Homeopathy for seasonal allergic rhinitis: rationale, design and methods of the three-armed randomized controlled HOMEOSAR trial.

BACKGROUND: Patients with seasonal allergic rhinitis (SAR) frequently use homeopathic therapy. Although there is some evidence that homeopathy may be effective in treating symptoms of SAR, there is a lack of high-quality clinical trials. Therefore, the aim of the homeopathy for SAR (HOMEOSAR) trial is to determine the efficacy of individualized or standardized homeopathic drug treatment compared to placebo regarding rhinitis-related quality of life in patients with SAR. METHODS: This randomized, placebo-controlled, double-blind, three-armed intervention study will be conducted at two university hospital outpatient clinics for complementary and integrative medicine in Berlin and in 12 office-based practices specializing in homeopathic treatment in Germany. A total of 270 patients with clinical symptoms of SAR and positive allergy test to birch and grass pollen will receive homeopathic anamnesis and subsequently be randomized into (a) standardized homeopathic drug treatment with Galphimia Glauca (potency D6), (b) individualized homeopathic drug treatment (D6), or (c) placebo. All three groups can receive on-demand rescue medication as needed. Treatment will consist of two consultations and daily intake of the study medication for 4 weeks during the pollen season. The primary outcome is the mean overall score of the Rhinitis Quality of Life Questionnaire (RQLQ) in weeks 3 and 4, analyzed using analysis of covariance (adjusted for baseline RQLQ overall score and study center). A closed testing procedure will be used to control the overall type I error comparing the 3 treatment groups. Secondary outcomes include the overall RQLQ and its seven domain scores, responder status (decrease in RQLQ overall score of at least 0.5 points compared to the baseline value), use of rescue medication, intensity of total and individual SAR symptoms based on visual analog scale, generic health-related quality of life, safety, utilization of health care resources and associated costs. In addition, a qualitative data analysis is planned. CONCLUSION: The results of our study will contribute to clarifying the possible therapeutic effects of homeopathic drug treatment for patients with SAR. TRIAL REGISTRATION: This study has been registered in the German Clinical Trial Registry with trial ID DRKS00018081 on June 09, 2020.

Quantification of left atrial contractile function using two-dimensional speckle tracking echocardiography in horses after conversion of atrial fibrillation to sinus rhythm.

INTRODUCTION/OBJECTIVES: In horses, persistent atrial dysfunction is a prognostic indicator of recurrence of atrial fibrillation (AF). The objective of this study was to quantify left atrial (LA) contractile function in Warmblood horses after successful cardioversion of AF to sinus rhythm, using standard two-dimensional echocardiography (2DE) and two-dimensional speckle tracking (2DST) analyses, and to provide proof-of-concept for use of 2DST to detect LA contractile dysfunction in horses. ANIMALS, MATERIALS, AND METHODS: Nineteen Warmblood horses with AF and successful transvenous electrical cardioversion (TVEC) or medical cardioversion using quinidine sulfate (QS) were included. Echocardiography was performed at 24 hr, 72 hr, and 1-6 months after cardioversion. Conventional 2DE-derived indices of LA size and function and global longitudinal strain (SL) and longitudinal strain rate (SRL) during LA contractile function were measured to detect differences in LA size and function over time and between treatment modalities. The association between 2DE-derived indices and global SL and SRL, respectively, and the agreement of the variables to detect LA dysfunction were assessed. RESULTS: Global SL and SRL, as well as active LA fractional area change (FAC) identified cases with LA dysfunction after TVEC and QS cardioversion and proved useful to demonstrate LA functional recovery over time. Agreement between active LA FAC and SL and SRL, respectively, to diagnose atrial dysfunction was substantial to fair at 24 hr after cardioversion and decreased with time. CONCLUSION: This study shows that 2DST is useful to quantify LA contractile dysfunction in horses after cardioversion of AF.

Quantification of left atrial wall motion in healthy horses using two-dimensional speckle tracking.

INTRODUCTION: The mechanical function of the left atrium (LA) plays a pivotal role in modulation of left ventricular filling. Assessment of LA function might be a clinically useful prognostic tool for horses with mitral regurgitation or atrial fibrillation. However, the most accurate, reliable, and clinically useful methods to assess LA myocardial function are yet to be determined. The objective of this study was to describe the methods for quantification of LA wall motion using two-dimensional speckle tracking (2DST) echocardiography in healthy Warmblood horses to quantify measurement variability, to calculate reference intervals for 2DST variables, and to investigate their relationship to sex, age, body weight, and heart rate. ANIMALS, MATERIALS, AND METHODS: Twenty-six healthy Warmblood horses were included. 2DST analyses of LA wall motion were performed on digitally stored cine-loop recordings of a standardized right-parasternal four-chamber view focusing on the LA. Longitudinal strain, longitudinal strain rate, and time to peak LA contraction were measured to characterize LA contractile, reservoir, and conduit function. Intraobserver and interobserver measurement variability was quantified, and reference intervals were calculated. RESULTS: The coefficient of variation for intraobserver and interobserver measurement variability ranged between 2.0-11.1% and 5.1-15.4%, respectively, for global strain, strain rate, and time to peak LA contraction. Reference intervals for healthy Warmblood horses were reported. CONCLUSION: This study shows that 2DST is a feasible and reliable method to quantify LA wall motion throughout the cardiac cycle in healthy Warmblood horses. Further studies are required to establish the clinical value of 2DST for assessment of LA function.

Multi-Stage Group Testing Improves Efficiency of Large-Scale COVID-19 Screening.

BACKGROUND: SARS-CoV-2 test kits are in critical shortage in many countries. This limits large-scale population testing and hinders the effort to identify and isolate infected individuals. OBJECTIVE: Herein, we developed and evaluated multi-stage group testing schemes that test samples in groups of various pool sizes in multiple stages. Through this approach, groups of negative samples can be eliminated with a single test, avoiding the need for individual testing and achieving considerable savings of resources. STUDY DESIGN: We designed and parameterized various multi-stage testing schemes and compared their efficiency at different prevalence rates using computer simulations. RESULTS: We found that three-stage testing schemes with pool sizes of maximum 16 samples can test up to three and seven times as many individuals with the same number of test kits for prevalence rates of around 5% and 1%, respectively. We propose an adaptive approach, where the optimal testing scheme is selected based on the expected prevalence rate. CONCLUSION: These group testing schemes could lead to a major reduction in the number of testing kits required and help improve large-scale population testing in general and in the context of the current COVID-19 pandemic.

Evaluation of the role of heterogeneities on transverse mixing in bench-scale tank experiments by numerical modeling.

In this work, numerical modeling is used to evaluate and interpret a series of detailed and well-controlled two-dimensional bench-scale conservative tracer tank experiments performed to investigate transverse mixing in porous media. The porous medium used consists of a fine matrix and a more permeable lens vertically aligned with the tracer source and the flow direction. A sensitivity analysis shows that the tracer distribution after passing the lens is only slightly sensitive to variations in transverse dispersivity, but strongly sensitive to the contrast of hydraulic conductivities. A unique parameter set could be calibrated to closely fit the experimental observations. On the basis of calibrated and validated model, synthetic experiments with different contrasts in hydraulic conductivity and more complex setups were performed and the efficiency of mixing evaluated. Flux-related dilution indices derived from these simulations show that the contrasts in hydraulic conductivity between matrix and high-permeable lenses as well as the spatial configuration of tracer plumes and lenses dominate mixing, rather than the actual pore scale dispersivities. These results indicate that local material distributions, the magnitude of permeability contrasts, and their spatial and scale relation to solute plumes are more important for macro-scale transverse dispersion than the micro-scale dispersivities of individual materials. Local material characterization by thorough site investigation hence is of utmost importance for the evaluation of mixing-influenced or -governed problems in groundwater, such as tracer test evaluation or an assessment of contaminant natural attenuation.

Evaluation of transverse dispersion effects in tank experiments by numerical modeling: parameter estimation, sensitivity analysis and revision of experimental design.

Transverse dispersion represents an important mixing process for transport of contaminants in groundwater and constitutes an essential prerequisite for geochemical and biodegradation reactions. Within this context, this work describes the detailed numerical simulation of highly controlled laboratory experiments using uranine, bromide and oxygen depleted water as conservative tracers for the quantification of transverse mixing in porous media. Synthetic numerical experiments reproducing an existing laboratory experimental set-up of quasi two-dimensional flow through tank were performed to assess the applicability of an analytical solution of the 2D advection-dispersion equation for the estimation of transverse dispersivity as fitting parameter. The fitted dispersivities were compared to the "true" values introduced in the numerical simulations and the associated error could be precisely estimated. A sensitivity analysis was performed on the experimental set-up in order to evaluate the sensitivities of the measurements taken at the tank experiment on the individual hydraulic and transport parameters. From the results, an improved experimental set-up as well as a numerical evaluation procedure could be developed, which allow for a precise and reliable determination of dispersivities. The improved tank set-up was used for new laboratory experiments, performed at advective velocities of 4.9 m d(-1) and 10.5 m d(-1). Numerical evaluation of these experiments yielded a unique and reliable parameter set, which closely fits the measured tracer concentration data. For the porous medium with a grain size of 0.25-0.30 mm, the fitted longitudinal and transverse dispersivities were 3.49×10(-4) m and 1.48×10(-5) m, respectively. The procedures developed in this paper for the synthetic and rigorous design and evaluation of the experiments can be generalized and transferred to comparable applications.

Isolation, characterization and establishment of an equine retinal glial cell line: a prerequisite to investigate the physiological function of Müller cells in the retina.

Retinal Müller glial cells are of vital importance for maintaining a physiological environment within the retina. To this end, they provide highly specialized physiological properties to support neurons in structure, nutrition and metabolism. The purpose of this study was to isolate Müller cells from the equine retina, determine their characteristics and subsequently establish a stable equine Müller cell line (eqMC) that will provide a prerequisite for investigations on their physiological properties. Dissociated retinal cells were obtained from equine retinas by a papain digestion technique followed by trituration and a cell attachment method by which pure Müller cell cultures were achieved. Morphological examination was performed using phase-contrast microscopy, and further characterization of different subcultures was accomplished by immunocytochemistry. Cells of passage 1 showed distinct signals for glutamine synthetase and vimentin, whereas glial fibrillary acidic protein expression was almost absent. Characteristic expression patterns remained unaltered in all subcultures. Furthermore, cultured Müller cells stably expressed the microfilament alpha-smooth muscle actin, the proliferation marker Ki67 and the membrane channels Kir4.1 and aquaporin 4. The present study introduces the eqMC-7 that will facilitate studies investigating the physiological role of Müller cells within the equine retina.

Functional results after giant cell tumor operation near knee joint and the cement radiolucent zone as indicator of recurrence.

BACKGROUND: Giant cell tumor of bone near the knee joints is a dilemma for the operating surgeon. Curettage and bone grafting have a high recurrence, whereas wide resection has a reduced recurrence rate with the compromise of limb function. MATERIALS AND METHODS: Thirty-eight patients with histologically proven giant cell tumor near the knee joint were treated. All patients were reviewed with regard to the operative method, recurrence rate, postoperative arthritis and functional results of the joint. In cases of cement filling, the radiolucent zone and the sclerotic rim were assessed as possible markers for recurrence. RESULTS: 14 male and 24 female patients were included in this study (mean age 28 years, range 13-56 years). All patients underwent surgery, 21 patients were treated with a bone cement filling and additional osteosynthesis after curettage. Seventeen patients were filled with cancellous bone or curettage alone. In the group with bone cement filling after curettage, the recurrence rate was 23.8%, whereas a recurrence rate of 52.9% was detected in the group with cancellous bone filling or curettage alone. The average time to recurrence was two years (5 months to 6 years). An increase of the radiolucent zone was seen in 80% of all patients with a recurrence. CONCLUSION: Cement filling after extensive curettage does not increase the recurrence rate and does not induce osteoarthritis, as long as the continuity of articular cartilage is maintained. Patients with giant cell tumor of bone near the knee joint can be treated satisfactorily with intralesional resection and bone cement packing. The extension of the radiolucent zone after bone cement filling is a reliable indicator for a possible local recurrence.

Orthopaedic limb salvage with a mega prosthesis in a patient with haemophilia A and inhibitors - a case report.

Inhibitors against FVIII or FIX in patients with haemophilia are a common and serious complication. Until recently, elective surgery was associated with major bleeding despite the availability of a sufficient substitution therapy. We report about the major orthopaedic reconstruction of the right limb in a patient with severe haemophilia A and inhibitors. This reconstruction was the after effect of a traumatic periprosthetic fracture of the right femur after total knee replacement 6 months ago. This fracture could be stabilized by internal fixation. Two months later, a non-traumatic femur fracture occurred. Therefore, we removed the distal part of the femur and the joint replacement, and implanted a custom made tumour prosthesis (Type MUTARS (c), Münster). These three successive operations, which included emergency and elective surgery, were performed within 8 months. This is, to the best of our knowledge, the first patient with inhibitors undergoing such a complicated reconstruction of a limb. We conclude that successful elective orthopaedic surgery could be accomplished safely in this patient with high responding inhibitors using recombinant FVIIa. After a follow-up of 9 months, no major complications were seen.

[The use of bisphosphonates in arthroplasty]. / Anwendungsmöglichkeiten der Bisphosphonate in der Endoprothetik.

The use of bisphosphonates in joint arthroplasty is the latest field of application for these agents. The mechanism of action of bisphosphonates suggests that they may optimize long-term survival of the implant. Most important is their potency in suppressing periprosthetic osteolysis due to the inflammatory foreign body reaction of wear debris, to decrease periprosthetic osteopenia caused by stress-shielding and to improve the osseointegration of cementless metal implants. The present review provides the latest information on definite and presumed mechanisms of action of bisphosphonates and their clinical importance.

Total hip replacement in patients with severe bleeding disorders. A 30 years single center experience.

Arthropathy of the hip is moderate in frequency in haemophiliac patients, but is less common than ankle, knee or elbow arthropathy. We report about our experience with total hip replacement in patients with severe bleeding disorders over a period of 30 years. Between July 1972 and 2002, 15 hips in 13 patients were replaced. The main bleeding disorders were Haemophilia A in ten patients and severe v. Willebrand disease in three patients. The mean follow-up was 132 months (range 12-363). We can demonstrate good long-term results, with only one aseptic loosening after 14 years and one septic loosening after 14 months in an HIV-positive patient. The Harris Hip Score increased from 48 points (32-66) preoperatively to 89 (76-100) postoperatively. In conclusion, total hip replacement performed in a specialised haemophiliac centre is a safe procedure, and results in pain relief and improvement of the quality of life in patients with severe bleeding disorders.

[Effects of bisphosphonates in arthroplasty]. / Bisphosphonatwirkungen in der Endoprothetik.

AIM: This study presents an overview of the general effects of bisphosphonates and in particular of their effects on different problems in joint arthroplasty. METHOD: First the chemical properties are described, then the biological effects. It is already known that bisphosphonates have effects on orthopaedic diseases and an increasing number of studies are investigating what effects can be achieved in joint arthroplasty with these substances. RESULTS: The bisphosphonates group was derived from industrial pyrophosphate which is used to prevent calcification. Bisphosphonates inhibit bone mineralisation and resorption. Several direct and indirect mechanisms are responsible for these effects. The inhibition of bone resorption is used to benefit patients suffering from various diseases causing increased bone resorption. Treatment with bisphosphonates results in greater bone density and improved mechanical bone quality. Indications for this treatment include osteoporosis, tumour-associated osseo-destruction, fibrous dysplasia and Paget's disease. Recent studies have shown that osseo-integration of metal implants is accelerated and periprosthetic bone loss, which is caused by various different mechanisms during the lifetime of an implant, can be reduced. CONCLUSION: Bisphosphonates have been an established element in the treatment of bone metabolic disorders for many years. Their use in joint arthroplasty could become increasingly important.

[Improved osseointegration and periprosthetic bone volume around cementless metal implants under bisphosphonate treatment]. / Verbesserung von Osteointegration und periprothetischem Knochenanteil zementfreier metallischer Implantate unter Bisphosphonatgabe.

AIM: The effects of a systemic treatment with the bisphosphonate ibandronate on osseointegration of uncoated and hydroxyapatite-coated titanium implants and on periprosthetic bone volume have been evaluated and the dosage of medication had to be defined. METHOD: We used an animal model of the rat, the animals were assigned to three treatment groups receiving 1 microg, 5 microg and 25 microg/kg body weight and one control group receiving NaCl 0.9%. An uncoated and a hydroxyapatite-coated titanium rod were inserted into the medullary canal of the femur. After 28 days the specimens were harvested and histomorphometric evaluation revealed extend of osseointegrated implant surface and changes of periprosthetic bone volume. RESULTS: Treatment groups receiving 5 microg and 25 microg ibandronate showed significant improvement of osseointegrated implant surface compared to the control group. Enhancement of periprosthetic bone volume was revealed in all treatment groups but only application of 25 microg ibandronate was significantly improved compared to the control group. CONCLUSION: A minor dose of 1 microg ibandronate is not effective to improve osseointegration. A high dosed bisphosphonate treatment with 5 microg or 25 microg ibandronate is potent to improve osseointegrated implant surface significantly compared to an untreated control in both uncoated and hydroxyapatite-coated titanium implants and to enhance periprosthetic bone volume. By that, improved secondary stability and prolonged survival time of cementless metal implants can be expected.

The bisphosphonate ibandronate improves implant integration in osteopenic ovariectomized rats.

Osteoporosis is known to impair the process of implant osseointegration. Bisphosphonates are drugs that inhibit osteoclast-mediated bone resorption and normalize the high rate of bone turnover that characterizes this disease. Consequently, there is a rationale for using bisphosphonates to enhance the early stabilization of implants in subjects with low bone mass. In this study, 84 rats received titanium-only or hydroxyapatite (HA)-coated titanium femoral implants, 3 months after being ovariectomized (OVX) or sham operated. They were then treated for 4 weeks. The OVX rats were randomly assigned to daily subcutaneous injections of either saline or the bisphosphonate ibandronate (at a dose of 1 microg/kg or 25 microg/kg), while the sham-operated animals received saline throughout. The 1 microg/kg or 25 microg/kg ibandronate doses are considered translatable to doses used to treat osteoporosis and metastatic bone disease (MBD), respectively, in rats, and roughly reflect those used in humans. At the end of the treatment period, bone mineral density (BMD) at the lumbar spine increased in both of the ibandronate-treated groups when compared with the OVX control animals and to a level similar to that of the sham-operated control group. Osseointegration, determined by histomorphometric analysis and expressed as percentage of osseointegration implant surface (OIS), did not differ between groups for the titanium-only implants. For the HA-coated implants, however, OIS was 113.5% and 185% higher in the groups receiving 1 microg/kg or 25 microg/kg ibandronate, respectively, relative to the OVX controls. In turn, the OIS of the HA-coated implants was 56.5% lower in the OVX control group than in the sham control group. These findings clearly demonstrate that OVX-induced osteopenia impairs the osseointegration of HA-coated titanium implants and that ibandronate, administered at doses analogous to those used to clinically treat osteoporosis and MBD, counters this harmful effect. Ibandronate may, therefore, have a role in improving the osseointegration of implants in patients with osteoporosis and MBD.

Early detection of skin cancer (EDISCIM) through the use of non-invasive confocal imaging.

In the past 15 years the number of malignant melanomas and non-melanoma skin cancer, (i.e. squamous cell carcinoma, basal cell carcinoma), have increased dramatically throughout the whole world, in particular among people with white skin. For example, in Germany the number of new cases of melanoma is about 10 to 12 per 100,000 people, (for basal cell carcinoma as a non-melanoma skin cancer 140 per 100,000), the absolute number of annual new cases of melanoma is an estimated 9,000 to 10,000, and the increasing rate is 5 to 10%. However, there are more than 40 differential diagnoses for skin cancer which makes it difficult even for expert dermatologists to give correct diagnosis, (estimated 75% correct diagnoses). This figure is even worse for doctors from other specialities. There is only a chance of high cure rates when skin tumours are detected at an early stage. The prognosis of skin cancer is dependent very much on the thickness, (as a sign of invasiveness), of the tumour and the number of mitotic figures in the tumour, (as a sign of proliferation activity). However, the final diagnosis of skin cancer is usually done by biopsy, the sample being investigated by a specialist. This is an invasive method, which is painful for the patient and might require several cuts and samples taken before being absolutely certain. Due to the potential risk of dissemination of tumour cells, taking an incisional biopsy is obsolete in malignant melanoma. Therefore the correct diagnosis of malignant melanoma can be made only after a total removal of the lesion and consecutive histopathological examination. The EDISCIM project intends to develop a system for the early diagnosis of skin cancer which uses confocal imaging for the non-invasive diagnosis of the upper layers of the skin that aids the physician in the analysis of the images and therefore with the diagnosis, allows for potential remote diagnosis by specialist dermatologists via tele-diagnosis if need be. The objectives of the system are Captures microscopic images of the skin by confocal imaging, Processes and records these images in real time, Compares these images against a knowledge base of known skin symptoms, Displays the results in a suitable interface to the physician performing the diagnosis, And supports the online telematic support by specialists.

[Rachitic knock knees in children]. / Das rachitische X-Bein im Kindesalter. Pathogenese und Therapie aus historischer Sicht.

Knee malpositions, for example valgus or varus deformations or flexion contractures, were often cited in the historical literature. In earlier times, clinical pictures such as rickets were often the reason for this kind of deformity. A causal therapy did not exist until the twentieth century. In most cases of rickets, genu valgum was reported as the typical knee deformation. The differential diagnosis for genu valgum caused by rickets was genu valgum traumaticum, paralyticum, and inflammatorium. The most important reports on the pathogenesis of valgus deformation can be found in publications by Hueter and von Mikulicz. The causal therapy of rickets was introduced at the beginning of the twentieth century.Vitamin therapy and UV phototherapy were developed during this period. Using these therapies, rickets decreased dramatically. Kurt Huldschinsky, a pediatrician from Berlin,was one of the main inventors of UV phototherapy in Germany. At the end of the nineteenth century, the operative correction of knee deformities increased while conservative treatment continued to be applied. Plaster casts,orthoses, and osteoclast therapy were the main noninvasive therapeutic possibilities. Positive aspects of the conservative techniques were mostly the good results and easy, timesaving technique compared with the operative treatment. The operative therapy increased with the knowledge of antisepsis and asepsis as well as advances in anesthetic procedures. Operative treatment modalities, for example tibial and femoral osteotomies, were more precise, but connected with multiple complications and greater time expenditure. Sufficient vitamin prophylaxis rendered knee deformations caused by rickets a rarity.

[Ten year follow-up after single incision anterior cruciate ligament reconstruction using patellar tendon autograft]. / 10-Jahres-Ergebnisse nach arthroskopischer vorderer Kreuzbandrekonstruktion mit dem Patellarsehnentransplantat.

AIM: We evaluated 74 patients 10 years after arthroscopically assisted ACL reconstruction using the central third of the patellar tendon as autograft. METHOD: IKDC, Tegner and Lysholm scores were used for clinical evaluation. Ligament stability was tested using the Rolimeter instrument. For statistics we used the Chi square test. RESULTS: At follow-up the Tegner activity level was 5.2, the Lysholm score was 93.6 points. Subjective assessment for function was rated normal or nearly normal in 83.7 %, for stability in 71.6 %. The side-to-side difference measured with the Rolimeter was normal in 87.8% and nearly normal in 12.2 %. Pivot shift was proven to be negative in 94.6 %. 29.7 % of patients showed degenerative changes in X-rays at follow-up. There was a significant correlation between time interval from injury to surgery and the grade of degenerative changes. Arthrosis significantly correlates with the rate of meniscus injury. Acute operative treatment increases the rate of arthrofibrosis significantly. CONCLUSION: To avoid osteoarthrosis we recommend an early (subacute) ACL reconstruction and meniscus refixation in the case of meniscus injury.