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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 523 records · Page 29Linked to original sources

[Unusual renal displacement due to extreme splenomegaly].

Report of a case of unusual renal displacement due to massive splenomegaly. The left kidney was displaced upwards by massive enlargement of the spleen. The own findings of ultrasonography, abdominal computed tomography and intravenous urogram are described and compared with the findings in the literature.

Adolescent↗

[Present status and limits of sonography in the diagnosis of hypertrophic pyloric stenosis].

Ultrasound studies of 46 infants with clinically suspected hypertrophic pyloric stenosis and of a control group of 30 infants were performed. The value and the limits of ultrasound in the diagnosis of hypertrophic pyloric stenosis, and the indications for upper gastrointestinal studies are discussed. Criteria for the ultrasound diagnosis of pyloric stenosis are established.

Female↗

[Sonographic findings in postpartum adrenal hemorrhage].

Report of 77 cases with postpartal adrenal hemorrhage. The diagnoses were made by ultrasonography. The ultrasonographic features, the findings of plain abdominal X-ray studies, and of intravenous urography are described.

Adrenal Gland Diseases↗

Evaluation of ethylene-vinyl acetate copolymer as a non-inflammatory alternative to Freund's complete adjuvant in rabbits.

Ethylene-vinyl acetate copolymer (EVAc) was evaluated as an antigen delivery device in laboratory rabbits. Bovine serum albumin (BSA) was incorporated with EVAc in a pellet, which was implanted subcutaneously. Serum antibody titers to BSA in four implanted rabbits were equal to titers in four rabbits injected twice with BSA in complete Freund's adjuvant. Three of four rabbits implanted with EVAc displayed no inflammation or systemic illness in response to the pellet. The fourth rabbit repeatedly developed a small abscess at the implantation site, but the lesions were less severe than complete Freund's adjuvant injection sites. The EVAc pellet is recommended as a non-inflammatory alternative method to Freund's adjuvants for producing serum antibody in rabbits.

Adjuvants, Immunologic↗

Sintering technique for the preparation of polymer matrices for the controlled release of macromolecules.

A new method for making polymeric systems for the controlled release of macromolecular drugs is described. The method consists of mixing drug and polymer (ethylene-vinyl acetate copolymer) powders below the glass transition temperature of the polymer and compressing the mixture at a temperature above the glass transition point. The macromolecule is not exposed to organic solvent during the fabrication process. Kinetic studies indicate that there is sustained release, and the bioactivity of macromolecules tested is unchanged throughout the sintering and release processes.

Delayed-Action Preparations↗

Value of computed tomography in the diagnosis of intrapulmonary arteriovenous shunts.

A case of intrapulmonary arteriovenous malformations (AVMs), its diagnosis, and a literature review is presented. We consider the diagnosis of intrapulmonary AVMs by noninvasive methods, such as plain chest radiography, fluoroscopy, computed tomography (CT), and particularly dynamic CT imaging of the thorax. To determine hemodynamic factors, oxygen consumption, oxygen saturation and blood gas analyses of the central pulmonary circulation digital subtraction angiography as well as invasive pulmonary angiography are needed.

Adult↗

An immobilized microbial heparinase for blood deheparinization.

A new medical application of an immobilized microbial enzyme is described. Extracorporeal devices require systemic heparin administration to prevent thrombus formation; however, the use of heparin often leads to serious hemorrhagic complications. Heparinase isolated from Flavobacterium has been immobilized and used in a fluidized bed reactor to eliminate heparin from blood passing through an extracorporeal circuit both in vitro and in vivo. This paper discusses the stepwise development of this heparinase reactor including: (1) improvements in the fermentation resulting in an inexpensive large-scale source of heparinase without the addition of the previously required inducer, heparin; (2) the use of batch processes to adapt previous purification schemes to large-scale heparinase production and the subsequent purification of heparinase to a single SDS-PAGE banding protein; (3) the immobilization of heparinase with a 91% activity recovery and good stability, (4) the design and successful testing of a fluidized bed reactor containing immobilized heparinase in the removal of clinically used quantities of heparin from both human blood in vitro and canine blood in vivo; and (5) the initiation of animal studies focusing on the toxicology of heparinase-derived heparin degradation products and the short and long term effects of exposure to these products and to heparinase.

Enzymes, Immobilized↗

Metachromatic activity of heparin and heparin fragments.

Heparin of an average molecular weight of 13,000 was fractionated on the basis of size into five fractions of different weight-average molecular weight ranging from 8500 to 20,000. The heparin was also degraded using microbial heparinase resulting in products ranging from a disaccharide of molecular weight 500 to an oligosaccharide of molecular weight 3100. These products were also size fractionated. The individual heparin fractions and products were tested for metachromatic activity with Azure A. The metachromatic activity of the heparin fractions was independent of molecular weight, while the metachromatic activity of the products was dependent on molecular weight. Metachromatic activity was found in a fragment as small as a tetrasaccharide. Anticoagulant activity was found in fragments of tetrasaccharide or larger by a Factor Xa clotting assay and in fragments of hexasaccharide or larger by a Factor Xa amidolytic chromogenic assay.

Animals↗

Controlled release of microquantities of macromolecules.

A technique for insuring the controlled release of small amounts of macromolecules such as polypeptides from polymeric delivery systems is described. We show that incorporation of albumin in milligram quantities into these delivery systems can facilitate the sustained release of nanogram or microgram quantities of a model macromolecule such as inulin. The albumin-containing controlled-release polymers did not cause inflammation or tissue damage in two commonly used assay sites for certain biological growth factors such as tumor angiogenesis stimulators and inhibitors--the chick chorioallantoic membrane (CAM) and the rabbit cornea. The method reported here should be particularly suited to the delivery of purified growth factors which are active and usually obtainable in microgram or smaller amounts.

Animals↗

Further characteristics of the ATP-stimulated uptake of calcium into chromaffin granules.

The ATP-stimulated uptake of 45Ca2+ [and [3H](-)-noradrenaline ([3H]NA)] into chromaffin granules and that into mitochondria are driven by a protonic gradient delta mu H+, composed of the components delta pH (concentration gradient of protons) and delta psi (electrical potential difference). The granular ATPase pumps protons into the matrix (delta pH inside acid, delta psi positive), but the mitochondrial ATPase ejects protons from the matrix (delta pH alkaline, delta psi negative inside). To show different driving forces of uptake, the rate of the ATP-stimulated uptake of 45Ca2+ (and [3H]NA) into chromaffin granules was compared with the rate of the ATP-stimulated uptake of 45Ca2+ into mitochondria (adrenomedullary or rat liver). In the presence of nitrate, the rate of the ATP-stimulated uptake of 45Ca2+ into chromaffin granules is higher than in the presence of acetate, because the lyotropic anion nitrate stimulates the granular ATPase and increases delta pH (acid inside). Compared with nitrate, the rate of the ATP-stimulated uptake of 45Ca2+ into mitochondria is higher in the presence of the proton-carrying anion acetate, which, after permeation, provides protons for ejection by the ATPase. In the absence of ATP, a valinomycin-mediated potassium influx (delta psi inside positive) stimulates the granular uptake of [3H]NA, which has an electrogenic component, but not the granular uptake of 45Ca2+, which is electroneutral. The electrogenic uptake of 45Ca2+ into mitochondria is stimulated by a valinomycin-mediated potassium efflux (delta psi negative inside). The ATP-stimulated uptake of 45Ca2+ into chromaffin granules is sensitive to ruthenium red, suggesting a carrier-mediated mechanism of uptake, and it is sensitive to atractyloside, indicating the simultaneous uptake of ATP. After collapse of delta pH by ammonia, the ATP-stimulated uptake of 45Ca2+ into chromaffin granules is abolished, but not that into mitochondria. In the presence of ammonia, the rate of the ATP-stimulated uptake of [3H]NA is very low, and an ATP-independent uptake of 45Ca2+ into chromaffin granules is observed which is similar to the ATP-independent Ca2+/Na+ exchange at the granular membrane.

Acetates↗

Effect of extracorporeal enzymatic deheparinization on formed blood components.

A stirred blood filter containing an immobilized enzyme, heparinase, has been used to neutralize heparin's anticoagulant activity at the outflow of an extracorporeal circuit in dogs. The hematocrit and red blood cell count remained unchanged throughout the 90-min perfusion period. Platelet and white blood cell counts decreased early in the procedure to approximately 20% of the initial levels, but then returned to 30 and 70%, respectively, of their initial values by the end of the procedure. After 24 h normal levels were reestablished. In vitro experiments with human blood were conducted to determine the principal cause of the observed decrease of formed blood components. An unstirred heparinase filter preserved platelets and white blood cells better than stirred filters possessing higher, the same, or no heparin-degrading capacity, suggesting that most of the loss of formed blood components is due to stirring and not to the heparinase or the Sepharose support on which the enzyme is immobilized.

Animals↗

Influence of indometacin administered in vivo on the synthesis of PGI2-like substances in human veins.

The effect of the cycloocygenase inhibitor indometacin (Indo) on the synthesis of prostacyclin-like substances (PGI2-LS) in human veins has been studied after in vivo and in vitro application of the drug. PGI2-LS were bioassayed by ADP-induced platelet aggregation during twenty minutes incubation time. We used human veins of varicose patients, which were removed during stripping operations. Indo was applied by rectal application in vivo or added to the incubation fluid. The synthesis of PGI2-LS was inhibited by Indo in both experiments in a time dependent manner.

Adult↗

Disposition and anticoagulant activity of biologically active heparin fragments in the rat.

The disposition of biologically active [35S]heparin fragments was studied in both normal and uremic rats after an i.v. dose of 1 mg/kg. In normal animals, the amount of radioactivity in the blood rapidly decreased with a half-life of less than 2 min whereas the anticoagulant activity showed a half-life of 30 min. By 5 hr, only 0.4% of the initial radioactivity was present in the blood whereas no anticoagulant activity could be detected. The heparin fragments were rapidly excreted: by 5 hr, 85% of the initial dose was excreted into the urine, whereas only 1% of the radioactivity was present in the feces. In contrast, 55% of the initial dose of the same amount of radioactive heparin was excreted into the urine after 5 hr. By 5 hr, 5.2% of the heparin fragments was organ-associated and 3.1% was present in the skin, muscle and bone. One week after injection, 3.9% of the radioactivity was still present in the body. In uremic animals, the radioactivity in the blood decreased to 12% of the initial dose by 5 hr whereas 13.5% was organ-associated and 64% was present in the skin, muscle and bone. Comparison of heparin with di- or hexasac-charide fragments indicated that both the clearance in the blood and the excretion into the urine are size-dependent. By 5 hr, the body burden of heparin is approximately five times higher than it is after the same dose of heparin fragments.

Animals↗