Procedural safeguards for euthanasia.
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Biomedical subjects
Publications and source records attributed to A Ritter.
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Anti-GOR is an autoantibody found in hepatitis C virus (HCV) infection. We have studied the specificity of this antibody for HCV infection in various groups of autoimmune liver diseases. Anti-HCV was detected by a second generation HCV enzyme-linked immunosorbent assay in 14 of 29 patients with liver-kidney-microsomal (LKM-1) -antibody-positive autoimmune hepatitis type 2 and in all 6 control patients with HCV-RNA-positive chronic hepatitis C. Anti-HCV was not found in those with antinuclear-antibody-positive autoimmune hepatitis type 1 (10 patients), with soluble-liver-protein-antibody-positive autoimmune hepatitis type 3 (8), with primary biliary cirrhosis (9), with systemic lupus erythematosus (SLE) (10), or in healthy controls (13). Anti-GOR was detected in 11 of 14 patients with autoimmune hepatitis type 2 who were all positive for anti-HCV but only in 1 of 15 LKM-1 patients who were negative for anti-HCV. We did not find anti-GOR in any other group of autoimmune liver disease, SLE, or control sera, but this antibody was detected in 3 of 6 patients with chronic hepatitis C. Autoimmune hepatitis type 2 patients who were anti-GOR positive and anti-HCV positive were less likely to be female, were older (p less than 0.001), and had lower LKM-1 antibody titres (p less than 0.001), lower disease activity, and responded less effectively to immuno- suppression than did those who were anti-HCV negative/anti-GOR negative. The findings show that anti-GOR reflects HCV-specific autoimmunity. HCV seems to induce autoimmunity to both GOR (an HCV-specific autoepitope) and LKM-1 (an epitope that is also recognised by autoimmune hepatitis sera of a different cause). Anti-GOR and LKM-1 antibodies contribute to a better differentiation of chronic hepatitis, a finding that has therapeutic implications.
OBJECTIVE: The question was to evaluate whether haemodilution or intraoperative autotransfusion have an influence on plasma levels and clearance of midazolam. DESIGN: The study was designed as a prospective evaluation of patients with total hip joint replacement. The patients received neuroleptanalgesia supplemented with enflurane. After induction of anaesthesia with midazolam (0.1 mg/kg body weight) haemodilution procedure was started. During surgery a cell saver was used for blood salvage. In the recovery room drainage blood was also being processed by a cell saver. PATIENTS: The study includes 10 patients belonging to ASA-group II with an average weight of 79.4 kg (53-100 kg), at an average age of 57.9 years (44-68 years). MEASUREMENTS AND MAIN RESULTS: Midazolam was measured in patient blood and in autologous blood units by gas chromatography. 151 micrograms of midazolam, i.e. 1.8% of the initial dose was retransfused in hemodilution blood. By processing of blood in the cell saver, 99.5% of the amount of midazolam found in the sample unit was eliminated. The maximum quantity was 5.5 micrograms in the washed autologous red cell concentrate. CONCLUSION: Considering the analytic limit of 2 micrograms/l of midazolam in plasma, retransfusion of autologous blood cannot influence the plasma concentration of midazolam. Therefore, there is no risk of re-sedation in retransfusing autologous blood postoperatively.
Although the accuracy in prenatal diagnosis and carrier detection with DNA probes in families with Duchenne and Becker's muscular dystrophies is very high, various factors limit the accuracy of these probes in many families. We report four potential pitfalls, ie, intragenic recombination, genetic heterogeneity, germline mosaicism, and an evolving genetic defect encountered in a population of Duchenne and Becker families, and describe a strategy to incorporate these factors into genetic counseling.
We have evaluated a young woman with segmental spinal muscular atrophy, who has a deletion of a portion of the long arm of chromosome 18. She also has vitiligo and lichen sclerosis et atrophicus. She has neither the facial dysmorphism nor the mental deficit usually associated with the 18q- syndrome. Magnetic resonance imaging scan of her brain demonstrates high signal intensity consistent with abnormal myelination. Southern blot analysis of her DNA demonstrates that the deletion includes the gene for human myelin basic protein. Neither spinal muscular atrophy nor this patient's skin manifestations have been previously reported in association with 18q-.
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Zinc is able to form complexes with 8-hydroxyquinoline (HC). Therefore the penetration of HC from topical formulations into the ear of guinea-pigs and into a multilayer membrane system was decreased by Zi. Using the AUC a suitable in vitro-in vivo correlation was obtained. An exception was observed when there were interactions between the ointment base and the in vitro model system. Furthermore, it was found that also zincoxinate is able to penetrate into the skin of guinea-pigs.
We investigated regulation of the dynamic state of enkephalin and endorphin brain stores during morphine tolerance and dependence using cDNA hybridization and radioimmunoassay of the biologically active peptide(s) and their respective peptide precursors. Rats were made tolerant to morphine with the subcutaneous implantation of three morphine pellets (75 mg each) for a period of five days. Hypothalamic proopiomelanocortin (POMC) mRNA, POMC, and corticotropin-like intermediate lobe peptide content were decreased by 50% in morphine-dependent rats. However, beta-endorphin content remained unchanged. Enkephalin and proenkephalin mRNA content in various brain structures failed to change. A single injection of naltrexone (2 mg/kg) 1 hour before decapitation did not reverse the decrease in POMC mRNA and POMC content elicited by morphine. However, a slower, spontaneous withdrawal caused by removal of the pellets did reverse (after two days) the down-regulation of the hypothalamic POMC system. A single injection of morphine (10 mg/kg) failed to affect any parameter used to assess the dynamic state of opioid peptides.
Based on in vitro results it was found that the pharmacokinetic parameters of the hydrophilic drug bretylium (2) can be influenced by an ion-pair-formation with the lipophilic hexylsalicyclic acid (1). After simultaneous i.v. application of 1 and 2 on rabbits a significant increase of the AUC of 2 was observed. Under these conditions a marked increase of the AUC and the MRT of 1 was also obtained, since the blood levels of 2 are high enough for such an influence. A combined rectal application of 1 and 2 causes an increase of the AUC of 2.
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The mechanistic and stereochemical features of a new organozinc-based substitution process [heteroatom-C-(R1,R2)-SPh + R3(2)Zn----heteroatom-C-(R1,R2,R3)], first discovered during a total synthesis of the alkaloid mycotoxin alpha-cyclopiazonic acid, are described. Phenyl thioglycosides were valuable substrates in studying the nature of this reaction process. Since these sulfur compounds are converted into C-glycosyl compounds with some degree of stereoselectivity, the organozinc chemistry does provide a new entry to these biologically active substances.
The neurotoxic compound 1-[methyl-3H]-4-phenylpyridinium ([3H]MPP+) was actively taken up by human, rabbit, and guinea pig platelets incubated in plasma. In human platelets, the apparent Km of this uptake (22.6 microM) was 50 times higher than that for serotonin [5-hydroxytryptamine (5-HT]). The uptake of [3H]MPP+ by human platelets was inhibited by selective 5-HT uptake blockers [cianopramine, (-)-paroxetine, and clomipramine], by metabolic inhibitors (KCN and ouabain), and by drugs that interfere with amine storage in the 5-HT organelles (reserpine, mepacrine, and Ro 4-1284). Impairment of the transmembrane proton gradient by ionophores (monensin and nigericin) induced a marked release of radioactivity from platelets preincubated with [3H]MPP+. Fractionation of homogenates of rabbit platelets preincubated with [3H]MPP+ showed that the drug was concentrated to a great extent in the 5-HT organelle fraction. MPP+ competitively inhibited [14C]5-HT uptake by human platelets and reduced the endogenous 5-HT content of human, rabbit, and guinea pig platelets. These investigations show that MPP+ is transported into the platelets via the 5-HT carrier and is accumulated predominantly in the subcellular organelles that store 5-HT and other monoamines. It is suggested that an accumulation of MPP+ in amine storage vesicles of neurons may be involved in the effects of the drug in the CNS, e.g., by protecting other subcellular compartments from exposure to high concentrations of MPP+, by sustaining a gradual release of the toxin, or both.
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Two alternating frames, each consisting of three square elements, were used to study bistable stroboscopic motion percepts. Bistable percepts were obtained which depend on the interstimulus interval (ISI) between the alternating frames. At short ISIs only end-to-end element motion was observed; and at higher ISIs only group motion was perceived. It was found that the progressive ISI-dependent transitions from element to group motion depended on element size and frame duration. These dependencies are predictable from the systematic influence which these variables are known also to exert on visual pattern persistence, indicating that such persistence contributes to determining which precept dominates during bistable stroboscopic motion sequences. These findings bear relevantly on recent attempts to conceptually relate bistable motion percepts to short-range stroboscopic motion processes.
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