Prophylaxis of deep venous thromboembolism. Literature review.

The prophylaxis of deep venous thrombosis is critically related to potentially life-threatening pulmonary embolism. Each of the available agents has benefits and drawbacks which are reviewed in this article. While the search for the ideal method of prophylaxis continues, the appropriate agent appears to be one that balances the risk of complication with the potential risk of development of thromboembolism. Recommendations for acceptable prophylaxis are made for various procedures.

Purification and properties of hyaluronidase from human liver. Differences from and similarities to the testicular enzyme.

Human liver hyaluronidase was purified to homogeneity by (NH4)2SO4 fractionation, chromatography on hydroxyapatite and DEAE-cellulose, and preparative disc polyacrylamide-gel electrophoresis. The enzyme had a pH optimum of 3.8-4.0, a molecular weight (determined by gel filtration) of 76000, and a Km of 0.05 mg/ml for purified human umbilical-cord hyaluronic acid. It generally resembled hyaluronidases studied in other tissues which are believed to be lysosomal, but shared a number of characteristics with a partially purified bovine testicular hyaluronidase. Neither enzyme exhibited inhibition by high concentrations of substrate, but both were competitively inhibited by dermatan sulphate and keratan sulphate. Both enzymes exhibited increased activity in the presence of albumin, probably owing to an increased susceptibility of substrate to enzyme action. The liver enzyme was inhibited by NaCl, but the testicular enzyme exhibited an increase in activity in the presence of the salt which was similar to the effect observed with albumin. The different response toward Cl- ion appeared to be the most significant difference between the two enzymes.

The quantitative spectrophotometric estimation of total sulfated glycosaminoglycan levels. Formation of soluble alcian blue complexes.

The formation of soluble complexes between alcian blue dye and sulfated glycosaminoglycans provides the basis for the quantitative spectrophotometric estimation of the total concentration of these polysaccharides. Samples containing microgram quantities of sulfated glycosaminoglycan are mixed with a stable dye solution prepared in 15% phosphoric/2% sulfuric acids and absorbance readings at 480 nm are compared to an appropriate standard curve. The method is rapid, convenient, and reproducible. Analyses are performed under conditions in which there is no interference from the non-sulfated glycosaminoglycan hyaluronic acid, or most other anionic macromolecules. In addition, estimations are not effected by small anions or individual monosaccharides. The method has been used for the determination of the purity of commercially available preparations of hyaluronic acid and for the estimation of the sulfated glycosaminoglycan content of various biological fluids including normal human urine and the synovial fluid of individuals with rheumatoid arthritis and osteoarthritis.

Incidence and pathogenesis of alcohol-induced osteonecrosis of the femoral head.

Anteroposterior pelvic roentgenograms of 790 patients admitted for treatment of alcoholism were examined for evidence of osteonecrosis of the femoral head. Laboratory data on these patients, obtained shortly after admission, demonstrated that average serum cholesterol levels were within normal limits and average serum triglyceride levels were moderately elevated only in those individuals classified as having a severe addition to alcohol. Non-juxta-articular radiographic abnormalities of the femoral head, neck and shaft were common but no changes were observed which were considered to be early indications of structural insufficiency. Two patients had advanced idiopathic bilateral osteonecrosis of the femoral head. One of these patients had undergone one total hip replacement prior to his current admission. This study indicates that there is a very low incidence of osteonecrosis among alcoholics (less than 0.3%). However, alcoholism may lead to osteonecrosis in certain predisposed individuals. A combination of several factors such as systemic fat embolism, elevated circulating levels of inflammatory fatty acids or prostaglandins, and osteoporosis and Charcot-like effects, which are also associated with corticosteroid-induced osteonecrosis, seem to be involved and may contribute, as well, to other instances of femoral head osteonecrosis.

The effect of physiological levels of non-esterified fatty acids on the radioimmunoassay of prostaglandins.

Non-esterified fatty acids (NEFA) can significantly interfere with the radioimmunoassay of PGE and PGF2alpha using commercially available anti-sera. PGB1 antigen-antibody binding is 50% inhibited by 110 pg of PGB1, 48 ng of PGE1, 3.5 microgram of PGF2alpha, or 9.0 microgram linoleic, 14 microgram arachidonic, 22 microgram delta-linoleic, 40 microgram palmitoleic or 45 microgram oleic acids. PGF2alpha antigen-antibody binding is 50% inhibited by 270 pg of PGF2alpha, 70 ng of PGE1, or 4.2 microgram arachidonic, 14 microgram delta-linoleic, 22 microgram linoleic, 70 microgram palmitoleic or 110 microgram oleic acids. Physiological levels of NEFA, such as the quantities found in small volumes of plasma, are sufficient to prohibit accurate prostaglandin measurements. Chromatography on small columns of silicic acid proved to be an effective technique for separation of NEFA and prostaglandin from lipid extracts, however, the results of this study suggest that the interference produced by the presence of NEFA in the measurement of prostaglandin from certain physiological fluids may be avoided if the prostaglandins are not extracted prior to radioimmunoassay.

Corticosteroid-induced avascular necrosis: an experimental study in rabbits.

New Zealand white rabbits were divided into 4 groups for the study of the etiology of corticosteroid-induced osteonecrosis (avascular necrosis). Group A and B received intramuscular injections of methylprednisolone acetate and methylprednisolone succinate respectively. Group C, on semirestricted diets, and Group D, on ad libitum diets, were controls. Osteocyte death, necrotic debris and intravascular fat emboli were evident in sections of proximal and distal femur by the 2nd week in experimental animals. Blood analysis revealed elevated lipid and prostaglandin levels. Osteoporosis was first observed at 6 weeks. Evidence of advanced osteonecrosis was present histologically at 18 weeks. It is concluded that osteonecrosis probably develops as the result of the interaction of several corticosteroid-induced alterations, including circulating fat emboli and inflammatory unbound free fatty acids or prostaglandins. Osteoporosis may also be a factor in explaining the sporadic nature of the disorder.

The effect of salicylate on prostaglandin levels in rabbit knees following inducement of osteoarthritic changes.

Surgical inducement of medial instability in the right knee of rabbits was used to produce joint changes which resemble those observed in human osteoarthritis. Ordinary tap water was supplied to half of the rabbits and tap water plus sodium salicylate to the others. Determinations of prostaglandin were made on the synovial fluid and cartilage from all rabbits five months after surgery. In both groups, the concentration of prostaglandin in synovial fluid was lower in the operated knees, but the total amount of prostaglandin was found to be approximately equal to that in the unoperated knees. The development of degenerative joint changes therefore was not accompanied by increases in prostaglandin content. Salicylate treatment did not alter this observation, however, it did reduce overall prostaglandin levels. These results suggest that prostaglandin interaction is not involved in osteoarthritic joint degeneration.

Effect of salicylate on the surgical inducement of joint degeneration in rabbit knees.

Degenerative joint changes were produced in one knee of each of fourteen rabbits by surgical induction of instability. The involved knee in rabbits with and without systemic salicylate treatment was compared with the knee not operated on. Salicylate did not significantly change the activities of lysosomal enzymes in cartilage or synovial fluid, the uptake of tritiated thymidine, glycine, or 35S-inorganic sulphate by cartilage, or the histological manifestations of cartilage degeneration.

Enzymes from human articular cartilage: isolation of arylsulfatase B and its comparison with arylsulfatase A.

This study describes the isolation of arylsulfatases A and B (arylsulfate sulfohydrolase EC 3.1.6.1) from human articular cartilage. These enzymes were extracted from collagenase digests of tissue homogenates. After fractionation with ammonium sulfate the enzymes were separated from each other by DEAE-cellulose chromatography and further purified by gel filtration on Sephadex G-200. Sulfatase B, subsequently chromatographed on CM-cellulose was apparently homogenous as judged by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate. The enzyme has a pH optimum of 5.6, a molecular weight of 51,000 and Km of 2.6 mM for 4-nitrocatechol sulfate. Sulfatase A was found to be a glycoprotein with a pH optimum of 4.8, a molecular weight of 105,000 and a Km of 0.16 mM for 4-nitrocatechol sulfate. The competitive inhibition of both enzymes by inorganic sulfate, sulfite and phosphate support the likelihood of a common reaction mechanism. In contrast to sulfatase B which showed minimal inhibition, sulfatase A was totally inhibited by 5 mM N-ethylmaleimide.