Peripartal anti-SARS-CoV-2-IgA/IgG in asymptomatic pregnant women during regional SARS-CoV-2-outbreak.

OBJECTIVES: The Severe Acute Respiratory Distress Corona Virus 2 (SARS-CoV-2) pandemic poses special challenges for the society and especially the medical staff. Even if a rather mild course is assumed among pregnant women the measures to prevent transmission of the infection are of outstanding importance. METHODS: To screen asymptomatic pregnant women during admission to our university maternal hospital we focused on anti-SARS-CoV-2-specific IgG and IgA antibody responses. Hundred and fifty one women admitted to the hospital for childbirth or caesarean delivery were included. In case of suspicious anti-SARS-CoV-2-antibody levels an RT-PCR was performed to confirm an ongoing infection with SARS-CoV-2. RESULTS: A total of 89% showed negative results for anti-SARS-CoV-2-IgA antibodies, whereas 3% were borderline and 7% positive (both labeled as suspicious). In only one patient with suspicious serology we detected SARS-CoV-2-RNA in the following RT-PCR. 2% presented anti-SARS-CoV-2-IgG antibodies, all being positive for anti-SARS-CoV-2-IgA. The observed positive rate of our study collective of 10.6% seemed much higher than the expected one (1.3%) based on the reports of the Robert Koch Institute and the specifications given by the test's manufacturer. The expected positive predictive value (PPV) was 4.3-6.7 times higher than the observed one. CONCLUSIONS: To our knowledge this is the first report of anti-SARS-CoV-2-antibody levels in the peripartum period of asymptomatic women. As the positive anti-SARS-CoV-2 serology poorly correlated with the confirmatory RT-PCR and the fact that mainly the detection of the virus by PCR correlates with the patient's infectiousness we suggest to rather perform a SARS-CoV-2-PCR-based admission screening in perinatal centers to prevent the spread of the disease.

Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak.

BACKGROUND: Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID-19 outbreak. METHODS: A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection, and SARS-CoV-2-specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate, or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS: Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non-COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION: We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.

Serum uromodulin-a marker of kidney function and renal parenchymal integrity.

Background: An ELISA to analyse uromodulin in human serum (sUmod) was developed, validated and tested for clinical applications. Methods: We assessed sUmod, a very stable antigen, in controls, patients with chronic kidney disease (CKD) stages 1-5, persons with autoimmune kidney diseases and recipients of a renal allograft by ELISA. Results: Median sUmod in 190 blood donors was 207 ng/mL (women: men, median 230 versus 188 ng/mL, P = 0.006). sUmod levels in 443 children were 193 ng/mL (median). sUmod was correlated with cystatin C (rs = -0.862), creatinine (rs = -0.802), blood urea nitrogen (BUN) (rs = -0.645) and estimated glomerular filtration rate (eGFR)-cystatin C (rs = 0.862). sUmod was lower in systemic lupus erythematosus-nephritis (median 101 ng/mL), phospholipase-A2 receptor- positive glomerulonephritis (median 83 ng/mL) and anti-glomerular basement membrane positive pulmorenal syndromes (median 37 ng/mL). Declining sUmod concentrations paralleled the loss of kidney function in 165 patients with CKD stages 1-5 with prominent changes in sUmod within the 'creatinine blind range' (71-106 µmol/L). Receiver-operating characteristic analysis between non-CKD and CKD-1 was superior for sUmod (AUC 0.90) compared with eGFR (AUC 0.39), cystatin C (AUC 0.39) and creatinine (AUC 0.27). sUmod rapidly recovered from 0 to 62 ng/mL (median) after renal transplantation in cases with immediate graft function and remained low in delayed graft function (21 ng/mL, median; day 5-9: relative risk 1.5-2.9, odds ratio 1.5-6.4). Immunogold labelling disclosed that Umod is transferred within cytoplasmic vesicles to both the apical and basolateral plasma membrane. Umod revealed a disturbed intracellular location in kidney injury. Conclusions: We conclude that sUmod is a novel sensitive kidney-specific biomarker linked to the structural integrity of the distal nephron and to renal function.

Increase of homogenous new bone formation using osteoinductive factor rhGDF-5 during sinus floor augmentation in Goettingen Minipigs.

OBJECTIVES: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) induces an increased and homogenous distribution of new bone formation across the entire volume of sinus floor augmentation in 12 Goettingen Minipigs. MATERIAL AND METHODS: In a randomized split-mouth design, one maxillary sinus was augmented with the bone substitute ß-TCP, whereas a combination of ß-TCP and the osteoinductive growth factor rhGDF-5 was used on the contralateral side. To evaluate the influence of dose and time on the effectiveness of the factor, two different concentrations of rhGDF-5 (400 µg and 800 µg) and healing periods (4 and 12 weeks) were each analysed. RESULTS: After 4 weeks, a homogenous gradient of bone formation could be observed for all dosage groups, with decreasing bone density from the local bone towards the sinus membrane. Both test groups, however, achieved a higher total level of bone formation compared with the control group, which was only significant in the low-dose group (P = 0.0184). After 12 weeks, the influence of the growth factor significantly depends on the region (P = 0.023). In the low-dose group, the new bone formation did not differ significantly within the examined regions of the graft (P = 0.1118), suggesting a homogeneous bone formation over the entire augmentation. The gradient of the high-dose group was similar to the control group with a decrease of local bone development. CONCLUSIONS: rhGDF-5 delivered on a ß-TCP scaffold material leads to an increase in homogeneous new bone formation across the entire volume of the sinus floor augmentation.

Influence of synthetic polyethylene glycol hydrogels on new bone formation during mandibular augmentation procedures in Goettingen minipigs.

Polyethylene glycol hydrogels (PEG) have been used as slow release carrier for osteoinductive growth factors in order to achieve a retarded delivery. However, there have been concerns about negative effects on bone regeneration. This study aims to test whether PEG hydrogels themselves affect new bone formation (NBF), when used as a carrier during mandibular augmentation procedures. In a randomized split-mouth design, bilateral mandibular bone defects were surgically created in 12 Goettingen minipigs, and subsequently augmented, using PEG hydrogel on one side of the mandible. The contralateral sides, without PEG, served as controls. After 4 and 12 weeks, bone formation was evaluated in six animals each. A comparison of the data, using a three-way analysis of variance (ANOVA), revealed a significant effect of the healing time and the region of the graft on the distribution and enhancement of NBF (P < .0001, respectively). Although a 0.3% (95%-CI [-5.5; 4.8]) lower volume density of newly formed bone could be observed over all PEG hydrogel sections, in contrast to the contralateral controls, the analysis revealed no clinically significant effects of the PEG hydrogel treatment on the total level (P = 0.90), and the distribution of NBF (P = 0.54). In conclusion, PEG hydrogels do not affect NBF when used as a carrier for osteoinductive growth factors during mandibular augmentation procedures.

Mandibular reconstruction using a calcium phosphate/polyethylene glycol hydrogel carrier with BMP-2.

AIM: To test the hypothesis that a synthetic hydroxyapatite/ß-tricalcium phosphate (HA/TCP) construct combined with polyethylene glycol (PEG) hydrogel including recombinant human bone morphogenetic proteins-2 (rhBMP-2) enhances new bone formation compared with bone morphogenetic proteins-2 (BMP-2) delivered using the HA/TCP construct alone. MATERIAL AND METHODS: Bilateral mandibular partial thickness 20 × 8 × 8 mm (L × W × H) alveolar defects were surgically created in the edentulated posterior mandible in 18 female minipigs. Randomized into two groups of nine animals each, the alveolar defects either received HA/TCP or HA/TCP/PEG with or without BMP-2 (105 µg/defect) in contra-lateral sites using a split-mouth design. Primary outcome, bone density (%) within four regions of interest, was evaluated following a 4-week healing interval when the animals were killed for histometric analysis. RESULTS: Bone morphogenetic proteins-2 loaded onto HA/TCP constructs significantly enhanced new bone formation compared with HA/TCP controls. Adding PEG apparently obstructed BMP-2 induced bone formation. CONCLUSION: Polyethylene glycol compromises the osteogenic effect of BMP-2.

Successful Nd:YAG laser therapy for hair removal in the oral cavity after plastic reconstruction using hairy donor sites.

BACKGROUND: Concepts of reconstruction of intraoral structures may often include the transfer of flaps composed of external skin with hairs. Given that intraoral hair growth following myocutaneous flaps can cause discomfort, there is a need for effective treatments to relieve cancer patients of these symptoms. OBJECTIVE: To describe the successful epilation of hairy intraoral flaps using Nd:YAG laser emitting a wavelength of 1,064 nm. METHODS: We performed an interdisciplinary prospective clinical study with 9 patients suffering from intraoral hair growth after plastic reconstruction of a hairy donor site due to cancer. Eight male and one female patients were treated with 1-4 sessions of Nd:YAG laser at 5-15-week intervals. RESULTS: Laser treatment resulted in effective hair reduction in 8/9 patients regardless of flap type. In 5/9 patients a hair clearance of >90% could be achieved, whereas laser treatment was ineffective in one male with white hair. Patients were very satisfied with the outcome and no side effects could be observed. CONCLUSION: Nd:YAG laser therapy appears to be a successful therapeutic option for patients suffering from growth of dark hair in the oral cavity after plastic reconstruction using a hairy donor site.

Chemical and biological differences between original and mimetic pentosan polysulfates.

Pentosan polysulfate sodium (PPS) is a semi-synthetic, heparin-like polysaccharide with manifold therapeutic actions. It is approved for treatment of bladder pain syndrome / interstitial cystitis in humans and treatment of musculoskeletal diseases in animals. PPS is produced by a complex procedure using beech wood as starting material. It consists of a mixture of sulfated glucuronoxylans, whose structural composition cannot be fully characterized by physicochemical analysis. The question arises whether PPS follow-on products are identical with the original and thus meet the requirement for generic drug application. The aim of this study was to investigate whether commercially available PPS products differ in physicochemical characteristics and biological effects from the original. Ten PPS preparations from different manufactures were analyzed using orthogonal analytical techniques including, inter alia, size exclusion chromatography with triple detection, nuclear magnetic resonance spectroscopy, and high-resolution mid-infrared spectroscopy in aqueous solution with chemometric evaluation. For functional analysis, we measured the plasma kallikrein generation in human plasma and FXII activation. The study revealed significant structural and biological differences between PPS from different sources. Therefore, follow-on products cannot be considered identical but at best similar to original PPS. However, their similar efficacy and safety have still to be proven by comprehensive studies.

Intracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6.

Several studies have shown an involvement of the immune system, in particular the monocytic system, in the pathophysiology of schizophrenia. Beside others, the monocyte-derived cytokines TNF-α, IL-6 and IL-10 were found to be affected. Since cytokines are secreted by several different cell types, the cellular source is only clear if intracellular levels are measured. Thus, in order to study the monocytic system in schizophrenia, the intracellular levels of TNF-α, IL-6 and IL-10 were determined. The intracellular concentration of TNF-α, IL-6 and IL-10 in CD33 positive monocytes was evaluated in schizophrenic patients and controls with monoclonal antibodies against these cytokines. In addition, in vitro stimulation with lipopolysaccharide (LPS) or poly I/C, which mimic a bacterial and viral infection, was performed before immunocytochemistry. At baseline, monocytic IL-6 levels were significantly lower in schizophrenic patients than in controls. After stimulation with LPS, compared with baseline, monocytic intracellular IL-6 production tended to increase more in schizophrenic patients. The present results provide further support for the hypothesis of an involvement of a dysfunction of the monocytic system in the pathophysiology of schizophrenia and indicate that especially the pro-inflammatory immune response seems to be impaired.

Altered monocyte activation markers in Tourette's syndrome: a case-control study.

BACKGROUND: Infections and immunological processes are likely to be involved in the pathogenesis of Tourette's syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. METHODS: In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14 (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by immunoassays. RESULTS: We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. CONCLUSIONS: The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

Pentosan Polysulfate Inhibits Attachment and Infection by SARS-CoV-2 In Vitro: Insights into Structural Requirements for Binding.

Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side effect. One alternative, with structural similarities to heparin, is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated, and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective in inhibiting cell infection than low-molecular-weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.

Combined quality of life and posttraumatic growth evaluation during follow-up care of patients suffering from oral squamous cell carcinoma.

Oral cancer therapy is associated with a loss in health-related quality of life (HRQOL) and can also lead to post-traumatic growth (PTG). The current study analyzed the relationship between HRQOL, PTG and influencing clinical factors after treatment. The coherent clinical data of 15 patients were retrospectively analyzed over a 1-year study period. HRQOL and PTG were studied using the University of Washington Quality of Life Version 4 (UW-QOL v4) and Posttraumatic Growth Inventory (PTGI) questionnaires. The results revealed that HRQOL was significantly decreased in a pre- to postoperative manner (P=0.011). Sex demonstrated a nearly significant effect on HRQOL (P=0.058). PTG was experienced the most after surgery, and continuously decreased over the 1-year study period. Patient age had a significant effect on PTG (P=0.040). A significant correlation was also established between HRQOL and PTG (P<0.05). HRQOL and PTG are important influencing factors during postoperative tumor follow-up care and should be simultaneously recorded to address individual patient needs and improve quality of treatment.

Torquing an upper central incisor with aligners--acting forces and biomechanical principles.

The forces delivered by aligners during torquing have still not been investigated. The purpose of this study was to measure the forces delivered to an upper central incisor during torquing with three different materials of the same thickness, and to describe the biomechanical principles of torquing with aligners. Five identical appliances were manufactured from each of three materials, all with a thickness of 1.0 mm (Ideal Clear®, Erkodur®, and Biolon®). An upper central incisor, as part of the measuring device, was torqued in defined steps in the vestibular and palatal directions with the respective appliance in place. For statistical analysis, the resulting forces, Fx (forces acting in the palatal and facial directions) and Fz (intrusive force as a side-effect) at a displacement of ±0.15 and ±0.8 mm from the tooth at the gingival margin were calculated. The mean Fx forces for ±0.15 mm displacement ranged from -1.89 N [standard deviation (SD) 0.48] to 0.11 N (SD 0.1). The mean Fz forces were between -0.97 N (SD 0.57) and -0.07 N (SD 0.22). The highest intrusive forces were measured during palatal displacement of the measuring tooth. An influence of direction of displacement on the levels of force was observed, especially for Fz at the greater displacement of ±0.8 mm. In relation to the intended amount of root movement during torquing, aligners tend to 'lift up' and therefore no effective force couple can be established for further root control. The force delivery properties are also influenced by the material used and the shape of the tooth.

Immune response to SARS-CoV-2 in health care workers following a COVID-19 outbreak: A prospective longitudinal study.

OBJECTIVE: Currently, little is known about the progression of an immune response against SARSCoV- 2 upon infection or sub-infection-exposure over time. We examined the serologic response in healthcare workers up to 12 weeks after a well-documented and contained outbreak and compared results with findings from earlier serologic testing in the same population. METHODS: This study followed 166 health care workers of the University Perinatal Care Center, Regensburg, Germany, for up to 12 weeks. 27 of the subjects had previously tested positive for the presence of SARS-CoV-2 by PCR testing and developed COVID-19. Serologic responses were tested with two independent commercially available test kits. RESULTS: 77.8 % of COVID-19 study subjects developed a specific IgG-response over the course of the 12-week study, while none of the COVID-19 contact groups had a detectable IgG response. Amongst most COVID-19 patients the values of detectable IgG-responses significantly increased over time as confirmed with both tests, while that of positive IgA responses decreased. Between the number of reported symptoms and antibody responses in COVID-19 patients no correlation was found and no new cases of seroconversion were identified in asymptomatic coworkers with negative PCR during the outbreak. CONCLUSIONS: Immune response after COVID-19 increases significantly over time but still approximately 22 % of COVID-19 patients did not mount a measurable serologic immune response within 60 days. Exposed co-workers did not develop any relevant antibody levels at all. We conclude that immunity after infection increases over time, but the antibody response does not develop reliably in all infected people.

Sinus floor augmentation with recombinant human growth and differentiation factor-5 (rhGDF-5): a pilot study in the Goettingen miniature pig comparing autogenous bone and rhGDF-5.

AIM: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) in combination with a beta-tricalcium phosphate (beta-TCP) scaffold material results in superior bone formation in sinus floor augmentations in miniature pigs compared with a particulated autogenous bone graft combined with the scaffold material. MATERIAL AND METHODS: Six adult female Goettingen minipigs underwent a maxillary sinus floor augmentation procedure. In a split-mouth design, the sinus floors were augmented with beta-TCP mixed with autogenous cortical bone chips, in a ratio of approximately 1 : 1, on one side. The contralateral test site was augmented using beta-TCP coated with two concentrations of rhGDF-5 (400 microg rhGDF-5/g beta-TCP or 800 microg rhGDF-5/g beta-TCP; three animals in each case). Simultaneously, one dental implant was inserted into each sinus floor augmentation. After 12 weeks, a histological and histomorphometric assessment of non-decalcified histological specimens was made. RESULTS: There were significantly higher mean values of volume density of newly formed bone using beta-TCP coated with two concentrations of rhGDF-5 (400 microg: 32.9%; 800 microg: 23.9%) than with the corresponding control (autogenous bone/beta-TCP) (14.6%, 12.9%) (P=0.012, P=0.049). The bone-to-implant contact rates (BIC) were significantly enhanced in test sites (400 microg: 84.2%; 800 microg: 69.8%) compared with the corresponding control sites (24.8%, 40.8%) (P=.027, P=.045). CONCLUSION: rhGDF-5 delivered on beta-TCP significantly enhanced bone formation compared with beta-TCP combined with autogenous bone in sinus lift procedures in miniature pigs.

Quality of life in school-age children with orofacial clefts and their families.

Nonsyndromic orofacial clefts might affect family functioning and probably reduce the quality of life in school-age children and their parents. One hundred seventy consecutive children with orofacial clefts between 8 and 12 years and their families were asked to answer the Impact on Family Scale and KINDL. The results were compared with the quality of life in an age- and sex-matched group of unaffected schoolchildren. One hundred thirty-two families participated in this study. Family functioning was found superior in families with children with cleft lip than in families with children with cleft palate only or cleft lip and palate. Sex had no significant influence on family functioning. The quality of life in schoolchildren with orofacial clefts was found superior to the control group. Reductions were observed in children with cleft lip and palate in the dimensions "family" and "friends," indicating problems in the social field. Boys with orofacial clefts experienced a lower quality of life than girls. Children with cleft lip and palate and cleft palate only experienced a lower quality of life than children with cleft lip. Even years after successful cleft reconstruction, coping and mastering the diagnosis of orofacial cleft is a relevant concern for affected families. Several limitations of the quality of life in schoolchildren were identified, mostly affecting their social role.

Initial forces generated by three types of thermoplastic appliances on an upper central incisor during tipping.

The force properties of thermoformed appliances have not been systematically investigated. Therefore, the aim of the present study was to quantify the forces delivered by thermoplastic appliances manufactured from three different materials, with the same thickness, on a central upper incisor, during tipping. Five identical appliances were manufactured from three different materials all with a thickness of 1.0 mm (Ideal Clear, Erkodur, and Biolon). For measuring the forces, an isolated measuring tooth, as part of a standardized resin model incorporated in a newly developed measuring device, was tipped in nine 2.7 arc minute (0.04629 degree) steps, from 0 to 0.416 degrees in the vestibular and palatal directions around a rotational axis through the virtual apex, after positioning an appliance on the model. For statistical analysis, the force components Fx/tipping and Fz/intrusion at a displacement of +/-0.151 mm from the incisor edge were determined. Means and standard deviations (SDs) were calculated. The Kruskal-Wallis test for overall effects and the Wilcoxon two-sample test for individual group pairings were used (P < 0.05 significance level). The mean Fx forces ranged from -2.82 N (SD 0.62) to 5.42 N (SD 0.56). The mean Fz forces were between -0.14 N (SD 0.52) and -2.3 N (SD 0.43). The highest intrusive forces were measured during vestibular displacement of the measuring tooth. The forces delivered by the Biolon appliance were found to be much greater (P < 0.01) than those of the other materials. The forces delivered by the materials investigated were mostly higher than those stated in the literature.

The association of high-normal international-normalized-ratio (INR) with mortality in patients referred for coronary angiography.

AIMS: The international-normalized-ratio (INR) is typically used to monitor patients on warfarin or related oral anticoagulant therapy. The aim of our study was to investigate the association of the INR with mortality in coronary artery disease (CAD) patients not on oral anticoagulant therapy. METHODS AND RESULTS: Between 1997 to 2000 the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study enrolled 3316 patients of German ancestry that had been referred for coronary angiography. We excluded patients on coumarin therapy (n = 222) and patients with an INR more than 5 standard deviations (SD) away from the mean (n = 30). During a median follow-up of 9.9 years, 884 patients died, 547 patients from cardiovascular causes. After adjustment for cardiovascular risk factors the INR was associated with all-cause mortality in all patients and the CAD positive group with HRs (95% CI) of 1.14(1.07-1.21) and 1.16(1.09-1.23) per 1-SD increase, respectively. Adjustment for NT-proBNP rendered the association insignificant. CONCLUSION: In LURIC, the INR was positively associated with mortality in patients with prevalent CAD not on oral anticoagulant therapy as well as in patients without CAD. Adjustment for NT-proBNP abolished the association suggesting clinical or subclinical heart failure strongly contributing to increased INR and higher mortality.

Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats.

The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 48 microg rhBMP-2 (Group 1) and blank implants without BMP (Group 0) each on one side of the mandible. Unfilled defects of the same size on the contralateral sides of the mandibles served as empty controls. After 6, 13 and 26 weeks, implants of each group were retrieved from five animals each and submitted to flat panel detector computed tomography. Bone formation and thickness of augmentation was assessed by computer-assisted histomorphometry. In Group 2 significantly more bone was produced than in Group 1. Implants of Group 1 induced significantly more bone than the blank controls only after 6 weeks, whereas the difference was not significant after 13 and 26 weeks. Differences between Group 2 and Group 1 were clearly significant after 26 weeks. The thickness of bone tissue was maintained in Group 2 whereas it decreased in Group 1 and was negligible in Group 0. It is concluded that the PLA implants with 96 microg rhBMP-2 were able to bridge a non-healing defect in the rat mandible and maintained the thickness of an augmented volume. However, continuous supply of osteogenic signals appears to be required to compensate for adverse effects during polymer degradation.

Sinus floor augmentation with recombinant human growth and differentiation factor-5 (rhGDF-5): a histological and histomorphometric study in the Goettingen miniature pig.

AIM: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) enhances bone formation in sinus floor augmentations in miniature pigs. MATERIAL AND METHODS: The maxillary sinus floors in 12 adult female Goettingen minipigs were augmented with beta-tricalcium phosphate (beta-TCP) on one side. The contralateral test side was augmented using two concentrations of rhGDF-5 (400 microg rhGDF-5/g beta-TCP; 800 microg rhGDF-5/g beta-TCP) delivered on beta-TCP (six animals each). One dental implant was inserted into each sinus floor augmentation. After 4 and 12 weeks, histological and histomorphometric assessment of non-decalcified histological specimens was performed. RESULTS: The results showed significantly higher mean values of volume density (VD) of newly formed bone using the concentration of 400 microg/g beta-TCP (22.8%) compared with the respective control (8%) after 4 weeks (P=0.05). The bone-to-implant contact rates were also significantly enhanced after 4 weeks between test sites (400 microg: 41.9%; 800 microg: 40.6%) and control sites (400 microg: 7.8%; 800 microg: 16.4%) (400 microg: P=0.024; 800 microg: P=0.048). CONCLUSION: It is concluded that rhGDF-5 delivered on beta-TCP significantly enhanced early bone formation compared with beta-TCP alone in sinus lift procedures in miniature pigs.