Effect of Subgingival Instrumentation on Neutrophil Elastase and C-Reactive Protein in Grade B and C Periodontitis: Exploratory Analysis of a Prospective Cohort Study.

Background: Assessment of the effect of subgingival instrumentation (SI) on systemic inflammation in periodontitis grades B (BP) and C (CP). Methods: In this prospective cohort study, eight BP and 46 CP patients received SI. Data were collected prior to and 12 weeks after SI. Blood was sampled prior to, one day, 6, and 12 weeks after SI. Neutrophil elastase (NE), C-reactive protein (CRP), leukocyte count, lipopolysaccharide binding protein, interleukin 6 (IL-6) and IL-8 were assessed. Results: Both groups showed significant clinical improvement. NE was lower in BP than CP at baseline and 1 day after SI, while CRP was lower in BP than CP at baseline (p < 0.05). NE and CRP had a peak 1 day after SI (p < 0.05). Between-subjects effects due to CP (p = 0.042) and PISA (p = 0.005) occurred. Within-subjects NE change was confirmed and modulated by grade (p = 0.017), smoking (p = 0.029), number of teeth (p = 0.033), and PISA (p = 0.002). For CRP between-subjects effects due to BMI (p = 0.008) were seen. Within-subjects PISA modulated the change of CRP over time (p = 0.017). Conclusions: In untreated CP, NE and CRP were higher than in BP. SI results in better PPD and PISA reduction in BP than CP. Trial registration: Deutsches Register Klinischer Studien DRKS00026952 28 October 2021 registered retrospectively.

Retrospectively analysed tooth loss in periodontally compromised patients: Long-term results 10 years after active periodontal therapy-Patient-related outcomes.

BACKGROUND AND OBJECTIVE: Long-term tooth retention is the ultimate goal of periodontal therapy. Aim of this study was to evaluate tooth loss (TL) during 10 years of supportive periodontal therapy (SPT) in periodontal compromised patients and to identify factors influencing TL on patient level. MATERIAL AND METHODS: Patients were re-examined 120 ± 12 months after active periodontal therapy. TL and risk factors [smoking, initial diagnosis, SPT adherence, interleukin-1 polymorphism, cardiovascular diseases, age at baseline, bleeding on probing (BOP), change of practitioner, insurance status, number of SPT, marital and educational status] influencing TL on patient level were assessed. RESULTS: One-hundred patients (52 female, mean age 65.6 ± 11 years) lost 121 of 2428 teeth (1.21 teeth/patient; 0.12 teeth/patient/y) during 10 years of SPT. Forty-two of these were lost for periodontal reasons (0.42 teeth/patient; 0.04 teeth/patient/y). Significantly more teeth were lost due to other reasons (P < .001). Smoking, baseline severity of periodontitis, non-adherent SPT, positive interleukin-1 polymorphism, marital and educational status, private insurance, older age at baseline and BOP, small number of SPT were identified as patient-related risk factors for TL (P < .05). CONCLUSION: During 120 ± 12 months of SPT, only a small number of teeth was lost in periodontally compromised patients showing the positive effect of a well-established periodontal treatment concept. The remaining risk for TL should be considered using risk-adopted SPT allocation.

Five-year stability of clinical attachment after regenerative treatment of infrabony defects compared to controls.

AIM: To evaluate the stability of attachment achieved in infrabony defects by regenerative treatment over 60 ± 12 months compared to control teeth. METHODS: Patients treated regeneratively in at least one infrabony defect between 2004 and 2010 were screened for this retrospective cohort study. Complete examinations available for baseline, 12 and 60 ± 12 months after surgery, and a respective control tooth without treatment, provided eligibility for analysis. RESULTS: Twenty-seven patients (age 58 ± 11.7 years; 12 females, five smokers) were included, each contributing one infrabony defect and one control tooth. Regenerative therapy resulted in significant attachment gain (2.7 ± 1.6 mm; p < 0.001) after 1 and (3.0 ± 2.2 mm; p < 0.001) 5 years. Control teeth were stable (vertical probing attachment level [PAL-V] change: 1 year: 0 ± 0.8 mm; 5 years: -0.2 ± 1.2 mm). The study did not detect any significant change of PAL-V from 1 to 5 years after surgery for regenerative (-0.3 ± 2.4 mm) and control teeth (-0.2 ± 1.4 mm). Multivariate analysis associated smoking and generalized recurrence of periodontitis (amount of sites with PPD > 5 mm) with attachment loss. CONCLUSIONS: PAL-V achieved by regenerative therapy in infrabony defects is as stable over 5 years as periodontally reduced but gingivally healthy or gingivitis sites. Smoking and periodontitis recurrence are associated with attachment loss.

Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis.

Membrane-bound proteinase 3 (PR3m) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3m triggers neutrophil activation with the secretion of enzymatically active PR3 and related neutrophil serine proteases, thereby contributing to vascular damage. PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis. We first studied neutrophilic PR3 from 24 patients with Papillon-Lefèvre syndrome (PLS), a genetic form of CatC deficiency. PLS neutrophil lysates showed a largely reduced but still detectable (0.5-4%) PR3 activity when compared with healthy control cells. Despite extremely low levels of cellular PR3, the amount of constitutive PR3m expressed on the surface of quiescent neutrophils and the typical bimodal membrane distribution pattern were similar to what was observed in healthy neutrophils. However, following cell activation, there was no significant increase in the total amount of PR3m on PLS neutrophils, whereas the total amount of PR3m on healthy neutrophils was significantly increased. We then explored the effect of pharmacological CatC inhibition on PR3 stability in normal neutrophils using a potent cell-permeable CatC inhibitor and a CD34+ hematopoietic stem cell model. Human CD34+ hematopoietic stem cells were treated with the inhibitor during neutrophil differentiation over 10 days. We observed strong reductions in PR3m, cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised.

Long-Term Stability After Regenerative Treatment of Infrabony Defects: A Retrospective Case Series.

BACKGROUND: This study aims to evaluate long-term stability of attachment achieved in infrabony defects (IBDs) by regenerative treatment. METHODS: All patients who had received regenerative treatment for at least one IBD between 2004 and 2010 were screened for this retrospective case series. If complete examinations (plaque/gingival index, probing depth [PD], vertical clinical attachment level [CAL-V]) were available for patients at baseline and 12 months after surgery, they were invited for reexamination 60 ± 12 months after surgery. Reexamination involved testing for interleukin (IL)-1 polymorphism and counting number of supportive periodontal treatment (SPT) visits. Forty-one patients (24 males and 17 females; age, median: 62.0 years, lower/upper quartile: 49.8/68.3 years; six smokers, and 9 IL-1 positive) were included for analysis, each contributing one IBD. RESULTS: Regenerative therapy resulted in significant attachment gain after 1 (median: -3 mm, lower/upper quartile: -1.5/-4 mm; P <0.001) and 5 (median: -3 mm, lower/upper quartile: -1.9/4.5 mm; P <0.001) years. The study failed to detect median change of CAL-V from 1 to 5 years after surgery (median: 0 mm; lower/upper quartile: -1/1.5 mm; P = 0.84). Multiple regression analysis identified that number of SPT visits is correlated with CAL-V gain from 1 to 5 years after surgery. IL-1 polymorphism and percentage of sites with PD >6 mm at 5-year reexamination are correlated with CAL-V loss from 1 to 5 years after surgery. CONCLUSIONS: CAL-V achieved by regenerative therapy in IBDs may have retained stability over 5 years. Frequent SPT is associated with stability. IL-1 polymorphism and generalized reinfection are associated with less stability.

Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.

Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles.

Generation of the soluble interleukin-6 receptor (sIL-6R) is a prerequisite for pathogenic IL-6 trans-signaling, which constitutes a distinct signaling pathway of the pleiotropic cytokine interleukin-6 (IL-6). Although in vitro experiments using ectopically overexpressed IL-6R and candidate proteases revealed major roles for the metalloproteinases ADAM10 and ADAM17 in IL-6R shedding, the identity of the protease(s) cleaving IL-6R in more physiological settings, or even in vivo, remains unknown. By taking advantage of specific pharmacological inhibitors and primary cells from ADAM-deficient mice we established that endogenous IL-6R of both human and murine origin is shed by ADAM17 in an induced manner, whereas constitutive release of endogenous IL-6R is largely mediated by ADAM10. Although circulating IL-6R levels are altered in various diseases, the origin of blood-borne IL-6R is still poorly understood. It has been shown previously that ADAM17 hypomorphic mice exhibit unaltered levels of serum sIL-6R. Here, by quantification of serum sIL-6R in protease-deficient mice as well as human patients we also excluded ADAM10, ADAM8, neutrophil elastase, cathepsin G, and proteinase 3 from contributing to circulating sIL-6R. Furthermore, we ruled out alternative splicing of the IL-6R mRNA as a potential source of circulating sIL-6R in the mouse. Instead, we found full-length IL-6R on circulating microvesicles, establishing microvesicle release as a novel mechanism for sIL-6R generation.

Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

BACKGROUND: Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. AIM: We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. METHODS: To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. RESULTS: Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. CONCLUSIONS: Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

An extraordinary form of the Melkersson-Rosenthal syndrome successfully treated with the tumour necrosis factor-α blocker adalimumab.

Melkersson-Rosenthal syndrome (MRS) is a rare granulomatous inflammatory disease characterised by the triad of orofacial oedema, facial nerve palsy and furrowed tongue. We describe the case of a 29-year-old patient suffering from an oligosymptomatic form of the disease with orofacial oedema, cobblestone pattern on the buccal mucosa and swelling of the tongue, accompanied by intermittent fatigue, influenza-like symptoms, intermittent tinnitus and acute hearing loss. An increase of several autoimmune-associated antibodies was also detected. Treatment with prednisolone, azathioprine or methotrexate failed to adequately control all symptoms in the long term. In the absence of a specific and well-established therapy for MRS, treatment with adalimumab was administered. Under adalimumab, total remission of all symptoms was achieved, indicating that tumour necrosis factor-α blockers are a promising therapeutic option for patients with Melkersson-Rosenthal syndrome.

Enamel matrix derivative in propylene glycol alginate for treatment of infrabony defects with or without systemic doxycycline: 12- and 24-month results.

BACKGROUND: This aim of this study is to compare regenerative therapy of infrabony defects with and without administration of post-surgical systemic doxycycline (DOXY) 12 and 24 months after therapy. METHODS: In each of 57 patients, one infrabony defect (depth ≥ 4 mm) was treated regeneratively using enamel matrix derivative at two centers (Frankfurt am Main and Heidelberg). By random assignment, patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Twelve and 24 months after surgery, clinical parameters (probing depths [PDs] and vertical clinical attachment level [CAL-V]) and standardized radiographs were obtained. Missing data were managed according to the last observation carried forward. RESULTS: Data of 57 patients (DOXY: 28; PLAC: 29) were analyzed (26 males and 31 females; mean age: 52 ± 10.2 years; 13 smokers). In both groups, significant (P <0.01) PD reduction (DOXY: 3.7 ± 2.2 mm; PLAC: 3.4 ± 1.7 mm), CAL-V gain (DOXY: 2.7 ± 1.9 mm; PLAC: 3.0 ± 1.9 mm), and bone fill (DOXY: 1.6 ± 2.7 mm; PLAC: 1.8 ± 3.0 mm) were observed 24 months after surgery. However, the differences between both groups failed to be statistically significant (PD: P = 0.574; CAL-V: P = 0.696; bone fill: P = 0.318). CONCLUSIONS: Systemic DOXY, 200 mg/day for 7 days, after regenerative therapy of infrabony defects did not result in better PD reduction, CAL-V gain, or radiographic bone fill compared with PLAC 12 and 24 months after surgery, which may be attributable to low power and, thus, random chance.

NSP4 is stored in azurophil granules and released by activated neutrophils as active endoprotease with restricted specificity.

Whereas neutrophil elastase, cathepsin G, and proteinase 3 have been known as granule-associated serine proteases of neutrophils for decades, a fourth member, called neutrophil serine protease 4 (NSP4), was just recently described and provisionally characterized. In this study, we identified NSP4 as a novel azurophil granule protein of neutrophils by Western blot analyses of subcellular fractions as well as by RT-PCR analyses of neutrophil precursors from human bone marrow. The highest mRNA levels were observed in myeloblasts and promyelocytes, similar to myeloperoxidase, a marker of azurophil granules. To determine the extended sequence specificity of recombinant NSP4, we used an iterative fluorescence resonance energy transfer-based optimization strategy. In total, 142 different peptide substrates with arginine in P1 and variations at the P1', P2', P3, P4, and P2 positions were tested. This enabled us to construct an α1-proteinase inhibitor variant (Ile-Lys-Pro-Arg-/-Ser-Ile-Pro) with high specificity for NSP4. This tailor-made serpin was shown to form covalent complexes with all NSP4 of neutrophil lysates and supernatants of activated neutrophils, indicating that NSP4 is fully processed and stored as an already activated enzyme in azurophil granules. Moreover, cathepsin C was identified as the activator of NSP4 in vivo, as cathepsin C deficiency resulted in a complete absence of NSP4 in a Papillon-Lefèvre patient. Our in-depth analysis of NSP4 establishes this arginine-specific protease as a genuine member of preactivated serine proteases stored in azurophil granules of human neutrophils.

Long-term results after treatment of periodontitis in patients with Papillon-Lefèvre syndrome: success and failure.

AIM: Retrospective evaluation of periodontal status in patients with Papillon-Lefèvre syndrome (PLS) observed for ≥10 years; identification of factors that may influence treatment outcome; and reporting of the outcome of dental implants in four PLS patients. METHODS: All PLS patients currently registered at the Department of Periodontology, Goethe-University Frankfurt with a follow-up ≥10 years (13-33 years; mean 22 years) were recruited. Eight patients (aged 17-46 years) from five families (three pairs of siblings) were included. RESULTS: After comprehensive periodontal therapy in eight PLS patients, teeth were retained in only two. In six patients, all teeth were extracted, almost entirely due to periodontal reasons. In four patients, teeth were prosthodontically restored with implants. Currently, three patients already show peri-implantitis. CONCLUSIONS: In some PLS patients, periodontitis may be arrested by: combined mechanical and antibiotic periodontal treatment; extraction of severely diseased teeth; oral hygiene instructions; intensive maintenance therapy; and microbiological monitoring and treatment of the infection with Aggregatibacter actinomycetemcomitans. Implants in PLS patients who did not follow any maintenance programme have a high risk of peri-implantitis and implant loss. Treatment of PLS patients has always to be considered as high-risk cases.

Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis.

AIM: Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. METHODS: Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. RESULTS: At baseline, serum elastase, CRP, and LBP were significantly (p < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. CONCLUSION: SRP results in serum elastase reduction in AgP but not in ChP.

Regenerative therapy of infrabony defects with or without systemic doxycycline. A randomized placebo-controlled trial.

AIM: Comparison of regenerative therapy of infrabony defects with and without administration of postsurgical systemic doxycycline (DOXY). METHODS: In each of 61 patients one infrabony defect was treated with enamel matrix derivative (EMD), EMD plus filler or membrane at two centres. By random assignment patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Prior to and 6 months after surgery probing pocket depths (PPD) and vertical attachment level (PAL-V) were obtained. RESULTS: Fifty-four patients (DOXY: 27; PLAC: 27) were re-examined after 6 months and had been treated exclusively with EMD. Seven to 8 days after surgery 81% of defects in both groups showed complete flap closure. In both groups significant (p < 0.001) PPD reduction (DOXY: 3.87 ± 1.44 mm; PLAC: 3.67 ± 1.30 mm) and PAL-V gain (DOXY: 3.11 ± 1.50 mm; PLAC: 3.32 ± 1.83 mm) were observed. However, the differences failed to be statistically significant (PPD: 0.20; p = 0.588; PAL-V: 0.21; p = 0.657). CONCLUSIONS: Two hundred milligram systemic DOXY administered for 7 days after therapy of infrabony defects with EMD failed to result in better PPD reduction and PAL-V gain compared with PLAC which may be due to low power (50%) and, thus, random chance.

Cytokine production by leukocytes of Papillon-Lefèvre syndrome patients in whole blood cultures.

Papillon-Lefèvre syndrome (PLS) is characterised by aggressively progressive periodontitis combined with palmo-plantar hyperkeratosis. It is caused by "loss of function" mutations in the cathepsin C gene. The hypothesis behind this study is that PLS patients' polymorphonuclear leukocytes (PMNs) produce more proinflammatory cytokines to compensate for their reduced capacity to neutralize leukotoxin and to eliminate Aggregatibacter actinomycetemcomitans. Production of more interleukin (IL)-8 would result in the attraction of more PMNs. The aim of this study was to evaluate the cytokine profile in PLS patients' blood cultures. Blood was sampled from eight PLS patients (one female) from six families (antiinfective therapy completed: six; edentulous: two) with confirmed cathepsin C mutations and deficient enzyme activity. Nine healthy males served as controls. Whole blood cultures were stimulated with highly pure lipopolysaccharide (LPS) from Escherichia coli R515 and IL-1ß plus tumor necrosis factor (TNF)-α. Thereafter, release of IL-1ß (stimulation: LPS and LPS plus adenosine triphosphate), IL-6, IL-8, interferon-inducible protein (IP)-10, and interferon (IFN)-γ (stimulation: LPS, IL-1ß/TNFα) were detected by ELISA. Medians of cytokine release were, with the exception of IP-10, slightly higher for PLS than for controls' cultures. None of these differences reached statistical significance. Increased production of IL-1ß, IL-6, IL-8, IP-10, or IFNγ as a significant means to compensate for diminished activity and stability of polymorphonuclear leukocyte-derived proteases could not be confirmed in this study. Cytokine profiles in blood cultures may not be used to identify PLS patients.

Increased systemic elastase and C-reactive protein in aggressive periodontitis (CLOI-D-00160R2).

The inflammatory mediators, serum elastase and C-reactive protein (CRP), are associated with an increased risk for coronary heart disease. Thus, the aim of this study is to compare systemic inflammatory mediators in periodontally healthy controls (C), patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. C [periodontal pocket probing depth (PPD) <3.6 or <5 mm without bleeding (BOP), BOP < 10%], ChP (PDD ≥ 3.6 mm and probing attachment loss ≥5 mm at >30% of sites; age >35 years), and AgP (clinically healthy; PDD ≥ 3.6 mm at >30% of sites, bone loss ≥50% at ≥2 teeth; age ≤35 years) were examined clinically, and the body mass index was assessed. Blood was sampled for assessment of serum levels of elastase, CRP, lipopolysaccharide binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts. Thirty C, 31 ChP, and 29 AgP were analyzed. Elastase, CRP, LBP, and IL-6 levels were elevated in AgP compared to C (p < 0.013), whereas leukocyte counts and IL-8 were similar. Multiple regression analysis identified AgP (p < 0.001) and education level (p < 0.001) to explain 47% of the variation of elastase. AgP (p = 0.003), African origin (p = 0.006), female sex (p = 0.002), and BMI (p < 0.001) explained 39% of the variation of CRP. Serum elastase and CRP are significantly elevated in AgP compared to C. AgP patients exhibit a stronger systemic inflammatory burden than C patients.

Evaluation of two siblings with Papillon-Lefèvre syndrome 5 years after treatment of periodontitis in primary and mixed dentition.

BACKGROUND: This case report describes the clinical and microbiologic long-term outcome 5 years after periodontal therapy of two siblings diagnosed with Papillon-Lefèvre syndrome (PLS) and tinea capitis. METHODS: In 2005, two brothers diagnosed with PLS and tinea capitis began periodontal treatment. Both of them showed premature mobility of the primary dentition, markedly increased probing depths, and subgingival Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; Aa). Initial therapy consisted of scaling and root planing based on the concept of full-mouth disinfection, extraction of periodontally hopeless deciduous teeth, and systemic antibiotics. Reevaluation of clinical parameters revealed a dramatic improvement. After that, the patients were enrolled in a stringent maintenance program. Microbiologic monitoring was performed 1 and 5 years after treatment. RESULTS: Five years after initial treatment, the periodontal situation was stable in both patients. Residual deciduous teeth, with the exception of one tooth, could be retained and no further teeth were lost. Further disease progression on the previously involved teeth was controlled, and development of periodontitis on erupting teeth was prevented for a period of 5 years. CONCLUSIONS: Even periodontally affected deciduous teeth can be treated successfully in patients with PLS. Suppression of Aa and a stringent maintenance program are of high importance.

Degree of gingivitis correlates to systemic inflammation parameters.

BACKGROUND: Investigation of interrelations between periodontal and systemic inflammatory parameters in periodontal health. METHODS: 40 periodontally healthy (probing pocket depths [PPD]<3.6 mm and from 3.6 mm to 4 mm without bleeding on probing [BOP]; up to 2 sites with a PPD from 3.6 mm to 5 mm and BOP or up to 4 sites with a PPD from 3.6 mm to 5 mm without BOP were accepted; BOP

Functional Cathepsin C mutations cause different Papillon-Lefèvre syndrome phenotypes.

AIM: The autosomal-recessive Papillon-Lefèvre syndrome (PLS) is characterized by severe aggressive periodontitis, combined with palmoplantar hyperkeratosis, and is caused by mutations in the Cathepsin C (CTSC) gene. This study aimed to identify CTSC mutations in different PLS phenotypes, including atypical forms and isolated pre-pubertal aggressive periodontitis (PAP). MATERIAL AND METHODS: Thirteen families with different phenotypes were analysed by direct sequencing of the entire coding region and the regulatory regions of CTSC. The function of novel mutations was tested with enzyme activity measurements. RESULTS: In 11 of 13 families, 12 different pathogenic CTSC mutations were found in 10 typical PLS patients, three atypical cases and one PAP patient. Out of four novel mutations, three result in protein truncation and are thus considered to be pathogenic. The homozygous c.854C>T nucleotide exchange (p.P285L) was associated with an almost complete loss of enzyme activity. The observed phenotypic heterogeneity could not be associated with specific genotypes. CONCLUSIONS: The phenotypic variability of the PLS associated with an identical genetic background may reflect the influence of additional genetic or environmental factors on disease characteristics. CTSC mutation analyses should be considered for differential diagnosis in all children suffering from severe aggressive periodontitis.

Non-surgical periodontal therapy with adjunctive topical doxycycline: a double-blind randomized controlled multicenter study.

AIM: Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy. METHODS: A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers (Heidelberg, Frankfurt, Nijmegen) were treated in this double-blind split-mouth study. In each patient, 3 different treatment modalities were assigned randomly to 3 test teeth: scaling and root planing alone (SRP), SRP with subgingival vehicle control (VEH), and SRP with subgingival application of a newly developed biodegradable 15% doxycycline gel (DOXI). At baseline, clinical parameters were measured at all single rooted teeth using a reference splint: PlI, PPD, relative attachment level (RAL-V), GI. 3 strata were generated according to baseline PPD: (i) 5-6 mm, (ii) 7-8 mm, (iii) > or =9 mm. Not more than 50% active smokers were allowed to each stratum. 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites. The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to Huynh & Feldt. The comparison of SRP versus DOXI was considered as the main study question. RESULTS: 110 patients finished the 3 months and 108 the 6 months examination. The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel. DOXI provided statistically significantly more favorable PPD reduction (SRP: -2.4+/-1.4 mm, VEH: -2.7+/-1.6 mm, DOXI: -3.1+/-1.2 mm; SRP versus DOXI p=0.0001, VEH versus DOXI p=0.0066) and RAL-V gain (SRP: 1.6+/-1.9 mm, VEH: 1.6+/-2.2 mm, DOXI: 2.0+/-1.7 mm; SRP versus DOXI p=0.027, VEH versus DOXI p=0.038) than SRP and VEH after 6 months. CONCLUSIONS: Adjunctive topical subgingival application of a biodegradable 15% doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH. Thus, by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets.