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Objective: The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies., Methods: In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set)., Results: We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R 2 = 0.423; C-index = 0.749) included residual tumor volume, age, O 6 -methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models., Conclusions: A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies., Competing Interests: The 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 © 2021 Skardelly, Kaltenstadler, Behling, Mäurer, Schittenhelm, Bender, Paulsen, Hedderich, Renovanz, Gempt, Barz, Meyer, Tabatabai and Tatagiba.)

Background: Intensive care unit-acquired weakness syndrome (ICUAWS) can be a consequence of long-term mechanical ventilation. Despite recommendations of early patient mobilisation, little is known about the feasibility, safety and benefit of interval training in early rehabilitation facilities (ERF) after long-term invasive ventilation., Methods and Results: We retrospectively analysed two established training protocols of bicycle ergometry in ERF patients after long-term (> 7 days) invasive ventilation (n = 46). Patients conducted moderate continuous (MCT, n = 24, mean age 70.3 ± 10.1 years) or high-intensity interval training (HIIT, n = 22, mean age 63.6 ± 12.6 years). The intensity of training was monitored with the BORG CR10 scale (intense phases ≥ 7/10 and moderate phases ≤ 4/10 points). The primary outcome was improvement (∆-values) of six-minute-walk-test (6 MWT), while the secondary outcomes were improvement of vital capacity (VC max ), forced expiratory volume in 1 s (FEV 1 ), maximal inspiratory pressure (PI max ) and functional capabilities (functional independence assessment measure, FIM/FAM and Barthel scores) after 3 weeks of training. No adverse events were observed. There was a trend towards a greater improvement of 6 MWT in HIIT than MCT (159.5 ± 64.9 m vs. 120.4 ± 60.4 m; p = .057), despite more days of invasive ventilation (39.6 ± 16.8 days vs. 26.8 ± 16.2 days; p = .009). VC max (∆0.5l ± 0.6 vs. ∆0.5l ± 0.3; p = .462), FEV 1 (∆0.2l ± 0.3 vs. ∆0.3l ± 0.2; p = .218) PI max (∆0.8 ± 1.1 kPa vs. ∆0.7 ± 1.3pts; p = .918) and functional status (FIM/FAM: ∆29.0 ± 14.8pts vs. ∆30.9 ± 16.0pts; p = .707; Barthel: ∆28.9 ± 16.0 pts vs. ∆25.0 ± 10.5pts; p = .341) improved in HIIT and MCT., Conclusions: We demonstrate the feasibility and safety of HIIT in the early rehabilitation of ICUAWS patients. Larger trials are necessary to find adequate dosage of HIIT in ICUAWS patients.

Introduction: Exercise pulmonary hypertension (exPH) has been defined as total pulmonary resistance (TPR) >3 mm Hg/L/min and mean pulmonary artery pressure (mPAP) >30 mm Hg, albeit with a considerable risk of false positives in elderly patients with lower cardiac output during exercise. Methods: We retrospectively analysed patients with unclear dyspnea receiving right heart catheterisation at rest and exercise (n=244) between January 2015 and January 2020. Lung function testing, blood gas analysis, and echocardiography were performed. We elaborated a combinatorial score to advance the current definition of exPH in an elderly population (mean age 67.0 years±11.9). A stepwise regression model was calculated to non-invasively predict exPH. Results: Analysis of variables across the achieved peak power allowed the creation of a model for defining exPH, where three out of four criteria needed to be fulfilled: Peak power ≤100 Watt, pulmonary capillary wedge pressure ≥18 mm Hg, pulmonary vascular resistance >3 Wood Units, and mPAP ≥35 mm Hg. The new scoring model resulted in a lower number of exPH diagnoses than the current suggestion (63.1% vs. 78.3%). We present a combinatorial model with vital capacity (VC max ) and valvular dysfunction to predict exPH (sensitivity 93.2%; specificity 44.2%, area under the curve 0.73) based on our suggested criteria. The odds of the presence of exPH were 2.1 for a 1 l loss in VC max and 3.6 for having valvular dysfunction. Conclusion: We advance a revised definition of exPH in elderly patients in order to overcome current limitations. We establish a new non-invasive approach to predict exPH by assessing VC max and valvular dysfunction for early risk stratification in elderly patients., (© 2021 The Author(s).)

Purpose: To evaluate long-term outcome after revitrectomy with autologous platelet concentrate (APC) or whole blood (WB) in persistent idiopathic macular hole (MH) after vitrectomy with internal limiting membrane (ILM) peeling., Procedures: Retrospective study of 75 eyes with persistent MH after vitrectomy with ILM peeling and gas. All patients underwent revitrectomy with gas and APC (n = 61) or WB (n = 14). Main outcome measures were anatomical closure rate and postoperative best-corrected visual acuity (BCVA)., Results: Closure rate after revitrectomy was 85.2% (52/61) in the APC group and 7.1% (1/14) in the WB group. Median follow-up was 58 (range 3-147) months. Median BCVA (logMAR) in patients with finally closed MHs was 0.4 ± 0.3. Patients with defects of the ellipsoid zone had significantly worse postoperative BCVA. Morphological MH configuration (atrophic or elevated edges) did not correlate with final closure rate., Conclusions: Revitrectomy with APC and gas is a very effective treatment in persistent MH after vitrectomy with ILM peeling and gas., (© 2017 S. Karger AG, Basel.)

Purpose: To evaluate the condylar displacement after mounting working casts using different interocclusal recording materials and to analyze the influence of the storage time and the recording technique on the displacement caused by the interocclusal record., Materials and Methods: Eight interocclusal records were made in each of the following groups: G1: Aluwax (aluminum wax), G2: Beauty Pink wax (hydrocarbon wax compound), G3: Futar D Fast, G4: Futar Scan (G3, G4: vinylpolysiloxane), G5: Ramitec (polyether), G6: LuxaBite (composite resin based on bis-acryl), G7: LuxaBite corrected with Aluwax. A condylar-positioning indicator measured the condylar displacement in the three planes after storage of the records for two periods of 1 and 48 hours. Two-way ANOVA was used to determine the influences of recording materials and each of the following factors: (1) region (record and non-record side), (2) storage time, and (3) recording technique. The statistical significance level was set at p < 0.05., Results: The vertical displacement caused by the interocclusal records in the record side after storage time of 1 hour ranged between 0.29 mm (Aluwax) and 0.14 mm (Futar Scan). The lateral displacement ranged between 0.13 mm (Aluwax) and 0.02 mm (Ramitec) while the anteroposterior displacement ranged between 0.15 mm (Ramitec) and 0.04 mm (Futar Scan). The corrected resin record showed generally lower displacement values than other materials tested (0.03, 0.02, and 0.07, respectively). On the non-record side, the values were lower than that on the record side. The condylar displacement increased after a storage time of 48 hours for all materials. Both factors, storage time and recording technique, had statistically significant influence on the condylar displacement., Conclusions: Based on the results, the vertical displacement of the condyle caused by the interocclusal records was higher than the lateral or the anteroposterior displacement. Elastomers caused statistically significantly less condylar displacement than waxes or uncorrected composite resin. Corrected LuxaBite records with Aluwax showed significantly less condylar displacement than all other materials., (© 2016 by the American College of Prosthodontists.)

Purpose: Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker., Methods: We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment., Results: The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis., Conclusions: Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Recurrent miscarriage (RM) is a stressful condition which gives rise to extensive diagnostic evaluation and is seen as a potentially curable maternal disease. Nevertheless, epidemiological data have shown that outcome is related to fertility. In addition to maternal age and number of preceding miscarriages, further markers derived from the past history may support counselling., Methods: Observational trial comprising 228 couples who were referred between 1996 and 2003 for immunological evaluation at maternal ages 20-39 years after three or more spontaneously conceived primary first trimester miscarriages. They were interviewed in 2005, ongoing pregnancies were followed up until birth in 2006. Past obstetric history was correlated with 2 year cumulative pregnancy and delivery rates (CPR, CDR)., Results: CPR and CDR were 206/228 (90.4 %) and 174/228 (76.4 %). Duration of infertility was associated with lower CPR (up to 3/>3 years, p < 0.01), whereas age and number of preceding losses inversely correlated with CDR (<35 years/35-39 years, p < 0.002; 3/>3 miscarriages, p < 0.002). Detection of an embryonic heart beat in 2-3 of the first three miscarriages resulted in favourable outcome (CPR: p < 0.02, CDR: p < 0.002). Prognosis was excellent in younger fertile women after three miscarriages where vital signs had been detected; under less favourable conditions not only risks for further miscarriage, but also for secondary infertility were elevated., Conclusion: Secondary infertility is a feature of RM. Embryonic vital signs in preceding pregnancies are prognostic markers and should be regarded as a strong confounding factor in trials on therapeutic interventions. Prevention may be more appropriate than treatment.

Omapatrilat (OMA), which simultaneously inhibits the angiotensin-converting enzyme (ACE) and the neutral endopeptidase (neprilysin (NEP)), is widely used in experimental protocols related to hypertension and heart failure. The penetration of OMA across the blood-brain barrier (BBB) and the effects of ACE/NEP inhibition on the recovery from ischaemic stroke have not yet been investigated. Angiotensin (Ang) I injected intracerebroventricularly (ICV) or intravenously (IV) is converted to Ang II by ACE and induces an immediate increase in blood pressure. The pressor responses to OMA administered ICV, orally or IV were studied in male Wistar rats instrumented with an ICV and arterial and venous catheters. OMA infused ICV rapidly appeared in the systemic circulation and more effectively attenuated the systemic than the central pressor responses to Ang I. OMA administered orally (5, 25, 100 μmol/kg body weight) or IV (0.5, 1, 5, 25 μmol/kg body weight) completely abolished increases in blood pressure to IV Ang I up to 2 h after treatment. The pressor responses to ICV Ang I were not altered, indicating that systemically administered OMA does not cross the BBB. To study the effects of ACE and NEP inhibition in the brain on the recovery from ischaemic stroke, OMA was infused ICV over a 5-day period before and 24 h after the occlusion of the middle cerebral artery (MCAO) for 90 min. ICV application of OMA had no effect on infarction volume and marginally improved neurological outcome. We demonstrate for the first time that simultaneous inhibition of ACE and NEP in the brain tissue does not alter the recovery from ischaemic stroke.

Recently, we showed that increased SLPI levels prevent human papillomavirus (HPV) infections and metastasis in smoking-induced, non-HPV-driven head and neck squamous cell carcinoma (HNSCC). Here, we focus on the role of SLPI in non-HPV-driven HNSCC, investigating tumor tissue and non-neoplastic mucosa from the same patients and from non-HNSCC patients. Gene and protein expression of SLPI and gene expression of annexin 2 (a SLPI receptor), nicotine receptor (α7AChR) and arylhydrocarbon receptor (AhR) were analyzed in HNSCC patients (20 smokers; 16 nonsmokers). SLPI-results were correlated with the patients' HPV status. Non-neoplastic mucosa of HNSCC patients and normal mucosa from non-HNSCC individuals (18 smokers; 20 nonsmokers) was analyzed for the same parameters. Tissue of the inferior turbinate (n = 10) was incubated with nicotine for analysis of the same genes. SLPI gene expression in tumor tissue was 109.26 ± 23.08 times higher in smokers versus nonsmokers. Non-neoplastic mucosa of smokers showed also higher SLPI gene expression (10.49 ± 1.89-fold non-HNSCC; 18.02 ± 3.93-fold HNSCC patients). Annexin 2 gene expression was also increased in smokers. SLPI data were corroborated by immunohistochemistry. A nicotine dependent correlation between SLPI and annexin 2 gene expression (r(2) = 0.15, p < 0.001) was shown ex vivo. Nicotine and smoking increased α7AChR and AhR gene expression. Five patients, showing no/low SLPI expression, were HPV16-positive. A significant correlation between smoking and SLPI expression in tumors and to our knowledge for the first time in mucosa of HNSCC and non-HNSCC patients was established. Together with the finding that all patients with HPV infection showed no/low SLPI expression, these data support our intriguing hypothesis that smoking induced upregulated SLPI prevents HPV infections., (© 2013 UICC.)

Study Objective: To evaluate 3 therapy strategies: hormone therapy, surgery, and combined treatment., Design: Prospective, randomized, controlled study (Canadian Task Force classification I)., Setting: University-based teaching hospital., Patients: Four hundred fifty patients with genital endometriosis, aged 18 to 44 years, before first laparoscopy., Interventions: Patients were randomly assigned to 1 of 3 treatment groups: hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focussed on the endometriosis stage, recurrence of symptoms, and pregnancy rate., Measurements and Main Results: All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of ≥50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options., Conclusion: In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group., (Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: The loss of jaw bone caused by different kinds of pathologies leads to dysfunction and reduced quality of life in affected patients. Thus, the pivotal goal in bone tissue engineering is to reconstruct these defects. The essential precondition for new tissue generation is an extracellular matrix which acts as a scaffold so that cells can migrate, differentiate, and proliferate. Fibrin, a biopolymer responsible for blood clot formation, has been shown to be suitable for tissue engineering applications. The aim of the present study is a comparison of platelet rich fibrin (PRF) with the commonly used collagen membrane BioGide(®) as a scaffold for human osteoblast cell seeding for bone tissue engineering., Material and Methods: Human osteoblasts were cultured with eluates from PRF (n = 7) and BioGide(®) (n = 8) membranes incubated in serum-free cell culture medium. Vitality of these cells was assessed by fluorescein diacetate and propidium iodide staining, biocompatibility with the lactate dehydrogenase test and proliferation levels with the MTT ([3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide]), and BrdU (5-bromo-2-deoxyuridine) tests. In addition, human osteoblasts were seeded on both membrane systems and cell growth was compared by the water soluble tetrazolium (WST-1) (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) test and scanning electron microscopy (SEM). Osteoblastic differentiation was assessed by alkaline phosphatase activity measured by ELISA in the supernatant of osteoblasts cultivated on PRF membranes (n = 10), PRF clots (n = 10), and BioGide(®) membranes (n = 10)., Results: Lactate dehydrogenase test values were higher for PRF compared to BioGide(®) . The BrdU test showed superior cell growth after cultivation in eluate from PRF than in eluate from BioGide(®) . The WST-1 assay demonstrated superior cell proliferation on PRF than on BioGide(®) . SEM revealed osteoblast colonization of both membranes. Cultivation of osteoblasts on PRF membranes and PRF clots showed significantly higher alkaline phosphatase activity than on BioGide(®) membranes., Conclusion: Metabolic activity and proliferation of human osteoblast cells in vitro were supported to a significant higher extent by eluates from PRF membranes. Both membranes are suitable as scaffolds for cultivation of human osteoblast cells in vitro; proliferation was significant higher on PRF membranes and on PRF clot than on BioGide(®) membranes., (© 2011 John Wiley & Sons A/S.)

Objectives: Granulomatosis with polyangiitis (GPA) frequently starts with an affection of the nasal and paranasal mucosa. Localised GPA of the nasal mucosa or persistent disease activity ('grumbling disease') is often encountered even under immunosuppressive therapy. Necessity for reconstructive surgery is common and careful scheduling to prevent failure and minimise revision rates is crucial. Therefore, reliable estimation of GPA activity in the upper airways using a score is mandatory for diagnosis, follow-up and scheduling reconstructive surgery., Methods: Fifty endoscopic, endonasal images of 45 patients with GPA were used. Twelve (4 German, 8 Mexican) experienced (n=7) and inexperienced (n=5) physicians assessed GPA-activity at two times (T1/T2) in dichotomy and in a grading approach (none, mild, moderate and high activity) using the novel ENT Activity Score (ENTAS). All documents were written in English., Results: Estimation of activity in dichotomy (none vs. mild/moderate/high): Cohen's Kappa (κ) for intra-rater reliability T1/T2 in inexperienced and experienced physicians was κ=0.58 (agreement 85%) and κ=0.72 (agreement 91%). The inter-rater reliability (Fleiss's κ) T1/T2 for inexperienced and experienced physicians was κ=0.62/κ=0.59 and κ=0.50/κ=0.58 respectively. Estimation of activity in grading approach (none, mild, moderate, high): for inexperienced physicians the intra-rater reliability T1/T2 was κ=0.67 (agreement 56%) and the inter-rater reliability at T1/T2 was κ=0.29 (intraclass correlation coefficient, ICC=0.69) and κ=0.27 (ICC=0.59). For experienced physicians the intra-rater reliability T1/T2 was κ=0.80 (agreement 67%) and the inter-rater reliability at T1 and T2 was κ=0.41 (ICC=0.77) and κ=0.39 (ICC=0.75) respectively., Conclusions: Intra-rater reliability is high in decision in dichotomy and even in grading activity. There is no difference for experienced or inexperienced physicians. Inter-rater reliability is high in dichotomy, but low for activity grading. Thus, the ENTAS provides a reliable instrument for assessing, documenting and following GPA-related disease activity in the upper respiratory tract. The relationship of activity and following damage needs to be investigated in further studies.

Objectives: Nasal S. aureus carrier rates are significantly higher in patients with Wegener's granulomatosis (WG) compared to healthy controls (HC), and nasal colonisation is a risk-factor for relapse. Antimicrobial peptides (AMP) are important defence molecules maintaining an intact barrier function. It is the aim of this study to see if there is a possible link between the nasal AMP pattern and S. aureus colonisation, a link which has not been investigated so far., Methods: ELISA was applied to quantify LL-37 and hBD-3 concentrations in nasal secretions (14 WG patients, 13 HC) with and without nasal S. aureus colonisation. Immunohistochemistry was used to detect the cellular sources of AMP in the nasal mucosa. Functional analyses of primary nasal epithelial cell cultures (NEC) of these groups stimulated with S. aureus were performed., Results: LL-37 was found in significantly higher concentrations in colonised individuals (WG: p=0.001; HC: p=0.014).Using immunohistochemistry, local cellular sources for AMP could be demonstrated. After stimulation with S. aureus, significantly higher concentrations of LL-37 and hBD-3 could be detected in the supernatant of NEC of WG patients (LL-37: p=0.001; hBD-3: p=0.001) and HC (LL-37: p=0.019; hBD-3: p=0.001). HBD-3 concentrations were significantly lower in the supernatant of stimulated NEC of WG patients compared to the NEC of HC (p=0.032), and the dynamic range of the hBD-3 answer was significantly smaller in WG compared to HC (p=0.016)., Conclusions: The dynamic response towards challenges with microbes is dysregulated in WG, and this might be one reason for higher S. aureus colonisation rates in WG.

Since the first patients underwent intracranial tumor removal with the radicality control of intraoperative MRI (ioMRI) in September 2005 in our department, the majority of operations performed in the ioMRI room have been indicated for high grade gliomas. In order to elucidate the role of ioMRI scanning in patients harboring high-grade gliomas (HGG) on their survival, one hundred ninety three patients with gliomas WHO grades III and IV were operated either in a standard microsurgical neuronavigated fashion or using additionally ioMRI and were included in a follow-up study. The series started with surgeries from September 2005 until October 2007. Patient attribution to the two groups was based on the logistical availability of the ioMRI on a scheduled surgery day, and on the assumed "difficulty" of the surgery based on the location of the glioma in or near to an eloquent area. Surgery was intended to be as radical as possible without reduction of quality of life. First surgery was performed in 103 patients (75 WHO IV and 28 WHO III) and will be the main topic of this paper. In 60 patients, ioMRI was used, while in 43 patients standard microsurgical neuronavigated resection techniques were applied. Patients were followed in regular intervals mostly until death. Statistical analysis showed a median survival time for patients in whom ioMRI had been used of 20, 37 months compared to 10, 3 months in the cohort who had undergone conventional microsurgical removal. Major influencing concomitants were WHO grades and age which were balanced in both groups.

Objectives: Nasal colonisation with Staphylococcus aureus (S. aureus) has been implicated in Wegener's granulomatosis (WG) disease activity. In this study, the frequency of nasal colonisation with S. aureus in WG was compared to healthy and disease control groups for the first time. Moreover, endonasal activity was correlated to colonisation., Patients and Methods: Nasal carriage of S. aureus of a well-defined group of 89 patients with WG was compared to 40 patients with chronic rhinosinusitis with nasal polyps (CRS), 35 patients with rheumatoid arthritis (RA), 50 hospital staff members and 25 subjects without regular hospital contact and correlation analysis of nasal carriage and endonasal activity of WG was performed., Results: WG patients showed significantly higher rates (72%) of nasal colonisation with S. aureus compared to CRS patients (28%) and healthy subjects without regular hospital contact (25%, 95%-CI), but not to RA patients (46%) and hospital staff members (58%). WG patients with nasal carriage of S. aureus had significantly higher endoscopically proven endonasal activity (p=0.01), significantly more often first manifestation of WG in the upper respiratory tract (p=0.02) and higher relapse-rates (p=0.052) than WG patients without such carriage., Conclusions: Endonasal activity in WG is associated with higher nasal S. aureus colonisation rates and subsequent higher relapse rates. The higher frequency of S. aureus colonisation could be a consequence of a recently shown mucosal barrier defect in WG and facilitate chronic inflammation and granuloma formation in the upper respiratory tract.

Unlabelled: It is well known that iontophoresis of norepinephrine in capsaicin treated skin is followed by an increase in thermal hyperalgesia. It is unclear if this action on nocicepitive afferents involves the release of prostaglandins. The aim of the present study was to determine: (1) the effect of norepinephrine iontophoresis on spontaneous and evoked pain in the human skin after topical application of capsaicin; (2) the effect of cyclooxygenase (COX) inhibition on changes in pain perception induced by norepinephrine application., Methods: Ten volunteers were included in the study. Iontophoresis of norepinephrine or saline was performed in a randomized cross over design on the volar aspect of the forearm after topical application of capsaicin. In the second part of the study single iv. injections of saline or acetylsalicylic acid were performed in a randomized double blind cross over design. After the injection norepinephrine iontophoresis was performed on the skin treated with topical capsaicin. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured before and after each iontophoresis., Results: Norepinephrine did enhance spontaneous pain and mechanical and thermal hyperalgesia in capsaicin treated skin. Inhibition of COX I and II had no effect on the norepinephrine induced changes in pain perception., Conclusion: The results do not support the assumption that in human skin sensitized by topical capsaicin application of norepinephrine acts on nociceptive afferents via the release of prostaglandins. Thus, a direct action of norepinephrine on adrenergic receptors in the membrane of the afferent fibers is most likely.

Glioblastoma is the most common primary brain tumor. Recent evidence suggests that aggressive treatment is also effective in elderly patients. However, large patient series are missing. The aim of this retrospective study was to determine prognostic factors in a large series (n=345) of elderly patients surgically treated for newly diagnosed glioblastoma (WHO grade IV) at a single institution between 1991 and 2002. U-tests (Mann Whitney), chi-square tests, log-rank tests/Kaplan-Meier plots and Cox regression models were used for statistical analysis. Based on the maximum difference in median survival, a threshold of 60 years was used to separate younger from older patients. In total, 185 patients (53.6%) were over 60 years old. In these individuals, total tumor resection, radiotherapy and reoperation for tumor recurrence were identified as independent prognostic factors. When total surgical resection was combined with radiotherapy and reoperation, Kaplan-Meier analysis revealed a median survival of up to 64 weeks in elderly patients. Our data indicate that total tumor resection, radiotherapy and reoperation should also be considered in selected elderly patients. Age alone should not generally exclude elderly individuals from aggressive treatment.

A major consideration in designing dental implants is to create a surface that provides strong attachment of the implant to bone, connective tissue and epithelium. The aim of the present study was to examine the influence of different treatments of titanium (Ti) implant surfaces on focal adhesion contact (FAC) formation in fibroblast cultures. Human gingival fibroblasts were cultured on glass sheets and polished Ti discs with different surface coatings (applied by physical vapor deposition (PVD): Ti, titanium nitride (TiN), zirconium nitride (ZrN)) or on Ti discs with different surface topographies. For characterization of all surfaces, modified estimation of surface roughness and spacing parameter was carried out using a contact stylus profilometer. Contact angle measurements were carried out to calculate surface energy. Fibroblasts were prepared for transmission electron microscopy at day 3 after seeding, and the number of FACs and the ratio FAC/cellular cross-sections was determined at a length of 300 microm in ultrathin sections. To visualize the extracellular fibronectin and vitronectin molecules and the intracellular actin and vinculin in FAC areas, immunogold labeling was performed. The results revealed a strong correlation between the number of FACs and the surface roughness. The highest number of FACs and the majority of the immunogold-labeled intra- and extracellular matrix molecules were counted on surfaces with the lowest surface roughness: glass sheets coated with either Ti, TiN or ZrN (roughness average=0.03-0.1 microm). These surfaces appear to favor cellular attachment of human gingival fibroblasts and moreover in previous studies the hard coatings have been shown to reduce bacterial adhesion.

Purpose: To evaluate the performance of a prototype membrane stent, MembraX, in the prevention of acute and late embolization and to quantify particle embolization during carotid stent placement in human carotid explants in a proof of concept study., Methods: Thirty human carotid cadaveric explants (mild stenoses 0-29%, n = 23; moderate stenoses 30-69%, n = 3; severe stenoses 70-99%, n = 2) that included the common, internal and external carotid arteries were integrated into a pulsatile-flow model. Three groups were formed according to the age of the donors (mean 58.8 years; sample SD 15.99 years) and randomized to three test groups: (I) MembraX, n = 9; (II) Xpert bare stent, n = 10; (III) Xpert bare stent with Emboshield protection device, n = 9. Emboli liberated during stent deployment (step A), post-dilatation (step B), and late embolization (step C) were measured in 100 microm effluent filters. When the Emboshield was used, embolus penetration was measured during placement (step D) and retrieval (step E). Late embolization was simulated by compressing the area of the stented vessel five times., Results: Absolute numbers of particles (median; >100 microm) caught in the effluent filter were: (I) MembraX: A = 7, B = 9, C = 3; (II) bare stent: A = 6.5, B = 6, C = 4.5; (III) bare stent and Emboshield: A = 7, B = 7, C.=.5, D = 8, E = 10. The data showed no statistical differences according to whether embolic load was analyzed by weight or mean particle size. When summing all procedural steps, the Emboshield caused the greatest load by weight (p = 0.011) and the largest number (p = 0.054) of particles., Conclusions: On the basis of these limited data neither a membrane stent nor a protection device showed significant advantages during ex vivo carotid angioplasty. However, the membrane stent seems to have the potential for reducing the emboli responsible for supposed late embolization, whereas more emboli were observed when using a protection device. Further studies are necessary and warranted.

Purpose: To test the hypothesis that the surrounding vascular plexus of the lacrimal sac and the nasolacrimal duct contributes to the regulation of tear outflow., Methods: Experiments in 30 probands aged between 15 and 37 years were performed in both nasolacrimal systems of each subject by observing with an endoscope the transit time of an applied tear drop containing fluorescein dye until its entry into the inferior meatus of the nose. Four different experiments were performed to determine the median transit time under normal conditions and the influence on transit time of a decongestant drug, a foreign body on the ocular surface, and a decongestant drug applied together with a foreign body on the ocular surface. Comparisons were made between the right and left nasolacrimal system, in males and females, eyeglass wearers and non-eyeglass wearers, and the different experiments and the results statistically analyzed., Results: The tear transit time was independent of side (right or left), gender, or eyeglass wear. It showed great individual variability. Application of a decongestant drug or placement of a foreign body on the ocular surface both prolonged the dye transit time significantly. Application of a decongestant drug simultaneously with placement of a foreign body shortened the dye transit time significantly compared with the effect of the decongestant drug alone but revealed no significant difference compared with application of a foreign body alone., Conclusions: The cavernous body of the lacrimal sac and nasolacrimal duct plays an important role in the physiology of tear outflow regulation. It is subject to autonomic control and is integrated into a complex neuronal reflex feedback mechanism starting with the dense innervation of the cornea. Moreover, its function can be pharmacologically influenced.