Early appearance of Laennec's cirrhosis in former heroin addicts on methadone maintenance.
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Biomedical subjects
Publications and source records attributed to J J Ryan.
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The only metabolite of 2'-chloronordiazepam, 7-chloro-1,3-dihydro-5-(2'-chlorophenyl)-2H-1,4-benzodiazepin-2-one (1), previously identified in the dog is lorazepam (2), which is a product of 3-hydroxylation. Two phenolic metabolites (3 and 4) in the dog corresponding to 4'-hydroxylation of the 5-phenyl ring and 9-hydroxylation of the fused benzene ring, respectively, have now been identified. The structure of the 9-hydroxy isomer 4 is deduced simply from the observed NMR spectral AB (J meta = 2.5 Hz) pattern of the protons of the fused benzene ring. In contrast, since a 2'-chloro substituent is present on the 5-phenyl ring of the parent drug, the usual method of recognizing 4'-hydroxylation of this ring by observation of AA'BB' multiplets in the proton nuclear magnetic resonance (1H NMR) spectra is inapplicable. Hence, a novel method is introduced to identify the 4'-hydroxy isomer 3, based on attributing different sets of NMR substituent effect parameters to hydroxyl groups, depending on whether these groups are meta or para to the benzodiazepinimine function. The urinary plus fecal excretion of 2-4 by one dog given in a single oral 10 mg/kg dose of 14C-labeled 1 amounted to 20, 5, and 7% of the dose, respectively; the urinary metabolites were excreted predominantly as conjugates of glucuronic acid and/or sulfate.
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Two heifers were implanted with 300 mg of the radiolabeled anabolic steroid, trenbolone acetate (TBA). After a 60 day slaughter and a 60 day removal followed by 76 day slaughter, total 3H-content in various tissues was 0.5--25 ng/g equivalents of TBA. Radioimmunoassay of the tissues showed that only 1--5% of the total residue present was TBA, its main metabolite trenbolone (TBOH), and TBOH glucuronide, plus up to 5% of other organic-soluble material. Of the radioactivity remaining about half was directly water-soluble, and the insoluble residue could be made water-soluble by treatment with the proteolytic enzymes pepsin and trypsin. These 2 portions were purified with Sephadex G-25 to give a low and high molecular weight fraction. Raney nickel reduction of sulfur bonds in either fraction released up to 50% of radioactivity into the organic phase. TLC showed that the latter contained 2 components which had characteristics similar to TBOH and its metabolites, and thus were at least partly drug-related metabolites. In vitro experiments with bovine liver also showed a small but definite protein binding. It is proposed that in dealing with these covalently bound residues, priority be given to the reactive drug intermediate and the type of binding to macromolecules rather than to the presence of the bound residue itself.
The gas chromatographic response of four perfluoro derivatives, of four agricultural chemical [diethylstilbestrol] (DES) clopidol, linuron and carbofuran] was examined. The derivatives varied in fluorine content from 3 to 30 atoms per molecule. The sensitivities of the derivatives were found to be ca. 10-100 times greater by electron-capture detection than by electrolytic conductivity detection (halogen mode). The sensitivity also was found to increase with increasing fluorine content for all derivatives by electrolytic conductivity, whereas by electron capture, DES and clopidol exhibited similar responses with either the penta-, hepta-, or pentadeca-fluoro derivatives. The sensitivity of linuron and carbofuran derivatives by electron capture varied with increasing fluorine content. For detection by electron capture, the hepta-fluorobutyryl derivatives were preferred for DES and clopidol, and either the hepta-fluorobutyryl or the pentadecafluorooctanoyl derivatives for linuron and carbofuran. For detection by electrolytic conductivity, the pentadecafluorooctanoyl derivatives were superior for all four compounds.
This study attempted to cross-validate an MMPI Key for the separation of brain-damaged and schizophrenic inpatients. MMPI profiles generated by 20 males with a variety of documented brain dysfunctions were compared to those of 20 heterogenous male schizophrenics. The groups were matched on the variables of age and education. The procedure provided 82.5% correct classification, which included 85% correct schizophrenic identification and 80% correct brain-damage identification. The Key was recommended for use as a rough screening device or as a supplement to appropriate neuropsychological procedures.
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The possibility of fibrous capsule calcification should be kept in mind when evaluating mammograms in patients who have had an augmentation mammaplasty. One of our 4 cases was examined radiologically and the calcifications were not characteristic of those associated with malignancy, but the appearance might be different in the next case. The etiology is undetermined.
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The concentration of cyclic AMP (cAMP) and cyclic GMP (cGMP) in slices of rat cerebellum was increased markedly in the presence of 100 muM kainic acid, a cyclic analogue of glutamic acid. No acitvity was detected in other brain areas at various dosed or incubation times. Ksainic acid was significantly more potent than glutamic acid and other glutamate-like compounds. The increases in cAMP and cGMP could be differentially inhibited with theophylline or cocaine respectively, but both systems required calcium. Compounds similar in structure to kainic acid or glutamate did not block the effects of kainic acid.
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