营养药理学--谷氨酰胺、n-3脂肪酸和精氨酸等简介

引言营养不良总是影响外科患者的预后,20世纪初就有人注意到伴有营养不良(以体重降低20%为依据)的消化性溃疡患者术后恢复较慢。后来几十年的研究证明,特殊营养素(如某些维生素和矿物质)缺乏能导致疾病,给予补充则可恢复健康。近年来研究发现,低蛋白血症等营养不良指标与并发症的发生率和死亡率相关。20世纪60年代至70年代的研究表明,对于严重烧伤儿童,只增加营养素(蛋白)的相对浓度而不增加总热卡摄入,可纠正免疫功能低下,提高生存率,改善患儿预后。谷氨酰胺、n-3脂肪酸和精氨酸对疾病的影响引起人们的特别关注,许多学者致力于研究这些营养…     

An empirical evaluation of the performance of antibody identification tasks

Four empirical studies were conducted for better understanding of the nature of problem-solving activities by medical technologists and medical technology students when performing antibody identification tasks. The results indicated the importance of strategies that ensure the collection of converging evidence, as these strategies protect against the fallibility of commonly used heuristics and against errors due to simple slips. The results also indicate that not only do students make significant numbers of errors, but so do practicing technologists. In one of the studies covering a 1-year period, for instance, a group of 16 technologists made a total of 41 errors in 1057 cases. On the basis of these findings, several alternatives are proposed to reduce errors.     

Withdrawing versus not offering cardiopulmonary resuscitation: Is there a difference?

Conflict between substitute decision makers (SDMs) and health care providers in the intensive care unit is commonly related to goals of treatment at the end of life. Based on recent court decisions, even medical consensus that ongoing treatment is not clinically indicated cannot justify withdrawal of mechanical ventilation without consent from the SDM. Cardiopulmonary resuscitation (CPR), similar to mechanical ventilation, is a life-sustaining therapy that can result in disagreement between SDMs and clinicians. In contrast to mechanical ventilation, in cases for which CPR is judged by the medical team to not be clinically indicated, there is no explicit or case law in Canada that dictates that withholding/not offering of CPR requires the consent of SDMs. In such cases, physicians can ethically and legally not offer CPR, even against SDM or patient wishes. To ensure that nonclinically indicated CPR is not inappropriately performed, hospitals should consider developing ‘scope of treatment’ forms that make it clear that even if CPR is desired, the individual components of resuscitation to be offered, if any, will be dictated by the medical team’s clinical assessment.     

Studies on levamisole--induced agranulocytosis

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet- induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.     

Cytogenetic clonality in myelodysplastic syndromes studied with fluorescence in situ hybridization: lineage, response to growth factor therapy, and clone expansion

Clonality in myelodysplastic syndromes (MDS) has been studied with various techniques including glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and cytogenetic analyses, and with molecular techniques such as gene deletion studies and the analysis of restriction fragment- length polymorphisms (RFLP) of X-linked genes. In this study, we investigated the use of fluorescence in situ hybridization (FISH) with a chromosome-specific probe to examine cytogenetic clonality in peripheral blood (PB) cells from three patients with MDS. In each case, trisomy 8 was shown by conventional cytogenetic analysis at the time of the initial diagnosis. By using FISH with a probe for the centromere of chromosome 8, we identified the trisomy in individual PB cells from Wright-stained smears. With this technique, we could determine the cell lineage involved by the trisomy, and through serial analyses we could assess the response of the clonal and nonclonal cells to growth-factor therapy, and the expansion of the trisomic clone over time. In each of the three cases, various proportions of granulocytes, monocytes, eosinophils, and basophils showed trisomy 8 by FISH analysis. In none of the cases did we detect trisomy 8 in lymphocytes. By analysis of PB cells before and during therapy with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), we found that GM-CSF stimulated both trisomic and disomic cells. During a 1-year period of sequential study, we detected an abrupt increase in the percentage of trisomic cells in one patient, a stable percentage in another, and a slowly increasing percentage in the third. The abrupt increase in the first patient preceded a transformation to a more acute phase by 2 months. We conclude that FISH analysis of PB cells of patients with MDS offers an additional approach to the study of clonality in this disorder. In some cases this analysis may provide a useful and simple means of assessing response to therapy and progression of disease.     

Molecular cloning, chromosomal location, and tissue-specific expression of the murine cathepsin G gene

We previously have characterized a cluster of genes encoding cathepsin G (CG) and two other CG-like hematopoietic serine proteases, CGL-1 and CGL-2, on human chromosome 14. In this report, we clone and characterize a novel, related murine hematopoietic serine protease gene using human CG (hCG) cDNA as the probe. This murine gene spans approximately 2.5 kb of genomic DNA, is organized into five exons and four introns, and bears a high degree of homology to hCG at both nucleic acid (73%) and deduced amino acid (66%) levels. The predicted cDNA contains an open reading frame of 783 nucleotides that encodes a nascent protein of 261 amino acids. Processing of a putative signal (pre) peptide of 18 residues and an activation (pro) dipeptide would generate a mature enzyme of approximately 27 Kd that has an estimated pI of 12.0. Conserved residues at His44, Asp88, and Ser181 form the characteristic catalytic triad of the serine protease superfamily. The gene is tightly linked to the CTLA-1 locus on murine chromosome 14, where the serine protease genes mCCP1-4 are clustered. Expression of this gene is detected only in the bone marrow and is restricted to a small population of early myeloid cells. These findings are consistent with the identification of the gene encoding murine CG.