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排序方式: 共有879条查询结果,搜索用时 109 毫秒
101.
The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy 总被引:4,自引:1,他引:4
Grever MR; Siaw MF; Jacob WF; Neidhart JA; Miser JS; Coleman MS; Hutton JJ; Balcerzak SP 《Blood》1981,57(3):406-417
A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration. 相似文献
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Although it is clear that hypertension accelerates the rate of progression of most forms of chronic renal disease, many unanswered questions remain concerning how to optimally preserve kidney function in patients with hypertension and renal insufficiency. The mechanisms by which hypertension accelerates progression of renal disease have been extensively studied in experimental models. Glomerular capillary hypertension, consequent to an increase in systemic blood pressure combined with a reduction in preglomerular resistance and/or an increase in postglomerular resistance, results in increased hydraulic stress to the glomerular capillary wall. This and other mechanisms result in the release of growth-promoting cytokines and soluble mediators of fibrosis that stimulate cellular proliferation and matrix accumulation, ultimately leading to glomerular sclerosis and interstitial fibrosis. Almost without exception, studies in animals demonstrate that blood pressure reduction reduces the rate of progression of experimental renal disease. Angiotensin-converting enzyme inhibitors and, possibly, calcium antagonists may have a therapeutic advantage compared with other antihypertensive drugs in preventing kidney damage. This has been linked to both blood pressure-dependent and -independent actions. However, most experimental studies have failed to reduce blood pressure to a level sufficient to establish the clinical relevance of potential blood pressure-independent effects. Experimental studies comparing various types of antihypertensive drugs in which a mean arterial pressure (MAP) of approximately 92 mm Hg is achieved are necessary to determine whether clinically important differences in the effects of these drugs on the rate of progression of renal disease exist. Clinical experience with high blood pressure and kidney disease in humans suggests that the risk of developing hypertension-associated renal disease is a continuous variable across the entire range of systolic and diastolic blood pressures. Logically, optimal protection of kidney function may therefore be a continuous function of declining systemic blood pressure. Consistent with this view, recent clinical trials suggest that reducing MAP to 92 mm Hg, corresponding to a blood pressure reading of 125/75 mm Hg, provides more optimal stabilization of renal function in patients with nondiabetic proteinuric kidney disease (>1 g/d) compared with more conventional therapy with a blood pressure goal of 140/90 mm Hg (MAP 107 mm Hg). Clinical trials in patients with diabetes mellitus and renal insufficiency also demonstrate the benefits of reducing blood pressure to approximately 95 mm Hg MAP. Dietary salt consumption may be another important variable affecting the rate of progression of renal disease due to both direct, salt-dependent effects on renal growth and the action of decreased salt intake to augment the antihypertensive and antiproteinuric properties of many drugs. The precise role of alterations in dietary salt consumption on progression of renal disease directly as well as on the effectiveness of various antihypertensive drugs has yet to be examined in clinical trials. 相似文献
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MR Nasca † C Panetta ‡ G Micali † D Innocenzi‡ 《Journal of the European Academy of Dermatology and Venereology》2003,17(3):337-339
The case of a 70-year-old white man with a 10-year history of penile lichen sclerosus (LS) who developed microinvasive squamous cell carcinoma on LS is described. A high incidence of penile cancer arising on genital LS has recently been observed. The authors stress the importance of an adequate diagnosis and long-term follow-up in patients with penile LS because of the malignant potential of the disease. 相似文献
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LC Edozien MRCOG FN Mayers FRCOG MR Gowland FRCR 《International journal of clinical practice》1997,51(5):305-307
Both the incidence of twin pregnancy and the demand for prenatal diagnosis are increasing. Unfortunately, biochemical screening and ultrasound scanning are less reliable for prenatal diagnosis in twin pregnancies than in singletons. Amniocentesis and chorionic villous biopsy are usually diagnostic in singleton pregnancies but may be marred by sampling errors in twin gestations. Where a congenital anomaly has been diagnosed in a twin pregnancy, difficult decisions may have to be made, especially if one twin is unaffected. In these cases, special skills are required to ensure that adequate information, psychological support and optimal medical care are provided. 相似文献
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用 DOCA-salt 高血压大鼠心肌肥厚模型,观察间硝苯地平(m-Nif)对肥厚心肌膜碎片二氢吡啶(DHP)结合位点的影响。结果显示:预防或治疗性给予m-Nif(20 mg·kg-1·d-1)12 或 9 周,血压降低,心室重和心肌线粒体钙含量减少,且肥厚心肌DHP结合位点密度显著降低(450±25, 462±36 fmol·mg-1 vs 836±47 fmol·mg-1 protein, P<0.001)。提示:m-Nif预防和逆转DOCA-salt 高血压大鼠心肌肥厚的作用可能与其减少肥厚心肌DHP 结合位点密度和血压降低有关。 相似文献
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