The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy

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.     

Orbital dermoids: features on CT

The computed tomographic (CT) features of orbital dermoids were retrospectively reviewed in 17 patients; 15 of the lesions were proved histologically. On the basis of clinical and CT features, the tumors were classified as superficial or deep. All but one were extraconal in location. Seven lesions appeared cystic; only six showed typical fat density. The presence of a margin or rim, often partially calcified, was identified in ten lesions. Irregular scalloping of adjacent bone was a highly suggestive feature, occurring with 11 dermoids. Other bone changes, such as linear defects, thinning, or sclerosis, also occurred. Superficial dermoids showed less apparent bone changes. An extraconal orbital lesion associated with adjacent bone thinning or notching should raise the possibility of a dermoid, especially if a rim with calcification is seen. The appearance is pathognomonic if fat density is also present.     

Biliary lithotripsy: early observations in 106 patients. Work in progress

One hundred six patients underwent extracorporeal shock wave lithotripsy for cholelithiasis. Of these, 28 patients underwent cholangiographically guided lithotripsy for bile duct stones to assist nonoperative stone removal by endoscopic or radiologic intervention. Fragmentation occurred in 20 of 28 cases (71%) with an average of two lithotripsy sessions. Hemobilia was observed in four patients (14%) for a 24-hour period. Seventy-eight of the 106 were outpatients with symptomatic cholecystolithiasis with one to five calculi who underwent cholecystographic or ultrasound-(US) guided shock wave lithotripsy as definitive therapy. US examination showed stone fragmentation in 86% of cases. With an average of 1.6 treatment sessions and 4,750 shocks, fragments were 4 mm or smaller in 46% of patients. Nine percent of patients had no fragments after an average of 10 weeks, but long-term follow-up is not yet available. Two patients developed acute pancreatitis attributable to fragment passage and one patient acute cholecystitis, likely due to cystic duct obstruction by a fragment.     

赛拉嗪对麻醉大鼠海马CA1区乙酰胆碱含量的影响

应用乙酰胆碱选择性微电极技术,观察到小剂量赛拉嗪(2.0和6.0mg·kg^-1)可显著增加大鼠海马CA1区ACh的含量,而大剂量赛拉嗪(10.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)则作用相反。咪唑克生虽可明显拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍显著低于正常水平。在去兰斑核的大鼠上,赛拉嗪(2.0和6.0mg·kg^-1)及咪唑克生(0.6mg·kg^-1)分别对海马CA₁区ACh的含量具有减少和增加作用,且咪唑克生拮抗赛拉嗪的作用后,海马CA₁区ACh的含量基本恢复至正常水平。结果提示,赛拉嗪对麻醉大鼠海马CA₁区ACh含量呈双相性影响,咪唑可生虽能显著拮抗赛拉嗪的作用,但海马CA₁区ACh的含量仍明显低于正常水平,可能分别与赛拉嗪和咪唑克生降低或提高中枢NE能系统的功能有关。     

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.