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Biomedical subjects

M Walther

Publications and source records attributed to M Walther.

At least 19 recordsLinked to original sources
PubMed2006

Safety of recombinant fowlpox strain FP9 and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers.

The ability to generate potent antigen-specific T cell responses by vaccination has been a major hurdle in vaccinology. Vaccinia virus and avipox viruses have been shown to be capable of expressing antigens in mammalian cells and can induce a protective immune response against several mammalian pathogens. We report on two such vaccine constructs, modified vaccinia virus Ankara and FP9 (an attenuated fowlpox virus) both expressing the pre-erythrocytic malaria antigen thrombospondin-related adhesion protein and a string of CD8+ epitopes (ME-TRAP). In prime-boost combinations in a mouse model MVA and FP9 are highly immunogenic and induce substantial protective efficacy. A series of human clinical trials using the recombinant MVA and FP9 malaria vaccines encoding ME-TRAP, both independently and in prime-boost combinations with or without the DNA vaccine DNA ME-TRAP, has shown them to be both immunogenic for CD8+ T cells and capable of inducing protective efficacy. We report here a detailed analysis of the safety profiles of these viral vectors and show that anti-vector antibody responses induced by the vectors are generally low to moderate. We conclude that these vectors are safe and show acceptable side effect profiles for prophylactic vaccination.

Adolescent↗
PubMed2006

[Grading of the functional sport shoe parameter "cushioning" and "forefoot flexibility" on running shoes].

On nearly every running event a heterogeneous structure of participants regarding body height and body weight can be observed. This study should figure out whether the running shoe manufacturers will consider this anthropometric variability. Moreover it should be investigated the runners needs based on different anthropometrics regarding preferred cushioning and forefoot flexibility properties. In order to check whether the running shoe manufacturers will apply a grading pattern, a dynamic material study with conventional running shoes in different sizes was conducted. In a second step a field study in Middle Europe and North America with 244 female and 227 male runners was organized. Every subject had to run and evaluate 7 different shoe modifications. Based on the material study it is to state, that the running shoe manufacturers currently do not consider a systematic grading of cushioning and forefoot flexibility properties. In contrast to this, the field study reveals the necessity to grade these properties. A shoe size dependent and a geographic grading concept are suggested. It is supposed, that the application of these grading concepts do not only provide a comfort improvement, but they also contribute to a reduction of joint loads of the lower extremities and consequently to a prevention of overuse injuries.

Adult↗
PubMed2006

A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge.

The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-gamma ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-gamma ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

Adolescent↗
PubMed2005

Blends of aqueous polymer dispersions used for pellet coating: importance of the particle size.

Blends of aqueous dispersions of a water-insoluble and an enteric polymer, namely ethyl cellulose:hydroxypropyl methylcellulose acetate succinate (EC:HPMCAS) and ethyl cellulose:methacrylic acid ethyl acrylate copolymer (EC:Eudragit L), were used as coating materials to control theophylline release from matrix pellets. Varying the polymer blend ratio, broad ranges of drug release patterns were obtained at low as well as at high pH. Interestingly, the resulting release profiles were rather similar for both types of blends in 0.1 M HCl, whereas significant differences were observed in phosphate buffer pH 7.4. Surprisingly, drug release at high pH was much slower for EC:HPMCAS blends compared to EC:Eudragit L blends, although HPMCAS leached out more rapidly (and to a higher extent) from the film coatings than Eudragit L. To explain these phenomena and to better understand the underlying drug release mechanisms, thin polymeric films of identical composition as the pellet coatings were prepared and physicochemically characterized before and upon exposure to the release media. Importantly, the polymer particle size was identified to be a very crucial formulation parameter, determining the resulting film coating structure and properties. The Eudragit L particles are much smaller than the HPMCAS particles (nano- vs. micrometer size range) and, thus, more effectively hinder the formation of a continuous and mechanically stable EC network. Consequently, the EC structures remaining after enteric polymer leaching at high pH are mechanically much weaker in the case of Eudragit L. Upon exposure to phosphate buffer, water-filled cracks are formed, through which the drug rapidly diffuses out. In contrast, the EC structures remaining upon HPMCAS leaching are mechanically stronger and drug release is controlled by diffusion through the polymeric remnants.

Cellulose↗
PubMed2005

[Injuries and response to overload stress in running as a sport].

Running is rarely associated with acute injuries (muscle injuries, ankle sprain, ruptures of the Achilles tendon). More than 80% of the complaints are due to overuse injuries, mainly concerning knee, foot and Achilles tendon. Risk factors are high-performance sports, high training quantity, rapid increase of training intensity, previous injuries, and skeletal axis malalignment. Running is not suitable for severely overweight people and those with significant skeletal malalignment, dysplastic hips, spondylolisthesis, or cartilage damage.

Ankle Injuries↗
PubMed2005

The German Short Musculoskeletal Function Assessment questionnaire: reliability, validity, responsiveness, and comparison with the Short Form 36 and Constant score--a prospective evaluation of patients undergoing repair for rotator cuff tear.

In a prospective clinical trial, first the German Short Musculoskeletal Function Assessment questionnaire (SMFA-D) was tested for reliability, validity, and responsiveness in 23 patients with rotator cuff tears, and secondly the Short Form (SF)-36, and the Constant score were evaluated comparatively in 45 patients with rotator cuff tear undergoing open repair. Retest reliability was excellent for the functional index of the SMFA-D and satisfactory for the bother index. The SMFA-D showed good validity and responsiveness. All three instruments demonstrated significantly the positive effect of rotator cuff repair at 12-month follow-up. Using comparable scales, effect sizes were bigger with the SMFA-D than with the SF-36 and as big as the Constant score. Significant correlations of the SMFA-D indices with the SF-36 scales and the Constant score could be shown preoperatively. At 12-month follow-up, all correlations between SMFA-D indices, SF-36 scales, and Constant score function scales were still significant. We recommend use of the SMFA-D to assess changes in functional status concerning patients with rotator cuff tear undergoing open repair.

Adult↗
PubMed2004

Polymer blends used for the aqueous coating of solid dosage forms: importance of the type of plasticizer.

The aim of this study was to investigate the importance of the type of plasticizer in polymer blends used for the coating of solid dosage forms, comparing a lipophilic and a hydrophilic plasticizer (dibutyl sebacate (DBS) and triethyl citrate (TEC)). In vitro drug release from propranolol hydrochloride (propranolol HCl)-loaded pellets coated with blends of ethyl cellulose (EC) and Eudragit L (100:0, 75:25, 50:50, 25:75 and 0:100 w/w) was investigated at low as well as at high pH. To better understand the underlying mass transport mechanisms, the physicochemical properties of the film coatings (e.g. mechanical resistance, water uptake and dry weight loss behavior) were determined. Interestingly, drug release strongly depended on the type of plasticizer. Importantly, not only the slope but also the shape of the release curves was affected, indicating that the chemical nature of the plasticizer plays a major role for the underlying drug release mechanisms. Diffusion through the intact polymer coatings and/or through water-filled cracks was found to be dominating for the control of drug release. The relative importance of these pathways strongly depended on the polymer blend ratio and type of plasticizer. In contrast to DBS, TEC rapidly leached out of the coatings, resulting in decreasing mechanical resistances of the films and, thus, facilitated crack formation. In addition, the hydrophilicity of the plasticizer significantly affected the water uptake behavior of the film coatings and, hence, changes in the coatings' toughness and drug permeability. Also the relative affinity of the plasticizer to the different polymers was found to be of significance. In contrast to TEC, DBS has a higher affinity to EC than to Eudragit L, resulting in potential redistributions of this plasticizer within the polymeric systems and changes in the release profiles during storage. Importantly, these effects could be avoided with appropriate curing conditions and preparation techniques for the coating dispersions.

Delayed-Action Preparations↗
PubMed2004

Low level of intracortical inhibition in children shown by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to evaluate the integrity and maturation of the corticospinal tract. TMS was used in this study to compare intracortical inhibition (ICI) in children, adolescents, and adults. The paired-pulse technique of TMS with interstimulus intervals of 2 ms was used to determine the ratio of conditioned (cMEP) and unconditioned amplitudes (ucMEP) that measures ICI. In experiment 1 (Exp 1) stimulus intensity was adapted to motor threshold (50 healthy subjects; 24 male, 26 female, median age 13.5 years, range 6.3 - 34 years) and in experiment 2 (Exp 2) stimulus intensity was adapted to the ucMEP (200 - 400 microV). Children (quotient of cMEP and ucMEP: Exp. 1: 0.71 +/- 0.41, Exp. 2: 0.82 +/- 0.25) had significantly less ICI compared to adults (Exp. 1: 0.21 +/- 0.19, mean +/- STD, Exp. 2: 0.35 +/- 0.22, in both experiments p < 0.001). Recently, ICI has been linked to the regulating function of GABAergic cortical interneurons on practice-dependent neuronal plasticity. Therefore, the lower ICI in children points to maturation processes that may have implications for the greater capacity of practice-dependent neuronal plasticity in children.

Adolescent↗
PubMed2003

Epidermoid cyst mimicking monoarticular arthritis of the great toe.

Local swellings of the foot are a common presentation in rheumatological practice. In the following case report, an epidermoid cyst presenting with the typical features of monoarticular arthritis is described in a 27-year-old woman. The differential diagnosis of forefoot swelling is discussed, with particular emphasis on epidermoid cysts and monoarticular arthritis.

Adult↗
PubMed2003

Arthrodesis in the treatment of hallux rigidus.

We reviewed 34 patients (38 joints) with hallux rigidus treated from 1989 to 1999 with arthrodesis of the first metatarsophalangeal joint. Average patient age at time of surgery was 52 (24-71) years, and the mean follow-up was 54 (18-116) months. There were six superficial infections, and all arthrodeses united. There was a good functional result with a significant pain reduction. The mean postoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 53 (5-84) points.

Adult↗
PubMed2003

Blends of enteric and GIT-insoluble polymers used for film coating: physicochemical characterization and drug release patterns.

THE OBJECTIVES OF THIS STUDY WERE: (i). to use blends of gastrointestinal tract (GIT)-insoluble and enteric polymers (ethyl cellulose and Eudragit L) as coating materials for multiparticulate controlled release dosage forms; (ii). to investigate the effects of the polymer blend ratio and coating level on the resulting drug release patterns; and (iii). to explain the observed phenomena based on the physicochemical properties of the systems. Propranolol HCl-loaded pellets were coated in a fluidized bed coater with organic polymer solutions; thin, drug-containing and drug-free, polymeric films were prepared using a casting knife. In vitro drug release, water uptake and dry weight loss studies were performed in 0.1 M HCl and phosphate buffer pH 7.4, respectively. The apparent drug diffusion coefficients within the polymeric systems were determined using different experimental and theoretical techniques (side-by-side diffusion cells, in vitro drug release from thin films; exact and approximate solutions of Fick's second law of diffusion). A broad range of drug release patterns from coated pellets could be achieved by varying the GIT-insoluble:enteric polymer blend ratio. With increasing relative amounts of Eudragit L, the release rates in both media significantly increased. The increase at low pH could be attributed to an increase in water uptake, as observed with thin films. Interestingly, only partial Eudragit L leaching occurred in phosphate buffer pH 7.4 even at high enteric polymer contents, indicating that the GIT-insoluble polymer effectively hindered the dissolution of the entrapped Eudragit L. At high pH, both polymer leaching and polymer swelling contributed to the control of drug release. The determined apparent drug diffusion coefficients take the two effects adequately into account.

Cellulose↗
PubMed2003

Transient marrow edema syndrome of the hip: results after core decompression. A prospective MRI-controlled study in 22 patients.

BACKGROUND: Transient marrow edema syndrome (TMES) of the hip is a disease of acute onset and severe functional disability. There is histological evidence for an ischemic etiology of TMES of the hip. Core decompression as applied for avascular necrosis (AVN) of the hip is therefore a therapeutic alternative to conservative therapy, the latter leading only to a reduction of symptoms but never a shortening of the course of the disease. METHODS: Between January 1998 and June 2000, 22 hips with TMES were treated with core decompression in our department. TMES was diagnosed by exclusion. MRI was done preoperatively and at 6 months postoperatively. The postoperative MRI result was classified into three categories. RESULTS: After an average of 7.2 (range 1-30) days, all patients were pain-free after core decompression. In 2 patients, TMES progressed to AVN despite core decompression. All others had no signal alterations of the head of the femur on MRI after 6 months. The postoperative Harris Hip Score (HHS) in patients with TMES was on average 93.7 (range 77-95); in patients with AVN, the postoperative HHS was 47 (range 45-49). CONCLUSION: Our results demonstrate that core decompression of the hip significantly shortens the natural course of disease of TMES of the hip.

Adult↗
PubMed2003

[Reliability, validity and responsiveness of the German short musculoskeletal function assessment questionnaire (SMFA-D) in patients with osteoarthritis of the hip undergoing total hip arthroplasty].

BACKGROUND: The aim of the present study was to check for reliability, validity and responsiveness of the Musculoskeletal Function Assessment questionnaire (SMFA-D) in patients with coxarthrosis undergoing total hip replacement. PATIENTS AND METHOD: In a prospective clinical trial the SMFA-D, the SF-36, the Harris Hip score, test of walking speed and the functional impairment according to the physician assessment were recorded. RESULTS: The reliability of the instrument could be demonstrated by a correlation coefficient of r = 0.78 for the function index and r = 0.84 for the bother index. Patients could be distinguished by the physician's assessment to show discriminative validity. Both indices correlated significantly with the Harris Hip score, scales of the SF-36 and the walking speed supporting the construct validity. The responsiveness could be shown with large effect sizes (1.04 for the function index and 1.02 for the bother index) at the three-month follow-up. CONCLUSIONS: The SMFA-D was found to be a reliable, valid and responsive instrument in patients with coxarthrosis undergoing hip replacement and the use of this instrument can be recommended.

Activities of Daily Living↗
PubMed2002

German short musculoskeletal function assessment questionnaire (SMFA-D): comparison with the SF-36 and WOMAC in a prospective evaluation in patients with primary osteoarthritis undergoing total knee arthroplasty.

In a prospective clinical trial, the German short musculoskeletal function assessment (SMFA-D), the short form (SF)-36, and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) were evaluated in 63 patients with primary osteoarthritis undergoing total knee arthroplasty. All instruments were sensitive to change, demonstrating the effect of total knee arthroplasty at 1-year follow-up. The SMFA-D effect sizes in comparable scales were bigger than in the SF-36 and similar to those of the WOMAC. Significant correlations of the SMFA-D indices with the SF-36 and WOMAC scales preoperatively could be shown. After 1-year follow-up, all correlations between the SMFA-D indices and SF-36 scales were significant. In other comparison, only the correlation between the SMFA-D function index and the WOMAC function scales remained significant. The correlation of the SMFA-D function index with external validation criteria was higher than that using the other instruments. We recommend the SMFA-D for assessing change in functional status of patients with primary osteoarthritis of the knee following arthroplasty.

Arthroplasty, Replacement, Knee↗
PubMed2002

Far-infrared vibrational modes of DNA components studied by terahertz time-domain spectroscopy.

The far-infrared dielectric function of a wide range of organic molecules is dominated by vibrations involving a substantial fraction of the atoms forming the molecule and motion associated with intermolecular hydrogen bond vibrations. Due to their collective nature such modes are highly sensitive to the intra- and intermolecular structure and thus provide a unique fingerprint of the conformational state of the molecule and effects of its environment. We demonstrate the use of terahertz time-domain spectroscopy (THz-TDS) for recording the far-infrared (0.5-4.0 THz) dielectric function of the four nucleobases and corresponding nucleosides forming the building blocks of deoxyribose nucleic acid (DNA). We observe numerous distinct spectral features with large differences between the molecules in both frequency-dependent absorption coefficient and index of refraction. Assisted by results from density-functional calculations we interpret the origin of the observed resonances as vibrations of hydrogen bonds between the molecules.

Adenine↗
PubMed2002

Collective vibrational modes in biological molecules investigated by terahertz time-domain spectroscopy.

We present well-resolved absorption spectra of biological molecules in the far-IR (FIR) spectral region recorded by terahertz time-domain spectroscopy (THz-TDS). As an illustrative example we discuss the absorption spectra of benzoic acid, its monosubstitutes salicylic acid (2-hydroxy-benzoic acid), 3- and 4-hydroxybenzoic acid, and aspirin (acetylsalicylic acid) in the spectral region between 18 and 150 cm(-1). The spectra exhibit distinct features originating from low-frequency vibrational modes caused by intra- or intermolecular collective motion and lattice modes. Due to the collective origin of the observed modes the absorption spectra are highly sensitive to the overall structure and configuration of the molecules, as well as their environment. The THz-TDS procedure can provide a direct fingerprint of the molecular structure or conformational state of a compound.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins.

beta1 integrins play a crucial role as cytoskeletal anchorage proteins. In this study, the coupling of the cytoskeleton and intracellular signaling pathways was investigated in beta1 integrin deficient (-/-) embryonic stem cells. Muscarinic inhibition of the L-type Ca2+ current (ICa) and activation of the acetylcholine-activated K+ current (IK,ACh) was found to be absent in beta1 integrin-/- cardiomyocytes. Conversely, beta adrenoceptor-mediated modulation of ICa was unaffected by the absence of beta1 integrins. This defect in muscarinic signaling was due to defective G protein coupling. This was supported by deconvolution microscopy, which demonstrated that Gi exhibited an atypical subcellular distribution in the beta1 integrin-/- cardiomyocytes. A critical role of the cytoskeleton was further demonstrated using cytochalasin D, which displaced Gi and impaired muscarinic signaling. We conclude that cytoskeletal integrity is required for correct localization and function of Gi-associated signaling microdomains.

Acetylcholine↗