Multimorbidity and polypharmacy are threats to elderly patients; improvement of medication is important and a novel listing approach (the FORTA list) should support this in clinical practice. Here we ...aim to describe procedural details of successful application of FORTA. FORTA labels range from A (indispensable), B (beneficial), C (questionable) to D (avoid), depending on evidence for safety, efficacy and overall age-appropriateness. As implicit tool it is only applicable if medical details of the patient are known; the drug selection process and secondary assessments are compiled into a manual for successful, embedded use of FORTA.
A flow chart is developed for the complex process of medication in the elderly starting from history taking and diagnostic assessment including disease grading. This is the base for FORTA-assisted selection of drugs to avoid overtreatment (drug not necessary), undertreatment (condition not or not sufficiently treated by positively labeled drugs) or mistreatment (drugs indicated, but negatively rather than positively labeled drug chosen). Selection is followed by secondary analyses, e. g. regarding contraindications (e. g. allergies), former drug responses, interactions, route of application, duration and dosing (e. g. renal adaptation). This may lead to iterative process optimization. The medication scheme is updated in reflection of clinical effects (e. g. blood pressure) and side effects (e. g. dizziness).
The FORTA approach as an implicit tool should be embedded into the diagnostic and therapeutic workup of elderly patients and can give pivotal hints for the choice of medications; however it should not be seen as an isolated instrument.
Traditionally, steroid hormone action has been described as the modulation of nuclear transcription, thus triggering genomic events that are responsible for physiological effects. Despite early ...observations of rapid steroid effects that were incompatible with this theory, nongenomic steroid action has been widely recognized only recently. Evidence for these rapid effects is available for steroids of all clones and for a multitude of species and tissues. Examples of nongenomic steroid action include rapid aldosterone effects in lymphocytes and vascular smooth muscle cells, vitamin D3 effects in epithelial cells, progesterone action in human sperm, neurosteroid effects on neuronal function, and vascular effects of estrogens. Mechanisms of action are being studied with regard to signal perception and transduction, and researchers have developed a patchy sketch of a membrane receptor-second messenger cascade similar to those involved in catecholamine and peptide hormone action. Many of these effects appear to involve phospholipase C, phosphoinositide turnover, intracellular pH and calcium, protein kinase C, and tyrosine kinases. The physiological and pathophysiological relevance of these effects is unclear, but rapid steroid effects on cardiovascular, central nervous, and reproductive functions may occur in vivo. The cloning of the cDNA for the first membrane receptor for steroids should be achieved in the near future, and the physiological and clinical relevance of these rapid steroid effects can then be established.
Several fly species have distinctly red‐coloured eyes, meaning that the screening pigments that provide a restricted angular sensitivity of the photoreceptors may perform poorly in the longer ...wavelength range. The functional reasons for the red transparency and possible negative visual effects of the spectral properties of the eye‐colouring screening pigments are discussed within the context of the photochemistry, arrestin binding and turnover of the visual pigments located in the various photoreceptor types. A phylogenetic survey of the spectral properties of the main photoreceptors of the Diptera indicates that the transition of the brown eye colour of the Nematocera and lower Brachycera to a much redder eye colour of the higher Brachycera occurred around the emergence of the Tabanidae family.
Functional interplay of visual and screening pigments in the eyes of long‐horned flies (left; Diptera: Nematocera) and short‐horned flies (right; Diptera: Brachycera). The seven circles in the central enlarged facet indicate the rhabdomeres, where the six peripheral rhabdomeres contain green‐sensitive rhodopsin (Nematocera) with a blue‐shifted metarhodopsin isoform (blue circle around the green dot), or blue‐sensitive rhodopsin (Brachycera) with a red‐shifted metarhodopsin isoform (red circle around the blue dot). The seventh, central rhabdomere (violet, green and blue spot) contains UV‐, blue‐ and green‐sensitive rhodopsins with the corresponding blue‐ or green‐sensitive metarhodopsins. The photoreceptor somas contain yellow screening pigment. The dark brown screening pigment (Nematocera) or red screening pigment (Brachycera) in the pigment cells optically isolate the ommatidia and produce the eye colour. The nematoceran dark brown pigment absorbs all UV and visible wavelengths, while the brachyceran red pigment allows red stray light (red arrow) to reisomerize the metarhodopsin into rhodopsin, thus restoring the peripheral photoreceptors’ sensitivity. The red stray light may cause reduction of the angular and contrast sensitivity of the green‐sensitive central photoreceptor.
We describe an imaging scatterometer allowing hemispherical reflectance measurements as a function of the angle of incidence. The heart of the scatterometer is an ellipsoidal reflector, which ...compresses the hemispherical reflection into a cone-shaped beam that can be imaged by a normal optical system. The instrument's performance is illustrated by measurements of the scattering profiles of the blue-iridescent dorsal wing scales of the nymphalid Morpho aega and the matte-green ventral wing scales of the lycaenid Callophrys rubi.
Paracetamol has become a focus of attention as being unsafe due to hepatic toxicity and market withdrawal or prescription status is presently under discussion in Germany. This drug is, however, ...effective and safe if notes of caution are applied. In Germany 38 fatal cases of analgesic poisoning were observed in 2010, only 4 of which were due to paracetamol and 16 were caused by diclofenac and ibuprofen. Alternative pain medications are obviously much less safe, in particular given the additional risk of sometimes fatal gastrointestinal bleeding and cardiovascular side effects. This review extensively analyzes the safety record of paracetamol and applies these findings to the treatment of elderly people. Even very elderly patients may be safely treated with this compound, although a dose limit of 3 g/day should be instituted. This renewed discussion was triggered by the uncontrolled availability of paracetamol in the USA but observations from this country should not be generalized and applied to the German situation and objective reasoning should be re-installed.
Dystrophin-deficient muscles experience large reductions in expression of nitric oxide synthase (NOS), which suggests that NO deficiency may influence the dystrophic pathology. Because NO can ...function as an antiinflammatory and cytoprotective molecule, we propose that the loss of NOS from dystrophic muscle exacerbates muscle inflammation and fiber damage by inflammatory cells. Analysis of transgenic mdx mice that were null mutants for dystrophin, but expressed normal levels of NO in muscle, showed that the normalization of NO production caused large reductions in macrophage concentrations in the mdx muscle. Expression of the NOS transgene in mdx muscle also prevented the majority of muscle membrane injury that is detectable in vivo, and resulted in large decreases in serum creatine kinase concentrations. Furthermore, our data show that mdx muscle macrophages are cytolytic at concentrations that occur in dystrophic, NOS-deficient muscle, but are not cytolytic at concentrations that occur in dystrophic mice that express the NOS transgene in muscle. Finally, our data show that antibody depletions of macrophages from mdx mice cause significant reductions in muscle membrane injury. Together, these findings indicate that macrophages promote injury of dystrophin-deficient muscle, and the loss of normal levels of NO production by dystrophic muscle exacerbates inflammation and membrane injury in muscular dystrophy.
Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older ...people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.
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