Ursula Range

Reduction of postoperative lymphedema after oral tumor surgery with sodium selenite

The objective of this double-blind, randomized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase (GPX) activity and oxygen radical production. Twenty patients were enrolled in the study. Each of the participants received 1000 μg sodium selenite intravenously or orally daily for 3 wk during the pre-, intra-, and postoperative period. The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration, GPX, reactive oxygen species (ROS), NO, and malonic dialdehyde were measured for 1 yr postoperatively. There was an inverse correlation between the severity of the lymphedema and the wholeblood/plasma selenium concentration and GPX activity. In addition, a positive correlation between the ROS concentration and the extent of lymphedema was observed. A significant reduction of lymphedema occurred in the sodium selenite-treated group. It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas. Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy cannot be applied.

Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia.

The flow cytometric detection of aberrant antigen expression is one method proposed for the quantification of minimal residual disease (MRD) in acute leukemias. The present study was designed to investigate the stability of the aberrant antigen expression at relapse or at treatment failure of initial chemotherapy. For this purpose, multiparameter immunophenotyping with a panel of 15 monoclonal antibodies was used at diagnosis as well as at relapse (43 patients with overall 65 aberrations) and at treatment failure (35 patients with overall 66 aberrations). There was a significant decrease in the percentage of the initially described aberrant antigen expression on leukemia blasts at relapse (P = 0.001; n = 65) as well as at treatment failure (P = 0.0001; n = 66) considering all aberrations in the whole leukemia population. Concerning only patients with acute myelogenous leukemia (AML), significant decreases in the aberrant expression could be detected at relapse (P = 0.031; n = 42) and at treatment failure (P = 0.0001; n = 52). The changes in patients with acute lymphoblastic leukemia (ALL) were significant only at relapse (P = 0.006; n = 23). Initially, the most informative aberration was not detectable in four patients at relapse and in seven patients at treatment failure. A decrease of under 50% of the initial value was observed in another 8 patients at relapse and in 10 patients at treatment failure. In further studies assessing the detection of aberrant antigen expression for MRD, quantification of the relapses should be explicitly analyzed regarding the persistence of the initially described aberrant antigen expression.

Surface-conditioned dental implants: an animal study on bone formation.

AIM The aim of this study was to determine whether bone formation around surface-conditioned implants is enhanced compared with non-surface-conditioned sandblasted acid-etched titanium implants. MATERIALS AND METHODS One hundred and forty-four implants were placed in the mandible of 18 minipigs. Before placement, implants were either surface conditioned in a solution containing hydroxide ions (conSF) or assigned to controls. Animals were euthanized after 2, 4 and 8 weeks of submerged healing, the 8-week group receiving polyfluorochrome labelling at week 2, 4, 6 and 8. One jaw quadrant per animal was selected for histological and histomorphometrical evaluation of mineralized bone-implant contact (mBIC), osteoid-implant contact (OIC) and bone volume (BV) analysis. RESULTS Polyfluorochrome labelling showed no general differences in bone dynamics. mBIC showed the most pronounced differences after 2 weeks, reaching 65.5% for conSF compared with 48.1% for controls, p=0.270. Differences levelled out after 4 weeks (67.4% control, 65.7% conSF) and 8 weeks (64.0% control, 70.2% conSF). OIC levels were initially comparable, showing a slower decline for conSF after 4 weeks. BV was higher for conSF at all times. No significant differences could be found. CONCLUSION A tendency towards increased mBIC was shown for surface-conditioned implants after short-term healing.

Chondroitin sulfate and sulfated hyaluronan‐containing collagen coatings of titanium implants influence peri‐implant bone formation in a minipig model

An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo.

Efficacy of tissue engineered bone grafts containing mesenchymal stromal cells for cleft alveolar osteoplasty in a rat model

UNLABELLED The development of sufficient tissue engineered bone grafts for alveolar cleft osteoplasty could reduce the necessity of autogenous bone grafts and its donor site morbidity. The aim of the study was to evaluate tissue engineered bone grafts in an artificially created bone defect. Bone grafts were created in vitro colonizing a synthetic hydroxyapatite-tricalciumphosphate scaffold (BONITmatrix(®)) with either undifferentiated mesenchymal stromal cells (group 1) or osteogenic differentiated mesenchymal stromal cells (group 2). Cells were multiplied from bone marrow of donor rats. Unmodified scaffolds (group 3) and the tissue engineered bone grafts were inserted into artificial maxillary defects of 54 Lewis rats. In 18 animals the defects remained unfilled (control). After one, three and six weeks the rats were sacrificed. The defect was evaluated radiologically and histologically with regard to the remaining defect volume and diameter. Statistical analysis followed. The bone grafts led to a specific bone formation at the defect margin. No complete reunion of any defect was observed within the healing time. After six weeks, the remaining defect volume was 6.86 ± 3.21 mm(3) (control), 4.08 ± 1.36 mm(3) (group 1), 5.00 ± 0.84 mm(3) (group 2) 5.50 ± 1.05 mm(3) (group 3). The remaining defect diameter measured 2.63 ± 0.52 mm (control), 2.39 ± 0.23 mm (group 1), 2.53 ± 0.22 mm (group 2) and 2.70 ± 0.66 mm (group 3). In all experimental groups the defect volume and diameter decreased over time, which was significant for group 1 (p = 0.014), group 2 (p = 0.025) and group 3 (p = 0.048). The defect volume and width was significantly reduced for bone grafts containing undifferentiated cells compared to control (p = 0.035) or scaffolds only (p = 0.05). CONCLUSION Tissue engineered bone grafts induce a pronounced bone formation in artificial bone defects compared to unfilled controls or scaffolds only.

Treatment Response and Longterm Outcomes in Children with Chronic Nonbacterial Osteomyelitis

Objective. The autoinflammatory bone disorder chronic nonbacterial osteomyelitis (CNO) covers a wide clinical spectrum, ranging from mild self-limited presentations to chronically active or recurrent courses, which are then referred to as chronic recurrent multifocal osteomyelitis (CRMO). Little is known about treatment options and longterm outcomes. We investigated treatment responses and outcomes in children with CNO. Methods. A retrospective chart review was conducted in a tertiary referral center, covering 2004–2015. Disease activity was measured at 0, 3, 6, 12, and 24 months after treatment initiation, and at the last recorded visit. Results. Fifty-six patients with CNO were identified; 44 had multifocal CNO. Fifty percent of patients relapsed after a median of 2.4 years, and as few as 40% remained relapse-free after 5 years. Nonsteroidal antiinflammatory drugs were used as first-line treatment in 55 patients, inducing remission after 3 months in all individuals with relapse rates of 50% after 2 years. Further treatment included corticosteroids (n = 23), tumor necrosis factor-α (TNF-α) inhibitors (n = 7), and bisphosphonates (n = 8). While 47% of patients with CNO relapsed within 1 year after corticosteroid therapy, favorable outcomes were achieved with TNF-α inhibitors or bisphosphonates (pamidronate). Conclusion. CNO is a chronic disease with favorable outcomes within the first year, but high relapse rates in longterm followup. Particularly, patients with CRMO with long-lasting, uncontrolled inflammation were at risk for the development of arthritis. Our findings underscore the importance of a timely diagnosis and treatment initiation. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Flow cytometric DNA-quantification of three-color immunophenotyped cells for subpopulation specific determination of aneuploidy and proliferation

A method is described for three-color immunophenotyping and simultaneous DNA-quantification using a flow cytometer equipped with a 488-nm argon laser and a mercury lamp (UV). The approach includes reproducible immunophenotyping comparing antigen expression before and after cell manipulation for DNA-measurement. The coefficients of variation after DNA-staining (CV=3.13 for T-cells in peripheral blood and CV=3.38 for T-cells in bone marrow) were adequate for exact DNA-analysis. For aneuploidy detection, a true internal standard was established measuring, for example, the DNA-content of T-cells in B-cell disease simultaneously with the DNA-content of the malignant cells. Using this method, aneuploidies could be unequivocally detected in 17 out of 24 patients with multiple myeloma. Furthermore, intratumor heterogeneities in DNA-content and antigen expression could be recognized, allowing an exact separation of tumor cells and normal hematopoiesis. The study also demonstrated the importance of exact immunophenotypic characterization of lymphocyte subpopulations and the determination of their specific proliferation, for example after proliferation induction in cell cultures. Future studies should address the applicability of this rather simple multiparameter approach for simultaneous immunophenotyping and DNA-measurement especially in the detection of minimal amounts of aneuploid cells after chemotherapy.

Loss and Gain of Tolerance to Pancreatic Glycoprotein 2 in Celiac Disease

Background Autoantibodies against pancreatic secretory-granule membrane glycoprotein 2 (GP2) have been demonstrated in patients with Crohn’s disease but recently also with celiac disease (CD). Both entities are characterized by intestinal barrier impairment with increased gut permeability. Pathophysiological hallmark of CD is a permanent loss of tolerance to alimentary gliadin and a transient loss of tolerance to the autoantigen human tissue transglutaminase (tTG). Therefore, we explored the behavior of loss of tolerance to GP2 reported in CD. Methods We assessed prevalences and levels of autoantibodies against GP2, CD-specific antibodies to endomysial antigens and tTG as well as Crohn’s disease-specific anti-Saccharomyces cerevisiae antibodies in sera of 174 patients with active CD, 84 patients under gluten-free diet (GFD) and 129 controls. Furthermore, we looked for an association between anti-GP2 antibody positivity and degree of mucosal damage in CD. Results We found significantly elevated anti-GP2 IgA positivity in active CD patients (19.5%) compared to CD patients under GFD (0.0%) and controls (5.4%, p < 0.001, respectively). Anti-GP2 IgA levels correlated significantly with CD-specific antibodies (p < 0.001). Anti-GP2 autoantibody positivity disappeared under GFD similarly to CD-specific autoantibodies against tTG and endomysial antigens. For the first time, IgA antibody levels to GP2 are demonstrated to be associated with degree of villous atrophy according to Marsh classification. Conclusions Anti-GP2 IgA seems to be associated with disease activity in a distinct subgroup of patients with CD. The observed loss of tolerance to GP2 in a subset of patients with CD is transient and disappears under GFD.

Experimental study on the behavior of primary human osteoblasts on laser-cused pure titanium surfaces

Mandibular tumor resection can lead to a mandibular segmental defect. LaserCUSING® is used to produce a mandibular implant, designed to be identical to the shape of the mandibular defect. Novel microrough surfaces result from this generative technology. In the current study, the behavior of human osteoblasts on untreated laser-cused titanium specimens or on specimens conditioned with different blasting agents was analyzed. The conditioning of these specimens resulted in surfaces with graded roughness. White light confocal microscopy and single-cell force spectroscopy were used to characterize the surface of the specimens and to quantify the initial adhesion of primary human osteoblasts to the specimens, respectively. Furthermore, cell growth, viability, apoptosis as well as mineralization of the specimens were analyzed over a time-period of 2 months. Compared to specimens that were treated with blasting agents, untreated specimens had the highest surface roughness. Quantitative SCFS measurements demonstrated that the adhesion of human primary osteoblasts was the highest on these specimens. Additionally, the untreated specimens allowed the highest number of osteoblasts to colonize. Mineralization studies showed increasing calcium and phosphor elemental composition for all specimen series. It can be concluded that untreated laser-cused titanium specimens are superior to promote the initial adhesion and subsequent colonization by osteoblast cells.

Effects of oxygen-enriched air on cognitive performance during SCUBA-diving – an open-water study

ABSTRACT Backround: Nitrogen narcosis impairs cognitive function, a fact relevant during SCUBA-diving. Oxygen-enriched air (nitrox) became popular in recreational diving, while evidence of its advantages over air is limited. Aim: Compare effects of nitrox28 and air on two psychometric tests. Methods: In this prospective, double-blind, open-water study, 108 advanced divers (38 females) were randomized to an air or a nitrox-group for a 60-min dive to 24 m salt water. Breathing gas effects on cognitive performance were assessed during the dive using a short- and long-term memory test and a number connection test. Results: Nitrox28 divers made fewer mistakes only on the long-term memory test (p = 0.038). Female divers remembered more items than male divers (p < 0.001). There were no significant differences in the number connection test between the groups. Conclusion: Likely owing to the comparatively low N2 reduction and the conservative dive, beneficial nitrox28 effects to diver performance were moderate but could contribute to diving safety.