[Treatment of rheumatic disease with renal insufficiency]. / Therapie rheumatischer Erkrankungen mit Niereninsuffizienz.

BACKGROUND: Reduced renal function is not rare in patients with inflammatory rheumatic diseases and is associated with an increased risk of treatment-induced and perioperative adverse events. METHOD: A literature search was carried out for the medical treatment and perioperative management of rheumatic disease in the presence of renal insufficiency. RESULTS: Patients with rheumatic disease and renal insufficiency have a higher risk of cardiovascular disease, bone loss and immunodeficiency than those without kidney disease. The perioperative rate of cardiovascular and infectious complications and the risk of acute kidney failure are elevated in these patients. The pharmacokinetics of many drugs used in rheumatology is influenced by the kidney function. Especially methotrexate is contraindicated in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. Nonsteroidal anti-inflammatory drugs (NSAIDS) and cyclooxygenase (COX)-2 inhibitors should not be used with renal insufficiency or only for a short term with the lowest effective dose. The treatment of osteoporosis with antiresorptive drugs may lead to adynamic bone disease in advanced kidney disease, and, therefore, the use of these drugs is controversial. CONCLUSION: Medication should be modified in patients with rheumatic disease and kidney involvement according the grade of renal insufficiency. There is also a need for special perioperative management in these patients, with interdisciplinary cooperation of rheumatologists, nephrologists and orthopedic doctors.

Functional genomics in the wild: a case study with paper wasps shows challenges and prospects for RNA interference in ecological systems.

RNA interference (RNAi) is a useful tool to assess gene function by knocking down expression of a target gene and has been used successfully in domestic and laboratory organisms. However, the use of RNAi for functional genomics has not fully extended into ecological model organisms in natural environments. Assessment of gene function in the wild is important because gene function can be environmentally and context dependent. Here, we present a case study using RNAi to assess gene function in wild paper wasps Polistes metricus, to test roles for two candidate genes (NADH dehydrogenase (NADHdh) and retinoid and fatty acid binding protein (RfaBp)) in the development of reproductive castes. Previous studies have shown that these genes are upregulated in larvae that become queens compared to workers, but this pattern was reversed in the laboratory, making field-based studies necessary. We orally administered dsRNA to larvae in field colonies and found evidence of a short-term knockdown followed by a compensatory rebound in expression for RfaBp. We also observed the predicted worker-like decrease in lipid stores in NADHdh dsRNA treated wasps, suggesting a possible role for NADHdh in caste development. We discuss our results in the context of challenges for using RNAi for functional genomics in ecological model organisms in the field.

Initial orthodontic tooth movement of a multirooted tooth: a 3D study of a rat molar.

OBJECTIVE: To elucidate the 3D interactions in the tooth-PDL-bone complex immediately after application of orthodontic forces and their implications on tooth movement and function. METHODS: A special visualization method using microCT allows us to directly image in 3D the movements of a multirooted molar tooth inside the alveolar bone as well as the collagenous network of the PDL. Using fresh, unstained rat mandibular 1st molar under mesial loads of 0.5-1 N, we address basic concepts in orthodontics during the initial stages of orthodontic movement. RESULTS: We show that immediately after the application of orthodontic load, direct distinct contacts between the tooth and the bone form in the furcation area. These contacts limit tooth movement and interfere with whole body translation. Only localized sites of highly compressed PDL between the root surfaces and the bone were observed. In general, the collagenous network of the PDL appeared loose and not densely packed in the compressed side. On the tension side, the fibers maintained their overall orientation without any significant extension of the fibers. CONCLUSIONS: Localized direct contact areas between the tooth roots and the bone at the furcation already form within a few minutes of orthodontic tooth movement. This direct and localized bone involvement guides the movement trajectory and provides a mechanism for the miscorrelation found between force levels and tooth movement during the initial stages of an orthodontic tooth movement.

[Dosage and toxicity of antirheumatic drugs in renal insufficiency]. / Dosierung und Toxizität von Antirheumatika bei Niereninsuffizienz.

BACKGROUND: Patients with inflammatory rheumatic diseases frequently have a reduced renal function. The risk of adverse events is increased in these patients and treatment options in patients with rheumatic disease and renal failure are poorly studied. METHODS: A selective literature search was carried out for pharmocokinetics, dosage and toxicity of antirheumatic drugs in patients with renal insufficiency. RESULTS: The use of nonsteroidal anti-inflammatory drugs (NSAID), cyclooxygenase(COX)-2 inhibitors, gold and cyclosporine is limited in renal insufficiency due to nephrotoxicity. Methotrexate should not be used in patients with a glomerular filtration rate (eGFR) < 45 ml/min, because of the unpredictable pharmacokinetics with a risk for fatal pancytopenia. The dosage of sulfasalazine, azathioprine, mycophenolate mofetil, cyclophosphamide and antimalarial drugs should be reduced in patients with moderate and severe renal insufficiency. In contrast, leflunomide and numerous biologics can be used without dosage modification; however, biologics with a molecular weight < 60 kDa (e.g. anakinra) are an exception and should be reduced in patients with renal insufficiency. Overall, there are only limited data on the use of biologics in this population. Numerous comorbidities and the high risk for infection should be kept in mind when patients with rheumatic disease and renal failure are treated with immunosuppressive drugs. CONCLUSION: Further studies are necessary to obtain more evidence on the use of disease-modifying antirheumatic drugs (DMARD) and biologics in patients with renal insufficiency.

Dorsal Root Ganglion Volumetry by MR Gangliography.

BACKGROUND AND PURPOSE: Dorsal root ganglion MR imaging (MR gangliography) is increasingly gaining clinical-scientific relevance. However, dorsal root ganglion morphometry by MR imaging is typically performed under the assumption of ellipsoid geometry, which remains to be validated. MATERIALS AND METHODS: Sixty-four healthy volunteers (37 [57.8%] men; mean age, 31.5 [SD, 8.3] years) underwent MR gangliography of the bilateral L4-S2 levels (3D-T2WI TSE spectral attenuated inversion recovery-sampling perfection with application-optimized contrasts by using different flip angle evolution, isotropic voxels = 1.1 mm³, TE = 301 ms). Ground truth dorsal root ganglion volumes were bilaterally determined for 96 dorsal root ganglia (derivation cohort) by expert manual 3D segmentation by 3 independent raters. These ground truth dorsal root ganglion volumes were then compared with geometric ellipsoid dorsal root ganglion approximations as commonly practiced for dorsal root ganglion morphometry. On the basis of the deviations from ellipsoid geometry, improved volume estimation could be derived and was finally applied to a large human validation cohort (510 dorsal root ganglia). RESULTS: Commonly used equations of ellipsoid geometry underestimate true dorsal root ganglion volume by large degrees (factor = 0.42-0.63). Ground truth segmentation enabled substantially optimizing dorsal root ganglion geometric approximation using its principal axes lengths by deriving the dorsal root ganglion volume term of [Formula: see text]. Using this optimization, the mean volumes of 510 lumbosacral healthy dorsal root ganglia were as follows: L4: 211.3 (SD, 52.5) mm³, L5: 290.7 (SD, 90.9) mm³, S1: 384.2 (SD, 145.0) mm³, and S2: 192.4 (SD, 52.6) mm³. Dorsal root ganglion volume increased from L4 to S1 and decreased from S1 to S2 (P < .001). Dorsal root ganglion volume correlated with subject height (r = . 22, P < .001) and was higher in men (P < .001). CONCLUSIONS: Dorsal root ganglion volumetry by measuring its principal geometric axes on MR gangliography can be substantially optimized. By means of this optimization, dorsal root ganglion volume distribution was estimated in a large healthy cohort for the clinically most relevant lumbosacral levels, L4-S2.

The Mac-2 antigen is a galactose-specific lectin that binds IgE.

A cDNA encoding the Mac-2 antigen, a surface marker highly expressed by thioglycollate-elicited macrophages, has been cloned by immunoscreening of a lambda gt11-P388D1 expression library. The nucleotide sequence of the cDNA is identical to that of carbohydrate-binding protein 35, a galactose-specific lectin found in fibroblasts and highly homologous to a rat IgE-binding protein from basophilic leukemia cells. The in vitro synthesized Mac-2 protein displayed the expected carbohydrate- and IgE-binding properties. By pulse-chase analysis and subcellular fractionation studies, the Mac-2 protein was found in the cytosol but was also seen to accumulate in the extracellular medium. The latter finding was surprising in view of the fact that the cDNA did not encode a signal peptide or transmembrane domain. An alternatively spliced cDNA with the potential to encode a NH2 terminally extended Mac-2 protein with a stretch of hydrophobic amino acids at its NH2 terminus was also found, but it is not clear whether it is the source of the extracellular Mac-2. Possible functions for the Mac-2 protein based on its lectin- and IgE-binding properties are discussed.

Training in Bariatric Surgery: a National Survey of German Bariatric Surgeons.

INTRODUCTION: Skill in bariatric surgery has been associated with postoperative outcome. Appropriate surgical training is of paramount importance. In order to continuously improve training strategies, it is necessary to assess current practices. AIM: To determine how German bariatric surgeons have been trained and to assess current training strategies. METHODS: Between February 2017 and March 2017, an online census of surgeons registered as members of the German Society for Bariatric and Metabolic Surgery was conducted. A total of three reminders were sent out. Data were analyzed using descriptive statistics. Data was reported as median (interquartile range); percentages were adjusted for completed answers only. RESULTS: A response rate of 51% (n = 214) was achieved. Surgeons reported a median of 14.5 (8-20) years of surgical experience after initial training, with a specific bariatric experience of 7 (4-13) years. The total cumulative bariatric case volume was 240 (80-500) cases, with an annual case volume of 50 (25-80). The most commonly applied approaches to bariatric skills acquisition were "learning by doing" (71%), "course participation" (70%) and "observerships" (70%). Fellowships and the use of operating videos were less frequently applied strategies (19%/ 47%). Interestingly, observerships (94%) and course participation (89%) were rated as very important/important, whereas "learning by doing" (62%), watching operation videos (59%), and fellowships (48%) were less frequently perceived as important/very important training strategies. CONCLUSIONS: The majority of surgeons performing bariatric cases were senior surgeons with more than 10 years of post-training experience; nevertheless, the survey revealed a lack of structured approaches to bariatric specialization training.

Soluble protein of the organic matrix of mollusk shells: a potential template for shell formation.

A significant proportion of the soluble protein of the organic matrix of mollusk shells is composed of a repeating sequence of aspartic acid separated by either glycine or serine. This regularly spaced, negatively charged aspartic acid may function as a template upon which mineralization occurs.

Transformation of amorphous calcium phosphate to crystalline dahillite in the radular teeth of chitons.

A comparison of infrared spectra from individual teeth along the radula of a chiton (Polyplacophora, Mollusca) shows that the first-formed calcium phosphate mineral is amorphous. Over a period of weeks the mineral transforms to dahllite. The c axes of the dahllite crystals are aligned approximately perpendicular to the tooth surface.

Biological control of crystal texture: a widespread strategy for adapting crystal properties to function.

Textures of calcite crystals from a variety of mineralized tissues belonging to organisms from four phyla were examined with high-resolution synchrotron x-ray radiation. Significant differences in coherence length and angular spread were observed between taxonomic groups. Crystals from polycrystalline skeletal ensembles were more perfect than those that function as single-crystal elements. Different anisotropic effects on crystal texture were observed for sea urchin and mollusk calcite crystals, whereas none was found for the foraminifer, Patellina, and the control calcite crystals. These results show that the manipulation of crystal texture in different organisms is under biological control and that crystal textures in some tissues are adapted to function. A better understanding of this apparently widespread biological phenomenon may provide new insights for improving synthetic crystal-containing materials.

Intercalation of sea urchin proteins in calcite: study of a crystalline composite material.

Sea urchin skeletal elements are composed of single crystals of calcite. Unlike their synthetic counterparts, these crystals do not have well-developed cleavage and are consequently much more resistant to fracture. This phenomenon is due in part to the presence of acidic glycoproteins occluded within the crystals. By means of x-ray diffraction with synchrotron radiation, it is shown that the presence of the protein in synthetic calcite only slightly decreases the coherence length but significantly increases the angular spread of perfect domains of the crystals. In biogenic calcite, the coherence length is 1/3 to 1/4 as much as that in synthetic calcite and the angular spread is 20 to 50 times as wide. It is proposed that the presence of macromolecules concentrated at mosaic boundaries that are oblique to deavage planes is responsible for the change in fracture properties. These results may be important in the material sciences, because of the unusual nature of this material, namely, a composite based on the controlled intercalation of macromolecules inside single-crystal lattices.

Assessment of the genotoxic and carcinogenic risks of p-nitrophenol when it is present as an impurity in a drug product.

According to the 2008 US FDA (draft) and 2006 EMEA guidance documents for genotoxic impurities, an impurity that is positive in an in vitro genotoxicity study, in the absence of in vivo genotoxicity or carcinogenicity data, should be treated as genotoxic and typically controlled to 1.5 microg/day for chronic use. For p-nitrophenol (PNP), existing study results (i.e., positive in vitro clastogenicity in mammalian cells, no information on its in vivo genotoxicity, and negative with respect to carcinogenicity in a dermal mouse study with no confirmation of systemic exposure) indicated that it should be considered genotoxic and exposure as a drug impurity limited. Therefore, to more completely characterize the genotoxic potential of PNP (consistent with the guidance documents), in vivo mouse micronucleus and dermal pharmacokinetic bridging studies were conducted. In the micronucleus study, PNP was negative, demonstrating that the reported in vitro clastogenicity is not present in vivo. In the pharmacokinetic study, PNP was well absorbed dermally, validating the negative dermal carcinogenicity assessment. These results indicate that PNP should be considered a non-genotoxic impurity and, as a drug impurity, a threshold limit of 4 mg/day would be set (per ICH Q3C). This threshold limit is higher than the EPA reference dose (listed in the 2006 Edition of the Drinking Water Standards and Health Advisories), so if present at such levels, the specification limits for PNP should be determined on a case-by-case basis, based on risk-benefit.

[Diagnostics of glomerulonephritis]. / Diagnostik der Glomerulonephritiden.

Glomerulonephritis occurs frequently in patients with multisystemic rheumatic disease, especially in collagen vascular disorders and vasculitides. From a clinical point of view nephrotic syndrome has to be distinguished from nephritic syndrome. Rapid deterioration of renal function is referred to as rapid progressive glomerulonephritis. The differential diagnosis of glomerulonephritis can be narrowed by the findings on urine sediment, amount of proteinuria, degree of renal insufficiency and serological findings. In particular, the presence of urine acanthocytes and cellular casts are diagnostic for glomerulonephritis or vasculitis. Renal biopsy is necessary to establish the final diagnosis in most cases; however, some histological pattern such as membranous glomerulonephritis may occur in several different etiopathogenetic diseases and one disease process may lead to different histomorphologic pictures. Rapid progressive glomerulonephritis is a nephrological emergency and should be diagnosed and treated early to prevent dialysis-dependent renal insufficiency.

Acidic macromolecules of mineralized tissues: the controllers of crystal formation.

The deposition of minerals within many biological tissues is a controlled process. Among the most active agents that control biological mineralization are a group of unusually acidic proteins and glycoproteins. These can interact specifically with some crystal faces but not others, induce oriented nucleation, or intercalate in a regular manner into the crystal lattice itself.

Ultrasonography in the assessment of peripheral joint involvement in psoriatic arthritis : a comparison with radiography, MRI and scintigraphy.

The objective of our study was to investigate the role of musculoskeletal ultrasound (US) in the assessment of hand and foot small joints in psoriatic arthritis (PsA). Thirteen consecutive patients with PsA of hands or feet underwent B-mode US using a 9- to 13-MHz transducer and simultaneous magnetic resonance imaging (MRI), bone scintigraphy and radiography. US findings were compared with radiography, MRI and scintigraphy in 190, 182 and 109 joints, respectively. To assess the sensitivity and specificity of US, radiography was considered as gold standard for the detection of erosions and osteoproliferations and MRI as gold standard for the detection of joint effusion and synovitis. US, MRI and scintigraphy had a higher sensitivity in the detection of overall joint pathology than radiography in painful and/or swollen joints (71%, 72%, 82% vs 32%) and clinically unaffected joints (17%, 21%, 9% vs 2%). US and radiography detected more erosions and osteoproliferations than MRI, with low agreement between the methods in the detection of erosions. Radiography was superior to US in the visualisation of osteoproliferations. Joint effusions and/or synovitis were more frequently detected by MRI than US. Agreement between both imaging methods was better in carpal joints, carpometacarpal joint I, metacarpophalangeal (MCP)/metatarsophalangeal (MTP) joint I, II and V than in MCP/MTP III, IV, PIP and DIP joints. Compared with MRI, radiography and scintigraphy, the specificity of US ranges between 0.84 and 0.94, depending on the joint pathology. In conclusion, the diagnostic sensitivity of US in the detection of PsA-related synovitis of hands and feet is lower than MRI and depends on the joint region. However, the low cost and the acceptable specificity suggest that US is a useful imaging method in addition to radiography in PsA of hands and feet.

[Barriers to the German Society for General and Visceral Surgery (DGAV) accreditation "Center for bariatric and metabolic surgery"]. / Barrieren auf dem Weg zur DGAV-Zertifizierung "Zentrum für Adipositas- und metabolische Chirurgie".

INTRODUCTION: The certification and accreditation process of the German Society for General and Visceral Surgery (DGAV) aims to improve the quality of care and enhance transparency in accredited centers. To achieve these goals a high level of infrastructural and staffing requirements are set out by the DGAV. AIMS: The Surgical Working Group on Obesity Treatment and Metabolic Surgery (CAADIP) survey 2017 of the members of the German Bariatric Society aimed to identify the perceived and encountered barriers in the DGAV accreditation process. METHODS: Between February and March 2017 an online poll was conducted of all members of the CAADIP on topics pertaining to the accreditation process. RESULTS: A total of 214 (51%) CAADIP members participated in the poll, 47% reported that they worked at a non-certified center and 53% worked at a DGAV certified center. Of these, 68% reported employment in a unit with the lowest accreditation level, 21% in an intermediate level center, 11% reported employment in a unit with the highest accreditation level (Center of Excellence) and 86% of those currently working in non-accredited units stated that they aimed for future accreditation. Reasons stated for not having obtained accreditation were recent establishment of the new bariatric specialty (54%), lack of bariatric case numbers (71%), lack of human resources and infrastructure (28% and 13%, respectively). Of those surgeons in non-accredited centers 24% stated that the hospital management had no interest in a certification and 12% of the surgeons themselves felt that accreditation was unnecessary. CONCLUSION: The majority of CAADIP members strived for DGAV certification. The main barriers encountered and perceived were the specific time (reference years) and caseload requirements.

Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 2.

In this second article, we continue the review of current health care economics as it relates to radiologists, specifically framed by topics defined by the Accreditation Council for Graduate Medical Education in the evaluation of neuroradiology fellows. The discussion in this article is focused on topics pertaining to levels 4 and 5, which are the more advanced levels of competency defined by the Accreditation Council for Graduate Medical Education Neuroradiology Milestones on Health Care Economics and System Based Practice.