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Biomedical subjects

U Krüger

Publications and source records attributed to U Krüger.

At least 19 recordsLinked to original sources

Correlation of intimal hyperplasia development and shear stress distribution at the distal end-side-anastomosis, in vitro study using particle image velocimetry.

Low shear areas at the distal anastomosis of peripheral bypasses are thought to promote neointimal hyperplasia. In this study we evaluated the fluid dynamic environment at the distal anastomosis of peripheral bypasses by means of a new method for in vitro flow visualization and quantitative velocity field measurement. A silastic model of a distal end-side anastomosis was attached to a mock circulation loop driven by an artificial heart. High resolution velocity fields were measured by means of particle image velocimetry (PIV). The velocity vector data were used to calculate vorticity omega, strain rates ex, shear rates h and shear stresses tau. Two separations and a stagnation zone were identified by means of flow visualization. Measured velocities inside the three zones were significantly lower than in the high velocity mainstream. Calculated shear rates and shear stresses inside the zones were significantly lower than human wall shear rates. At the transition between the effective mainstream and the boundary layers high vorticity and compressive strain fields existed, indicating the presence of high shear forces. The locations of these areas corresponded to the well known zones of intimal hyperplasia. The high resolution shear stress analysis supports the low shear theory of intimal hyperplasia development. A wall diversion angle greater than 6 degrees leads to flow separation and presumed IH promotion until high shear transition areas are reached.

Anastomosis, Surgical↗

Local haemodynamics and shear stress in cuffed and straight PTFE-venous anastomoses: an in-vitro comparison using particle image velocimetry.

OBJECTIVES: To use particle image velocimetry (PIV) to study the haemodynamics and shear stress associated with cuffed and straight PTFE-venous anastomoses. METHODS: Silastic models of a straight and cuffed (Venaflo) PTFE-venous anastomoses were attached to a pulsatile flow 'Berlin Heart' circuit filled with glycerine/water and hollow glass tracer spheres. Instantaneous velocity fields were obtained PIV and shear rates and patterns calculated from frame-by-frame analysis. RESULTS: A high velocity jet struck the anastomotic 'floor' and was deflected toward the venous outflow. Shear stresses near the floor were significantly higher, in the straight anastomosis. Sites of high shear stress correlated well with the known sites of intimal hyperplasia. CONCLUSIONS: A cuffed anastomosis type may be favourable in terms of local haemodynamics so enhancing the long-term patency of PTFE-venous grafts.

Anastomosis, Surgical↗

Performance of a bioreactor with submerged membranes for aerobic treatment of municipal waste water.

Aerobic treatment of municipal waste water in a membrane bioreactor was studied for 535 d. Apart from sampling, sludge was retained completely by a submerged hollow fibre membrane with a pore-size of 0.2 microm. The pilot plant comprised an anoxic zone to enable denitrification. The maximum liquid hold-up of the plant was 3.9 m3. In this study the reactor performance and the stability of the process and the membrane capacity were investigated. A stable flux of 181 m(-2)h(-1) could be realised with a mean transmembrane pressure difference of 0.3bar with air-bubbling and backflushing the membrane and cleaning it in place every two months for one or two hours. For about 140d, a flux of 271 m(-2)h(-1) was achieved, but cleaning became necessary more often. The hydraulic retention time (HRT) varied between 10.4 and 15.6h. Accordingly the volumetric loading rate was between 1.1 and 1.7kg CODm(-3)d(-1). No inoculum was used. The mixed liquor suspended solids (MLSS) concentration gradually increased to 18-20g MLSSl(-1). The feed to microorganism (F/M) ratio varied according to the operation conditions but decreased against a value of 0.07 kg COD kg(-1) MLSSd(-1). Treatment performance was very stable and on a high level. The COD was reduced by 95%. Nitrification was complete and up to 82% of the total nitrogen could be denitrified.

Bacteria, Aerobic↗

Use of near-infrared reflection spectroscopy to study the effects of X-ray contrast media on renal tolerance in rats: effects of a prostacyclin analogue and of phosphodiesterase inhibitors.

RATIONALE AND OBJECTIVES: Use of near-infrared reflection spectroscopy (NIR-RS) as a new model to assess renal tolerance of contrast agents and determination of the effects of a prostacyclin analogue and of two phosphodiesterase inhibitors on renal tolerance. MATERIALS AND METHODS: NIR-RS was used to measure total hemoglobin, oxygenated hemoglobin and tissue oxygen saturation in the renal cortex of rats and the effect of diatrizoate, iopromide and iotrolan injected at 1 g iodine/kg alone or together with the prostacyclin derivative, iloprost, or the phosphodiesterase inhibitors, rolipram and mesopram, on these parameters. RESULTS: Injection of the contrast media alone resulted in a 10% to 35% depression of total hemoglobin, oxygenated hemoglobin, and tissue oxygen saturation approximately 40 to 100 seconds after administration, whereas saline showed no effect and mannitol solution only a minor effect. Coadministration of iloprost or pretreatment with the phosphodiesterase inhibitors, rolipram or mesopram, significantly attenuated the contrast media-induced effects. CONCLUSION: NIR-RS might be useful for the determination of contrast media-induced side effects. Stable prostacyclin analogues or phosphodiesterase inhibitors have the potential to mitigate these side effects.

Animals↗

Immunohistochemical detection of components of the insulin-like growth factor system during skeletal muscle growth in the pig.

The insulin-like growth factor (IGF) system plays an important role in postnatal somatic and skeletal muscle growth in pigs. There is little information on the occurrence and distribution of components of the IGF system in postnatal porcine skeletal muscle. IGF-I, IGF receptor 1 (IGF1R) and the IGF-binding proteins IGFBP-1 and -3 in longissimus dorsi and triceps brachii were localized in muscle biopsies from 12 commercially crossbred pigs aged from 28 to 199 days as well as from the sire generation, by immunohistochemistry. Plasma IGF-I concentrations were also determined using radio-immunoassays. Unlike other species, IGF-I was localized in porcine skeletal muscle fibres. Staining intensity correlated with the highest plasma IGF-I levels and phases of intensive muscle growth from the 11th to 22nd week. The pattern of IGF1R immunostaining, which was strong, correlated with that of IGF-I, IGF1R was also localized in endomysial tissues. IGFBP-1 was not detected within muscle fibres, but was found in the endomysium and vessel walls, while IGFBP-3 was localized with IGF-1 and its receptor. Higher magnification revealed that IGF1R, IGFBP-3 and probably IGF-I appeared in the tubular system. Inhibitory as well as stimulating controls of IGFBP-1 and -3 on IGF functions are discussed, which may maintain a balance between autocrine growth promoting activities of IGF-I and IGF1R.

Aging↗

The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance and infrainguinal graft patency.

OBJECTIVES: To evaluate the influence of intraoperative arterial prostaglandin E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency. METHODS: Hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0)) impedances as well as phase relations were derived and related to graft outcome after three years. RESULTS: Significant changes after administration of prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An increase of at least one degree of the first harmonic phase angle following alprostadil injection in the crural bypass group was associated with a significant better graft prognosis of crural (p<0.01) but not popliteal grafts. Primary and secondary patency rates after three years for crural grafts with an increase of at least one degree were 62% and 63% (n=45) and for non-responders 18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor prostaglandin reaction occluded within 9 months (n=12) after the operation. CONCLUSIONS: The EBF method allows a combined assessment of peripheral resistance and impedance parameters. The response of the first harmonic phase angle provides important predictive information regarding femoro-crural grafts.

Adult↗

[Femoro-distal ePTFE bypass grafting using femoro-crural patch prosthesis (FCPP). Results of a prospective clinical study].

Femorodistal bypass using exclusively PTFE is known to have a poor prognosis, mostly because of the development of myointimal hyperplasia (MIH). Several vein patch techniques are established but the role of hemodynamics within the anastomotic site has only been explained insufficiently and is hardly considered clinically. In a prospective study, between 6/1992 and 7/1998 129 patients (89 m/40 f, mean age 65.2 +/- 10.0 years) with critical limb ischemia and no usable saphenous vein were included to undergo femorodistal ePTFE bypass grafting with a new, hemodynamically optimized distal end-to-side anastomosis. Patients were followed at 6-month intervals with clinical investigation and color-coded Doppler sonography. Primary and secondary graft patency (PPR, SPR), limb salvage, and patient survival were calculated according to Kaplan-Meier. With a median follow-up of 45 (range 6 to 72) months, PPR and SPR at 1, 3 and 5 years were 63.0, 35.7 and 27.6% and 74.5, 44.8%, and 37.6%, respectively. Limb salvage at 1, 3 and 5 years was 86.4%, 78.7% und 73.2%. There was no perioperative mortality. Graft infection occurred in 7 patients (5.2%). ePTFE bypass grafting represents a valuable option for infragenicular and crural reconstruction in the absence of autologous vein. The new anastomotic design was feasible and represents another adjunct to possibly improve patency of femorodistal bypass allografts.

Aged↗

Immunohistochemical localization of components of the insulin-like growth factor-system in human deciduous teeth.

To investigate the occurrence of components of the insulin-like growth factor (IGF) system during the resorption process of shedding human deciduous teeth, we investigated sections of 13 decalcified and paraffin-embedded deciduous teeth immunohistochemically with antibodies against IGF-I and -II, six IGF binding proteins (IGFBPs 1-6) and the IGF receptors IGF1R and IGF2R. The teeth were in different stages of resorption and all showed reparative cementum formation. It was found that acellular extrinsic fiber cementum, reversal lines and reparative cellular intrinsic fiber cementum were immunoreactive for both IGFs and various IGFBPs. Therefore, in human deciduous teeth, all subgroups of cementum, but not dentine, may represent sources of components of the IGF system. Odontoclasts did not carry IGFs or the IGF1R, but IGFBPs and the IGF2R. Therefore, these cells, in contrast to osteoclasts, may not respond to IGFs, but may be involved in the release and sequestration of IGFs from cementum during the resorption process. In contrast to odontoclasts, cementoblasts and periodontal ligament (PDL) fibroblasts carried IGF1R. The influence of the IGF system on the function of these cells with respect to periodontal matrix turnover and cementogenesis is discussed. On the behalf of the IGFBP immunoreactivities found, the PDL extracellular matrix can be considered to be a reservoir for IGF system components, where binding proteins may regulate IGF distribution and activity.

Child↗

[Reduction of colonization of new mattresses with bacteria, moulds and house dust mites by complete mattress covers].

BACKGROUND AND OBJECTIVE: We investigated if the colonisation of new mattresses with house dust mites, bacteria, and fungi could be reduced by using synthetic mattress covers as compared to common cotton covers. PATIENTS/METHODS: 84 healthy volunteers were assigned to two groups. Group A (n = 43) received the cotton covers, group B (n = 41) the synthetic covers which were made of a polyester microfaser with a polyurethane surface layer (Pro-Tex, Germed, Schwarzenbek, Germany). RESULTS: The mite antigen concentration after six months was significantly lower in group B. Three months after the start of the study counts of bacteria and moulds were significantly higher in group A compared to group B. CONCLUSIONS: It can be recommended that patients suffering from an allergy to mites or moulds may reduce their domestic allergen exposure by using the synthetic mattress covers tested in this study. Since cotton covers are very likely to become colonised by bacteria and moulds, they must be cleaned periodically (at least every 2nd-3d month).

Animals↗

Femorodistal PTFE bypass grafting for severe limb ischaemia: results of a prospective clinical study using a new distal anastomotic technique.

OBJECTIVES: To analyse graft patency and limb salvage following femorodistal bypass with ePTFE using a new distal anastomotic technique. Design prospective non-randomised study. MATERIAL AND METHODS: One hundred and twenty-nine patients (M:F; 2.23:1; mean age 65.2+/-10.0 years) underwent 135 operations for severe limb ischaemia. The new anastomosis, constructed entirely from ePTFE, was attached to the popliteal (21), anterior (46) and posterior (52) tibial, and peroneal (16) arteries. Cumulative primary (PPR) and secondary patency rates (SPR), limb salvage and survival were analysed using the Kaplan-Meier method. RESULTS: Median follow-up was 45 (range 6 to 72) months. There was no perioperative mortality. PPR and SPR at 1, 2, 3, 4, and 5 years were 63.0%, 44.9%, 35.7%, 33.1% and 27.6% and 74.5%, 55.2%, 44.8%, 43.0%, and 37.6%, respectively. Cumulative limb salvage was 86.4%, 78.7%, and 73.2% at 1, 3, and 5 years, respectively. CONCLUSIONS: This new anastomotic design was feasible and resulted in acceptable long-term results.

Adult↗

Membrane-supported biological wastewater treatment.

Research for a feasible method of complete pathogen removal from municipal wastewater has now arrived at a new stage of biological sewage treatment. Microfiltration membranes are integrated into the biological stage where they replace conventional sedimentation for the separation of treated water from sludge. These membranes form a physical barrier that even particles as small as bacteria cannot penetrate. Thus, the biological stage can be operated at higher biomass concentrations, which leads to better treatment performances and drastically reduces the excess sludge production. Results of test runs with pilot plants and municipal sewage suggest that the degradation and elimination potential of optimised membrane bioreactors will result in effluent concentrations as low as natural background concentrations of surface waters. Microfiltration membranes with a pore-size of 0.2 micron or less do not only retain bacteria but also viruses almost completely, and the clarified wastewater is practically free of pathogens. In consequence of these effluent qualities a much higher rate of wastewater can potentially be reclaimed. This paper includes results gained at a pilot plant operated at the Institute for Water, Soil and Air Hygiene of the Federal Environmental Agency in Berlin.

Humans↗

A new method of intraoperative hydraulic impedance measurement provides valuable prognostic information about infrainguinal graft patency.

PURPOSE: Prognostic information about graft outcome, obtained by using a new method for intraoperative measurement of vascular impedance, was evaluated. METHODS: Hydraulic impedance was measured in 136 infrainguinal bypass grafts that were entered into a multicenter trial. Seventy femoropopliteal and 66 femorocrural polytetrafluoroethylene (PTFE) grafts were used. The arterial impedance measurement involved a silicon bypass graft temporarily inserted between the proximal and distal anastomoses sites. A flowmeter probe and a pressure transducer were incorporated into the tube. The digitally stored waveforms were subjected to a fast Fourier transformation and both input (Z(x)) and characteristic (Z(0)) impedances, as well as phase relations, were computed and related to graft outcome after 3 years. RESULTS: Significant prognostic information for both popliteal and crural grafts was provided by means of the phase angle of the first harmonic. Primary and secondary patency rates for popliteal bypasses were 45% +/- 1% and 65% +/- 2% for phase angles greater than -40 degrees (n = 57) and 37% +/- 1% and 40% +/- 1% for phase angles less than -40 degrees (n = 13, p(prim ) = not significant, p(sec) < 0.01). For crural grafts, the secondary patency rates were 49% +/- 1% and 61% +/- 2% for phase angles greater than -40 degrees (n = 53) and 15% +/- 1% and 0% for phase angles less than -40 degrees (n = 13, P <.01). All crural bypass grafts with phase angles less than -40 degrees occluded within 16 months. Steady flow resistance, as well as Z(x) and Z(0), failed to indicate a significant relation to graft prognosis. CONCLUSION: This method provides reliable prognostic information regarding graft patency and opens hydraulic impedance measurement to clinical surgery. The phase lag between flow and pressure curves, as expressed by the phase angle of the first harmonic, provides significant prognostic information.

Adult↗

Disseminated tumor cells in pancreatic cancer patients detected by immunocytology: a new prognostic factor.

Using an immunocytological approach, we previously showed that disseminated cancer cells are frequently found in peritoneal cavity and bone marrow samples of gastrointestinal and pancreatic cancer patients. Recently, we demonstrated that the detection of isolated tumor cells could serve as a new prognostic factor in gastric and colorectal cancer. Thus far, no conclusive data concerning the clinical implication of minimal residual disease in pancreatic cancer exist. In this study, we investigated peritoneal lavage and bone marrow samples of 80 pancreatic cancer patients to determine the predictive value of immunocytologically detected disseminated tumor cells. Therefore, immunocytological findings were correlated with the clinical follow-up data (median observation time, 10.7 months; range, 2-61 months), and the findings in peritoneal cavity and bone marrow samples were compared. Fifty-two % of the patients showed minimal residual disease at least in one compartment (39% positive lavage and 38% positive bone marrow samples). The detection rate of isolated tumor cells increased in parallel to the tumor stage. The presence of tumor cells in the peritoneal cavity significantly correlated with the survival time of the patients (P = 0.0035). In bone marrow samples, a strong trend was seen (P = 0.06). The evaluation of both compartments increased the number of positive patients and resulted in a highly significant correlation: all patients who were positive in at least one compartment died within 18 months, whereas negative patients showed a 5-year survival rate of 30% (P<0.0001). We recommend immunocytological investigation of peritoneal cavity and bone marrow samples as a new prognostic marker in pancreatic cancer patients.

Bone Marrow↗

Synthesis and structural characterization of human-identical lung surfactant SP-C protein.

An efficient synthesis for human-identical lung surfactant protein SP-C is described with a semi-automated solid phase synthesizer using Fmoc chemistry. Double coupling and acetic anhydride capping procedures were employed for synthetic cycles within the highly hydrophobic C-terminal domain of SP-C. Isolation of the protein was performed by mild cleavage and deprotection conditions and subsequent HPLC purification yielding a highly homogeneous protein as established by sequence determination, electrospray, plasma desorption and MALDI mass spectrometry. A general method has been employed for the preparation of Cys-palmitoylated protein by using temporary Cys(tButhio) protection, in situ deprotection with beta-mercaptoethanol and selective palmitoylation of resin-bound SP-C. The mild synthesis and isolation conditions provide SP-C with a high alpha-helical content, comparable to that of the natural SP-C, as assessed by CD spectra. Furthermore, first biophysical data indicate a surfactant activity comparable to that of the natural protein.

Amino Acid Sequence↗

Differences in pH-dependent activation rates of substituted benzimidazoles and biological in vitro correlates.

Gastric proton pump inhibitors (PPIs) are substituted benzimidazole prodrugs that require an acid-induced activation. Its rate depends on the reactivity of the molecule relative to the environmental pH and determines the drug's tissue selectivity. Factors affecting the exposure of moderately acidic tissues to the activated PPI are the area under the serum concentration-time curve (AUC), serum protein binding, the partition coefficient logP and the serum elimination half-life relative to the chemical activation half-life at a critical tissue pH of about 5. These parameters have therefore been determined in a comparative fashion in the present study. The data shows that pantoprazole is less likely to undergo unwanted activation at moderately acidic targets as opposed to the parietal cell, compared to omeprazole. Actually, although 40 mg pantoprazole (steady state) gave a slightly higher serum AUC of the total parent compound than 40 mg omeprazole (10.5 vs. 7.1 micromol x h x l[-1]), a higher serum protein binding of pantoprazole versus omeprazole (98 vs. 96%) reversed the AUC values for the free drug in favor of a lower value for pantoprazole (0.19 vs. 0.28 micromol x h x l[-1]). It is the free parent compound that equilibrates across cell membranes to be activated in acidic tissue compartments. At pH 5.1, the activation half-life of pantoprazole was 4.7 versus 1.4 h for omeprazole, the latter being in the order of the common serum elimination half-life determined in an intraindividual comparison (1.24 vs. 1.25 h). Thus, pantoprazole is eliminated faster from blood than it is activated at a pH of about 5, while omeprazole is as quickly activated at this pH as it is eliminated from blood. Biological in vitro experiments confirmed that pantoprazole displays a lower liability to interfere with unwanted biological targets. This has been demonstrated in vitro for inhibition of both renal Na+/K+-ATPase, lysosomal acidification and the production of reactive oxygen species by neutrophils.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.

We investigated 141 bone marrow and 104 venous blood isolates from gastrointestinal cancer patients with a cytokeratin (CK) 20-specific nested reverse transcription PCR for the detection of disseminated tumor cells at time of primary tumor resection. In colorectal cancer patients, 20 of 65 (31%) bone marrow and 9 of 52 (17%) venous blood isolates yielded a CK 20 mRNA-positive result in a stage-dependent manner. The detection rates for gastric cancer patients were 11 of 49 (22%) and 5 of 30 (17%) for bone marrow and venous blood, respectively. In pancreatic cancer patients, positive signals were found in advanced tumor stage. A duplex PCR system improved the feasibility of the test. After analyzing 70 sets of bone marrow and venous blood isolates from colorectal, gastric, and pancreatic cancer patients, we observed a higher detection rate in bone marrow isolates. Survival of patients with CK 20 mRNA-positive findings was significantly shorter than that of negatively tested patients.

Biomarkers, Tumor↗

Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41.

To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.

Animals↗