[Treatment of hip dysplasia in young adults]. / Behandlung der Hüftgelenkdysplasie beim jungen Erwachsenen.

Developmental dysplasia of the hip (DDH) is one of the most common disorders of hips in children. The deformity can remain asymptomatic into adolescence and adulthood; however, it is considered to be a form of prearthritis and is the main cause of premature osteoarthritis of the hip. The deformity affects the acetabulum but can also be accompanied by changes in the shape of the proximal femur. If conservative treatment for mild DDH is insufficient, or in cases of moderate to severe DDH, operative treatment should be carried out, for example by corrective osteotomy of the pelvis and/or the proximal femur and hip arthroscopy may be considered adjunctively in order to resolve the prearthritis and prevent premature osteoarthritis of the hip. This manuscript elucidates the deformity, the diagnostic measures required to make the diagnosis and the treatment options available for prevention of arthritis.

Femoral Cementation in Knee Arthroplasty-A Comparison of Three Cementing Techniques in a Sawbone Model Using the ATTUNE Knee.

Femoral component loosening is a rare but severe complication in total knee arthroplasty. Former studies have repeatedly demonstrated radiolucent lines behind the ventral and dorsal anchoring shields of the femoral components, which has led us to investigate this matter further. Therefore, three different cementing techniques were tested in a group of nine Sawbone samples each. These differed in the amount of cement applied on the femoral component as well as in the pressure application. Computed tomography was performed to evaluate and classify the cement penetration into the bone adjacent to the prosthesis according to the zones defined by the Knee Society scoring system. The results show significantly deeper cement penetration in all zones when a pressurizer is used. In the other two groups, no significant difference in the dorsal bevel cement penetration was noted. Additionally, no difference in ventral and dorsal cement penetrations (Zones 1 and 4) was delineated. In contrast, there was a significant difference in both the ventral bevel (Zone 2) as well as the distal anchoring surface (Zones 5-7). The use of a pressurizer results in greater cement penetration into all anchoring areas. Completely covering the component back surface results in a significantly higher penetration, which is mainly due to differences in volume. These data show significantly improved cementation results when using a pressurizer. Whether this improves the biomechanical properties and ultimately the revision rate requires further investigation.

Revision of a blade cut-out in PFN-A fixation: Blade exchange, cement augmentation and a cement plug as a successful salvage option.

A potential and feared complication of proximal femur nails with cephalomedullary fixation is migration of the cephalomedullary screw or blade (cut-out or cut-through). In patients not suitable (e.g. low demand, comorbidities) for conversion to total hip arthroplasty blade exchange with cement augmentation may be an option. This article describes the first successful clinical use of a salvage procedure of a previously published technique, which allows the surgeon to avoid intraarticular cement leakage by using a standard cement plug to close the defect in the femoral head.

Comparison of the stability of three fixation techniques between porous metal acetabular components and augments.

OBJECTIVES: In order to address acetabular defects, porous metal revision acetabular components and augments have been developed, which require fixation to each other. The fixation technique that results in the smallest relative movement between the components, as well as its influence on the primary stability with the host bone, have not previously been determined. METHODS: A total of 18 composite hemipelvises with a Paprosky IIB defect were implanted using a porous titanium 56 mm multihole acetabular component and 1 cm augment. Each acetabular component and augment was affixed to the bone using two screws, while the method of fixation between the acetabular component and augment varied for the three groups of six hemipelvises: group S, screw fixation only; group SC, screw plus cement fixation; group C, cement fixation only. The implanted hemipelvises were cyclically loaded to three different loading maxima (0.5 kN, 0.9 kN, and 1.8 kN). RESULTS: Screw fixation alone resulted in up to three times more movement (p = 0.006), especially when load was increased to 100% (p < 0.001), than with the other two fixation methods (C and SC). No significant difference was noted when a screw was added to the cement fixation. Increased load resulted in increased relative movement between the interfaces in all fixation methods (p < 0.001). CONCLUSION: Cement fixation between a porous titanium acetabular component and augment is associated with less relative movement than screw fixation alone for all implant interfaces, particularly with increasing loads. Adding a screw to the cement fixation did not offer any significant advantage. These results also show that the stability of the tested acetabular component/augment interface affects the stability of the construct that is affixed to the bone.Cite this article: N. A. Beckmann, R. G. Bitsch, M. Gondan, M. Schonhoff, S. Jaeger. Comparison of the stability of three fixation techniques between porous metal acetabular components and augments. Bone Joint Res 2018;7:282-288. DOI: 10.1302/2046-3758.74.BJR-2017-0198.R1.

Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions.

Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanut allergic reactions using serial peripheral blood samples obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4+ T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.

Case study: failure of superior capsular reconstruction using dermal allograft.

Superior capsular reconstruction (SCR) is a novel technique for treating irreparable rotator cuff tears in younger patients in whom a reverse total shoulder arthroplasty is not the optimal treatment choice. This case study describes a middle-aged male with a recurrent, massive, irreparable rotator cuff tear treated with SCR that subsequently failed at the glenoid attachment. The patient underwent successful arthroscopic revision of the SCR. The case illustrates the MRI and arthroscopic correlations of the failed dermal allograft reconstruction, which to our knowledge has not been previously shown in the radiology literature.

[Functional Electrical Stimulation in a Case of Drop Foot and Atactic Gait: Expert Assessment of Contested Medical Aids]. / Funktionelle Elektrostimulation bei Fußheberschwäche und ataktischem Gangbild: Gutachterliches Vorgehen bei streitiger Hilfsmittelversorgung.

Expert medical opinions are necessary in pretrial cases and other legal matters. They act as means of evidence for administrative bodies and courts. It may be necessary to adapt the method of evaluation depending upon the issue or subject matter to be evaluated. We report on a social court case, which needed to answer the question of the medical necessity of a functional electrical stimulation orthosis prescribed to improve the function of a drop foot accompanied by an atactic gait disorder. The claimant suffered from a stroke, which had occurred several years before. Her aids were an ankle-foot-orthosis for foot lift and a wheeled walker. The current treatment was to be augmented by the disputed device. The statutory health insurance declined to meet the costs. They failed to find relevant benefits after analysis of video tapes of the patient's gait while using an electrical stimulation orthosis. The social court requested an expert opinion to answer the question as to whether or not there was a relevant functional benefit to using functional electrical stimulation over the existing orthosis or to an alternative treatment. Video documentation was desired by the court. We used the clinic's gait analysis laboratory, which is equipped with a gait course and the claimed video documentation. Standardised video documentation offers substantial advantages for answering forensic questions such as these. It assures reproducibility and comparability of all tested scenarios, with objectification of the individual advantages or limitations. This gain in both validity and reliability fulfills the scientific requirements placed upon an expert assessment.

Meditation and vacation effects have an impact on disease-associated molecular phenotypes.

Meditation is becoming increasingly practiced, especially for stress-related medical conditions. Meditation may improve cellular health; however, studies have not separated out effects of meditation from vacation-like effects in a residential randomized controlled trial. We recruited healthy women non-meditators to live at a resort for 6 days and randomized to either meditation retreat or relaxing on-site, with both groups compared with 'regular meditators' already enrolled in the retreat. Blood drawn at baseline and post intervention was assessed for transcriptome-wide expression patterns and aging-related biomarkers. Highly significant gene expression changes were detected across all groups (the 'vacation effect') that could accurately predict (96% accuracy) between baseline and post-intervention states and were characterized by improved regulation of stress response, immune function and amyloid beta (Aß) metabolism. Although a smaller set of genes was affected, regular meditators showed post-intervention differences in a gene network characterized by lower regulation of protein synthesis and viral genome activity. Changes in well-being were assessed post intervention relative to baseline, as well as 1 and 10 months later. All groups showed equivalently large immediate post-intervention improvements in well-being, but novice meditators showed greater maintenance of lower distress over time compared with those in the vacation arm. Regular meditators showed a trend toward increased telomerase activity compared with randomized women, who showed increased plasma Aß42/Aß40 ratios and tumor necrosis factor alpha (TNF-α) levels. This highly controlled residential study showed large salutary changes in gene expression networks due to the vacation effect, common to all groups. For those already trained in the practice of meditation, a retreat appears to provide additional benefits to cellular health beyond the vacation effect.

Non-invasive imaging demonstrates clinical features of ankylosing spondylitis in a rat adjuvant model: a case study.

Ankylosing spondylitis is a common rheumatic disease involving both inflammatory erosive osteopenia and bony overgrowth. Main disease features are recapitulated in small rodents challenged with complete Freund's adjuvant. MRI was used to follow longitudinally in vivo changes induced in the rat spine and micro-CT as terminal assessment of bone damage. Histochemistry methods were used to validate these imaging modalities in view of preclinical drug testing and translational applications of spine imaging. Animals were examined using a 3D fat-suppressed gradient-echo sequence, following the injection of gadolinium. At the end of the study, spines were excised for micro-CT and histological examination. Signals reflecting inflammation were detected at levels L5-L6 of the lumbar spine throughout the experimental period, peaking at day 27 after adjuvant. At day 14 the inflammatory response occurred along ligaments but it expanded to nearby soft tissues at later time points. From day 27 onwards inflammation was also detected within the bone, in areas where erosion occurred, and bone-like structures were formed. Micro-CT showed bone remodeling. Histology of isolated spines confirmed the inflammation and bone remodeling observed in vivo. The present study including three complementary approaches clearly demonstrates the potential of imaging for longitudinal assessments of changes in the spine in this animal model in view of preclinical pharmacological studies. The excellent correlation seen between the in vivo images and the histology underlines its fundamental role in the validation of non-invasive imaging readouts.

The stability of the femoral component in the Oxford unicompartmental knee replacement: a comparison of single and twin peg designs.

Aseptic loosening of the femoral component is an important indication for revision surgery in unicompartmental knee replacement (UKR). A new design of femoral component with an additional peg was introduced for the cemented Oxford UKR to increase its stability. The purpose of this study was to compare the primary stability of the two designs of component. Medial Oxford UKR was performed in 12 pairs of human cadaver knees. In each pair, one knee received the single peg and one received the twin peg design. Three dimensional micromotion and subsidence of the component in relation to the bone was measured under cyclical loading at flexion of 40° and 70° using an optical measuring system. Wilcoxon matched pairs signed-rank test was performed to detect differences between the two groups. There was no significant difference in the relative micromotion (p = 0.791 and 0.380, respectively) and subsidence (p = 0.301 and 0.176, respectively) of the component between the two groups at both angles of flexion. Both designs of component offered good strength of fixation in this cadaver study.

ENaC-mediated effects assessed by MRI in a rat model of hypertonic saline-induced lung hydration.

BACKGROUND AND PURPOSE: The epithelial sodium channel (ENaC) regulates airway mucosal hydration and mucus clearance. The lack of such regulation in cystic fibrosis patients leads to desiccation of the airway lumen, resulting in mucostasis that establishes the environment for infections. Osmotic agents and negative ENaC regulators can be used to restore mucosal hydration. We aimed to assess whether: (i) osmotically driven fluid flux into the rat lung could be quantified in vivo by magnetic resonance imaging (MRI); and (ii) the MRI signals could be modulated through the regulation of ENaC function. EXPERIMENTAL APPROACH: Lung images from spontaneously breathing rats were acquired following intra-tracheal (i.t.) administration of physiological or hypertonic saline (HS). Compounds known to modulate the ENaC function were given i.t. prior to saline. Volumes of fluid signals were quantified on the images. KEY RESULTS: A tonicity-dependent increase in lung fluid was demonstrated following HS administration. Pretreatment with the ENaC blockers, amiloride or 552-02, resulted in an enhancement of HS-induced lung fluid signals, which were detectable for up to 4 h, consistent with a role for ENaC in fluid clearance. Aprotinin, a serine protease inhibitor that attenuates ENaC function, likewise enhanced the HS-induced increase in lung fluid signal, while alpha(1)-anti-trypsin was without significant effect. CONCLUSIONS AND IMPLICATIONS: Proton MRI provides a non-invasive technique for studying modulators of lung fluid hydration in rat lung in vivo. The pharmacological sensitivity of MRI-detected fluid signals is consistent with ENaC-mediated fluid reabsorption after HS. This target-related readout may be used to characterize new ENaC modulators.

Treatment of periprosthetic femoral fractures with two different minimal invasive angle-stable plates: Biomechanical comparison studies on cadaveric bones.

INTRODUCTION: The introduction of fixed-angle plate osteosynthesis techniques has provided us a further means to treat periprosthetic femoral fractures. The goal of this experimental study is to evaluate the biomechanical properties and stability of treated periprosthetic fractures when using two different plate systems, which vary in the locking mechanism and the screw placement (monocortical or bicortical) with respect to the prosthesis stem. MATERIALS AND METHODS: Using five pairs of formalin-fixed femora, a Vancouver B1 periprosthetic fracture was treated either with a 13-hole LISS(®) titanium plate using four monocortical periprosthetic screws or with a non-contact bridging plate (NCB) DF(®) plate using bicortical angle-stable blocked screws positioned ventrally or dorsally to the prosthesis stem. Bones were loaded under axial and cyclic compression with a progressively increased load until failure. Displacement at the osteotomy gap was measured during loading using an ultra-sound measuring system. RESULTS: The mean displacement in the region of the fracture gap was not significantly different at any time during the experiments for the two models. The mean force resulting in subsequent model failure was similar in both models; the failure morphology varied slightly between the models, however. Four of the five LISS(®) models exhibited either a tear-out of the monocortical screws or a decortication from the bony shaft of the cortical lamella surrounding the screws. On the other side, two of the NCB models showed macroscopically visible fissures along the osteosynthesis plates at the height of the osteotomy gap, and were hence considered implant failures. Only one NCB model showed tear-out of the bicortically placed screws. CONCLUSION: Bicortical screw placement provides more stable anchoring when compared to monocortical screw fixation. However, in relation to the amount of motion at the osteotomy gap and to failure loads, stabilisation of periprosthetic femoral fractures can be equally well achieved using either the LISS(®) plate with periprosthetic monocortical screws or the NCB plate with poly-axially placed bicortical screws.

Activation of the lung S1P(1) receptor reduces allergen-induced plasma leakage in mice.

BACKGROUND AND PURPOSE: It has been suggested that intratracheal administration of the immunomodulator, FTY720, could have anti-inflammatory effects without causing a decrease in blood lymphocyte counts. However, the receptor responsible for this effect has not been defined. EXPERIMENTAL APPROACH: We have described, in a mouse model of allergen-induced inflammation, the use of proton magnetic resonance imaging to non-invasively assess lung fluid accumulation and inflammation. Here, we used this model to investigate the sphingosine-1-phosphate (S1P) receptor responsible for the anti-inflammatory effect of FTY720. KEY RESULTS: When given intranasally, FTY720 (3 and 10 microg.kg(-1)) inhibited by approximately 50% the allergen-induced accumulation of fluid in the lung detected by magnetic resonance imaging, but had no effect on the cellular inflammation in the airway space or on circulating blood lymphocytes. Inhibition of the infiltration of inflammatory cells into the airways was only observed at a dose of FTY720 that induced lymphopenia (100 microg.kg(-1)). Similar results were observed in S1P(3)-deficient mice. The effect of FTY720 was mimicked by intranasal treatment of wild-type mice with a S1P(1)-specific agonist, AUY954. CONCLUSIONS AND IMPLICATIONS: Thus, in contrast to previously published work, our results suggest that systemic exposure of FTY720 is necessary to obtain an airway anti-inflammatory effect. On the contrary, inhibition of the allergen-induced accumulation of fluid in the lung, via activation of the S1P(1) receptor, is obtainable without systemic effects.

In vivo pharmacological evaluation of compound 48/80-induced airways oedema by MRI.

BACKGROUND AND PURPOSE: Allergen-induced airways oedema in actively sensitized rats has been studied earlier by magnetic resonance imaging (MRI). We used MRI to follow the consequences of non-immunological mast cell activation induced by compound 48/80 in the rat lungs in vivo. EXPERIMENTAL APPROACH: Male naïve rats were scanned by MRI prior to and at several time points following intratracheal administration of the mast cell secretagogue, compound 48/80. The effects of a range of drugs on the response induced by compound 48/80 were studied. KEY RESULTS: Strong fluid signals were detected by MRI in the lungs at 24 h after compound 48/80, correlating with increased protein concentration and inflammatory cell infiltration in bronchoalveolar lavage, and with perivascular oedema observed histologically. Pharmacological intervention demonstrated that the increase in MRI signal volume induced by compound 48/80 24 h after challenge was blocked by disodium cromoglycate and the glucocorticoid, budesonide. Pretreatment with wortmannin, capsazepine, DNK333 (a dual neurokinin (NK) 1 and NK2 antagonist) or the anti-allergy drug CGS8515, but not indomethacin, resulted in partial inhibition. CONCLUSIONS AND IMPLICATIONS: Compound 48/80 induced a complex inflammatory reaction which did not solely involve mast cell degranulation but also activation of sensory nerves and was qualitatively similar to allergen challenge. Changes observed by MRI correlated with decreases in protein concentration in BAL fluid. However, the magnitude of the changes detected was greater using MRI. Our results demonstrate that MRI is a sensitive and efficient tool to assess the effects of drugs on lung inflammation.

Magnetic resonance methods and applications in pharmaceutical research.

This review presents an overview of some recent magnetic resonance (MR) techniques for pharmaceutical research. MR is noninvasive, and does not expose subjects to ionizing radiation. Some methods that have been used in pharmaceutical research MR include magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) methods, among them, diffusion-weighted MRI, perfusion-weighted MRI, functional MRI, molecular imaging and contrast-enhance MRI. Some applications of MR in pharmaceutical research include MR in metabonomics, in vivo MRS, studies in cerebral ischemia and infarction, degenerative joint diseases, oncology, cardiovascular disorders, respiratory diseases and skin diseases. Some of these techniques, such as cardiac and joint imaging, or brain fMRI are standard, and are providing relevant data routinely. Skin MR and hyperpolarized gas lung MRI are still experimental. In conclusion, considering the importance of finding and characterizing biomarkers for improved drug evaluation, it can be expected that the use of MR techniques in pharmaceutical research is going to increase in the near future.

Capsaicin-induced mucus secretion in rat airways assessed in vivo and non-invasively by magnetic resonance imaging.

BACKGROUND AND PURPOSE: An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI). EXPERIMENTAL APPROACH: Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 microg kg(-1)) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin. KEY RESULTS: Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mg kg(-1)), DNK333 (10 mg kg(-1)) but not DSCG (10 mg kg(-1)) administered prophylactically were able to block the effect of capsaicin in the airways. CONCLUSIONS AND IMPLICATIONS: These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD.

Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation.

Anatomical and functional information (renography, perfusion) was obtained by MRI in a life-supporting transplantation model, in which Lewis rats received kidneys from Fisher 344 donors. Renography and perfusion analyses were carried out with Gd-DOTA and small particles of iron oxide (SPIO), respectively. Starting 12 weeks posttransplantation, images from grafts of untreated recipients exhibited distinctive signal attenuation in the cortex. Animals treated with cyclosporin (Sandimmune Neoral; Novartis Pharma, Basel, Switzerland) to prevent acute rejection showed a signal attenuation in the cortex at 33 weeks posttransplantation, while kidneys from rats treated additionally with everolimus (Certican; Novartis), a rapamycin derivative, had no changes in anatomical appearance. A significant negative correlation was found between the MRI cortical signal intensity and the histologically determined iron content in macrophages located in the cortex. Renography revealed a significantly reduced functionality of the kidneys of untreated controls 33 weeks after transplantation, while no significant changes in perfusion were observed in any group of rats. These results suggest the feasibility, by labeling macrophages with SPIO, of detecting signs of graft rejection significantly earlier than when changes in function occur. Monitoring early changes associated with chronic rejection can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies for transplantation.

MRI of lung parenchyma in rats and mice using a gradient-echo sequence.

Signal of lung parenchymal tissue from the living rat and mouse lung was detected at 4.7 T with a good signal-to-noise ratio and motion-suppressed artifacts using a short TE gradient-echo sequence. Neither cardiac nor respiratory gating were applied, and animals respired freely during data collection. Mean T(2)* relaxation times of parenchyma in the anterior, middle and posterior regions of both lungs ranged between 403 and 657 micros and 397 and 751 micros, respectively for the rat and mouse. For the rat in the prone position, there was a gradient in T(2)* values, from the posterior to the anterior regions of both lungs. In the supine position, however, T(2)* values were larger in the posterior and in the anterior portions. For the mouse in both prone and supine positions, there was a tendential gradient in T(2)* from the anterior to the posterior portions. The robustness of the approach renders it well suited for routine applications, e.g. in pharmacological studies concerning asthma models in small rodents. The method was applied to lung inflammation models involving challenge with ovalbumin or lipopolysaccharide.

Non-invasive, quantitative assessment of the anatomical phenotype of corticotropin-releasing factor-overexpressing mice by MRI.

High resolution magnetic resonance imaging (MRI) was applied to quantify alterations in thymus and adrenal volumes, as well as body fat in genetically engineered corticotropin-releasing factor (CRF)-overexpressing mice. When compared to the organs in age-matched wild-type animals, the adrenals in CRF-overexpressing male mice were significantly enlarged and the thymus volume in females was significantly smaller. The fat content was significantly larger in CRF-overexpressing mice. The anatomical alterations observed in the MRI studies were in perfect line with post-mortem data (weights of organs). Furthermore, the observed interstrain differences are in agreement with recently published data on (i) the effect of continuous, intraventricular infusion of CRF in rats and (ii) the presence of atrophic adrenals in CRF-knockout mice. The present studies demonstrate that MRI can provide reliable measures of relatively small structures such as the adrenal glands and the thymus in mice. This makes MRI an attractive, non-terminal tool to monitor in laboratory animals, including transgenic mice, the consequence of continuous stress on relevant organs.