ACE抑制剂卡托普利对实验性围手术期心肌缺血的影响

目的:图手术期心肌缺血主要是因为应激引起冠状动脉内皮功能障碍所致,所以观察卡托普利对其影响。方法:杂种犬20只均分为4组:Ⅰ组(对照组),Ⅱ组(心肌梗塞模型组),Ⅲ组(心梗 胃大部切除术)和Ⅳ组(心梗 卡托普利 胃大部切除术)。心梗2周后行胃大部分切除术,测定Ⅲ、Ⅳ两组的基础状态、术前和术后的血流动力学指标、血浆内皮素(ET)及一氧化氮(NO)。用组织原位杂交方法观察4组非梗塞区冠脉内皮-氧化氮合酶(NOS)mRNA表达水平。结果:在Ⅲ组,手术使LV dP/dt_(max)、心脏指数(CI)及NO下降,引起LVEDP、PCWP、总外周阻力(TPR)、左室舒张压力下降时间常数(T值)和ET升高。在Ⅳ组,用卡托普利后40min,TPR下降,T值升高;手术使血流动力学指标回降,不影响其它指标。组织原位杂交示,NOS mRNA在Ⅰ组高度表达,Ⅱ组和Ⅳ组次之,Ⅲ组最低。结论:卡托普利能预防胃大部切除术引起的左室舒缩障碍和冠脉内皮功能障碍。     

Identification of human juvenile chronic myelogenous leukemia stem cells capable of initiating the disease in primary and secondary SCID mice

Most juvenile chronic myelogenous leukemia (JCML) cells have limited long-term proliferative capacity, and only a minority of immature cells give rise to colonies in semisolid cultures. Clonogenic JCML progenitors cannot be maintained in culture because they differentiate, and within a few weeks the leukemic clone is lost. This makes it difficult to identify the cell that initiates and maintains the disease in patients. To determine the proliferative capacity of JCML cells in vivo, bone marrow (BM), peripheral blood, or spleen cells from eight patients with JCML either at diagnosis or during treatment were transplanted into sublethally irradiated severe combined immune deficient (SCID) mice. JCML cells from all patients homed to the murine BM and proliferated extensively in response to exogenous stimulation with granulocyte-macrophage colony-stimulating factor. Within a few weeks, highly engrafted mice became ill and cachectic due to infiltration of leukemic cells and secretion of tumor necrosis factor- alpha. Murine BM, spleen, and liver were infiltrated with leukemic blasts, and typical JCML colony-forming progenitors could be recovered. Kinetic experiments demonstrated that only a small minority of transplanted cells homed to the murine BM, and that these cells initiated and maintained the disease in vivo by extensive proliferation and differentiation. To characterize the cell-surface phenotype of the JCML initiating cell (JCML-IC), JCML blood or spleen cells were fractionated on the basis of CD34/CD38 marker expression and transplanted into SCID mice. Only immature CD34+ cells could initiate the disease, while mature CD34- cells did not engraft. Within the CD34+ compartment, there was enrichment for JCML-ICs by immature cells with a CD34+/CD38- stem-cell-like phenotype. Mice transplanted with more mature CD34+/CD38+ populations that also contained clonogenic JCML progenitors were poorly engrafted. These results indicate that the JCML- IC is an earlier stage of development than clonogenic JCML progenitors. Additional evidence that the JCML-IC has stem-cell properties comes from secondary transplant experiments that test the self-renewal capacity. The JCML-IC from all three patients tested could successfully reinitiate the disease in secondary murine recipients. Thus, we have developed a functional in vivo model that replicates many aspects of human JCML, and have used this model to identify and characterize JCML- ICs and their stem-cell properties.     

Glucose intolerance during pregnancy. II. A comparative study of diagnostic screening methods.

The present study was designed to compare the relative validity of the 2-hour postprandial glucose test (2hpp) and the rapid intravenous glucose tolerance test (IVGTT) as predictors of the outcome of pregnancy. Both tests were performed at the onset of the third trimester of pregnancy in each of 77 women who constituted a selected group of patients considered to be at high risk of developing gestational diabetes. Data concerning newborns were recorded in each case. The IVGTT was found to give a significantly larger yield of positive results (44.15%) as compared to the 2hpp test (35.06%). Furthermore, significantly heavier babies and higher rates of perinatal morbidity were noted in those cases with abnormal IVGTT results as compared to those with normal values. No such association was seen in those cases with abnormal values of 2hpp. These results suggest that the rapid IVGTT is a more dependable test than a single postprandial blood glucose estimation in screening pregnant women for gestational diabetes.     

Analgesic nephropathy

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.