical excision and 23 with diode laser treatment. The laser session consisted in diode laser photocoagulation ensued by diode laser excision of the lesion, preceded by treated areas cooling to avoid the tissue demage. According to the literature were used the following specification: wavelength 808nm, 10W power. Histological evaluation showed hyperplastic stratified squamous epithelium with stroma consisted of a large number of budding and dilateted capillaries and a dens chronic inflammatory cell infiltrate. Diagnosis of PG was confirmed. RESULTS AND CONCLUSION: Rapid healing can be observed within a few days of treatment, and as blood vessels are sealed, there is an improvement of haemostasis and coagulation compared with surgical excision. Post-operative pain discomfort, edema and bleeding are notably reduced. In conclusion, the use of diode laser offers a new tool that can change the way in which existing treatments are performed.
Simple epithelial keratins appear early during embryonic development and are expressed in non-stratified, ductal and pseudo-stratified epithelial tissues. CK19, the lowest molecular weight keratin, is also expressed in basal layer of squamous epithelia of mucosal surfaces. Previous studies have shown that High Risk-Human Papilloma Virus (HR-HPV) epithelial infection induces cell immortalization via E6 and E7 viral proteins and this, in turn, impairs cytokeratin expression in cancerous cells lines derived from uterine cervix. Here, we demonstrate the possible relationship between HR-HPV(+) oral/oropharyngeal cancer and the high levels of CK19 expression.
Early diagnosis of oral squamous cell carcinoma (OSCC) still represents an important challenge for clinicians and patients. Vital staining such as toluidine blue and Lugol's iodine solution, are routinely used in the OSCC detection but few data exist about the last one. A literature review is made to evaluate the effectiveness and safety of Lugol's iodine solution in OSCC detection and in its margins demarcation. A review was made of the studies published between 1990 and 2010 in relation to the application of Lugol's iodine for OSCC detection and a better definition of its margins. Data obtained point to the utility and the safety of Lugol's iodine when employed for detection and margins delineation of OSCC and dysplasia. All the studies consulted found the Lugol's iodine to be effective, cheap and easy to use and they emphasized its importance in clinical practice. There is need for larger controlled, randomized studies with carefully selected and standardized outcome measures and patients.
Mucinous adenocarcinoma (MAC) is a malignancy rarely affecting the salivary glands, with fewer than 30 cases described in the medical literature. MAC is mostly observed in the minor salivary glands of the palate, and to date, no case of salivary MAC has been reported in the mandible. Identifying a salivary MAC may be both clinically and histopathologically challenging, as differential diagnosis must consider not only other salivary malignancies expressing a mucinous component but also metastases from MACs of the gastrointestinal tract, breast, and sweat glands that strongly resemble a salivary MAC on histopathology. We describe an 80-year-old man with a gingival overgrowth of the left mandible for the past 9 months, who was referred to our institution with an initial diagnosis of a periodontal reaction. On clinical examination, the mass mimicked a hyperplastic lesion; but after biopsy, the histopathologic pattern suggested a diagnosis of MAC. Herein, we present how comprehensive physical examination of the patient, immunohistochemistry study of the specimen, and radiological features helped in establishing the diagnosis of intraosseous salivary MAC, ruling out metastatic disease or other salivary neoplasms.
Recurrent aphtous stomatitis (aphthae, canker sores) is ones of the most common and painful oral mucosal inflammatory ulcerative conditions; etiopathogenesis is uncertain and only symptomatic therapy is available. We used a dessicating agent based on a concentrated mixture of sulfates. The rationale for use of this product on canker sores is that it cauterises the epithelial tissue affected by the immune response. The aim of this study was to evaluate the topical application of this dessicating agent on aphtous ulcers, and verify its efficacy in reducing pain. Fifty-seven patients, with oral minor aphtous lesions and a history of recurrent aphtous stomatitis were enrolled into this study and were assigned into two groups: 30 patients were treated with a single topical application of a dessicating agent and 27 without any treatment. A subjective evaluation of symptoms was completed by each patient using a visual analog scale (VAS) of 0-10. Patients oral lesions were clinically observed at days 0 (before entering the study) and at day 6. We found that from day three the mean differences in pain score between the two groups was about 16.33% with a decrease of symptoms of 49.57% compared with pretreatment VAS score at baseline (P 0.001). Unfortunately, if we compare the mean differences from baseline in the range of 6 days of pretreatment until day 6 in the group treated with the dessicating agent and in the one receiving no treatment, performing an unpaired t-test, no significant differences appeared (P>0.05). These data suggest that a single application of this medicament could become a valid support in the management of recurrent aphtous stomatitis.
The use of a hydropneumatic balloon for the elevation of the sinus membrane is a new technique for sinus floor augmentation procedures. Few cases using such a technique are reported in the English medical literature. This report describes 40 patients who were treated with this technique and studied retrospectively. Forty consecutive patients with an alveolar crest-sinus floor distance (bone height) ≤ 12 mm were enrolled. Under microscopy (40x) and using piezosurgical instruments, hydropneumatic sinus membrane elevation was performed, and a calcium sulphate solution was injected under the elevated antral membrane using a syringe. In the same surgical session, 4.00- to 6.50-mm-diameter implants were placed. Bone height at 12 months, complications related to the surgical technique, and implant failure were all recorded. Bone height at 12 months was 14.66 ± 1.48 mm, with a sinus membrane elevation of 9.01 ± 3.01 mm. Fifty-six implants were placed, and no failures were observed after 1 year. One macrolaceration and two microlacerations were the only complications related to the technique. Minimal invasiveness and reduced trauma characterize this new approach. In fact, gradual balloon inflation provides a controlled and atraumatic preparation of the sinus floor membrane. Piezoelectric instruments and microscopy make this technique predictable and safe. The relatively short learning curve of this approach for sinus floor elevation allows for its use in private practice
Objectives The hypothesis was that the daily use of a high dose of a xylitol chewing gum for 6 months would reduce the increment of decayed permanent first molar surfaces (ΔD6S) in high-risk schoolchildren after 2 years. Methods In this randomised, clinical trial, 204 schoolchildren with a high caries risk were assigned to two experimental groups, xylitol and non-xylitol. Caries status, salivary mutans streptococci, and lactobacilli were reevaluated 2 years later in 74 xylitol-treated and 83 nonxylitol- treated schoolchildren. Differences in mean ΔD6S between groups registered at baseline and at follow-up were evaluated using the nonparametric Mann–Whitney U test. Results Outcome was the development of detectable carious lesions initial (D1–D2) and manifest (D3) in the permanent first molars. In the xylitol group, the difference in proportion of children with decayed first permanent molars at baseline and follow-up was 1.43 % for manifest lesion and 2.86 % for initial lesions; while in the non-xylitol group was 10.26 % (p<0.01) and 16.66 % (p<0.01), respectively. A statistically significant difference regarding means was also observed in the non-xylitol group: the ΔD6S for manifest lesion was 0.18 (p00.03) and 0.67 (p00.02) for initial lesion. Conclusion The use of a chewing gum containing a high dose of xylitol for a period of 6 months has been shown to produce a long-term effect on caries development in high caries-risk children. Clinical relevance A school-based preventive programme based on 6 months’ administration of a high dose of xylitol via chewing gum proved to be efficacious in controlling caries increment in high-risk children.
Candidiasis is a relevant problem in oral medicine practice. We compared the antimycotic activity of nystatin with a solution of sodium iodide associated to salicylic acid (SISA) in the topical management of chronic candidiasis. Consecutive patients affected by chronic candidiasis were randomly allocated to SISA (group A) or nystatin (group B). VAS and swab scores were recorded at the beginning and at the end of the study while the healing index was evaluated at the end of the study only. Data were analyzed by STATA 10 MP. Forty patients (20 male, 20 female) were randomized. SIAS was as effective as nystatin in affecting VAS (p greater than 0.05) and swab score (p greater than 0.05). A statistically significant reduction (p less than 0.05) of healing index was observed in both groups. No side effects were reported. SISA topical application, shows a comparable efficacy to the nystatin in the management of chronic oral candidiasis. Its use could represent an adequate alternative to the nystatin above all in the cases of drug-resistance. Further large scale randomized trials are warranted to confirm these preliminary findings.
Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.
INTRODUCTION: The popularity of one-piece implants has increased considerably among patients and dentists. The advantages of one-piece immediate loading are to reduce the number of interventions. These parameters can be better controlled with a one-piece implant. METHODS: We considered 21 patients with one-piece implants inserted in mandible for this retrospective study. Inclusion criteria were: good oral hygiene, absence of lesions of the oral mucosa, no smoking or smoking less than 20 cigarettes a day, drinking less than two glasses of wine a day, good general health and no pregnancy. RESULTS: We enrolled 21 (12 women and 9 men) patients in this retrospective study. The mean follow-up was 1 year. A total of 84 one-piece implants were inserted in mandible to replace 42 lower first and 42 second incisors. The diameter of the implants was 3.0mm in all fixtures. The length of the implants was equal to or longer than 12mm in 44 and 40 fixtures respectively. Of these, 48 were inserted in women and 36 in men (age range 33 to 67; mean age 58.3 years). CONCLUSIONS: There is no difference between the survival rates of one-piece immediate loading implants and two-piece implants and delayed loading. In conclusion, a one-piece immediate loading implant is a reliable device for mandible rehabilitation.
Orofaciodigital syndromes (OFD) are rare genetical disorders characterized by malformations of the mouth (oris), face (facies), hands and feet (digitus = finger, toe). It is still impossible to fully understand the whole spectrum of all dysfunctions due to OFD, since the expressions of the syndrome vary in each patient. There are various alterations, thoroughly described in literature that can affect the oral cavity such as dental caries, abnormal teeth, enamel hypoplasia, supernumerary teeth and dental agenesis. A syndromic patient with a complex picture showing conditions such as palatine fissures and a severe hypodontia has to be treated using a multidisciplinary approach, and in particular, needs a prosthetic rehabilitation for the restoration of missing dental elements in the arch.
Background: Treatment of oral lichen planus (OLP) is a major challenge for clinicians and patients. There is limited scientific evidence about topical treatment with retinoids. We conducted a literature review of data on the effectiveness and safety of topical retinoids in OLP patients. Materials and Methods: We searched the MEDLINE, Embase and Cochrane databases for articles on topical retinoids treatment on OLP patients (searches from 1970 to February 2012). Results: Sixteen studies (280 OLP patients topically treated with different classes of retinoids) met the inclusion criteria. Isotretinoin was the most frequently employed retinoid in the treatment of OLP. The clinical and/or histopathological efficacy of retinoids was recorded in the majority of the selected studies. A transient and moderate burning sensation was the most frequently reported side effect. Conclusions: Topical retinoids appear as an alternative choice in OLP treatment. Whether keratotic OLP better responds to topical retinoids than erosive OLP is still an open question that deserves further comparative and controlled clinical trials. The benefits and harms of using topical retinoids in people with OLP require thorough evaluation in properly designed controlled studies.
Early diagnosis of oral squamous cell carcinoma (OSCC) still represents an important challenge for clinicians and patients. Vital staining such as toluidine blue and Lugol’s iodine solution, are routinely used in the OSCC detection but few data exist about the last one. A literature review is made to evaluate the effectiveness and safety of Lugol’s iodine solution in OSCC detection and in its margins demarcation. A review was made of the studies published between 1990 and 2010 in relation to the application of Lugol’s iodine for OSCC detection and a better definition of its margins. Data obtained point to the utility and the safety of Lugol’s iodine when employed for detection and margins delineation of OSCC and dysplasia. All the studies consulted found the Lugol’s iodine to be effective, cheap and easy to use and they emphasized its importance in clinical practice. There is need for larger controlled, randomized studies with carefully selected and standardized outcome measures and patients
Increased use of smartphone and related software applications has created a new era in clinical data exchange among patients and clinicians. This study describes use of the smartphone-based application WhatsApp to share clinical oral medicine information.
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