MR cholangiography enables accurate detection and localization of PSC.

A LITERATURE extending over four centuries cannot be checked experimentally by any one observer. The writer has, therefore, contented himself in this paper with recording the observations of others, and has not attempted too critical a review of their works. Conflicting statements, where they occur, must be judged on their merits, but it should not be forgotten in this connexion that the wide variations found in the venous system as a whole have a parallel in the particular part of that system now under consideration. To individual differences, and to differences between individual veins, must be added those due to age, sex and species, and possibly also others.(I) TERMINOLOGY.(See fig. 1.) The valves of veins have been called by various names, membranGe [155], membranulam, ostiola [1], apophyses membrac&arum [47, p. 1221, membranarum epiphyses [47, p. 357; 147], valvulam and Oty/goeE86t& membran.e [1]. In this last,the word sigmoid refers to the old Greek letter sigma, which was semilunar in shape, like a capital C. In addition to the above names, exilia opercula [115] and f7rav6ta-1ol [132] are terms which some writers have referred to valves.Valves have been divided into two classes, first, those over the entries of trib.utary veins, variously called platismata or platismnatia [123], soupapes [140],

Analogues of the competitive angiotensin antagonist [Sar1,Tyr(Me)4]ANG II (sarmesin) in which the sarcosine-1, O-methyltyrosine-4, and phenylalanine-8 residues were modified have been synthesized by the solid-phase method. The agonist and antagonist potencies of the 23 peptides synthesized were determined in the rat isolated uterus assay. At position 1, replacement of Sar with Asp, Ala, or Pro gave inactive analogues, and deletion of the N-terminal amino acid produced inactive heptapeptides for all analogues investigated. At position 4, substitution of Tyr with Tyr(Et), D-Tyr, D-Phe, Ile, Thr, or Hyp resulted in inactive analogues, whereas substitution of Phe gave a potent competitive antagonist (pA2 = 7.9), which retained significant agonist activity (22%). For position 8, [Sar1,Tyr(Me)4,Ile8]ANG II and [Sar1,Phe4,Ile8]ANG II were weaker antagonists (pA2 = 6.6 and 6.7, respectively) than [Sar1,Ile8]ANG II (pA2 apparent = 8.1) and, moreover, were reversible competitive antagonists. These findings demonstrate that the structural requirements for receptor blockade by sarmesin are remarkably stringent--modifications at positions 1, 4, and 8 markedly reduce the antagonist activity of this peptide.

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Analogues of angiotensin II and III (ANG II and ANG III) in which the tyrosine and/or phenylalanine residues were substituted have been synthesized by the solid-phase method and purified by (carboxymethyl)cellulose chromatography and reversed-phase HPLC. The antagonist and agonist potencies of these peptides were determined in the rat isolated uterus assay. [Sar1,Tyr(Me)4]ANG II, [Tyr(Me)3]ANG III, [Sar1,D-Trp4]ANG II, [D-Trp3]ANG III, [Sar1,D-Trp8]ANG II, [D-Trp7]ANG III, [Sar1,Tyr(Me)4,Ile8]ANG II, [Tyr(Me)3,Ile7]ANG III, [Sar1,D-Trp4,Ile8]ANG II, [D-Trp3,Ile7]ANG III, [Sar1,Tyr(Me)4,D-Trp8]ANG II, and [Tyr(Me)3,D-Trp7]ANG III had antagonist activities (pA2) respectively of 8.1, less than 6, less than 6, less than 6, (7.7), (6.7), 7.2, less than 6, less than 6, less than 6, 7.1, and less than 6. The agonist activity of each peptide was less than 0.1% of that of ANG II. Analogues in which only the Phe residue was substituted were not readily reversible in the bioassay, whereas analogues in which only the Tyr residue or both the Tyr and Phe residues were substituted were reversible antagonists. Peptides that were twice substituted had lower antagonist activities than peptides having a single aromatic residue substitution. Substitution of the Tyr residue in ANG II, but not ANG III, provides a new route for the synthesis of potent and competitive angiotensin antagonists. Differences in the biological properties of ANG II and ANG III analogues substituted at the Tyr residue suggest different binding/conformation requirements for the two endogenous ligands at angiotensin receptors in smooth muscle.

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Intravenous PPI prescribing habits in this military hospital facility are poor. A multifaceted approach including physician/pharmacist education, IV PPI ordering templates, and a consensus medical position statement from a major gastroenterological or prominent medical association may lead to more appropriate use.