Practical implementation of the planar and spatial rotator in a complex tissue: the brain.

In neuroscience, application of widely used stereological local volume estimators, including the planar rotator, is challenged by the combination of a complex tissue organisation and an estimator requirement of either isotropic or vertical sections, i.e. randomly oriented tissue. The spatial rotator is applicable with any tissue orientation but is sensitive to projection artefacts. The challenge is thus to select the most appropriate method for individual analyses. In this study, agreement between estimates of mean cell volume acquired with the vertical planar and the spatial rotator is assessed for two brain regions with different types of cytoarchitecture (motor cortex and hippocampal cornu ammonis 1). The possibility of using the planar rotator in tissues cut in an arbitrary direction is explored and requirements for a theoretically unbiased result as well as histological considerations are provided. LAY DESCRIPTION: Cells may change volume both during disease and with advancing age. Assessment of the volume of individual cells can therefore serve as a useful indicator of general tissue state. Most available methods to estimate cell volume in tissue sections, however, require that the tissue analysed has random orientation. Particularly for complex tissues such as the brain this is a challenge as identification, delineation and subdivision of many brain areas rely heavily on the use of anatomical atlases where illustrations depict the tissue in a few well-known orientations. In this study, the practical application of two different methods for estimating mean cell volumes in tissues cut in a preferred orientation is evaluated. Requirements for the feasibility of cell volume estimation without random tissue orientation as well as histological considerations are provided.

[Glaucoma in inpatient care in Germany in 2015]. / Glaukome im stationären Leistungsgeschehen in Deutschland in 2015.

AIM: Analysis of structural characteristics of inpatient treatment of glaucoma in clinical units run by affiliated physicians and those run by hospital physicians in Germany are described. The frequency and distribution of glaucoma diagnoses as the main and secondary diagnosis at different departments and glaucoma diagnoses, number of cases, surgeries and procedures and patient characteristics of the four glaucoma-specific diagnosis-related groups (DRG) are presented. METHOD: Secondary data analysis using the G­DRG browser from 2015/2016 provided by the German Institute for Remuneration Systems in Hospitals. RESULTS: In 30% of the 156,524 cases glaucoma was classified as the main diagnosis, in 24% as secondary diagnosis in ophthalmological departments and 46% as secondary diagnosis in other departments. Primary open angle glaucoma was reported most frequently (40%), whilst non-ophthalmological departments mainly coded as "other" or "unspecified types of glaucoma". Glaucoma was coded in 20 DRGs as the main diagnosis and in all ophthalmic DRGs as secondary diagnosis. The number of cases and procedures differed among the four glaucoma-specific DRGs (C06Z, C07A, C07B, C64Z), the diagnostic spectrum, however, was similar. Patients were mainly women, older and with few comorbidities or complications. The C64Z was mainly characterized by cases with "suspected glaucoma" and only conservative procedures. Only 6% of the glaucoma patients were treated in clinical units run by affiliated physicians. In contrast to units run by hospital physicians surgical DRGs and operations prevailed but the diagnostic spectrum and patient characteristics were not different. DISCUSSION AND CONCLUSION: With 20% of the main diagnoses, glaucoma was highly relevant for inpatient ophthalmological care. Glaucoma as a secondary diagnosis was also common in other medical specialties, though no diagnostic differentiation was made here. Patients with glaucoma are mainly treated in clinical units run by hospital physicians. Nevertheless, patients of affiliated physicians showed the same characteristics.

Activating KIR Haplotype Influences Clinical Outcome Following HLA-Matched Sibling Hematopoietic Stem Cell Transplantation.

Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B haplotype which contain more activating receptors in the donor, in particular centromeric B haplotype genes (Cen-B), was associated with improved overall survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT and receiving myeloablative conditioning. Donor Cen-B haplotype was also associated with reduced acute graft versus host disease grades II-IV whereas donor telomeric-B haplotype was associated with decreased incidence of CMV reactivation. In contrast, we were not able to demonstrate a reduced rate of relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A haplotype was a competing risk factor to poor overall survival. Here we show that the presence of donor activating KIR led to improved outcome for the patient, potentially through reduced relapse rates and decreased incidence of acute GvHD translating to improved overall survival. This article is protected by copyright. All rights reserved.

[Employed and self-employed specialists in outpatient ophthalmological care : Comparison with other specialist fields]. / Angestellte und selbstständige Fachärzte in der vertragsärztlichen ophthalmologischen Versorgung : Ein Vergleich mit anderen Fachgebieten.

AIM: The aim of the study was to evaluate the contribution to outpatient care and the perspectives of employed and self-employed ophthalmologists in isolation and in comparison to other professional groups. METHOD: Based on statistical data (source: statistical information provided by the National Association of Statutory Health Insurance Physicians) from 31 December 2015, newly admitted physicians in 2015 and their contribution differentiated by employment relationships were evaluated according to head count and working time equivalents (using "planning of demand equivalents"). The results were subdivided into type of outpatient facility, e.g. single practice, group practice and medical care centers (MVZ). RESULTS: The proportion of employed ophthalmologists (head count) in outpatient care (23%) and newly admitted physicians (81%) is above the interdisciplinary average (16% and 65%, respectively). In all medical professional groups the contribution according to time equivalents of employed physicians compared to self-employed physicians is lower (utilization rate: 65% in total and 70% in ophthalmology). In ophthalmology employment is seen in all types of outpatient practices: the number of ophthalmologists working in group practices is above average, compared to other groups they are underrepresented in MVZ and are working in single practices as frequently as all other specialties. DISCUSSION AND CONCLUSION: Employment of physicians is more common in all types of outpatient ophthalmological facilities than in other specialized professional groups. Possible reasons are the working conditions in ophthalmology attracting physicians preferring employment and the competitive situation for practice takeover. Since employed physicians contribute less time to medical care than self-employed physicians, ophthalmology has a higher risk of a shortage in medical care despite an increasing number of physicians. An increasing number of employed physicians has an impact on the structures of outpatient care; however, the intensity of concentration in healthcare structures can only be partially evaluated due to insufficient data. Based on the available data there is no end in sight for the trend towards employment in outpatient ophthalmological care.

[Systematic Review of the Application of Complementary and Alternative Medicine and their Potential Therapeutic Benefits in the Treatment of Ophthalmology Patients]. / Ergebnisse eines systematischen Reviews zu Einsatz und berichtetem therapeutischem Nutzen komplementärmedizinischer Methoden in der Augenheilkunde.

Purpose A systematic review was carried out of the reported therapeutic effects of complementary and alternative medicine methods as supplementary or primary treatments for patients suffering from glaucoma, cataract or age-related macular degeneration (AMD). Material and Methods For the years 1990 to 2013, the following databases were screened for reports of the application of complementary and alternative treatments: PubMed, Cochrane Library, EMBASE, CAMbase and AMED. Both randomised and prospective non-randomised patient trials were included in the review; results were evaluated in the following classes: "phytotherapy", "acupuncture/acupressure", "biofeedback" and "other alternative treatments". The studies were evaluated by measures of clinical effect, statistical significance (p value and/or confidence interval) and the underlying trial design. Results 30 clinical trials were included, including 13 on glaucoma, 5 on cataract and 12 on AMD patients. These trials were based on patient numbers of 6 - 332, 27 - 157 and 6 - 328 patients, respectively. Phytotherapy was applied in 14 trials, including 6 on glaucoma patients (all 6 with a controlled design, and 3 of which reporting statistically significant results); 5 trials were on cataract patients (3 with a controlled design and 2 with a significant result) and 3 on AMD patients (only 1 with a controlled design, with a significant result). Acupuncture/acupressure was investigated in 9 trials, 5 on glaucoma patients (3 with a controlled design, 1 with a significant result); no acupuncture/acupressure trial was found in cataract patients, but 4 trials in AMD patients (none with a controlled design). Biofeedback was studied in 4 trials, all on AMD patients (only one with a controlled design, without statistically significant findings). Conclusion Despite its rigorous inclusion criteria, this review identified several clinical trials on complementary and alternative medicine in ophthalmological patients. Phytotherapeutic methods gave significant results in half of the reported controlled trials, whereas there were few significant benefits with acupuncture or acupressure.

[Conception and Content Validation of a Questionnaire Relating to the Potential Need for Information of Visually Impaired Persons with Regard to Services and Contact Persons]. / Konzeption und Inhaltsvalidierung eines Fragebogens zu Informationsbedürfnissen bezüglich Dienstleistungen und Ansprechpartnern von sehbehinderten Menschen (FIDAS).

A questionnaire was drafted to identify the needs of visually impaired persons and to optimize their access to non-medical support and services. Subjects had to rate a list of 15 everyday activities that are typically affected by visual impairment (for example, being able to orient themselves in the home environment), by indicating the degree to which they perceive each activity to be affected, using a four-stage scale. They had to evaluate these aspects by means of a relevance assessment. The needs profile derived from this is then correlated with individualized information for assistance and support. The questionnaire shall be made available for use by subjects through advisers in some ophthalmic practices and via the internet. The validity of the content of the proposed tool was evaluated on the basis of a survey of 59 experts in the fields of medical, optical and psychological care and of persons involved in training initiatives. The experts were asked to rate the activities by relevance and clarity of the wording and to propose methods to further develop and optimize the content. The validity of the content was quantified according to a process adopted in the literature, based on the parameters Interrater Agreement (IRA) and Content Validity Index (CVI). The results of all responses (n = 19) and the sub-group analysis suggest that the questionnaire adequately reflects the potential needs profile of visually impaired persons. Overall, there was at least 80% agreement among the 19 experts for 93% of the proposed parameterisation of the activities relating to the relevance and clarity of the wording. Individual proposals for optimization of the design of the questionnaire were adopted.

A new compact soft x-ray spectrometer for resonant inelastic x-ray scattering studies at PETRA III.

We present a newly designed compact grating spectrometer for the energy range from 210 eV to 1250 eV, which would include the Kα(1,2) emission lines of vital elements like C, N, and O. The spectrometer is based on a grazing incidence spherical varied line spacing grating with 2400 l/mm at its center and a radius of curvature of 58 542 mm. First, results show a resolving power of around 1000 at an energy of 550 eV and a working spectrometer for high vacuum (10(-4) mbar) environment without losing photon intensity.

Thalidomide in angiodysplasia-related bleeding.

Gastrointestinal haemorrhage from angiodysplastic lesions is not only difficult to identify, but often refractory to endoscopic intervention. Patients often require substantial transfusion support. Thalidomide has emerged as a promising medical strategy in angiodysplasia-related bleeding. We present our experience and report the findings from a review of the literature. Despite its side-effect profile, thalidomide remains the therapeutic modality with the best evidence in this difficult clinical scenario.

[Case numbers and revenues of main and affiliated ophthalmological departments: Developments since 2005]. / Fallzahlen und Erlöse in ophthalmologischen Haupt- und Belegabteilungen : Entwicklungen seit 2005.

BACKGROUND: Currently, very little data exist on the development of healthcare-related and financial parameters of both types of inpatient treatment: clinical units run by affiliated physicians and those run by hospital physicians. AIM: This study used a methodology based on published secondary data to estimate the annual number of cases and revenues for in inpatient ophthalmological treatment differentiated into clinical units run by affiliated physicians and those run by hospital physicians. MATERIAL AND METHODS: The case-based flat-rate catalogs and accompanying research data published annually by the Institute for the Hospital Remuneration System (Institut für Entgeltsysteme im Krankenhaus, InEK) served as a data source. The numbers of annual cases according to major diagnostic categories (MDC) and diagnosis-related groups (DRG), stratified by the unit type are reported for the period 2005-2012. The cumulative total revenues were calculated based on the number of ophthalmological cases, the effective DRG cost weighting, the length of stay and the national basic case values. RESULTS: Between 2005 and 2012 the units run by affiliated physicians showed a contrasting trend to those run by hospital physicians: the number of cases in units run by hospital physicians increased by 14 %, while those in units run by affiliated physicians decreased by 6 %. Up to 2012 the effective cost weighting for cases in units run by hospital physicians decreased to 0.60 (- 3 %) and increased to 0.43 (+ 5 %) for units run by affiliated physicians. In 2012 the corresponding effective case revenue accounted for 1767 euros and 1271 euros, respectively. Total revenue estimates for all inpatient ophthalmological treatment increased from 549 million euros in 2005 to 630 million euros in 2012, while the share of units run by affiliated physicians amounted to 10.6 % and 9.7 %, respectively. CONCLUSION: According to the indicators "number of cases" and "total revenue", the affiliated ophthalmologists lost ground compared with inpatient units run by hospital physicians over the period from 2005-2012.

Azithromycin analogue CSY0073 attenuates lung inflammation induced by LPS challenge.

BACKGROUND AND PURPOSE: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulating effects. Long-term azithromycin therapy in patients with chronic lung diseases such as cystic fibrosis has been associated with increased antimicrobial resistance, emergence of hypermutable strains, ototoxicity and cardiac toxicity. The aim of this study was to assess the anti-inflammatory effects of the non-antibiotic azithromycin derivative CSY0073. EXPERIMENTAL APPROACH: We compared the effects of CSY0073 with those of azithromycin in experiments on bacterial cultures, Pseudomonas aeruginosa biofilm, lung cells and mice challenged intranasally with P. aeruginosa LPS. KEY RESULTS: In contrast to azithromycin, CSY0073 did not inhibit the growth of P. aeruginosa, Staphylococcus aureus or Haemophilus influenzae and had no effect on an established P. aeruginosa biofilm. Bronchoalveolar lavage (BAL) fluids and lung homogenates collected after the LPS challenge in mice showed that CSY0073 and azithromycin (200 mg·kg(-1), i.p.) decreased neutrophil counts at 24 h and TNF-α, CXCL1 and CXCL2 levels in the BAL fluid after 3 h and IL-6, CXCL2 and IL-1ß levels in the lung after 3 h compared with the vehicle. However, only azithromycin reduced IL-1ß levels in the lung 24 h post LPS challenge. CSY0073 and azithromycin similarly diminished the production of pro-inflammatory cytokines by macrophages, but not lung epithelial cells, exposed to P. aeruginosa LPS. CONCLUSIONS AND IMPLICATIONS: Unlike azithromycin, CSY0073 had no antibacterial effects but it did have a similar anti-inflammatory profile to that of azithromycin. Hence, CSY0073 may have potential as a long-term treatment for patients with chronic lung diseases.

Improving efficiency in stereology: a study applying the proportionator and the autodisector on virtual slides.

Cell counting in stereology is time-consuming. The proportionator is a new stereological sampling method combining automatic image analysis and non-uniform sampling. The autodisector on virtual slides combines automatic generation of disector pairs with the use of digital images. The aim of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned in a digital slide scanner and the autodisector was applied on the obtained virtual tissue slides. Every slide was partitioned into fields of view, and cells were counted in all of them. Based on the original exhaustive data set comprising 100% of fields of view and covering the total section area, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology.

The spatial rotator.

This paper presents a new local volume estimator, the spatial rotator, which is based on measurements on a virtual 3D probe, using computer assisted microscopy. The basic design of the probe builds upon the rotator principle which requires only a few manual intersection markings, thus making the spatial rotator fast to use. Since a 3D probe is involved, it is expected that the spatial rotator will be more efficient than the the nucleator and the planar rotator, which are based on measurements in a single plane. An extensive simulation study shows that the spatial rotator may be more efficient than the traditional local volume estimators. Furthermore, the spatial rotator can be seen as a further development of the Cavalieri estimator, which does not require randomization of sectioning or viewing direction. The tissue may thus be sectioned in any arbitrary direction, making it easy to identify the specific tissue region under study. In order to use the spatial rotator in practice, however, it is necessary to be able to identify intersection points between cell boundaries and test rays in a series of parallel focal planes, also at the peripheral parts of the cell boundaries. In cases where over- and underprojection phenomena are not negligible, they should therefore be corrected for if the spatial rotator is to be applied. If such a correction is not possible, it is needed to avoid these phenomena by using microscopy with increased resolution in the focal plane.

[Potentials and limitations of the planned compulsory quality assurance program for cataract surgery (Qesü)]. / Potenziale und Grenzen der geplanten obligatorischen Qualitätssicherung für Kataraktoperation (Qesü).

Cataract surgery is scheduled for a federal program for quality improvement across the different sectors of care (outpatient care and hospitals). In case of implementation not only ophthalmic surgeons but all ophthalmologists would have to contribute to the documentation. Urgency, potential benefits and limitations of a compulsory compared to a voluntary quality assessment system are analyzed.

[Result-related success rates of cataract operations. Results of a systematic literature review]. / Ergebnisbezogene Erfolgsraten der Kataraktoperation. Ergebnisse einer systematischen Literaturübersicht.

This systematic literature review, including 7 publications released since 2000, provides references for outcome indicators of cataract surgery for quality management initiatives. The reported relative numbers of cases achieving visual rehabilitation and refractive accuracy were determined and compared. With one exception the success rates did not represent benchmarks defined as best possible outcome but describe the results of data collected in a population during routine clinical practice. A best corrected visual acuity (BCVA) of ≥ 0.5 was achieved in 84-93% of all patients and in 95-99% of patients without preoperative visually impairing comorbidities. A refractive accuracy (absolute deviation of target refraction from spherical equivalent) of ≤ 1 D was reported in 72-97% of the patients. The success rates of these well established outcome indicator levels were high. Differences between operators were more distinguishable and the clinical relevance higher with less liberal indicator levels. A BCVA ≥ 1 was realized in 30-47% of all patients and in 52-62% of patients without visually impairing comorbidities. A total of 45-80% of the patients showed a refractive accuracy of ≤ 0.5 D. Exogenous factors not influencable by the surgeon have a relevant impact on the success rates. The literature review confirms the strong association of visually impairing comorbidities and BCVA outcome. Based on literature methodological problems of quality management systems for cataract surgery are discussed. While voluntary initiatives have the ability to solve these difficulties appropriate concepts for mandatory procedures are currently lacking.

Humanized theta-defensins (retrocyclins) enhance macrophage performance and protect mice from experimental anthrax infections.

Retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of B. anthracis. Nevertheless, we also found that retrocyclins protected mice challenged in vivo by subcutaneous, intraperitoneal, or intranasal instillation of B. anthracis spores. Retrocyclin 1 bound extensively to B. anthracis spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by "piggyback phagocytosis," model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective in vivo against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.

The saucor, a new stereological tool for analysing the spatial distributions of cells, exemplified by human neocortical neurons and glial cells.

The 3D spatial arrangement of particles or cells, for example glial cells, with respect to other particles or cells, for example neurons, can be characterized by the radial number density function, which expresses the number density of so-called 'secondary' particles as a function of their distance to a 'primary' particle. The present paper introduces a new stereological method, the saucor, for estimating the radial number density using thick isotropic uniform random or vertical uniform random sections. In the first estimation step, primary particles are registered in a disector. Subsequently, smaller counting windows are drawn with random orientation around every primary particle, and the positions of all secondary particles within the windows are recorded. The shape of the counting windows is designed such that a large portion of the volume close to the primary particle is examined and a smaller portion of the volume as the distance to the primary object increases. The experimenter can determine the relation between these volumina as a function of the distance by adjusting the parameters of the window graph, and thus reach a good balance between workload and obtained information. Estimation formulae based on the Horvitz-Thompson theorem are derived for both isotropic uniform random and vertical uniform random designs. The method is illustrated with an example where the radial number density of neurons and glial cells around neurons in the human neocortex is estimated using thick vertical sections for light microscopy. The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other.

[Diagnosis of fever of unknown origin (FUO). Positron emission tomography/computed tomography (PET-CT)]. / Diagnostik bei Fieber unklarer Genese (FUO) - Positronen-Emissions-Tomographie/Computertomographie(PET-CT).

Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas. (18)F(Fluor-18)-Fluordeoxyglucose-PET ((18)F-FDG PET) has made it possible to localize symptomatically occult changes with a high diagnostic accuracy and to achieve differentiation between benign and malignant changes.

Spinal cord compression through extraosseous extension of a vertebral low-grade hemangioendothelioma with histiocytoid differentiation.

Herein, we report the case of a 47-year-old man clinically presenting a slow progressive loss of lower extremity functions within 8 weeks followed by an acute neurogenic bladder dysfunction. The patient exhibited high-grade paralysis of both legs with reduced sensation from dermatome Th11 downwards as well as marked spasticity of the lower extremity. Neuroradiological examinations revealed a protruding spinal tumor with extraosseous-intraspinal extension. The resected tumor mass exhibited a highly vascularized tumor with architectural complexity and high cellularity finally leading to the diagnosis of a hemangioendothelioma. Interesting was the fact that the tumor vasculature exhibited many CD68-positive cells protruding into the lumen and, therefore, being part of a partially histiocytoid differentiation which is all the more uncommon in hemangioendothelioma. The time frame of 3 hours between embolization and tumor resection is too short to explain a monocytic intravascular reaction. Usually, hemangioendotheliomas arise from the soft tissue, lungs or liver, but intraspinal manifestations are only rarely observed. Furthermore, the clinical course with a progressive development of a paraparesis due to a hemangioendothelioma is very uncommon.

[Morphological magnetic resonance imaging: its value for the diagnosis of neurodegenerative diseases]. / Morphologische Magnetresonanz-Tomographie: Ihre Wertigkeit bei der Diagnose neurodegenerativer Erkrankungen.

Magnetic resonance imaging (MRI) plays an important role in differentiating idiopathic Parkinson's disease (PD) from its atypical forms. Causes like chronic vascular disease and normal-pressure hydrocephalus are easily visualized. Furthermore, specific atrophy patterns can be found with multi-system atrophies, corticobasal degeneration and progressive supranuclear palsy. In addition the review also deals with specific imaging criteria of other neurodegenerative disorders, such as Wilson's disease, neurodegeneration with iron accumulation in the brain and Huntington's chorea. MRI is of minor importance for differentiating Alzheimer's disease from frontotemporal dementia or dementia with Lewy bodies. However, specific patterns are found in cerebral amyloid angiopathy and prion diseases..