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The purpose of this study was to assess implant survival and 1-year clinical performance of implants placed in the posterior maxilla that had been subjected to maxillary sinus floor elevation surgery with bovine bone mineral (BioOss®) mixed with autogenous bone marrow concentrate or autogenous bone. In a randomized, controlled, split-mouth design study, a bilateral sinus floor augmentation procedure was performed in 12 edentulous patients. At random, one side was treated with BioOss® seeded with an iliac crest bone marrow concentrate enriched in mesenchymal stem cells (test side) and the other with BioOss® mixed with autogenous bone (control side). Three to four months after augmentation, 66 implants were placed. Implant survival, plaque, gingival, and bleeding indices, probing depth, and peri-implant radiographic bone levels were assessed at baseline and 12 months after functional loading. During osseointegration, three implants failed on the test side (two patients) and no implants failed on the control side, resulting in 3-month survival rates of 91% and 100%, respectively. No implants were lost after functional loading and no differences in soft tissue parameters or peri-implant bone loss were observed between the control and test sides. After 1 year in function, no clinically relevant differences were observed regarding soft tissue parameters or peri-implant bone loss.

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Literature regarding the outcome of maxillary sinus floor elevation to create sufficient bone fraction to enable implant placement was systematically reviewed. Bone fraction and implant survival rate were assessed to determine whether grafting material or applied growth factor affected bone fraction. Trials where sinus floor elevations with autogenous bone (controls) were compared with autogenous bone combined with growth factors or bone substitutes, or solely with bone substitutes (test groups) were identified; 12 of 1124 fulfilled all inclusion criteria. Meta-analyses comparing the bone fraction after applying: autogenous bone; autologous bone with growth factors (platelet rich plasma); or autogenous bone and bone substitutes (bovine hydroxyapatite, bioactive glass, corticocancellous pig bone) revealed no significant differences in bone formation after 5 months. A significantly higher bone fraction was found in the autogenous bone group compared to the sole use of ß-tricalciumphosphate (P=0.036). The one-year overall implant survival rate showed no significant difference between implants. Bone substitutes combined with autogenous bone provide a reliable alternative for autogenous bone as sole grafting material to reconstruct maxillary sinus bony deficiencies, for supporting dental implants after 5 months. Adding growth factors (platelet rich plasma) to grafting material and the sole use of ß-tricalciumphosphate did not promote bone formation.

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AIM: To assess whether differences occur in bone formation after maxillary sinus floor elevation surgery with bovine bone mineral (BioOss(®)) mixed with autogenous bone or autogenous stem cells. The primary endpoint was the percentage of new bone three months after the elevation procedure. MATERIAL AND METHODS: In a randomized, controlled split-mouth design, in 12 consecutive patients (age 60.8 ± 5.9 years, range 48-69 years) needing reconstruction of their atrophic maxilla, a bilateral sinus floor augmentation procedure was performed. Randomly, on one side the augmentation procedure was performed with bovine bone mineral (BioOss(®)) seeded with mononuclear stem cells harvested from the posterior iliac crest (test group) while BioOss(®) mixed with autogenous bone (harvested from the retromolar area) was applied on the contra-lateral side (control group). On 14.8 ± 0.7 weeks after the sinus floor elevation, biopsies from the reconstructed areas were taken at the spots where subsequently the endosseous implants were placed. The biopsies were histomorphometrically analyzed. RESULTS: Significantly more bone formation was observed in the test group (17.7 ± 7.3%) when compared with the control group (12.0%± 6.6; P=0.026). In both the test and control group, all implants could be placed with primary stability. In one patient, not all biopsies contained BioOss(®). This patient was excluded from analysis. CONCLUSION: Mesenchymal stem cells seeded on BioOss(®) particles can induce the formation of a sufficient volume of new bone to enable the reliable placement of implants within a time frame comparable with that of applying either solely autogenous bone or a mixture of autogenous bone and BioOss(®). This technique could be an alternative to using autografts.

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Isoforms of the enzyme lactate dehydrogenase (LDH) were found in almost all cells of the organism and an elevated activity of LDH in the circulation is thought to be a clear indicator of elevated cell destruction coinciding with an increased release of components from the cellular cytoplasm, e.g. LDH. Here, we report on an in-vitro examination to test whether radiographic contrast media (RCM) could induce cell destruction followed by an increase in LDH release. The RCM were tested in non-flow cultures of human umbilical venous endothelial cells (HUVEC) of the fourth passage seeded on extracellular matrix and the results were compared to those from control cultures not exposed to contrast media. The examination revealed that the addition of contrast media to the cell culture media supplemented with pooled human serum (HSP) as source of exogenous LDH was followed by a strong decrease in LDH activity both in the absence and presence of HUVEC. Within 1.5 min after the addition of contrast media to the culture medium supplemented with HSP (30% vol of the culture medium were replaced by either of two contrast media, Iodixanol or Iopromide) the LDH activity decreased about 80% compared to the initial values. In contrast, the LDH activity did not change in cell culture media not supplemented with RCM. The partial replacement of HSP supplemented cell culture medium by RCM will cause a dilution of cell culture medium constituents. The decrease of LDH activity, however, was much stronger than the decrease thought to be attributable to the effects of dilution of cell culture medium, so that the role of dilution seems to be a minor one in this case. It has to be assumed that the RCM could interact with the LDH available in the culture medium as well as with the substrates delivered with the measurement system for the assessment of LDH activity, so that both, the amount of LDH and the activities of enzymes involved might be influenced. In the presence of HUVEC a similar effect was observed. Here, a little less strong decrease of LDH activity occurred compared to the decrease in cell culture medium without HUVEC. This was unexpected because a considerable amount of HUVEC were detached after the addition of contrast media and many of these cells were damaged seriously so that a significant amount of endogenous LDH should have been released. These unexpected results make it necessary to re-evaluate those past time examinations focussed on cell damage/destruction in the presence of contrast media, where the measurement of LDH activity was used as indicator or cell vitality and where cell decease rates were correlated to questionable toxic influences. According to the results of the examination reported here it is difficult to uphold the interpretation of recently published findings that contrast media almost exclusively induce cellular apoptosis and not necrosis.

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The existing therapeutical options for the tracheal and pharyngeal reconstruction by use of implant materials are described. Inspite of a multitude of options and the availability of very different materials none of these methods applied for tracheal reconstruction were successfully introduced into the clinical routine. Essential problems are insufficiencies of anastomoses, stenoses, lack of mucociliary clearance and vascularisation. The advances in Tissue Engineering (TE) offer new therapeutical options also in the field of the reconstructive surgery of the trachea. In pharyngeal reconstruction far reaching developments cannot be recognized at the moment which would allow to give a prognosis of their success in clinical application. A new polymeric implant material consisting of multiblock copolymers was applied in our own work which was regarded as a promising material for the reconstruction of the upper aerodigestive tract (ADT) due to its physicochemical characteristics. In order to test this material for applications in the ADT under extreme chemical, enzymatical, bacterial and mechanical conditions we applied it for the reconstruction of a complete defect of the gastric wall in an animal model. In none of the animals tested either gastrointestinal complications or negative systemic events occurred, however, there was a multilayered regeneration of the gastric wall implying a regular structured mucosa. In future the advanced stem cell technology will allow further progress in the reconstruction of different kind of tissues also in the field of head and neck surgery following the principles of Tissue Engineering.

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Echinocyte formation is associated with a rigidification of the cells that possibly affects capillary diffusion and, consequently, the tissue's oxygen supply. This study examines how many echinocytes appeared after the addition of various concentrations of radiographic contrast media (RCM) (Iodixanol 320, Iohexol 350, Iopromide 370, Iomeprol 350 and Iomeprol 400 mg Iodine/ml) compared to red blood cells in isotonic saline solution as well as in autologous plasma. Isotonic saline solution, Iodixanol, Iohexol, Iomeprol 350, Iomeprol 400 and Iopromide in concentrations of 10%, 20% or 40% were added to the plasma of six healthy subjects. Subsequently, the erythrocytes were resuspended in these RCM/plasma mixtures, incubated for 5 minutes at 37 degrees C and then examined under the microscope.The various mixtures and concentrations of the RCM in the mixture all had a significant effect on the number of discocytes (p<0.0001). The percentage of discocytes for all concentrations significantly depended on the RCM/plasma mixture (p=0.0097). Of all the RCM/plasma mixtures used as well as of the NaCl/plasma mixtures, the Iodixanol/plasma mixture showed the most similar discocyte fraction compared to red blood cells in the autologous plasma. At the same time, while Iodixanol in this respect differed from all other RCMs, the other RCMs only differed little from one another with respect to the discocyte fraction.

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Radiographic contrast media (RCM) can affect the morphology of red blood cells in very different ways but research on how they affect endothelial cell morphology is rudimentary. The effect of two conventional RCMs on human umbilical venous cells over the short term was studied in vitro under static conditions. Cell circumference length, the number of dissolved cell contacts and the number of denuded subendothelial matrix areas were interactively quantified by a computer imaging system after histochemical processing. 1.5 minutes after RCM exposure a significant effect of both RCMs on cell circumference length (CCL) compared to the control cells was evident (p=0.0001 each). The increase after iodixanol was larger than after iomeprol (p=0.0087). After five minutes of exposure, the CCL of exposed cells were significantly larger than those of control cells (p<0.0001 each). The CCL after exposure hardly differed anymore at that time (iomeprol/iodixanol: p=0.0547), though cells exposed to iomeprol tended to be bigger. After both iomeprol (p<0.0001) and iodixanol (p=0.0018), the number of dissolved cell contacts (DCC) increased compared to the control cells. The increases after either RCM were similar (p=0.9633). After five minutes of RCM exposure, the number of DCC was significantly higher than for the control cells (control/iomeprol: p<0.0001; control/iodixanol: p=0.0012). After exposure to iodixanol, significantly fewer DCC were recorded than after iomeprol (p=0.0018). At 1.5 minutes after RCM exposure, the number of denuded subendothelial matrix areas (DSMA) in the cell layer increased both after iomeprol (p<0.0002) and after iodixanol (p=0.0002) compared to the control cells. The increases with the two RCMs were similar (p=0.8618). After five minutes of exposure, the number of DSMA in the cell layer was significantly higher than for the control cells (control/iomeprol: p<0.0001; control/iodixanol: p=0.0015). However, after iodixanol significantly fewer DSMA were recorded than after iomeprol (iomeprol/iodixanol: p=0.0353). The number of dissolved cell/cell contacts and the number of denuded subendothelial matrix areas in the confluent endothelial layer were significantly greater after exposing the endothelial cells for five minutes to iomeprol than after iodixanol.

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OBJECTIVE: To evaluate the consistency and quality of immunization monitoring systems in 27 countries during 2002-03 using standardized data quality audits (DQAs) that had been launched within the framework of the Global Alliance for Vaccines and Immunization. METHODS: The consistency of reporting systems was estimated by determining the proportion of third doses of diphtheria-tetanuspertussis (DTP-3) vaccine reported as being administered that could be verified by written documentation at health facilities and districts. The quality of monitoring systems was measured using quality indices for different components of the monitoring systems. These indices were applied to each level of the health service (health unit, district and national). FINDINGS: The proportion of verified DTP-3 doses was lower than 85% in 16 countries. Difficulties in verifying the doses administered often arose at the peripheral level of the health service, usually as the result of discrepancies in information between health units and their corresponding districts or because completed recording forms were not available from health units. All countries had weaknesses in their monitoring systems; these included the inconsistent use of monitoring charts; inadequate monitoring of vaccine stocks, injection supplies and adverse events; unsafe computer practices; and poor monitoring of completeness and timeliness of reporting. CONCLUSION: Inconsistencies in immunization data occur in many countries, hampering their ability to manage their immunization programmes. Countries should use these findings to strengthen monitoring systems so that data can reliably guide programme activities. The DQA is an innovative tool that provides a way to independently assess the quality of immunization monitoring systems at all levels of a health service and serves as a point of entry to make improvements. It provides a useful example for other global health initiatives.

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Using standard cell biological and biochemical methods we were able to test the ability of a degradable, thermoplastic block copolymer to support the adhesion, proliferation, and the cellular activity of primary cell cultures of the oral cavity in vitro. The delicate balance between a group of endogenous enzymes, Matrix Metalloproteinases (MMPs), and their inhibitors (Tissue Inhibitor of MMPs, TIMPs) have a decisive function in the remodeling of the extracellular matrix during processes like wound healing or the integration of biomaterials in surrounding tissues after implantation. Recently developed, biodegradable thermoplastic elastomers with shape-memory properties may be the key to develop new therapeutical options in head and neck surgery. Primary cell cultures of the oral cavity of Sprague-Dawley rats were seeded on the surface of a thermoplastic block copolymer and on a polystyrene surface as control. Conditioned media of the primary cells were analyzed for MMPs and TIMPs after different periods of cell growth. The MMP and TIMP expression was analysed by zymography and a radiometric enzyme assay. No statistically significant differences in the appearance and the kinetic of MMP-1, MMP-2, MMP-9 and TIMPs were detected between cells grown on the polymer surface compared to the control. An appropriate understanding of the molecular processes that regulate cellular growth and integration of a biomaterial in surrounding tissue is the requirement for an optimal adaptation of biodegradable, polymeric biomaterials to the physiological, anatomical, and surgical conditions in vivo to develop new therapeutic options in otolaryngology and head and neck surgery.

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Moli1901 is a 19 residue polycyclic peptide antibiotic which increases chloride transport and water mobilization in airway epithelium. These properties suggest that it may be a useful treatment for cystic fibrosis (CF). In this study, we used accelerator mass spectrometry (AMS) to quantify Moli1901 following administration of only 0.045 microCi of 14C-Moli1901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Administration of 14C-Moli1901 by intratracheal instillation (approximately 100 microg) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. Whole blood and plasma concentrations of 14C were <5 ng/ml at all times after the dose. Concentrations of 14C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of 14C in whole blood, but after that time, plasma accounted for only 25-30% of the 14C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using 14C-Moli1901 and AMS.

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INTRODUCTION: Using standard cell biological and biochemical experimental approaches we were able to test the ability of a particular polymer construct to support the adhesion, proliferation, and the cellular acitivity of pharyngeal cells. The delicate balance between Matrix Metalloproteinases (MMPs) and their endogenous inhibitors (Tissue Inhibitor of MMPs, TIMPs) have a decisive function in the remodeling of the extracellular matrix during cellular ingrowth. Novel polymeric biomaterials may be useful to develop new therapeutic options in head and neck surgery. METHODS: Primary cell cultures of the pharynx of Sprague-Dawley rats were seeded on the surface of a thermoplastic multi-block copolymer and on a polystyrene surface as control. Conditioned media of the primary cells was analyzed for MMPs and TIMPs. The MMP and TIMP expression was analysed by zymography and a radiometric enzyme assay. RESULTS: No statistically significant differences in the levels of MMP-1, MMP-2, MMP-9 and TIMPs were detected between cells grown on the novel polymer surface versus control. CONCLUSION: An appropriate understanding of the molecular machinery that regulates gene expression and cellular growth in tissue engineered constructs is the requirement for an optimal adaptation of biodegradable biomaterials to develop new therapeutic options in otolaryngology and head and neck surgery.

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Biomaterial research is expected to forward new materials to be used as, e.g., implant materials or as scaffolds for tissue engineering. It is central for such a scaffold material to create the track on which those cells can inhabitate the scaffold needed to rebuild functional tissue substitutes. For the biointegration of the implant with the native cellular tissue this must be able to grow on the material surface. For the elimination of the degradation products and the adeqaute transport of nutrients/gases within the newly formed tissue the angiogenesis of new blood vessels is thought to play an important role. In the present study, a new biomaterial, a non-porous polymeric AB-network based on oligo (epsilon-hydroxycaproat) and oligobutylacrylat, was implanted in animals. Male NMRI mice were implanted subcutaneously for one week to nine weeks. Immediately after the explantation, the probes were examined histologically. Already one week after implantation, there was a strong tissue-integration of the polymer. Importantly, blood vessels appeared at the polymer surface. At nine weeks after implantation the tissue integration was stronger than after one week and blood vessels were still observed in the periimplant tissue. The mechanism of the early integration of the polymer is not clear. The relationship between the new periimplant vessels and the integration of the polymer has to be studied.

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Biomaterials research is expected to forward new materials to be used as, e.g., implant materials or as scaffolds for tissue engineering. It is central for such a scaffold material to create the track on which those cells can inhabit the scaffold needed to rebuild functional tissue substitutes. The tissue engineering concept expects a gradual gain in functionality of the newly created tissues while the scaffold materials are degraded and subsequently eliminated. Not only for the elimination of the degradation products the angiogenesis of new blood vessels is thought to play an important role. In the present study, a new biomaterial, a non-porous polymeric AB-network based on oligo (epsilon-hydroxycaproate) and oligobutylacrylate, was implanted in animals. Male NMRI mice were implanted subcutaneously for one week. Immediately after the explantation, the probes were examined histologically. Already one week after implantation, there was a strong tissue-integration of the polymer. Importantly, blood vessels occurred at the polymer surface. There were also clusters of cells around the vessels, which were phenotypically similar to fat cells. The mechanism of the early integration of the polymer is not clear. The relationship between the new periimplant vessels and the integration of the polymer has to be studied.

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In addition to sterilizability, biocompatibility is a further necessary property of biomaterials. The agarose diffusion test is an established standard in vitro procedure for investigating this property. The usual method of evaluating the agarose diffusion test, based on macroscopic determination of the size of the zone of decoloration, and microscopic assessment of cell lysis, limits the power of the test. To obtain more information on the impact of plasma sterilization on the biocompatibility of a new polymer, a high-resolution computer-aided morphometric image analysis system for the quantification of the agarose diffusion test at the cellular level has been developed. This was able to detect statistically significant differences in the cell lysis rate of plasma sterilized polymer specimens before and after 4 weeks of incubation in a physiological solution. The new method provides highly detailed information on the interaction of soluble material elements and cells. In addition to cell damage by potentially toxic elements, the sensitivity of the L929 fibroblasts used in the agarose diffusion test to mechanical stress also needs to be considered and verified by further investigations.

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This study is the first empirical test of the strategic importance of member autonomy and open access in a managed care environment. The model utilized in this study assesses the relative importance of autonomy in selecting specialists (open access), service convenience, value/pricing, and HMO resources on member satisfaction with care and intentions to remain with the HMO.

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The vascularity of cervical lymph nodes can be documented by means of color-coded duplex sonography and malignant and benign lymph nodes distinguished on the basis of typical patterns of vascularity. However, not all intranodal vessels can be visualized by color-coded duplex sonography, and minute vessels are detectable only after the administration of a signal enhancer. This also makes it possible to assess the morphology of cervical lymph nodes that are inaccessible on plain sonography. In the present study we examined acute and chronic inflammatory and metastatic lymph nodes as well as malignant lymphomas to determine the extent to which a specific pattern of vascularity can be detected with color-coded duplex sonography after the injection of Levovist as a signal enhancer. In addition, digital image processing was used to quantify the vascularity detected in relation to the cross-sectional area of the lymph nodes as seen at sonography and to determine whether there are any differences in lymph node types as regards an increase in the detection of vascularity. After injection of the marker a typical pattern of vascularity could be assigned to all lymph nodes examined and differences shown in quantifying vascularity: This increase was greatest in the acutely inflamed lymph nodes (36.0 +/- 5.0%) and smallest in lymph nodes with chronic inflammation (2.3 +/- 1.3%). These findings show that cervical lymph nodes of varying origin differ by virtue of their pattern of vascularity, with increased vascularity detectable after administration of a signal enhancer.

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A large fraction of globally produced methane is converted to CO2 by anaerobic oxidation in marine sediments. Strong geochemical evidence for net methane consumption in anoxic sediments is based on methane profiles, radiotracer experiments and stable carbon isotope data. But the elusive microorganisms mediating this reaction have not yet been isolated, and the pathway of anaerobic oxidation of methane is insufficiently understood. Recent data suggest that certain archaea reverse the process of methanogenesis by interaction with sulphate-reducing bacteria. Here we provide microscopic evidence for a structured consortium of archaea and sulphate-reducing bacteria, which we identified by fluorescence in situ hybridization using specific 16S rRNA-targeted oligonucleotide probes. In this example of a structured archaeal-bacterial symbiosis, the archaea grow in dense aggregates of about 100 cells and are surrounded by sulphate-reducing bacteria. These aggregates were abundant in gas-hydrate-rich sediments with extremely high rates of methane-based sulphate reduction, and apparently mediate anaerobic oxidation of methane.

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OBJECTIVE: To analyze cellular proliferative activity, MIB-1 immunopositivity of normal tissue (n = 20), follicular adenoma (n = 30) and follicular carcinoma (n = 32) of the thyroid gland was analyzed by means of immunohistometry. STUDY DESIGN: Immunohistochemical reactions were performed on 3-micron sections from routinely formalin fixed and paraffin embedded surgical specimens using an indirect peroxidase method. The rate of immunostained cells was determined using the CM-2 TV image analysis system (Hund, Wetzlar, Federal Republic of Germany). Forty viewing fields (1.94 mm2) were measured with 20:1 objective magnification. An average of 5,965 cells were assessed in each case. RESULTS: Mean MIB-1 immunopositivity was higher in follicular carcinoma (average, 2.30%) and follicular adenoma (0.58%) than in normal thyroid tissue (0.14%). The distribution of single values differed significantly between groups (P < .001). To test the suitability of MIB-1 immunohistometry for the differential diagnosis of follicular adenoma and follicular carcinoma, different four-field tables with varying thresholds were calculated. Using a threshold of 0.9%, follicular carcinoma could be detected with a sensitivity of 75% (24/32) and a specificity of 83% (25/30). If a specificity of 90% is required (27/30), the sensitivity of the test decreases to 69% (22/32), based on a threshold of 1.1%. CONCLUSION: As some overlap of single values has to be considered, MIB-1 immunohistometry, although presenting new insights into the proliferative potential of thyroid lesions, is of only limited value for the differential diagnosis of follicular lesions in routine surgical pathology.

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