Efficacy and safety of an intraoral electrostimulation device for xerostomia relief: a multicenter, randomized trial.

OBJECTIVE: To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex. METHODS: The device was tested on a sample of patients with xerostomia due to Sjögren's syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage designed to assess the long-term effects of the active device. Improvement in xerostomia severity from baseline was the primary outcome measure. RESULTS: A total of 114 patients were randomized. In stage I, the active device performed better than the sham device for patient-reported xerostomia severity (P<0.002), xerostomia frequency (P<0.05), quality of life impairment (P<0.01), and swallowing difficulty (P<0.02). At the end of stage II, statistically significant improvements were verified for patient-reported xerostomia severity (P<0.0001), xerostomia frequency (P<0.0001), oral discomfort (P<0.001), speech difficulty (P<0.02), sleeping difficulty (P<0.001), and resting salivary flow rate (P<0.01). CONCLUSION: Our findings indicate that daily use of the device alleviated oral dryness, discomfort, and some complications of xerostomia, such as speech and sleeping difficulties, and increased salivary output. The results show a cumulative positive effect of the device over the period of the study, from baseline to the end of the trial.

[Electrostimulation for the treatment of dry mouth].

Xerostomia is a very common condition, which not only involves dry mouth feeling, but can also lead to psychosocial distress, impaired quality of life, and complications, such as dental caries and oral candidiasis. It is generally induced by hypofunction of salivary glands, which has a wide variety of etiologies, such as Sjögren's syndrome, radiotherapy to the head and neck and side effects of medications. Current therapies rely on saliva substitutes and pharmacological stimulation of the parasympathetic system. These treatment modalities are somewhat limited by their short-term efficacy, high cost and drug interactions or other adverse effects. Local transcutaneous or permucosal electrostimulation in areas close to the nerves participating in the salivary autonomic reflex has been found to increase salivary secretion in animal and clinical experiments and to relieve symptoms of dry mouth in patients with salivary gland hypofunction. This concept is reviewed to update the readers on the current status and potential of intraoral miniature electrostimulating devices. They offer promise as an optional safe and non-chemical treatment of xerostomia.

Emulating the early phases of human tooth development in vitro.

Functional in vitro models emulating the physiological processes of human organ formation are invaluable for future research and the development of regenerative therapies. Here, a developmentally inspired approach is pursued to reproduce fundamental steps of human tooth organogenesis in vitro using human dental pulp cells. Similar to the in vivo situation of tooth initiating mesenchymal condensation, a 3D self-organizing culture was pursued resulting in an organoid of the size of a human tooth germ with odontogenic marker expression. Furthermore, the model is capable of epithelial invagination into the condensed mesenchyme, mimicking the reciprocal tissue interactions of human tooth development. Comprehensive transcriptome analysis revealed activation of well-studied as well as rather less investigated signaling pathways implicated in human tooth organogenesis, such as the Notch signaling. Early condensation in vitro revealed a shift to the TGFß signal transduction pathway and a decreased RhoA small GTPase activity, connected to the remodeling of the cytoskeleton and actin-mediated mechanotransduction. Therefore, this in vitro model of tooth development provides a valuable model to study basic human developmental mechanisms.

Comparative Clinical Study of Conventional Dental Implants and Mini Dental Implants for Mandibular Overdentures: A Randomized Clinical Trial.

BACKGROUND: Dental implant-retained overdentures have been chosen as the treatment of choice for complete mandibular removable dentures. Dental implants, such as mini dental implants, and components for retaining overdentures, are commercially available. However, comparative clinical studies comparing mini dental implants and conventional dental implants using different attachment for implant-retained overdentures have not been well documented. PURPOSE: To compare the clinical outcomes of using two mini dental implants with Equator® attachments, four mini dental implants with Equator attachments, or two conventional dental implants with ball attachments, by means of a randomized clinical trial. MATERIALS AND METHODS: Sixty patients received implant-retained mandibular overdentures in the interforaminal region. The patients were divided into three groups. In Groups 1 and 2, two and four mini dental implants, respectively, were placed and immediately loaded by overdentures, using Equator® attachments. In Group 3, conventional implants were placed. After osseointegration, the implants were loaded by overdentures, using ball attachments. The study distribution was randomized and double-blinded. Outcome measures included changes in radiological peri-implant bone level from surgery to 12 months postinsertion, prosthodontic complications and patient satisfaction. RESULTS: The cumulative survival rate in the three clinical groups after one year was 100%. There was no significant difference (p < 0.05) in clinical results regarding the number (two or four) of mini dental implants with Equator attachments. However, there was a significant difference in marginal bone loss and patient satisfaction between those receiving mini dental implants with Equator attachments and conventional dental implants with ball attachments. The marginal bone resorption in Group 3 was significantly higher than in Groups 1 and 2 (p < 0.05); there were no significant differences between Groups 1 and 2. There was no significant difference in patient satisfaction between Groups 1 and 2 but it was significantly higher than that in Group3 (p < 0.05). CONCLUSIONS: Two and four mini dental implants can be immediately used successfully for retaining lower complete dentures, as shown after a 1-year follow up.

Healing pattern of bone defects covered by different membrane types--a histologic study in the porcine mandible.

Few investigations on guided bone regeneration (GBR) focus on the behaviour of tissues adjacent to barrier membranes. This study was conducted to (1) evaluate the barrier function potential of different resorbable and nonresorbable membranes for GBR, (2) investigate their structural changes after different intervals, and (3) characterize tissue composition and reaction adjacent to the barrier by qualitative histologic evaluation. Seven barriers for GBR were used per animal (made of dense or expanded polytetrafluoroethylene (d/ePTFE), titanium, polyetherurethane, collagen and two polylactide-polyglycolide-/-trimethylenecarbonate-co-polymers (PLPG, LPGTC) in standardized defects not exceeding the critical size) without using bone substitution material or autogenous bone at the right inferior margin of the mandibles of six domestic pigs. Samples of the defect areas with membranes were harvested after 2 days (one animal), 4 and 8 (two animals, each) and 12 weeks (one animal), respectively. The healing of bone defects was completed in all animals after 12 weeks. Nonresorbable barriers prevented the soft tissue in-growth into standardized defects. Thinner layers of fibrous tissue were seen underneath the dense and rigid barriers (dPTFE, titanium) when compared with collagen and PLPG/LPGTC, in which soft-tissue plugs occupied the crestal defect portion. PLPG-/LPGTC-barriers underwent structural changes after 4 weeks and revealed blistered central layers, whereas structural changes were not evident in nonresorbable barriers. The degradation of PLPG-/LPGTC-membranes was present with in-growth of fibres, vessels, and cells. Using collagen or synthetic polymer barriers for GBR, the application of bone or bone substitutes to prevent membrane prolapse into the defect is suggested.

Tissue-engineered bone for lateral alveolar ridge augmentation: a case report.

Bone matrix derived from mandibular periosteal cells and cultivated by tissue engineering on a polymer fleece has recently been used for sinus floor elevation and augmentation. This case report focuses on clinical and histologic results after lateral ridge augmentation of a localized non-space maintaining defect in the right posterior area of the mandible using tissue-engineered bone. Implant supported prosthetic rehabilitation of a partially edentulous 32-year-old woman was planned involving a fixed partial denture. Preoperative investigations revealed a transversely reduced alveolar ridge width on the right side of the posterior mandible. Lateral augmentation was performed using tissue-engineered bone obtained by autogenous periosteum cells from the same area. Six months after augmentation 2 implants were placed and a bone biopsy was obtained from the augmented area. Transverse ridge dimensions were found to be enhanced. Histologic examination of the biopsy revealed dense lamellar bone. Wound healing was uneventful after all surgical interventions. This case report demonstrates the successful clinical application of tissue-engineered bone for lateral augmentation of the transversely reduced alveolar ridge. The results suggest that periosteum-derived tissue-engineered bone can be used to create a sufficient implant site not only for the sinus floor elevation and augmentation procedure for vertical bone enhancement but also for lateral augmentation.

Implant-prosthetic treatment in HIV-infected patients receiving highly active antiretroviral therapy: report of cases.

PURPOSE: Since 1997, the use of highly active antiretroviral therapy (HAART) has significantly improved systemic health and life expectancy of patients who test positive for the human immunodeficiency virus (HIV) in industrialized countries. Therefore, although implant-supported prosthetic rehabilitation has been restricted to immunocompetent individuals, it may be considered for these patients. CASE REPORTS: The treatment course of implant-prosthetic rehabilitation in 3 patients is reported. Patient 1 (male, age 64 years) was under 4-drug therapy; patient 2 (male, age 38 years) and patient 3 (female, age 49 years) were under 3-drug therapy. Two patients had suffered from AIDS-defining diseases prior to HAART. Oral manifestations of HIV infection were not diagnosed throughout the observation period. Patients had CD4+ cell counts between 250 and 800/mL, and viral load was below 50/mL. Perioperative antibiotic treatment was not applied. Two patients presented with edentulous mandibles. In the third patient, single-tooth replacement of both mandibular first molars was performed. A total of 10 Frialit-2 implants were placed without augmentation procedures. RESULTS: One implant failed after 3 months and was successfully replaced. Two patients received magnet-retained overdentures in the mandible, and 1 patient was treated with single crowns. All implants and restorations are successfully in function. Neither radiographic nor clinical signs of inflammation were detected during the observation period (range, 7 to 32 months). CONCLUSIONS: The outcomes of the 3 patients suggest that immunologically stable HIV-positive patients on HAART may be considered for implant-prosthetic rehabilitation.

Electrostimulation of the lingual nerve by an intraoral device may lead to salivary gland regeneration: A case series study

BACKGROUND: Salivary gland function is controlled by the salivary reflex, whose efferent arm is composed by the parasympathetic and the sympathetic divisions of the autonomic nervous system. Parenchymal injury is the main salivary gland involvement of Sjögren's syndrome and head and neck radiotherapy, but neural damage has been reported as well. Recently an intraoral device for electrostimulation of the lingual nerve in vicinity to the lower third molar has been introduced. At this point this nerve carries efferent fibers for the innervation of the submandibular, sublingual and several minor salivary glands and afferent fibers of the salivary reflex. Therefore, excitation of these fibers potentially leads to increased secretion of all salivary glands. Thus, the study objective was to assess whether comprehensive neural activation by electrostimulation of the lingual nerve carries the potential to induce the regeneration of damaged salivary glands. MATERIAL AND METHODS: The device was tested on three patients with no collectable resting and stimulated secretion of saliva during a double blind, sham controlled period of two months and nine open-label months. RESULTS: All three subjects developed the capacity to spit saliva, not only in direct response to the electrostimulation but also after free intervals without electrostimulation. In addition, their symptoms of dry mouth severity and frequency improved. CONCLUSIONS: This recovery is probably due to the combined effect of increase in secretory functional gland mass and regain of nervous control of the secretory elements and blood vessels. Both are phenomena that would contribute to gland regeneration

Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial.

OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.