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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 127 records · Page 7Linked to original sources
PubMed2000

Do antisiphon valves reduce flow irregularities during vertical displacement of infusion pump systems?

Vertical displacement of syringe pumps may cause irregular drug delivery due to hydrostatic pressure changes in the infusion line. The extent of flow fluctuations depends on the internal compliance of infusion lines, syringes and syringe pumps. We evaluated whether pressure regulation by antisiphon valves (ASV) reduces the flow variation during vertical displacement of 50 ml standard syringes and infusion pumps. An infusion assembly comprising a standard 50 ml BD Plastipak or a 50 ml Fresenius syringe, with syringe pump and 2 m low compliance infusion line was used for in vitro measurement of fluid delivery. The assembly was tested without ASV, and with two ASVs of differing operating pressure (ASV:75: valve opening pressure = 75 mmHg; ASV:155, 155 mmHg). Retrograde aspiration volume, zero-drug delivery time and valve opening bolus were determined after lowering the syringe pump by 50 cm. After elevating the syringe pump to its initial position the ensuing infusion bolus was recorded. Without an antisiphon valve the observed zero-drug delivery times after lowering the syringe pump were (mean +/- SD) 2.4 +/- 0.2 min using the BD Plastipak syringe and 4.09 +/- 0.55 min using the Fresenius syringe. Introduction of the antisiphon valve prolonged the zero drug delivery time 58% (ASV:75) and 88% (ASV:155) in the BD Plastipak syringe assembly and 43% (ASV:75) and 81% (ASV:155) in the Fresenius syringe assembly (P < 0.001). Antisiphon valves worsen flow irregularities caused by vertical displacement of syringe pumps and when used with delivery of concentrated inotropic drugs at low infusion rates, they may aggravate haemodynamic consequences of inconstant drug delivery.

Infusion Pumps↗
PubMed2000

Incomplete inhibition of platelet aggregation and glycoprotein IIb-IIIa receptor blockade by abciximab: importance of internal pool of glycoprotein IIb-IIIa receptors.

Resting platelets contain a substantial internal pool of GPIIb-IIIa complexes that is exposed on the surface of activated platelets. Whether the exposure of internal GPIIb-IIIa complexes on the activated platelet surface affects therapy with GPIIb-IIIa antagonists is poorly understood. We addressed this issue in thirteen patients who underwent elective coronary stenting and received abciximab. Platelet aggregation, surface expression of GPIIb-IIIa and P-selectin, receptor blockade of GPIIb-IIIa, and platelet release in response to ADP and thrombin-receptor activating peptide (TRAP) were determined ex vivo by Lumi-aggregometry and flow cytometry before, during and after abciximab administration. We found that inhibition of aggregation and GPIIb-IIIa blockade of ADP-stimulated platelets was almost complete during abciximab administration. In contrast, when TRAP was used to stimulate platelets ex vivo aggregation was only partially inhibited, most likely due to release of internal pool of unblocked GPIIb-IIIa complexes. Using electron microscopy we found that 7E3-occupied GPIIb-IIIa complexes are internalized into the surface connected system (SCS) and the alpha-granules of washed platelets which was associated with a reduced degranulation of the alpha-granula membrane protein P-selectin. We conclude, that despite internalization of abciximab into the internal pool of GPIIb-IIIa, upon strong platelet activation with thrombin a significant amount of unblocked internal GPIIb-IIIa can be exposed on the platelet surface and mediate platelet aggregation. Incomplete blockade of the internal GPIIb-IIIa pool may limit clinical efficacy of abciximab.

Abciximab↗
PubMed2000

C-Reactive protein and cardiac troponin T in risk stratification: differences in optimal timing of tests early after the onset of chest pain.

BACKGROUND: Increased C-reactive protein (CRP) is an important prognostic indicator for early risk stratification in patients with an acute coronary syndrome (ACS), independent of, and in combination with, increased cardiac troponin T (cTnT). However, increases in both cTnT and CRP also occur secondary to myocardial damage. METHODS AND RESULTS: In 156 consecutive patients, early release kinetics of CRP and cTnT were analyzed. The cutoff values were 3.0 mg/L for CRP and 0.1 microgram/L for cTnT. In the 75 patients with a CRP below the cutoff on admission, there was little change in CRP until 8 h after the onset of symptoms. At 12 h after the onset of symptoms, the cumulative proportions of abnormal CRP and cTnT in non-ST elevation ACS patients were 27% and 89%, respectively (P <0.01). During the first 24 h after the onset of symptoms, the median time above the cutoff was 20 h for CRP and 5 h for cTnT (P <0.0001). CRP was below the cutoff on admission significantly more often among patients receiving thrombolytic therapy than in patients without an indication for reperfusion therapy (51% vs 28%; P = 0.004). CONCLUSIONS: Increased CRP as an early independent risk indicator should be measured as soon as possible after the onset of symptoms, whereas increased cTnT is most reliable at 12 or more hours after the onset of symptoms.

Acute Disease↗
PubMed1999

The 5/2,3/2 Spin Admixture in the Chloroiron(III) Derivative of the Sterically Crowded 2,3,7,8,12,13,17,18-Octaethyl-5,10,15,20-tetraphenylporphyrin.

Despite similar ring deformations in solution and in the solid state, the chloroiron(III) derivative of 2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin ([FeCl(oetpp)], shown schematically) prepared in this study exhibits only a very weak quantum-mechanical admixture of spin S=3/2 (only 4-10 %) with spin S=5/2. In contrast, for the variety of [FeCl(oetpp)] studied earlier by other researchers a 40 % contribution of the S=3/2 state was found.

Journal Article↗
PubMed1999

Analytical monitoring of the production of biodiesel by high-performance liquid chromatography with various detection methods.

Gradient elution reversed-phase high-performance liquid chromatography (RP-HPLC) was used for the determination of compounds occurring during the production of biodiesel from rapeseed oil. Individual triacylglycerols (TGs), diacylglycerols, monoacylglycerols and methyl esters of oleic, linoleic and linolenic acids and free fatty acids were separated in 25 min using a combined linear gradient with aqueous-organic and non-aqueous mobile phase steps: 70% acetonitrile+30% water in 0 min, 100% acetonitrile in 10 min, 50% acetonitrile+50% 2-propanol-hexane (5:4, v/v) in 20 min and 5 min final hold-up. Another method with a non-aqueous linear mobile phase gradient [from 100% methanol to 50% methanol+50% 2-propanol-hexane (5:4, v/v) in 15 min] was used for fast monitoring of conversion of rapeseed oil triacylglycerols to fatty acid methyl esters and for quantitation of residual TGs in the final biodiesel product. Sensitivity and linearity of various detection modes (UV detection at 205 nm, evaporative light scattering detection and mass spectrometric detection) were compared. The individual sample compounds were identified using coupled HPLC-atmospheric pressure chemical ionization mass spectrometry in the positive-ion mode.

Chromatography, High Pressure Liquid↗
PubMed1999

Thermal creep analysis of noble metal alloys for the ceramic-fused-to-metal technique.

Distortion of metal frameworks for the ceramic fused to metal technique during firing is attributed to thermal creep of the alloys. Usually thermal creep measurements are performed at constant load and constant temperature over varying time periods. Because metal frameworks for the ceramic-fused-to-metal technique are cyclically stressed, a three-point bending test for dynamic measurement of creep in a modified dilatometer was developed. Bending of 14 commercially available noble metal alloys was determined in the as-cast state, as well as after simulation of the firing process. The sag at 950 degrees C, which is the firing temperature of the ceramic, was chosen as an indicator for creep. No correlation of this value to other technical data of the alloys was observed, but it was found that sag correlates with the sum of the Au and Ag content of the alloys. A strong sag was observed with high (Au + Ag) content. The lowest sag values were found with a content in the range of 50 atom % (Au + Ag). At lower (Au + Ag) content Pd becomes the main component in the alloys, and the values for sag increased slightly. The method for dynamic measurement of creep gave reproducible results and offers a possible test for rapid qualitative creep assessment.

Biocompatible Materials↗
PubMed1999

"Growing fontanelle": a serious complication of difficult vacuum extraction.

Growing skull fractures in combination with leptomeningeal cysts are well known in childhood. A rare case of a growing fontanelle due to a leptomeningeal cyst is presented. The cyst occurred due to a traumatic delivery with vacuum extraction. Operative repair of the cyst revealed a dural tear at the border of the fontanelle. The imaging findings are discussed.

Arachnoid Cysts↗
PubMed1999

Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma.

We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5-50 microg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 microg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 microg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2-5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2x10(6) CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 microg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2x10(6) CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 microg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 microg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.

Adult↗
PubMed1999

Parental attitude towards alternative medicine in the paediatric intensive care unit.

UNLABELLED: The interest in alternative medicine (AM) is growing. In the USA and Canada, studies showed that 34% of adults and 11% of children use AM. In a prospective cohort study, we investigated the interest in AM among parents of critically ill children in the paediatric Intensive Care Unit (ICU) of a university hospital. From January 1996 to April 1997, we distributed questionnaires to the parents of critically ill children. These strictly anonymous questionnaires were completed at home and returned by mail. Exclusion criteria were short ( < 1 day) or repeated hospitalizations, and insufficient proficiency of the German language. The inclusion criteria were fulfilled by 591 patients; 561 received the questionnaire (95%) and 289 (52%) were returned. Of the respondents, 70% would appreciate AM as a complementary therapy on the ICU, 23% found AM equally or more important than conventional medicine whereas only 7% regarded AM as unimportant. On the ICU, 18% used AM; surprisingly 41% of them did not discuss it with physicians or nurses. An additional 21% would have liked to use AM, but did not do so. Typically, AM-users administered AM also at home to their children and themselves. Their children were however, older. CONCLUSIONS: A substantial proportion of parents used measures of alternative medicine in the intensive care unit, or would have like to do so. However, few had the confidence to discuss this wish with the medical personal. This suggests that alternative medicine is of great interest, even on an intensive care unit. Nevertheless, discussion about alternative medicine seems to be taboo in doctor-patient relations.

Adolescent↗
PubMed1999

A germline hMSH2 alteration is unrelated to colonic microsatellite instability in patients with ulcerative colitis.

Recently, a polymorphism in the hMSH2 DNA mismatch repair gene has been associated with the development of dysplasia in ulcerative colitis (UC) patients. This polymorphism is of interest because DNA mismatch repair defects result in alterations in microsatellite stability. The current study was designed to determine whether this hMSH2 polymorphism associates with the development of microsatellite instability and dysplasia in UC patients. The hMSH2 genotype of 96 UC patients was determined by direct DNA sequencing. In addition, we examined 363 samples of colonic mucosa from 93 of these UC patients for microsatellite mutation by polymerase chain reaction (PCR) at eight loci. Three cases had insufficient DNA for microsatellite instability studies. The hMSH2 polymorphism was identified in 13 of the 96 patients examined (13.5%). The polymorphism was observed in 7 of 46 patients with dysplasia (15.2%), and in 6 of 50 patients without dysplasia (12.0%). Microsatellite instability was identified in 35 tissue samples (25 regenerative, one indefinite for dysplasia, eight dysplasias, and one invasive carcinoma) from 26 patients. Two patients with microsatellite instability had the hMSH2 alteration. The 11 remaining patients had the hMSH2 polymorphism, but no evidence of microsatellite mutations with any of the markers tested. We were unable to confirm the previously reported findings that the specific germline hMSH2 alteration represents a marker for increased risk of dysplasia in patients with UC, nor is it responsible for the development of microsatellite instability in these patients.

Carcinoma↗
PubMed1999

Immunocytochemical evidence of vesicular localization of the orphan transporter RXT1 in the rat spinal cord.

Rxt1, a member of the Na+/Cl- orphan transporter family, exhibits numerous features suggesting a role as plasma membrane transporter. Despite numerous attempts, its substrate has not yet been identified, although immunocytochemical studies have shown that Rxt1 distribution generally matches that of glutamate or GABA. In order to further characterize Rxt1, its detailed immunocytochemical distribution in the rat spinal cord and dorsal root ganglia was studied at both light microscope and ultrastructural levels. The widespread distribution of Rxt1 in spinal cord and ganglia cannot be correlated with any known classical or peptidergic transmitter. Rxt1 is expressed in a subpopulation of glutamatergic primary afferent fibers, in large and medium-sized ganglion cells, while small glutamate cells exhibit generally no Rxt1-like immunoreactivity. In the spinal cord, Rxt1-immunoreactive cell body distribution is quite ubiquitous since Rxt1 is expressed in all laminae in various neuronal types like interneurons, some projection neurons and motoneurons. Some of these neurons are cholinergic. At the electron microscope level, the peroxidase labeling was never localized to the plasma membrane, but rather associated with different organelles including the outer membrane of small synaptic vesicles and large granular vesicles. This localization resembles that of vesicular transporters detected with the same method and suggests that Rxt1, in contrast to other Na+/Cl- transporters, is expressed on vesicles. This was confirmed using a pre-embedding silver-intensified colloidal gold method. Indeed, most gold particles appeared to be localized into the axoplasm on synaptic vesicle accumulations; only few gold particles were observed close to the plasma membrane. These results suggest that Rxt1, despite its molecular characteristics predicting a plasma membrane localization, might be a vesicular transporter.

Animals↗
PubMed1999

Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo.

Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, although its use could be limited by the potential induction of tumor necrosis factor alpha (TNFalpha)-mediated septic shock stimulated by lipid A. Genetic modifications of tumor-targeting Salmonella that alter lipid A and increase safety must, however, retain the useful properties of this bacteria. We report here that disruption of the Salmonella msbB gene reduces TNFalpha induction and increases the LD50 of this pathogenic bacteria by 10,000-fold. Notwithstanding this enormous difference, Salmonella retains its tumor-targeting properties, exhibiting tumor accumulation ratios in excess of 1000:1 compared with normal tissues. Administration of this bacteria to mice bearing melanoma results in tumors that are less than 6% the size of tumors in untreated controls at day 18. Thus, the antitumor activity previously demonstrated using tumor-targeting Salmonella with normal lipid A is retained. Lipid modification of tumor-specific bacterial vectors provides a means for reducing septic shock and further suggests that the antitumor activity of these bacteria may be independent of TNFalpha.

Acyltransferases↗
PubMed1999

Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia.

In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 x 10(9) NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 x 10(8) NC CliniMACS selected CD34+ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day -10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13+, CD15+), about 30% myelomonocytic cells (CD14, HLA-DR+), 5.2% megakaryocytes (CD61+) and 1.2% CD34+ cells. The proportion of T (CD3+), NK cells (CD56+) as well as dendritic cells (CD83+) was below 0.2%. The unseparated CB infused at day 0 and +1 consisted of a total of thawed 4.4 x 10(7) NC/kg BW, 5.8 x 10(4) CFU-GM/kg BW, 1.54 x 10(5) CD34+cells/kg BW and 7. 73 x 10(2) LTC-IC/kg BW. In addition, the 1 x 10(7) NC/kg BW ex vivo expanded cells representing 1.9 x 10(4) CFU-GM/kg BW, 1.13 x 10(5) CD34 cells/kg BW and 4.37 x 10(2) LTC-IC/kg BW, were infused at day +1. At day +2 after transplantation the patient revealed a focal pneumonia on X-ray with generalized sepsis and became catecholamine dependent. From day +4 the patient received 280 microg/m2 G-CSF. At day +5 she developed an erythroderma, which could not be identified as acute GVHD by biopsy. Early engraftment with leukocyte counts at days 8 and 14 were 350 and 700/microl, ANC 310 and 410/microl, respectively. Donor cells determined by chimerism analysis were 97% and 98% in the periphery at this early time. Most importantly, the pneumonia as well as the septicemia subsided within a few days. Notably, as well is the clearly shortened aplastic phase observed after this simultaneous CB cell component transplantation. The patients T cell and NK cell reconstitution could be detected at day +37 with 330 CD3+ cells/microl and 40 CD56+ cells/microl, respectively. The time to reach an absolute platelet count of 20 000 (50 000)/microl was 75 (103) days. The disease-free survival now exceeds 1 year in complete remission without chronic GVHD or any other health problems. These data show that the applicability of ex vivo expanded committed progenitors and LTC-IC, even in high risk leukemia at the time of transplantation, is feasible and can provide sufficient myeloid progenitors resulting in rapid engraftment able to clear bacterial pneumonia and sepsis. In addition, accelerated hematopoietic reconstitution apparently served as a well functioning platform for definitive graft-versus-leukemia activity. This transplantation of defined ex vivo generated components presents a feasible and generally applicable approach and may open a promising new avenue for cell therapy in malignant diseases.

Cell Culture Techniques↗
PubMed1999

Selective modulation of phosphatidylserine exposure on subpopulations of human peripheral blood lymphocytes by a plant lectin, Viscum album agglutinin (VAA)-I and its recombinant form (rVAA) in vitro.

Growing evidence suggests that lectin-carbohydrate interactions are involved in the regulation of the balance between cell growth and programmed cell death. Viscum album agglutinin (VAA)-I is a galactoside-specific, type II ribosome-inactivating plant lectin. At concentrations less than 10 ng/ml, VAA-I has been shown to induce gene expression and secretion of proinflammatory cytokines as well as apoptosis in cultures of human peripheral blood mononuclear cells (PBMC). This study analyzes the effects of VAA-I and its recombinant nonglycosylated form (rVAA) on alterations of cell membrane permeability of cultured human peripheral lymphocytes (PBL) and on membrane exposure of phosphatidylserine characteristic of apoptosis. Analyses were performed by flow cytometry after staining with propidium iodide (PI) and/or with FITC-Annexin V/PI. After 24 h incubation of PBMC with 100 ng/ml VAA-I and rVAA, staining with supravital concentration of PI (20 microg/ml) for 1 h revealed no differences in percentages of PI-positive cells induced by the two forms of lectin (32.3% and 29.4%), but the exposure to 5 microg/ml PI for 15 min resulted in a significant difference: 35.1% and 8.0% after VAA-I and rVAA treatment, respectively. Kinetic analysis of membrane alterations showed mainly Annexin V positivity after 24 h, whereas after 48 h and 72 h incubation with 100 ng/ml VAA-I or rVAA loss of membrane integrity occurred, as demonstrated by PI staining. Similar to VAA-I, rVAA showed a higher binding affinity for monocytes and granulocytes than for lymphocytes. In cultures of PBL, the binding rank order of both lectins to lymphocyte subsets was NK, CD19+ > CD8+ > CD4+. The amount of Annexin/PI staining of PBL subsets corresponds to the degree of their binding capacity. In conclusion, present results demonstrate that VAA-I and its nonglycosylated recombinant form rVAA exhibit comparable effects on cell membrane alterations in the subsets of human PBLs.

Annexins↗