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Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 19 recordsLinked to original sources
PubMed2003

Tetramethylphosphonium fluoride: "naked" fluoride and phosphorane.

Me(4)PF was investigated in the solid state, in the gas phase, and in solutions. Vibrational spectra of the solid and a single-crystal structure show an ionic tetramethylphosphonium fluoride. The compound crystallizes in the space group Pbca with a = 1016.0(1), b = 1018.0(1), c = 1205.8(4) pm, and Z = 8. The fluoride ion is nearly trigonal planar surrounded by three Me(4)P+ cations forming six H...F contacts between 218 and 240 pm. The compound is stable below 120 degrees C and sublimes in a vacuum. It possesses a phosphorane structure in the gas phase that was studied by electron diffraction and vibrational spectra, and additionally by theoretical calculations. The Me(4)PF molecule has a trigonal bipyramidal structure with one methyl group and the fluorine atom in axial positions and bond lengths of d(PC(eq)) = 182.6(4) pm, d(PC(ax)) = 188.4(8) pm, and d(PF) = 175.3(6) pm. The compound is remarkably soluble in acetonitrile, water, and alcohols, and slightly soluble in benzene, dimethyl ether, and diethyl ether. The solutions were studied by (1)H, (13)C, (19)F, and (31)P NMR spectroscopy. The hygroscopic Me(4)PF forms a tetrahydrate which crystallizes in the space group I4(1)/a with a = 1106.1(1) pm, c = 816.3(1) pm, and Z = 4. The fluoride ion in Me(4)PF.4 H(2)O is surrounded by four water molecules. These units form a three-dimensional network in which the Me(4)P+ cations are embedded without any contacts.

Journal Article↗
PubMed2003

Predictors of falls in elderly people during rehabilitation after hip fracture--who is at risk of a second one?

BACKGROUND: A fall in old age is known as a common consequence of frailty and decline as well as a risk factor for further falls. Studies identifying hip fracture patients who are at risk of a further fall are lacking. Therefore it was of interest to evaluate the risk factors for falling in a high-risk population, i.e., patients during rehabilitation after recent proximal femur fracture. METHODS: 935 consecutive patients who had surgical intervention after acute fracture of the proximal femur underwent a multidimensional assessment within the first two days after admission to the rehabilitation ward. Falls during the stay on the rehabilitation ward were registered. The baseline data were compared between fallers and non-fallers. FINDINGS: 11.8% of the patients fell during rehabilitation. Risk factors associated with a fall were increasing age, male gender, type of surgery, the use of a rollator and nocturnal urinary incontinence. The risk of falling increased in the middle of the second week of rehabilitation, when frailer patients gained mobility and ability to walk by themselves, while they were not yet safe enough. INTERPRETATION: It was possible to compose a risk profile for future falls. Those identified as 'at risk of a further fall' should be selectively offered protective devices and special training programs in order to prevent future fractures. As for the surgical intervention, the type of surgery in relation to age and long-term outcome is of particular interest since the use of the more expensive total hip arthroplasty procedure may be more cost effective in the long term.

Accidental Falls↗
PubMed2001

Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Vascular infection with Chlamydia pneumoniae might boost inflammatory responses that play a pivotal part in neointima formation, which is the main cause of restenosis after stenting. Our aim was to investigate whether or not treatment of C pneumoniae infection with antibiotics prevents restenosis after coronary stent placement. METHODS: We enrolled 1010 consecutive patients with successful coronary stenting into a randomised, double-blind trial. Patients received the macrolide antibiotic roxithromycin 300 mg once daily for 28 days (506), or placebo (504). Primary endpoint was frequency of restenosis (diameter stenosis >50%) at follow-up angiography, and secondary endpoint was rate of target vessel revascularisation during the year after stenting. A prespecified secondary analysis addressed treatment effect with respect to titre of C pneumoniae in serum. Analysis was by intention to treat. FINDINGS: Rate of angiographic restenosis was 31% (157 lesions) in the roxithromycin group and 29% (148) in the placebo group (relative risk 1.08 [95% CI 0.92-1.26]; p50.43), corresponding to a rate of target vessel revascularisation of 19% (120) and 17% (105), respectively (1.13 [0.95-1.36]; p50.30). The combined 1-year rates of death and myocardial infarction were 7% (36) in the roxithromycin group and 6% (30) in the placebo group (p50.45). We showed a significant interaction between treatment and C pneumoniae antibody titre (p50.038 for restenosis, p50.006 for revascularisation), favouring roxithromycin at high titres (adjusted odds ratios at a titre of 1/512 were 0.44 [0.19-1.06] and 0.32 [0.13-0.81], respectively). INTERPRETATION: Non-selective use of roxithromycin is inadequate for prevention of restenosis after coronary stenting. There is, however, a differential effect dependent on C pneumoniae titres. In patients with high titres, roxithromycin reduced the rate of restenosis.

Aged↗
PubMed2001

Transcriptome analysis reveals a role of interferon-gamma in human neointima formation.

The most effective immediate cure for coronary stenosis is stent-supported angioplasty. Restenosis due to neointima proliferation represents a major limitation. We investigated the expression of 2435 genes in atherectomy specimens and blood cells of patients with restenosis, normal coronary artery specimens, and cultured human smooth muscle cells (SMCs). Of the 223 differentially expressed genes, 37 genes indicated activation of interferon-gamma (IFN-gamma) signaling in neointimal SMCs. In cultured SMCs, IFN-gamma inhibited apoptosis. Genetic disruption of IFN-gamma signaling in a mouse model of restenosis significantly reduced the vascular proliferative response. Our data suggest an important role of IFN-gamma in the control of neointima proliferation.

Animals↗
PubMed2001

Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFalpha antibody.

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated four patients with severe aGVHD refractory to steroids with infliximab, a chimeric human/mouse antiTNFalpha antibody. Patients (CML 2, MM 1, AML 1) developed grade III-IV GVHD at a median of 34 days (range 15-76) after myeloablative PBSCT (two), donor lymphocyte infusion for relapsed CML (one) or non-myeloablative PBSCT (one), respectively. All patients had severe intestinal involvement in addition to skin and/or liver disease and had received treatment with high-dose steroids (four) for a median of 11 days (range 5-17) in addition to CsA (four) and MMF (three). Infliximab (10 mg/kg) was given once a week until clinical improvement. In three of four patients a complete resolution of diarrhea and significant improvement of skin and liver disease were observed. Two patients received one, one patient two and one patient three infliximab infusions. At present two patients are alive >200 days after therapy, one with limited cGVHD. Two patients died, one of progressive malignant disease without GVHD and one of refractory GVHD. Infliximab is apparently an active drug for the treatment of aGVHD.

Acute Disease↗
PubMed2000

Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis.

Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-1) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with alpha-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P<0.01) that could be inhibited by interleukin-1 (IL-1) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappaB (NF-kappaB) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-1 mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and kappaB-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-1) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.

Blood Platelets↗
PubMed2000

Staged growth of optimized arterial model trees.

There is a marked difference in the structure of the arterial tree between epi- and endocardial layers of the human heart. To model these structural variations, we developed an extension to the computational method of constrained constructive optimization (CCO). Within the framework of CCO, a model tree is represented as a dichotomously branching network of straight cylindrical tubes, with flow conditions governed by Poiseuille's law. The tree is grown by successively adding new terminal segments from randomly selected points within the perfusion volume while optimizing the geometric location and topological site of each new connection with respect to minimum intravascular volume. The proposed method of "staged growth" guides the generation of new terminal sites by means of an additional time-dependent boundary condition, thereby inducing a sequence of domains of vascular growth within the given perfusion volume. Model trees generated in this way are very similar to reality in their visual appearance and predict diameter ratios of parent and daughter segments, the distribution of symmetry, the transmural distribution of flow, the volume of large arteries, as well as the ratio of small arterial volume in subendocardial and subepicardial layers in good agreement with experimental data. From this study we conclude that the method of CCO combined with staged growth reproduces many characteristics of the different arterial branching patterns in the subendocardium and the subepicardium, which could not be obtained by applying the principle of minimum volume alone.

Algorithms↗
PubMed1999

Shear stress distribution in arterial tree models, generated by constrained constructive optimization.

Models of arterial trees are generated by the algorithm of Constrained Constructive Optimization (CCO). Straight cylindrical, binary branching tubes are arranged in an optimized fashion so as to convey blood to the terminal sites of the tree, which are distributed over a predefined area, representing the tissue to be perfused. All terminal segments supply equal flows at a unique terminal pressure, and the radii of parent and daughter segments are related via a bifurcation law. The connective structure and geometry of the model are optimized according to a target function such as total intravascular volume. The shear rate between blood and the vessel walls is computed in each segment and a new method is presented for rescaling a given CCO tree to a desired value of shear rate in the root segment. The effect of viscosity varying with shear rate is evaluated and a new method is presented for rescaling a CCO-tree segment by segment to consistent values of radii and variable viscosity. Shear stress is evaluated for its deviation from being proportional to shear rate and then subjected to various types of analyses. Usually both, shear stress and its variability, are found to be larger in the smaller than in the larger segments of the CCO-model trees. However, it is shown how the shear-stress distribution can be reshuffled between small and large segments when rescaling a CCO tree to obey a different bifurcation law, while its whole geometry remains unchanged and all boundary conditions remain fulfilled. The selection of optimization target is found to drastically affect shear-stress variability within bifurcations, which reaches a distinct minimum if the model is optimized according to intravascular volume. Finally, a rank-analysis of shear stress within each bifurcation shows that only two out of six possible rank patterns actually occur: the parent segment always experiences medium shear stress while minimum shear stress resides mostly in the larger, less frequently in the smaller daughter.

Arteries↗
PubMed1999

Pharmacokinetics of meropenem in critically ill patients with acute renal failure undergoing continuous venovenous hemofiltration.

OBJECTIVE: Meropenem is a broad-spectrum antibiotic used for severe infections. In patients with chronic end-stage renal failure, meropenem clearance is reduced and doses must be adjusted according to the creatinine clearance. The aim of this study was to assess pharmacokinetic data of meropenem in patients with acute renal failure and to determine the amount of drug removed by continuous venovenous hemofiltration, an often-used renal replacement therapy in patients with acute renal failure. METHODS: Nine critically ill anuric patients with acute renal failure undergoing continuous venovenous hemofiltration received 500 mg meropenem 2 or 3 times daily. Plasma and hemofiltrate concentrations were determined during 1 dosing interval at steady state. Pharmacokinetic parameters were calculated for a 2-compartment open model and dose requirements were calculated. RESULTS: The total meropenem clearance was 52.0 +/- 8.4 mL/min, with a hemofiltration clearance of 22.0 +/- 4.7 mL/min and a nonrenal-nonhemofiltration clearance of 29.9 +/- 5.4 mL/min; 235.9 +/- 88.6 mg, or 47.2% +/- 17.7%, of the dose were removed through continuous venovenous hemofiltration. The terminal elimination half-life was 8.7 +/- 3.5 hours and the volume of distribution at steady state was 12.4 +/- 1.8 L. Peak and trough concentrations for a dosing interval of 12 hours were 38.9 +/- 9.7 mg/L and 7.3 +/- 1.3 mg/L, respectively. The corresponding concentrations for a dosing interval of 8 hours were 44.7 +/- 10.4 mg/L and 11.9 +/- 0.7 mg/L, respectively. CONCLUSION: Pharmacokinetic data of anuric patients with acute renal failure were similar to those of patients with end-stage renal failure. Because hemofiltration contributes significantly to meropenem elimination, the recommended dose for critically ill anuric patients receiving continuous venovenous hemofiltration should be increased by 100% to avoid potential underdosing.

Acute Kidney Injury↗
PubMed1999

A three-dimensional model for arterial tree representation, generated by constrained constructive optimization.

The computational method of constrained constructive optimization (CCO) has been generalized in two important respects: (1) arterial model trees are now grown within a convex, three-dimensional piece of tissue and (2) terminal flow variability has been incorporated into the model to account for the heterogeneity of blood flow observed in real vascular beds. Although no direct information from topographic anatomy enters the model, computer-generated CCO trees closely resemble corrosion casts of real arterial trees, both on a visual basis and with regard to morphometric parameters. Terminal flow variability was found to induce transitions in the connective structure early in the trees' development. The present generalization of CCO offers--for the first time--the possibility to generate optimized arterial model trees in three dimensions, representing a realistic geometrical substrate for hemodynamic simulation studies. With the implementation of terminal flow variability the model is ready to simulate processes such as the adaptation of arterial diameters to changes in blood flow rate or the formation of different patterns of angiogenesis induced by changing needs of blood supply.

Algorithms↗
PubMed1999

Dentin dysplasia type I--a case report.

A case report on dentin dysplasia type I, a congenital disease (autosomal dominant gene defect) affecting deciduous and permanent teeth, is depicted including representations of clinical and histological features, X-ray and CT-findings. Therapy includes extraction of all teeth, ectomization of cystic alteration, revision of paranasal sinus. Aesthetic and functional rehabilitation by means of insertion of a complete denture was achieved.

Adult↗
PubMed1999

Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.

AIMS: To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. METHODS: Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. RESULTS: The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. CONCLUSIONS: Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.

Adult↗
PubMed1999

Exploitation of the antibody repertoire of cancer patients for the identification of human tumor antigens.

The screening of tumor-derived expression libraries for antigens which are recognized by high titered IgG antibodies present in autologous sera of the cancer patients by SEREX (serological identification of antigens by recombinant expression cloning) allows for the systematic identification of antigens in human cancers. SEREX has led to the definition of a plentitude of new tumor antigens in many different tumor entities. The majority of the antigens are encoded by hitherto unknown genes and can be grouped into different classes of antigens. The abundance of serologically defined human tumor antigens is not only of relevance for tumor biology and serodiagnosis of cancer, but also facilitates the identification of proteins recognized by tumor specific T lymphocytes, thus providing a molecular basis for polyvalent peptide-based and gene-therapeutic vaccine strategies in a wide variety of human neoplasms.

Antibodies, Neoplasm↗
PubMed1998

Morphometry of human coronary arterial trees.

BACKGROUND: Some groups, including ours, have been generating arterial tree models using constrained constructive optimization (CCO). Arterial trees have been grown to arbitrary resolution without input of anatomical data. We performed this study to learn about the shortcomings that might have resulted from neglecting the anatomical data in CCO models. METHODS: In a total of 450 segments obtained from 4 human cast hearts, the ratio ofbifurcating daughter segment radii (O < Sbif = r(2)/r(1) < 1) was examined, which corresponds to the split of the total flow of the mother segment. For any complete bifurcation, where the radii of the parent segments and the radii of daughters were known, the area expansion ratio was computed (Aexp = [r(1)2 + r(2)2]/r(parent)2). RESULTS: The bifurcating ratio was found to be distributed in a nonnormal fashion, with a median of 0.76. The average area expansion ratio Aexp, characterizing the change of cross-sectional area of the vasculature from proximal to distal, was 0.93+/-0.26. The 'rate of branching' (d(i)/(d(0)) was defined by the segment diameter relative to the diameter of the root segment. Averaging the rate of branching over segments within each bifurcation level resulted in a decreasing function of bifurcation level. CONCLUSIONS: This article provides new experimental data on branching geometry of coronary arteries (i.e., the trees evaluated in this study are purely delivering rather than conveying). Based on these facts, we suggest that the analytical bifurcation law in CCO might be replaced by the bifurcation rule obeyed on a stochastic basis only.

Anthropometry↗
PubMed1998

Analysis of left ventricular function after emergency coronary artery bypass grafting for life-threatening ischaemia following primary revascularization.

OBJECTIVE: Severe ischemic injury in the first few hours following primary revascularization necessitates acute reoperation. To study the effect of emergency coronary artery bypass grafting, we followed 18 patients for up to 8 years, relating their changes of global and regional myocardial function during the acute event and after secondary revascularization to final outcome. METHODS: A total of 16 patients with coronary artery bypass grafting (CABG) and 2 PTCA were treated for coronary heart disease between 1989 and 1993 and experienced life-threatening ischemic events (94% cardiogenic shock, 39% ventricular fibrillation, 67% ischemic electrocardiograph (ECG) changes) within 2.3+/-1.6 h after primary revascularization. Reoperation was carried out 1.0+/-1.3 h after the occurrence of acute ischemia. Serial echoes were obtained during the acute event and after reoperation as well as during the follow-up period. RESULTS: Of the 18 patients, 8 are currently alive, 5 died within 30 days and 4 within the 1st year. There was one late death 5 years after surgery. Global and regional wall motion was evaluated using short axis views of transesophageal echoes taken during the acute event and after secondary revascularization, and compared with transthoracic echoes in long-term survivors up to 5 years after surgery. During the acute event left ventricular ejection fraction (LVEF) was reduced in 83% of the patients and improved significantly after reoperation (chi2 = 11.74, df= 2, P < 0.01). As to regional wall motion, 50% of the segments in non-revascularized areas remained abnormal. Regional wall motion after reoperation was significantly better in the surviving patients compared with patients dying in the post-operative course (chi2 = 6.23, df= 1, P < 0.05). The revascularization score ( > 75%) of abnormal contracting segments during the acute ischemic event was a significant determinant for long-term survival. CONCLUSION: We conclude that patient outcome is determined by the severity of regional wall motion abnormality during the acute ischemic event, the aggressiveness of the attempt to revascularize these perfusion territories and their improvement after revision. Long-term survival reflects, therefore, the extent of emergency revascularization and therefore the ability to identify ischemic perfusion territories for surgical strategy planning.

Aged↗
PubMed1998

Outer radius-wall thickness ratio, a postmortem quantitative histology in human coronary arteries.

Although the anatomy, histology and pathology of human coronary arteries have been studied extensively, little is known about the functional relationship between vessel radius and wall thickness. It is the purpose of this study to present detailed measurements and to describe this relationship covering the range from the feeding coronary artery to the arterioles. Human hearts of 10 adults less than 36 +/- 3 years old were investigated immediately postmortem. Ten cubic tissue blocks, measuring about 10 mm in length on each side, were dissected from the left ventricular wall. After fixation by immersion, 15-microm sections were prepared and outer and inner perimeters of 52 arterial segments were digitalized. Vessel radius and wall thickness were calculated and plotted to show their relationship over the whole range of vessel calibers. Outer vessel radii ranged from 100 to 3,000 microm and wall thickness from 80 to 800 microm. Plotting the outer vessel radius against the wall thickness, the data points were found to cluster around a straight line. A significant correlation between the two parameters was found (R2 = 0.79). This mathematical correlation and the good agreement of the presented results with data from other species indicate a common physiologic concept.

Adult↗
PubMed1998

Biochemical markers of perioperative myocardial ischemia in patients with coronary artery bypass grafting.

Aims of the study: The evaluation of significant perioperative ischemic processes after coronary artery bypass grafting from postoperative ECG, creatine kinase (CK) and CK iso-enzyme MB remains unreliable and, hence, insufficient. Additional, early available biochemical markers could improve the diagnostics of ischemia. Methods: In 86 patients with multiple vessel disease, activity of serum CK and CK-MB as well as mass of CK-MB, myoglobin and troponin-T were analyzed before and after surgery. Twelve-lead electrocardiograms were evaluated before surgery, 3h postoperatively, and before discharge from hospital. Results: In patients with signs of perioperative ischemia in the 3-hour ECG, primary postoperative peak values of myoglobin and CK were distinctly higher than in patients without signs of ischemia, with median values of 1437 ng/ml vs. 986 ng/ml for myoglobin and of 632 U/l vs. 481 U/l (n.s.) for CK. Sensitivity and specificity of myoglobin were 64 % and 69 %, followed by CK with 61 % and 62 %, respectively. Conclusions: Myoglobin, indicating the risk of perioperative ischemia approximately 45 minutes after declamping of the aorta, is suggested as a candidate for early available routine monitoring.

Journal Article↗