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Pluda JM; Yarchoan R; Smith PD; McAtee N; Shay LE; Oette D; Maha M; Wahl SM; Myers CE; Broder S 《Blood》1990,76(3):463-472
We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) administered by the subcutaneous route, first alone and then alternating with azidothymidine (AZT), in leukopenic patients with severe human immunodeficiency virus (HIV) infection. Ten patients with acquired immunodeficiency syndrome (AIDS) or related disorders, five of whom could not tolerate conventional doses of AZT, were administered rGM-CSF subcutaneously for 12 days. They then were administered an alternating regimen using AZT for 1 week, followed by 5 days of subcutaneous rGM-CSF and 2 days without any medication. During the initial 12 days of GM-CSF administration, there was an increase in the mean white blood cell (WBC) value. In addition, rGM-CSF stimulated circulating monocytes as evidenced by an increase in superoxide anion production and expression of surface HLA-DR antigen. However, at the same time rGM-CSF increased the serum HIV p24 antigen in each of the six evaluable patients from 189 x/divided by 2.02 pg/mL (geometric mean x/divided by SEM) at entry to 375 x/divided by 2.11 pg/mL (P less than .05). During the subsequent period of alternating AZT and rGM-CSF treatment, serum HIV p24 antigen fell below the day 14 value in most patients, particularly after the weeks of AZT administration. The mean T4 cell value increased in patients who had not previously received AZT, but generally did not change in those who had prior AZT exposure. Hematologic toxicity appeared to be somewhat reduced compared with continuous full-dose AZT therapy, and two patients with previous AZT hematologic toxicity tolerated this alternating regimen for 25 weeks. Additional regimens simultaneously combining these two agents are worth exploring. 相似文献
636.
Stephen M. Hamlet Richard D. Gordon Celso E. Gomez-Sanchez Terry J. Tunny Shelley A. Klemm 《Clinical and experimental pharmacology & physiology》1988,15(4):317-322
1. The adrenal cortical 'hybrid' steroids 18-oxocortisol (18-OF) and 18-hydroxycortisol (18-OHF) are elevated in patients with typical angiotensin-unresponsive aldosterone-producing adenoma (AII-unresponsive APA) and fall to normal following surgical removal of the adrenal containing the tumour. Since 18-OF was six times the upper limit of normal pre-operatively, the tumour was the site of overproduction of hybrid steroids. 2. The failure of angiotensin-responsive APA to overproduce the hybrid steroids may be linked to their more 'normal' production of cortisol, which falls significantly on removal of the tumours. 3. Hybrid steroid levels were also normal in patients with idiopathic hyperplasia of the adrenals (IHA) and in low renin essential hypertension. 4. In AII-responsive APA, glucocorticoid-suppressible hyperaldosteronism (GSH) and IHA, the hybrid steroids showed brisk responses to stimulation by ACTH and suppression by dexamethasone of endogenous ACTH. 5. Long-term suppression by dexamethasone of hybrid steroids in GSH is consistent with ACTH dependence, rather than angiotensin dependence. 6. Studies of the regulation of hybrid steroid secretion in various categories of hypertension will further define the biosynthetic distinctiveness which is already useful diagnostically. 相似文献
637.
The methodology of sodium-23 (Na-23) imaging is reported in relationship to the physiological factors that determine the chemical environment of the Na-23 nucleus. Contrast resolution is given as a function of imaging time and spatial resolution. Data showing the optimal relaxation time for sodium imaging are given, and the linear quantitative relationship between sodium concentration and voxel intensity for our imaging system is confirmed. The major problem facing in vivo sodium imaging is the ability to differentiate intracellular sodium from extracellular sodium. The sodium in blood serum (extracellular) and packed red blood cells (intracellular) both exhibit biexponential T2 decay. These results indicate that T2 measurements alone will be insufficient for discriminating extracellular from intracellular sodium. Instead, other methods based on the underlying physiological properties of in vivo sodium imaging, such as the diffusion coefficient, will be necessary to truly separate extracellular from intracellular sodium. 相似文献
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C E Gomez-Sanchez O B Holland R Upcavage 《The Journal of clinical endocrinology and metabolism》1985,60(2):234-238
The urinary excretion of deoxycorticosterone (DOC) and 19-nor-deoxycorticosterone (19-nor-DOC) was measured using a technique which consisted of the purification of both steroids by high pressure liquid chromatography followed by RIA using specific antibodies. The urinary excretion of DOC was 29.4 +/- 25 ng/24 h (mean +/- SD) in 35 normal subjects, 26 +/- 21 ng/24 h in 46 patients with low renin hypertension (LRHT), and 32 +/- 23 ng/24 h in 16 patients with normal renin hypertension (NRHT). The urinary excretion of 19-nor-DOC was 287 +/- 178 ng/24 h in normal subjects, 224 +/- 167 ng/24 h in LRHT patients, and 235 +/- 170 ng/24 h in NRHT patients. There were no hypertensive patients with increased excretion of 19-nor-DOC. The excretion of 19-nor-DOC increased after 3 days of sodium depletion in normal and hypertensive subjects, but the increment was significantly higher in normotensive subjects. There was no correlation between the excretion of 19-nor-DOC and that of DOC or urinary aldosterone. This study suggests that DOC or 19-nor-DOC does not play a role in the pathogenesis of either LRHT or NRHT and disagrees with previous reports suggesting such a role. 相似文献