[High burden of disease in patients with ANCA-associated vasculitis : A claims data study in Germany]. / Hohe Krankheitslast bei Patienten mit ANCA-assoziierter Vaskulitis : Versorgungsdatenstudie in Deutschland.

BACKGROUND & OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare chronic autoimmune diseases characterized by recurrent systemic inflammation provoking multiple morbidities. AAV patients suffer from various organ manifestations and treatment-related severe adverse effects. This retrospective study investigated the concrete burden of AAV disease on patients in Germany. METHODS: Based on anonymized longitudinal German statutory health insurance (SHI) claims data from the years 2011-2016, a representative cohort of approximately 3 million insured persons was used to identify patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and selected clinical aspects were systematically assessed. RESULTS: The most frequent concomitant morbidities of GPA and MPA were renal and respiratory disorders. Severe renal involvement occurred in 11.6% of GPA and 24.3% of MPA patients within 15 quarters of diagnosis. Severe infections developed in one third of AAV patients within the first three quarters post-diagnosis. The annual rate of major relapses was 5-8%. AAV patients with renal impairment or infections showed increased annual mortality rates of 14.4 and 5.6%, respectively. CONCLUSION: Based on this analysis of German health care data, disease-specific assumptions regarding the burden on AAV patients were confirmed and concretized for the German context. AAV patients suffer from a high burden of morbidity, including multiple disease manifestations, relapses, and severe complications due to AAV treatment.

[Acceptance, utility and practicality of a questionnaire to define rehabilitation goals before the commencement of the medical rehabilitation]. / Akzeptanz, Nutzen und Praktikabilität eines Fragebogens zur Definition von Reha-Zielen vor Antritt der medizinischen Rehabilitation.

BACKGROUND AND GOALS: In a multicenter study, patients of the German statutory insurance were encouraged to deal with their own rehabilitation goals using a questionnaire sent in advance of rehabilitation. How patients and physicians assess the benefits and practicability of this method should, in particular, be examined. METHODS: In a randomized controlled study a questionnaire, based on the preparation booklet of the DRV Bund, was sent by the German statutory insurance to 2782 rehabilitation patients (n(ortho)=1406, n(onco)714, n(psy)=662). For the intervention group, the questionnaire included, in addition to general information about rehabilitation goals, free text fields for the formulation of own goals. Patients were asked to bring the completed questionnaire to the admission interview. At the end of rehabilitation, satisfaction with participation in the goal-setting process and perceived usefulness of information on rehabilitation goals were captured. The doctors/psychologists responded to standardized items regarding various aspects of utility and practicability of the questionnaire. RESULTS: 34% of the targeted rehabilitation patients brought the completed questionnaire to the admission interview. For most of the rehabilitation patients goal setting is important; 31.4% reported the information obtained to rehabilitation goals to be very, and 62.9% particularly helpful. For practitioners, the questionnaire is likely to orient rehabilitation patients to rehabilitation goals: they reported that 56.6% of the patients reflected about their goals and that 50% were more familiar with the subject. Physicians rated the handling and integration of the questionnaire into the interview, its format and layout as well as its benefits more positively than the surveyed psychologists. These were more optimistic about the ability of rehabilitation patients to answer the questionnaire (62.5%, physicians 47.2%) and define own goals (77.8%, physicians 41.7%). CONCLUSIONS: The applied questionnaire has been well accepted by the majority of rehabilitation patients and practitioners as well as was judged to be practical and useful in important aspects. A comprehensive implementation of the questionnaire proves to be promising, particularly in the context of oncological and orthopedic rehabilitation. To increase the return of the questionnaire, alternative delivery options should be explored in future. Against the background that rehabilitation patients and practitioners of psychosomatic medicine perceived the questionnaire as less helpful, it is also prudent to investigate whether indication-specific implementation strategies would be advantageous.

[Patient goals for medical rehabilitation - overview of the current state of research in Germany]. / Ziele von Patienten der medizinischen Rehabilitation - Eine Übersicht zum Forschungsstand in Deutschland.

GOALS: It is widely known that goals and goal agreement are important components of a modern approach to medical rehabilitation. The present work gives an overview of the current state of research regarding patient goals for medical rehabilitation by reviewing relevant German pub-lications between 2000 and 2010. This review focused on (1) data collection methods of rehabilitation goals, (2) patient goals, and (3) agreement between the goals of patients and their clinicians. METHODS: A search strategy combining electronic databases and hand search was applied. A priori inclusion and exclusion criteria were applied. A self-developed goal-catalogue was used to synthesize the literature. RESULTS: A total of 20 publications were included, 11 of which explored both patient and clinicians perspectives. ad (1): Only 4 goal-assessment instruments in the field of medical rehabilitation exist, but none has been established as a standard. The instruments differ in how differentiate they depict different goals areas. ad (2): The goal structure of medical rehabilitation patients corresponds to the respective indications. The 3 top goals in all patient groups included physical and/or psychosocial objectives. Information and occupational goals are rarely represented among the 3 top goals mentioned. ad (3): Patients have more numerous as well as differing goals then their treating clinicians. Goals of physical functions (e. g., enhancement of stamina) and superior rehabilitation goals (e. g., return to work) have the best agreement. Mental and maintenance goals are more frequently mentioned by the patients while pain and symptom-related goals are more frequently mentioned by the doctors. There are indication-specific differences for goals regarding information. CONCLUSION: Rehabilitation goals are highly valuable in the rehabilitation process. Finding only 20 relevant publications, generalizability of study results is limited. Due to high variability in methodological approach and presentation of results, comparisons of results across studies reviewed are severely limited. Developing survey standards and using uniform metrics could contribute to standardizing study endpoints. The goals of patients and clinicians are formed in individual life or work contexts, which are influenced by numerous factors (e. g., knowledge, illness/health concepts, assumptions regarding rehabilitation treatment), representing individual expertise that complement one another. Since compatible goals are essential for successful rehabilitation treatment, an exchange of goals and expectations as well as the establishment of joint target agreements should precede any rehabilitation programme.

Plasma and tissue concentrations of beta-carotene and vitamin A in rats fed beta-carotene in various fats of plant and animal origin.

We investigated the effects of various types of dietary fat of plant and animal origin on beta-carotene absorption and tissue accumulation in rats. Rats were fed 1 mL of butter fat, lard, tallow, sunflower, arachidonic, soya, olive, or linseed oil containing 175 mg beta-carotene/mL fat by gavage, twice a week for 4 weeks. The beta-carotene and vitamin A levels in plasma and tissues were determined by rp-HPLC. The highest levels of absorbed beta-carotene were observed in the liver of animals fed olive and arachidonic oil (p < 0.001), and in the lungs of animals fed sunflower oil. Histomorphological studies showed that the observed highly variable accumulation of beta-carotene in lung tissue was most probably due to an endogenously caused lipid pneumonia. No beta-carotene was observed in blood plasma, kidney, and spleen in any group. Plasma vitamin A levels (retinol) were increased with tallow, olive, and arachidonic oil (p < 0.05). The most obvious influence was found for vitamin A in the spleen. Levels in rats fed tallow (p < 0.05), butter, or lard (p < 0.001) were higher than in controls. The lowest vitamin A levels were found in rats fed fat of plant origin. Our results suggest that the type of dietary fat can modulate the absorption of beta-carotene as well as the distribution of vitamin A in plasma and selected tissues.

Effect of age on the levels of retinol and retinyl esters in blood plasma, liver and kidney of dogs.

The effect of age on plasma levels and tissue distribution (liver, kidney) of retinol and retinyl esters was studied in dogs from birth to the age of 18 months. In newborn dogs vitamin A in plasma was low and increased within four weeks to levels found in adult dogs. At four weeks retinyl esters (stearate > palmitate) dominated over retinol in plasma. Liver levels increased over 400 times from 10 micrograms/g at birth within six months. At all times retinyl esters represented the majority of vitamin A (> 70%). In kidneys, highest levels were observed not before 18 months after birth. Results indicate obvious quantitative and qualitative differences concerning vitamin A accumulation in plasma and tissue possibly associated with changes from fetal development to suckling stage and later to the uptake of feed.

[Pupil physiology after cataract surgery]. / Pupillomotorik nach Kataraktoperation.

BACKGROUND: The goal of a cataract operation is to achieve an optimal outcome, which includes a round and functioning pupil. The goal of this study was to analyze the influence of cataract operations on pupils that appear to be normal on slit-lamp examination postoperatively. PATIENTS AND METHODS: A videopupillography was performed on 47 eyes of 47 patients after phacoemulsification without complications in the first eye, and on 12 eyes of 12 patients after phacoemulsification without complications in the second eye. RESULTS: After surgery, the first eyes showed a significantly more constricted pupil compared to the non-operated eye independently of the stage of irritation. After surgery of the second eye, this was only observed under near dark conditions. CONCLUSION: Even the morphologically normal pupil shows a change in motility postoperatively. We believe that the reason for this is the mechanical manipulation of the iris during cataract operation. During this, the sensitive dilator muscle of the pupil is affected, leading to temporary or permanent changes in pupillary function. The change in motility of the contralateral, non-operated eye cannot be easily explained. The pupil size is important for the visual process and alteration of its function allows an evaluation of the quality of the operation.

Breathing, voice, and movement therapy: applications to breathing disorders.

Elsa Gindler (1885-1961) developed a holistic approach to the human body and psyche via the movement of breath. Gindler experimented with movements to strengthen the deeper layers of the muscular system and improve the circulation of oxygen, movements that reduced tensions that had been preventing the breathing muscles from functioning properly. Subsequently, she founded a school for breathing and body awareness. The biggest breathing muscle in the human body is the diaphragm, the lowering of which can only take place when the jaw and the throat are relaxed, the belly is free, and the psoas (major and minor) and hip joints allow free leg-movement and flexibility in the lower back. When these conditions do not obtain, the body compensates by lifting the shoulders, pulling up the chest bone, and contracting the sphincter muscles in the throat, movements which weaken the muscles which assist the breathing process. Thus, the compensatory muscles are overburdened and the fine organization of the body is disturbed; the natural capacity to use the breath as a healing force is lost. The goal of breath therapy is to recognize and reestablish this capacity. Training sessions are devoted to relaxation; to exercises to rebuild muscle tone, strengthen weakened muscles, release contracted areas, and the use of the voice to stimulate the respiratory system. Sessions typically consist of (a) relaxation, (b) activation (experimenting with new, freer ways of moving), and (c) integration (application to everyday life). The therapist analyzes incidents of stress in the client's life where breathing is likely to be disturbed. This is especially important for asthmatics who can learn how to deal with an attack by relaxing rather than contracting. This work is especially beneficial for problems in (a) the skeletal structure, (b) respiration, (c) vital organs, and (d) general symptoms.

Distribution of vitamin A, retinol-binding protein, cellular retinoic acid-binding protein I, and retinoid X receptor beta in the porcine uterus during early gestation.

Retinol and retinol-binding protein (RBP), among the major secretory products of the uterine endometrium in the uterine fluid of pigs, are assumed to be of importance for early embryonic development. While uterine RBP has been widely characterized, little information is available on the metabolism of vitamin A itself or other specific binding proteins or nuclear receptors in the uterus of pigs. In the present study, the content and distribution of vitamin A in uterine tissue of pigs during early gestation (Days 14-30) were examined macroscopically and microscopically via autofluorescence and HPLC. In addition, the distribution of specific proteins involved in vitamin A metabolism at the cellular and nuclear level was investigated. Macroscopically, the yellowish-greenish autofluorescence characteristic of vitamin A was observed in uterine endometrium. Microscopy showed that the autofluorescence was associated with glandular and surface epithelium of the endometrium. In these structures, immunoreactive RBP was localized, as was cellular retinoic acid-binding protein I. Retinoid X receptor beta was observed in the nucleus of myometrium and endometrium. The intensity of fluorescence decreased with the progress of gestation. This decrease was paralleled by a decrease in vitamin A content of endometrium and myometrium. In general, vitamin A concentration in the endometrium was higher than in the myometrium (P < 0.01). In the myometrium, if present at all, vitamin A was found almost exclusively as retinyl esters. In the endometrium, the dominant fraction was retinol, representing more than 90% of total vitamin A. These results show for the first time that the yellowish-greenish autofluorescence in the pig uterus can be attributed to vitamin A. Differences in the form of vitamin A present in endometrium and myometrium might point to differences in metabolism. In the myometrium, vitamin A might be stored, and in the endometrium, vitamin A is present primarily as retinol-the form in which it is secreted into the uterine fluid.

Effect of dietary beta-carotene on the accumulation of beta-carotene and vitamin A in plasma and tissues of gilts.

The absorption of beta-carotene in pigs is limited. Nevertheless beta-carotene might positively affect reproduction. In this study the absorption and tissue distribution of beta-carotene as well as its function as precursor of vitamin A was investigated in gilts that were fed according to one of three dietary treatments: VA (4000 IU vitamin A), VA + VA (4000 IU + 8300 IU) and VA + BC (4000 IU + 100 mg beta-carotene per kg diet) for 14 weeks. Only in the VA + BC group was beta-carotene detected in plasma (1-8 ng x mL(-1)), liver, adrenals and corpora lutea, indicating that pigs absorb intact beta-carotene at low rates. Liver levels of vitamin A were higher (P < 0.01) at comparable levels in the VA + VA and VA + BC group than in the VA group, indicating a conversion rate of beta-carotene to vitamin A of 40 to 1 on the basis of weight for beta-carotene at this level (100 mg x kg(-1)) in the diet. Higher levels of vitamin A in the uterus of the VA + BC group (P < 0.01) as well as the accumulation of beta-carotene in adrenals and corpora lutea might reflect some influence of beta-carotene on local vitamin A metabolism which might be of importance for reproductive performance in gilts.

[Changes in the plasma concentration of vitamin A, vitamin E and beta-carotene in polytrauma patients and in patients with osteitis in relation to course of illness]. / Veränderungen in der Plasmakonzentration von Vitamin A, Vitamin E und beta-Karotin bei Polytraumatisierten und Patienten mit Osteitis in Abhängigkeit vom Krankheitsverlauf.

In 17 patients with osteitis and 16 polytraumatized patients changes in the plasma levels of vitamin A, vitamin E and beta-carotene were investigated. Plasma samples taken preoperatively, daily during the first three days and then twice a week postoperatively were analysed for fat-soluble vitamins by high performance liquid chromatography (HPLC). Significant changes in plasma levels of all three components depending on the outcome of injury were found in all patients. Increased levels were observed in patients that survived the injury, while in those who died a significant decrease was observed. Recommendations regarding the supplementation with these vitamins in clinical practice can not be made based on these results, but substitute might prove beneficial for vitamin E in certain types of injury.

Passive transport of macromolecules through Xenopus laevis nuclear envelope.

Although nuclear pore complexes (NPC) are considered to be key structures in gene expression, little is known about their regulatory control. In order to explore the regulatory mechanism of passive transport of small macromolecules we examined the influence of different factors on the diffusional pathway of NPCs in isolated Xenopus laevis oocyte nuclei. Diffusion of fluorescence-labeled 10-kD dextran was measured across the nuclear envelope with confocal fluorescence microscopy. Surprisingly, the filling state of the perinuclear Ca(2+) store had no influence on passive transport of 10-kD dextran. Furthermore, nuclear envelope permeability was independent of cytoplasmic pH (pH range 8.3-6.3). In contrast, nuclear swelling, induced by omission of the endogenous cytosolic macromolecules, clearly increased nuclear permeability. An antibody against the glycoprotein gp62, located at the central channel entrance, reduced macromolecule diffusion. In addition, nuclei from transcriptionally active, early developmental stages (stage II) were less permeable compared to transcriptionally inactive, late-developmental-stage (stage VI) nuclei. In stage II nuclei, atomic force microscopy disclosed NPC central channels with plugs that most likely were ribonucleoproteins exiting the nucleus. In conclusion, the difference between macromolecule permeability and previous measurements of electrical resistance strongly indicates separate routes for macromolecules and ions across the nuclear envelope.

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores.

The contents of retinol and retinyl esters as well as retinol-binding protein (RBP) in the plasma, urine, liver and kidneys of dogs, raccoon dogs and silver foxes were investigated. In the plasma and urine of all three species, vitamin A was present as retinol and retinyl esters. Vitamin A levels (1376+/-669 microg x g(-1)) were significantly higher in the livers of dogs than in the kidneys (200+/-217 microg x g(-1), P < 0.001 ). However, vitamin A levels in the kidneys of raccoon dogs (291+/-146 microg x g(-1)) and silver foxes (474+/-200 microg x g(-1)) were significantly higher than in the liver (67+/-58 microg x g(-1) and 4.3+/-2.4 microg x g(-1), respectively, both P < 0.001). RBP was immunologically detected in the blood plasma of all species, but never in the urine. In the liver, immunoreactive RBP was found in hepatocytes. In the kidneys of all species, RBP was observed in the cells of the proximal convoluted tubules. The levels of vitamin A in the livers of raccoon dogs and silver foxes were extremely low, which would be interpreted as a sign of great deficiency in humans. This observation might indicate that the liver status cannot be used as an indicator of vitamin A deficiency in canines. The high levels of vitamin A in the kidneys in all three species may indicate a specific function of the kidney in the vitamin A metabolism of canines.

Transient permeability leak of nuclear envelope induced by aldosterone.

The mineralocorticoid hormone aldosterone controls fluid and electrolyte transport in target cells of the kidney and the cardiovascular system. Classic genomic aldosterone action involves the activation of cytosolic mineralocorticoid receptors and translocation into the cell nucleus where specific transcription processes are initiated. A key barrier of the intracellular signalling pathway is the nuclear envelope, which physically separates the nucleoplasm from the cytoplasm. It was shown recently that aldosterone changes ion conductivity of the nuclear envelope mediated by nuclear pore complexes. The latter are supramolecular nanomachines responsible for import and export of inorganic ions and macromolecules. The aim of the present study was to test whether aldosterone changes the macromolecule permeability of the nuclear envelope. Aldosterone-responsive Xenopus laevis oocytes were used as a model system. We isolated the cell nuclei at defined times after hormone injection. By means of confocal fluorescence microscopy and fluorescence-labelled dextrans we evaluated passive macromolecule import and export in isolated nuclei. 10 minutes after aldosterone injection nuclear envelope permeability of 10 kD dextran was found sharply increased. At the same time cell nuclei were found swollen by about 28%. Changes in nuclear volume and nuclear envelope permeability lasted 5 to 15 minutes and could be inhibited by the mineralocorticoid receptor blocker spironolactone. We conclude that aldosterone transiently changes the barrier function of the nuclear envelope. This short-lasting permeability change signals the start of a sustained transcription process that follows in response to steroids.

Luminal salmonella endotoxin affects epithelial and mast cell function in the proximal colon of pigs.

BACKGROUND: Salmonellosis and systemic endotoxaemia affect intestinal function. However, little is known about the functional importance of luminal Salmonella (S.) endotoxin during intestinal infection. METHODS: Pigs were either given or not given lipopolysaccharide (LPS, 30 mg day(-1)) of S. Typhimurium DT-104 orally for 14 days. Blood samples were taken weekly. After slaughter (day 14), epithelia of the proximal colon were investigated in Ussing chambers. Bacterial translocations to lung, liver, spleen and several lymph nodes were determined by culture. RESULTS: Endotoxin feeding increased plasma C-reactive protein (CRP) and histamine levels without evoking clinical signs. Postmortem, proximal colonic epithelia of LPS-treated animals showed both a decreased histamine release after mast cell stimulation with A23187 and a smaller increase in short-circuit current after A23187 application. Addition of the nitric oxide donor, sodium nitroprusside (SNP), also elicited lower increases in short-circuit current in the proximal colon of endotoxin-treated pigs. Endotoxin pre-feeding decreased colonic ion conductance, although mannitol and histamine fluxes were high in some epithelia of this group. Luminal Salmonella endotoxin increased bacterial translocation to proximal jejunal lymph nodes. LPS applied to colonic epithelia in vitro had no electrophysiological effects. CONCLUSIONS: Luminal endotoxin elicits an acute phase response and affects intestinal electrolyte transport and mast cell function. Furthermore, LPS induces epithelial spots of increased mannitol permeability that could be identical to spots of enhanced bacterial translocation.

Short-term glucocorticoid treatment of piglets causes changes in growth plate morphology and angiogenesis.

OBJECTIVE: Glucocorticoid treatment of children often leads to growth retardation, and the precise target(s) in the growth plate responsible for this effect are unknown. Angiogenesis is an important part of the endochondral ossification process, and VEGF expressed in the growth plate is essential for proper angiogenesis to occur. Since glucocorticoid treatment down-regulates VEGF expression in cultured chondrocytes, we hypothesized that in vivo glucocorticoid treatment could result in VEGF down-regulation in the growth plate and disturbed angiogenesis, thus contributing to the growth retardation. DESIGN: We treated 6-week-old prepubertal piglets (10 kg) for 5 days with prednisolone (50 mg/day). Tibial growth plate sections were studied for apoptosis and the expression of VEGF protein and mRNA and MMP-9 protein. Capillaries in the metaphysis were visualized by CD31 immunostaining. Growth plate morphology (width of various zones) was determined by interactive measurements on hematoxylin/eosin stained sections and apoptotic cells were detected by TUNEL assay. RESULTS: In the prednisolone-treated animals, the total width of the growth plate decreased to 81% of controls (P<0.02), which was explained by a decrease of the width of the proliferative zone to 73% (P<0.05). The treatment had no effect on the orderly organization of the chondrocyte columns. In the growth plates of control animals, apoptosis was shown in 5.8% of the hypertrophic chondrocytes and was limited to the terminal hypertrophic chondrocytes. In prednisolone-treated animals, 40.5% of the hypertrophic chondrocytes was apoptotic (P<0.02), with apoptotic chondrocytes also appearing higher in the hypertrophic zone. We observed fewer capillaries and loss of their parallel organization in the metaphysis in the prednisolone-treated animals. The capillaries were shorter and chaotic in appearance. In contrast to controls, in prednisolone-treated animals VEGF mRNA and protein could not be detected in the hypertrophic zone of the growth plate. Trabecular bone length in the primary spongiosa was also diminished by the treatment. No changes were observed in the expression pattern of MMP-9, a matrix metalloproteinase, which is also important for angiogenesis and bone formation. CONCLUSIONS: These results indicate that short-term glucocorticoid treatment of growing piglets severely disturbs the width of the growth plate, apoptosis of chondrocytes, VEGF expression by hypertrophic chondrocytes, the normal invasion of blood vessels from the metaphysis to the growth plate and bone formation at the chondro-osseous junction. These effects could alter the dynamics of endochondral ossification and thus contribute to glucocorticoid-induced growth retardation.