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Effectiveness of different interdental brushes on cleaning the interproximal surfaces of teeth and implants: a randomized controlled, doubleblind crossover study

Nardnadda Chongcharoen Effectiveness of different interdental brushes on cleaning the interproximal surfaces of teeth and implants: arandomized controlled, double-blindcross-over study Authors' affiliations: Key words: Circum® brush, efficacy, implant dentistry, interdental brushes, interproximal Nardnadda Chongcharoen, Martina Lulic, Niklaus cleaning, oral hygiene, periodontology, plaque removal P. Lang, Implant Dentistry, Prince Philip DentalHospital, The University of Hong Kong, Hong KongSAR, China Objectives: To compare the interproximal cleansing efficacy of the novel, waist-shaped Circum® Corresponding author:Prof. Niklaus P. Lang brush (Topcaredent®, Switzerland; CB) with that of a straight soft interdental brush (IB) (TePe®, The University of Hong Kong Sweden; SB) on posterior surfaces.
Prince Philip Dental Hospital34 Hospital Road Material & methods: Eight patients after completion of initial periodontal therapy abolished oral hygiene for 3 days. Baseline plaque scores (PlI, Silness & Lo¨e 1964) were assessed on eight surfaces Hong Kong SAR China of all premolars and molars. Subsequently, an instructed nurse applied at random one of the two Tel.: + 852 2859 0526Fax: + 852 2858 6114 IB, three times per interdental space . Following this, registration of the PlI was repeated by the same blinded examiner. After a 2-week recovery, patients abolished oral hygiene practices for another 3 days. Again, pre-and post-brushing PlI were recorded by the same examiner. The second IB was now applied.
Results: Patient mean PlI and site PlI were evaluated before and after application of the SB or CB respectively. Paired t-tests were performed to yield statistically significant differences. Thereduction of biofilm from before to after the use of the IB on a subject basis was highly significant (P < 0.0001). The mean PlI after the use of the CB was significantly lower than after the use of theSB (P < 0.0001). Comparing the PlI of the line angles (MB, ML, DB, DL), significantly more biofilmhad been removed by applying CB compared with SB (P < 0.0001). Moreover, comparing the PlI ofthe buccal (MB, DB) or the lingual line angles (DL, ML) yielded a significantly higher reduction of biofilm in favour of the CB (P < 0.0001). The reduction of the PlI in the mid-interproximal portion,both mesially and distally did not differ significantly between CB and ST. No biofilm reduction was seen on the buccal sites with either IB.
Conclusion: The application of the waist-shaped Circum® IB resulted in significantly lower PlI scores than the use of a straight IB. This was predominantly due to the higher cleansing effect of the waist-shaped CB on the buccal and lingual line angles.
Interproximal areas of the dentition are the in reducing the severity of periodontal dis- most difficult areas to clean and to keep eases (Ash et al. 1964; Lo¨e et al. 1965; Lindhe clean (Lang et al. 1977; Galgut 1996). Implant & Koch 1967; Lo¨e 1969; Suomi et al. 1971).
sites are even more difficult for cleansing.
The primary cleansing devices for home Toothbrush bristles alone will not penetrate care biofilm removal are manual tooth- and clean interproximal spaces (Lang et al.
brushes (Bass 1954). Nevertheless, these will 1973; Caton et al. 1993). As a consequence, not be sufficient to clean the dentition inter- periodontal disease most commonly develops proximally (Caton et al. 1993). Today, many in interproximal areas (Lo¨vdal et al. 1958; devices for cleansing interproximal spaces are Date:Accepted 30 October 2011 Lo¨e et al. 1965).
available on the market. One of the problems To cite this article: The removal of both supra and sub-gingival encountered may lie within the patient's Chongcharoen N, Lulic M, Lang NP. Effectiveness of different plaque is important in reducing the onset compliance to use these devices for an ade- interdental brushes on cleaning the interproximal surfaces ofteeth and implants: a randomized controlled, double-blind and severity of gingival disease (Carter et al.
quate time necessary for interdental cleans- 1975; Bergenholtz & Brithon 1980). Regular ing, usually requiring 4 min or more (Gjermo Clin. Oral Impl. Res. 23, 2012, 635–640doi: 10.1111/j.1600-0501.2011.02387.x and complete biofilm removal therefore helps & Flo¨tra 1970). Studies have demonstrated 2011 John Wiley & Sons A/S Chongcharoen et al  Interproximal area cleansing with two interdental brushes that approximately 10% of population only is between the devices. When all devices were the patients signed consent forms. Patients regularly applying interdental devices (Ronis compared, the results favoured the interden- were recruited from January 2011 to May et al. 1993; Bakdash 1995; Kalsbeek et al.
tal brush (P < 0.001) only at the buccal sites.
Another study (Jackson et al. 2006) confirmed The superiority in effectively penetrating these findings and revealed a significant Inclusion criteria the interproximal spaces axially and subgin- reduction of plaque with both devices, but A subject had to meet all of the inclusion cri- givally for both dental floss and interdental with no differences between dental floss and teria listed to participate in this study: brushes has been clearly documented (Waerh- the interdental brush both for supra and sub- • Open interproximal spaces from the aug 1976 & 1981). In wide interdental spaces, gingival plaque. However, the patients pre- canines to the second molars both in interdental brushes were the most effective ferred interdental brushes.
mandible and maxilla devices for cleaning (Gjermo & Flo¨tra 1970).
Until now, there is limited evidence on the • Size of resulting interproximal spaces had Although efficient, dental floss is difficult comparison of the plaque removing effective- to be fit for the placement of a Top Care- to use, especially by older people and those ness of more recently propagated interdental dent Circum® brush No. 3 (diameter 5-3- patients with special needs. In such cases, brushes. When comparing the cleansing effi- 5 mm) or a No. 5 (diameter 7-4-7 mm).
the use of interdental brushes seems to be cacy of dental floss with that of cylindrical- more preferable for optimal oral cleansing brushes (Ro¨sing et al. 2006), significant pla- Exclusion criteria Brithon 1980; Christou et al. 1998). Interden- que reduction after usage was found in all Subjects with any of the following criteria at tal brushes used in combination with tooth- three groups. However, both shapes of inter- baseline would be excluded from the study: brushes have been more effective in biofilm dental brushes removed more plaque than did • Presence of oral diseases other than peri- removal in interproximal spaces than tooth dental floss.
brushing alone or the use of them in a com- A waist-shaped interdental brush (Cir- • Drugs consumption that may cause gingi- bination with dental floss (Kiger et al. 1991).
cum®) presents with more diameter at the val enlargement such as Phenytoin®, In recent years, studies have shown that base and tip and hence, may result in more Cyclosporin etc.
the maintenance care and the standard of the contact to the teeth or prostheses at the lin- • Presence of uncontrolled Diabetes mell- patient's home care were key factors for long- gual and buccal line angles when passing term stability of dental implants and the pre- through the interproximal area. Moreover, • Tabacco consumption: Heavy smokers (a vention of biological complications (Bauman when retrieved, the bristles might drag out pack/day or more) et al. 1991; Silverstein & Kurtzmian 2006; more biofilm at the tooth angles resulting in • Presence of gingival tissue swelling or Serino & Stro¨m 2009).
a better cleansing effect than that of regular suppuration with impossibility to apply Biofilm build-up is associated with clinical signs of inflammation both at implant and Hence, the purpose of this study was to tooth sites (Zitzmann et al. 2001). Conse- assess the cleansing capacity of two interden- quently, the regular and complete removal of tal brushes in cleaning interproximal surfaces it remains the key prerequisite in the preven- in the posterior region of the mouth both at A cross-over design was used for the present tion of such host responses. The effectiveness tooth and implant sites: The waist-shaped clinical experiment (Fig. 1).
of interproximal cleaning devices used in Top Caredent Cirum®brush and the straight Each subject was asked to attend three interproximal areas between implants or Extra soft TePe® Interdental brush. The Null- implants and teeth therefore is of utmost hypothesis of this study was that of no differ- In the first visit, interdental spaces from the distal of the canines to the second molars The cleansing effect of interproximal clean- between the two interdental brushes at both were assessed, and the size of the interdental ing devices was investigated in several stud- implant and tooth sites.
brushes to fit the interdental space was deter- ies throughout the years.
Forty years ago, one of the first studies eval- Prior to the application of the brushes, bio- uated three interdental cleansing devices Material and methods film build-up was allowed for 3 days of abol- (Gjermo & Flo¨tra 1970). The first experiment ished oral hygiene practices. The patient's compared the plaque removal effect of tooth- The study protocol has been submitted to mouth was used as a model, and all the picks against that of dental floss. Both devices cleaning procedures were performed by the yielded significant plaque reductions compar- Review Board of the University of Hong same trained dental surgery assistant. The ing before and after (P < 0.001) scores. When Kong/Hospital Authority Hong Kong West interdental brush was guided through the used in open wide interdental spaces, no dif- Cluster (HKU/HA HKW IRB) (IRB Ref. UW interdental spaces of all molars and premo- ference between the cleansing effect of tooth- lars three times. The respective sizes of the picks and that of dental floss was observed.
interdental brushes for the cleansing are indi- More recently, Yost et al. (2006) compared cated in Table 1.
the cleansing effect of the interdental brush Eight patients who had been treated in Cen- Randomization was performed by the toss Go-between® with two types of floss and an tre of Advanced Dental Care in the Prince of a coin. In Group 1, every interproximal interdental cleaner. The result has shown sig- Philip Dental Hospital at the University of posterior space was cleaned three times nificant differences of the plaque scores after Hong Kong were recruited for the study on applying the Top Caredent waist-shaped having used the devices. However, there was the basis of their availability. After having Circum® brush first (Fig. 2). Following this, no significant difference in plaque reduction been informed about the study procedures, the residual plaque deposits were assessed.
636 Clin. Oral Impl. Res. 23, 2012 / 635–640 2011 John Wiley & Sons A/S

Chongcharoen et al  Interproximal area cleansing with two interdental brushes Assesment of interdental spaces & interdental brush size selection 3 days of abolished oral hygiene Fig. 4. Graphic scheme showing the area of plaquescore assessments (DB, distobuccal; B, buccal; MB, me-siobuccal; M, mesial; ML, mesiolingual; L, lingual; DL, distolingual; D, distal).
Extra soft Tepe ® Interdental brush interproximal brush and the Top Caredent Circum® brushes inthe second test period after 3 days of abol- 3 days of abolished oral hygiene ished oral hygiene practices.
Extra soft Tepe ® Clinical parameters Interdental brush interproximal brush The Plaque Index (Silness & Lo¨e 1964) wasassessed by one blinded and calibrated exam- Fig. 1. Flow chart of clinical procedures.
iner (NPL) at eight areas of the teeth orimplants separately (buccomesial, buccodis-tal. linguomesial, linguodistal, midbuccal, Table 1. Sizes of waist-shaped Circum® brush (Topcaredent®; CB) as test and straight soft inter- dental brush (Tepe®; SB) as control applied in the eight volunteers of the study midlingual, mesial and distal; Fig. 4). Thereproducibility of the examiner was 92% (Lang et al. 2010).
Statistical analysis Microsoft® Excel for Windows® 7 was used for data collection. Statistical analysis was calculated by The Statistical Package for the Social Science for Windows (SPSS v19.0; SPSS Inc, Chicago, IL, USA).
Mean PlI of before and after cleansing were compared using Student's t-test for pairedsamples. Level of significance is set at Mean PlI of between cleansing procedures were compared using Student's t-test forpaired samples. Level of significance is set at Frequency analyses of individual PlI scores of 0,1 vs. 2,3 were compared using Mc Ne-mar test for 1. mesio-lingual and disto-lin-gual line angles, 2. mesio-bucal and disto-buccal line angles, 3. buccal, 4. lingual, 5.
Distal, 6. Mesial, 7. mesio-lingual, disto-lin-gual,mesio-buccal and disto-buccal line angle Fig. 2. Waist-shaped Circum® (Topcaredent; CB): No. 3 Fig. 3. Straight soft IB (TePe®; SB) : red 3 mm diameter, – white (5-3-5 mm), No. 5 – red (7-4-7 mm).
blue 4 mm diameter.
Subsequently, the patients were dismissed three times in each posterior interdental and asked to come back for a second perfor- space, following which the residual plaque The subjects consisted of four men and four mance after another abolishment of oral deposits were again assessed.
hygiene practices for 3 days.
Group 2 performed the same procedures as 46.75 years). Four patients used Circum® In the second test, the patients applied the Group 1, except that the Extra soft TePe® Extra soft TePe® Interdental brush (Fig. 3) Interdental brush was applied in the first, Circum® brushes size 5 for the study.
2011 John Wiley & Sons A/S 637 Clin. Oral Impl. Res. 23, 2012 / 635–640 Chongcharoen et al  Interproximal area cleansing with two interdental brushes The dentition of the patients merely repre- Circum® IB was significantly lower than the the test device (Circum ®) was PlI = 0.0 (SD: sents a model to test the efficacy of the IB in 0.0). The difference was highly significant removing biofilm in the interproximal area.
PlI = 1.39 (SD: 0.63) of the TePe® IB (P < 0.0001).
Both teeth and implants present were used.
(P < 0.0001) as well.
The mean baseline mesial and distal pla- A total of 102 teeth and implants and 816 que score applying the control device (TePe®) sites were assessed.
Mean plaque score at buccal sites (Table 2) was PlI = 1.98 (SD: 0.20) and PlI = 1.99 (SD: The mean baseline buccal plaque score apply- 0.17) respectively. After intervention, the Overall mean plaque score (Table 2) ing the test device (Circum ®) was PlI = 1.72 mean mesial and distal plaque score applying Mean baseline plaque score applying the test (SD: 0.48). After intervention, the mean buc- the control device (TePe ®) was PlI = 0.0 (SD: device (Circum ®) was PlI = 1.89 (SD: 0.03).
cal plaque score applying the test device (Cir- 0.0). Again, the difference was highly signifi- After intervention, the mean plaque score cum ®) was PlI = 1.33 (SD: 0.62). The cant (P < 0.0001).
applying the test device (Circum ®) was difference was highly significant (P < 0.0001).
After intervention, the mean mesial and PlI = 0.45 (SD: 0.08). The difference was The mean baseline buccal plaque score distal score was PlI = 0.0 (SD: 0.0) for the highly significant (P < 0.0001).
applying the control device (TePe®) was Circum® IB, and the mean mesial and distal Mean baseline plaque score applying the PlI = 1.67 (SD: 0.53). After intervention, the score was PlI = 0.0 (SD: 0.0) for the TePe® IB.
control device (TePe®) was PlI = 1.88 (SD: mean buccal plaque score applying the con- There was no statistically significant differ- 0.10). After intervention, the mean plaque trol device (TePe ®) was PlI = 1.42 (SD: 0.42).
score applying the control device (TePe ®) Again, the difference was highly significant was PlI = 1.02 (SD: 0.21). Again, the differ- (P < 0.0001).
Frequency analyses of sites with PlI = 0 &1 vs.
ence was highly significant (P < 0.0001).
After intervention, the mean buccal score After intervention, the mean plaque score was PlI = 1.33 (SD: 0.62) for the Circum® IB, At the line angles (total of 408 sites), the Mc (mean PlI = 0.45 (SD: 0.08) for the Circum® and the mean buccal score was PlI = 1.42 Nemar test revealed a significant improve- IB was significantly lower than the mean pla- (SD: 0.62) for the TePe® IB. This difference, ment of the plaque score categories from que score (mean PlI = 1.02 (SD: 0.21) of the however, was not statistically significant.
before to after the interventions (P < 0.0001) TePe® IB (P < 0.0001) as well.
for both test and control devices (Fig. 5).
The PlI for both test (Circum®) and control At the buccal line angles and lingual line Mean plaque score at lingual sites (Table 2) (TePe®) interdental brushes before and after The mean baseline lingual plaque score angles (total of 204 sites each)(Mesio-buccal the cleansing procedures are indicated in applying the test device (Circum ®) was Table 2. Overall, mean PlI, mean PlI of the PlI = 1.55 (SD: 0.56). After intervention, the showed a significant improvement of the pla- four line angles, mean PlI of the buccal line mean lingual plaque score applying the test que score categories from before to after the angles, the lingual line angles and the four device (Circum ®) was PlI = 0.91 (SD: 0.51).
interventions (P < 0.0001) for both test and sites are separately presented (Mesial, distal, control devices (Fig. 6). Note that following (P < 0.0001).
the cleansing procedure, none of the lingual The mean baseline lingual plaque score line angle sites demonstrated a PlI = 2 & 3after applying the Circum® brush.
Mean plaque scores at line angles applying the control device (TePe®) was PlI = 1.55 (SD: 0.52). After intervention, the Disto-lingual) (Table 2) mean lingual plaque score applying the con- The mean baseline line angle plaque score trol device (TePe ®) was PlI = 1.21 (SD: 0.53).
applying the test device (Circum®) was Again, the difference was highly significant PlI = 1.97 (SD: 0.17). After intervention, the This study has clearly demonstrated the (P < 0.0001).
mean line angle plaque score applying the superiority in cleansing effectiveness of the After intervention, the mean lingual plaque test device (Circum ®) was PlI = 0.33 (SD: Circum® interdental brush (CB) over the score (mean PlI = 0.91 (SD: 0.51) for the Cir- 0.53). The difference was highly significant straight control brush (TePe®) (SB). Eight sub- cum® IB was significantly lower than the (P < 0.0001).
jects had been drawn to the study contribut- mean lingual plaque score (mean PlI = 1.21 The mean baseline line angle plaque score ing with a total of 816 tooth and implant (SD: 0.53) of the TePe® IB (P < 0.0001) as applying the control device (TePe®) was sites. The subjects merely represented a PlI = 1.96 (SD: 0.21). After intervention, the model for testing the efficacy of the IB mean line angle plaque score applying the brushes. To determine the size of the differ- Mean plaque score at interproximal sites control device (TePe ®) was PlI = 1.39 (SD: ence in removing biofilm between the two 0.63). Again, the difference was highly signif- The mean baseline mesial and distal plaque brushes, a reverse power analysis was per- icant (P < 0.0001).
score applying the test device (Circum ®) was formed (Cohen 1988). Following the equation After intervention, the mean line angle pla- PlI = 1.99 (SD: 0.10). After intervention, the (; Power ¼ ESa n when ES = (the effect size or que score (mean PlI = 0.33 (SD: 0.53) for the mean mesial and distal plaque score applying the mean difference), n = the number of Table 2. Mean (SD) of plaque score for all sites assessed before and after the cleansing procedure (a) plaque score before and after application is sig- nificantly different (P < 0.0001) (b) plaque score after application of Circum® and Tepe® is significantly different (P < 0.0001) Buccal line angles Lingual line angles 638 Clin. Oral Impl. Res. 23, 2012 / 635–640 2011 John Wiley & Sons A/S Chongcharoen et al  Interproximal area cleansing with two interdental brushes firmed a power of 80% of the present study the interdental or inter-implant region to fit at an a = 0.05.
Circum® IB of the sizes No.3 or No. 5. The The cleansing effectiveness for both the CB control SB was chosen accordingly. Hence, and the SB resulted in significant mean bio- the cleansing procedure that was standard- film reductions, when before and after appli- ized and performed by a specially trained cer- cation was compared at the subject and site tified dental surgery assistant allowed the levels in this study. This cleansing effect is direct comparison between the two devices.
in agreement with previous studies (Kiger For this evaluation, the original Plaque et al. 1991; Jared et al. 2005, Jackson et al.
Index (Silness & Lo¨e 1964) was modified for 0+1 After 2+3 After 2006; Ro¨sing et al. 2006; Yost et al. 2006).
the assessment of the line angles.
However, when the two interdental brushes A similar approach was chosen in a com- of the present study were compared after parative study to evaluate the cleansing effi- application, there was no significant differ- cacy of IB and dental floss in periodontitis Fig. 5. Plaque score distribution (PlI 0 & 1 vs. 2 &3) ence at both mesial and distal sites, both patients (Christou et al. 1998). In this study, before and after the cleansing procedure for Circum®and TePe® brushes respectively.
yielding zero scores. This, in turn, means special attention was given to the biofilm that both CB and SB are effective in purely reduction at the four line angles. Indeed, IB d = the standard deviation) application resulted in superior efficacy in assuming power of 80% and a level of signifi- However, there were highly significant dif- biofilm removal than did dental floss.
cance (a) at 0.05, the minimum detectable ferences in biofilm removal after the applica- There are only very few studies that com- effect size (MDES) can be calculated. For the tion of the CB compared with SB at the line pared the efficacy of two different interdental patient level, the effect size of mean plaque angles, both buccally and lingually. Hence, brushes in removing biofilm. In one study scores before and after using CB = 0.41, the the cleansing efficacy of the CB clearly sur- (Ro¨sing et al. 2006), the plaque removal effect effect size of mean plaque scores before and passes that of the SB. It has to be kept in of conical IBs vs. cylindrically shaped IBs was after using SB = 0.8 and the effect size of mind, however, that the efficacy of the brush compared. Although a significant biofilm mean plaque scores after using CB and itself, and not the capacity of the subject to removal from baseline was documented with SB = 1.2. A high ES of 1.2 means that the clean interproximally, was evaluated in the both brushes, there were no significant differ- mean plaque score difference between the present study. Obviously, better cleaning ences between the two different designs indi- two brushes after application had to be at- effects may be obtained with straight IB by cating that both cylindrical as well as conical least PlI = 1.2 to be detected. As the detect- well-instructed patients under the correct IB may have satisfactory cleansing efficacy. It able size was high (PlI = 1.2) and yet, the anatomical conditions and adequate time has to be realized, however, that the biofilm result indicated significantly differences, the allocation. In the present study, subjects removal at the line angles was not assessed reverse power analysis of this study con- were selected to provide adequate space in in the said study.
The present study aimed at a comparison of two completely different IB design. Anovel product, the waist-shaped Circum® Circum®-Li line angles brush (CB) was to be tested against a standard Tepe®-Li ®line angles size and straight interdental brush (SB). The Circum®-B line anglesTepe®-B line angles results showed significant differences in bio- fim removal effectiveness for CB over SB forall aspects of the tooth or implant evaluatedexcept the buccal sites that were not affectedby IB application. The waist-shaped brush that had a larger diameter at the base and thetip when passed through the proximal con-tact certainly provided more friction to the teeth or prosthesis at the lingual line angles.
In addition, when retrieved, the bristles mayhave removed more biofilm at the lineangles, thus resulting in a better cleansing effect than the SB. Biofilm removal at lingualsites was also superior with the CB, althoughIBs are not necessarily designed to clean onthe lingual aspects of teeth or implants. This, in turn, means that the larger diameter end Circum®-Li line angles bristles even reach to the mid-lingual aspect.
Tepe®-Li ®line angles The present study is different from many Circum®-B line angles of the studies that instructed the patients of Tepe®-B line angles how to use interdental brushes and asked Fig. 6. Plaque score distribution (PlI 0 & 1 vs. 2 &3) before and after application of Circum® and TePe® IB at lingual them to come back for examination later on (Li) and buccal (B) line angles.
(e.g. Bassiouny & Grant 1981, Christou et al.
2011 John Wiley & Sons A/S 639 Clin. Oral Impl. Res. 23, 2012 / 635–640 Chongcharoen et al  Interproximal area cleansing with two interdental brushes 1998, Jared et al. 2005). In those studies, an Both CB and SB used in the present study effect in biofilm removal is the combined were of a super soft type. These characteris- been supported by the Clinical Research result of the efficacy of the IB applied, the tics may be addressed when elaborating on Foundation (SKF) for the Promotion of Oral design of the handle of the IB, the skills and the cleansing efficacy of a brush. However, Health, Brienz, Switzerland. The products dexterity of the patient and the motivation to no influence of bristle stiffness on cleansing used in this study were kindly provided by devote sufficient time and energy into inter- efficiency has been documented in an in vitro the manufacturers, Top Caredent® AG, proximal cleansing. Moreover, studies with study comparing hard and soft bristle IBs Zu¨rich, Switzerland and TePe AB, Malmo¨, patient performance usually provide data on (Wolff et al. 2006).
Sweden. No other financial means have been the changes in the host response, such as In conclusion, the application of the waist- provided. The help of the dental surgery reduction in bleeding on probing and/or prob- shaped Circum® IB resulted in significantly assistants of the Centre of Advanced Dental ing depth reduction. The present study was lower PlI scores than the use of a straight IB.
Care at the Prince Philip Dental Hospital is not designed to test those possible effects.
This was predominantly due to the much highly appreciated. The competent assistance Standardization was the important feature of higher cleansing effect of the waist-shaped of Ms. Camie So Kam Fung is acknowledged.
the study design, and only the effectiveness Circum® brush on the buccal and lingual line The authors declare no conflict of interest.
in cleansing was to be evaluated.
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Operative risks of digestive surgery in cirrhotic patients

ARTICLE IN PRESS Gastroentérologie Clinique et Biologique (2009) xxx, xxx—xxx Vous êtes autorisé à consulter ce document mais vous ne devez en aucun cas le télécharger ou l'imprimer. Operative risks of digestive surgery incirrhotic patients Risque opératoire du patient cirrhotique en chirurgie digestive drogen 02.indd

medizinische informationen für menschen mit hiv 2016 Drogen begleiten menschliche Gemeinschaften seit Urzeiten. Offenbar ist die Sehnsucht nach einer Veränderung des Bewusstseins, einer „Alternative zur Realität" ein Grundbedürfnis. In der Vergangenheit waren es zunächst Stoffe pflanzlicher und tierischer Herkunft, die zu diesem Zweck verwen­det wurden. Durchbrüche in der synthetischen Chemie führten jedoch dazu, dass „Designerdrogen" zunehmend populär wurden.