Effect of N-acetylcysteine on the oxidative burst induced by phagocytosis of bacteria in human leukocytes.

The basal peroxide production and the oxidative burst induced by phagocytosis of opsonized E. coli was studied by flow cytometry using dihydrorhodamine 123. The human leukocytes were incubated in the absence and presence of N-acetylcysteine. The oxidative response to the phagocytosis of bacteria differed among cell populations. Thus, 90% of granulocytes and 50% of monocytes showed an oxidative burst in response to opsonized bacteria while less than 1% of lymphocytes showed a fluorescence signal. N-Acetylcysteine (4.7, 9.5, 19, 38 or 76 mM) produced a dose-dependent inhibition of the oxidative response to phagocytosis in the three cellular populations reaching almost complete inhibition for 76 mM. This protective effect of N-acetylcysteine against oxidative stress in leukocytes was obtained without cytotoxicity (assessed by flow cytometry with staining with propidium iodide) or changes in the pH of the medium. These results give further support to the antioxidant effect of N-acetylcysteine in human peripheral blood cells.

[Second neoplasms as a late complication of the treatment of Hodgkin's disease]. / Segunda neoplasia como complicación tardía del tratamiento de la enfermedad de Hodgkin.

PURPOSE: To determine the incidence of a second malignancy in patients with Hodgkin's disease (HD) diagnosed and treated in the same hospital. PATIENTS AND METHODS: A retrospective study was performed on 99 patients diagnosed and treated for HD in the Hospital San Carlos, in Madrid, between January 1976 and december 1987. The clinical records were revised; the diagnosis and staging followed the Rye and Ann Arbor criteria, and the treatment included radiation therapy (RT), chemotherapy (CT), or a combination of both. The diagnosis of the second malignancy was based upon clinical, analytical, radiological and histological records. RESULTS: The median age in the series was 31 years (16-82) and the M/F ratio was 61/38. The stage distribution was: I-9; II-29; III-31, and IV-30. Twenty-six patients received RT alone, 59 were treated with CT, and 14 received RT plus CT. A second neoplasm was found in 6 patients (6%), of whom 4 developed a myelodysplastic syndrome (MDS) and 2 a solid tumour. All the patients who had MDS had received MOPP or C-MOPP chemotherapy, associated in two of them with extensive RT. Both patients with solid tumour had been given CT+RT. The median time of presentation of the second malignancy since the diagnosis od HD was 89 months (48-174) for MDS and 120 months for the solid tumours. The four MDS patients have died, 2 for ANLL-M5, one for SRA and the remainder for cerebral haemorrhage, not yet evolved into acute leukaemia. The two patients which solid tumours are alive and seemingly in complete remission at 12 and 10 months, respectively, of the diagnosis of the second malignancy. CONCLUSIONS: 1) All the patients with second neoplasms had been previously treated with CT (MOPP or C-MOPP) or CT+RT. 2) Non-Hodgkin's lymphoma has not appeared in any of the patients in this series. 3) An endless follow-up of patients with HD seems important in order to achieve an early diagnosis of other malignant complications which, although in case of MDS have poor prognosis, in case of solid tumours may do well with adequate treatment.

Occurrence of antibodies to protease-treated histones in a patient with vasculitis.

We describe the presence of IgG antibodies reacting with histones previously treated with proteases in a patient with vasculitis. The patient's serum did not react with nontreated histones and when several enzymes were tested separately, only alpha-chymotrypsin reproduced the effect. Reactivity was directed against histone fraction H2B and no other autoantibody was found in the patient's serum. This could represent an autoantigen-driven response, histones hydrolyzed in vivo with proteases being the immunogenic stimulus. Diagnostic and pathogenic implications derived from the existence of such autoantibodies are discussed.