Journ. Dept. Educ., Teikyo Univ. 31: 1–6 Treatment of hypereosinophilic syndrome with the anti-allergic drugs azelastine hydrochloride or fexofenadine, and biscoclaurine alkaloids* Department of Education, School of Liberal Arts, Teikyo University 359 Otsuka, Hachioji-shi, Tokyo 192-0395 This is the first report which suggests the azelastine hydrochloride (AZE) or fexofenadine (FEX)
Dans la pharmacie en ligne Viagra-représenté Paris large éventail de la dysfonction érectile anti-plus consommée. Générique Levitra (vardenafil), Cialis (tadalafil) et achat viagra pour homme, dont le prix est acceptable pour tous les budgets.1
Yo no soy un gran amante de pedir medicamentos por internet. Pero a veces la necesidad de herramientas, que en las farmacias regulares o no, o rara vez cialis generico Recibes como un paquete, todo montado y embalado.
Orofacial.com.auORAL APPLIANCES FOR THE TREATMENT OF SNORING AND OBSTRUCTIVE SLEEP APNEA: A REVIEW
Oral Appliances for the Treatment of Snoring and ObstructiveSleep Apnea: A ReviewAn American Sleep Disorders Association Review Wolfgang Schmidt-Nowara1, Alan Lowe2, Laurel Wiegand3, Rosalind Cartwright4, Francisco Perez-Guerra5 and Stuart Menn6 1Pulmonary Division, Department of Medicine, University of New Mexico, Albuquerque, NM; 2Department of ClinicalDental Sciences, University of British Columbia, Vancouver, British Columbia, Canada; 3Department of Medicine,Pulmonary/Critical Care Division, Penn State College of Medicine, Hershey, PA; 4Sleep Disorders Service and ResearchCenter, Rush-Presbyterian-St. Luke's Medical Center, Rush University, Chicago, IL; 5Division of Pulmonary Disease, Scottand White Clinic, Temple, TX; and 6Division of Sleep Disorders, Scripps Clinic, La Jolla, CA Summary: This paper, which has been reviewed and approved by the Board of Directors of the American Sleep Disorders
Association, provides the background for the Standards of Practice Committee's parameters for the practice of sleep medicine in
North America. The 21 publications selected for this review describe 320 patients treated with oral appliances for snoring and
obstructive sleep apnea. The appliances modify the upper airway by changing the posture of the mandible and tongue. Despite con-
siderable variation in the design of these appliances, the clinical effects are remarkably consistent. Snoring is improved and often
eliminated in almost all patients who use oral appliances. Obstructive sleep apnea improves in the majority of patients; the mean
apnea-hypopnea index (AHI) in this group of patients was reduced from 47 to 19. Approximately half of treated patients achieved
an AHI of < 10; however, as many as 40% of those treated were left with significantly elevated AHIs. Improvement in sleep quality
and sleepiness reflects the effect on breathing. Limited follow-up data indicate that oral discomfort is a common but tolerable side
effect, that dental and mandibular complications appear to be uncommon and that long term compliance varies from 50% to 100%
of patients. Comparison of the risk and benefit of oral appliance therapy with the other available treatments suggests that oral appli-
ances present a useful alternative to continuous positive airway pressure (CPAP), especially for patients with simple snoring and
patients with obstructive sleep apnea who cannot tolerate CPAP therapy.
Key Words: Sleep apnea syndromes; Snoring; Orthodontic appliances; Diagnosis; Therapy.
An oral appliance was considered as treatment for 2.1 Selection of papers
mandibular deficiency and upper airway obstruction as The data for this review were derived from computer early as 1902 (1). With the recent interest in sleep apnea, searches of the clinical literature (MEDLINE, July 1994; oral appliances of various designs have been proposed and search terms: orthodontic appliances, activator appliances studied, and are used increasingly to treat snoring and sleep or related subjects; sleep apnea syndromes, snoring; search apnea. The purpose of this review is to evaluate evidence period 1966—1994) and from consultation with experts.
regarding the effectiveness of these devices. The term "oral We selected articles, principally from peer-reviewed publi- appliance" is used as a generic term for devices inserted cations, that describe the patients, the treatments and the into the mouth in order to modify the position of the measurements in sufficient detail to allow reproduction of mandible, the tongue, and other structures in the upper air- the study. Abstracts and review papers were not considered.
way for the purpose of relieving snoring or sleep apnea.
Although many of these devices attach to the teeth and use 2.2 Validity of published data
conventional dental technology, we use the more generalterm to include devices that are used intraorally but are not Our search strategy identified 21 papers suitable for this necessarily retained directly by the teeth.
review (Table 1). Each paper was evaluated according to Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al Table 1—Papers meeting the selection criteria for this review of oral appliances: effects on obstructive sleep apnea, sleep and
recommended validity criteria (2). None of the studies used strengthens the identification of a treatment effect (18,19).
a randomized control design. Instead, this literature con- Furthermore, the average effect on the apnea-hypopnea sists entirely of case series (Sackett's Level V, reference 2) index (AHI), the main outcome variable for obstructive with comparisons of conditions before and with treatment.
sleep apnea (OSA), is greater than what might be attribut- Although this design allows for confounding by other time- ed to random variability (23). All the patients were adults related changes, the interval between studies is usually who appeared to be similar to OSA patients in other case brief, and other interventions have been excluded. In two series: predominantly male, middle-aged and overweight.
studies, polysomnography was performed with and without However, selection bias based on the clinician's judgment the appliance during the same night, a study design that and the patient's preference may limit the ability to gener- Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al alize to other populations of sleep apnea patients. The diag- Upper airway resistance is relatively increased in sleep nosis of OSA was validated with polysomnography in all apnea patients (39,40). The resulting more negative inspirato- but one study (14). Outcomes were assessed with subjective ry pressure is thought to be an important factor in airway reports (4,10,14,17-21) and objective measurements (3-22,24) that collapse and obstruction (41). Increased airway compliance are widely used in clinical practice and research.
may also contribute to airway collapse in apnea patients (42).
Inspiratory excitation of upper airway muscles maintains patency when awake (43). Excessive relaxation or loss of 3.1 Snoring
compensatory excitation of upper airway muscles explainsthe propensity to collapse during sleep (41,43).
Snoring is a common affliction, affecting persons of all ages, but particularly middle-aged and elderly men and 3.4 Treatments of snoring and OSA
women who are overweight (25-27). Snoring has been identi- Treatments of snoring and OSA are directed at the upper fied as a risk indicator of and possible risk factor for hyper- airway and have included tracheostomy, surgery of the soft tension, ischemic heart disease and stroke, although its eti- palate and oropharynx [uvulopalatopharyngoplasty ologic role in these conditions is controversial (28).
(UPPP)], reconstructive surgery of the facial skeleton, Although not all snorers have sleep apnea, snoring is a car- nasal continuous positive airway pressure (CPAP) and dinal symptom of OSA and may by this mechanism be medications (44,45). Weight reduction is an important adjunct associated with increased morbidity. Furthermore, snoring in obese patients. These treatments are limited by a low and in some patients without apnea has been associated with unpredictable success rate (UPPP, medication, weight significant sleep disturbance and sleepiness. This so-called reduction), inconvenience (tracheostomy, CPAP), cost "upper airway resistance syndrome" is characterized by (reconstructive surgery) and/or patient noncompliance repeated arousals related to increased upper airway resis- tance without recognizable hypopneas or apneas; treatmentof the upper airway obstruction improves sleepiness in 3.5 Central sleep apnea
these patients (29). Thus, snoring is now recognized as asymptom that may be related to clinical conditions with Infrequently a clinically significant sleep disorder significant morbidity. In addition, the social embarrassment occurs due to periodic breathing and central apneas caused and distress of loud snoring often motivate individuals to by intermittent reductions in respiratory effort. The patho- request professional help.
physiology of this central sleep apnea syndrome is not wellunderstood, although upper airway obstruction may be a factor in some cases (46). Oral appliances have been usedalmost exclusively for snoring and OSA, but one report of Obstructive sleep apnea syndrome is a common, chron- successful treatment of 2 patients with central sleep apnea ic disorder of sleep and breathing that causes disability with the tongue-retaining device (TRD) has appeared in the from pathologic sleepiness and respiratory and cardiovas- literature (47). The subsequent discussion of oral appliances cular complications (30,31). OSA is related to upper airway will be restricted to their use for the treatment of snoring obstruction that develops during sleep with manifestations that include snoring, apneas and hypopneas.
4.0 ORAL APPLIANCES
3.3 Pathophysiology of OSA
The pathophysiology of OSA includes factors related to upper airway anatomy, upper airway resistance and upper Oral appliances are used by dentists for many purposes, airway muscle function during sleep (32). Upper airway including correction of various types of occlusal disorders.
anatomy varies considerably among patients, so that no sin- The techniques often modify the position of the mandible gle finding is pathognomonic of obstructive apnea.
within the restricted mobility defined by the temporo- However, narrowing of the upper airway is commonly mandibular joint (TMJ) and the pterygoid muscles. In the observed, especially at the level of the soft palate and the last decade, a variety of dental devices have been devel- base of the tongue (33,34). Cephalometric variants of the oped for treatment of snoring and OSA. A recent review facial skeleton have been described, including a relative summarizes design features and claims and/or proofs of retrognathia and a low position of the hyoid bone (35,36).
efficacy of 13 devices (48). Oral appliances offer an alterna- Soft tissue changes include a decrease in the posterior air- tive that may be attractive for OSA patients dissatisfied way space (35,36), an increase in tongue volume (37) and, in with other therapies or unwilling to accept more complex some cases, pathologic enlargement of the palatine or ade- noidal tonsils (38).
Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al 4.2 Types of oral appliances used for snoring and OSA
secure the tongue by means of negative pressure in a softplastic bulb; a flange, which fits between the lips and teeth, The appliances evaluated in this review include predom- holds the device and tongue anteriorly in the oral cavity. It inantly devices that are designed to advance the mandible.
should be noted that these devices also modify mandibular Because of this shared design feature, these appliances are posture, at least by downward rotation. The TRD has been treated in the following discussion as one class, although fabricated from dental impressions, but a prefabricated ver- individual design differences may have important effects sion, suitable for molding to the patient's teeth in the clin- on their clinical utility. Also included in the review is one ic, is now available (6).
well-studied appliance that modifies tongue position (6). Wehave not found studies of other devices that modify tongue 5.0 MECHANISM OF ACTION OF ORAL APPLIANCES
position that meet our selection criteria, nor have we foundsuch studies of the several devices with posterior extension The goal of therapy with an oral appliance is to modify to the soft palate or the base of the tongue. For all appli- the position of upper airway structures so as to enlarge the ances, proper fitting and alignment is important. A profes- airway or otherwise reduce its collapsibility. In addition to sional society of dentists interested in sleep disorders has airway size, the effects on muscle function or airway com- issued recommendations for the implementation of oral pliance may also be important. Mandible-advancing oral appliance therapy (48). However, we have not found infor- appliances have been shown, via cephalometric radio- mation that allows us to critically evaluate this element of graphs, to increase various upper airway dimensions in the treatment. The potential for worsening upper airway patients when they are awake. In 12 patients, the consistent function should be recognized: patients with worse apnea- change caused by an oral appliance that produced advance- hypopnea frequencies with treatment than before are ment and downward rotation of the mandible was an described in several of the selected reports (4,7-11,19). For all increase in the superior airway space, i.e. the space these reasons, conclusions regarding clinical effects should between the soft palate and the posterior nasopharynx (4).
be limited to the devices specified by citation.
The posterior airway space, i.e. the space between the baseof the tongue and the posterior oropharynx, was signifi- 4.2.1 Mandibular advancing devices
cantly increased with one oral appliance (19), but was notincreased with two others (4,11). Another cephalometric Of the many oral appliances that have been proposed for study of 10 patients with OSA showed a 56% mean the treatment of snoring or sleep apnea, most have designs increase in posterior airway space when maximal mandibu- that use traditional dental techniques to attach the device to lar protrusion was compared to the rest position (49). Hyoid one or both dental arches and to modify the mandibular bone position was important in one series both as a pre- posture. Construction requires dental impressions, bite reg- treatment predictor and as a posttreatment indicator of a istration and fabrication by a dental laboratory. However, at successful reduction of AHI (11). This same study also asso- least one device is now available in a prefabricated form ciated shortening of the soft palate length with a good treat- with a thermolabile material that can be molded to the ment response. Each study revealed considerable variation patient's teeth in the clinician's office (19). Several appli- between patients. In a complex computerized tomographic ances allow readjustment of the mandibular position after study of one patient, an oral appliance increased the airway initial construction, but for others this requires refabrica- space but also changed the shape of the tongue and soft tion of the entire device. All oral appliances produce down- palate (20).
ward rotation of the mandible to varying extents; many also Each of these studies has a bias to external validity advance the mandible by design. Of the appliances that because the observations were made in the awake state and attach to both dental arches, some restrict mouth opening oral appliances are intended to be used for sleeping by means of clasps and elastic bands, whereas others allow patients. The studies indicate that dental devices produce relatively unhindered mouth opening. Some designs complex changes in the shape and function of the upper air- include tubes or openings for oral breathing or pressure way that may positively influence airway patency during relief. Several appliances feature a posterior extension of the maxillary component that is designed to modify theposition of the soft palate or tongue. Illustrations of 13 oral 6.0 EFFICACY OF ORAL APPLIANCES
appliances, including mandibular advancing devices andtongue-positioning devices, have been published (48).
6.1 Evaluation of clinical utility
4.2.2 Tongue retainers
The clinical utility of a treatment consists of its benefit, including efficacy and patient compliance, and its cost, A second class of oral appliance is designed to keep the including side effects, complications and the financial cost tongue in an anterior position during sleep. These devices of treatment and related diagnostic procedures. Efficacy for Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al Table 2—Reviewed publications reporting the effect of oral appliances on snoring
these oral appliances includes their effects on snoring and tance syndrome. Oral appliances may be effective in this sleep apnea as well as their secondary consequences, condition, because they improve snoring in a high propor- including sleep disturbance, sleepiness and any putative tion of patients. However, the studies neccessary to identi- long-term sequellae. The subsequent discussion reviews fy this condition and the effect of oral appliance therapy the evidence regarding oral appliances in each of these have not been performed.
6.3 Sleep apnea
This review includes 20 publications reporting the All published clinical studies in which snoring was effects of oral appliances on OSA in 304 patients (Table 1).
assessed, representing a variety of devices, show improve- All reports showed improvement with an appliance in the ment in a high proportion of patients (Table 2). For exam- average AHI. Inspection of this table shows similar treat- ple, a follow-up study of 68 patients reported reduced snor- ment effects in the peer-reviewed and other papers and ing in all but one patient, and 50% of patients reported shows no consistent differences among the various devices.
elimination of snoring (19). In another study of 48 patients, When statistics were provided, the decrease in AHI was 17% of bed partners reported snoring to be eliminated, 75% always significant (p < 0.05). Of the 271 cases with data reported snoring to be much improved, and 8% reported reported in a form suitable for calculation, the mean AHIs improvement of a lesser extent (18). The effect of the TRD before and with treatment were 42.6 and 18.8, respectively, on snoring has not been reported in the several publications an average reduction of 56%. The degree of improvement describing this device. However, in a retrospective tele- varied: although 70% of the patients in these studies had at phone survey of 36 patients who had successfully adapted least a 50% reduction in AHI, many did not correct to nor- to chronic use (duration 1 month to 12 years), all but one mal levels, and some patients did not improve or became patient reported a decrease in their snoring; 19 patients worse. Fifty-one percent of patients achieved normal reported that their snoring was "eliminated" (Rosalind breathing, defined as an AHI of < 10, with treatment.
Cartwright, personal communication, 1994).
Conversely, 39% of patients with an initial AHI of >20 In the majority of studies, improved snoring has gener- remained above that level with treatment. In the 14 papers ally been inferred from the reports of patients or bed part- presenting data for individual patients, 20 patients (13%) ners. However, laboratory recording documented improved had a greater AHI with treatment with the device than snoring with an appliance in one case report (20).
before treatment (4,7-11,19).
Additionally, a recent report documented a significant With oral appliance treatment, eight of nine studies reduction of laboratory-recorded snore frequency and reported an improvement in oxygenation assessed by the sound intensity in 51 patients after treatment with a minimum oxygen saturation, although the changes were "mandibular advancement splint"; each of these patients modest (Table 1). In one study, the median oxygen satura- with a bed partner reported improved snoring (18). Although tion during sleep remained unchanged, but the time in sleep limited in number, these objective observations support the with oxygen saturation of < 90% was reduced from 4.4% to consistent improvement reported by patients and bed part- Treatment success was related to the initial AHI in three Patients with snoring and without apnea or hypopnea studies (11,18,19), but not in a fourth (13). Two studies suggest- may have sleep pathology due to the upper airway resis- ed success would be unlikely with an AHI of > 50 or > 60, Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al respectively (18,19), but substantial improvement has been are not always described (Table 3). Excessive salivation reported in other patients with AHIs of >60 (10-12,20). In and transient discomfort for a brief time after awakening another study, consideration of several cephalographic are commonly reported with initial use and may prevent parameters in addition to the initial AHI significantly early acceptance of oral appliances (18,19). With regular use improved the ability to predict posttreatment AHI (11).
and adjustment of fit, these symptoms subside. Later com- These observations represent attempts to predict treatment plications may include TMJ discomfort and changes in success with oral appliances, but the data are too limited to occlusive alignment. In one study, 3 of 20 patients reported formulate any general recommendations.
TMJ pain as a reason for discontinuing treatment; the The effect of the TRD on apnea and "low" oxygen satu- symptoms remitted after treatment was stopped (10). In ration is similar to that achieved with other oral appliances another study, 3 of 14 surveyed patients reported a sense of (Table 1). Two studies noted that a reduction in AHI of at altered occlusion, but the severity was not specified (17).
least 50% was associated with a significant positional Other reports examined but did not find these problems effect before treatment, i.e. a greater apnea frequency in the (11,19,21,22,49). Thus, published reports suggest that TMJ pain supine than the side position (7,8). Predictors of treatment and occlusal changes are relatively uncommon occur- success were body weight less than 125% of ideal and an rences, but the long-term risk of these complications is not AHI at least twice the frequency in the supine position of well defined. With the TRD, 8 of 12 respondents to a 6- that in the lateral position. Additional reports suggest that month survey admitted some discomfort with this therapy the TRD is a useful adjunct to failed UPPP surgery (5) and (6). The potential for an adverse effect on breathing exists, to position training (to avoid sleep in the supine position) but the frequency of this complication is not known. Other side effects or complications for this device have not beenreported.
6.4 Sleep and sleepiness
Polygraphic assessments of sleep before and during oral appliance treatment have shown a reduction in stage 1 A formal survey of the costs of devices and service has sleep, an increase in slow wave and stage REM sleep and a not been performed for oral appliances. The production reduction in sleep fragmentation, mid-sleep wake time and cost of the device varies depending on whether a dental lab- arousals (Table 1). Most, but not all, patients reported an oratory is required for custom fitting or a prefabricated unit improvement in daytime sleepiness. One study showed can be adapted in the clinician's office. The TRD is provid- improvement in 2 vigilance tests associated with improve- ed in one clinical laboratory for $200. The lowest cost of ment of AHI (21). Multiple sleep latency testing with oral dental services known to the task force is $300 for fitting appliance use has not been reported.
and adjustment of a prefabricated appliance. More typicalcosts for custom-fitted appliances and service range from 7.0 SIDE EFFECTS, COMPLICATIONS, AND COST
$400 to $900 (Great Lakes Orthodontics, Tonawanda, NY,personal communication, October 1993). When cephalo- 7.1 Side effects and complications
metric radiographs or other airway studies are performed as Nine reports on oral appliances mention side effects and part of the procedure, the cost increases accordingly.
complications, although the methods for their investigation Table 3—Reviewed publications reporting the side effects, complications, and patient compliance with oral appliances
Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al acceptance without complications. Nasal CPAP hasbecome the consensus first choice because of its efficacy Data on long-term compliance are limited in number and (44,45), but patient acceptance and compliance are significant are all based on patient reports (Table 3). The experience problems. On average, 10% of patients offered CPAP with nasal CPAP, however, indicates that self reports may choose not to try the treatment (56). At follow-up 2—48 significantly overestimate objectively determined actual months after starting CPAP, 50—90% of patients are still use (50,51). Patients need instruction regarding the proper use using this form of treatment (56). Of those using CPAP, of all oral appliances. Some patients do not initially use the many do not use it all night or every night (50,51).
device for the whole night (6). One study reported that, after Tracheostomy is the only other treatment with an efficacy adaptation, patients used an oral appliance "the entire night comparable to CPAP (57), but given today's alternatives, few and almost every night" (19). Overall compliance rates vary patients select a treatment requiring a permanent prosthesis in different studies and may be related to the length of fol- in the neck. Oral appliances and all the other alternatives to low-up. Compliance with oral appliance use ranged from nasal CPAP and tracheostomy, either medical or surgical, 100% in 14 patients followed for 3 to 21 months (14), to are effective in a lower proportion of patients. The widely 75% in 68 patients queried after a median of 7 months (19), applied UPPP surgery is effective, depending on the crite- to 52% in 24 patients queried after 3 years (10). The reasons rion for success, in 50—80% of patients (53,55,58), which is for discontinuing appliance use include the side effects and no better than the oral appliances reviewed here (Table 1).
complications noted above and lack of efficacy.
Compared with UPPP or the more complex facial, recon- 9.0 COMPARISON WITH OTHER THERAPIES
struction pioneered by Riley and Powell (59), oral appliancetherapy costs less and has the advantage of being easily ter- A direct comparison of oral appliance therapy to other minated without sequelae. Compared to protriptyline, the treatments has not been published. In the absence of a con- principal medication used for OSA (60), the efficacy of oral trolled trial, selection bias could produce important differ- appliance therapy is better and side effects appear to be ences between groups of patients receiving different treat- more tolerable. Compared to weight loss, the effect of oral ments, and these differences could bias any comparison appliances is realized more quickly and the rate of success between treatments. With this important caveat, it may be is higher (61). Thus, oral appliances, though providing a useful to compare oral appliances to the major treatments lower rate of AHI reduction, offer an alternative to nasal of snoring and OSA in terms of efficacy, compliance, com- CPAP; the combination of side effects, complications, plications and cost. It is beyond the scope of this paper to reversibility and cost compares favorably to the non-CPAP critically review all these other therapies for snoring and treatments of moderate to severe OSA.
OSA. Readers are referred to illustrative citations and tworecent reviews (44,45).
10.0 LIMITATIONS IN THE DATA
For primary snoring, oral appliances and soft palate The critical reader of this literature may be dismayed by surgery (presently UPPP) are the principal considerations.
the relatively small size of most case series, the lack of ran- Treatment of rhinitis and nasal obstruction, weight loss and domized controlled studies, the often sparse description of alcohol restriction are important adjuncts, but patients who the patients and the study methods. Nevertheless, the con- request medical relief from snoring have usually tried these sistency of the findings among the many studies suggests remedies. Laser surgery of the soft palate, a new procedure that larger studies would come to the same conclusions.
attracting considerable public attention, cannot be evaluat- The absence of controls has been noted but was no differ- ed because of insufficient data (52). UPPP reduces snoring ent in the studies that established nasal CPAP and the other intensity in 90% of patients and eliminates it in a smaller treatments of OSA. The problem of publication bias should proportion (53,54), a success rate similar to that of oral appli- always be considered. How many negative experiences ances (Table 2). Compliance is a problem with oral appli- have gone unreported? Furthermore, to what extent are the ance treatment. Relapse of snoring after surgery has not results in this literature dependent on the special expertise been examined in published reports, but probably does of the authors and can they be reproduced in regular clini- occur since relapse of OSA is well documented (55).
Complications are relatively infrequent with both treat- Clearly there is a great need for more information. Most ments but appear to be less severe with the oral appliances studies have focused on the acute effect of oral appliance (54) (Table 3). Cost is substantially less for oral appliances.
treatment on sleep apnea. Future studies must better define Thus, oral appliance therapy and palatal surgery offer a the effect on oxygenation in various types of patients and similar rate of treatment success for primary snoring, but the effect on sleep per se and sleepiness. Patients with well- they differ significantly in terms of cost and compliance.
defined upper airway resistance syndrome should be stud- For OSA, no currently available treatment provides the ied with oral appliance treatment. More follow-up data are ideal combination of a high rate of success and patient needed to define the rate of compliance, the risk of compli- Oral Appliances for the Treatment of OSA - Schmidt-Nowara et al cations and the need for adjustment of the appliance.
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14. Ichioka M, Tojo N, Yoshizawa M, et al. A dental device for the 11.0 SUMMARY
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Determination of the minimum inhibitory concentration of four medicaments used as intracanal medication
Aust Endod J 2007; 33: 107–111 Determination of the minimum inhibitory concentration of fourmedicaments used as intracanal medication Raul C. Pallotta, DDS, MDSc, PhD1; Mariangela S. Ribeiro, MMSc2; and Manoel E. de Lima Machado, DDS,MDSc, PhD3 1 Department of endodontics, University Cruzeiro do Sul, Sao Paulo, Brazil2 Department of Microbiology, PUCCAMP, Campinas, Brazil3 Department of Endodontics, University Camilo Castelo Branco, Sao Paulo, Brazil