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Ibrahim Gueler,1 Susanne Mueller,1 Matthias Helmschrott,1 Christian U Oeing,1 Christian Erbel,1 Lutz Frankenstein,1 Christian Gleißner,1 Arjang Ruhparwar,2 Philipp Ehlermann,1 Thomas J Dengler,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, University of Heidelberg, Heidelberg, 2Department of Cardiac Surgery, University of Heidelberg, Heidelberg, 3Department of Cardiology, SLK-Kliniken Heilbronn, Bad Friedrichshall, Germany Background: Type 2 Diabetes mellitus (T2DM) is a common comorbidity in patients after heart transplantation (HTx) and is associated with adverse long-term outcomes. Methods: The retrospective study reported here analyzed the effects of vildagliptin therapy in stable patients post-HTx with T2DM and compared these with control patients for matched-pairs analysis. A total of 30 stable patients post-HTx with T2DM were included in the study. Fifteen patients (mean age 58.6 ± 6.0 years, mean time post-HTx 4.9 ± 5.3 years, twelve male and three female) were included in the vildagliptin group (VG) and 15 patients were included in the control group (CG) (mean age 61.2 ± 8.3 years, mean time post-HTx 7.2 ± 6.6 years, all male). Results: Mean glycated hemoglobin (HbA1c) in the VG was 7.4% ± 0.7% before versus 6.8% ± 0.8% after 8 months of vildagliptin therapy (P = 0.002 vs baseline). In the CG, HbA1c was 7.0% ± 0.7% versus 7.3% ± 1.2% at follow-up (P = 0.21). Additionally, there was a significant reduction in mean blood glucose in the VG, from 165.0 ± 18.8 mg/dL to 147.9 ± 22.7 mg/dL (P = 0.002 vs baseline), whereas mean blood glucose increased slightly in the CG from 154.7 ± 19.7 mg/dL to 162.6 ± 35.0 mg/dL (P = 0.21). No statistically significant changes in body weight (from 83.3 ± 10.8 kg to 82.0 ± 10.9 kg, P = 0.20), total cholesterol (1.5%, P = 0.68), or triglyceride levels (8.0%, P = 0.65) were seen in the VG. No significant changes in immunosuppressive drug levels or dosages were observed in either group. Conclusion: Vildagliptin therapy significantly reduced HbA1c and mean blood glucose levels in post-HTx patients in this study with T2DM and did not have any negative effects on lipid profile or body weight. Thus, vildagliptin therapy presented an interesting therapeutic approach for this selected patient cohort. Keywords: immunosuppression, glycated hemoglobin, mean blood glucose

Purpose: The aim of this preliminary in vitro study was to evaluate the effect of a casein phosphopeptide and amorphous calcium phosphate (CPP-ACP) paste on untreated enamel surfaces that had previously been exposed to an erosive challenge.Materials and Methods: Over a period of 6 h, enamel samples from five fully erupted, caries-free molars were incubated with apple juice and later covered with CPP-ACP paste for 15 min. Enamel samples incubated with physiological sodium chloride solution or with apple juice alone served as controls. The quantitative elementary analysis for calcium and phosphorus in various depths ranging from 5 to 50 microm was performed using an electron-probe microanalyser.Results: Exposure to apple juice resulted in a loss of minerals down to a depth of 30 microm with a mean loss of 13% at 5 microm and 6% at 10 microm. After treatment with CPP-ACP paste, the mineral loss decreased to a mean of 9% at 5 microm and remained at 5% at a depth of 10 microm (not a statistically significant difference). At a depth of 20 microm, no further mineral loss was recorded.Conclusions: This study demonstrated that there is a slight gain in the mineral contents after the application of a CPP-ACP paste, mainly in the upper enamel layer. Within the limitations of this in vitro study, the application of CPP-ACP paste may enhance the remineralisation after an erosive challenge and thus offer some protection for patients who are at risk for erosion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study examined the effect of an alkaline, salt-containing toothpaste, a toothgel of similar contents, and a conventional toothpaste on gingival inflammation. METHOD AND MATERIALS: One hundred fifteen patients suffering from mild to moderate chronic gingivitis were enrolled in a double-blind clinical study. All subjects had at least 20 teeth, probing depths of less than 6 mm, and a sulcular bleeding index of 50% or more. At the beginning of the study period, the subjects were randomly assigned to 3 study groups. The baseline examination recorded the number of decayed, missing, and filled teeth, an approximal plaque index, a sulcular bleeding index, and the gingival index. RESULTS: After an 8-week study period, statistically significant reductions in the plaque and bleeding indexes were observed in all 3 groups. There were no significant differences among the 3 dentifrices examined. CONCLUSION: The effectiveness of salt-containing dentifrices in patients with gingivitis was comparable to that of a conventional toothpaste. [ABSTRACT FROM AUTHOR]

Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Christian Erbel,1 Christian A Gleissner,1 Fabrice F Darche,1 Dierk Thomas,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, Heidelberg University Hospital, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Purpose: Early posttransplant atrial fibrillation (AF) has been associated with worse clinical outcomes after heart transplantation (HTX). The type of surgical technique may constitute a relevant risk factor for AF. Patients and methods: This retrospective single-center study included 530 adult patients. Patients were stratified by surgical technique (biatrial, bicaval, or total orthotopic HTX) and early posttransplant heart rhythm (AF or sinus rhythm). Univariate and multivariate analyses were performed to evaluate risk factors for AF. Results: A total of 161 patients received biatrial HTX (30.4%), 115 bicaval HTX (21.7%), and 254 total orthotopic HTX (47.9%). Sixty-one of 530 patients developed early posttransplant AF (11.5%). Patients with AF showed a statistically inferior 5-year survival compared to those with sinus rhythm (P

Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Patrick A Schweizer,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, Heidelberg University Hospital, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX).Aim: The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX.Methods: Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or

Matthias Helmschrott,1 Rasmus Rivinius,1 Arjang Ruhparwar,2 Bastian Schmack,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: Nephrotoxicity is a serious adverse effect of calcineurin inhibitor therapy in patients after heart transplantation (HTX).Aim: In this retrospective registry study, renal function within the first 2 years after HTX in patients receiving de novo calcineurin inhibitor treatment, that is, cyclosporine A (CSA) or tacrolimus (TAC), was analyzed. In a consecutive subgroup analysis, renal function in patients receiving conventional tacrolimus (CTAC) was compared with that of patients receiving extended-release tacrolimus (ETAC).Methods: Data from 150 HTX patients at Heidelberg Heart Transplantation Center were retrospectively analyzed. All patients were continuously receiving the primarily applied calcineurin inhibitor during the first 2 years after HTX and received follow-up care according to center practice.Results: Within the first 2 years after HTX, serum creatinine increased significantly in patients receiving CSA (P

Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Berthold Klein,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch11Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyObjective: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX) and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR) containing immunosuppressive regimen.Methods: A total of 381 patients (age ≥18 years) receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA) and azathioprine (AZA) was replaced by CsA and mycophenolate mofetil (MMF) in 2001 and by tacrolimus (TAC) and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus) were applied since 2003.Results: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total). Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%), 56 patients with noncutaneous malignancy only (14.7%), and 16 patients with both cutaneous and noncutaneous malignancy (4.2%). Statistically significant risk factors associated with an increased risk of malignancy after HTX were older age (P1 treated rejection episode (TRE) in the first year after HTX (P=0.0091). Administration of CsA (P=0.0195), AZA (P=0.0008), or steroids (P=0.0018) for >1 year after HTX was associated with increased development of malignancy, whereas administration of MMF (P

Mohammadreza Akhavanpoor,1,2,* Christian A Gleissner,1,2,* Stephanie Gorbatsch,1,2 Andreas O Doesch,1,2 Hamidreza Akhavanpoor,1,2 Susanne Wangler,1,2 Frederik Jahn,1,2 Felix Lasitschka,3 Hugo A Katus,1,2 Christian Erbel1,2 1Department of Cardiology, University of Heidelberg, 2DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, 3Institute of Pathology, University of Heidelberg, Germany *These authors contributed equally to this work Abstract: Despite advances in the pharmacologic and interventional treatment of coronary artery disease, atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is a chronic inflammatory disease, and elevated expression of CCL19 and CCL21 has been observed in ruptured lesions of coronary arteries of patients with myocardial infarction and carotid plaques of patients with ischemic symptoms, as well as in plasma of coronary artery disease patients. However, the exact role of CCL19 and CCL21 in atherosclerosis remains unknown. In order to identify CCL19 and CCL21 as a novel therapeutic target, we performed bone marrow transplantation as an immunomodulatory treatment concept. Bone marrow of plt/plt mice (lacking CCL19 and CCL21-Ser) was transplanted into atherogenic Ldlr-/- mice. The study demonstrated a significantly increased inflammatory cellular infiltration into the lesions of plt/plt/Ldlr-/- mice versus controls. Although the level of chemoattraction was increased, messenger ribonucleic acid and protein levels in thoracic aorta and serum of several proinflammatory cytokines (TNFα, IFNγ, IL-6, IL-12, and IL-17) were significantly reduced in plt/plt/Ldlr-/- versus control mice. Increased influx, accompanied by reduced activation of leukocytes in atherosclerotic lesion, was accompanied by increased plaque stability but unchanged lesion development. In conclusion, modulation of the chemokines CCL19 and CCL21 represents a potent immunoregulatory treatment approach, and thus represents a novel therapeutic target to stabilize atherosclerotic lesions. Keywords: atherosclerosis, chemokines, immunomodulatory therapy, bone marrow trans­plantation

Matthias Helmschrott,1 Jan Beckendorf,1 Ceylan Akyol,1 Arjang Ruhparwar,2 Bastian Schmack,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany; 2Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: The use of tacrolimus (TAC) in patients after heart transplantation (HTX) has increased over the last few years. Aim: In this retrospective study, we evaluated the effects of a TAC (conventional and extended-release TAC)-based immunosuppressive therapy regarding rejection profile in comparison to a cyclosporine A (CSA)-based regimen in patients after HTX.Methods: The data of 233 patients who underwent HTX at the Heidelberg Heart Transplantation Center from May 1998 until November 2010 were retrospectively analyzed. Primary immunosuppressive therapy was changed from a CSA (n=114) to a TAC (n=119)-based regimen in February 2006 according to center routine. Follow-up period was 2 years post-HTX. Primary endpoint was time to first biopsy-proven rejection requiring therapy. In all patients, routine follow-up at the Heidelberg Heart Transplantation Center was mandatory. Results: Multivariate risk factor analysis regarding time to first rejection episode showed no statistically significant differences regarding recipient age, donor age, recipient sex, donor sex, sex mismatch, ischemic time, and diagnosis leading to HTX between the two groups (all P= not statistically significant). Time to first biopsy-proven rejection was significantly longer in the TAC group (intention-to-treat analysis, n=233, log-rank test P

Andreas O Doesch,1,* Li Zhao,1,* Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 David Rohde,1 Deniz Okuyucu,1 Maani Hakimi,2 Thomas J Dengler,3 Hugo A Katus,1 Christian Erbel1 1Department of Cardiology, 2Department of Vascular Surgery, University of Heidelberg, Germany; 3Department of Cardiology, SLK Hospital Heilbronn, Bad Friedrichshall, Germany*These authors contributed equally to this articleBackground: Atherosclerosis is based on a chronic inflammatory process including the innate and adaptive immune response. Costimulatory molecules and their receptors provide decisive signals for antigen-specific cell activation. The contribution of B7-related pathways to atherosclerosis has hardly been explored. Methods: In the present study, we investigated the contribution of B7-1 to inflammation and tissue injury in the human plaque microenvironment in order to identify possible target structures of future therapeutic agents ex vivo and in vitro.Results: Carotid artery plaque stimulation with lipopolysaccharides (LPS) could be significantly inhibited by RhuDex®, a specific inhibitor of the costimulatory molecule B7-1 ex vivo (P

Andreas O Doesch,1 Susanne Mueller,1 Christian Erbel,1 Christian A Gleissner,1 Lutz Frankenstein,1 Stefan Hardt,1 Arjang Ruhparwar,2 Philipp Ehlermann,1 Thomas Dengler,3 Hugo A Katus1 1Department of Cardiology, 2Department of Cardiovascular Surgery, University of Heidelberg, Heidelberg, 3SLK Plattenwald Hospital, Bad Friedrichshall, Germany Background: Due to graft denervation, sinus tachycardia is a common problem after heart transplantation, underlining the importance of heart rate control without peripheral effects. However, long-term data regarding the effects of ivabradine, a novel If channel antagonist, are limited in patients after heart transplantation. Methods: In this follow-up analysis, the resting heart rate, left ventricular mass indexed to body surface area (LVMI), tolerability, and safety of ivabradine therapy were evaluated at baseline and after 36 months in 30 heart transplant recipients with symptomatic sinus tachycardia versus a matched control group. Results: During the study period, ivabradine medication was stopped in three patients (10% of total). Further analysis was based on 27 patients with 36 months of drug intake. The mean patient age was 53.3±11.3 years and mean time after heart transplantation was 5.0±4.8 years. After 36 months, the mean ivabradine dose was 12.0±3.4 mg/day. Resting heart rate was reduced from 91.0±10.7 beats per minute before initiation of ivabradine therapy (ie, baseline) to 81.2±9.8 beats per minute at follow-up (P=0.0006). After 36 months of ivabradine therapy, a statistically significant reduction of LVMI was observed (104.3±22.7 g at baseline versus 93.4±18.4 g at follow-up, P=0.002). Hematologic, renal, and liver function parameters remained stable during ivabradine therapy. Except for a lower mycophenolate mofetil dose at follow-up (P=0.02), no statistically significant changes in immunosuppressive drug dosage or blood levels were detected. No phosphenes were observed during 36 months of ivabradine intake despite active inquiry. Conclusion: In line with previously published 12-month data, heart rate reduction with ivabradine remained effective and safe in chronic stable patients after heart transplantation, and also during 36-month long-term follow-up. Further, a significant reduction of LVMI was observed only during ivabradine therapy. Therefore, ivabradine may have a sustained long-term beneficial effect with regard to left ventricular remodeling in heart transplant patients. Keywords: heart transplantation, heart rate control, ivabradine, left ventricular mass

Maximilian Kraeuter,1 Matthias Helmschrott,1 Christian Erbel,1 Christian A Gleissner,1 Lutz Frankenstein,1 Bastian Schmack,2 Arjang Ruhparwar,2 Philipp Ehlermann,1 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, 2Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany Background: Cyclosporine A (CSA) is a narrow therapeutic index drug. Available CSA products differ in the constitution of their emulsion. To compare intra-individual differences after a conversion to a generic CSA, a retrospective single-center study was initiated. Methods: Twenty adult stable chronic (>24 months post heart transplant) recipients were included in the present retrospective study. These patients were previously switched from Sandimmune Neoral® to the generic CSA (Equoral®) according to the patients’ preference during the clinical routine. Dose-normalized trough levels (DNL) and trough levels (C0) at 8 months, 4 months, and 2 weeks before the switch were retrospectively compared with the corresponding values at 2 weeks, 4 months, and 8 months after the switch to the generic CSA. Additionally, changes in the routine laboratory parameters, the number of treated rejection episodes, and the adherence to the CSA target levels were compared. Results: The mean DNL (adapted to the daily CSA dose in mg) was 0.71±0.26 (ng/mL)/mg on Neoral therapy; on Equoral it was 0.68±0.23 (ng/mL)/mg, (P=0.38). In comparison to the CSA daily dose prior to the conversion, at postconversion, no significant changes of CSA daily dose were observed (Neoral 140.67±39.81 mg versus Equoral 134.58±41.61 mg; P=0.13). No rejection episodes requiring therapy occurred prior to or postconversion (P=0.99). Additionally, no statistically significant changes of routine laboratory parameters regarding the Modification of Diet in Renal Disease or hematological parameters were seen (all P=not significant). No adverse events after the conversion were observed. Conclusion: This study in chronic and stable HTx patients demonstrated no statistically significant differences in the CSA DNL after a conversion to generic CSA (Equoral). The generic CSA was generally well-tolerated. We concluded that a conversion from Neoral to Equoral is safe and clinically feasible in this distinct patient population. However, multiple switches between different generic immunosuppressants must especially be avoided in the interest of patient safety, and close follow-up examinations must be warranted. Keywords: heart transplantation, immunosuppression, generic cyclosporine A

Andreas O Doesch,1 Janika Repp,1 Nina Hofmann,1 Christian Erbel,1 Lutz Frankenstein,1 Christian A Gleissner,1 Constanze Schmidt,1 Arjang Ruhparwar,2 Christian Zugck,1 Paul Schnitzler,3 Philipp Ehlermann,1 Thomas J Dengler,4 Hugo A Katus11Department of Cardiology, 2Department of Cardiac Surgery, 3Department of Infectious Disease, Virology, University of Heidelberg, Heidelberg, 4Department of Cardiology, SLK Kliniken Heilbronn, Bad Friedrichshall, GermanyBackground: Cytomegalovirus (CMV) infection is a serious complication following heart transplantation. This study (June 2003-January 2010) retrospectively assessed the effects of oral valganciclovir prophylaxis in adult heart transplant recipients during the first year after transplantation.Methods: In patients with normal renal function, 900 mg of oral valganciclovir was administered twice daily for 14 days after heart transplant followed by 900 mg per day for following 6 months. In the event of renal insufficiency, valganciclovir was adjusted according to the manufacturer's recommendations. Antigenemia testing for pp65 antigen and simultaneous polymerase chain reaction (PCR) were used to document exposure to CMV. From 2003 to 2010, 146 patients (74.0% men) of mean age 50.7 ± 10.3 years at the time of heart transplant were included.Results: A total of 16 patients (11.0% of total, 75.0% male) had a positive pp65 and PCR result (ie, CMV infection) during the year following heart transplant; three of these patients had discontinued valganciclovir prophylaxis within the first 6 months following transplant because of leukopenia, including one patient developed CMV colitis. Two further patients developed CMV pneumonia during prophylactic valganciclovir therapy. Eight patients had positive pp65 and PCR tests in the 6–12 months after heart transplant following cessation of routine prophylaxis. One of these patients developed CMV pneumonia and another developed CMV colitis and CMV pneumonia. Thirty-seven of the 146 (25.3%) patients were CMV donor-seropositive/recipient-seronegative, and seven (18.9% of this subgroup) had a positive CMV test. In patients who were CMV donor-seropositive/recipient-seronegative, the risk of a positive CMV test (ie, CMV infection) was significantly elevated (P = 0.023).Conclusion: CMV prophylaxis with oral valganciclovir for 6 months following heart transplant is clinically feasible. In line with previous studies, CMV donor-seropositive/recipient-seronegative patients have a significantly elevated risk of CMV infection. In patients who prematurely discontinue valganciclovir, close monitoring of CMV antigenemia appears warranted. No significantly elevated rate of CMV infection was observed after 6 months of valganciclovir prophylaxis.Keywords: cytomegalovirus infection, heart transplantation, valganciclovir prophylaxis

Abstract Objective Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood. Methods Male Apoe-/- mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks. Results Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03). Conclusions Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.

Integrated safety sensors for personal protection equipment increasingly attract research activities as there is a high need for workers in delicate situations to be physically monitored in order to avoid accidents. In this work, we present a simple approach to generate thin, homogeneous polypyrrole (PPy) layers on flexible textile polyamide fabrics. PPy layers of 0.5-1 µm were deposited on the fabric, which thus kept its flexibility. The conductive layers are multifunctional and can act as temperature and gas sensors for the detection of corrosive gases such as HCl and NH 3 . Using three examples of life-threatening environments, we were able to monitor temperature, atmospheric NH 3 and HCl within critical ranges, i.e., 100 to 400 ppm for ammonia and 20 to 100 ppm for HCl. In the presence of HCl, a decrease in resistance was observed, while gaseous NH 3 led to an increase in resistance. The sensor signal thus allows for distinguishing between these two gases and indicating critical concentrations. The simple and cheap manufacturing of such PPy sensors is of substantial interest for the future design of multifunction functional sensors in protective clothing.

Background: Internal carotid artery stenosis (ICAS) can cause stroke and cognitive decline. Associated hemodynamic impairments, which are most pronounced within individual watershed areas (iWSA) between vascular territories, can be assessed with hemodynamic-oxygenation-sensitive MRI and may help to detect severely affected patients. We aimed to identify the most sensitive parameters and volumes of interest (VOI) to predict high-grade ICAS with random forest machine learning. We hypothesized an increased predictive ability considering iWSAs and a decreased cognitive performance in correctly classified patients., Materials and Methods: Twenty-four patients with asymptomatic, unilateral, high-grade carotid artery stenosis and 24 age-matched healthy controls underwent MRI comprising pseudo-continuous arterial spin labeling (pCASL), breath-holding functional MRI (BH-fMRI), dynamic susceptibility contrast (DSC), T2 and T2 * mapping, MPRAGE and FLAIR. Quantitative maps of eight perfusion, oxygenation and microvascular parameters were obtained. Mean values of respective parameters within and outside of iWSAs split into gray (GM) and white matter (WM) were calculated for both hemispheres and for interhemispheric differences resulting in 96 features. Random forest classifiers were trained on whole GM/WM VOIs, VOIs considering iWSAs and with additional feature selection, respectively., Results: The most sensitive features in decreasing order were time-to-peak (TTP), cerebral blood flow (CBF) and cerebral vascular reactivity (CVR), all of these inside of iWSAs. Applying iWSAs combined with feature selection yielded significantly higher receiver operating characteristics areas under the curve (AUC) than whole GM/WM VOIs (AUC: 0.84 vs. 0.90, p = 0.039). Correctly predicted patients presented with worse cognitive performances than frequently misclassified patients (Trail-making-test B: 152.5s vs. 94.4s, p = 0.034)., Conclusion: Random forest classifiers trained on multiparametric MRI data allow identification of the most relevant parameters and VOIs to predict ICAS, which may improve personalized treatments., Competing Interests: SK was employed by Philips GmbH Market DACH, Hamburg, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gleißner, Kaczmarz, Kufer, Schmitzer, Kallmayer, Zimmer, Wiestler, Preibisch and Göttler.)

Atherosclerosis is studied in models with dysfunctional lipid homeostasis-predominantly the ApoE -/- mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c + cells were enriched in aortae of ApoE -/- mice. Systemic long-term depletion of CD11c + cells in ApoE -/- mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11c cre+ ApoE fl/fl and Albumin cre+ ApoE fl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c + cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c + cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c + cells and demonstrated that CD11c + cells ameliorate atherosclerosis by the secretion of ApoE., Competing Interests: The authors declare no competing financial interests., (© 2021 The Author(s).)

Diabetes represents one of the most important risk factors for atherosclerosis, which is the leading cause of mortality worldwide. Recent imaging studies employing intravascular ultrasound or computed coronary angiography tomography clearly confirm that diabetes is associated with larger plaque burden and with more lesions displaying features of instability. Various molecular mechanisms promoting atherogenesis and plaque destabilization in diabetics have been described in the past. The current review specifically focuses on recent papers that have addressed the effects of diabetes and hyperglycemia (i) on myeloid cells, (ii) on oxidative stress, and (iii) on protein kinase C (PKC) activation. Thus, it has been demonstrated that hyperglycemia may promote myelopoiesis and differentiation of pro-inflammatory macrophages. Furthermore, novel studies emphasize the interplay between inflammation and oxidative stress at both the molecular and the genetic level. Finally, experimental studies shed light on the role of PKC-β in diabetes-associated atherosclerosis. Several of these recent studies suggest that atherogenesis and plaque destabilization in diabetic individuals may be mediated by diabetes-specific mechanisms. This may open the door for developing tailored anti-atherosclerotic therapies for diabetic patients.

Most oral diseases show gender-specific differences in prevalence. This is true for common diseases such as caries and periodontitis, which are considered the main causes of tooth loss, affecting women more often than men. Furthermore, other diseases, e.g. temporomandibular joint dysfunction, malignant oral tumours, and several diseases of the oral mucosa show differing incidences between men and women. This is confirmed by empirical evidence from studies in Germany and other European countries, the USA, and emerging nations in Amercia and Southeast Asia. The present article aims to summarize gender-specific knowledge on oral health and present perspectives for future research. The main focus is on tooth loss and edentulism, a key measure of oral health, and their main causes, i.e. caries and periodontitis.

Objective: Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) may be associated with atherosclerosis and vascular disease. Macrophages are a major component of atherosclerotic plaque, and classically activated (M1) macrophages contribute to plaque instability. Our goal was to identify plasma biomarkers that reflect macrophage inflammation and are associated with subclinical atherosclerosis., Approach and Results: We tested whether M1 macrophages produce galectin-3-binding protein in vitro. Then, we measured galectin-3-binding protein and the soluble macrophage biomarkers soluble cluster of differentiation (CD) 163 and soluble CD14 in 264 participants in the Women's Interagency HIV Study. Women were positive for HIV, HCV, both, or neither (66 in each group, matched for age, race/ethnicity, and smoking status). Carotid artery disease was assessed by ultrasound measurement of right distal common carotid artery intima-media thickness, distensibility, and presence of atherosclerotic lesions (intima-media thickness >1.5 mm). Plasma galectin-3-binding protein was higher in HCV+ than HCV- women (P<0.01) but did not differ by HIV status. The 3 inflammatory macrophage markers were significantly correlated with each other and negatively correlated with CD4+ counts in HIV-infected women. We defined a macrophage score as 1, 2, or 3 biomarkers elevated above the median. In models adjusted for traditional risk factors, higher macrophage scores were significantly associated with increased atherosclerotic lesions and lower carotid distensibility. Receiver-operator curve analysis of lesions revealed that the markers added predictive value beyond traditional risk factors and C-reactive protein., Conclusions: The macrophage inflammatory markers galectin-3-binding protein, soluble CD163, and soluble CD14 are significantly associated with carotid artery disease in the setting of HIV and HCV infection.

Purpose: The aim of this study was to determine the prognostic accuracy of a new chair-side test, determination of lactic-acid production on the tongue, for caries-risk assessment according to caries increment within two years., Methods: 35 children (6-8 years old) participated in the study. The past caries experience (df-t1, DF-T1), caries at second deciduous molars (df-2.mol), approximal plaque index (API) were the clinical, and salivary counts of mutans streptococci (MS)/lactobacilli (LB) and lactic-acid production on the tongue (LAP) the subclinical predictors recorded at baseline. Two years later, the dental examination was repeated (df-t2/DF-T2). According to the increase in DF-T (delta DF-T), caries-risk groups (delta DF-T = 0 versus delta DF-T > or = 0) were built. To assess the prognostic accuracy sensitivity and specificity were calculated. Statistical analysis was performed using Spearman's test for nonparametric correlations., Results: The DF-T increased from 0.3 +/- 0.8 to 1.2 +/- 1.6. 20 children were in the no-caries-risk and 15 in the caries-risk group. The p-value for the correlation of delta DF-T to API was 0.007 and to LB counts 0.069. The highest sensitivity and specificity levels were found for LB (65%/70%), LAP reached a maximum sensitivity of 33% with a specificity of 55%., Conclusion: According to the results, because of its insufficient prognostic accuracy the LAP test is not suitable as a sole screening-tool for an accurate caries-risk assessment.

Purpose: The aim of this study was to compare the results of a new method, measurement of lactic-acid production on the tongue (LAP), with established methods of caries risk assessment in children., Methods: One hundred nineteen children (6-10 years old) participated in the study. Data collection included number of carious lesions (D-T) and filled teeth (F-T), approximal plaque index (API), LAP, buffering capacity (BC), counts of mutans streptococci (MS) and lactobacilli (LB) in stimulated saliva. According to caries presence, the children were divided into low risk (LR group; D-T = 0) and high risk (HR group; D-T > or = 1) groups. Statistical analysis was performed using Chi-square test, Spearman's test for nonparametric correlations, uni- and multivariate regression analysis., Results: Seventy-two children (F-T = 0.4 +/- 1.4) were in the LR and 47 (D-T = 2.5 +/- 2.7; F-T = 1.5 +/- 1.9) in the HR group. The correlation analysis verified statistically significant correlations between D-T and the salivary counts of MS/LB and between D-T and F-T. API correlated with F-T and LB, while F-T and LB also correlated with each other significantly. The counts of MS and LB showed also a significant correlation. The LAP showed a significant correlation only to F-T. Significances in univariate regression analysis were found for F-T, counts of LB and MS in saliva, and for LAP. The multivariate regression analysis indicated significances only for F-T and LB in saliva, but not for LAP., Conclusion: LAP might be useful only as a supplementary screening tool for caries risk assessment, but not as a sole predictor.

The aim of this study was to establish correlations of clinical and radiological dental findings, alone or in combination, with chronological age in adults. Dental findings and orthopantomograms of 984 patients (aged 20-60 years; 524 females/460 males) were analyzed. DMF-T index and distance (alveolar bone level, ABL) between cemento-enamel junction and alveolar bone margin were recorded. Additionally, clinical and radiological findings at each tooth crown and root were collected according to the actual status of destruction and restoration, and a total score for each dentition (TSD) was calculated. After univariate correlation analysis, correlation coefficients for ABL and TSD were improved by using square root (sqrt). However, the determination accuracy was still not satisfactory; 90% of the residuals were in the range of about +/-10. The present study showed that clinical and radiological dental findings could not be used, not even in combination, for accurate age estimation as a single method, but that they could support other methods.

Background: This investigation aimed to: 1) develop a method to obtain reproducible laser Doppler flow readings (LDFRs) at the gingiva of the maxillary front teeth; 2) evaluate regional gingival blood flow (GBF) in healthy gingiva by laser Doppler flowmetry; 3) compare hand-held LDFR (H-LDFR) with splint LDFR (S-LDFR); and 4) monitor changes in GBF in experimental gingivitis (EG) and chronic gingivitis (CG)., Methods: The LDFR, gingival index (GI), and plaque index (PI) were measured at 13 gingival sites (teeth #6 to #11) in 10 healthy volunteers (five males and five females), 23 to 34 years of age, over a period of 12.5 +/- 3.27 days employing a partial-mouth EG model and in 11 patients (three males and eight females), 20 to 63 years or age, with CG. LDFRs were obtained by S-LDFR or H-LDFR., Results: H-LDFRs were significantly higher than S-LDFRs (P <0.05). All EG subjects developed gingivitis (PI: 2.77 +/- 0.23; GI: 1.5 +/- 0.53). EG-LDFRs at diseased sites increased slightly but not significantly over the study period. All CG-patients had high plaque and inflammation scores (PI: 2.8 +/- 0.2; GI: 1.63 +/- 0.78). CG-LDFRs at sites with GI >1 were significantly higher than LDFRs at healthy sites (P <0.05). CG-LDFRs were significantly higher than EG-LDFRs at sites with a comparable GI (P <0.05)., Conclusions: LDFRs are positively correlated with the degree of gingival inflammation. GBF demonstrated significant differences in EG and CG. Modifications of the probe are needed to enhance its clinical applicability in clinical research of periodontal diseases.

Dystrophic epidermolysis bullosa (DEB) is one of the three major types of epidermolysis bullosa (EB), an inherited cutaneous disease with blister formation following minor trauma. A subtype of DEB is recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type (RDEB-HS), where marked scarring leads to deformities of extremities. In RDEB-HS the mucous membranes may also be involved and form adhesions with ankyloglossia and microstomia. Oral hygiene is difficult. A 7-year-old boy with RDEB-HS was brought to the Johannes Gutenberg University dental clinic with dental pain. He had multiple carious lesions, poor oral hygiene and gingivitis. Because he was noncompliant and had microstomia, he required dental therapy under general anesthesia. The recall visits over the past two years had demonstrated that the dental health of this patient with RDEB-HS could be maintained by means of improved oral home care, using antibacterial agents.

Background: The effect of pre- or post-operatively acquired diabetes mellitus on survival after heart transplantation remains controversial. The influence of transplant era on diabetes-associated survival is unknown., Methods: A retrospective database analysis was performed on all cardiac transplant recipients followed up at our institution between 1986 and 2003. Diabetes mellitus was diagnosed based on oral glucose tolerance testing., Results: Survival was analyzed in 243 patients (80% male, mean age 52.2 years, mean follow-up 5.22 years). Kaplan-Meier survival analysis demonstrated significantly worse (p = 0.0001) survival both early (months 0 to 12) and late (>5 years) after transplantation in pre-operative diabetics (n = 53) compared with non-diabetics (n = 190). Pre-operative diabetes was identified as the only independent risk factor for decreased long-term (>1 year) survival (p = 0.004). In contrast, no effect on survival (p = 0.5) was demonstrated in patients becoming diabetic only after heart transplantation (n = 39). At 12 months post-transplant renal function was significantly impaired in diabetics (p = 0.025); acute rejection, cytomegalovirus (CMV) infection and transplant vasculopathy occurred with similar frequency. Causes of death were similar in diabetics and non-diabetics. Reduced long-term survival in pre-operative diabetics was seen in the early transplant era (1986 to 1994) (p < 0.0001), but not in the more recent era (1995 to 2003) (p = 0.5)., Conclusions: Pre-transplant but not post-transplant diabetes confers an adverse risk for survival (short and long term). Diabetes-associated long-term survival appears to have improved in the recent era, supporting continued transplantation in diabetics under close surveillance and aggressive medical management.

Purpose: The aim of this study was to identify microorganisms which might be present in closed periapical lesions and to determine their relationship to conventional clinical parameters. -, Methods: In 11 patients, samples were taken with paper points from 14 teeth with periapical radiolucency, in seven cases two samples were taken from two different sites of the same tooth (n=21). Clinical parameters were determined. The 16S rDNA of eleven bacterial species could be simultaneously detected via a modified polymerase chain reaction (PCR) based technique. -, Results: All samples contained more than one bacterial species. Most frequently, M. micros was detected alone or in combination with E. faecalis, P. aeruginosa, E. coli, F. nucleatum or S. sanguinis. When apical palpation was positive, often M. micros and F. nucleatum were both present. Other clinical symptoms like tenderness to percussion were not associated with a particular microflora. -, Conclusions: In closed periapical lesions detected by radiography, specific bacteria were identified by means of a modified PCR technique. No clear associations between clinical symptoms and these bacteria were found. Surgical intervention might be indicated for some of the persistent lesions.

The role of costimulatory molecules other than CD80/CD86 in endothelial cell (EC)-dependent CD8(+) T cell activation including the generation of a distinct subset of endothelium-specific CTL (EC-CTL) remains unclear. Inducible costimulator (ICOS) and its ligand (ICOSL) are new members of the CD28 family mediating effector T cell differentiation and graft rejection in animal models. In this study endothelial ICOSL expression/regulation and effects on CD8(+) T cell allo-activation were analyzed. Constitutive expression of ICOSL was found on human EC. IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB-dependent manner on human umbilical vein endothelial cells (HUVEC). ICOS receptor was not detected on resting CD8(+) T cells but was induced in co-cultures with HUVEC. ICOSL blockade reduced CD8(+) T cell proliferation by 70% along with a marked decrease of IL-2 and IFN-gamma production in co-cultures with HUVEC. IL-2 supplementation of co-cultures could overcome the effect of ICOSL blockade; similarly the generation of EC-CTL was not impaired by ICOSL blockade in an IL-2-containing system. In vivo, weak constitutive ICOSL expression was found on coronary microvessels, which was significantly up-regulated during acute cardiac allograft rejection (p=0.04). Our data indicate a distinct role for ICOSL in EC-mediated CD8(+) T cell costimulation with implications for human cardiac allograft rejection.

Determinants of B-type natriuretic peptide (BNP) plasma levels in the chronic phase after heart transplantation remain unclear. BNP was measured in 105 stable long-term heart transplant recipients with normal left ventricular function by echocardiography and correlated with clinical, demographic and hemodynamic parameters. Multivariate analysis revealed a significant correlation of BNP with female recipient gender (P = 0.006), time post-transplant (P =0.006), donor age (P = 0.007), angiographic signs of transplant vasculopathy (TVP) (P = 0.03), serum creatinine level (P = 0.04), and a strong trend for diastolic dysfunction (P = 0.09). Donor gender, recipient age, cyclosporin A blood levels, rejection history, and pulmonary artery pressure had no independent effect on BNP. BNP after heart transplantation appears to be influenced both by established general determinants (female gender, renal function) and transplant-specific determinants such as time post-transplant, donor age and potentially also TVP. In order to determine the value of BNP as a potential surrogate marker of TVP serial intraindividual measurements appear appropriate.

Purpose: Temporomandibular joint (TMJ) dysfunction in rheumatoid arthritis (RA) occurs in 2 % to 86 % of RA patients. Dental factors possibly contributing to the development of TMJ dysfunction in RA patients have rarely been investigated in controlled studies. The present clinical study aimed 1) to compare patients with active, longstanding RA and healthy control subjects matched for age, sex, periodontal risk factors, dental and prosthetic status in order to obtain data on the prevalence of TMJ dysfunction in dentate RA patients and 2) to investigate a possible relationship between RA activity, general functional state and the severity of TMJ involvement., Methods: 50 RA patients (38 F, 12 M; 54 +/- 9 years) were compared with 101 control subjects (76 F, 25 M; 54 +/- 11 years) with regard to dental, periodontal and prosthetic status and clinical TMJ findings as measured by the Helkimo indices. Clinical evaluation of RA patients included serological parameters, pain as measured by visual analog scale (VAS), a 28-joint count, a radiological destruction score, a functional status and measurement of grip strength., Results: The sum of carious, missing and filled teeth was similar in both groups. RA patients had more missing teeth (p < 0.01), more gingival bleeding, deeper pockets and more attachment loss (p < 0.0001). They showed no differences with regard to the mean number of occluding pairs of teeth, tooth support, the percentage of dentures, the grade of prosthetic support. 36 % of RA patients had a unilaterally shortened dental arch compared with 11.9 % in controls (p < 0.05). 32 % of RA patients and 27.7 % of the control subjects reported TMJ or facial pain. The mean VAS was 50 +/- 19 for RA patients and 52 +/- 21 for controls. The anamnestic data and the clinical symptoms grouped according to the Helkimo index showed no significant differences between both subject groups. However, the maximal mouth opening capacity in RA patients was significantly lower (40.6 +/- 6.5 mm) than in controls (45.8 +/- 5.5 mm; p < 0.001). Analysis of the Helkimo symptom groups revealed a significantly reduced mobility index in the RA group and impaired TM-joint function in controls (p < 0.05). Grip strength was significantly correlated with mouth opening capacity, TMJ pain with tooth support., Conclusion: The prevalence of TMJ dysfunction in dentate patients with longstanding RA does not exceed that of healthy controls when structural risk factors predisposing to the development of temporomandibular dysfunction are taken into consideration. Maintaining adequate tooth support might help to prevent progressive TMJ impairment in the course of disease.

Purpose: The identification of active disease sites is a leading goal in basic periodontal research. Of toxic bacterial metabolites detectable in gingival crevicular fluid, volatile sulphur compounds (VSC) have been implicated in periodontal tissue destruction. Several bacteria associated with active destructive disease are capable of producing VSC, this fact supporting the idea of sulcular VSC being a possible marker of disease activity. A new portable sulphide monitor providing chairside information on sulcular sulphide level (SU) has been developed. The aim of this study was 1) to monitor the effect of mechanical therapy on SU and clinical parameters and 2) to clarify whether SU-measurements might have the potential to detect disease activity., Methods: 34 patients (22 M, 12 F) with generalized or localized chronic periodontitis received periodontal treatment in a private practice consisting of an oral hygiene phase (HP) lasting several weeks, scaling and root planing (SRP), and flap surgery at sites >5 mm or with furcation involvement. Subjects were examined three times (1 week after the diagnosis was made, at the end of HP and at the 1st maintenance session 3 months after SRP) recording clinical parameters (clinical attachment loss CAL, probing depth PD, bleeding on probing intensity BI, plaque index PI) and sulcular sulphide level (SU) measured by the portable monitor as as digital score ranging from 0.0 (<10 superset 6 M of S superset 2-) to 5.0 (10 superset 2 M of S superset 2-) in increments of 0.5., Results: 23 patients (15 M, 8 F, 47.5 +/- 9 years) were included in the data analysis. Periodontal therapy resulted in a significant reduction of mean BI by 0.69 +/- 0.45, of mean PD by 1.39 +/- 0.33 mm and in a mean gain of attachment of 1.07 +/- 0.38 mm (p = 0.0001). The clinical improvement was accompanied by a reduction of mean SU by 0.20 +/- 0.13 and of the mean percentage of SU-positive sites per patient (SUp) by 20.09 +/- 13. SU-positive sites were located at all types of teeth. 67.9 % of SU-positive sites and 83.8 % of sites with a SU > 1 were found at the molars. 16.1 % of initially 579 SU-positive sites remained SU-positive. For these sites, BI reduction by treatment was significantly lower compared with SU-negative sites (p < 0.01). SU was significantly correlated with PD, CAL, BI and PI (p = 0.0001). Sensitivity and specificity of SU related to BOP (BI > 0) was 29.3 % and 96.8 %, respectively., Conclusions: Sulcular VSC as measured by the portable sulphide monitor may be an indicator of therapeutical success and periodontal stability. The sensor system offers chairside information on sulcular sulphide production at specific sites and is a valuable supplementation of traditional clinical methods in periodontal examination. More controlled longitudinal studies are needed to clarify the role of sulcular VSC at sites undergoing periodontal destruction.

Purpose: Volatile sulphur compounds (VSC) such as hydrogen sulphide and methyl mercaptan are toxic bacterial metabolites considered to contribute to the progression of periodontitis. However, the quantitative determination of sulcular VSC concentration requires costly time-consuming laboratory methods limiting its evaluation in large clinical trials. Recently, a portable monitor with a sulphide microsensor has been developed to measure sulcular VSC levels (SU). This cross-sectional study evaluated 1) the clinical usage of the sulphide sensor system, 2) the reproducibility of SU-measurements, 3) the distribution of SU-values in periodontal health and disease and 4) the relationship between SU and clinical parameters documenting periodontal disease severity., Methods: The specificity, the measuring range and the reproducibility of the sensor system were tested with reference solutions in vitro. 10 probands with healthy gingiva, 23 patients with gingivitis and 30 patients with chronic periodontitis were examined recording periodontal parameters (clinical attachment loss, CAL, probing depth, PD, bleeding on probing intensity BI, plaque and gingival index PI, GI) and sulcular sulphide level (SU) measured by the portable monitor as a digital score ranging from 0.0 (< 10 superset -6 M of S2-) to 5.0 (10 superset -2 M of S superset 2-) in increments of 0.5., Results: The in vitro testing confirmed the sensor s specificity for sulphide ions. The intraexaminer agreement (Pearson correlation coefficient) was 0.91 between two measurements (p < 0.05). However, positive SU-values decreased with measurement repetition due to the volatility of the sulphur compounds. SU and the percentage of positive SU-values per patient were correlated with disease severity. There were no positive SU-values in healthy probands, a mean SU of 0.11 +/- 0.08 in gingivitis and of 0.22 +/- 0.15 in periodontitis (p <0.001). SU was significantly correlated with PD in gingivitis, PD and CAL in periodontitis and the bleeding index in the analysis of all data., Conclusion: The portable sulphide monitor is a reliable method for the chairside determination of sulcular sulphide level in periodontal disease and in spite of its limitations a valuable supplementation of traditional clinical examination methods. It offers the possibility of relating in vitro results on the toxicity of VSC to clinical findings and might provide new insight into the impact of sulcular sulphide on the pathophysiology of periodontitis.

There are conflicting reports whether patients with rheumatoid arthritis (RA) are at a higher risk for periodontal disease (PD). Analogous mechanisms of tissue destruction have been reported for both diseases. This cross-sectional study should quantify PD in patients with longstanding RA and examine a possible association between the two diseases. It should also be investigated whether PD in RA patients could be the result of reduced functional capacity or be amplified by concomitant medical treatment. 50 RA patients were matched for age, sex, smoking and oral hygiene with 101 healthy controls. Data on the medication over the last three years was obtained by questionnaire. Among the rheumatological parameters recorded were a 28-joint-count, C-reactive protein (CRP), grip strength testing, upper extremity function (Keitel Index) and the Larsen-score of radiological joint destruction. The oral examination included the recording of individual oral hygiene measures and sicca symptoms, a modified Approximal Plaque- and Sulcus-Bleeding-Index (SBI), probing depths and clinical attachment loss and the Community Periodontal Index of Treatment Needs. The mean duration of RA was 13 (+/- 7.9) years. RA patients under treatment with disease modifying antirheumatic drugs (DMARDs, n = 46; 92%), corticosteroids (n = 38; 76%) and non steroidal antirheumatic drugs (NSAIDs, n = 43; 86%) had a higher rate of gingival bleeding (+ 50%), probing depth (+ 26%), clinical attachment loss (+ 173%) and number of missing teeth (+ 29%) compared with controls. While no correlation between the rheumatological variables (radiological destruction, functional capacity, grip strength) and the periodontal measurements (SBI, probing depth, clinical attachment loss) could be demonstrated, a positive correlation was observed between the CRP and the periodontal attachment loss (r = 0.32; p <0.05). In spite of a strong correlation between the duration of DMARD- and cortisone-medication and the Larsen-score (r = 0.48 and 0.64; p = 0.0005 and 0.0001, rsp.), no correlation between the duration of pharmacotherapy and the periodontal parameters could be established. Patients with long-term active RA present a substantially higher degree of PD including loss of teeth compared with controls. Functional impairment of the upper extremity might amplify present PD. The longterm use of NSAIDs, corticosteroids and DMARDs shows no connection with the severe PD observed in these patients. Oral hygiene amplifies PD severity and treatment need. Intensive prophylactic measures are required to prevent or reduce the damage of the periodontal tissues in RA patients.