[What do orthopedic and trauma surgeons expect from radiologists when interpreting imaging of the elbow?] / Was erwarten Orthopäden und Unfallchirurgen vom Radiologen bei der Beurteilung der Bildgebung des Ellenbogens?

CLINICAL ISSUE: The elbow is a complex joint with a multitude of acute and chronic pathologies. In addition to the clinical examination, radiological diagnostics play a decisive role in the further therapeutic management. DIAGNOSTIC WORK-UP/PERFORMANCE: While acute traumatic injuries often present with obvious structural changes and the need for rapid treatment decisions, chronic processes can present with less evident alterations. Especially in these cases there is a need for clear communication between the treating physician and the radiologist with respect to managing optimal imaging as the basis for a certain diagnosis and therefore optimal treatment. Basic prerequisites on both sides are detailed knowledge of all elbow pathologies, classifications and the spectrum of radiological diagnostic imaging. ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: From the point of view of orthopedic surgeons the radiologist is responsible for the correct performance and interpretation of the necessary imaging procedures. The aim of this article is to give an overview of important aspects in the imaging of typical orthopedic/traumatic pathologies.

Optimizing protein stability in vivo.

Identifying mutations that stabilize proteins is challenging because most substitutions are destabilizing. In addition to being of immense practical utility, the ability to evolve protein stability in vivo may indicate how evolution has formed today's protein sequences. Here we describe a genetic selection that directly links the in vivo stability of proteins to antibiotic resistance. It allows the identification of stabilizing mutations within proteins. The large majority of mutants selected for improved antibiotic resistance are stabilized both thermodynamically and kinetically, indicating that similar principles govern stability in vivo and in vitro. The approach requires no prior structural or functional knowledge and allows selection for stability without a need to maintain function. Mutations that enhance thermodynamic stability of the protein Im7 map overwhelmingly to surface residues involved in binding to colicin E7, showing how the evolutionary pressures that drive Im7-E7 complex formation have compromised the stability of the isolated Im7 protein.

[Muscle, tendon and joint injections : What is the evidence?]. / Injektionen an Muskeln, Sehnen und Gelenken : Was ist die Evidenz?

Injections at tendon insertions, in muscles and in joints are an important instrument in the conservative treatment of musculoskeletal diseases, for acute injuries as well as for chronic degenerative diseases. Local anesthetic agents and glucocorticoids are well-established medications; however, severe side effects, such as chondrolysis have sometimes been reported, particularly for local anesthetic agents. In addition platelet rich plasma (PRP) and hyaluronic acid are also widely used; however, the clinical effectiveness has not always been proven. This article gives an overview on the most commonly used medications for injections and the mechanisms of action. The indications for treatment and the evidence for the clinical adminstration of muscle, tendon and joint injections are described based on the currently available literature.

Comparison between low-dose, high-sort and high-dose, low-sort semen on conception and calf sex ratio in Jersey heifers and cows.

The objective of this clinical trial was to compare conception and newborn calf sex ratios among Jersey heifers and lactating cows inseminated with either standard sex-sorted semen (low-dose, high-sort; LDHS) containing 2.1 × 10(6) sorted sperm at 90% purity or high-dose, low-sort (HDLS) semen containing 10 × 10(6) sorted sperm at 75% purity. After a specified voluntary waiting period (VWP), female subjects, consisting of nulliparous heifers (VWP 10 mo of age) and lactating cows (VWP 50d in milk), received their first service and were systematically allocated to each treatment group in the order in which they presented for artificial insemination (AI). Females were bred to the same sire and type of sex-sorted semen for up to 2 additional services. Animals that were not pregnant after 3 breeding attempts were excluded. A total of 1,846 services were performed on 1,011 eligible females (LDHS; n=494, HDLS; n=517), which consisted of 516 nulliparous heifers and 495 lactating cows. Study groups were comparable with respect to the mean age at first AI for nulliparous heifers and the mean days in milk at first AI for parous cows. Insemination with HDLS semen did not result in a higher proportion of pregnancies per AI (P/AI) compared with LDHS semen for either nulliparous heifers (P/AI=43 vs. 38%) or parous cows (P/AI=47 vs. 43%). Insemination of nulliparous heifers using HDLS resulted in a lower proportion of newborn female calves compared with those bred to LDHS (76% vs. 87%). Similarly, lactating cows bred to HDLS gave birth to a lower proportion of newborn female calves compared with those bred to LDHS (79 vs. 90%). The odds ratio for a female calf to be born to an animal inseminated with HDLS compared with LDHS was 0.32 for nulliparous heifers and 0.19 for parous cows. Overall, the use of HDLS resulted in fewer females compared with LDHS, which may be explained by the lower concentration of X-bearing spermatozoa in HDLS compared with LDHS.

[Musculoskeletal modeling of the patellofemoral joint. Dynamic analysis of patellar tracking]. / Muskuloskelettale Modellierung des patellofemoralen Gelenks. Dynamische Analyse der patellaren Führung.

Numerical simulations contribute to the understanding of patellofemoral diseases. Whereas cadaveric studies are limited with respect to reproducibility of results, the impact of different operative approaches can be systematically evaluated based on mathematical models. The objective of this study was to introduce a musculoskeletal model which is capable of describing the dynamic interactions within the patellofemoral joint. It contains major bony and soft tissue structures of the right leg including the medial patellofemoral ligament (MPFL). Two operative approaches were considered based on the model to illustrate the effect on patellofemoral biomechanics during active knee flexion: On the one hand the effect of femoral insertion during MPFL reconstruction on medial soft tissue tension, and on the other hand the difference in patella kinematics before and after total knee arthroplasty. Finally, the potential of musculoskeletal models is discussed.

[Biphosphonate-induced femoral stress fractures : A new problem and knowledge so far - case report]. / Bisphosphonatinduzierte Stressfrakturen am Femur : Ein neues Problem und bisherige Erkenntnisse - Fallbericht.

During the last several years the treatment of osteoporosis with bisphosphonates has become accepted as a safe and effective procedure. However, recently there have been increasing numbers of reports of rare complications in the literature. Particularly the occurrence of atypical fractures of the femur has become a focus of interest but the problem is insufficiently known and only rarely addressed in the scientific discussion. The case illustrated here and a survey of the important facts in the recent literature highlight essential aspects of long-term bisphosphonate therapy.

CREBBP and WDR 24 Identified as Candidate Genes for Quantitative Variation in Red-Brown Plumage Colouration in the Chicken.

Plumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signalling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilising a domestic × wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red-brown colouration in chickens. By treating colour as a quantitative rather than qualitative trait, we have identified both QTL and genes of small effect. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.

Effect of sex-sorted sperm dosage on conception rates in Holstein heifers and lactating cows.

Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 x 10(6) sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 +/- 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire x sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 x 10(6) (59.5%) than for the 2.1 x 10(6) (46.4%) sperm dose and intermediate for the 3.5 x 10(6) sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 +/- 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are warranted to determine whether and how such a practice can be implemented cost effectively for the benefit of the dairy industry.

Improving pathway compliance and clinician performance by using information technology.

To deliver patient-specific advice at the time and place of a consultation is an important contribution to improving clinician performance. Using computer-based decision support on the basis of clinical pathways is a promising strategy to achieve this goal. Thereby integration of IT applications into the clinical workflow is a core precondition for success. User acceptance and usability play a critical role: additional effort has to be balanced with enough benefit for the users and interaction design and evaluation should be handled as an intertwined, continuous process. Experiences from routine use of an online surgical pathway at Marburg University Medical Center show that it is possible to successfully address this issue by seamlessly integrating patient-specific pathway recommendations with documentation tasks which have to be done anyway, by substantially reusing entered data to accelerate routine tasks (e.g. by automatically generating orders and reports), and by continuously and systematically monitoring pathway conformance and documentation quality.

The Alzheimer's Prevention Initiative Generation Program: Evaluating CNP520 Efficacy in the Prevention of Alzheimer's Disease.

Alzheimer's disease pathology begins decades before the onset of clinical symptoms. This provides an opportunity for interventional clinical trials to potentially delay or prevent the onset of cognitive impairment or dementia. CNP520 (a beta-site-amyloid precursor protein-cleaving enzyme inhibitor) is in clinical development for the treatment of preclinical Alzheimer's disease under the Alzheimer's Prevention Initiative Generation Program. The Alzheimer's Prevention Initiative is a public-private partnership intended to accelerate the evaluation of Alzheimer's disease prevention therapies. The Generation Program comprises two pivotal phase II/III studies with similar designs to assess the efficacy and safety of investigational treatments in a cognitively unimpaired population at increased risk for developing Alzheimer's disease based on age and apolipoprotein E (APOE) genotype (i.e., presence of the APOE ε4 allele). The program has been designed to maximize benefit to Alzheimer's disease research. Generation Study 1 (NCT02565511) and Generation Study 2 (NCT03131453) are currently enrolling; their key features are presented here.

IT support for clinical pathways--lessons learned.

Clinical pathways are an effective instrument to decrease undesired practice variability and improve clinician performance. IT applications embedded into clinical routine work can help to increase pathway compliance. Successfully implementing such applications requires both a responsive IT infrastructure and a participatory and iterative design process aimed at achieving user acceptance and usability. Experiences from the implementation and iterative improvement of an online surgical pathway at Marburg University Medical Centre have shown that pathway conformance actually could be improved by the use of IT. An analysis of the iterative design process has shown that future pathway projects can benefit from the lessons learned during this project. Based on these lessons a method for developing well adapted interaction mechanisms is presented, which is aimed at improving process alignment. Our goal is to build up a library of tested reusable components to reduce the number of iterations for pathway implementation.

Removing seminal plasma improves bovine sperm sex-sorting.

Bull ejaculates with sperm concentrations of less than 1 billion sperm sort poorly for sex chromosomes, but whether this is because of the sperm concentration or the concomitant seminal plasma content has not been elucidated. Experiments were conducted to determine why ejaculates with lower sperm concentrations sort poorly and develop a protocol to increase sorting efficiency. In Experiment I, spermatozoa at 160 or 240 × 106 sperm/mL were stained at 49, 65 or 81 µm Hoechst 33342 with 0 or 10% seminal plasma and then sex-sorted. In Experiment II, seminal plasma was adjusted to create samples with sperm concentrations of 0.7, 1.4 and 2.1 × 109 sperm/mL, prior to sex-sorting. In Experiment III, spermatozoa were diluted to 0.7, 1.4 and 2.1 × 109 sperm/mL using TALP containing 0 or 10% seminal plasma prior to sex-sorting and cryopreservation. In Experiment I, the optimal staining combination was 160 × 106 sperm/mL stained with 65 µm Hoechst 33342 and no seminal plasma. In Experiment II, the percentages of membrane-impaired sperm were lower for sample concentrations of 2.1 × 109 sperm/mL (15%) than for samples at 1.4 × 109 (17%) or 0.7 × 109 sperm/mL (18%; p < 0.01). The X sort rate was slower for samples stored at 0.7 × 109 sperm/mL (3.45 × 103 sperm/sec) than for samples stored at 1.4 × 109 and 2.1 × 109 sperm/mL (3.85 and 3.94 × 103 sperm/sec, respectively; p < 0.05). In Experiment III, samples containing 0% seminal plasma had higher percentages of live-oriented cells (54 vs. 50%; p < 0.05), fewer dead sperm (19 vs. 22%; p < 0.01) and higher post-thaw motility (41 vs. 35%; p < 0.05) than samples containing 10% seminal plasma. Ejaculates with high sperm concentrations result in superior sorting because these samples have less seminal plasma during staining than ejaculates with lower initial sperm concentrations as all samples are diluted to 160 × 106 sperm/mL for staining. Therefore, sorting efficiency appears to be affected by seminal plasma concentration, not by the original sperm concentration.

Demand-driven evolution of IT systems in healthcare--a case study for improving interdisciplinary processes.

OBJECTIVES: To analyze and to optimize interdisciplinary clinical processes, to introduce an IT-supported model for demand-driven system evolution in healthcare, and to demonstrate the feasibility of the approach for a clinical example and to present an evaluation. METHODS: System evolution and change management are viewed as two sides of the same coin, thus formal methods for process analysis and IT system evolution were embedded into a goal-oriented change management model. Based on a process model, a Failure Mode and Effects Analysis (FMEA) and a computer simulation were performed. A tool for rapid application development (RAD) was used to incrementally improve the healthcare information system according to newly arising needs. RESULTS: Each of the formal methods used contributed to the successful reorganization of the interdisciplinary clinical process. An evaluation demonstrated significant improvements. An integrated IT application was implemented to support the optimized process. CONCLUSIONS: Process improvement is feasible and effective when formal methods for process analysis and requirements specification are used in a reasonable and goal-oriented way. It might be necessary to trade off costs and benefits or simplify a given method in the context of a particular project. As the same information is utilized in different tools, it is supposed that the efforts for process analysis, documentation and implementation of adapted applications could be reduced if different tools were integrated and based on a single coherent reference model for description of clinical processes.

Inhibition by cholera toxin of clonal growth of murine granulocyte/macrophage progenitor cells in soft agar cultures.

Proliferation in vitro of the committed granulocyte-macrophage progenitor cell (CFUC) is inhibited by cholera toxin (CT) in a dose-dependent manner. This inhibition is reduced and counteracted by higher doses of colony stimulating factor (CSF), an obligatory growth stimulator of CFUC. Mixing of CT with its specific receptor, the monosialoganglioside, GM1, before exposure to bone marrow (BM) cells, blocks the toxin's effect, and a restoration of colony formation is achieved. A dose-dependent inhibition of CSF-induced colony formation is also observed in the presence of choleragenoid, the B subunit of the toxin which binds to the specific receptor on the cell surface, but is biologically inactive. Incubation of BM cells with CT prior to cloning in soft agar cultures supplemented with CSF inhibits clonal proliferation of CFUC, whereas a brief in vitro exposure of BM cells to CSF prior to CT protects the cells against subsequent CT inhibition. The ability of CT to inhibit the CSF-induced clonal proliferation of CFUC and the effectiveness of CSF in reducing and even counteracting CT inhibition suggests that CT, by binding to BM cells through the B subunit, might either directly or indirectly interfere with the stimulatory activity of CSF upon its target cells.

Possible role of gangliosides in the interaction of colony-stimulating factor with granulocyte-macrophage progenitor cells.

Our previous studies have shown that preincubation of murine bone marrow (BM) cells with cholera toxin (CT) or with its B subunit inhibited their responsiveness to colony-stimulating factor (CSF). Because ganglioside GM1 is a component of the CT receptor, the present study was undertaken to determine whether gangliosides interact with CSF and therefore might play a role in the binding sites for CSF. Preincubation of CSF with increasing concentrations of bovine-brain mixed gangliosides resulted in decreased numbers of colonies of BM-derived granulocyte-macrophage progenitor cells (CFU-C) in soft agar. The inhibitory effect of the gangliosides could be reduced by increasing the concentrations of CSF. Evidence for direct binding of CSF to gangliosides was obtained by affinity chromatography of CSF on gangliosides-sepharose beads. CSF activity was retained on the beads and could be eluted with 6 M guanidine HCl. Four different individual gangliosides (GM1, GM2, GD1a, GT1b) were tested for their inhibitory effect on CSF-induced clonal growth of CFU-C. GM1 was the most effective with a 50% inhibition (I50) of clonal growth at a concentration of 15 microM. while the other three gangliosides had slight inhibitory activity (I50 at a concentration greater than 100 microM). In addition, preincubation of BM cells with rabbit anti-GM1 antibodies before addition of CSF reduced the clonal growth of CFU-C to 45%. These data indicate that GM1 interacts with CSF and suggest that gangliosides may play a role in the interaction of CSF with CFU-C and that the binding site for CSF on the surface of these cells might either consist of or contain this ganglioside.

Proteoglycan production by bovine granulosa cells in vitro is regulated by calmodulin and calcium.

Proteoglycan production by granulosa cells in vitro is regulated by gonadotropins. The objective of this study was to determine if FSH stimulation of proteoglycan synthesis was modulated by calmodulin or calcium. Assay for calmodulin using an ATPase assay dependent on calmodulin yielded concentrations of 7.7 microM. Bovine granulosa cells from follicles 1-9 mm diameter were incubated for 45 minutes in a chemically defined medium containing 5 microCi/ml 3H-glucosamine and various phenothiazine drugs which are inhibitors of calmodulin. In response to oFSH or rFSH at equivalent biological potencies, proteoglycan production decreased with increasing concentrations of phenothiazines from 1 to 50 microM. Addition of EGTA at 0.0, 0.5, 1.0 or 2.0 mM showed decreased proteoglycan production with increased amounts of the chelator. These data suggest that calmodulin and calcium are necessary for proteoglycan production by granulosa cells in response to FSH in vitro.

Proteoglycan production by bovine granulosa cells in vitro occurs in response to fsh.

Bovine granulosa cells from small (1-9 mm) or large (10-20 mm) follicles were incubated in a chemically defined medium containing 5 muCi/ml [3H]glucosamine, gonadotropins or polypeptide hormones, 8-Br-cAMP, theophylline or trifluoperazine (TFP). Radiolabeled proteoglycans were precipitated with 10% phosphotungstic acid. Maximum incorporation of isotope occurred in 45-60 min. Radiolabeled products were completely hydrolyzed with chondroitinase ABC. FSH, but not LH or hCG, yielded a significant log-dose response. High doses of hCG inhibited the ability of granulosa to respond to FSH. No other hormone altered the FSH dose-response curve. Addition of 8-Br-cAMP or theophylline mimicked the FSH response. The FSH effect was blocked by TFP, an inhibitor of calmodulin, but cAMP or theophylline overcame the effect of TEP. No distinct difference in response to these various compounds was noted between granulosa from small or large follicles. This system provides a biochemical marker for evaluating a mechanism of action for FSH.

In vivo biocompatibility and degradation studies of polyhydroxyoctanoate in the rat: a new sealant for the polyester arterial prosthesis.

The present study examined the biocompatibility and degradation properties of poly (beta-hydroxy octanoate) (PHO) as an impregnation substrate on arterial prostheses. PHO-impregnated polyester grafts sterilized by ethylene oxide (EO) or gamma (gamma) radiation, and polyester Dacron(R) prostheses impregnated with fluoropolymer, gelatin, or albumin were implanted subcutaneously in rats for periods ranging from 2 to 180 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion while performing histological studies at the tissue/prosthesis interface. The degradation was determined by chemical analysis of the EO and gamma-sterilized PHO after implantation using differential scanning calorimetry (DSC), wide angle x-ray diffraction (WAXD), and size exclusion chromatography (SEC). Alkaline phosphatase activity by the sterilized PHO and by the gelatin and albumin grafts was significantly elevated early after implantation in contrast to that of the Dacron and fluoropolymer grafts that occurred later, at 7 and 5 days, respectively The peak of acid phosphatase activity for all of the grafts occurred between 5 and 10 days postimplantation, with the gamma-sterilized PHO grafts recording the greatest activity. Histological study revealed that the tissue incorporation into the graft wall was earlier and more complete for the Dacron and fluoropolymer grafts after 6 months than for the gelatin and albumin grafts, because the latter induced important inflammatory reactions during the resorption of the cross-linked protein substrates. The EO and gamma-sterilized PHO grafts exhibited a similar healing sequence characterized by the development of a collagenous tissue surrounding the prostheses. However, no infiltration of tissue into the graft wall was observed after 6 months, mainly because of the presence of the PHO. Degradation of the EO and gamma-sterilized PHO occurred preferentially by a hydrolytic mechanism as shown by a 30% molecular weight decrease after 6 months. In conclusion, PHO showed good biocompatibility in terms of enzyme activity and tissue reaction. Degradation was a slow, in vivo process controlled primarily by a random hydrolytic reaction and by a local enzymatic attack by macrophages and giant cells.

Quantitative determination of intracellular depolymerase activity in Pseudomonas oleovorans inclusions containing poly-3-hydroxyalkanoates with long alkyl substituents.

Research regarding the accurate, quantitative degradation of novel poly-3-hydroxyalkanoates has been restricted by the absence of an appropriate monitoring technique. The calibration of a gas chromatograph to poly-3-hydroxyoctanoate reveals a linear relationship between the area under gas chromatograph tracings and polymer weight. With this new method, poly-3-hydroxy-octanoate granules isolated from Pseudomonas oleovorans, which were incubated at 30 degrees C in an alkaline buffer, exhibited a linear degradation rate. Degradation was inhibited by the presence of Triton X-100 and phenylmethylsulfonyl fluoride. The depolymerase was demonstrated to be associated with the polymer granule complex and most likely possessed serine residues at its active site.