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Biomedical subjects

A Stadler

Publications and source records attributed to A Stadler.

34 records · Page 2Linked to original sources

Treatment of aluminum overload using a cartridge with immobilized desferrioxamine.

Intravenous desferrioxamine (DFO) is the method commonly used to treat aluminum toxicity. This laboratory has developed a hollow fiber device with immobilized DFO, an "Aluminum DFO-HP" (DFO-HP), for the purpose of removing aluminum without the chelator (DFO) entering the blood. With Food and Drug Administration approval, a polysulfone DFO-HP, placed in the extracorporeal circuit in series with the patient's customary dialyzer, was tested for its safety and ability to remove aluminum in patients with ESRD who had aluminum overload. During treatment with this device, no toxic reactions, side effects, or hematologic or clinical laboratory changes were seen other than those associated with dialysis. Average aluminum clearance with the DFO-HP device was 25.3 mL/min with a range of 7.2 to 52.4 mL/min, whereas aluminum clearance with the F-60 polysulfone high-flux dialyzer was 8.4 mL/min. Aluminum clearance of the cuprophane dialyzers in series with the DFO-HP was negligible. The amount of aluminum removed over a 2-h treatment with DFO-HP ranged from 94 to 628 micrograms, which corresponded to 32 to 199% of the initial aluminum in the circulation before that particular treatment. The excess 99% was provided from aluminum released from tissue sites into the circulation throughout the duration of the treatment. It is expected that, because of the efficiency and safety of the DFO-HP device, the time presently needed for aluminum depletion using intravenous DFO will be greatly shortened and the potential toxicity of intravenous DFO will be eliminated.

Aluminum↗

Mechanical fragility of erythrocyte membrane in neonates and adults.

The shortened life span of neonatal red blood cells (RBC) is associated with accelerated membrane loss. The present study was designed to measure the critical shear force that causes membrane failure and the rate of membrane failure for neonatal and adult RBC. A micropipette technique was used to determine the membrane extensional (shear) elastic modulus (i.e. resistance of the membrane to extensional elastic deformation), the rate of extensional membrane deformation (i.e. surface viscosity), and the tension for local membrane fragmentation. A flow channel system was used to determine the critical shear force of plastic membrane deformation (i.e. beginning of membrane tether formation), the rate of plastic deformation, and the plastic shear viscosity coefficient. The extensional elastic modulus of neonatal RBC was 18% smaller and the rate of elastic deformation was 25% longer compared with adult cells (p less than 0.05). Membrane surface viscosity was similar for both cell types. The tension for local membrane fragmentation in the micropipette was 23% lower in neonates than in adults. However, the strain (i.e. extent of membrane deformation calculated as ratio of the stress resultant and the elastic modulus) at which membrane rupture in the micropipette occurred was similar for neonatal and adult RBC. This indicates that the smaller critical tension for neonatal RBC membrane failure was due to increased membrane elastic deformability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Flow behavior of neonatal and adult erythrocytes in narrow capillaries.

This study was designed to analyze the flow behavior of red blood cells (RBCs) in circular vessels with diameters of 3 to 6 microns by means of a mathematical model. According to this model, the RBC flow velocity is 1 mm/sec, RBCs assume axisymmetric shape, and the gap between the RBC and the vessel wall allows sufficient lubrication. The flow resistance depends on the surface area and volume of RBCs, the plasma viscosity, and the vessel diameter. Surface area and volume of RBCs from 10 term neonates and 10 adults were determined by means of a micropipet system and plasma viscosity was measured using a capillary viscometer. Neonatal RBCs had larger volumes (107 +/- 6 fl vs 90 +/- 4 fl) and surface areas (154 +/- 7 microns 2 vs 137 +/- 7 microns 2) than adult RBCs (P less than 0.005). Plasma viscosity was lower in neonates than in adults (1.04 +/- 0.10 cP vs 1.26 +/- 0.13 cP; P less than 0.005). The flow model leads to the following conclusions: During the passage of 3- to 6- microns vessels, the large neonatal RBCs are more elongated than the smaller adult RBCs. In vessels with diameters of less than 3.3 microns, the rear of neonatal RBCs becomes convex, whereas this critical vessel diameter is 3.1 microns for adult RBCs. If the cells are suspended in the same medium, neonatal RBCs require a 31% higher driving pressure than adult RBCs to achieve the necessary elongation for passing through a narrow capillary. However, both cell types require similar driving pressures, if the cells are suspended in the corresponding plasma. The tube/discharge hematocrit ratio of neonatal RBCs is 1 to 6% higher than that of adult cells. Relative viscosity of neonatal RBCs is approximately 7% higher compared with adult RBCs, whereas the blood viscosity (relative viscosity times plasma viscosity) is 12% less in neonates than in adults. We conclude that the large size of neonatal RBCs may cause impaired flow in narrow vessels with diameters below the critical value of 3.3 microns. In vessels with diameters of 3.3-6.0 microns, the disadvantage of the large size of neonatal RBCs appears to be completely compensated for by the lowr plasma viscosity in the neonate.

Adult↗

Kinetics and disposition of fluorescein-labelled liposomes in healthy human subjects.

The in vivo kinetics and organ uptake of multilamellar liposomes have been studied in healthy volunteers. Sodium fluorescein-containing liposomes composed of equimolar amounts of egg phosphatidylocholine and cholesterol were injected into a peripheral vein in 4 healthy subjects. Blood samples collected from the femoral artery, hepatic vein and pulmonary artery, were analysed for liposomal dye content. The results, showing involvement of the reticuloendothelial system (RES) in the removal of liposomes, confirmed those previously obtained with radiolabelled preparations. Use of an innocuous liposomal marker (sodium fluorescein) and conventional vascular catheterization techniques, as employed here, may provide a reliable and clinically acceptable approach to establishing disease-induced changes in the kinetics of uptake of drug-containing liposomes by the RES, and thus help in the design of protocols for effective treatment.

Adult↗

Measurement of intact human parathyrin by an extracting two-site immunoradiometric assay.

This is an immunoradiometric assay of intact human parathyrin, hPTH(1-84). One antibody, directed against the N-terminal part of the hormone, was produced in goats and conjugated covalently to cellulose particles. hPTH(1-84) and the N-terminal fragments were extracted from EDTA-treated plasma by these particles and thus concentrated. Another antibody, against synthetic hPTH(53-84), was raised in rabbits; this bound to the C-terminal part of the hormone. The final step was labeling the second free binding site of this antibody with 125I-labeled Tyr52-hPTH(53-84) and measuring the bound radioactivity. This assay can detect intact PTH in concentrations as low as 0.6 pmol/L (1.2 X 10(-16) mol per tube). The assay did not cross react with hPTH(1-34), hPTH(1-44), hPTH(28-48), hPTH(39-84), hPTH(44-68), or hPTH(53-84) in concentrations up to 6400 pmol/L. In 60 normal subjects, hPTH(1-84) concentrations ranged from 1.9 to 6.8 pmol/L; in 32 patients with primary hyperparathyroidism, from 7.0 to 80 pmol/L. The hormone was not detected in four patients with hypoparathyroidism.

Antibodies, Monoclonal↗

Studies on the clinical significance of nonesterified and total cholesterol in urine.

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean +/- 2 SD) of 0.2-2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3-3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasizing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers.

Adolescent↗

Automated library generation using sequential microwave-assisted chemistry. Application toward the Biginelli multicomponent condensation.

The concept of automated sequential microwave-assisted library synthesis is introduced. For this purpose a dedicated single-mode microwave reactor with a robotics interface including a liquid handler and gripper was employed. The liquid handler allows dispensing of reagents into the Teflon sealed reaction vials, while the gripper moves each sealed vial in and out of the microwave cavity after irradiation. This technology was employed for the Biginelli three-component cyclocondensation reaction. A diverse set of 17 CH-acidic-carbonyl compounds (1A-Q), 25 aldehydes (2a-y), and 8 urea/thioureas (3alpha-varphi) was used in the preparation of a dihydropyrimidine (DHPM) library. Out of the full set of 3400 possible DHPM derivatives, a representative subset of 48 analogues was prepared using automated addition of building blocks and subsequent sequential microwave irradiation of each process vial. For most building block combinations 10 min of microwave flash heating at 120 degrees C using AcOH/EtOH (3:1) and 10 mol % Yb(OTf)(3) as solvent/catalyst system proved to be successful, leading to an average isolated yield of 52% of DHPMs with >90% purity. For some building block combinations the general conditions were modified, for example, by changing the solvent, catalyst, reaction temperature, or irradiation time. This flexibility is a distinct advantage of sequential over parallel microwave-assisted processes where all reactions are exposed to the same irradiation conditions. When the unattended automation capabilities of the microwave synthesizer are used, a library of this size can be synthesized within 12 h.

Journal Article↗