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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2004

[The Guideline Clearing Project COPD. Recommendations for a National Guideline].

In order to promote the care of patients with COPD in Germany a national guideline clearing project was initiated jointly by autonomous corporate bodies of the German health care system. Following a systematic search of literature data bases between 1992 and 2002, 20 guidelines were identified that met the inclusion criteria and were evaluated with the German Checklist for Methodological Guideline Appraisal. Following this, a multidisciplinary expert group appointed by the German Guideline Clearinghouse (Leitlinien-Clearingstelle im Arztlichen Zentrum fur Qualitat in der Medizin, AZQ) reviewed the suitability of these guidelines for the use in the German health care system. Referring to methodological aspects, criteria were best met by the guideline of the Veteran's Health Administration/Department of Defense (US), followed by the one of the Deutsche Atemwegsliga and the Deutsche Gesellschaft fur Pneumologie. Aiming at the production respectivly a revision of a German national guideline for COPD the expert group agreed on recommendations organized in 19 chapters. Among others these strengthened the role of a precise definition of COPD based primarily on the pathogenesis, of a subtle description of all diagnostic and therapeutic tools and of a detailed description of quality assurance and quality management. The feasability of recommendations were demonstrated by examples chosen from the evaluated guidelines. Additionally the presented findings may be used as steering tools in the German Health care system.

Delivery of Health Care↗
PubMed2003

Expression and G-protein coupling of mu-opioid receptors in the spinal cord and dorsal root ganglia of polyarthritic rats.

Although chronic inflammatory pain is known to be associated with hypersensitivity to mu opioid receptor agonists, no evidence for changes in the expression and/or characteristics of central mu opioid receptors has yet been reported in relevant models of this type of pain. In the present study, both immunohistochemical and autoradiographic approaches were used to address this question in polyarthritic rats, on the 4th week after intradermal injection of complete Freund's adjuvant, when inflammatory pain was at its maximum. Immunohistochemical labeling with specific anti-mu opioid receptor antibodies and autoradiographic labeling with [3H]DAMGO showed an upregulation of mu opioid receptors in the dorsal root ganglia but no changes in the density of these receptors in the dorsal horn at the level of L4-L6 segments in polyarthritic compared to age-paired control rats. On the other hand, autoradiographic quantification of the concentration-dependent increase in [35S]GTP-gamma-S binding by the mu-opioid receptor agonist DAMGO did not show any significant differences within the lumbar dorsal horn between polyarthritic and control rats. These data indicate that chronic inflammatory pain caused by polyarthritis was associated with an increased expression of mu-opioid receptors in dorsal root ganglion sensory neurones that did not result in an increased spinal density of these receptors, in spite of their well established axonal transport in the central portion of primary afferent fibres to the dorsal horn. In contrast, axonal transport of mu-opioid receptors in the peripheral portion of these fibres probably accounts for the increased receptor density in inflamed tissues already reported in the literature.

Analgesics, Opioid↗
PubMed2003

The role of inflammation in vascular injury and repair.

Inflammation plays a critical role in the vascular response to injury. In particular, mechanical injury using techniques such as balloon angioplasty and stenting results in complex inflammatory reactions which influence proliferation of vessel wall constituents such as endothelial cells, smooth muscle cells, and extracellular matrix proteins. Inflammatory cells are recruited to the injured vessel wall initially as a reparative mechanism; however, these same inflammatory processes are also pivotal in the development of restenotic lesions. Leukocytes serve as the primary inflammatory cells but we now know that platelets produce a number of important inflammatory mediators. This review describes the mechanisms that regulate endothelial cell migration, smooth muscle cell activation, and extracellular matrix protein production, all of which are key components in the inflammatory response to vascular injury.

Angioplasty, Balloon↗
PubMed2003

Increased apoptosis of neutrophils in a case of clozapine-induced agranulocytosis - a case report.

A 45-year-old female suffering from severe chronic schizophrenia of the paranoid type did not respond to typical antipsychotics. Five weeks after starting therapy with clozapine, she developed a clozapine-induced agranulocytosis (CA). Discontinuation of clozapine and treatment with granulocyte colony-stimulating factor (G-CSF) led to normalization of blood neutrophil counts within three weeks. This report suggests enhanced apoptosis of blood neutrophils during the acute phase of CA resulting from enhanced expression of the pro-apoptotic proteins Bax and Bik and from a decrease of the anti-apoptotic BCl-X(L) mRNA. The time course of decline and recovery of neutrophilic cells, as well as the release pattern of endogenous G-CSF, resembles those of chemotherapy-induced neutropenia. The kinetics of CD 34-positive cells mimics that of cytotoxic progenitor cell mobilization, e. g., after cytostatic drug administration. Our findings argue against the hypothesis that clozapine-mediated inhibition of G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF) release is involved in CA development. Because clozapine-induced cell death mainly affects the neutrophil lineage, the elucidation of the exact mechanism of CA may open new perspectives for the treatment of psychiatric and possibly hematological disorders.

Agranulocytosis↗
PubMed2003

Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats.

1. The pharmacokinetics of eplerenone (EP) were examined in rats following single or repeated dosing with (14)C-labelled or unlabelled EP to characterize absorption, metabolism and excretion. Rates of EP metabolism and cytochrome P450 activities were determined in vitro after repeated dose administration of EP. 2. Following a single i.v. dose (15 mg kg(-1)), the elimination half-life of EP was 0.80 and 1.14 h in male and female rats, respectively. Plasma clearances (CL) of EP were 1.62 and 1.20 l kg(-1) h(-1) in males and females, respectively. Following a single oral dose (15 mg kg(-1)), C(max) and T(max) of EP were 1.71 micro g ml(-1) and 0.5 h in male rats. The corresponding values in female rats were 3.54 micro g ml(-1) and 1.0 h. The systemic availability of EP was 25.6% in male rats and 66.4% in female rats, demonstrating sex differences in the pharmacokinetics of EP. 3. In the 8-day study, the AUC(0-24h)'s of total EP (closed lactone ring form plus open form) following 100 and 200 mg kg(-1) oral doses were approximately half those on day 1 in male rats. After repeated dosing for 13 weeks, the pharmacokinetics of total EP did not change with study duration at the 20 mg kg(-1) dose in both males and females. However, at the 100 mg kg(-1) dose, AUC(0-24h)'s were notably reduced on day 24 but progressively increased on subsequent days to approximate day 1 levels by day 86 in both sexes. At the 500 mg kg(-1) dose, the AUCs on day 86 remained lower than those on day 1. Reductions in AUCs on days 8 and 24 appeared to be the result of metabolism induction. 4. EP was extensively metabolized in male rats and most faecal and urinary radioactivity was in the form of metabolites. In female rats, the vast majority of urine and faecal radioactivity was associated with total EP. Thus, the sex difference in the pharmakokinetics of EP was due to more extensive metabolism in male rats. 5. The major metabolite in the rat was 6beta-OH EP. EP 6beta-hydroxylase activity was well correlated with testosterone 6beta-hydroxylase activity, indicating that EP metabolism to 6beta-OH EP was mediated primarily by CYP3A in the rat. 6. After repeated dose administration, EP increased 6beta-hydroxylase activities of testosterone and EP itself in a dose-dependent manner in both male and female rats, indicating that EP was a CYP3A inducer in the rat. There appeared to be no effects on activities of CYP1A1, 2B and 2E1.

Administration, Oral↗
PubMed2003

[Cost-benefit analysis in patients with sleep-related breathing disorders - diagnosis and ncpap therapy during medical rehabilitation].

In a multi-centre study, 745 patients undergoing internal medical rehabilitation (for hypertension, coronary heart disease, gastrointestinal and respiratory diseases) were investigated. The health economic benefit was evaluated during the 3 weeks of medical rehabilitation, during which a sleep-medical diagnostic work-up and treatment were applied. Ambulatory screening for sleep-related breathing disorders was carried out in all patients. In positive cases (Apnoea-Hypopnoea Index > or = 10) transfer to our sleep lab was recommended. 103 patients were found to be positive, of whom 47 attended the lab; 23 of these accepted nCPAP therapy, while 24 did not. The costs of the additional diagnosis and treatment were considered incremental costs--and the benefit identified as the decrease in days off work as revealed by a comparison of the year before with the year after rehabilitation. Days off work decreased by 38.4 days in the treated group, and increased by 25.4 days in the untreated group. The results were extrapolated to all patients in internal medical rehabilitation in Germany, and a cost-benefit analysis showed that the benefit of expanding the additional investigation to cover all patients would far exceed the incremental costs in the first year after rehabilitation by 58.26 Mio [symbol: see text] and in the second year by 81.15 Mio. [symbol: see text].

Continuous Positive Airway Pressure↗
PubMed2002

Pressurized bag pump and syringe pump arterial flushing systems: an unrecognized hazard in neonates?

OBJECTIVE: Hand-held flushing of radial arterial lines at 0.5 ml/s in neonates can result in retrograde embolization of flush solution into the central arterial circulation. We studied flush flow velocities during intermittent arterial line purging using a flow regulating device with an infusion bag pump and a syringe pump system. MEASUREMENTS AND INTERVENTIONS: In this in vitro experiment we simulated flushing of a 24- and a 22-G cannula against a mean arterial pressure of 45 mmHg. Fluid flow velocities were gravimetrically measured during flushing from an infusion bag system pressurized to 100, 200, and 300 mmHg and from a syringe pump flush system after initialization of boluses of 0.5, 1.0, 1.5, 2.0, and 2.5 ml. The flow regulating device was opened for 1, 2, and 5 s. RESULTS: Both flush systems tested allowed delivery of flush flow velocities exceeding 0.5 ml/s (e.g., 22-G cannula; bag system, pressure 300 mmHg up to 0.64+/-0.08 ml/s; syringe pump, 2 ml bolus up to 0.74+/-0.05 ml/s). In syringe pump systems the main determinant of flow velocity was bolus size, in bag pump systems flushing time and bag pressure. CONCLUSIONS: Based on data about critical flow velocities through an radial arterial cannula in neonates, both tested flushing systems carry the risk of exceeding the critical value of 0.5 ml/s. They are likely to cause retrograde embolization of flushing solution into the central arterial circulation with the associated risk of clot and air embolization. In vivo studies should identify margins of safety to minimize the risk of retrograde flushing into the central arterial circulation.

Catheters, Indwelling↗
PubMed2002

Side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of tennis elbow.

Apart from a few observational reports, there are no studies on the side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of insertion tendopathies. Within the framework of a randomised, placebo-controlled, single-blind, multicentre study to test the effectiveness of ESWT in the case of lateral epicondylitis (LE), side-effects were systematically recorded. A total of 272 patients from 15 centres was allocated at random to active ESWT (3 x 2000 pulses, energy flux density ED(+) 0.04 to 0.22 mJ/mm(2) under local anaesthesia) or placebo ESWT. In all, 399 ESWT and 402 placebo treatments were analysed. More side-effects were documented in the ESWT group (OR = 4.3, CI = [2.9; 6.3]) than in the placebo group. Most frequently, transitory reddening of the skin (21.1%), pain (4.8%) and small haematomas (3.0%) were found. Migraine was registered in four and syncopes in three instances after ESWT. ESWT for LE with an energy flux density of ED(+) 0.04 to 0.22 mJ/mm(2) is a treatment method which has very few side-effects. The possibility of migraine being triggered by ESWT and the risk of a syncope should be taken into account in the future. No physical shock wave parameters could be definitely identified as the cause of the side-effects observed.

Adult↗
PubMed2002

Effect of small additions of Ir on properties of a binary Au-Ti alloy.

OBJECTIVES: Previous investigations in the binary system Au-Ti have shown that a Au based alloy with 1.7 wt% Ti reveals properties, which are appropriate to dental applications. Aim of this investigation was to refine the coarse grained dendritic microstructure of the alloy. Derived from experience with traditional high gold alloys and based on theoretical considerations, Ir was chosen as potential grain refiner and its influence on grain size, hardness, and thermal distortion was investigated. METHOD: Seven different Au-Ti alloys with Ir contents of 0-0.5 wt% were prepared in an arc furnace and test pieces cast by the dental casting technique. Microstructures of the alloys were documented by light microscopy. Grain size was assessed by a comparison procedure, hardness was measured by the indentation test, and thermal distortion by a three point bending test in a modified dilatometer. RESULTS: It revealed that Ir has a grain refining effect on the alloy with smallest grain sizes at a concentration of at least 0.3 wt%. It seems that the alloy with 0.5 wt% Ir shows slight grain growth during firing. Little homogenization was observed after firing. The influence of Ir on hardness was negligible. Thermal distortion is minimized with a concentration of 0.1 wt% Ir. In order to profit by the high thermal distortion resistance, the alloy Au(98.2)Ti(1.7)Ir(0.1) (wt) was chosen as definite composition, although 0.1 wt% Ir does not satisfactorily refine the alloy. SIGNIFICANCE: The alloy Au(98.2)Ti(1.7)Ir(0.1) (wt) revealed properties appropriate for the crown and bridge technique.

Corrosion↗
PubMed2002

Ceramic bonding to a dental gold-titanium alloy.

Investigations of the metal-ceramic bonding of the alloy Au98.2Ti1.7Ir0.1 (wt) in comparison with a well-approved traditional Au-Pt-Pd-based alloy were performed. Bond strength of both alloys, measured with a three-point flexure bond test, was in the same order of magnitude. Failure mode was different for both alloys. Failure of the bonding of the Au-Ti-Ir alloy predominantly occurred at the alloy-oxide interface. On the Au-Pt-Pd alloy more ceramic residues were observed. Sandblasting the metal surface with alumina increases the roughness of the surface, but only slightly increases the bond strength, independent of the grain size of the alumina. Immersion in a corrosive solution of sodium chloride and lactic acid reduced the bond strength of both alloys by about 35%. While this decrease for the Au-Pt-Pd alloy occurred after an immersion time of only two days, it took about 35 days for the Au-Ti alloy. The results indicate that the alloy Au98.2Ti1.7Ir0.1 (wt) provides sufficient ceramic adherence. The results also proved that the three-point flexure bond test used is a sensitive method for measuring metal-ceramic bond strength, thus supporting the decision to integrate this test within the international standard ISO 9693.

Alloys↗
PubMed2002

Pre- and postsynaptic localizations of the CB1 cannabinoid receptor in the dorsal horn of the rat spinal cord.

Several lines of evidence show that endogenous and exogenous cannabinoids modulate pain transmission at the spinal level through specific cannabinoid-1 (CB1) receptors. Since anatomical data concerning spinal CB1 receptors are rather contradictory, we studied the cellular and subcellular localizations of the CB1 receptors by immunocytochemistry. Results show a dual pre- and postsynaptic localization of CB1 receptors. Presynaptic receptors are evidenced by the labeling of (1) heterogeneous dorsal root ganglion neurons and (2) axons of Lissauer's tract. Postsynaptic receptors are shown by the labeling of numerous interneurons in the outer part of lamina II. Double immunolabelings show that lamina II outer CB1 neurons, probably islet cells, may also contain GABA or nitric oxide synthase. Numerous CB1-containing neurons in lamina X are also immunostained with anti-nitric oxide synthase (NOS) antibody. Under the electron microscope, CB1 immunoreactivity is exclusively localized postsynaptically in both somatic and dendritic compartments. The absence of labeling on primary afferent axon terminals is discussed and compared to the absence of labeling on terminals or vesicle-containing dendrites of islet cells, where a presynaptic localization was expected according to data of the literature.

Afferent Pathways↗
PubMed2002

Early clinical experience with the novel NMDA receptor antagonist CNS 5161.

AIMS: To investigate the safety, tolerability and pharmacokinetics of the novel NMDA antagonist CNS 5161 in humans. Excessive activation of glutamate receptors, especially of the N-methyl-d-aspartate (NMDA) subtype has been associated with neuropathic pain, and brain damage caused by focal ischaemia in mature brain or hypoxia-ischaemia (HI) in neonates. CNS 5161 is a novel NMDA ion-channel antagonist that interacts with the NMDA receptor/ion channel site to produce a noncompetitive blockade of the actions of glutamate. Pre-clinical studies have demonstrated neuroprotective effects of CNS 5161 in the adult rat model of focal cerebral ischaemia, as well as anticonvulsant and analgesic effects. This study reports the first administration of CNS 5161 to man. Its objectives were to investigate the haemodynamic effects of the compound, to assess its safety and tolerability in healthy male volunteers, and to provide some preliminary human pharmacokinetic data. METHODS: We performed a randomized, double-blind placebo controlled phase 1 dose escalation study of CNS 5161. Volunteers were randomized to receive CNS 5161 or placebo in a ratio of 3:1. Twenty-four of 32 healthy volunteers received intravenous infusion of CNS 5161 over 15 min, followed by serial measurements of plasma drug concentration and haemodynamic observations over 24 h. A dose escalation design was adopted and the volunteers were stratified into eight dosage groups, ranging from 30 microg to 2000 microg. RESULTS: The drug was well tolerated by recipients. Side-effects were dose-related, self limiting and comprised minor subjective sensory symptoms. A dose dependent rise in systolic, mean arterial and diastolic blood pressure was seen in subsequent dosage groups, reaching 23/19 mmHg. Maximal effects were seen between 60 and 120 min after commencement of infusion. All subjects returned to baseline haemodynamic values within 24 h. Putative neuroprotective concentrations of CNS 5161 were achieved transiently, although these levels were not sustained. The pharmacokinetic data were best described by a two compartment model. The mean half-life was 2.95 h (s.d. 0.75). Mean clearance was 106 l h(-1) (s.d. 17.8) mean volume of distribution was 296 l (s.d. 69). These parameters were not significantly affected by body weight. CONCLUSIONS: This study suggests that CNS 5161 is well tolerated in healthy volunteers within the dose range studied. In addition, information concerning the pharmacokinetics of the compound has been acquired. Studies to investigate the efficacy of the compound in man may now be justified.

Adolescent↗
PubMed2002

The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.

AIMS: The acute phase reactant C-reactive protein is an important prognostic risk factor in patients with both stable and unstable coronary artery disease. The potential prognostic implications of an abnormal pre-procedural C-reactive protein concentration in patients undergoing elective coronary angioplasty may be relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma levels of C-reactive protein were measured in 501 patients with stable coronary artery disease undergoing elective coronary angioplasty. The incidence of death or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9). Survival without death, myocardial infarction, urgent revascularization or hospital admission for unstable angina was significantly lower in patients with an increased C-reactive protein vs patients with a normal C-reactive protein (log-rank 14.62, P<0.0001). Logistic regression analysis identified an increased C-reactive protein level as a strong independent predictor of event-free survival (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive protein levels are increased in 45% of patients undergoing elective coronary angioplasty. An increased C-reactive protein level is a powerful independent prognostic indicator for subsequent cardiac events, suggesting that late clinical outcome is markedly influenced by pre-procedural systemic activation of inflammation.

Aged↗
PubMed2002

Infectious animal diseases: the wildlife/livestock interface.

The long-standing conflict between livestock owners and animal health authorities on the one hand, and wildlife conservationists on the other, is largely based on differing attitudes to controlling diseases of livestock which are associated with wildlife. The authors have attempted to highlight the fact that these disease problems are frequently bi-directional at the wildlife/livestock interface. The different categories of diseases involved are presented. A new dimension being faced by veterinary regulatory authorities is the spectre of emerging sylvatic foci of diseases, such as bovine tuberculosis, bovine brucellosis and possibly rinderpest; these diseases threaten to undermine national and international eradication schemes, which have been implemented and executed with significant success, and at great cost. Conversely, wildlife-based ecotourism world-wide has expanded rapidly over the past decade and is the source of lacking foreign revenue for many developing countries. Traditional subsistence farming is still the largest source of much-needed protein on some continents and this, together with the growth and hunger of historically disadvantaged communities for land, is forcing enterprises and communities with markedly different objectives and land-use practices to operate effectively in close proximity. Some land-users rely exclusively on wildlife, others on livestock and/or agronomy, while yet others need to combine these activities. The net result may be an expansion or intensification of the interface between wildlife and domestic livestock, which will require innovative control strategies that permit differing types of wildlife/livestock interaction, and that do not threaten the land-use options of neighbours, or the ability of a country to market animals and animal products profitably.

Animals↗
PubMed2002

The value of wildlife.

The value of wildlife has been widely ignored or under-rated in the past by the international community. At most, wildlife was considered from the limited aesthetic and touristic aspects. This situation has changed somewhat. In the majority of the veterinary profession, which is largely livestock-oriented, wildlife is increasingly considered in terms of wild animal production and occupies just as relevant a position as domestic animal production. Some economists are now trying to quantify the informal nature of a large portion of the wildlife sector. The importance of wildlife to local communities is now globally recognised in community-based or participatory natural resources management programmes. The authors highlight not only the economic importance of wildlife (which amounts to billions of United States dollars world-wide), through consumptive and non-consumptive uses, but also the present and potential nutritional value, the ecological role as well as the socio-cultural significance of wildlife for human societies of both the developed and the developing worlds. Also addressed in this chapter is a discussion on one of the main threats to wildlife conservation which consists of the reduction or even retrieval of the different values wildlife can offer.

Animal Husbandry↗