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Biomedical subjects

A Seibert

Publications and source records attributed to A Seibert.

14 recordsLinked to original sources
PubMed2001

Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study.

OBJECTIVE: To identify a safe and potentially effective recombinant tissue factor pathway inhibitor (rTFPI) dose for further clinical evaluation in patients with severe sepsis. DESIGN: Prospective, randomized, single-blind, placebo-controlled, dose escalation, multicenter, multinational phase II clinical trial. SETTING: Thirty-eight intensive care units in the United States and Europe. PATIENTS: Two hundred and ten subjects with severe sepsis who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Subjects received a continuous intravenous infusion of placebo or rTFPI at 0.025 or 0.05 mg/kg/hr for 4 days (96 hrs). MEASUREMENTS AND MAIN RESULTS: There were no significant imbalances in demographics, severity of illness, or source of infection in patients randomized to placebo or either dose of rTFPI. A 20% relative reduction in 28-day all-cause mortality was observed when all rTFPI-treated patients were compared with all placebo patients. An improvement in pulmonary organ dysfunction score and in a composite intensive care unit score (pulmonary, cardiovascular, and coagulation) were also noted in the rTFPI-treated patients. Logistic regression modeling indicated a substantial treatment by baseline laboratory international normalized ratio (INR) interaction effect when only treatment and INR were in the model (p =.037) and when baseline Acute Physiology and Chronic Health Evaluation (APACHE II) and log10 interleukin 6 were adjusted for (p =.026). This interaction effect indicates that higher baseline INR is associated with a more pronounced beneficial rTFPI effect. There was no increase in mortality in subjects treated with either dose of rTFPI compared with placebo. Biological activity, as detected by a statistically significant reduction in thrombin-antithrombin complexes (TATc), was noted in the all rTFPI-treated patients compared with those receiving placebo. There were no major imbalances across all treatment groups with respect to safety. The frequency of adverse events (AEs) and severe adverse events (SAEs) was similar among the treatment groups, with a slight increase in SAEs and SAEs involving bleeding in the 0.05 mg/kg/hr rTFPI group. The overall incidence of AEs involving bleeding was 28% of patients in the all placebo group and 23% of patients in the all rTFPI-treated group; a slight but statistically insignificant increase in incidence of SAEs involving bleeding was observed in the all rTFPI group (9%) as compared with the all placebo group (6%; p =.39). CONCLUSIONS: Although the trial was not powered to show efficacy, a trend toward reduction in 28-day all-cause mortality was observed in the all rTFPI group compared with all placebo. This study demonstrates that rTFPI doses of 0.025 and 0.05 mg/kg/hr could be safely administered to severe sepsis patients. Additionally, rTFPI demonstrated bioactivity, as shown by reduction in TATc complexes and interleukin-6 levels. These findings warrant further evaluation of rTFPI in an adequately powered, placebo controlled, randomized trial for the treatment of severe sepsis.

APACHE↗
PubMed1999

[Test construction, analysis and trial of the Heidelberg Sound Discrimination Test for measuring auditory-kinesthetic perceptual discrimination acuity].

The provisional trial was carried out in a sample of 133 second- and 139 fourth-graders from the Heidelberg area. The HD-LT was subjected to an item selection, test criteria were ascertained and temporary percentile norms for the second and fourth grades were established. High item difficulty resulted for both grades, i.e. the test was relatively easy. Test criteria were generally satisfactory. Significant correlations were found in both grades between the HD-LT and the children's spelling ability. The HD-LT accounted for 30% of the spelling variance among second-graders as compared to 10% of that among fourth-graders. This reflects the specific significance of phonetic discrimination ability in the first years of elementary school. Children with spelling difficulties were compared to those with good spelling abilities in respect to their ability to discriminate sound. Spelling-impaired children in both grades exhibited a significantly lower overall HD-LT score. No significant sex differences were found with regard to the auditory and kinesthetic phonetic discrimination ability. Since the HD-LT turns out to be well-suited to indicate a phonetic discrimination disability during the initial phases of acquisition of written language, its further development and extension of its application to the pre-school level are recommended.

Child↗
PubMed1998

Mammography spectrum measurement using an x-ray diffraction device.

The use of a diffraction spectrometer developed by Deslattes for the determination of mammographic kV is extended to the measurement of accurate, relative x-ray spectra. Raw x-ray spectra (photon fluence versus energy) are determined by passing an x-ray beam through a bent quartz diffraction crystal, and the diffracted x-rays are detected by an x-ray intensifying screen coupled to a charge coupled device. Two nonlinear correction procedures, one operating on the energy axis and the other operating on the fluence axis, are described and performed on measured x-ray spectra. The corrected x-ray spectra are compared against tabulated x-ray spectra measured under nearly identical conditions. Results indicate that the current device is capable of producing accurate relative x-ray spectral measurements in the energy region from 12 keV to 40 keV, which represents most of the screen-film mammography energy range. Twelve keV is the low-energy cut-off, due to the design geometry of the device. The spectrometer was also used to determine the energy-dependent x-ray mass attenuation coefficients for aluminium, with excellent results in the 12-30 keV range. Additional utility of the device for accurately determining the attenuation characteristics of various normal and abnormal breast tissues and phantom substitutes is anticipated.

Biophysical Phenomena↗
PubMed1990

U74500A inhibition of oxidant-mediated lung injury.

Toxic oxygen species are thought to play a primary role in the pathophysiological mechanisms responsible for a diverse group of lung diseases. In this study, isolated perfused rat lungs were subjected to oxidant injury induced by ischemia-reperfusion (IR) and t-butyl hydroperoxide (t-buOOH) challenge. Both forms of injury caused large increases in capillary permeability as assessed by the capillary filtration coefficient (Kfc). IR and t-buOOH challenge caused increases in the Kfc of 0.95 +/- 0.22 and 0.30 +/- 0.06 ml.min-1.cmH2O-1.100 g lung tissue-1, respectively. U74500A, a potent inhibitor of iron-mediated lipid peroxidation, significantly attenuated the endothelial damage seen in both forms of injury. In lungs pretreated with U74500A, the Kfc increased 0.01 +/- 0.02 and 0.11 +/- 0.03 ml.min-1.cmH2O-1.100 g lung tissue-1 following IR and t-buOOH challenge, respectively. In lungs pretreated with the iron binding protein transferrin the Kfc increased 0.31 +/- 0.11 and 0.19 +/- 0.03 ml.min-1.cmH2O-1.100 g lung tissue-1 following IR and t-buOOH challenge, respectively. In these studies, transferrin significantly attenuated permeability in the IR group only. However, the attenuation of injury in IR due to U74500A was significantly greater (P less than 0.05) than the attenuation provided by transferrin. Both forms of injury also caused small but statistically significant increases in pulmonary artery pressure. These results suggest that the increase in capillary permeability seen after IR and t-buOOH is in part mediated by iron-dependent mechanisms.

Animals↗
PubMed1990

Normal versus sickle red blood cells: hemodynamic and permeability characteristics in reperfusion lung injury.

Decreased deformability and increased internal viscosity of the sickle red blood cell (SRBC) contribute to abnormal flow in the microcirculation. Since the lungs are commonly affected in sickle cell disease, we compared the hemodynamics of the normal human red blood cell (NRBC) with the SRBC in the pulmonary circulation. The SRBC has decreased antioxidant enzyme activities compared with the NRBC. Thus, using the capillary filtration coefficient (Kfc), we determined the ability of the NRBC and the SRBC to attenuate the increased permeability and resulting edema seen in the oxidant stress of reperfusion lung injury (RLI). We found that lungs perfused with a 5% SRBC perfusate had higher pulmonary arterial pressures (Ppa) and resistances than lungs perfused with a 5% NRBC perfusate. Lungs made ischemic and reperfused with a physiologic cell-free perfusate resulted in a significant increase (P less than .05) in Kfc compared with the preischemic Kfc (.45 +/- .06 to 1.4 +/- 22 mL.min-1.cm H2O.100 g-1). In lungs reperfused with 5% RBC-containing perfusates, the Kfc did not change from preischemic Kfc with NRBCs and decreased from the preischemic Kfc with SRBCs. These findings suggest that the SRBC causes physiologically significant increases in Ppa and resistances and the SRBC, like the NRBC, offers apparent protection in RLI.

Anemia, Sickle Cell↗
PubMed1989

31P spectroscopy in thrombolytic treatment of experimental cerebral infarct.

Ischemic changes produced by autogenous clot embolization of intracranial arteries were monitored by continuous surface-coil 31P spectroscopy in 12 rabbits: six were used as controls and six were treated intravenously with tissue-type plasminogen activator. The animals were sacrificed and the brains were fixed with intravital stains. The results indicate that spectral changes are reversible only when thrombolysis therapy is started within 30 min after ischemic changes are detected. The improvement of the 31P spectrum correlated with postmortem changes.

Animals↗
PubMed1986

Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism.

The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2-deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage.

Animals↗
PubMed1984

P-31 nuclear magnetic resonance analysis of brain: II. Effects of oxygen deprivation on isolated perfused and nonperfused rat brain.

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th

Animals↗
PubMed1984

[Comparison of the effects of piracetam and methohexital on cerebral energy metabolism].

Several authors suggest an influence of piracetam on brain energy metabolism. Therefore, we examined the effect of this drug on the levels of high-energy phosphates, glucose, some metabolites of glycolysis and free amino acids in the rat brain under normoxic, ischemic and postischemic conditions. In order to eliminate peripheral effects on the cerebral metabolism the isolated perfused rat brain was used as a model for this study. Methohexital was also administered for demonstrating protective effects on energy metabolism under the experimental conditions employed. The barbiturate, not piracetam, reduced the recovery time of the EEG after 1.5 or 2 min of ischemia. The depletion of energy reserves after the ischemic periods was diminished by methohexital but not by piracetam. The substrate and metabolite levels removed faster to the control levels under methohexital in the postischemic period whereas the piracetam treated brains did not differ from the controls. The subchronical treatment of rats in vivo with piracetam only caused a slightly smaller increase in the cerebral lactate concentration after anoxic periods. These results do not suggest an acute effect of piracetam on rat brain energy metabolism whereas the barbiturate methohexital may protect the brain against ischemic damage in a certain extent.

Amino Acids↗
PubMed1983

Measurement of left ventricular ejection fraction by videodensitometric analysis of digital subtraction angiograms.

Left ventricular ejection fraction (LVEF) was calculated from 25 first-pass digital subtraction angiograms using a densitometric analysis. Digital subtraction angiograms are obtained in a computerized format; therefore, they can be readily analyzed with computer software to measure the density of the iodine signal within the image. The video signals from the image intensifier were logarithmically amplified so that there was a linear correlation between the video signal intensity and the depth of the iodine contrast material represented by that video signal. LVEF was also calculated by the area-length method from the same digital subtraction angiograms. There was close correlation between these two techniques (r = 0.94, standard error of the estimate = 5.04%). The videodensitometric EF technique is simple to perform, it correlates well with the standard area-length method, and is not dependent on geometric assumptions of LV geometry.

Absorptiometry, Photon↗
PubMed1983

Digital angiography in assessment of ventricular function and wall motion during pacing in patients with coronary artery disease.

Using digital subtraction angiography, left ventriculograms were obtained with 10 ml of iodinated contrast material in 21 patients both at rest and during atrial pacing. In 15 patients with significant coronary artery lesions (CAD) (greater than 50% diameter narrowing in at least 1 major artery), ejection fraction decreased during atrial pacing from a mean of 62 +/- 14% to 51 +/- 15% (p less than 0.001). In 14 (93%) of 15 patients, ejection fraction decreased or was unchanged during pacing. In 6 patients with chest pain but normal coronary arteries, ejection fraction increased from a mean of 66 +/- 9% at rest to 72 +/- 6% during atrial pacing (p less than 0.01). Ejection fraction increased by greater than or equal to 5% during pacing in 5 of 6 patients with normal coronary arteries. Patients with CAD also had an abnormal response in end-systolic volume during atrial pacing (50 +/- 31 ml at rest versus 47 +/- 24 ml during pacing) compared with patients with normal coronary arteries (46 +/- 16 ml at rest versus 26 +/- 9 ml during pacing; p less than 0.01). The digital ventriculograms demonstrated new or increased wall motion abnormalities during atrial pacing in 4 of 5 patients with CAD who had wall motion abnormalities at rest and in 8 of 10 patients with CAD who had normal wall motion at rest. Moreover, these wall motion abnormalities occurred in myocardial wall segments that were supplied by coronary arteries with significant lesions. Thus, because digital subtraction angiography allows multiple left ventriculograms to be obtained during routine cardiac catheterization, intervention studies such as atrial pacing can be used to obtain a functional assessment of the severity of coronary arterial lesions.

Adult↗
PubMed1983

Correlation of 10-milliliter digital subtraction ventriculograms compared with standard cineangiograms.

Left ventriculograms were obtained with the use of 10 ml of contrast media by passing fluoroscopic video images through a video image processor. The low concentration of dye in the left ventricle was enhanced by the technique of mask mode subtraction, and the images were postprocessed to increase visibility by manipulation of the gray scale and contrast levels. These digital subtraction angiograms were compared to standard cineangiograms by means of 40 ml of contrast media. Of 30 patients studied, six (20%) had runs of ventricular tachycardia during the cineangiogram and had to be excluded. In the remaining 24 patients, there was a good correlation between the two techniques for left ventricular end-diastolic volume (r = 0.77, end-systolic volume (r = 0.95), and ejection fraction (r = 0.97). Spatial resolution in the digital studies was adequate to appreciate wall motion abnormalities that were visualized on the cineangiograms. Left ventricular end-diastolic pressure (LVEDP) did not change after the 10 ml injection, but the mean LVEDP rose 6.0 mm Hg after the 40 ml cineangiograms (p less than 0.01). Digital subtraction angiography can be used to obtain left ventriculograms with one-fourth the amount of contrast media and one-fourth the x-ray exposure compared to standard cineangiograms. This technology will permit multiple left ventriculograms to be obtained which, in turn, will allow intervention studies to be performed in the catheterization laboratory.

Adult↗