Further study of taxol is warranted. In future studies, taxol should be combined with other agents, and granulocyte colony-stimulating factor should be used to ameliorate myelosuppression.

A retrospective review was performed of 473 consecutive patients with malignant lymphoma referred to the National Cancer Institute. All patients had their clinical and pathologic material reviewed and where necessary reclassified. Using a modification of the Rappaport system, 180 (38.1%) patients had a nodular lymphoma, 293 (61.9%) had a diffuse lymphoma. Nodular lymphoma patients usually presented with lymphadenopathy; diffuse lymphoma patients often presented with extranodal disease, particularly those patients with poorly differentiated lymphocytic, ‘histiocytic’, and Burkitt's lymphoma. Median age for all patients was 46 years, but was lower for diffuse poorly differentiated lymphocytic, diffuse undifferentiated, and Burkitt's lymphoma patients. Women were more likely to have a nodular rather than diffuse lymphoma, P < 0.05. Analyzed by clinical staging, most nodular lymphoma patients had CS III (66.1%) disease, while most diffuse lymphoma patients had either CS III (31.1%) or CS IV (38.9%) disease. Analyzed by pathologic staging, most nodular lymphoma patients had PS III (34.8%) or PS IV (49.4%) disease, most diffuse lymphoma patients had PS IV (56.3%) disease. Only 7% of all lymphoma patients had PS I disease, only 14.9% were PS II. Systemic symptoms were more likely to be found in diffuse lymphoma and/or advanced stage patients.

No abstract

No abstract

5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU. Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit. No statistically significant survival differences were observed among the three treatment groups.

Serial studies were performed in two patients with cyclic thrombocytopenia to investigate the pathogenesis of this disorder. Mean life span of autologous platelets when platelet levels were declining was subnormal (2.4 and 0.8 days), and megakaryocytes were abundant in the bone marrow during thrombocytopenia. Megakaryocyte colony- stimulating activity could not be detected in the serum of either patient at any point of their cycles. In each patient, total platelet- associated IgG varied inversely with platelet levels. Surface platelet- associated IgG was measured only in patient 2 and was significantly elevated (greater than 1,280 IgG molecules per platelet) at all stages of the cycle, even during thrombocytosis. However, the highest values were observed during thrombocytopenia. Platelet-bindable IgG in plasma declined to normal immediately before platelet levels began to rise. IgG eluted from the platelets of this patient reacted strongly with autologous and homologous platelets in contrast to a “mock eluate” prepared from platelets of a normal subject. The eluate from the patient's platelets reacted strongly with immobilized autologous and homologous glycoprotein IIb/IIIa complex and weakly with GPIb but not with isolated GPIIIa alone. In each patient the decline in platelet levels was significantly delayed following administration of intravenous gamma globulin 0.4 g/kg body weight for five days. These findings suggest that platelet-reactive autoantibodies are of pathogenic significance in some patients with cyclic thrombocytopenia.

A B S T R A C T The diabetogenic activity of streptozotocin has been correlated with a reduction in pyridine nucleotide synthesis in the mouse pancreatic islet. To determine the specificity of this reduction for diabetogenicity, a comparative study of streptozotocin, its cytotoxic moiety, 1-methyl-1-nitrosourea, and alloxan was performed. Streptozotocin administered intraperitoneally (i.p.) producd a dose-related reduction in islet NAD which was proportional to the degree of diabetogenicity. A diabetogenic dose, 200 mg/kg, attained a peak plasma N-nitroso intact streptozotocin concentration of 0.224 F'mol/ml and reduced the mean islet NAD from a control of 0.78 to 0.15 pmol. At borderline, 150 mg/kg, and nondiabetogenic, 100 mg/kg, doses, plasma concentrations reached 0.161 and 0.136 pmol/ml, and NAD was 0.36 and 0.86 pmol/islet, respectively. 1-Methyl-1-nitrosourea, 100 mg/kg, attained a maximum N-nitroso intact 1-methyl-1-nitrosourea concentration of 0.162 /mol/ ml and reduced the mean NAD to 0.58 pmol/islet, and was nondiabetogenic; 200 mg/kg attained a peak plasma concentration of 0.344 /mol/ml and depressed NAD to 0.38 pmol/islet, and was inconsistently diabetogenic. Islet NAD of 0.4 pmol/islet or greater is required for integrity of the beta cell. A diabetogenic dose of alloxan, 500 mg/kg, did not depress NAD, 0.85 pmol/islet, therefore confirming that its mechanism of diabetogenicity differs from that of streptozotocin.In vivo uptake of [methyl-"4C]streptozotocin by islets was 3.8 times that of [methyl-14C]-1-methyl-1-nitrosourea, whereas uptake by the exocrine pancreas favored 1-methyl-1-nitrosourea over streptozotocin 2.4:1. The decreased islet uptake of 1-methyl-1-nitrosourea correlates with the 3.5 times increased molar dosage required to produce islet NAD depression comparable to that of 3treptozotocin, 150 mg/kg. These studies indicate that

No abstract