Pentagastrin stimulation of human colon carcinoma.

This study examines the trophic effects of pentagastrin administration on the growth of transplanted human colon carcinoma in mice. Three different human colon carcinomas were implanted into dorsal subcutaneous pouches of BALB-C athymic mice-tumor A, COLO 320 DM undifferentiated carcinoma; tumor B, WiDr epithelial carcinoma; and tumor C, mucus-producing signet-ring cell adenocarcinoma from a patient volunteer. Tumors grew for four to six weeks and then groups were randomly assigned to receive either saline injections or pentagastrin, 2.0 mg/kg three times a day for 14 days before harvest. Tumors were homogenized and analyzed for DNA, RNA, and protein contents. Each tumor type showed a different biochemical pattern of response to pentagastrin stimulation. The data confirm that pentagastrin is trophic to human colon carcinoma and suggest a possible clinical role for hormonal manipulation.

Diagnosis of pulmonary masses by fine-needle aspiration.

Ninety-two fine-needle aspiration biopsies (FNAB) were performed in 79 patients, yielding a sensitivity of 90 percent and specificity of 100 percent for malignancy. Seven different malignant cell types were identified: squamous cell, adenocarcinoma, large cell, small cell, carcinoid, embryonal cell, and malignant fibrous histiocytoma. A 94 percent correct correlation between the cytologic and histologic specimens was achieved. Pneumothorax requiring tube thoracostomy complicated 11 percent of the biopsies. Thoracotomy was avoided in 35 percent of patients considered for operation because FNAB documented benign disease, metastatic disease, or small-cell carcinoma. FNAB was able to provide a pathologic diagnosis for chemotherapy and radiotherapy in patients with metastatic disease. A diagnosis was obtained prior to operation in 98 percent of thoracotomies. Only one diagnostic thoracotomy and one thoracotomy for unresectable pulmonary malignancy were required in a 4-year period. We concluded that FNAB, a highly sensitive and specific procedure with a low morbidity rate and a high correlation with histologic findings, reduces the need for diagnostic thoracotomy.

Sequential administration of cyclophosphamide and granulocyte-colony stimulating factor relieves impaired myeloid maturation in Felty's syndrome.

A patient with Felty's syndrome (FS) and persistent profound neutropenia developed recurrent infections and sepsis syndrome. No impairment of granulocyte-macrophage colony development was observed in vitro. Marrow morphology revealed an absence of mature neutrophil forms despite administration of granulocyte-colony stimulating factor (G-CSF). However, pretreatment with bolus cyclophosphamide (CY) permitted the growth factor to relieve this impairment of late myeloid maturation and resulted in a brisk, albeit short, burst of neutrophilia. This suggests that immune interference in myelopoiesis can be overcome by growth factor administration if immune activity is adequately dampened by immunosuppressive therapy.

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver.