Early loading after 21 days of healing of nonsubmerged titanium implants with a chemically modified sandblasted and acid-etched surface: two-year results of a prospective two-center study

PURPOSE: The aim of this two-center study was to evaluate screw-type titanium implants with a chemically modified, sandblasted and acid-etched surface when placed in the posterior maxilla or mandible, and loaded 21 days after placement. MATERIAL AND METHODS: All 56 patients met strict inclusion criteria and provided informed consent. Each patient displayed either a single-tooth gap, an extended edentulous space, or a distal extension situation in the posterior mandible or maxilla. Eighty-nine dental implants (SLActive, Institut Straumann AG, Basel, Switzerland) were inserted according to an established nonsubmerged protocol and underwent undisturbed healing for a period of 21 days. Where appropriate, the implants were loaded after 21 days of healing with provisional restorations in full occlusion. Definitive metal ceramic restorations were fabricated and positioned on each implant after 6 months of healing. Clinical measurements regarding soft tissue parameters and radiographs were obtained at different time points up to 24 months after implant placement. RESULTS: Of the 89 inserted implants, two (2.2%) implants failed to integrate and were removed during healing, and two (2.2%) additional implants required a prolonged healing time. A total of 85 (95.6%) implants were therefore loaded without incident after 21 days of healing. No additional implant was lost throughout the study period, whereas one implant was lost to follow-up and therefore left unaccounted for further analysis. The remaining 86 implants all exhibited favorable radiographic and clinical findings. Based on strict success criteria, these implants were considered successfully integrated 2 years after insertion, resulting in a 2-year success rate of 97.7%. CONCLUSION: The results of this prospective two-center study demonstrate that titanium implants with a modified SLA surface can predictably achieve successful tissue integration when loaded in full occlusion 21 days after placement. Integration could be maintained without incident for at least 2 years of follow-up.

2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

ABSTRACT:

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades.

Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism

Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein-generating antigenic determinants for T cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of physiologically relevant Ags to functional immune responses is lacking. The aim of this study was to develop an integrated approach using animal and human experimental systems to characterize sulfamethoxazole (SMX) metabolism-derived antigenic protein adduct formation in immune cells and define the relationship among adduct formation, cell death, costimulatory signaling, and stimulation of a T cell response. Formation of SMX-derived adducts in APCs was dose and time dependent, detectable at nontoxic concentrations, and dependent on drug-metabolizing enzyme activity. Adduct formation above a threshold induced necrotic cell death, dendritic cell costimulatory molecule expression, and cytokine secretion. APCs cultured with SMX for 16 h, the time needed for drug metabolism, stimulated T cells from sensitized mice and lymphocytes and T cell clones from allergic patients. Enzyme inhibition decreased SMX-derived protein adduct formation and the T cell response. Dendritic cells cultured with SMX and adoptively transferred to recipient mice initiated an immune response; however, T cells were stimulated with adducts derived from SMX metabolism in APCs, not the parent drug. This study shows that APCs metabolize SMX; subsequent protein binding generates a functional T cell Ag. Adduct formation above a threshold stimulates cell death, which provides a maturation signal for dendritic cells.

Stimulation of human T cells with sulfonamides and sulfonamide metabolites

Exposure to sulfonamides is associated with a high incidence of hypersensitivity reactions. Antigen-specific T cells are involved in the pathogenesis; however, the nature of the antigen interacting with specific T-cell receptors is not fully defined.

Declines of managed honey bees and beekeepers in Europe

Growing evidence indicates that European managed honey bees are in decline, but information for Europe remains patchy and localized. Here we compile data from 18 European countries to assess trends in the number of honey bee colonies and beekeepers between 1965 and 2005. We found consistent declines in colony numbers in central European countries and some increases in Mediterranean countries. Beekeeper numbers have declined in all of the European countries examined. Our data support the view that honey bees are in decline at least in some regions, which is probably closely linked to the decreasing number of beekeepers. Our data on colony numbers and beekeepers must, however, be interpreted with caution due to different approaches and socioeconomic factors in the various countries, thereby limiting their comparability. We therefore make specific recommendations for standardized methodologies to be adopted at the national and global level to assist in the future monitoring of honey bees.

Glycomic analysis of human mast cells, eosinophils and basophils

In allergic diseases such as asthma, eosinophils, basophils and mast cells, through release of preformed and newly generated mediators, granule proteins and cytokines, are recognized as key effector cells. While their surface protein phenotypes, mediator release profiles, ontogeny, cell trafficking and genomes have been generally explored and compared, there has yet to be any thorough analysis and comparison of their glycomes. Such studies are critical to understand the contribution of carbohydrates to the induction and regulation of allergic inflammatory responses and are now possible using improved technologies for detecting and characterizing cell-derived glycans. We thus report here the application of high-sensitivity mass spectrometric-based glycomics methodologies to the analysis of N-linked glycans derived from isolated populations of human mast cells, eosinophils and basophils. The samples were subjected to matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) screening analyses and MALDI-TOF/TOF sequencing studies. Results reveal substantive quantities of terminal N-acetylglucosamine containing structures in both the eosinophil and the basophil samples, whereas mast cells display greater relative quantities of sialylated terminal epitopes. For the first time, we characterize the cell surface glycan structures of principal allergic effector cells, which by interaction with glycan-binding proteins (e.g. lectins) have the possibility to dictate cellular functions, and might thus have important implications for the pathogenesis of inflammatory and allergic diseases.

Specific attentional impairments and complex visual hallucinations in eye disease

OBJECTIVE: To test the prediction by the Perception and Attention Deficit (PAD) model of complex visual hallucinations that cognitive impairment, specifically in visual attention, is a key risk factor for complex hallucinations in eye disease. METHODS: Two studies of elderly patients with acquired eye disease investigated the relationship between complex visual hallucinations (CVH) and impairments in general cognition and verbal attention (Study 1) and between CVH, selective visual attention and visual object perception (Study 2). The North East Visual Hallucinations Inventory was used to classify CVH. RESULTS: In Study 1, there was no relationship between CVH (n=10/39) and performance on cognitive screening or verbal attention tasks. In Study 2, participants with CVH (n=11/31) showed poorer performance on a modified Stroop task (p<0.05), a novel imagery-based attentional task (p<0.05) and picture (p<0.05) but not silhouette naming (p=0.13) tasks. Performance on these tasks correctly classified 83% of the participants as hallucinators or non-hallucinators. CONCLUSIONS: The results suggest that, consistent with the PAD model, complex visual hallucinations in people with acquired eye disease are associated with visual attention impairment.

ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)

Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies’ Task forces on CVD prevention in clinical practice.2 – 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.