Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease

Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease.     

MACOP-B regimen in non-Hodgkin's lymphoma.

Two university centers in Finland used MACOP-B regimen as first-line treatment of intermediate and high-grade non-Hodgkin's lymphomas in 1986-1990. The clinical records of all 41 patients treated with this regimen were analyzed. The median age was 47 years (range 16-65), 24% of the patients had WHO performance status > 1, 49% had B-symptoms, 46% had Ann Arbor stage III or IV disease, and 39% had bulky disease. Twenty-three (58%) of the 40 patients who were evaluable for response had CR. The survival rate 36 months after the start of MACOP-B was 62%, but failure-free survival rate only 36%. Among several analyzed factors a lactate dehydrogenase level < 500 U/l before treatment showed the strongest association to failure-free survival. The planned dose intensity was not achieved mainly because of toxicity, and the ratio of the actual dose intensity given to the planned dose intensity varied for the different drugs between 0.77 and 0.92.     

DNA aneuploidy in follicular adenomas of the thyroid gland.

The nuclear DNA content of 67 follicular adenomas and 7 adenomatous goiters was determined by flow cytometry. The DNA analysis was done with the use of paraffin-embedded tissue, but in 14 cases of follicular adenoma fresh material obtained by fine needle aspiration biopsy was also available. An abnormal DNA stemline was found in 27% (18/67) of the adenomas and in 1 (14%) of the adenomatous goiters. Four (29%) of the 14 adenomas analyzed from fresh samples were aneuploid. In none of the 12 aneuploid or 40 diploid adenomas followed for more than 5 years (mean, 7.2 years) did distant metastases develop after surgical removal of the adenoma. The paraffin blocks of cases with DNA aneuploidy were sectioned subserially at 1-mm intervals, but none of these tumors showed invasion into the capsule or blood vessels. It is concluded that DNA aneuploidy is common in histologically benign follicular adenomas of the thyroid, and that DNA aneuploidy does not appear to be associated with adverse prognosis in follicular adenomas if the tumor is surgically removed.     

Secretion of vascular endothelial growth factor/vascular permeability factor from human luteinized granulosa cells is human chorionic gonadotrophin dependent

Vascularization is a prominent event during corpus luteum formation, providing low density lipoproteins for steroid biosynthesis and enabling transport of secreted steroids. The process of vascularization is controlled by specific regulators. Vascular endothelial growth factor (VEGF), otherwise named vascular permeability factor (VPF), induces endothelial cell proliferation as well as angiogenesis in vivo and increases capillary permeability. Here we report the expression of VEGF/VPF mRNA by cultured human luteinized granulosa cells (GC) for at least 10 days. Without HCG VEGF/VPF expression declined after day 4 and by day 10 was reduced to approximately 30% of the value at day 4. However, after culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG), expression of VEGF/VPF mRNA by GC was four times greater than control experiments by day 10, and increased 100% from day 4 to day 10. Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC. Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results suggest that vascularization of the corpus luteum is induced by HCG-mediated effects of VEGF/VPF.      

Diagnostic value of DNA flow cytometry combined with fine needle aspiration biopsy in lymphomas

The nuclear DNA content of cells from 45 malignant lymphomas and from 60 benign lymph nodes obtained by fine needle aspiration was analysed to investigate the diagnostic value of DNA flow cytometry combined with routine diagnostic cytology in lymphomas. DNA aneuploidy was found in 43 per cent of lymphomas of high grade malignancy (NCI Working Formulation) but only rarely in lymphomas of intermediate- or low-grade malignancy or in Hodgkin's disease, and never in benign lymph nodes. The median percentage of proliferative cells (S + G2/M) was 22.6 per cent in diploid high-grade lymphomas, 15.3 per cent in intermediate-, and 8.1 per cent in low-grade lymphomas, as compared with 4.9 per cent in benign lymph nodes (P less than 0.0001). If the presence of DNA aneuploidy or more than 12 per cent of proliferative cells is used as a criterion for malignancy, the diagnostic accuracy of DNA flow cytometry in detecting lymphoma is 81 per cent. DNA flow cytometry suggested correct diagnosis in 10 of the 19 false positive, false negative, or indeterminate cytological findings encountered during the study. It is concluded that DNA flow cytometry combined with fine needle aspiration biopsy has diagnostic value in lymphomas, but false negative results are common especially in low-grade lymphomas; the method should therefore be used in conjunction with light microscopy.