[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases]. / Orale Glukokortikoide : Anwendung und Therapiemonitoring bei entzündlich-rheumatischen Erkrankungen.

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins. Indications for the use of GC in high doses in rheumatology are always given when a life-threatening, dangerous or treatment-resistant situation is involved. Lower doses of GC, usually administered orally, are particularly used in rheumatoid arthritis, vasculitis and collagenosis. In clinical practice the general principle is to use the smallest possible effective dose of GC for the shortest possible time in order to achieve the therapeutic effect of GC without running the risk of unacceptably severe side effects.

[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases]. / Orale Glukokortikoide : Anwendung und Therapiemonitoring bei entzündlich-rheumatischen Erkrankungen.

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins. Indications for the use of GC in high doses in rheumatology are always given when a life-threatening, dangerous or treatment-resistant situation is involved. Lower doses of GC, usually administered orally, are particularly used in rheumatoid arthritis, vasculitis and collagenosis. In clinical practice the general principle is to use the smallest possible effective dose of GC for the shortest possible time in order to achieve the therapeutic effect of GC without running the risk of unacceptably severe side effects.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.

[Long-term glucocorticoid therapy : Is there a safe dosage?]. / Langzeittherapie mit Glukokortikoiden : Gibt es eine sichere Dosierung?

Glucocorticoids have been successfully used for a long time to treat a wide range of chronic inflammatory diseases. Despite the well-accepted efficacy, possible adverse effects still provoke discussions among patients and physicians. In particular, the long-term use of glucocorticoids at higher dosages may cause unwanted adverse effects; therefore, the question arises if conditions for a safe long-term treatment regimen with these drugs can be defined. Studies specifically and comprehensively addressing this question are missing; therefore, a multidisciplinary task force comprised of medical experts and patients was formed to analyze and discuss the existing literature in order to identify conditions where long-term glucocorticoid treatment has an acceptably low level of harm. The group agreed that the actual level of harm of long-term glucocorticoid therapy depends on both drug (dose and duration) and patient-specific characteristics. The patient-specific parameters (some of which can be modified by patients and/or physicians) should always be monitored before and during treatment with glucocorticoids and optimized if necessary. A positive benefit-risk ratio can be achieved when current knowledge and existing recommendations are kept in mind and implemented in clinical practice.

Pharmacodynamics of glucocorticoids.

Exogenous glucocorticoids (GCs) are used as anti-inflammatory and immunosuppressive drugs in the treatment of a wide range of rheumatic and other inflammatory diseases. GCs exert their immunosuppressive, anti-inflammatory and anti-allergic effects on primary and secondary immune cells, tissues and organs via different mechanisms of action in a dose-dependent manner. However, their pleiotropic effects also lead to numerous adverse effects such as unwanted metabolic effects and osteoporosis. The mechanisms of action include the classical genomic mechanism resulting from activation of the cytosolic glucocorticoid receptor (cGCR), non-specific, non-genomic effects caused by interactions with cellular membranes, secondary non-genomic effects initiated by the cGCR and specific interactions with a membrane-bound glucocorticoid receptor (mGCR). Optimised glucocorticoids, such as selective glucocorticoid receptor agonists, are being developed to minimise the adverse effects many patients experience, especially if GCs are given at higher dosages over longer periods of time. Immunostimulatory effects of low concentrations of endogenous glucocorticoids and the influence of pre-receptor metabolism appear of interest for further investigation. The most important approach to optimise the risk-benefit ratio of GCs is to understand in more detail how the molecular mechanisms of genomic and non-genomic GC actions - and their dose-dependency - mediate the clinically wanted benefits but also the known adverse effects.

Determinants of intracolonial relatedness in Pogonomyrmex rugosus (Hymenoptera; Formicidae): mating frequency and brood raids.

The genus Pogonomyrmex is one of three ant genera with an effective mating frequency (me) > 2.0. We developed microsatellites to determine me for P. rugosus because mating frequency of P. rugosus was known only from observational data which do not allow an estimate of me. We genotyped 474 workers from 20 colonies for two microsatellite loci. Observed mating frequencies ranged from 3 to 12 and me for P. rugosus was 4.71. Observed patriline frequencies were significantly different from the expected patriline frequencies generated with a simulated data set under the assumption of equal patriline representation. The available mating frequency data and phylogenetic information of the genus Pogonomyrmex suggest that multiple mating is the ancestral state in the North American Pogonomyrmex sensu stricto. Established P. rugosus colonies raid and destroy smaller conspecific colonies. During these raids ant workers were observed carrying pupae and larvae from the raided colony into the nest of the raiding colony. However, it was not clear whether raided brood emerged in the raiding colony and were subsequently recruited into the work force (intraspecific slavery) or were used as food (predation). Our analyses indicate 6 of 14 field colonies contained foreign P. rugosus workers (43%). The range of the intracolonial frequency of foreign workers collected directly from the nest entrance was between 4 and 28%.

[Lay help in rehabilitation of psychiatrically handicapped patients--report of two comparative empirical studies]. / Die Laienhilfe in der Rehabilitation psychisch Behinderter-Bericht über zwei vergleichende empirische Studien.

Two studies on lay helping in the rehabilitation of persons with chronic mental illness are reported. Lay helpers, clients and staff from two social psychiatric centres participated in structured interviewing; supplementary procedures were used on some aspects. The findings show that interaction of the three groups included is moulded by a multitude of expectations and incompatibilities, which are of relevance to the very concept of lay help. "Lay helping" is set out as a very meaningful and urgently needed approach in the rehabilitation of persons with chronic mental illness- at the same time however characterized as a transition toward developing an independent conception in terms of community psychology and community psychiatry.