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Background Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries. Methods Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques. Results Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed. Conclusion The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Background Osseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions. Methods The surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces. Results The results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Student's t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces. Conclusion The study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.
Background Heme oxygenase-1 is an inducible cytoprotective enzyme which handles oxidative stress by generating anti-oxidant bilirubin and vasodilating carbon monoxide. A (GT)n dinucleotide repeat and a -413A>T single nucleotide polymorphism have been reported in the promoter region of HMOX1 to both influence the occurrence of coronary artery disease and myocardial infarction. We sought to validate these observations in persons scheduled for coronary angiography. Methods We included 3219 subjects in the current analysis, 2526 with CAD including a subgroup of CAD and MI (n = 1339) and 693 controls. Coronary status was determined by coronary angiography. Risk factors and biochemical parameters (bilirubin, iron, LDL-C, HDL-C, and triglycerides) were determined by standard procedures. The dinucleotide repeat was analysed by PCR and subsequent sizing by capillary electrophoresis, the -413A>T polymorphism by PCR and RFLP. Results In the LURIC study the allele frequency for the -413A>T polymorphism is A = 0,589 and T = 0,411. The (GT)n repeats spread between 14 and 39 repeats with 22 (19.9%) and 29 (47.1%) as the two most common alleles. We found neither an association of the genotypes or allelic frequencies with any of the biochemical parameters nor with CAD or previous MI. Conclusion Although an association of these polymorphisms with the appearance of CAD and MI have been published before, our results strongly argue against a relevant role of the (GT)n repeat or the -413A>T SNP in the HMOX1 promoter in CAD or MI.
Introduction Impaired renal function and/or pre-existing atherosclerosis in the deceased donor increase the risk of delayed graft function and impaired long-term renal function in kidney transplant recipients. Case presentation We report delayed graft function occurring simultaneously in two kidney transplant recipients, aged 57-years-old and 39-years-old, who received renal allografts from the same deceased donor. The 62-year-old donor died of cardiac arrest during an asthmatic state. Renal-allograft biopsies performed in both kidney recipients because of delayed graft function revealed cholesterol-crystal embolism. An empiric statin therapy in addition to low-dose acetylsalicylic acid was initiated. After 10 and 6 hemodialysis sessions every 48 hours, respectively, both renal allografts started to function. Glomerular filtration rates at discharge were 26 ml/min/1.73 m2 and 23.9 ml/min/1.73 m2, and remained stable in follow-up examinations. Possible donor and surgical procedure-dependent causes for cholesterol-crystal embolism are discussed. Conclusion Cholesterol-crystal embolism should be considered as a cause for delayed graft function and long-term impaired renal allograft function, especially in the older donor population.
Visual information is processed hierarchically in the human visual system. Early during processing basic features are analysed separately while at later stages of processing, they are integrated into a unified percept. By investigating a basic visual feature and following its integration at different levels of processing one can identify specific patterns. In certain visual impairments, these patterns can function defectively and their detailed study can clarify the cause of the visual deficit. Here we investigate orientation as a basic feature and use a property of the visual system called adaptation. Adaptation occurs as a decrease in the level of neural activity during repetitive presentation of the same stimulus. Psychophysical studies have shown that adaptation transfers interocularly, meaning that if only one eye is adapted the other eye shows also adaptation effects. Our aim was to investigate interocular transfer by means of functional magnetic resonance imaging (fMRI). Even though adaptation was demonstrated in the fMRI environment, the interocular transfer was never investigated in such a setup. First, we developed a method to measure interocular transfer of adaptation to gratings with fMRI. We then went further to test it in various groups of subjects. In normally sighted humans interocular transfer was present both in early (striate) as well as later visual areas (extrastriate). In subjects with impaired stereovision (with or without normal visual acuity) interocular transfer was absent in the investigated regions. Detailed analysis of the recorded differences between subjects with and subjects without stereovision was performed. The results of this analysis are presented in detail in this book. These results suggest that the neuronal mechanisms involved in the interocular transfer of pattern adaptation share, at least in part, the neural circuitry underlying binocular functions and stereopsis. We conclude that fMRI adaptation can be used for the assessment of cortical binocularity in humans with normal and impaired stereopsis. Further investigations are needed to address more subtle aspects of the lack of interocular transfer. Towards this purpose, through a fourth experiment we propose further directions that might shed more light on the issue of stereovision and its clinical implications. We show that carefully tuned variations in our experimental procedure might reveal other aspects of binocularity in the human visual system. We believe that the method we developed, apart from the interesting results shown here, has a high potential to be further used for other research questions. Following the above summarized ideas, the thesis comprises of three parts (chapters). The first chapter provides the main theoretical backgrounds of the visual system and of the MRI imaging technique, chapter two describes the experimental procedures while the results and their detailed discussion are detailed in chapter three.
Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933
Aims: The purpose of this study was to evaluate the feasibility and short-term efficacy of transcatheter paravalvular leak closure using different occlusion devices. Methods and Results: Twenty one patients underwent transcatheter closure of either aortic or mitral paravalvular leak from June 2002 to February 2006 using the Amplatzer PDA, ASD or VSD occluder. All patients had symptoms and signs of haemolysis and/or cardiac decompensation with dyspnoea. Implantation of a device was technically successful in twenty patients (95 %). Immediate residual leak was found in seventeen patients (85 %). Significant shunting persisted in nine cases during follow up (45 %). Permanent leaflet obstruction was observed in one patient. Severe complications during follow up led to early death in one patient and surgical intervention in three. A successful second catheter treatment was performed in another three patients. The event-free survival from reoperation, death and stroke at the end of the observation period was 80 %. Conclusion: Transcatheter closure of paravalvular leaks is a technically feasible, but demanding procedure. Residual leaks are common and may worsen pre-existing haemolysis. Due to the significant ongoing morbidity in this group of patients and the complexity of follow up individual patient results differ considerably. Nevertheless, it is possible to achieve some symptomatic relief, thus an interventional approach should be discussed as a potential treatment option for those patients with a limited defect and who are not deemed suitable for another operation.
Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.
Biventricular pacing has been suggested in end-stage heart failure. We present a 59-year-old patient undergoing second re-do CABG (coronary artery bypass graft) and carotid artery endarterectomy. Ejection fraction was 15%, QRS-width 175 ms. Following the carotid and CABG procedure, an implanted single-chamber ICD (implantable cardioverter defibrillator) was upgraded to permanent biventricular DDD pacing by implantation of one epicardial left ventricular and one epicardial atrial electrode. At follow-up two months postoperatively ejection fraction had significantly improved to 45%, the patient underwent stress test with adequate load and reported a good quality of life.
Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.