Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.     

Salvage of tourniquet-induced thumb necrosis by a modified wraparound procedure

Rolled finger gloves were used as ring tourniquets on a case of amputation injury of bilateral thumbs. Necrosis of soft tissue of the right thumb occurred due to mistakenly prolonged use of the tourniquet. Later the patient successfully underwent a toe-to-thumb transfer (modified wraparound procedure). The precautions in using finger tourniquets are stressed.     

Orthotopic liver transplantation in children

Between 1-1-1982 and 1-1-1988 52 children with an end-stage liver disease were evaluated to determine whether orthotopic liver transplantation (OLT) would be appropriate. 24 children were accepted as candidates in the long term. Twelve were not accepted as potential recipients. The parents of 3 decided not to accept OLT as treatment for their children. Two children died before a suitable donor liver was available, so that OLT was carried out in 11 children. Two of these children needed a second transplant. In 3 children only a part of a donor liver was transplanted. Shortage of donor livers of small size is partly alleviated by using a part of a larger liver. The underlying diseases of the transplanted children were cryptogenic cirrhosis (1x), biliary atresia with a hepatoportoenterostomy (8x) and cirrhosis following neonatal hepatitis (2x). Ten children with OLT are clinically and physically well. Postoperatively a primary graft dysfunction occurred in one child. He was retransplanted. The median waiting time for a donor liver was 5 months. The timing for OLT has to take this in account. In treating children with end-stage liver disease (partial) OLT should be considered.     

Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Human glomeruli release fatty acids which stimulate thromboxane synthesis in platelets

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)