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Biomedical subjects

C Wagner

Publications and source records attributed to C Wagner.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2000

Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice.

Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS-/-), and eNOS-deficient (eNOS-/-) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg(-1) day(-1)). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS-/- mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS-/- mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS-/- mice, but not in eNOS-/- mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.

Animals↗
PubMed2000

Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5 years, and treated with NSAIDs for more than 50 months, were included in the study. Besides conventional markers of renal function (i.e. plasma creatinine, estimated glomerular filtration rate, creatinine clearance), we analysed plasma cystatin C by an automated, nephelometric immunoassay on a Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels of plasma cystatin C, whereas only three out of 56 patients showed an elevated plasma creatinine, even though the creatinine clearance was decreased in 57% of these patients. Cystatin C exhibited a by far better correlation with creatinine clearance than plasma creatinine. In conclusion, patients with prolonged RA for more than 50 months, show a disturbed renal function despite normal plasma creatinine. Elevated cystatin C indicates such incipient renal disease, and is, not least because of a simple, well reproducible technique, more recommendable for screening purposes than tedious clearance determinations.

Aged↗
PubMed2000

Living related liver transplantation in infants and children: report of anesthetic care and early postoperative morbidity and mortality.

STUDY OBJECTIVE: To determine those infants at high risk for perioperative complications and mortality following living, related liver transplantation. DESIGN: Retrospective chart review. SETTING: Large metropolitan teaching hospital. MEASUREMENTS AND MAIN RESULTS: The charts and anesthetic records of the 12 infants and children who received the left lateral hepatic segment from a living relative the past 2 years at our institution were reviewed. The records were examined to determine the causes of perioperative morbidity and to identify patients at high risk for serious complications and mortality. All infants and children (mean +/- SD age, 29+/-30 months; weight, 13.6 +/-6.8 kg) survived the operation (8.3+/-1.7 hours) without intraoperative complications. The average blood loss, including 500 mL of recipient blood used to flush the liver before reperfusion, was 1483 +/-873 mL (119+/-70 mL/kg). Three infants developed portal vein thrombosis, and one of these infants also had hepatic artery thrombosis. The risk of vessel thrombosis was significantly higher (3/3 vs. 0/9; p<0.0045) in infants less than 9 kg body weight, as was the risk of death (2/3 vs. 0/9; p<0.045). Both children who died had vascular thrombosis. Other serious complications were bleeding, 6; infection, 7; acute rejection, 3; and bile leak, 2. CONCLUSIONS: Infants and children can successfully undergo living, related liver transplantation. However, the risks of vascular complications and death are greater in infants less than 9 kg body weight.

Anesthesia↗
PubMed2000

Fibronectin synthesis by activated T lymphocytes: up-regulation of a surface-associated isoform with signalling function.

Fibronectin (FN) is a major constituent of the extracellular matrix. We now provide evidence for a surface-associated isoform of FN that is synthesized by T cells upon activation. The T-cell-derived FN has an unusual splice pattern: an additional domain, EDB, is produced whereas sequences within another domain, IIICS, are spliced out. CS1, the binding domain for very late antigen-4 (VLA-4), however, is still generated. To study the potential function of surface-associated FN its synthesis was down-regulated by an antisense oligonucleotide, then proliferation of T cells was induced by cross-linked anti-CD3. Proliferation was reduced as was expression of CD25. Moreover, when T cells were cultured in high density, the synthetic peptide QILDVPST, corresponding to CS1, inhibited proliferation, as did antibodies to VLA-4. We propose that surface-associated FN is a ligand for VLA-4, which by binding to VLA-4 on an adjacent cell, provides a costimulatory signal, thus sustaining T-cell proliferation.

Antibodies, Monoclonal↗
PubMed2000

Technical advance: simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry.

A new method is presented in which gas chromatography coupled to mass spectrometry (GC-MS) allows the quantitative and qualitative detection of more than 150 compounds within a potato tuber, in a highly sensitive and specific manner. In contrast to other methods developed for metabolite analysis in plant systems, this method represents an unbiased and open approach that allows the detection of unexpected changes in metabolite levels. Although the method represents a compromise for a wide range of metabolites in terms of extraction, chemical modification and GC-MS analysis, for 25 metabolites analysed in detail the recoveries were found to be within the generally accepted range of 70-140%. Further, the reproducibility of the method was high: the error occurring in the analysis procedures was found to be less than 6% for 30 out of 33 compounds tested. Biological variability exceeded the systematic error of the analysis by a factor of up to 10. The method is also suited for upscaling, potentially allowing the simultaneous analysis of a large number of samples. As a first example this method has been applied to soil- and in vitro-grown tubers. Due to the simultaneous analysis of a wide range of metabolites it was immediately apparent that these systems differ significantly in their metabolism. Furthermore, the parallel insight into many pathways allows some conclusions to be drawn about the underlying physiological differences between both tuber systems. As a second example, transgenic lines modified in sucrose catabolism or starch synthesis were analysed. This example illustrates the power of an unbiased approach to detecting unexpected changes in transgenic lines.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Transgenic potato plants reveal the indispensable role of cystathionine beta-lyase in plant growth and development.

Methionine (Met) is an essential amino acid that is often unavailable at sufficient dietary levels. In order to better understand Met pathway regulation, a cDNA encoding cystathionine beta-lyase (CbL; EC 4.4.1.8) has been cloned from Solanum tuberosum. An antisense construct of this gene was used to generate transgenic potato plants with reduced CbL levels. Transgenic plants exhibiting leaf CbL activity levels of up to 50% below wild-type levels were obtained. Metabolite analysis revealed a reduction in Met levels in these CbL antisense plants, as well as remarkable increases in the pathway intermediates cystathionine, homoserine and cysteine. Unexpectedly, an increase in homocysteine was also observed. Levels of aspartate amino acid pathway intermediates (including aspartate, lysine and threonine) remained essentially unaffected. Neither transcript levels nor protein products of other pathway-relevant genes were altered significantly in these plants. CbL antisense plants exhibited an altered phenotype characterized by a bushy growth habit, small light-green leaves and small tubers. This phenotype could be alleviated upon Met supplementation, suggesting that low Met levels, rather than pathway intermediate accumulation, is responsible for the phenotypic effects of CbL transgene expression. These data unequivocally demonstrate the central role of CbL in Met biosynthesis, and, subsequently, in plant growth and development.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗