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Biomedical subjects

Daniel van Steenberghe

Publications and source records attributed to Daniel van Steenberghe.

At least 19 recordsLinked to original sources

Benefit of "one-stage full-mouth disinfection" is explained by disinfection and root planing within 24 hours: a randomized controlled trial.

OBJECTIVES: The beneficial effects of the one-stage, full-mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full-mouth treatment strategies with each other. MATERIAL AND METHODS: Seventy-one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two-week intervals (negative control, NC), full-mouth scaling and root planing within 2 consecutive days (FRP), or three one-stage, full-mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded. RESULTS: All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter-treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance. CONCLUSION: These observations indicate that the benefits of the "OSFMD" protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time.

Adult↗

Development of a novel digital subtraction technique for detecting subtle changes in jawbone density.

The objective of this paper is to develop a novel digital subtraction technique for serial intra-oral radiography, which would allow the detection of subtle variations in grey values. Digital images of the maxilla of a dried human skull and of a fresh pig mandible were acquired using intra-oral photostimulable phosphor plates (Digora FMX, Soredex, Helsinki) with an aluminium calibration stepwedge incorporated in the filmholder. Exposures were made with an X-ray tube for intra-oral radiography (Prostyle Intra, Planmeca, Helsinki). During pilot testing, parameter settings were adapted to reach an optimal contrast. Exposures were repeated within a 1-week interval to determine the test-retest reliability of the development. After in vitro and in vivo testing, the exposure technique and software development were used to evaluate its applicability in a pilot clinical case. Although parameter settings remained stable during the in vitro studies, the clinical exposures yielded non-linear digital images, thus, not readily suitable for data acquisition and comparison of the regions of interest. To allow further analysis, image processing was carried out using self-developed software for semi-automated linearisation and optimised contrast normalisation. This processing significantly increased the precise quantisation of jawbone density and the assessment of subtle bone density changes in arbitrarily selected regions of interest of in vivo exposures. The clinical applicability of the technique is demonstrated in a pilot case. It was demonstrated that minute densitometric deviations could be detected. The present technique and image processing may allow the quantification of jawbone density.

Animals↗

State-of-the-art on cone beam CT imaging for preoperative planning of implant placement.

Orofacial diagnostic imaging has grown dramatically in recent years. As the use of endosseous implants has revolutionized oral rehabilitation, a specialized technique has become available for the preoperative planning of oral implant placement: cone beam computed tomography (CT). This imaging technology provides 3D and cross-sectional views of the jaws. It is obvious that this hardware is not in the same class as CT machines in cost, size, weight, complexity, and radiation dose. It is thus considered to be the examination of choice when making a risk-benefit assessment. The present review deals with imaging modalities available for preoperative planning purposes with a specific focus on the use of the cone beam CT and software for planning of oral implant surgery. It is apparent that cone beam CT is the medium of the future, thus, many changes will be performed to improve these. Any adaptation of the future systems should go hand in hand with a further dose optimalization.

Anatomy, Cross-Sectional↗

Dynamics of initial subgingival colonization of 'pristine' peri-implant pockets.

BACKGROUND: Periodontitis and peri-implantitis are linked to the presence of several key pathogens. The treatment of these infectious processes therefore involves the reduction/eradication of bacteria associated with periodontitis. METHODS: This prospective, split-mouth, single-blind study followed the colonization of 'pristine' sulci created in 42 partially edentulous patients during implant surgery (e.g. abutment connection). The hypothesis was that the composition of the maturing subgingival plaque in these 'fresh' peri-implant pockets would soon (within 2 weeks) be comparable to the subgingival microbiota of teeth with similar clinical parameters (reference sites), including the presence of bacteria associated with periodontitis. Per patient, four subgingival plaque samples were taken from shallow and medium pockets around implants (test sites), and teeth within the same quadrant (undisturbed microbiota as control sites), 1, 2, 4, 13, 26 and 78 weeks after abutment connection, respectively. The samples were analysed by either checkerboard DNA-DNA hybridization, or cultural techniques, or real-time polymerase chain reaction (PCR) for intra-subject comparisons (teeth vs. implant, for comparable probing depths). RESULTS: Checkerboard DNA-DNA hybridization and real-time PCR revealed a complex microbiota (including several pathogenic species) in the peri-implant pockets within 2 weeks after abutment connection. After 7 days, the detection frequency for most species (including the bacteria associated with periodontitis) was already nearly identical in samples from the fresh peri-implant pockets (5% and 20% of the microbiota belonging to red and orange complex, respectively) when compared with samples from the reference teeth. Afterwards (e.g. between weeks 2 and 13), the number of bacteria in peri-implant pockets only slightly increased (+/-0.1 log value), with minor changes in the relative proportions of bacteria associated with periodontitis (8% and 33% of the microbiota belonging to red and orange complex, respectively). Although small differences were seen between teeth and implants at week 2 with cultural techniques, a striking similarity in subgingival microbiota was found with this technique from month 3 on, with nearly identical detection frequencies for bacteria associated with periodontitis for both abutment types. CONCLUSIONS: This study indicates that the initial colonization of peri-implant pockets with bacteria associated with periodontitis occurs within 2 weeks.

Bacteria↗

Comparison between jaw bone augmentation by means of a stiff occlusive titanium membrane or an autologous hip graft: a retrospective clinical assessment.

OBJECTIVES: Patients in need of bone augmentation procedures can be treated with a traditional hip graft or by neogenesis under a stiff occlusive titanium membrane, custom-fit on the basis of CT-scan data. MATERIAL AND METHODS: Eighteen patients treated by means of a hip graft (H) were compared with 11 patients using a full titanium membrane (M) for the rehabilitation of upper jaws. In the H group, 17 patients (62 implants) in the anterior region (Ha) and 14 patients (23 implants) in the posterior region (Hp) were included. In the M group, nine patients (30 implants) in the anterior region (Ma) and seven patients (16 implants) in the posterior region (Mp) were included. RESULTS: In group Ha, the CFR was 13.3% after 14 years compared with group Ma where the CFR was 17.4% after 9 years. In group Hp, the CFR was 22.8% after 16 years compared with group Mp where the CFR was 23.4% after 6 years. The marginal bone loss for group Ha after 20 years was 2.7 mm, for group Ma it was not even 1 mm after 9 years; for group Hp, it was 2.5 mm after 15 years compared with less than 1 mm after 3 years in group Mp. CONCLUSIONS: The success rate of alveolar ridge augmentation therapy is lower than in a classical approach. These augmentation procedures, however, show acceptable results. The titanium membrane augmentation leads to less marginal bone loss probably because neo-formed bone has a better chance to adapt its mineralization to occlusal forces encountered. This technique could offer improvement if membrane exposure can be avoided.

Adult↗

Periodontology as a recognized dental speciality in Europe.

The impetus of the Bologna Process under the auspices of European Union governments has raised enormous expectations. It is the major educational change in Europe within the last 50 years and all the focus from university institutions, learned societies and thematic networks has shifted to this process, with the aim of developing consensus schemes in order to arrive at the expected European Convergence in Higher Education (to be completed by 2010). Dentistry as one of the health professions with clear Educational Standards, as defined by the European Dental Directives, is also reviewing its educational processes within this Bachelor-Master-Doctorate scheme and evaluating how the current and future dental specialities should be accommodated within this framework. Among these specialities, Periodontology is currently considered a formal dental speciality in 11 countries belonging to the EU however it lacks this legal status in the rest of the 14 EU countries. The purpose of this position paper is to provide evidence for the need for a recognized specialty in Periodontology at European level focusing on both the educational and professional perspective, with the hope of providing discussions that may contribute to facilitate its legal establishment as a new dental speciality in Europe.

Chronic Disease↗

Histologic evaluation of Brånemark clinic oral implants retrieved from grafted sites.

PURPOSE: The aim of this report is to quantitatively and qualitatively describe the bone tissue response to Brånemark implants retrieved from grafted sites in patients. MATERIALS AND METHOD: The material consists of consecutively received Brånemark implants retrieved from grafted sites. Thirty-five of these implants, retrieved from 16 patients, were suitable for the histologic evaluation of undecalcified sections in the light microscope. RESULTS: The unloaded implants were mainly lined with soft tissue, and sparse bone-implant contact was observed only in some sections. The loaded implants, with the exception of one implant removed due to mobility, had mature and new bone-implant contact. Resorption of graft through cutting cone structures was detected. Cement lines were found separating bone-like tissue albeit no cellular content and bone tissue with detectable osteocytes. CONCLUSION: In this heterogeneous group of implants from grafted sites, the unloaded implants showed limited bone-implant contact. The autografts showed seemingly mixed viability as judged by the cell content in the osteocyte lacunae and cement lines separating areas with filled and empty lacunae.

Bone Transplantation↗

Microbiological and clinical outcomes and patient satisfaction for two treatment options in the edentulous lower jaw after 10 years of function.

BACKGROUND: Long-term data on microbiological and clinical outcome as well as on patient satisfaction after implant therapy in the edentulous mandible are limited. Especially comparisons between fixed full prostheses (FFPs) and overdentures (ODs), or between anchoring systems for the latter are scarce. AIM: This study aimed to evaluate both of these parameters at the 10-year follow-up in a group of fully edentulous patients rehabilitated via an OD or a FFP (the latter to allow inter-group comparison). MATERIAL AND METHODS: A total of 37 fully edentulous patients (25 ODs, 12 FFPs, age at implant installation ranged from 36 to 85 years) participated in this study. All subjects received their implants (Branemark System, Nobel Biocare AB, Gothenburg, Sweden) 10 years previously. For the ODs different attachment systems (bar, magnets, ball) had been applied that allowed a further intra-group comparison. At the follow-up visit, 10 years after the abutment insertion, a series of periodontal parameters were recorded, long-cone radiographs were taken and subgingival plaque samples were collected for analysis using checkerboard DNA-DNA hybridization. The clinical and radiographic data were recorded at abutment connection and after 1 and 10 years. RESULTS: After 10 years of loading, mean plaque and bleeding indices and changes in attachment or marginal bone level were not significantly different, neither between the OD and FFP group, nor within the OD group. The marginal bone loss between abutment connection and year 10 was 0.86 and 0.73 mm for OD and FFP groups, respectively. The subgingival microbiota at implant sites from all (sub)-groups was comparable, with low numbers of DNA counts (+/-10 x 10(5)) but high detection frequencies of Actinobacillus actinomycetemcomitans (>90%), Porphyromonas gingivalis (>85%) and Tannerella forsythensis (30%). The composition of the subgingival microbiota was influenced by probing depth and bleeding tendency. Patient satisfaction was very high for both types of prosthetic rehabilitation. The FFP group scored only slightly better for chewing comfort and general satisfaction. CONCLUSION: These data indicate that from the clinical and microbiological standpoint, as well as patient satisfaction, both an OD and a FFP offer a favourable long-term outcome.

Adult↗

Predisposing conditions for retrograde peri-implantitis, and treatment suggestions.

BACKGROUND: Recent case reports introduced the term retrograde peri-implantitis as a lesion (radiolucency) around the most apical part of an osseointegrated implant. It develops within the first months after insertion. This retrospective study aimed to find predisposing conditions for such peri-apical lesions and to evaluate treatment strategies. METHODS: All single implants (426 in the upper, 113 in the lower jaw, all Brånemark system type) placed at the department of Periodontology of the University Hospital (Catholic University Leuven) were included in this retrospective evaluation to check the incidence of retrograde peri-implantitis. Eventual predisposing factors such as patient characteristics (age, medical history), recipient site (local bone quality and quantity, cause of tooth loss), periodontal and endodontic conditions of neighboring teeth, implant characteristics (length, surface characteristics), and surgical aspects (guided bone regeneration, osseous fenestration, or dehiscency) were considered. Moreover, implants with retrograde peri-implantitis were followed longitudinally to verify their treatment outcome by means of different parameters (Periotest values (PTV), marginal bone level, radiological size of peri-apical defect). RESULTS: Seven implants in the upper (1.6%) and 3 in the lower jaw (2.7%) showed retrograde peri-implantitis, before or at abutment connection. In comparison with successful implants, such peri-apical lesions occurred preferably at sites with a history of an obvious endodontic pathology of the extracted tooth to be replaced. The incidence of retrograde peri-implantitis was significantly higher (P<0.0001) for TiUnite implants when compared with the machined implants (8/80 vs. 2/459). The machined implant surface, however, showed a higher failure rate (6.8%) than the TiUnite implants (2.5%). Failures with machined surfaces preferably occurred at extraction sites of teeth with a history of endodontic pathology or sites adjacent to teeth with an obvious endodontic pathology. No other predisposing factors could be identified. A curettage of the peri-apical lesions and the use of a bone substitute material prevented further progression of such lesions in the upper jaw (implants maintained their marginal bone and low PTV scores). A treatment in the lower jaw was less successful. CONCLUSIONS: Within the limitations of a retrospective study, these results seem to indicate that retrograde peri-implantitis is provoked by remaining scar or granulomatous tissue at the recipient site: endodontic pathology of extracted tooth (scar tissue-impacted tooth) or possible endodontic pathology from a neighboring tooth.

Causality↗

A 0.05% cetyl pyridinium chloride/0.05% chlorhexidine mouth rinse during maintenance phase after initial periodontal therapy.

BACKGROUND: Chlorhexidine (CHX) mouth rinse/spray can still be considered the gold standard in the chemical prevention of plaque formation and development of gingivitis. The product unfortunately has some side effects, such as extrinsic tooth staining, poor taste, taste disturbance, sensitivity changes in tongue, pain and irritation because of the alcohol content. These side effects led to the search of new formulations. METHODS: In this double-blind, randomized, long-term, parallel study, 48 moderate periodontitis patients rinsed for 6 months (starting immediately after a "one-stage, full-mouth" disinfection) with one of the following products: CHX 0.2%+alcohol (Corsodyl), CHX 0.05%+ cetyl pyridinium chloride (CPC) 0.05% and no alcohol (Perio-Aid Maintenance, a new formulation), or the placebo of the latter. After 1, 3 and 6 months a series of clinical and microbiological parameters were recorded for the supra- and subgingival area as well as for saliva. RESULTS: Although there was a significant treatment impact (mechanical debridement) in all groups, both CHX solutions further decreased both plaque and gingivitis indices (p<0.001 and p<0.05, respectively), when compared with placebo. This was also reflected by additional reductions in the number of CFU/ml of aerobic and especially anaerobic species and by a suppression of Streptococcus mutans (versus an overgrowth for the placebo), in all niches. Differences between both CHX solutions were never encountered. The subjective ratings were slightly in favour of the new CHX-CPC formulation when compared with the other CHX-alcohol formulation, especially for taste of the product (p<0.05), but less impressive for the staining of teeth and tongue. CONCLUSIONS: The results of this study demonstrated the potential of a new CHX 0.05%+CPC 0.05% non-alcoholic formulation as an effective antiplaque agent for long-term use with reduced subjective side effects.

Anti-Infective Agents, Local↗

A computed tomographic scan-derived customized surgical template and fixed prosthesis for flapless surgery and immediate loading of implants in fully edentulous maxillae: a prospective multicenter study.

BACKGROUND: Based on three-dimensional implant planning software for computed tomographic (CT) scan data, customized surgical templates and final dental prostheses could be designed to ensure high precision transfer of the implant treatment planning to the operative field and an immediate rigid splinting of the installed implants, respectively. PURPOSE: The aim of the present study was to (1) evaluate a concept including a treatment planning procedure based on CT scan images and a prefabricated fixed prosthetic reconstruction for immediate function in upper jaws using a flapless surgical technique and (2) validate the universality of this concept in a prospective multicenter clinical study. MATERIALS AND METHODS: Twenty-seven consecutive patients with edentulous maxillae were included. Treatments were performed according to the Teeth-in-an-Hour concept (Nobel Biocare AB, Göteborg, Sweden), which includes a CT scan-derived customized surgical template for flapless surgery and a prefabricated prosthetic suprastructure. RESULTS: All patients received their final prosthetic restoration immediately after implant placement, that is, both the surgery and the prosthesis insertion were completed within approximately 1 hour. In the 24 patients followed for 1 year, all prostheses and individual implants were recorded as stable. CONCLUSION: The present prospective multicenter study indicates that the prefabrication, on the basis of models derived from three-dimensional oral implant planning software, of both surgical templates for flapless surgery and dental prostheses for immediate loading is a very reliable treatment option. It is evident that the same approach could be used for staged surgery and in partial edentulism.

Adult↗

The impact of periodontal therapy and the adjunctive effect of antiseptics on breath odor-related outcome variables: a double-blind randomized study.

BACKGROUND: Bad breath is often caused by periodontitis and/or tongue coating. This study followed the impact of initial periodontal therapy on several halitosis-related outcome variables over a 6-month period. Organoleptic ratings are often uncomfortable for the patient and have several disadvantages. They are, for instance, influenced by external parameters (e.g., food intake and cosmetics) and need to be calibrated among researchers worldwide. A second aim was to evaluate the reliability of saliva incubation as an in vitro indirect test for breath recording. METHODS: In this double-blind, randomized, medium-term, parallel study 45 moderate periodontitis patients without obvious tongue coating were enrolled. Besides a one-stage, full-mouth disinfection and oral hygiene improvement (including daily tongue scraping), patients were instructed to rinse daily for 6 months with one of the following products (randomly allocated): chlorhexidine (CHX) 0.2% + alcohol, CHX 0.05% + cetyl pyridinium chloride (CPC) 0.05% without alcohol (a new formulation), or a placebo solution. At baseline and 3 and 6 months, a series of parameters were recorded including: concentration of volatile sulfide compounds (VSC), tongue coating, and an estimation of the microbial load (at anterior and posterior parts of the tongue, saliva, dental plaque). The intraoral VSC ratings were compared to in vitro VSC recordings and organoleptic evaluations of the headspace air from 1 and 2 hours incubated saliva (0.5 ml, 37 degrees C, anaerobic chamber). RESULTS: Even though the initial VSC values were not high (+/-90 ppb with only 18 patients revealing more than 100 ppb), significant (P <0.05) reductions could be achieved in the CHX and CHX + CPC group, and to a lower extent in the placebo group (P = 0.10). Tongue scraping resulted in a significant reduction (P < or =0.05) of the tongue coating up to month 6 in the placebo and CHX + CPC group, but not in the CHX group (confusion due to staining). The CHX and CHX + CPC group showed, in comparison to baseline, significant (P <0.001) reductions in the number of anaerobic species in the supragingival plaque, in the saliva, and on the anterior part of the tongue. For the posterior part of the tongue the microbial changes remained < or =0.3 log values (P >0.05). For the placebo group, the microbial changes never reached a level of significance (< or =0.3 log values). A strong correlation was found between the intraoral VSC ratings and the 1-hour (r = 0.48, P <0.0001; r = 0.54, P = 0.0003 for baseline data only) and 2-hour (r = 0.43, P <0.0001) VSC production of incubated saliva. The latter also correlated very strongly (r = 0.71) with the number of anaerobic species in the saliva. The VSC values and organoleptic ratings of the incubated saliva also correlated strongly with each other (r = 0.64 for 1-hour and 0.73 for 2-hour incubation). CONCLUSIONS: The results of this study indicate that in patients with moderate periodontitis, initial periodontal therapy including tongue scraping did not have a significant effect on the microbial load of the tongue and had only a weak impact on the VSC level, except when combined with a mouthrinse. Saliva incubation can be used as an indirect way to score breath odor. It offers simplicity, objectivity, and is less invasive.

Anti-Infective Agents, Local↗

Influence of nicotine and cotinine on epithelial colonization by periodontopathogens.

BACKGROUND: Since smoking is an established risk factor for the development of periodontitis, the present study investigated whether nicotine and cotinine can make epithelial cells more prone to colonization by periodontopathogens. METHODS: Primary epithelial cell mono-layers were inoculated with nicotine and cotinine prior to adhesion experiments with Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The number of bacteria associated with cells inoculated or not with nicotine or cotinine were assessed by an indirect culture viability assay. The same experimental set-up was used for assessing HeLa cells exposed to cigarette smoke extract (CSE). RESULTS: Primary epithelial cells inoculated with concentrations of nicotine and cotinine, found in smokers and non smokers, did not show significant differences (P>0.05) in colonization susceptibility to A. actinomycetemcomitans. When these concentrations were increased to 1 mg/ml, a significant (P<0.05) and species-specific effect of the colonization susceptibility of epithelial cells was observed: It increased for A. actinomycetemcomitans, while it decreased for P. gingivalis. For both species the effects were more pronounced for nicotine, although this was not statistically significant. The change in colonization susceptibility did not result from alterations of the bacterial viability due to nicotine or cotinine. Treatment of HeLa cells with CSE also led to a species-specific variation in colonization tendency; i.e., increased for A. actinomycetemcomitans (P<0.05), but not for P. gingivalis. CONCLUSIONS: The susceptibility of epithelial cells to become colonized by either A. actinomycetemcomitans or P. gingivalis could be altered by nicotine, cotinine, or CSE in a time-dependent, species-specific manner. Whether these findings that support the hypothesis of an increased patient susceptibility for bacterial adhesion to epithelial cells in smokers are clinically relevant remains to be proven.

Aggregatibacter actinomycetemcomitans↗

Periodontal parameters around implants anchoring orthodontic appliances: a series of case reports.

BACKGROUND: Implants replacing missing teeth provide advantages over clinical orthodontic treatment as compensation for reaction forces is no longer necessary and the lack of teeth is immediately resolved. METHODS: A total of 38 two-stage implants were inserted (16 in maxilla, 22 in mandible) in 10 partially edentulous patients with orthodontic problems. Osseointegration and marginal bone levels were assessed via intra-oral radiographs taken at the abutment stage and at the completion of the orthodontic treatment and also via probing depth, measurement of recession toward the implant/abutment (I/A) interface, and sulcus bleeding index, recorded after completion of orthodontic treatment. RESULTS: In the maxilla, the cumulative survival rate was 87.1% after 2 years; for the mandible, it remained 100%. Mean amount of bone loss was 1.6 mm for maxilla and 0.8 mm for mandible. No correlation could be found between directions of orthodontic forces and marginal bone loss. Mean percentage of bleeding sites was 38.5% and 25%, respectively, for implants in the maxilla and mandible. Attachment level was 1.2 mm (SD: 1.2) below I/A interface after completion of the orthodonic treatment. CONCLUSION: No significant marginal bone loss was present. Using implants during orthodontics can result in an easier and more predictable treatment.

Adolescent↗

Patients' experience of pain and discomfort during instrumentation in the diagnosis and non-surgical treatment of periodontitis.

BACKGROUND: The present multicenter study aimed to survey the patients' experiences in relation to the diagnosis and non-surgical treatment of periodontitis according to current treatment routine. METHODS: Patients (N = 268) treated for plaque-related periodontitis were enrolled in two groups: group 1 received primary probing of pocket depths (PD 1) and/or primary scaling and root planing (SRP 1); group 2 consisted of patients who were scheduled in the different centers for recall PD/scaling/subgingival instrumentation. Data collection included a full periodontal status, anesthesia employed, procedure time, and patient self-completed questionnaires to assess their previous and current experience of pain and discomfort during anesthesia and periodontal treatment. RESULTS: Ninety percent of the patients received infiltration anesthesia during primary SRP, compared to only 2% during recall scaling/instrumentation and none during PD. Many patients (40% in SRP group 1 and 52% in the recall scaling/instrumentation group) were most bothered by the scaling procedure, while others (35% in the primary SRP patients) by the anesthetic injection. Painful experiences during previous primary PD and present SRP were highly correlated (r = 0.6). CONCLUSIONS: From these results, it is evident that subgingival instrumentation causes pain and discomfort, an aspect that should be considered in periodontal therapy. Unfortunately, the use of local infiltration anesthesia to reduce pain is in itself a cause of discomfort. Attractive alternatives for anesthetic applications are much needed.

Adult↗