Biomedical subjects

C Wagner

Publications and source records attributed to C Wagner.

At least 19 recordsLinked to original sources

PubMed2006

Molecular and pharmacodynamic characteristics of the novel multi-target tumor growth inhibitor ZK 304709.

Loss of cell cycle control and tumor-induced neovascularization are major drivers of human tumor growth. The multi-target tumor growth inhibitor ZK 304709 is a nanomolar inhibitor of cyclin-dependent kinases 1, 2, 4, 7 and 9, as well as vascular endothelial growth factor receptor tyrosine kinase 1-3 and of platelet-derived growth factor receptor beta tyrosine kinase. The multi-targeted mode of action of ZK 304709 acting on cell cycle and angiogenesis resulted in superior efficacy compared to standard chemotherapeutic compounds both in s.c. human tumor xenografts as well as orthotopic human pancreatic carcinoma models.

Angiogenesis Inhibitors↗

PubMed2006

S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man.

This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects.

Adenosylhomocysteinase↗

PubMed2006

The implementation of quality management systems in hospitals: a comparison between three countries.

BACKGROUND: Is the implementation of Quality Management (QM) in health care proceeding satisfactorily and can national health care policies influence the implementation process? Policymakers and researchers in a country need to know the answer to this question. Cross country comparisons can reveal whether sufficient progress is being made and how this can be stimulated. The objective of the study was to investigate agreement and disparities in the implementation of QMS between The Netherlands, Hungary and Finland with respect to the evaluation model used and the national policy strategy of the three countries. METHODS: The study has a cross sectional design, based on measurements in 2000. Empirical data about QM-activities in hospitals were gathered by a self-administered questionnaire. The questionnaires were answered by the directors of the hospitals or the quality coordinators. The analyses are based on data from 101 hospitals in the Netherlands, 116 hospitals in Hungary and 59 hospitals in Finland. Outcome measures are the developmental stage of the Quality Management System (QMS), the development within five focal areas, and distinct QM-activities which were listed in the questionnaire. RESULTS: A mean of 22 QM-activities per hospital was found in the Netherlands and Finland versus 20 QM-activities in Hungarian hospitals. Only a small number of hospitals has already implemented a QMS (4% in The Netherlands,0% in Hungary and 3% in Finland). More hospitals in the Netherlands are concentrating on quality documents, whereas Finnish hospitals are concentrating on training in QM and guidelines. Cyclic quality improvement activities have been developed in the three countries, but in most hospitals the results were not used for improvements. All three countries pay hardly any attention to patient participation. CONCLUSION: The study demonstrates that the implementation of QM-activities can be measured at national level and that differences between countries can be assessed. The hypothesis that governmental legislation or financial reimbursement can stimulate the implementation of QM-activities, more than voluntary recommendations, could not be confirmed. However, the results show that specific obligations can stimulate the implementation of QM-activities more than general, framework legislation.

Cross-Cultural Comparison↗

PubMed2006

Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon.

BACKGROUND: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. METHODS: This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by videolaparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n=7, 5 ml/kg) or c5N (n=11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. RESULTS: Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. CONCLUSION: In baboons with induced endometriosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.

Animals↗

PubMed2006

Measuring the transverse magnetization of rotating ferrofluids.

We report on measurements of the transverse magnetization of a ferrofluid rotating as a rigid body in a constant magnetic field, H0, applied perpendicular to the axis of rotation. The rotation of the fluid leads to a nonequilibrium situation, where the ferrofluid magnetization M and the magnetic field within the sample, H, are no longer parallel to each other. The off-axis magnetization perpendicular to H0 is measured as a function of both the applied magnetic field H0 and the angular frequency Omega. The latter ranges from a few hertz to frequencies well above a characteristic inverse Brownian relaxation time. Our experimental results strongly indicate that the transverse magnetization is caused only by a small fraction of the colloidal ferromagnetic particles. The effect of the polydispersity of the ferrofluid is discussed. Experimental results are compared to predictions based on several theoretical models. A single-time relaxation approach for the so-called effective field and a field-dependent Debye relaxation of M yield reasonably good shapes of the curves of transverse magnetization vs Omega. However, like the other models, they overestimate their magnitudes.

Journal Article↗

PubMed2006

[Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of long bones].

BACKGROUND: Nonunions of long bone fractures are considerable therapeutic and economic problems with increasing tendency. Basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation with compression, and bone transport techniques. If these methods fail to work, alternative treatment options are needed. MATERIAL AND METHODS: Since May 2001 treatment with recombinant human (rh) bone morphogenic protein 7 [BMP-7 or osteogenic protein 1 (OP-1)] in combination with a type one collagen carrier has gained interest. BMP 7 induces the formation of new bone by differentiation of stem cells, thereby initiating the reaction cascade of osteogenesis. Nonunions over 9 months and unsuccessful bone grafting delineate the indication. RESULTS: We report our experience with 21 patients and nonunion of long bone fractures. Between July 2002 and June 2004, 23 units of BMP 7 were implanted. The implantation sites were 7 femora, 12 tibias, 2 humeri, and 2 forearms. In ten cases BMP 7 was combined with a new osteosynthesis and bone grafting and in five patients with bone grafting alone. In contrast in eight patients BMP 7 was applied as a single procedure without any bone grafting or any change of the osteosynthesis. CONCLUSION: There were no peri- or postoperative complications. Follow-up was obtained for a minimum of 6 months. Of 23 implantations, 22 were successful with bony healing revealed by clinical and radiological evaluation. In one patient no bony consolidation of the nonunion has been seen so far. In summary, based on our results we propose BMP 7 as an additional innovative therapy of long bone nonunions.

Adult↗

PubMed2006

[Implant-associated post-traumatic osteomyelitis. Bacterial biofilms and the immune defence as protagonists of the local inflammatory process].

BACKGROUND: Formation of bacterial biofilms on implants is a severe complication following orthopaedic surgery. In the present study we addressed the role of the immune response, particularly with regard to the pathogenesis of the disease. METHODS: In a prospective study comprising 74 patients with implant-associated post-traumatic osteomyelitis, peripheral blood cells as well as cells recovered from the infected site during surgery were characterised phenotypically and functionally. RESULTS: We found massive infiltration of polymorphonuclear neutrophils (PMN), which were highly activated, particularly regarding their bactericidal potential, such as increased production of superoxides and upregulation of activation-associated surface receptors. CONCLUSION: PMN are activated in response to the implant-associated osteomyelitis; they also infiltrate the infected tissue, but cannot control the infection. By release of their cytotoxic entities they could contribute to tissue destruction and eventually to osteolysis.

Adolescent↗

PubMed2006

An update on acid secretion.

Gastric acid secretion is a complex process that requires hormonal, neuronal, or calcium-sensing receptor activation for insertion of pumps into the apical surface of the parietal cell. Activation of any or all these pathways causes the parietal cell to secrete concentrated acid with a pH at or close to 1. This acidic fluid combines with enzymes that are secreted from neighbouring chief cells and passes out of the gland up through a mucous gel layer covering the surface of the stomach producing a final intragastric pH of less than 4 during the active phase of acid secretion. Defects in either the mucosal barrier or in the regulatory mechanisms that modulate the secretory pathways will result in erosion of the barrier and ulcerations of the stomach or esophagus. The entire process of acid secretion relies on activation of the catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of acid into the parietal cell canaliculus, with K+ being the important and rate-limiting ion in this activation process. In addition to K+ as a rate limiter for acid production, Cl- secretion via an apical channel must also occur. In this review we present a discussion of the mechanics of acid secretion and a discussion of recently identified transporter proteins and receptors. Included is a discussion of some of the recent candidates for the apical K' recycling channel, as well as two recently identified apical proteins (NHE-3, PAT-1), and the newly characterized calcium-sensing receptor (CaSR). We hope that this review will give additional insight into the complex process of acid secretion.

Animals↗

PubMed2006

A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme.

Three human cases having mutations in the glycine N-methyltransferase (GNMT) gene have been reported. This enzyme transfers a methyl group from S-adenosylmethionine (SAM) to glycine to form S-adenosylhomocysteine (SAH) and N-methylglycine (sarcosine) and is believed to be involved in the regulation of methylation. All three cases have mild liver disease but they seem otherwise unaffected. To study this further, gnmt deficient mice were generated for the first time. This resulted in the complete absence of GNMT protein and its activity in livers of homozygous mice. Compared to WT animals the absence of GNMT resulted in up to a 7-fold increase of free methionine and up to a 35-fold increase of SAM. The amount of SAH was significantly decreased (3 fold) in the homozygotes compared to WT. The ratio of SAM/SAH increased from 3 in WT to 300 in livers of homozygous transgenic mice. This suggests a possible significant change in methylation in the liver and other organs where GNMT is expressed.

Animals↗

PubMed2006

[Independent dental patient consultation service--experiences of the information center for the Rhine-Neckar district].

Patients should be the focus of health care - or so resounds the frequently heard cry of politicians, consumer protection groups and patient representatives. It cannot be denied that the increased co-determination of the insured and of patients in the health service is a sign of the times. Demanding ever increasing health insurance premiums and exacting higher additional contributions from patients on the one hand without increasing their say and their rights on the other hand meets with little sympathy. Spouting like a mantra about "personal responsibility", the "voice of the patient" or the "sovereignty of the consumer" in talk-shows or studio debates is not sufficient. Words must be followed up by actions in order to give patients the necessary skills to enable them to make autonomous decisions. One step in this direction is the model of an independent dental consumer and patient advisory service in the Rhine-Neckar district health authority presented here and sponsored by the central associations of the health insurance companies in the scope of the funding provided under section sign 65 b SGB V [Social Security Code]. Since 2001 over 4000 people seeking advice have received information about dental treatment, planned therapies or legal issues. More than half of those seeking advice are between 40 and 70 years old and the number of women outweighs the number of men. The majority of patients want an independent second opinion, demonstrating the limits of call centres or Internet advice services. The anonymity of the consultation is an important factor for those seeking advice. The successful integration of the advisory service is evident, not only from the high number of consultations, but also from the fact that the majority of those seeking advice have been referred to the service by their respective health insurance company. For various reasons it can be assumed that there will be an increasing demand for qualified dental advice. It is therefore incumbent on health policy to create a regulatory framework and to ensure the funding on a broader base. Wherever possible the public health service can take control, ensuring the independence of the advisory service and guaranteeing that group interests remain outside.

Adolescent↗

PubMed2006

Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria.

Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,on intensified (>or=4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day,p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit ofSMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.insulin therapy and center difference, the SMBG frequency was associated with better metabolic control (HbA1c-reduction of0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,insulin therapy and center difference, the SMBG frequency wasassociated with better metabolic control (HbA1c-reduction of 0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients on intensified (>or= 4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day, p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit of SMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.

Austria↗

PubMed2006

Cellular inflammatory response to persistent localized Staphylococcus aureus infection: phenotypical and functional characterization of polymorphonuclear neutrophils (PMN).

Persistent, localized Staphylococcus aureus infections, refractory to antibiotic treatment, can result in massive tissue destruction and surgical intervention is often the only therapeutic option. In that context, we investigated patients with S. aureus-induced infection at various sites, apparent as either olecranon bursitis, empyema of the knee joint or soft tissue abscess formation. As expected, a prominent leucocyte infiltrate was found, consisting predominantly of polymorphonuclear neutrophils (PMN) (up to 75%) and to a lesser extent of T lymphocytes and natural killer (NK) cells. In line with their bactericidal capacity, PMN expressed the high-affinity receptor for IgG, CD64 and the lipopolysaccharide (LPS) receptor CD14; moreover, the oxygen radical production in response to the bacterial peptide f-MLP was enhanced, while chemotactic activity was greatly reduced. The more intriguing finding, however, was that a portion of PMN had acquired major histocompatibility complex (MHC) class II antigens and CD83, indicative of a transdifferentiation of PMN to cells with dendritic-like characteristics. Of note is that a similar transdifferentiation can be induced in PMN in vitro, e.g. by gamma interferon or by tumour necrosis factor alpha. Co-cultivation of transdifferentiated PMN with autologous T lymphocytes resulted in prominent T cell proliferation, provided that S. aureus enterotoxin A was added. Taken together, persistent S. aureus infection induces PMN to acquire characteristics of dendritic cells, which in turn might promote the local immune response.

Aged↗

PubMed2005

Droplet detachment and satellite bead formation in viscoelastic fluids.

The presence of a very small amount of high molecular weight polymer significantly delays the pinch-off singularity of a drop of water falling from a faucet and leads to the formation of a long-lived cylindrical filament. In this Letter, we present experiments, numerical simulations, and theory which examines the pinch-off process in the presence of polymers. The numerical simulations are found to be in good agreement with experiment. As a test case, we establish the conditions under which a small bead remains on the filament; we find that the presence of a bead is due to the asymmetry induced by the self-similar pinch off of the droplet.

Journal Article↗

PubMed2005

Functional stoichiometric analysis of metabolic networks.

MOTIVATION: An important tool in Systems Biology is the stoichiometric modeling of metabolic networks, where the stationary states of the network are described by a high-dimensional polyhedral cone, the so-called flux cone. Exhaustive descriptions of the metabolism can be obtained by computing the elementary vectors of this cone but, owing to a combinatorial explosion of the number of elementary vectors, this approach becomes computationally intractable for genome scale networks. RESULT: Hence, we propose to instead focus on the conversion cone, a projection of the flux cone, which describes the interaction of the metabolism with its external chemical environment. We present a direct method for calculating the elementary vectors of this cone and, by studying the metabolism of Saccharomyces cerevisiae, we demonstrate that such an analysis is computationally feasible even for genome scale networks.

Algorithms↗

PubMed2005

[Patient safety in hospitals].

In various studies outside the Netherlands, it has been shown that a substantial number of patients suffer some kind of damage during their treatment in a hospital. The incidence of these so-called adverse events varies between 2.9% and 16.6%; of these, estimates between more than a quarter and up to half are considered to have been avoidable. Preventable adverse events can offer a starting point for interventions to increase patient safety. Therefore, a study has been initiated in Dutch hospitals investigating the nature and extent of adverse events and their causes. Important goals of the study are to reach a consensus on basic concepts and to improve the research methodology.

Hospitalization↗

PubMed2005

Spatiotemporal characterization of interfacial Faraday waves by means of a light absorption technique.

We present measurements of the complete spatiotemporal Fourier spectrum of Faraday waves. The Faraday waves are generated at the interface of two immiscible index matched liquids of different density. By use of a light absorption technique we are able to determine the bifurcation scenario from the flat surface to the patterned state for each complex spatial and temporal Fourier component separately. The surface spectra at onset are found to be in good agreement with the predictions from the linear stability analysis. For the nonlinear state our measurements show in a direct manner how energy is transferred from lower to higher harmonics and we quantify the nonlinear coupling coefficients. Furthermore we find that the nonlinear coupling generates static components in the temporal Fourier spectrum leading thus to a contribution of a nonoscillating permanent sinusoidal deformed surface state. A comparison of hexagonal and rectangular patterns reveals that spatial resonance can give rise to a spectrum that violates the temporal resonance conditions given by the weakly nonlinear theory.

Journal Article↗

PubMed2005

Faraday instability in a surface-frozen liquid.

Faraday surface instability measurements of the critical acceleration, a(c), and wave number, k(c), for standing surface waves on a tetracosanol (C24H50) melt exhibit abrupt changes at T(s)=54 degrees C, approximately 4 degrees C above the bulk freezing temperature. The measured variations of a(c) and k(c) vs temperature and driving frequency are accounted for quantitatively by a hydrodynamic model, revealing a change from a free-slip surface flow, generic for a free liquid surface (T>T(s)), to a surface-pinned, no-slip flow, characteristic of a flow near a wetted solid wall (T<T(s)). The change at T(s) is traced to the onset of surface freezing, where the steep velocity gradient in the surface-pinned flow significantly increases the viscous dissipation near the surface.

Journal Article↗

PubMed2005

Transdifferentiation of polymorphonuclear neutrophils to dendritic-like cells at the site of inflammation in rheumatoid arthritis: evidence for activation by T cells.

OBJECTIVES: To investigate infiltrated cells in the synovial fluid (SF) of inflamed joints of patients with rheumatoid arthritis (RA), with special reference to polymorphonuclear neutrophils (PMN) and their interaction with T cells. METHODS: Expression on PMN of activation associated receptors CD14, CD64, CD83, and major histocompatibility complex (MHC) class II was examined in the SF of 15 patients with RA, as were the infiltrated T cells. SF cytokines were determined by enzyme linked immunosorbent assay (ELISA). To mimic the in vivo situation, co-culture experiments were carried out using PMN and T cells of healthy donors. RESULTS: The SF contained activated T lymphocytes and abundant PMN. SF PMN expression of CD14 and CD64 was enhanced compared with peripheral blood. Of special interest was the observation that only the SF PMN expressed MHC class II antigens and CD83. Exposure to SF, which contained considerable amounts of cytokines (for example, interferon gamma (IFNgamma), tumour necrosis factor alpha, and interleukin 2), induced a similar receptor pattern on blood derived PMN of healthy donors. Furthermore, PMN acquired MHC class II and CD83 within 24 to 48 hours, when co-cultured with autologous T cells or T cell lines. This effect was also achieved by T cell supernatants, was dependent on protein synthesis, and could be inhibited by antibodies against IFNgamma. CONCLUSIONS: SF PMN from patients with RA undergo major alterations, including transdifferentiation to cells with dendritic-like characteristics, probably induced by T cell derived cytokines. Because MHC class II positive PMN are known to activate T cells, the mutual activation of PMN and T cells might contribute to the perpetuation of the local inflammatory process, and eventually to the destructive process in RA.

Antigens, CD↗