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C Wagner

Publications and source records attributed to C Wagner.

At least 37 records · Page 2Linked to original sources
PubMed2001

The impact of legislative versus non-legislative quality policy in health care: a comparison between two countries.

UNLABELLED: An important aim of the government's quality policy is to stimulate quality management (QM) in health care organizations. The relationship between the government's quality policy and QM in health care organizations is unknown. This article explores that relationship by comparing two countries with different quality policies, The Netherlands and Finland. In The Netherlands QM is required by law and health care is organized at national level. In Finland, QM is not required by law and the responsibilities for organizing health care are delegated to the municipalities. The question is whether or not these differences in national policy are reflected in the extent and effectiveness of QM in health care organizations in the two countries. A cross sectional survey was conducted in late 1999. Data about QM in both countries were gathered by questionnaire. The subsectors involved were hospitals, care for the disabled and care for the elderly. A total of 1172 health care organizations participated in the study (response rate 64%). The results show that-in keeping with our hypothesis-slightly more QM-activities and more patient participation were found in Dutch health care organizations compared with the Finnish ones. However, contrary to our expectations, the Finnish organizations reported more perceived effects of their QM-activities. Further analyses showed that some QM-activities are more closely related to the effectiveness of QM than others. In particular, cyclic quality improvement procedures, human resource management and the flexible attitude of employees showed the strongest relationship with the perceived effects of QM. The difference between the national approach in The Netherlands and the decentralized approach in Finland did not, as we had assumed, result in more regional variation in QM in Finland. CONCLUSIONS: a government's quality policy may have some influence on the extent of QM in health care organizations. However, more QM-activities do not necessarily imply more effects. RECOMMENDATIONS: since QM-activities differ in the degree to which they bring about changes and improvements in care, it is recommended that policy makers promote those QM-activities, which are the most potent, in order to improve the quality of care.

Aged↗
PubMed2001

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.

Alanine Transaminase↗
PubMed2001

Hyaluronan-independent adhesion of CD44H+ and CD44v10+ lymphocytes to dermal microvascular endothelial cells and keratinocytes.

We have recently shown the CD44 variant isoform 10 (CD44v10) to be expressed on reactive as well as malignant cutaneous lymphocytes; however, the functional consequences of CD44v10 expression on lymphocytes are not elucidated. By using appropriately transfected lymphatic cells we analyzed the role of CD44v10 on lymphocytes in cell-matrix adhesion and homotypic and heterotypic cell-cell adhesion assays. Despite a low binding affinity to hyaluronan, CD44v10-expressing lymphocytes exhibited heterotypic cell-cell adhesion to inflamed dermal microvascular endothelium and keratinocytes, as indicated by Stamper-Woodruff assays on tissue sections of delayed type hypersensitivity reactions and adhesion assays with cultured keratinocytes and cytokine-stimulated human dermal microvascular endothelial cells. Antibody-blocking assays excluded interaction of CD44v10 with the principal CD44 ligand hyaluronan as well as involvement of selectins or integrins in these heterotypic cell-cell adhesion assays. In contrast, cellular aggregation assays with fluorescence-labeled CD44v10- and CD44H-expressing lymphocytes revealed homotypic CD44v10/CD44v10 binding as well as binding of CD44v10 with CD44H. Heterotypic cell-cell adhesion assays with ultraviolet-A-irradiated CD44v-negative cytokine-stimulated endothelial cells demonstrated binding kinetics of CD44v10-expressing lymphocytes paralleling those of endothelial CD44H expression. These results imply that a hyaluronan-independent CD44v10/CD44H-mediated pathway is involved in lymphocyte infiltration into the dermis and epidermis of inflamed skin and suggest modulation of CD44H expression on inflamed dermal microvascular endothelium as a mechanism of ultraviolet-A-induced therapeutic effects on the skin.

Cell Adhesion↗
PubMed2001

Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease.

BACKGROUND: Anti-TNFalpha therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNFalpha, a cytokine involved in host-defence against certain infections. AIM: To evaluate the effects of infliximab on the gut and peripheral immune system functions. METHODS: Biopsies and blood samples from three clinical trials of infliximab in Crohn's disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed. RESULTS: Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNgamma and TNFalpha did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy. CONCLUSION: The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn's disease patients.

Antibodies, Monoclonal↗
PubMed2001

The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the pleiotropic repressor Sin3 and the transcriptional activator Ino2.

Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcriptionally co-regulated by ICRE (inositol/choline-responsive element) promoter motifs. Gene activation by an ICRE is mediated by binding of the Ino2/Ino4 transcription factor, whereas repression in the presence of high concentrations of inositol and choline (IC) requires an intact Opi1 repressor. However, the mechanism of specific repression and the functional interplay among these regulators remained unclear from previous work. Using in vivo as well as in vitro interaction assays, we show binding of the pleiotropic repressor Sin3 to the pathway-specific regulator Opi1. The paired amphipathic helix 1 (PAH1) within Sin3 and OSID (Opi1-Sin3 interaction domain) in the N-terminus of Opi1 were mapped as contact sites. The regulatory significance of the Opi1-Sin3 interaction was shown by the obvious deregulation of an ICRE-dependent reporter gene in a sin3 mutant. Opi1 also interacts with a newly identified functional domain of the transcriptional activator Ino2 (RID, repressor interaction domain). These results define the molecular composition of the transcription complex mediating control of ICRE-dependent genes and allow a hypothesis on the flow of regulatory information in response to phospholipid precursors.

Amino Acid Sequence↗
PubMed2001

Polymorphonuclear neutrophils in Wegener's granulomatosis acquire characteristics of antigen presenting cells.

BACKGROUND: Constitutive expression of major histocompatibility complex (MHC) class II antigens and of the co-stimulatory receptors CD80 and CD86 is restricted to professional antigen presenting cells. Polymorphonuclear neutrophils (PMN) of healthy donors are negative for those antigens. Our recent study, however, found that PMN of patients with active Wegener's granulomatosis acquired MHC class II antigens. METHODS: To continue and extend the previous study results, PMN and monocytes of 60 patients with Wegener's granulomatosis, 24 patients with microscopic polyangiitis (MPA), 20 patients with acute bacterial infection, and 53 healthy donors were analyzed for the expression of MHC class II antigens as well as of CD80 and CD86. Moreover, induction on PMN of MHC class II expression was studied, as was antigen presentation as a possible functional consequence. RESULTS: PMN of patients with acute, active Wegener's granulomatosis expressed MHC class II antigens, CD80 and CD86; on monocytes up-regulation of MHC class II was seen. In contrast, PMN of patients with inactive disease, or with relapse, patients with microscopic polyangiitis or with bacterial infections expressed neither MHC class II, nor CD80 or CD86. PMN of healthy donors acquired these antigens when cultured in the presence of T cells or T cell-derived cytokines. The PMN were then able to present to T cell antigens in a MHC-class II restricted manner. CONCLUSION: During active disease, the PMN of patients with Wegener's granulomatosis acquire characteristics of antigen presenting cells, whereas the PMN of patients with MPA or bacterial infection do not. The finding reflects differences in the pattern of the respective inflammatory response and suggests new effector functions of PMN. Moreover, MHC class II expression on PMN could serve as a novel marker for active Wegener's granulomatosis.

Adult↗
PubMed2001

Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine.

BACKGROUND: Although plasma total homocysteine has been identified as an independent risk factor for vascular disease in a multitude of studies, there is a considerable overlap in values between patients at risk and control subjects. The difference in values can be used to distinguish statistically between the 2 groups, provided each group is large enough; however, discriminating between individual patients at risk and control subjects is difficult. OBJECTIVE: We investigated whether the precursor of homocysteine, S-adenosylhomocysteine, is a more sensitive indicator of risk. DESIGN: We measured plasma total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, creatinine, folate, and vitamin B-12 in 30 patients with proven cardiovascular disease and 29 age- and sex-matched control subjects. RESULTS: The homocysteine values (+/-SD) were 12.8 +/- 4.9 (95% CI: 11.0, 14.7) micromol/L for patients and 11.0 +/- 3.2 (9.8, 12.2) micromol/L for control subjects. The S-adenosylhomocysteine values were 40.0 +/- 20.6 (32.3, 47.7) nmol/L for patients and 27.0 +/- 6.7 (24.5, 30.0) nmol/L for control subjects (P = 0.0021). The S-adenosylmethionine values were 121.8 +/- 42.9 (105.8, 137.8) nmol/L for patients and 103.9 +/- 21.8 (95.6, 112.2) nmol/L for control subjects (P = 0.0493). The creatinine values were 110 +/- 27 (97, 120) micromol/L for patients and 97 +/- 9 (80, 100) micromol/L for control subjects (P = 0.0025). Values for folate and vitamin B-12 did not differ significantly between groups. CONCLUSIONS: Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine. Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients.

Adult↗
PubMed2001

A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse.

Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day the aqueduct becomes obliterated and severe hydrocephalus develops. The aim of the present investigation was to investigate the mechanism of this hydrocephalus, probably starting during fetal life when the cerebral aqueduct is still patent. By use of immunocytochemistry and scanning electron microscopy, mutant (n = 54) and normal (n = 61) hyh mouse embryos were studied at various developmental stages to trace the earliest microscopic changes occurring in the brains of embryos becoming hydrocephalic. The primary defect begins at an early developmental stage (E-12) and involves cells lining the brain cavities, which detach following a well-defined temporo-spatial pattern. This ependymal denudation mostly involves the ependyma of the basal plate derivatives. There is a relationship between ependymal denudation and ependymal differentiation evaluated by the expression of vimentin and glial fibrillary acidic protein. The ependymal cells had a normal appearance before and after detachment, suggesting that their separation from the ventricular wall might be due to abnormalities in cell adhesion molecules. The process of detachment of the ventral ependyma, clearly visualized under scanning electron microscope, is almost completed before the onset of hydrocephalus. Furthermore, this ependymal denudation does not lead to aqueductal stenosis during prenatal life. Thus, the rather massive ependymal denudation appears to be the trigger of hydrocephalus in this mutant mouse, raising the question about the mechanism responsible for this hydrocephalus. It seems likely that an uncontrolled bulk flow of brain fluid through the extended areas devoid of ependyma may be responsible for the hydrocephalus developed by the hyh mutant embryos. The defect in these embryos also includes loss of the hindbrain floor plate and a delayed in the expression of Reissner fiber glycoproteins by the subcommissural organ.

Animals↗
PubMed2001

Environmental and organizational determinants of quality management.

The aim of the study was to obtain more insight into the organizational and environmental determinants of the implementation of quality management in health care organizations. Primary survey data were collected in 1995 in a large nationwide study within 15 fields of health care and health care-related social services in The Netherlands. In general, there are more differences between health care organizations than between fields of health care. Environmental influence was found to be less important than was expected. Care-oriented organizations have a greater opportunity to involve their patients. It seems that apart from patients, the perceived pressure from other third parties has little influence on the implementation of quality management in health care organizations.

Cross-Sectional Studies↗
PubMed2001

Impact of extracellular folate levels on global gene expression.

Methylation of DNA is associated with gene silencing. DNA methylation uses S-adenosylmethionine (SAM) as the methyl donor and the formation of SAM requires a continuous supply of folate from the extracellular milieu. Low extracellular folate levels are known to result in induction of expression of the human alpha folate receptor in nasopharyngeal epidermoid carcinoma cells. Low folate levels have been implicated in global activation of gene expression. We have investigated the impact of lowering the level of extracellular folate by performing cDNA microarray analysis of global gene expression in human nasopharyngeal carcinoma KB cells grown in folate-deplete and folate-replete medium. We found that expression of only eight genes reproducibly responded to variation of folate levels. Among those, three were up-regulated and five were down-regulated. Examination of one gene, H-cadherin, demonstrated down-regulation in response to folate depletion. Despite the low level of extracellular folate, there was hypermethylation of H-cadherin 5' sequences. These data indicate that low extracellular folate positively and negatively influences the expression levels of a small cohort of genes. The data suggest that folate deficiency is associated with gene-specific methylation/demethylation, rather than global DNA demethylation and transcriptional activation.

Cadherins↗
PubMed2001

The effectiveness of quality systems in nursing homes: a review.

BACKGROUND: The need for quality improvement and increasing concern about the costs and appropriateness of health care has led to the implementation of quality systems in healthcare organisations. In addition, nursing homes have made significant investments in their development. The effects of the implementation of quality systems on health related outcomes are not yet clear. OBJECTIVE: To examine evidence in the literature on whether quality systems have an impact on the care process and the satisfaction and health outcomes of long term care residents. METHODS: Review of the literature. RESULTS: The 21 empirical studies identified concerned quality system activities such as the implementation of guidelines; providing feedback on outcomes; assessment of the needs of residents by means of care planning, internal audits and tuition; and an ombudsman for residents. Only four articles described controlled studies. The selected articles were grouped according to five focal areas of quality. The opinion of residents was seldom used to evaluate the effectiveness of quality systems. The effects on care processes and the health outcomes of long term care residents were inconsistent, but there was some evidence from the controlled studies that specific training and guidelines can influence the outcomes at the patient level. CONCLUSIONS: The design of most of the studies meant that it was not possible to attribute the results entirely to the newly implemented quality system. As it is difficult in practice to design a randomised controlled study, future research into the effectiveness of quality systems should not only focus on selected correlates of quality, but should also include a qualitative and quantitative (multivariate and multilevel) approach. The methods used to measure quality need to be improved.

Aged↗
PubMed2001

[Decade of quality health care: dentists in comparison with other health professionals].

In 1990 the Dutch organisations for health care providers, patients-organizations and insurance companies agreed on the implementation of quality systems in health care. Ever since, the health care professions--including dentists--are being involved in the development of quality systems to assure and improve the quality of care. In 2000 a national survey has been conducted to investigate which quality systems already were developed by Dutch health care professions and a comparison between the professions has been made. It appeared that the quality systems of the professions are characterised by four pillars. 1. professional expertise; 2. evidence based guidelines for good practice; 3. peer review directed at continuous improvement; and 4. re-licensing or certification to guarantee the quality. The study showed that the professions differ in the quality policies they pursue and in the progress which has been made. In dental practice an accent in the quality policy is on peer review (whereas in general practice the accent is on guidelines). Ranking the professions in the degree in which the quality system are developed, medical doctors and pharmacists are front-runners, dentist are in the middle rank whereas nurses and psychologists are lagging behind. For the years to come, a priority has been set on further implementation of the quality systems.

Certification↗
PubMed2000

Optimized chaos control with simple limiters.

We present an elementary derivation of chaos control with simple limiters using the logistic map and the Henon map as examples. This derivation provides conditions for optimal stabilization of unstable periodic orbits of a chaotic attractor.

Journal Article↗
PubMed2000

Two novel residues in M2 of the gamma-aminobutyric acid type A receptor affecting gating by GABA and picrotoxin affinity.

An amino acid residue was found in M2 of gamma-aminobutyric acid (GABA) type A receptors that has profound effects on the binding of picrotoxin to the receptor and therefore may form part of its binding pocket. In addition, it strongly affects channel gating. The residue is located N-terminally to residues suggested so far to be important for channel gating. Point mutated alpha1beta(3) receptors were expressed in Xenopus oocytes and analyzed using the electrophysiological techniques. Coexpression of the alpha(1) subunit with the mutated beta(3) subunit beta(3)L253F led to spontaneous picrotoxin-sensitive currents in the absence of GABA. Nanomolar concentrations of GABA further promoted channel opening. Upon washout of picrotoxin, a huge transient inward current was observed. The reversal potential of the inward current was indicative of a chloride ion selectivity. The amplitude of the inward current was strongly dependent on the picrotoxin concentration and on the duration of its application. There was more than a 100-fold decrease in picrotoxin affinity. A kinetic model is presented that mimics the gating behavior of the mutant receptor. The point mutation in the neighboring residue beta(3)A252V resulted in receptors that displayed an about 6-fold increased apparent affinity to GABA and an about 10-fold reduced sensitivity to picrotoxin.

Amino Acid Sequence↗
PubMed2000

Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance.

The neutral amino acid transporter ASCT2 mediates electroneutral obligatory antiport but at the same time requires Na(+) for its function. To elucidate the mechanism, ASCT2 was expressed in Xenopus laevis oocytes and transport was analysed by flux studies and two-electrode voltage clamp recordings. Flux studies with (22)NaCl indicated that the uptake of one molecule of glutamine or alanine is accompanied by the uptake of four to seven Na(+) ions. Similarly to the transport of amino acids, the Na(+) uptake was mediated by an obligatory Na(+) exchange mechanism that depended on the presence of amino acids but was not stoichiometrically coupled to the amino acid transport. Other cations could not replace Na(+) in this transport mechanism. When NaCl was replaced by NaSCN in the transport buffer, the superfusion of oocytes with amino acid substrates resulted in large inward currents, indicating the presence of a substrate-gated anion channel in the ASCT2 transporter. The K(m) for glutamine derived from these experiments is in good agreement with the K(m) derived from flux studies; it varied between 40 and 90 microM at holding potentials of -60 and -20 mV respectively. The permeability of the substrate-gated anion conductance decreased in the order SCN(-)>>NO(3)(-)>I(-)>Cl(-) and also required the presence of Na(+).

Amino Acid Transport Systems↗
PubMed2000

Differentiation of polymorphonuclear neutrophils in patients with systemic infections and chronic inflammatory diseases: evidence of prolonged life span and de novo synthesis of fibronectin.

Polymorphonuclear neutrophils (PMN) are considered to be short-lived, terminally differentiated cells undergoing spontaneous apoptosis if not appropriately stimulated. In patients with systemic infections and inflammatory disease, however, PMN have an extended life span and acquire new surface receptors and functions. Expression of CD64, the high-affinity receptor for immunoglobulin, has been found, and functionally active elastase and surface-associated fibronectin as well. The latter is of particular interest since fibronectin is known as a multifunctional, multimodal extracellular matrix protein, participating in cell adherence, cell signaling, and cell cycle control. To study the surface-associated fibronectin further, PMN of healthy donors were cultivated to induce de novo synthesis of fibronectin. PMN produced fibronectin, which remained associated with the cell surface, where it was partially cleaved. PMN derived fibronectin exhibited a rare splice pattern: predominantly fibronectin containing the extradomain B (EDB) was generated, but evidently no IIICS domain; the latter is known as a receptor for beta1 integrins. How the presence of EDB affects the properties of fibronectin is not yet understood. Studies with recombinant EDB have failed to show a membrane-binding site or a direct participation of EDB in the adhesion process. The function of PMN-associated fibronectin is still under investigation. The rapid cleavage by surface-associated proteases suggests that fibronectin acts as a tightly regulated adhesion protein, and probably also as a precursor molecule for fibronectin-derived biologically active mediators.

Alternative Splicing↗
PubMed2000

Endogenous nitric oxide attenuates erythropoietin gene expression in vivo.

This study aimed to investigate the role of endogenous nitric oxide (NO) in erythropoietin (EPO) gene expression in mice in vivo. For this purpose EPO mRNA was semiquantitated by ribonuclease protection assay in livers and kidneys of three groups of mice: wild-type (wt), endothelial NO-synthase (NOS) knockout mice (eNOS-/-), and wt treated with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (50 mg x kg(-1) x day(-1)) for 4 days (wt+L-NAME). EPO gene expression was stimulated by normobaric hypoxia (8% O2) or by 0.1% carbon monoxide (CO) inhalation for 4 h each, or by intraperitoneal injection of 60 mg/kg cobaltous chloride (CoCl2) for 6 h. Renal EPO mRNA in wt increased 12-, 40-, and 13-fold over normoxic levels in response to hypoxia, CO and CoCl2 respectively. EPO mRNA was detectable in the livers only after CO exposure. Renal and hepatic EPO gene expression in wt+L-NAME appeared moderately increased relative to wt with a maximal 2.5-fold enhancement after CO exposure. EPO mRNA levels in eNOS-/- mirrored those of wt+L-NAME, but the effects were less prominent. Our data suggest that endogenous NO attenuates EPO gene expression in mice. This effect is dependent on the rate of EPO gene induction.

Animals↗